摘要:

4 Free-radical Reactions and Electron Spin Resonance Spectroscopy By A. R. FORRESTER Department of Chemistry University of Aberdeen AB9 2UE In this year's Report the sections on free-radical chemistry and e.s.r. spectroscopy have been combined. In the main emphasis has been placed on new applications of the latter technique to the solution of chemical problems as wider coverage of the spectroscopic results will be given in a forthcoming Specialist Periodical Report.'" 1971 has also seen the retirement of Professors Hey and Waters whose enormous contribution to the field of free-radical chemistry has been commemo- rated by the publication of a most useful volumelb containing essays on a wide variety of aspects of free-radical chemistry. 1 Carbon Radicals 2-Methylpropenyl(l) exhibits a selectivity similar to that of phenyl in its reactions with benzylic hydrogen atoms (primary :secondary :tertiary ; 1.0:3.9 :8.6).In this respect its behaviour is intermediate between that of non-discriminating atomic chlorine and more-stable carbon radicals such as trichloromethyl.2" Decomposition of trans-and cis-a-phenylcinnamoyl peroxides and t-butyl tram-and cis-a-phenylperoxycinnamatesin carbon tetrachloride and other solvents has led to a reappraisal of the stereochemistry of the 1,2-diphenylvinyl radical thus formed.2b Although the results do not completely exclude the linear structure (2),previously advocated for this radical they can be accounted for best by an equilibrating pair of radicals [(3) (4)]which even at 80 "C,react with (a) 'Electron Spin Resonance,' ed.R. 0. C. Norman (Specialist Periodical Reports) The Chemical Society London vol. I in the press; (b) 'Essays on Free Radical Chemistry,' ed. R. 0. C. Norman Special Publication No. 24 The Chemical Society London 1970. (a) P. G. Webb and J. A. Kampmeier J. Amer. Chern. Soc. 1971,93 3730; (b)N. Wada K. Tokumaru and 0. Simamura Bull. Chem. SOC.Japan 1971,44 11 12. 187 A. R.Forrester solvent sufficiently rapidly to ensure a preponderance of that vinyl chloride which has the same stereochemistry as its peroxide precursor. Interconversion of cis-and trails-methoxypropenyl radicals is also slow relative to the rate at which they are trapped by reaction with cumene and it would seem that both the size and the electronegativity of substituents affect the rate of inversion of vinyl radical^.^ Stereochemistry of the products in the above reactions depends upon the rate at which the radicals are trapped and it is significant that addition of toluene-p-sulphonyl iodide to a series of alkynes gave,4 in almost all cases exclusively the 1:1 trans-adduct (9,which implies that the sulphonyl iodide is R SO,C,H,Me-p \/ I /c=c\* an extremely efficient chain-transfer reagent.4 Consideration5 of the known rate (k 2 3 xlo7s-') of inversion of vinyl radicals at -180 "C (extrapolated to ca.10' s-'for propenyl at 25 "C)appears to exclude the mediation of propenyl radicals in the production of 2,4-hexadienes (with retention of configuration at the olefinic bond) from cis- and trans- 1-propenylcopper and related organo- metallics.It was estimated that the rate constant for dimerization would have to be about 10l2mol-' s-' to produce this result and this value is much greater than known values for rate constants of radical-radical coupling reactions in solution. The reactions of vinyl radicals have been critically reviewed.6 Geometrical isomerization of substituted allyl radicals [(6a) S(6b)l in the gas phase has been demonstrated by the isolation of six isomeric dienes in R3 (64 (6b) proportions which suggest that a 'nearly equilibrated' mixture of epimeric allyl radicals was the so~rce.~ 1,l-Dichloroallyl radicals (7) also dimerize to give a mixture of tetrachlorohexadienes in which (8) predominates.' '(a) M.S. Liu S. Soloway D. K. Wedegaertner and J. A. Kampmeier J. Amer. Chem. Soc. 1971,93 3809; (6) R. C. Neuman and G. D. Holmes J. Amer. Chem. Soc. 1971 93 4242. W. E. Truce and G. C. Wolf J. Org. Chem. 1971 36 1727. 'G. M. Whitesides C. P. Casey and J. K. Krieger J. Amer. Chem. Soc. 1971 93 1379. 'L. A. Singer in 'Selective Organic Transformations,' ed. B. S. Thyagarajan Wiley New York vol. 11 p. 239. 'R.J. Crawford J. Hamelin and B. Strehlke J. Amer. Chem. Soc. 1971 93 3810. *W. R. Dolbier and C. A. Harmon Chem. Comm. 1971 150. 189 Free-radical Reactions and Electron Spin Resonance Spectroscopy (7) Further evidence that cyclopropyl radicals are not planar comes from the isolation of small quantities of optically active l-methyl-2,2-diphenylcyclopro-pane on decomposition of the optically active peroxide precursor in carbon tetrachloride.' The product arises by rapid disproportionation within the solvent cage.Additionally a radical-pair mechanism has been advanced to account for the formation of a series of 2,2-diphenyl- 1-substituted cyclopropanes (in which there is 83-86 % retention of configuration) by decarboxylation of the corresponding aldehydes with tris(tripheny1phosphine)rhodium chloride.' Although interconversion of the exo- and endo-isomers [(9a) and (9b)I was more rapid than their reactions with either toluene or di-isopropylbenzene and the same ratio of exo- to endo-chlorohydrocarbon was produced irrespective of the stereochemistry of the radical precursor,' ' complete equilibration of the 7-chloronorcaranyl radicals [( 10a) (lob)] was not achieved before their reduction with triphenyltin hydride.lZ Unlike a-fluorocyclopropyl radicals (1l) a-fluoro-cyclobutyl radicals (12) (if they are indeed non-planar) invert faster than they can be reduced by triphenyltin hydride. CND0/2 calculations predict that the barriers to inversion of the radicals (1 1H14) are 10.5,1.9,4.0 and 0.8 kcal mol-' respectively.' Rearrangement of cyclopropyl radicals to allyl radicals depends upon the stability of the latter. Thus 2,2-and 1,2-diphenylcyclopropyl radicals (15 ; R' = Ph R2 = H; R' = H R2 = Ph) gave the corresponding resonance-stabilized allyl radicals (16) and thence the dimers (17) (30% yield) whereas phenylcyclopropyl radicals (15; R' = R2 = H) under the same conditions ' H.M. Walborsky and J.-C.Chen J. Atner. Chern. Soc. 1971 93 671. lo H. M. Walborsky and L. E. Allen J. Amer. Chem. Soc. 1971 93 5465. L. A. Singer and J. Chen Tetrahedron Letters 1971 939. l2 L. J. Altmann and R. C. Baldwin Tetrahedron Letters 1971 2531. A. R.Forrester merely gave phenylcyclopropane. ' By comparison for rigid cyclopropyl- carbinyls or cyclopropylcarbinyls with a strong conformational preference as in the cholestan-6-yls (18a) and (1 8b) rearrangement may be stereoelectronically controlled. In the rearrangement of (18a) and (18b) to (19) and (20) respectively the bonds which are broken are those which overlap most closely with the orbital of the unpaired electron.l4 Another instance' in which this principal may well apply is the preferred rearrangement of the radical (21) to the primary homoallylic radical (22) rather than to the more stable secondary radical (23). A more complex example is the apparently equilibrating mixture of radicals [(24H28)] derived from bullvalene which gave rise to a series of trienes but l3 J. C. Chen Tetrahedron Letters 1971 3669. l4 A. L. J. Beckwith and G. Phillipou Chem. Comm. 1971 658. l5 E. C. Friedrich and R. L. Holmstead J. Org. Chem. 1971,36 971. Free-radical Reactions and Electron Spin Resonance Spectroscopy 191 here prediction of products is compounded by uncertainties in the stereochemistry of the intermediates. l6 (27) (28) Factors which affect the norbornenyl-nortripticyl radical equilibrium [(29a) (29b)+(29c)] and the nature and stereochemistry of the products that they give rise to has greatly intrigued chemists in the past and last year was no exception.Results obtained by reduction of 3-acetoxynorborn-2-en-5-ylmer-cury(I1) chloride and related acetoxy-mercurials with sodium boro-deuteride (294 (29b) (294 and -hydride strongly suggest that hydrogen (deuterium) abstraction by (29a and 29c; R = OAc) is highly stereoselective but is not so for (29b; R = OAc).17 However reduction of the radical (29b; R = OAc) (in modest yield) by reaction with sodium-naphthalene is faster than skeletal rearrangement to (29a or 29c ; R = OAc) and hence may proceed in a stereospecific manner.'* Products formed by free-radical addition of trimethyltin hydride to norbornadiene have been accounted for" by consideration of the likely modes of approach of the trimethyltin radical (endoor exo)and of the steric effects of the bulky trimethyltin group on the intermediate equilibrating radicals corresponding to (29).Further evidence that 'non-classical' radicals do not intervene in these reductions has been obtained2' from a study of the addition of thiophenol to 3-methylenenor- tricyclene (30). In a series of papers dealing with reactions of polychlorinated H.-P. Loffler Chem. Ber. 1971 104 1981. G. A. Gray W. R. Jackson and V. M. A. Chambers J. Chern. SOC.(C),1971 200. " T. C. Morrill and F. L. Vandemark Terrahedron Letters 1971 181 I. l9 H. G.Kuivila J. D. Kennedy R. Y.Tien I. J. Tyminski F. L. Pelczar and 0.R. Khan J. Org. Chem. 1971 36 2083. 2o S. J. Cristol and R. Kellman J. Org. Chem. 1971 36 1866. A. R.Forrester norbornenyl radicals generated in several ways but generally by standard free- radical procedures Davies and his colleagues2 ’ have shown that these radicals undergo rearrangements as indicated for (29),and that two of the most important A factors which decide the composition of the product mixtures are the tendency for rearrangement from unstabilized to chlorine-stabilized radicals and the effect \ (,tH -+ \kc,) / which the relatively bulky chlorine substituents have on chain-transfer reactions of the equilibrating radicals. The reversibility of intramolecular homolytic alkylation in which the spiro- tetraenyl (32) intermediate is implicated has been elegantly demonstrated22 by isolation of mixtures of (34) and (35) on decomposition of the acyl peroxide precursors of both (31) and (33).For other pairs of radicals as well e.g. (36) and 1 1 (34) (35) ” D. 1. Davies and P. Mason J. Chem. SOC.(C) 1971 288 295; R. Alexander and D. I. Davies J. Chern. SOC.(C),1971 896; R. Alexander D. I. Davies D. H. Hey and J. N. Done J. Chem. Sor. (C) 1971 2367. 22 J. C. Chottard and M. Julia Tetrahedron Letters 1971 2561; see also M. Julia and B. Malassine Tetrahedron Letters 1971 987. Free-radical Reactions and Electron Spin Resonance Spectroscopy (37),23 and (38) and (39),24 there is good reason to believe (from product analysis) that equilibration with an open-chain radical occurs but the evidence at present is less conclusive than that given for (31) (32)C(33).By comparison i'l: \ H CH2I \O 0 / the diphenylcyclohexadienyl radical (40) does not rearrange but fragments as shown only at relatively high temperature^.^ 5a This observation indicates that homolytic arylation is not an appreciably reversible process under the usual conditions,25b and the suggestion has been made that in cases where reversibility has been observed under mild conditions it has been due to special structural or other features of the particular system. Although para-electron-withdrawing substituents facilitate intramolecular alkylation with rearrangement of the radical (41; R = C1) to the phenanthrene (42; R = C1) the effect is relatively slight and consequently the derived relative rates of migration provide little conclusive information on the nature of the transition state leading to rearrangement.26 The nucleophilic character of 23 D.H. Hey Quarf.Rev. 1971 25 483; D. H. Hey G. H. Jones and M. J. Perkins J. Chem. Soc. (C) 1971 116. 24 P. S. Dewar A. R. Forrester and R. H. Thomson J. Chem. SOC.(C) 1971 3950. *' (a) M. J. Perkins and P. Ward Tetrahedron Lerters 1971 2379; D. J. Atkinson M. J. Perkins and P. Ward J. Chem. Sor. (C),1971,3240; (b)J. Saltiel and H. C. Curtis J. Amer. Chem. SOC.,1971 93 2056. 26 P. N. Cote and B. M. Vittimberga J. Amer. Chem. Soc. 1971 93 276. A. R.Forrester alkyl radicals is clearly shown by the high yields of mono- and di-substituted products obtained on methylati~n,~’ of benzylation,’* and cyclohe~ylation~~ protonated pyridines quinolines and related bases3’ Displacement of the nitro-group of a series of nitrofurans by methyl generated as shown from ferrous ions and hydrogen peroxide in dimethyl sulphoxide occurs under unusually mild condition^:^' Fe2+ + H202 + Fe(OH)2++ -OH .OH + MeSMe -+ --+ Me.+ MeS0,H II 0 The phenylfluorenyl radical (43) dimerizes to give an ethane (whose structure was confirmed by 3Cn.m.r. spectro~copy),~~ but not so the bis(t-butylpheny1)- methyl radical (44) [a,(CH) = 1.818,a(o-H) = 0.413,a(m-H) = 0.153 and a(p-H) = 0.366 mT] which like triphenylmethyl gives a 2,5-cyclohexadiene dimer.3 The dimer of triphenylmethyl may be converted into (49,even on treatment with weak acids such as E.s.r.evidence has been presented35 in support of 27 F. Minisci K. Bernardi F. Bertini R. Galli and M. Perchinummo Tetrahedron 1971 3575 H. J.-M. Dou G. Vernin and J. Metzger Bull. SOC. chim. France 1971 1021. 28 H. J.-M. Dou G. Vernin M. Dufour and J. Metzger Bull. SOC. chim. France 1971 111. 29 H. J.-M. Dou G. Vernin and J. Metzger Bull. SOC. chim. France 1971 3553. 30 M. Baule G. Vernin H. J.-M. Dou and J. Metzger Bull. SOC. chim. France 1971 208 3. 31 U. Rudqvist and K. Torssell Acta Chem. Scand. 1971 25 2183. 32 H. A. Staab K. S. Rao and H. Brunner Chem. Ber. 1971 104 2634. ” F. Bolsing and K.-D. Korn Tetrahedron Letters 1971 3865.34 H. Takeuchi T. Nagai and N. Tokura Bull. Chem. SOC. Japan 1971 44 753. 35 D. Braun U. Platzek and H. J. Hefter Chem. Ber. 1971 104 2581. Free-radical Reactions and Electron Spin Resonance Spectroscopy the proposal that the polymer formed on treatment of p-tolyldiphenylmethyl chloride with pyridine arises by addition of p-tolyldiphenylmethyl radicals (47) to the dimethide (46). The growing polymer radical is easily detected by e.s.r. and its spectrum is generally similar to that of (47). Highly conjugated molecules e.g. Tschitschibabin’s hydrocarbon (48) which may be formulated as either singlets or triplets usually have singlet ground states but in solution form mono- radicals by hydrogen abstraction from the solvent by the thermally populated triplet Such is the case with a number of nitrones isatogens and bian- throne.36b However for Schlenk’s hydrocarbon (49) no conventional singlet structure can be formulated and this hydrocarbon has now been shown36c to Ph Ph Ph Ph I I I I Ph-q Ph-q uc-ph exist as the triplet in the solid state (D = 192 MHz E = 17 MHz); in solution in toluene it behaves more like (48),forming two monoradicals one of which is (50).Similar con~lusions~~ have been reached for the diradical (51). Perchlorinated triphenylmethyls e.g. (52) are much more stable than their hydrocarbon ana- logues and not only withstand high temperatures and do not dimerize but are ’‘ (a)G. R. Luckhurst G. F. Pedulli and M. Tiecco J. Chem. SOC.(B) 1971 329 and refs.therein; (6)L. S. Singer I. C. Lewis T. Richerzhagen and G. Vincow J. Phys. Chem. 1971 75 290; (c) H.-D. Brauer Chem. Ber. 1971 104 909. ’’ R. Schmidt and H.-D. Brauer Angew. Chem. internat. Edn. 1971 10 506. A. R. Forrester inert to corrosive reagents such as concentrated nitric or sulphuric acids powdered sodium hydroxide bromine or chlorine.38 The principal stabilizing factor is the protection which the ortho-chlorine atoms afford the central carbon prohibiting bond formation at this centre. However this protection does not prevent electron-transfer reactions of the radical (or the corresponding carbonium ion39) such as that which occurs with hydroxide ion in dimethyl sulphoxide nor does it make the radical insensitive to light.On irradiati~n,~' the very stable CI CI CI clQcl CI CI' CI (54) fluorenyl(53) is formed which can be more conveniently obtained by thermolysis of (52) at 25&320°C [cf triphenylmethyl which gives the fluorenyl (43) on irradiation but this dimerizes rapidly]. The e.s.r. spectra of (52) and related radicals (g z 2.0026) show splittings attributed to a(ci-13C)= 3.0mT and a(Ar-13C)= 1.0mT; the chlorodiaryl radical (54) has g = 2.0055 and a(a-Cl) = 0.22mT. An X-ray analysis of an impure crystal of the latter radical revealed that the rings are twisted by 47" and 43" with respect to the trigonal plane of the central carbon4' There is an increasing awareness aided by three reviews,42 of the importance of hydrocarbon radical-anions as reactive intermediates and of their synthetic 38 M.Ballester J. Riera J. Castaner C. Badia and J. M. Monso J. Amer. Chem. SOC. 1971,93,2215. 3y M.. Ballester J. Riera-Figueras J. Castaner and A. Rodriguez-Siurana Tetrahedron Letters 1971 2079. 40 M. Ballester J. Castaner and J. Pujadas Terraheriron Letters 1971 1699. 41 J. Silverman L. J. Soltzberg N. F. Yannoni and A. P. Krukonis J. Phys. Chem. 1971 75,1246. 42 N. L. Holy and J. D. Marcum Angew. Chetn. Internat. Edn. 1971,10 115; L. L. Miller J. Chem. Ediic. 1971 48 168; L. Eberson and H. Schafer Fortschr. Cheni. Forsch. 1971 21 5. Free-radical Reactions and Electron Spin Resonance Spectroscopy usefulness. Thus 3-nitroperylene may be conveniently obtained (66% yield) by treatment of the radical-cation of perylene with nitrite ion whereas its preparation by direct nitration of perylene is tedious.43 Adaptation of this procedure to the nitration of other hydrocarbon radical-ions is under investigation.The heat of dimerization of the perylene radical-cation (8.8 kcal mol- ') has been evaluated from electronic absorption meas~rements.~~ Reaction of the radical-anion of naphthalene (55) with aryl halides in THF gave mainly benzene and products derived therefrom by reaction with phenyl radicals generated as shown [equation (l)]."' A preparation of aryltrimethyl- and benzyltrimethyl-silanes has been devised46 in which a mixture of the benzyl or aryl halide and trimethylchlorosilane is treated with (55). However triphenylchlorosilane reacted preferentially with (55) to give he~aphenyldisilane."~ The radical-anions of [2,2]cyclophanes e.g.(56),and diarylalkanes e.g. (57),are much less stable than those of their simple mononuclear aromatic counterparts disproportionating at ca. -60 "C to the parent hydrocarbon and dianions ; the latter subsequently fragment to two monoanions [equation (2)] easily trapped by pr~tonation.~~ The electron- exchange rates measured by e.s.r. between the two n-systems of the diarylalkanes PhCH2CH,Ph2--* 2PhCH,--* 2PhCH (2) [lo6-lo8 s-for (57 ;Ar = 1-naphthyl)] are predictably much smaller than those of the [2,2]paracyclophanes (> lo8 s-') in which there is considerable n-n overlap because of the constrained geometry of these molecules.49 Similarity in the e.s.r.spectra of the radical-anions of t-butylbenzene and the bicyclo[2,2,2]- '' C. V. Ristagno and H. J. Shine J. Amer. Chem. Soc. 197 1 93 18 11. 44 K. Kimura T. Yamazaki and S. Katsumata J. Phys. Chem. 1971 75 1768. 45 T. C. Cheng L. Headley and A. F. Halasa J. Amer. Chem. Sac. 1971 93 1502. 46 S. Bank and J. F. Bank Tetrahedron Letters 1971 458 1 see also H. Sakurai A. Okada M. Kira and K. Yonezawa Tetrahedron Letters 197 1 15 1 1. " F. W. G. Fearon and J. C. Young J. Chem. Soc. (B),1971,272. '' J. M. Pearson D. J. Williams and M. Levy J. Amer. Chetn. Sac. 1971 93 5478. '' D. J. Williams J. M. Pearson and M. Levy J. Amer. Chem. Soc. 1971 93 5483. A. R.Forrester octane (58) obviates the possibility that there is electron transfer between the two n-systems via the bicyclo-octane skeleton.However this non-conjugated bridg- ing group does permit intramolecular transmission of singlet excitation in (59) COPh from naphthyl to benzoyl and triplet excitation from benzoyl to na~hthyl.~' The hyperfine splitting uH= 0.23 mT in the seven-line e.s.r. spectrum of the triptycene radical-cation has been attributed to interaction with the six protons indicated in (60),these being rendered magnetically equivalent by electronic 11 t I I H transannular interaction. Among several other interesting e.s.r. studies of aromatic radical-anions reported this year is that in which the coupling constants of the annulene (61)are compared with those of the radical-anion of naphthalene (55) over a wide temperature range.52 The a(&-H) values (0.24mT) for (61) are much smaller than those of (55) (0.49mT) because of deviations from planarity and are [unlike those of (55)] very sensitive to the small changes in geometry that a change in temperature inevitably produces in a non-planar molecule.The e.s.r. spectrum of the radical-anion produced from the atropisomers of the novel hexaphenylene (62) shows53 two different types of coupling a(1-H) = 0.082 and 42-H) = 0.033 mT. 5" H. E. Zimmerman and R. D. McKelvey J. Amer. Chem. Soc. 1971,93 3638. " R. M. Dessau J. Chem. Phys. 1971 54 5430. 52 F. Gerson K. Miillen and E. Vogel Helv. Chim. Acra 1971 54 2731. '' G. Wittig and D. Riimpler Annalen 1971 751 1. Free-radical Reactions and Electron Spin Resonance Spectroscopy 199 The most obvious mechanism for the radical rearrangement [(63) j (65) via (64)] has been discounted54 because the intermediate radical (64) could not be detected by e.s.r.in a flow-system whereas the initial and final radicals [(63) and 0 Me II I C-Me '5 0' -+ I 0I -+ MeCHCH,OCOMe Me AH-kH MeCH-CH (65) (65)] could. The alternative routes (cage process or three-membered-ring transi- tion state) seem unattractive possibilities but experiments with *O-labelled acetate are clearly required. The e.s.r. spectra of (64) (generated by hydrogen abstraction from the corresponding cyclic acetal) and those of a large number of related cyclic and acyclic radicals in which the tervalent carbon is linked to one or two oxygen atoms have been reported at some length and the considerable amount of information which may be derived from such spectra about the ge- ometry of the radicals has been ernphasi~ed.~~9'~ The conclusion of these reports is that the introduction of oxygen substituents adjacent to the tervalent carbon and/or a reduction in the size of the ring containing the tervalent carbon tend to increase the degree of bending and hence the s-character of the half-filled orbital at the radical centre.However use of absolute values of u(a-l3C)and u(a-H)to gauge the degree of bending can be misleading because the signs of these values may change as the mechanism of spin transmission varies with the geometry. Oxyalkyl radicals also participate in the reaction of enols and enol ethers with hydroxyl radicals.56 Thus the adduct radicals (66) [a(cc-H)= 1.7 a(P-H) = 0.86 ..q.n-30 + + H,O MeOCH=CH + -OH * MeO-CH-CH .-MeO=CHkH * MeO-CH-CH, I jb OH H+ and adOMe) = 0.18 mT] and (68) [a(a-H)= 2.24 and a(P-H) = 1.89 mT] were detected when hydroxyl radicals were allowed to react with methyl vinyl ether in a flow system and are considered to undergo acid-catalysed intercon- version via (67).Attempts' to detect aminoalkyl radicals directly during the reaction of amines with hydroxyl radicals (from H202-Ti1") in a flow system were unsuccessful but their presence was established by 'spin trapping' experiments with nitroso-t- butane. Ease of oxidation by hydrogen peroxide [equation (3)] was suggested 54 A. L. J.Beckwith and P. K. Tindal Austral. J. Chrm. 1971 24 2099. " A. J. Dobbs B. C. Gilbert and R. 0. C. Norman J. Chem. SOC.(A) 1971 124. D. J. Edge B. C. Gilbert R. 0. C. Norman and P. R. West J. Chem. SOC.(B),1971 189. 57 N. H. Anderson and R. 0. C. Norman J. Chrm. SOC.(B),1971,993. 200 A. R.Forrester to account for this failure. Such radicals have been detected after irradiation of for example ethylamine trapped in a crystal of adamantane and are considered to be intermediates in the formation of iminyls (R'R2C=N.) in this way (vide infr~).~~" For the radical (69; R' = Me R2 = H) aN= 0.48 a,(NH) = 0.50 H202 + R'R'CNH -R'R2C=&H +.OH + -OH (3) (69) and a(a-H) = a(,$-H) = 1.48 mT. They have also been detected after irradiation of aqueous solutions of amines and amino-acids with high-energy electrons in the cavity of the ~pectrorneter.~~' Phenylthioalkyl radicals generated in a number of way^,^^,^' gave an array of products most of which may be accounted for by the usual dimerization disproportionation and radical-coupling processes.However formation of diphenyl disulphide as a principal product ( -30 % yield) of the electrolysis of PhSCH,CO,-Na' PhSCHzC03Bu' (70) (71) the salt (70) and thermolysis of the ester (71) requires an explanation. Fragmenta- tion of the thioalkyl radical (72) to methylene and thiophenoxyl has been pro- posed but convincing evidence for the mediation of substantial amounts of PhSCH -+ PhS. + :CH2 -+ PhSSPh (72) methylene is lacking at present." Rate constants for the thermal decomposition of t-butyl a-arylthioperacetates and a-aryloxyperacetates in ethylbenzene were similar ( -4.0-5.0 x lo4s-') electron-donating puru-substituents increasing the rate in each case.Formation of diphenyl disulphide in the decomposition of the former esters was not recorded.60b Thermolysis of the ethane (73)in xylene at cu. 100 "Cgave a radical which was easily detected by e.s.r. but whose spectrum showed no fine structure. Identification of this species as tris(pheny1thio)methyl (74) has now been achieved by '3C isotopic labelling.61 The large a(a-' 3C) value observed (4.37 mT) suggests that (74) is considerably bent. (PhS),C-C(SPh) --* 2 (PhS),C* (73) (74) 58 (a)D. E. Wood and R. V. Lloyd J. Chem. Phys. 1970,52 3840; T.Richerzhagen and D. H. Volman J. Amer. Chem. SOC.,1971 93 2062; (b)P. Neta and R. W. Fessenden J. Phys. Chem. 1971 75 738. 5y K. Uneyama S. Torii and S.Oae Bull. Chem. SOC.Japan 1971 44 815. 6o (a) A. Ohno N. Kito and Y. Ohnishi Bull. Chem. SOC.Japan 1971 44 463 467; A. Ohno and Y. Ohnishi Tetrahedron Letters 1969,4405; (6)C. Ruchardt and H. Bock Chem. Ber. 1971 104 577 CJ C. Riichardt and I. Mayer-Ruthardt Chem. Ber. 1971 104 593. 61 A. K. Beck D. Seebach and H. B. Stegmann Angew. Chenz. Internat. Edn. 1971 10. 500. Free-radical Reactions and Electron Spin Resonance Spectroscopy 20 1 Although the relative stabilities (based on their ease of formation by hydrogen abstraction from the parent compound62 and on other chemical evidence6') of the radicals (75H78) is that shown the lifetimes of the e.s.r.signals of a number of related radicals generated by thermolysis of the corresponding azo-compounds Me ArCH < ArOkH < ArSeH < Ar?!4CH2 (75) (76) (77) (78) did not bear out this order.63 However in such comparisons it is important that a clear distinction be made between thermodynamic and kinetic stability due account being taken of the circumstances under which the radicals are generated (see for example ref. 64). 2 Nitrogen Radicals Esr. spectra of the aziridinyl and azetidinyl radicals have been obtained by measuring irradiated solutions of the corresponding amines in cyclopropane containing di-t-butyl peroxide.6s The coupling parameters uN = 1.25 and 1.4 and a(a-H)= 3.07 and 3.83mT and g-values 2.0043 and 2.0045 respectively confirm that in these radicals the unpaired electron is in the 2p orbital of the nitrogen as depicted in (79).A kinetic study of the decomposition of dimethyl- aminyl and di-isopropropylaminyl has led to the prediction (supported by pre- liminary results) that di-t-alkylaminyls should be 'stable' in the absence of solvents with readily abstractable hydrogen atoms.66 N-Alkoxy-N-alkylaminyls (81) are formed on irradiation of t-butyl peroxycarbamates [equation (4)] or directly from (80) by photolysis in the presence of di-t-butyl peroxide. The alkoxy-group (79) is effective in removing spin density from the nitrogen atom since for (81; R = Me) aN= 1.45 and a(a-H) = 2.15 mT (cj dimethylaminyl which has a(a-H) = 2.74 mT).67 N-Alkoxy-N-arylaminyls (83) generated68 by addition of relatively bulky alkyl groups (R ') to 2,4,6-tri-t-butylnitrosobenzene (82) predict-ably have smaller aNvalues (-1.1 mT).These aminyls react further with bulky RNHCOOBU~--+ RNH + coz+ .OBU~+ RNHOBU' 3 RNOB~' (4) II 0 (80) (81) '" K. Uneyama H. Namba and S. Oae Bull. Chem. SOC.Japan 1968 41 1928. O3 A. Ohno N. Kito and Y. Ohnishi Bull. Chem. SOC.Japan 1971,44,470. " R. S. Davidson and P. R. Steiner J. Chem. SOC.(C) 1971 1682. h5 W. C. Danen and T. T. Kensler Tetrahedron Letters 1971 2247. " J. R. Roberts and K. U. Ingold J. Amer. Chem. SOC.,1971,93 6687. " W. C. Danen and C. T. West J. Amer. Chem. SOC..1971 93 5582. '* S. Terabe and R. Konaka J.Amer. Chem. SOC.,1971,93,4306. A. R. Forrester t alkyl groups to give the cyclohexadienes (84).6g Since relatively small alkyl radi- cals (R2)add to the nitrogen of (82) giving a nitroxide (85) and (83) and (85) are easily distinguished the nitroso-compound (82) is a novel 'spin trap' for dif- ferentiating between 'large' and 'small' alkyl radicals. A well-resolved e.s.r. spectrum of diphenylaminyl has now been re~orded.~' This shows aN= 0.89 a(o-H) = 0.37 a(m-H) = 0.15 and a(p-H) = 0.43mT from which it may be deduced that the unpaired electron is delocalized to the extent of about 60 on to the phenyl groups. Protonated diphenylaminyl gives a remarkably similar ~pectrum.~ 'Diphenylaminyl radicals generated by thermo- lysis of diphenylnitrosamine in the absence of air coupled N to ortho-C and N to para-C to give semidines and structurally related polymeric material.In the presence of air p-nitrodiphenylamine was a main pr~duct.~ para-Substituted diphenylaminyls (but not di-p-anisylaminyl) gave mainly the parent amines and diaryldihydrophenazine~.~~ Crystalline diarylaminyls containing germanium e.g. (86) have been prepared by treatment of the corresponding tin or lead com-pounds with diarylgermanium halides. Hyperfine structure (a = 0.3 mT) due to coupling with 73Ge (I = 9/2) was detected in the spectra of these radicals at high spectrometer gain.73 The phenoxazinyl (87) exists to the extent of 85 % as the radical but its e.s.r. spectrum has defied interpretati~n.~~ Position of the equilibrium [2 (88) (89)l is determined to some extent by substituents in the Ar' Ar2 and Ar3 rings.ortho-Substituents in the Ar' ring have most effect 69 T. Hosogai N. Inamoto and R. Okazaki J. Chem. SOC.(0,1971 3399. 'O F. A. Neugebauer and S. Bamberger Angew. Chem. Znternat. Edn. 1971 10 71. " P. Welzel Chem. Ber. 1971 104 808. 72 F. A. Neugebauer and H. Fischer Chem. Ber. 1971 104 886. 73 H. B. Stegmann K. Schemer and F. Stocker Angew. Chem. Internat. Edn. 1971 10 499. 74 J. Brandt G. Fauth W. H. Franke and M. Zander Chem. Ber. 1971 104 519. Free-radical Reactions and Electron Spin Resonance Spectroscopy Ph// Ph (86) (87) greatly destabilizing the monomer relative to the dimer.7 Triarylimidazyls (88) are relatively mild oxidizing agents the most reactive being those with bulky electron-withdrawing groups in the ortho-positions of the Ar' ring.76 Oxidation may proceed either by hydrogen (e.g.from phenols and thiols) or by electron ArZ 2 Ar3 Ar' (89) (e.g.from t-amines) removal. 77 Combination of improved e.s.r. measurements on partially and completely deuteriated triphenylimidazyl (88 ; Ar' = Ar2 = Ar3 = Ph) and simple MO calculations has led to the assignment of all the splittings in its spectrum aN= 0.144 a(o-H) = 0.137 a(m-H) = 0.053 and a(p-H) = 0.151 mT (for Ar2 and Ar3 rings) and a(o-H) = 0.24 a(m-H)= 0.089 and a(p-H) = 0.288 mT (for Ar' ring).78 The assignment79 of the spectrum obtained on y-irradiation of malonamide at 77 K (aN,,= 3.6 aNL= 0.7 aH= 8.0mT) to the o-radical (89a) has been ques- tioned" because of the relatively small aNvalue and the alternative suggestion was made that NH is also present in such systems and that it gives rise to some of the lines in the spectrum attributed to (89a).In support of this view irradiation (89a) (90) 75 L. A. Cescon G. R. Coraor R. Dessauer E. F. Silversmith and E. J. Urban J. Org. Chem. 1971,36 2262. 76 R. L. Cohen J. Org. Chem. 1971 36 2280. " L. A. Cescon G. R. Coraor R. Dessauer A. S. Deutsch H. L. Jackson A. MacLachlan K. Marcali E. M. Potraflce R. E. Read E. F. Silversmith and E. J. Urban J. Org. Chem. 1971 36 2267; A. MacLachlan and R. H. Riem J. Org. Chem. 1971 36 2275. N. Cyr M. A. J. Wilks and M. R. Willis J. Chem. SOC.(B) 1971 404.79 N. Cyr and W. C. Lin J. Chem. Phys. 1969 50 3701. 8o M. C. R. Symons J. Chem. Phys. 1971 55 1493; J. Chem. Soc. (A) 1971 3205. A. R.Forrester of urea at 77 K with 'OCo y-rays has been shown to give a radical with spectral parameters deemed8' to be those expected of the n-type amidyl (90). Chemically amidyls show a strong but not always exclusive preference for reaction on nitrogen e.g. the NO-diacylhydroxamic acid (91) on photolysis gave mainly the amide (92) (15%) but also a trace of the ester (93).82 However photolysis of N-chloro- and N-bromo-acetanilides in the presence of an alkene gave a mixture of cis-and trans-1,2-adducts (both coupled tlia N) in good yield.83 When carbon PhCONHCHMeEt 0 IIPhCONHOCCHMeEt -+ PhCONH -t C02 + CHMeEt /" (92) (91) \i NHII PhCOCHMeEt 1 0 I1 Ph COCH MeEt tetrachloride was used as solvent in the reaction of N-bromoacetamide with cyclohexene the main product was the bromoacetimidate (94) but this is formed by an ionic process.84 A long-held misconception that N-bromoacetamides I Me behave like N-bromosuccinimide under Wohl-Ziegler conditions has thus been removed.In the Reporter's view the chemical and spectroscopic information available at present does not allow an unequivocal classification of amidyls as 0-or n-radicals. Synthetic applications of the re?ctions of aminyls amidyls (including sulphonamidyls) and ammoniumyls (R,NH) have been reviewed.85 Addition of alkyl acyl or aryl radicals to nitrile N-oxides with formation of stable iminoxyls provides another method by which reactive radicals may be 'spin trapped'.86" 'Spin adducts' obtained with acyl radicals give e.s.r.spectra in which splittings due to !he protons in the acyl group are distinguishable. An imminoxyl [(Bu'),C=NO] which is sufficiently stable to be isolated has been reported.86b Iminyls (RRC=N-) previously generateds8 by irradiation of amines H. Bower J. McRae and M. C. R. Symons J. Chein. Soc. (A) 1971 2400. B. Danieli P. Manitto and G. Russo Chem. and Ind. 1971 203. D. Touchard and J. Lessard Tetrahedron Letters 1971 4425. 84 S. Wolfe and D. V. C. Awang Cunad. J. Chetn. 1971 49 1384. R. S. Neale Synthesis 1971 1. 86 (a) B. C. Gilbert V. Malatesta and R. 0.C. Norman J. Amer. Chem. Soc. 1971 93 3290; (b)J.L. Brokenshire G. D. Mendenhall and K. U. Ingold J. Amer. Chem. SOC. I97 I 93 5278. Free-radical Reactions and Electron Spin Resonance Spectroscopy 20 5 are thought to be the intermediates in the phot~lysis~~ and thermolysis8* of azines and in the rearrangement of oxime thionocarbamates to thioxime carba-mates [equation (5)].89 R R The rapid growth in the number of publications on nitroxides makes the reviews dealing with spin trapping,” stereochemistry of nitroxides,’ electron resonance of bisnitroxides in anisotropic reactions of N-nitroso-a~etaniIide,~~’and a general review93most welcome. A claim94that the aziridinyl nitroxide (95) is formed on decomposition of the dihydroxylamine (96) has been refuted95 and the product (which is difficult to separate from small quantities of paramagnetic impurities) assigned structure (97) mainly on the basis of its reactions with bifunctional acylating agents.However in a very recent report96 the product has been shown to be identical with acetoxime. Over-reliance on mass spectral data seems to have provided the root for this confusion. Crystallo-graphic analysis of the bicyclic nitroxide (98) has revealed” that like Fremy’s Me Me Me Me NHOH k-i Me N Me NHOH Me (96) \ (97) Me,C=NOH \/ N--O EtN-0 I ONEt I I +- 1.289A CH .:.‘ O--N 7/ / Me \ H’ 2.278k ‘ (99) ” M. Kamachi K. Kuwata and S. Murahashi J. Phys. Chem. 1971 75,164. ” W. J. Middleton J. Amer. Chem. SOC.,1971 93 423.‘9 R. F. Hudson A. J. Lawson and E. A. C. Lucken Chem. Comm. 1971 807. 90 M. J. Perkins ref. 1(6) p. 97; E. G. Janzen Accounts Chem. Res. 1971 4 31. 91 E. G. Janzen in ‘Topics in Stereochemistry,’ ed. N. L. Allinger and E. L. Eliel Wiley New York 1971 vol. 6 p. 177; A. Rassat Pure Appl. Chem. 1971 25,623. 92 (a)G. R. Luckhurst Roy. Znst. Chem. Rec. 1970 3 61 ;(6) J. I. G. Cadogan ref. I(h) p. 71 ; Accounts Chem. Res. 1971 4 186. 43 E. G. Rozantsev and V. D. Sholle Russ. Chem. Reti. 1971,40 233. ’‘ G. R. Luckhurst and F. Sundholm Tetrahedron Letters 1971 675. 9s P. Singh D. G. B. Boocock and E. F. Ullman Tetrahedron Letters 1971 3935. 9h J. F. W. Keana R. J. Dinerstein and D. P. Dolata Tetrahedron Letters 1972 119. ’’ A. Capiomont B. Chion and J. Lajzerowicz Arta Cr-vst.1971 B27,322. A. R. Forrester salt [(KSO,),NO.] 'dimers'98 are formed in the solid state in which the nitrogen and oxygen atoms of molecular pairs are 2.28A apart (99). This structure contrasts with the dimeric transition state (100) which has been proposed9' for the disproportionation of diethyl nitroxide. Reaction of bistrifluoromethyl nitroxide with alkanes gave the corresponding alkenes as intermediates which reacted further with the radical to give 2 1 (nitroxide :alkene) ad duct^.^* With alkynes the initial 2 1 adduct gave rise to a number of products including the corresponding 1,2-diketones. loo Of the numerous reports on the use of spin traps perhaps the most significant is that which describes the trapping of the penta- cyanocobaltate(I1) anion [-Co(CN),l3 -,with nitrosobenzene.The organometallic nitroxide thus formed [aN= 1.38 a(o-,p-H) = 0.32 a(m-H) = O,ll and aco = 1.06 mT] has been compared both with alkyl aryl nitroxides and nitroaromatic radical-anions. lo' Several new spin labels have been synthesized the steroidal nitroxide (101 ;R' = P-OH R2 = R3 = CH,CH=CH,) in which the nitroxide group is incorporated into the molecular skeleton being especially novel.'02 0-I (101) Much publicitylo3 has been given to a new nitroxide spin label (structure un- specified) which may be utilized in the assay of morphine and other opiates in urine. The method seems to depend upon the drug releasing nitroxide spin labels bound to antibodies the concentration of the released spin labels then being measured by e.s.r.The sensitivity of the method is claimed to be 1000 times greater than that of comparable methods using thin layer chromatography. 3 Oxygen Radicals Reviews surveying reactions of oxygen radicals with metal ions,' O4 hydrogen abstraction from O-H bonds lo5 reactions of peroxides with phosphates sul- phides and amines,'06 synthetic applications of the hypoiodite reaction lo7 and 98 K.E. Banks R. N. Haszeldine and B. Justin J. Chem. Soc. (C),1971 2777. y9 K. Adamic D. F. Bowman T. Gillan and K. U. Ingold J. Amer. Chetn. Soc. 1971 93 902. loo R. E. Banks R. N. Haszeldine and T. Myerscough J. Chem. SOC.(C),1971 1951. lo' M. G. Swanwick and W. A. Waters J. Chem. SOC.(B) 1971 1059. lo' R. Ramasseul and A.Rassat Tetrahedron Letters 1971 4623. Varian Instrument Applications 1971 vol. 5 no. 3. Io4 E. T. Denisov Russ. Chem. Rev. 1971,40 24. '05 M. Simonyi and F. Tudos Ado. Phys. Org. Chem. 1971 9 127. lob D. G. Pobedimskii Russ. Chem. Ret;. 1971 40 142. lo' J. Kalvoda and K. Heusler Synthesis 1971 501. Free-radical Reactions and Electron Spin Resonance Spectroscopy a further volume"' in the series entitled 'Organic Peroxides' have been pub- lished. The rates and activation parameters for decomposition of di-t-butyl peroxide in cyclohexane and acetonitrile over a temperature range wider than that previously employed have been re-evaluated and confirmation obtained that they are dependent on the nature of the solvent. However the magnitude of the solvent effect is much smaller than that previously recorded."' The effect which the stability of the incipient radicals have on the rate of thermal decomposition of peresters is thought to be slight because of the surprising thermal stability of the esters (102).Formation of the relatively stable iminoxyl (103) appears to provide little driving force for this decomposition and it was concluded that the R' R' polarity of the R group (in RCOOBu') was the critical factor.' lo Pyrolysis or photolysis of the perfluoro-peroxide (104),which is more stable than dimethyl peroxide in the gas phase gave mainly carbon dioxide and carbonyl fluoride. CF30-OCF3 -+CF300. + CF + CF + F-// (104) 0-0 (1051 J\ COF + F. CO + 2F. These are considered to arise t.ia the novel intermediate (105)(detected by its i.r.spectrum) formed by initial 0-C fission.' ' Generation of benzyl radicals (106) by reaction of the parent peroxide with N-bromosuccinimide did not initiate an intramolecular-induced decomposition of the peroxide group the final product being the corresponding brominated peroxide. 'l2 This result lends support to the mechanism of Cadogan et al.' l3 [Scheme 1 route (a)]rather than to that of Walling et ~1."~[route (b) represented in this case by (107)] for the radical- induced decomposition of dibenzoyl peroxide with formation of a bond between the attacking radical and the ortho or para carbon atom. The mode of thermal decomposition of rn-nitrobenzenesulphonyl peroxide (108) depends critically I"* 'Organic Peroxides' ed.D. Swern Wiky New York 1971 vol. 11. C. Walling and D. Bristol J. Org. Chem. 1971 36 733. C. Ruchardt and R. Pantke Chem. Ber. 1971 104 3456. ''I K. 0. Christe and D. Pilipovich J. Amer. Chem. Soc. 1971 93 51. M. M. Schwartz and J. E. Leffler J. Amrr. Chem. SOC.,1971 93 919. J. I. G. Cadogan D. Hey and P. G. Hibbert J. Chem. Soc. 1965 3939; C. Walling and Z. Cekovic J. Amer. Chem. SOC.,1967 89 6681. A. R. Forrester R-OJ" C=O + PhCOO-+ PhCOO. Scheme 1 upon the solvent. In aromatic solvents an ionic process prevails and electro- philic sulphonyloxylation occurs but in chloroform products derived from rn-nitrobenzenesulphonyloxylradicals were obtained. l4 The mixed peroxide (109) on decomposition in benzene gave products mainly derived from radicals PMe \ only when a base (MgO) was present to remove the toluene-p-sulphonic acid formed during the reaction.' Details of the oxidation of phenols with silver carbonate supported on celite have now been disclosed. This oxidant which is claimed to be highly specific gives products derived exclusively from C-C coupling of the intermediate phenoxyls.'' A new reagent hydrogen[hexacyanoferrate(~~~)] (from K,FeCN and HCl) which is soluble in methanol oxidizes phenols with low oxidation potentials but not phenol itself nor p-cresol. l7 With 2,6-di-t-butyl-4-methyl-phenol the dienone (110) (28 %) was the main product formed it is thought by further oxidation of the initial phenoxyl to a phenoxonium ion which is then solvolysed.Evidence for the intermediacy of phenoxonium ions in anodic 'I4 Y. Yokoyama H. Wada M. Kobayashi and H. Minato Bull. Chetn. SOC.Japan 1971,44 2479. 'I5 R. Hisada H. Minato and M. Kobayashi Bull. Chem. Soc. Japan 1971 44 2541. 'Ih V. Balogh M. Fetizon and M. Golfier J. Org. Chem. 1971 36 1339. G. Biggi F. Del Cima and F. Pietra Tetrahedron Li.trers 1971 281 1. Free-radical Reactions and Electron Spin Resonance Spectroscopy 209 0 HO,Il,O" 1-0-0 0' 0 00'0 tPH2 (1 10) oxidations of 2,4,6-di-t-butylphenol,' ' autoxidations of 2,4-di-t-butylphenols catalysed by aminesopper salt catalysts l9 oxidations of certain hydroxy- diphenyl ether and diphenylmethane derivatives with lead dioxide and tetra- acetate,120 oxidations of bisphenols related to a-tocopherol,12 ' and oxidation of salicyl alcohols and similar phenols by periodate'22 has been presented.Oxidation of salicyl alcohol is particularly interesting since it gives a Diels-Alder dimer of the dienone (112). However the possibility that the monomer arises not from the cation (1 11) but from the periodic ester (1 13) cannot be discounted. Disproportionation of aryloxyl radicals to aryloxy-anions and -cations [equation (6)] at low pH values (by analogy with semiquinone radical-anions) has been 2ArO. S ArO' + ArO-(6) proposed by Waters.'23 Consideration of the extensive data available on phenol oxidations led him to the further proposal that oxidations in acidic solution especially with reagents of high potential gave phenoxonium ions which prefer to couple 0-C whereas reagents such as alkaline ferricyanide gave phenoxyls which prefer to couple C-C.It is difficult to make generalizations in this field because of the complexity of the product mixtures frequently encountered and the lack of detailed information on iizter alia the role of ligand molecules in many oxidations. Nevertheless the above rationalization could serve as a useful guide although it undoubtedly requires qualification in many instances. Con- trary to Waters' proposals Scheme 2 has been devised to account for the produc- tion of aryloxyls in the autoxidation of certain phenols in the presence of copper salt-pyridine catalyst the radicals coupling 0-C to yield commercially sig- nificant polymers.' 24 This scheme accommodates observations such as the coupling process is first order in oxygen pressure and copper catalyst and is independent of phenol concentration but not phenol structure.t-Butylperoxyl radicals bound to cobalt and formed by treatment of acetylacetonatocobalt(I1) with t-butyl hydroperoxide oxidized 2,4,6-tri-t-butylphenol to the corresponding '" A. Ronlan and V. D. Parker J. Chem. Soc. (C) 1971 3214. '" D. G. Hewitt J. Chem. Soc. (0,1971,2967. ''O D. G. Hewitt J. Chem. Soc. (C) 1971 1750. ''I M. Chauhan F. M. Dean K. Hindley and M. Robinson Chem. Comm. 1971 1141. '*' E. Adler S. Brasen and H. Miyake Acta Chem. Scand. 1971 25 2055. W. A. Waters J. Chem. SOC.(B) 1971 2026. lZ4 C. C. Price and K. Nakaoka Macromolecules 1971 4 363.A. R. Forrester 2 ArOH 1-2A~O. 1-2ArO. HO CI (PY)2 2ArOH \culI &/ 'cu,I k/ -2HzO 'OH Scheme 2 'unbound' and 'bound' phenoxyls. Both species (g = 2.006 and 1.996 respec- tively) were detected by e.s.r. the latter showing in addition to an octet splitting due to coupling with the cobalt a doublet splitting which could not be assigned.125 The exact nature of these 'bound' radicals has not yet been clearly defined but comparison of their reactions with those of the corresponding 'unbound' radicals should be revealing. A review describing mechanisms of hydroxylation of aro- matic compounds has been published in which phenol oxidation is given con- siderable attention.' 26 Oxidation of a number of 2- and 4-halogenphenols and 2-nitrophenol with hydroxyl radicals (Ti"'-H202) resulted in a displacement of the substituent with formation of the 1,2- or 1,4-benzosemiquinone.127 The instability of benzo- semiquinones in aqueous alkaline solution has been attributed to their autoxida- tion to more highly oxygenated radical-anions.28 Thus 2-methylquinol gave a mixture of three isomeric radical-anions one of which [( 114); 43-H) = 0.055 a,(Me) = 0.095 and 45-H) = 0.415 mT] is shown. The semiquinone of naphtha- zarin (115) (aH= 0.238 and a,(OH) = 0.051 mT) generated in pyridine-tri- ethanolamine coupled C-C to give a dimer (5%) and a cyclotrimer (1 1%) ;'29 0. HO 0-0-HO 0. (1 14) (1 15) (1 16) some related radical-anions behaved similarly. The semiquinone (116) derived from [2,2]paracyclophane showed an interesting splitting in its e.s.r.spectrum attributed to coupling with the nitrogen (aN= 0.215 rnT).I3' '" A. TkaC K. Vesely and L. Omelka J. Phys. Chem. 75 2580 2575. lZ6 D. I. Metelitsa Russ. Chem. Rer. 1971 40 563. 12' K. Gunther W. G. Filby and K. Eiben Teiruhedroti Leiiers 1971 251. P. Ashworth and W. T. Dixon Chern. Cornm. 1971 1150. H. Brockmann H. Greve and K. Hoyermann Tetrahedron Letters 1971 1493. A. R. Forrester and R. Ramasseul J. Chem. SOC.(B) 1971 1638. Free-radical Reactions and Electron Spin Resonance Spectroscopy 21 1 Spectra of the semidiones of a varied collection of bicyclo[n,l,O]-and bicyclo-[n,l,l]-alkanes have been described from which a wealth of information about the dynamic stereochemistry and other structural features of the carbon skeleton has been gained.Of particular interest is the conversion of the semidione (117) (coupling constants in mT) to the ortho-benzosemiquinone (118) on treatment with an excess of oxygen. An unusual carbonyl insertion has been uncovered during an attempt to make the ketyl (119) from the corresponding ketone by alkali-metal reduction. The spectrum observed was identical with that of the semidione (120) produced from the diketone (121) and had uH = 0.269 uHb= nH = 0.044 mT. The mechanism of this change has not been elucidated. 132 Spectra of the semidiones (122)derived from ferrocene showed no coupling with protons of the interannular ring and only a small splitting (0.05mT) attributable to the ‘ortho’ protons.’33 Evidence134has been presented that reduction of 0-0.90-C=C-Me Fe t R ,Q Hc Hh Ha perfluorobiacetyl with lithium gives in addition to the monomeric semidione (tight and loosely bound ion pairs detected) a triplet species (aF= 1.067 mT-six equivalent fluorines) formulated as (123).Dialkoxy-semidiones (124) formed by electrolytic reduction of dialkyl oxalates have coupling constants for their 131 G. A. Russell J. J. McDonnell P. R. Whittle R. S. Givens. and R. G. Ke5ke J. Amer. Chem. Soc. 1971 93 1452; G. A. Russell P. R. Whittle and R. G. Keske J. Amer. Chem. SOC., 1971 93 1467. 132 J. P. Dirlam and S. Winstein J. Org. Chem. 1971 36 1559. I33 J. J. McDonnell and D. J. Pochopien J.Org. Chem. 1971 36 2092. I34 G. A. Russell. J. L. Gerlock and D. F. Lawson J. Amer. Chem. SOC.,1971 93 4088. 2 12 A. R.Forrester a-protons which depend upon the size of the /?-substituent this controlling the time-averaged dihedral angle. ' For example (124 ;R = Et) has a(a-H) = 0.134 mT and (124; R = Pr') has a(a-H) = 0.71 mT. A number of relatively stable ketyl radical-anions of cyclic a/?-unsaturated ketones in which both hydrogens a to the x-system have been replaced by alkyl or aryl groups e.g. (125) have been produced by electrolytic reduction of the ketones in DMF.'36 For (125) the values (in mT) shown for the coupling con- stants and the absence of a detectable splitting for the protons in the 6-methyl 0-0-(1.18) (0.034) A Me Me (0.08) groups indicate that spin density at the fi-position is greater than not only that at the a-position but also that at the carbon of the carbonyl group.Spectral interpretation was assisted by both Huckel and McLachlan MO calculations. Cyclic dienones were surprisingly easily reduced to the corresponding ketyl radical-anions e.g.(126) (coupling in mT) by reaction with potassium t-butoxide in dimethyl sulphoxide in a flow ~ystem.'~' Good agreement between experi- ment [a(/?-F)= 5.85 and 8.44mT respectively for the ketyl radical-anions of perfluorodiethyl ketone and perfluorocyclobutanone] and theory (INDO cal- culations) supports the notion that spin delocalization into the perfluorinated alkyl groups of the above radicals occurs uia overlap of fluorine p-orbitals and 2p orbitals of the x-system..' 38 Fluorine hyperfine coupling constants for the ketyl radical-anion [(ArF)2CO-] of perfluorobenzophenone [a(o-F) = 0.480 a(m-F) = 0.106 and a(p-F) = 0.836mTl and the ketyl [(AT~)~COH] are unex- pectedly larger than those of their partially fluorinated analogues (in 4,4'-difluoro-benzophenone ketyl radical-anion aFis 11 smaller).' 39 The structure of ion 135 J.Voss Tetrahedron 1971 27 3753. IJ6 G. A. Russell and G. R. Stevenson J. Amer. Chem. Soc. 1971,93 2432. 137 G. A. Russell and R. L. Blankespoor Tetrahedron Letters 1971 4573. 138 W. R. Knolle and J. R. Bolton J. Amer. Chem. Soc. 1971 93 3337. "9 F. P. Sargent and M. G. Bailey Canad. J. Chem. 1971 49 2351. Free-radical Reactions and Electron Spin Resonance Spectroscopy 213 pairs of fluorenone and xanthone radical-anions have been described in terms of a dynamic model in which the cation can 'jump' between two positions of minimum energy the relative populations of these states depending inter ah on the ~olvent.'~' Several simple methyl ketones gave (e.s.r.) complex mixtures of radicals on U.V.irradiation at low temperature in a flow system. The product radicals included ketyls (by photoreduction) alkyl radicals and the protonated semidione MeCOC(0H)Me (by Norrish Type I cleavage of the excited ketone) acylmethyl radicals (by hydrogen abstraction) and solvent-derived radicals (by hydrogen abstraction or induced decomposition of solvent). The radicals detected from a particular ketone depended upon the structure of the ketone and the solvent.141 4 Sulphur Radicals Homolytic bimolecular substitution (S,2) of alkylboranes by alkylthiyl radicals has been established by the detection (esr.) of the displaced radical (R2-)[equation (7)].'42 Similar reactions with Grignard reagent^'^^,'^^ and with organo-bismuth and -antimony compounds have also been observed and it appears that this is R'S.+ R2,B -+ R'SBR' + R2-(7) a common reaction of thiyl radicals and organometallic reagents. The reaction with trialkylboranes has been utilized'44 in a new preparation of unsymmetrical sulphides in which the trialk ylborane and a symmetrical disulphide are heated in THF in the presence of air or U.V. light. Yields of sulphide formed in this chain process [equations (7) and (8)] are -90%.The extensive and frequently contro- versial literature on S,2 reactions has been sifted in a recent m~nograph.'~~ R2. + R'SSR' + R2SR1 + R'S. (8) The reversibility of the intramolecular addition of thiyl radicals has been convincingly dem~nstrated'~~ by the isolation of the same ratio of (134 133; R' = Me) (95 :3) on irradiation of either of the thiol precursors of the radicals (127 and 128 ; R' = Me) at 80 "C. The high proportion of (134) implies that the radical (131 ; R' = Me) is thermodynamically more stable than either (129 or 130; R' = Me) since at -65°C the ratio (134 133; R' = Me) from (127; R' = Me) is 22 :76 and from (128; R' = Me) is 50 50. Significantly the principal product (67 %) from (128 ;R' = H) under conditions of thermodynamic 14" K.S. Chen S. W. Mao K. Nakamura and N. Hirota J. Amer. Chern. SOC.,1971 93 6004; CJ B. J. Tabner and J. R. Zdysiewicz J. Chem. Soc. (B) 1971 1659. 14' H. Paul and H. Fischer Chem. Comm. 1971 1038. 142 A. G. Davies and B. P. Roberts J. Chem. SOC.(B) 1971 1830. 143 A. W. P. Jarvie and D. Skelton J. Organometallic Chem. 1971 30 145. 144 H. C. Brown and M. M. Midland J. Amer. Chem. Soc. 1971,93 3291. 145 K. U. Ingold. and B. P. Roberts 'Free-Radical Substitution Reactions Bimolecular Homolytic Substitutions (S,2 reactions) at Substituted Multivalent Atoms,' Wiley New York 1971. '46 J.-M. Surzur M.-P. Crozet and C. Dupuy Tetrahedron Letters 1971 2025 2031 ; J.-M. Surzur R. Nouguier M.-P.Crozet and C. Dupuy Tetrahedron Letters 1971 2035. A. R. Forrester R' control (80 "C)was (134; R' = H) [which arises viu the primary radical (131 ; R' = H)] and not (133; R' = H) (which arises via a secondary radical). Product (132) was only formed (13%) from (127) when R' = H and then only under conditions of kinetic control (-65 "C). Spontaneous decomposition of arenediazothiolates on heating [equation (9)] is assisted by a radical-induced decomposition in which probably both aryl and ArN=NSR + AP + N + RS. (9) arylcyclohexadienyl radicals (from Ar. and aromatic solvent) participate. 47 The large difference between the coupling constants of the a-and P-protons of the adducts of alkylthiyl radicals and alkenes e.g. (135) (coupling constants in mT) CH ,SCH,CH S,CH3 ?f I.\ (1.489)(2.16) H,C-CH (135) (136) excludes the symmetrically bridged structures (136) previously proposed for such species.14' However the P-coupling constants are smaller than those expected for the favoured conformation (137) and a model (138) has been designed in which the sulphur is distorted somewhat towards the half-filled p-orbital (with a corresponding movement of the B-hydrogens from their tetrahedral positions) not enough to create the bridged species (136) but sufficiently to control the stereochemistry of the subsequent reactions of radical.14' H. Van Zwet J. Reiding and E. C. Kooyman Rec. Trac. chirn. 1971 89 21. 148 P. J. Krusic and J. K. Kochi J. Amer. Chem. Soc. 1971 93 846; T. Kawamura M.Ushio T. T. Fujimoto and T. Yonezawa J. Amer. Chem. Soc. 1971 93 908. Free-radical Reactions and Electron Spin Resonance Spectroscopy 21 5 H Electrochemical reduction of aromatic thiocarbonyls yielded thioketyl radical- anions whose aromatic proton coupling constants are much smaller than those of the corresponding ketyls thus reflecting the less-efficient transfer of free spin from the CS group compared with the CO group to the ring position^.'^^ Spectroscopic features of a wide variety of radicals and radical-ions derived from thiophen have been summarized.' 50 Similarity in the e.s.r. and electronic spectra of the radical-cations (139) and (140)has been attributed to some degree of S-S bonding in (140). ' (139) lJ9 L. Lunazzi G.Maccagnani G. Mazzanti and G. Placucci J. Chem. Soc. (B) 1971 162. I5O L. Lunazzi A. Mangini G. F. Pedulli and M. Tiecco Gazzetta 1971 101 1. Is' B. I. Stepanov W. Ya. Rodionov A. Ya. Zheltov and V. V. Orlov Terruhedron Letters 197 1 1079.

ISSN:0069-3030    

DOI:10.1039/OC9716800187

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

5 Arynes Carbenes Nitrenes and Related Species By J. T. SHARP Chemistry Department University of Edinburgh Edinburgh 1 Arynes Structure.-The interaction of orbitals through bonds and through space has been reviewed,' and there have been several theoretical treatments of the isomeric ben~ynes~-~ and perfluorobenzynes. INDO results agree with previous work in predicting that the closed shell singlet o-isomer is the most stable species in each case ;however contrary to earlier extended Huckel calculations p-benzyne is found to be less stable than the rn-isomer. It is predicted that rn-and p-benzyne constrained to benzene-like geometry have triplet ground states but that singlet- triplet energy separations are small and calculations at equilibrium geometry could result in an inverted order.For rn-benzyne it was concluded5 that the formation of (l) understood to have a shortened distance across the ring owing to the a-bond was a distinct possibility. Methods of Generation.-The photolysis of phthaloyl peroxide through Pyrex has been shown to be a convenient method of generating benzyne at low temper- atures ;6 the intermediate formed in this way underwent stereospecific [4 + 21 and non-stereospecific [2 + 21 cycloadditions in the usual manner of thermally generated benzyne. The precursor (2) has been synthesized and used to prepare triptycene (20%) by pyrolysis at 200 OC7 The indazolone adduct of cyclopenta- diene (3) was pyrolysed' at 500°C under vacuum to give biphenylene (64%); ' R. Hoffmann Accuunts Chem.Res. 1971 4 1. D. L. Wilhite and J. L. Whitten J. Atner. Chrm. Soc. 1971 93 2858. J. F. Olsen J. Mol. Structure 1971 8 307. P. Millie L. Praud and J. Serre Internat. J. Quantum Chem. Symp. 1971 no. 4,187. ' B. A. Hess jun. and L. J. Schaad Tetrahedron Letters 1971 17. M. Jones jun. and M. R. De Camp J. Org. Chem. 1971,36 1536. ' ' A. T. Fanning jun. and T. D. Roberts Tetrahedron Letters 1971 805. D. L. Forster T. L. Gilchrist C. W. Rees and E. Stanton Chem. Comm. 1971 695. 217 218 J. T. Sharp Q(k0 0 N' 0 however the analogous adduct of phthalazine- 1,4-dione (4) retained the carbonyl groups under similar conditions to give benzocyclobutenedione (88 %). The pyrolysis of phthalic anhydride is well known to produce benzyne; it has now been suggested' that the analogous decomposition of 4-nitrophthalic anhydride proceeds via a benzynyl free radical.Phthalic anhydride is also decomposed in the plasma of a glow discharge" to give biphenylene and triphenylene as the main products. The intermediates C6H4C0 C6H4 and C,H,-C,H were trapped with a variety of reagents e.g. ammonia to give (5) and (6). The stability of o-halogenophenyl-lithium compounds in various solvents at -150-+ 20 "C has been studied by d.t.a. and the mechanism of their decomposition to arynes is discussed. The decomposition of acylarylnitrosamines has long been used as a source of aryl radicals,12 particularly for the preparation of biaryls. Full reports and a review12 have now appeared on the use of these reagents as aryne precursors.N-Nitrosoacetanilide (NNA) (7) and substituted analogues have been decom- posed in benzene in the presence of various aryne traps to give adducts in yields from 4 to 82 %.I3 It appears that the presence of certain arynophiles diverts the E. K. Fields and S. Meyerson Tetrahedron Letters 1971 719. lo H. Suhr and A. Szabo Annalen 1971,752 37. 'I 0. M. Nefedov and A. I. D'yachenko Doklady Akad. Nauk S.S.S.R. 1971 198 593. l2 J. I. G. Cadogan Accounts Chem. Res. 1971 4 186. l3 D. L. Brydon J. I. G. Cadogan J. Cook M. J. P. Harger and J. T. Sharp J. Chem. Soc. (B) 1971 1996. 219 Arynes Carbenes Nitrenes and Related Species xa-Radical NIOAC products I NNA decomposition from the chain sequence (a)leading to phenyl radicals into one (b)leading to benzyne adducts.The presence of an aryne intermediate in these reactions is confirmed by the results of competition experiments.13914 NNA is unusual among aryne precursors in that its reactions with furans do not produce the usual 1,4-epoxynaphthaIene adducts. Furan itself reacts to give only ca. 5 % of aryne adduct and a higher yield of 2-phenylfuran,' 3,1 whereas 2,5- dimethylfuran gives 2-methyl-5-benzylfuran,' the last two products being formed by non-aryne routes. The utility of the NNA reaction has been extended by the use of in situ nitrosating reagents to provide a convenient and mild method of generating some arynes from aromatic amines.' The abnormally facile reactions of o-t-butylbenzynes generated from acylarylnitrosamines with acetic acid were attributed to steric hindrance of alternative reactions.' * 1,2-Triptycene has been reported as an intermediate in the reaction of 2-bromo- triptycene with potassium amide." Potassium t-butoxide in DMSO has been used to generate 1,2-dehydronaphthalene2'and a 1,2-dehydrophenothiazinehas been formed by dehydrochlorination of 1-or 2-chloro- 10-methylphen~thiazine.~ ' A new aryne the highly reactive dehydrocyclopentadienyl anion (8) has been formed by the thermal or photochemical decomposition of the diazocyclopenta- diene-2-carboxylate anion22 and trapped with tetraphenylcyclopentadienone to give (9) and with 1,4-diphenyl-sym-tetrazine.Following the postulation of 1,3-dehydroarenes as intermediates in the explosive thermal decomposition of solid m-carboxybenzenediazonium salts (lo),it has been suggested23 that their decom- position in solution involves the same intermediate but not in the major reaction path.Thermal decomp~sition~~ of (1 1)did not produce 1 &dehydronaphthalene l4 B. H. Klanderman D. P. Maier G. W. Clark and J. A. Kampmeier Chem. Comm. 1971 1003. l5 V. Hassmann C. Ruchardt and C. C. Tan Tetrahedron Letters 1971 3885. '' J. I. G. Cadogan M. J. P. Harger J. R. Mitchell and J. T. Sharp Chem. Comm. 1971 1432. l7 J. I. G. Cadogan J. R. Mitchell and J. T. Sharp Chem. Comm. 1971 1. J. 1. G. Cadogan J. Cook M. J. P. Harger P. G. Hibbert and J. T. Sharp J. Chrm. Soc. (B) 1971 595. l9 C. E. L. Peterson and A. Berg Acta Chem. Scand.1971 25 375. *' R. H. Hales J. S. Bradshaw and D. R. Pratt J. Org. Chem. 197I 36 3 14 3 18. D. H. Jones J. Chem. Soc. (C) 1971 132. 22 J. C. Martin and D. R. Bloch J. Amer. Chem. SOC.,1971 93 451. '' R. A. Rossi R. H. de Rossi and H. E. Bertorello J. Org. Chem. 1971 36 2905. 24 D. C. De Jongh and G. N. Evenson Tetrahedron Letters 1971 4093. 220 J. T. Sharp 0-so but rather a symmetrical oxygen-containing intermediate thought to be (12) which in the presence of carbon monoxide gave (13). Cycloaddition Reactions.-The bulk of experimental evidence to date has indi- cated that the reactive species and hence the ground state of o-benzyne is a symmetrical singlet diradical which undergoes concerted [4 + 21 cycloaddition with 1,3-dienes and stepwise [2 + 21 cycloadditions.However Tabushi2’ has reported that benzyne generated thermally from benzenediazonium carboxylate undergoes a [6 + 21 cycloaddition with cycloheptatriene to give (14) as well as the ene product (15). The absence of [4 + 21 and [2 + 21 cycloaddition products led these workers to propose that (14) is formed by a concerted [6 + 21 cyclo- addition requiring an A-form of benzyne (18) on the basis of orbital symmetry considerations and to suggest a general mechanism of concurrent contribution of S-and A-benzyne. This formulation of the product as (14) and hence the implication regarding the structure of benzyne has been challenged by two (17)s-(18) A-X (19) 25 I. Tabushi H. Yarnada Z. Yoshida and H. Kuroda Terruhedron Letters 1971 1093.Arynes Carbenes Nitrenes and Related Species 22 1 gro~ps~~,~’ who consider the sole cycloaddition product to be the [2 + 21 adduct (16)formed by a stepwise route. Effective competition of the [2 + 21 (30%) compared with [4+ 21 (70%) cycloaddition is also observed in benzyne addition to ~yclohepta-1,3-diene.~~*~~ In these cases it is suggested” that the diene systems are so distorted from planarity that stepwise cycloaddition becomes energetically quite favourable. It is however interesting to note that other reactive dienophiles give exclusively [4 + 21 cycloaddition with these olefins. The planar substituted tropones react with benzyne mainly uia [4 + 21 cycloaddition.28 Compared with other arynes tetrafluorobenzyne shows an abnormally high preference for [2 + 21 addition to bicyclo[2,2,l]heptadieneto give (19; X = F) compared with the [2 + 2 + 21 rea~tion,’~ although the latter would be the orbital symmetry allowed reaction for the S-form of the aryne (17).The argu- mentZ5 that the major product (19; X = H) may be formed via a concerted reaction involving the A-form of benzyne may not be valid29 and seems less likely for the tetrafluoroaryne in view of the much larger S-A splitting predicted for the latter.3 In the presence of silver ions the course of the reaction of cycloheptatriene with benzyne is completely changed and gives the [4 + 21 adduct as the only product.27 The effect of Ag+ on the reactions of benzyne has been attributed to the formation of a benzyne-silver complex which on reaction with cyclo- octatetraene3’ leads to the homotropylium ion (20).It has now been suggested3’ that the collapse of (20) would not lead only to the observed product (21) and additional complexation of (20) with Ag2 + is proposed. An alternative scheme32 suggests that the ability of Ag’ to modify the reactivity of benzyne is attributable to those silver atoms initially o-bonded in the benzyne-silver complex and not to extraneous silver ions and a generalized electrophilic scheme formally the reverse of the addition of Ag’ to strained a-bonds is proposed. 26 L. Lombard0 and D. Wege Tetrahedron Letters 1971 3981. 27 P. Crews and M. Loffgren Tetrahedron Letters 1971 4697. 28 M. Kato Y. Okamoto and T. Miwa Tetrahedron 1971 27 4013.29 H. Heaney J. M. Jablonski K. G. Mason and J. M. Sketchly J. Chem. Soc. (0 1971 3129. 30 E. Vedijs and R. A. Shepherd Tetrahedron Letters 1970 1863. ” P. Warner Tetrahedron Letters 1971 723. 32 L. A. Paquette Chem. Comm. 1971 1076. 222 J. T. Sharp Earlier calculations on 1,s-dehydronaphthalene (22) predicted that unlike o-benzyne the antisymmetric combination of 1,8-dehydro-orbitals would be of lower energy than the symmetric combination and hence that 1,2-addition to alkenes should be concerted and favoured over 1,4-addition to dienes. The first reaction33 with a conjugated diene is reported reaction of (22)with cyclopenta- diene gave the 1,6adduct in low yield (9%) and the 1,2-adduct in higher yield (47%) as predicted but surprisingly also gave the pentacyclic 1,3-adduct (23) in good yield (44%); (23) and the 1,4-adduct are possibly formed via (24).Benzo- phosphabarrelenes have been ~ynthesized~~ by the 1,4-addition of benzyne and tetrachlorobenzyne to substituted phosphorins. Other Reactions.-Recent aspects of aryne chemistry have been re~iewed.~ N-Alkylanilines have been synthesized in good yield (7&75 %) by the addition of aliphatic amines to base-generated benzyne. 36 Ketones their enamines and nitriles have been arylated in the a-position with aryl halides in the presence of ~odamide.~Amurine and domesticine have been synthesized via intramolecular cy~lization.~~ The reaction of p-fluorotoluene with lithium diethylamide pro- duced3' a-@-toly1)diethylamine (25)and its m-isomer and NN-diethyl-p-toluidine and its rn-isomer; the former compounds are thought to be formed via hydride transfer to the aryne (26).CIDNP effects have been observed in the additions of dibenzyl su1phide4* and NN-dirnethylben~ylamine~'to benzyne ; these are attributed to a free-radical dissociation-recombination mechanism of the inter- mediate ylides [e.g.(27)]. 33 J. Meinwald and G. W. Gruber J. Amer. Chem. SOC.,,1971 93 3802. 34 G. Markl F. Lieb and C. Martin Tetrahedron Letters 1971 1249. 35 S. Krishnappa J. Sci.Ind. Res. India 1970 29 538. 36 E. R. Biehl S. M. Smith and P. C. Reeves J. Org. Chem. 1971,36 1841. 37 T. Kametani S. Noguchi I. Agata T. Aono Kigasawa M. Hiiragi T. Hayasaka and 0. Kusama J. Chem. SOC.(C) 1971 1047; T.Kametani K. Kigasawa M. Hiiragi T. Hayasaka and 0.Kusama J. Chem.SOC.(C),197 1,105 1 ;T. Kametani K. Kigasawa M. Hiiragi T. Aoyama and 0. Kusama J. Org. Chem. 1971 36 327. 38 T. Kametani S. Shibuya K. Kigasawa M. Hiiragi and 0. Kusama J. Chem. SOC.(C) 1971 2712. 39 G. Wittig C. N. Rentzea and M. Rentzea Annalen 1971 744 8. 40 H. Iwamura M. Iwamura T. Nishida M. Yoshida and J. Nakamaya Tetrahedron Letters 1971 63. 41 A. R. Lepley R. H. Becker and A. G. Giumanini J. Org. Chem. 1971 36 1222. Arynes Carbenes Nitrenes and Related Species 22 3 Me Attempts to isolate a benzyne-platinum complex were unsuccessful ;42 how-ever the presence of platinum(0) was found to affect the reactions of several benzyne precursors and in particular to induce the formation of triphenylene.[z::? PhCH-;-CH,Ph PhCHSPh PhI * LH,Ph (27) It has now been that the product of the reaction of nickel carbonyl and o-di-iodobenzene which was originally reported44 to be n-benzynedi-iodo-p-carbonylnickel is not a benzyne complex. The nickel complex (28) has been added to ben~yne~~ to give (29) as the proximate product from which (30) is derived. PhC ZCNi(C C13) (PEt J2 a aczCph (28) (PEt3) 2 C2CI3 (29) (30) The chemistry of hetarynes has been reviewed.46 3,4-Dehydropyridines have been suggested as intermediates in the formation of 2,6-or 2,7-diazabiphenyl- ene,47 in the high-temperature basic hydrolysis of 3-halogenopyridine~,~~ and in 42 T. L. Gilchrist F. J. Graveling and C. W. Rees J.Chem. SOC.(C),1971 977. 43 N. A. Bailey S. E. Hull R. W. Jotham and S. F. A. Kettle Chem. Comm. 1971 282. 44 E. W. Gowling S. F. A. Kettle and G. Sharples Chem. Comm. 1968 21. 45 R.G. Miller and D. P. Kuhlman J. Organometallic Chem. 1971 26 401. 46 T. Kauffmann and R. Wirthwein Angew. Chem. Internat. Edn. 1971 10 20. 47 J. M. Kramer and R. S. Berry J. Amer. Chem. SOC. 1971,93 1303. 48 J. A. Zoltewicz and A. A. Sale J. Org. Chem. 1971 36 1455. 224 J. T. Sharp the reactions of trichloro-4-pyridyl-lithium derivative^.^^ The reaction of 2- bromo-5-aminopyridine with lithium piperidide has raised again the question of the existence of 2,6-dehydr0pyridine.~' A pyridazyne is possibly involved in the ring contraction of a pyridazinone to a pyra~ole.~' 2 Carbenes Structure and Reactivity.-Ab initio calculations have been carried out on the electronic structures of CH, CHF and CF .52 Good correlation is obtained between predicted and experimentally determined bond angles and these results agree with the consensus of opinion based on experimental evidence that CHF and CF are ground-state singlets whereas CH is a triplet.Correlating the number of electrons in the carbene carbon pK orbital with the ease with which these species attack an olefin it is predicted that electrophilicity will decrease along the series CH > CHF > CF . Extended to other halogens the following order is expected CH > CI > CBr > CCI > CF . An SCF-MO study has been made of the relative effects of N and/or S adjacent to a carbene and the results compared with experimental data.53 E.s.r.spectra of CD and CHD in a solid matrix differ significantly from that of CH, and it has been calculated54 that these species are substantially bent with an HCH angle of 136". It is thought that methylene is sufficiently free in the matrix to assume its preferred geometry and that free methylene has the same bond angle. The e.s.r. spectrum of the ground state of 9,9'-dianthryl- methylene has been observed and is consistent with a linear structure (31) with the ring planes perpendicular; this differs from other arylmethylenes which have a bond angle at the bivalent carbon of 135-140".55 Free radicals for e.s.r. study have been generated in an argon matrix by the reactions of triplet methylene e.g.CHD and CH,NO were formed in the 49 D. J. Berry B. J. Wakefield and J. D. Cook J. Chem. SOC.(C) 1971 1227. 50 H. N. M. van der Lans H. J. den Hertog and A. van Weldhuizen Tetrahedron Letters 1971 1875. 51 Y. Maki G. P. Bearsdley and M. Takaya Tetrahedron Letters 1971 1507. 52 J. F. Harrison J. Amer. Chem. Soc. 1971 93 41 12. 53 H. C. Sorensen and L. L. Ingraham J. Heterocyclic Chem. 1971 8 551. 54 E. Wasserman V. J. Kuck R. S. Hutton and W. A. Yager J. Amer. Chem. Sac. 1970,92 749 1. 55 E. Wasserman V. J. Kuck W. A. Yager R. S. Hutton F. D. Green V. P. Abegg and N. M. Weinshenker J. Amer. Chem. SOC.,1971 93 6335. Arynes Carbenes Nitrenes and Related Species 225 presence of D,O and NO re~pectively.~~ Methylene produced as a singlet- triplet mixture by the photolysis of keten has been reacted with 1,2-dichloro- ethane.57 By using carbon monoxide to suppress the reactions of triplet methyl- ene it was shown that the chlorine and hydrogen atoms were abstracted mainly by the singlet and triplet species respectively.Aryl carbenes although having triplet ground states usually react as excited singlets giving >95 % of stereospecific addition to alkenes. Attempts have been made to observe the reactions of the triplet state of phenylcarbene with cis-butene by two methods (a) dilution and (b)carrying out the photolysis of the diazo- precursor in frozen olefin matrices.58 Dilution was found to have little effect on the products but (b) gave reduced and less stereospecific cyclopropanation and products (32)-(34) in much higher yield than the liquid-phase reaction.CH2Ph PhCH2v CH2Ph (33) (34) (32) These products were thought to be formed by reaction of triplet phenylcarbene via abstraction-recombination and double-bond addition. 3-Nitrophenylcarb-ene has now been successfully trapped with olefins and exhibits an unusually high degree of non-stereospecificity attributed to participation of the triplet ~arbene.~~ u-Ferrocenylcarbenes are all triplet species owing to the adjacent ferrocenyl group ; ferrocenophane-/3-carbene (35) also appears to react as a triplet in spite of the insulation of the bivalent carbon from the aromatic rings. This species reacted readily with oxygen and gave a high yield of adduct with 1,l-diphenyl- ethylene but not with dec-l-ene.60 This is the first example of a carbene with aralkyl substituents reacting as a triplet and it is suggested that its spin state is affected by interaction with the Fe atom.s6 J. B. Farmer C. L. Gardner M. C. L. Gerry C. A. McDowell and P. Raghunathan J. Phys. Chem. 1971 75,2448. 5’ K. Dees D. W. Setzer and W. G. Clark J. Phys. Chem. 1971 75,2231. s8 R. A. Moss and U-H. Dolling J. Amer. Chem. SOC.,1971 93 954. 59 S. H. Goh J. Chem. SOC.(C) 1971 2275. 6o A. Sonoda and I. Moritani J. Organometallic Chem. 1971 26 133. 226 J. T. Sharp The two-step mechanism presumed to occur for the addition of triplet carbenes to acetylenes obviously cannot be inferred from product stereochemistry ; how-ever this has now been demonstrated by an intramolecular trapping experi- ment.6 The intermediate diradical (36),formed by reaction of triplet diphenyl- carbene with an acetylene undergoes intramolecular substitution to give the indene (37) as a primary product as well as ring closure to a cyclopropene.R Irradiation of di- tri- and tetra-phenyldiazocyclopentadienesin the presence of some acetylenes also gave an indene (39) as product probably formed62 in this case via the spirol[2,4]heptatriene intermediate (38). Similarly triplet bismethoxy- carbonylcarbene generated by the benzophenone-sensitized photolysis of methyl diazomalonate reacted with acetylenes to give furans [e.g. (41)] in high yield via (40). In the absence of the triplet sensitizer the expected cyclopropene was the major product (99 %).63 H 61 M.E. Hendrick W. J. Baron and M. Jones jun. J. Amer. Chem. SOC.,1971 93 1554. 62 H. Diirr L. Schrader and H. Seidl Chem. Ber. 1971 104 391. 63 M. E. Hendrick J. Amer. Chem. SOC.,1971 93 6337. Arynes Carbenes Nitrenes and Related Species 227 The carbene (42) is extruded by irradiation of (43) and has a reactivity to olefins identical with that of the product of photolysis of 4,4-dimethyldiazocyclo- hexadiene. It is concluded from this that excited diazo-compounds do not contribute significantly to product formation in their photochemical reactions with 01efins.~~ The relative rates of addition of di-t-butylvinylidenecarbeneto olefins have been compared with similar data for dimethylvinylidenecarbene and apparently the bulky t-butyl groups have little effect on the reactivity.From this and other results it was concluded that vinylidenecarbenes are essentially uncomplexed in the transition state of addition to 01efins.~~ Carbenes rarely react with unsaturated systems via 1,4-addition ; however it has now been shown that dicyanocarbene adds to cyclo-octatetraene to give the 1,4-adduct (45) as a primary product (18 %) as well as (44).66 Dilution experiments indicate that (45) and (44)are formed from triplet and singlet carbenes respectively. The reaction NC CN V (45) (44) OMe OMe H of difluorocarbene with (46) to give (47) does not proceed via 1,4-addition but rather by 1,2-addition to the olefin followed by thermal rearrangement and loss of hydrogen fl~oride.~’ Two different types of transition state for carbene insertion into C-H bonds have previously been proposed the Doering-Skell theory involves a triangular transition state and Benson and De More have suggested direct attack by the 64 R.H. Levin and M. Jones jun. Tetrahedron 1971 27 2031. ‘j H. D. Hartzler J. Amer. Chem. SOC.,1971 93 4527. ‘’ A. G. Anastassiou R. P. Cellura and E. Ciganek Tetrahedron Letters 1970 5267. ’’ M. Derenberg and P. Hodge Chem. Comm. 1971 233. 228 J. T. Sharp carbene on the hydrogen atom. Theoretical and experimental evidence has been reported this year which supports both of these postulates. Hoffmann has studied the potential energy surface for the insertion of singlet methylene into a C-H bond of methane by the extended Huckel method.68 The approach of the methylene is abstraction-like supporting the suggestion by Benson with the methylene oriented so that it ‘leads’ with its unoccupied electrophilic p-orbital.Reaction continues with the hydrogen-transfer stage during which the C-C bond distance changes little and concludes with the collapse to ethane. G~tsche~~ has examined the reactions of (48) and measured the relative amounts of the various possible intramolecular insertion products. It is suggested that the results are most reasonably explained on the basis of the Doering-Skell type of triangular transition state rather than the alternative which would require prefer- ential migration of those hydrogens closest to the carbene centre.Reactions of [3-2H]cyclohexene with fluorenylidene have shown that the mechanism of the insertion into the allylic position involves abstraction of allylic hydrogen by triplet fluorenylidene followed by collapse of the geminate radical pair.” Sey-ferth’s group have previously suggested a concerted mechanism for dichloro- carbene insertion with a transition state such as (49) or a hydride abstraction involving a tight ion pair [e.g. (50)]. In continuation of this work they have reinvestigated the insertion into optically active 2-phenylb~tane.~ They report that this process occurs with retention of configuration contrary to the recent suggestion that a practically inactive product was formed. This result therefore supports the mechanism previously suggested.[>c+CC4 (49) ‘’ R. C. Dobson D. M. Hayes and R. Hoffmann J. Amer. Chem. SOC.,1971 93 6188. 69 C. D. Gutsche G. L. Bachman W. Udell and S. Bauerlein J. Amer. Chem. SOC. 1971,93,5172. ’O J. E. Baldwin and A. H. Andrist Chem. Cornm. 1971 1512. ’‘ D. Seyferth and Y. M. Cheng J. Amer. Chem. SOC.,1971,93,4072. Arynes Carbenes Nitrenes and Related Species 229 Insertion of dichlorocarbene into tertiary C-H bonds not activated by neighbouring phenyl or ether groups does not require thermal excitation of the carbene as had been thought earlier.72 It was recently suggested that the singlet ground state of certain carbenes could be stabilized by a ‘foiled methylene’ inter- action with a double bond when cyclopropane formation was sterically impos- sible and that this interaction could have a directive effect on product formation.Several further examples of non-classical carbenes of this type have now been reported e.g. (51) gave (52) as the major product.73 Delocalized intermediates are also suggested for the reactions of (53)74 and (54).75 .. .. (53) (54) Generation.-The formation of carbenes by thermal76 and photo~hemical~~ extrusion reactions and the chemistry of fluorinated diazo-cornpo~nds~~ have been reviewed and a second edition of ‘Carbene Chemistry’ has been published.79 The decomposition of dimethyl diazomalonate in the presence of olefins is catalysed by the homogeneous trialkyl phosphite-copper(1) halide complex.80 The reaction has been shown* to proceed via a rate-determining displacement of halide by the diazo-compound.The spin-multiplicity distribution of the carbenoid species formed is strongly influenced by the leaving group ability of the counter ion. It has also been observed82 in these systems that the activity of the catalyst is greatly enhanced by peroxidic impurities in the olefin and that a far superior catalyst can be produced by pretreatment of the catalyst with benzoyl peroxide in benzene before addition of the olefin or diazo-compound. 72 E. V. Dehmlow Tetrahedron 1971 27 4071. 73 R. A. Moss U.-H. Dolling and J. R. Whittle Tetrahedron Letters 1971 931. 74 P. K. Freeman R. S. Raghavan and D. G. Kuper J. Amer. Chem. Soc. 1971 93 5288.75 P. K. Freeman and K. B. Desai J. Org. Chem. 1971 36 1554. 76 R. W. Hoffmann Angew. Chem. Internat. Edn. 1971 10 529. ” G. W. Griffin Angew. Chem. Internat. Edn. 1971 10 537. 78 C. G. Krespan and W. J. Middleton Fluorine Chem. Rev. 1971 5 57. 79 W. Kirmse ‘Carbene Chemistry,’ Academic New York 1971 2nd edn. B. W. Pearce and D. S. Wulfman Tetrahedron Letters 1971 3799. D. S. Wulfman B. W. Pearce and E. K. Steffen Chem. Comm. 1971 1360. 82 B. W. Pearce and D. S. Wulfman Chem. Comm. 1971 1179. 230 J. T. Sharp The thermal decomposition of diphenyldiazomethane is catalysed by copper@) carboxylates dissolved in aqueous DMF to give (59 in addition to (56) and (57).83The benzopinacol dicarboxylates are thought to arise by a one-electron oxidation of the diphenylcarbene-acetate ion adduct by Cu" ion to give Ph,cOAc radicals which dimerize.Acetylacetonatocopper(1) is an effective catalyst in the addition of diazoketone-derived ketocarbenes to 01efins.~~ PhZC -CPh2 Ph,C=CPh Ph2C=N-N=CPhz It ROC0 OCOR (55) (57) A variety of organomercurial reagents has been developed for the generation of dihalogenocarbenes at room temperature. PhHgCC1,I is a useful source85 of CCl and PhHgCClBrI and PhHgCFBr although less reactive,86 provide CClBr and CFBr respectively ;all give high yields of olefin adducts in 14 days. PrHgCCl and PrHgCBrC1 have also been used as dichloromethylating reagents at low temperature^.^^ Halogenocarbenoids of zinc have been formed for the first time by the reaction of polyhalogenomethanes with diethylzinc and used in the preparation of 7-halogenonor~aranes.~~ This reaction is said to be more versatile than the Simmons-Smith method.Dichlorocyclopropanes which are difficult to prepare by the potassium t-butoxideshloroform-olefin reaction can more readily be obtained from chloroform-aqueous sodium hydroxide with a catalytic amount of triethylbenzylammonium chloride.89 Similar conditions have also been used for preparing olefin adducts of CBr ,90 CFC1,91 and CFBr.91 In the cyclopropanation of olefins with diethylzinc-methylene iodide the yields were improved and the reaction greatly accelerated by the presence of oxygen ;92 no explanation was offered for this effect. The thermal decomposition of diphenylsulphonium allylide (58) has been shown not to give vinylcarbene ;however cyclopropene is formed on photolysis probably via the ~arbene.~~ Vinylidenecarbenes have been generated by the reaction of strong base with 1-bromoalk-1-ynes (59) and their insertion into Si-H and C-H bonds studied.94 Methylenecarbenes are also produced by photolytic extrusion from arylmethylenecyclopropanes (60); when R = H the carbene rearranges to acetylene faster than it can be trapped by solvent but when R = Me the carbene can be trapped by addition to cy~lohexene.'~ 83 T.Shirafuji Y. Yamamoto and H. Nozaki Tetrahedron 1971 27 5353. J. E. McMurray and T. E. Glass Tetrahedron Letters 1971 2575. 85 D. Seyferth and C. K. Haas J. OrKanometaffic Chem. 1971,30 C38. 86 D. Seyferth C. K. Haas and S.P. Hopper J. Organornetalfic Chem. 1971 33 C1. V. I. Shchervakov Zhur. obshchei Khim. 1971 41 1095. J. Nishimura and J. Furukawa Chem. Comm. 1971 1375. 89 E. V. Dehmlov and J. Schonefeld Annalen 1971 744 42. M. Makosa and M. Fedorynski Bull. Acad. polon. Sci. Se'r. Sci. chim. 1971 19 105. 91 P. Weyerstahl G. Blume and C. Muller Tetrahedron Letters 1971 3869. 92 S. Miyano and H. Hashimoto Chern. Comm. 1971 1418. 93 R. W. LaRochelle B. M. Trost and L. Krepski J. Org. Chem. 1971,36 1126. 94 J. C. Craig and C. D. Beard Chem. Comrn. 1971 691 692. 95 J. C. Gilbert and J. R. Butler J. Amer. Chem. SOC.,197@,92 7493. 231 Arynes Carbenes Nitrenes and Related Species RCH,C-CBr +-Ph,S CHCH=CH p0 -PhF: Ph RCH =C=C (58) (59) There is continued interest in the preparation of silylsubstituted carbenes from diazo-c~mpound~~ and organomercurialg7 precursors.Bis(trimethylsily1)diazo-methane previously thought incapable of existence has been found to be extremely stable.98 Rearrangements.-The photochemical conversion of ketone (61) to oxycarbene (62) has been known for some time; the reverse isomerization has now been demonstrated by the thermal generation of (62) which gives [(61) 70x1 in addition to [(63) 30%].99 The furfurylidene (64) generated by pyrolysis of its diazo precursor at 250 "C rearranges to (65).'0° The mechanism probably involves an electrocyclic process of the singlet carbene. (Diphenylphosphiny1)- carbenes (67) rearranged to phosphonic acid derivatives (69) via a new class of reactive heterocumulenes (68).lo' However the carbenes derived from (66) 0 N II R -C-P(OMe) (66) Ph Ph Ph Ph CH,Ph '' A.G. Brook and P. F. Jones Canad. J. Chem. 1971,49 1841. 97 D. Seyferth and E. M. Hanson J. Organometallic Chem. 1971 27 19. 98 D. Seyferth and T. C. Flood J. Organometallic Chem. 1971 29 C25. 99 W. A. Agostaand A. M. Foster Chem. Comm. 1971,433. loo R. V. Hoffman and H. Shechter J. Amer. Chem. SOC.,1971 !43 5940. lo' M. Regitz A. Liedhegener W. Anschutz and H. Eckes Chem. Ber. 1971 104 2177. 232 J. T.Sharp underwent various rearrangements depending on the nature of R which did not affect the dimethylphosphono-group.lozThe migratory aptitudes of hydrogen and fluorine have been compared by the generation of (70),which rearranged by hydrogen migration only to give (71); (72) rearranged by migration of the di- fluoromethyl group.' O3 The mechanism previously suggested for the high- temperature rearrangement of m-and p-tolylcarbene to o-tolylcarbene via CH3CCF2C2FS CH2=CHCF2CF3 CHF2CF,CH (70) (71) (72) reversible conversion into cycloheptatrienylidene has been confirmed by labelling studies.lo4 The remarkable elimination of phosphorus in the reaction of car- benes/carbenoids with phosphorins (73) also involves a ring expansion/con- traction sequence.'05 The retention of dissymmetry in the ring opening of optically active cyclopropylidenes to allenes is not due to steric effects but reflects the electronic effects of substituents on the ring-opening process.lo' There has recently been some interest in photochemically induced Wolff rearrangements of alkoxycarbonylcarbenes and the first example of a thermally induced rearrangement has now been reported (74) rearranges to (75) at high temperaturelo7 to give products derived from (76) and further Wolff rearrange- ments. However when generated thermally and photochemically from a tosyl- hydrazone sodium salt (76)is reported to dimerize without undergoing a Wolff rearrangement. Me02C Me02C Me02C \ \c -+ \c=c=o -+ C / / / Me0,C Me0 Me0 (74) (75) (76) lo2 R. S. Marmor and D. Seyferth J. Org. Chem. 1971,36 128. J. H. Atherton R. Fields and R. N. Haszeldine J. Chem. SOC.(C),1971 366. '04 E. Hedaya and M. E. Kent J. Amer. Chem.SOC.,1971 93 3283. lo5 G. Mark1 and A. Merz Tetrahedron Letters 1971 1269. lob W. M. Jones and D. L. Krause J. Amer. Chem. SOC.,1971 93 551. lo' D. C. Richardson M. E. Hendrick and M. Jones jun. J. Amer. Chem. SOC.,1971 93 3790. J. Gehlaus and R. W. Hoffmann Tetrahedron 1970 26 5901. Arynes Carbenes Nitrenes and Related Species Reactions.-In the reaction of phenyl(trihalogenomethyl)mercury-derived di-chlorocarbene with a series of cyclic allylic alcohols the relative reactivity of the 0-H and C=C bonds is considered to be controlled by the nucleophilicity of the C=C bond."' In these and related reactions the addition of the carbene to the double bond does not appear to be directed by prior complexation of the reagent with the hydroxy-group as has previously been demonstrated in similar reactions involving iodomethylzinc iodide.Similarly the lone-pair electrons on the oxygen atoms of 2-phenyl-l,3-dioxacyclohept-5-ene do not exert a cis directing influence on the addition of dichlorocarbene. 'lo The donation of elec- trons by oxygen has however been found to affect the reactivity of carbenoids such as (77).' ' ' A useful method of preparing chlorides by the reaction of dichlo- rocarbene with alcohols under alkaline conditions at room temperature proceeds mainly with retention of configuration.' l2 The reaction between phenyl- (bromodichloromethy1)mercury and benzophenone gives dichlorodiphenyl- methane and chlorodiphenylacetyl chloride as major products and is con-sidered to involve a carbonyl ylide (78) and/or a dichloro-oxiran intermediate.' ' 0 0 /\ -Ph,C/ 'CCI + Ph,C-CC12 A similar intermediate is proposed for the analogous reaction with benzalde- hyde.'14 A stable ylide has been prepared by the thermolysis of diazatetra- phenylcyclopentadiene in pyridine but the ylides of di- and tri-phenylamine could not be prepared in this way. '' Dichlorocarbene reacts with phenyl azide to give (79) which reacts further to give (80).'16 A simple synthesis of benzocyclopropene has been achieved by a dichlorocarbene addition to cyclohexa-l,4-diene and subsequent reaction of the lo') D. Seyferth and V. A. Mai J. Amer. Chem. Soc. 1970 92 7412. 'lo G. R. Clark B. Fraser-Reid and G. J. Palenik Chern. Cornm. 1970 1641. 'I' K. G.Taylor W. E. Hobbs and M. Saquet J. Org. Chem. 1971,36 369. 'I2 I. Tabushi Z. Yoshida and N. Takahashi J. Arner. Chem. SOC.,1971 93 1820. " C. W. Martin and J. A. Landgrebe Chem. Comm. 1971 15. C. W. Martin J. A. Landgrebe and E. Rapp Chem. Comm. 1971 1438. l5 D. Lloyd and M. I. C. Singer J. Chem. SUC.(C),1971 2939. H. H. Gibson jun. J. R. Cast J. Henderson C. W. Jones B. F. Cook and J. B. Hunt Tetrahedron Letters 1971 1825. 234 J. T. Sharp adduct with potassium t-butoxide in DMS0.'17 A novel synthesis of the B-lactam ring (81) by a carbene insertion has been reported.' '*Similarly insertion of a 'carbenacyclopropane' into a C-H bond adjacent to oxygen provides a route to alkyl-substituted 3-oxabicyclo[3,l,0]hexanes e.g. [(82) 48 %] was prepared from (83) by treatment with methyl-lithium." Ph N =CCI PhN-CCI, \/ (79) CCI 3 Nitrenes Structure and Reactivity.-E.s.r.studies of nitrenes have been reviewed. 120 The spin state of photogenerated phenylnitrene has been investigated viu product studies in alcohol-hydrocarbon mixtures and it was concluded that the nitrenes are formed mainly in an excited singlet state with only 12-13 % formed directly in the triplet state.' Further evidence against the intermediacy of discrete nitrenes in the photolysis of alkyl azides has been inferred from the non-statistical migra- tion of alkyl and aryl groups in the photolysis of tertiary alkyl azides,lZ2 and a new model for the photochemical process has been suggested. Little or no nitrene formation was observed in the photochemical decomposition of methyl azidoformate in rare-gas matrices ;reaction is thought to occur uia a vibrationally excited state with concerted loss of nitrogen and rearrangement to methoxy- isocyanate.l2 The reactivity of nitrenes in hydrogen-abstraction reactions has 'I7 W.E. Billups A. J. Blakeney and W. Y. Chow Chem. Cumm. 1971 1461. N. G. Johansson and B. Akermark Acta Chem. Scand. 1971,25 1927. 'I9 M. S. Baird Chem. Comrn. 1971 1145. E. Wasserman Progr. Phys. Org. Chem. 1971 8 319. I * A. Reiser and L. J. Leyshon J. Amer. Chem. SOC.,1971 93 405 1. R. A. Abramovitch and E. P. Kyba J. Amer. Chem. Soc. 1971 93 1537. R. E. Wilde T. K. K. Srinivasan and W. Lwowski J. Amer. Chem. Sac. 1971 93 860. Arynes Carbenes Nitrenes and Related Species been correlated with the magnitude of the negative charge on the nitrogen arylnitrenes where the charge is high exhibit low reactivity whereas carbonyl- and sulphonyl-nitrenes where the charge is reduced are more reactive.124 Reactions.-The synthesis of organic azides has been reviewed. 25 The intra- molecular cyclization of aromatic nitrenes continues to provide considerable mechanistic interest and a fruitful source of old and new heterocyclic systems. The arylnitrenes are usually generated by the thermolysis of azides or by Cadogan's deoxygenation of nitro-groups with tervalent phosphorus reagents. Typical of this sort of reaction is the formation of benzo[b]thieno[3,2-b]indoles(84) from (85) or the azide.126 Similarly (87) produced by flash vacuum pyrolysis of 7-phenyloxindole (86) gave 1-methylcarbazole.12' Much of the interest in this field has lately centred on reactions of nitrenes of the general type (88) which often involve unusual rearrangements. (84) (85) The reaction of the N-acetyl-2-nitrodiphenylamine(89) with triethyl phos- phite12* gave the dihydrophenazine (91) as the major product formed via a rearrangement involving a spirodiene intermediate (90) analogous to that pro- posed earlier for phenothiazine formation from 2-nitrophenyl phenyl sulphides. 124 A. Reiser and L. J. Leyshon J. Amer. Chem. Soc. 1970 92 7487. 125 A. Hassner Accounts Chem. Res. 1971,4,9; G. L'Abbe and A. Hassner Angew. Chem. Internat. Edn. 1971 10 98. "' K. E. Chippendale B.Iddon and H. Suschitsky Chem. Comm. 1971 203. R. F. C. Brown and M. Butcher Tetrahedron Letters 1971 667. Y. Maki T. Hokosami and M. Suzuki Tetrahedron Letters 1971 3509. 236 J. T. Sharp A variety of o-benzylphenyl azides (92) has been decomposed usually to give 1OH-azepinol[ 1,2-a] indoles (93) as the major products.' 29 In cases where R' or R2 = OMe the major products were acridines and acridans (94). The formation of these products was rationalized in terms of azanorcaradiene e.g. (99 rather than spirodiene intermediates although a nitrogen-shift in the latter leads to the same products. Acridine (96) is thought to be formed directly uia elimination of methanol. (92) (93) P' R2 (94) (95) The full report13' on the 'blocked ortho' effect in the cyclization of aryl 2- nitrophenyl and aryl2-azidophenyl sulphides includes additional examples which contribute to the understanding of the mechanism of these rearrangements.It is thought that all reactions in this series involve the formation of a spirodiene inter- mediate such as (97) the subsequent reactions of which depend on the nature of R. When R = Me the main product was (98) formed via (99) but when R = OMe the intermediate rearranged further to (100) which either eliminated formalde- hyde to give (101) or formed (102) by a 1,4-methoxy migration. In the case where R = CO,Et the intermediate (103) analogous to (100) proved stable enough to be isolated. When R = C1 the major product of the azide decomposition was 1-chlorophenothiazine with a little of the 4-isomer.However in the analogous (97) (98) (99) 12' G. R. Cliff and Gurnos Jones J. Chem. SOC.(C) 1971 3418; Chem. Comm. 1970 1705. I3O J. I. G. Cadogan and S. Kulik J. Chem. SOC.(0,1971 2621. Arynes Carbenes Nitrenes and Related Species \ \+ r\r N " OMe OMe OMe C0,Et (1 03) nitro-phosphite reaction the major product (52%) was the 4-chlorophenothia- zine and it was suggested that in this case the reaction could be occurring via a scheme involving the nitrene precursor (104). In general it was suggested that nitrenes may not be formed on the deoxygenation of all nitro-compounds but that intermediates such as (104) could be involved in some cases. Similarly thermolysis of 2-azidophenyl 2,6-dimethoxyphenyl ether gave 4-methoxy-phenoxazine and 1,2-dimethoxyphenoxazine,and 2-azidophenyl 2,4,6-trimethyl- phenyl ether gave mainly (105).' Photochemical decomposition of o-azidobenzamides gave only ring-expanded products with no intramolecular insertion into the carbamoyl side-chain.32 The azide precursor to (106) exhibited quite different behaviour on thermal and photochemical decomposition. The photochemically generated nitrene reacted both by R-group migration and by ring expansion to provide a new route to azocines (107).'33 Thermal generation of (106; R = 1-naphthyl) produced 9-(1-naphthy1)anthracene (88%) '34 probably formed by transannular addition of the nitrene to the double bond to give an unstable azasemibullvalene followed by rearrangement to (108) and loss of hydrogen cyanide by a retro-Diels-Alder reaction.13' J. I. G. Cadogan and P. K. K. Lim Chem. Comm. 1971 1431. 13* A. C. Mair and M. F. G. Stevens J. Chem. Snc. (C),1971 2317. 133 J. J. Looker J. Org. Chem. 1971 36 2681. 134 J. J. Looker J. Org. Chem. 1971 36 1045. 238 J. T. Sharp H (106) (107) (108) Although phenylnitrene generated from phenyl azide reacts readily in intra- molecular additions and cyclizations it fails to add to benzene. It has now been reported' 35 that the reaction of nitrosobenzene with triethyl phosphite in benzene in the presence of trifluoroethanol gives 1-phenyl- 1N-azepine (34%) probably via a nitrenoid mechanism involving an intermediate [Ph-N-0- + P(OEt),] similar to (104).The promoting effect of trifluoroethanol on this reac- tion is not yet understood. A technique has been described for the isolation of a-alkyl-N-ethoxycarbonylazepinesfrom the complex mixture produced by the decomposition of ethyl azidoformate in substituted benzenes.136 The method depends on the slower rate of hydrolysis of the a-isomer owing to steric hindrance. Both 1,2,3- and 1,2,4-benzotriazines can be synthesized by ring-expansion reactions of aminonitrenes e.g. (109) formed by the oxidation of 1-amino-2- quinoxalones undergoes ring expansion and extrusion of carbon monoxide to give (1 The nitrenes derived from the oxidation of 1- and 2-aminoindazofes R I :N (109) [e.g. (1 1l)] likewise do not extrude nitrogen but ring expand to give 1,2,3-benzo- friazine~.'~~ Thermal or photochemical cleavage of sulphoximides has previously been used as a source of stable aminonitrenes ; higher-temperature pyrolysis,'39 however has now been shown to proceed via extrusion of nitrogen to give for example (113) from (112).This suggests that the previously drawn distinction between 'fragmenting' and 'non-fragmenting' aminonitrenes is due only to differences in activation energy. The full paper on the fragmentation of the aminonitrene (1 14) to give benzocydopropene and 3-indazolone has now appeared ;l4' also the full report on the photochemical olefin-exchange reaction 135 R. J. Sundberg and R. H. Smith Tetrahedron Letters 1971 267. J. M. Photis J. Heterocyclic Chem. 1971 8 167. 37 B.Adger C. W. Rees A. A. Sale and R. C. Storr Chem. Cornm. 197 1 695.-13' D. J. C. Adams S. Bradbury D. C. Horwell M. Keating C. W. Rees and R. C. Storr Chem. Comm. 1971 828. 13' T. L. Gilchrist C. W. Rees and E. Stanton Chem. Comm. 1971 801. 140 J. Adamson D. L. Forster T. L. Gilchrist and C. W. Rees J. Chem. Soc. (C),1971 981. Arynes Carbenes Nitrenes and Related Species of 1-phthalimidoaziridines (115).14' The mechanism of the latter involves concerted fragmentation to give olefins and phthalimidonitrene which is trapped by the added olefin. The formation of benzophenone oxime from [Ph,CHONTs Li'] is thought to involve oxygen to nitrogen migration in an oxynitrene intermediate. 14' Evidence for the intermediacy of fluoronitrene in the base-promoted hydrolysis of difluoramine has been obtained by hydrogen abstraction studies using added 'lures'.' 43 Photolysis and thermolysis of ferrocenyl azide gave both ferrocenyl radicals and the nitrene which was oxidized to nitroferrocene with air or trapped with cy~lohexene.'~~ The metal-nitrene complex [(116) cf (35)]is suggested to account for the high yield of hydrogen-abstraction products in the decomposition of ferrocenylsulphonyl a~ide.'~~ (117) is also formed but only in the photo- t- chemical reaction.Stable iminosulphuranes [R,S-NCO,Me] have been pre- pared by the irradiation of methyl azidoformate in alkyl ~u1phides.l~~ The intermediacy of singlet rather than triplet nitrenes was inferred from the failure of the reaction in the presence of acetophenone.Fe=N 14' T. L. Gilchrist C. W. Rees and E. Stanton J. Chem. Soc. (C),1971 988. 14' F. A. Carey and L. J. Hayes J. Amer. Chem. Soc. 1970 92 7613. L43 W. J. le Noble E. M. Schulman and D. N. Skulnik J. Amer. Chem. Soc. 1971 93 4710. 144 R. A. Abramovitch C. I. Azogu and R. G. Sutherland Chem. Comm. 1971 134. 14' R. A. Abramovitch C. I. Azogu and R. G. Sutherland Tetrahedron Letters 1971 1637. 146 W. Ando N. Ogino and T. Migita Bull. Chem. SOC.Japan 1971 44 2278.

ISSN:0069-3030    

DOI:10.1039/OC9716800217

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

6 Molecular Rearrangements By G. TENNANT Department of Chemistry University of Edinburgh The third volume of a series on molecular rearrangements has been published.’ 1 Aliphatic Rearrangements Anionic Rearrangements.-The Sommelet-Hauser2 v3 and Stevens2 rearrange- ments have been reviewed. Further mechanistic studies on the competing Sommelet and Stevens rearrangements of quaternary ammonium salts have been p~blished.~ In general 1,2-shifts are promoted by non-polar solvents and elevated temperatures whereas increase in base concentration favours the ortho-Sommelet rearrangement at the expense of the para-Sommelet and Stevens The formation of cleavage products in the latter reactions supports a radical-pair me~hanism.~~ A study of the effect of pressure on such rearrangements indicates that ylide formation is the rate-determining step in the ortho-Sommelet rearrange- ment whereas in the Stevens rearrangement ylide cleavage is rate-limiting.4c Pressure effects may provide an alternative means to c.i.d.n.p.for the diagnosis of the mechanisms of such intramolecular rearrangement^.^^ It has been pointed out’ that c.i.d.n.p. has been successfully detected only in those intramolecular rearrangements for which a concerted pathway is forbidden on orbital symmetry grounds. The demonstration of c.i.d.n.p. in the addition-rearrangement reactions of benzyne with tertiary amines,6 and in the rearrangements of the cyclic amini- mide (1)7 and the sulphonium ylide (2)’ provides support for radical dissociation- recombination mechanisms.Additional support for a non-concerted mechanism is adduced from the formation of both stereoisomers (4) and (5) in the Stevens rearrangement of the bis-ylide (3).* The first examples of the Stevens rearrange- ‘Mechanisms of Molecular Migrations,’ ed. B. s.Thyagarajan Interscience New York 1971 Vol. 3. A. R. Lepley and A. G. Giumanini ref. 1 p. 297. ’ G. Wittig Bull. Soc. chim. France 1971 1920. (u) S. H. Pine E. M. Munemo T. R. Phillips G. Bartolini W. D. Cotton and G. C. Andrews J. Org. Chem. 1971 36 984; (b) A. R. Lepley and A. G. Giumanini ibid. p. 1217; (c) D. A. Archer J. Chem. Soc. (0, 1971 1329. ’ H. Iwamura M. Iwamura T. Nishida M. Yoshida and J. Nakayama Tetrahedron Letters 197 1 63. ‘A. R. Lepley R. H. Becker and A.G. Giumanini J. Org. Chem. 1971 36 1222. H. P. Benecke and J. H. Wikel Tetrahedron Lerters 1971 3479. * R. H. Mitchell and V. Boekelheide Chem. Comm. 1970 1555. 241 242 G. Tennunt 0 Ph \+ ~ /S-cH.PhPhCH Me Me (3) (4) ment in an acyclic aminimide' and in an electrolytic process" have been reported. Details of the scope and mechanism of the thiomethoxymethylation of phenols by dimethylsulphoxide alone' la or in the presence of the pyridine-sulphur trioxide complex or dicyclohexylcarbodi-imide-phosphoricacid have been published. Predominant formation of ortho-thiomet hoxyme thylated products is explained in terms of the [2,3] sigmatropic rearrangement of an intermediate ylide [cf (6)-+(7)+(S)]. Ortho-blocked phenols give the corresponding para-thiomethoxymethylated phenol in a fragmentation-recombination process involving the methylmethylenesulphonium cation which can be trapped by an external nucleophile.N-Aryl-SS-dimethylsulphimidesare similarly re-arranged to ortho-thiomethoxymethylanilines in the presence of trieth~larnine.'~ The stereospecificity of a Wittig-type rearrangement has been elegantly demonstrated. In accord with a [2,3] sigmatropic process involving a doubly suprafacial transition state the chiral ether (9) undergoes 100% stereospecific rearrangement to a cis-trans mixture of the alcohols (10) and (11) on treatment E. A. Sedor Tetrahedron Letters 1971 323. lo P. E. Iversen Tetrahedron Letters 1971 55. (a) P. Claus N. Vavra and P. Schilling Monatsh.1971 102 1072; (6) P. Claus ibid. p. 913. l2 (a) J. P. Marino K. E. Pfitzner and R. A. Olofson Tetrahedron 1971 27 4181; (6) R. A. Olofson and J. P. Marino ibid. p. 4195. " P. Claus W. Vycudilik and W. Rieder Monarsh. 1971 102 1571. Molecular Rearrangements 243 Ph L Ph OH :nH BuLi ' HL 4-Me Me Me Me with butyl-1ithi~m.l~ The rare migration of a phenyl group in a Wittig rearrange- ment has been reported. ' The base-catalysed conversion of benzyloxytriethyl- silane into the corresponding a-silyl carbinol is an example of the hitherto unknown Wittig rearrangement of alkoxysilanes.' The driving force for this reversal of the well-known 'anti' Wittig rearrangement of silyl carbinols to silyl ethers is apparently the stability of the oxyanion which overrides the normal preference shown for formation of an Si-0 bond.The silyl carbinol to silyl ether transformation involves inversion at carbon and not retention as previously believed.' The [2,3] sigmatropic rearrangements of nitrogen and sulphur ylides continue to stimulate much experimental effort. A study of the effects of torsional strain on the course of the [2,3] sigmatropic rearrangements of ammonium ylides has produced the first example of a carbonyl-stabilized allylic ammonium ylide (12). Sigmatropic rearrangement of this compound is precluded by the rigid geometry of the azabicyclo[2,2,2]octane ring system which prevents efficient orbital overlap in the transition state. The greater efficiency of orbital overlap in the more flexible azabicyclo[3,3,l]nonane ring system is demonstrated by the smooth thermal rearrangement of the ylide (13) to the compound (14).18 On the basis of these findings it is suggested' * that sigmatropic rearrangements which involve considerable twisting of the n-system in the transition state (e.g.the [3,3]antara-antara type) probably follow non-concerted pathways. An ammonium ylide rearrangement which occurs with retention of configuration '' J. E. Baldwin and J. W. Patrick J. Amer. Chem. Soc. 1971 93 3556. Is D. R. Dimmel and S. B. Gharpure J. Amer. Chem. SOC., 1971 93 3991. R. West R. Lowe H. F. Stewart and A. Wright J. Amer. Chem. SOC.,1971 93 282. " M. S. Biernbaum and H. S. Mosher J. Amer. Chem. SOC.,1971,93,6221;A. G. Brook and J.D. Pascoe ibid.,p. 6224. Is S. Mageswaran W. D. Ollis I. 0.Sutherland and Y. Thebtaranonth Chem. Cnmm. 1971 1494. 244 G. Tennant at the carbanionic centre has been reported. The [2,3] sigmatropic rearrange- ment of dipolar diazene intermediates (16)is proposed to account for the oxidative formation of azo-compounds (17) from allylic hydrazines (1 5).20 Me Me Me -I Ph/N N Further examples of the [2,3] sigmatropic rearrangements of sulphonium ylides have been described.21 The isomer (19) is favoured in the novel thio- sulphinate-thiosulphoxylate equilibrium (18) (1 9)].22 The activation para- meters of the first-order rearrangements [(20)-(22)]of allylic disulphides are in accord with sequential [2,3] sigmatropic shifts in thiosulphoxide intermediates (21) which can be intercepted by triphenylph~sphine.~~ Delocalization of the l9 G.V. Kaiser C. W. Ashbrook and J. E. Baldwin f.Amer. Chem. SOC., 1971,93 2342. J. E. Baldwin J. E. Brown and G. Hofle J. Amer. Chem. SOC., 1971 93 788. 21 J. F. Biellmann and J. B. Ducep Tetrahedron Letters 1971 33; V. Rautenstrausch Hefu. Chim. Acta 1971 54 739; R. W. La Rochelle B. M. Trost and L. Krepski f. Org. Chem. 1971 36 1126. 22 J. E. Baldwin G. Hofle and S. C. Choi f.Amer. Chem. SOC.,1971 93 2810. 23 G. Hofle and J. E. Baldwin J. Amer. Chem. SOC.,1971 93 6307. 245 Molecular Rearrangements Me R R Me e' I Me (20)(R = H or Me) R Me negative charge in sulphonium ylides has been shown not to be a barrier to rapid sigmatropic rearrangement.24 The a-chlorination of dialkyl sulphoxides by sulphuryl chloride involves chlorination at sulphur rather than at carbon followed by a Pummerer-type rearrangement.2 The Pummerer rearrangements of sulphonium ylides [(23-P (24)]'1n312,13 and thioanhydrohexitol sulphoxides26 have also been reported.R' R2 /Ar.X.S -+ Ar-X-dHSR' \ CH.R~ (23)(X = 0 or NH) (24) The demonstration of e.s.r. and c.i.d.n.p. effects in the Martynoff rearrangement of nitrones implies a caged radical-pair mechanism.27 Thermodynamic parameters have been reported for thenilic acid rearrange- ments. The Hammett relationship is followed (p = +2.62-2.67).28 The quasi- Favorskii rearrangement of a-bromoketones involves inversion at the brominated carbon atom thereby providing firm support for a semibenzilic me~hanisrn.~~ Cyclobutanedione undergoes spontaneous rearrangement in aqueous solution affording 1-hydroxycyclopropane carboxylic acid.30 The first example of a base- catalysed Tiffeneau rearrangement has been rep~rted.~' Interest in the fast 24 J.E. Baldwin and W. F. Erickson Chem. Comm. 1971 359. 25 T. Durst and K. C. Tin Canad. J. Chem. 1971 49 2374. 26 J. Kuszmann P. Sohar and G. Horvath Tetrahedron 1971 27 5055. 2' D. G. Morris Chem. Comm. 1971 221 ; I. W. Jones D. A. Kerr and D. A. Wilson J. Chem. SOC.(0,1971 2595. '' G. P. Nilles and R. D. Schuetz J. Org. Chem. 1971 36 2489. 29 D. Baudry J. P. Begue and M. Charpentier-Morize Buff. Soc. chim. France 1971,1416.30 J. M. Coniaand J. M. Denis Tetrahedron Letters 1971,2845; H. G.Heine Chem. Ber. 197 1,104,2869. 31 B. J. Herold and J. J. R. P. Queiroga Angew. Chem. Internat. Edn. 1971 10 834. 246 G. Tennant reversible acyloin rearrangements of bridgehead ketols continues. In the equili- brium mixture of 3,3-dimethyl- 1-hydroxynorbornan-2-one (I-hydroxycampheni-lone) (25) and 1-hydroxyapocamphor (26) the latter isomer is favoured by a factor of two at 31 0C.32A variable-temperature n.m.r. study of the equilibrium of the anions derived from (25)and (26) gives a value of 1.1-1.3 for the equilibrium constant with AGO = -180ca1 ASo = -1.2 eu and E = 24.1 1.0 k~a1.~~ The rate of rearrangement of a-halogenoketones increases significantly with increase in the number of a-aryl groups.Rate enhancement is attributed to stabilization of a zwitterion intermediate produced by rate-determining halide release.34 The rare homo-Favorskii rearrangement is shown to occur readily in suitably constituted fi-halogenoketones. Base-catalysed rearrangement of the Me Mc M,e ,C02H dichloromethylcyclohexenone (27) yields the homo-Favorskii products (28) and (29) together with the bicyclo[3,1,0] hexenyl acids (30) and (31).35 The products (30) and (31) are rationalized in terms of the formation and subsequent semibenzilic rearrangement of a bicyclo[3,2,0]heptenone intermediate.3s The first examples of the Favorskii-type rearrangements of a-bromoketimines have been reported. The cyclopropanimine intermediates can be isolated and they 32 A.Nickon T. Nishida J. Frank and R. Muneyuki J. Org. Chrm. 1971 36 1075. 33 J. V. Paukstelis and D. N. Stevens Tetrahedron Letters 1971 3549. 34 F. G. Bordwell and R. G. Scamehorn J. Amer. Chem. Sue. 1971 93 3410. 35 E. Wenkert P. Bakuzis R. J. Baumgarten C. L. Leicht and H. P. Schenk J. Amer. Chem. Soc. I97 1.93 3208. Molecular Rearrangements 247 show the same regiospecificity of ring-opening as cyclopropanones. 36 Base-catalysed rearrangement of bicyclic sulphones (32) and subsequent extrusion of sulphur dioxide from the products (33) provides a valuable synthetic route to cyclo-octatetraenes. 37 The novel transformations (32) -+ (33) can be formulated either as bishomoconjugative Ramberg-Backlund rearrangements or as normal 1,3-eliminations followed by the bond reorganizations shown (Scheme l).37 (33) Scheme 1 The synthetic versatility of the Ramberg-Backlund rearrangement is exploited in a general synthesis of unsaturated propel lane^.^^ An unsuccessful attempt to synthesize bicyclopropylidene by Ramberg-Backlund rearrangement of a di- cyclopropyl sulphone is attributed to the instability inherent in cyclopropyl car bani on^.^^ Thiirene S-dioxides have been isolated from the Ramberg-Backlund reactions of zx-dihalogenodibenzyl s~lphones.~' Cationic Rearrangements.-Ester group migrations have been re~iewed.~ Equilibrium deuterium isotope effects provide detailed information on the mechanisms of fast degenerate Wagner-Meerwein rearrangements in acyclic carbonium ions.42 This powerful new method has been used to study rapid methyl and hydride shifts in the 2,3-dimethylb~tyl~~"~' 2,2,3-trimethylb~tyl,~~' 36 H.Quast E. Schmitt and R. Frank Angew. Chem. Internat. Edn. 1971 10 651. 37 L. A. Paquette R. E. Wingard and R. H. Meisinger J. Amer. Chem. Sac. 1971 93 1047. 38 L. A. Paquette J. C. Philips and R. E. Wingard J. Amer. Chrm. Sor. 1971 93 4516 4522. 39 L. A. Paquette and R.W. Houser J. Org. Chrm. 1971 36 1015. 4o L. A. Carpino L. V. McAdams R.H. Rynbrandt and J. W. Spiewak J. Amer. Chem. Sot... 1971 93 476; J. C. Philips J. V. Swisher D. Haidukewych and 0. Morales Chem. Comm. 197I 22. 4' R. M. Acheson Accounts Chem. Res. 1971,4 177. 42 (0)M. Saunders M. H. Jaffe and P. Vogel J. Amer. Chem. Soc.1971 93 2558; (h) M. Saunders and P. Vogel ihid. p. 2559; (r) M. Saunders and P. Vogel ihid. p. 2561. 248 G. Tennant and ~yclopentyl~~~ cations. A new degenerate rearrangement involving conver- sion into and return from a singly branched species is demonstrated by label scrambling in 2-trideuteriomethyl-2,3-dimethylbutyl It has been demonstrated that methyl participation is not important in the rearrangement of neopenty1-2,4-dinitrobenzenes~lphonate.~~ Deaminative rearrangements of primary aliphatic amines have been reviewed,44 and a series of papers con- cerning the steric course of such processes has been published.45 Rearrangements involving cyclopropylvinyl cations are attracting increasing attention. Treatment of 1 -iodovinylcyclopropane (34a) with silver acetate results mainly in solvent capture ring expansion to cyclobutene derivatives occurring only to a minor extent.46 In contrast predominant formation of hydroxycyclobutenes is observed in the solvolysis (AgN0,-CaC0,-H20 100 "C 12 h) of trans-(l-chlorovinyl)-l,2-dimethylcyclopropane.Product ratios and stereochemistry are explained in terms of vinylcyclopropyl and methylene- cyclobutyl cation intermediates4' Ring expansion of a vinylcyclopropyl cation to a cyclobutenyl cation is implicated in the conversion of l-bromovinylcyclo-propane (34b) into cyclo butanone by a smooth first-order process in aqueous trie thylamine at elevated temperature.48 The cy clopropylcar binylkyclo bu ty1 rearrangement provides a simple rationale for the key role played by presqualene alcohol pyrophosphate in squalene bio~ynthesis.~~ A similar homoallyl-cyclo- propylcarbinyl-cyclobutyl carbonium ion sequence has been demonstrated in the terpene Methanolysis of the labelled exo- and endo-bicyclo[3,1,0]- hexenyl trifluoroacetates (35) and (36)results in the sole formation of the exo-ether (37) which is exlusively deuteriated at positions 2 and 4.The absence of label scrambling to the 1 3 and 5 positions indicates that in these systems the rate of solvent capture is at least 1.6 x lo3faster than the rate of sigmatropic rearrange- ment.50 Photolysis of benzene in deuteriophosphoric acid results in specific incorporation of deuterium into the 6-endo position of the bicyclo[3,l,0]hexeny1 products.This specificity is incompatible with a mechanism involving the direct X (34) a; X = I b;X = Br 43 W. M. Schubert and W. L. Henson J. Amer. Chem. Soc. 1971 93 6299. 44 C. J. Collins Accounts Chem. Res. 1971 4 315. 45 W. Kirmse H. Arold and B. Kornrumpf Chem. Ber. 1971 104 1783; W. Kirmse and W. Gruber ibid. p. 1789 1795; W. Kirmse and H. Arold ibid. p. 1800. 46 S. A. Sherrod and R. G. Bergman J. Amer. Chem. SOC., 1971 93 1925; D. R. Kelsey and R. G. Bergman ibid. p. 1941. 47 M. Santelli and M. Bertrand Tetrahedron Letters 1971 3767. 48 T. Bassler and M. Hanack Tetrahedron Letters 1971 2171. 49 (a) E. E. van Tamelen and M. A. Schwartz J. Amer. Chem. Sac. 1971 93 1780; (b) L. J. Altman R. C. Kowerskii and H. C. Rilling ibid. p. 1782; H. C.Rilling C. D. Poulter W. W. Epstein and B. Larsen ibid. p. 1783. J. A. Berson and N. M. Hasty J. Amer. Chem. SOC.,1971,93 1549. Molecular Rearrangements OMe (37) rearrangement of benzeneonium ion to the bicyclohexenyl cation and supports the intermediacy of benzvalene in such proce~ses.~' Mechanisms proposed5 for the benzeneonium ion -+ bicyclohexenyl cation photosiomerization merit reconsideration in view of these results. Sequential sigmatropic shifts have been successfully demonstrated in the parent bicyclo[3,l,0]hexeny1 cation.52 However the activation energy required (AF* = 15 f1 kcal mol- at -90 "C) is sub- stantially higher than that found for the corresponding heptamethyl derivative (AF* = 9 kcal mol- ' at -89 0C).52A new and intriguing degenerate rearrange- ment in a carbonium ion has been reported.Treatment of the benzobicyclo- [3,2,1 Joctenone (38) with deuteriotrifluoroacetic acid results in deuterium exchange ofonly five of the six methyl groups that at the 8-anti position (labelled with an asterisk in Scheme 2) being ~naffected.~~ These results are reconciled by a stepwise (or possibly concerted) migration of the three-carbon bridge round the periphery of the five-membered ring in the protonated ketone accom- panied by stereospecific methyl shift in the same direction (Scheme 2). Deu- terium labelling demonstrates the operation of similar sequential migrations in the bicyclo[3,2,l]octenone (39).53 The 13C and 'H n.m.r. and Raman spectra of the 1,2-dimethylnorbornyl cation are in accord with a partially o-delocalized structure which is undergoing a rapid degenerate hydride shift [cf:(40)S(41)S(42)].54 Examples of hitherto unknown 2,3-endo endo methyl and hydride shifts have been observed in the deaminative rearrangements of norbornyl derivatives.These rearrangements " R. F. Childs and B. Parrington Chem. Comm. 1971 1540. " P. Vogel M. Saunders N. M. Hasty and J. A. Berson J. Amer. Chem. SOC., 1971,93 1551. 53 H. Hart and G. M. Love J. Amer. Chem. SOC.,1971,93 6264. 54 G. A. Olah J. R. DeMember C. Y. Lui and R. D. Porter J. Amer. Chem. SOC.,1971 93 1442. 55 S. Rengaraju and K. D. Berlin Tetrahedron 1971 27 2399; P. Wilder and W. C. Hsieh J. Org. Chern. 1971 36 2552. 250 G.Tennant -Me ___) *?jT \ Scheme 2 Molecular Rearrangements 251 must either involve a concerted process which bypasses the normal bicyclic carbonium ion or must occur by a fast 1,2-shift to the ‘hot’ carbonium ion produced on initial loss of nitrogen. Carbonium ion rearrangements of janusene (43)and its derivatives have been described [e.g.(43)-+ Rearrangement to bicyclo[4,3,1]-decatrienes [e.g.(47)]via the corresponding bishomotropylium cation [e.g. (46)]occurs on electrophilic addition to bicyclo[4,2,2]decatetraene (4515’The transformation “48)+(5O)Jrepresents a novel example of a Wagner- Meerwein shift in an organometallic complex. Deuterium labeiling showed that though the 1,2-shift in the cation (49)occurs predominantly by the direct pathway (a) rearrangement by pathway (b)is also in~olved.’~ Treatment of (43) (44) H Br H Br [2-14C]adamantane with aluminium bromide at 110“C results in extensive (78.4%) label scrambling.This unprecedented automerization (degenerate isomerization) of adamantane is viewed in terms of bond reorganization within the framework of the adamantyl cation.59 1,2-Hydride shifts on the adamantane skeleton are subject to an energy barrier of at least 2G30.5 kcal mol- and 5h S. J. Cristol and M. A. Imhoff J. Org. Chem. 1971,36 1849; 1854. ’’ G. Schroder U. Prange B. Putze J. Thio and J. F. M. Oth Chem. Ber. 1971 104 3406. 58 A. Eisenstadt and S. Winstein Tetrahedron Letters 1970 4603. 59 Z. Majerski S. H. Liggero P. von R. Schleyer and A.P. Wolf Chem. Comm. 1970 1596. 252 G. Tennanl consequently are strongly inhibited.60 Hydride shifts occurring in the course of the Koch-Haaf carboxylation of adamantanes have been shown to be inter- molecular processes.61 The versatility of the protoadamantane to adamantane rearrangement as a synthetic entry to otherwise inaccessible 1,2- and 2,4-di- substituted adamantanes has been demonstrated by two research groups.62 Reaction of 1-bromoadamantane with prop-2-ynyl alcohol results in ring ex- pansion to homoadamantyl methyl ketone.63 Ring expansion of the adamantane skeleton is also involved in the acid-catalysed conversion of the novel spiro- adamantane-homoadamantane (51) into a mixture of the fused bishomoadaman- tane (52) and adamantylidene adamantane (53).64 The Rupe and Meyer-Schuster rearrangements have been reviewed.65 The critique by Bordwel166 published last year has polarized the controversy sur- rounding the S,2‘ mechanism of allylic rearrangement and the criticisms have been ref~ted.~’ A major factor contributing to this problem is the lack of suitable analytical methods which are capable of distinguishing unequivocally between the various mechanistic possibilities.An analytical procedure based on isotopic labelling which is claimed to circumvent these difficulties has been described.68 Entry of hydride ion and loss of chloride ion are shown to occur synfacially in the hydride-ion-induced rearrangement of an allylic chloride. It is concluded that such processes are best designated as SNi’and that ‘the SN2’myth should no longer be perpet~ated’.~~ Ring-opening in the cyclo- propyl-ally1 chloride rearrangement is at least 95 % stereospecific recapture of 6o P.Vogel M. Saunders W. Thielecke and P. von R. Schleyer Tetrahedron Letters 1971 1429. 6* D. J. Raber R. C. Fort E. Wiskott C. W. Woodworth P. von R. Schleyer J. Weber and H. Stetter Tetrahedron 197 1 27 3. 62 D. Lenoir R. Glaser P. Mison and P. von R. Schleyer J. Org. Chem. 1971,36 1821 ; D. Lenoir P. von R. Schleyer C. A. Cupas and W. E. Heyd Chem. Comm. 1971,26; B. D. Cuddy D. Grant and M. A. McKervey ibid. p. 27. 63 J. K. Chakrabarti and A. Todd Chem. Comm. 1971 556. 64 E. Boelema H. Wynberg and J. Strating Tetrahedron Letters 1971 4029. 65 S. Swaminathan and K.V. Narayanan Chem. Ret;. 1971,71,429. 66 F. G. Bordwell Accounts Chem. Res. 1970 3 281. 67 P. B. D. de la Mare and C. A. Vernon J. Chem. SOC.(B) 1971 1699. 68 M. M. Shemyakin L. A. Neiman S. V. Zhukova Y. S. Nekrasov T. J. Pehk and E. T. Lippmaa Tetrahedron 1971 27 281 1. 69 C. W. Jefford A. Sweeney D. T. Hall and F. Delay Helv. Chim. Acta 1971,54 1691. Molecular Rearrangements the chloride ion following rapidly on its release.70 Valency isomerism of acyloxo- nium cations is described in a series of paper^.^' The acyloxonium cation(s) (54) derived from pentahydroxycyclopentanes are shown by n.m.r. to exhibit remarkable valency isomerism whereby the acyloxonium unit undulates round the five-membered ring in a ten-step cycle [i.e.(54) S(55)S(56)G (54)].'Ib Me OAc Me Me (54) (55) The first example of a 1,3-halogen shift in a chlorocarbonium ion has been re- ported.72 Rearrangements of Electron-deficient Intermediates.-The operation of the hitherto unknown thermal Wolff rearrangement of alkoxycarbonylcarbenes is implied by the formation of a product mixture containing methyl vinyl ether methyl acetate and methyl pyruvate in the gas-phase pyrolysis (>280 "C)of dimethyl diaz~malonate.~~ Photochemical Wolff rearrangement is involved in the formation74 of propargylene (58) from the diazoketone (57) and has also been employed in the first syntheses of [3,3,2]- and [4,2,2]-propellane~.~~ The ring expansion [(59)-+ (60)] represents the first example of dichlorocarbene c1 CI CHCI 'O I.Fleming and E. J. Thomas Tetrahedron Letters 1971 2485. 71 (a)H. Paulsen and H. Behne Chem. Bet-. 1971 104 1281 1311; (b) H. Paulsen and H. Behne ibid. p. 1299. 72 P. E. Petersen and W. F. Boron J. Amer. Chem. SOC.,1971,93 4076. 73 D. C. Richardson M. E. Hendrick and M. Jones J. Amer. Chem. SOC.,1971,93,3790; S. Julia H. Ledon and G. Linstrumelle Compt. rend. 1971 272 C 1898. 74 R. Selvarajan and J. H. Boyer J. Org. Chem. 1971 36 1679. 75 P. E. Eaton and K. Nyi J. Amer. Chem. SOC.,1971,93 2786. 254 G. Tennant insertion into a silicon-carbon bond.76 Flash vacuum pyrolysis (700 "C)of o- rn- and p-tolylcarbenes yields benzocyclobutene and styrene in 50 % overall yield. 3C-labelling supports a mechanism for these novel rearrangements involving interconversion of rn-and p-tolylcarbene with o-tolylcarbene by sequential bicyclo[4,l,0]heptatriene-cycloheptatrienylidene valence isomerism and subsequent cycli~ation.~ The quest continues for processes involving non-classical carbene intermediates ('foiled carbene' additions).The formation of tetracyclo[3,3,0,0,2.80,4~6]octane (64) in (63) and tricycl0[3,3,0,O,~~~]oct-2-ene the base-catalysed decomposition of endo-8-tricyclo[3,2,1,02~4]octanonetosyl-hydrazone (61) is adduced as evidence for trishomocyclopropenyl participation and hence non-classical character in endo-8-carbenatricyclo-octane(62).78 N-NHTs Migratory aptitudes in the Beckmann rearrangements of cyclic ap-unsaturated ketoximes have been and the thermal and solvolytic rearrangements of oxime-sulphur trioxide complexes have been described.8o A free-radical rather than an ionic process is favoured for the thermal rearrangement of benzo-hydroxamic chloride to phenylisocyanate.' I The mechanism of photochemical Beckmann rearrangement appears to be solvent dependent.In propan-2-01 formation of open-chain amides by cleavage of the most highly substituted bond implies a free-radical process. Conversely rearrangement in methanol is stereospecific and proceeds with retention of configuration at the migrating carbon atom supporting the concerted breakdown of an oxaziridine inter- mediate.82 Anilide oximes are rearranged in moderate yield to carbodi-imides by treatment with phosphorus oxychloride in pyridine.The migration aptitude (p-Me0 > p-Me > H > p-C1 > p-Ph > p-NO,) observed in these reactions and the absence of insertion products (benzimidazoles) indicate that aryl migra- tion is concerted with departure of the leaving Tetrazole formation '' D. Seyferth R. Damrauer S. B. Andrews and S. S. Washburne J. Amer. Chem. Soc. 197 1,93 3709. '' E. Hedaya and M. E. Kent J. Amer. Chem. Soc. 1971,93 3283. '' P. K. Freeman R. S. Raghavan and D. G. Kuper J. Amer. Chem. SOC., 1971 93 5288. 79 T. Sato H. Wakatsuka and K. Amano Tetrahedron 1971 27 5381; Y. Tamura Y. Kita and M. Terashima Chem. and Pharm. Bull. (Japan),1971 19 529. K. K. Kelly and J. S. Matthews J. Org. Chem. 1971 36 2159. " Y. H. Chiang J. Org. Chem. 1971 36 2155. 82 M. Cunningham L.S. Ng Lim and G. Just Canad. J. Chem. 1971,49 2891 ;see also H. Suginome and H. Takahashi Tetrahedron Letters 1970 51 19. 83 J. Garapon B. Sillion and J. M. Bonnier Tetrahedron Letters 1970 4905. Molecular Rearrangements in the Schmidt rearrangement of adamantanone is indicative of a stepwise process involving iminium cation intermediate^.^^ The rearrangement [(65)-+(66)]represents one of the first examples of a Schmidt reaction involving migration to oxygen rather than nitrogen.85 The nitrone to amide transforma- tion [(67) +(69)] is thoughtg6 to proceed via an intermediate hydroxylamine tosylate (68) and provides a valuable complement to Beckmann rearrangement for ring expansion of this type. N-Tosyloxy-2-azanorbornenesand norbornanes undergo novel concerted Lossen-type rearrangements to afford the corres- ponding 1-azanornornene and norbornane derivatives [e.g.(70)-+ (71)Jg7 HN &I \ / NC C0,Et v \ OTs (70) The Hofmann-Loeffler and Stieglitz rearrangements and rearrangements involving nitrenium ions have been reviewed.gg Kinetic parameters determined for the Hofmann rearrangements of N-chloro-and N-bromo-benzamides and 84 T. Sasaki S. Eguchi and K. Toru J. Org. Chem. 1971 36 2454. 85 D. H. R. Barton P. G. Sammes and G. G. Weingarten J. Chem. SOC.(0,1971 729. 8h D. H. R. Barton M. J. Day R. H. Hesse and M. M. Pechet Chem. Comm. 1971,945. " J. M. Biehler and J. P. Fleury Tetrahedron 1971 27 3171; J. Heterocyclic Chem. 1971 8 431. 88 P. Kovacic M.K. Lowery and K. W. Field Chem. Rev. 1970,70 739. 256 G. Tennant their derivatives support fully concerted mechanisms for these reaction^.^' Rearrangements involving nitrenium ions continue to attract attention. Genera- tion of singlet nitrenium ion exocyclic to a four-membered ring results in direct ring expansion to a pyrrolidine cation which can be trapped after reductive work-up [cf. (72) +(73) +(74)]. Hydrogen abstraction after spin inversion to triplet nitrenium ion competes with rearrangementg0 Conversely generation of the nitrenium ion on a four-membered ring is rapidly followed by ring con- traction to an aziridinium cation [ct (75) +(76) +(77)] whose formation is inferred from the nature of the products obtained after hydrolytic work-up in the presence of benzoyl ~hloride.~' The reverse of this ring contraction is exemplified by the silver nitrate-catalysed ring expansion of N-chloroamino- cyclopropanols to azetidin~nes.~' Full details of the aluminium chloride (73) Me catalysed nitrenium ion rearrangements of NN-dichloro-1 -aminoadamantane have been Skeletal rearrangements of nitrenium ions generated by nitrous acid deamination of N-aminoazanorbornanes have also been re- ported.93 89 T.Imamoto Y. Tsuto and Y. Yukawa Bull. Chem. SOC. (Japan) 1971 44 1632 1639 1644; (Chem. Abs. 1971 75 62 899 62 901 62 908). 90 P. G. Gassman and A. Carrasquillo Tetrahedron Letters 1971 109. 91 H. H. Wasserman H. W. Adickes and 0. Espejo de Ochoa J. Amer. Chem. SOC. 1971,93 5586. 92 P.Kovacic J. H. Liu E. M. Levi and P. D. Roskos J. Amer. Chem. SOC.,1971 93 5801. 93 P. G. Gassman and K. Shudo J. Amer. Chem. SOC.,1971,93 5899. Molecular Rearrangements 257 There is now a considerable body of evidence which supports the operation of fully concerted processes in a number of photolytic and pyrolytic azide rearrangements. Further support comes from the demonstration of non-statistical migration of alkyl and aryl groups in the photolysis of azides the least bulky group invariably undergoing preferential migration.94 This specificity is interpreted in terms of fully concerted non-nitrene processes in which the migration aptitude is determined by conformational preferences in the ground state. This interpretation is supported by the observation that rearrangement product ratios tend to the statistical value with increase in temperature a feature which militates against the involvement of a symmetrical nitrene intermediate.94 In contrast to photolysis which produces rearrangement thermolysis of the geminal diazide of dimethyl malonate results in insertion into the C=O bond.95 This clear-cut example of dichotomy in the behaviour of azides is rationalized by the proposal that the photochemical and thermal processes are respectively concerted and non-~oncerted.~' In the photochemical rearrangement of 1-azidonorbornane (78) the one- and two-carbon bridges migrate with equal facility to yield (79) and (80).The same product mixture is obtained in lower yield by thermolysis of (78) at 140-170 0C.96Nitrene and nitrenium ion intermediates can be excluded and a mechanism involving bridge migration concerted with loss of nitrogen from the solvated azide is suggested.96 The thermal decom- position of dichlorocyclopropyl azides is highly regiospecific and provides an excellent method for the synthesis of azetine~.~~ Ring expansion concerted with nitrogen loss is indicated by the negative entropy of activation (AS* = -18 eu) observed for these rearrangement^.^^ The thermal ring expansion of 2-azidoindane-l,3-dionesto azanaphthoquinones is an example of a rare acyl migration to nitr~gen.~' 0-N aryl migration has been reported in oxyni- trenes.Inhibition of ozonide formation by added aldehyde or ketone is attributed to formal reduction of the Staudinger molozonide in a Baeyer-Villiger type process [cJ(Sl)].The recognition of this phenomenon has led to a new rationale for the mechanism of ozonolysis."' An example of the rare Baeyer-Villiger oxidation of an afi-unsaturated carbonyl compound has been described. lo' Migration aptitudes have been reported for the Baeyer-Villiger rearrangements of a1dehydes,lo2 cycloalkyl ket~nes,''~ and a cage ketone.lo4 In the latter case exclusive migration of the cage structure is observed. The incidence of acid- y4 R. A. Abramovitch and E. P. Kyba J. Amer. Chem. Sac. 1971 93 1537. 95 R. M. Moriarty and P. Serridge J. Amer. Chem. Soc. 1971 93 1534. y6 J. 0. Reed and W. Lwowski J. Org. Chem. 1971,36,2864. Y'A. B. Levy and A. Hassner J. Amer.Chem. Soc. 1971 93 2051. 98 H. W. Moore and D. S. Pearce Tetrahedron Letters 1971 1621. 99 F. A. Carey and L. J. Hayes J. Amer. Chem. Soc. 1970 92 7613. loo P. R. Story J. A. Alford W. C. Ray and J. R. Burgess J. Amer. Chem. Sac. 1971 93 3044. lo' D. L. Coffen and D. G. Korzan J. Org. Chem. 1971 36 390. lo' J. Royer and M. Beugelmans-Verrier Compt. rend. 1971 272 C 1818. lo' S. A. Monti and C. K. Ward Tetrahedron Letters 1971 697. Io4 B. Zwanenburg and A. J. H. Klunder Tetrahedron Letters 1971 1717. 258 G. Tennant catalysed 1,2-shifts in alkyl hydroperoxides is governed by the strength of the acid medium. Strongly acid media promote rearrangement in accordance with preferential protonation of the hydroxyl-oxygen. 'O5 Acid-catalysed re-arrangement of tertiary cycloalk yl hydro peroxides occurs with predominant ring-bond migration; in the examples studied alkyl migration was not observed.Thermal Photochemical and Metal-catalysed Rearrangements.-The 'abnormal' Claisen rearrangement has been reviewed. lo' Aspects of concerted sigmatropic rearrangements are discussed in review articles by Dewar'08 and Fukui."' The effect of steric constraint on the transition state for Claisen rearrangement is illustrated by the thermal behaviour of the isomeric vinylfurans (82) and (83). Concerted thermal rearrangement of (82) is disallowed on steric grounds but occurs by initial isomerization to the exo-methylene compound (83) in which the requisite transition-state geometry is more readily attained.' ' The novel thermal transformation [(84)-+(86)] is formulated' '' as a bicyclic Claisen rearrangement [(84)-+(85)+(86)].The formation of a single phenolic product Me Me Me lo5 J. 0.Turner Tetrahedron Letters 1971 887. Io6 R. D. Bushick Tetrahedron Letters 1971 579. lo' H. J. Hansen ref. I p. 177. lo' M. J. S. Dewar Angew. Chem. Internat. Edn. 1971 10 761. lo9 K. Fukui Accounts Chem. Res. 1971 4 57. lo S. J. Rhoads and C. F. Brandenburg J. Amer. Chem. SOC.,1971,93 5805; S. J. Rhoads and J. M. Watson ibid. p. 5813. 'I' J. W. Hanifin and E. Cohen J. Org. Chem. 1971 36 910. Molecular Rearrangements 2 59 excludes a biradical pathway."' The rearrangements [(87)+(88)+(89)l show first-order kinetics and are relatively insensitive to radical inhibitors or to changes in solvent polarity.Cyclic concerted mechanisms are therefore proposed.' l2 The Claisen-type rearrangement of an allyl system containing three hetero-atoms has been reported.' l3 The Cope rearrangement is a classic example of a narcissistic reaction. ' l4 Full details of a kinetic study of the parent Cope rearrangement of 1,l-dideuterio- hexa-1,5-diene have been published.' ' The finely balanced interplay between steric and electronic factors in determining the preferred transition-state geo- metry for the Cope rearrangement is demonstrated by the thermal transformation of meso-3,4-diphenylhexa-1,5-dieneinto a mixture of cis,trans- and trans trans-1,6-diphenylhexa- 1,5-dienes in a combination of four-centre and six-centre pathways."6 Doubt has been cast on the antara-antara Cope mechanism pro- posed' '' for the thermal isomerization of bicyclo[3,2,0]hepta-2,6-dienes.' ' Me OCOAr Me I 'Me ee-3 0 O.COAr 0 -OH (87) (88) D JZD D An alternative mechanism' l8 involving conrotatory ring opening to a cis,-trarqcis-triene [cf (91)] and subsequent reclosure via the cis double bond to product is supported by the key role played by the cyclobutene ring in the closely related thermal rearrangement [(90) +(91)-+(92)]. The elusive sulpho-Cope rearrangement has been successfully demonstrated for allyl vinyl sulphone. ' ' Two remarkable new degenerate rearrangements of C,,H hydrocarbons have been described. The extent of label scrambling in hypostrophene (93) at 'I2 D.H. R. Barton P. D. Magnus and M. J. Pearson J. Chem. Soc. (0,1971 2231. 'I3 N. D. Heindel and M. C. Chun Tetrahedron Letters 1971 1439. L. Salem Accounts Chem. Res. 1971 4 322. 'I5 W. von E. Doering V. G. Toscano and G. H. Beasley Tetrahedron 1971 27 5299. 'I6 R. P. Lutz S. Bernal R. J. Boggio R. 0. Harris and M. W. McNicholas J. Amer. Chem. Soc. 1971 93 3985. 117 T. M'iyashi M. Nitta and T. Mukai J. Amcr. Chem. Soc. 1971. 93. 3441. J. E. Baldwin and M. S. Kaplan J. Amer. Clrrm. Soc. 1971 93 3969. 'I9 J. F. King and D. R. K. Harding Chem. Comm. 1971. 959. 260 G. Tennant 35 "C indicates fluxional behaviour which rivals that of bullvalene.'20 The cage hydrocarbon snoutene (94) undergoes deuterium scrambling at 500 "C by a formal [,2 + ,2 + .2,] process [(94)S(95)].12 A theoretical treatment (MIND0/2) correctly predicts rates and activation energies for the degenerate Cope rearrangements of bullvalene barbaralene and semibullvalene.122 The report'23 that the tautomer (96) is favoured in the equilibrium (96),(97) appears to vindicate the prediction that structures having electron-withdrawing substituents at the bridgehead are preferred in such equilibria. However it is interesting to note that in the barbaralone equilibrium a methyl group shows the same preference.' 24 Retention of configuration at the migrating centre and at both allylic centres has been established for the photochemically induced 1,3-allylic shift of a benzyl group. 12' Unexpectedly the corresponding thermal 1,3-allylic shift [(98) -+ (99)] also occurs with > 90% retention of configuration at the migrating centre.This apparent violation of orbital symmetry control is attributed to orbital perturba- tion in the highly polarized dicyanoallyl system.' 26 Two examples of thermal [ 1,5] sigmatropic acyl shifts have been reported. '27 The thermal rearrangement of 2-bromocyclobutanone ketals to cyclopropyl carboxylates occurs with inver- sion of configuration at the migrating centre demonstrating the absence of orbital symmetry control.12* The ob~ervation'~~ a linear correlation between of A L 7 hv Ph Me Ph Me NC. CN (99) (97) (98) lZo J. S.McKennis L. Brener J. S. Ward and R. Pettit J. Amer. Chem. SOC.,1971 93 4957. lZ1 L. A. Paquette and J.C. Stowell J. Amer. Chem. SOC.,1971 93 2459. lZ2 M. J. S. Dewar and W. W. Schoeller J. Amer. Chem. SOC.,1971 93 1481. 12' G.R.Crow and K. C. Ramey Tetrahedron Letters 1971 3141. J. C. Barborak S. Chari and P. von R. Schleyer J. Amer. Chem. SOC.,1971,93 5275. R. C. Cookson J. Hudec and M. Sharma Chem. Comm. 1971 107 108. lZ6 R. C. Cookson and J. E. Kemp Chem. Comm. 1971 385. I" J. A. Berson and R. G. Salomon J. Amer. Chem. SOC.,1971,93,4620; R. A. Baylouny ibid. p. 4621; D. W. Jones and G. Kneen Chem. Comm. 1971 1356. 12* J. Salaun and J. M. Conia Tetrahedron Letters 1971 4023. lZ9 J. E.Baldwin and A. H. Andrist J. Amer. Chem. SOC.,1971 93 3289. Molecular Rearrangements 261 U.V. transition energies and activation energies for the thermal bicyclo[2,1,0]- pentene4yclopentadiene rearrangement' 30 may indicate that low-lying excited states play an important role in such [,2 + ,2,] interconversions.The demonstration' ' that cis,2trans,cis-cyclonona-tetraene(CNT) (102) is probably an intermediate in the thermal reorganizations of cis-bicyclo[6,1 ,O]-nona-2,4,6-triene (100) to 8g-dihydroindenes has shed new light on the vexatious question of the mechanisms of these transformations. It is suggested that the preferred pathway for rearrangement involves initial Cope rearrangement from a folded conformation of (100) to afford bicyclo[5,2,0]nona-1,4,7-triene(101) followed by symmetry-allowed conrotatory ring-opening to the tetraene (102) and subsequent closure to trans-8,9-dihydroindene (103).Alternatively (101) undergoes symmetry-forbidden rupture of the cross-link to all-cis-(CNT) (1 04) the precursor of cis-8,9-dihydroindene (105). Where a folded conformation in (100)is not accessible [as in 9,9-disubstituted derivatives of (loo)] rearrangement takes place from an extended conformation by direct symmetry-allowed rupture of the cross-link in (100) to give ~is,~trmzs-(CNT), a known precursor of trans-8,9-dihydroindene (103).' 31 These proposals are in accord with the results of other ~tudies,'~' but it is of interest that the reversal of a Cope rearrangement of the type [(loo)+ (101)] has been The remarkable alteration in stereospecificity represented' 33b by the Rh'-catalysed rearrangement of the 9,9- dimethyl derivative of (100) to the corresponding cis-8,9-dihydroindene also remains to be clarified.The results of deuterium-labelling studies support either a concerted [,2 + ,2,] or a biradical mediated pathway for the penultimate I3O J. E. Baldwin and A. H. Andrist Chem. Comm. 1970 1561. ''I A. G. Anastassiou and R. C. Griffith J. Amer. Chem. SOC.,1971 93 3083; A. G. Anastassiou and R. C. Griffith Chem. Comm. 1971 1301. 132 J. C. Barborak T. M. Su P. von R. Schleyer G. Boche and G. Schneider J. Amer. Chem. SOC.,197 1,93 279. (a)L. A. Paquette and M. J. Epstein J. Amer. Chem. SOC., 1971,93 5936; (b)R. Grigg R. Hayes and A. Sweeney Chem. Comm. 1971 1248. 262 G. Tennant step [( 101)-+(104)] leading from (100) uia all-cis-(CNT)(104)to cis-8,9-dihydro- indene (105).'34 The Agl-catalysed rearrangements of strained o-bonded hydrocarbons have been reviewed.' The controversy surrounding the mechanism(s) of these and related transition-metal-catalysed skeletal reorganizations has stimulated much experimental effort during the past year. The recognition that these rearrange- ments formally represent metal-catalysed symmetry-disallowed thermal pro- cesses is particularly intriguing because of the implied capacity of the metal to modify the orbital symmetry requirements of the transition state. The question of the timing of these remarkable metal-catalysed transformations appears definitely to have been resolved in favour of a stepwise process (cf:refs. 136a-c and other recent work cited therein) in which the metal acting as a weak Lewis acid interacts with the o-bonded structure to give directly (or after formation of an initial complex) a discrete intermediate variously formulated as a metal- bonded carbonium ion '353'36b or as a metal-complexed-carbene-metal-bonded carbonium ion hybrid'36" [(106)++ (107)l.Rearrangement by a formal carbe- noid or carbonium ion process within such an intermediate to give the observed products is supported by results obtained in recent studies.' 36a*c However the precise role played by the metal catalyst'36a and by the attached ligands'37 in determining the electronic character of the intermediate (and hence the mode of rearrangement) remains to be clarified. Pentafluorophenylcopper 38 is an effective catalyst for strained a-bond rearrangements ; new examples of these processes have been reported for the bicyclo[2,1,0]pentane ring system.39 M-yq-yyf (106) ( 107) 2 Aromatic Rearrangements Spirodiene rearrangements were the theme of last year's Pedler Lecture. 140 The dienone-phen01,'~' ph~to-Fries,'~~ and nitramine 144 H~fmann-Martius,'~~ rearrangements have been reviewed. Other review articles deal with aspects of dienone-phenol '45 and benzidine'08 rearrangements. 134 J. E. Baldwin and A. H. Andrist J. Amer. Chem. SOC. 1971 93 4055. 135 L. A. Paquette Accounts Chem. Res. 1971 280. 13' (a) P. G. Gassman and T. J. Atkins J. Amer. Chem. Soc. 1971 93 4597; (6) L. A. Paquette R. P. Henzel and S. E. Wilson ibid. p. 2335; L. A. Paquette and S. E. Wilson ibid. p. 5934; (c) M.Sakai and S. Masamune ibid. p. 4610; M. Sakai H. H. Westberg H. Yamaguchi and S. Masamune ibid. p. 461 1. 13' P. G. Gassman G. R. Meyer and F. J. Williams Chem. Comm. 1971 842. 38 P. G. Gassman and F. J. Williams Tetrahedron Letters I97 1 1409. 13' P. G. Gassman T. J. Atkins and J. T. Lumb Tetrahedron Letters 1971 1643. 140 D. H. Hey Quart. Rev. 1971 25 483. 14' H. Hart Accounts Chem. Res. 1971 4 337. 14* D. Bellus Adv. Photochem. 1971 8 109. 143 G. F. Grillot ref. 1 p. 237. 14' W. N. White ref. I p. 109. R. M. Acheson Accounts Chem. Res. 1971 4 179. Molecular Rearrangements Methyl shifts in intermediate benzeneonium ions [e.g.(108)+(log)] account for the fragmentation of t-butyl groups observed in the course of nitration of 14' 2,4,6-tri-t-butylnitrobenzene.Deuterium and ''N-labelling studies reveal that the methyl group originates in the t-butyl group displaced. '46 Preferential migration of methyl groups is observed in the acid-catalysed rearrangements of the very crowded allyl benzene derivative (l10).'47 N.m.r. studies exclude a concerted mechanism for hydrogen migration 14' in benzeneonium ions and Me +I Me demon~trate'~~ the operation of sequential 1,2-methyl shifts in heptamethyl- benzeneonium ion rather than direct methyl transfer to non-adjacent positions. Jacobsen rearrangements induced in polymethyl-benzenes by trichloromethyl cations have been shown to occur by initial attack at a substituted carbon atom followed by a 1,2-methyl shift in the cation produced.' 50 The acid-catalysed [2,2]paracyclophane to [2,2]metaparacyclophane rearrangement [(1 1 1) -+(1 14)] involves a formal 1,2-alkyl shift in the benzeneonium ion intermediate (1 12) formed by preferential protonation at the bridgehead.' ' The demonstration' 52 that the conversion of (11 1) into (1 14) proceeds with retention of configuration is rationalized in terms of a bridged intermediate (or transition state) (113).The racemization observed in the photochemical rearrangement of the [2,2]- metaparacyclophane (1 14) to the [2,2]metacyclophane (115) is attributed to free rotation in a zwitterionic intermediate produced by cleavage of one of the benzyl-benzyl bonds.' 52 The extent of Ar '-5 rearrangement in cationic' and free-radical '54 cyclization reactions of benzene derivatives has been elegantly demonstrated by deu terium-la belling techniques.The available evidence suggests that the semibenzene rearrangement [( 116a)-+ (1 17a)l occurs by radical dissociation-recombination rather than sequential [3,3] sigmatropic allyl shifts. '' A thermally allowed [5,5] sigmatropic benzyl shift in the semibenzene (1 16b) is excluded by the formation of (1 17b) as the sole product. However rearrangement is not completely inhibited by radical traps 146 P. C. Myhre M. Beug K. S. Brown and B. Ostman J. Arner. Chern. SOC.,1971 93 3452. 14' K. H. Lai and B. Miller Tetrahedron Letters 1971 3575. A. J. Kresge Y.Chiang and S. A. Shapiro Canad. J. Chem. 1971 49 2777. 149 B. G. Derendyaev V. I. Mamatyuk and V.A. Koptyug tzvest. Akad. Nauk. S.S.S.R. Ser. khim. 1971 5 972 (Chern. Abs. 1971 75 62 855). H. Hart and J. F. Janssen J. Org. Chem. 1970 35 3637. D. T. Heffelfinger and D. J. Cram J. Amer. Chem. SOC.,1971 93 4754. lS2 M. H. Delton R. E. Gilman and D. J. Cram J. Amer. Chem. SOC.,1971 93 2329. V. R. Haddon and L. M. Jackman J. Arner. Chern. SOC.,1971 93 3832. J. C. Chottard and M. Julia Tetrahedron Letters 1971 2561. Is' B. Miller and K. H. Lai Tetrahedron Letters 1971 1617. 264 G. Tennant / and may involve at least in part an intramolecular pathway.'55 The isolation of oxepin derivatives in the dienol-benzene rearrangements of highly hindered cyclohexadienediols is explained by the valence isomerism of benzene oxide inter- mediates.' A 1,2-cyclopropyl shift in a dienone-phenol rearrangement has been reported.57 Exclusive aralkyl migration in competition with aryloxy migration is exemplified by the transformation [(118)-P (119)].158 A similar migration preference is shown in the rearrangements of the spirolactones (120) to coumaranones.l5 Tosylhydrazones of allylcyclohexadienones [e.g. (1 2 l)] -Me&: Me@ Me\ Me Me Me Me Me (1 16) (117) a; R = CH-CH b; R = Ph 156 S. Berger G. Henes and A. Rieker Tetrahedron Letters 1971 1257; A. Rieker Angew. Chem. Internat. Edn. 1971 10 425. 15' R. C. Hahn and G. W. Jones J. Amer. Chem. SOC., 1971 93 4232. 15* A. M. Choundhury K. Schofield and R. S. Ward J. Chem. SOC.(C),1970 2543. lS9 J. L. Chitwood P. G. Gott J. J. Krutak and J.C. Martin J. Org. Chem. 1971,36,2216. Molecular Rearrangements 0 0 (120) a; R = Me b;R=Ph undergo mild acid-catalysed [3,3] sigmatropic rearrangement to allylphenyl- hydrazines [e.g.(122)l. The product of a 1,2-shift was not detected.16' Fries rearrangement of 2-bromophenyl acetate affords products derived by intermolecular bromine and acyl migration. 16' This behaviour contrasts with the 'clean' rearrangement undergone by 2-chlorophenyl acetate. The formation of biradical intermediates in the photo-Fries rearrangements of phenolic car- bonates has been demonstrated by flash photolysis.'62 In support of a solvent cage radical-pair mechanism photo-Fries rearrangements of aryloxy-s-triazines are unaffected by changes in substrate concentration or by the presence of oxygen or triplet quenchers.63 Photo-Fries rearrangements have also been reported for ethyl phenyl carbonate 164aryloxya~etonitriles,~~~ and N-acyl-'66 and N-alkyl-arylamines. 165,167 The small positive p value ( + 0.426) observed for aryl migration accompanying peroxide-induced decarbonylation of fluorene derivatives [(123) -+(124)] is indicative of a high degree of free-radical character in the transition state for rearrangement.' 68 Alkali-metal-catalysed phenyl shifts in indene derivatives are claimed as the first examples of sigmatropic phenyl I6O M. Schmid H. J. Hansen and H. Schmid Helo. Chim. Acta 1971 54 937. J. A. Donnelley and J. J. Murphy J. Chem. SOC. (0,1970,2596. 16' J. S. Humphrey and R. S.Roller Mol. Photochem. 1971 3 35 (Chem. Abs. 1971 75 87 822). 163 H. Shizuka T. Kanai T. Morita Y. Ohoto and K. Matsui Tetrahedron 1971 27 4021. E. A. Caress and I. E. Rosenberg J. Org. Chem. 1971 36 769. 16' K. J. S. Arora M. K. M. Dirania and J. Hill J. Chem. SOC.(C) 1971 2865. Ih6 D. H. Hey G. H. Jones and M. J. Perkins J. Chem. SOC.(C) 1971,116;L. Munchausen 1. Ookuni and T. D. Roberts Tetrahedron Letters 1971 1917. 67 S. Naruto and 0.Yonemitsu Tetrahedron Letters 1971 2297. 16' P. N. Cote and B. M. Vittimberga J. Amer. Chem. SOC.,1971 93 276. 266 G. Tennant O R PhO R /I / h \/ Ar-C-C-Ph A \ /c=c\ R Ar R (125) (126) migrations in radical anions. '69 The corresponding thermally induced re-arrangements which show first-order rates and involve specific phenyl migration to the 2-position are thought to involve a transition state having a high degree of biradical character.' 70 The novel photochemical 1,3-aryl shift [(125) +(126)] has been reported.17' Deuterium labelling demonstrates that the aryl borate rearrangement [(127) +(128)] involves preferential phenyl migration in a radical fragmentation-recombination process.'' Further results supporting the polar transition state mechanism for the benzidine rearrangement have been published. 73 A benzidine-like rearrange- ment [(129) +(130)] of an intermediate ON-diarylhydroxylamine is proposed to account for the formation of biphenyl derivatives in the reactions of N- hydroxycarbamates with o-fluoronitro benzene. 174 Analogy with the benzidine rearrangement is further substantiated by the isolation of semidine- and di- phenyline-like by-products.'74 A comprehensive investigation' 75 of the thermal (129) H. 'H (130) L. L. Miller and R. F. Boyer J. Amer. Chem. SOC.,1971 93 646. L. L. Miller and R. F. Boyer J. Amer. Chem. Soc. 1971 93 650. 17' H. G. Heine Tetrahedron Letters 1971 1473. 17' P. J. Grisdale J. L. R. Williams M. E. Glogowski and B. E. Babb J. Org. Chem. 197 1 36 544. D. V. Banthorpe A. Copper and M. O'Sullivan J. Chem. SOC.(B) 1971 2054. T. Sheradsky and G. Salemnick Tetrahedron Letters 1971 645. 175 P. Wetzel Chem. Ber. 1971 104 808. Molecular Rearrangements rearrangements of N-nitroso-and N-nitro-diphenylamines demonstrates a close relationship to the thermal transformations of tetra-arylhydrazines '76 and provides compelling evidence for a radical fragmentation-recombination mechanism for these rearrangements.Conversely failure to detect c.i.d.n.p. in the nitramine rearrangement of N-nitroaniline is cited' as evidence against a radical mechanism. The intramolecular character of the thermal nitramine rearrangements of 1-nitropyrazoles to 3(5)-nitropyrazoles is strongly supported by the inability of such systems to initiate nitration of substrates such as anisole and by the failure of 2,3-dinitroindazole to undergo rearrangement. '77 In contrast the capacity of l-nitropyrazoles to effect the nitration of anisole under the conditions of their acid-catalysed rearrangement to 4-nitropyrazoles clearly reflects the intermolecular character of these processes.77 The photochemical rearrange- ment of "'-dimethylhydrazobenzenes leads predominantly to the formation of o-semidine derivatives. 78 The absence of o-benzidine products indicates a mechanism differing from that of the acid-catalysed benzidine rearrangement. The operation of a radical fragmentation-recombination process implied by the concomitant formation of scission products (N-methylarylamines) of the hydrazobenzene requires further substantiation. l7 Labelling studies demon- strate that the acid-catalysed rearrangement of sodium 1-naphthylsulphamate to l-aminonaphthalene-4-sulphonicacid is partly intramolecular. Bimolecular sulphonation by a multiply sulphonated intermediate is suggested as an alterna- tive to a n-complex mechanism which is considered unlikely.' 79 However the precise mechanism of this intriguing sulphamic acid rearrangement awaits the outcome of further experimentation.Rearrangements of the sulphamic acid type have also been reported for aryl-N-sulphohydroxylamines. '8o Ar0 0 \ I1 C=N.NHPh A Ph.C.NH.N/Ar / \ Ph Ph Aryl hydrazonates (13 1) undergo smooth thermal rearrangement at 100 "C to afford the hydrazides (132). It is tentatively suggested that this new type of O-+ N aryl migration involves an intramolecular process akin to that of the Chapman rearrangement. ' ' Smiles rearrangements involving nova1 intra- "' F. A. Neugebauer and H. Fischer Chem. Ber. 1971 104 886. '" J. W. A. M. Janssen and C.L. Habraken J. Org. Chem. 1971 36 3081; P. Cohen-Fernandes and C. L. Habraken J. Org. Chem. 1971 36 3084. "* €3. J. Shine and J. D. Cheng J. Org. Chem. 1971 36 2787. W. J. Spillane F. L. Scott and C. B. Goggin J. Chem. SOC.(B) 1971 2409. I8O D. Manson J. Chem. SOC.(0,1971 1508. A. F. Hegarty J. A. Kearney M. P. Cashman and F. L. Scott Chem. Comm. 1971 689. 268 G. Tennant (133) (134) molecular 0-0 [e.g. (133)+ (134)]'82 and N+N [e.g. (13.5)-(136)]'83 nucleophilic displacements have been described. Full details of the remarkable potassium anilide-catalysed isomerizations of trihalogenobenzenes (the 'base-catalysed halogen dance' !) have been pub-lished.'84 Compelling evidence is presented for a mechanism in which the key step is positive halogen transfer from a tetrahalogenobenzene intermediate (the '7-halogen' mechanism).An analogous process in a trihalogenobenzene intermediate (the '6-halogen' mechanism) may also intervene. 84 3 Heterocyclic Rearrangements Aziridine rearrangements ' heterocyclic valence isomerizations 86 and photo- chemical rearrangements '87 have been reviewed. The thermally disallowed aziridine rearrangement (137) +(138) has been reported.'88 The stimulus for this forbidden reaction is provided by relief of strain in (137) and the resonance stabilization attained in (138). Orbital symmetry Ph N.C,H, 18* M. Harfenist and E. Thom J. Org. Chem. 1971 36 1171; D. Horton and A. E. Luetzow Chem. Comm. 1971 79. lE3 N. W. Gilman P. Levitan and L. H.Sternbach Tetrahedron Letters 1970 4121; H. H. Otto ibid. p. 5189. J. F. Bunnett and C. E. Moyer J. Amer. Chem. SOC. 1971,93 1183; J. F. Bunnett and G. Scorrano ibid. p. 1190; D. J. McLennan and J. F. Bunnett ibid. p. 1198; J. F. Bunnett and I. N. Feit ibid. p. 1201. H. G. Heine ref. 1 p. 145. '" L. A. Paquette Angew. Chem. Internat. Edn. 1971 10 11. '*' A. Lablanche-Combier and M. A. Remy Bull. SOC. chim. France 1971 679; H. Wynberg Accounts Chem. Res. 1971 4 71. 18' J. W. Lown and K. Matsumoto J. Org. Chem. 1971 36 1405. Molecular Rearrangements 0-35°C tx 4 I OH (139) control has been demonstrated for the thermal ring-opening reactions of oxi- rans' 89 and oxaziridines. 190 Aziridine N-oxides [e.g. (139 ; X = NBu' R = H)]I9' and episulphoxides [e.g.(139; X = S; R = Me)]22 rearrange spontane- ously at &35 "C to afford allylic hydroxylamines [e.g. (140;X = NBu' R = H)] and unstable ally1 sulphenic acids [e.g. (140; X = S R = Me)]. In highly substi- tuted derivatives (139) fragmentation to the alkene and t-nitrosobutane or sulphur monoxide competes with rearrangement. The rate dependence on solvent polarity observed in the thermal interconversions of 3-chloro-1-azirines is interpreted in terms of an azacyclopropenyl cation or bridged chloronium ion intermediate. 192 A kinetic study of the thermal rearrangement of 2,3,4,4-tetra- methyloxeten to 1,2-dimethylpent-2-en-4-one reveals a marked rate acceleration in comparison with the thermal ring-opening of a structurally analogous cyclo- butene.l9 Similar electrocyclic ring-opening is illustrated by the thermal rearrangement of fused dioxetans to glycol diformates. 94 A number of novel heterocyclic rearrangements which derive their stimulus from the inherent reactivity of nitrene intermediates have been reported. The varied rearrangements observed in the nitrene-induced cyclizations of ortho-nitro and ortho-azido diaryl sulphides 195 and diaryl ethers,' 96 can all be attri- buted to the propensity of a zwitterionic spiran intermediate (141) to regain aromatic stability. In simple cases (141 ;R = H) this is achieved by the exclusive 1,2-shift of sulphur [cf (141; X = S R = or by competing oxygen and nitrogen 1,2-shifts [cf (141; X = 0,R = Nor is rearrangement deterred by the presence of substituents in both ortho-positions of the cyclohexadiene ring.Where the substituent is methyl proton transfer (from the methyl group) precedes the hetero-atom shift and the net result is ring expansion to a dibenzo- heterazepine. 195,196 On the other hand when the o-substituent is methoxy ultimate stabilization is achieved via an unprecedented transannular 1,4-migra- tion of a methoxy-group. 195,196 Nitrene-induced rearrangements are also observed in the reductive cyclizations of 2-nitrodiphenylamines to phenazine 189 A. Dahmen H. Hamburger R. Huisgen and V. Markowski Chem. Comm. 1971 1192. 190 J. S. Splitter T. M. Su H. Ono and M. Calvin J. Amer. Chem. Soc. 1971 93 4075. 191 J. E. Baldwin A. K. Bhatnagar S. C. Choi and T. J.Shortridge J. Amer. Chem. SOC. 1971 93,4082. 192 J. Ciabattoni and M. Cabell J. Amer. Chem. SOC.,1971 93 1482. 193 L. E. Friedrich and G. B. Schuster J. Amer. Chem. Soc. 1971,93,4602. 194 A. P. Schaap Tetrahedron Letters 1971 1757. 195 J. I. G. Cadogan and S. Kulik J. Chem. SOC.(0, 1971 2621 and references cited therein. 196 J. I. G. Cadogan and P. K. K. Lim Chem. Comm. 1971 1431. 270 G. Tennant derivatives,' 97a and in the pyrolytic cyclization of o-azidodiphenylmethanes to acridans and acridines. 197b N-Nitrenes are implicated in the novel oxidative ring-expansions of 1-and 2-aminoindazoles to benzo- 1,2,3-triazines 19' and in the oxidative rearrangements of N-aminoquinoxalones to benzo- 1,2,4-tri- azines.199 The latter reactions are particularly noteworthy in providing an elegant synthetic entry to the relatively inaccessible benzo-1,2,4-triazine ring system.The novel degenerate thermal valence isomerism exhibited by 7-acetyl- 3-methylanthranil (142)- (144) is claimed2'' as the first example of a con- certed [1,9] sigmatropic shift. R A mechanism involving intramolecular nucleophilic aromatic substitution is proposed to account for the novel base-catalysed rearrangements of N-aryloxypyridinium salts to 2-(2'-hydro~yaryl)pyridines.~~ Thermal N-oxide rearrangements [(145) -+(146)] involving the concerted suprafacial [1,4] sigma- tropic shift of alkyl and phenyl groups have been reported.202 However a 19' (a)Y. Maki T. Hosokami and M. Suzuki Tetrahedron Letters 1971 3509; (6) G.R. Cliff and G. Jones J. Chem. SOC.(0,1971 3418. 19' D. J. C. Adams S. Bradbury D. C. Horwell M. Keating C. W. Rees and R. C. Storr Chem. Comm. 1971 828. 19' B. Adger C. W. Rees A. A. Sale and R. C. Storr Chem. Comm. 1971 695. 2oo K. P. Parry and C. W. Rees Chem. Comm. 1971 833. 201 R. A. Abramovitch S. Kato and G. M. Singer J. Amer. Chem. SOC.,1971 93 3074. 202 U. Schollkopff and I. Hoppe Tetrahedron Letters 1970 4527. Molecular Rearrangements 27 1 radical-pair mechanism for the particular case of a 1,4-benzhydryl shift is sup- ported by the zero entropy of activation and c.i.d.n.p. observed. The demonstra- tion of c.i.d.n.p. in the acetic anhydride-catalysed rearrangement of 4-picoline N-oxide provides support for the oft-disputed radical-pair mechanism without excluding the simultaneous operation of an ion-pair process.203 The photo- chemical rearrangement of pyridine N-oxide to 2-formylpyrrole is shown to originate from a singlet excited state.204 Deuterium-labelling studies fully substantiate the mechanisms proposed to account for the products of the photochemical rearrangement of quinoline N-~xide.~'~ The first example of the photorearrangement of a 4H-pyran-4-one to the corresponding 2H-pyran- 2-one has been described.'06 Bridged structures [e.g.(147)] formed by the (4 + 2) cycloaddition of dieno-philes (e.g. keten acetals) to polycyclic azonia hydrocarbons followed by acid treatment are smoothly converted by warming with sodium acetate in acetic anhydride into products of the type (148).Despite the obvious driving force for formation of an aromatic system these rearrangements are remarkable because of the highly crowded nature of the products [cf (148)].207 Photochemical AcO Ac,O A R rearrangement of pentakis(pentafluoroethy1)pyridine affords the aza Dewar ben- zene (149) and the azaprismane (150) the first relatively stable examples of the valence-bond isomers of a six-membered heterocycle.208 Photorearrangement of a perfluoropyridazine is also reported to yield the diaza Dewar benzene (151).209 This result considered in conjunction with other studies210 of the perhalogenopyridazine to perhalogenopyrazine photorearrangement implies that a diaza Dewar benzene rather than a diazaprismane is the key intermediate'" in such photoisomerizations.Courses involving retro-Diels-Alder reaction followed by Cope rearrangement and subsequent extrusion of hydrogen cyanide are proposed to account for the deep-seated rearrangements of diazabasketene '03 H. Iwamura M. Iwamura T. Nishida and S. Sato J. Amer. Chem. SOC.,1970,92,7474. 'O' F. Bellamy L. G. R. Barragan and J. Streith Chem. Comm. 1971 456. 205 0. Buchardt K. B. Tomer and V. Madsen Tetrahedron Letters 1971 131 1. 206 N. Ishibe M. Odani and M. Sunami Chem. Comm. 1971 1034. '07 D. L. Fields and T. H. Regan J. Org. Chem. 1971 36 2986 2991; D. L. Fields T. H. Regan and R. E. Graves ihid. p. 2995; D. L. Fields ibid. p. 3002. 208 M. G. Barlow J. G. Dingwall and R. N. Haszeldine Chem. Comm. 1970 1580. '09 R.D. Chambers W. K. R. Musgrave and K. C. Srivastava Chem. Comm. 1971,264. 'lo D. W. McNeil M. E. Kent E. Hedaya P. F. D'Angelo and P. 0. Schissel J. Amer. Chem. SOC.,197I 93 38 17. 272 G. Tennant to azocine2" and of diazabasketene N-oxide to benzaldoxime.21 A number of new valence isomerizations involving sulphur heterocycles have been des- cri bed. * In conclusion attention is drawn to what is perhaps the year's most individual molecular rearrangement namely the remarkable transformation (152)-P (153). Readers are referred to the original paper213 for the mechanism proposed. J. P. Snyder L. Lee and D. G. Farnum J. Amer. Chem. SOC.,1971 93 3816. 'I2 M. S. Ao and E. M. Burgess J. Amer. Chem. SOC. 1971 93 5298; D. L. Coffen Y. C. Poon and M.L. Lee ibid.,p. 4627; R. M. Kellogg ibid. p. 2344; L. A. Paquette and S. Maiorana Chem. Comm. 1971 313. '13 G. Just and W. Zehetner Chem. Comm. 1971 81.

ISSN:0069-3030    

DOI:10.1039/OC9716800241

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

7 Organometallic Compounds of the Transition Elements By J. P. CANDLIN and K. A. TAYLOR lC1 Ltd Corporate Lab. PO Box I I The Heath Runcorn Cheshire and A. W. PARKINS Department of Chemistry Queen Elizabeth College London W8 The same format as last year has been used. Wherever possible catalytic aspects have been stressed which has necessitated omitting the section on novel com- plexes. Two areas have grown at a remarkable rate uiz. organopalladium chemistry and metal-catalysed skeletal isomerization. A review on the use of metal complexes in asymmetric synthesis has also been included. 1 Reviews The proliferation of organometallic literature has continued and we record the appearance of a new journal Synthesis in Inorganic and Metal-Organic Chemistry.Two multi-author book^^,^ which deal with several aspects of homogeneous catalysis and monographs describing organopalladium chemistry4" and metal olefin chemistry4' have been published. The special lectures of the 23rd IUPAC Congress have been published in book form,5 and contain ten reviews on various topics in organo-transition-metal chemistry and homogeneous catalysis. Specific reviews on optical a~tivity,~,~ n-complex intermediates,'~~ catalysis of olefin reactions lo catalysis by ruthenium complexes,'' silver-catalysed 1 Marcel Dekker New York. 2 'Aspects of Homogeneous Catalysis,' ed. R. Ugo Carlo-Manfredi Milan 1970. 3 'Transition Metals in Homogeneous Catalysis,' ed. G. N. Schrauzer Marcel Dekker New York 197 1. 4 (a) P. M. Maitlis 'The Organic Chemistry of Palladium' Academic Press New York 1971;(b) P.Heimbach and R. Traunmiiller 'Metal-Olefin Komplexe,' Verlag Chemie Weinheim 1970. 5 23rd IUPAC Congress. Special Lectures Vol. 6 Butterworths London 1971. 6 G. Paiaro Organometallir Chrm. Rev. (A) 1970 6 319. 7 H. Brunner Angew. Chem. Internat. Edn. 1971 10 249. 8 J. L. Garnett Catalysis Rev. 1971 5 229. 9 J. F. Biellmann H. Hemmer and J. Levisalles in 'The Chemistry of the Alkenes,' ed. J. Zabicky Interscience London 1970 p. 215. 10 C. W. Bird Topics in Lipid Chem. 1971 2 247. 11 B. R. James Inorg. Chim. Acta Rev. 1970 4 73. 27 3 274 J. P. Candlin K. A. Taylor andA. W. Parkins skeletal rearrangements,’ olefin disproportionation,’ homogeneous hydro- genation of olefins,14 ~xidation,’~ the use of R,CuLi in synthesis,16 and carbene complexes’ have appeared.A highly readable account of the general area has been written. l8 The uses of organometallic compounds in industry l9 and as polymerization catalysts2’ have been reviewed and a correlation of the influence of ligands on the activity and specificity of soluble transition-metal catalysts has been pub- lished.21 2 Organometallic Compounds o-Complexes-As noted last year,22 transition-metal alkyls are being studied more widely. The recent work directed towards the early members of the transi- tion-metal series is especially important as these compounds are potential catalysts for the polymerization of olefins. The reaction of Me3SiCH2MgCl with NbCl produces a dimeric compound (1) which may contain a bridging carbene ligand.23 A dimeric molybdenum compound Mo,(CH,SiMe,) with a direct metal-metal bond has also been reported.SiMe, I Me,SiCH C CH Si Me Nb Nb Me,SiCH ’\ \c’ /\ ‘CH,SiMe / I SiMe Tetramethyltitani~m~’has been known for several years and recently the reports of several groups working on Group IV metal alkyls have appeared e.g. the formation of Lewis-base adducts of TiMe426 and its exchange reaction lz L. A. Paquette Accounts Chem. Res. 1971 4 280. l3 M. L. Khidekal A. D. Shebaldova and I. V. Kalechitis Russ. Chem. Rev. 1971,40 669. l4 R. L. Augustine and J. F. Van Peppen J. Amer. Oil Chemists’ SOC. 1970 47 478. W. A. Waters J. Amer. Oil Chemists’ Soc.1971 48 427. l6 I. Kuwajima J. Synth. Org. Chem. Jap. 1971 29 616. l7 E. 0.Fischer Pure Appl. Chem. 1970 24 407. l8 F. G. A. Stone Nature 1971 232 534. * Fortschr. chem. Forsch. (‘Topics in Current Chemistry,’ Springer-Verlag Berlin) 1971 vol. 16. 2o G. Henrici-Olive and S. Olive Chem.-Ing.-Tech. 1971 43 906. 21 G. Henrici-Olive and S. Olive Angew. Chem. Internat. Edn. 1971 10 105. 22 P. S. Braterman Ann. Reports (A) 1970 67 391. 23 F. Huk W. Mowat A. C. Skapski and G. Wilkinson Chem. Cornm. 1971 1477. 24 F. Huk W. Mowat A. Shortland A. C. Skapski and G. Wilkinson Chem. Comm. 1971 1079. 25 K. Clauss and C. Beermann Angew. Chem. 1959 71 627. 26 K.-H. Thiele and J. Muller Z. anorg. Chem. 1968 362 113 120. Orgunometullic Compounds of the Transition Elements 275 with B(benzyl) to produce Ti(benzyl) .27 This latter compound is accessible more directly from TiCl and (ben~yl)MgCl’’,~~ or (ben~yl),Mg.~’ The preparation of the paramagnetic compound Cr(CH,SiMe,) has been described3 and this has been followed by the synthesis of two new paramagnetic alkyls Ti(ben~yl),~’ and V(benzyl) .33 A new diversion in transition-metal alkyl synthesis has been the use of alkyl-ating agents e.g.(2) in which the alkyl group contains a donating ~entre.~~,~~ An unusual tetrasubstituted ethylene (3)can be made by the thermal or photo- chemical reaction of Ph,PAuMe with CF3C=CCF3 .36 Ph,PAu AuPPh (2) (3) Carbene Complexes.-This year the major feature of transition-metal carbene- complex chemistry has been the diversification of the types of carbene complex which may be prepared by an ever-increasing variety of methods.For example the use of the electron-rich olefin (4)yields a Pt carbene (5)by a new route.37 Bivalent germanium or tin co-ordinated to a transition metal (6) may be obtained using a doubly charged metal carbonylate anion.38 Ph Ph Ph I Et3P c1 I N c1 ‘ [Z)=C:~] ‘ -**’I1 L/ + 4 -+ Et,P-Pt-C c1/Pt/2 I “N I I I Ph Ph (5) Ph (4) Cr,(CO),,’-+ R,MX2 + R,M-Cr(CO) where M = Ge or Sn (6) This reaction is similar to that reported for the preparation of the chromium carbene (7) from dichlorodiphenylcyclopropene. 39 27 P. Zdunneck and K.-H. Thiele J. Organometallic Chem. 1970 22 659. 28 W. Briiser K.-H. Thiele P.Zdunneck and F. Brune J. Organometallic Chem. 1971 32,335. 29 U. Zucchini E. Albizzati and U. Giannini J. Organometallic Chem. 1971 26 357. 30 A. Jacot-Guillarmod R. Tabacchi and J. Porret Helv. Chim. Acta 1970 53 1491. 31 G. Yagupski W. Mowat A. Shortland and G. Wilkinson Chem. Comm. 1970 1369. 32 K.-H. Thiele and W. Schafer Z. anorg. Chem. 1970 379,63. 33 S. D. Ibekwe and J. Myatt J. Organometallic Chem. 1971 31 C65. 34 G. Longoni P. Chini F. Canziani and P. Fantucci Chem. Comm. 1971 470. 35 M. Aresta and R. S. Nyholm Chem. Comm. 1971 1459. 36 C. J. Gilmore and P. Woodward Chem. Comm. 1971 1233. 37 D. J. Cardin B. Cetinkaya M. F. Lappert L. J. Manojlovic-Muir and K. W. Muir Chem. Comm. 1971,400. 38 T. J. Marks J. Amer. Chem. Soc. 1971 93 7090.39 K. bfele Angew. Chem. Internat. Edn. 1968 7 950. 276 J. P. Cundlin K. A. Taylor and A. W.Purkins Ph >;c -cr (CO) Ph (7) The first example of a carbene co-ordinated to a Pt'" centre (8) has been des- cribed. The mechanism of formation may be by intra-nucleophilic attack by the co-ordinated hydroxy-group on a stabilized carbonium ion.40 Me Me,PtL,CF,I + HCGCCH,CH,OH *A Mqz:F.3 Pt" carbenes have also been prepared using Pt" precursor^.^ 1*42 Some cationic iron-carbene complexes (9) derived from acetyliron compounds have been reported.43 /Me (n-C H )Fe-C 57\ \ L co 0 An extraordinary reaction in which a reducing agent Et3SiH reduces a co- ordinated carbonyl group to a co-ordinated methylene group to yield a rhodium carbene complex (lo) has appeared in an abstract.44 40 M.H. Chisholm and H. C. Clark Chem. Comm. 1971 1484. 41 M. H. Chisholm and H. C. Clark Inorg. Chem. 1971 10 1711. 42 M. H. Chisholm H. C. Clark and D. H. Hunter Chem. Comm. 1971 809. 43 M. L. H. Green L. C. Mitchard and M. G. Swanwick J. Chem. SOC. (A) 1971 794. 44 L. Yu. Ukhin and Y. A. Shvetsov Abstracts Fifth tnternational Conference Organo- metallic Chem. (Moscow) 1971 I 128. Organometallic Compounds of the Transition Elements 277 [Rh(CO)Br,PPh,]-X+ + Et,SiH -P [Rh(CH,)Br,PPh,]-X+ where X = PhC(OH)=CN (10) Carbene complexes or their precursors have also been used in organic syn- thesis and catalytic reactions. For example the carbene salt obtained from Ni(CO) and LiNMe reacts with alkyl halides to give amide~,~ and the carbene complexes [M(CO),COR]- where M = Mo or W together with aluminium co-catalysts have been used to disproportionate 01efins.~~ 3 Hydrogenation and Hydrogen Exchange Reactions Hydrogenationof Oleh.-Although new homogeneous catalysts for the hydro- genation of carbon-carbon unsaturation are still being discovered e.g.(n-C,H,),-Ti(methally1)-H ,47 (n-C,H,),MoH ,48 (n-C,H,),NbH Mo”’-cysteine-BH,-,” [(n-C,Me,)MCl,] where M = Rh or Ir,’l RuH(NO)(PR,) RhL(NO)(PPh,) where L = 1,4-benzoquinone or maleic anhydride,53 or RhHC1,(PBu‘Pt”,),-NaOPrn,s4 most of the work appears to be in the.area of substantiation and utilization of existing catalysts.The equilibrium constant for the dissociation of RhCl(PPh,) in benzene has been determined spectrophotometrically as 1.4 x lop4moll-’ in agreement with earlier qualitative data., The use of RhCl(PPh,) as a catalyst for specific cis-hydrogenation with very little isomerization or hydrogen exchange is now accepted.Thus the deuteriation of ole fin^,'^ (for use in mass-spectral analysis) cyclohexene5’-but not other cyclic 01efins~~ (for radiation studies) deuteriationS9 and tritiation6’ of steroids (for subsequent metabolic and mass-spectral studies) and hydrogenation of cyclohexene derivatives6 (for synthetic purposes) have been carried out with confidence using RhCl(PPh,) as catalyst. Care should be taken to use purified hydrogen since traces of oxygen can promote isomeriza- tion and hydrogen e~change.~,.~ The decrease in hydrogenation with increasing 45 S.Fukuoka M. Ryang and S. Tsutsumi J. Org. Chem. 1971 36 2721. 46 W. R. Kroll and G. Doyle Chem. Comm. 1971 839. 47 H. A. Martin and R. 0. De Jongh Rec. Trau. chim. 1971 90 713. 48 A. Nakamura ref. 44 11 550. 49 F. N. Tebbe and G. W. Parshall J. Amrr. Chem. SOC.,1971,93 3793. 50 G. N. Schrauzer and P. A. Doemeny J. Amer. Chem. SOC., 1971,93 1608. 5’ C. White D. S. Gill J. W. Kang H. B. Lee and P. M. Maitlis Chem. Comm. 1971,734. 52 S. T. Wilsonand J. A. Osborn J. Amer. Chem. SOC.,1971 93 3068. 53 G. La Monica G. Navozio P. Sandvini and S. Chenini J. Organometallic Chem. 1971 31 89. 54 C. Masters W. S. McDonald G. Raper and B. L. Shaw Chem. Comm. 1971 210. 55 H. Arai and J. Halpern Chem.Comm. 1971 1571. 56 D. G. Earnshaw F. G. Doolittle and A. W. Decora Org. Muss Spectrometry 1971 5 801. 57 M. Ballenegger A. Ruf and T. Gaumann Helu. Chim. Acta 1971 54 1373. 58 J. G. Atkinson and M. 0. Luke Canad. J. Chem. 1970,48 3580. 59 W. H. Fad A. Failli and C. Djerassi J. Org. Chem. 1970 35 2571. 6o Y.Osawa and D. S. Spaeth Biochemistry 1971 10 66. 6‘ W. C. Agosta and W. L. Schreiber J. Amer. Chem. SOC.,1971 93 3947. 62 J. F. Biellmann M. J. Jung and W. R. Pilgrim Bull. Soc. chim. France 1971 2720. 6’ M. Wharen and B. Bayerl Z. Chem. 1971 11 263. J. P. Candlin K. A. Taylor and A. W.Parkins substitution is illustrated in the following examples using RhCl(PPh,) as cata- lyst (ref. 64) (ref. 64) (ref. 65) '-" A Some failures in hydrogenation experiments have been noted e.g.the acetylenic compound dehydro[ 1Slannulene was not hydrogenated to [18lannulene using RhCl(PPh,) as catalyst.66 An interesting and potentially useful modification of a hydrogenation catalyst is the use of polymeric ligand~.~'-~~ Thus a rhodium-phosphine catalyst using polyphosphines derived from polystyrene showed unusual activity patterns when treated with various 01efins.~' It was found that when the olefinic sub- strates were large (e.g.cholestene) there was a dramatic decrease in rate (32 1) when compared with non-sterically hindered a-olefins. This decrease does not occur with the homogeneous RhCl(PPh,) system. Known catalysts studied further include [R~(OAC)(PP~,),]+,~~ which although it will catalyse the reduction of unsubstituted olefins will not affect internal olefins e.g.cyclohexene. The use of the Rh(py),CI,-BH,- system7' has now been extended to the reduction of olefins and olefinic steroids. Chro- 'I4 A. J. Birch and K. A. N. Walker Austral. J. Chem. 1971 24 5 13. 65 E. Piers R. W. Britton and W. De Waal Canad. J. Chem. 1971 49 12. 6h R. Wolovsky E. P. Woo and F. Sondheimer Tetrahedron 1971 26 2133. 67 J. Manassen Plat. Met. Rev. 1971 15 142. '* M. Capka P. Svoboda M. Cerny and J. Hefflegs Tetrahedron Letters 1971 4787. 69 H. Hirai and T. Furnta J. Polymer Sci.,Part B Polymer Letters 1971 9 459. 'O R. H. Grubbs and L. C. Kroll J. Amer. Chem. SOC.,1971,93 3062. " R. W. Mitchell J. D. Ruddick and G.Wilkinson J. Chem. Sac. (A) 1971 3224. 72 P. Abley and F. J. McQuillin J. Chem. SOC.(0,1971 840. Organometallic Compounds of the Transition Elements 279 mium carbonyl derivatives have been used for the hydrogenation of and also bi- and tri-cyclic olefins;7s a new catalyst for these reactions is photo- activated Cr(CO) .76,77 Olefinic iron carbonyls have also been employed as catalysts for the hydrogenation of substituted diene~.~~ The recognized catalysts for the reduction of di- and tri-ene esters are Group VIII metal phosphine complexes (e.g.Ni Pd Pt),79 often in the presence of a hydrogen-donor solvent e.g methanol or propan-2-01. These complexes have now been found to catalyse hydrogenation of mono-olefins when a more acidic hydrogen donor is used e.g.dihydroxybenzene.80 The effect on rate of hydrogenation by changing the anionic (X) and phosphine (L) ligands in the complexes MX(CO)L, where M = Rh or Ir shows that on increasing the electronegativity of the halide ligand (X) the rate increases whereas alteration of the donor ligand (L) produces little change in the rate.81 86 The hydride complexes MH(CO)L, where M = Rh or Ir both have catalytic properties ; the active species is believed to be MH(CO)L .87,88 In many examples of catalytic hydrogenation the solvent in which the reduc- tion is carried out can effect both the rate of reaction and the nature of the product. In the hydrogenation of butadiene using pentacyanocobalt(I1) as catalyst the composition of the products alters from 1 to 45 % cis-but-2-ene when the solvent changes from water to 80 % ethylene glycol-20 % water.89390 The use of soluble Ziegler hydrogenation catalysts continues,” and the novel application of these systems to produce a butene+thylene copolymer from a butadiene-ethylene copolymer has been demon~trated.~ Hydrosilylation of 0lefins.-Group VIII metal complexes continue to be used as hydrosilylation catalysts.Most of the recent work is directed towards an examina- tion of the mechanism of this reaction using known catalysts e.g. H,PtCl, 73 E. N. Frankel J. Amer. Oil Chemists’ SOC. 1970 47 1133. ‘4 E. N. Frankel F. L. Thomas and J. C. Cowan J. Amer. Oil Chemists’ SOC.,1970,47 497. ” M. Cais and D. Fraenkel ref. 44 11 620. ’’ J. Nasielski P.Kirsch and L. Wilputte-Steinhert J. Organometallic Chem. 1971 27 C13. ” I,. Wilputte-Steinhert and P. Kirsch ref. 44 I 428. 78 M. Cais and N. Maoz J. Chem. SOC. (A) 1971 1811. ”) J. C. Bailar jun. J. Amer. Oil Chemists’ SOC. 1970 47 475. no T. Nishigachi and K. Fukuzumi Chem. Comm. 1971 139. W. Strohmeier W. Rehder-Stirnweiss and G. Reischig J. Organometallic Chern. *’W. Strohmeier 1971 27 393. R. Fleischmann and T. Onoda J. Orgunometallic Chem. 1971 28 28 1. 83 W. Strohmeier and R. Fleischmann J. Organometallic Chem. 1971 29 C39. 84 W. Strohmeier J. Orgunometallic Chern. 1971 32 137. 85 W. Strohmeier and W. Rehder-Stirnweiss Z. Naturforsch. 1971 26b 61. n6 W. Strohmeier and R. Endres Z. Nuturforsch. 1971 26b 730. ” W. Strohmeier and W.Rehder-Stirnweiss Z. Naturforsch. 1971 26b 193. 8R M. G. Burnett and R. J. Morrison J. Chem. SOC. (A),1971 2325. 89 T. Funabiki and K. Tamara Bull. Chem. SOC. Jupan 1970 43 3965. 90 T. Funabiki and K. Tamara Tetrahedron Letters 1971 1111. 91 J. C. Falk J. Org. Chem. 1971 36 1445. 92 J. C. Falk and R. J. Schlott Macromolecules 1971 4 152. 280 J. P. Candlin K. A. Taylor and A. W.Parkins RhCl(PPh,) Co,(CO) NiCl,(PBu,) .93-100The potential synthetic applica- tion of the reaction R,SiH + CH,=CHR' -+ R3SiCH,CH2R' (and iso-isomer) appears to have been neglected. Since the hydrosilylation reaction involves insertion into a Si-H bond a logical extension is the insertion into Si-Si compounds. This has now been achieved using platinum compounds e.g.PtCl,(PEt,) as catalysts :Io1 p 2Me3Si-SiMe,H + 2PhC=CPh -+ph~~ + ~2Me3SiHh Ph Ph Co-ordinated silylene intermediates Pt-SiR are postulated. Metal-catalysed Intermolecular Hydrogen Exchange.-A goal of many organo- metallic chemists namely the activation of saturated unsubstituted organic compounds by metal complexes under mild conditions has now been achieved. By using complexes of Pt"' and Ir and Ru,'03 H-D exchange occurs between CH or C,H and D,O. Exchange between CH and D has been claimed using trihydride complexes MH,(PPh,), where M = Co or Ir as catalyst^."^ Similar work involves the H-D exchange of alkyl aromatic compounds using Pt co~nplexes.'~~ An important paper in this respect concerns the formation of stable Pt complexes involving metallation of alkyl groups attached to the aro- matic ring.'05 The disproportionation of 4-vinylcyclohex-1-ene into equimolar amounts of ethylbenzene and ethylcyclohexene can be achieved using catalytic amounts of RhCl in ethanol.lo6 The hydride-transfer reaction resulting in reduction of ketones by secondary alcohols using Ir"' with phosphite or sulphoxide (Henbest sy~tem'~','~~) 93 M.Capka P. Svoboda V. Bazant and V. Chvalovsky Coll. Czech. Chem. Comm. 1971,36,2735. 94 E. W. Bennett and P. J. Orenski J. Organometallic Chem. 1971 28 137. 95 W. Fink Helv. Chim. Acta 1971 54 1304. 96 M. Kumada Y. Kiso K. Maeda K. Sumitani and K. Tamao ref. 44 11 177 97 K. Yamamoto T. Hayashi and M. Kumada J. Organometallic Chem. 1971 28 C37. 98 V.0. Reihsfeld and M. I. Astrakhanov ref. 44 11 198. 99 S. Takahashi T. Shibano H. Kojima and N. Hagihara Organometallic Chem. Synth. 1971 1 193. loo M. Hara K. Ohno and J. Tsuji Chem. Comm. 1971 247. lo' K. Yamamoto H. Okinoshima and M. Kumada J. Organometallic Chem. 1971 27 C31. lo' R. J. Hodges D. E. Webster and P. B. Wells J. Chem. SOC.(A) 1971 3230. lo3 N. F. Goldschleger M. B. Tjabin A. E. Shilov and A. A. Steinmann ref. 44 I 328. Io4 J. L. Garnett and R. S. Kenyon Chem. Comm. 1971 1227. lo5 D. F. Gill and B. L. Shaw Chem. Comm. 1972 65. lo6 C. J. Attridge and P. J. Wilkinson Chem. Comm. 1971 620. lo' Y. M. Y. Haddad H. B. Henbest J. Husbands and T. R. B. Mitchell Proc. Chem. SOC.,1964 361. W. I. Fanta and W. F. Erman J. Org. Chem. 1971 36,358.Organometallic Compounds of the Transition Elements 28 1 has been extended to show that the hydride source can be hydrogen gas.'" Inter- and Intra-molecular Oxidative Addition Reactions.-These reactions may be steps in many metal-catalysed organic transformations involving C-C and C-H bond breakage. As a consequence of this there have been many studies on model stoicheiometric reactions. The complexes are generally those of Group VIII metals usually in a low oxidation state but recent work has extended the range to include most transition metals. Intramolecular ortho-metallation reactions continue to be investigated. Commonly these reactions take place with aryl phosphite' lo-' l2 and azo benzene An interesting application of this work is the reduction of azobenzene by LiAlH in the presence of catalytic amounts of [Rh(CO),Cl],.The sole product is hydrazobenzene no aniline is formed."5 Oxidative addition resulting in the breakage of a C-H bond of an unsubsti- tuted aromatic compound e.g. naphthalene has been known since 1965.'I6 This has now been broadened to include benzene as a reactant resulting in the isolation of (n-C,H,)2Mo(H)Ph."7 (R-C~H~)~MH~P~ = Ta"* or where M Nb4' may be formed as intermediates in the interaction between (n-C,H,),MH and benzene. The nickel triad has been extensively studied. The zerovalent metal complexes (d' systems) are particularly prone to oxidative addition reactions and mechan- istic studies have been performed using phosphine complexes and aryl halides,' 19,' 2o aryl cyanides,12' ZH where Z = S or Se,'22 o-q~inones,'~~ HX where X = Br,'24 SAC.'^^ or CN,'25 ArN2+,'26 nitromethane,',' azo-benzene,'28.'29 and fluorinated hydrocarbon derivatives.' 30 lo9 M.Gullotti R. Ugo and S. Colonna J. Chem. Soc. (C) 1971 2652. ll0 M. A. Bennett and R. Charles Austral. J. Chem. 1971 24 427. E. W. Ainscough and S. D. Robinson Chem. Comm. 1971 130. 112 E. W. Ainscough S. D. Robinson and J. J. Levison J. Chem. SOC.(A) 1971 3413. M. I. Bruce M. Z. Iqbal and F. G. A. Stone J. Organometallic Chem. 1971,31,275. 11' M. I. Bruce M. Z. Iqbal and F. G. A. Stone J. Chem. SOC.(A) 1971 2820. 115 M. I. Bruce B. L. Goodall M. Z. Iqbal and F. G. A. Stone Chem. Comm. 1971,661. U.A. Gregory S. D. Ibekwe B. T. Kilbourn and D.R. Russell J. Chem. Sac. (A) 1971 11 18. 11' M. L. H. Green and P. J. Knowles J. Chem. SOC.(B) 1971 1508. lL8 E. K. Barefield G. W. Parshall and F. N. Tebbe J. Amer. Chem. SOC.,1970,92 5234. 119 P. Fitton and E. A. Rick J. Organometallic Chem. 1971 28 287. 120 M. Hidai T. Kashiwagi T. Ikeuchi and Y. Uchida J. Organometallic Chem. 1971 30 279. lZ' D. H. Cerlach A. R. Kane G. W. Parshall J. P. Jesson and E. L. Muetterties J. Amer. Chem. SOC.,1971 93 3543. 122 R. Ugo G. La Monica S. Cenini A. Segre and F. Conti J. Chem. SOC.(A),1971 522. 123 S. Cenini R. Ugo and G. La Monica J. Chem. SOC.(A) 1971,416. 124 D. M. Roundhill P. B. Tripathy and B. W. Renoe Inorg. Chem. 1971 10 727. 125 C. Corain P. Rigo and G. Favero Inorg. Chem. 1971 10 2329. 126 S.Cenini R. Ugo and G. La Monica J. Chem. SOC.(A) 1971 3441. W. Beck K. Schorpp and F. Kern Angew. Chem. Internat. Edn. 1971 10 66. lZ8 H. F. Klein and J. F. Nixon Chem. Comm. 1971 42. 129 S. Otsuka T. Yoshida and Y. Tatsuno Chem. Comm. 1971 67. 130 H. D. Empsall M. Green S. K. Shakshooki and F. G. A. Stone J. Chem. Soc. (A) 197 1. 3472. 282 .I.P.Cundlin K. A. Taylor and A. W.Parkins Rh' and Ir' complexes (d8 systems) containing ph~sphite,'~~ n-C,H ,132-134 and isocyanide' ligands have been shown to undergo intermolecular oxidative addition reactions. The d6 complexes containing Ru" and Moo also undergo oxidative addi- tion. 136.137 4 Isomerization Metal-catalysed C=C Isomerhation.-Many homogeneous hydrogenation catalysts are also olefin isomerization catalysts.RuC1,(PPh3) PtCl,(PPh,),-SnCl,-H, and IrClCO(PPh,) have been studied as selective isomerization catalysts for converting vinyl alicyclic compounds into the corresponding exo- cyclic derivative^.'^^ Conventional strong acid or base catalysts tend to promote the incorporation of the double bond into the alicyclic ring. RhCl(PPh,), initially noted for its catalytic hydrogenation activity converts linoleate esters into the conjugated isomers in over 95% yield.'39 Other hydrogenation catalysts showing isomerization activity include the Ziegler systems -Fe Co or Ni with AIEt314' and CoN,(PPh,) .14' The nickel-based dimerization catalysts are also known to be active for isomeriza- tion.142,t43 (1,5-Cy~lo-octadiene)W(CO)~ has been found to possess high selectivity for double-bond isomerization without concurrent carbon rearrangement or decomp~sition.'~~ 100% yields of pent-2-ene from pent-1-ene can be obtained at 60 % conversions.Metal-catalysed Carbon Skeletal 1somerization.-This area has mushroomed during the last year and as a result this section has been subdivided by substrate. It will be appreciated however that a common mechanism may be operative. Linear Olejinic Substrates. This involves skeletal isomerization of an unstrained olefin by homogeneous catalysts e.g. in the reaction cis-hexa- 1,4-diene -+truns-2-methylpenta-1,3-diene.The known active catalysts are of the type NiX,(PR),),- R' AlCI . Nickel hydride species have been predicted as the active component and their generation by more conventional routes has substantiated these 131 L.M. Haines Inorg. Chem. 1971 10 1693. 132 A. J. Hart-Davis and W. A. G. Graham Inorg. Chem. 1971 10 1653. 33 A. J. Oliver and W. A. G. Graham Inorg. Chem. 1971 10 1165. 134 R.B. King and A. Efraty J. Organometallic Chem. 1971 27 409. A. L. Balch and J. Miller J. Organometallic Chem. 1971 32 263. 136 A. L. Balch and Y.S. Sohn J. Organometallic Chem. 1971 30 C31. 13' J. R.Moss and B. L. Shaw J. Chem. SOC. (A) 1970 595. 38 J. E. Lyons J. Org. Chem. 197 1 36 2497. 139 W. J. Dejarkis and L. E. Gast J. Amer. Oil Chemists' SOC. 1971 48 21. 40 T. Suzuki and Y.Takegami Kogyo Kagaku Zusshi 1971 74 1371. J. Kovacs W. Pritzhow and L. Marki ref. 44 1 426. 14' F. Hojabri J.Appl. Chem. Biotechnol. 1971 21 90. 143 J. Thomson and M. C. Baird Canad. J. Chem. 1970,48 3443. 144 J.-L. Wang and H. R. Menapace J. Catalysis 1971 23 144. Orgunometallic Compounds of the Transition Elements 283 claims. Thus Ni(C H4)[OP(o-t01)J ,-HCll 4s and N i[OP(o-t01)J ,-He1 46 are active catalysts for the above reaction. A mechanism proposed for the isomeriza- tion involves addition of the Ni-H component across a C--L group with subsequent metal P-carbon elimination. 14' Reactions involving Strained Rings. Three-membered rings. The catalytic con- version of bicyclic systems by various metal complexes e.g. [Rh(CO),Cl] [Ru(CO),Cl,] ,[C,F,Cu], AgBF, into the more thermally stable isomer can be illustrated by the following examples (alkyl substituents have been omitted) @ .(refs.148-156 160) @ + (refs. 150 151 154 155 4 157 158) rJ+o (refs. 159 160) 14' R. G. Miller P. A. Pinke R. D. Stauffer and H. J. Golden J. OrganometallicChem. 1971 29 C42. 14' L. W. Gosser and G. N. Parshall Tetrahedron Letters 1971 2555. 14' R. G. Miller H. J. Golden D. J. Baker and R. D. Stauffer J. Amer. Chern. SOC. 1971,93,6308. J. P. Candlin,K. A. Taylor and A. W.Parkins The distribution of products depends on the catalysts used and varies with both metal and ligand. In the isomerization reaction (1 l).+ products,' 57 the products can be varied from 100% yield of (1 la) (AgBF catalyst) to 98 % yield of (1lb) {[Rh(CO),CI],) to 40% yield of (1 lc) (SnCl, 2H,O). It is thought that this may be due to the position of the equilibrium involving metal carbenes and co- ordinated carbonium ions.'59 The skeletal isomerization of cyclopropane rings into various isomers could be synthetically important since the starting materials can be conveniently prepared from the olefin precursor and CH,I,-Zn-Cu (Simmons-Smith reaction).Substituted prismane derivatives are isomerized into a variety of products including benzene products and also substituted bi- and tri-cyclic hexenes.16 ' Ring contraction utilizing epoxides has been catalysed by transition-metal complexes. Thus cyclo-octatetrene epoxide (12) can be catalytically isomerized at -50 "C to the seven-membered ring aldehyde using [Rh(CO),Cl] .16 The stoicheiometric production of cycloheptatriene iron tricarbonyl can also be achieved using the epoxide and Fe,(CO), Four-membered rings.The cleavage of methylene cyclobutane by PdCI and [Rh(CO),Cl] results in the formation of metal n-ally1 compounds' 64 whereas cleavage of 1 -methylcyclobutene using the oxidative compounds Pd" Hg" and TI"' yields cyclopropyl derivatives ; this is in accord with the oxidative addition of cyclobutane derivatives to metal ions with subsequent skeletal rearrange- men t. ' 148 P. G. Gassman and F. J. Williams J. Amer. Chem. Sor. 1970 92 7631. 49 P. G. Gassman and F. J. Williams Tetrahedron Letters 197 1 1409. P. G. Gassman and E. A. Armour Tetrahedron Letters 197 1 143 1. P. G. Gassman T. J. Atkins and F. J. Williams J. Amer. Chem. SOC., l5 197 1,93 18 12.lS2 P. G. Gassman T. J. Atkins and J. T. Lumb Tetrahedron Letters 1971 1643. lS3 P. G. Gassman G. R. Meyer and F. J. Williams Chem. Comm. 1971 842. lS4 M. Sakai H. Yamaguchi and S. Masamune Chem. Comm. 1971 486. 15' M. Sakai and S. Masamune J. Amer. Chem. SOC.,1971 93 4610. M. Sakai H. Yamaguchi H. H. Westberg and S. Masamune J. Amer. Chem. SOC. 1971,93 1043 4611. 15' P. G. Gassman and T. J. Atkins J. Amer. Chem. SOC. 1971 93 4597. 15* P. G. Gassman and T. J. Atkins J. Amer. Chem. SOC. 1971 93 1042. lS9 T. J. Katz and S. A. Cerefice J. Amer. Chem. SOC., 1971 93 1049. 160 L. A. Paquette R. P. Henzel and S. E. Wilson J. Amer. Chem. SOC. 1971 93 2335. 161 K. L. Kaiser R. F. Childs and P. M. Maitlis J. 4mer. Chem. SOC.,1971.93 1270. 16' R.Grigg R. Hayes and A. Sweeney Chem. Cornm. 1971 1248. 163 H. Maltz and G. Deganello J. Organometallic Chem. 1971 27 383. 164 P. Rossi P. Diversi and L. Porri J. Organometallic Chem. 1971 31 C40. J. E. Byrd L. Cassar P. E. Eaton and J. Halpern Chem. Comm.. 1971.40. Organometallic Compounds of the Transition Elements 285 Work continues on metal-catalysed skeletal rearrangements involving cubane- type precursors e.g. (13)-( 15). C0,Me C0,Me C0,Me C0,Me Ag' f3 C0,Me C0,Me C0,Me C0,Me 8 (14) It is of interest to note that when stable compounds (e.g.iron carbonyl deriva- tives) are made from these multiple ring systems fluxional behaviour can be detected by variable-temperature n.m.r.169 Olejn Disproportionation. The conventional catalysts for this type of reaction include molybdenum tungsten and rhenium complexes usually together with an alkyl aluminium co-catalyst.The range of metals has not been extended but several new combinations have been discovered e.g. ReCl ,-BuiSn,' 70 WC16-RMgX,'7' W(CO),PPh and W(C0)3(PPh3)2C12-EtAlC12 ,172-'74 [M(CO),COR]-R,A12C1346 [these carbonyl precursors resemble the hetero- geneous system Mo(CO),-alumina<hlorocarbons' '1 and tungsten ally1 derivatives.' 76 L. A. Paquette R. S. Beckley and T. McCreadie Tetrahedron Letters 1971 775. 167 L. A. Paquette and J. C. Stowell J. Amer. Chem. SOC. 1971 93 2459. 168 P. E. Eaton and S. A. Cerefice Chem. Comm. 1970 1494. R. Aumann Angew. Chem. Internat. Edn. 1971,10 189 560. 170 J.A. Moulijn and C. Boelhouwer Chem. Comm. 1971 1170. 17' M. L. Khidekel V. I. Martin A. D. Shebaldova T. A. Bol'shinskova and I. V. Kalechits Bull. Acad. Sci. U.S.S.R. 1971 20 601. ' L. Ramain and Y. Trambouze Compt. rend. 197 1,273 C,1409. '73 L. Bencze and L. Marko J. Organometallic Chem. 1971 28 271. '74 L. Bencze G. Palyi and L. Marko ref. 44 11 194. 17' E. S. Davie D. A. Whan and C. Kemball Chem. Comm. 1971 1202. 176 I. A. Oreshkin L. I. Red'kina K. L. Makovetskii E. I. Tinyakova and B. A. Dolgo-plosk Bull. Acad. Sci. U.S.S.R. 1971 20 1044. 286 J. P. Candlin K. A. Taylor and A. W. Parkins A most comprehensive study on the screening of potential catalysts for dis- proportionation of pent-2-ene (into but-2-ene and hex-3-ene) has been carried out.'77 The most active system was found to be MoCl,(NO),(OPPh,),- Me,Al,CI,.Rate studies using pent-2-ene have also been performed using the known catalyst WC1,-aluminium alkyls.178 This catalyst combination has also been found to be a good Friedel-Crafts catalyst e.g. benzene and propylene yield isopropylbenzene. '79 Perhaps the most powerful use of these catalysts is in the ring-opening poly- merization of cyclic olefins e.g. cyclopentene gives a polymer with elastomeric properties.'80-'84 Molecular weight modification and degradation of un-saturated polymers e.g. cis-polybuta-l,4-diene can also be achieved. 85 In-terestingly traces of cyclododecatriene were found. Papers on the theoretical and mechanistic aspects of olefin disproportionation have appeared.'86 19' The involvement of a (bonded) cyclobutane species is ~ still open to question. One pr~posal'~~,'~~ suggests that the olefinic C-C bond remains whilst the n-electrons rearrange to form a cyclobutane intermediate whereas another theory'86' '87 proposes the formation of a tetramethylene moiety. Experimental evidence for this latter suggestion is that when the dis- proportionation reaction is catalysed by (toluene)W(CO) the presence of excess toluene or CO inhibits the disproportionation by preventing the formation of the tetramethylene intermediate. 5 Oligomerization of Unsaturated Hydrocarbons Conjugated Dio1ehs.-There continues to be a steady flow of papers dealing with the cyclo-oligomerization reactions of conjugated dienes although the mechanism of these reactions is still in doubt.Intermediates (16t(18) which are thought to participate in the catalytic cycle using nickel compounds have been isolated as the tricyclohexylphosphine adducts. 192 Equilibrium between "' W. B. Hughes E. A. Zuech E. T. Kittleman and D. H. Kubicek 23rd IUPAC(Boston) Macromolecular Preprint 1971 11 1063. '* A. Uchida Y. Mukai Y. Hamano and S. Matsuda Ind. and Eng. Chem. (Product Res. and Development) 1971 10 369 372. J. R. Graham and L. H. Slaugh Tetrahedron Letters 1971 787. J.-L. Herisson and Y.Chauvin Makromol. Chem. 1970 141 161. 18' P. Gunther F. Haas G. Marwede K. Nutzel W. Oberkirch G. Pampus N. Schon and J. Witte Angew. Makromol. Chem. 1971 16/17 27. G. Dall'Asta and G. Motroni Angew.Makromol. Chem. 1971 16/17 51. G. Dall'Asta and G. Motroni European Polymer J. 1971 7 707. H. Lammens G. Sartori J. Siffert and N. Sprecher J. Polymer Sci. Part B Polymer Letters 1971 9 34 1. E. N. Kropacheva B. A. Dolgoplosk D. E. Sterenzat and Y. U. Patrushin Doklady Chem. Technol. 1970 195 216. G. S. Lewandos and R. Pettit Tetrahedron Letters 1971 789. G. S. Lewandos and R. Pettit J. Amer. Chem. SOC. 1971 93 7087. "' F. D. Mango Tetrahedron Letters 1971 505. F. D. Mango and J. A. Schachtschneider J. Amer. Chem. SOC.,1971 93 1 23. G. L. Caidow and R. A. MacGregor J. Chem. SOC. (A) 1971 1654. 191 F. D. Mango ChemTech. 1971 1 758. 19' P. W. Jolly I. Tkatchenko and G. Wilke Angew. Chem. Internat. Edn. 1971 10 328 329. Organometallic Compounds of the Transition Elements 287 qwcy3 ==/&? Ni+-PCy z\ a+pCy3 (16) (17) (18) these species has been shown to exist in solution and it is proposed that a step- wise rather than concerted mechanism is operative in the catalytic reaction.The existence of (17) in the solid state has been disputed.’93 A detailed i.r. study’ 93 of the parent molecule and its dodecadeuterium analogue suggests that the solid has the same structure as is found in solution i.e. (18). A recent example’94 of the use of phosphine nickel catalysts in organic chemistry is the synthesis of tricyclic systems (19) from dienes and acetylenes. The influence of co-catalyst ligand and solvent on the course of butadiene oligomerization reactions is well illustrated by the catalytic synthesis of l-vinyl- 2-methylenecyclopentane using (PBu,),NiBr,-Bu”Li or (PEt,),NiX(o-tolyl) where X = halide in methan~l.’”~ The use of MeOD produces the mono- deuteriated dimer.The synthesis of cycloheptenone rings e.g. (20) from dibromoketones and conjugated dienes has been achieved using ‘Fe(CO),’ as the template. 96 Buta-diene reacts in a similar way to give a low yield of the cycloheptenone although this can be increased by using (butadiene)Fe(CO) as the reactant. There has been considerable progress made in extending the scope of the reaction between two butadiene molecules and alcohols to yield octadienyl ethers.’97 Thus although the reaction between butadiene and H,O catalysed *93 J. M. Brown B. T. Golding and M. J. Smith Chem.Comm. 1971 1240. 94 P. Heimbach K.-J. Ploner and F. Thomel Angew. Chem. Internat. Edn. 197 I 10,276. 195 J. Kiji K. Masui and J. Furukawa Bull. Chem. SOC.Japan. 1971,44 1956. 19‘ R. Noyori S. Makino and H. Takaya J. Amer. Chem. SOC.,1971 93 1272. 19’ E. J. Smutny J. Amer. Chem. SOC.,1967 89 6793. J. P. Candlin K. A. Taylor and A. W.Parkins by Pd(acac),-PPh, gives octa-1,3,7-triene the presence of CO changes the course of the reaction to yield (21) and (22).'98 Changing the solvent from Bu'OH to acetonitrile alters the ratio (21) :(22) from 3 1 to 14 I. The role of CO in these reactions is not clearly understood although a direct reaction with the catalyst is a possibility. -OH / OH (21) (22) The telomerization of nitroalkanes and butadiene is also catalysed by Pd**- PPh mixtyres.The resulting nitro-products can easily be reduced (Raney Ni) to yield long-chain amine~.'~~ ,Tertiary amines can also be prepared by the telomerization of butadiene and NH using Pd" catalysts. Reduction of the products of the reaction with Raney nickel results in tri-(n-octy1)amine.' 99 The carbonylation of butadiene in ethanol to give ethyl 2-methylpent-3-enoate is well known. Using Pd(acac),-PPh as catalyst at 75 "C and 5 atm CO pressure the product is ethyl nona-3,8-dienoate. Scheme 1 shows the suggested mechanism.' O0 Scheme 1 Conjugated dienes react with isocyanides to give vinyl piperidones e.g. (23) using (PPh,),Pd(maleic anhydride) as catalyst." ' 19' K. E. Atkins W. E. Walker and R.M. Manyik Chem. Comm. 1971 330. 199 T. Mitsyasu M. Hara and J. Tsuji Chem. Comm. 1971 345. W. E. Billups W. E. Walker and T. C. Shields Chem. Comm. 1971 1067. '01 K. Ohno and J. Tsuji Chem. Comm. 1971,247. Organometallic Compounds of the Transition Elements Nickel compounds in general appear to be less effective as catalysts in pro- moting diene oligomerization reactions than their palladium analogues. How-ever by using phenyldi-isopropoxyphosphine (P)as ligand the system Ni(acac),- P-BH -in methanol catalyses the dimerization of butadiene to yield methyl octadienyl ethers.202 Electrolysis of nickel2' and cobalt204 compounds in the presence of butadiene yields mixtures of linear oligomers. Allen=.-Catalytic cyclo-oligomerization of allenes has been known for several years.Typical products are trimethylene-cyclohexanes tetramethylene-cyclo-octanes and pentamethylene-cyclodecanes together with spiro-nonanes. Little is known about the mechanism but intermediates are now being prepared giving indications of the reaction pathways. Thus (24) has been obtained by the reaction of allene with Pd(OAc) ,205 and similar trimeric allene units have been prepared206 from allene and Fe,(CO) (25)-(27). Nio catalyses the conversion Me / (25) (26) (27) (24) of allene to 1,2,4,6,9-pentamethylene-cyclodecane207 or to 1,2,4-trimethylene- cyclohexane2" depending on the type of ligand attached to the nickel. The reaction of Ni(cod) with allene at -70 "C in THF gives an unstable complex which reacts with PPh to give (28) which is similar in structure to the Pd com- pound (24).Carbon disulphide displaces the trimeric allene to give 1,2,4-tri- methylene-cyclohexane.,09 Since allene tetramers can also be formed by using PPh and a large excess of allene it appears that higher oligomers are syn- thesized stepwise from the complex (28). 'O' T. C. Shields and W. E. Walker Chem. Comm. 1971 193. '03 T. Ohta K. Ebina and N. Yamazaki Bull. Chem. Sac. Japan 1971,44 1321. '04 H. Matschiner H. J. Kerrinnes and K. Issleib Z. anorg. Chem. 1971 380 1. '05 T. Okamoto Bull. Chem. SOC.Japan 1971,44 1353. '06 S. Otsuka A. Nakamura and K. Tani J. Chem. SOC.(A) 1971 154. 'Oi S. Otsuka A. Nakamura K. Tani and S. Ueda Tetrahedron Letters 1969 297. 208 M. Englert P.W. Jolly and G. Wilke Angew. Chem. Internat. Edn. 1971 10 77. '09 S. Otsuka A. Nakamura S. Ueda and K. Tani Chem. Comm. 1971 863. 290 J. P. Candlin,K. A. Taylor and A. W.Parkins Allene polymers can also be produced catalytically. A new type of stereo- regularity in linear polymers has been reported from studies of the stereospecific polymerization of (R)-penta-2,3-diene using allylnickel iodide as catalyst.2 Olefins and Acetylenes.- Olefin dimerization has been achieved using catalytic quantities of arylnickel(I1) compounds,21 1,2l2 allylnickel(1I) derivatives,2 and nickel phosphine complexes.2 l4 Di- and tri-merization of acetylenes has been promoted by PdCl ,21 iron carbonyls,2 '6i2 ' organochromium compounds,2 cobalt,219 and rhodium22o derivatives.The stoicheiometric oligomerization of fluorocarbons using metal centres as templates continues to be investi-gated.221-226 6 Insertion Reactions Many of the insertion reactions studied are stoicheiometric addition reactions very little attempt being made to promote catalytic usuage of the metal com- pound. The mechanism of these reactions is thought to involve intra-nucleophilic attack by the a-bonded ligand on the x-bonded unsaturated ligand.227 This is probably operative in the insertion of olefins and acetylenes into metal- hydride49*228*229 and metal-alkyl' 30-2 33 complexes. The formation of [IrH,- (NH=NPh)(PPh,),] from the trihydride and diazonium reagent could involve + a similar mechanism.234 It is also tempting to suggest that this is the mode of 210 L.Porri R. Rossi and G. Ingrosso Tetrahedron Letters 1971 1083. K. Maruya. T. Mizoroki and A. Ozaki BUN.Chem. SOC.Japan 1970 43 3630. 212 K. Maruyama T. Kuroki T. Mizoroki and A. Ozaki Bull. Chem. SOC. Japan 1971 44,2002. F. Dawans Tetrahedron Letters 197 1 1943. 214 C. Dixon E. W. Duck and D. K. Jenkins Organometallic Chem. Synth. 1971 1 77. 215 M. Avram E. Avram M. Elian F. Chiraleu I. G. Dinulescu and C. D. Nenitzescu Chem. Ber. 1971 104 3486. 216 K. Nicholas L. S. Bray R. E. Davis and R. Pettit Chem. Comm. 1971 608. 217 H. Kolshorn H. Meier and E. Muller Tetrahedron Letters 1971 1469. R. P. A. Sneeden and H. H. Zeiss J. Organometallic Chem. 1971 28 259. 219 C. Agnes and G. Cometti Organometallic Chem. Synth. 1971 1 185.220 E. Muller R. Thomas M. Sanerbier E. Langer and D. Streichfuss Tetrahedron Letters 1971 521. 221 J. Browning C. S. Cundy M. Green and F. G. A. Stone J. Chem. SOC.(A) 1971,448. 222 J. Browning M. Green and F. G. A. Stone J. Chem. SOC. (A) 1971 453. 223 M. Green S. K. Shakshooki and F. G. A. Stone J. Chem. SOC.(A) 1971 2828. 224 A. Greco M. Green and F. G. A. Stone J. Chem. SOC. (A) 1971 3476. 225 T. Blackmore M. I. Bruce F. G. A. Stone R. E. Davis and A. Garza Chem. Comm. 1971 852. 226 D. M. Barlex J. A:Evans R. D. W. Kemmitt and D. R. Russell Chem. Comm. 1971 331. 227 R.Ugo Chimica e Industria 1969 51 1319. 228 H. C. Clark and H. Kurosawa Chem. Comm. 1971 957. 229 P. C. Wailes H. Weigold and A. P. Bell J. Organometallic Chem. 1971 27 373.230 H. C. Clark and R. J. Puddephatt Inorg. Chem. 1971 10 18. 231 C. K. Brown D. Georgiou and G. Wilkinson J. Chem. SOC.(A) 1971 3120. 232 M. E. Vol'pin L. G. Volkova I. Y. Levitin N. N. Boronina and A. M. Yurkevich Chem. Comm. 1971 849. 233 R. P. Hughes and J. Powell J. Organometallic Chem. 1971 30 C45. 234 L.Toniolo and R. Eisenberg Chem. Comm. 1971,455. OrganometalIic Compounds of the Transition Elements 291 attack of a-bonded perfluoro-ketones on cy~lobutadiene~ and oxygen2 36 adducts. The insertion ofCO and CS into metal-ar~l~~’ bonds and -h~dride,~~ respectively has been shown to occur. Insertion of an isocyanide ligand into a metal-alkyl bond occurs when alkyl platinum isocyanide compounds are heated ; imino products are The incorporation of SO into metal-~arbon~~’-~~~ bonds and -oxygen244v245 is superficially analogous to many CO insertions but doubts have been expressed as to a similarity in mechanism.246 7 Carbonylation Reactions Used in Organic Synthesis An important industrial application for the preparation of acetic acid from methanol using homogeneous rhodium catalysts in the presence of iodide promoters has been announced during the year.247,248 The proposed reaction sequence is shown in Scheme 2 ;Rh* is believed to be a Rh’ species.MeOH + HI * Me1 + H,O Me1 + Rh* -+ ‘Rh*(Me)I’ 3 ‘Rh*(Me)(CO)I’ 1insertion ‘Rh*(COMe)I’ iH*O Rh* + MeC0,H + HI Scheme 2 The hydroformylation of olefins using CO and H, to yield aldehydes and/or alcohols continues to be investigated.With cobalt compounds e.g. HCo(CO) the stoicheiometric addition to propylene proceeds -70% by Markovnikoff addi- ti~n.~~’ This mode of addition probably controls the product distribution in the 235 A. Bond and M. Green Chem. Comm. 1971 12. 236 P. J. Hayward and C. J. Nyman J. Amer. Chem. SOC.,1971 93 617. 231 I. S. Kolomnikov T. S. Lobeeva W. V. Gorbachevskaya G. G. Aleksandrov Y. T. Struckhov and M. E. Vol’pin Chem. Comm. 1971 972. 238 A. Palazzi L. Busetto and M. Graziani J. Organometallic Chem. 1971 30 273. 239 Y. Yamamoto and H. Yamazaki Bull. Chem. Soc. Japan 1971 44 1873. 240 M. R. Churchill and J. Wormald J. Amer. Chem. SOC.,1971 93 354. 24 I W. D. Bannister B. L. Booth R. N. Haszeldine and P. L. Louder J.Chem. Soc. (A) 1971,930. 242 S. R. Su and A. Wojcicki J. Organometallic Chem. 1971 27 23 1. 243 J. E. Thomasson P. W. Robinson D. A. Ross and A. Wojcicki Znorg. Chem. 1971 10,2131. 244 M. Graziani R. Ros and G. Carturan J. Organometallic Chem. 1971 27 C19. 245 J. Valentine D. Valentine and J. P. Collman lnnorg. Chem. 1971 10 219. 246 G. M. Whitesides and D. J. Boschetto J. Amer. Chem. SOC.,1971 93 1529. 24’ Chem. Eng. News 1971,49 (35) 19. 248 J. F. Roth J. H. Craddock. A. Hershman and F. E. Paulik ChemTech. 1971 1 600. 249 P. Taylor and M. Orchin J. Amer. Chem. SOC.,1971,93 6504. 292 J. P. Candlin K. A. Taylor and A. W. Parkins catalytic reaction although subsequent reactions such as metal-alkyl to metal- acyl conversion may contribute to the proportion of products (aldehydes) obtained.250 The use of phosphine-modified cobalt catalysts to modify product distributi~n~~' has been examined and also mechanistic studies of the hydro- formylation of ethylene using Rh,(C0),2252 have been made.The metal-alkyl/metal-acyl rearrangement is thought to occur by alkyl migra- tion rather than by CO insertion into a metal-alkyl bond. Recent papers have substantiated this view.253 257 The hydroformylation of butadiene using rhodium catalysts gives predomi- nantly the monoaldehyde as product. 58 Carbonylation of ethylene using Rh,(CO), catalyst in methanol gives polyketonic materials,259 e.g. MeCH,-CO(CH,),COCH,Me. The stoicheiometric use of metal carbonyls is well illustrated by the formation of aldehydes from acyl halides using [Fe(CO),12-.Yields as high as 95% are claimed.260 8 Nucleophilic Attack on Co-ordinated Ligands A large amount of detailed work has been reported in this area during the year; contributions on palladium chemistry have been particularly numerous. The oxidation of ally1 alcohol to acrolein by Pd" in aqueous solution has been shown to proceed via P-hydroxypropionaldehyde26 although in the absence of water propylene and 4-methylenetetrahydrofurfuryl alcohol are the products and [(allyl)PdCl] is formed as a by-product.262 The reaction of cyclohexene with Pd" salts is extremely complex. trans-Addition of XPdAc across the double bond is considered as the first step and this is followed by a stepwise movement of the Pd around the ring.263,264 Displacement of the PdX moiety by a nucleo- phile with or without retention of configuration can explain the formation of the saturated products the unsaturated products being formed by cis elimination of HPdX.An alternative pathway to the allylic derivatives is uia n-ally1 inter- mediate~.~~ '" J. Falbe H. Feichtinger and P. Schneller Chem.-Ztg. 1971 95 644. 251 W. Rupilus J. J. McCoy and M. Orchin Ind. Eng. Chem. (Product Res. and Develop- ment) 1971 10 142. 252 B. Heil L. Marks and G. Bor Chem. Ber. 1971 104 3418. 253 M. Kubota and D. M. Blake J. Amer. Chem. SOC.,1971 93 1368. 254 M. Kubota D. M. Blake and S. A. Smith Inorg. Chem. 1971 10 1430. 25s M. Pankowski and M. Bigorgne J. Organometallic Chem.1971 30 227. 256 G. M. Whitesides and D. J. Boschetto J. Amer. Chem. SOC.,1969 91 4313. 257 C. P. Casey and C. A. Bunnell J. Amer. Chem. SOC.,1971 93,4077. 258 C. K. Brown W. Mowat G. Yagupsky and G. Wilkinson J. Chem. SOC.(A) 1971 850. 259 Y. Iwashita and M. Sakuraba Tetrahedron Letters 1971 2409. 260 Y. Watanabe T. Mitsudo M. Tanaka K. Yamamoto T. Okajima and Y.Takegami Bull. Chem. SOC.Japan 1971,44,2569. 26 ' R.Jira Tetrahedron Letters 1971 1225. 262 W. Hafner H. Prigge and J. Smidt Annalen 1966 693 109. 263 P. M. Henry and G. A. Ward J. Amer. Chem. SOC.,1971 93 1494. 264 S. Wolfe and P. G. C. Campbell J. Amer. Chem. SOC.,1971 93 1496. 265 S. Wolfe and P. G. C. Campbell J. Amer. Chem. SOC. 1971 93 1499. Orgunometullic Compounds of the Transition Elements An addition-elimination mechanism (Scheme 3) explains very neatly how ortho-and para-directing groups give predominantly the meta-product in the nuclear acetoxylation of alkylbenzenes using Pd(OAc) in AcOH in the presence of oxygen.266 This is not the only way in which Pd" salts interact with aromatic R Scheme 3 compounds and the conventional electrophilic substitution pattern is obtained when other oxidizing agents (e.g.K,Cr,O, KMnO,) are Reaction of the alkyl side-chains is also known.268 Two interesting examples of competitive nucleophilic attack demonstrate the contrasting relative reactivity of similar groups in different environments. In particular whereas the carbonyl group in (29) is attacked by OMe-,269 it is the thiocarbonyl group in (30) which is more reactive.270 + [(PPh,),Ir(CO),CS] + OMe-+ (PPh,),IrCO(CS)CO,Me (29) [(n-C,H,)Fe(CO),CS]+ + OMe-+ (71-C,H,)Fe(CO),CSOMe (30) 9 Electrophilic Attack on Co-ordinated Ligands There have been several studies of protonation of diene systems co-ordinated to d8 ions.In both (cyclo-octatetraene)R~(CO~)~~~ and (cyclo-0ctatriene)- R~(z-C,H,)~~~ the first step in the protonation is the formation of a complex in 266 L. Eberson and L. Gommez-Gonzales Chem. Comm. 1971 263. 267 P.M. Henry J. Org. Chem. 1971 36 1886. "* J. M. Davidson and C. Triggs J. Chem. Soc. (A),1968 1331. ''' M. J. Mays and F. P. Stefanini J. Chem. Soc. (A) 1971 2747. *'' L. Busetto M. Graziani and U. Belluco Znorg. Chem. 1971 10 78. 271 M.Cooke P. T. Draggett M. Green B. F. G. Johnson J. Lewis and D. J. Yarrow Chem. Comm. 1971,621. 272 J. Evans B. F. G. Johnson and J. Lewis Chem. Comm. 1971 1252. J. P. Candlin K. A. Taylor and A. W.Parkins which the metal is bonded to the eight-membered ring by a o-bond and co- ordination from an olefinic fragment. Successive protonation and deprotona- tion of (tetramethylallene)Fe(CO) produces2’ the butadiene complex (31). Me Addition of HCl to (butadiene)Fe(CO) has previously274 been thought to occur with geometric inversion to give the syn-isomer (32) but in the case of (l-phenyl-3-methylbutadiene)Fe(CO),(33) addition of DCl gives a complex (34) with deuterium in the anti position.275 This paper also describes n.m.r. studies F~(co) I Fe(CO),C1 (33) (34) on deuteriated (cyclohexadienyl)Fe(CO),cations and concludes that protonation occurs by endo attack on the ligand.The contrasting reactivity of exo-and endo-substituents has been explored in the (cyclopentadiene)Fe(CO) series.276 Thus (35) is readily solvolysed to (36) but the corresponding compound in which the tosyl group is endo is unreactive. CH20Ts H t I Usually the stereochemical rode of nucleophilic attack on unsaturated hydro- carbon ligands attached to the metal centre appears to be exo whereas endo attack often occurs with electrophilic reagents. This general rule could have 273 D. H. Gibson R. L. Vonnahme and J. E. McKierhan Chem. Comm. 1971 720. 274 G. F. Emerson J. E. Mahler and R. Pettit Chem.andznd. 1964 836. 275 T. H. Whitesides and R. W. Arhart J. Amer. Chem. SOC.,1971 93 5296. 276 0.H. Herberich and H. Muller Chem. Ber. 1971 104 2781. Organometallic Compounds of the Transition Elements important synthetic organic applications since the metal fragment can often be removed from the complex leaving the organic moiety with a known stereo- chemical configuration. 10 Asymmetry and Asymmetric Induction The study of asymmetry in organometallic chemistry is not a new field of study but is being increasingly investigated in the hope that it may be possible to influence the stereospecificity of catalytic transformations. Recent indications have suggested that -80 % optical yields of L-dopa by catalytic hydrogenation of P-substituted a-acylamidoacrylic acids can be achieved and commercial exploitation appears to be feasible.277 There are two types of optically active organometallic compounds those in which the metal atom is the asymmetric centre and those whose activity is due to asymmetry in the ligand.The latter type are more important in organic syn- thesis and there are numerous examples of successful asymmetric synthesis. Hydrogenation of atropic acid (37) to hydratropic acid (38) and of a-ethyl- styrene to optically active 2-phenylbutane can be catalysed by RhI-phosphine complexe~.~ 79 When optically active methylpropylphenylphosphine(optical 7872 purity 69 %) is used,280 the product (38) has an optical purity of 15% but higher * CH,=C(Ph)CO,H -+Me-CH(Ph)CO,H (37) (38) selectivities can be achieved using the chelating phosphine (39).281 The use as a ligand of neomenthyldiphenylphosphine which is easily obtained from (-)-menthyl chloride and LiPPh, has been recommended.282 As the solvent acts as ligand in the hydrogenating system Rh(py),(amide)Cl,-BH,- optically active amide solvents can be used to promote asymmetric hydr~genation.,~~ Me ,0,c,CH2PPh2H 277 W.S. Knowles and M. J. Sabacky G.P. 2 123 06311971. 278 W. S. Knowles and M. J. Sabacky Chem. Comm. 1968 1445. 279 W. S. Knowles M. J. Sabacky and B. D. Vineyard Ann. New York Acad. Sci. 1970 172 232. L. Horner H. Siegel and H. Biithe Angew. Chem. Innternat. Edn. 1968 7 942. '*' T. P. Dang and H. B. Kagan Chem. Comm. 1971,481. 282 J. D. Morrison R. E. Burnett A.M. Aguiar C. J. Morrow and C. Phillips J. Amer. Chem. SOC.,1971,93 1301. 283 P. Abley and F. J. McQuillin J. Chem. SOC.(C),1971 844. J. P. Candlin K. A. Taylor and A. W.Parkins Hydrogenation of carbonyl groups to alcohols can be carried out to give an optically active product using a Raney nickel catalyst which has been modified by treatment with optically active tartaric acid.28L286 Hydrosilylation of olefins may also be influenced by using a Pd catalyst containing chiral phosphines [(R)-PhBzMeP] MeMgBr CH =CMePh + HSiC1,Me + MeCl,SiCH,;HMePh -Me,SiCH2EHMePh The product contained 5 % enantiomorphic excess of R-i~omer.~~~ Reactions involving carbon-carbon bond formation in which the products are optically active have been briefly reported.288 Asymmetric phosphines contain- ing menthyl groups in combination with n-allylnickel halides are the catalyst system used and 5&60 optical yields are claimed.Ziegler catalysts which use optically active alkylating agents e.g. tris-(S)-2-methylbutylaluminium have been shown to polymerize one enantiomorphic monomer in preference to another when present in a racemic These catalyst systems polymerize a m-mixture of propene oxide by a similar asymmetric selection.293 Nucleophilic attack on co-ordinated olefins in asymmetric systems has been studied extensively.6 This is important work because it is possible to examine the changes which occur in a single stoicheiometric step and it may eventually be possible to explain the action of catalysts producing stereoregular polymers from vinyl monomers.294 284 S.Tatsumi Bull. Chem. Soc. Japan 1968 41 408. 285 Y. Izumi Angew. Chem. Internat. Edn. 1971 10 871. 286 C.-Y. Chen H. Yamamoto and T. Kwan Chem. Pharm. Bull. 1970 18 1305. 2n7 K. Yamamoto T. Hagashi and M. Kumanda J. Amer. Chem. Soc. 1971 93 5301. 2n8 B. Bogdanovic H.-G. Karmann B. Meister H.-G. Nussel and G. Wilke ref. 44 I 201 ; Naturwiss. 1970 57 616. 289 P. Pino F. Ciardelli and G. P. Lovenzi J. Amer. Chem. Soc. 1963 85 3888. 290 P. Pino F. Ciardelli and G. P. Lorenzi Makromol. Chem. 1964 70 182. 291 J. Boor jun. Ind. Eng. Chem. (Product Res. and Development) 1970 9 437. 292 P. Pino F. Ciardelli and M. Zandomeneghi Ann. Rev. Phys. Chem. 1970,21 561. 293 M. Nakanima I. Kameoka K.Ozaki and J. Furukawa Makromol. Chem. 1970 138 209. 294 P. Corradini G. Paiaro and A. Pananzi J. Polymer Sci.,Part C Polymer Symposia 1967 2905.

ISSN:0069-3030    

DOI:10.1039/OC9716800273

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

8 EIectro-organic Chemistry By K. KORINEK and T. F. W. McKlLLOP I.C.I. Ltd. Corporate Laboratory Runcorn Cheshire 1 Introduction Consolidation rather than major innovation seems to characterize the period covered by this Report. There is however evidence in the literature of a willingness to employ a wider variety of techniques in tackling problems. The value of product analysis is increasingly appreciated in mechanistic studies and the proper application of electroanalytical techniques coupled with the use of controlled-potential electrolysis is resulting in better reproducibility and improved yields. It would seem that the organic chemist and the electrochemist are at last coming to terms with each other. It is interesting that the organic molecules now being studied are structurally much more complex than those of a few years ago and that there is a growing awareness of the synthetic utility of particular reactions.One feature of electro-organic reactions that is being increasingly considered is the stereochemical consequence of reaction in the heterogeneous environment near the electrode. Numerous interesting effects of fundamental interest and potential value in synthesis have already been observed. The proliferation of literature in organic electrochemistry ensures that a review of this length cannot be comprehensive and this contribution is to be considered complementary to the exhaustive treatment of the topic which is a regular feature of the Specialist Periodical Reports series on Electrochemistry.* Indeed we have neglected the majority of electroanalytical studies and a sub- stantial proportion of papers which we consider to exhibit further exemplification rather than novel features.One manifestation of the growing interest in the subject is the appearance of a new journal’ and three books.2 In addition the most recent volume^^.^ in two ’ Journal of’ Applied Electrochemistry ed. D. Inman Chapman Hall London vol. 1 1971. ‘Progress in Electrochemistry of Organic Compounds,’ ed. A. N. Frumkin and A. B. Ershler Plenum Press London 197 1. ‘Reaction of Molecules at Electrodes,’ ed. H. S. Hush Wiley-Interscience London 1971. ‘Industrial Electrochemical Processes’ ed. A. T. Kuhn Elsevier Amsterdam 197 1. ‘Physical Chemistry -An Advanced Treatise vol.IXB -Electrochemistry,’ ed. H. Eyring Academic Press New York 1970. ‘Advances in Electrochemistry and Electrochemical Engineering; vol. 8 -Electro-chemistry,’ ed. P. Delahay Wiley -Interscience New York 1971. * ‘Electrochemistry’ ed. G.J. Hills (Specialist Periodical Reports) Thechemical Society London vol. 1 1971 vol. 2 1972. 297 298 K. Korinek and T. F. W. McKillop well-established series have been issued and one volume5 of Fortschritte der Chemischen Forschung has been devoted to the subject. The present state and future trends in organic electrochemistry have been reviewed,6 as have the industrial aspects of the subject.’ Of particular interest to the synthetic chemist is a review of Wawzonek,* complemented by one in Norwegian’ and one in Japanese.’ 2 Reduction Hydrocarbons.-Aromatic.Electrochemical studies often provide a useful insight into the properties and behaviour of aromatic compounds. The half-wave reduction potentials for a series of helicenes’ do not fit the normal linear relation- ship between E and ionization potential as calculated by Huckel methods. The enforced deviation from planarity is presumed to be the cause. In similar fashion the fusion of strained rings to naphthalene and naphthaquinone produces noticeable shifts in E which can be correlated” within the framework of Huckel calculations and rationalized on the basis of Streitwieser’s hybridization model. The reduction of compounds with eight rc-electrons to aromatic ten n-electron dianions has been studied by various workers.Cyclo-octatetraene,’ a number of phenyl-substituted cyclo-~ctatetraenes,’~ and the isoelectronic methyl-substituted 2-methoxyazocines’ all show different behaviour ; cyclo-octatetraene exhibiting two non-nernstian one-electron waves the azocines a single irreversible two-electron wave whereas the tetraphenylcyclo-octatetraene undergoes a reversible two-electron reduction. In all cases for which electro- kinetic data are available the first electron addition is very slow. The explanation of these differences lies in the varying degree of planarity of the radical anions and in the balance between gain in delocalization energy and the energy expended in flattening the ring. OleJins. The reduction of activated olefins still commands attention.Although most electrochemical interest centres on the hydrodimerization reaction the utility of electrochemical hydrogenation as a synthetic tool should not be neglected as demonstrated in the elegant synthesis of racemic deoxypicropo- dophyllin (1).l6 The a/?-unsaturated lactone (2) obtained by intramolecular Diels-Alder reaction of the trans-cinnamyl phenylpropiolate as shown undergoes L. Eberson and H. Schafer Fortschr. Chem. Forsch. 1971 21 1. G. Faita Chimica e Industria 1971 53 472. U. R. Mehta Indian Chem. Manufr. 1971 9 12. * S. Wawzonek Synthesis 1971 285. ’ W. Lund Kjemi 1971 31 18. loT. Shono J. Synthetic Org. Chem. Japan 1971 29 865. W. H. Laarhoven and G. J. M. Brus J. Chem. SOC.(B) 1971 1433. l2 R.D. Rieke W. E. Rich and T. H. Ridgway J. Amer. Chem. Sot.. 1971. 93 1962. I J. Huebert and D. E. Smith J. Electroanalyt. Chem. Interfacial Electrochem. I97 1 31 333. l4 R. D. Rieke and K.A. Copenhafer Tetrahedron Letters 1971 4097. l5 L. B. Anderson J. F. Hansen T. Kakahana and L. A. Paquette J. Amer. Chetn. Soc. 1971 93 161. L. H. Klemm R. D. Olson and D. V. White J. Org. Chem. 1971 36 3740. Electro-organic Chemistry hydrogenation of ring A and dehydrogenation of ring B on attempted catalytic reduction of the double bond. Specific reduction can be achieved electrochemic- ally however using anhydrous acetonitrile as solvent HBr as proton source and tetraethylammonium bromide as supporting electrolyte. Further the reduction is stereospecific yielding approximately 60 % of pure trans,cis-tetrahydrolactone.OMe Digital simulation techniques are assuming an increasingly important role in the investigation of mechanistic detail in electrochemistry. The industrially important electrohydrodimerization process has been examined in this way by various authors. The two most likely mechanisms involve either direct dimeriza- tion of the radical anion (3),ie. EC mechanism or Michael-type addition of the radical anion to a neutral molecule of substrate followed by a second electron addition i.e. ECE (Scheme 1). Bard and co-workers" have studied the reduction of diethyl fumarate in tetra-n-butylammonium iodide-DMF solutions by a variety of electroanalytical methods. In particular digital simulation for double-potential-step chrono- amperometry strongly supports the EC mechanism.This conclusion also finds favour with Evans er a/.,'* who have examined the reduction of aryl-substituted W. V. Childs J. T. Maloy C. P. Keszthelyi and A. J. Bard J. Electrochern. Soc. 1971 118 874. I' J. P. Zimmer J. A. Richards J. C. Turner and D. H. Evans AnciL.vz. Clzem. 1971 43,1000. K. Korinek and T. F. W.McKillop R1R2C=CHX I+,. (3) ji2H' R 'R2C-CH2X R'R'C-CH2X I (EC) Scheme 1 ap-unsaturated ketones in DMSO with tetrabutylammonium perchlorate as supporting electrolyte by polarography cyclic voltammetry and controlled- potential coulometry. It is evident from both these papers however that the presence of the lithium ion and water have marked effects on the reaction-en- hancing the rate and suppressing oligomerization.Petrovich and Baizer '' have examined the effect of the counterions Li' Na' K+ Rb+ and R4N+ on the reduction of 1,2-diactivated olefins XCH=CHY by cyclic voltammetry and bulk electrolysis. Comparison of plots of observed i$Vt versus T/* with those theo- retically computed for the EC and ECE mechanisms leads Baizer to conclude that either mechanism and combinations of both are observable depending on the substrate and counterion. Generally quaternary ammonium ions favour the ECE pathway and lithium favours the EC mechanism. This is interpreted in terms of ion-pair behaviour. The small cation is believed to allow formation of a tight ion pair and consequently the organic radical ion reacts predominantly by radical coupling whereas the larger counterion encourages anionic behaviour.Interesting effects of the counterion on the nature of the dimeric products are also observed. Reduction of a-phenylcinnamonitrile in the presence of tetraethyl- ammonium ion yielded 86 % of the cyclic dimer (4) and 14 of (9,whereas with lithium ions 89 % of (5) is obtained. The hydrated alkali-metal ion is believed to assist hydration of the common anionic intermediate (6)before cyclization occurs as is found with unhydrated quaternary ammonium ion. k:b * ph -eCN eN N CN Ph Ph Ph Ph l9 J. P. Petrovich and M. M. Baizer J. Electrochem. SOC., 1971 118 447 Electro-organic Chemistry 301 The mechanistic complexity of electrohydrodimerization is magnified many- fold in crossed-coupling reactions.Baizer and Chruma2’ report their latest studies and show that by operating at the potential required for reduction of the less easily reduced olefin current efficiencies for crossed products are increased and that couplings which otherwise fail can occur. Yields are still poor however. Nonaka and Sekine2’ have also reported their latest work on the mechanism of crossed hydrocoupling of acetone with activated olefins. Another interesting hydrodimerization involves the reduction of 3-methyl- crotonaldehyde at -1.3V (versusthe s.c.e.) in acetate buffer at pH 5.0.22A small amount of pinacol is obtained but the major product (67%) is the hydroxy- tetrahydrofuran (7) plus some olefin (8).CarbonylCompounds.-The factors controlling the stereoselectivity of pinacoliza- tion are still poorly understood. Stocker has argued from electrochemical and photochemical studies in protic media that dimerization occurs in the bulk solution. [‘Electrochemistry’ (Specialist Periodical Report) vol. 1 p. 108.1 The ratio of racemic to meso product is characteristically -1.2 in neutral or acidic media but -2.9 in alkaline media. The same authors have now published results obtained from the bimolecular reduction of acetophenone in aprotic media.23 In high yields of total pinacol a racemic :meso ratio of 7.0-9.0 is obtained which is contrary to the author’s expectations on the basis of conformational preference in the coupling of two radical anions.Rationalization after the event allows this result to conform to the authors’ previous scheme. Their whole framework however must be seriously in doubt in the light of Horner and Degner’s studies24 with a series of aryl alkyl ketone reductions in aprotic solvents containing optically active supporting electrolytes. The base electrolytes employed were (1R ,2S)-ephedrine hydrochloride (1R,2S)-ephedrine methochloride (S)-deoxyephedrine methochloride and tetramethylammonium chloride. Reduction of isobutyro- phenone yielded 13-38% of pinacol depending on the nature of the base electrolyte. In (1R,2S)-ephedrine methochloride (38 % pinacol) the racemic/meso ratio was 19 but in the other three base electrolytes (13-18 % pinacol) the meso product was preferred by a ratio between 2 1 and 5 1.These results strongly suggest that much of the dimerization occurs at or near the electrode surface and is dependent on the ordering of base electrolyte substrate and solvent molecules. ’’ M. M. Baizer and J. L. Chruma J. Electrochem. Soc. 1971 118 450. ” T. Nonaka and T. Sekine Denki Kagaku 1971,39,29. ’’ D. Miller L. Mandell and R. A. Day jun. J. Org. Chem. 1971 36 1683 23 J. H. Stocker and R. M. Jenevein Coll. Czech. Chem. Comm. 1971 36 925. ’‘ L. Horner and D. Degner Tetrahedron Letters 1971 1241. K. Korinek and T. F. W.McKillop In the same paper Horner and Degner discuss the ratio of carbinol to pinacol formed in reductions of aryl alkyl ketones. Not surprisingly large alkyl substi- tuents on the ketone lead to a preference for carbinol.More surprising is the dependence of the ratios on the base electrolyte. In a second related paper25 the variation of optical purity in the carbinol products with the absolute configuration of the base electrolyte is described. Optical purities up to 10% can be obtained. The authors promise to discuss these results more fully in a later publication. The importance of the medium in determining the stereochemical outcome in ketone reductions has also been emphasized by Utley and co-workers.26 With conformationally rigid cyclic ketones reduction in basic medium gives the thermo- dynamically more stable equatorial alcohol whereas in the presence of acid almost equal amounts may result but with lower yields and current efficiencies.The electroreduction of certain non-conjugated enones promises to be a useful synthetic reaction. Ring closure is found to occur when the double bond and carbonyl group are so disposed as to allow formation of a five- or six-membered ring.27 Thus reduction of (9) in 5 1 dioxan-water with tetraethylammonium toluene-p-sulphonate as base electrolyte at constant current gives (10)in 66 % yield. It is significant from a synthetic viewpoint that only the cis-dialkyl product is formed and that the reduction proceeds equally well in going from a medium-ring compound like (1 1) to a bicyclic product (12) as shown. CH,=CH(CH,),COMe + Ho&Me (9) Compounds exhibiting P-diketone functionality have been the subject of an unusually large number of papers.Generally these have been concerned with the electroanalytical aspects product analysis playing a supporting role. Kariv and Gileadi have examined the behaviour of enolizable and non-enolizable P-diketones and compared it with that of saturated mono-carbonyl and crp-’ L. Horner and D. Degner Tetrahedron Letters 1971 1245. 26 J. P. Coleman R. J. Kobylecki and J. H. P. Utley Chem. Comm. 1971 104. 2’ T. Shono and M. Mitani J. Arner. Chem. SOC.,1971,93 5284. ’* E. Kariv B. J. Cohen and E. Gileadi Tetrahedron 1971 27 805. 29 E. Kariv J. Hermolin I. Rubinstein and E. Gileadi Tetrahedron 1971 27 1303. ’O E. Kariv and E. Gileadi COIL Czech. Chem. Comm. 1971 36 476. 31 K. Kariv J. Hermolin and E. Gileadi Electrochim. Acta 1971 16 1437. Electro-organic Chemistry 303 unsaturated ketone ' The ease of reduction is ap-unsaturated ketone > 2-unsubstituted 1,3-diketone > 2,2-disubstituted 1,3-diketone > satu-rated ketone.The stability of allylic and homoallylic radicals is proposed as the explanation. A~etylacetone,~~ dehydroacetic acid,33 various phthalimide~,~~~~ and 1,3-indanediones have also been ~tudied.~ 7-39 During studies of the reduction of crotonaldehyde Barnes and Zuman have observed an interesting is~merization.~' At pH > 8 the unprotonated aldehyde which is predominantly the cis-isomer is reduced at Hg surfaces to give crotyl alcohol in which the trans-form is the major constituent. Reductive Cleavage of Halides.-A review covering the nature of the orientation of a carbon-halogen dipole in an electric field and a discussion of the stereo- chemistry obtaining in the electroreduction of mono- and di-halogen compounds has a~peared.~ ' Industrial interest in processes giving lead tetra-alkyls has encouraged work on the reduction of alkyl halides at sacrificial electrodes.The importance of the solvent is emphasized by the work of the Southampton In contrast to recent studies in propylene carbonate which indicated that lead tetra-alkyl was formed only in the presence of tetra-alkylammonium or trialkylsulphonium ions high yields (based both on the amount of lead consumed and on the electricity passed) can be obtained using sodium halides in DMF. Careful potential control however is essential. Low potentials are believed to favour formation of di- or tri-alkyl-lead and too high a potential causes formation of alkyl anions which undergo protonation.Using a pulse technique analysis of the resulting current- time transients suggests to the authors that a catalytic mechanism with a species such as PbEt as catalyst may be operating. Reduction of benzyl halides on mercury yields the dibenzylmercury complex and toluene as the major products and it has been shown that the ratio of yields of these is dependent on the potential.43 Kosower has used polarography and cyclic voltammetry on a hanging mercury drop to determine the life-times of the radical anions obtained by reduction of 4-nitrobenzyl corn pound^.^^ The radical-anion decomposition rate constants vary from that for the nitrotoluene '' A.D. Thomsen and H. Lund Acta Chern. Scand. 1971 25 1576. 33 G. Le Guillanton Compt. rend. 1971 272 C 11. 34 D. W. Leedy and D. L. Muck J. Amer. Chem. Soc. 1971,93,4264. 35 G. Farnia A. Romanin G. Capobianco and F. Torzo J. Electroanalyt. Chem. Interfacial Electrochem. 197I 33 3 1. 36 A. Ryvolova-Kejharova and P. Zuman Coll. Czech. Chem. Comm. 1971,36 1019. 37 D. Zacharova-Kalavska I. Zelensky and A. Perjessy Coll. Czech. Chem. Comm. 1971,36 2716. 38 D. Zacharova-Kalavska A. Perjessy and I. Zelensky Coll. Czech. Chem. Comm. 1971 36 2712. 39 D. Zacharova-Kalavska and A. Perjessy Coll. Czech. Chem. Comm. 1971 36 1406. 'O D. Barnes and P. Zuman J. Chem. Soc. (B),1971 1 118. " K. P. Butin Uspekhi Khim. 1971 40 1058.42 M. Fleischmann D. Pletcher and C. J. Vance J. Electroanalyr. Chem. Interfacial Electrochem. 1971 29 325. 43 0. R. Brown H. R. Thirsk and B. Thornton Electrochim. Acta 1971 16 495. 44 M. Mohammad J. Hajdu and E. M. Kosower J. Amer. Chem. Sac. 1971 93 1972. K. Korinek and T.F W.McKillop which is stable to that for the bromide which is at least > 100s-; there is a parallel between rate constants and the carbon-substituent bond strength. Nadjo and Saveant have examined the reduction mechanisms operating in the case of halogeno-substituted benzophenones and fluorenones in DMF.45 The vinylic chloride or-cyano-P-chlorostyrene (13) has been reduced in a variety of solvent systems. The reduction is by two discrete two-electron steps as shown in Scheme 2.46 The second two-electron step which proceeds only in Ph Ph Ph \ \ +e \ C=CHCl 3 C=CH 3 / / /C=CHz NC NC NC Ph Ph \ \ C=CH 3 CH-CH, / / NC NC ' Scheme 2 neutral or basic conditions gives very high yields of the saturated nitrile.In- terestingly the cis-compound is more easily reduced than the trans. Allenic and acetylenic halides have also been studied on mercury by polarography and controlled-potential electr~lysis.~~ The reductive cleavage of dihalogeno-compounds has been shown to provide interesting synthetic routes to highly strained hydrocarbons. In his most recent cornm~nication,~~ Rifi has shown that reduction of 1,3-dibromobis(brorno-methy1)propane (14) on Hg in DMF containing tetrabutylammonium perchlorate shows two discrete two-electron waves at -1.8 and -2.33 V (versus s.c.e.).BrHzC ,CH2Br \/ +2e +2e (-1.8 V) CH,Br (XDa -wCHzBr /\ BrH2C' 'CH,Br (16) (14) Macro-scale electrolysis employing a controlled potential of between -1.2 and -1.4 V allowed the dibromide (15) to be isolated. Further reduction at -2.2 V yielded the spiropentane (16)in good yield and without the attendant by-products resulting from the use of conventional reducing agents. Rifi has suggested that the electrochemical data for reduction of 1,3-dihalides are best interpreted on the 4s L. Nadjo and J. M. Saveant J. Electroanalyt. Chem. Interfacial Electrochem. 1971 30 41. 46 G. Le Guillanton and A. Daver Compt. rend. 1971 212 C 421. 47 H. Doupeux P. Martinet and J.Sirnonet Bull. SOC.chim. France 1971 2299. 48 M. R. Rifi J. Org. Chem. 1971 36 2017. Electro-organic Chemistry basis of a concerted mechanism.49 If true this is of considerable significance particularly in the light of the recent interest in concerted mechanisms in organic chemistry. The proposal however seems to be convincingly refuted by a recent study of stereoisomeric 2,4-dibromopentanes5' in DMSO or DMF with tetra- ethylammonium bromide as supporting electrolyte. If the reductions are concerted each isomer (i.e. racemic or meso) would be expected to lead to either pure cis-or pure trans-dimethylcyclopropane. In the event approximately half of each is formed in addition to small amounts of reduced aliphatic compounds. The authors propose a scheme to account for these products based on the inter- mediacy of the monobromo-carbanion.Nitro- and Nitroso-compounds.-Numerous papers describing electroanalytical studies on the reduction of nitro-group-containing compounds have appeared but only those involving the nitro-group in an unusual molecular environment will be described. Chemical reduction of nitrobenzenes substituted in the ortho-position with a group terminating as a carboxylic acid (17 ;X = CH ,CHOH or CO) can lead to high yields of the lactam (18) but cyclization to the hydroxamic acid (19),corres-ponding to partial reduction is less efficient. It has been shown that by careful choice of medium and by control of the potential almost quantitative yields of either of the cyclized products are obtainable electrochemically.s Armand and ~o-workers~~*~~ have continued their examination of various functionalized aliphatic nitro-compounds with recent publications concerning the reduction of species such as (20) (21) and (22) where X = halogen.R'R2C=C(X)N02 R' XC=C(R2)N0 02N(R')C=C(R2)NO (20) (21) (22) In contrast to saturated gem-halogeno-nitro-compounds which eliminate the halide ion after one-electron reduction,54 the alkene (23) exhibits a single pH- dependent six-electron wave. In addition to some aldehyde derivable by partial 4y M. R. Rifi Coll. Czech. Chem. Comm. 1971 36 932. '' A. J. Fry and W. E. Britton Tetrahedron Letters 1971 4363. A. Tallec G. Mennereau and G. Robec Compt. rend. 1971 272 C 1378. s2 J.Armand and 0. Convert Coll. Czech. Chem. Comm. 1971 36,351. s3 0. Convert P. Bassinet J. Pinson and J. Armand Compr. rend. 1970 271 C 1602. g4 D. E. Bartak and M. D. Hawley J. Electroanalyr. Chem. Interfacial Electrochem. 1971 33 13. 306 K. Korinek and T.F. W.McKillop hydrolysis preparative electrolysis in water-dioxan yields the nitrile (24) as the major product. In methanol-water however substantial amounts of a further compound (25) are obtained. Eliminating some alternatives the authors propose Scheme 3 to account for their observations. The postulate of the presence of carbonium ion (26) is particularly intriguing to the organic chemist. /NO2 NO / Ph-CH=C +2e +2Hf + Ph-CH=C + H20 ‘Br ‘Br (23) 2e; 2H’ I + H+ Ph-CH-C-N + Ph-CH=C=N-OH (26) + dioxan-Ph-CH-CEN + 2e + 2H+ water Ph-CH2-CN (24) OMe t MeOH-I Ph-CH-C-N wate; Ph-CH-C-N (25) Scheme 3 Various mechanisms have been proposed for the reduction of aliphatic nitro- compounds.It has now been shown that the nature of the solvent and the ability of the medium to protonate have a pronounced effect three basic mechanisms being di~cernible.~~ Generally however it is assumed that reduction stops at the hydroxylamine although there have been indications that 2-aminobutan-1-01 can lead to the fully reduced amino-alcohol. This system has now been examined in more detail and the have established that at higher temperatures and particularly in the presence of hydrochloric acid the amount of amino-alcohol product can be enhanced.A polarographic examination of the reduction of N-nitrosamines has been reportedY5’ and Iversen has described a general electrosynthetic method for the preparation of 1,l-dialkylhydrazines from N-nitro~amines.~~ Yields of isolated product vary from 40 to 80% for current efficiencies of 70-100”/,. 55 G. Battistuzzi Gavioli G. Grandi and R. Andreoli Coll. Czech. Chem. Comm. 1971 36 730. 56 B. Lovrecek Z. Vajtner and J. Hranilovic Tetrahedron Letters 1971 3319. 57 G. Borghesani F. Pulidon R. Pedriali and C. Bighi J. Electroanalyt. Chem. Interfacial Electrochem. 1971 32 303. 58 P. E. Iversen Acta Chem. Scand. 1971 25 2337. Electro-organic Chemistry Carbon-Nitrogen Double Bonds-A synthesis of a-amino-acids has been described involving reductive carboxylation of a Schiff base." The reduction is carried out in molten tetraethylammonium toluene-p-sulphonate which is reported to be an excellent medium for electroreductions; the melt is stable at between 125 and 185 "C for several days the solubility of organic substrates in it is high and there is no difficulty with reference systems.In the example reported uiz.benzalalanine the current efficiency to isolated product is 60%. Molecules containing the -N=C -C=N-grouping have been investigated by Pinson and Armand,60*6 particularly quinoxalines 6,6-dihydropyrazines and di-imines of various aliphatic diketones. They have demonstrated that the primary mode of reduction leads to the 1,4-dihydro-product as shown in Scheme4.Scheme 4 Depending on the relative stabilities however rearrangement to the imine may occur. In some instances electroreduction could be a useful synthetic procedure for the preparation of secondary enediamines. Closely related work involves the reduction of O=C -C=N gro~ps.~~,~~ Again 1,4-dihydro-products result from such a reaction (Scheme 5),but the intermediates have not been isolated owing to Scheme 5 the rapid rearrangement to keto-amines. One exception to this is the isolation of the hydroxy-amine when R2 is a-pyridyl presumably on account of intra- molecular hydrogen-bonding. Fleury and Fle~ry~~ have also reported a polaro- graphic study on the mono-semicarbazones of a-diketones and other a-substituted ketones. Reduction of Bonds involving Sulphur.-The nature of bond cleavage in the reduction of arylsulphonamides would now appear to be resolved two reports indicating that the sulphur-nitrogen bond is cleaved ~electively.~',~~ The tosyl group is useful as a protecting group for amines but has found limited use in amino-acids owing to the relatively severe conditions required for its removal.By 59 N. L. Weinberg A. Kentaro Hoffmann and T. B. Reddy Tetrahedron Letters 1971 227 1. 6o J. Pinson and J. Armand Coll. Czech. Chem. Comm. 1971,36 585. 61 J. Pinson and J. Armand Bull. SOC. chim. France 1971 1764. h2 J. Armand L. Boulares and J. Pinson Compt. rend. 1971 273 C 120. ' J. Armand L. Boulares J. Pinson and P. Souchay Bull. SOC. chim. France 1971 1918. 64 D.Fleury and M. B. Fleury Coll. Czech. Chem. Comm. 1971 36 331. 65 K. Okumura T. Iwasaki M. Matsuoka and K. Matsumato Chem. and Ind. 1971,929. 66 P. T. Cottrell and C. K. Mann J. Amer. Chem. SOC. 1971 93 3579. 308 K. Korinek and T. F. W.McKillop reduction in MeOH-NaOH solution at a lead cathode yields of amino-acid from 74 to 92 were obtained via the reaction indicated in Scheme 6.65 Typical acid-protecting groups such as urethanes are unaffected although the benzoyl Me~S02-NH-~~-COR2 +2H+I Me Osoy + H,N-CH-COR, +2e I I R’ Scheme 6 group is attacked. Cottrell and Mann’s investigations66 with a variety of aryl- sulphonamides substantiate these results. In aprotic conditions however these authors report that for primary and secondary amides the maximum yield based on the amount of starting material is SO% resulting from the abstraction of a proton from a molecule of starting sulphonamide by the amide ion (27).Ar-SO2-NRH 2ArS0,- +NRH (27) NRH + Ar-SO2-NRH -+ [Ar-S02-NR]-+ NRH Other sulphur-containing systems that have been investigated include aromatic thio~arbonyls,~’ aryl sulphones,68 p-nitrophenyl and p-nitrobenzyl thi~cyanate,~~ purine 2,6-disulphonic acid,” and /?-mercaptopyruvic acid.’ Miscellaneous Reductions.-Iversen has published the second paper under the general title of ‘Electrolytic Generation of Strong Bases’.72 On this occasion the Stevens rearrangement is effected electrochemically but the yields are poor and the author states that it has no synthetic value.The reduction of quaternary ammonium groups is of considerable interest and has been the subject of much discussion particularly since these salts are frequently used as base electrolytes. Tyssee and Baizer’ have examined the electrochemically more manageable aziridinium salts and not surprisingly find that the medium has a very pro- nounced effect on the mode ofreduction and decomposition. Ozonides on reduc- tion have been shown to give almost quantitative yields of the corresponding aldehydes.74 The mechanism is discussed and for substituted styrene ozonides a Hammett relationship is observed for half-wave potentials. 6-L. Lunazzi G. Maccagnani and G. Mazzanti J. Chem. Soc. (B) 1971 162. 68 J. Simonet and G. Jeminet Bull. Soc. chim.France 1971 2754. 69 D. E. Bartak T. M. Shields and M. D. Haelwy J. Electroanulyt. Chem. Interfacial Electrochem. 1971 30 289. 70 D. L. McAllister and G. Dryhurst J. Electroanalyt. Chem. Interfacial Electrochem. 1971 32 387. 71 M. B. Fleury and J. Tohier Bull. Soc. rhirn. France 1971 2760. 72 P. E. Iversen Tetrahedron Letters 1971 3523. 73 D. A. Tyssee and M. M. Baizer J. Electrochem. Soc. 1971 118 1420. 74 J. Grignon and S. Fliszar Canad. J. Chern. 1971 49 3127. Electro-organic Chemistry 3 Oxidation Hydrocarbons.-A major target for electrochemists has been the efficient oxida- tion of hydrocarbons either partially (leading to specific oxidized products) or totally (as desired in fuel cells). Progress in fuel cell technology over the last decade has been re~iewed’~ and the outstanding problems seem to be (i) a proper understanding of why platinum and other platinized electro.des are electrocatalytic and (ii) the development of more effective electrodes (possibly using supported platinum) electrode structures and cell configurations.The synthetic possibilities of electro-oxidation have been of considerable interest recently. In a long series of papers Parker76 has examined the oxidation of various anthracenes in acetonitrile. The mechanism of oxidation and the role of added reagents were studied by cyclic voltammetry coulometry and product analysis. Bianthrone was shown to be the main product of anthracene oxidation in solutions containing water ethanol and acetic acid.In particular the electro- chemical oxidation of anthracene in alcohol-acetonitrile mixtures is reported to be an excellent method for the preparation of bianthrone. The proposed mechanism for the production of bianthrone is shown in Scheme 7. The anodic H OR 0 2&% R = Me Et or MeCO II 0 Scheme 7 l5 E. .I.Cairns Adv. Electrochetn. Electrochemical Engineering 1971 8 337. 7h V. D. Parker Actu Chem. Scund. 1970 24 2757 2768 2778 3151 3162 3171 3454. 3 10 K. Korinek and T.F. W.McKillop acetoxylation and methoxylation of anthracene 9-methylanthracene and 9,lO- dimethylanthracene were shown to produce mainly trans-9,lO-disubstituted 9,lO-dihydroanthracenes.The mechanism shown in Scheme 8 in which attack by the second nucleophile occurs from the side not shielded by the electrode was postulated to account for the trans-addition.Scheme 8 N~berg~~ has reported the oxidation of mesitylene in acetonitrile containing different supporting electrolytes at carbon and platinum anodes. The optimum yield (50%) of bimesityl was obtained by electrolysis of a 2 moll-solution of mesitylene at a platinum anode using tetrabutylammonium tetrafluoroborate as the base electrolyte. The use of carbon anodes results in markedly lower yields of bimesityl probably owing to a weaker adsorption of mesitylene on carbon than occurs on platinum. Oxidation reactions of aliphatic hydrocarbons have received further attention. An interesting example of the formation of UP-unsaturated ketones has been observed during the study of the oxidation of alkanes in fluorosulphonic Using acetic acid (which in this medium is a strong base) as a supporting electro- lyte cyclohexane was shown to be oxidized to an UP-unsaturated ketone.The formation of this product was explained as shown in Scheme 9. Other alkanes containing more than four carbon atoms were also oxidized but the product analysis has not yet been reported. Shono et al.79have continued their study of the oxidation of substituted cyclopropanes. The anodic oxidation of bicyclo[4,1,0]heptane and bicyclo[3,1,0]- hexane in methanolic solution using tetraethylammonium toluene-p-sulphonate as a supporting electrolyte commences with the direct oxidation of the carbon- carbon single bond of the cyclopropane ring yielding methoxycycloalkenes as the final products.This behaviour is different from that of arylcyclopropanes which l7 K. Nyberg Acta Chem. Scand. 1971 25 534. ’* J. Bertram M. Fleischmann and D. Pletcher Tetrahedron Letters 1971 349. ’’ T. Shono Y. Matsumura and Y. Nakagawa J. Org. Chem. 1971,36 1771. Elec tro -organic Chemistry 311 Scheme 9 were reported to be oxidized by an electron transfer from the aromatic ring rather than from the cyclopropane system. An electrochemical halogeno-functionalizationof olefins which allows for the introduction of both nitrogen- and oxygen-containing substituents has been realized.*' l-Phenylbut-2-ene on electrolysis in acetonitrile solution containing Et,NX (X = C1 Br or I) was converted to a corresponding halogeno-amide derivative.Vicinal dihalides were also formed in appreciable amounts in the case of chloride and bromide electrolytes. In the case of iodide or iodine formation of the vicinal di-iodide was hindered for steric reasons. Alcohols.-The anodic oxidation of absolute methanol and ethanol at a platinum electrode has been studied by Sundholm.81 A potential-time square profile was applied to the working electrode during the measurement of the i versus E curves and in preparative electrolysis. The alcohols yielded 6690% of the corresponding acetals presumably by the mechanism shown in Scheme 10. Higher aliphatic alcohols were oxidized with fission of the carbon-carbon bond. RCH,OH + R~HOH+ 2e + H+ OCH,R RCH OH / RCH,OH /°CH2R R~HOH 'RCHOH * RCH -;+ -H,O \ OCH,R Scheme 10 N.L. Weinberg and A. K. Hoffman Cunad. J. Chem. 1971,49 740. G. Sundholm J. Electroanalyt. Chem. Interfacial Electrochem. 1971 31 265. K. Korinek and T.F. W.McKillop In ally1alcohol either the double bond or the hydroxy-group could conceivably be oxidized. In sulphuric acid the major product of oxidation was acraldehyde,82 and consequently it is concluded that the hydroxy-group is preferentially oxidized. A novel method of synthesizing cyclic ethers by the anodic oxidation of olefinic alcohols was reported by Shono et 121.~~ The electro-oxidation of citronellol (28) in acetonitrile with tetraethylammonium toluene-p-sulphonate as the base electrolyte gave rose oxide (29) in 26% yield.The anodic oxidation of endo-norbornenemethanol (30) under similar conditions formed 2-oxa-tetracyclo-[4,2,1,04*805.9]nonane(31). In methanol a mixture of (31) and the methoxy-product (32)was formed. 14 % B+Meob 22 % 12 ”/ Carbonyl Compounds and Ethers.-Electro-oxidative fragmentation of benzylic esters and ethers has been reported by Miller et ~21.~~ The compounds of the type (33) have been oxidized at a platinum electrode at potentials between 0.7 and 1.9 V us. 0.1 N Agf/Ag in acetonitrile. The anode was pulsed to a lower potential ’’ T. Watanabe Metn. Fuc. Eng. Kobe Unir.. 1971 239. 83 T. Shono A. Keda and Y. Kimura Tetrahedron Letters 1971 3599. 84 L. L. Miller J. F. Wolf and E. A. Maydea J. Amer. Chem. SOC.,1971 93 3306.Electro-organic Chemistry (-0.0 V) for a short period to maintain the current. High yields of carbonyl compounds were obtained and the mechanism suggested for the oxidative cleavage of ethers and esters is shown in Scheme 11. Ph-CH-OR' 3 Pi-CH-OR' 3 Ph-6-OR' +H+ I I I R2 RL R2 Ph-;-OR' soPhCOR2 + R'OH + H' I R2 R' = H alkyl or acyl; RZ = H alkyl or aryl Scheme 11 A similar oxidative cleavage was observed in the electro-oxidation of benzylic aldehydes and ketones." These fragmentations are similar to those occurring in the mass spectrometer. Carboxylic Acids and Anions.-The study of anodic oxidation of carboxylic acids (the Kolbe reaction) still remains of interest to organic chemists and electro- chemists alike. It is now established that the use of a carbon anode favours the formation of carbonium ion intermediates while at a platinum electrode the products derived from radical formation are preferred.Some other factors e.g.of a structural nature or adsorption can also affect the product distribution. The major factors influencing the competition between radical and carbonium ion pathways for substituted phenylacetate ions at a platinum electrode have been investigated by Utley et aLS6 It is shown that the addition of a small amount of perchlorate completely suppresses the formation of the Kolbe dimer. Steric factors also play an important role. Mesomerically electron-donating substituents lead to high yields of carbonium ion products whereas the best yield of coupled product is obtained from the acid containing the electron-withdrawing penta- fluorophenyl group.Eberson and Coleman8' have investigated the anodic oxidation of arylacetate ions which can theoretically proceed uia two different mechanisms (Scheme 12). The electrochemical evidence suggests that 9-methylanthracene-10-acetic acid is oxidized via route B -the pseudo-Kolbe reaction. L. L. Miller J. F. Wolf V. R. Koch and M. E. Lanscheid Tetrahedron Letters 1971 1389. '' J. P. Coleman J. H. P. Utley and B. C. L. Weedon Chem. Comm. 1971 438. J. P. Coleman and L. Eberson Chem. Comm. 1971 1300. 314 K. Korinek and T.F. W.McKillop ArCH,CO,-ArCH,CO,-P ArCH,. -+(ArCH,), -%'f ArCH,CO -I-. ArCH,' -+ Products Scheme 12 Electrochemical synthesis of compounds of general formula (R1CH2CR2Y) has been achieved8' in good yields by the anodic oxidation of organic acids R'CO H in the presence of substrates of the type CH2=CR2Y where Y = CHO COMe C02Et or CN.The reaction was carried out in 8 moll-water-acetoni-trile solution. The electrolysis of a-chlorovaleric a-chlorocaproic and a-chloroisobutyric acids in methanol-water mixtures was shown89 to give chloro-esters and hydrogen esters together with small amounts of aldehydes and acetals. None of the Kolbe dimer was formed. The results were similar to those obtained for a-bromo-acids. The electrolysis of a-fluorocaproic and a-fluoroheptanoic acids gave high yields of the Kolbe dimer. The size of the halogen substituent obviously affects the dimerization steps.Kolbe oxidation of sodium glycidates (34;R = But or cyclohexyl) is reported" to give a/?-unsaturated ketones and a-methoxy-ketones. Scheme 13 shows the mechanism suggested by the authors for the decarboxylation and ring opening. This reaction was applied successfully to the steroidal sodium glycidate (35) which gave high yields of a/?-unsaturated ketone (36) and small amounts of the methox y-compound. C-Me I1 0 Me Scheme 13 88 M. Uhkir and D. Lelandais Chem. Comm. 1971 1369. 89 P. C. Arora and R. G. Woolford Canad. J. Chem. 1971,49 2081. 90 Y. A. Waters and B. Witkop J. Org. Chem. 1971 36 3232. Electro-organic Chemistry R R (35) (36) Nitrogen-containingCompounds.-The effect of electrode material on the reaction mechanism has been demonstrated in the anodic oxidation of aliphatic amines.Oxidation of secondary and tertiary amines at a glassy carbon electrode'' resulted in partial dealkylation with the formation of secondary and primary amines and the appropriate aldehydes. The oxidation mechanism involves an initial rate-determining abstraction of an electron from the lone pair of electrons on the nitrogen atom followed by a rapid deprotonation further oxidation and hydrolysis. The isolated products and the E+ us. cr* correlation support this view. A different mechanism has been postulated for the oxidation of aliphatic amines at a nickel anode.92 In this case the electrode takes part directly in the oxidation mechanism by the formation of a surface intermediate NiOOH.The oxidations proceed by a kinetically controlled mechanism involving hydrogen abstraction from the carbon Q to the functional group followed by rapid oxidation to the product. The rate-determining step is believed to be the reaction between the organic substrate and the surface intermediate. Anodic oxidation of aromatic amines and other nitrogen-containing compounds in different media has been the subject of numerous paper^'^^'' and a review.'00 In general no fundamentally new principles have emerged. The growing interest in applying electrochemistry to more complex organic systems is typified by the work of several groups on the electro-oxidation of natural products. Oxidative coupling of phenols is an important reaction in biogenesis and is frequently employed in natural product synthesis.With tradi- tional oxidative coupling reagents yields tend to be low and specificity in the direction of coupling may be poor. Bobbit and Hallcher'" have investigated the electro-oxidation of armepavine and some of its derivatives in 10% aqueous M. Masui and H. Sayo J. Chem. SOC. (B),1971 1593. 92 M. Fleischmann K. Korinek and D. Pletcher J. Electroanalyt. Chem. Interfacial Electrochem. 1971 31 39. 93 M. Breitenbach and K.-H. Heckner J. Electroanalyt. Chem. Interfacial Electrochem. 1971 29 309; 1971 33 45; P. G. Desider L. Lepri and D. Heimler ibid. 1971 32 225. 94 G. Cauquis and J. L. Cros Bull. SOC. chim. France 1971 3760 3765. y5 G. Cauquis H. Delhomme and D. Serve Tetrahedron Letters 1971 4645 41 13.9b G. Cauquis A. Rassat J. P. Ravet and D. Serve Tetrahedron Letters 1971 971. " M. Libert C. Coullet and S. Longchamp Bull. Soc. chim. France 1971 2367. " G. Barley D. Delahaye and C. Caullet Bull. SOC. chim. France 1971 3377 3082. 99 S. Huing and F. Linhart Tetrahedron Letters 1971 1273. loo G. Cauquis Pure Appl. Chem. 1971 25 365. lo' J. M. Bobbit and R. C. Hallcher Chem. Comm. 1971 543. K. Korinek and T. I;. W.McKillop acetonitrile with added sodium methoxide and quaternary ammonium perchlo- rate as supporting electrolyte. Armepavine (37 ;R = Me) and N-norarmepavine (37 ; R = H) undergo fragmentation reactions similar to enzymatic oxidation but N-ethoxycarbonyl-N-norarmepavine (37;R = C0,Et) yields carbonsarbon dimers and for the first time the carbon-oxygen dimer which on benzylation reduction and debenzylation gave dauricine (38).(37) (38) OMe I Me0 \ MeoqNMe NMe \ Me0 Me0Q' OMe 0 (39) Intramolecular couplings can also be effected by electro-oxidation as shown in the conversion of laudanosine (39) to a morphinandienone (40).'02 A yield of 52 % is reported representing a substantial improvement on normal chemical techniques whose yields seldom exceed 10%. Where a phenolic group exists oxidation presumably occurs at the phenoxide centre but in the course of the cyclization of the tetra-ether laudanosine oxidation of the dimethoxybenzene ring is proposed. In addition to an improved yield stereoselectivity has been observed in the oxidative couplings of yet another tetrahydro-isoquinoline (41).Chemical oxidation yields mixtures of the three enantiomeric pairs shown in Scheme 14 whereas electro-oxidation on a graphite felt electrode yielded 69 % of the SS-rot A pair only and 7% of carbon-oxygen dimer.'03 This striking difference in specificity is explained on the grounds of the steric constraints implied by radical coupling on the electrode surface. lo* L. L. Miller F. R. Sternitz and R. Falck J. Amer. Chem. Soc. 1971 93 5941. '03 J. M. Bobbit I. Noguchi H. Yagi and K. H. Weisgwaler J. Amer. Chem. SOC.,1971 93 3551. Electro-organic Chemistry Me Me I RS-pair MeN Me SS-rot A SS-rot B Scheme 14 Prompted by the interest in the enzymatic oxidations of the biologically important purines Dryhurst and Hansenio4 have extended their studies on the electro-oxidation of these systems.In general oxidation proceeds at the N(9)=C(8) double-bond but usually involves more complex secondary oxida- tions resulting in the production of the appropriately substituted alloxans allantoins and ureas. Miscellaneous 0xidatims.-The catalytic effect of different electrode materials and the mechanism of the anodic oxidation of carbohydrates have been discussed by Appleby and Van Drunen.”’ Rhodium and Pt-Ru alloy electrodes are more effective than Pt for glucose oxidation but the inverse is true for gluconic acid. The oxidation was found to be kinetically controlled the production or reaction of adsorbed OH radical with the carbohydrate being the rate-determining step depending on the substrate.Diacetone-2-keto-~-gulonicacid which is a key ‘04 G. Dryhurst and El. H. Hansen J. Electroanalyt. Chem. interfacial Electrochem. 1971 30 407 417; 1971 32 405. lo’ A. J. Appleby and C. Van Drunen J. Electrochem. SOC. 1971 118,95. K. Korinek and T.F. W.McKillop intermediate in ascorbic acid synthesis has been obtained in high yields by electro- chemical oxidation of diacetone-L-sorbose in the presence of bromide ions and either nickel or cobalt halides as catalysts. lo' A nickel(I1r) oxide and hypobromite both of which would be regenerable electrochemically have been proposed as oxidants. Several authors have reported mechanistic and product studies on the anodic oxidation of organic sulphur compounds.lo7-' O9 Th ioxanthone 10,lO-dioxide (42) a compound which for many years eluded preparation by traditional oxidation methods has now been produced in good yield by an electrochemical oxidation of thioxanthene in aqueous acet0nitri1e.l~~ An example of allylic rearrangement and participation of the phenyl group in the rupture of the C-I bond has been observed during the electro-oxidation of organo-iodides in acetonitrile.' lo Phenonium ion (43) which reacts with the solvent to form substituted acetamides in 1 1 ratio has been postulated to be an intermediate in this oxidation. Ph-CH,-CD,-NHCOMe + 0- Ph-CH2-CD2-I Ph-CD2 -CH2 -NHCOMe I\ H2C-CD2 (43) The introduction of specific functionality into organic compounds continues to receive attention.Several papers have been published dealing with anodic fluorination,' cyanomethoxylation,' l4 and thiocyanation and selenocy- '06 M. Y. Fioshin I. A. Avrutskaya A. I. Borisov and L. A. Chupina Electrokhimiya 1971 7 380. lo' K. Yoshida T. Saeki and T. Fueno J. Org. Chem. 1971 36 3671. lo* K. Uneyama and S. Torii Tetrahedron Letters 1971 329. log P. T. Kissinger P. T. Holt and C. N. Reilley J. Electroanalyt. Chem. Interfacial Electrochem. 1971 33 1. 'lo A. Laurent and R. Tardivel Compt. rend. 1971 272 C,8. 'I1 H. M. Fox F. N. Ruehlen and W. V. Childs J. Electrochem. SOC.,1971 118 1246. B. Chang H. Hanase K. Nakanishi and N. Watawabe Electrochim. Acta 1971 16 1179. V. S. Plashkin and Y.P. Dolnakov J. Appl. Chem. (U.S.S.R.),1971 44 1181. K. Yoshida and T. Fueno,J. Org. Chem. 1971 36 1523. Electro-organic Chemistry anation. A new process for continuous and efficient electrochemical fluorina- tion has been described by Fox et d."' High yields of fluorinated products from alkanes and some aliphatic chlorides have been achieved using a porous carbon electrode in KF-HF mixture at 100 "C. Carbon-carbon bond scission a common difficulty encountered in fluorination procedures was negligible in this system. 'lS G. Cauquis and G. Pierre Compt. rend. 1971 272,C 609.

ISSN:0069-3030    

DOI:10.1039/OC9716800297

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

9 Photochemistry By A. GILBERT Chemistry Department The University Reading THEvolume of literature concerned with the many and varied aspects of photo-chemistry continues to expand and this is reflected by the now annual increase in size of the Chemical Society’s Specialist Periodical Report’ on this topic. Ac- cordingly the present review is restricted to some of the publications from the 1971 literature which in the author’s opinion are significant in their own special- ized area or are of general interest. It may have been true in the past that organic photochemists did not pay sufficient attention to the mechanistic features of reactions. This criticism is rapidly becoming less true as judged by the detailed study which is now evident in a good proportion of reports from this area of the effects of solvent concentra- tion atmosphere quenchers and temperature on quantum yields.Concern over the possible involvement of ground-state complexes and/or excimers and exci- plexes in such processes also is increasing. The effect of heavy-atom solvents in enhancing the yield of dimeric products has been previously attributed to an increase in the rate of intersystem crossing. Work on the dimerization of coumarin now suggests that this is not the case as the enhanced formation of the cis-anti-cis cyclobutane dimer in CC14 is not accompanied by the expected increase in intersystem crossing.2a Formation of this dimer is a triplet process but the solvent effect seems to be that of increasing the fraction of coumarin triplets which dimerize.The cis-s~v~-cis dimer arises by a singlet process involving an excimer as previously postulated. Methanol is a favoured solvent in photochemical reactions but a change in media to this protic solvent can have a marked effect on the reaction pathways as several workers have reported. For example the formation of (1) from (2) in benzene has been previously noted but in methanolic solution the product is (3).2b This change in reaction is undoubtedly related to the ability of methanol to solvate the developing charge centres in the intermediate (4). Excitation of charge-transfer bands in molecular complexes is often a fruitful source of photochemical reaction and such a process has been studied with some ’ ‘Photochemistry,’ ed.D. Bryce-Smith (Specialist Periodical Reports) The Chemical Society London vol. 1 1970 470 pp.; vol. 2 1971 817 pp.; vol. 3 1972 876 pp. (a) R. Hoffman P. Wells and H. Morrison J. Org. Chem. 1971 36 102; (b) A. Padwa and E. Glazer Chem. Comm. 1971 838. 32 1 322 A. Gilbert Ph &Ph NXN H Ph toluene c~mplexes.~ Formation of (5) from the toluene-1,2,4,5-tetracyano-benzene complex is accounted for in terms of a proton transfer from a cation- radical to an anion-radical in the excited state of the complex by a process some- what reminiscent of the first step in the Birch reaction this is followed by the loss of HCN. There is seemingly no evidence for a ground-state complex in the toluene-tetramethylpyromellitate system but reaction ultimately resulting in the formation of (6) is suggested to involve an exciplex and a mechanism of proton transfer to the carbonyl group similar to the first step in the acyloin condensation.NcDcH2Ph Meo2cG NC CN Me0,C H Ph (5) (6) Consideration of orbital symmetry factors now seems to be a very necessary part of the interpretation of photoprocesses and a short elementary review dealing with this topic has been p~blished.~ An earlier suggestion concerning such considerations that the simple rule of ‘ground state forbidden = excited state allowed’ was more readily applicable than the more precise Woodward- Hoffmann postulatzs has been criticized by Michl who considers that this is an overgeneralization and cites the ground-state-forbidden (7) to (8) conversion which does not arise from the first excited singlet or triplet states but involves a higher tri~let.~ Cookson and co-workers have reported further examples of A.Yoshino M. Ohashi and T. Yonezawa Chem. Comm. 1971 97. H. Katz J. Chem. Educ. 1971 48 84. J. Michl J. Amer. Chem. SOC.,1971 93 523. Photo chemistry light-induced 1,3-allylic migrations with such systems as (9),6 but have pointed out from subsequent work with the optically pure dinitrile (10) the danger in uncritical extension to strongly perturbed derivatives of orbital symmetry rules which were devised from parent systems.' (7) Ph As may be expected the photochemistry of the carbonyl group has again attracted numerous workers and a multitude of reports concerned with reduction oxetan formation Norrish Type I and I1 reactions and sensitization processes have appeared.The original observation that the relatively short triplet lifetime of benzophenone in benzene indicates a possible specific quenching process which does not lead to significant reduction,' has received further consideration. It also appears that in this system not all the benzophenone consumed had been accounted for in terms of product. Complementary studies of flash photolysis and continuous irradiation of benzophenone in ultra-pure benzene have now been made and a primary hydrogen abstraction by the ketone triplet to yield ketyl and phenyl radicals is consistent with the observed products and inter- mediate~.~," Biphenyl had been previously observed but now benzpinacol and 4-biphenyldiphenyl carbinol have been detected and again the presence of the unidentified yellow compound is noted.Experiments with deuteriated solvents confirm the solvent origin of the biphenyl and an isotope effect consistent with primary hydrogen abstraction from the solvent is also observed. It is known that di-p-t-butyl substituents in benzophenone cause complication and a deviation from parent ketone behaviour in propan-2-01. Thus the effect on the ketone ' ' R. C. Cookson J. Hudec and M. Sharma Chem. Comm. 1971 107 108. R. C. Cookson and J. E. Kemp Chem. Comm. 1971 385. J. A. Bell and H. Linschitz J. Amer. Chem. SOC.,1963 85 528. A. V. Buettner and J. Dedinas J. Phys. Chem. 1971,75 187.lo J. Dedinas J. Phys. Chem. 1971 75 181. 324 A. Gilbert photochemistry of varying the size of the p-alkyl substituents has been investi- gated.' Short irradiation of (1 1) with R = Me Et or Pr' results in a clean con- version into the transient intermediate observed for the parent ketone and for which structure (12) has been suggested. At conversion of <50% this inter- mediate reacted with the ketone to yield acetone and the benzpinacol for R = Me R but at higher conversions for R = Et or Pr' a stable yellow species as with R = Bu' was formed in a competing process. It has been assumed that the products (except oxetan) from irradiation of acetone in olefins particularly cyclohexene may be accounted for by the formation of free ketyl and cyclohexenyl radicals.The new products (13) and (14) have now been found in this fundamental system and a different primary course of reaction has been proposed.12 A dual mechanism is now suggested which involves both the acetone triplet and an acetone<yclohexene exciplex. Seemingly the reaction of acetone with cyclo- octene and cyclo-octa-1,3-diene is not so complex and in both cases the cis and trans fused oxetans are formed.' The principal difference between the two reac- tions is that the olefin process occurs from the triplet state whereas that of the diene involves a singlet state as had been previously reported for the reaction of acetone with conjugated acyclic dienes.14 The involvement of the oxetan (15) in the formation of (16) from the reaction of benzophenone with 2,3-dimethylbuta- 1,3-diene had earlier been postulated,' and has now been verified by its isolation I' N.Filipescu L. M. Kindley and F. L. Minn J. Org. Chem. 1971 36 861. l2 P. Borrell and J. Sedlar Trans. Faraday SOC.,197 1 66 1670. l3 K. Shima Y. Sakai and H. Sakurai Bull. Chem. SOC.Japan 1971,44 215. l4 J. A. Barltrop and H. A. J. Carless Chem. Comm. 1970 1637. l5 J. Saltiel R. M. Coates and W. G. Dauben J. Amer. Chem. SOC.,1966 88 2745. Photochemistry 325 from the process.I6 The lack of detection of (15) earlier is attributed to its sen- sitivity towards acid. Oxetan formation has thus been studied with a wide range of ketones and generally triplet state reactions are encountered except in reactions with dienes (refs.13 and 14) and relatively few cases involving electron-deficient olefins. The oxetan-forming process has now been investigated with esters of aromatic carboxylic acids and olefins and dienes by a group of Japanese wor- kers.17,18 With 1,l-diphenylethylene tetramethyl pyromellitate yields a mono- oxetan as an intermediate which loses formaldehyde to form (17) in 95% yield. Ph / Similar reaction occurs with butadiene but with cyclo-octene as olefin the product is reported to be an unstable oxetan and reaction of this olefin with the triester of trimesic acid results in addition to the aromatic ring. The mechanism of the ester-oxetan reactions has been studied with dimethyl terephthalate and isophthalate with trimethyl ethylene and the involvement of exciplexes is clearly indicated.l8 Although @-unsaturated ketones readily form oxetans tropone is found to undergo a [8 + 21 cycloaddition forming (18) via the nn* triplet state.” The Norrish Type I reaction continues to be investigated with a wide range of carbonyl compounds. The hydrocarbon tetrahedrane remains elusive but forma- tion of acetylene propylene and but-2-yne from the tricyclopentanone (1 9) suggests that it may have been formed following the decarbonylation.20 A general photodecarbonylation of phenol lactones and carbonates (20) has been reported to yield the quinone methides o-quinones or o-thioquinones.21 Evi- dence for formation of the more unstable of these intermediates was obtained from low-temperature i.r. studies and their Diels-Alder reaction with electron- rich olefins.Type I reactions have also been observed for the naturally occurring l6 J. A. Barltrop and H. A. J. Carless J. Amer. Chem. SOC.,1971 93 4794. Y. Katsuhara Y. Shigemitsu and Y. Odaira Bull. Chem. SOC.Japan 1971 44 169. Is Y. Shigemitsu Y. Katsuhara and Y. Odaira Tetrahedron Letters 1971 2887. l9 T. S. Cantrell J. Amer. Chem. SOC.,1971 93 2540. lo H. Ona H. Yamaguchi and S. Masamune J. Amer. Chem. SOC.,1970 92 7495 0. L. Chapman and C. L. McIntosh Chem. Comm. 1971 383. 326 A. Gilbert OH-OX0 coronopilin (21),22 and siduloses (22) too are reported to yield decarbonylated products.23 Carbonyl compounds with y-hydrogens undergo a Norrish Type I1 process to given an enol and olefin.The reaction is one of the most widely studied mecha- nistically and a review of recent advances in this area was published within the year.24 The 1,4-biradicals produced by this process continue to stimulate interest and the properties of such radicals produced by different methods have been c~mpared.’~ In the Type I1 process alkyl ketones react from both the nn* singlet and triplet states whereas phenyl alkyl ketones do so only from the triplet state. It was thus of interest to examine the process with P-naphthyl alkyl ketones and with the n-butyl derivative the reaction was found to arise exclusively from the nn* singlet state.26 Surprisingly cyclobutanol formation which is the major process with corresponding phenyl and alkyl ketones was not observed in the present case it may thus be that the cyclobutanol arises mainly by a triplet process.Both singlet and triplet states are however involved in the inefficient Norrish Type I1 elimination from aromatic esters (23).27 Results from quenching studies show that certain of the esters [e.g. (23a)l react from the singlet state whereas others [e.g. (23b)l involve triplet intermediates. It is concluded that the main reason for such low efficiency of the process with aromatic esters is that a back hydrogen transfer occurs from the initially formed biradical. The analogy between the Type I1 photoelimination of carbonyl compounds and their McLaf- ferty rearrangement under electron impact has been commented upon in the past 0 (23) (a) R’ = R3 = H R2= Me (b)R’ = R2= Me,R3 = OH 22 H.Yoshioka T. H. Porter A. Higo and T. J. Mabry J. Org. Chem. 1971 36 229; J. Kagan S. P. Singh K. Warden and D. A. Harrison Tetrahedron Letters 1971 1849. ’’ P. M. Collins J. Chem. Soc. (0,1971 1960. 24 P. J. Wagner Accounts Chem. Res. 1971 5 168. ” L. M. Stephenson and J. I. Brauman J. Amer. Chem. Soc. 1971,93 1988. 26 N. C. Yangand A. Shani Chem. Comm. 1971 815. ’’ J. A. Barltrop and J. D. Coyle J. Chem. Soc. (B),1971 251. Photochemistry 327 (but see ref. 28). A further example of these comparative processes has been observed with P-ketoanilides which although in principle could yield the elimina- tion process or a Fries reaction photochemically give a quantitative yield of acetophenone and phenylisocyanate on photolysis this result is paralleled by electron impact studies.29 Many other elimination processes continue to be investigated and it is especially interesting to read of a useful photochemical route to ben~yne.~' The inter- mediate is generated by photolysis of phthaloyl peroxide and undergoes stereo- specific [2 + 41 and non-stereospecific [2 + 21 cycloadditions :such reactions are identical in symmetry properties with those found by conventional decomposi- tion of benzenediazonium-2-carboxylate.Di-n-methane rearrangements of non-conjugated dienes [i.e.(24)-+(25)]are still stimulating interest and Zimmerman and co-workers who have added much of the useful data to this area have continued their studies on the factors which affect or divert the process.Photolysis of 1,1,4-triphenyl-3,3-dimethyl-penta- 1,4-diene is found to yield 1 ,a-styryl-2,2-diphenyl-3,3-dimethylcyclopro-pane as the major product and the alternative di-n-methane rearrangement prod- uct 1-(2,2-diphenylvinyl)- l-phenyl-2,2-dimethylcyclopropane ' is not f~rmed.~ This rearrangement is discussed in terms of control by electron delocaliza- tion during the reaction and it is found to involve the excited singlet state. Reaction of the methylene analogues of 4,4-diphenyl- and 4,4-dimethyl-cyclo- hexadienones in the present process has also been considered and the observations are compared with those of the acyclic di-n-methane rearrangement^.^^ The dimethyl derivative yields (26) superficially by a process analogous to that of the dienone but with the hydrocarbon reaction occurs from the singlet rather than the triplet state.The diphenyl derivative differed in that phenyl migration oc-curred to yield cis- and trans-isomers (27) but again via a singlet pathway. Photolysis of the allylic alcohol (28)has been studied and a novel rearrangement elimination reaction is observed to yield o-terphenyl via it is suggested the 6,6- diphenyl bicyclo[3,1,0]hexene (29). 33 The irradiation of 1,1,2,2-tetraphenyl ethane has led to the discovery of a new reaction involving a 'di-n-ethane' *' M. M. Bursey D. G. Whitten M. T. McCall W. E. Punch h4. K. Hoffman and S. A. Benezra Org. Mass. Spectrometry 1970 4 157. 29 W. R. Oliver and L. R. Hamilton Tetrahedron Letters 1971 1837. 30 M. Jones and M.R. Decamp J. Org. Chem. 1971,36 1536. H. E. Zimmerman and A. A. Baum J. Amer. Chem. SOC., 1971.93 3646. 32 H. E. Zimmerman P. Hackett D. F. Juers J. M. McCall and B. Schroeder J. Amer. Chem. SOC.,1971,93 3653. 33 W. G. Dauben W. A. Spitzer and R. M. Boden J. Org. Chem. 1971 36 2384. 328 A. Gilbert R3 (26) R' = R2 = Me,R3 = H (27) R' = R3 = Ph,R2 = H Biphenyl and cis-and trans-stilbenes are the minor products and have been shown to result by such a rearrangement whereas formation of (30) the major product has possibly the same origin but studies at present are in- conclusive. The conversion of bicyclo[2,2,l]hepta-2,5-dienesinto quadricyclanes (31) is a well-known and general process largely because of the research efforts of Prinzbach and co-workers.Such conversion with (32)is reported to be a singlet process even in the presence of trans-~iperylene,~~ and the rearrangement is found to be non-~oncerted.~~ Direct irradiation of such phenyl-substituted diene esters as (33)yields the appropriate quadricyclane whereas acetone sensiti- zation leads to tricyc10[3,2,0,0~~~]heptene derivatives uiua di-n-methane (31) (32) R' = R2= H,R3 = R4= Ph (33) R' = R2 = Ph,R3 = C02Me,R4 = H Formation of 'caged' compounds continues to be of interest and has been reported for two Diels-Alder adducts of cy~lo-octatetraene.~~,~~ Diene-p-quinone adducts have always been favoured compounds for such investigations 34 J. A. Ross W. C. Schumann D. B. Vashi and R.W.Binkley Tetrahedron Letters 1971 3283. 35 G. Kaupp and H. Prinzbach Chem. Ber. 1971 104 182. 36 G. Kaupp Angew. Chem. Internat. Edn. 1971 10 273. 37 H. Prinzbach and M. Thyes Chem. Ber. 1971 104,2489. 38 W. G. Dauben C. H. Schallhorn and D. L. Whalen J. Amer. Chem. SOC.,1971 93 1446. 39 L. A. Paquette J. Amer. Chem. SOC.,1970 92 5765. Photochemistry but it seems that a cyclic diene must be used in the original thermal process to ensure a successful light-induced ‘caging’ reaction since the non-bridged adduct from p-benzoquinone and butadiene only yields polymer on photolysis. With light of A > 340nm however the process is more specific leading to (34) and (35).40 Compound (34) possesses a previously unknown carbon skeleton but formation of (35) provides a facile entry into copaborneol ring systems.Intra- molecular photocyclization is also reported for the Diels-Alder adduct of cyclopentadiene and 1,4-naphthoquinone :41 in this case the product (36) shows that a [6 +21 1,2-cycloaddition to the aromatic ring has occurred. The photochemistry of aromatic molecules generally has again this year attracted much attention. The photoisomerization of benzene into the ‘Dewar’ isomer is now reported to arise from the S state of benzene by a symmetry- allowed process and this appears to provide the first example of a non-dissociative reaction from an upper singlet state.42 The involvement of the valence bond isomer benzvalene in the photochemistry of benzene in the presence of acids and water has been commented upon by two groups.Berson and Hasty have ration- alized the observations and products from their work in acidic solution as arising from acidolysis of ben~valene,~~ and workers in the Argonne Laboratories have again sorted out a problem in benzene photochemistry by re-investigating its reactions in aerated water.44 The product from this latter reaction is now found to be penta-1,3-diene-l-carboxylateand not 2-formyl-4H-pyran as previously reported and oxygen is not essential to the process. In the presence of the strong acid CF3C0,H the photochemistry of benzene is further modified and irradiation of this system is reported to yield am-trifluoroacetophenone as the primary product which subsequently yields the meso-pinacol and trifluoro- methyl diphenyl carbin01.~~ Until recently the photoaddition of simple olefins to benzene had essentially only been found to yield products (37) of a formal 1,3-addition.Three groups of workers have carried out further studies on this topic and describe that as well as ‘O J. R. Scheffer J. Trotter R. A. Wostradowski C. S. Gibbons and K. S. Bhandari J. Amer. Chem. Sor. 1971 93 3813. 41 A. S. Kushner Tetrahedron Letters 1971 3275. 42 D. Bryce-Smith A. Gilbert and D. A. Robinson Arzgew. Chem. 1971 83 803. 43 J. A. Berson and N. M. Hasty J. Amer. Chem. SOC.,1971 93 1549. 44 L. Kaplan L. A. Wendling and K. E. Wilzbach J. Amer. Chem. SOC., 1971,93 3821. 4s D. Bryce-Smith G. B. Cox and A. Gilbert Chem. Comm. 1971 914. 330 A.Gilbert 1,3-type products both 1,2-46,47 and 1,4-46,48 cycloaddition processes occur. Formation of the 1,2-adducts is favoured by high olefin concentrations and with some olefins quantum yields for the process are high but the adducts are generally photolabile which limits their isolation.46 With tetramethylethylene as olefin the major product (38)is that resulting from an ‘ene type’ process and its formation is favoured in proton donor solvent~.~’ More and more workers are concerning themselves with the effect of solvents and acids on the course of photo-reactions. Thus formation of (39) from tertiary amines and benzene is greatly accelerated in the presence of a proton donor,49 and the analogous product (40)from diethyl ether and benzene is only formed in the presence of acid.50 (39) x = NR; (40)X = OEt R = Me In the past there has been some disagreement as to the structure of the photo- dimer of p-alkoxynaphthalenes.The fact that the dimers revert to the monomers on dissolution has suggested to some workers that crystal forces contribute significantly to dimer ~tability.~’ This aspect has been investigated and naphtha- lene-2-carbonitrile has been dimerized in hexane-benzene solution. Unlike the other naphthalene derivative dimers the present dimer is suficiently stable for its n.m.r. spectrum to be recorded and only products of 1,4-1,4-type dimerization are consistent with the data. Such a mode of reaction had been originally deduced for the P-alkoxy-derivatives. Topochemical control in photo-reactions has been studied for both trans-cinnamic acid and anthracene dimerizations.Formation of the trans-dimer from 9-cyanoanthracene is however not in accord with such an approach. A detailed examination of this system has led Cohen and co-workers to suggest that dimeriza- tion occurs within stacking fault regions (bounded by dislocations) in which the monomer molecules are in a trans ~rientation.~~ Some sixteen years ago the photolability of the nitrobenzene-olefin system was described and now de Mayo and co-workers following their preliminary 46 K. E. Wilzbach and L. Kaplan J. Amer. Chem. Soc. 1971 93 2073. 47 D. Bryce-Smith B. E. Fougler A. Gilbert and P. J. Twitchett Chem. Comm. 1971 794. 48 R. Srinivasan I.B.M. J. Res. Develop. 1971 15 34.49 D. Bryce-Smith M. T. Clarke A. Gilbert G. Klunklin and C. Manning Chem. Comm. 1971 916. D. Bryce-Smith and G. B. Cox Chem. Comm. 1971 915. 5’ T. W. Mattingly J. E. Lancaster and A. Zweig Chem. Comm. 1971 595. ’’ M. D. Cohen Z. Ludmer J. M. Thomas and J. 0. Williams Proc. Roy. SOC.,1971 A324,459. Photochemistry 331 communication in 1968 of this interesting process have published full details and have described the isolation at low temperature in a pure crystalline form of the previously postulated 1,3,2-dioxazolidine intermediates (41).53 Evidence is presented to show that the addition proceeds via the nn* triplet state in a two- step electrophilic process. Modification of the photochemistry of nitrobenzene by complexation has been studied by Trotter and Testa who find that although the uncomplexed species yields phenylhydroxylamine in propan-2-01 and is inert in cyclohexane the complex with boron trichloride in cyclohexane yields nitrosobenzene H3BO3 and chlorocyclohexane.54 N.m.r.studies indicate that the co-ordination is confined to the nitro-group. Nitrobenzenes with ortho bulky substituents provide interesting compounds for study since intermolecular hydrogen abstraction by the nitro-group should be hindered and an alternative pathway of intramolecular abstraction is pro- vided. With 2,6-dialkyl derivatives two types of process are reported the photoreduction and nitro-nitrite rearrangement are suggested to arise from the triplet state whereas singlet intermediates are postulated for the intramolecular oxygen transfer involving CI-and 0-attack on the alkyl ~ide-chain.’~ Dopp has studied the o-t-butylnitrobenzenes in detail and has expanded his earlier results as well as reporting on mechanistic considerations.56 The processes have been examined in a series of common solvents when the indolene is formed in the presence of amines solvent-derived products are obtained. Crystalline 173,5-tri-t-butylnitrobenzene yields a variety of product^.^' The field of photo-oxidation processes is large and is the subject of numerous publications each year involving a wide variety of organic compounds. Reports of the formation of dioxetans from oxidation of electron-rich oiefins last year however must have interested all photochemists particularly because of the involvement of such compounds in certain chemiluminescence reactions.58 Inevitably the process has now been extended to other systems and dioxetans have been isolated from p-dioxan and 173-dioxole at -78 “C,and their n.m.r. spectra have been recorded.59 Interest in the use of photochemistry in synthesis continues of course par- ticularly with natural products. Seemingly however even the most well-known 53 J. L. Charlton C. C. Liao and P. de Mayo J. Amer. Chem. Soc. 1971 93 2463. 54 W. Trotter and A. C. Testa J. Phys. Chem. 1971 75 2415. 55 Y. Kitaura and T. Matsuura Tetrahedron 1971 27 1583. 56 ’ D. Dopp Chem. Ber. 1971 104 1035 1043 1058. D. Dopp and K. H. Sailer Tetrahedron Letters 197I 276 1. ’* P. D.Bartlett and A. P. Schaap J. Amer. Chem. Soc. 1970 92 3223; S. Mazur and C. S. Foote ibid. p. 3225. 59 A. P. Schaap Tetrahedron Letters 1971 1757. 332 A. Gilbert photosynthetic procedure of oximation is not fully understood and further evidence against a free-radical chain mechanism involving C1. has been re-ported. ' It is again encouraging to see the amount of effort which is being devoted to the sociological aspects of photochemistry and research into the degradation of herbicides pesticides etc. continues as does the concern over the medical and meteorological aspects of photochemical air pollution and smog formation6 M. W. Mosher and N. J. Bunce Cunud. J. Chcm. 1971,49 28. J. F. McKellar and P. H. Turner Phorochem. and Phorobiol.1971 13 437; P. E. Joosting Chem. Weekblad 1971 67 1; J. A. Wisse ibid. p. 19; J. Van-Ham and H. Nieboer ibid. p. 15.

ISSN:0069-3030    

DOI:10.1039/OC9716800321

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

10 Alicyclic Compounds By B. T. GOLDING Department of Molecular Sciences University of Warwick Coventry CV4 7AL and A. P. JOHNSON The Polytechnic of North London Holloway Road London N7 806 1 Topographical Analysis General.-The proceedings of a symposium on conformational analysis held at Brussels in September 1969 have now been published. ‘y2 These publications provide an excellent survey of the current state of conformational analysis (or topographical analysis as Prelog3 suggests we should now call it). Calculations.-Several years ago Liehr‘ described some familiar terminology for conformers -twist-chair twist-boat etc.-as ‘mentally deficient’ and pleaded for its replacement by precise mathematical specifications. A relatively simple mathe- matical treatment has now been devised5 for cyclohexane which when coupled with calculations based on structural and vibrational data leads to conformational energy maps that provide a useful picture of the topological course of chair-chair interconversion.An important series of papers‘ describes the development of an improved force field for ‘molecular mechanics’ calculations and its application to the calculation of geometries and energies of a wide variety of hydrocarbons. The agreement achieved between computed and measured parameters is very im- pressive (bond lengths usually within 0.001 nm angles within lo). Strain energies were also assessed and their values agree well with those calculated by Schleyer [cf Aiinual Reports(B),1970,67,365] However Allinger‘ disagrees with Schleyer’s ‘ Various authors Piiw Appl.Chem. 1971 25 465-666. ‘Conformational Analysis Scope and Present Limitations,’ ed. G. Chiurdoglu Academic Press New York 197 1. V. Prelog p. 465 of ref. 1. A. D. Liehr J. Phys. Chem. 1963 67 471 (footnote 19). H. L. Strauss J. Chern. Ediic. 1971 48 221; H. M. Pickett and H. L. Strauss J. Amcr. Chem. Soc.. 1970 92 728 1. N. L. Allinger M. T. Tribble M. A. Miller and D. H. Wertz J. Aiuer. Chein. Soc. 1971 93 1637. i_ N. L. Allinger B. J. Gorden I. J. Tyminski and M. T. Wuesthoff J. Org. Chern. 1971 36 739. N. L. Allinger and M. T. Wuesthoff J. Org. Chein. 1971 36 2051. N. L. Allinger and F. Wu Tetrahedron,1971 36 739. 333 3 34 B. T. Golding and A. P. Johnson suggestion that across-ring C-C repulsions are the source of strain in cyclo- hexane and adamantane.According to Allinger,6 the main cause of this strain is repulsive vicical H-H interactions ( +0.42 kcal mol- each) and not C-C or C-H interactions since these are calculated to be slightly attractive (-0.13 and -0.05 kcal mol -I respectively). These effects render 1,3,5,7-tetramethyladamantane (calculated strain energy of 2.07 kcal mol-') less strained than adamantane (6.81kcal mol-I) whilst diamantane is much more strained (10.34 kcal mol- '). Allinger's group have also synthesized all possible perhydr~phenanthrenes~ and perhydroanthracenes,* and four androstanes' (5a,14a- 5a,14fi- 5/3,14a- and 5/3,14p-) [cf (1) which shows the 5a,14p isomer]. Relative energies within each group were measured by equilibration over palladium and compare favourably with calculated values (N.B.the order of stability found by both methods applied to androstanes is 5a,14P- > 5/?,14p-> 5a,14a-> 5/3,14a-).It is pointed outg that the calculations required 204 minutes of computer time for the androstanes were 10-100 times less expensive than the experimental work involved in their synthesis and equilibrations and gave structural parameters as a bonus. An excellent review" of the ab initio SCF LCAO MO method for the calcula- tion of conformations and their interconversion barriers has appeared. This method has been used to compute electron density maps for cyclopropane which illustrate well its bent bonds.' '*l Semi-empirical calculations (INDO type) suggestI3 that in a series of trans-2-vinylcyclopropylcarbinylderivatives (2) conjugation between the n-bond and the carbinyl centre is present in only one (2) R = Me CH,.CH2+,CF,' CF,. or BH case (2;R = CH +) but even then is of small magnitude. The MIND0/2 method has been used' to calculate activation energies for the degenerate rearrangements (constitutional topomerizations)' ' of bullvalene (3) barbaralene (4) and semi- bullvalene (5) [calculated values (experimental values bracketed) 11.3 (1 1.8 and 10 J.-M. Lehn in ref. 2 p. 129. I1 R. M. Stevens E. Switkes E. A. Laws and W. N. Lipscomb J. Ainu. Chern. Soc. 1971 93 2603. 12 H. Marsmann J.-B. Robert and J. R. Van Wazer Tetrahedron 1971 27 4377. 13 L.D. Kispert C. Engelman C. Dyas and C. U. Pittman J. Atner. Chem. Soc. 1971 93 6948. 14 M. J. S. Dewar and W. W. Schoeller J. Amer. Chem. SOC.,1971 93 1481. 15 See G. Binsch. E. L. Eliel and H. Kessler Angew Chem. Internal. Edn. 1971 10 570. 335 Alicyclic Compounds (3) X = CH=CH (4)X = CH (5) X = direct bond 12.8) 5.9 (8.6) and 2.3 (indeterminate by n.m.r.) kcal mol-' respecJively]. The decreaseinactivationenergyobservedonpassingfrom(3) to(4) to(5) i~suggested'~ to be due to increasing release of strain (cf:calculated distances r) and decreasing antibonding 1,4-interaction (cf distances s) in the transition state (6). The question is raised as to what modifications of semibullvalene might produce an isolable non-classical mesovalent system.r S 1.626 2.608 (3) 1.720 2.680 (4) 1.752 2.806 (5) Dewar14 implies that the calculations are so quick and reliable that they obviate synthetic exploration toward such molecules! In a later communication,' he presents the results of a calculation on a diazasemibullvalene which suggest that it will exist as the non-classical structure (7). In a beautifully illustrated paper by R. Hoffmann,' the problem of stabilizing a non-classical semibullvalene is explored using orbital symmetry arguments supported by extended Huckel F F calculations. It is concluded that a molecule of type (8) should be non-classical (as shown). A synthesis of either (7) or (8)is awaited with interest. Synthetic (and other) chemists may also find stimulation in an important paper'* entitled 'Symmetry topology and aromaticity' which considers many novel alicyclic structural types and their potential aromatic properties.Other Valence Tautornem.-The problem of explaining the position of the norcaradiene cycloheptatriene equilibrium in certain derivatives of the parent molecules continues to sustain interest [cf Annual Reports (B) 1970 67,3701. '' M. J. S. Dewar Z. Nahlovska and B. D. Nahlovsky Chern. Comm. 1971 1377 R. Hoffmann and W.-D. Stohrer J. Arner. Chern. SOC.,1971 93 6941. M. J. Goldstein and R. Hoffmann J. Arner. C'hem. So<,.,1971 93 6193. B. T. Golding and A. P.Johnson Whilst new equilibria have been discovered ' and octachlorocycloheptatriene has been shown to be a triene,20 perhaps the most intriguing current results are those of Roberts,21 who investigated equilibria between (9a) and (9b) (lOa) and (lob) and (lla) and (llb).Ar C0,Me 0 ?YMe (9a) Ar = Ph (9b) (10a) Ar = p-methoxyphenyl (lob) (lla) Ar = p-nitrophenyl (1 lb) The enthalpy for the reaction norcaradiene 3cycloheptatriene increases in the order (10) < (11) < (9). Roberts2' concludes that none of the existing theories ex- plain his results convincingly. A study22of equilibria in barbaralones has given A B (12) R' = D,R2 = H (55.5XB) (13) R' = H R2 = Me (B predominates) (14) R' = Me R2 = H (76.6% A) (1 5) R' = H R2 = D (A predominates) the results shown [(12H15)],for which an explanation is promised. The 'H n.m.r. spectroscopic properties of dimethyl cyclo-octatetraene- 1,2-dicarboxylate are con- ~istent~~ with the dominance of conformer (16) over (1 7).When the diacid (I 8) R' (16) R' = H R2 = R3 = C02Me @)--~2 (17) R3 = H,R' = R2 = C0,Me (18) R' = H,R2 = R3 = C02H (19) R3 = H,R'R2 = -CO-O-CO- R3 '' W. Betz and J. Daub Angew. Chem. Internat. Edn. 1971 10. 269 H. Diirr and H. Kober ibid. p. 342; H. Giinther B. D. Tunggal M. Regitz H. Scherer and T. Keller ibid.,p. 563. K. Kusuda. R. West and V. N. M. Rao J. Amer. Chem. SOC.,1971. 93 3627. 21 G. E. Hall and J. D. Roberts J. Amer. Chetn. SOC.,1971 93 2203; see also E. Ciganek ibid. p. 2207. 22 J. C. Barborak S. Chari and P. von R. Schleyer J. Amer. Chetn. SOC.,1971 93 5275. 23 D. Bryce-Smith A.Gilbert and J. Grzonka Angew. Chem. Infernat. Edn. 1971 10 746. Alicyclic Compounds 337 is treated with dicyclohexylcarbodi-imideit forms the corresponding anhydride which is unstable but does not rearrange to (19). Structure Determination.-Mainly by N.M.R . Spectroscopy. Reviews have been published on double-resonance technique^,^^ on 3C n.m.r. spectroscopy,2 and on the nuclear Overhauser effect,26 and include many examples of applications in the field of alicyclic chemistry. Using an approach based on the McConnell equation Allinger and his co-~oikers~~ have developed a successful semi- empirical method for calculating chemical shifts in hydrocarbons [cf.observed and calculated data for norbornane (20)]. 'Its improvement over earlier approaches lies in the recognition of the importance of van der Waals effects.Among the glut of papers on shift reagents are reports of useful new reagent^^',^^ and some instructive application^.^'-^^ There has been a degree of uncertainty with respect to the positioning of a lanthanide atom relative to a molecule under examination. It has now been shown3 that non-linear regression analysis permits an estimation of that position of the lanthanide which gives the best fit when the shift data are plotted against (3cos2 8 -l)r-3. In this way excellent linear correlations were obtained for shifts induced by Eu(tmhd),* with ada- mantan-2-01 and trans-4-t-butylcyclohexanol.This technique may be useful in structure determination. The importance of the angle factor is illustrated by specific upfield shifts of H(3') and H(4')caused by Eu(tmhd) with the cis-isomer of 3-(cr-naphthyl)-1,3,5,5-tetramethylcyclohexanol, which therefore exists as con- former (2 ICH 6 1.21 (calcd.1.195) H 1.49 (1.341) H 1.18(1.257) Since the range of I3C chemical shifts is approximately 10 times greater than that of protons it is more likely that distinct signals will be observed for con- 24 W. von Philipsborn Angew. Chern. Internat. Edn. 1971,10,472. " E.Breitmaier G. Jung and W. Voelter Angew. Chem. Internat. Edn. 1971 10,673; E.W. Randall Chem. in Britain 1971 371. *' G.E. Bachers and T. Schaefer Chem. Rev. 1971,71,617. *' M. T. Tribble M. A. Miller and N. L. Allinger J. Amer. Chem. SOC.,1971,93 3894. 2n J. K.M. Sanders and D. H. Williams J. Amer. Chem. Soc. 1971,93 641. 29 R. E. Rondeau and R. E. Sievers J. Amer. Chem. SOC.,1971,93 1522. 30 R. von Ammon R. D. Fischer and B. Kannelakopulos Chem. Ber. 1971,104,1072. 31 S.Farid A. Ateya and M. Maggio Chem. Comm. 1971 1285. 32 B. L. Shapiro J. R. Hlubucek G. R. Sullivan and L. F. Johnson J. Amer. Chem. Soc. 1971,93 3281. * tris-(2,2,6,6-tetramethylheptanedionato)europium. 338 B. T. Golding and A. P. Johnson formational isomers under conditions of slow exchange. With this in mind and helped by a variable-temperature Fourier-transform instrument the axial con- former of methylcyclohexane could be detected at -110"C.33 On cooling from -65 to -162 "C the I3C n.m.r. spectrum of cyclononane changes from a single peak to two sharp singlets (ratio 1 :2) separated by 8.9~.p.m.~~ This is consistent with the dominance of the TBCconformer (22) assuming that fortuitous equivalence is not concealing signal(s) from other conformer(s).The TBC form is that independently calculated by Hendrickson Lifson and Allinger* to be most stable [cf also Annual Reports (B),1970,67 371 and the results of an X-ray study on cyclononanone-HgCI reported below]. Low-temperature 3C n.m.r. spectro- scopy has also been used3 to study conformational inversion in dimethylcyclo- hexanes cis-decalin and cis-9-methyldecalin. Quantitative measurements of exo-endo equilibria in norbornanes that the conformational free energy differences for the groups Me (0.89 kcal mol-I) OH (1.05),CO,Me (0.65) and NO (1.38) bear no relationship to their A-values (1.70,0.95 1.27 and 1.20 kcal mol- ',respectively).A new compilation of A-values is available3 [recent A-value determinations include those for azido- (0.80 f0.06 kcal mol- in CS,),38 trimethylsilyloxy- (0.89 kcal mol- 1),39 and phthalimido-groups (3.8-3.9 kcal mol- By careful measurement of coupling constants and using the Karplus equation to derive dihedral angles two gro~ps~',~' have attempted to determine the in-fluence of bulky substituents on the shape of the cyclohexane ring in solution. Booth and Thornburrow4' interpret their results for a series of cis-l-substituted-4-phthalimido-cyclohexanes in terms of ring flattening. A Dutch group4 explain their results for t-butylcyclohexane by postulating increased puckering at the t-butyl 'end' which causes H(l) to lean inwards.This effect is not seen with methylcyclohexane (23) but both this compound and t-butylcyclohexane (24) show a substantial upfield shift for H(2,) [actual chemical shifts 6 0.90 for (23) 0.87 for (24); cf 1.20 for cyclohexane]. In the case of (24) but not (23) H(4,) is also shifted upfield (appears at 6 1.10). The shift for H(2,) is not convincingly rationalized whilst that for H(4,) again shakes one's confidence in the practice of assessing chemical shifts in equilibrating conformers by using those in the corre- sponding 'frozen' t-butyl derivatives. Dissolution of several 2-halogeno- and 2,6-dihalogeno-cyclohexanonesin a 'superacid' medium at -60 "C has a remarkable effect on their conformational preferences because of the creation of a strong hydrogen-bond which bridges " F.A. L. Anet C. H. Bradley and G. W. Buchanan J. Amer. Chrin. Soc. 1971,93 258. 34 F. A. L. Anet and J. J. Wagner J. Aiwr. Cheiri. Soc. 1971 93 5266. 35 D. K. Dalling D. M. Grant and L. F. Johnson J. Amer. Chein. SOC. 1971 93 3678; H.-J. Schneider R. Price and T. Keller Angew. Chrm. Inrprnat. Edn. 1971 10. 730. 36 R. J. Ouellette J. D. Rawn and S. N. Jreissaty J. Amer. Chem. Sor. 1971 93 71 17. 37 F. R. Jensen and C. H. Bushweller Adu. Alicyciir Chem. 1971 3 139. 38 D. N. Jones K. J. Wyse and D. E. Kirne J. Chein. SOC.(C),1971 2763. 39 J. P. Hardy and W. D. Curnming J. Atner. Chetn. SOC.,1971 93 928. H. Booth and P. R. Thornburrow J.Chem. SOC.(B) 1971 1051. " J. D. Rernijnse H. Van Bekkum and B. M. Wepster RPC'.Trui,.chim. 1971 90 779. * c-1footnotes 5-7 in ref. 34. Alicyclic Compounds 339 oxygen to halogen.42 For example 2-fluoro-6-methylcyclohexanone ordinarily prefers to exist as conformer (25) but is converted into (26) on protonation. Certain trans-isomers [e.g. (27)] of 2-alkyl-2-methyl-4-t-butylcyclohexanones fluoresce more strongly than the corresponding cis-isomers because intra- molecular y-hydrogen abstraction which deactivates the S state of the ketone occurs more easily in the cis-i~omer.~~ This promises to be a useful method for structure determination in a specific area. .. F .H'+ Me (25) By Electron and Neutron Difraction X-Ray Crystallography and Microwave Spectroscopy.A large number of exact structure determinations have been carried out (e.g. refs. 44-57). Among notable features of the findings are the following :the F-C -F angle (1 12.2") in hexafluorocyclopropane is smaller than the H-C-H angle in cyclopropane (115.1°) but accords with the expectation that the electronegative fluorine atoms will decrease the s-character of the hybrids at carbon directed towards F;44two four-membered rings in (28) are puckered whilst the others are planar46 (this paper contains a useful summary of 42 R. Jantzen and J. Cantacuzene Tetrahedron Letters 197 1 2925. 53 K. Dawes N. J. Turro and J. M. Conia Tetrahedron Letters 1971 1377. 54 J. F. Chiang and W. A. Bernett Tetrahedron 1971 27 975.45 H. J. Mair and S. H. Bauer J. Phys. Chem. 1971 75 1681 (perchlorocyclopropene). 46 J. P. Schaefer and K. K. Walthers Tetrahedron 1971 27,5281. 47 H. J. Geise and F. C. Mijlhoff Rec. Trac. chirn. 1971 90 577. an J. W. Bevan and A. C. Legon Chern. Cotnm. 1971 1136. 4') C. H. Chang and S. H. Bauer J. Phys. Chem. 1971 75 1685 (perfluoro- and per- chlorocyclopentadiene). 50 H. J. Geise H. R. Buys and F. C. Mijlhoff J. Mol. Siructure 1971 9 447 (cyclohexane and methylcyclohexane). 51 V. J. James and J. F. McConnell Tetrahedron 1971 27 5475. 52 D. H. Faber and C. Altona Chern. Camrn. 1971 1210. s3 S. Dahl and P. Groth Acta Chern. Scund. 1971 25 1114. 51 0. Ermer and J. D. DunitL Chern. Cornrn. 1971 178. 55 A. Almenningen B. Andersen and B.A. Nyhus Acra. Chern. Scund. 1971 25 1219. 56 A. Yokozeki and K. Kuchitsu Birll. Chetn. SOC.Japan 1971 44 1783. 57 0. Ermer R. Gerdil and J. D. Dunitz Helv. Chim. Actu 1971 54 2476. 340 B. T. Golding and A. P.Johnson X-ray structural data for cyclobutanes) ; cyclopentanone is less puckered than cyclopentane ;47 cyclopent-3-enone is flat ;48 there is slight ring-flattening in cyclohexyl toluene-p-sulphonate ;5 in cis7trans-2,5-di-t-butylcyc10hexy1 toluene-p-sulphonate the H atoms at C(2) and C(5) tilt towards the centre of the ring in order to allow unusually large exocyclic angles (1 13-1 18")to the t-butyl groups and there is imperfect staggering about the C(2)-But and C(S)-Bu' bonds;52 in its 1 1 adduct with HgCl, cyclononanone is present as the TCB form (29)53 (c$ discussion on cyclononane on p.338); neutron diffraction analysis reveals a transannular separation of 0.191 nm between two hydrogen atoms in cyclo- decane-176-diol;54 another electron diffraction study of bicycle[ l,l,l]pentane has given results55 at variance with those previously reported [see Anrzual Reports (B) 1970 67 3721; bicyclo[2,2,2]octene and bicyclo[2,2,2]octadiene both have C, symmetry ;56 the structure of [4,4,4]propellane is all-chair but the central C-C bond (0.1556 nm) is significantly longer than Information on ring puckering inversion barriers and conformational energies has been gained from i.r. and Raman studies of some derivatives of cy~lobutane,~~ and bromo- and chloro-cyclopentane.60 cyclopentan01,~~ 2 Synthesis Novel Hydrocarbons.4ne of the recurrent themes in the synthesis of alicyclic compounds has been the search for new hydrocarbons possessing structural features which promise exceptional reactivity.The past year has seen further progress in this area. The pioneering work of van Tamelen which led to the synthesis of Dewarbenzene,61 bicycl0[2,1,O]pent-2-ene,~~ and cyclodecapenta- ene63 in the sixties has now been fully described. Other compounds of this ilk whose synthesis has been claimed include A'*4-bicyclo[2,2,0]hexene(30),which can be detected spectroscopically at -52 "C (and trapped by cyclopentadiene) but which dimerizes to (31) at -20 0C;64A'.2-bicyclo[2,2,1]heptene (eroding still further Bredt's rule) which cannot be isolated but can be trapped by furan ;65 and 1-methylpentalene (32) which can be detected spectroscopically at -196°C but dimerizes at -100°C.66 A simple new route to benzvalene (33) utilizes the reaction of lithium cyclopentadienide with methylene chloride and methyl-lithi~m.~~ While this route permits the preparation of (33) in bulk this should only be attempted with expendable co-workers since even '' F.A. Miller and R. J. Capwell Spectrochitn. Acta 1971 27A 11 13; J. R. Durig and W. C. Harris ibid. 649; J. R. Durig J. N. Willis and W. H. Green J. Chem. Phys. 197 1 54 1547. 59 J. R. Durig J. M. Karriker and W. C. Harris Spectrochirn. Acta 1971 27A 1955. 6o W. C. Harris J. M. Karriker and J. R. Durig J. Mol. Srructure 1971 9 139. 61 E.E. van Tamelen S. P. Pappas and K. L. Kirk J. Ainer. Chern. Sac. 1971 93 6092. 62 E. E. van Tamelen J. I. Brauman and L. E. Ellis J. Atner. Chem. Sac. 1971 93 6145. 63 E. E. van Tamelen and R. H. Greeley Chem. Comm. 1971; 601; E. E. van Tamelen and B. C. T. Pappas J. Amer. Chem. Soc. 1971 93 61 11 ; E. E. van Tamelen T. L. Burkoth and R. H. Greeley ibid. p. 6120. 64 K. B. Wiberg G. J. Burgmaier and P. Warner J. Amrr. Chem. SOC.,1971 93 246. " R. Keese and E.-P. Krebs Angew. Chetn. Internat. Edn. 1971 10 262. 66 R. Bloch R.A. Marty and P. de Mayo J. Atner. Chern. Soc. 1971 93 3071. 6' T. J. Katz E. J. Wang and N. Acton J. Amer. Chem. SOC.,1971 93 3782. Alicyclic Compounds 341 m 8 small quantities of (33) can explode violently. Cycloheptyne itself enjoys only a fleeting existence but a substituted cycloheptyne (34) has now been shown to be more stable.Oxidation of the bis-hydrazone (35) leads to (34) which has a half- life of one day in solution (0.2mol I-' in CC1,).68 Me 0H NNH Me Me Me Me The isolation of the [lOIannulenes (36) and (37) in the crystalline state by Masamune and his collaborators is a superb practical a~hievement.~~ These compounds were prepared by a modification of an earlier procedure and isolated by chromatography at -80 "C! Their properties indicate that they are clearly not aromatic. Other (CH), hydrocarbons which have been synthesized for the first time are (38) (39) and (40). Tricyc10[4,4,0,0~,~]deca-3,7,9-triene (38) is thought to be a key intermediate in the thermal rearrangements of several (CH), hydrocarbons.It was synthesized by a route which might be extended to permit the synthesis of other compounds which are formally Diels-Alder adducts of A. Krebs and H. Kimling Angew. Chern. Internat. Edn. 1971 10 509. 69 S. Masarnune K. Hojo K. Hojo G. Bigam and D. L. Rabenstein J. Amer. Chem. SOC.,1971 93 4966. B. T. Golding and A. P. Johnson benzene.70 'Hypostrophene' (39) was prepared by the action of sodium on (41),7 which was itself prepared in several steps from cyclobutadieneiron tricarbonyl and benzoquinone. (39) undergoes a degenerate Cope rearrangement at 35 "Cwhich has been detected by deuterium labelling. (40) is a bridged cis-trishomobenzene which was synthesized by irradiation of the bridged bishomo- barrelene (42).7 On warming (40) undergoes a cycloreversion to quinacene (43).(41) (42) (43) With the reported synthesis of [2O]ann~lene~~ (which is of course not aromatic) all the annulenes up to [24]annulene have now succumbed to attempts to synthesize them.74 Other Systems.-General. Enone pho toannelation free-radical c ycli~ations,~ the synthetic uses of halogenated keten~,~~ and the synthesis of adamantanes and related hydrocarbons have been reviewed.78 Three-and Four-membered Rings. Modifications which increase the utility of the Simmons-Smith reaction are always welcome and this includes the finding that the presence of oxygen appreciably increases both the rates and yields of olefin cyclopropanation by the methylene iodide-diethylzinc system.79 Substituted cyclopropanes are formed in moderate yield from the reaction of a-chloro- ketones -esters or -nitriles with electron-deficient olefins in the presence of a copper(I) oxide -isonitrile complex.80 Further examples of the usefulness of quaternary ammonium halides in facilitating cyclopropanation with halogenb- alkane-base combinations have appeared.81*82 Thus chloroform aqueous sodium hydroxide and a catalytic quantity of triethylammonium chloride give high yields of dichlorocyclopropanes from olefins such as trans-stilbene which fail to react with potassium t-butoxide-chloroform.82 A new cyclopropane synthesis is initiated by Michael addition of acidic methy- lene compounds to (dimethylamino)phenyI-(2-phenylvinyl)oxosulphoniumfluo-70 E.Vedejs Chem. Comm. 1971 536. 71 J. S. McKennis L. Brener J. S. Ward and R. Pettit J. Amer. Chem. Soc. 1971 93 4957. 72 A. de Meijere D. Kaufmann and 0. Schallner Angew. Chem. lnrrrnut. Edn. 1971 10 417. 73 B. W. Metcalf and F. Sondheimer J. Amrr. Chem. Soc.. 1971. 93 6675 74 R. M. McQuilkin B. W. Metcalf and F. Sondheimer Chem. Comm. 1971 338; F. Sondheimer Pure Appl. Chem. 1971 28 331. 75 P. de Mayo Accounts Chem. Res. 1971 4 41 16 M. Julia Accounts Chem. Res. 1971 4 386. 7' W. T. Brady Synthesis 1971 415. 7n R. C. Bingham and P. von R. Schleyer Forrschr. Chem. Forsch. 1971 18 1. 79 S. Miyano and H. Hashimoto Chem. Cornm. 1971 1418. no T. Saegusa Y. Ito K. Yonezawa Y. Inubushi and S.Tomita J. Atner. Chem. SOC. 197 1 93 4049. 81 M. Makosza and E. Bialecka Tetrahedron Letters 1971 4517. 82 E. V. Dehmlow and J. Schonefeld Annulen 197 1 744 42. A licyclic Compounds Ph H H A C0,Me H-Ac02 343 Me M++O HS Ph CN Ph' "Me2 (45) n R'CO CH=CH (46; R' = Me or Ph; R2 = H Me or Ph) roborate (44);83e.g. (44) reacts with methyl cyanoacetate and base to give (45). cis-8-Ketols of the type (46) are dehydrated in acid to give cis-vinylcyclopropyl ketones (47).84Irradiation of the polyacetylene (48) leads to the epimeric cyclo-propanes (49).8 Other ally1 chlorides where the double bond is conjugated with an alkyne grouping behave similarly. MeCH =CH[C C] C H =CHCHCH 0Ac I 3 CI MeCH=CH[C-C]; 'CH,OAc A useful addition to the established photochemical routes to cyclobutanes is the synthesis of acylcyclobutanes from certain a-methylene ketones ; e.g.(50) gives (51).86 The lithium-iodide-catalysed rearrangement of methylenecyclopropane epoxide provides a mild route to cy~lobutanone.~~ Cyclobutenone88 and cyclob~tenedione~~ have been prepared for the first time the latter by hydrolysis of (52) the product of photoaddition of acetylene to dichlorovinylene carbonate. 0 0 CI " C. R. Johnson and J. P. Lockard Tetrahedron Letters 1971 4589. n4 Y. Bahurel F. Collonges A. Menet F. Pautet A. Poncet and G. Descotes Bull. Soc. chim. France I97 I 2209. 8s F. Bohlmann W. Skuballa C. Zdero T. Kuhle and P. Steirl Annalen 1971 745,176. 86 W. L. Schreiber and W.C. Agosta J. Amer. Chem. SOC.,1971 93 6292. " J. R. Salaiin and J. M. Conia Chem. Comm. 1971 1579. 88 J. B. Sieja J. Amer. Chem. SOC.,1971 93 2481. 89 J. C. Hinshaw Chem. Comm. 1971 630. 344 B. T. Golding and A. P.Johnson Five- und Six-membered Rings. The compound (53) is a key intermediate in one of Corey's prostaglandin syntheses. A new high-yield procedure for its synthesisg0 uses the reaction of chloromethyl methyl ether with thallous cyclopentadienide a method which avoids prototropic rearrangements. The base-induced conversion of 2-chlorocyclohexane- 1,3-diones to 2-cycl~pentenones~ is a useful variation of an older cyclopentanone synthesis. The pyrolytic conversion of (54) into (55) by a retro-Diels-Alder reaction provides another versatile synthesis of 2-cyclopen- ten one^.'^ (55)isomerizes to (56) in the presence of acid or base.Dialuminium- substituted cyclopentyl derivatives (57)are available via the hydroalumination of Me S2OMe +; .;i.. RI(R~) R' 0 (53) 0' R2 (54) R1 = R2 = H or R' = H R2 = Me or R' = H R2 = CH -Et he~-l-en-Syne.~~ Because of the reactivity of the C-A1 bond compounds of this type should become useful synthetic intermediates. Electrochemical reduction of non-conjugated ketones such as (58;n = 3 or 4) leads to tertiary alcohols (59) with a high degree of stereoselectivity ;94 e.g. hept-6-en-2-one forms (60) ex-clusively. yH,AIR2 R 'CH =CH( CH 2),C0R2 0"'"' (58) R2 \ JCH,)" ,c CHCH,R' HO (59) '" E.J. Corey U. Koelliker and J. Neuffer J. Atizrr. Clzetn. Soc. 1971 93 1489. 91 G. Biichi and B. Egger J. Org. Chern. 1971 36 2021. 92 G. Stork G. L. Nelson F. L. Rouessac and 0. Gringore J. Alner. Chern. Soc. 1971 93 3091. 93 G. Zweifel G. M. Clark and R. Lynd Chem. Comm. 1971 1593. 94 T. Shono and M. Mitani J. Amrr. Ctietn. Soc. 1971 93 5284. Alicyclic Compounds Large Rings. The oxy-Cope rearrangement has been used to synthesize large carbocyclic rings but the yields are often low. A new high-yield variation is the siloxy-Cope rearrangement ;9 e.g. pyrolysis of (61)followed by hydrolysis yields undec-7-enone (62) as a mixture of geometrical isomers. Two new routes96 to macrocyclic ketones begin with the methyl enol ether of cyclododecanone.The size of the ring can be increased by either two or four carbon atoms as shown in Scheme 1. The key step in the two-carbon expansion is a photo-induced 1,3-acyl migration. .OMe Reagents i 2-methylbut-3-yn-2-ol-toluene-p-sulphonic acid; ii hv; iii vinylmagnesium bromide iv 350 “C Scheme 196 Bicyclic and Polycyclic Systems. A number of substituted bicyclobutanes have been prepared by base-induced elimination of HCl from chlorocyclobutanes such as (63; X = CN CO,R CONH, or COR).97 The action of magnesium on (63;X = OEt) leads to the parent bicy~lobutane.~~ The cyclopropyl-sulphonium ” R. W. Thies Chrm. Cow~nz.,1971 237. 96 R. C. Cookson and P. Singh J. Chem. Soc. (C),1971 1477. 97 H. K. Hall jun. E. P. Blanchard jun. S.C. Cherkofsky J. B. Sieja and W. A. Sheppard J. Amer. Chem. Soc. 1971 93 110; H. K. Hall jun. C. D. Smith E. P. Blanchard jun. S. C. Cherkofsky and J. B. Sieja ibid. p. 121. ” J. B. Sieja J. A/iier. Chem. Soc. 1971 93 130. B. T. Golding and A. P.Johnson and -sulphoxonium ylides (64)9g and (65)"' react with @unsaturated ketones to form spiropentane products; e.g. (65) with mesityl oxide gives (66)."' An improved method for the 1,4-addition of the methyienecarbonyl unit (-CH,CO-) to dienes is shown in Scheme 2."' The yields at each stage are almost quantitative. The l-hydroxy-7-methylenebicyclo[3,2,l]octane system ZCH ZCH, g2z cly""':' i+&&-& 0 Z = OMe OCH,Ph or NHCOPh Reagents i 0 "C 18 h; ii NaN, dimethoxyethane 25 "C;iii reflux; iv HOAc-H,O 55-60 "C.Scheme 2lo' has aroused much interest because of its presence in the gibberellins. The key step in a new synthetic approachlo2 to this system is the solvolysis of (67) to (68) the former being prepared by photoannelation. Photosensitized cycloaddition of dichlorovinylene carbonate to benzene leads to (69) which yields the hitherto unknown bicyclo[2,2,2]octadiene-2,3-dione(70) on hydroly~is.''~ Consecutive enamine alkylations form the basis of a new synthesis of spiro- cyclic ketones.lo4 An example of the process is the stereospecific conversion of (71) into (72) by the action of (73). 99 B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. Soc. 1971 93 3773. loo C. R. Johnson G. F. Katekar R. F. Huxol and E. R. Janiga J.Amer. Chem. Soc. 1971 93 3771. lo' E. J. Corey T. Ravindranathan and S. Terashima J. Amer. Chem. Soc. 1971 93 4326. lo' F. E. Ziegler and J. A. Kloek Tetrahedron Letters 1971 220 1. '03 H.-D. Scharf and R. Klar Tetrahedron Letrers 1971 517. lo4 D. J. Dunham and R. G. Lawton J. Amer. Chem. Soc. 1971,93 2074. Alicyclic Compounds Fresh aspects of the Robinson-Mannich annelation continue to be un-covered. In the preparation of (74) from but-3-en-2-one and 2-methylcyclo- pentane-1,3-dione the use of natural amino-acids as catalysts for the cyclization step leads to optically active (74) with optical purity of up to 84%.'05 The (S)-enantiomer predominates when (S)-amino-acids are employed. Although in the past the reaction of trans-pent-3-en-2-one with unactivated cyclohexanones such as 2-methylcyclohexanone has proceeded poorly under the usual reaction conditions the use of the preformed sodium enolate of 2-methylcyclohexanone gives a high yield of (75) and (76).'06 The stereoselectivity of the reaction is very (75) R' = Me R2 = H (77) (76) R' = H RZ= Me high and remarkably solvent dependent the isomeric purity of the product being greater than 95% with either dioxan or dimethyl sulphoxide as solvent.The cis-product (75) predominates in the former case and the trans-product (76) in the latter possibly because of the operation of the mechanism shown in Scheme 3 where the role of the dimethyl sulphoxide is to facilitate proton transfer. The stereochemical outcome of the reaction between (77) and trans-pent-3-en-2-one is also markedly solvent dependent,"' the cis-product (78) predominating in tertiary alcohols at low temperature and the trans-product in aprotic solvents.Several hydroazulene syntheses have been reported and some are summarized in Scheme 4. lo5 U. Eder G. Sauer and R. Wiechert Angew. Chem. Internat. Edn. 1971 10 496. Io6 C. J. V. Scanio and R. M. Starrett J. Amer. Chem. SOC.,1971 93 1539. lo' J. A. Marshall and T. M. Warne jun. J. Org. Chem. 1971 36 178. B. T. Golding and A. P.Johnson 1 Scheme 3 H Ref. 108. P 03 H R R OAc Ref. 109. R = H Ref. 110. R = Me Scheme Aontinued on next page lo* J. B. Hendrickson and R. K. Boeckman jun. J. Amer. Chem. Soc. 1971,93 1307 Io9 C.J. V. Scanio and L. P. Hill Chetn. Comm. 1971 242. ‘lo J. A. Marshall and A. E. Greene Tetrahedron Letters 1971 859. Alicyclic Compounds 349 C0,Me Ref. 112. & a H2C Me 0 Reagents i MeI; ii OH-; iii HOAc; iv ION-HC1; v polyphosphoric acid; vi MeO-; vii 380 "C Scheme 4 Intramolecular transfer of methylene seems to be involved in the stereospecific base-induced conversion of (79) to (80).' ' The functionality of compounds such as (80) should make them useful synthetic intermediates. Intramolecular acid- catalysed alkylations by diazoketones are also potentially useful cyclization processes; e.g. (81) gives (82)'14 and (83) gives (84).'" + ,S-Me COCH=N2 Me 'I' G. L. Buchanan and G. A. R. Young Chem.Comm. 1971 643. R. A. Kretchmer and W. J. Frazer J. Org. Chem. 1971 36 2855. ' l3 R. S. Matthews and T. E. Meteyer Chem. Comm. 1971 1576. D. J. Beames T. R. Klose and L. N. Mander Chem. Comm. 1971 773. 'Is W. F. Erman and L. C. Stone J. Amer. Chem. Soc. 1971 93 2821. B. T. Golding and A. P. Johnson Biogenetic-like olefin cyclizations are now well established. As shown in Scheme 5 participation of an acetylenic bond in such cyclizations is a useful modification the resulting vinylcarbonium ion being trapped to give a ketone or masked ketone. Further examples of cycloalkanone synthesis by intramolecular OH I (a) HCO,H R = OCHO (b) MeCN-CF,CO,H R = NHCOCH Et I OH i Formic or trifluoracetic acid Ref. 117. t ii Hydrolysis :5" Ratios vary between 60 :40 and 80 20 Scheme 5 alkylation of chloro-olefins are reported [cf Annual Reports (B),1970 67 3741.The acid-catalysed conversion of (85)into a 2 :1 mixture of (86) and (87) shows the utility and stereoselectivity of this process.' Diamondoid hydrocarbons such as adamantane are usually prepared by isomerization of other hydrocarbons. The specificity and yield in this process can 'I6 W. S. Johnson M. B. Gravestock R. J. Parry R. F. Myers T. A. Bryson and D. H. Miles J. Arner. Chem. SOC.,1971 93 4330. 'l7 P. T. Lansbury and G. E. DuBois Chem. Comm. 1971 1 107. 'I8 P. T. Lansbury P. C. Briggs T. R. Demmin and G. E. DuBois J. Amer. Chem. Soc. 1971 93 131 1. Alicyclic Compounds 35 1 be markedly improved if chlorinated platinum-aluminium catalysts are employed instead of the usual Lewis acids."' Barton and his co-workers have published details of their synthetic approach to the tetracyclines.12' One of the many impressive reactions therein is the acid- catalysed photocyclization of (88)to (89) via the hexatriene (90).0 TlH Ph 0 OCH,CH,OH 3 Reactions Metal-promoted Transformations.-Last year we indicated the upsurge of activity in this field which has led to the discovery of many new reactions [see An-nual Reports (B) 1970,67,399]. There was some uncertainty however regarding 'I9 D. E. Johnston M. A. McKervey and J. J. Rooney J. Amer. Chem. Soc. 1971 93 2798. I2O D. H. R. Barton and P. D. Magnus J. Chern. Soc. (C) 1971 2164; D.H. R. Barton B. Halpern Q. N. Porter and D. J. Collins ibid. p. 2166; E. Aufderhaar J. E. Baldwin D. H. R. Barton D. J. Faulkner and M. Slaytor ibid. p. 2175; J. E. Baldwin D. H. R. Barton N. J. A. Gutteridge and R. J. Martin ibid. p. 2184; D. H. R. Barton D. L. J. Clive P. D. Magnus and G. Smith ibid. p. 2193; D. H. R. Barton L. Bould D. L. J. Clive P. D. Magnus and T. Hase ibid. p. 2204; D. H. R. Barton P. D. Magnus and T. Hase ibid. p. 2215; D. H. R. Barton P. D. Magnus and M. J. Pearson ibid. pp. 2225 2231; D. H. R. Barton (Mrs.) J. A. Challis P. D. Magnus and J. P. Marshall ibid. p 2241. 352 B. T. Golding and A. P.Johnson the mechanisms of catalysis. The proposal that the metals promote reactions by relieving orbital symmetry constraints within the organic substrate has been re- iterated'" for some reaction-types (2 + 2 cycloadditions and reversions).A qualitative rule has been proposed :'22 'Transition metals may catalyse pericyclic reactions if and only if they involve antiaromatic transition states' (in the uncatalysed reaction). For metal-catalysed rearrangements of bicyclo[l,l ,O]-butane tricyclo[4,1 ,0,OZy7]heptane (91) and their alkyl derivatives much experimental evidence now shows that these are stepwise reactions. In the presence of a catalytic amount of silver(1) ions endo,exo-2,4-dimethyIbicyclo[ l,l,O]butane (92) gives cis,trans-hexa-2,4-diene (93) [99 % at 5 "C] whilst the exo,exo-isomer (94)gives mainly the trans,trans-diene (95) [73 % + 22 %cis,trans-diene (93)]' 23,1 24 [in thermolyses (92) +(95) and (94) -+ (93)].Although this behaviour might be expected from one-step reactions proceeding under orbital symmetry control a kinetic analysis of the reaction of tricyclo[4,1 ,0,02.7]heptane (9 I) giving cis,cis-cyclohepta-1,3-diene in the presence of silver(1) ions showed that at least one intermediate must be involved.' 24 (91) R' = R4 = H R2R3 = -(CH2)3-(92) R' = R3 = H R2 = R4 = Me (94) R2 = R3 = H R1 = R4 = Me Meanwhile at Ohio within shouting distance of Paquette Gassman and his students were studying the rearrangements of bicyclo[l,l,0]butanes and tri- cyclo[4 1,0,02.7]heptanes catalysed by other metal ions.' 5-' 29 The nature of the products formed is very dependent on the metallic catalyst used (cf.Scheme 6).Gassman suggests'29 that the metal ion functions as a very selective Lewis acid which triggers the transformations shown in Scheme 7. An earlier suggestion of catalysis by a Lewis acid was made in connection with the rearrange- ment of 1,2,5-tri-t-butylprismane (96) to 1,2,5-tri-t-butylbicyclo[2,2,0]hexa-2,4-diene (97) and other products which is catalysed by a host of metallic reagents and even by 1,3,5-trinitrobenzene.' I2l F. D. Mango and J. H. Schachtschneider J. Amer. Chetn. Soc. 1971 93 1123. 122 M. J. S. Dewar Angew. Chem. Internat. Edn. 1971 10 761 "' M. Sakai H. Yamaguchi H. H. Westberg and S. Masamune J. Amer. Chern. Soc. 1971,93 1043. 12' L. A. Paquette S. E. Wilson and R. P. Henzel J. Amer. Chem. Soc. 1971 93 1288. P. G. Gassman and F.J. Williams J. Arner. Chem. SOC.,1970 92 7631. '26 P. G. Gassman G. R. Meyer and F. J. Williams Chem. Comm. 1971 842. "' P. G. Gassman and T. J. Atkins J. Amer. Chem. SOC., 1971 93 1042. lZ8 P. G. Gassman T. J. Atkins and F. J. Williams J. Amer. Chem. Soc. 1971 93 1812. 129 P. G. Gassman and T. J. Atkins J. Amer. Chem. Soc. 1971 93 4597. I3O L. A. Paquette R. P. Henzel and S. E. Wilson J. Amer. Chem. Soc. 1971 93 2335. 13' K. L. Kaiser R. F. Childs and P. M. Maitlis J. Amer. Chern. SOC.,1971 93 1270. Alicyclic Compounds Scheme 6 1"' 1 1-M" v 9 H Scheme 7 B. T. Golding and A. P.Johnson Evidence for the metalkarbene complex (98) of Scheme 7 comes from the finding that bicyclobutanes [e.g. (94)] and diazomethylpentenes [eg.(99)] give similar product distributions on treatment' 32 with (PhCN),PdCl (cf:ref. 128). The intermediacy of (100) [cf:Scheme 71 is supported by the isolation of epimeric methyl ethers (101) from treatment of (91) with either [(CO),RhCl] (ref. 133) or AgClO (ref. 129) in methanol. Also solvolysis of the mesylate (102) gives a similar product mixture to that obtained by treating (92) with silver ions while solvolysis of (103) gives products similar to those obtained from (94)with silver ions.'33 Paquette has provided evidence for the intermediacy of an 'argento- carbonium ion'130*134 (104)* in the rearrangement of l-methyltricyclo[4,1,0,02~7]-heptane (105) to 3-ethylidenecyclohexenes by a study of deuterium-isotope effects on the rate of this rea~ti0n.l~~ He has also invoked intermediate argentocar- bonium ions to explain the steric course of Ag'-catalysed reactions of bicyclo- butanes (92) and (94),' 30 but these ideas have been criticized.' 33 H MeYAg 'R2 R' (102) R' = Me R2 = OMS (103) R' = OMS R2 = Me Ms = MeSO Among other noteworthy contributions are papers by Pettit' 35 and Grigg;' 36 syn-tricyclo-octane (106)rearranges rapidly in the presence of AgBF at 56 "C to give a 4 1 mixture of tetrahydrosemibullvalene (107) and cyclo-octa-1,5-diene whereas the anti-isomer (108)is stable for at least 5 days under these conditions ;l 35 a catalytic amount of [(CO),RhCl] converts cyclo-octatetraene monoepoxide 13' M.Sakai and S. Masamune J. Amer. Chem. SOC.1971 93 4610. 133 M. Sakai H. H. Westberg H. Yamaguchi and S. Masamune J. Amer. Chem. Soc. 1971,93,461I. 134 L. A. Paquette Accounts Chem. Res. 1971 4 280; L. A. Paquette and S. E. Wilson J. Amer. Chem. SOC.,1971 93 5935. 135 J. Wristers L. Brener. and R. Pettit J. Amer. Chem. Sac. 1970 92 7499. 13' R. Grigg and G. Shelton Chem. Comm. 1971 1247; R. Grigg R. Hayes and A. Sweeney ihid. p. 1248. * This is formally equivalent to the metal-carbene complex suggested earlier by Gassman'2S (Scheme 7) although the distribution of charge in these intermediates will obviously vary with the nature of the metal and its ligands. Alicyclic Compounds 355 into (109) at -50 "C and cis-bicyclo[6,l,0]nonatrieneto cis-8,9-dihydroindene at 35 "C,l36 whereas the thermal rearrangements require higher temperatures and are less clean.Specific Lewis acid catalysis is invoked to explain the latter reactions.' 36 0 Several novel metal-catalysed cycloadditions have been discovered' ',' (Scheme 8). Norbornadienone has not been isolated because of its ready cyclo- reversion to carbon monoxide and benzene but a stable (at -5 "C) iron carbonyl complex (1 10)of this molecule has now been ~ynthesi2ed.l~~ 65 % 35 % I 16% 47 % CN 29 % ref. 137 71 % Reagents i CH,=CHCO,Me Ni(CH,=CHCN), 60 "C 3h; ii CH,=CHCN. Ni(CH,=CHCN), 70 "C 3h; iii Fe,(CO), 60 "C 40 h Scheme 8 13' R. Noyori T. Suzuki Y. Kumagai and H. Takaya J. Amu. C/wm. Snc. 1971 93 5894; R. Noyori T. Suzuki and H. Takaya ibid. p. 5896. 13* R.Noyori S. Makino and H. Takaya J. Amer. Chem. SOC.,1971 93 1272. 139 J. M. Landesberg and J. Sieczkowski J. Amer. Chem. SOC.,1971 93 972. B. T. Golding and A. P. Johnson A re-inve~tigation'~' of the reaction between bullvalene and Fe2(C0)9 has shown that as well as 20 % of the previously rep~rted'~' product (1 1 l) six other isomeric complexes are formed including (1 12) (major product) and (1 13). Changes in the 'H n.m.r. spectrum of (113) occur on warming from 10 to 45 "C and are most economically explained by postulating interconversion of enantio- meric forms via 1,2-shifts of Fe(C0)3 groupings. On heating complex (113) at 120 "C it rearranges quantitatively to (114) oia a 1,2-shift of C(2) to C(9). [14]Annulene reacts with (NH3)3Cr(C0)3 to give a complex (115)derived from its valence isomer tran~-6a,l2a-dihydro-octalene.'~~ Solutions of (1 15) re-generate [14]annulene on standing.Pericyclic Reactions.-Reactions of this type are thoroughly reviewed in Chap- ter 3 (Reaction Mechanisms Part ii). Conformation and Reactivity.-The factors governing the steric outcome of the reactions of cycloalkanones with hydrides and organometallic reagents continue to be investigated. t-Butylallylmagnesium bromide appears to be a useful aid in such investigations since its reaction with ketones (R'COR2) can lead to two isomeric products (116) and (117) and it is claimed that the product ratio (1 16):(117) provides a sensitive measure of the steric hindrance in the neighbour- hood of the carbonyl By this test the carbonyl groups of cyclopenta- none and trans-Zhydrindanone (ratios 65 and 50 respectively) are more hindered than those of cyclohexanone and acetone ( ratios 3 and 3.4 respectively).I4O R. Aumann Angew. Chem. Internat. Edn. 1971 10 188 189 190. 14' G. N. Schrauzer P. Glockner K. I. G. Reid and I. C. Paul J. Amer. Chern. SOC. 1970. 92. 4479. 14' K. Stockel F. Sondheimer T. A. Clarke M. Guss and R. Mason J. Amer. Chem. SOC.. 1971 93,2571. 143 M. Cherest H. Felkin and C. Frajerman Tetrahedron Letters 1971 379. Alicyclic Compounds 357 Me,C-CH=CH -CH Ho-c‘R 1R2 Me3C-CH-CH=CH,IR1R2C-OH (1 16) (1 17) The equatorial alcohol derived from addition of t-butylallylmagnesium bromide to 4-t-butylcyclohexanone is solely (1 18),’44indicating that steric strain is the im- portant factor impeding axial attack (‘steric approach control’).In contrast the ratio of axial products (119) :(120)is very small (1.3),which leads to the conclusion that torsional strain is the major factor impeding equatorial attack. Thus the steric outcome of additions of hydrides and Grignard reagents to cyclohexanones is ascribed to the net difference between the steric strain in the transition state leading to the equatorial alcohol and the torsional strain the transition state leading to the axial In marked contrast to the reaction of most methyl organometallic reagents with 4-t-butylcyclohexanone trimethylaluminium under certain conditions (ketone :AlMe = 1 :2 ; benzene solution) gives mainly the trans-alcohol (121).145 A six-centred transition state containing two molecules of trimethyl-aluminium is invoked as a possible explanation.Certain P-hydroxy-ketones such Ph OH Ph OH OH Me3C (121) (122) (123; R = Me or Ph) as (122) react stereospecifically with phenyl or methyl Grignard reagents to form the cis-diols (123).146This is attributed to initial formation of the chelate (124) which is then attacked on the less hindered face. A similar explanation is ad- vanced for the stereospecific conversion of (125) into (126). 144 M. Cherest and H. Felkin Terrahedron Lerfers 1971 383. 14’ E. C. Ashby and S. Yu Chem. Cnrnrn. 1971 351. 146 E. Ghera and S. Shoua Chem. Comm. 1971 398. B. T. Golding and A. P. Johnson Lithium dimethyl cuprate adds to 3,4-epoxycyclohexene to form (127) and the conjugate addition product (128).14’ The trans stereochemistry of the latter is the reverse of that expected from an SN2’ process.Lithium methyl gives no conjugate addition but instead the major product is benzene hydrate (129) from a base- induced isomerization reaction. The lithium-diethylamide-induced rearrange- ment of a series of propylidene-cycloalkane oxides (130) to allylic alcohols148 exhibits a marked regioselectivity the endocyclic olefin product (13 1) predominat-ing except when n = 6. In the latter case (132) is formed after a slower reaction. These results are interpreted in terms of a syn elimination mechanism via a specific cis-coplanar transition state (which would be energetically unfavourable when n = 6).I Me OH n = 4 5 7 8 or 12 Schleyer’s proposal149 that torsional strain is responsible for the exo selectivity in the reactions of various norbornyl derivatives has been que~tioned.’~~ A comparative study of the rates of base-catalysed deuterium exchange of the 14’ J. Staroscik and B. Rickborn J. Amer. Chem. SOC.,1971 93 3046; D. M. Wieland and C. R. Johnson ibid. p. 3047. R. P. Thummel and B. Rickborn J. Org. Chem. 1971 36 1365. 149 P. von R. Schleyer J. Amer. Chem. SOC.,1967 89 701. S. P. Jindal S. S. Sohoni and T. T. Tidwell Tetrahedron Letters 1971 779; S. P. Jindal and T. T. Tidwell ibid. 1971 783. Alicyclic Compounds bicyclic ketones (133) (134) and (135) shows that the relative rates are 2s shown.The authors contend that angle strain and non-bonded repulsions adequately account for these rates. Further evidence for the unimportance of torsional strain in these reactions comes from the finding that there is little difference in the relative rates of exchange for camphor (136) and 4-methylcamphor (137). If torsional strain were important this should be accentuated by the CH,-H interaction in (1 37). Me-Me& J '2.4 ZoMetJ t 0.58 0.61 (1 36) (137) On the other hand equilibration studies show that endo-1-methyl-2-cyano-bicyclo[2,2,l]hept-5-ene (1 38) is more stable than the corresponding exo-com- pound (139) by 0.39 kcal mol-' and this is attributed to a torsional CH,-CN interaction,lS1 which it is argued should be even larger in a transition state where the degree of eclipsing is greater.Acetoxymercuration of cis-3,5-dimethylcyclohexeneand 3,5,5-trimethylcyclo- hexene (followed by treatment with NaBH,) gives the C(3)-acetates (140) and (141) respectively as major products.152 It is suggested that this unexpected result is due to a torsional effect whereby the C(3)-pseudo-equatorial methyl group disfavours attack of acetate ion at C(2) by disdaining to let H(2) pass ref (WI. ' ' J. M. Mellor and C. F. Webb Tetrahedron Letters 197 1 4025. 15* D. J. Pasto and J. A. Gontarz J. Amer. Chem. SOC.,1971 93 6909. B. T. Golding and A. P. Johnson OAc Calculations by Schleyer and Bingham of the differences in strain energy between bridgehead carbonium ions and the corresponding hydrocarbons in most cases show an excellent correlation with experimental solvolysis rates of suitably functionalized derivatives.' s3 As one might expect systems with larger bridges are more reactive because there is less strain in attempting to form a planar carbonium ion.However the treatment breaks down for (143) which solvolyses lo9 times more slowly than predicted. Of the compounds studied (143) is unique in that it lacks a P-alkyl group or hydrogen atom which is trans-periplanar to the bond carrying the leaving group and it is suggested that this structural feature greatly assists ionization by hyperconjugative stabilization of the transition state Similar calculations of the relative reactivities of the various bridgehead positions of protoadamantane (144) predict a reactivity order (position 6 > 3 > 1 or 8) which accords with the finding that 6-bromoprotoadamantane is the sole bromination product.' 54 ?Ts Q (143) (145) X = ODNB (3,5-dinitrobenzoate) or OPNB (p-nitrobenzoate) Wiberg's outstanding work' 5s on the solvolysis of derivatives of strainea bicycloalkanes has now been extended to the 3,5dinitrobenzoates of the isomeric bicyclo[6,l,0]nonan-2-ols[cf (145)I.l56*157 An explanation of the relative rate constants found [for solvolysis at 100 "C in 80 % aqueous acetone trans'trans-(1 43 krel 18 200 ; trans,cis-( 149 krel I ; cis,trans-(149 krel 65 ;cis,cis-(145) kre 14101 requires a careful consideration of subtle conformational factors in the molecules concerned.Thus Gassman s~ggests'~' that in trans,cis-(145) the R. C. Bingham and P. von R. Schleyer J. Amer. Chem. Soc. 1971,93 3189. '" A. Karim M. A. McKervey E. M. Engler and P. von R. Schleyer Tetrahedron Letters 1971 3987. 155 K. B. Wiberg R.A. Fenoglio and V. Z. Williams J. Amer. Chem. SOC.,1970 92 568 and references therein. 156 K. B. Wiberg and T. Nakahira J. Amer. Chem. Soc. 1971 93 5193. 15' P. G. Gassman E. A. Williams and F. J. Williams J. Amer. Chem. Soc. 1971 93 5199; for a related study cf P. G. Gassman J. Seter and F. J. Williams ihid. p. 1673. Alicyclic Compounds 36 1 H H 4opNB 4H (146) (147) bPNB leaving group lies astride a cyclopropyl bond [as in (146)] and participation is not possible whereas in trans,trans-( 145) the leaving group is trans to a cyclopropyl bond and participation occurs [as in (147)l.Last year we reported [Annual Reports (B) 1970,67,388] that the cycloaddition of unsymmetrical ketens to cyclopentadiene is usually highly stereoselective. It now seems that this is not the case with most other olefins,' s8 and the anomalous behaviour of cyclopentadiene is attributed to its planarity. Elimination reactions of alicyclic compounds have been reviewed.' 59 Miscellaneous Reactions.-Carbocyclic ring contractions,' 6o thermal addition of carbon<arbon multiple bonds to strained carbocyclics,' ' photochemical transformations of small-ring carbonyl compounds,' 62 and the chemistry of adamantane~'~ and cyclopropanones' 63 have all been reviewed.Triallylborane adds to 1-methylcyclopropene to give the product of cis-addition across the double bond (148; R = H) and the ring-cleaved product (149).'64 With trL(2-butenyl)borane the product is (148; R = Me) indicating the possibility of a concerted reaction via a cyclic transition state. L"Z /I ! RCH=CHCH CH,CH= CHR CH=CH (148) (1 49) Certain masked cyclopropanones are readily converted into p-lactams as shown in Scheme 9. Whereas trialkylboranes do not usually react with olefins the photochemically induced cis-addition of tri-n-alkylboranes to cyclohexenes has been accom-15' W. T. Brady F. H. Parry tert. and J. D. Stockton J. Org. Chem. 1971 36 1486; W. T. Brady and R. Roe jun. J. Atner. Chem. Soc. 1971 93 1662. 159 N.A. Lebel Adu. Alicyclic Chern. 1971 3 195. Ih0 D. Redmore and C. D. Gutsche Adu. Alicyclic Chem. 1971 3 1. '" P. G. Gassman Accounts Chem. Res. 1971 4 128. 'b2 A. Padwa Accounts Chem. Res. 1971 4,48. lb3 N. J. Turro R. B. Gagosian S. E. Edelson T. R. Darling J. R. Williams and W. B. Hammond Trans. N. Y. Acad. Sci. 1971 33 396. Yu. N. Bubnov 0. A. Nesmeyanova T. Yu. Rudashevskaya B. M. Mikhailov and B. A. Kazansky Tetrahedron Letters 1971 2153. 362 B. T. Golding and A. P. Johnson c1 I R = C,H Bun Bus Bu' or CH,-CH I CO Et Ref. 166. 95% when X = OH Y = OMe X=Y=N fi orX=OH,Y=N LJ or X = OH Y = OMe Reagents i Me,COCI; ii Ag+;iii NaN, pH 5.5 Scheme 9 pli~hed,'~'e.g. (150) gives (151) with triethylborane. Cyclo-octa-2,7-dienone behaves similarly but cyclopentene cyclo-octene and cyclododecene do not which supports the postulated intermediacy of a highly reactive trans-cycloalkene.R = H or Et Tricyclic cyclopropanols of the type (152) are readily available by metal- ammonia reduction of ketones such as (153).16* As shown in Scheme 10 these cyclopropanols can be made to undergo stereospecific rearrangements to give high yields of a variety of bicyclic systems. 165 H. H. Wasserman and M. S. Baird Tetrahedron Letters 1971 3721. '66 H. H. Wasserman H. W. Adickes and 0. E. de Ochoa J. Amer. Chern. SOC.,1971 93 5586. 16' N. Miyamoto S. Isiyama K. Utimoto and H. Nozaki Trtruhedrarz Letters 1971 4597. 168 P. S. Venkataramani and W. Reusch Tetrahedron Letters 1968 5283.Alicyclic Compounds Ref. 169 '0 Reagents i toluene-p-sulphonic acid-benzene reflux or alternatively KOH-MeOH ; ii NaH-benzene; iii MeOH ; iv toluene-p-sulphonyl chloride-pyridine ; v HOAc Scheme 10 169 P. S. Venkataramani J. E. Karoglan and W. Reusch J. Amer. Chem. SOC. 1971 93 269; K. Grimm P. S. Venkataramani and W. Reusch ibid. p. 270.

ISSN:0069-3030    

DOI:10.1039/OC9716800333

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

11 General Methods By P. G. SAMMES Chemistry Department Imperial College London SW7 2AY 1 Reduction Catalytic Hydrogenation.-Development of homogeneous catalysts has turned a full circle with the preparation of rhodium(1) catalysts chelated to a phosphine polymer.' The advantages of such heterogeneous catalysts are that they have uniform properties and that they can be easily recovered and re-used.2 Whereas normal heterogeneous catalysts often cause disproportionation and hydrogeno- lysis it is becoming apparent that the homogeneous catalysts such as chlorobis- (triphenylphosphine)rhodium(r),are much more selective. Thus cyclohexadienes are reduced with little or no formation of benzene derivatives. The griseofulvin precursor (l) for example is reduced to the compound (2) with no hydrogeno- lysis of the spiro-ether link in contrast to the result observed with heterogeneous X0ZPPh2 0 H PPh (3) catalyst^.^ In the year under review emphasis has been on the development of asymmetric reducing agents in particular of homogeneous catalysts bearing asymmetric ligand~.~ For example use of the ligand (3) in the reduction with ' M.Capka P. Svoboda M. Cerny and J. Hetfleje Tetrahedron Letters 1971 4787. R. H. Grubbs and L. C. Kroll J. Amer. Chem. SOC.,1971 93 3062. A. J. Birch and K. A. M. Walker Austral. J. Chem. 1971 24 513. (a) T. P. Dang and H. B. Kagan Chem. Comm. 1971 481; (b) P. Abley and F. J. McQuillin J. Chem. SOC.(0,1971 844; (c) J. D. Morrison R. E. Burnett A. M. Aguiar C. J. Morrow and C.Phillips J. Amer. Chem. SOC.,1971 93 1301. 365 P.G.Sammes rhodium of r-acetamidocinnamic acid gives (R)-N-acetylphenylalanine in an optical yield of 72 %.4a Heterogeneous catalysts on an asymmetric support generally only give a few percent of enantioselectivity. Metal Reductants.-The reduction of ketones with active metals in liquid ammonia is subject to stereochemical control,6 but the mechanism for such reductions has not hitherto been completely resolved. It has now been found that the nature of the associated cation is imp~rtant.~ With d-camphor the yield of isoborneol relative to that of borneol was found to increase as the cation size increased from Li' to Cs'. The reaction scheme is outlined (Scheme 1). M + M'Br + M+ + M'' + e-+ Br-(1) \ \ 2 C'-O-+ M+ + M'' + \C-0-Mi + C-0-M'' (3) / / / Scheme 1 After reduction in the absence of a proton donor an irreversible complexing of the metal cations with the radical anion occurs (step 3).It is this step which determines the stereochemical result. Thus use of the dangerous and expensive metal caesium to control the stereochemistry of the reduction can be avoided by the simple expedient of using a caesium salt in the presence of a simpler alkali metal such as lithium. The hydrogenolysis of aromatic ketones and benzylic alcohols by lithium in liquid ammonia has also been rescrutinized. In the absence of a proton source the initial product is the corresponding alcoholate salt. If the reaction mixture is worked up in the normal manner with ammonium chloride the alcoholate is immediately quenched and the initial reaction is followed by a very rapid reduc- tion by the excess of lithium generally present eventually producing the hydro- carbon.If an aprotic quenching agent such as sodium benzoate is used the excess of lithium is destroyed without further reduction of the substrate and the benzylic alcohol can be recovered.8 The intramolecular cyclization of radical anions on to olefinic bonds is a well- established reaction. A remarkably efficient and stereoselective electrolyte reduction occurs with non-conjugated olefinic ketones at a carbon electrode in methanolic dioxan. Thus the ketone (4)produces the tertiary alcohol (5) in 66% yield.' Zinc dust is a very mild and useful reducing agent.It has now been used to reduce epoxides to olefins by heating them with a zinc-copper couple in ethanol ' Y. Izumi Angew. Chem. Internat. Edn. 1971 10 871. G. Ourisson and A. Rassat Tetrahedron Letters 1960 16. ' W. S. Murphy and D. F. Sullivan Tetrahedron Letters 1971 3707. S. S. Hall S. D. Lipsky F. J. McEnroe and A. P. Bartels J. Org. Chem. 1971,36,2588. T. Shono and M. Mitani J. Amer. Chem. SOC., 1971 93 5285. General Methods for several days." Reduction of ethynyl acetates with zinc dust gives allenes [e.g. (6)-(7)],and this reaction h6s been used as an entry into the dihydroxy- acetone side-chain of the corticoid steroids. Aluminium Hydrides.-Lithium aluminium hydride will reduce 1-fluoro-1-bromocyclopropanes in a stereospecific manner retention of configuration being observed ; a four-membered transition state was postulated.l2 Reduction of 2-phenyl-allylic alcohols' 3n produces the reduced isomeric olefin in contrast to cinnamic alcohols in which reduction of the double bond occurs.13b Thus the alcohol (8) gives the olefin (9). An elegant example of the addition of hydride ions H)J+3d Ph H >-( H OH Me Bu' across triple bonds has been provided by the reduction of the diacetylene (10) with lithium aluminium hydride in the presence of sodium meth~xide.'~ The complex (11) forms which reacts with iodine to give the vinyl iodide (12) that is used in a route to the Cecropiu juvenile hormone. lo S. M. Kupchan and M. Manyama J. Org. Chem. 197 1 36 1187.'I M. Biollaz W. Haefliger E. Velarde P. Crabbe and J. H. Fried Chem. Comm. 1971 1322. I' H. Yamanaka T. Yagi K. Teramura and T. Ando Chem. Comm. 1971 380. " (u) W. T. Borden and M. Scott Chem. Comm. 1971 381 ; (6) W. T. Borden J. Amer. Chem. SOC.,1970 92,4898. l4 E. J. Corey J. A. Katzenellenbogen S. A. Roman and N. W. Gilman Tetrahedron Letters I97 1 182 1. P.G. Sammes Further reductions with sodium bis-(2-methoxyethoxy)aluminiumhydride have been revealed. Epoxides are more readily reduced than with lithium aluminium hydride and the reduction is more selective;” sodium and mag- nesium salts of carboxylic acids are also reduced.16 Mixtures of lithium alu- minium hydride and cupric chloride reduce allylic sulphides and this reduction has been used to develop a new method for preparing olefins (Scheme 2).17 Reagents i 2-mercaptopyridine; ii PhLi; iii RBr; iv 1 2 CuC1,-LiAIH,.Scheme 2 Because of its dimeric nature in concentrated solutions lithium trimethoxy- aluminium hydride is often more stereoselective than the tri-t-butoxy-deriva- tive. Boron Hydrides-Sodium borohydride in sulpholane is an efficient reducing agent for nitro-groups yielding azo- and azoxy-compounds. l9 Organomercury compounds are also readily reduced by sodium borohydride. Since mercuric acetate metallates enamines at the P-position consequent reduction affords a simple route to tertiary amines; mercuric chloride or bromide tends to give N-metallated derivatives which with sodium borohydride do not lead to reduc- tion of the enamine.20 Epimerization of asymmetric ketones can occur at a greater rate than reduction under the basic conditions associated with sodium borohydride and this danger can be averted by using instead sodium cyanoborohydride.21 Full details of the use of the latter reagent have now appeared.22 Oximes are reduced to alkyl- hydroxylamines and enamines to amines at pH 7.The combination of sodium cyanoborohydride and toluene-p-sulphonylhydrazide is an efficient reagent for the complete reduction of ketones and aldehydes to the corresponding l5 T. K. Jones and J. H. J. Peet Chem. and Ind. 1971 995. l6 M. Cerny and J. Malek Coil. Czech. Chem. Comm. 1971 36 2394. T. Mukaiyama K. Narasaka K. Maekawa and M. Furusato Bull. Chem. Soc.Japan 197 1,44 2285. E. C. Ashby J. P. Serenain and F. R. Dobbs J. Org. Chem. 1971 36 197. l9 R. 0. Hutchins D. W. Lamson L. Rua C. A. Miiewski and B. E. Maryanoff J. Org. Chem. 1971 36 803. ’ R. D. Bach and D. K. Mitra Chem. Comm. 1971 1433. V. Hach E. C. Fryberg and E. McDonald Tetrahedron Letters 197 1 2629. ’’ R. F. Borch M. D. Bernstein and H. D. Durst J. Amer. Chem. Soc. 1971 93 2897. General Methods hydrocarbon^.^^" The reaction proceeds cleanly at 100 "C in a mixture of sul- pholane and dimethylformamide and is more selective than that which occurs using the analogous reagent incorporating sodium b~rohydride.~ Alkyl 3b iodides bromides and primary toluene-p-sulphonates are selectively reduced by sodium borohydride in hexamethylphosphoramide even in the presence of carbonyl or epoxide functions.24 Considerable effort has been made in the current year to develop asymmetric reducing agents.Reaction of ( +)-limonene with thexylborane followed by reaction of the resultant borane with n-butyl-lithium produced the hydride reagent (13).25 This reduced an aP-unsaturated ketone to give a 4.5 1 ratio of Li + -H CMe,CHMe, ".J'*' the two epimeric alcohols (optical yield ca. 64 %). Similarly lithium butyl- (hydro)dipinan-3a-y1 borate prepared from the reaction of diborane with ( +)-pin-2-ene followed by reaction of the product with butyl-lithium also reduced ketones producing optical yields of 5-45 %.26 Sulphurated borohydrides prepared by the addition of sulphur to sodium borohydride in tetrahydrofuran sometimes have advantages over the virgin reagent.Aromatic nitro-groups are completely reduced to yield the corres- ponding aniline whilst nitrile amide and nitroso-groups are also reduced with this reagent.27 A novel route to allylic alcohols has been devised. Addition of diborane to enamines followed by oxidation produces P-hydroxy-amines. Oxidation of the amine function to the corresponding N-oxide and pyrolysis affords the allylic alcohols.28 Reduction of hindered esters can lead to ether formation rather than alcohol^.^ Hindered boranes such as dicyclohexylborane and thexylborane (1,1,2-trimethylpropylborane),add to acetylenes to give mainly mono-adducts. After peroxide oxidation these mono-adducts afford the corres- ponding ketones.For monoalkylated acetylenes addition gives the terminal borane whereas with disubstituted acetylenes steric effects are important with these reagents and addition is predominantly with the boron attached to the 23 (a) R. 0. Hutchins B. E. Maryanoff and C. A. Milewski J. Amer. Chem. Soc. 1971 93 1793; (b)cJ L. Cagliotti Tetrahedron 1966 22 487. 24 R. 0. Hutchins B. E. Maryanoff and C. A. Milewski Chem. Comm. 1971 1097. 2s E. J. Corey S. M. Albonico K. Koeliker T. K. Schaaf and R. K. Varma J. Amer. Chem. SOC.,1971,93 1491. 26 M. F. Grundon W. A. Khan D. R. Boyd and W. R. Jackson J. Chem. SOC.(C),1971 2557. 21 J. M. Lalanchette and J. R. Brindle Canad. J. Chem. 1971 49 2990. 28 J.-J. Barieux and J. Gore Bull. SOC.chim.France 1971 3978. 29 J. R. Dias and G. R. Pettit J. Org. Chem. 1971 36 3485. 370 P.G. Samrnes less hindered side.30 Borane-sulphide adducts are more stable than the corres- ponding borane-tetrahydrofuran complex but as a consequence they are slightly less active.31 The adduct (1.4)can be distilled and should be of use in synthetic I Me (14) OtherMethods.-Titanous chloride in buffered acetic acid is an efficient reducing agent for converting oximes into imines and hence for the re-conversion of oximes into the parent carbonyl compounds.33 Nitro-compounds can also be reduced with this reagent to give ketones and this reaction has been used in a route to cyclopentenones including the perfume jasmone (Scheme 3).34 The jasmone Reagents i base; ii TiCl ; iii Lindlar reduction.Scheme 3 reduction of dihalogenocyclopropanes to cyclopropanes and monohalogeno- cyclopropanes has been re~iewed.~ The reductants sodium hydride in hexa-methylph~sphoramide~~ behave as one-electron and sodium na~hthalenide~~ reducing agents towards these systems. The former reagent is also strongly basic so that with medium-ring adducts such as (15a) reduction is followed by an elimination reaction to give the allene (15b). 30 G. Zweifel G. M. Clark and N. L. Polston J. Amer. Chem. SOC. 1971 93 3395. L. M. Braun R. A. Braun H. R. Crissman M. Oppenauer and R. M. Adams J. Org. Chem. 1971 36 2388. ” R.A. Braun D. C. Brown and R. M. Adams J. Amer. Chem. SOC. 1971,93 2823. 33 C. H. Timms and E. Wildsmith Chem.Comm. 1971 195. 34 J. E. McMurray and J. Melton J. Amer. Chem. SOC. 1971 93 5309. 35 R. Barlet and Y. Vo Quang Bull. SOC. chim. France 1969 3729. 36 J. Moreau and P. Caubere Tetrahedron 1971 27 5741. 37 D. B. Ledlie R. L. Thorne and G. Weiss J. Org. Chem. 1971 36 2186. General Method 371 (154 (133) a-Diketones can be selectively reduced to a-hydroxy-ketones by heating them with benzpinacol. The reaction proceeds by initial homolysis of the benz- pinacol. The diphenylcarbinol radicals so formed donate hydrogen to the substrate in collapsing to ben~ophenone.~~ Allylic sulphoxides are in thermal equilibrium with their isomeric sulphenate esters the equilibrium generally favouring the sulphoxide form. Alkylation of allyl sulphoxide (Scheme 4) followed by heating the sulphoxide in the presence R 0 0 Reagents i BuLi; ii RX; iii heat; iv (MeO),P-MeOH.Scheme 4 of trimethyl phosphite in methanol results in desulphurization and formation of the isomerized allyl alcohol.39 Cyclic thiolsulphonates react with tris(di- methy1amino)phosphine to give cyclic thiolsulphinates and not sulphites as reported previou~ly.~~ 2 Oxidation Oxidations by organic peracids are enhanced in the presence of a strong mineral acid. In this way the N-oxidation of polyhalogenated N-heteroaromatic com- pounds becomes possible and as catalyst concentrated sulphuric acid is re- ~ommended.~' Internal acid catalysis is observed with the sulphonic acid deriva- tive of perbenzoic acid (16). Olefins produce trans-glycols directly with this peracid.42 Oxidation of imines produces oxaziridines and a useful reagent for this purpose is t -amyl hydroperoxide in benzene using molybdenum hexacarbonyl as a catalyst.With this reagent pyridine gives the N-~xide.~~ Amides can also be (16) 38 M. B. Rubin and J. M. Ben-Bassat Tetrahedron Letters 1971 3403. 39 D. A. Evans G. C. Andrews and C. L. Sims J. Amer. Chem. SOC.,1971,93,4956. 40 Ann. Reports (B),1969 66 250. 41 G. E. Chivers and H. Suschitzky Chem. Comm. 1971 28. 42 J. M. Bachawat and N. K. Mathur Tetrahedron Letters 1971 691. 43 G. A. Tolsts'kov U. M. Jemilov V. P. Jurgev F. P. Gershanov and S. R. Rafikov Tetrahedron Letters 1971 2807. 372 P.G. Sammes indirectly oxidized to the corresponding hydroxamic acids via peracid oxida- tion of the derived imino-ethers.Better yields albeit still low are obtained with the cinnamyl ethers rather than the methyl ethers.44 The combination of hydrogen peroxide and aluminium chloride is useful for the selective hydroxylation of aromatic substrates anisole for example giving 70 % of the monohydroxylated phenols.45 An interesting appraisal of a variety of inorganic oxidants has been made using the Zimmerman treatment of electrocyclic reactions. For example a simple rationale for the different behaviour towards olefins of manganese(viI) which cis-hydroxylates them and the isoelectronic chromium(vI) which initially epoxidizes them is possible.46 Various modified inorganic oxidants have also been reported.Two variants of the chromium trioxide oxidation have been suggested. Dipyridine chromium(v1) oxide in acetic acid is recommended as a rapid and efficient oxidant of alcohols to aldehydes and ketones. The reagent is not quite as selective as the Collins reagent using dichloromethane as solvent but has the advantage of being easily prepared.47 The use of a two-phase ether- aqueous chromic acid system for the oxidation of secondary alcohols gives remarkably clean products and gives no epimerization in alcohols with an adjacent chiral carbon atom.48 Allylic oxidation of acetylenes is a relatively rare achievement. It has now been found that either the use of an excess of Collins reagent or of sodium chromate in acetic acid-acetic anhydride produces the conjugated acetylenic ketones ; terminal alkynes do not react.49 Oxidation of alkylcarboxylic acids with the PbIV Co"' and Tl"' ions generally occurs via decarboxylation with concomitant formation of the alkyl radical.However the thermal decomposition of manganic carboxylates can proceed via the alternative non-decarboxylative route to produce the a-carboxy-radical.50" It has now been shown that ceric carboxylates decompose in a similar way and that the radicals produced add across double bonds. The final products are lactones formed in synthetically useful amounts. Manganic and ceric ace- tates will also oxidize ketones to the a-keto-radical which can also add to alkenes to produce y-keto-radicals (Scheme 5).51 These adduct radicals are further oxidized by the metal salt to the corresponding carbonium ion which can then collapse either by quenching with acetate ion or by elimination of a proton.The success of this reaction and of the lactone-forming reaction relies on the selective nature of the oxidant. Because of the electron-withdrawing nature of the carbonyl group a-carbonyl radicals are not easily oxidized to the corres- ponding carbonium ion. 44 D. St. C. Black R. F. C. Brown and A. M. Wade Tetrahedron Letters 1971 4519. 45 M. E. Kurz and G. J. Johnson J. Org. Chem. 1971 36 3184. 46 J. S. Littler Tetrahedron 1971 27 81. 47 K.-E. Stensio Acta Chem. Scand. 1971 25 1125. 48 H. C. Brown C. P. Garg and K.-T. Liu J. Org. Chem. 1971 36 387. 49 J. E. Shaw and J. J. Sheng Tetrahedron Letters 1971 4379.50 (a) E. 1. Heiba R. M. Dessau and W. J. Koehl jun. J. Amer. Chem. SOC.,1969 91 138; (b) E. I. Heiba and R. M. Dessau ibid. 1971 93 995. 51 E. I. Heiba and R. M. Dessau J. Amer. Chem. Soc. 1971 93 524. General Methods R’COCH -$ R’COkH 4 R2kHCH2CH2COR’ + R2CHC H ,C H ,CO R -+ R2C H =CHCH ,CO R + R2CH(0Ac)C H ,CH ,CO R ’ Reagents i Ce(OAc),; ii R2CH =CH2 Scheme 5 Further selective oxidations have been reported. p-Benzoquinone can be cis-hydroxylated by osmium tetr~xide,’~ and ruthenium oxide will oxidize non-terminal alkynes to a-diketones. Sodium metaperiodate is a useful oxidizing agent for the preparation of di-imide from hydrazine and hence for the reduction of ole fin^,^^ and periodic acid will convert aryl azines into the corres- ponding aryl aldehydes in high yield thus representing a useful method for the removal of the azine group; azine oxides are not atta~ked.’~ Thallic sulphate is an excellent reagent for the oxidation of rigid olefins producing the corresponding trans-diols.56 Further ramifications of thallium(II1) nitrate oxidations have also been reported. For example oximes can be oxi- datively deoximated with the reagent to regenerate the aldehyde or ketone function.57 Oxidation of acetophenones with this reagent in methanol produces the corresponding methyl arylacetate by rearrangement.’ * Palladium(I1) acetate is also a valuable oxidant. With aromatic compounds acetoxylation occurs but with a reversal of the normal isomer distribution QAC PdOAc H pattern.Thus anisole mainly gives rn-acetoxyanisole presumably through an initial adduct such as (17).59 The oxidation of a-amino-ketones to the corres- ponding 1,2-dicarbonyl compounds is readily effected with mercury(1r) acetate and this is an efficient method for the preparation of glyoxals.60 ’’ J. Y. Savoic and P. Brassard Canad. J. Chem. 1971 49 3515. 53 H. Gopal and A J. Gordon Tetrahedron Letters 1971 2941. 54 J. M. Hoffman and R. H. Schlessinger Chem. Comm. 1971 1245. 55 A. J. Fatiadi Chem. and Znd. 1971 64. 56 C. Freppel R. Favier J.-C. Richer and M. Zador Cunud. J. Chem. 1971 49 2586. 57 A. McKillop J. D. Hunt R. D. Naylor and E. C. Taylor J. Amer. Chem. Soc. 1971 93 4918. 58 A. McKillop B. P. Swann and E.C. Taylor J. Amer. Chem. SOC.,1971 93 4912. 59 L. Eberson and L. Gomez-Gonzales Chem. Comm. 1971 263. 6o H. Mohrle and D. Schittenhelm Chem. Ber. 1971 104 2475. P.G.Sammes Organoboranes are generally oxidized with alkaline hydrogen peroxide to the corresponding alcohols. It has now been found that stoicheiometric amounts of oxygen also effect the same oxidation in almost quantitative yield.61 A detailed re-examination of the ozonolysis of olefins has revealed a unified picture which serves to correlate the diverse aspects of this reaction.62 Three ozonide intermediates are postulated which form in the sequence a-complex (18) Staudinger molozonide (19) and trioxolan (20). The intermediates (18) and (19) may form directly from the olefin (Scheme 6).Formation of the initial inter- mediate (18) can be used to explain the occasional formation of epoxides from o-o-0-I +/ 0 0-0 /O; R'CH,CH=CHR2 -+ R'CH,CH-CHR' -+ R'CH,&H-&HR' -+ (18) (19) (20) 0-0 R'CH,OOOCH=CHR~ reduction R'CHO + OCHCH,R2 0-0 (23) R4CH0 J (21) 0-0 R"C/H ,kHR2 0 (24) Scheme 6 olefins by loss of oxygen and the formation of anomalous products (path a) as observed for some isopimarane derivative^.^^ Subsequent formation of the molozonide (19) can lead to redox reactions with an aldehyde (path b) or ketone 61 H. C. Brown M. M. Midland and G. W. Kabalka J. Amer. Chem. SOC.,1971 93 1024. " P. R. Story J. A. Alford W. C. Ray and J. R. Burgess J. Amer. Chem. SOC.,1971,93 3044.63 Cf. C. R. Enzell and B. R. Thomas Tetrahedron Letters 1965 225. General Methods 375 (path c) producing the dioxetan (21). Dioxetans readily collapse into the car- bony1 components. In the absence of these reducing agents the molozonide (19) can rearrange to the trioxolan (20) or the ozonide (22),or the Criegee zwitterion (23) the latter allowing the formation of crossed ozonides (24) in the presence of low concentrations of aldehydes. Acetals can be ozonized to produce the corresponding ester and this reaction has been adapted for the cleavage of tetrahydropyranyl ethers and benzylidene and ethylidene protecting-groups under non-acidic condition^.^^ The scope of the triphenylmethyl cation (trityl cation) as an oxidizing agent has been greatly extended by the discovery that it will abstract hydride ions from a~etals~~ and benzyl ethers.Thus trityl fluoroborate with 3~-benzyloxycholest- 5-ene gave >90% cholesterol and benzaldehyde as the products.66 Since the trityl cation is a hindered species it shows selectivity in its hydride-abstracting properties. With the even more hindered perchlorotriphenylcarbonium hexa-chloroantimonate or the perchlorodiphenylcarbonium salt (25) a two-step hydride shift occurs via a one-electron transfer mechanism. With aromatic substrates radical cations are rapidly f~rrned.~' (C6C15)2CCI+ SbC1,- OCO(CH,) @4(=J\ / (25) CfP (26) The biomimetic oxidation of remote carbon atoms in steroid substrates has been gaining increased attention.A highly successful method involves photo- chemical intramolecular hydrogen abstraction with a rigid benzophenone reagent. Thus the derivative (26) undergoes selective attack at positions 9 and 14 on photolysis. Subsequent oxidation with lead tetra-acetate gives the olefins (27) and (2Q6* (27) (28) 65 P. Deslongchamps and C. Moreau Canad. J. Chem. 1971 49 2463. " D. H. R. Barton P. D. Magnus G. Smith and D. Zurr Chem. Comm. 1971 861. 6h D. H. R. Barton P. D. Magnus G. Streckert and D. Zurr Chem. Comm. 1971 1109. " M. Ballester J. Riera-Figueras J. Castaiier and A. Rodriguez-Siurana Tetrahedron Letters 1971 2079. 68 R. Breslow and P. Kalicky J. Amer. Chem. SOC.,1971 93 3540. 376 P.G.Sammes 3 Olefins The Chugaev reaction involves pyrolysis of xanthate esters.It has now been shown that the reaction can often be improved by pyrolysis of the potassium xanthate salts thus avoiding the need to prepare the corresponding esters. l'er- tiary alcohols are efficiently dehydrated in this manner the olefin distribution being similar to that obtained with the esters.69 Radical coupling is an efficient method for making carbonsarbon bonds and the principle has now been adapted for the preparation of 01efin.s.~' Coupling of a-bromonitroalkanes with the anion from a nitroalkane proceeds via a radical reaction to the vic-dinitroalkane. These can be made to undergo reduc- tive elimination reactions with sodium sulphide or sodium thiophenoxide to give the olefin. A simple geometrical isomerization of olefin bonds is effected by epoxidation reaction with lithium diphenylphosphide methylation with methyl iodide and then heating (Scheme 7).71 ..... 1 Reagents i peracid; ii LiPPH,; iii MeI; iv heat. Scheme 7 Cyclopropyl ring formation by the reaction of epoxides with simple Wittig reagents is well established. Use of the Wittig ylide (29) prepared via the stable enaminophosphonates (30) allows extension of this reaction to the formation of cyclopropyl ketones and ketimine~.~~ A timely review on the reactions and stereoselectivity of P-oxidophosphorus ylides has appeared.73 HNR' Ph2P(0)CH=LR2 (30) An isomerization of allylic esters is effected by palladium(rr) acetate. The reaction proceeds via the n-metal complex which then collapses to the a-complex [e.g.(31)] in a reversible manner eventually leading to equilibration of the two 69 K. G. Rutherford R. M. Ottenbrite and B. K. Tang J. Chem. SOC.(C),1971 582. 70 N. Kornblum S. D. Boyd H. W. Pinnick and R. G. Smith J. Amer. Chem. SOC. 1971,93 4317. E. Vedejs and P. L. Fuchs J. Amer. Chem. SOC.,1971 93 4070. l2 N. A. Portnoy K. S. Yang and A. M. Aguiar Tetrahedron Letters 1971 2559. 73 M. Schlosser F. K. Christmann A. Piskala and D. Coffinet Synthesis 1971 29. General Methods possible allylic esters.74 Catalysts such as chlorobis(tripheny1phosphine)rho-dium(r) normally give very little olefin isomerization. The addition of hydro- peroxides to such olefin+atalyst mixtures enhances double-bond migration and the reasons for this have been given7' R X OAO x-Ph C =C =CN 0 S (32) 02 Pd X (31) (33) The diazoallene (32) has been prepared.On heating the corresponding carbene is produced and this adds across olefins to form the corresponding cyclo- propyl addu~t.~~ Full details of the preparation of l,l-dialkyl-3-iodoallenes and 1,l-dihalogenoallenes have now been reported.77 Sulpholene undergoes cheletropic elimination of sulphur dioxide on heating. The homologues (33)have now been used for the formation of divinyl carbamates and divinyl Skipped dienes can be prepared from the corresponding cyclopropyl deri~ative.~~ Interest in the stereoselective synthesis of trisubstituted olefins continues.80 Two modified sigmatropic reactions have been reported.In the first the silyl ether (34)rearranges to the diene (39 which with acid yields the py-unsaturated aldehyde. Alternatively the cyclopropyl derivative (36) undergoes a similar OSiMe OSiMe F' 4 G (34) (35) 74 P. M. Henry Chern. Cornrn. 1971 328. 75 J. E. Lyons Chern. Cornrn. 1971 562. 76 D. J. Northington and W. M. Jones Tetrahedron Letters 1971 317. 77 P. M. Greaves M. Kalli P. D. Landor and S. R. Landor J. Chern. Soc. (C),1971,667. 78 A. I. Meyers and T. Takaya Tetrahedron Letters 1971 2609. 79 W. L. Mock J. Arner. Chern. SOC.,1970 92 6918. J. Reucroft and P. G. Sammes Quart. Rev. 1971 25 135; D. J. Faulkner Synthesis 1971 175. 378 P.G. Sammes 1,Shydrogen shift to give the 76-unsaturated aldehyde (37) (Scheme 8) of use in the preparation of Cecropiajuvenile hormone.81 Silyl ethers of allylic alcohols have also been used in a ring-expansion reaction.The derivative (38) reacts to give the isomer (39) by a 1,3-sigmatropic shift. The competing Cope rearrange- ment product (40)is formed reversibly; the protection of the alcohol prevents ketonization and hence the thermodynamic product is produced.82 The use of optically active allylic ethers in Claisen rearrangements leads to induced asym- metry in the products. This method allows the direct preparation of optically active juvenile h~rmone.~ A potentially useful procedure for protecting acetylenic bonds is to make their dicobalt hexacarbonyl complex. These complexes are remarkably stable to a wide range of reaction conditions for example hydrogenation but the acetylenic group can be released by mild oxidation with cerium(1v) salts.84 New electrophilic addition reagents for olefins include dipyridine iodonium nitrate (41) which can lead to vicinal iodo- nitrate^.^ Nitrosonium fluoroborate in acetonitrile adds to 1,2-disubstituted olefins to form salts of the type (42) which can easily be reduced to the corresponding irnida~ole.~~ Allylic anions RR rr (PY),i + NO -H py = pyridine HNYNoH (41) Me BF4-(42) " E.J. Corey and D. K. Herron Tetrahedron Letters 1971 1641. R. W. Thies Chem. Comm. 1971 237. 83 P. Loew and W. S. Johnson J. Amer. Chem. SOC.,1971,93 3765. K. M. Nicholas and R. Pettit Tetrahedron Letters 1971 3475.U. E. Diner and J. W. Lown Canad. J. Chem. 1971,49,403; U. E. Diner M. Worsley and J. W. Lown J. Chem. Soc. (C) 1971 3131. n6 M. L. Scheinbaum and M. B. Dines Tetrahedron Letters 1971 2205. General Methods react with diborane to form the 1,3-disubstituted adduct. Oxidation produces the corresponding 1,3-di0ls.~~9-Borabicyclo[3,3,1]nonane will add across trisubstituted olefins in an anti-Markovnikoff manner. Reaction of the resulting borane with bromine gives high yields of the corresponding alkyl bromide i.e. with the overall anti-Markovnikoff addition of hydrogen bromide.88 A promising new method for the preparation of benzynes has appeared,89 which involves diazotization of acetanilides under anhydrous conditions. The diazotization reagent of choice is the mixed anhydride p-chlorobenzoyl nitrite.The reaction proceeds via diazonium-acylate ion pairs and with care the com- peting radical reaction pathway can be avoided." 4 Carbonyl Compounds A new synthesis of aldehydes has been devised (Scheme 9) starting with 2-methyl- thiazoles.' + Reagents i BuLi ; ii RX; iii Me,O BF -;iv NaBH ;v HgO-H jO + Scheme 9 A problem often encountered with the use of dithioketals as protecting groups is how to remove them to release the carbonyl group. In a modified synthesis of aldehydes via the 1,3-dithian the hydrolysis was smoothly carried out by using a combination of mercuric oxide or acetate with boron trifluor- ide.92b Oxidative conditions have also been recommended the resulting mono- or di-sulphoxides hydrolysing under much milder conditions.Amongst oxidants recommended have been l-chlorobenzotriazole,93"N-halogenosuccini-mide~,~~~ In the synthesis of alde-chloramine T,93c and sodium peri~date.~~~ hydes a further modification is to alkylate methyl methylthiomethylsulphoxide (43) rather than use 1,3-dithians. The resulting dithioacetal monosulphoxides are relatively easily hydroly~ed.~~ '' J. Klein and A. Medlik J. Amer. Chem. Sac. 1971 93 6313. '' C. F. Lane and H. C. Brown J. Organornetallic Chem. 1971 26 C51. 89 J. I. G. Cadogan J. R. Mitchell and J. J. Sharp Chem. Comm. 1971 1. 90 B. H. Klanderman D. P. Maier G. W. Clark and J. A. Kampmeier Chem. Comm. 1971 1003. 91 L. J. Altman and S. L. Richheimer Tetrahedron Letters 1971 4709.92 (a) D. Seebach Angew. Chem. 1965 77 1134 1135; (b) E. Vedejs and P. L. Fuchs J. Org. Chem. 1971 36 366. 93 (a)P. R. Heaton J. M. Midgley and W. B. Whalley Chem. Comm. 1971 750; (b) E. J. Corey and B. W. Erickson J. Org. Chem. 1971,36 3553; (c) D. W. Emerson and H. Wynberg Tetrahedron Letters 1971 3444; (d) H. Nieuwenhuyse and R. Louw ibid. 1971 4141. 94 K. Ogura and G. Tsuchihashi Tetrahedron Letters 197I 3151. P.G. Sammes Aldehydes can be homologated by reaction with the ylide (44) to form the keten-dithioacetal (45) which can then be reduced and hydr~lysed.~~ Vinyl-silanes formed by the addition of trialkylsilanes across terminal acetylenes can also be used to prepare aldehyde^,^^ via epoxidation and mild hydrolysis.Hindered ketones can be prepared by the alkylation of a-bromoketones with lithium cuprates. 97 1,4-Diketones are of interest in the preparation of cyclopentenones. A new route to these involves condensation of 1,2-diketones with the Wittig reagent (46) followed by reduction with sodium hydr~sulphite.~' An alternative novel route to 1,4-diketones makes use of the intermolecular copper-catalysed addition of diazoketones to vinyl acetates. The resulting cyclopropyl acetate [e.g. (47)] is hydrolysed by base to the corresponding 1,4-diketone and hence to a cyclo- penten~ne.~~ A clever route to cyclopentenones is by ring contraction of a cyclohexane-l,3-dione. Monochlorination of these and treatment with base gives the unstable Favorski intermediate (48),which eliminates carbon monoxide to form the cyclopentenone (49).'0° 0 Poly-/3-ketomethylenes (polyketides) are of interest in biosynthetic-type studies.The 1,3,5,7,9-pentacarbonyl chain (50) has now been synthesized. The method used involved the poly-anion of the trione (51) generated by use of an excess of lithium di-isopropylamide at low temperatures followed by condensation with methyl benzoate. Previously diazoalkanes have received little notice as potential C -alkylating agents under acidic conditions. Diazoketones have now been used for this PhCOCH,COCH,COCH,COCH~COPh MeCOCH,COCH,COMe (50) (51) 95 F. A. Carey and J. R. Neergaard J. Org. Chem. 1971 36 2731. 96 G. Stork and E. Colvin J. Amer. Chem. Soc. 1971 93 2080. 97 J.-E. Dubois C.Lion and C. Moulineau Tetrahedron Letters 1971 177. 98 E. Ritchie and W. C. Taylor Austral. J. Chem. 1971 24 2137. 99 J. E. McMurry and T. E. Glass Tetrahedron Letters 1971 2575. loo G. Buchi and B. Eggers J. Org. Chem. 1971 36 2021. lo' T. M. Harris and G. P. Murphy. J. Amer. Chem. SOC.,1971 93 6708. General Methods 381 purpose.1oZa For example the phenol (52) produces the bridged dienone (53) in good yield by treatment with trifluoroacetic acid in nitromethane.'02b Enol acetates can also be used as alkylating agents in the presence of Lewis acid cata- lysts such as boron trifluoride.' O3 (52) (53) Several interesting routes to ap-unsaturated ketones have been devised. Enamine phosphonates can be prepared from ethynyl phosphonates and amines (Scheme 10) and they react with ketones to give conjugated imines which can HNR~ NR2 11 (EtO),POC=CR' 1,(EtO),POCH=LR' 3R3R4C=CHCR' 3 R3R4C=CHCOR1 Reagents i RZNH,;ii NaH; iii R3R4CO; iv H30+.Scheme 10 readily be hydrolysed to the unsaturated ketone.lo4 Reduction of the acetal (54) with lithium in liquid ammonia produces the dihydro-compound (55) which with dilute acid produces the enone (56).'05 (54) (55) (56) The products from the Robinson annelation reaction of 2-methylcyclo-hexanone with methyl propenyl ketone depend on the conditions selected and the reaction is remarkably stereoselective. When the cyclohexanone is pretreated with sodium hydride in dioxan followed by addition of the enone condensation produces the compound (57).By a similar sequence but in dimethyl sulphoxide as solvent the isomer (58) is formed. The course of reaction under the two sets of conditions is explained by proton transfer in dimethyl sulphoxide producing the anion of the acyclic ketone; such an exchange does not occur in dioxan.'06 Robinson annelation reactions can proceed efficiently under acid-catalysed condition^.'^' A further modification of this reaction is to condense an enolate 102 (a)W. F. Erman and L. C. Stone J. Amer. Chem. SOC.,1971,93,2821; (b)D. J. Beames T. R. Klose and L. N. Mander Chem. Comm. 1971 773. 103 G. L. Hodgson D. F. MacSweeney and T. Money Chem. Comm. 1971 766. 104 M. S. Chattha and A. M. Aguiar Tetrahedron Letters 1971 1419. 105 L. J. Dolby and E. Adler Tetrahedron Letters 1971 3803.'06 C. J. V. Scanio and R. M. Starrett J. Amer. Chem. SOC.,1971 93 1539. lo7 C. H. Heathcock J. E. Ellis J. E. McMurry and A. Coppolino Tetrahedron Letrers 1971,4995. P.G. Sammes anion from a cyclohexanone with 1,4-dichlorobutan-2-one; the product is mainly the epoxy-ketone [e.g.(59)],notable in being the trans-fused isomer. lo8 Chloro-olefins are useful since they can be considered to be potential carbonyl groups. A simple method for their incorporation into carbon systems is by Claisen rearrangement. Thus the ether (60) rearranges to the ketone (61) on heating and this in turn is transformed into the cyclopentenone (62) with sulphuric acid.' O9 Cyclopropanols are becoming attractive synthetic intermediates.Thus the alcohol (63) prepared by reduction of the diketone (64) using lithium in ammonia can react in several ways leading to azulene indane and spiro-type carbon skeletons (Scheme 1l).' lo Another route to spiro-ketones is via a double enamine Reagents i Li-NH,; ii NaH-THF; iii MeOH (rapid addition); iv MeOH (slow addi- tion); v TsC1-pyridine; vi NaOAc-HOAc. Scheme 11 S. Danishefsky and G. A. Koppel Chem. Comm. 1971 367. Io9 P. T. Lansbury P. C. Briggs T. R. Demmin and C. E. DuBois J. Amer. Chem. SOC. 1971 93 1311. 'lo P. S. Venkataramani J. E. Karoglan and W. Reusch J. Amer. Chem. SOC.,1971 93 269; K. Grimm P. S. Venkataramani and W. Reusch ibid. p. 270. General Methods alkylation using the reagent (65). Thus with the enamine (66),the spiro-derivative (67) is produced.''' Enamines have also been used as an entry into the perhydro- azulene system. '' Under appropriate conditions imines which can tautomerize into enamines behave as effectively as enamines in Michael addition reactions. For example the imine (68) adds to acrylamide to give the lactam (69) in good yield.'' 0 Factors affecting the extent of O-versus C-alkylation of b-dicarbonyl systems such as ethyl acetoacetate continue to be explored. As established previously lithium derivatives give rise to more C-alkylation than salts of the higher alkali metals ;conformations of the enolate anions are also important. 'l4 Bromination of ketones in methanol occurs at the least substituted carbon atom in contrast to the result obtained in ether or carbon tetrachloride.This is explained in terms of rapid formation of the ketal in methanol the species brominated being the vinyl ether rather than the eno1."5 Various methods for controlling the direction of alkylation of ketones have been devised. Selectivity is obtained by using lithium di-isopropylamide in dimethoxyethane the least sterically hindered enolate ion forming. In contrast silylation gives the enol ether directed towards the most hindered carbon atom and these ethers can be selectively alkylated at this point.'16 Regiospecific enolate formation also occurs in the reaction of methyl-lithium with enol phosphates [e.g.(70)]and related derivatives.' D. J. Dunham and R. G. Lawton J. Amer. Chem. SOC.,1971,93 2074. '' J.B. Hendrickson and R. K. Boeckman J. Amer. Chem. SOC.,1971 93 1307. l3 I. Ninomiya T. Naito S. Higuchi and T. Mori Chem. Comm. 1971 457. A. L. Kurts A. Macias I. P. Beletskaya and 0. A. Reutov Tetrahedron Letters 1971 3037. M. Gaudry and A. Margult Tetrahedron 1970 26 561 1. H. 0. House M. Gall and H. D. Olmstead J. Org. Chem. 1971,36 2361. 1. J. Borowitz E. W. R. Casper and R. K. Crouch Tetrahedron Letters 1971 105. 384 P.G.Sammes The y-halogenation of ap-unsaturated aldehydes is readily achieved by initial preparation of their enol acetates which can be made by exchange with iso- propenyl acetate using cupric acetate as catalyst.' l8 Selective dehydrobromination of a-bromo-ketones is effected with either tetramethylammonium dimethyl phosphate or the salt of methyl methyl- phosphonate.'' 5 Carboxylic Acids and Derivatives Isonitriles can be prepared from primary formamides by reaction with carbon tetrachloride and triphenylphosphine in the presence of a tertiary base. 120 Normal nitriles can be obtained from aldoximes by dehydration with titanium(1v) chloride in pyridine. l2 Formerly the formation of enolate ions from simple esters has been frustrated by problems such as self-condensation. Conditions whereby such anions can be formed have now been elucidated. Low temperatures are essential and lithium salts of hindered secondary amines are recommended as the base; the use of lithium N-isopropylcyclohexylamide has been advocated. '22a The resulting ester enolates can be alkylated,'22a halogenated,' 22b and acylated ;122c carboxyl-ation has also been reported,'23 The lithium salt (71) has also been made and Li I EtCCO Et I OC0,Et (71) used in a synthesis of the alkaloid ~amptothecin.'~~ The dianions of P-keto-esters can also be prepared the bases of choice again being the lithium salts of hindered secondary amines in this case lithium di-isopropylamide.As expected alkylation or condensation with aldehydes or ketones initially occurs at the least substituted point.'25 Dianions from carboxylic acids126a can be oxidized by air to the corresponding a-hydroxycarboxylic acids in good yields.'26b They can also participate in Michael condensation reactions. 126c P-Hydroxy-acids are obtained 'lS M. J. Berenguer J. Castells J.Fernandez and R. M. Galard Tetrahedron Letters 1971,493. 'I9 J. L. Kraus and G. Sturtz Bull Sac. chim. France 1971 2551. R. Appel R. Kleinstiick and K.-D. Ziehn Angew. Chem. Internat. Edn. 1971 10 132. 12' W. Lehnert Tetrahedron Letters 1971 559. lZ2 (a) M. W. Rathke and A. Lindert J. Amer. Chem. Soc. 1971 93 2318; (6) M. W. Rathke and A. Lindert Tetrahedron Letters 1971 3995; (c) M. W. Rathke and J. Deitch ibid. p. 2953. 123 S. Reiffers H. Wynberg and J. Strating Tetrahedron Letters 1971 3001. Iz4 G. Stork and A. G. Schultz J. Amer. Chem. Soc. 1971 93 4074. 125 G. Brieger and D. G. Spencer Tetrahedron Letters 1971 4585; S. N. Huckin and L. Weiler ibid. p. 4835. (a)Ann. Reports (B) 1970 67 260; (b)G. W. Moersch and M. L. Zwiesler Synthesis 1971 647; (c) Y.-N.Kuo J. A. Yahnev and C. Ainsworth J. Amer. Chem. Soc. 1971,93,6321. General Methods 385 by carrying out the Reformatsky reaction with the carboxylic acid function protected as its trimethylsilyl ester.'27 Phenols are often difficult to esterify but the reaction can be smoothly and efficiently catalysed by the use of a mixture of boric and sulphuric acids.128 Sterically hindered acids can be alkylated with trialkyloxonium salts in the presence of a hindered base such as di-isopropylethylamine. '29 Furthermore hindered esters can also be selectively cleaved in the presence of phenyl ethers by reaction with boron trichloride in dichloromethane.' 30 The trans-esteri- fication of esters is enhanced by carbon dioxide which catalyses the exchange via formation of the monoalkylcarbonate with the alcohol.31 A catalytic de- hydrator for producing acetates of alcohols has been de~cribed'~'" and the system has also been adapted for the preparation of acetals from the lower ketones and a1deh~des.I~~' A new synthon for the nucleophilic introduction of acyl groups has been de~cribed.'~~ This is the oxazolinone derivative (72) prepared from a carboxylic acid and valine. Alkylation or Michael addition reactions occur at position 2. Subsequent hydrolysis of the product leads to the corresponding ketone. + Me2N=CC1 C1- I (74) R C02Bu' (72) (73) Mixed carboxylic-sulphonic acid anhydrides are extremely powerful acylating agents.' 34a They cleave alkyl ethers and aromatic substrates can be acylated.134b These mixed aghydrides are simply prepared by mixing carboxylic anhydrides with sulphonic acid anhydrides.' 34c A simple method for the trifluoroacetylation of amino-acids is to use 1,l,l-trifluoro-3,3,3-trichloroacetone in dimethyl sulphoxide.'35 A further useful acylating agent is the water-soluble and stable salt (73) which can be used to insert t-butyloxycarbonyl groups into amines in aqueous solution.'36 Phosgene immonium chloride (74) is another stable com- pound useful for the introduction of carboxy-groups.'37 '27 A. Horeau Tetrahedron Letters 1971 3227. W. C. Lowrance Tetrahedron Letters 1971 3453. lZ9 D. J. Raber and P. Gariano Tetrahedron Letters 1971 4741. 130 P. S. Manchand Chem. Comm. 1971 667.13' Y. Otsuyi N. Matsumura and I. Imoto Bull. Chem. SOC.Japan 1971 44 852. 132 (a)G. F. Vesley and V. I. Stenberg J Org. Chem. 1971 36 2548; (6)V. I. Stenberg G. F. Vesley and D. Kubik ibid. p. 2550. 133 W. Steglich and P. Gruber Angew. Chem. Internat. Edn. 1971 10 655. 134 (a) M. H. Karger and Y. Mazur J. Org. Chem. 1971 36 532; (6) ibid. p. 540; (c) ibid. p. 528. '35 C. A. Panetta and T. G. Casanova J. Org. Chem. 1970 35 4275. 136 E. Guibe-Jampel and M. Wakselman Chem. Comm. 1971 267. 13' H. G. Viehe and Z. Janousek Angew. Chem. Internat. Edn. 1971. 10. 573. 386 P. G. Sammes Mercuric carboxylates can be converted into the corresponding acid anhydrides by reaction with a thione ester.I3* Thione esters can also be made to rearrange into the corresponding thiol ester by the use of catalytic quantities of triethyl-oxonium fluoroborate.' 39 Keten does not react with 1,3-dienes in a Diels-Alder manner cyclobutane formation being preferred.A useful 'keten synthon' is 2-chloroacryloyl chloride a powerful dienophile. Addition across dienes can be followed by liberation of the masked carbonyl group by a Curtius reaction.'40 6 Alkylation and Coupling Reactions Steric effects are often difficult to separate from strain effects etc. A useful probe for assessing the steric bulk of ketones appears to be their reaction with t-butyl- allylmagnesium bromide. The ratio of the allylic adducts obtained is a measure of the bulkiness of the ketone used.14' In the alkylation of allylic carbanions the nature of the leaving group affects the orientation of substitution with un- symmetrical substrates.In methylation reaction at the most stabilized carbanion centre increases in the order 1 < Br < C1 < tosylate when steric effects are not predominant. 14' Grignard additions to ketones often follow an abnormal course resulting in reduction. In a comparative study of a variety of organometallic compounds it has been established that organocadmium reagents gave the least amount of reduction besides giving a good yield of the addition ~r0duct.l~~ Whereas Grignard reactions on a-hydroxy-ketones are extremely stereoselective additions to acyclic P-hydroxy-ketones show little selectivity. ln contrast it has now been established that 2-a-hydroxyalkyl-cyclopentanonesreact with Grignard reagents in a highly stereoselective manner.'44 The addition of organolithium compounds to olefins is aided by neighbouring sulphur and nitrogen groups provided they are near enough to complex the adduct initially formed in an unstrained manner.145 Primary amines however react in an anomalous manner resulting in the formation of lithium hydride and the formation of a ketone after hydrolysis (Scheme 12).146 Interest in the use of lithium dialkylcuprates for conjugate addition to un- saturated ketones continues. A novel method for making substituted cyclo- pentenones is by alkylation of the ketone (75) in the P-position with these reagents. The enolate ion initially produced can be further alkylated in the a-position by *''J.Ellis R. D. Freier and R. A. Schibecki Austral. J. Chem. 1971 24 1527. T. Oishi M. Mori and Y. Ban Tetrahedron Letters 1971 1777. 140 E. J. Corey T. Ravindranathan and S. Terashima J. Arner. Chem. Sac. 1971 93 4326. 14' A. J. Kresge and V. Nowlan Tetrahedron Letters 1971 4297; M. Cherest H. Felkin and C. Frajeman ibid. p. 379. 142 W. S. Murphy R. Boyce and E. A. O'Riordan Tetrahedron Letters 1971 4157. 143 P. R. Jones W. J. Kauffman and E. J. Goller J. Org. Chem. 1971 36 186. 144 E. Ghera and S. Shoua Chern. Cornrn. 1971 398. 14' A. H. Veefkind J. V. D. Schaaf F. Bickelhaupt and G. W. Klumpp Chem. Cornrn. 1971 722. 146 H. G. Richey W. F. Erickson and A. S. Heyn Tetrahedron Letters 1971 2183. General Methods R'CH,NH 1,R'CH,NLi R'CH=NLi -$ R'R'CHNLi -% R'RZC-NLi 3 R'R2CO Reagents i R'Li; ii -LiH; iii H,O+.Scheme 12 alkyl iodides. Pyrolysis then lea& to elimination of a 4,5-disubstituted cyclo- pent-2-enone.14' Addition of lithium dimethylcuprate to cyclohexenones probably proceeds via a step involving electron transfer to form a complexed radical anion. Thus the cyclopropyl enone (76) reacts to give both the exDected 0 -0 023 product (77) and the ring-opened product (78) which must arise via collapse of the radical anion (79) followed by aikylati~n.'~~ A similar mechanism may be involved in the alkylation of allylic epoxides with lithium dialkylcuprates. Conjugate addition occurs in a trans-manner p.g. (80)-+(Sl)] indicating a non-concerted transfer of the alkylating agent.49 6 14' G. Stork G. L. Nelson F. Rouessai and 0. Gringore J. Amer. Chem. Soc. 1971 93 3091. 14' J. A. Marshall and R. A. Ruden Tetrahedron Letters 1971 2875. 149 D. M. Wieland and C. R. Johnson J. Amer. Chem. SOC.,1971 93 3047; J. Staroscik and B. Rickborn ibid. p. 3046. 388 P.G. Sammes Lithium dialkenylcuprates also add to a/3-unsaturated ketones in a 1,4-manner.' 50 However with the vinylic reagents isolated free-radical species are not involved in either the conjugate addition reaction to unsaturated ketones' la or in self-coupling reactions,I5 lbsince in both of these the stereochemical integrity of the alkenyl groups is maintained. The effect of various metal cations on Grignard reagents has also been re- examined.Copper@) halides have been used to moderate the addition of both lithium and magnesium Grignard reagents to acid chlorides ; hindered ketones can be prepared in this way.' 52 Copper(1) is particularly effective for the cross- coupling of alkylmagnesium halides with alkyl halides provided the reaction is carried out at low temperatures with tetrahydrofuran as solvent.' 53a Primary halides react most efficiently whereas secondary and tertiary halides tend to disproportionate before coupling. Silver(1) ions are recommended for symmetrical coupling reactions,' 3b and vinyl bromides can be coupled with Grignard reagents most effectively in the presence of iron(m) salts.' 53c Trialkylboranes can be alkylated with chloroform in the presence of the hindered alkoxide base (82).Oxidation gives the corresponding carbinol ; thus tributylborane gives tributylcarbinol in high yield. '54 The selective transfer of an alkyl group from certain trialkylboranes can now be achieved. For example B-butyl-3,5-dimethylborinane(83) reacts with ap-unsaturated ketones under radical-induced conditions by selective transfer of the butyl group.' 55 Alkylated olefins can be prepared by the hydroboration of acetylenes using a dialkylborane followed by coupling of the alkyl and alkenyl units by oxidation with iodine and base (Scheme 13).'56" 1,4-Dienes can be made in a similar manner.'56b Allylic epoxides also react with trialkylboranes by conjugate addition of an alkyl group and formation of the alkylated allylic alcohol.' 57 Di-isobutylaluminium hydride is becoming of increasing importance for use in synthetic work.It adds in a trans-fashion across acetylenic bonds and 150 E. J. Corey and R. L. Carney J. Amer. Chem. Soc. 1971,93 7318. (a) C. P. Casey and R. A. Boggs Tetrahedron Letters 1971,2455;(6)G. M. Whitesides C. P. Casey and J. K. Krieger J. Amer. Chem. SOC., 1971 93 1379. J. E. Dubois M. Boussu and C. Lion Tetrahedron Letters 1971 829. 153 (a) M. Tamura and J. Kochi J. Amer. Chem. SOC.,1971 93 1485; (b) ibid. p. 1483; (c) ibid. p. 1487. 154 H. C. Brown B. A. Carlson and R. H. Prager J. Amer. Chem. Soc. 1971,93 2070. 15' H. C. Brown and E. Negishi J. Amer. Chem. Soc. 1971 93 3777. 156 (a)G. Zweifel R. P. Fisher J. T. Snow and C. C. Whitney J.Amer. Chem. Soc. 1971 93 6309; (6) B. M. Mikhailov and Y. N. Bubnov Tetrahedron Letters 1971 2127. 15' A. Suzuki N. Miyaura M. Itoh H. C. Brown G. W. Holland and E. Negishi J. Amer. Chem. Soc. 1971 93 2792. General Methods Reagents i RCEECH; ii I,-NaOH. Scheme 13 the vinylalane so formed adds across ketones to form allylic aic~hols.'~~ Vinylic alanes also react with the Simmons-Smith reagent to give cyclopropylalanes which react with acid to give the hydrocarbon and with halogens to form cyclo- propyl halides. 59 Several new ylide-type reagents have been reported. Lithiumbromomethanes prepared from gem-dibromoalkanes are carbenoid precursors. They react with a variety of ketones to form epoxides.16' Spirocyclopropanes can be made by reaction of ap-unsaturated carbonyl compounds with the ylide (84).16' Thus methyl acrylate forms the product (85).Spirocyclopropanation is also 0 0 wco2Me PSPh Ph!d 7. I1 Bu-S-Me (84) (85) NMe2 effected with the reagent (86).162 Ylide intermediates prepared from the optically active sulphoxide (87) have also been used in the preparation of optically active cyclopropanes and epoxides. 163 An interesting method for the preparation of cyclopropanes is by use of the vinyloxosulphonium salts such as (88) (Scheme 14). Nucleophiles add at the 0 0 II . )I ..... AC0,Me PhCH=CHSPh 1 PhCH=CHSPh '3 II II NMe BF,-+NMe Ph CN Reagents i Me,O+ BF,-; ii MeO,CCH,CN; iii base. Scheme 14 58 H. Newman Tetrahedron Letters 197 1 457 1. G.Zweifel G. M. Clark and C. C. Whitney J. Amer. Chem. SOC.,1971 93 1305. I6O G. Cainelli A. U. Ronchi F. Bertini P. Grasselli and G. Zubiana Tetrahedron 1971 27 6109. 16' B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1971 93 3773. 16' C. R. Johnson G. F. Katekar R. F. Huxol and E. R. Janiga J. Amer. Chem. SOC. 1971,93 3773. 163 C. R. Johnson and C. W. Schroeck J. Amer. Chem. SOC.,1971,93 5303. 390 P.G. Sammes /3-position7 and further treatment with base catalyses the elimination of the sulphinamide group.' 64 1,3-Bismethylthioallyl-lithium(89) behaves as a masked aldehyde group. For example alkylation of (89)with pentyl bromide followed by hydrolysis with mercuric chloride in aqueous acetonitrile leads to oct-2-enal in high yield.'6s Li + (89) The a-butylthiomethylene group has been recommended for directing alkyl- ation in cyclic ketones in much the same way as the hydroxymethylene group is used. Its advantage over the latter is that it can be used in reductive alkylation reactions for example with lithium in liquid ammonia followed by addition of an alkylating agent conditions under which the butylthiomethylene group is reduced to the corresponding methyl group.'66 Dimethyl oxalate has also been recommended as a means of activating ketones by condensing with them.'67 Details of the use of propane-1,3-dithiotoluene-p-sulphonatehave emerged. This reagent reacts with ketones possessing a-methylene groups to form the act-dithioacetal. Hydrolysis produces a-diketones. '68 The monoalkylation of a/3-unsaturated ketones is often complicated by dialkylation which occurs by proton transfer from the monoalkylated product.By using imine derivatives the proton transfer is curtailed and selective monoalkylation is effected. Cyclo- hexylamine and 1,l-dimethylhydrazine derivatives are re~0mmended.I~~ The coupling of alkyl halides can be aided by first making the thiazoline derivative (Scheme 15). Generation of the alkyl anion with butyl-lithium is aided by chela- tion to the thiazoline nitrogen. Alkylation with an alkyl halide followed by Raney nickel reduction liberates the coupled product. "* Arylpalladium salts are extremely useful in coupling reactions (the Heck reaction). It has now been found that vinylpalladium compounds can be made by exchange of palladium salts with vinylsilanes themselves readily accessible by the addition of trialkylsilanes across acetylenic bonds.l7 ' These vinyl- palladium derivatives also participate in coupling reactions. 7 Miscellaneous Alkyl and ally1 cations can easily be generated by the reaction of the appropriate halides with silver trifluoroacetate in either liquid sulphur dioxide or n-pentane. 164 C. R. Johnson and J. P. Lockard Tetrahedron Letrers 1971 4589. 165 E. J. Corey B. W. Erickson and R. Noyori J. Amer. Chem. Sac. 1971 93 1724. 166 R. M. Coates and R. L. Sowerby J. Amer. Chem. SOC.,1971 93 1027. 167 E. Brown M. Ragault and J. Touet Tetrahedron Letters 1971 1043. 168 R. B. Woodward I. J. Pachter and M. L. Scheinbaum J.Org. Chem. 1971,36 1137. G. Stork and J. Benam J. Amer. Chem. SOC.,1971,93 5938. I7O K. Hirai H. Matsuda and Y. Kishida Tetrahedron Letters 1971 4359. 171 W. P. Weber R. A. Felix A. K. Willard and K. E. Koenig. Tetrahedron Letters f971 4701. 39 1 li 1iii R' R~CH Reagents i BuLi; ii R2X; iii Raney nickel. Scheme 15 Collapse of the cations by further reactions to the ester or olefin is slow thus allowing the chemistry of these species to be studied.'72 A large number of substrates form 1,l-dianions with butyl-lithium. For example phenylacetonitrile and sulphones give such species which can be dia1k~lated.l~~ Acetophenone oxime can also form a dianion (90). With car- boxylic esters this forms iso~azoles.'~~ Polymetallation of alkynes is also possible and in this way alkylated allenes can be prepared.'75 PhCCH Lit Q+S JQ II NO-Li' SPPh (90) N-Alkylated sulphenamides can be made either by the reaction of an amine with N-alkylthiophthalimide' 76 or by the reaction of a disulphide with an amine in the presence of a silver salt.'77 Bis-(2-pyridyl) disulphide is a useful reagent for condensation reactions.With triphenylphosphine the intermediate salt (91) forms. This reacts with carboxylate anions and the product reacts with an amine to form an amide; 17' H. M. R. Hoffmann G. F. P. Kernaghan and G. Greenwood J. Chem. Soc. (B) 1971 2257. E. M. Kaiser L. E. Solter R. A. Schwarz R. D. Beard and C. R. Hauser J. Amer. Chem. Soc. 1971,93,4237; W. E. Truce and L. W.Christensen Chem. Comm. 1971 588. 174 J. S. Griffiths C. F. Beam and C. R. Hauser J. Chem. SOC.(0,1971 974. '' Y. Leroux and R. Mantione Tetrahedron Letters 197 1 59 1. 176 D. N. Harpp and T. G. Back Tetrahedron Letters 1970 4953. 177 M. D. Bentley 1. B. Douglass J. A. Lacadie D. C. Weaver F. A. Davis and S. J. Eitelman Chem. Comm. 1971 1625. 392 P.G. Sammes peptide bonds can be efficiently formed in this way'7a and phosphate esters can also be prepared in a similar manner. 179 Tertiary phosphine dihalides also react with epoxides to give the cis-and trans-172-dihalides. The ratio of the isomeric addition products depends on the solvent and a considerable degree of control is possible by selecting the solvent used.lBO Cyanuric chloride is a useful reagent for converting alcohols into the corres- ponding chlorides.It does not require the presence of a base and rearrangements are avoided.lB1 The bromine derivative (92) is a selective brominating agent ; it gives only monosubstitution with phenols. '82 Tetra-alkylammonium salts are in some ways superior to salts of alkali metals in specific reactions. Thus tetrabutylammonium cyanide is far superior to sodium cyanide as a catalyst for the benzoin condensation. lB3 Me,SiN=NSiMc I1 0 (93) Amines can be deaminated with dinitrogen tetroxide to give nitrate esters often in high yields. '84 Another nitrogen derivative nitrosyl cyanide formed in situ from silver cyanide and nitrosyl chloride adds across dienes to form N-cyano-oxazines a potentially useful way of introducing amino-groups.'* Bistrimethylsilyldi-imine (93) is another interesting compound which can be used either to transfer azo-groups or as an oxidizing agent.'86 The salt (94) can be isolated and finds use as a Mannich reagent.'87 + Me,NCH,I I-(94) Amongst new protecting groups developed in the current year are mesitylene- sulphonates prepared with the selective sulphonating agent mesitylenesulphonyl chloride.'88 N-Toluene-p-sulphonyl groups are useful for the protection of '18 R. Matsueda H. Maruyama M. Ueki and T. Mukaiyama Bull. Chem. SOC.Japan 1971,44 1373. '19 T. Mukaiyama and M. Hashimoto Bull. Chem. Soc. Japan 1971,44 196. A. N. Thakore P. Pope and A. C. Oehlschlager Tetrahedron 1971 27 2617. la' S.R. Sandler J. Org. Chem. 1970 35 3967. V. Calo F. Cinimale L. Lopez and P. E. Todesco J. Chcm. SOC.(0,1971 3652. Ia3 J. Solodar Tetrahedron Letters 1971 287. F. Wudl and T. B. K. Lee J. Amer. Chem. SOC.,1971 93 271. Ig5 P. Horsewood and G. W. Kirby Chem. Comm. 1971 1139. 186 N . W'iberg Angew. Chem. Internat. Edn. 1971 10 374. J. Schrieber H. Maag N. Hashimoto and A. Eschenmoser Ancew. Chem. Internat. Edn. 1971 10 330. '*' S. E. Creasey and R. D. Guthrie Chem. Comm. 1971 801. General Methods indoles; they can be removed by hydrolysis with dilute base.lE9 The acetylene derivative of amines (95) can be removed from sulphur-containing peptides by hydrogenolysis.' 90 Anew photosensitive protecting group for acids is the benzoin derivative (96),' 91 which is a useful complement to those already described.19' I (95) Me0 (96) la9 R. E. Bowman D. D. Evans and P. J. Islip Chem. and Ind. 1971 33. I9O G. L. Southard B. R. Zabrowsky and J. M. Petter J. Amer. Chem. SOC.,1971 93 3302. 19' J. C. Sheehan F. M. Wilson and A. W. Oxford J. Amer. Chem. SOC.,1971,93 7222. 19' A. Patchornik B. Amit and R. B. Woodward J. Amer. Chem. SOC.,1970 92 6333.

ISSN:0069-3030    

DOI:10.1039/OC9716800365

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

12 Biosynthesis By E. McDONALD University Chemical Laboratory Lensfield Road Cambridge CB2 1EW MUCHof the work published in 1971 has strengthened the evidence for the major biosynthetic pathways the studies on presqualene pyrophosphate filling a particularly important gap. Mechanistic studies and the use of 13C n.m.r. were more prominent than before and glucose was shown to be a key precursor for a number of otherwise unrelated compounds. There were some surprises too notably in the indole-monoterpene alkaloid family. 1 Triterpenes and Steroids The conversion of farnesyl pyrophosphate (3) into squalene (2) is the starting point for the biosynthesis of the whole triterpene family and in 1966 Rilling isolated an intermediate presqualene pyrophosphate (1).At least four different structures have been proposed to account for the spectral properties of pre-squalene pyrophosphate and its degradation products,’ but new synthetic evidence from several independent sources seems finally to settle the matter in favour of structure (1). The gross structure of presqualene alcohol rests on its total synthesis by two groups :Crombie’s key step2 is the base-catalysed reaction H c J. Edmond G. Popjak S.-M. Wong and V. P. Williams J. Biol. Chem. 1971 246 6254. ’ R. V. M. Campbell L. Crombie and G. Pattenden Chem. Comm. 1971 218. 395 396 E. McDonald of phenyl farnesyl sulphone (4)with ethyl farnesoate (9,whereas Altman used3 the zinc-iodide-catalysed reaction of diazo-compound (6) with farnesol.Both routes gave mixtures of isomers one of which (as the pyrophosphate) was con- verted with high efficiency into squalene (2) by yeast microsomes. The relative stereochemistry of presqualene alcohol was assigned by correlation4 of its (3; R = CH,OPP) (5; R = C0,Et) (4; R = CH,SO,Ph) (6; R = CHN,) degradation product (7) with synthetic material of known stereochemistry. This result is confirmed by a third synthesis5 of presqualene alcohol the stereo- chemical environment of the cyclopropane ring being set up in an elegant and unambiguous manner as shown in the sequence (9)- (12). Finally the fact that presqualene alcohol and (+)-chrysanthemyl alcohol (8) exhibit Cotton effects of opposite sign in their 0.r.d. spectra defines4 the absolute stereochemistry shown in structure (1).,CH,OAc AcoH2c% H' Me AcOH,Cu' Me-The specificity of oxidosqualene cyclase from rat liver has been further de- lineated by incubation with the unnatural substrate de-6-methyl-2,3-oxido- squalene (13). Both Corey6 and van Tamelen7 find that this compound is efficiently converted into 19-norlanosterol. Although fl-sitosterol (14) is derived L. J. Altman R. C. Kowerski and H. C. Rilling J. Amer. Chem. SOC.,1971 93 1782. H. C. Rilling C. D. Poulter W. W. Epstein and B. Larsen J. Amer. Chem. SOC.,1971 93 1783. R. M. Coates and W. H. Robinson J. Amer. Chem. SOC.,1971 93 1785. E. J. Corey A. Krief and H. Yamamoto J. Amer. Chem. SOC.,1971,93 1493. E. E. van Tamelen J. A. Smaal and R. B. Clayton J. Amer. Chem. SOC., 1971 93 5279.Biosyn thesis 397 from 2,3-oxidosqualene Barton finds' that in the same plant Polypodium vulgure fern-9-ene (15) is formed from squalene (2) itself presumably by proton- initiated cyclization. Yet another variation was observedg in Ononis spinosu cell-free extracts incubated anaerobically have no effect on squalene (2) or oxido- squalene (l6) but transform the dioxide (17) into onocerin (18) in 44% of the theoretical yield. (13; R = H) (16; R = Me) (17; R = Me; A22'23'-o~ide) The key steps in the conversion by yeast of 4R-[2-'4C,4-3H]MVA (19) into lanosterol (21) and cholesterol (22) are outlined in Scheme 1. The proof of tritium labelling at (2-17 and C-20 was a relatively straightforward chemical problem assisted in practice" by the microbiological introduction of a double bond at A21(22).However the assignment of absolute configuration at C-23 and C-24 where chirality depends only on isotopic substitution is a problem incapable of solution by current chemical methods. Caspi therefore resorted to enzymology and found'' that the degradation product (23) retains all its tritium during conversion to the corresponding aldehyde by yeast alcohol * D. H. R. Barton G. Mellows and D. A. Widdowson J. Chem. Sac. (C) 1971 110. M. G. Rowan P. D. G. Dean and T. W. Goodwin F.E.B.S. Letters 1971 12 229. lo L. J. Mulheirn and E. Caspi J. Biol. Chem. 1971 246 3948. " J. B. Greig K. R. Varma and E. Caspi J. Amer. Chem. Sac. 1971,93 760. 398 E. McDonald T TfioZH HOH2C C02H J T T R T GH] [22;R= -22 24 .- G14C Scheme 1 dehydrogenase the known stereospecificity of this enzyme therefore defines the absolute configuration at C-23.A second enzyme oxidizes stereospecifically only one of the prochiral methyl groups at C-24 that which carries the 14C label the absolute configuration of the product (24) was discovered12 by an X-ray structure determination. Taken together these results prove that the enzymatic reduction of lanosterol proceeds by cis addition of H2 to the si-face. The presence of tritium at C-17 and C-20 in Caspi's cholesterol (22) might result from either a 1'3-H shift (C-13-+(2-20) or two 1,2 shifts (C-13-P C-17 D. J. Duchamp C. G. Chidester J. A. F. Wickramsinghe E.Caspi and B. Yagen J. Amer. Chem. Sac. 1971 93 6283. Biosynthesis 399 and C-17 -+ C-20) induced by the carbonium ion (20). Barton has proved the latter mechanism by the synthesis of [ll,14-3H,]squalene oxide (16) which is incorporated’ by yeast into lanosterol exclusively labelled at C-17. Further-more in peas the same precursor is converted into P-amyrin labelled at C-9 and C-18. Both results are in agreement with Ruzicka’s hypotheses for triterpene biosynthesis. The same authors find14 that in yeast the diene (25) is a precursor of ergosterol (26) the reverse reaction does not occur. Synthesis of the precursor Y HO (25;Y = =CHJ (25) required the development of a selective protection for the diene system a further example of a general method becoming available as a result of the stimu- lus posed by a biosynthetic problem.In his CIBA medal lecture Goodwin’ has reviewed his extensive contribution to the biosynthesis of plant triterpenes and carotenoids. 2 Sesquiterpenes Cornforth has extended his work with chiral methyl groups to the studyI6 of farnesol biosynthesis. 2R-[2-3H]MVA (27) was incubated in D,O with an enzyme preparation from pig liver. Farnesol(28) with a chiral methyl group was formed and its absolute configuration was determined after degradation to chiral acetic acid by employing enzymatic transformations of established stereospecificity. An exactly complementary result was obtained when 2S-[2-3H]MVA was substituted for the 2R-enantiomer thus demonstrating the reliability of the assay.This result can be combined with previous biosynthetic evidence to define precisely the isomerization of isopropenyl pyrophosphate as shown. A reasonable scheme for the biosynthesis of the tricothecane skeleton has been proposed by Hanson on the basis of his feeding experiments (Scheme 2).” Thus [2-3H]geraniol and [2-3H]farnesol give trichodermol (29) specifically labelled l3 D. H. R. Barton G. Mellows D. A. Widdowson and J. J. Wright J. Chem. SOC.(C) 1971 1142. l4 D. H. R. Barton T. Shioiri and D. A. Widdowson J. Chem. SOC.(C) 1971 1968. *’T. W. Goodwin Biochem. J. 1971 123 293. l6 K. Clifford J. W. Cornforth R. Mallaby and G.T. Phillips Chem. Comm. 1971 1599. ” P. M. Adams and J. R. Hanson Chem. Comm. 1971 1414.400 E. McDonald CH,OPP at C-2 and C-10 respectively and the label of the former precursor is retained in a related metabolite helicobasidin (30). In an independent investigation’ [2-3H]MVA was shown to give verrucarol (31) labelled as shown another two Scheme 2 tritium atoms were not located though this is a matter of some interest as it would define which of the gem-dimethyl groups of farnesol has migrated in the Hanson scheme. l8 R. Achini B. Miiller and Ch. Tamm Chem. Comm. 1971 404. Biosynthesis 40 1 3 Monoterpenes Sweroside (32) has recently been shown18" to serve as a precursor of the mono- terpene indole alkaloids in Vinca rosea. Since the ester methyl group of loganin (33)is known to be retained during its further transformation this result implies that the plant has esterase activity.Methylation of loganic acid (34)has now been demonstrated both in 21iuo'~and in a cell-free extract" from Vinca rosea. Young ,,OGlu RO,C 0 (33; R = Me) (34;R = H) seedlings of the same plant were used by Scott in a studyz1 of the incorporation of radioactivity from [2- 14C]tryptophan into various indole alkaloids as a func- tion of time. The characteristic curve for each alkaloid indicates its role as a metabolicintermediate or end product and a new compound has been discovered an intermediate between vincoside (35) and geissoschizine (36). This work (35) appears in the first issue of a new journal likely to be a forum for future bio- synthetic reports and in the same publication Kutney reviews22 his recent contributions to indole-alkaloid biosynthesis.A new development* in the Cinchona area is the incorporation of vincoside (35 ; 0.07 %) and corynantheal (37;0.13 %) into cinchonine (38). In' H. Inouye S. Ueda and Y.Takeda Chem. and Pharm. Bull. (Japan) 1971,19 587. '' R. Guarnaccia and C. J. Coscia J. Amer. Chem. Soc. 1971 93 6320. 2o K. M. Madyastha R. Guamaccia and C. J. Coscia F.E.B.S. Letters 1971 14 175. A. I. Scott P. B. Reichardt M. B. Slaytor and J. G. Sweeny Bio-organic Chem. 1971,1 157. 22 J. P. Kutney J. F. Beck C. Ehret G. Poulton R. S. Sood and N. D. Westcott Bio-organic Chem. 197 1 1 194. 23 A. R. Battersby and R. J. Parry Cheni. Comm. 1971 30. 402 E. McDonald (37) (38) An X-ray determinati~n~~ on dimethylipecoside (39) and independent degra- dative experiments on ~trictosidine~(isovincoside) and vincoside lactam26 have posed a new question in indole alkaloid biosynthesis.Thus the configuration of vincoside (35) at C-1 is opposite to that of its derived alkaloids yet [5-3H]-loganin (33) is incorporated into vincoside (35) and the derived alkaloids without loss or migration27 of the tritium label. Similarly [5-3H]loganin (33) is incor- porated intact into the Zpecac alkaloidsY2' but the wrong C-1 epimer of deacetyl- ipecoside (40) is also a precursor. Thus an epimerization is occurring but there are powerful restrictions on its mechanism (these have been discussed else- where29). R'O .,OGlu H' (39; R' = Me R2 = Ac) (40;R' = R2 = H) 4 Shikimate Metabolites A wide variety of aromatic natural products are formed biosynthetically from shikimic acid (41).Normally chorismic acid (42) is an intermediate but in Neurospora crassa protocatechuic acid (44) is formed by a different pathway via 3-dehydroshikimic acid (43). The stereospecificity of the dehydration has now been established :30 as shown 6S-3-dehydr0[6-~H]shikimicacid retains 91 % of its tritium in the aromatization sequence. As a cross check the 6R-[fS3H] '' 0. Kennard P. J. Roberts N. W. Isaacs F. H. Allen W. D. S. Motherwell K. H. Gibson and A. R. Battersby Chem. Comm. 1971 899. 25 K. T. D. DeSilva G. N. Smith and K. E. H. Warren Chem. Comm. 1971,905. 26 W. P. Blackstock R. T. Brown and G.K. Lee Chem. Comm. 1971,910. 27 A. R. Battersby and K. H. Gibson Chem. Comm. 1971,902. 28 A. R. Battersby and R.J. Parry Chem. Comm. 1971,901. 29 J. Staunton in 'The Alkaloids,' ed. J. E. Saxton (Specialist Periodical Reports) The Chemical Society London 1972 vol. 2 p. 1. 30 K. H. Scharf M. H. Zenk D. K. Onderka M. Carroll and H. G.Floss Chem. Comm. 1971. 765. Biosynthesis 403 0 00.-liCO2H OH OH OH OH (43) HOJ$ OH (44) compound was found to retain only 15% of its tritium whereas both enantiomers were aromatized chemically with retention of 86 % tritium (owing to the kinetic isotope effect). In plants phenylalanine and tyrosine are usually derived independently from non-aromatic precursors but is has now been shown31 that barley can effect para-hydroxylation of phenylalanine or a close relative.Thus [4-3H,3-’4C]- phenylalanine is converted into hordenine (45) with 88% retention of tritium T (45) as a consequence of the NIH shift. A different pathway for the modification of the C,-C3 unit of phenylalanine commences with elimination of ammonia to generate cinnamic acid. The stereochemistry of this process has been investigated by two gro~ps~’,~ using the enzyme L-phenylalanine ammonia lyase obtained from potatoes. They agree that the 3-pro4 proton is stereospecifically removed and this is in accord with an anti-periplanar elimination [(46) -+(4711. This (46) (47) ’’ E. Leete R. M. Bowman and M. F. Manuel Phytochemistry 1971 10 3029. ’’ R. Ife and E.Haslam J. Chem. SOC. (C) 1971 2818. K. R. Hanson R. H. Wightman J. Staunton and A. R. Battersby Chem. Comm. 1971 185. 404 E. McDonald problem was solved only after the synthesis of aromatic amino-acids labelled stereospecifically at C-3 and two routes are now available. These amino-acids are the established precursors of many complex natural products and therefore the tools are now available for probing the mechanisms in more complicated cases. An early illustration of the approach can be seen in the work on hae- man thamine. 29*34 It has often been assumed that the C,-C units of eugenol (48) and related compounds are derived from phenylalanine (46) uia cinnamic acid (47). In Ocyrnurn hasilicurn these compounds are incorporated but they provide only a C,-C unit3 radioactivity from S-[’4C]methylmethionine is also incorporated and it is probably located at the terminal carbon atom but this will not be certain until a degradation is carried out.The fascinating metabolite xanthocillin-X (49) was radioactive after isolation36 from Penicilliurn notaturn grown with [2-’ 4C]phenylalanine but no further information is reported. 3 M e o m +N Nf HO \ HO \ IIIIII -c c- \ OH (48) (49) The alkaloid narciclasine (50)is of special biosynthetic interest because it has a structural relationship to both of the established precursors [(51) and (52)] of the Amaryllidaceae alkaloids. At Liverp~ol,~’ evidence was obtained in favour of the dienone pathway,29 and this study has been followed up in Milan and the results have been confirmed by the specific incorp~ration~~ of compounds (53a-).The aminal group appears in several Amaryllidaceae alkaloids including haemanthidine (57). It has now been shown39 that hydroxylation occurs at a late stage is stereospecific and involves the removal of that hydrogen atom which is introduced stereospecifically at C-6 earlier in the biosynthetic pathway. 34 G. W. Kirby and J. Michael Chem. Comm. 1971 187,415. 3s L. Canonica P. Manitto D. Monti and M. Sanchez Chem. Comm. 1971 1108. 3h H. Achenbach and F. Konig Experientia 1971 27 1250. ” A. R. Battersby J. Staunton and C. Fuganti Chem. Comm. 1971. 1154. 38 C. Fuganti and M. Mazza Chem. Comm. 1971 1388. 39 C. Fuganti and M. Mazza Chem. Comm.1971 1196. Biosynthesis 405 MeO& .lo&' R20 \ HO \ H 53a; R' = Me R2 = H Y = =O ! OH b; R' = Me R2 = H Y = 1 \ H Thus haemanthamine (56) randomly tritiated at C-6 lost half of its label on conversion by daffodils into haemanthidine (57) but stereospecifically tritiated haemanthamine (56)gave haemanthidine (57)with complete retention of tritium. The labelled samples of haemanthamine for these experiments were prepared biosynthetically from norbelladine (55) and 3,4-di-hydroxybenzaldehyde(54) respectively. HO C' 0 HO H 0 I (54) T R (55) (56;R = H) (57; R = OH) A long and frustrating study of the biosynthesis of aporphine alkaloids in Dicentra exirnia has been rewarded by the discovery4' of the unexpected pathway outlined in the sequence (58 -P 60).29 Me0O T N H -+ Me0 'OvzMe ' OqNR -+ Me0 40 A.R. Battersby J. L. McHugh J. Staunton and M. Todd Chem. Comm. 1971 985. 406 E. McDonald 5 Polyketides A review of cyclopropane biosynthesis has a~peared,~' principally concerned with the transfer of a methylene group from S-adenosylmethionine to unsaturated fatty acids. The reduction of linoleic acid (61) to trans-11-octadecenoic acid involves42 the cis addition of two hydrogens one of which may originate from the protic solvent. When [2-'4C]malonic acid was fed to the mushroom Clitocybe rhizophora the labelling pattern in the C diacetylene (64) suggested that it was in fact a pruning from a longer polyketide chain the amputation having occurred next to the terminal CH,OH.This hypothesis was confirmed43 by the incor- poration of the methyl esters of the C, compounds [10-'4C]oleic acid and was shown to be an intermediate. The anthraquinones emodin (65) and chrysophanol (66) in Rhamnus frangula and Rumex ~lpinus,~~ were shown to be and pachybasin (67) in Phom~fooeata~~ wholly acetate-derived like their fungal relatives (other plant anthraquinones use a pathway involving shikimic acid and MVA). Preliminary studies suggest that chartre~sin~~ (68)and curcumin (69)47 are also acetate-derived whereas the chromone (70) is an intermediate in the conversion of acetate into khellin (71).48 The inter-relation of certain phenalenones in Penicillium herquei has been el~cidated.~' 41 J.H. Law Accounfs Chem. Res. 1971 4 199. 42 I. S. Rosenfeld and S. B. Tove J. Biol. Chem. 1971 246 5025. 43 G. C. Barley A. C. Day U. Graf Sir Ewart R. H. Jones I. O'Neill R. Tachikawa V. Thaller and R. A. V. Hodge J. Chem. Soc. (C),1971 3308. 44 E. Leistner Phytochemistry 1971 10 3015. 45 C. H. Hassal R. F. Curtis and D. R. Parry Chem. Comm. 1971,410. 46 J. R. Brown M. S. Spring and J. R. Stokes Phytochemisrry 1971 10 2059. 47 P. J. Roughley and D. A. Whiting Tetrahedron Letters 1971 3741. 48 P. G. Harrison B. K. Bailey and W. Steck Canad.J. Biochem. 1971,49,964. 49 A. B. Kriegler and R. Thomas Chem. Comm. 1971,738. (63)compound lachnophyllum ester ,,C,and the (62),1 ,9-14C2]crepenynic acid [ Biosynthesis 407 R2 0 (65; R' = R2 = OH) (66; R' = OH R2 = H) (67; R' = R2 = H) (68) H 0' 0 Radioactive sclerin (72) has been obtained by feeding [l -l 4C]acetate [2-I4C]-acetate and ['4C]formate to Sclerotiniu sclerotiorum.The labelling pattern established by degradation5' is difficult to reconcile with a straight-chain poly- ketide methylated only at the non-carbonyl carbon atoms and the authors CH,CO,H .-j M. 13f.47 2.,:C-6 C-7 C-5 1 A HC02H 14 C-12 C-13 C-14 2A 1. OH 0 c CI J.1 / (72) 50 T. Tokoroyama and T. Kubota J. Chem. SOC.(C),1971 2703. 408 E. McDonald propose that the metabolite is formed from two distinct chains as shown. The same two units joined in a different manner could generate the skeleton of other metabolites of this fungus such as sclerotinin A(73).The origin of mycophenolic acid (77) has been much clarified as a result of recent experiments. The first aromatic compound on the pathway appears5 1952 to be 3-methylorsellinic acid (74) which is next converted5* into the lactone (75). The isolations2 of the sesquiterpenoid derivative (76) from Penicillium breui- compactum and its efficient incorporation into mycophenolic acid (77) demon-strate that the C side-chain is a degraded sesquiterpene unit. 3-Methylorsellinic acid (74) is involved also in the biosynthesis of the very different metabolite stipitatonic acid (78) thus proving53 that rearrangement to the tropolone takes place after forming the aromatic system. HO Me Me (74) (75;R = H) 'C0,H (76 R = farnesyl) (77) Biosynthetic Experiments with I3C.-It is appropriate to deal with this topic in the section on polyketides because the great majority of I3C-feedings to date have been with labelled acetate.The relative merits of the carbon isotopes in biosynthetic studies have been discussed recently,54 but some comments on experimental technique may now be helpful. The location of a 13Clabel in a metabolite has been detected by both 'H and '3C n.m.r. The former method relies upon the large coupling constant J(' H-' 3C) (-100 Hz) and the effect of a carbon atom enriched with 13C is to enhance the well-known 13C satellites of the protons to which it is directly bonded. The 51 C. T. Bedford J. C. Fairlie P. Knittel T. Money and G. T. Phillips Chem. Comm.1971 323. 52 L. Canonica W. Kroszczynski B. M. Ranzi. B. Rindone and C. Scolastico Chem. Comm. 1971 257. 53 A I. Scott H. Guilford and E. Lee J. Amer. Chem. SOC.,1971 93 3534. 54 J. Staunton Ann. Reports (B),1970 67 535. Biosyn thesis 409 enhancement is proportional to the enrichment which can therefore be quantified. This approach has been used suc~essfully~~ for studying the biosynthesis of piericidin A (79) in Streptornyces rnabaraensis but its obvious limitation is that it fails to give information about fully-substituted carbon atoms. Clearly I3C n.m.r. has considerable advantages and it is replacing the former method as instruments become available but two experimental points should be noted. CH 3CH zC02H +A S-CH3-methionine OCH,A (79) Firstly proton-noise decoupling is commonly employed to achieve a simple 3C spectrum but the procedure induces a nuclear Overhauser effect which enhances some signals more than others.Secondly the rapid-pulsing Fourier- transform technique will often be used to obtain spectra on small samples in the shortest possible time but the possibility arises that carbon atoms with long relaxation times will become saturated and their signal intensities diminished. These two points must be considered before quantitative conclusions are drawn from spectra of biosynthetically labelled samples they do not receive comment COMe I a. / m. CH,CO,H * A HC0,H \ OMe M.Tanabe and H.Seto J. Org. Chem. 1970,35 2087. 410 E.McDonald in the report56 on cephalosporin C derived biosynthetically from [1-13C]- and [2-3C]-acetate. The labelling patterns illustrated for aspergillin’ (80) sepe-donin’* (81) and prodigio~in~~ (82) were assigned on the basis of 13C n.m.r. after feedings of the appropriate precursors to Aspergillus nidulans Sepedonium chrysospermum and Serratia marcescans respectively. The accuracy of these assignments is of course directly dependent on the reliability of the 3Cchemical shift assignments. 6 Piperidine Alkaloids Leete has reviewed6’ the known biosynthetic pathways to the piperidine alka- loids highlighting the discovery that coniine (83)is formed in Conium maculatum wholly from acetate 5-0x0-octanoic acid. However acetate provides only the non-piperidine portion of dioscorine (84) in the yam,61 and in Haloxylon sali-cornicum62 and Lobelia ~ardinalis~~ [6-14C]lysine is incorporated specifically into the piperidine rings of halosaline (85) and lobinalirie (86) as shown.The specificity of labelling in these and several earlier examples rules out any sym- metrical intermediate and so the discovery64 that the same lysine yields lobeline (87) equally labelled at C-2 and C-6 in Lobelia inJIatawas surprising until it was demonstrated that the symmetrical lobelanine (88) is also incorporated with high efficiency. Ph-N” ‘Ph Me Hi s6 N. Neuss C. H. Nash P. A. Lemke and J. B. Grutzner J. Amer. Chem. SOC.,1971,93 2337. ’’ M. Tanase T. Hamasaki D. Thomas and L. Johnson J. Amer. Chem.SOC.,1971 93 273. ’* A. G. McInnes D. G. Smith L. C. Vining and L. Johnson Chem. Comm. 1971 325. ” R. J. Cushley D. R. Anderson S. R. Lipsky R. J. Sykes and H. H. Wasserman J. Amer. Chem. SOC.,1971,93 6284. ‘’ E. Leete Accounts Chem. Res. 1971 4 100. E. Leete and A. R. Pinder Chem. Comm. 1971. 1499. 62 D. G. O’Donovan and P. B. Creedon Tetrahedron Letters 197 1 1341. 63 R. N. Gupta and I. D. Spenser Canad. J. Chem. 1971,49 384. 64 D. G. O’Donovan and T. Forde J. Chem. SOC.(C) 1971 2889. Biosynthesis 411 The biosynthesis of the Lycopodium alkaloids has already been studied ex- tensively and it is known that pelletierine (89) is specifically incorporated into lycopodine (91) in the manner illustrated. The same precursor has now been incorporated6’ by Lycopodium cernuum into cernuine (92)whose labelling pattern was determined by degradation.In both cases the remainder of the molecule derives from a C,-N unit (lysine via A1-piperideine) and a C unit (acetate) presumably via an intermediate closely resembling pelletierine. The compound (90)seems a likely candidate. (89; R = H) (90; R = CO2H) Santiaguine (94)was obtained66 without alteration of the 14C ratio when the monomer (93)was fed to Adenocarpus foliosus :the synthesis of precursor (93) from [6-3H]lysine is noteworthy. Phenylalanine and cinnamic acid were also incorporated into santiaguine in an unexceptional way. 0 OiPh [94; R as in (93)] 7 Metabolites of Glucose A variety of structural types has now been shown to incorporate glucose in a specific manner.In several cases a comparison was made against numerous alternatives representing the other biosynthetic pathways and their poor in- corporations have strengthened the case for glucose (95). In Chelidonium majus [6-4C]glucose yields6 chelidonic acid (97) specifically labelled at the ring carbonyl group. [1-14C]Ribose is also incorporated and a pathway involving phosphoenol pyruvate and the C4sugar (96)is proposed. 65 Y. K. Ho R. N. Gupta D. B. MacLean and I. D. Spenser Canad. J. Chem. 1971,49 3352. 6b D. G. O’Donovan and P. B. Creedon J. Chem. SOC.(C) 1971 1604. 67 M. J. Malcolm and J. R. Gear Canad. J. Biochem. 1971,49,412. 412 E. McDonald &. €40 OH + CH208 HO2C bC02H (97) 4' CH,08 CH,OH ,CHO +HOT CH20H 02H208 + fOH -+ HofY Me i-CH20H CHO CH208 Me N Me OH Vitamin B biosynthesis has been studied in a mutant of Escherichia coli and the results are consistent with the scheme shown.68 Thus [l-'4C]glucose (95) gave pyridoxol (98)carrying 40 % of its activity at C-4 (theoretical value 33 %).Furthermore [1-14C]-and [2-'4C]-glycerol gave results which demonstrate that this precursor may independently provide all of the three fragments involved in the biosynthetic pathway. In Streptomyces jlavopersicus [6-''C]glucose is converted into spectinamycin (101) labelled in both C fragments. The intermediacy of myoinositol (99) and spectinamine (100)in the formation of ring A was proved by sound degradative experiment^.^^ A Canadian group has found7' that glucose is a good precursor for mito- mycin C (103)in Streptomyces uerticillatus but the available degradative methods do not give the precise location of the 14C label.A second team has confirmed the glucose result and reports7 that glucosamine (102) is also incorporated. '* R. E. Hill R. N. Gupta F. J. Rowell and I. D. Spenser J. Amer. Chem. Soc. 1971,93 518. 69 L. A. Mitscher L. L. Martin D. R. Feller J. R.Martin and A. W. Goldstein Chem. Comm. 1971 1541. 70 G. S. Bezanson and L. C. Vining Canad. J. Biochem. 1971 49 91 1. U. Hornemann and J. C. Cloyd Chem. Comm. 1971 301. Biosynthesis 413 Both papers contain proposals for the later stages of the biosynthetic pathway but the confirmation of these ideas must await further experimental evidence.8 Compounds of Mixed Biosynthetic Origin Oxygen Heterocycles.-The transformation of the phenolic chalcone ( 104) into cyanidin (106)uia the flavanone dihydrokaempferol (105) has been demon- ~trated~~ in Haplopappus gracilis. Cell cultures were used for these experiments and high incorporations were achieved in a few hours. By analogy with earlier work the 1,3,5trioxygenated benzene ring should be acetate-derived the re- mainder of the molecule originating from phenylalanine. The same pathway is the starting point for production of the rotenoids and the chalcone (107) (104; R = OH) (107; R = H) OH is a good precursor73 for amorphigenin (109) in germinating seeds of Amorpha fruticosa. Formononetin (108) is also incorporated showing that 172-phenyl migration occurs at quite an early point.The most recent supports the pathway for the later stages given in Scheme 3. H. Fritsch K. Hahlbrock and H. Grisebach Z. Naturforsch. 1971 26b 581. " L. Crombie P. M. Dewick and D. A. Whiting Chem. Comm. 1971 1183. '4 L. Crombie P. M. Dewick and D. A. Whiting Chem. Comm. 1971 1182. 414 E. McDonald ‘OH Scheme 3 The trioxygenated ring of gentisin (I 11)is known to be acetate-derived. New experiments with a tissue culture of Gentiunu Iutea show that phenylalanine contributes the remaining C,-C unit and that the benzophenone (110) is an intermediate. Nitrogen Heterocycles.-The macrocyclic nuclei of haemin the cytochromes the chloropylls and vitamin B, have a common biosynthetic origin in the simple pyrrole porphobilinogen (PBG 112) which is enzymatically converted into uroporphyrinogen I11 (113).The pattern of the peripheral substituents in uroporphyrinogen 111 is found (suitably modified) in all the biologically important porphyrin and corrin derivatives and it reveals that a rearrangement has occurred during the formation of the macrocycle (thus ring D has the wrong pattern for a simple linear cyclopolymerization of PBG). The demonstrations 75 P. Gupton and J. R.Lewis J. Chem. SOC.(0,1971,629. Biosynthesis 415 P P A = CHzCOzH P = CH2CH2COzH that iso-PBG (114) ospopyrrole dicarboxylic acid (115) and formaldehyde are not involved in porphyrin biosynthesis rules out the possibility of rearrange- ment at the monopyrrole level and supports an intramolecular rearrangement.Furthermore although uroporphyrinogen I (unrearranged skeleton) accumulates in partly denatured systems this isomer is not converted into uroporphyrinogen 111 (1 13) by any known enzyme. H (1 14; R = CHZNHZ) (115; R = H) The rearrangement must therefore occur at a stage intermediate between PBG and porphyrinogen formation and the reports of biosynthetic experi- ments involving the dipyrrylmethane (1 16) reveal a determination to solve this problem. The work is still at a preliminary stage but the results do show that the compound (116) may serve as a porphyrin precursor in in wheat germ,77 and in duck blood,78 and on this basis a solution to the ‘Twe-I11 problem’ is foreseeable.76 J. Pluscec and L. Bogorad Biochemistry 1970 9 4736. ” B. Frydman S. Red A. Valasinas R. B. Frydman and H. Rapoport J. Amer. Chem. Sor. 1971 93 2738. 78 A. R. Battersby Pure Appl. Chem. 1972 in the press. 416 E. McDonald A CH,(CHOH)3CHZOH I -x"0: N N The coenzyme form of vitamin BI2 has as a ligand the base 5,6-dimethyl- benzimidazole (118) which has now been shown to share a pathway with riboflavin. Their common precursor 6,7-dimethylribityllumazine (1 17) is incorporated specifically into coenzyme B by Propionobacteriurn sherrnanii.79.80 The antibiotic indolomycin (1 19) is biosynthesized by Streptornyces griseus and the pathway illustrated has been carefully delineated (Scheme 4).81 H R=H R = Me R = Me R = Me ___) -H y==o y= I' \ i 7' '=<" NH2 y=' NH2 OH S-methylmethionine arginine 1H Scheme 4 Naphthoquinones.-These natural products may share a common structural feature but the same cannot be said for their origins for during 1971 alone three distinct pathways were demonstrated.In PIumbago europaea acetate may pro- vides2 all the carbon atoms of plumbagin (120) as shown whereas shikimic acid 79 S-H. Lu M. F. Winkler and W. L. Alworth Chem. Comm. 1971 191. W. L. Alworth S-H. Lu and M. F. Winkler Biochemistry 1971 10 1421. U. Hornemann L. H. Hurley M. K. Speedie and H. G. Floss J. Amer. Chem. Soc. 1971,93 3028. R. Durand and M. H. Zenk Tetrahedron Letters 1971 3009. Biosynthesis 417 contribute^^^ a C,-C unit towards vitamin K (121) in Bacillus megaterium the side-chain being mevalonoid.Alkannin (122) is also formed from shikimate and MVA but probably in a different way. p-Hydr~xy[Ar-'~C]benzoicacid is a good precursors4 of ring A and [2-I4C]MVA labels two carbon atoms as shown. It seems possible that MVA also provides four of the ring B carbon atoms and a feeding with [5 or 6-14C]MVA or the corresponding geraniols would provide an experimental test. (120; R' = OH R2 = H) (122) 121; R' = H R2 = ";I" 1.) CH2CH=CCH2 83 K. H. Scharf M. H. Zenk D. K. Onderka M. Carroll and H. G. Floss Chem. Comm. 1971 576. 84 H. V. Schmid and M. H. Zenk Tetrahedron Letters 1971,4151.

ISSN:0069-3030    

DOI:10.1039/OC9716800395

出版商:RSC    

年代:1971

数据来源: RSC

摘要:

13 Nucleic Acids By R. T. WALKER Department of Chemistry Birmingham University Birmingham B 15 2TT THEPAST YEAR has seen a continuing increase in the number of publications dealing with advances in our knowledge of nucleic acids. Several new journals have appeared but have yet to establish themselves except for one-the New Biology edition of Nature-which from the first issue contained and has con- tinued to attract papers dealing particularly with the field covered by the term ‘Molecular Biology’ from leading laboratories all over the world. In an attempt to try to resolve the growing problem of ‘keeping up with the literature’ of such a wide-ranging subject an abstracting journal has started publication. This contains a classified list of the majority of papers in the field together with an abstract as soon as possible after the appearance of the paper in the primary journal.A yearly author and subject index will also be issued and it can now be seen that some 7000 papers a year are being published in this field. Several books have made a welcome appearance this year particularly those dealing with chemical aspects. Among these are books on purines,2 and a second volume in the series of ‘Synthetic Procedures in Nucleic Acid Chemi~try’.~ A translation (edited by Lord Todd and Brown) of a book first published in Russian entitled ‘The Organic Chemistry of Nucleic Acids’ is about to appear4 and another by Hall’ deals with the modified nucleosides. There are also books dealing with physical constants,’ ~tructure,~ and biological effects’ of poly-nucleo tides.’ ‘Nucleic Acids Abstracts,’ ed. E. S. Krudy and A. Williamson Information Retrieval Ltd. London 1971. * J. H. Lister ‘Pnrines,’ Wiley London 1971. ’ ‘Synthetic Procedures in Nucleic Acid Chemistry,’ ed. W. W. Zorbach and R. S. Tipson Wiley London 1972 vol. 2. ‘Organic Chemistry of Nucleic Acids,’ ed. N. K. Kochetkov and E. I. Budovskii (translated by B. Haigh ed. Lord Todd and D. M. Brown) Plenum London 1971. R. H. Hall ‘The Modified Nucleosides in Nucleic Acids’ Columbia University Press London 197 1. B. Janik ‘Physicochemical Characteristics of Oligonucleotides and Polynucleotides,’ Plenum London 1971. ’ ‘Fine Structure of Proteins and Nucleic Acids,’ ed. G. D. Fasman and S. N. Timasheff Dekker New York 1970.‘Biological Effects of Polynucleotides,’ ed. R. F. Beers and W. Braun Springer- Verlag New York 1971. 419 420 R. T. Walker Many other books and over one hundred review articles have been published,' so that it is impossible to mention them all. This review it is hoped covers the areas where really significant advances have been made. Much of the work of greatest significancecontinues to come from the molecular biologist. Crick has started to unravel the eukaryotic chromosome" and has given us another of his now familiar triangles (Figure l) which links the highly specific interactions between proteins and paired and unpaired nucleic acids thus making no distinction between DNA' and RNA. Protein \\ UnDaired / \ Paired Nucleic Acid 4 - - - - - - - +Nucleic Acid (3 Figure 1 A claim to have transduced human cells by transducing derivatives of phage lambda has been made,'* and if substantiated will raise many moral issues as to how this line of research might be developed.A precursor tyrosine tRNA molecule which contains few if any modified bases has been sequenced13 and can be cleaved to give a 4Smolecule by an Escherichia coli crude extract. Contrary to previous e~idence,'~ the -CCA terminus is coded for in the tRNA gene. Khorana continues to synthesize genes and has announced progress in the synthesis of the gene for this same tyrosine tRNA;I5*l6presumably the gene for the precursor molecule will be the next goal. At last the synthesis of poly-ribonucleotides seems to be possible,' with such an elegant method that the use of a polymer support and the accompanying automated methods is in sight.Reverse transcriptase-the unfortunate name given to the RNA-directed DNA polymerase from the oncogenic RNA viruses-has continued to receive much attention," and no doubt with the Americans planning to spend $1600 million in three years to cure cancer much more work on the same lines can be See index of reviews in ref. 1. lo F. H. C. Crick Nature 1971 234 25. Abbreviations used are in accord with the recommendation of the IUPAC-IUA Commission J. Biol. Chem. 1970 245 5171. C. R. Merril M. R. Geier and J. C. Petricciani Nature 1971 233 398. l3 S. Altman and J. D. Smith Nature New Biol.1971 233 35. l4 V. Daniel S. Serid and U. Z. Littauer Science 1970 167 1682. H. G. Khorana I.U.P.A.C.Journal 1971,25,91. l6 P. Besmer K. Agarwal M. H. Caruthers P. J. Cashion M. Fridkin E. Jay A. Kumar P. C. Loewen E. Ohtsuka J. H. van de Sande N. Siderova and U. L. RajBhandary Fed. Proc. 1971,30 1314. J. K. Mackey and P. T. Gilham Nature 1971 233 551. R. C. Gallo Nature 1971 234 194. Nucleic Acids 421 expected. Whether the outcome will be successful remains a matter of opinion but the American politicians in this pre-election year obviously do not agree with Sir MacFarlane Burnet who was quoted as saying that he thought all the brilliant work in molecular biology had made no contribution of any significance to medicine and he was even convinced that it never would.1 Bases Nucleosides and Nucleotides A spray reagent for adenine compounds has been described the result of which sounds like real chromatography”-pink spots on a gold background. Nucleo- sides characterized by a high positive charge such as 7-methylguanosine and/or with strong hydrophobic substituents such as 2-methylthio-N6-isopentenyl-adenosine have been rapidly eluted from cation-exchange columns by incor- porating ethanol in the solvent.20 Bernardi2’ has further developed his poly- acrylamide gel columns so that the eight nucleosides obtained from a digest of RNA and DNA can be separated in five hours. Bio-Gel P2 (<400mesh) which has been fractionated to give particles of uniform (-10-20 pm dia.) size is used. The advantages of the method are speed reusability of the columns and quanti- tative recovery of the nucleosides each of which is eluted in a very small volume which gives a clean spectrum.Analysis of DNA can be achieved on only 0.5 pg DNA. The method has again been refined22 to enable computerized quantitative evaluation of each nucleoside at a 1-10nmol level. Other nucleic acid com- ponents have been separated on Sephadex gels,23 and an investigation of the mechanism of the adsorption of purines onto Sephadex G-10 has been made.24 Purines,” pyrimidines,26 and their derivatives have been separated by g.1.c. and nucleosides nucleotides and dinucleotides have been estimated by pyrolysis gas ~hromatography.~’ Perhaps the time has come to assess the reaction of nucleic acid bases with diethylpyrocarbonate (DEP; ethoxyformic anhydride) which is being widely used as an inhibitor of ribonuclease in the isolation of RNA.As was reported last year,28 Leonard29 showed that DEP reacts with adenine to give 5(4)-N- ethoxycarbonylaminoimidazole-4(5)-N’-ethoxycarbonylcarboxamidine(1). In a recent paper,30 Leonard has shown that 9-propyladenine and adenosine have the imidazole ring opened. Treatment of the adenosine reaction products with l9 M. E. Wright and D. G. Satchell J. Chromatog. 1971 55 413. 2” M. Uziel and C. Koh J. Chromatog. 1971,59 188. 21 G. Piperno and G. Bernardi Biochim. Biophys. Acta 1971 238 388. 22 S. D. Ehrlich J.-P. Thiery and G. Bernardi Biochim. Biophys. Acta 1971 246 161. 23 I. Reifer K.Strzaka and E. Machowicz Bull. Acad. polon. Sci. Ser. Sci. Biol. 1971 19 1. 24 L. Sweetman and W. L. Nylan J. Chromatog. 1971,59 349. 25 C. W. Gehrke and D. B. Lakings J. Chromatog. 1971 61 45. 26 V. Pacakova V. Miller and I. J. Cernohorsky Analyr. Biochem. 1971,42 549. ’’ L. P. Turner and W. R. Barr J. Chromatog. Sci 1971,9 176. 28 G. M. Blackburn Ann. Reports (B) 1970 67 489. 29 N. J. Leonard J. J. McDonald and M. E. Reichmann Proc. Nut. Acad. Sci. U.S.A. 1970 67 93. 30 N. J. Leonard J. J. McDonald R. E. L. Henderson and M. E. Reichmann Bio-chemistry 1971 10 3335. 422 R.T. Walker NHR I Et0,CN Ftn-f"' Ribosyl (2; R = H) (3; R = C0,Et) ethanolic ammonia gave (2) and (3). Adenosine has a half-life of 10min under the conditions used for RNase inhibition (dilute solution pH 7,23 "C).Tobacco mosaic virus (TMV) RNA infectivity was completely destroyed by DEP at 23 "C. Spectroscopic evidence only was obtained for the reaction of DEP with AMP GMP UMP but probably not with CMP;31reaction of radioactive DEP with ribosomal preparations showed that the reaction with nucleic acids was dependent upon the degree of secondary structure and in any case reaction proceeded preferentially with the protein.31 The template activity of TMV RNA,32 and the acceptor activity of several ~RNAs,~~ has been claimed to be normal when DEP has been used in the isolation procedure but the activity of other tRNAs has been affected together with a change in their chromatographic mobility,33 and this change can be obtained by incubating the isolated active tRNAs with DEP.Another report34 states that the presence of RNA interferes with the inhibition of ribonuclease by DEP and it would appear that a fine balance between the reaction of DEP with protein and nucleic acid bases exists which is dependent upon too many variables for the reagent to be used with any guarantee of success. A purine base which has caused the chemist many problems since it was first discovered in tRNA is the base 'Y'. This base occurs adjacent to the 3'-end of the anticodon in tRNAPhe in yeast,35 wheat germ,36 and rat liver37 but the structure was not determined until last year.38 This structure (4) has now been independently confirmed39 with the exception that the proton previously assigned to N-7 is preferred on the oxygen at C-6.The base has now been found in several other tRNAPhe samples4' but it is very labile and easily modified,41 and evidence 31 F. Solymosy P. Hiivos A. Gulyas I. Kapovits 0.Gaal G. Bagi and G. L. Farkas Biochim. Biophys. Acta 1971 238 406. 32 M. Denic L. Ehrenberg I. Fedorcsak and F. Solymosy Acta Chem. Scand. 1970 24 3753. 33 B. J. Ortwerth Biochim. Biophys. Acta 1971 246 344. 34 D. G. Humm J. H. Humm and L. I. Shoe Biochim. Biophys. Acta 1971,246,458. 35 U. L. RajBhandary R. D. Faulkner and A. Stuart J. Bid. Chem. 1968 243 575. 36 G. Katz and B. S. Dudock J. Bid. Chem. 1969 244 3062. 37 L. M. Fink T. Goto F. Frankel and I. B. Weinstein Biochem. Biophys. Res. Comm. 1968 32 963 38 K.Nakanishi N. Furutachi M. Funamizu D. Grunberger and I. B. Weinstein J. Amer. Chem. Sac. 1970 92 7617. 39 R. Thiebe H. G. Zachau L. Baczynskyj K. Biemann and J. Sonnenbichler Biochim. Biophys. Acta 1971 240 163. 40 L. M. Fink K. W. Lanks T. Goto and I. B. Weinstein Biochemistry 1971 10 1873. 41 D. Yoshikami and E. B. Keller Biochemistry 1971 10 2969. Nucleic A cids 423 has been obtained that 'Y' in yeast tRNA is different to the 'Y' in beef and wheat germ tRNA.41 The structure of another 'Y'obtained from Torulopsis utilis tRNAPhe is reported to have structure (5)."* The chiral centre in (4)is L."~ A base isolated from rat beef calf and chicken liver tRNAPhe has been named 'peroxy Y' (6)."" The base in rat-liver tRNAPhe appears to be a mixture of 'Y' and 'peroxy Y'.The biosynthetic route and the purpose of this modification remain to be discovered. Me (4;X = H) (5;R = X = H) (6;X = 02H) Another series of purine derivatives which has received much attention during the year is the cytokinins. These again sometimes occur in tRNA adjacent to the 3'-end of the anticodon,"' and the tRNA isolated from tobacco callus grown in the presence of the synthetic cytokinin N6-benzylaminopurine contained small amounts of this unnatural ~ytokinin."~ A stereospecific synthesis of cis-eati in^^ and ribosyl-~is-zeatin,"~ has been described. Silica t.1.c. in chloroform- methanol easily separates the cis- and trans-isomers of the ribosides. The ribosyl- zeatin from tobacco callus and wheat germ tRNA is the cis-isomer whereas that from pea epicotyls is a mixture of cis-and trans-zeatin ribosides."* 3-Methyl-7-(3-methylbutylamino)pyrazalo[4,3-d]pyrimidine(7) has been syn- thesi~ed~~ and found to be a cytokinin inhibitor when used in 10@-200-fold excess by competing with the cytokinin for receptor sites." A series of N6-42 H.Kasai M. Goto S.Takemura T. Goto and S. Matsura Tecrahedron Letters 1971 2725. 43 M. Funamizu A. Terahara A. M. Feinberg and K. Nakanishi J. Amer. Chem. Soc. 197 1,93,6706. 44 K. Nakanishi S. Blobstein M. Funamizu N. Furatachi G. van Lear D. Grunberger, K. W. Lanks and I. B. Weinstein Nature New Biol. 1971 234 107. 4s Y.Yamada S. Nishimura and H. Ishikura Biochim. Biophys. Acta 1971,247 170. 46 W.J. Burrows F. Skoog and N. J. Leonard Biochemistry 1971,10,2189. 47 N. J. Leonard A. J. Playtis F. Skoog and R. Y.Schmitz J. Amer. Chem. SOC., 1971 93 3056. 48 A. J. Playtis and N. J. Leonard Biochem. Biophys. Res. Comm. 1971 45 I. 49 S. M. Hecht R. M. Bock R. Y.Schmitz F. Skoog N. J. Leonard and J. L. Occolowitz Biochemistry 1971 10 4224. so S. M. Hecht R. M. Bock R. Y.Schmitz F. Skoog and N. J. Leonard Proc. Nut. Acad. Sci. U.S.A.,1971 68 2608. 424 R.T. Walker purinyl amino-acids5' and urei~lopurines~~~~~ have been synthesized and their cytokinin activities measured. Reaction of the appropriate isocyanate with a 9-protected adenine followed by removal of the protecting group gave a series of N6-alkyl- or aryl-ureidopurines (8).52 l-Ethoxyethyl was used for N-9 protection owing to its ease of addition and removal and the distinctive contribution it makes to the n.m.r.spectrum. Eight N6-ureidopurines synthesized had lower cytokinin activities than did N6-benzylaminopurine but N6-phenylureidopurine (9) had appreciable activity. Chheda' has synthesized naturally occurring N6-ureidopurines and their nucleosides. Reaction of adenine and ethyl chloro- formate in pyridine in a bomb at 115 "C gave a 52 % yield of N6-ethoxycarbonyl- adenine. Displacement of the ethoxy-group of the urethane or urethane riboside with L-threonine and glycine gave the naturally occurring (10) and (11) and their ribosides. The threonine in the natural compound was confirmed to have the L-configuration.i-0 ) ii NH RNH-C-NH NkN kN Me (7) (8) (9; R = Ph) (10; R = HO,CCH.CHOH.Me) (1 1 ; R = -CH2COZH) Several methods for the incorporation of radioactivity into nucleic acid derivatives have been suggested. Uracil can be quantitatively tritiated to give [5-3H]uracil by electrolytic reduction of 5-bromouracil in tritiated water.54 C-Deuteriated (or tritiated) pyrimidines (in particular [5- and/or 6-3H]uracil) can be made from tritiated water via a 1,3-thiazine (12) which can be rearranged to the corresponding uracil (13).55 Cytidine and cytidine 5'-phosphate when treated with 1M ammonium bisulphite at pH 7.5 and 37 "C for 25 h in tritiated water give a slow incorporation (10%) of tritium via the 5,6-dihydrocytidine-6- sulphonate (14).56 No deamination takes place and the conditions are mild enough for the reaction to be considered for labelling cytosine in polynucleotides particularly as phosphodiester bonds are not cleaved." D. S. Letham and H. Young Phytochemistry 1971 10 23. 52 J. J. McDonald N. J. Leonard R. Y. Schmitz and F. Skoog Phytochemisrry 1971,10 1429. 53 G. B. Chheda and C. I. Hong J. Medicin. Chrm. 1971 14 748. 54 C. Bratu J. Lubelled Compounds 1971 7,161. 55 J. F. B. Mercer and R. N. Warrener Chem. and Znd. 1970 927. 56 K. Kai Y.Wataya and H. Hayatsu J. Amer. Chem. SOC.,1971 93 2089. Nucleic Acids 425 0 0 NH [14C]Methyl iodide has been used in the preparation of ['4C]methyl-thymine57 and -th~midine~~ from the corresponding 5-bromouracil derivative.['"C]-Labelled adenosine guanosine and inosine phosphates can be isolated from human erythrocyte preparations incubated with the corresponding labelled purine bases.59 High incorporation (>80 % for ATP incorporation) is possible. Another more doubtful method for the in vitro labelling of polynucleotides by treatment with NaB[3H] in the presence of u.v. irradiation has been suggested.60 Specific activities of up to 8700c.p.m. per pg DNA have been obtained but degradation and chemical changes in the molecule must be taking place. It is suggested that the DNA would be suitable for physical and hybridization studies. Friedel-Crafts catalysts have been used in the preparation of guanine nucleo- sides." N '-Nonanoylguanine when heated under reflux with a fully acetylated sugar in chlorobenzene in the presence of aluminium chloride for 2 h gave a mixture of the N-7-and N-9-substituted nucleosides in high yield.2'-Deoxy- uridine (1 7) has been prepared6' by the catalytic hydrogenation and debenzoyla- tion of 3'-0-benzoyl-2',5-dibromo-2'-deoxyuridine (16) which can be prepared by the reaction of 2',3'-O-benzylideneuridine (15) and N-bromosuccinimide (2.2 molar equivalents) in a mixture of 1,1,2,2-tetrachloroethaneand carbon tetrachloride. 0 0 0 Ph H OX0 57 L. Pichat J. Deschamps B. Masse and P. Dufay Bull. SOC.chim. France 1971 6 2110. 58 L. Pichat B. Masse J. Deschamps and P. Dufay Bull. SOC.chim. France 1971,6,2102. 59 B. S. Vanderheiden Anu/.vt. Biochem. 1971 40 331.6o V. F. Lee and M. P. Gordon Biochem. Biophys. Acta 1971 238 174. '' W. W. Lee A. P. Martinez and L. Goldman J. Org. Chem. 1971 36 842. 62 M. M. Ponpipom and S. Hanessian Curbnhydrate Res. 1971 17 248. 426 R.T. Walker Deoxyuridine crystallizes to give two independent molecules in the asymmetric unit. The nucleosides are in the anti-c~nfiguration.~~ Dihydrouridine also crystallizes with two independent molecules in the asymmetric unit both in the ~nti-configuration,~~ and it is suggested that the nucleoside can promote loop formation in a sugar phosphate chain.65 The first purine nucleoside analogues containing a bridgehead nitrogen atom (18) and (19),have bzen synthesized by conventional methods.66 One of these (1 8) may be regarded as an inosine analogue.0 0 Ribosyl Ribosyl (18) (19) 6-Selenoguanosine has been prepared by the nucleophilic displacement of the chlorine atom from 2-amino-6-chloro-9-(~-~-ribofuranosyl)purine with either selenourea or sodium hydrogen ~elenide.~ 5-Hydroxyuracils [and their nucleosides (20)]have been converted into 6-alkyluracils via a Claisen rearrange- ment.68 Allylation of 5-hydroxyuridine gives the 5-allyloxy-compound (2 I) which rearranges in 10min at 120°C to the 6-ally1 derivative (22). I I I Ribosy 1 Ribosy1 Ribosyl Diazotization of 2‘,3’,5‘-tri-O-acetyI-8-aminoadenosine with sodium nitrite in 40 % HBF at -20 “C gives 8-fl~oroadenosine.~~ Syntheses of 3’-fluoro- and 3’-chloro-3’-deoxythymidine,70 9-(5‘-amino-5’-deoxy-fi-~-arabinofuranosyl)ade- Z’-amin0-2’-deoxycytidine,~~ nine,71 2’-amin0-2’-deoxyuridine,~~ and a new approach to the synthesis of 3’-amino-3’-deoxynucleosides from a glucopyrano- 63 A.Rahman and H. R. Wilson Nature 1971 232 333. h4 D. Suck and W. Saenger F.E.B.S. Letters 1971 12 257. 65 M. Sundaralingam S. T. Rao and J. Abola Science 1971 172 725. 66 M. W. Winkley G. F. Judd and R. K. Robins J. Heterocyclic Chem. 1971 8 237. ‘’ G. H. Milne and L. B. Townsend J. Heterocyclic Chem. 1971 8 379. 68 B. A. Otter A. Taube and J. J. Fox J. Org. Chem. 1971.36 1251. 69 M. Ikehara and S. Yamada Chem. and Pharm. Bull. (Japan) 1971 19 104. ’O G. Etzold R. Hintsche G. Kowollik and P. Langen Tetrahedron 1971 27 2463. ” M. G. Stout and R. K. Robins J. Heterocyclic Chem.1971,8 515. 72 J. P. H. Verheyden D. Wagner and J. G. Moffatt J. Org. Chem. 1971,36 250. Nucleic Acids 427 side7j have been reported. The previously reported synthesis of pse~douridine~~ has been investigated the intermediates have been isolated and the stereo- chemistry of the reaction has been ~larified.~' Conditions have been found which favour the formation of the 8-isomer. The reaction of chloroacetaldehyde with cytosine,76 or the reaction of chloro-acetic acid with cytosine or cytidine followed by ring closure under basic con- dition~,~ yields [1,2-~]pyrimidines. Chloroacetaldehyde also reacts with adenine to give an imidaz0[2,l-i]purine.~~ The N4-acyl group of a tetra-acylated cytidine can be selectively removed under acidic conditions7 and the N4-amino-group can be selectively acylated with an excess of carboxylic acid in dimethylformamide in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquin0~ine.~~ The mechanism of the mutagenic action of hydroxylamine with cytosine continues to receive attention.79 It is now realised that adenine also reacts with hydroxylamine80*8 although at 0.005 of the rate of the corresponding reaction with cytidine.Adenosine reacts to give N6-hydroxyadenosine which isomerizes to adenosine-1-oxide," which may also be a primary product of the reaction. A mechanism is postulated and it is emphasized that although the rate of reaction is slow these reactions could occur in uivo and it is interesting to note that whereas hydroxylaminopurines are mutagenic adenine-1 -oxide is carcinogenic.Some purine 1-and 3-N-oxides have also been prepared by oxidation of purine and 6-methylp~rine.'~ In a study of the effect of methylamine on the rate of inorganic phosphate release by periodate-oxidized adenosine 5'-phosphate the optimum conditions of dependence upon the pH solvent and amine concentration have been found.83 Uracil thymine and some derivatives have been oxidized by hydrogen peroxide.84 Near neutrality free-radical pathways are the most important but under alkaline conditions the predominant reaction is that of the anion of the hydroperoxide with the neutral substrate. Thymidine thymidylic acid,*' and the thymine residues in DNA86have been oxidized by permanganate under mild conditions.The former compounds give predominantly the corresponding thymidine glycol at pH 8.6 and the 5-hydroxy-5-methylbarbituricacid deoxy- riboside at pH 4.3. The permanganate oxidation of cytosine and cytidine gives 73 H. H. Baer and M. Bayer Canad. J. Chem. 1971,49 568. 74 D. M. Brown M. G. Burdon and R. P. Matcher J. Chem. SOC. (C),1968 1051. 75 U. Lerch M. G. Burdon and J. G. Moffatt J. Org. Chem. 1971,36 1507. 7h N. K. Kochetkov V. N. Shibaev and A. A. Kost Tetrahedron Letters 1971 1993. '7 R. S. Goody and R. T. Walker J. Org. Chem. 1971,36,727. 78 J. F. B. Mercer and R. H. Symons Biochim. Biophys. Acta 1971,238,27. 79 E. I. Budowsky E. D. Sverdlov R. P. Shibaeva G. S. Monastyrskaya and N. K. Kochetkov Biochim. Biophys. Acra 1971 246 300. no E.I. Budowsky E. D. Sverdlov and G.S. Monastyrskaya Biochim. Biophys. Acta 1971 '' 246 320. D. M. Brown and M. R. Osborne Biochim. Biophys. Acta 1971,247 514. 82 A. Giner-Sorolla C. Gryte M. L. Cox and J. C. Parham J. Org. Chem. 1971 36 1228. 83 A. Steinschneider Biochemistry 1971 10 173. 84 L. R. Subbaraman and E. J. Behrman J. Org. Chem. 1971,36 1256. n5 S. Iida and H. Hayatsu Biochim. Biophys. Acta 1971 228 1. " S. Iida and H. Hayatsu Biochim. Biophys. Acra 1971 240 370. 428 R.T. Walker urea and biuret derivatives but 2’,3’,5’-tri-O-benzoylcytidine gives only urea derivatives as the intermediates formed deaminate more readily than those of the free base or nu~leoside.~’ Cytidine 5’-phosphate cytidine and cytosine are easily converted into the 4-thiouridine derivatives with an isolated yield of 70 % by heating the starting material in a steel container at 60°C for 41 h with liquid hydrogen sulphide solution in pyridine.” The reaction pathways of 4-thiouracil derivatives with nitrous acid,89 bisulphite,” and cyanogen bromide,’ to give the corresponding uracil derivatives have been investigated.The 2‘-0- and 3’-O-methyl nucleosides can be prepared from the nucleoside catalytic amounts of stannous chloride dihydrate and diaz~rnethane.’~ Yields are high and the mono-0-benzyl nucleosides can be prepared from phenyl- diazomethane. The catalyst-solvent system dioxan-acetonitrile-hydrogen chloride converts uridine into 2’,3’-O-ethylideneuridine in 74 % yield and under the same conditions gives 3’,5’-di-O-acetylthymidine in 56 % yield from th~midine.~ In the absence of dioxan uridine gives 5’-O-acetyluridine (46 %) and 2’,3’,5’-tri-O-acetyluridine (23%).Reaction of adenosine with p-nitrobenzal- dehyde ethyl orthoformate and trifluoroacetic acid in dimethylformamide results in two blocking groups being added simultaneously to give N6-(a-ethoxy- ~-nitrobenzyl)-2’,3‘-O-ethoxymethyleneadenosine in 80 % yield.94 Ribonucleo- tides react in the order pG > pA > pU = pC with benzoic or acetic anhydrides in aqueous solution to give selective O-a~ylation.’~ 2,4-Dinitrofluorobenzene reacts with nucleotides in the absence of trialkyl- amines to give a 2,4-dinitrophenyl cster whereas the addition of the base catalyses the reaction of fluoride ion to give the nucleoside phosph~fluoridate.’~ Many physicochemical studies on bases nucleosides and nucleotides have been reported.’ All that can be mentioned here is the growing use of mass spectrometry as a tool for the identification of nu~leotides’~ and a preliminary investigation into the use of chemical ionization mass spectrometry of nucleo- sides,98 where the ion spectrum is formed not by electron bombardment but by low-energy collisions with ions derived from a reagent gas such as methane present in the ion source at relatively high pressure.One advantage over con- ventional techniques appears to be the high relative abundance of the protonated molecular ion. ’’ R. S. Goody A. S. Jones and R. T. Walker Tetrahedron 1971 27 65.** T. Ueda M. Imazawa K. Miura R. Iwata and K. Odajima Tetrahedron Letters 1971 2507. 89 S. Iida and H. Hayatsu Biochem. Biophys. Res. Comm. 1971 43 163. 90 H. Hayatsu and M. Inoue J. Amer. Chem. Soc. 1971 93 2301. ” ’* R. T. Walker Tetrahedron Letters 1971 2145. M. J. Robins and S. R. Naik Biochirn. Biophys. Acta 1971 246 341. 93 J. Zemlicka J. Org. Chem. 1971 36 2383. 94 J. Zemlicka and J. P. Horwitz J. Org. Chem. 1971 36 2809. 95 R. J. Cedergren B. Larue and P. Laporte Canad. J. Biochem. 1971 49 730. y6 P. W. Johnson and M. Smith Chem. Cornm. 1971 379. ’’ A. M. Lawson R. N. Stillwell M. M. Tacker K. Tsuboyama and J. A. McCloskey J. Amer. Chem. Soc. 1971 93 1014. 98 M. S. Wilson I. Dzidic and J. A. McCloskey Biochim. Biophys. Arta 1971 240 623.Nucleic Acids 429 2 Oligonucleotides Polyethyleneimine-impregnated cellulose t.1.c. has been used for the separation of complex mixtures of oligonucleotides obtained during the sequence analysis of RNA and Oligodeoxynucleotides can be sequenced after their limited degradation with snake venom phosphodiesterase into a population of oligonucleotides of successively smaller chain lengths ' ' by labelling these small chains with a [32P]riboadenylic acid residue with terminal deoxynucleotidyl transferase. 'O2 The oligonucleotides are then separated according to chain length and their degradation with spleen phosphodiesterase allows the original sequence of the oligodeoxynucleotide to be determined. Terminal deoxynucleotidyl transferase has also been used in the synthesis of po1ydeoxynucleotides.' O3 A ribonucleoside residue is added by the enzyme to the 3'-terminus of a chemically synthesized hexathymidylate oligomer which is then used as a primer for the acceptance of dAMP residues with the same enzyme.The polymeric product can now be cleaved from the primer by alkaline hydrolysis due to the ribo- nucleotide linkage and the polydeoxynucleotide can be obtained free from primer. Khorana has reported that the chemical synthesis of oligonucleotides which make up the gene for tRNAzh,+ is complete'5 and the enzymatic joining of these is making progress.16 No doubt the synthesis will be modified to make the gene for the precursor molecule,' which 'only' involves modifying the end oligonucleotides to provide overlaps with the precursor and the synthesis of the gene coding for this precursor sequence.The synthesis of oligodeoxynucleotides is now a routine operation (at least in Khorana's laboratory) from where a general method for the preparation in high yield (50%) of all 16 dinucleoside diphosphates (dpXpY) on a large scale has been published.' O4 Intermediate phosphoramidates formed by reaction of a nucleotide with the highly lipophilic aromatic amine p-aminophenyl triphen ylmethane and dicyclohexylcarbodi-imide have enabled the products of the reaction to be isolated by solvent extraction rather than by time-consuming anion-exchange or gel filtration procedures. dpTpT has been prepared by a similar method with NN-dimethyl-p-phenyl- enediamine used to give a phosphoroanilidate which can be selectively absorbed on an ion-exchange column.'O5 Deoxyguanosine-containing deoxyoligonucleo-tides have been prepared on a polymer support using conventional blocking groups and condensation techniques.' 06,' O7 The methodology of oligodeoxy-ribonucleotide synthesis does not yet seem to be at a stage where the insoluble support method offers any advantages. 99 B. E. Griffin F.E.B.S. Lerters 1971 15 165. loo E. M. Southern and A. R. Mitchell Biochem. J. 1971 123 613. R. Roychoudhury D. Fischer and H. Kossel Biochem. Biophys. Res. Comm. 1971,45 430. H. Kossel and R. Roychoudhury European J. Biochem. 1971,22,271. lo' R. Roychoudhury and H. Kossel European J. Biochem. 1971,22,310. '04 K.L. Agarwal A. Yamazaki and H. G. Khorana J. Amer. Chem. Soc. 1971,93,2754. lo' T. Hata K. Tajima and T. Mukaiyama J. Amer. Chem. Soc. 1971 93 4928. 'Oh T. Shimidzu and R. L. Letsinger Bull. Chem. Soc. Japan 1971,44 1673. lo' V. F. Zarutova V. K. Potapov Z. A. Shabarova and D. G. Knorre Dokludy Akad. Nuuk S.S.S.R. 1971 199 1072. 430 R. T. Walker Guanylo-ribonuclease from Actinomyces aureoverticillatus,' O8 ribonuclease T ,Io9 and ribonuclease U,' lo have been used for the small-scale synthesis of oligoribonucleotides. Dinucleotide 2',3'-cyclic phosphates have been prepared in quantitative yield from the corresponding dinucleoside diphosphates in aqueous solution with a water-soluble carbodi-imide.' ' ' These can be converted by the addition of pancreatic ribonuclease and a nucleoside into triribonucleoside diphosphates in 40 yield.' '* Ribonuclease A in solution' '3,1 ' and bound to a polymer support,' ' has been used to synthesize codons containing modified nucleosides in the wobble position" and termination codons;l15 yields are 618%.Gilham '' has synthesized pApApApUpA (from pApApA) in quantitative yield. The method depends upon the enzymatic (polynucleotide phosphorylase) addition of one suitably blocked nucleoside 5'-diphosphate to a growing poly- nucleotide chain such that no further addition is possible until the blocking group is removed. The blocking group needs to be stable under the conditions of the enzymatic addition easily removable without affecting the growing chain and must not alter the nucleoside 5'-diphosphate such that the enzyme can no longer recognize it.The 2'(3')-O-(a-methoxyethyl) group which can be added by direct acid catalysis of the reaction of the 2'(3')-OH group of a nucleoside 5'-diphosphate with methyl vinyl ether has proved to be satisfactory. So far product separation has been effected by ion-exchange chromatography but the method is ideally suited to an automated support procedure as the yields are quantitative and only simple manipulations are required. Apparently we can now look forward to the 'chemical' synthesis of quite long (1&20) oligoribo-nucleotides. Isotactic succinylated polystyrene has been used as a support for the attach- ment of a ribonucleoside via a 5'-ester for the synthesis of triribonucleotides using conventional condensing agents.' ' A hexaribonucleotide albeit a repeating trimer with the same sequence as the 3'-end of yeast tRNAA'" has been synthesized.' ' The trinucleotide was synthesized by conventional means and then polymerized to give the hexanucleotide with a terminal 3'-phosphate.The o-chlorophenyl group has been used to protect the phosphate group in the phosphotriester approach to oligoribonucleotide synthesis. '' The products of the reaction can be quickly separated on silica and a significantly higher yield lo* L. P. Shershneva and T. V. Venkstern Mulekulyarnuyu Bid. 1971,5,480. '09 M. J. Rowe and M. A. Smith Biochim. Biophys. Acta 1971 247 187. lo T. Koike T. Uchida and F. Egami J. Biochem. Japan 1971 69 11 I.'I1 A. P. Kavunenko E. N. Morozova and N. S. Tikhomirova-Sidorova Zhur. obshchei Khim. 1971,41 226. 'I2 A. P. Kavunenko V. Sukharevich and N. S. Tikhomirova-Sidorova Zhur. obshchei Khim. 1971 41 679. 'I3 H. G. Gassen F.E.B.S. Letters 1971 14. 225. E. Ohtsuka H. Tegawa and M. Ikehara Chem. and Pharm. Bull. (Japan) 1971,19 139. 'I5 H. G. Gassen and R. Nolte Biochem. Biophys. Res. Comm. 1971 44 1410. 'l6 K. F. Yip and K. C. Tsou J. Amer. Chem. Soc. 1971,93,3272. 'I7 E. Ohtsuka M. Ubasawa and M. Ikehara J. Amer. Chem. Soc. 1971 93,2296. J. H. van Boom P. M. J. Burgers G. R. Owen C. B. Reese and R. Saffhill Chem. Comm. 1971 869. Nucleic Acids 431 than has previously been claimed (76% for UpUpU) is reported. Necessary intermediates for insertion into oligoribonucleotides in a stepwise synthesis N6-benzoyl-2'-0-tetrahydropyranyladenosine and N4-benzyl-2'-O-tetrahydro-pyranylcytidine and their corresponding 5'-O-p-methoxytrityl derivatives have been synthesized.* Polynucleotide ligase has been shown to catalyse the joining of DNA duplexes at their base-paired ends if a 5'-phosphate and 3'-hydroxy-group are adjacent.I2' The ligase from phage T4 in contrast to the ligase from E. coli catalyses the joining of any combination of ribo- and deoxyribo-oligonucleotides on a ribo- or deoxyribo-nucleotide template except when both strands are ribopoly-nucleotides. 21 Polynucleotide phosphorylase from Micrococcus luteus cata-lyses the synthesis of copolymers several hundred nucleotide residues long containing both AMP and dAMP residues.' 22 The fourth in a series of vinyl analogues of polynucleotides (general formula [-CHX-CH,] where X is N-1-substituted uracil or cytosine or N-9-substi- tuted adenine or hypoxanthine) has been prepared.lz3 These form soluble non-aggregated complexes with the complementary polynucleotide in solution which have broad and incompletely reversible melting profiles and a stoicheio- metry favouring the vinyl component.Electron microscopy has shown that the poly( 1-vinyluracil).poly-A complex is filamentous with the excess of uracil residues (stoicheiometry 9U :1A) looped out from the strand of poly-A which is stiffened by the binding of one or several strands of the neutral polymer. Poly- I.poly( 1-vinylcytosine) shows as high an antiviral activity as poly-1.p0ly-C.'~~ 5'-O-Acryloyl esters of cytidine guanosine and adenosine have been prepared and copolymerized with acrylamide or 6-0-acryloylgalactose to give water- soluble polynucleotide analogues.' 2s Methacryloyl chloride has been used to 0-acylate the four common ribonucleosides,'26 which have been polymerized and used to quantitatively separate several nucleoside mixtures.' 27 The results of the separation are claimed to show that in water nucleosides are paired by base stacking whereas in dimethyl sulphoxide-chloroform base pairing is by hydrogen-bonding.Ribonucleosides after treatment with periodate have been condensed with polyacrylic acid hydrazide to produce polymers containing one base residue per 10 acrylic acid hydrazide residues.The purine-containing poly- mers were retained on a DNA-agar column and exhibited large hypochromic effects when mixed with denatured DNA in Analogues of trinucleo- "'T. Neilson and E. S. Werstiuk Canad. J. Chern. 1971 49 493. 12* V. Sgaramella J. H. van de Sande and H. G. Khorana Proc. Nut. Acad. Sci. U.S.A. 1970 67 1468. ''I G. C. Fareed E. M. Wilt and C. C. Richardson J. Biol. Chem. 1971 246 925. J. Y. Chou and M. F. Singer Biochem. Biophys. Res. Comm. 1971 42 306. J. Pitha P. M. Pitha and E. Stuart Biochemistry 1971 10 4595. J. Pitha and P. M. Pitha Science 1971 172 1146. M. J. Cooper R. S. Goody A. S. Jones J. R. Tittensor and R. T. Walker J. Chem. Soc. (C) 1971 3183. ''' H. Schott and G. Greber Makromol.Chem. 1971 144 333. ''' H. Schott and G. Greber Mukromol. Chenz. 1971 145 11. M. G. Boulton A. S. Jones and R. T. Walker Biochim. Biophys. Acta 1971,246 197. 432 R. T. Walker side diphosphates with the nucleoside units linked by acetate ester (OCH,COO = ~ mand carbonate (OCOO)129b~ ) ~ ~ ~ linkages have been prepared. The former have been shown by n.m.r. and U.V. spectroscopy to have their bases stacked.129" An oligomer (dA cm),A hybridizes with poly-U in solution specifically inhibits the poly-U-stimulated binding of tRNAPhe to ribosomes,' 30 but does not stimu- late the binding of tRNALys. 3 Pairing and Stacking Conformations The conformations in solution as obtained from n.m.r. and c.d. studies of ApA ApU Ap$ ApiPA and iPApA (iPA = isopentenyl) have been compared.The last two are slightly less folded than ApA whereas there is greater base attraction in Apt$ than ApU.' 31 IpA ApI and IpI stack whereas IpU stacks very little.132 Somewhat more surprising is the fact that photochemically reduced UpA in which the uracil ring is reduced to dihydrouracil also shows considerable hypochromicity' 33 which is not affected by heat. If the dihydrouracil is further reduced to give a ureidopropionic acid derivative the hypochromicity is even greater and although the effect can be destroyed by methanol heat has no effect. Similar effects can be obtained with ApU and GpU. The crystal struc- ture of UpA has been obtained.' 34 The asymmetric unit contains two inde- pendent molecules which are hydrogen-bonded together with the purines and pyrimidines bonded to each other.All four bases are in the anti-conformation with all four sugars 3'-endo but in one molecule the sugar residues are oppositely aligned such that a sharp bend can occur in a single strand of RNA without it being necessary to invoke loop formation. A comprehensive examination' 35 of over 70 published solid-state base-stacking patterns in nucleic acid consti- tuents and polynucleotides has been made. Several recurrent stacking patterns were found. The vertical stacking of purines and pyrimidines in polynucleotides is similar to that observed in crystals of nucleic acid constituents with dipole- induced dipole forces largely responsible for the solid-state base packing. ApA forms a triple-stranded structure with poly-U at temperatures below 32 "C.'36 Further investigation of the simultaneous binding of adenosine and guanosine to poly-U previously noted,13' has shown that the binding of guano- sine is a secondary absorption of some kind onto the existing [2 poly(U + A)] com- ~1ex.l~'Poly-A forms both 1 1 and 2 1 complexes with 3-methylxanthine 129 (a)M.D. Edge and A. S. Jones J. Chem. SOC.(C),1971 1933; (6)J. R. Tittensor ihid. 1971 2656. 130 G.J. Cowling A. S. Jones and R. T. Walker Biochim. Biophys. Acta 1971 254 452. 131 M. P. Schweizer R. Thedford and J. Slama Biochim. Biophys. Acra 1971 232 217. 132 C. Formoso and I. Tinoco Biopolymers 1971 10,531. 133 C. Formoso and I. Tinoco Biopolymers 1971 10 1533. 134 N.C. Seeman J. L. Sussman H. M. Berman and S.H. Kim Nature New Biol. 1971 233 90. 135 C. E. Bugg J. M. Thomas M. Sundaralingam and S. T. Rao Biopolymers 1971 10 175. 136 G. P. Kreishman and S. I. Chan Biopolymers 1971 10 159. 137 P. M. Pitha W. M. Huang and P. 0. P. Tso Proc. Nut. Acad. Sci. U.S.A. 1968 61 332. 138 K. S. Schmitz and J. M. Schurr Biopolymers 1971 10 1075. Nucleic A cids 433 in a co-operative process but intermediate species are present during thermal dissociation. '39 Nucleoside binding to single-stranded polynucleotides has been shown to be co-operative and the stoicheiometry in all cases studied was 2 :1 in favour of the polymer even when polymers such as poly-UC and poly-AC were Poly-U adopts a single hairpin structure at -5 "C and on heating branching takes place leading to formation of multi-hairpins which finally melt in a co-operative proce~s.'~' Poly-C and copolymer I,U with differing contents of uridylic acid form double helical structures with 1..-C inter-base pairing and the U residues looped out of the helix.'42 At acid pH values poly-C and poly-G can form a three-stranded poly-G.poly-C-poly-C+ ~tructure.'~~ It is quite clear that guanosine (or inosine) can form Hoogsteen pairs with a shared proton in a triple-stranded structure only if this proton is present to bind the second cytidine strand to guanosine. This confirms earlier findings'44 and throws doubt on work which suggested that protonation of poly-G-poly-C involved a changed base pairing with the proton on N-1 of cytidine bound to the keto-group of g~an0sine.l~~ A warning about the chain length of some commercially available samples of poly-G is given.143 Little has been done to clarify the role of the 2'-OH group in the stability and conformation of polynucleotides in the papers published this year which have if anything further confused the issue. 2'-0-Methyl-containing heteropolymers poly-(Cm U ;-1 :5) and poly-(Am C) directly incorporate the correct amino- acids into protein'46 but the methylated homopolymers do not even in the presence of neomycin. Poly-2'-deoxy-2'-chloro-uridylic and -cytidylic acids (prepared from the corresponding nucleoside 5'-diphosphates and polynucleotide phosphorylase) are not bihelical in structure over a temperature range of 4-5OoC and it is suggested that helix formation requires an oxygen or -OH group in the 2'-position of ribose.147 The uracil-containing polymer however forms a comple- mentary structure with poly-A.Apurinic acid has a remarkably similar con- formation to poly-U and behaves like a random coil with no interaction between the bases. 14' The similarity between the deoxyribopolymer and poly-U has been taken as indicating that the interaction between the 2'-OH group of the ribose and the phosphate group is not a cause of rigidity in ribopolymers. Self- association of oligonucleotides occurs at much shorter chain lengths in the deoxy- than in the ribo-series. Trimers of dA and dT will give base-paired com- plexes whereas oligomers of rU and rA shorter than 7 residues do not a~sociate.'~~ Interactions between oligo rA and oligo dT have also been studied.'50 139 R.J. H. Davies and N. Davidson Biopolyrnrrs 1971 10 21. 14' R. J. H. Davies and N. Davidson Biopolymers 1971 10 1455. 141 J. C. Thrierr M. Doulent and M. Leng J. Mol. Biol. 1971 58 815. 142 H. Akutsu and M. Tsuboi Bull. Chem. Sac. Japan 1971,44 20. IJ3D. Thiele and W. Guschlbauer Biopolymers 1971 10 143. 144 G. Green and H. R. Mahler Biochemistry 1970 9 368. 145 A. M. Michelson and F. Pochon Biochim. Biophys. Acra 1969 174 604. 14' B. E. Dunlap K. H. Friderici and F. Rottman Biochemistry 1971 10 2581. 14' J. Hobbs H. Sternbach and F. Eckstein F.E.B.S. Letters 1971 15 345. lJ8J. Achter and G. Felsenfeld Biopolymers 1971 10 1625.J. C. Maurizot J. Blicharski and J. Brahms Biopolymers 1971 10 1429. 15' J. G. Hoggett and G. Mass Chem. Ber. 1971 75,45. 434 R.T. Walker tRNAPhe (anticodon GAA) and tRNAG1" (anticodon probably UUC) form a complex with a much stronger association constantl'l than is found for the binding of UUC to tRNAPhe which emphasizes the effect that a rigid and accep- table conformation has on the stability of base-base interactions. Studies on the interaction of adenylic acid-uridylic acid block copolymers have given enthalpy changes per base pair AH, that increase from -6.4kcal mo1-l for (Ap),(Up),U to -7.6kcal mol-' for (A~),(Up)~u.l~~ When a G or C is inserted between the blocks the stability of the bimolecular helical complex is reduced.C is the more destabilizing resulting in a reduction of the T of 10-1 7 "C,equivalent to the removal of 2 A-U pairs. The duplex apparently rearranges to accommodate G opposite a U residue. When one oligomer con- tains a C between the blocks and the other a G the stability of the bimolecular helix is enhanced. The replacement of A-U by G-C in a decamer raised the T by 8.5 "C.153 The stability constant of the duplex GpGpGpU :GpCpCpC containing the G-U wobble pair is 9.5 fold smaller than that of the perfectly paired GpGpGpC GpCpCpC.' 54 Results obtained for the stability of double-stranded regions loops and bulges in a single polynucleotide chain have been used to calculate the stability of various structures proposed for 5s RNA and sequences of R17 viral RNA."' The stability values used are (i) A-U pairs + 1 ; (ii) G-C pairs +2; (iii) G -U pairs 0; (iv) hairpin loops -5 to -7 ;(v) interior loops -4to -7;(vi) bulges -2 to -6.This calculation of the free energy of single-stranded loops has been criticized by Delisi and Crothers,' 56 who have calculated the size-dependent free energy required to close single-stranded loops by the formation of a base pair in a double helical nucleic acid.The free energy of RNA secondary structures at high salt concentrations can be calculated. No doubt these calculations will be further refined as more data are accumulated and they should be very useful in assessing the thermodynamically most favourable secondary structure for single-stranded polynucleotides. 4 RNA An automated RNA sequenator has been used to determine the 3'-terminal hexanucleotide sequence of a polynucleotide with an average yield at each stage of 98 %.' 57 A modified RNase (~-carboxymethyl-lysine-41-pancreatic RNase A) with a low but specific activity has been used to determine the sequence of oligonucleotides obtained by partial RNase T digestion.' The preference of the enzyme for CpA and UpA can be emphasized by varying the digestion 15' J.Eisinger Biochem. Biophys. Res. Comm. 1971 43 854. 152 F. H. Martin 0.C. Uhlenbeck and P. Doty J. Mol. Biol. 1971 57 201. 0.C. Uhlenbeck F. H. Martin and P. Doty J. Mol. Biol.,1971 57 217. '54 S. K. Podder Nature New Biol. 1971 232 1 15. 155 1.Tinoco 0.C. Uhlenbeck and M. D. Levine Nurure 1971 230 362.156 D. C. Delisi and D. M. Crothers Proc. Nar. Acad. Sci. U.S.A. 1971 68 2682; Biopolymers 1971 10 1809. 15' M. Uziel J. W. Starken J. W. Eveleigh and W. F. Johnson Cfin.Chem. 1971,17,740. 158 R. Contreras and W. Fiers F.E.B.S. Letters 1971 16 281. Nucleic Acids 435 conditions. 3'-Terminal polynucleotides can be selectively bound to columns of cellulose derivatives containing covalently bound dihydroxyboryl groups. 59 A new species of 5s RNA (5sRNA,,,) has been found in Novikoff hepatoma ascites cell nuclei and has been partially sequenced.'60 5s RNA molecules cleaved between nucleotides 41 and 42 by RNase T have been reconstituted to give native 5s RNA,16' showing that the RNA has a specific conformation and that specifically modified molecules are now available for structural and functional studies.Reconstitution experiments have shown that 5s RNA is essential for the ribosomes to have full biological activity and in the absence of this RNA molecule some proteins fail to join the particle.'62 The nucleotide sequences of 5s RNA (from Pseudomonas jluores~ens),'~~ which is similar to but not identical with E. coli 5s RNA of a 6s RNA from E. ~oli,'~~ and of a 3'-terminal sequence of 16s RNA from E. coli of40 nu~leotides'~~ have been reported and secondary structures proposed. The state of the art of determining the sequences of long RNA molecules has been dramatically demonstrated by the discovery that E. coli which is resistant to Kasugamycin has a 16s RNA containing the sequence AACCUG whereas in the sensitive strain both the adenylic acid residues have an N6N6-dimethyl group.'66 The specific methylase present in the wild type E.coli has been identi- fied and shown to methylate 16s RNA from the resistant strain only while present as a 21s ribonucleoprotein methylation being on the expected two adenylic acid residues.'67 This modification then renders the reconstituted ribosome sensitive to the drug. Treatment of sensitive E. coli cells in uiuo with colicin E3 results in a specific cleavage of the 16s RNA ca. 50 nucleotides from the 3'-end. 168 This was originally thought to have been due to a colicin-mediated change of the cell surface but it has now been shown that the in vitro reaction of colicin E3 on ribosomes has the same effect.'69 A remarkable coincidence resulted in the simultaneous publication of four papers concerned with the discovery of a precursor 16s RNA from E.coli. 70-1 73 The precursor has a considerably greater molecular weight differs in the base Is' M. Rosenberg and P. T. Gilham Biochirn. Biophys. Acru 1971 246 337. I6O T. S. Ro-Choi R. Reddy D. Henning and H. Busch Biochem. Biophys. Res. Comrn. 1971 44 963. 16' B. R. Jordan and R. Monier J. Mof.Biof. 1971 59 219. 16' V. A. Erdmann S. Fahnestock K. Higo and M. Nomura Proc. Nut. Acad. Sci. U.S.A. 1971 68 2932. 163 B. Du Puy and S. M. Weissman J. Biol. Chern. 1971 246 747. lh4 G. G. Brownlee Nature New Biol. 1971 229 147. 16' C. Ehresmann P. Fellner and J. P. Ebel F.E.B.S. Letters 1971 13 325.166 T. L. Helser J. E. Davies and J. E. Dahlberg Nature New Biol. 1971 233 12. lh7 T. L. Helser J. E. Davies and J. E. Dahlberg Nature New Biof. 1972 235 1. lhK C. M. Bowman J. E. Dahlberg T. Ikemura J. Konisky and M. Nomura Proc. Nut. Acad. Sci. U.S.A. 1971 68 964. 16' C. M. Bowman J. Sidikaro and M. Nomura Nature New Biol. 1971 243 133. M. Sogin B. Pace N. R. Pace and C. R. Woese Nature New Biol. 1971 232 48. ''I G. G. Brownlee and E. Cartwright Nature New Bioi. 1971 232 50. C. V. Lowry and J. E. Dahlberg Nature New Biol. 1971 232 52. F. Hayes D. Hayes P. Fellner and C. Ehresmann Nature New Biol. 1971 232 54. 436 R. T. Walker sequence of both ends and is under-methylated compared to the mature molecule. The sequence of some of the additional nucleotides has been obtained.E. coli 50s subunits have been assembled in vitro from a single mixture of the three ribosomal RNA species and all the necessary proteins.' 74 The mechanism of the assembly of tobacco mosaic virus from RNA and protein has been ex- plained.' 75 Viral coat protein containing ester linkages' 76 and a polyester of phenyl-lactic acid' have been produced in a cell-free synthesizing system containing aminoacyl-tRNAs the amino-acids of which had been chemically deaminated with nitrous acid. Poly-1,Poly-C has been found to inhibit or stimulate depending upon the age of the animal Moloney sarcoma virus-induced tumours in mice,'74 and it causes the death of mouse bone-marrow and spleen colony-forming cells.' 7s Despite this the double-stranded polynucleotide has been injected into humans with advanced cancer.It has failed to show a toxic effect but unfortunately has failed to show anti-tumour effects.' 76 The uptake of polynucleotides by cells has been demonstrated. In the poly-A- poly-U or poly-A-2-poly-U systems both strands enter Ehrlich ascites tumour cells but with poly-I-poly-C the poly-C remains on the cell surface while the poly-I enters the cells.'77 The uptake of polynucleotide is stimulated by the addition of deoxyribonuclease to the cell culture. ' DEAE-dextran increases the infectivity of many viral RNA molecules'79 and has been shown to increase the antiviral activity of poly-I-poly-C,' 80,18 ' probably by protecting the nucleic acid from ribonuclease attack and also increasing the binding of the poly- nucleotide to the cell surface.Poly-I has been covalently bound through its terminal 5'-phosphate to Sepharose'82 and then annealed with poly-C to give an insoluble matrix-bound poly-1-poly-C which has a similar activity to that of the normal molecule. Both the toxicity and biological activity of poly-I.poly-C are dependent upon the homopolymer molecular weights' and are both drastically reduced if these fall below lo5. It seems unlikely that a signficant separation of antiviral activity and toxicity can be made by simple manipulation of the homopolymer molecular weights. Other double-stranded RNA molecules synthetic' 84 and naturally occurring,' 85 also stimulate interferon production but evidence is accumulating that the stimulation of synthetic and natural inducers is not by the 1'4 E.de Clercq and T. C. Merigan Proc. Soc. Exp. Biol. Med. 1971 137 590. P. Jullien and J. de Maeyer-Guignard Internat. J. Cancer 1971 7 468. C. W. Young Med. Clin. North Amer. 1971 55 721. P. L. Schell Biochim. Biophys. Acta 1971 240 472. P. L. Schell and W. Muller Biochim. Biophys. Acta 1971 247 502. R. Hall J. Gen. Virol. 1971 11 111. lE0 P. M. Pitha and W. A. Carter Virology 1971 45 777. 181 F. D'ianzani S. Baron C. E. Buckler and H. B. Levy Proc. Soc. Exp. Bio. Med. 1971 136 1111. A. F. Wagner R. L. Bugianesi and T. Y. Shen Biochem. Biophys. Res. Comm. 1971 45 184. J. F. Niblack and M. B. McCreary Nature New Biol. 1971 233 52. E. de Clercq and T.C. Merigan J. Gen. Virol. 1971 10 125. 85 W. F. Long and D. C. Burke J. Gen. Virol. 1971 12 1. Nucleic Acids 437 same mechanism. However much work remains to be done since a lack of correla- tion between interferon production and anti-tumour effect is claimed,' 86 and the anti-tumour effects of synthetic polynucleotides have been explained as due to a stimulation of classical immune response rather than to interferon effects.'87 Successive administration of poly-I followed by poly-C has as great an effect if not greater than when both are administered together,188 and addition of poly-C-oligo-I under conditions above the T of the complex also stimulates the induction of interfer~n.'~~ 5 Viral RNA Significant progress has been reported in the sequence determination of the RNAs of the phages MS2 R17 f2,and QB.The A protein cistron is closest to the 5'-terminus in MS2 with the initiator codon starting at position 130.'90*191 The previous 129 nucleotides have been sequenced and have been shown to be identical with those of R17192 and RNA whereas in the next 237 nucleo- tides which can be compared for MS2 and R17 nine differences in sequence have been detected although the phages produce identical A proteins. These differences only occur because of code degeneracy and the identity of the leader sequences suggests that the tertiary structure of this part of the molecule is important. This sequence defines the sequence at the 3'-end of the complementary minus strand which may serve as a recognition site for the viral RNA polymerase complex.'94 The 5'-terminal sequences can be arranged in a cloverleaf-like fashion with a CCA end but with longer loops and one additional loop compared to the conventional tRNA cloverleaf (Figure 2).Other nucleotide sequences corresponding to amino-acid sequences of the coat protein cistron" and other parts of the MS2 molecule'96 and further sequences of R17 RNA have been obtained. 197 With the determination of the sequence of the ribosome binding sites for the initiation of translation of the Qp assembly protein'98 and the replicase gene,'99 the sequences of all six sites (for the three protein cistrons in QB and R17) are A. J. Weinstein A. F. Gazdar H. L. Sims and H. B. Levy Nature New Biol. 1971 231 53.lS7 W. Braun 0. J. Plescia J. Raskova and D. Webb fsraef J. Med. Sci. 1971 7 72. E. de Clercq and P. de Somer Science 1971 173 260. P. M. Pitha and W. A. Carter Nature New Biol. 1971 234 105. 190 R. de Wachter A. Vandenberghe J. Merregaert R. Contreras and W. Fiers Proc. Nut. Acad. Sci. U.S.A. 1971 68 585. 191 W. Fiers R. Contreras R. de Wachter G. Haegeman J. Merregaert W. Min Jou and A. Vandenberghe Biochimie 1971 53 495. 192 R. de Wachter A. Vandenberghe J. Merregaert R. Contreras and W. Fiers Arch. Internat. Physiol. Biochim. 197I 79 199. 193 V. Ling Biochem. Biophys. Res. Comm. 1971 42 82. 194 R. de Wachter J. Merregaert A. Vandenberghe R. Contreras and W. Fiers European J. Biochem. 1971 22 400. 195 W. Min Jou G. Haegeman and W. Fiers F.E.B.S.Letters 1971 13 105. 19h G. Haegeman W. Min Jou and W. Fiers J. Mol. Biol. 1971 57 597. 19' P. G. N. Jeppesen Biochem. J. 1971 124 357. 198 D. H. Staples J. Hindley M. A. Billeter and C. Weissmann Nature New Biol. 1971 234 202. 199 D. H. Staples and J. Hindley Nature New Biol. 1971 234 21 1. 438 R. T. Walker A/A \ \/ U-A U-A A-U C-G A-G A-A G-c G' A A-A \/ A-U C-G A-U C-G U-A C-G C-G C-G G-c A-U c-u G-c &''A U-C G-c G C-G A' \G \ U-A A c' A, ,C-G A\ \U-Ac-G-c 'A G G A/\G U U G A-G' C-C-C-AOH IG I A UAGCC IIIIIIIII C C U C A A C U-G I IIIII A/ U I C AUCGG C-A I 'G, 'A 'c-G' 4 \"JC C-G U-A U-A A-U /\ A@ Figure 2 Proposed secondary structure of the 3'-terminal sequence of MS2 RNA comple-mentary strand now known.Despite the fact that the ribosome specifically binds at these sites even in alkali-treated RNA and ignores the many other initiator codons present in internal sites of the molecule it is still not possible to define the specific recog- nition signal which tells a ribosome to initiate translation. Comparing this with the analogous situation of protein-nucleic acid recognition in the tRNA field this result is perhaps not really very surprising. So much work has been published on the RNA-directed DNA polymerase of the oncogenic viruses that two long and comprehensive reviews have already and the reader is referred to these. The status of the enzyme after a year of conflicting reports is that definite evidence is still needed to prove the requirement of the enzyme for initiation of neoplastic transformation and more evidence is needed before it can be concluded that it is not required for maintenance of transformation.Early reports that the enzyme was present in most cells have been shown to be due to the use of incorrect assay procedures for the enzyme. 6 tRNA Many reviews of the subject have been published.' A rapid dialysis method2" for the assay of tRNA's is claimed to be accurate over a wide range of tRNA concentration (0.5-200pg) enables the tRNA to be reused and is adaptable *"" S. Spiegelman Proc. Roy. Soc. 1971 B177 87. 201 H. C. Chen C. H. O'Neal and L. C. Craig Analyt. Chem. 1971 43 1017. Nucleic Acids 439 to a continuous and automated assay procedure.A statistically designed series of experiments to establish optimum assay conditions for several tRNAs by changing each of a dozen qualitative and quantita$ve variables and evaluating the results by computer,202 confirms that optimum charging conditions for different tRNAs vary widely; it will be of great use if the range of tRNAs covered can be extended. In uivo transcription of a tRNA gene and the isolation and nucleotide sequence of a precursor tRNA have all used the 680 phage carrying various E. coli tRNATy' genes in the phage genome. Smith203 has reported the isolation of a tyrosine tRNA-tsDNA hybrid by allowing tRNATy' to hybridize with the denatured DNA from phage @3Opsu& a phage which carries two structural genes speci- fying tRNATy'.Subsequent treatment with Neurospora crassa endonuclease which is specific for single-stranded nucleic acids releases regions of reannealed DNA and hybrid molecules composed of tRNATyr and the complementary DNA (tsDNA) which can be separated on Sephadex G-100. The locations and orientations of the Su& gene in transducing phages 480 psu& and the defective phage +80dsuil suithave been determined.204 Labelled E. coIi tRNA2' hybridized with the r strand of the former phage. As SuittRNA had previously been found to hybridize with the 1 strand of the defective phage,205 it was concluded that an inversion of the E. coEi DNA fragment carrying the Suit gene occurred before its incorporation into the +8Opsu& genome.These phages have been used to isolate the tRNATyr gene206 by a method similar to that used by Beckwith for the isolation of the lac ~peron.~" The separated heavy strands of the phage DNAs containing the tRNATY' genome inserted into their DNA in opposite directions were annealed the single-strand tails of the resulting hybrid removed with N. crassa endonuclease and the resulting DNA was used for the in uitro transcription of tRNATYr-like molecules. The assay was based on their ability to compete with tRNATy' in hybridization experiments with complementary DNA. The DNA-directed cell-free synthesis of biologically active tRNATJ:tI has been reported.'08 The DNA from ~8Opsu& was transcribed by E. coli RNA polymerase. The product was assayed by taking advantage of the specific suppressor properties of the mutant SU;~ tyrosyl-tRNA which stimulated DNA- directed /?-galactosidase synthesis using a DNA with an amber triplet in the /?-galactosidase gene.202 I. B. Rubin T. J. Mitchell and G. Goldstein Analjlr. Chem. 1971 43 717. 203 A. Marks E. Keyhani S. Naono F. Gros and J. D. Smith F.E.B.S.Letters 1971 13 110. 204 R. C. Miller P. Besmer H. G. Khorana M. Flandt and W. Szybalski J. Mol. Bid. 1971 56 363. '05 H. Lozeron W. Szybalski A. Landy J. Abelson and J. D. Smith J. Mol. Biol. 1969 39 239. '06 V. Daniel J. S. Beckmann S. Sarid J. I. Grimberg M. Herzberg and U. Z. Littauer Proc. Nat. Acad. Sci. U.S.A.,1971 68 2268. '07 J. Shapiro L. MacHattie L. Eron G. Ihler K. Ippen and J. Beckwith Narure 1969 224 768.20R G.Zubay L. Cheong and M. Gefter Proc. Nat. Acad. Sci. U.S.A.,1971 68 2195. 440 R.T. Walker Tyrosine tRNA precursor molecules have been isolated by a rapid phenol extraction technique without collection of the cells from E. coli infected with $80 phage carrying a mutant Su,, gene which results in a much higher yield of precursor than can be obtained from the original strain with the Su& gene.209 In addition to the expected tyrosine tRNA sequence these molecules contained 41 additional bases at the 5'-end and 3 at the 3'-end.13 The 5'-terminal residue was found to be pppGp which indicates that this end of the molecule is as initially transcribed. Nucleotide modification is absent and as the precursor molecule can be enzymatically cleaved by an E.coli crude cell extract to a 4s molecule this modification is apparently not required for this step in the tRNA biosynthesis. Moreover the cleavage points in the molecule when subjected to partial enzy- matic hydrolysis are the same as those in the 4s molecule indicating that the precursor probably contains the normal cloverleaf configuration. The CCA 3'-terminus is coded for in the DNA genome. As a result of experiments with other mutants the significance of the lengthy 5'-segment is thought to be con- cerned with defining the specificity of the cleavage point and to protect the molecule during transcription by hydrogen-bonding to the molecule near the cleavage point (Figure 3 a) until transcription is complete when the cloverleaf configuration (Figure 3,b) is assumed and the 4s molecule is enzymatically cleaved from the precursor molecule.The precursor molecule of normal tRNA may be even longer but will differ only at the 3'-end. An in oitro synthesis of tRNATy' precursor and its conversion into 4s RNA have also been described.210 A tryptophan tRNA suppressor has been isolated from a UGA suppressor strain of E. coli21 and the sequence differs from that of the normal tRNAT'p by a G +A mutation at position 24 in the dihydrouridine loop.212 The anticodons for both molecules are CCA which would only be expected to code for tryptophan (codon UGG). This is the first reported instance of a tRNA molecule reliably recognizing a sequence other than its complementary one. The suppressor tRNA has been shown to stimulate the synthesis of lysozyme in ~,itro~'~ by trans- lation of the phage T4 lysozyme mRNA bearing a UGA mutation.An E. coli leucine suppressor tRNA which can be used in the in oitro poly-leucine formation from poly-r (AUG) has been purified.214 Five leucine tRNAs have been purified,2 '5-2 ' and there is evidence that they can all be amino- acylated by the same en~yme.~'~,~'' Two of these tRNAs have a chain length of 87 nucleotides but differ in 22 positions of their primary sequence.218 Yeast 209 S. Altman Nature 1971 229 19. H. Ikeda Nature 197 1 234 198. 211 T. S. Chan R. E. Webster and N. D. Zinder J. Mol. Biol. 1971,56 101. 212 D. Hirsh J. Mol. Biol. 1971 58 439. D. Hirsh J. Mol. Biol. 1971 58 459.'14 H. Hayashi and D. Soll J. Biol. Chem. 1971 246,4951. 215 D. W. Holladay R. L. Pearson and A. D. Kelmers Biochim. Biophys. Acta 1971 240 541. 216 J. Kan and N. Sueoka J. Biol. Chem. 1971 246,2207. '17 H. U. Black and D. SOH J. Biol. Chem. 1971 246 4947. 218 H. U. Black and D. Soll Biochem. Biophys. Res. Comm. 1971 43 1192. Nucleic Acids 441 AU G A C A C-G U C-G G U U-G G-C U-A G-C C-G G-C G.*. PPPG-C A G G-U C-G C-G/ A-U GC G-C C U-A A-U A-U A A AGC A U G A C A C-G . . C-G U-A Ll-G G-C Ll-A \G-C C--G U-A pppG-C A G G C C A G U A A A A G C A U U A C CC G-C C A Figure 3 Possible conjiguration for tyrosine precursor tRNA during transcription (a) and after completion of transcription(b).I3 The arrows indicate the beginning of the 5'-end of the tRNA moiety 442 R.T. Walker tRNA has been labelled with 32Pin viv0219 with sufficient activity to enable a tRNAL"" to be purified and its sequence determined22o by the Sanger method. This advance enables the sequence of small amounts of yeast tRNAs to be quickly determined but before the method can be applied to tRNAs from other sources media have to be developed in which practically all the phosphate is [32P]-labelled. Among the many tRNA sequences reported this year are the following:- E. coli tRNAyd,221 tRNAVd 222 tRNAVd 222 tRNA%r223 tRNAIle 224 2A 3 2B 9 2,226 tRNA7'y,225 and tRNAgz;225 brewers yeast tRNAVa' I tRNAASp3.22 7,22 8 rat liver tRNAS"';229 Staphylococcus epidermidis tRNAy'y.230 These sequences can all be written in the cloverleaf form but they do little to clarify the structure-function relationship of a tRNA and its amino-acylating enzyme.Two of the three tRNAVal now sequenced222 have similar sequences differing only in three base pairs located in double-stranded regions. Their affinity for the synthetase is an order of magnitude greater than that of the tRNA:"' species whose sequence differs in 22 positions. It is suggested that the synthetase recognition site may be formed by the interaction of two or more of the sequences common to all three tRNAVal. The E. coli tRNApr can be efficiently charged by the yeast and rat liver synthetase but comparison of the sequences of these three tRNAS"' ~pe~ie~~~~,~~~,~~~ shows nothing which can give any definite indication of the recognition site.The sequence of tRNA;"' from brewers yeast226 differs in four positions from a previously published sequence,233 and in the few cases where tRNAs have been sequenced independently by more than one group there is an uncomfortably high percentage of cases where the results do not agree. Complexes (1 1)of tRNAG1" from E.c01i234and its synthetase and of a purified methionyl-tRNA transf~rmylase~ have been reported. It is hoped that even- tually one of these complexes will be obtained crystalline so that the enzyme recognition sites can be located. 21y S. Kowalski and J. R. Fresco Science 1971 172 384. 220 S. Kowalski T. Yamane and J.R. Fresco Science 1971 172 385. 221 F. Harada F. Kimura and S. Nishimura Biochemistry 1971 10 3269. 222 M. Yaniv and B. G. Barrell Nature New Biol. 1971 233 113. 223 H. Ishijura Y. Yamada and S. Nishimura F.E.B.S.Letters 1971 16 68. 224 M. Yarus and B. G. Barrell Biochem. Biophys. Res. Comm. 1971 43 729. 225 C. Squires and J. Carbon Nature New Biol. 1971 233 274. 226 J. Bonnet J. P. Ebel and G. Dirheimer F.E.B.S.Letters 1971 15 286. 227 J. Gangloff G. Keith J. P. Ebel and G. Dirheimer Nature New Biol. 1971 230 125. 228 G. Keith J. Gangloff J. P. Ebel and G. Dirheimer Compt. rend. 1970 271 D 613. 229 T. Ginsberg H. Rogg and M. Staehelin EuropeanJ. Biochem. 1971,21,249. Also see preceding two papers. 230 T. S. Stewart R. J. Roberts and J. L. Strominger Nurure 1971 230 36.231 H. G. Zachau D. Dutting and H. Feldman Z. Physiol. Chem. 1966 347 212. 232 M. Staehelin H. Rogg B. C. Baguley T. Ginsberg and W. Wehrli Nature 1968 219 1363. 233 A. A. Bayev T. V. Venkstern A. D. Mirzabekov A. I. Krutilina L. Li and V. D. Axelrod Molekulyarnaya Biol. 1967 I 754 (English Edn. p. 63 1). 234 W. R. Folk Biochemistry 1971 10 1728. 235 H. W. Dickerman and B. C. Smith J. Moi. Biol. 1971 59 425. Nucleic Acids 443 The tRNAE',Y (ins = insensitive to tryptophan)225 is of interest as it is a new species of tRNA which appears as a result of a mutation causing the loss of tRNA:'Y. The tRNAy'y compensates for this loss (which is normally lethal) with a G +U mutation in the 5'-end of the anticodon triplet so that the tRNA can recognize GGA/G instead of GGU/C and thus all glycine codons can still be translated.The tRNAs tRNA?lY and tRNATi' have a 78 %sequence homology with the differences located in hydrogen-bonded stems suggesting that these may be of key importance in the synthetase recognition process. This sequence similarity further confirms that three base pairs of the CCA-stem do not constitute the synthetase recognition point because the three are identical in tRNAyIY and tRNAzi' but different in tRNATi' and tRNA7"'. tRNAyi, from S. epiderrnidi~~~' fails to participate in protein synthesis and functions only in peptidoglycan synthesis. The tRNAs contain few modified bases and have several other pecularities (Figure 4),236 including the replacement of the common sequence GTrl/C by the sequence GUGC.The tRNA will not bind to ribosomes even non-specifically and this may well be due to the lack $OH C U pG-C C-G G-C G-C A G-U f A-U <:p C G-CUAUCCU A u 4tU A IIIII !A ?- AUAGGu c A C U UIGjA G U I I I jIj '<:&,-A v A G A A LCJA 'D / AG C-G r---L'I32-C JU-A G U-A C-G CG U C uCc Figure 4 Structure of S. epidermidis tRNAYAy and tRNA7; (alternative sequence indicated) 236 R. J. Roberts paper submitted to Nature. 444 R.T. Walker of this common sequence which has previously been implicated in ribosome binding. The enzymatic modification of tRNA has been reviewed237 but the function of the modified bases is still not understood.238 4-Thiouridine has still only been found in bacterial tRNA (and in mouse and chick mitochondria1 tRNA239) and its biosynthesis has been clarified.240 An E.coli tRNA lacking ribothy- midine behaves normally241 and tRNAs containing only 16% of their normal 5,6-dihydrouridine 4-thiouridine pseudouridine and ribothymidine content appear to have the same stability as normal ~RNAs.~~~ The search for the synthetase recognition site in tRNA continues by the conventional methods of the dissected molecule243 and chemical modifica- tion244,245 approaches. Methoxylamine failed to react with a cytidine residue at the 5’-end of the anticodon in a tyrosyl-tRNA despite reacting with several other cytidine residues in the Moreover the residue was still unreactive in a dissected anticodon loop and stem.The results can only be explained in terms of a model which differs from the Fuller-Hodg~on~~~ model for the anticodon loop. The covalent bond formed by U.V. irradiation between the 4-thiouridine residue at position 8 and a cytidine at position 13has continued to excite Work on model compounds suggests247 that the two bases must be close together and oriented geometrically so that a thietan and ultimately a covalently linked can 5-(1’-~-~-ribofuranosyl-4’-pyrImidin-2‘-one)cytidinebe readily formed. The covalently linked tRNA molecule has a reduced (i)affinity for the synthetase complex but the bond can still be formed by irradiation of the tRNA-synthetase tRNAPhe,249 and tRNAArg,249 complex.248 tRNAVa1,248 containing the link have been shown to function in all steps of protein synthesis albeit at a somewhat reduced rate.Results from X-ray experiments on crystalline tRNA continue to be dis- appointing. It has been suggested that conformations of tRNA molecules are too dependent upon the influence of counterions and hydration to enable anything other than the overall shape of the molecule to be deduced from a comparison of experimental curves with scattering curves calculated from atomic co-237 D. Soll Science 1971 173 293. 238 A. Peterkofsky M. Litwack and J. Marmor Cancer Res. 1971,31,675. 239 Y. Lalyre and E. B. Titchener Biochem. Biophys. Res. Comm. 1971 42 926. 240 J. W. Abrell E. E. Kaufman and M. N. Lipsett J. Biol. Chem.1971 246 294. 24’ I. Svensson L. Isaksson and A. Henningsson Biochim. Biophys. Acta 1971 238 33 1. 242 I. I. Kaiser Biochemistry 1971 10 1540. 243 A. D. Mirzabekov D. Lastity E. S. Levina and A. A. Bayev Nature New Biol. 1971 229 21. 244 For example M. A. Q. Siddiqui and J. Ofengand F.E.B.S. Letters 1971 15 105; M. Krauskopf and J. Ofengand ibid. 1971,15,111;Z. Kucan K. A. Freude I. Kucan and R. W. Chambers Nature New Biol. 1971 232 177. 245 A. R. Cashmore D. M. Brown and J. D. Smith J. Mol. Biol.,1971 59 359. 246 W. Fuller and A. Hodgson Nature 1967 215 817. 247 N. J. Leonard D. E. Bergstrom and G. L. Tolman Biochem. Biophys. Res. Comm. 1971 44 1524. 248 M. Yaniv A. Chestier F. Gross and A. Favre J. Mol. Biol. 1971 58 381. 249 L. J. Chaffin D.R. Omilianowski and R. M. Bock Science 1971 172 854. Nucleic Acids 445 ordinate^.^" Only results which are consistent with the cloverleaf form~lation~~ ' and show the presence of short parallel double-helical segments in tRNA molecules252 have been obtained. Other physical techniques have been used temperature-jump relaxation,254 n.m.r.,255*256 including fl~orescence,~~ and ~.d,~~~9~~~ the last showing curves reminiscent ofa globular protein rather than of a polyn~cleotide.~~~ fdr people to demolish have been Two new models258~259 suggested. 7 DNA The secondary structure of DNA depends upon the base composition.260 DNA molecules with a high A + T (366%) content give distinctly different X-ray scattering patterns in solution from other DNA molecules and do not seem to adopt the B conformation.This may provide regions of DNA which are specific markers for control and recognition.26 ' A circular bihelical synthetic DNA has been prepared for use as a substrate in enzyme recognition studies.262 Single- stranded complementary deoxyribopolynucleotides d(T-G) and d(C-A) were mixed under dilute condition in the presence of T4-polynucleotide ligase and treated with DNA polymerase the four deoxyribonucleoside triphosphates and more ligase. Density gradient centrifugation of the products digested with exonuclease I11 enabled double-stranded circular DNA to be isolated in 4% yield. The chromosomes of higher organisms have been st~died,'~*~~~ and it has been suggested by Crick that DNA is of two types globular DNA (which con- tains unpaired regions for control purposes) and a much smaller fraction consist- ing of fibrous DNA which alone codes for proteins.The forces and energy needed to unpair the recognition stretches of the DNA are provided for by the combination of DNA with chromosomal proteins. It has been shown that histones are not evenly distributed in chromatin,263 and extensive contiguous regions of the DNA helix are completely free of chromatin protein. Satellite DNA has been the subject of two and the location of satellite and homogeneous DNA sequences on human chromosomes has been 250 I. Pilz 0. Kratky F. Von Der Haar and F. Cramer European J. Biochem. 1971 18 436. 2s1 S. H. Kim G. Quigley F. L. Suddath and A.Rich Proc. Nut. Acad. Sci. U.S.A. 1971 68 841. 2s2 T. Sakurai S. T. Rao J. Rubin and M. Sundaraiingam Science 1971 172 1234. "' B. Robison and T. P. Zimmerman J. Biol. Chem. 1971 246 110. 254 M. Dourlent M. Yaniv and C. Htlene European J. Biochem. 1971 19 108. 2s5 D. R. Kearns D. J. Patel and R. G. Shulman Nature 1971 229 338. 25f' S. I. Chan and M. P. Schweizer Biochem. Biophys. Res. Comm. 1971,44 1. 257 G. Melcher D. Paulin and W. Gruschlbauer Biochimie 1971 53 43. 258 D. J. Abraham J. Theor. Biol. 1971 30 83. 259 A. Danchin F.E.B.S. Letters 1971 13 152. 26') S. Bram Nature New Biol. 1971 232 174. 261 K. Shishido and Y. lkeda Biochem. Biophys. Res. Comm. 1971,44 1420. 262 V. H. Paetkau and H. G. Khorana Biochemistry 1971,10 1511. "' P.J. Clark and G. Felsenfeld Nature New Biol. 1971 229 101. 26J P. M. B. Walker Nature 1971 229 306. 26s R. J. Britten and E. H. Davidson Quart. Reti. Biol.,1971 46 11 1. 446 R.T. Walker determined by the in situ RNA-DNA hybridization technique.266 Satellite I1 appears to be close to the centromeres of three pairs of chromosomes. A new method for RNA-DNA hybridization which can be used to analyse for any defined fraction of cellular RNA in terms of the reiteration frequencies of the complementary DNA sequences has been described.267 The DNA is added in such a vast excess that the DNA withdrawn into DNA-RNA hybrids does not significantly reduce the concentration of denatured DNA sequences and so the renaturation rate is essentially independent of the hybridization reaction.DNA polymerase has been used to determine the sequence of the termini of two phage [32P]-Labelled T7 phage DNA was subjected to exonucleolytic degradation with T4 DNA polymerase in the presence of each of the deoxynucleoside triphosphates in turn. The nucleotides released were quantitatively estimated and the results were consistent with the previously determined sequence.268 1 DNA has the 5’-terminal strands longer than the 3’-terminal strands. The sequence in both protruding single strands has been determined by partial and complete repair with DNA polymerase followed by sequencing of the isolated oligonucleotides. Each of the two oligonucleotides was confirmed to be 12 units long and they had complementary sequences.269 The conclusions of a paper2” on the intercalation of ethidium bromide into the DNA molecule are going to cause a drastic rethinking of the subject of intercalation and the conformation of DNA in solution if as is claimed inter- calation of ethidium bromide does cause the winding of the DNA helix by 13 f4” instead of unwinding it as has previously been assumed.A protein with similar properties to the gene-32 protein discovered last year in T4 phage has now been found in meiotic cells of lili~rn~~’ and the spermatocytes of rat bull and man.272 It would now appear that this protein which binds co- operatively to single-stranded DNA and catalyses DNA denaturation and renaturation in uitro may occur universally. It is probable that this protein plays an important part is meiosis and also in genetic recombination.It is reassuring to realise that occasionally even molecular biologists cannot find instant answers to problems or even to problems which have been recognized since the birth of the subject. DNA duplication is an outstanding example of this and despite a proliferation of theories-mostly conflicting-little progress has been reported this year. Kornberg’s enzyme DNA polymerase I has definitely been shown to have a repair function in uivo273 and has now by (al- most !274) universal consent been removed from the list of acceptable candidates for the DNA replication enzyme in uiuo. This leaves two candidates polymerases 266 K. W. Jones and G. Corneo Nature New Biol. 1971 233 268. 267 M. Melli C.Whitfield K.V. Rao M. Richardson and J. 0.Bishop Nature New Biol. 1971 231 8. 268 P. T. Englund J. Biol. Chem. 1971 246 3269. 269 R. Wu and E. Taylor J. Mol. Biol. 1971 57 491. 270 J. Paoletti and J. B. Le Pecq J. Mol. Biol. 1971 59 43. 271 Y.Hotta and H. Stern Develop. Biol. 1971 26 87. 272 Y.Hotta and H. Stern Nature New Biol. 1971 234 83. 273 W. S. Kelly and H. 0. Whitfield Nature 1971 230 33. 274 V. H. Paetkau and A. R. Morgan Nature New Biol. 1971 234 36. Nucleic Acids 447 11275 and 111,275*276 and the claims of both have been ad~anced.’~~.’~~ There is also a pertinent report which suggests that as most people insist on using Kornberg’s assay system for detecting new repair enzymes it is not surprising that enzymes with similar properties to his enzyme are found which may well have no more to do with in vim replication than the original p~lyrnerase.’~~ Evidence is provided which suggests that deoxyribonucleoside triphosphates are not the precursors used by the replicating enzyme in uivo and that there may be some activated form of nucleoside monophosphate instead.For all those who like to see their molecular biology Kornberg has provided some superb electron microscope photographs of E. coli DNA polymerase I attached to nicks in the helical structure formed between p01y-dA.oligo-dT.’~~ 275 T. Kornberg and M. L. Gefter Proc. Nut. Acad. Sci. U.S.A. 1971 68 761. 276 V. Nusslein B. Otto F. Bonhoeffer and H. Schaller Nature New Biol. 1971,234 285. 277 G.V. R. Reddy M. Goulian and S.S. Hendler Nature New Biol. 1971 234 286. 278 R. Werner Nature New Biol. 1971 233 99. 279 J. Griffith J. A. Huberman and A. Kornberg J. Mol. Biol. 1971 55 209.

ISSN:0069-3030    

DOI:10.1039/OC9716800419

出版商:RSC    

年代:1971

数据来源: RSC