摘要:

7 Photochemistry By A. COX Department of Chemistry and Molecular Sciences University of Warwick Coventry CV4 7AL A review has appeared' surveying some of the more complex adiabatic photo- reactions of organic molecules such as fragmentations electrocyclic rearrangements and geometrical isomerizations. The effect of pulsed infrared radiation on cis-3,4-dichlorocyclobutene has been examined.* Despite the fact that the experimental conditions used were probably sufficient to raise the substrate to vibrational levels considerably in excess of the normal lowest reaction channel cis,trans-1,4-dichlorobuta-1,3-dienewas the only product detected clearly showing an adherence to the Woodward-Hoff mann Rules for this thermally-allowed transformation. Further investigations into the field of cyclopropene photochemistry have been disc~ssed,~ with particular reference to 1-methyl-2,3 -diphenyl-3 -isobutenylcyclopropene and 1,2-diphenyl- 3 -methyl-3 -isobutenylcyclopropene.The results are interpreted in terms of the participation of a biradical rather than a carbene pathway in both the direct and triplet reactions. Interconversions of different vinylcyclopropenes are seen as an incipient di-r- methane rearrangement involving a biradical mechanism. It has been shown4 that in contrast to its thermal processes the photoreactions of bicyclo[4.2.0]octa-2,4,7-trienes are substituent-dependent. Thus irradiation of the 2,5-dimethyl-3,4- diphenyl-substituted compound leads to a mixture of aromatic and acetylenic products whose formation can be rationalized in terms of thermal equilibria and further photoprocesses.The corresponding tetraphenyl-substituted triene however yields only the 1,2,3,4-tetraphenylcyclo-octatetraene. A good deal of interest is still being shown in the di-r-methane rearrangement. An investigation of some 5-methylenenorborn-2-eneshas revealed' that in com- mon with many other rigid 1,4-diene systems di-r- methane rearrangements can occur from both singlet and triplet excited states. The efficiency of the triplet reaction is highly substituent-dependent and it is demonstrated that the structural constraints of the product control the regiospecificity. Direct irradiation of (-)-3-(p-methoxyphenyl)-3-methyl-l,l-diphenylpent-l-ene has been found6 to lead to a mixture of ( -)-cis-and ( +)-trans-2-ethyl-2-methyl-3,3-diphenyl-l-(p-methoxy-phenyl)cyclopropane in which the methane carbon has undergone an inversion ' N.J.Turro J. McVey V. Ramamurthy and P. Lechtken Angew. Chem. Internat. Edn. 1979,18 572. W. C. Danen D. F. Koster and R. N. Zitter J. Amer. Chem. Soc. 1979,101,4281. H.E.Zimmerman and M. C. Hovey. J. Org. Chem. 1979,44,2331. R. N.Warrener I. W. McCay R. Y. S. Tan and R. A. Russell Tetrahedron Letters 1979,3183. Z. Goldschmidt and M. Shefi J. Org. Chem. 1979,44 1604. H. E.Zimmerman T. P. Gannett and G. E. Keck J. Org. Chem. 1979,44,1982. 114 A. Cox h Me0 + Me0 t I J I pentadienyl;orbital f Ph Ph." Scheme 1 (Scheme 1). This stereochemistry is in accordance with the predicted allowed stereochemistry arising from a Mobius transition state.The photoreactions of a series of 5,6-benzo-2-azabicyclo[2.2.2]octa-7,8-dien-3-ones have been used' as a probe to study structural and electronic substituent effects on the di-rr-methane rearrangement. A phenyl substituent is found to reverse the previously observed regioselectivity and a solvent effect is also apparent. The synthesis of a cyclopropane sesquiterpenoid taylorione has been reported,8 using the di-n-methane rearrangement. This represents only the second example of the use of this reaction in natural product synthesis. An investigation of the photochemistry of cross-conjugated trienes has shown' that whereas irradiation of the dicyano-compound (1) leads to a 'toluene' type of product the corresponding tetraphenyl compound (2) reacts by a vinyl-vinyl bridg- ing process (Scheme 2).Using SCF-CI calculations along various reaction co- ordinates a theoretical analysis of the system has been made. This suggests that in the excited state phenyl-substitution on the em-methylene group alters vinyl-vinyl bridging from a forbidden to an allowed process. Ph Ph Ph Ph-'Ph The photochemistry of 2-halogeno-1,l -diphenylethylenes has been examined" and the product distribution found to depend on both the halogen and the solvent. Cleavage of the C-X bond may occur to give a radical pair and may be followed by eIectron transfer to give an ion pair. This leads to competing ionic and radical behaviour. Products derived from a stabilized triplet state are also possible and the proportions of the three pathways are dependent on the halogen.A report has appeared" of the first example of an olefin analogue of the Type I1photoelimination 'M. Kuzuya M. Ishikawa T. Okuda and H. Hart Tetrahedron Letters 1979 523. * G. Pattenden and D. Whybrow Tetrahedron Letters 1979 1885. H. E. Zimmerman and D. R. Diehl J. Amer. Chem. Soc. 1979,101,1841. lo B. Sket and M. Zupan J.C.S. Perkin Z 1979,752. H. Aoyama T. Hasegawa M. Okazaki and Y. Omote. J.C.S. Perkin Z 1979 263. Photochemistry 115 of ketones. Using a low-pressure mercury arc photocyclization of NN-dibenzyl- methacrylamide (3a) to the p-lactam (4) and photodealkylation of NN-di-iso-propylmethacrylamide (3b) to N-isopropylisobutyramide both proceed via dimethylketen and the corresponding amine.The first step in both of these trans- formations is intramolecular hydrogen abstraction by the p-carbon (Scheme 3). 0 0 ,CHR1R2 (3) (a) R'=H R2=Ph (b) R'=Ri=Me J Me \ c=c=o / Me (R1=H,R2/ R> C=NCHR~R~ + \ RZ 0 Me,EAN,CHR'R2 II Ph CH,Ph Me H (4) Scheme 3 Chemical evidence has now been presented12 which adds further weight to an earlier rep~rt'~ that direct irradiation of cis-1-phenylcyclohexene affords the corresponding trans-isomer. At -75 "C and in methanol irradiation of cis-1-phenylcyclohexene gives rise to a dimer (5) thought to arise by a Woodward- Hoffmann-allowed concerted [7r4,+ 7r2,] addition of cis-1-phenylcyclohexene to the endocyclic trans double-bond of trans- 1-phenylcyclohexene.(5) 12 W. G. Dauben H. C. H. A. van Riel C. Hauw F. Leroy J. Joussot-Dubien and R. Bonneau J. Amer. Chem. SGC., 1979 101 1901. 13 R. Bonneau J. Joussot-Dubien L. Salem and A. J. Yarwood J. Amer. Chem. SOC.,1976 98,4329. 116 A. Cox It has been ob~erved'~ that the quantum yields of the direct trans-cis photo- isomerization of some p- rn- and m,m'-bromine-substituted stilbenes show larger quenching effects by azulene than do the trunslcis-photostationarycompositions. Together with measurements of the temperature-dependence of the quantum yield of fluorescence of each trans-isomer it is concluded that the positional dependence previously inferred for the heavy-atom effect is incorrect.It also emerges that 'p* cannot be the exclusive intermediate in the mechanism of photoisomerization of the cis-bromostilbenes. In some related work evidence has been presented" support- ing the view that between -155 and -100 "C the trans-cis photoisomerization of 4-bromostilbene occurs mainly via an upper excited triplet state. At temperatures above -100 "C it is suggested that the upper excited triplet mechanism competes with twisting in the lowest excited singlet state and even at room temperature this may still be the case. The photocyclization of stilbenes has been used16 in the synthesis of juncusol an anti-cancer agent but in the key step (6)+(7) the unwanted isomer (8) is found to predominate (Scheme 4).This result is consistent hv ,Me09 + MeOq / NC\ OMe NC\ OMe MeO\ CN Me Me Me (6) (6:1,E:Z) (7) Scheme 4 with both the Giisten-Klasinc ground-state model and with simple frontier MO calculations. The trans *cis photointerconversion of 1,2-di-(2'-naphthyl)ethyl-enes and the photocyclization of the cis-isomer to 4a,4b-dihydrophenanthrene derivatives has been investigated" over the temperature range +25 to -180 "C. For the cis-isomers the presence of conformer equilibria has been established spec- troscopically and the results also indicate the presence of potential barriers on the pathway between the excited-state starting materials and the products. CIDNP effects have been used" to examine the photosensitized photoisomerization of electron-donor and electron-acceptor styrenes and two different mechanisms of isomerization seem to operate.For the electron-transfer-induced isomerization of donor olefins the effects are compatible with the interconversion of two different radical ions of different energies. On the other hand the effects for acceptor styrenes with photoexcited electron donors suggest a single intermediate in the isomerization. Irradiation of 1,2,4,5-tetracyanobenzenein either diethyl ether tetrahydrofuran or tetrahydropyran leads to replacement of one cyano-group by an ether residue." l4 J. Saltiel A. Marinari D. W.-L. Chang J. C. Mitchener and E. D. Megarity J. Amer. Chem. SOC.,1979 101,2982. H. Gorner and D. Schulte-Frohlinde J. Amer. Chem. SOC.,1979 101,4388. l6 A.S. Kende and D. P. Curran J. Amer. Chem. SOC.,1979 101 1857. " T. Wismonski-Knittel and E. Fischer J.C.S. Perkin II 1979,449. H. D. Roth and M. L. M. Schilling J. Amer. Chem. SOC.,1979,101 1898. l9 M. Ohashi K. Tsujimoto and Y. Furukawa J.C.S. Perkin I 1979 1147. Photochemistry 117 Three possible mechanisms are considered One of these in which a tetrahydrofuran radical cation reacts with a neighbouring tetrahydrofuran molecule was definitely eliminated on kinetic grounds. However no decision was possible between a path involving charge-transfer exciplexes and a zwitterionic mechanism. A novel photo- chemical aromatic amination has been reported2' by irradiation of a solution of 9,lO-dicyanoanthracene and an amine in acetonitrile. The initial step appears to be transfer of an electron from amine to anthracene via an encounter complex or exciplex.Water is also apparently necessary to hydrolyse the intermediate imine. Evidence has been presentedz1 on the mechanism of the diene-induced photodech- lorination of chloro-aromatics. The reaction involves both exciplex and triplex formation and also a protonation step and is shown to proceed via a long-lived ion-radical intermediate. A study has been made22 of the orbital topology in a photochemical carbanionic ring-opening using the anion generated from cis,fruns-2,3-diphenylcyclopropanecarbonitrileby treatment with lithium di-isopropylamide. The results show that the process is stereochemically non-random but fail to distinguish between disrotatory photochemical opening of an anion and thermal opening of a radical.Irradiation of naphthalene in trifluoroacetic acid has been to lead to bimolecular hydrogen exchange via a singlet-state process. Consistent with the observed small kinetic isotope effect the incoming hydrogen is found to be lost about one hundred times more readily than one originally present and it is concluded that a wcomplex is formed. The three-membered ether chain CH2-0-CH2 has been to hold two anthracene chromophores in close proximity while the photobehaviour of the entire system is studied at low tempera- ture. The spectroscopic properties of a series of derivatives of bis-9-anthrylmethyl ethers and their photocyclodimerization reactions have been studied in this way. A study has been madez5 of the photochemistry of a series of bicyclic Py-cyclopropyl ketones.The behaviour of these ketones suggests a stepwise sequence of events involving opening of the three-membered ring by a-cleavage followed by rearrangement of the initial cyclopropylcarbinyl radical under stereoelectronic control to a homoallylic radical. The photochemistry of Py -cyclopropyl ketones derived from bicyclo[4.2.l]nona-2,4,7-trien-9-oneand possessing structural fea- tures which under irradiation tend to promote decarbonylation has been examined.26 Relative rates of decarbonylation 1,3-acyl shifts and a-cleavage are established; for the compounds chosen this sequence is found to be in agreement with qualitative information in other systems. Photoisomerization about a carbon-xygen partial double bond has been obser- ~ed~~ (Scheme 5).Irradiation of (9) in FS03H at -7O"C promotes partial iso- merization to give a photostationary state comprising (10) (73%) and (11)(27%). It has been suggested that this same photoinduced stereomutation might occur with protonated carbonyl compounds and that this could be a way for protonated 2o M. Ohashi H. Kudo and S. Yamada J. Amer. Chem. SOC.,1979,101,2201. 21 W. K. Smothers K. S. Schanze and J. Saltiel J. Amer. Chem. SOC.,1979 101 1895. 22 M. A. Fox J. Amer. Chem. SOC.,1979,101,4008. 23 N. J. Bunce Y. Kumer and L. Ravanal J. Org. Chem. 1979,44 2612. 24 A. Castellan J.-M. Lacoste and H. Bouas-Laurent J.C.S. Perkin 11,1979,411. 25 I. M. Takakis and W. C. Agosta J.Amer. Chem. SOC.,1979,101 2383. 26 I. M. Takakis and W. C. Agosta J. Org. Chem. 1979 44 1294. " R. F. Childs and M. E. Hagar J. Amer. Chem. SOC.,1979,101 1052. 118 A. Cox (9) R=HorMe Scheme 5 carbonyls to relax to their ground state. In a related paper2* the photoisomerization of protonated 4,4-dimethylcyclohex-2-enonein FS03H at -85 "C is reported. Incorporation of the chromophore into a ring system renders isomerization about the double bond more difficult and protonated 6,6-dimethylbicyclo[3.1 .O] hexan-2-one is produced. The effect of methyl substituents on the stereochemistry of the photoinduced addition of methanol to seven- and eight-membered cycloalk-2- enones has been st~died.~' It is concluded that the photoinduced addition of the nucleophile to cis-cyclohex-2-enones involves photoisomerization to the trans- isomer followed by syn-addition of the nucleophile.Proton transfer is probably the rate-determining step. trans-Fused [2s +2a] addition products are formed3' in the photocycloaddition of 17P-hydroxyandrosta-4,6-dien-3-one acetate to the elec- tron-deficient olefin methyl acetate. This breakdown in stereospecificity of cyclo- addition confirms a theoretical prediction31 based on a calculation of the potential energy surface for 3(7r,7r*) cycloadditions which indicates that if the enone and olefin are a good donor-acceptor pair then non-Woodward-Hoff mann addition should occur. The regioselectivity of enone photodimerization appears to be profoundly influenced by irradiating in potassium dodecanoate micelle~.~* Thus 3-alkyl- pentenones are observed to give ratios of head-to-head to head-to-tail dimers of up to 98 :2.The efflciency of the dimerization is also greatly increased. Photolysis of 2-arenesulphonyloxy-cyclohex-2-~nones leads33 to 2-hydroxy-3- phenylcyclohex-2-enones in about 40% yield. The reaction which probably pro- ceeds uia a triplet state is not of the photo-Fries type but may involve S-0 cleavage as the primary photochemical step However a mechanism involving cyclization to a biradical is also a possibility. A new method for the preparation of bicyclo- [3.2.0]heptan-2-ones has appeared34 and is especially interesting as on thermal fragmentation these compounds lead cleanly to cyclopentenones (Scheme 6).The Scheme 6 R. F. Childs K. E. Hine andF. A. Hung Canad. J. Chem. 1979,57 1442. 29 H. Hart B. Chen and M. Jeffares J. Org. Chem. 1979,44,2722. 30 G. R. Lenz and L. Swenton J.C.S. Chem. Comm. 1979,444. 31 S. Shaik and N. D. Epiotis J. Amer. Chem. SOC.,1978,100 18. 32 K.-H. Lee and P. de Mayo J.C.S. Chem. Comm. 1979,493. 33 A. Feigenbaum J.-P. Pete and D. Scholler Tetrahedron Letters 1979 537. 34 R. G. Salomon D. J. Coughlin and E. M. Easler J. Amer. Chem. SOC.,1979 101 3961. Photochemistry 119 key reaction is the photobicyclization of hepta- 1,6-dien-3-0ls using copper(1) trifluoromethanesulphonate as the catalyst. In the absence of copper(I) this reaction is suppressed. Hitherto it has generally been accepted that whereas electroisomeric linearly conjugated cyclohexa-2,4-dienones of predominantly n,v* character afford iso- meric dienylketens those of predominantly v,v* character lead to isomeric bicy- cl0[3.1 .O]hex-3-en-2-ones.However a recent paper3' now suggests that bicyclic ketones may also be the products of n,v* states and a study of a family of methylated o-quinol acetates indicates that the reaction channel depends on such factors as reaction r,iedium and substitution pattern. A paper describing the photoinduced cycloaidition of sterically hindered p-quinones to diphenylketen has appeared.36 This reaction the first example of its type involving diphenylketen affords a mixture of a spiro-oxetanone and a cyclobutanone. Both products are considered to arise from the 3(7r,7r*) state of the quinone and the predominance of the oxetanone product is attributed to the degree of dipole-dipole interaction between the excited state of the quinone carbonyl and the ground state of the diphenylketen.In a related paper,37 the photoreaction of p-benzoquinone with unsymmetrical keten dimers is discussed. A temperature-dependent photo-CIDNP study has revealed3' that on irradiation certain by- unsaturated ketones yield radical pairs (Scheme 7) from either the S1 or T2state depending upon the reaction temperature. Before collapsing to products one reaction channel that is open to the radicals is a 1,3-acyl shift. * Y eOMe 9I I X=Y=Me 1 MeCHO X = Me,Y= H X=Y=H 0 Scheme 7 As part of a series of studies in the field of py-unsaturated ketones the stereo- chemistry of the oxa-di-v- methane rearrangement of 2-substituted-2-(cyclopent-1-eny1)cyclopentanones has been in~estigated.~~ The main conclusions drawn are that the triplet-sensitized oxa-di-v- methane rearrangement involves [1,2]-supraf acial carbonyl migration and that this proceeds with inversion of configuration at the 35 G.Quinkert F. Cech E. Kleiner and D. Rehm Angew. Chem. Internat. Edn. 1979 18 557. 36 K. Ogino T. Matsumoto and S. Kozuka J.C.S. Chem. Comm. 1979 643. 37 K. Ogino T. Matsumoto T. Kawai and S. Kozuka J.C.S. Chem. Comm. 1979 644. 38 A. Henne N. P. Y.Siew and K. Schaffner J. Amer. Chem. SOC., 1979,101,3671. 39 R. L. Coffin W. W. cox R. G. Carlson and R. S. Givens J. Amer. Chem. SOC.,1979 101 3261.120 A. Cox methane carbon. [1,3]-Rearrangement of the singlet state seems to occur suprafacially to give a substituted bicyclo[5.3.0]dec-l-en-6-one. Flash photolysis of various methylated indan-2-ones indicates4' the presence of a transient identified as an o-xylylene and which in the case of 1,1,3,3-tetra-methylindan-2-one has been shown to be 7,7,8,8-tetramethyl-o-xylylene.Thermal decay of these transient non-planar xylylenes may proceed via the hitherto unknown antarafacial [1,5]-shift to give styrenes. An examination of the photochemistry of the 2-spirocyclopropylindan-1-one (12) in a rigid matrix at 77K affords4' (E)-2- ethylideneindan-1-one formed exclusively from the 3(n,7r*)state in a monopho- tonic process; no reaction however occurs in fluid solution.It is suggested that since the rate of ring-closure in fluid solution is rapid under these conditions the biradical simply returns to the starting material (Scheme 8). O* 0 hv and iMf ring fission T[~,~IH shift 6-ringclosllre \ \ Scheme 8 It has been reported4* that irradiation of certain methoxy-acetophenones together with cyanide ion in acetonitrile can lead to the formation of methoxy-benzonitriles in high yield. The reaction is inhibited by water and although no mechanism has yet been suggested the transformation is known not to involve a ground-state complex between nucleophile and aromatic substrate. The triplet state of P-(dimethyl- amino)propiophenone decays in aqueous solution by a charge-transfer interaction to give intramolecular electron transfer and results in a biradical zwitterionic product which has been trapped43 by the l,l'-dimethyl-4,4'-bipyridyliumdication acting as an electron acceptor.The lifetime of this triplet is dependent on the pH of the medium and at values below the pK of the dication the triplet may decay before acid-base equilibrium has been established. CIDNP studies of the photoreduction of 4-substituted acetophenones by NN-dimethylanilines suggest the presence of two pathways for formation of radical i0n-pai1-s.~~ Triplet ion-pairs are formed by excitation of the ketone followed by electron abstraction from the ground-state amine and electron-transfer from the singlet excited amine to the ground-state ketone gives a singlet ion-pair.The influence of mercaptans on the photoreduction of various aromatic ketones by alcohols has been st~died.~' Retardation of the 40 K. K. De Fonseka J. J. McCullough and A. J. Yarwood J. Amer. Chem. SOC.,1979,101,3277. " R. 0.Loutfy and P. Yates J. Amer. Chem. SOC.,1979 101,4694. 42 A. L. Colb J. Amer. Chem. SOC.,1979,101,3416. 43 M. V. Encinas and J. C. Scaiano J. Amer. Chem. SOC.,1979 101,2146. B. M. P. Hendriks R. I. Walter and H. Fischer J. Amer. Chem. SOC.,1979,101,2378. 45 S. G. Cohen A. W. Rose P. G. Stone and A. Ehret J. Amer. Chem. SOC.,1979 101 1827. Photochemistry 121 process occurring between triplet benzophenone and propan-2-01 is largely due to hydrogen-transfer reactions from mercaptan to the 2-hydroxy-2-propyl radical and from the benzophenone ketyl radical to the thiyl radical.For 2-mercaptomesitylene the decrease in rate using deuteriated propan-2-01 is greater than in the protio system. A study of the photochemistry of a-benzoyl-w-azido-ketones of the type PhCO(CH2).N3 has revealed46 the existence of a competition between the carbonyl and azide (nitrene) photoprocesses namely y-hydrogen abstraction to give Type I1 products and energy transfer from the triplet ketone to the azide to form nitrene products. The positions of the two chromophores on the molecular skeleton have been varied systematically so that the rate constants for interaction between the two groups could be compared with their distances apart. The rate variations for n = 3 to 5 have been interpreted in terms of the strain present in medium-sized rings.A hydrophilic polymer-immobilized photosensitizer that is useful for photo- oxygenations in aqueous solution has been described.47 It is prepared by copoly- merization of chloromethylstyrene and the monomethacrylate ester of ethylene glycol as cross-linking agent. This is then heated with Rose Bengal in dry NN-dimethylformamide giving the hydrophilic sensitizer @-Rose Bengal. Singlet oxygenation of cyclo-octa-1,3,5-triene leads48 to (2 +4) adducts (Scheme 9). This represents a convenient route to novel [4.2.2]- and [2.2.2]-type endoperoxides which themselves have synthetic potential. There is considerable current interest in the quenching and reaction of singlet molecular oxygen with a-tocopherol as this may be the basis of its biological function as an anti-oxidant.It is now that at low temperatures the primary product of photo-oxygenation is the relatively stable hydroperoxy-dienone (13). Although simple acetylenes do not react with singlet oxygen that has been generated by using Methylene Blue or Rose Bengal in methanol photosensitized oxygenation of aromatic acetylenes has been shown” to yield benzils (Scheme 10). An electron-transfer mechanism similar to that suggested for the photosensitized oxygenation of alkenes has been advanced and the reactivity (13) 46 P. J. Wagner and B. J. Scheve J. Amer. Chem. SOC.,1979,101,378. 47 A. P.Schaap A. L. Thayer K. A. Zaklika and P. C. Valenti J Amer. Chem. SOC.,1979,101,4016. 48 W. Adam and I.Erden Tetrahedron Letters 1979,2781. 49 R.L.Cough B. G. Yee and C. S. Foote J. Amer. Chem. SOC.,1979,101,683. N. Berenjian P. de Mayo F. H. Phoenix and A. C. Weedon Tetrahedron Letters 1979,4179. 122 A. Cox sens sens* RCfCR_ [sens'] C[RC=CR'] RC0,H Scheme 10 of the acetylenes is in accordance with the predictions of the Weller equation. Results have now been published5' which cast doubt on earlier suggestions concerning the dye-sensitized photo-oxygenation of a-0x0-carboxylic acids in which decarboxyl- ation occurs. Measurements of the rates at which a-0x0-acids react with singlet oxygen in competition with 1,3-diphenylisobenzofuranindicate that reaction with the triplet dye is more efficient than with singlet oxygen. Consequently singlet oxygen appears not to play a significant role.The Rose-Bengal- or Methylene-Blue- sensitized photo-oxidation of 2-(2-quinolyl)indane-1,3-dionein solution has been showns2 to lead to a mixture of products including phthalic acid quinoline-2- carbaldehyde and quinoline-2-carboxylic acid (Scheme 11).Of the two forms of the fly)JpJ \ I \ 0 .. . . . ..... . H 0-H (14) 110 0 Scheme 11 quinophthalone derivative which exist in equilibrium in solution (14) is the more susceptible to photo-oxidation. On oxidation an unstable peroxide is produced by an ene reaction but a perepoxide-type intermediate is also a possibility. Further photolysis or possibly thermolysis leads to a breakdown to products. Photo-oxygenations of different types of sulphides have been carried out using both dye and dicyanoanthracene (DCA) as sensitizers and it appearss3 that although those reactions involving DCA do not proceed by singlet oxygen both involve the same intermediate.A superoxide may participate. Photosensitized oxygenations of various diazo-compounds in the presence of oxygen-atom acceptors have showns4 51 R. S. Davidson D. Goodwin and G. Smith J.C.S. Chem. Comm. 1979,463. '* N. Kuramoto and T. Kitao J.C.S. Chem. Comm. 1979,379. 53 W. Ando T.Nagashima K. Saito and S. Kohmoto J.C.S. Chem. Comm. 1979,154. 54 W. Ando. H. Miyazaki and S. Kohmoto Tetrahedron Letters 1979 1317. Photochemistry 123 that the products depend on the electrophilicity of the oxenoid intermediate. Thus the yields of diphenyl sulphoxide formed in the photosensitized oxygenation of benzoylphenyldiazomethane are very different from those obtained from diphenyl- diazomethane and diazofluorenone.A simple device for moving the position of a keto-group with concomitant introduction of a double bond has been ann~unced.’~ Thus dye-sensitized oxygenation of vinylsilanes leads to a hydroperoxide which can be transformed into an allylic alcohol (Scheme 12). This transformation depends on OOH SiMe 2 SiMe --* Reagents i ‘02; ii NaBH,; iii Bu”,N’F- dry MeCN Scheme 12 the fact that cup-epoxysilanes ring-open with a regioselectivity opposite to that followed by epoxides lacking carbon-metal bonds. A new reaction has been reported56 in which carbonyl oxides from diazo-compounds oxidize silyl ketones to esters.Thus irradiation of a solution of diphenyldiazomethane phenyltrimethylsilyl ketone and meso-tetraphenylporphin under oxygen leads to a high yield of tri-methylsilyl benzoate. A plausible mechanism is shown in Scheme 13. Ph2CN2 SiMe3 + I + -+ Me3SiCOR + Ph,C=O-O-C-O-+ Ph2C=O-O-C-OSiMe3 I I R 1 Ph2C0 + Me3SiOCOR Scheme 13 Irradiation of 4-cyanopyridine in 2,3-dimethylbut-:!-ene a mixture of 4- (1’,1’,2’-trimethylprop-2‘-enyl)pyridine and 4-(2’,3’-dimethylbut-2’-enyl)pyridine; 2-cyanoquinoline undergoes an analogous reaction. It is suggested that the addition proceeds by electron transfer from the r-system of the olefin to the r-system of the aromatic base. However since no products of photocyclization are apparent monophotonic hydrogen abstraction from the olefin by the n,r* state of the base followed by cross-dimerization of the radicals is also a possibility.Formation of 1H-1,3-benzodiazepines in the photolysis of isoquinoline N-imides has been anno~nced,~~ and probably occurs via ring-expansion of an aziridine intermediate (Scheme 14). Although this process is known for aromatic amine N-oxides it is the first example reported involving aromatic amine N-imides. A new high-yield synthesis of quinolines has been p~blished.~’ This transformation involves an ” W. E. Fristad T. R. Bailey L. A. Paquette R. Gleiter and M. C. Bohm J. Amer. Chem. SOC.,1979,101 4420. ’‘ A. Sekiguchi Y.Kabe and W. Ando J.C.S. Chem. Comm. 1979,233. 57 T. Caronna S. Morrocchi P.Traldi B. M. Vittimberga J.C.S. Chem. Comm. 1979,64. ’’ T. Tsuchiya M. Enkaku J. Kurita and H. Sawanishi,J.C.S. Chem. Comm. 1979 534. 59 P. de Mayo L. K. Sydnes and G. Wenska J.C.S. Chem. Comm. 1979,499. 124 A. Cox .\ C0,Et I 1 T Qy -Q N\ IR C0,Et C0,Et R = Meor COzEt Scheme 14 intramolecular cycloaddition of substituted thioanilides and is thought to proceed via a ‘(T,w*) state. High concentrations of HC104 or &SO4 increase the fluorescence of a variety of quinolinium ions in the Hammett acidity region but without any shift in the fluorescence or absorption wavelength.60 These observations have been inter- preted in terms of the formation of an adduct on substitution of the solvation sphere around the cation by entering C104-or HS04-ions.Quenching of the excited state by water molecules is consequently reduced leading to fluorescence enhancement but no fluorescence shift. The photocyclization of 1,3-diphenyl-5-(2’-halogeno-pheny1)pyrazoles has been shown61 to proceed with high quantum yield through the So”state and to involve homolysis of a carbon-halogen bond affording (15) as an intermediate. Replacement of the halogen by groups having a higher bond strength leads to a change in mechanism. This could be an electrocyclic process proceeding via (16) and if so would be consistent with the observed polarity dependence. The first report of a photoinduced [4 + 21-cycloreversion of a hexasubstituted 2,3-diazabicyclo[3.1 .O]hex-2-ene has appeared6* in which large groups are present at C-4 and C-6.Interest in this process stems from the fact that the [~f +v:] has hitherto been seen only for carbon systems. The photochemical rearrangement of oxaziridines to amides has been investigated theoretically using an ab initio 6o S. C. Chao J. Tretzel and F. W. Schneider J. Amer. Chem. SOC.,1979,101 134. 61 J. Grimshaw and A. P. de Silva J.C.S. Chem. Comm. 1979 193. 62 G. Ege. K. Gilbert and B. Hahn Tetrahedron Letters 1979 1571. Photochemistry 125 method.63 The lowest energy transition results from an n.,. +cr& excitation promoting rupture of the N-0 bond. Migration of hydrogen occurs in a separate step and probably does so on the ground-state energy surface. Irradiation of 6-methylflavone in aqueous methanol containing sodium sulphite two dimers.The mechanism of this process is unclear but it is suggested that following excitation of the flavone an electron is transferred from SO:-to give a radical anion; after abstraction of a proton from the solvent this dimerizes. The photoaddition reactions of the electron-deficient alkene thiochromone 1,l-dioxide with benzene and some simple derivatives have been inve~tigated~~ and an attempt has been made to establish a link between the ionization potential of the aromatic and the course of the phototransformation. It has been shown that the presence of electron-donating groups suppresses the formation of 2 1 adducts the degree of charge transfer involved possibly promoting dissociation to the ground state.If the ionization potential of the aromatic lies closer to that of thiochromone 1,l-dioxide the extent of formation of 2 :1adduct correlates well with the difference between the ionization potentials of the arene and the dioxide. Irradiation of 2-methylthianaphthalene 1,l-dioxide affords66 anti-head-to-head (HH) and anti-head-to-tail (HT) dimers. It has been suggested that the (HH) dimer results from a monomeric excited triplet and that an excimer is the precursor of the (HT) dimer. An external heavy-atom effect was detected and this has been interpreted in terms of a spin-orbital perturbation on the intersystem crossing in the 1,4-biradical. 63 E. Oliveros M. Riviere J. P. Malrieu and C. Teichteil J. Amer. Chern. SOC., 1979,101 318. I. Yokoe M. Taguchi Y.Shirataki and M. Komatsu J.C.S. Chem. Comm. 1979,333. 65 I. W. J. Still and T. S. Leong Tetrahedron Letters 1979 1097. 66 M. J. Hopkinson W. W. Schloman B. F. Plummer E. Wenkert and M. Raju J. Amer. Chem. SOC., 1979 101,2157.

ISSN:0069-3030    

DOI:10.1039/OC9797600113

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

8 Aliphatic Compounds Part (i) Hydrocarbons By K. J. TOYNE Department of Chemistry The University of Hull Hull HU6 7RX 1 Alkanes Alkynes and some alkenes are reduced to alkanes in high yields by a complex species prepared from sodium borohydride and a cobalt(I1) salt (e.g. CoC12.6H20 NaBH, and EtOH).' Monosubstituted terminal alkenes are most easily reduced and although disubstituted alkenes react more slowly they are also reduced efficiently; more highly substituted alkenes are virtually inert. This high steric selectivity permits the less substituted double bond in dienes to be reduced. Tri-n-butyltin hydride has been used for many years as an excellent reagent for the hydrodehalogenation of alkyl halides but a major disadvantage in its use is the difficulty in separating the products from the tin residues.Two simple procedures have been reported which overcome this problem. The first method2 is based on converting the soluble organotin halide R3SnX (X = C1 Br or I) that is produced in the reaction into the insoluble organotin fluoride R3SnF by washing the reaction mixture (in a non-polar solvent) with aqueous potassium fluoride. The organotin fluoride is easily removed by filtration and the organic layer contains the reduction product. The second method3 advocates a two-phase solvent system of hexane- acetonitrile in the work-up procedure. The tri-n-butyltin species are soluble in hexane and the required product partitions preferentially into acetonitrile. A variation on a standard route to alkanes by decarboxylation has been described (Scheme 1);"yields of 50-70'/0 are obtained for primary or secondary alkyl groups RCOCl 4 RH Pr3Si.+ RCOCl -B Pr3SiC1 + RCO-(1) RCO* -B Re + CO R-+ Pr3SiH + RH + Pr3Si. -Reagents i Pr,SiH (Bu'O), 140-170 "C in ampoules Scheme 1 ' S.-K. Chung J. Org. Chem. 1979,44 1014. ' J. E.Leibner and J. Jacobus J. Org. Chem. 1979,44449. J. M. Berge and S. M. Roberts Synthesis 1979,471. N. C. Billingham R. A. Jackson and F. Malek J.C.S. Perkin I 1979 1137. 128 K. J. Toyne but the method is unsatisfactory for tertiary benzylic or phenyl groups. A radical chain reaction has been proposed in which the tripropylsilyl radical (1) (generated via the t-butoxyl radical) initiates the formation of the alkyl radical (Scheme l) which then abstracts hydrogen giving the alkane and regenerating (1).Electrochemical reduction of methanesulphonates of alcohols (ROH) to alkanes (RH) can be achieved even when functional groups such as ester nitrile epoxide olefin or aromatic nucleus are present.' A divided cell is used with a lead cathode and a platinum anode and isolated yields of 70% are reported. 2 Alkenes Synthesis.-Allylic acetates and allylic phenyl ethers are converted into alk-1 -enes in high yields by using a palladium catalyst and ammonium formate as shown in Scheme 2 for geranyl acetate (2) or linalyl acetate (3).6 &O Ac (2) 94% 6Yo &OAc (3) Reagents i HC02NH, [PdCI2(PPhJ2] dioxan reflux Scheme 2 Terminal alkenes can be prepared in high yield from alkyl halides that contain one carbon atom less via the formation of alkyl selenides (Scheme 3).' Methylation of the selenium atom generates a good leaving group which is eliminated on treatment with base.R'CH2Br A R1CH2CH2SeR25R'CH=CH2 Reagents i R2SeCH2Li THF HMPT (R2 = Me or Ph); ii MeS0,F or MeI AgBF,; iii Bu'OK DMSO Scheme 3 A versatile synthesis of terminal alkenes makes use of the fluoride-ion-induced elimination of -trimethylsilylsulphones in refluxing THF. An attractive feature of this method is that the alkylated p-silylsulphones can be prepared from (4) or from (5) (Scheme 4).* A second alkylation of (6) and subsequent elimination gives a 1,l-disubstituted ethene; depending upon the nature of R' and R2 a variety of dienes can be prepared.1,l-Dialkyl-ethenes can also be prepared directly from terminal alkenes (Scheme 4 reaction iv),' and although the reaction uses organo- 'T. Shono Y.Matsumura K. Tsubata and Y. Sugihara Tetrahedron Letters 1979,2157. J. Tsuji and T. Yamakawa Tetrahedron Letters 1979,613. S. Halazy and A. Krief Tetrahedron Letters 1979 4233. * P. J. Kocienski Tetrahedron Letters 1979 2649. J. J. Barber C. Willis and G. M. Whitesides J. Org. Chem. 1979 44 3603. Aliphatic Compounds -Part (i) Hydrocarbons SiMe R'CH=CH SiMe 3 R1 \ (4) C=CH SiMe / Y R2 R '-SO Ph R' ~2 SO2Ph (5) Reagents i BuLi THF; ii R'Br; iii Bu4NF.3H,0 THF heat; iv [Cp,TiCl,] A1R23 CH,Cl,; v Me,SiCH,I; vi R'Br Scheme 4 aluminium and titanium reagents inefficiently it tolerates the presence of certain functional groups and achieves a transformation in one step which is difficult to accomplish in other ways.Several Wittig-like reactions involving the conversion of a carbonyl function into an alkene have been reported. The lithium derivative of aldehyde tosylhydrazones (7) and the a-1ithio species (8) are generated and a condensation-fragmentation reaction gives the alkene (Scheme 5)." In many cases this procedure is more R2CH2X R2CH(Li)X X = e.g. S02R3,SPh or CN Reagents i Pr',NLi THF at -20°C Scheme 5 convenient than the Wittig reaction but it offers less stereochemical control; using a-branched nitriles trisubstituted alkenes can be prepared. Terminal alkenes can also be prepared from ketones using (chloromethy1)trimethylsilane and tri- phenylphosphine which produce methylenetriphenylphosphorane Ph3P=CH2 (9) as the reactive intermediate." The reaction is carried out at 150"Cin sealed tubes and although it is not suitable for ketones that have a-hydrogen atoms because of competing formation of silyl enol ether it is a simple and clean procedure.A silylated derivative of (9) prepared from methyltriphenylphosphonium bromide and (iodomethyl)trimethyIsilane leads to an allylsilane R'R2C=CHCH2SiMe3 (lo) after reaction with a carbonyl compound. Compound (10)reacts with a variety of alkylating agents in the presence of titanium(1v) chloride to give R'R2CZCH=CH2 (11;Z = e.g. CH2CH20H,R3,COMe CH2CH2COMe) or on protodesilylation (10) gives (11;Z=H).12 E.Vedejs J. M. Dolphin and W. T. Stolle J. Amer. Chem. SOC.,1979,101 249. A. Sekiguchi and W. Ando J. Org. Chem. 1979,44,413. I. Fleming and I. Paterson Synthesis 1979,446. 130 K. J. Toyne Several syntheses of alkenes based on 0-hydroxy-sulphur or -selenium compounds continue to be published. Mono- di- and tri-substituted alkenes have been prepared by making use of the reductive elimination of P-hydroxy-sulphox- imines (12) but the reaction was not successful for tetrasubstituted alkenes (Scheme 6).13The procedure gives dienes and trienes from enones and dienones respectively 0 0 0 OH II I1 II Ph-S-CH2R' 2Ph-S-CHLiR' Ph-S-CHR1~R2R3 -% R'CH=CR2R3 II II I1 NMe NMe NMe (12) Reagents i BuLi THF; ii R2COR3; iii Al(Hg) THF H20 HOAc Scheme 6 and in some cases gives better yields than the Wittig reaction although the latter reaction is more generally useful.The preparation of di- tri- and tetra-substituted alkenes has also been achieved from compounds similar to (12) by using a mild elimination of P-hydroxy-sulphides which are readily prepared from a-thioalkyl-lithium and carbonyl compounds (Scheme 7).l4 The regiospecific reaction involves anti-elimination of the hydroxy- and sulphenyl groups probably via a thiiranium ion as an intermeaiate which is then attacked by iodide ion. The similar deoxygenation of oxirans to alkenes of the same configuration has also been achieved using diphosphorus tetraiodide. l5 RSC(Li)R1R2 + R3COR4+ RSC(R'R2)C(OH)R3R4b R1R2C=CR3R4 Reagents i P,14 or PI or SOCI (for tetrasubstituted alkenes) CH2C12 Et3N reflux.Scheme 7 a-Lithio-selenides prepared from alkyl aryl selenides react with aldehydes and ketones to give /3 -hydroxy-selenides which are readily converted into alkenes by an anti -reductive elimination similar to those described above. The mild conditions used for the elimination are compatible with nearly all functional groups except the hydroxy-group of an alcohol (Scheme 8).16 The a-lithio-selenides can also be alkylated and then converted into selenoxides which decompose to alkenes. OH PhSeCH2X PhSeCH(Li)X A PhSeCHX-AR1R2 5 XHC=CR'R2 1 iv PhSeCHX V PhSeCHX + XHC=CHR3 [" ] I CHzR3 CH2R3 X = e.g. Ar vinyl ethynyl or OMe Reagents i Pr',NLi or lithium 2,2,6,6-tetramethylpiperidide THF; ii R'COR'; iii MeSO,Cl Et3N CH,Cl,; iv R3CH,Y (Y = Br or I); v NaIO, or H202 or O3 Scheme 8 l3 C.R. Johnson and R. A. Kirchhoff J. Arner. Chem. SOC., 1979,101,3602. l4 J. N. Denis W. Dumont and A. Krief Tetrahedron Letters 1979 4111. lS H. Suzuki T. Fuchita A. Iwasa and T. Mishina Synthesis 1978,905. l6 H. J. Reich F. Chow and S. K. Shah J. Amer. Chem. SOC., 1979,101,6638. Aliphatic Compounds -Part (i) Hydrocarbons 131 Techniques for the preparation of cy -1ithio-selenoxides have been developed and these reagents react with most aldehydes and ketones to give @ -hydroxy-selenox-ides which can be reduced to p-hydroxy-selenides (and subsequently converted into alkenes; see Scheme 8) or thermally decomposed to ally1 alcohols (Scheme 9).17 Alkylation of (13)and thermal decomposition of the product also leads to alkenes.0 CH2=CR2CR3R4(0H) II PhSeCHR1R2 & PhSeCHR'RZX heat (R'=Me; R2 = R' or H) 0 T I1 II PhSeC(Li)R'R2 -% PhSeCR'R2CR3R4(0H) (13) 0 Y II alkenes PhSeCR'R'R' PhSeCR' R2CR3R4(0H) R' R2C=CR3R4 Reagents i 0 or m-chloroperbenzoic acid; ii Pr',NLi THF; iii R3COR4; iv HOAc NaI and NaHSO, or (MeO),P; v MeSO,Cl Et,N CH2Cl (see Scheme 8); vi R5X Scheme 9 A more detailed account has appeared of a procedure reported in 1975 for converting aromatic and aliphatic esters into isopropenyl compounds by reaction with methylenetriphenylphosphorane or its derivatives (Scheme 10).l8An excess of n-alkylidenetriphenylphosphoraneconverts the ester into a branched alkene such that the oxygen atoms in the original ester are replaced by the phosphorane moiety and the double bond remains at the position of the original carbonyl group.0 CHR3 R'-C // R'-C \0-R2 \CH2R3 Reagents i NaH DMSO Ph,kH2R3 I-Scheme 10 A further account of a convenient method reported last yearlga uses a terminal alkyne (R'CrCH) and a Grignard reagent (R2MgBr) to prepare 2,2-disubstituted alkenyl-copper intermediates (14) which are then allowed to react with electrophiles R2 Cu(Me2S)MgBr2 \/ c=c R' ' \H (14) to give trisubstituted alkenes stereoselectively.*' The sequence can be adapted to produce compounds with repetitive trisubstituted alkene units as seen in many naturally occurring compounds such as terpenoids.21 Trisubstituted alkenes have also been prepared stereoselectively from a-trialkylsilyl-substitutedketones and alkyl-lithium reagents (Scheme 11).22The l7 H.J. Reich S.K. Shah and F. Chow J.Amer. Chem. SOC.,1979,101,6648. A. P. Uijttewaal F. L. Jonkers and A. van der Gen J. Org. Chem. 1979,44,3157. l9 K. J. Toyne Ann. Reports (B),1978,75,(a)p. 161,(b)p. 163,(c) p. 166. 2o A. Marfat P. R. McGuirk and P.Helquist J. Org. Chem. 1979,44,3888. 21 A. Marfat P. R. McGuirk and P.Helquist J. Org. Chem. 1979 44 1345. 22 M. Obayashi K.Utimoto and H. Nozaki Bull. Chem. SOC.Japan 1979,52 1760. 132 K.J. Toyne R' H \/ R" /c=c\R2 R2 IR'COCHSiR R'R4C-CHR2 IOLi AiR u/ R' R2 /\c=c R"' 'H Reagents i R4Li THF; ii KOBu'; iii HOAc NaOAc Scheme 11 elimination of the silyl and oxy-functions occurs mainly by a syn -process under basic conditions or mainly by an anti-mechanism on treatment with acid.Alkenyl halides undergo stereoselective cross-coupling with organolithium compounds to give alkenes and with thiolate anions to give alkenyl sulphides (Scheme 12).23 Although stoicheiometric and catalytic processes already exist for the preparation of alkenes from alkenyl halides the new methods which have been used with alkyl aryl and heterocyclic lithium compounds in both stoicheiometric and catalytic conditions offer advantages in certain cases. R' H R' H R' H c=c _I\c-c/ \c=c' \/' -Reagents i R'Li [Pd(PPh,),]; ii R4SLi [Pd(PPh,),] Scheme 12 threo-3-Hydroxycarboxylicacids* (19 obtained from metallated carboxylic acids and aldehydes can be converted into (2)-or (E)-alkenes as shown in Scheme 13.24 The ratio of (E)-/(Z)-isomers from each procedure is >99/1 and <3/97 so that practically pure material can be obtained in good yield.In the examples reported R' is Ph or OPh and R2 is alkyl. Two related have described the thermal decomposition at 150-250 "C,of magnesium zinc and aluminium amides R'MNR2 (M =metal) into hydrocarbon (R'H) alkene (from R2) and a residue which on hydrolysis yields primary amine (R2NH2)25 and secondly the thermal decomposition at 195- 340 "C of magnesium zinc and aluminium alkoxides R'MOR2 (M =metal) into hydrocarbon (R'H) alkene (from R2) and metal oxide (MO).26 The former reaction *The use of 'threo' by the authors of ref. 24 is not consistent with the normal IUPAC convention but has been retained. Senior Reporter. 23 S. Murahashi M. Yamarnura K. Yanagisawa N. Mita and K. Kondo J. Org. Chem. 1979,44,2408. 24 J. Mulzer A. Pointner A. Chucholowski and G. Briintrup J.C.S. Chem. Comm. 1979,52. 25 E. C. Ashby and G. F. Willard J. Org. Chem. 1978 43 4750. 26 E. C. Ashby G. F. Willard and A. B. Goel J. Org. Chem. 1979,44 1221. Aliphatic Compounds -Part (i) Hydrocarbons R2 R' \/ c=c H/\ H (2) He R1CHLiC02Li+R'CHO HOzC R' Reagents i PPh, EtO,CN=NCO,Et; ii PhS02Cl pyridine; iii heat to eliminate CO Scheme 13 allows the conversion of a secondary amine into a primary amine and an alkene and it is an alternative to the Hoffman and the Cope eliminations; the latter reaction is an alternative to Chugaev and acetate pyrolysis procedures for the dehydration of alcohols.Reactions.-The hydroalumination of alkenes continues to provide the basis for several important synthetic procedures and the difficulty in removing the catalyst from the organoaluminium product when LiAIH.,-TiCI is used for hydro- alumination can now be avoided. Heterogeneous immobilized titanium catalysts such as Si02-supported titanium (IV) chloride and polystyrene-supported titanocene dichlorides have been shown to be excellent catalysts which are easily recovered from the reagents by filtration and can be re-used many Lithium alkyl-trihydroaluminates (16)28and lithium tetra-alkyl-aluminates (17)29 undergo alkyl-alkyl coupling upon treatment with copper(I1) acetate and an alkyl- allyl cross-coupling is also possible28 (Scheme 14 reagents ii and iii); a similar reaction catalysed by copper(1) chloride using allyl halide has been reported previo~sly.'~~ The alkyl-alkyl coupling reaction therefore provides a new prep- arative route to alkanes by the dimerization of alkenes and also enables a variety of dienes to be prepared by coupling the mono-hydroalumination product of a diene (e.g.hexa- 1,4-diene to dodeca-2,lO-diene).When the reaction of organoaluminates with copper(I1) acetate is carried out under a carbon monoxide atmosphere ketones are formed in about 20-30% yield (reagent v),~' but better routes to aldehydes and ketones from organoaluminates have been rep~rfed.~'*~' The reaction of (18) and acrolein or methyl vinyl ketone in the presence of stoicheiometric amounts of copper(I1) acetate gives aldehydes or methyl ketones in excellent yield3' (Scheme 14; reagent vii) and the reaction of (17)with acid chlorides or anhydrides in the presence of catalytic amounts of copper(1) chloride gives ketones (reagent ~i).~' Tri-alkylboranes have been used previously in similar reactions but only one of the three alkyl groups on boron is used.The hydroalumination methods appear to give better 27 F. Sato H. Ishikawa Y. Takahashi M. Miura and M. Sato Tetrahedron Letters 1979 3745. 28 K. Isagawa M. Ohige K. Tatsumi and Y. Otsuji Chem. Letters. 1978 1155.29 F. Sato Y. Mori and M. Sato. Chem. Letters 1978 1337. 30 F. Sato T. Oikawa and M. Sato Chem. Letters 1979 167. 31 F. Sato H. Kodama Y. Tomuro and M. Sato Chem. Letters 1979,623. 134 K. J. Toyne RCHZCH2CH2CH2R ii 7 LiAIH3(CH2CH2R)/ (16) RCH2CH2CH2CH=CH2 (17) k~ RCH2CH2COR LiAIH2(CH2 CH2 R)2 RCH2 CH2 CH2 CH2 COMe (H) (18) Reagents i LiAlH4 [Cp,TiCl,]; ii [Cu(OAc),] THF; iii CH,=CHCH,Hal [Cu(OAc),J; iv LiAlH,- TiCl,; v CO [Cu(OAc),]; vi R’COCl or (R’CO),O CuCl; vii CH,=CHCOMe(H) [Cu(OAc),]; viii [Pb(OAc),] Scheme 14 yields and to permit the selective introduction of the carbonyl group to one double bond of a non-conjugated diene. Another hydroalumination sequence which is an attractive alternative to hydroboronation methods uses the reaction of (18) with lead(rv) acetate to give primary alkyl acetates (Scheme 14; reagent ~iii);~’ once again the preparation of an unsaturated acetate or an aw-diacetate is possible.Organoaluminium compounds can also be obtained from complexes produced by hydrozirconation of alkenes and alkynes (Scheme 15).33 Alkyl alkenyl or acyl groups in (19)are transferred rapidly and stereospecifically to aluminium chloride to give organoaluminium dichlorides which can be acylated to yield saturated and ap-unsaturated ketones; in a similar way alkenyl-alanes can be prepared from (19). This work illustrates how transmetallation of a readily prepared transition-metal complex can be exploited to produce a more reactive organometallic species.[Cp2Zr(H)C1] [Cp2Zr(R*)Cl]-% [R1A1C12] R’COR2 (19) R’AIR32 Reagents i alkene or alkyne; ii AlCI, CH2C12; iii R’COCI CH,C12; iv R3,A1Cl CH,Cl (for R’ = alkenyl) Scheme 15 A standard route to cyclopropanes is by the Simmons-Smith cycloaddition to alkenes. A new reaction which is superficially similar to this procedure but which is more versatile uses the reaction of alkenes with organic gem-dihalides and copper powder in an aromatic solvent to give cyclopropane derivatives in good yield.34 The reaction is electrophilic apparently proceeding via an organocopper intermediate and the cyclopropane products retain the stereochemical configuration of the alkene 32 F. Sato Y.Mori and M. Sato Tetrahedron Letters 1979 1405. 33 D. B. Carr and J. Schwartz J.Amer. Chem SOC.,1979,101,3521. N. Kawabata I. Kamemura and M. Naka J. Amer. Chem. Soc. 1979,101,2139. Aliphatic Compounds -Part (i) Hydrocarbons 135 from which they are made. A variety of organic gem -dihalides can be used including trihalogenomethanes and dibromoacetic esters which give monohalogenocyclo- propanes and alkoxycarbonyl-cyclopropanesrespectively. Another procedure for the preparation of monohalogeno-cyclopropanes from olefins has also been described.35 Not only may alkenes be used for preparing three-membered rings but their importance in the synthesis of four- and five-membered ring systems is illustrated by two interesting Cycloaddition of dichloroketen to alkenes (for reaction with alkynes see Scheme 31) gives cyclobutane derivatives which may then be ring-expanded to cyclopentanes.Dichloroketen reacts with mono- di- tri- and tetra-substituted alkenes to give 2,2-dichlorocyclobutanones,and the chlorine atoms in the product can be reductively removed (Scheme 16).36 The cycloaddition of chloroketen has been accomplished in a similar manner.36 The 2,2-dichloro- cyclobutanones undergo a highly regioselective ring-expansion reaction with diazomethane to give 2,2-dichlorocyclopentanones,which in their turn can either be completely hydrodechlorinated to cyclopentanones or be partially hydro- dechlorinated to monochlorocyclopentanones and so converted into cyclo-pentenones or into cyclopentene~.~~ With other diazoalkanes (e.g. MeCHN2) CY -alkyl-substituted cyclopentanones can be prepared.R2 R3 \ / -* $V4 R'-C-C-R4 IV iii I\ R1R2C=CR3R4 1 c-CCl H2C 912 O4 C I\ 0 0 I R334 0 Reagents i CCl,COCl Zn Et,O; ii Bun3SnH or Zn HOAc; iii CH,N,; iv Zn HOAc Scheme 16 Another route to cyclobutane derivatives uses the reaction of methyl propiolate with mono- and 1,2-di-substituted ethenes in the presence of aluminium trichloride or ethylaluminium dichloride which appears to act both as a Lewis acid and a proton scavenger [Scheme 17; reaction (a)].38However withmonosubstituted ethenes both possible cyclobutenes are formed as well as some of the ene adduct. The reaction with 1,l-disubstituted trisubstituted and tetrasubstituted alkenes followed a different course and only the ene adducts were obtained [Scheme 17; reaction (b)].The preparation of reactive oxirans by direct epoxidation has been achieved using m -chloroperbenzoic acid in a two-phase system and the method has been successful 3s N. Kawabata M. Tanimoto and S. Fujiwara Tetrahedron 1979 35 1919. 36 D. A. Bak and W. T. Brady J. Org. Chem. 1979,44 107. 37 A. E. Greene and J.-P.Depres J. Amer. Chem. SOC.,1979,101,4003. 38 B. B. Snider D. J. Rodini R. S. E. Conn and S. Sealfon J. Amer. Chem. SOC.,1979 101 5283. 136 K.J. Toyne C02Me R'CH=CHR2(H) y$ and "P V)R2 W)R2 C02Me R4 R5 .R5 CH 111 + C II E I /c\ / \ C02Me R' R2H C02Me Reagents i HC=CCO,Me AlCl or EtAlCl, C6H6 or CH2C1 Scheme 17 in the synthesis of cis- trans- and aryl-~xirans.~~ An aqueous phosphate buffer is used to prevent the reaction of the oxirans with acid.Hydrogen peroxide alone is not able to epoxidize a non-conjugated double bond but when the OOH group is linked to a multiple bond as in percarboxylic acids the reactivity of the reagent is increased. Alternative reagents would be peroxycarbonic acids ROC(O)O,H which could be used without isolation and which would yield innocuous by-products (ROH and COz).A new procedure has been devised which uses 0-ethylperoxycarbonic acid EtOC(0)02H prepared in situ from hydrogen peroxide and ethyl chlor~formate.~~ The method can be carried out in mildly acidic or basic conditions in a two-phase system and gives good to excellent yields in all cases except for terminal double bonds. As in the case of alkynes (see Scheme 30) a variety of products can be obtained in the oxidation of non-terminal alkenes by potassium permanganate.Cleavage products 1,2-diones or 1,2-diols have been produced and now a-hydroxy-ketones can be obtained from non-terminal alkenes in good yield [Scheme 18; reaction (a)].41The small amount of acetic acid is added to neutralize the hydroxide ions that are formed during the reaction. Different products can also be obtained if the homogeneous reaction mixture from the oxidation of alkenes with potassium R COCH(OH)R~ iii R'CH(OH)CH(OH)R~ R'CHO and R'CHO RICH0 and R2CH(OR3)02H + R'C02R3 and R2C02R3 (20) (21) Reagents i KMnO, Me,CO H,O 2-5% HOAc; ii KMnO, (PhCH,)Et,NCI CH,CI,; iii 3% NaOH; iv aq. AcOH-AcONa; v 03,R'OH HCI at -50 to -70 "C and then -10 to +20 "C Scheme 18 39 M.Imuta and H. Ziffer J. Org. Chem. 1979,44. 1351. 40 R. D. Bach M. W. Klein R. A. Ryntz and J. W. Holubka J. Org. Chem. 1979,44,2569. N. S. Srinivasan and D. G. Lee Synthesis 1979 520. Aliphatic Compounds -Part (i) Hydrocarbons permanganate solubilized in CH2Cl2 is decomposed by aqueous solutions of different pH [Scheme 18; reaction The reaction yields mainly 1,2-diol when quenched with sodium hydroxide solution whereas aqueous sodium acetate-acetic acid can give the aldehyde exclusively. 1,2-Disubstituted ethenes can be ozonolysed directly to esters in good yield if the reaction is carried out in the presence of anhydrous hydrochloric acid in an alcohol [Scheme 18; reaction (c)].~~ The Criegee fragments [i.e.(20) and (21) or with R' and R2interchanged] are formed initially and (21) is dehydrated to an ester and (20) is converted into the acetal which on further treatment with ozone gives an ester.Further methods for preparing a-phenylseleno-ketones from alkenes are avail- able (Scheme 19),44 and subsequent alkylation of (22) at C-1 followed by reductive or oxidative removal of the phenylseleno-group allows a variety of ketones and @-unsaturated ketones respectively to be prepared (see also ref. 19c). The hydroxpelenation of alkenes has been achieved in excellent yield with two new readily available reagents N-phenylselenophthalimide (N-PSP) and N-phenyl- selenosuccinimide(N-PSS) (Scheme 19).45 By using this procedure or an alternative the hydroxyselenation of certain dienes leads to oxygen heterocycles such as tetrahydrofuran and tetrahydropyran derivatives the ring size of the product being determined by the nature of the diene and by the relative thermodynamic stability of the ring.i /Rcog2sePh or 11 RCHzCH;? RCH(OH)CH2SePh Reagents i Bu'OOH (PhSe), CCl, heat to give (PhSeOSePh); ii 2(PhSe), (PhSeO),O to give (PhSeOSePh); iii N-PSP or N-PSS toluene-p-sulphonic acid CH,Cl, H,O Scheme 19 Several terminal alkenes have been converted into methyl secondary and tertiary alkyl-lithium reagents in two stages (Scheme 20).47 Last year the same authors reported a radical-catalysed addition of thiophenol to terminal alkenes and they have now described an acid-catalysed addition which proceeds with the opposite orientation.In each case the alkyl phenyl sulphides could be cleaved with lithium in THF. R1R2CHCH2SPh-hR'R2CHCH2Li / R'R~C=CH~ iii LR1 R2C(SPh)CH3 -% R'R2C(CH3)Li Reagents i PhSH hv or aa -azoisobutyronitrile; ii lithium-naphthalene THF;iii PhSH 70% HClO,; iv Li THF Scheme 20 42 T. Ogino and K. Mochizuki Chem. Letters 1979 443. 43 J. Neumeister H. Keul M. P. Saxena and K. Griesbwm Angew. Chem. Znternat. Edn. 1978,17,939. 44 M. Shimizu R. Takeda and I. Kuwajima Tetrahedron Letters 1979 419. 4s K. C. Nicolaou D. A. Claremon W. E. Barnette and S. P. Seitz J. Amer. Chem. Soc. 1979,101,3704. 46 R.M.Scarborough A. B. Smith W. E. Barnette and K. C. Nicolaou J. Org. Chem. 1979,44,1742. 47 C. G.Screttas and M.Micha-Screttas J. Ore. Chem. 1979,44713. 138 K.J. Toyne 3 Dienes 4-Hydroxytricyclo[4.2.1 .02*5]non-7-en-3-one (23) which is readily obtainable from cyclopentadiene and maleic anhydride has been used as the basis for the preparation of stereochemically defined 1,4-disubstituted 1,3-dienes (Schemes 2 l).48For example alkylation of (24) and reduction of the carbonyl group followed by esterification gives a sample of compound (25) of known stereochemistry. Mild flash vacuum pyrolysis of (25) generates cyclopentadiene and a 3,4-disubstituted cyclo- butene which undergoes spontaneous conrotatory ring-opening to give diene (26) of predictable stereochemistry in almost quantitative yield. Although the full sequence is rather long its value has been demonstrated by the synthesis of dienes with oxygen sulphur and alkyl groups and with a chiral directing substituent.i,ii ++ R’COO-$R 1 HO H (23) OCOR2 Reagents i C,H,N p-MeC,H,SO,CI; ii chromous chloride Scheme 21 Symmetrical (E,E)-1,3-dienes of isomeric purity >99% have been prepared in high yields by a silver(1)-catalysed coupling reaction of (E)-al kenyl-pentafluorosil- icates (Scheme 22).49 Since the dipotassium salts (27) are virtually insoluble in common organic solvents reaction probably occurs at the surface of the insoluble silicate. This observation has prompted an investigation of the solid-state reactions of organopentafluorosilicates which has revealed two types of rea~tion.~’ One is a copper(1)-promoted coupling of alkenyl-silicates [Scheme 22; reagent iii(c)] to give symmetrical (E,E)-1,3-dienes (isomeric purity >92%) which is similar to the silver(1)-catalysed reaction mentioned above and the other is a ‘protonolysis’ of alkenyl-silicates (Schemes 22; reagent iv).The ‘protonolysis’ product is also obtained as the major product from alkyl-pentafluorosilicates. The preparation of allylic alcohols from oxirans has been reported previously; an extension of this reaction is to start with an ally1 alcohol and so produce an enediol B. M. Trost S. A. Godleski and J. Ippen J. Org. Chem. 1978 43,4559. 49 K.Tamao H. Matsumoto T. Kakui and M. Kumada Tetrahedron Letters 1979 1137. J. Yoshida K.Tamao T. Kakui and M. Kurnada Tetrahedron Letters 1979 1141. Aliphatic Compounds -Part (i) Hydrocarbons R' R2 \/ H c=c /\/ H RZ/C=C\Rl R' R2 \/ R'CSCR~ L c=c H/ (27) R' R2 \/ H'c=c \H (R~H or R') = Reagents i HSiCI, [H,PtCI,I; ii KF H20or EtOH; iii (a) AgF MeCN or (b)AgNO, H,O ether or (c)CuCl (solid state) 200-300 "C 3-20 mmHg; iv CuF2.2H20 heat (solid state) Scheme 22 which can be converted into a 1,3-diene (Scheme 23).51 Epoxidation of the allylic alcohol and silylation of the alcohol is followed by ring-opening of the oxiran and desilylation and finally both hydroxy-groups are removed via the dibromide.Reagents i [VO(acac),] Bu'OOH; ii Me,SiC1 (Me,Si)2NH C,H,N; iii diethylaluminium 2,2,6,6- tetramethylpiperidide; iv KF;v PBr, CuBr Zn Scheme 23 1-Alkenyl-boranes prepared from terminal alkynes react with (E)-1-alkenyl halides or 1-alkynyl halides to give conjugated (E,E)-dienes or (E)-enynes respec- tively by regio- and stereo-specific reactions; these occur in good yield in the presence of base and tetrakis(tripheny1phosphine)palladiumas catalyst (Scheme 24 reagents i and ii)." Attempts to prepare (E,Z)-dienes directly by using a (2)-1-alkenyl halide were unsatisfactory but the (E)-enynes (28) can be readily converted into the corresponding (E,Z)-dienes via hydroboronation-protonolysis.1-Alkenyl-boranes from terminal and internal alkynes can similarly be coupled with aryl halides to provide a new stereoselective synthesis of arylated alkenes (29) in high yield.53 51 A.Yasuda S. Tanaka H. Yamamoto and H.Nozaki Bull. Chem. SOC.Japan 1979,52,1752. '*N. Miyaura K. Yamada and A. Suzuki,Tetrahedron Letters 1979,3437. 53 N. Miyaura and A. Suzuki,J.C.S. Chem Comm.,1979,866. ;+3 140 K. J. Toyne y R2 R4 R' H \/ R'C=CH + HBX2 --* /c=c\ H BX 2 HBX2 = (a)HB(CHMeCHMe& \tL R' H or (b) HB >=( loo 0 H CECRs HH (28) Br R3 Reagents i R2>=(R" (R3= H or R4) [Pd(PPh,),] aq. NaOH or NaOEt EtOH; ii R5C=CBr [Pd(PPh,),] aq. NaOH or NaOEt EtOH [for reagent (a)] Scheme 24 The hydroboronation of internal or terminal alkynes by 9-borabi-cyclo[3.3.l]nonane can be readily controlled to give either vinyl-bora- or gem -dibora-intermediate~.~~ The vinyl-bora-intermediates are formed exclusively by cis-addition and although they undergo rapid protonolysis to the alkene they can be oxidized to the corresponding ketone or aldehyde under aprotic conditions with trimethylamine N-oxide or even under protic conditions by inverse addition to buffered hydrogen peroxide.1,4-Dienes can be prepared in excellent yield by a rapid regiospecific general method which starts with an crpy6-unsaturated ketone (Scheme 25)." Addition of an alkyl-lithium to the carbonyl group gives an unsaturated alkoxide (30),which is reduced in the same reaction vessel to the corresponding 1,4-diene. The position of Reagents i R'Li Et,O; ii Li NH3 EtOH or Bu'OH Scheme 25 54 H. C. Brown C. G. Scouten and R. Liotta J. Amer. Chem. SOC.,1979,101,96. " J. S.R. Zilenovski and S. S.Hall J. Org. Chem. 1979,44 1159.Aliphatic Compounds -Part (i)Hydrocarbons 141 the double bond is predictable although the product is a mixture of (E)-and (Z)-isomers at the newly developed double bond. Another procedure also gives 1,4-dienes without isomerization to 1,3-dienesaS6 The sequence starts with a terminal or internal alkyne although an unsymmetrical alkyne will give a mixture of products (Scheme 26). Initially the alkyne inserts into a Pd-halogen bond of the palladium complex catalyst and then an allyl halide inserts into the Pd-vinyl bond so formed; subsequent eliminaton of a palladium-halogen species completes the catalytic cycle. The overall reaction represents the addition of an allyl halide to a triple bond and provides a convenient synthesis of substituted vinyl halides as well as of 1,4-dienes.PdX X=ClorBr Reagents i [PdX,(PhCN),]; ii CH2=CHCH,X Scheme 26 A new procedure which is complementary to that described above for the preparation of (E)-enynes (28) allows the preparation of conjugated (2)-enynes in good yield and so provides a route to (2,Z)-dienes (Scheme 27).57 R'CECMgBr i,R1C=CCH(OH)CH=CH2 A R'C=CCH(OAc)CH=CH2 iiil H H H\ / / +-R'C=C-C; ,H R'\ p=c\cH2R2 'C I c=c /\ CH,R~ H H Reagents i CH,=CHCHO; ii Ac20,pyridine; iii R'MgX CuCl THF,H' Scheme 27 An attractive route to terminal enynes and to 1,3-dienes which introduces the four-carbon-atom conjugated unit in one stage is the ring-opening of pyridazine 1-oxide by Grignard reagents (Scheme 28).58Alkyl Grignard reagents give 1,3- dienes as a mixture of geometrical isomers by substitution whereas aryl or alkynyl Grignard reagents which are less nucleophilic lead exclusively to terminal (E)-enynes.The latter can be metallated and then allowed to react with electrophilic reagents to give internal enynes and these can then be reduced to conjugated dienes of predictable geometry. 56 K. Kaneda T. Uchiyama Y.Fujiwara T. Imanaka and S. Teranishi J. Org. Chem. 1979 44 55. 57 G. Cassani P. Massardo and P. Piccardi Tetrahedron Letters 1979 633. 58 L. Crombie N. A. Kerton and G. Pattenden J.C.S. Perkin Z,1979 2136. 142 K J. Toyne CGCH H\ ,c=c \ / R H Reagents i RMgX if R = aryl or alkynyl; ii RMgX if R =alkyl RCH=CHCH=CHR Scheme 28 An improved synthesis of 1,4-diynes (RC=CCH2C~CH) from alkynyl Grignard reagents (RCGCMgBr) and 3-tosyloxypropyne (HC_CCH,OTs) has been repor- ted,59 and details have been published of a study of some reactions of crystalline dienyl anions prepared from conjugated and non-conjugated dienes.60 4 Alkynes Synthesis.-A volume in the series on 'The Chemistry of Functional Groups' describes the chemistry of the carbon-carbon triple bondd1 and will take its place with other volumes in the series as an important reference work.Two papers this year are linked with publications referred to in the previous Annual Report. First a surveyd2* of the applicability of several syntheses of alkynes with two branched groups indicates the best method for preparing alkynes (R1C~CR2) in which both R' and R2 are a-branched or P-branched and those in which R' is a-branched and R2 is p-branched.The previous reportd2' considered internal or terminal alkynes containing one branched group. Secondly further details have appearedd3 of the synthesis of disubstituted alkynes from P-keto- sulphones. The examples given show how two primary alcohols can be linked to form alkynes (R'C _CR2) and now the method permits the stereoselective synthesis of alkenes (R'CH=CHR2) and conjugated trienes. A new route to terminal alkynes containing one carbon atom more than the primary alkyl halide that is the starting material gives excellent yields (Scheme 29).64 The alkyl halide is alkylated by dichloromethyl-lithium in hexamethylphosphoric triamide (HMPT) and dehydrochlorination of (31)is achieved by the slow addition of n-butyl-lithium to produce the lithium acetylenide which can be protonated or modified further as shown in Scheme 29.The method can be used for the synthesis of alkynes with a branched R group but in these cases the primary alkyl iodide must be used. 59 H. D. Verkruijsse and M. Hasselaar Synthesis 1979 292. 6o H. Yasuda Y. Ohnuma M. Yamauchi H. Tani and A. Nakamura Bull. Chem. SOC.Japan 1979,52 2036. 61 'The Chemistry of the Carbon-Carbon Triple Bond' ed. S. Patai Wiley/Interscience New York 1978. F. Bernadou D. Mesnard and L. Miginiac (a)J. Chem. Res. 1979 (S)190 (M)2201; (b)ibid. 1978 (S) 106 (M)1501. 63 B. Lythgoe and I. Waterhouse J.C.S. Perkin I 1979 2429. 64 J. Villieras P.Perriot and J. F. Normant Synthesis 1979 502. Aliphatic Compounds -Part (i) Hydrocarbons RCH2X RCHzCHClz -% RCECH or RCGCCHZOEt (31) X=BrorI Reagents i LiCHCl, HMPT H,O'; ii Bu"Li THF H30+ or ClCH,OEt Scheme 29 Reactions.-Many papers have discussed methods to obtain various products by the oxidation of alkynes. Four reports are mentioned here of which two deal with oxidation of the triple bond and two with oxidation at the a-carbon atoms. Oxidation of internal alkynes by potassium permanganate can occur in three different ways; (i) to give a-diketones (ii) by cleavage of the initially formed a-diketone to give carboxylic acids or (iii) by cleavage of the enol of the a-diketone to give carboxylic acids with the loss of one carbon atom.Conditions suitable for each of these reactions are shown in Scheme 30.65Both of the oxidative cleavages require the presence of aqueous potassium permanganate and it has been suggested that the symmetrical cleavage occurs by a more polar transition state which is stabilized by solvation in aqueous solvents whereas the oxidation of enols does not involve the formation of highly charged intermediates. RCHZCZCCHzR -B RCHzCOCOCH2R + RCHzCOzH (33) f3*) RCH2COC(OH)=CHR + RCH2COC02H + RCHO 1 RCHzCOzH + RCOzH + C02 (34) Reagents €or preparing (32) KMnO, anhyd. CH,Cl, phase-transfer assisted" or KMnO, acetone HzO,NaHCO, MgS04;66 €or (33) aq. KMn0,;65 €or (34) aq. KMnO, CH2C12 phase-transfer assisted6' Scheme 30 Alternative conditions for the preparation of a-diketones are potassium perman- ganate in aqueous acetone (Scheme 30).66In the simple general method sodium bicarbonate and magnesium sulphate are used as a buffer (initially pH 7.0-7.5) and so they neutralize the hydroxide ions produced during the reaction.Several chromium(v1) reagents have been compared with regard to their ability to effect a-oxidation of alkynes and the chromium trioxide-pyridine complex or pyridinium chlorochromate were found to be the best reagents for preparing conjugated ~nones.~' Oxidation at the a-carbon has also been achieved by using selenium dioxide and t-butyl hydroperoxide;68 in contrast to the behaviour of alkenes internal alkynes give (35).A comparison of the oxidation of several alkynes shows that an a-methylene or an a-methine atom are almost identical in their 65 D.G. Lee and V. S. Chang J. Org. Chem. 1979,44,2726. cx N. S. Srinivasan and D. G. Lee J. Org. Chem. 1979,44 1574. '' W. B. Sheats L. K. Olli R. Stout J. T. Lundeen R. Justus and W. G. Nigh J. Org. Chem. 1979,44 4075. B. Chabaud and K.B. Sharpless J. Org. Chem. 1979,44,4202. 144 K.J. Toyne reactivity and both are much more reactive than methyl. When the alkyne has a!-methylene and a!-methine atoms e.g. CH3CH2CrCCH(CH3)2 the enynone CH3COC=CC(CH3)=CH2 is the major product which is presumably formed by dehydration at the diol or ketol stage. R’R2C(OH)C=CC(OH)R3R4 (35) CH2R Br RCH2#CH2R Br br (36) (37) The reaction of anhydrous hydrogen bromide with alkynes in the liquid phase has been shown to produce a variety of products in addition to those expected to arise by the normal ionic or radical additi~n;~’ some terminal alkynes (RCH2C=CH) also give cyclodimerization products such as (36) and (37) and cyclobutene products were detected in the reaction of internal alkynes.Cyclobutene derivatives have also been made by the cycloaddition of dichloroketen to alkynes (Scheme 31;70 see Scheme 16 for a similar reaction with alkenes). This general and useful method for the synthesis of cyclobutenones uses dichloroketen (generated in situ from trichloroacetyl chloride) in the presence of the alkyne. The reaction is successful with terminal and internal alkynes and enynes react by cycloaddition to the triple bond.Reagents i Zn(Cu) POCl,; ii Zn HOAc Scheme 31 Two papers report syntheses of 1,3-dialkyl-butenynes by ‘head-to-tail’ dimeriza- tion of terminal alkynes (Scheme 32).”s7* One procedure” uses a rhodium(1) catalyst at room temperature to give (38) as the main product along with smaller amounts of (39). The second procedure’’ uses di-isobutylzinc and the catalyst fH2 RC-CH %RCCECR (+ RCH=CHCECR) (38) (39) Reagents i [RhCl(PPh,),] room temperature (ref. 71); ii (a) ZnBu’, [Ni(mesal),] PPh, heptane reflw (6) dilute H,SO (ref. 72) Scheme 32 69 K.Griesbaum W. Seiter H. Schneider M. El Abed and Z. Rehman Annalen 1979,1137. ’O A. Hassner and J. Dillon Synthesis 1979 689. 71 L. Carlton and G. Read J.C.S. Perkin I 1978 1631. ” G. Giacomelli F.Marcacci A. M. Caporusso and L. Lardicci Tetrahedron Letters 1979,3217. Aliphatic Compounds -Part (i)Hydrocarbons bis-[(N-methylsalicylaldimine)]nickel [Ni(me~al)~].The yields decrease with increased size of the alkyl group and with a-or @-branching but this can be overcome by adding triphenylphosphine. Finally some 1,3-disubstitution reactions of propyne are worthy of mention because they permit such a large variety of alkyne derivatives to be prepared. Dilithiopropyne can be prepared from propyne and then used in reactions with various electrophiles (Scheme 33).73 Regiospecific reaction occurs first at the pro- pargylic carbon (allowing the formation of alk-1-ynes; reagents ii and iii) and when alkylation at C-3 is followed by addition of various electrophiles chain extension at both C-1 and C-3 of propyne is possible by a ‘one-flask’ procedure (reagents iv-vii).Terminal alkynes terminal dialkynes internal alkynes and various functionalized internal alkynes can all be prepared as shown in Scheme 33 and aw-dilithio- dialkynes (the intermediates with reagent iii) will also react with electrophiles and permit further extension of the chain. Clearly 1,3-dilithiopropyne is a most useful synthon in alkyne chemistry. BuCH~C-CH HC=CCH2(CH2)l&H2C=CH ii iii] /BuCH~CECBU CH3CsCH i,(CH2CrC)Li2kBuCH,C-’CI ii vii \ BUCH~C-CCH~OH BuCH~C~CCH~CH~OH Reagents i BuLi hexane NNNN-tetramethylethylenediamine at -60 “C; ii BuBr; iii H’; iv Br(CH2),,Br; v BuBr ether and then BuBr HMPT; vi I,; vii (CH,O),; viii CH,CH ‘0’ Scheme 33 5 Allenes A new general route has been presented for the synthesis of allenes from terminal alkynes (Scheme 34),”’ and the procedure has been used on acetylenic alcohols ethers and acetates as well as on unsubstituted terminal alkynes.The reaction probably involves the Mannich base as an intermediate but the mechanism of the reaction has not been established. RC=CH -% RCH=C=CH2 Reagents i CH20 HNPr’, CuBr dioxan reflux Scheme 34 73 S. Bhanu and F. Scheinmann J.C.S. Perkin I 1979,1218. ’4 P.CrabbB H. Fillion D. AndrC. and J.-L. Luche J.C.S.Chem. Comm. 1979,859.

ISSN:0069-3030    

DOI:10.1039/OC9797600127

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

8 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By A. R. TATCHELL School of Chemistry Thames Polytechnic Wellington Street London SE18 6PF An attempt has been made in this Report to provide some continuity with previous years though with a slightly different order of sections; a section on phosphorus compounds has been omitted since a complete chapter deals with this topic. Partic- ular interest over the past year has arisen from developments in chromatographic procedures for the resolution of racemic compounds the careful selection of chiral inducing agents in asymmetric synthesis simplification of multi-stage reaction sequences and selective epoxidation methodology. 1 Alcohols and Ethers The chiral2,2,2-trifluoro- 1-(9-anthryl)ethanol has previously been used as a solvat- ing agent for the determination of enantiomeric purity and absolute configurations by n.m.r.spectroscopy of the derived diastereoisomeric solvates. Consideration of the stability differences of these solvates has led to the design of a chiral stationary phase that has enabled enantiomers of a wide range of functionality to be separated by h.p.1.c.' The stationary phase (1)was prepared from Porasil by treatment first with (3-mercaptopropyl)trimethoxysilane and then with ( -)-(R)-2,2,2-trifluoro-l-[9-(10-a-bromomethyl)anthryl]ethanol. More than fifty resolutions have been effected and it has been possible to develop a simple concept of the interactions between the solute enantiomers and the stationary phase for assessment of the probability of a successful resolution and a prediction of elution order.W. H. Pirkle and D. W. House J. Org. Chem. 1979,44 1957. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Full details have been reported of a general method that has been developed for the preparation of l-deuterio primary alcohols of high enantiomeric purity by using chiral trialkylboranes as reducing agents2 The most effective reagent was B-(3- pinanyl)-9-borabicyclo[3.3.1]nonane derived from (+)-a-pinene and 9-BBN which then rapidly reduced [1-2Hl]benzaldehyde to ( +)-(S)-[l-2Hl]benzyl alcohol; using optically pure ( +)-a-pinene none of the (R)-enantiomer could be detected by n.m.r. if one used a chiral shift reagent. With deuteriated /3 -([2-2H]-3-pinanyl)-9-BBN a range of saturated unsaturated and aromatic aldehydes were converted into the corresponding (R)-l-deuterio primary alcohols frequently in enantiomeric yields of greater than 90%.A critical study of the synthesis configurations and optical rotations of enantiomerically pure ( +)-(R)-[2-2H,]-2-phenylethanol,( +)-(R)-[1,1,2-2H3]-2-phenylethanol,and variously deuteriated phenylethanes has been rep~rted.~ Arsonated polystyrene resins have been employed as catalysts for the epoxidation of olefins with aqueous hydrogen per~xide;~ a useful expoxidizing reagent 0-ethylperoxycarbonic acid formed in situ from ethyl chloroformate and hydrogen peroxide under buffered conditions has also been de~cribed.~ Insertion of a methylene group into the carbonyl group of aldehydes and ketones to form oxirans using lithiated derivatives of N-(toluene-p-sulphony1)sulphimideshas much to commend it.6 Scheme 1illustrates a specific example.H MeC,&S02N Naf PhSCH3 4PhSCH2Li 5PhC-CH2 I I1 II c1 NTs NTs '0' Reagents i PhSCH3 CH,Cl, phase-transfer catalyst; ii BuLi DMSO; iii PhCHO Scheme 1 Epoxidation of polyunsaturated substrates (e.g. arachidonic acid eicosa-cis- 5,8,11,14-tetraenoic acid) with peroxy-acid reagents is largely non-selective; thus a methodology leading to specific epoxidation of the 5,6- and of the 14,15-double bonds has been de~eloped.~ The 5,6-epoxide was obtained by treatment of the acid (as its potassium salt) with potassium tri-iodide isolation of an unstable iodo-S -lactone followed by nucleophilic replacement of iodide with hydroxyl; the hydroxy S-lactone then collapses to give the 5,6-epoxide.The 14,15-epoxide was obtained by conversion of the carboxyl group into the corresponding peroxy-acid which on standing slowly underwent exclusive intramolecular oxygen transfer via a favourable fifteen-membered cyclic intermediate. The ring-opening of epoxides with the anion from trimethylsilylacetonitrile affords a route to y-trimethylsiloxy-nitriles which may then be readily converted into y -1actones.' Reductive ring-opening of epoxides with L~(OBU')~AIH in THF is usually very slow but may be remarkably facilitated by the addition of molar quantities of triethylborane .9 M. M. Midland S. Greer A. Tramontano and S. A. Zderic J.Amer. Chern. SOC.,1979 101,2352. R. L. Elsenbaumer and H. S. Mosher J. Org. Chern. 1979,44,600. S. E. Jacobson F. Mares and P. M. Zambri J. Amer. Chem. SOC.,1979,101,6946. R. D. Bach M. W. Klein R. A. Ryntz and J. W. Holubka J. Org. Chem. 1979,44 2569. C. R. Johnson K. Mori and A. Nakanishi J. Org. Chern. 1979,44,2065. 'E. J. Corey H. Niwa and J. R. Falck J. Amer. Chern. SOC.,1979,101 1586. I. Matsuda S. Murata and Y. Ishii J.C.S. Perkin I 1979,26. H. C. Brown and S. Krishnamurthy J. Org. Chern. 1979.44,3678. 148 A. R. Tatchell 2 Aldehydes and Ketones X-Ray photoelectron spectroscopy has been used to measure the OIs bonding energies of enolizable and non-enolizable dicarbonyl compounds." Essentially the aim was to determine whether the enol form exists in two asymmetric C forms rapidly interconverting via the symmetric C,,,or whether it exists entirely in the latter state.Since the method enables determinations to be made on a time scale of s some clear evidence on molecular symmetry was anticipated. Two dominant ionizations arising from the two non-equivalent oxygens of the C forms were found for malonaldehyde hexafluoroacetylacetone tropolone 9-hy- droxyphenalenone (2),and 6-hydroxy-2-formylfulvene (3). The last example is of particular interest since the oxygen-hydrogen-oxygen exchange process would be expected to be extremely rapid owing to the close proximity of the atoms concerned and their nearly linear relationship. /?-Thioxo-ketones exist exclusively in the (2)-en01 form (4) at 95 K but on irradiation (Aex 353 nm) are converted into the (2)-enethiol tautomer (5);on irradiation (Aex 288 nm) (5) reverts to (4)." The formation of (S)-2-methoxy-2-phenylpropionaldehyde(7)(see Scheme 2) in 97 f2% enantiomeric excess as judged after conversion into the corresponding methyl ester and subsequent n.m.r.spectroscopy with added chiral reagents,I2 and of (R)-2-methoxy-2-phenylacetaldehyde(10) (see Scheme 3) in greater than 70% enantiomeric excess13 illustrates the value of careful selection of the chiral inducing substrate [(6)or (8)] and the necessity of considering the probable transition state [e.g.(9)]of the reaction. It might be expected that both procedures will be exploited to prepare (in very high optical purity) a range of chiral a-hydroxy-aldehydes and their derived acids and alcohols.The asymmetric reduction of unsymmetrical ketones to chiral secondary alcohols has been an area of activity for over a decade. Chiral ligands that have been popular favourites for complexing with metal hydrides are derived from amines or alcohols lo R. S.Brown A. Tse T. Nakashima and R. C. Haddon J. Amer. Chem. SOC.,1979,101,3157. l1 L. Carlsen and F. Duus,J.C.S. Perkin ZZ,1979 1532. l2 E. L. Eliel and W. J. Frazee J. Org. Chem. 1979,44,3598. l3 L. Colombo C. Gennari C. Scolastico G. Guanti and E. Narisano J.C.S. Chem. Comm. 1979,591. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds \/ \/ Qo i-iii ( \-\ \ c\ \ c.\ Reagents i Bu'Li PhCHO; ii (COCI), DMSO Et,N; iii MeMgI; iv NaH MeI; v hydrolysis Scheme 2 p-tol-SOCHS-p-to1 CHO ... OH. -ii..0 + H+OH %H+OM~ ,&=... p-tol-SCH Lp:tol ph& Ph Ph -H \p-toI (10) (9) p-tol= p-tolyl Reagents i BuLi; ii PhCHO at -78 "C; iii Me,SO, H20 CH,Cl, Bu"0H; iv NaI I, Ph,P; v I, NaHCO, H20 dioxan Scheme 3 or from carbohydrates and the alkaloids. Currently the enantiomeric excesses in such reductions need to be high if they are to merit attention. For example the asymmetric reduction of a range of acetylenic ketones utilizing the complex [LiAIH(OR*)(OAr),] which arises from LiAI& and N-methylephedrine (R*OH) modified by the further addition of 3,5-dimethylphenol (ArOH) gives enantiomeric excesses in the range 75-90'/0.'~ Reduction of ketones with optically pure 6-hydroxysulphoximine-borane complexes has also been reported." Attention has now been turned to improving the enantiomeric excess arising from the addition of an alkyl group to the carbonyl group of aldehydes and ketones for the formation of chiral secondary and tertiary alcohols.In one method16 the lithium (or sodium) tetra-alkylaluminate was treated with either ( -)-N-methylephedrine ( -)-quinine or (+)-cinchonhe (R*OH) to give the chiral reagent [LiAI(R),(OR*)] which then reacted with carbonyl compounds to give chiral secondary and tertiary alcohols of useful optical purity. By employing chiral ligands derived from (S)-proline,17 reaction with alkyl-lithium (and also dialkylmagnesium) gave chiral reagents which then effected asymmetric addition to the carbonyl group of aldehydes to yield secondary alcohols in high optical yields (up to 95Y0).Although several methods for the selective reduction of aldehydes in the presence of ketones are available and indeed a further variant using lithium borohydride adsorbed on molecular-sieve zeolites has been shown to be effective,18 there are no efficient and simple methods for a selective reduction in the opposite sense. An attractive solution to the problem has utilized the lanthanoids as catalysts in the J.-P.Vigneron and V. Bloy Tetrahedron Letters 1979,2683. Is C. R. Johnson and C. J. Stark Jr. Tetrahedron Letters 1979,4713. l6 G.Boireau D. Abenhairn and E. Henry-Basch Tetrahedron 1979,35 1457. l7 T.Mukaiyarna K. Soai T. Sato H. Shirnizu and K.Suzuki J. Amer. Chem. SOC.,1979,101 1455. l8 P. A. Risbood and D. M. Ruthven J. Org. Chem. 1979,44,3969. 150 A. R. Tatchell reaction sequence~.'~ In the one-pot method the addition of cerium(II1) to an aqueous ethanolic solution of a mixture of an aldehyde and ketone or indeed to a compound containing both functional groups results in increased stability of the geminal diol from the aldehyde function and hence protection during the subsequent reduction with sodium borohydride. The synthesis of 2-hydroxy-3-methylcyclopent-2-enone (11) from methyl acryl- ate," of dihydrojasmone (12; R=C5H11) and cis-jasmone (12; R= CH,CHGCHEt) from undecane-2,5-dione and (Z)-undec-8-ene-2,5-dione respectively,2' and of squaric acid (13) and some new derivatives,22 utilizing a [2 + 21-cycloaddition reaction of tetra-alkoxy-ethylenes and oxy-ketens generated in situ have been effected in high yield and avoiding lengthy or multi-step pro- cedures and expensive chemicals.3 Carboxylic Acids A flexible method which (in principle) allows for the preparation of all the chiral methyl chiral lactic acids having all the possible permutations of the isotopes of hydrogen has been de~eloped.'~ The strategy for one such isomer is shown in Scheme 4. The conversion of (14) into (15) proceeds via a a-vinyl complex; the process by which this is formed is completely stereospecific as is the subsequent cleavage of the metal-vinyl bond. . H)=(CO,Et ii,iii H C02H CH,BrCOCO,Et 4 3D-H-D -kco2Et Br OCOMe T OCOMe T OH (14) (15) Reagents i (MeCO),O; ii [Pd(PPh,),]; iii CF,CO,T (CF,CO),O; iv Dz,[Rh{(R)-prophos}nbd]' ClO,-; v -OH HCI crystallize from Et,O-Pr',O Scheme 4 The stereospecific chain extension of an aldehyde to give a 5-substituted-2- methyl-(22,4B)-pentadienoicacid rather than the more stable (2E,4E)-isomer has been because of its relevance to the construction of the ansa bridge in the rifamycin~,~~' although the method clearly has more general applications (Scheme 5).l9 J. L. Luche and A L. Gemal J. Amer. Chem. SOC., 1979,101,5848; J. Org. Chem. 1979,44,4187. 2o R. C. Cookson and S. A. Smith J.C.S. Perkin I 1979,2447. 21 C. S. Subramaniam P. J. Thomas V. R. Mamdapur and M. S. Chadha J.C.S. Perkin I 1979,2346. 22 D. BelluS J. Org. Chem.1979,44 1208. 23 M. D. Fryzuk and B. Bosnich J. Amer. Chem. SOC., 1979,101 3043. 24 (a) E. J. Corey and G. Schmidt Tetrahedron Letters 1979,2317;(b)W. Oppolzer and V. Prelog Helo. Chim. Actu 1973,56 2287. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Br Me ... MeS )+Me 5 Me>=( MeSMMe COzH Me C0,Et %H CO,Et MeS Me C02H Do C6H11d M e C6H11 C6Hll Reagents i EtI K2C03 DMF,ii NaSMe iii LiNPr',; iv C,H,,CHO; v Raney nickel; vi KOBu' Scheme 5 Full details are now available25 of the formation of chiral a-hydroxy-acids (89-98'/0 optical purity) by stereoselective bromolactonization of for example ( -)-(S)-N-tigloylproline followed by debromination and hydrolysis. An efficient one-pot procedure for the exclusive formation of either the erythro- or of the threo-2-amino-3-hydroxy-acids is an example of the application of the stereoselective reaction between lithiated derivatives and carbonyl compounds.26 For the ( f)-erythro -isomer (17) NN-bis(trimethylsily1)glycine trimethylsilyl ester (16) as its anion was treated appropriately with the carbonyl compound whereas for the threo-isomer (f)-threonine (18) the anion was derived from N-carbo- benzoxyglycine ethyl ester (19); in this latter case the initial product was an oxazolidone derivative which was then hydrolysed under acidic conditions.Scheme 6 illustrates both reactions using acetaldehyde. @le,Si),NCH ,CO,SiMe PhCH,OCONHCH,CO,Et (16) \ C0,H fl (19) H21'+4'+4H HO OH Me Me (17) (18) Reagents i LiNPr',; ii CH,CHO; iii HCl; iv conc.HCl Scheme 6 An asymmetric synthesis of a-alkyl-a -amino-acids using ( -)-(S)-1-dimethoxymethyl-2-methoxymethyl-pyrrolidine (20),which is readily prepared from (S)-proline as the chiral auxiliary reagent has been achieved with moderate enantiomeric excess.27 The racemic acid reacts with the reagent to form a mixture of the diastereoisomeric amidine esters (21). Deprotonation with lithium di-iso- propylamide gives a derivative (22) which then undergoes regiospecific and 25 S.-S. Jew S. Terashima and K. Koga Tetrahedron 1979,35 2337 2345. 26 A. Shanzer L. Somekh and D. Butina J. Org. Chem. 1979,44 3967. *' M. Kolb and J. Barth Tetrahedron Letters 1979 2999. 152 A. R. Tatchell OMe R2 R'CHC0,Me R '+CO,Me I I CH(OMe)* NY diastereoselective alkylation to form (23) on treatment with an alkyl halide; hydrolysis gives the a-alkyl-a-amino-acid.Novel approaches to the synthesis28 of (R)-6-methyltryptophan (a potential sweetening agent) and of ( f)-gabac~line~~ (5-amino-cyclohexa-l,3-dienoicacid) have been devised to enable these compounds to be prepared in more useful amounts. The resolution and order of elution of the enantiomers of racemic a- p- and y-amino-acids as their corresponding N-trifluoroacetyl isopropyl esters by g.l.c. using N-dodecanoyl-L-valine-t-butylamideas the stationary phase has provided a basis for a provisional hypothesis of selective intermolecular solute-solvent inter- actions. Coupled with a related study on the N-trifluoroacetyl-0-acyl derivatives of 2-amino-alkan-1 -oh a better appreciation of the influence of the function of the size of the 0-acyl substituent on retention values has been demon~trated.~' 4 Esters and Lactones Simple procedures whereby sterically hindered acids may be esterified in high yields with unactivated alkyl halides which involve the use of an anion-exchange resin in either a bi- or a tri-phase system have been described.31 Re-conversion into the hindered carboxylic acids has been found to take place smoothly when the ester reacts with propyl-lithi~m.~~ The alkylation of malonic ester is one of the oldest reactions in organic synthesis.However the formation of w -bromoalkyl malonic esters (for subsequent nucleo- philic replacement reactions of the halogen) presents obvious difficulties.This has been overcome by the use of trialkyl sodiomethanetricarboxylates which readily react with ao-dihalides; removal of the blocking alkoxycarbonyl group is effected by alkoxide ion lithium di-isopropylamide or boron trifl~oride.~~ /3-Keto-esters of the type R1COCH2C02R2 also occupy a position of central importance in the history of organic synthesis. New and convenient procedures for their preparation in high yield by the acylation of malonic acid derivative^,^^ or U. Hengartner D. Valentine K. J. Johnson M. E. Larscheid F. Piggott F. Scheidl J. W. Scott R. C. Sun J. M. Townsend and T. H. Williams J. Org. Chem. 1979 44 3741. 29 B. M. Trost and E. Keinan J. Org. Chem. 1979 44 3451; J.-P. Francois and M.W. Gittos Synth. Comm. 1979,9,741. 30 B. Feibush A. Balan B. Altman and E. Gil-Av J.C.S. Perkin 11 1979 1230. 31 G. M. Moore T. A. Foglia andT. J. McGahan J. Org. Chem. 1979 44 2425. 32 C. Lion J.-E. Dubois J. A. MacPhee and Y. Bonzougou Tetrahedron 1979,35,2077. 33 H. C. Padgett I. G. Csendes and H. Rapoport J. Org. Chem. 1979,443492,4173. 34 D. W. Brooks L. D.-L. Lu and S. Masamune Angew. Chem. Infernat. Edn. 1979,18,72;J. W. F. K. Barnick J. L. van der Baan and F. Bickelhaupt Synthesis 1979,787; W. Wierenga and H. I. Skulnick J. Org. Chem. 1979,44 310. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 153 from the conversion of a-diazo-P-hydroxy-esters catalysed by rhodium(I1) acetate,35 offer promise to supplement the methods already available.The absolute configurations of glycidic esters are required both for a study of the stereochemical consequences of their rearrangement with Lewis acids to the cor- responding formyl and for a study of the stereoselectivity of epoxidation of an &-unsaturated eFter having a chiral O-alkyl group.37 The specific example that has currently been selected for both these aspects is ethyl ( +)-(2S,3R)-3-methyl-3-phenylglycidate (24) ;the configuration at C-3 has been unambiguously determined by the sequence of conversions shown in Scheme 7. /OH Me Me J Ph )\OH PhAOH Me + Ph Reagents i LiAIH,; ii HIO, NaHSO,; iii TsC1; iv KMnO Scheme 7 The Diels-Alder reaction of dimethylfulvene with methyl acrylate provides an adduct (25) which when treated with lithium di-isopropylamide and an alkyl halide gives the product (26) in which the alkyl group occupies the exo-position.Pyrolysis effects the retro-reaction to yield methyl 2-alkyl-prop-2-en0ate.~~ A synthetic route to 2-alkyl-but-2-eno-lactones (27) has been developed from this procedure and its utility demonstrated by the synthesis of some relevant naturally occurring lac tone^.^^ The formation of a-methylene- y-butyrolactones from 1-phenyl-6-propane lactam offers a synthetic route that should be of wide appli~ability.~'" In essence the sequence involves the formation of 3-alkylideneazetidin-2-one (28) sequential isomerization and epoxidation of the double bond and finally an acid-catalysed 35 R. Pellicciari R. Fringuelli P.Ceccherelli and E. Sisani J.C.S. Chem. Comm. 1979 959. 36 J. M. Dornagala and R. D. Bach J. Org. Chem. 1979,44,2429 3168. 37 S. L. Abidi and J. L. Wolfhagen J. Org. Chem. 1979 44 433. '' R. Kimara A. Ichihara and S. Sakamura Synthesis 1979 516. 39 A. Ichihara N. Nio Y. Terayarna R. Kimura and S. Sakarnura Tetrahedron Letters 1979 3731. 40 (a)S. Kano T. Ebata K. Funaki and S. Shibuya J. Org. Chem. 1979,443946,(b)L. G.Mueller and R. G. Lawton ibid. p. 4741. 154 A. R. Tatchell rearrangement to the anilinomethyl-butenolide (29). Catalytic hydrogenation over Raney nickel followed by a Hofmann degradation of the derived quaternary methiodide gives the a-methylene-y-butyrolactone (30). When cyclic ketones are employed in the formation of the alkylidene derivative the ultimate product is the cis-fused ring system e.g.(31). The trans-a-methylene-y-lactone system(32) has been obtained by an acid-catalysed rearrangement of t-butyl 2-exo-(bicyclo- [4.1.O]hept-2-en-7-yl)pr0penoate.~'~ R' R2 R' R2 U CH2NHPh &o R2)50 a0 R' H H (31) The formation of large ring lactones by the tetrakis(tripheny1phos-phine)palladium-catalysed cyclization of allylic acetates having a sulphone function at a more remote position in the carbon chain which was noted in earlier Reports has now been applied to the formation of medium-sized ring lactones. The cycliza- tion process allows for the alternative formation of products of two ring-sizes; however a preference for the larger ring in the 8/6 9/7 and 10/8 possibilities is observed.This finding which is contrary to expectations on the basis that the formation of the smaller ring is kinetically more favoured means that these less accessible lactones may be prepared more readily (Scheme 8).41 HOWOAc PhS02y ,ow OAc 0 1 ii 0 S02Ph &S02Ph t- ;.t52ph (6%) " (94%) /\ Reagents i PhS02CH2C02H PPh3 EtO,CN=NCO,Et; ii NaH [(PPhJ4Pd] diphos Scheme 8 41 B. M. Trost and T. R. Verhoven J. Amer. Chem. SOC.,1979,101,1595. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds 155 5 Amides and Lactams N-Alkyl- and N-aryl-amides may be prepared in a one-pot reaction directly from aliphatic and aromatic acids; the species (33) has been proposed as the intermediate (Scheme 9).The reaction which proceeds to give almost quantitative yields of product has been adapted for the synthesis of five- six- and seven-membered ring lactams from o-amino-carboxylic acids4' o-NCsC6H4NO2 Bu3k6H4NO2 [R'C026Bu3] 5R'CONHR' (33) Reagents i Bu,P; ii R'C0,H; iii R2NHz Scheme 9 Liquid chromatographic separation of diastereoisomeric amides derived from either racemic carboxylic acids or lactones and optically pure amines followed by hydrolysis provides an efficient preparative method for optically pure acids and act ones.^^ Two /3 -1actam syntheses have been reported. The first involves cyclization of the 1,3-dianion from an a-phenyl-thioacetamide derivative with di-iodomethane (Scheme 10); subsequently oxidation at sulphur gave separable diastereoisomeric sulphoxides or alkylation at C-3 was effected after formation of an anion by reaction with b~tyl-lithium.~~ In the second synthesis the C-4-N bond was formed under milder conditions than those hitherto reported for the cyclization of /3 -halogeno-amides (34; X = Cl) and hence provided a reaction sequence that was compatible with the presence of substituents on C-3 which could result in facile racemization; the il Phs PhSCH PhSCH Reagents i NaH; ii CHz12 Scheme 10 ii 2 -* OR2 R' = COZBu' R2 = CH2Ph Reagents (X= Cl) i 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(WSC),DMF,NH,OCH,Ph; ii NaH DMF; iii H2 Pd/C (X = OH) i WSC DMF NH,OCH,Ph; ii Ph,P EtO,CN=NCO,Et; iii H2 Pd/C Scheme 11 42 P.A. Grieco D. S. Clark and G.P. Withers J. Org. Chem. 1979,44 2945. 43 H. Helmchen G. Nill D. Flockerzi W. Schuhle and M. S. K. Yousset Angew. Chem. Internat. Edn. 1979,18,62,63,65. 44 K. Hirai and Y. Iwano Tetrahedron Letters 1979 2031. 156 A. R. Tatchell sequence provided a route to substituted N-hydroxy-2-azetidinones(35).45 The success of the method depends on the selective ionization of the N-H bond in the hydroxamic acid derivative (34). Indeed the reaction was developed for direct use with the P-hydroxy-acid derivative (34; X = OH) as a convenient alternative to the P-halogeno-amide route (Scheme 11). Three novel fused p-lactam compounds (36) have been isolated from media after culture of Streptornyces cluvuligerus and they have been shown to be structurally related to the previously reported clavulanic acid (37).46 0LL3R 0nYH2OH C02H (36) R = CH20H CH20CH0 or COzH (37) 6 Amines and Imines The conversion of a primary amine into an aldehyde by amine oxidases may proceed via the removal of either the pro-R-hydrogen or the pro-S-hydrogen (Scheme 12).H H 02 HzOz H2O [RCHzNH] -LRCHO +NH3 RANH Scheme 12 Previous work had shown that the diamine oxidase from pea seedlings removes the pro-S-hydrogen from the methylene group of benzylamine. In an extension of this work to other amine oxidases (1R)- and (1S)-[l-3Hl]heptylamine have been synthesized and their configuration assigned on the basis of correlation with the known monodeuteriosuccinic The key intermediate for the synthesis of these labelled amines was (Z)-hept-3-enal (38) prepared from acrolein (Scheme 13).Deuterium and tritium labelling was introduced to give the corresponding alcohols (39) (see Scheme 14) by stereospecific transfer from labelled ethanol in a reaction that was mediated by liver alcohol dehydrogenase in the presence of the coenzyme Reagents i HC(OMe), HBr; ii PPh,; iii Pr'OH H' iv MeSOCH2Na DMSO C3H7CHO; V (C02W2,KO Me&O Scheme 13 " P.G. Mattingly J. F. Kerwin Jr. and M. J. Miller J. Amer. Chem. SOC.,1979,101 3983. 46 D.Brown and J. R. Evans J.C.S. Chem. Comm. 1979,282. 47 A. R. Battersby D. G. Buckley J. Staunton and P. J. Williams J.C.S. Perkin I 1979 2550. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds Scheme 14 NAD'. Standard conversions (toluene-p-sulphonate into nitrile; then into amide) gave the labelled amides (40) of inverted configuration.The deuteriated acid on ozonolysis gave 94 f5% optically pure ( +)-(2S)-[2-*H,]succinic acid; the tritiated amide by way of hydrogenation hydrolysis and Schmidt degradation gave (1s)-[ 1-3Hl]heptylamine. The enantiomeric amine was formed by a similar route but using the tritiated analogue of (38) ((2)-[ 1-3Hl]hept-3-enal} formed by the reaction of (38) with sodium borotriti-ide followed by oxidation with chromium trioxide in pyridine wherein the favourable 3H isotope effect was clearly beneficial. The configurationally authenticated amines when studied with the monoamine oxidase from rat liver mitochondria unequivocally demonstrated that the pro-R -hydrogen was stereospecifically removed during oxidative deamination.(R)-a-Phenylalkyl-amines have been formed in high optical purity (76-96%) by the stereoselective alkylation (Grignard reagent) of the hydrazone (41) derived from an aryl-aldehyde and ( -)-N-aminoephedrine (Scheme 15) .48 The stereoselectivity was considered to be due to the (E)-stereochemistry of the hydrazone and complex- ation of the hydrazone with the magnesium of the Grignard reagent before attack by the alkyl group. Ph H w Me H Ph I,HHH Me R&H,N<*Ar HO NNH,I HO NN=CHAr I H Me Me (41) Reagents i ArCHO; ii RMgX; iii Pd/C Scheme 15 The reductive alkylation of azoxy-compounds affords a route whereby a-alkyl- ation of a primary amine may be efficiently carried out (Scheme 16).49 The intermediate (42) was seen to arise from the homolysis of the di-iodo-amine (formed from iodination under oxidizing conditions) followed by trapping with nitrosoben- zene.The same intermediate could equally well arise from homolysis of the monoiodo-amine trapping and further iodination. Characteristically the examples selected for illustrating the value of the method were drawn from simple aliphatic amines steroidal amines and amino-glycosides. 48 H. Takahashi K. Tomita and H. Otomasu J.C.S. Chem. Comm. 1979,668. 49 D. H. R. Barton G. Lamotte W. B. Motherwell and S. C. Narang J.C.S. Perkin Z,1979,2030. 158 A. R. Tatchell R'CHzNHZ A -R1CH2N=NPh R1CHNH2 J. I 0 R2 (42) Reagents i I, Bu'OCl PhNO; ii R2Li; iii Zn H' Scheme 16 Full details are now available for the conversion of primary amines into iodides,50" bromides and chloride~,'~~ fl~orides,'~~ aldehyde^,^" and hydrocarbon^.^^' With each conversion a range of alkyl- arylalkyl aryl- and heteroaryl-amine systems were studied and the limitations of the method with respect to each of these systems noted.( +)-2-Amino-l-methoxymenth-8-ene reacts with (*)-aldehydes that are chiral at the a-position to give diastereoisomeric aldimines (43). The ratio of dia- stereoisomers and hence the optical purity of the aldehyde may be assessed with good accuracy from integration of the signals corresponding to the pair of doublets from the proton attached to C-1 of the aldimine.'l This methoxy-amine may also be used as a chiral inducing agent since the aldimine (43; R1= H R2= Hex or Me) after conversion into the lithiated derivative readily undergoes a stereoselective reaction at C-2 with a range of electrophiles; subsequent hydrolysis yields the chiral a -alkyl-aldeh~de.'~Similar alkylations of the aldimine derived from the tertiary amine (44) show somewhat lower stereoselectivity.In the case of aldjmines derived from (-)-(S)-phenylethylamine where the absence of a chelatable group might be expected to reduce the stereoselectivity of an alkylation reaction the yields and optical purities of the chiral aldehydes finally isolated are most en~ouraging.~~ In both these alkylation reactions interestir. conceptsof the transition states and of the conformation of the intermediates have been suggested to explain the stereoselec- tivity of the reactions.A A (43) (44) 7 Other Nitrogen Compounds A conventional synthetic sequence for conversion of an aldehyde (R'CHO) into the nitrile (R1R2CHCN)may proceed through as many as eight stages in overall yields (a) A. R. Katritzky N. F. Eweiss and P.-L. Nie J.C.S.Perkin I 1979,433; (6)A. R. Katritzky U. Gruntz A. A. Ikizler D. H. Kenny and B. P. Leddy ibid. p. 436; (c)A. R. Katritzky A. Chermprapai and R. C. Patel J.C.S. Chem. Comm. 1979,238; (d)A. R. Katritzky U. Gruntz,D. H. Kenny M. C. Rezende and H. Shiekh J.C.S.Perkin I 1979,430; (e)A. R. Katritzky M. J. Cook A. Ikizler and G. H. Millet ibid. p. 2500; (f)A. R. Katritzky J. Lewis and?.-L.Nie ibid. p. 442. A. I. Meyers and Z. Brich J.C.S. Chem. Comm. 1979,566. A. I. Meyers Z. Brich G. W. Erickson and S. G. Traynor J.C.S. Chem. Comm.. 1979,567. R. R. Fraser F. Akiyama and J. Banville Tetrahedron Letters 1979,3929; R. R. Fraser and J. Banville J.C.S. Chem. Comm. 1979,47. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds which rarely exceed 12%. An ingenious continuous process has been devised which allows for the quenching of the intermediate tertiary halide by allowing the reaction mixture to flow into a phase-transfer catalytic system to give finally the nitrile in > 90% yield.54 Alkyl and aryl isocyanates are formed in excellent yield by heating dry 2,4,6- triphenylpyridine N-acyl-imines (45) under reduced pressure.The acyl-imines are prepared either from l-amino-2,4,6-triphenylpyridinium perchlorate (46) or from 2,4,6-triphenylpyrylium perchlorate as shown in Scheme 17.55 Alkyl isocyanates (and also substituted ureas and urethanes) may also be synthesized in wide variety from the reagent (48),56 which incidentally has also been used for the preparation of N-t-butoxycarbonyl-amino-acidesters.57 Ph 3”2 (48) Reagents i RCOCl K,CO,; ii RCONHNH,; iii KOH; iv RNH Scheme 17 The coupling reaction between lithium acetylides and 2-chloro-2-nitropropane gives high yields of nitro-acetylenes which may then be elaborated to crp-unsaturated ketones (Scheme 18).58 RCrCLi & RCrCCMe2N02 [RCOCH2CMe2N02]-RCOCH=CMe2 Reagents i CICMe,NO,; ii Hg2+ H,SO Scheme 18 A nitro-group sited in an aliphatic or alicyclic system may be replaced with hydrogen by reaction with the sodium salt of methanethiol in HMPT or DMSOby a sequence which proceeds via a radical mechanism.With p -aryl-nitro-alkanes where the aryl residue is unsubstituted replacement with hydrogen occurs similarly in both HMPT and DMSO; when the aryl residue has electron-withdrawing 54 J. A. Foulkes and J. Hutton Synth. Comm. 1979,9,625. ’’ A.R. Katritzky L. Lewis and P-L. Nie J.C.S.Perkin I 1979.446. 56 H. Schmidt 0.Hollitzer A. Seewald and W. Steglich Chem. Ber. 1979 112,727. ” G.Schnorrenberg and W. Steglich Angew. Chem. Zntemat. Edn. 1979,18,307. 58 M. Jawdosiuk M. Makasza B. Mudryk and G. A. Russell J.C.S. Chem. Comm. 1979,488. 160 A.R. Tatchell substituents the reaction becomes solvent-dependent and replacement of the nitro-group with the thiomethyl group predominates in DMSO. With branched- chain nuclear-substituted @-aryl-nitro-alkanes rearrangment of the carbon skeleton side-chain during reaction provides a rationale of the mechanism of this interesting reaction.'' 8 Sulphur Compounds Application of flash vacuum pyrolysis and microwave spectroscopic techniques has enabled the structure of the lachrymatory factor of the onion to be finally identified as (2)-propanethial S-oxide (49).60 A new method for the formation of a range of episulphides in high yield from for example styrene and cyclic alkenes uses either succinimide N-sulphenyl chloride (50)or the corresponding phthalimide derivative.The adducts (51)were reduced to the episulphides by addition to LiAIa in THF at low temperaturea61 0 H \+ c=s Et/\ 0- 0 (49) (50) Alkyl phenyl sulphides may be oxidized to chiral sulphoxides having reasonable optical purity (up to 81%)by sodium metaperiodate or hydrogen peroxide in buffer solution with bovine serum albumin. Prolonged oxidation gave lower chemical yields of sulphoxide but usually of greater optical purity. This was seen to arise from a two-stage oxidation process the first stage being an oxidation to the chiral sulphoxide having excess of one enantiomer and the second a preferential oxidation of the less abundant enantiomer to the sulphone.62 Prediction of the configuration of the sulphoxides from a consideration of the nature of the substituents is at present premature.Racemic 2-alkyl-tetrahydrothiopyran-4-ones( f)-(53) readily formed from methyl acrylate (52) as shown in Scheme 19 give the optically pure cis-and trans-2-alkyl-tetrahydrothiopyran-4-01s (54) and (53 each having (S)configura-tion at C-4 when submitted to horse liver alcohol dehydrogenase (HLADH)-mediated reduction. These products which may be readily separated by chromatography were converted into the optically pure (3S)-alcohols (56) by desulphurization. The latter are not obtained in an optically pure state by the enzymic reduction of the corresponding acyclic s9 N. Kornblum S. C. Carlson and R. C. Smith J. Amer. Chem. Soc. 1979 101 647; N.Kornblum J. Widmer and S.C. Carlson ibid. p. 658. " E. Block R. E. Penn and L. K. Revelle J. Amer. Chem. SOC.,1979,101,2200. '' M.V. Bombala and S. V. Ley J.C.S. Perkin I 1979 3013. 62 T.Sugimoto T. Kokubo J. Miyazaki S. Tanimoto and M. Okano J.C.S. Chem. Comm. 1979,402 1052. ''J. Davies and J. B. Jones J. Amer. Chem. SOC.,1979,101,5405. Aliphatic Compounds -Part (ii) Other Aliphatic Compounds viil QR t viii OR + Q "R Reagents i H,S; ii NaH; iii H' A; iv (HOCH,), H'; v N-chlorosuccinimide; vi RMgX H'; vii HLADH NAD'; viii Ni Scheme 19 9 Alkyl Halides The nucleophilic substitution reactions of alkyl halides are the most widely used and the most effective monitor of the efficiency of bi- and tri-phase catalytic systems. Catalysts currently being further studied for value in this type of reaction are principally though not exclusively quaternary ammonium and phosphonium salts immobilized on a polystyrene matrix? or on silica gel.65 Polymer-bound acyclic poly(oxyethy1ene) monomethyl ethers have been used for generation of dichloro-carbene and for Michael addition and Wittig reactions.66 Apart from surveying the preparative value of these systems attention is being directed to correlating such factors as for example the distance between the anionic and cationic centres the length of the carbon chain linking the ionic site to the polymer matrix (which influences the degree of protrusion of the site into the reaction medium) and the porosity of the resin.Alumina has also been shown to catalyse nucleophilic substitutions and the oxidation of alcohols by pe~manganate.~' Polymer-immobilized quaternary ammonium fluorides have been effectively used for the introduction of fluorine (by replacement of sulphonyloxy-groups) into the steroid nucleus and into monosaccharide residues.68 The synthetic value of lithium organocuprates is likely to be enhanced by recent studies on polymer-bound iodo(triarylphosphine)copper(I) in contact with a solution of the alkyl- or aryl- lithium.69 64 S.L. Regen J. C. K. Heh and J. McLick J. Org. Chem. 1979,44,1961; S. L. Regen and J. J. Besse J. Amer. Chem. SOC.,1979,101,4059; H. Molinari F. Montanari S. Quici and P. Tundo ibid. p. 3920; M. S. Chiles and P. C. Reeves Tetrahedron Letters 1979 3367. 65 P. Tundo and P.Venturello J. Amer. Chem SOC.,1979,101,6606. 66 S. Yanagida K. Takahashi and M. Okahara J. Org. Chem. 1979,44 1099. " S.-J. Liaw S. Quici and S. L. Regen J. Org. Chem. 1979,44,2029; S. Quid and S. L. Regen ibid. p. 3436; S. L. Regen S. Quici and M. D. Ryan J. Amer. Chem. SOC.,1979,101,7629. " S. Colonna A. Re G. Gelbard and E. Cesarotti J.C.S. Perkin I 1979,2248. 69 R. H. Schwartz and J. S. Filippo Jr. J. Org. Chem. 1979,44,2705. 162 A. R. Tatchell 10 Reviews Reviews have appeared on esterification and alkylation reactions employing iso- thi~ureas;~' on the synthesis of carbonyl compounds by coupling reactions of lower homologue~;~' on the chemistry of formamide acetal~?~ on halogeno-la~tones;~~ he~arnethylenetetramine,~~ alkenediazonium salts," and nitroacetic and on organic synthesis using supported there has also been a survey of tri-phase catalysis.78 'O L.J. Mathias Synthesis 1979 561. '' S.F.Martin Synthesis 1979,633. 72 M.D. Dowle and D. I. Davies Chem. SOC.Rev. 1979,8 171. 73 R.F.Abdulla and R. S. Brinkmeyer Tetrahedron 1979,35 1675. 74 N.BlaieviE D. Kolbah B. Belin V. sunjik and F. Kadfei Synthesis 1979 161. 75 K. Bott Angew. Chem. Internat. Edn. 1979,18 259. 76 M.T.Shipchandler,Synthesis 1979,666. 77 A. McKillop and D. W. Young Synthesis 1979,422 481. 78 S.L.Regen Angew. Chem. Internat. Edn. 1979,18,421.

ISSN:0069-3030    

DOI:10.1039/OC9797600146

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

9 AIicyclic Chemistry By A. COX Department of Chemistry and Molecular Sciences University of Warwick Coventry CV4 7AL 1 Introduction Reviews have been published on the potential of electrophilic cyclopropanes in synthesis,’ on the preparation of squaric acid and derivatives,2 and on methods available for the synthesis of bicyclo[3.3. lln~nanes.~ 2 Synthesis Monocyc1es.-A new facile synthesis of cyclopropyl-alkadienes has appearedV4 The reaction of diazo-compounds with (E,E)-octa-1,3,5-triene and with (2)-and (E)-hexa- 1,3,5-trienes gives 1-pyrazolines resulting from regiospecific 1,3-dipolar addition of the diazo-compound to the triene at the terminal double bond. Thermal or photochemical decomposition of the pyrazoline leads exclusively to the desired product in high yield.This method provides access to a large number of different cyclopropyl-alkadienes. At moderate temperatures the reaction of olefins with gem -dihalides in an aromatic solvent and in the presence of copper powder leads to the formation of cycl~propanes.~ Similarly trihalogeno-methanes afford mono- halogeno-cyclopropanes and dibromoacetic esters give alkoxycarbonyl-cyclo- propane derivatives. This reaction displays high stereospecificity in that cis- and trans-olefins usually lead to cyclopropanes having cis-and trans-substituents. The aromatic hydrocarbon solvent appears to play an important role in the formation of the organo-copper intermediate with which it probably forms a complex. The cis-/trans- ratio of the dicyanocyclopropanes produced in a catalytic two- phase system using a tetra-alkylammonium salt derived from 2-chloro-alkane- nitriles with 1-cyano-alkenes has been shown6 to depend on whether the catalyst is present or not.This difference is believed to originate from the fact that in the absence of catalyst both intermediate carbanions are present in the interfacial region whereas in the catalytic reaction they are in the organic phase. This causes two different transition-state interactions. A new ring-enlargement route to 2-alkynyl-cyclobutanoneshas appeared.’ The key step involves treatment of a crude mixture of tosylates of l-hydroxy-’ S. Danishefsky Accounts Chem. Res. 1979,12,66. * A. H. Schmidt and W. Reid Synthesis 1978,869. ’J. A. Peters Synthesis 1979 321.M. Schneider and A. Rau Angew. Chem. Znternat. Edn. 1979,18 231. N. Kawabata I. Kamemura and M. Naka J. Amer. Chem. SOC.,1979,101,2139. A. Jonczyk and A. Kwast Tetrahedron Letters 1979 541. ’J. Salaiin A. Fadei and J. M. Conia Tetrahedron Letters 1979 1429. 164 A. Cox cyclopropylcarbinol that have the tertiary hydroxy-group protected by a p-methoxyethoxymethyl group with LiCl in THF. A mixture of the 2-alkynyl- cyclobutanone and an enol ether is formed. Treatment of this with anhydrous zinc chloride in methylene dichloride causes the enol ether to rearrange to the desired cyclobutanone. Cycloaddition of dichloroketen to acetylenes has been reported' to be a general synthesis of cyclobutenones. Both mono- and di-substituted acetylenes participate successfully and enynes react preferentially at the triple bond.The reaction of bis-dithioacetals with methyl-lithium in THF containing tetra- methylethylenediamine (TMEDA) at 0 "C under argon causes a base-induced This constitutes a new route to functionalized cyclobutanes ring-closure to OCCU~.~ and cyclopentanes and may prove to be especially useful in view of the known synthetic versatility of sulphur in organic chemistry (see Scheme 1). PhS' 'SPh Reagents i MeLi THF,TMEDA at 0 "C Scheme 1 A new synthesis of cyclopentanones involves cycloaddition of dichloroketen to o1efins.l' Following ring-expansion of the product aa-dichlorocyclobutanones using diazomethane 2,2-dichlorocyclopentanonesare produced in good yields. The reaction conditions are mild and most significantly the intermediates offer the possibility of other synthetic transformations such as simple dechlorination using zinc or some more elaborate reaction.Palladium acetate has been observed" to catalyse the cyclization of 4,4-disubstituted 1,6-dienes to give good yields of substituted cyclopentenes. Varying the substituents shows that chelate action by these groups is unimportant. Thermolysis of pent-1-yn-3-ones in the gas phase has been observed to lead to substituted ~yclopent-2-enones,'~ and provides a new simple tool for the prep- aration of monocyclic bicyclic and spiro compounds containing this structural moiety. The reaction involves formation of a new carbon-carbon bond between an acetylenic and a non-activated carbon atom followed by [1,2]migration of one of the substituents at the triple bond.This may be explained by the formation of an alkylidenecarbene intermediate which inserts into a C-H bond that is five carbon atoms away at the non-acetylenic part of the ketone. Another paper13 reports the A. Hassner and J. Dillon Synthesis 1979 689. T.Cohen D. Ouellette. and W. M. Daniewski Tetrahedron Letters 1979,5063. lo A.E. Greene and J.-P. DeprCs J. Amer. Chem. Soc. 1979,101,4003. R. Grigg T. R. B. Mitchell and A. Ramasubbu J. C. S.Chem. Comm. 1979,669. l2 M.Karpf and A. S. Dreiding Helv. Chim. Acra 1979.62 852. l3 H. Sakurai A. Shirahata and A. Hosomi Angew. Chem. Znternat. Edn. 1979,18 163. Alicyclic Chemistry 0 0 Rk++yyj+,(y R Br 27'/o 16% R =P-CH~C~H~ 0 0 33% 18% Reagents i ZnCl, CH2Cl Scheme 2 use of 3-bromo-3-methyl-2-trimethylsiloxybut-l-ene in the synthesis of five- and seven-membered cyclic ketones (Scheme 2).Yields varying between 10and 97%are reported for a range of different alkenes and alkadienes.A new method for annulation to form cyclopentene which promises to have many applicationsin synthesis has been ann0~nced.l~ It is based on the conjugate addition of a synthon for the p -oxo-carbanion(1)to produce 1,6-dicarbonyl compounds; the chosen synthon is the acetal-containing Grignard reagent (2).As shown in Scheme 3 0 i,ii < BrMg (2) Reagents i CuBr Me2S,THF at -78 "C; ii (CHd./ ;iii HCI H20; iv. NH,Cl H,O 4 Scheme 3 '4 A.Marfat and P. Helquist Tetrahedron Letters 1979,4217. 166 A. Cox quenching of the reaction with aqueous ammonium chloride permits isolation of the products resulting from conjugate addition; by treatment with HCl these lead to the annulation products (3). Quenching of the Grignard reagent with HCl gives (3) directly. In another general cyclopentenone ann~lation~~ the key features are acylation of a vinyl-silane with an ap-unsaturated acid chloride followed by Nazarov cyclization. For example the reaction of 3-methyl-2-trimethylsilylcyclopent-1-ene with pp-dimethylacryloyl chloride in the presence of aluminium chloride at -78 "C followed by treatment with stannic chloride gives a mixture of 2,6,6-tri-methylbicyclo[3.3 .O]oct- 1-en-8-one and 2,6,6-trimethylbicyclo[3.3.O]oct-1(5)-en-8-one.Following reaction with rhodium trichloride the latter compound is obtained exclusively (55%). The synthesis has been reported16 of the highly strained eight-membered-ring compound cyclo-octa- 1,5-dien-3-yne (Scheme 4). The compound begins to de- compose at about -15 "C and at 27 "C it has a half-life of about 2 hours. This short lifetime is consequent upon facile di- and oligo-merization and also upon a low thermal barrier for transformation into cyclo-octatetraene The molecule exists in a C conformation and is thus a relatively rare case of a chiral hydrocarbon without an asymmetric carbon atom. o&BoAHbs (82%) (82%) (70%) 9 (80%)liv N sc NHCONH N4 'Se VI t .O ;ii NaHCO, H,O; iii CrO,; iv H,NNHCONH,; v SeO,; vi 170 "C Scheme 4 Some medium-sized and large ring cycloalk-2-ene- 1,4-diones have been pre- pared" by the reaction of certain ao-bis-diazoketones with [Cu(acac),].Successive treatment of the enediones with sodium dithionite and NaOH leads to their conversion into fused-ring cyclopentenones. This appears to be a general process offering a direct route to a variety of medium-sized and large rings. l5 W. E. Fristad D. S. Dime T. R. Bailey and L. A. Paquette Tetrahedron Letters 1979 1999. l6 H. Meier T. Echter and H. Petersen Angew. Chem. Internat. Edn. 1978,12 942. " S. Kulkowit and M. A. McKervey J. C. S. Chem. Comm. 1978.1069. Alicyclic Chemistry 167 Polycyc1es.-A new synthesis has been described" of variously substituted spiro[2.4]heptadienes from fulvenes using S-and N-ylides.Irradiation of the isopropylidene diazomalonate (4) leads to the corresponding spiro-activated cyclo- propanes in high yield and this forms the key step in a new synthesis of these compounds.l9 The cyclopropanation of cis- and trans -but-2-ene is stereospecific and high stereoselectivity is reported with such alkenes as 3- and 4-t-butyl- dimethylsiloxycyclopent-1-eneand with 1,3,3-trimethylcyclohex-l-ene.Insertion into C-H bonds was rarely observed and the simplicity and scope of the method suggest that it will be a powerful tool in synthesis. ox0 With a view to devising a route to bicyclo[3.1.O]hexatriene the elimination reactions of 4,6-dibromobicyclo[3.1 .O]hex-2-ene have been studied.20 Depending upon the base used either bromobenzene or 6-substituted fulvenes are formed.However labelling experiments show that bicyclo[3.1.O]hexatriene is an inter- mediate on the reaction pathway to the fulvene. The chemistry of the triene is as anticipated for an azulenoid hydrocarbon but so far trapping experiments using diphenylisobenzofuran have failed and only nucleophilic addition products have been found. 1,6-Dimethylbicyclo[4.4.l]undeca-2,4,7,9-tetraene,a vinylogue of norborna-diene has been synthesized.21 The U.V. spectrum shows a bathochromic shift of 17 nm compared with cyclohepta-1,3-diene and this can be attributed either to planar fixation of the diene units or to some homoconjugation. The compound is also thermally very labile and at room temperature it is converted into 5,7-dimethyl-cis- bicyclo[5.4.0]undeca-2,4,8,lO-tetraene in 100% yield in a process which although formally a [1,5]-sigmatropic shift of a butadiene bridge probably proceeds as in Scheme 5.In a study of the intramolecular Diels-Alder reaction the equilibrium constant for the transformation of 3-methyleneocta-1,7-diene into bicyclo-[3.3.l]non-l-ene has been determined22 as K(427 "C) = 0.28. However an Scheme 5 '' W.-D. Schrober and W. Friedrichsen Annalen 1978,1648. l9 T. Livinghouse and R. V. Stevens J. Amer. Chem. SOC.,1978,100,6479. 'O W. N. Washburn R. Zahler and I. Chen J. Amer. Chem. SOC.,1978,100,5863. J. Frank W. Grimme and J. Lex Angew. Chem. Internat. Edn. 1978,17,943. 22 K. J.Shea and S. Wise Tetrahedron Letters 1979 1011. 168 A. Cox unfavourably high entropy of reaction precludes a high yield of product. In an effort to enhance the synthetic potential electron-withdrawing groups have been placed on the dienophile; in all cases examined activated triene esters and ketones undergo cycloaddition under milder conditions and in higher yield than unactivated hydro- carbons. Another inside-outside bicyclic molecule 10,1 1-bistrifluoromethyl-i,o-bicyclo[7.2.2]trideca-lO,l2-diene (9,has been It is prepared by the thermal reaction between cis,trans-cycloundeca- 1,3-diene and hexafluorobut-2- yne and its structure has been proved by X-ray analysis of the complex with iron tricarbonyl. It has been that the highly strained bridgehead olefin tetracyclo[3.2.0.02*7.04~6]hept-1(7)-ene(6) is formed as an intermediate when 1-chloroquadricyclane is treated with a base such as n-butyl-lithium.Addition of methyl bromide to the reaction gives n-butylmethylquadricyclane,probably accord- ing to Scheme 6. Support comes from the observation that if 1-chloroquadricyclane in THF is allowed to react with a mixture of anthracene and lithium 2,2,6,6- tetramethylpiperidide the Diels-Alder adduct of (6) and anthracene can be isolated in 40% yield. The corresponding adduct from (7)was not however detected. __I) -LiO [g] (6) c1 uLi BuMe ~ (7) Scheme 6 23 P. G.Gassman S. R. Korn T. F. Bailey T. H. Johnson J. Finer and J. Clardy Tetrahedron Letters 1979 3401. J. Harnisch 0.Baumgartel G.Szeimies M. van Meerssche G. Germain and J.-P. Declercq J. Amer. Chem. SOC.,1979,101 3370. Alicyclic Chemistry Experimental evidence has been described25 attesting to the existence of tri- cyclo[3.1.0.02*6]hex-1(6)-ene (8),a homologue of tricyclo[4.1.0.02*7]hept-1(7)-ene as a reactive species. l-Chlorotricyclo[3.1.0.02~6]hexane is observed to react with n-butyl-lithium to give l-n-butyltricyclo[3.1.0.02*6]hexane.This and related obser- vations have been interpreted in terms of lithiation of the chlorocarbon to give (9). Following elimination of LiCl (8)is formed which in turn adds the lithium base to its highly strained double bond. An improved synthesis of 4e-~hloroadamantylideneadamantane* has been reported.26 This involves treatment of adamantylideneadamantane with phenyl- sulphenyl chloride to afford the product directly probably uiu the intermediacy of a thiiranium salt.A paper has also appeared27 that describes the systematic classification and nomenclature of the subset of diamond hydrocarbons known as ‘polymantanes’ using a graph-theoretical approach. As part of an investigation of structural aspects of planoid deformation of the tetraco-ordinate carbon atom 13 -oxa- 14-oxopentacyclo[ 5.5.2.1 .O4.l5. 0’0*’’]-pentadecane a bridged tetraquinacane has been synthesized.*’ Since this compound has specific functionality at two bridgeheads it is well suited for the preparation of new bridgehead olefins and of annulenes with a central carbon atom. Deslongchamps’ full paper has now appeared,29 giving experimental details for a synthesis of triquinacene and of 2,3-dihydrotriquinacen-2-one,starting from Thiele’s acid.Hitherto the synthesis of molecules constructed of repeating alicyclic units has largely been restricted to those homologous series such as the adamantanes and related families. This has been largely because thermodynamic factors have made them readily available by Lewis-acid-catalysed cationic rearrangements. A new approach based on a two-fold cation-olefin cyclization has now been anno~nced,~’ and the synthesis of syn -[3.2. 1I2geminane (octahydro-3H,8H-3,5a 8,1 Oa-dimethanoheptalene) (10) and [2. 2.2I2geminane (octahydro-2,4a 6,8a- diethanonaphthalene) (11)described (see Scheme 7). Some evidence has been advanced31 for the existence of naphtharadialene 1,2,3,4,5,6,7,8-octakis(methy1ene)-A9-octalin, as a reactive intermediate.Pyrolysis of either 1,4,5,8-tetrakis(chloromethyl)-2,3,6,7-tetramethylnaphthalene or the * Chlorine is equatorial in the cyclohexylidene ring. Senior Reporter. 25 U. Szeimies-Seebach J. Harnisch G. Szeimies M. Van Meerssche G. Germain and J.-P. Declercq Angew. Chem. Zntemat. Edn. 1978,17 848. 26 J. Bolster R. M. Kellogg E. W. Meijer and H. Wynberg Tetrahedron Letters 1979 285. 27 A. T. Balaban and P. von R. Schleyer Tetrahedron 1979 34 3599. 28 R. Keese A. Pfenninger and A. Roesle. Helv. Chim. Acta. 1979 62 326. 29 P. Deslongchamps U. 0.Cheriyan Y. Lambert J.-C. Mercier L. Ruest R. Russo and P. Soucy Canad. J. Chem. 1978,56,1687.30 H. Park P. F. King and L. A. Paquette J. Amer. Chem. SOC.,1979,101,4773. 31 H. Hart M. Jeffares A. Teuerstein and D. L. Ward J. Amer. Chem. SOC.,1978,100,8012. 170 A. Cox CH2CH2Br CH2CH2Br Reagents i silica gel stir at room temperature for 48 h (10) Scheme 7 corresponding 2,3,6,7-tetrakis(chloromethyl)-1,4,5,8-tetramethylnaphthaleneboth lead to (12) via it is suggested naphtharadialene. Support for this postulate comes from the observation that pyrolysis of 2,3-bis(chloromethyl)-1,4,5,6,7,8-hexamethylnaphthalene gives a good yield of the relatively stable (1 3). The synthesis of the bridgehead alkene bicyclo[4.2.2]deca- 1,5-diene has been Its Raman spectrum shows a band at 1620 cm-' and at 25 "C its half-life for conversion into 2,5-dimethylenebicyclo[4.2.0]octaneis reported to be 314 min.3 Stereochemistry Using a variety of force fields calculations have been performed33 on tetra-t- butyltetrahedrane; the results show the molecule to possess T symmetry and to be chiral. The four t-butyl groups are twisted by about 14" and all twelve methyl groups by about 2-6" in the same direction from a staggered Td conformation. Enan- tiomerization is however expected to be facile since the structure having Td symmetry is a possible transition state and lies 8-21 kJ mol-' above the ground state. A study of the conformations of cyclohexanecarboxaldehyde in the gas phase using microwave spectroscopy has revealed34 the presence of two stable conformers. In both of these the ring assumes a chair conformation but different torsional angles are 32 J.R. Wiseman and J. J. Vanderbilt J. Amer. Chem. SOC.,1978 100 7730. 33 W. D. Hounshell and K.Mislow TetrahedronLetters 1979 1205. 34 P. N. Kao and P.H. Turner 1Amer. Chem. SOC.,1979,101,4497. Alicyclic Chemistry 171 displayed about the C-1-CHO bond. The gauche conformer in which the carbonyl group eclipses the C-1-C-2 ring bond has been shown to be 3.0*0.8 kJ mol-' more stable than the cis conformer in which the carbonyl group eclipses the axial C-1 -H bond. These results are in good agreement with those obtained theoretically and also by n.m.r. spectroscopy. The first example has appeared3' of an electrochemical reduction showing a separate cyclic voltammetric peak for each of two interconverting conformers.At room temperature solutions of trans-1,2-dibromocyclohexane in DMF and containing tetraethylammonium bromide show a single reduction peak due to the totally irreversible two-electron reduction of the rapidly interconverting diaxial and diequatorial conformers. Lowering the temperature causes a second peak to appear attributable to reduction of the longer-lived diequatorial conformer. At -90 "C the relative heights of the two peaks due to the diaxial and diequatorial conformers are independent of the scan rate so that peak heights reflect the equilibrium concen- trations of the two conformers and K is directly derivable. Low-temperature 13C n.m.r. spectroscopy has revealed36 that in those con- formations of 2,2-dimethyl- and 2,2,6,6-tetramethyl-cyclohexaneshaving the 1-substituent in an axial position an additional destabilization exists as compared with monosubstituted cyclohexanes.The effect is consequent upon the equatorial methyl group being pushed towards the axial substituent by the reflex effect of the axial methyl group. This view is supported by considerations involving a force-field calculation which correctly predicts the experimentally determined conformational equilibria In order to assess the effect of bulky substituents on the conformation of cyclohexa- 1,4-diene the crystal and molecular structures of trans-1,4-dihydro-4-tritylbiphenyl have been dete~mined.~' These studies agree with previously pub- lished n.m.r. data that the cyclohexadiene ring is relatively flat (a = 171.8"),* with the trityl group located pseudo-axially and they stand in contrast to suggestions obtained from space-filling models that there is a pseudo-equatorial environment.Investiga- tion of cis-l,4-dihydro-4-tritylbiphenylshows3' that the ring is only slightly puckered (a,,,, = 175") but somewhat distorted (aC-l-Ph = 177" whereas aC-44ph3 = 173") and that both substituents are pseudo-equatorial. This suggests that a trityl group does not lock a cyclohexadiene ring into a boat geometry. A planar conformation of the ring appears to be favoured in which the controlling factor is packing of the substituents about the central trityl carbon atom. The first absolute configurational assignments of two chiral [8]annulenes namely 1,2,3-trimethyl- and 1,2,3,4-tetramethyl-cyclo-octatetraenes,have been they are (14) and (15) respectively.The chiroptical properties of the molecules have been determined and these show that there are four essentially unconjugated ethylene chromophores coupled principally by electrostatic potential between the T -+n* transition dipoles. * a is the angle between the planes of the two double bonds. 35 A. J. Klein and D. H. Evans J. Amer. Chem. Soc. 1979 101,757. 36 H.-J. Schneider and W. Freitag Chem. Ber. 1979,112 16. " M. C. Grossel A. K. Cheetham and J. M. Newsam Tetrahedron Letters 1978,5229. 38 M. C. Grossel A. K. Cheetham D. A. 0.Hope K. P. Lam and M. J. Perkins Tetrahedron Letters 1979 1351. 39 J. M. Gardlik L. K. Johnson L. A. Paquette B. A. Solheim J.P. Springer and J. Clardy,J. Amer. Chem. Soc. 1979,101 1615. 172 A. Cox A new way of resolving chiral cyclo-octatetraenes has a~peared,~' using a Diels- Alder reaction of chiral triazolinediones. Enantiomerically pure (-)-endo-bornyl- 1,2,4-triazolinedione is prepared and allowed to react with racemic 1,2,3-tri- methylcyclo-octatetraene giving a mixture of two stereoisomeric urazoles. Repeated crystallization separates the two diastereomers from which the parent polyolefin can be obtained in a high state of enantiomeric purity by a hydrolysis- oxidation procedure. The importance of this procedure stems from the significance of the cyclo-octatetraene nucleus as the annulene ring system that is most nearly ideally suited for probing the asymmetry of cyclic polyolefins.Iterative force-field calculations have been used4' to investigate the conformations of cycloundecane cyclotridecane and cyclopentadecane. At -150"C,cyclo-undecane is found to be a mixture of the [12323]* and [335] conformations with the latter predominating. Cyclotridecane is predicted to exist mainly in the [133331 conformation and cyclopentadecane at low temperatures probably prefers the highly symmetrical [33333] conformation. Using iterative force-field calculations the strain-energy barrier for pseudorotation of the [3333] conformation of lowest energy of cyclododecane has been found4* to be 33.1 kJmo1-'. This result is in agreement with the free-energy barrier obtained from n.m.r. data. Evidence is now available,43 from dynamic n.m.r.spectroscopy and from iterative force-field cal- culations on the conformations of cis-cyclododecene. Low-temperature 13Cn.m.r. suggests the presence of two conformations in the ratio 2 :1 with AG'(-120 "C)= 29 kJ mol-'. The calculations indicate that the conformation of lowest energy is [1,,,2333] and the next higher one is [1,,,2342]. If it is assumed that the only mechanism of exchange is interconversion of these two conformers and their mirror images then the barrier observed spectroscopically can be ascribed to the separation of these two conformations A similar method has been to determine the conformations of cyclododecyne. The results show the major conformation to be symmetrical and to have a [3,,,333] structure which may be regarded as being derived from the conformation of lowest energy of cyclododecane i.e.the [3333] conformation; the minor conformation could not be identified. Assuming that the only exchange mechanism is interconversion of [3yne333] and [4yne332] the con- formational barrier at -95 "Chas been assessed at -33 f1.2 kJ mol-'. * The description of these conformersuses the notation of Dale (J. Dale Acta Chem. Scand. 1973 27 1115.) *O J. M. Gardlik and L. A. Paquette Tetrahedron Letters 1979 3597. " F. A. L. Anet and T. N. Rawdah J. Amer. Chem. SOC., 1978,100,7810. 42 F. A. L. Anet and T. N. Rawdah J. Amer. Chem. SOC.,1978,100,7166. 43 F. A. L. Anet and T. N. Rawdah Tetrahedron Letters 1979 1943. 44 F. A. L. Anet and T. N. Rawdah J. Amer. Chem. SOC.,1979,101,1887.Alicyclic Chemistry Low-resolution microwave spectroscopy has been used4' to obtain the con-formations of some bicyclic monoterpenes based on the bicyclo[3.1 .O]hexane skele- ton. For thujone and some related compounds a boat-like conformation has been established for the bicyclic system and the puckering angle has also been derived. The synthesis has been of the first optically active anti-Bredt-rule compound that has known absolute configuration. The compound (-)-(5s)-bicy- clo[3.3.l]non-l-ene (16) [a], = -720" (by calculation) can be regarded as a me thylene -bridge derivative of (-)-(I?)-trans-cyclo-octene. (17) a; m =O b; m=2-c; m=2+ Pure enantiomers of tricyclo[6.4.0.04~9]dodecanehave been prepared and found to have easily measurable optical rotations ([a],,-30.0") despite the fact that = according to Brewster's rules they ought to be almost optically ina~tive.~' It has been suggested that the reason for the high optical rotation is that all three cyclohexane rings exist in slightly twisted chair conformations.In order to throw light on whether the central tetraco-ordinate carbon atom that is enclosed by a [12]annulene may be planar MIND0/3 calculations have been carried on (17a-c). The results show that all structures attempt to avoid a planar conformation and that those having a planar central carbon atom are of much higher energy than those that do not. The strain is distributed over all carbon centres and this leads to highly directed .rr-orbitals at C-1 C-4 C-7 and C-10.These observations have some important implications for synthetic endeavours directed at molecules of this type. 4 Structural Properties and Orbital Interactions Using ab initio SCF calculations some theoretical studies have been made49 on the singlet and triplet cyclopropylidene-allene system. These have shown that triplet cyclopropylidene (18) is lower in energy than singlet cyclopropylidene (19) by 35.1 kJ mol-' and that triplet allene is a bent planar molecule that is 33.4 kJ mol-' lower in energy than the corresponding structure with a linear geometry. The barrier height for disrotatory opening of (19) is 75.3 kJ mol-' and for (18)is 79.5 kJ mol-'. The structure of C4H7+has been the subject of further investigation^,^' and the existence of a second minimum-energy form (20) has been revealed.This should be regarded as being made up equally from the classical forms (21) and (22). 45 2.Kisiel and A. C. Legon J. Amer. Chem. SOC.,1978,100 8166. 46 M. Nakazaki K.Naemura and S. Nakahara J. C.S. Chem. Comm. 1979,82. 47 H. Buding and H. Musso Angew. Chem. Internat. Edn. 1978,17,851. M. C. Bohm R. Gleiter and P. Schang Tetrahedron Letters 1979 2575. 49 D. J. Pasto M. Haley and D. M. Chipman J. Amer. Chem. SOC.,1978,100 5272. 50 B. A. Levi E. S. Blurock and W. J. Hehre J. Amer. Chem. SOC.,1979,101 5537. An exploration of the electronic hypersurface of the thermal transformation of vinylcyclopropylidene to cyclopentenylidene has shown51 that in its singlet state the reaction is initiated by the formation of a .rr-complex between the double bond and the empty p atomic orbital at the carbene site.The reaction proceeds via a non-classical carbene in which electron density is shifted from the initial double bond toward the carbene site and which is relatively unstable toward deformation to cyclopentenylidene. Evidence has now been presented5* arguing strongly that cyclobutadiene is definitely not square (D4h)but is probably rectangular. This conclusion is based on the appearance of four bands below 1700cm-* in the i.r. spectrum of cyclobutadiene produced from several precursors and is consistent with a rectangular geometry for both cyclobutadiene and tetradeuteriocyclobutadiene,of point group D2h.In a related paper53 supporting these conclusions an ab initio SCF method has been used to calculate the vibrational frequencies of cyclobutadiene assuming a rectangular geometry for the ground state.However the authors do point out that the electronic energy obtained by this method does exceed a better published value. As part of a study of pupu bonding the .rr-face bonding of cyclobutadiene and CO HCN and benzene has been Total energies obtained by the CND0/2 method have been found to be unreliable for several possible intermolecular geometries when compared with minimal ab initio results which all show repulsive interactions except at long range for CO. The results suggest that benzene CO and HCN should not be considered as ligands of cyclobutadiene. (2,2’-Bipyridyl)(tetramethylcyclobutadiene)nickel(0) a member of a previously unknown class of complexes has been ~repared.~’ These complexes are of in- tered6 in relation to the nickel-catalysed synthesis of cyclo-octatetraene.A quan-tum-mechanical study has been ~ndertaken,~’ using the MIND0/3 technique to determine the electronic hypersurf ace for the conversion of cyclobutylidene into methylenecyclopropane. The results show that the facile reaction is initiated by formation of the non-classical carbene (23) which has a bicyclobutane-like structure and in which electron density is shifted towards the carbene site. Ring opening 51 W. W. Schoeller and U. H. Brinker J. Amer. Chem. Soc. 1978,100,6012. 52 S. Masamune F. A. Souto-Bachiller T. Machiguchi and J. E. Bertie J. Amer.Chem. SOC.,1978 100 4889. 53 L. 3. Schaad B. A. Hess and C. S. Ewig J. Amer. Chem. Soc. 1979,101,2281. 54 K. B. Lipkowitz J. Amer. Chem. Soc. 1978 100 7535. ” U. Griebsch and H. Hoberg Angew. Chem. Internat. Edn. 1978 17 950. 56 P. W. Jolly and G. Wilke ‘The Organic Chemistry of Nickel’ Academic Press New York 1975 Ch. 2 p. 94. 57 W. W. Schoeller J. Amer. Chem. SOC.,1979 101,4811. Alic yclic Chemistry [(23)-+(24)] is controlled by orbital-symmetry considerations and proceeds in a conrotatory fashion relative to the residue. Since there is a strong separation of charge in the transition state electron-donating substituents at C-4 and/or C-2 should enhance the rate. H An investigation of the electronic structure of 1,2- and 1,3-dimethylenecyclo- butane has been carried using photoelectron spectroscopy in conjunction with ab initio MO calculations.In the 1,3-derivative the through-bond interaction dominates the through-space interaction of the two localized n-orbitals leading to an inverted sequence of the orbitals. The splitting of the n MO's in the 1,2- derivative on the other hand is explained by the fact that the n-~ interaction typical of conjugated dienes is effectively reduced by a through-space interaction across the ring between the n-and pseudo-n-orbitals of CH2. Calculations have also been made59 of the potential surface of D2h1,3-dirnethylenecyclobutadiene.These show that the lowest singlet is 'A but that the ground state is 3B2u. The 1,6-dimethylcyclodecy1 cation has been generated from the corresponding alcohol using FS03H-SbF in S02ClF at -120 "C.A study of this species using 'H and 13C n.m.r. has shown6' that it exists as a symmetrical p-hydrido-bridged structure. It has been suggested that the dominant factor in promoting such a 'tertiary' ion is the release of steric strain in achieving relatively strainless decalin- type geometry from the strained cyclodecyl geometry. The electronic structure and photoelectron spectrum of cyclododeca- 1,5,9-triyne have been determined,61 and suggest that the molecule adopts a conformation that is a quasi-chair having D3 symmetry. Substantial interaction appears to exist between the non-conjugated acetylenic .rr-orbitals. The difference between 'JC-1-C-3 in (25) and 'JC-1-C-3 in (26) is very large (-5.4 Hz) and it has been concluded62 that substituents and/or steric influences exert a powerful effect on the value of 1Jc-1-c-3 in bicyclobutanes.Using the Muller- Pritchard relationship between 'JCHand s character gives 36.9% s character in C-1-H of (25) and 41.0% in bicyclobutane itself. 'JC-14-3 is -17.49 Hz and any of H Ph H/ H-C I P. Hemmersbach M. Klessinger and P. Bruckmann J. Amer. Chem. Soc. 1979,100,6344. 59 E. R. Davidson W. T. Borden and J. Smith J. Amer. Chem. Soc. 1978,100,3299. 6o R. P. Kirchen and T. S. Sorensen. J. C. S. Chem. Comm. 1978,769. 61 K. N. Houk R. W. Strozier C. Santiago R. W. Gandour and K. P. C. Vollhardt J. Amer. Chem. Soc. 1979,101,5183. 62 H. Finkelmeier and W. Liittke J. Amer. Chem.Soc. 1978 100 6261. 176 A. Cox the available coupling constant-hybridization relationships give a negative value for s2. Since this leads to an imaginary s character for its orbitals it follows that none of the available equations can be applied to the central bond. A study of the conformationally rigid a-diketones (30) (31) and (32) has permitted63 assignment of some of the p.e. bands and has also revealed a close similarity to the spectra of (27) (28) and (29). The first band (n tn,) in the electronic spectra of (30)-(32) shows a hypsochromic shift through the series and has been explained in terms of interaction involving the TT -orbital of the C202fragment and the .rr-orbitals of the olefinic moiety in (30) and (31). 0 0 A quantitative assessment of pp-u overlap has appeared64 for CI6-hexaquinacene (33).Relative to other related molecules e.g. (34) and (39 models suggest that (33) has an enhanced sphericality resulting in an increased degree of in-plane alignment of the pv-orbital triad. However the study shows that although the geometry is favourable the longer inter-atomic distances have a counterbalancing effect on the magnitude of the p-p overlap integral. (33) (34) (35) R. Bartetzko R. Gleiter J. L. Muthard and L. A. Paquette J. Amer. Chem. SOC.,1978,100,5589. 64 G. G. Christoph J. L. Muthard L. A. Paquette M. C. Bohm and R. Gleiter J. Amer. Chem. SOC.,1978 100,7782. AI icyclic Chemistry 177 5 Reactions Metal-promoted Reactions.-The reaction of 2,2,3,3-tetradeuteriomethylene-cyclopropane (36)with dimethyl fumarate has been carried out in the presence of bis(acrylonitrile)nickel(o) in benzene solution (Scheme 8).Spectroscopic analysis of the products shows65 that the deuterium atoms are completely statistically scrambled over three carbons in cyclo-adduct (37). It was concluded that a tri-methylenemethane-nickel(0)complex of type (38),or the related rapidly equili- brating a-complex is responsible for the formation of such adducts. CH30CO D28,. HHH C02CH C CHZ=CHZ nicksl(0) H2C91 *cH2 ] --[ H2C NiL (38) Z Z Z= C02Me L =olefinic ligand Scheme 8 Co-deposition of 6,6-dimethylfulvene and nickel vapour at -196 "Chas been shown66 crystallographically to lead to a mixture of 4,4,8,8-tetramethyl-1,4,5,8-tetrahydro-s-indacene and its 1,4,7,8-tetrahydro-isomer, both of which are formally derivable by a thermally forbidden [6 +61 cycloaddition followed by [1,5]-hydrogen shifts.It has been suggested that the mechanism involves a stepwise dimerization on a nickel atom template. The eighteen-electron tetrahedral complex (39)appears to be the initial product which then gives (40); finaily coupling of the two r-ally1 I t-) ___) Ni (40) (41) 6s R. Noyori M. Yamakawa and M. Takaya Tetrahedron Letters 1978,4823. N. Hao J. F. Sawyer B. G. Sayer and M. J. McGlinchey J. Amer. Chem. SOC.,1979,101 2203. 178 A. Cox moieties leads to (41) which rearranges to the product. That the reaction takes this route rather than leading to the twenty-electron nickelocene system is presumably a consequence of thermodynamic factors.An investigation of reactions between metal atoms and organocyclopropanes has revealed6’ that co-condensation of chromium and quadricyclane followed by a 1 hour warm-up of the matrix promotes an efficient isomerization to norbornadiene. Together with other observations on related systems the intervention of any carbon-carbon bond-insertion reaction is precluded and the observed isomerization is thought to be heterogeneously catalysed. It has been concluded that the metal atoms re-aggregate much faster than they react with a cyclopropane molecule. Evidence has been presented6’ to show that the metal-complex-induced insertion of CO into the cyclopropenium cation to give cyclobutenoyl complexes involves attack on co-ordinated CO to afford an intermediate co-ordinatively unsaturated cyclopropenylcarbonyl-metal species (42); this complex then undergoes ring expan- sion.Typically the reaction of 2,3-diphenylcycloprop-2-ene-l-carbonylchloride with [Co(CO)3L]-Na’ (L= CO or PPhJ leads to the cyclobutenoyl complex (43). Ph oc’ A ‘co Ph L Thermally Promoted Reactions.-Two distinct secondary deuterium isotope effects have been in the stereomutations of cis-and trans-1-cyano-2-phenyl-cyclopropane. Replacement of hydrogen by deuterium at C-1 gives a normal secondary isotope effect of about 1.07*0.02. However a value of 1.13*0.02 is obtained if the hydrogen at C-3is replaced. Such a large effect suggests a high degree of interaction between C-1and C-2and with the H-C-3 bond in the transition state.A study has also been made7’ of the thermal reactions of some 1-aryl-2-vinyl- cyclopropanes. Between 100 and 200 “C,cis-trans isomerization of the three- membered ring occurs along with rearrangement to phenylcyclopentenes or to benzocycloheptenes; polar solvents appear to enhance the yield of benzo-cyclo hep tenes. Evidence has been presented7* that supports a concerted mechanism (1) as opposed to a stepwise mechanism (2) for the gas-phase pyrolysis of some cyclo- propylacetic acids (Scheme 9). This includes a measurement of entropies and enthalpies of activation together with a determination of the deuterium isotope effect. 67 J. A. Gladysz J. G. Fulcher R. C. Ugolick A.T. L. Hanlan and A. B. Bocarsly J. Amer. Chem. SOC. 1979,101,3388. 6a C. E. Chidsey W. A. Donaldson R. P. Hughes and P. F. Sherwin J. Amer. Chem. SOC.,1979,101,233. 69 J. E.Baldwin and C. G. Carter J. Arner. Chem. Soc. 1979,101 1325. 70 G. Maas Chem. Ber. 1979,112,3241. ” D.B.Bigley and C. L. Fetter J. C. S. Perkin 11 1979 122. Alicyclic Chemistry 56 H' H s 0 Scheme 9 In a study of the thermal processes of 2-vinylcyclobutylidene (44) no cyclohex-3- enylidene [analogous to the cyclopent-3-enylidene produced from 2-vinylcyclo- propylidene (45)] was detected.'* Instead 2-vinylcyclobutylidene that has been generated by flash pyrolysis of the sodium salt of 2-vinylcyclobutanone tosyl- hydrazone gives a mixture of vinylmethylenecyclopropane and allylidenecyclo- propane from cleavage of the C-3-C-4 and C-2-C-3 bonds respectively.Although conformational effects and different methods of generation may in part be responsible for the difference in behaviour between (44) and (45),thermochemical studies show (45) to be less strained than (44) by 42-54 kJ mol-l. The vinylcyclobutane-cyclohexene rearrangement is known to occur at elevated temperatures but examples that occur at room temperature are rare. However it has been reported73 that the reaction of l,l-dicyclopropylbuta-1,3-diene with TCNE gives 1-(2',2'-dicyclopropylvinyl)-2,2,3,3-tetracyanocyclobutane,and if allowed to react for longer periods 3,3-dicyclopropyl-4,4,5,5-tetracyanocyclohex-l-ene (46). Although (46) is formally the product of a (4 + 2) cycloaddition these observations can also be interpreted in terms of a vinylcyclobutane-cyclohexene rearrangement.Following solvent and substituent studies the rearrangement was concluded to be a heterolytic process involving a zwitterionic intermediate (47). In a of the thermolysis of t-butyl cubaneperoxycarboxylate measurements of the rate and activation parameters show that the cubyl radical is formed 220-fold less rapidly than the t-butyl radical under the same conditions. It has been suggested that this is a consequence of the hybridization of the exocyclic bonding orbital of the bridgehead carbon atom and the polar character of the endocyclic carbon-carbon bonding orbitals. On pyrolysis 1,3-dimethylenecyclopentane(48) has been shown7' to behave similarly to 1,2-dimethylenecyclobutane.Thus at 370.5 "C (48) undergoes random 72 U.H. Brinker and L. Konig J. Amer. Chem. SOC.,1979,101,4738. 73 N. Shimizu and S. Nishida J. C. S. Chem. Comm. 1978,931. 74 T.-Y. Luh and L. M. Stock J. Org. Chem. 1978,43 3271. '' J. J. Gajewski and J. Salazar J. Amer. Chem. SOC.,1979 101 2739. 180 A. Cox TCNE ___ a 8: CN CN CN scrambling of the methylene groups with an activation energy of approximately 222 kJ mol-' implying that there is cleavage to 2,2'-bisallylmethane followed by random closure (Scheme 10). The ring-opening was shown to be almost stereo- specific and this has been attributed to steric effects. A companion paper that pyrolysis of (-)-(4R,SR)-trans-4,5-dimethyl-1,3-dimethylenecyclopentane gives (+)-(4S)-4-methyl-(E)-l-ethylidene-3-methylenecyclopentane with 11.!I% preservation of optical purity.Along with other results this implies that the 2,2'-bisallylmethane biradical undergoes closure with stereospecificity to the [1,3]-shift product with partial inversion of configura- tion of the migrating carbon. This stereospecificity has been suggested to arise as a consequence of stereospecific generation of a biradical followed by ring-closure (via a least-motion path) which is faster than bond rotation. In a study that was mounted to investigate the processes involved in the thermal decomposition of cyclohexene 3,3,6,6-tetradeuteriocyclohexene has been pyr~lysed.~~ Four primary unimolecular processes i.e.retro-Diels-Alder elimina- tion of D2,elimination of HD and elimination of H2 appear to be involved in the ratio 20 1:0.1 :0.02. If concerted the last two processes are symmetry-forbidden and have an activation energy -25 kJ mol-' larger than the symmetry-allowed elimination of D2. The first example of a cyclic conjugated ene-allene cis-cyclodeca- 1,2,4-triene has been isolated; on thermolysis at 100"Cthis gives trans-bicyclo[4.4.0]deca-2,4-diene quantitatively." This reaction appears to proceed via a stereospecific [131-hydrogen migration to give trans,cis,cis -cyclodeca-l,3,5-triene as an intermediate and as such it stands in contrast to thermal reactions of the acyclic ene-allenes whose degree of stereoselectivity is much smaller. '' J.J. Gajewski and J. Salazar J. Amer. Chem. SOC.,1979 101 2740. 77 D. C. Tardy R. Ireton and A. S. Gordon J. Amer. Chem. SOC., 1979 101 1508. 78 D. E. Minter G. J. Fonken and F. T. Cook Tetrahedron Letters 1979 711. Alic yclic Chemistry 181 The optically active systems 2,7-dimethyl[norcaradiene $cycloheptatrienel-7-carbonitrile and the corresponding carboxylate have been used7' to investigate the stereochemistry of the thermal norcaradiene-norcaradiene rearrangement. Contrary to the predictions of the Woodward-Hoff mann rules the rearrangement proceeds highly stereoselectively and with inversion at C-7. The results have been interpreted in terms of biradical transition states. Kinetic data have been published" on the Cope rearrangement of some cis-1,2- dialkenyl-cyclopropanes.The steric effects of substituents clearly support the view that the Cope reaction is a concerted [at+7rz + 7rnf] process involving a boat-like conformation in the transition state.In order to probe further the influence of molecular conformation on the direction of the Cope rearrangement the thermal behaviour of (49) a compound that is free to adopt one of two possible con- formations has been studied.8' The results indicate that (49) cleanly rearranges in hot benzene via transposition of the weaker cyclopropane cross-link to give (50) which under the conditions employed rearranges further. %I The thermal isomerization of 6-difluoromethylenebicyclo[3.2.0]hept-2-ene(51) occursgz exclusively through two competing 1,3-sigmatropic processes (53) formally arising by shift of C-7 from C-1 to C-3 and (54) by shift of C-1 from C-7 to C-8.Absence of the Cope-derived product (55)would appear to be due to conformational processes in the initially formed radical (52) in that there is a significantly greater barrier for passage of the CF end of the ally1 radical in (52) past the CHz group at C-4 than for the comparable rotation of the analogous protio-radical. The thermal reaction of bicyclo[5.l.0]octa-2,5-diene (56) with SO2 affordsg3 7-thiabicyclo[4,2.l]nona-2,4-diene 7,7-dioxide (Scheme 11). An additional mechanism involving prior isomerization of a double bond in (56),is also possible since a facile reaction occurs between 1,2-homotropylidene and dry SOz in [zH8]toluene giving an almost quantitative yield of the same ~ulphone.~~ A new member of the C7H6 energy-surface i.e.7-norbornadienylidene,* has been generated by pyrolysis of the corresponding N-nitro~ourea.~~ It is a compound of special interest as it is the premier example of the foiled carbenes. Depending on the temperature 7-norbornadienylidene may lose carbon to give benzene or rearrange * Bicyclo[2.2.l]hepta-2,5-dien-7-ylidene.Senior Reporter. 79 F.-G. Klarner S. Yaslak and M. Wette Chem. Ber. 1979,112 1168. M. P.Schneider and A. Rau J. Amer. Chem. SOC.,1979,101,4426. A. G.Anastassiou and R. L. Mahaifey. Tetrahedron Letters 1979 3349. 82 W. R. Dolbier C. A. Piedrahita and B. H. AI-Sader Tetrahedron Letters 1979 2957. 83 J. Dalling J. H. Gall and D.D. MacNicol Tetrahedron Letters 1979,4789. 84 D. D. MacNicol personal communication. W. T. Brown and W. M. Jones J. Org. Chem. 1979,443090. 182 A. Cox to bicyclo[3.2.0]heptatriene which in turn may dimerize or cross into the cyclo- heptatrienylidene-cycloheptatetraene manifold. Gas-phase pyrolysis of 6-methylenespiro[2.4]hepta-1,3-diene leads to a monomeric product which has been unambiguously characterizeds6 both chemically and spectroscopically as the highly strained 6,6-dimethylenefulvene.* The U.V. spectrum is interesting in that despite strain caused by the cyclopropane ring it is very similar to that of dialkyl-fulvenes. These results cast further doubt on an earlier claim" to the synthesis of this compound. Scheme 11 A report hat appeareds8 on the possibility of preferential double inversion via a n-spiropentane in the geometrical isomerization of 1,2,4-trimethylspiropentane.The results show that the trans-isomers undergo conrotatory double inversion and that the cis-isomers undergo disrotatory double inversion. Double inversion appears to be favoured by a factor of three over single inversion and the mutual direction of rotation is dependent on steric and dynamic effects rather than electronic ones. * 5 -Cyclopropylidenecyclopenta-l,3-diene.Senior Reporter. 86 R. D. Miller and D. Kaufmann J. C. S. Chem. Comm. 1978,496. a7 H.Schaltegger and M. Neuenschwander Chimia (Switz.) 1962,16,231. 88 J. J. Gajewski R. J. Weber and M. J. Chang J. Amer. Chem. SOC.,1979,101 2100. A1icy c lic Chemistry In an investigation of the reactivity of cyclopentadiene and di-exo -methylene compounds in Diels-Alder reactions the frontier-orbital method has been used8’ to show that the distance between C-1 and C-4 of the diene is significant for the reaction.Reactivity has been shown to be inversely dependent on this distance and a linear dependence between this distance and log kz has been demonstrated experimentally. As part of a study of the effect of pressure on the [2 + 2 -+ 41 cycloaddition of tetracyanoethylene to enol ethers the general volume profile has been measured for a number of different enol ethers. The results obtained” accord with a mechanism involving a zwitterionic intermediate and a ‘dead-end’ charge-transfer complex.The timing of bond changes on the way from reactants to products has been investigated’’ for the allyl-cation route to seven-membered rings. Using the sodium-iodide-induced debromination of mu’-dibromo-ketones in the presence of copper and a conjugated diene it has been found that cycloaddition of the W conformation of 1,3-dimethy1-2-oxyallyl cations to electron-rich cyclic conjugated dienes is accompanied by configurational loss. It was concluded that a push-pull mechanism is involved in which the first c+-bond is formed in an electrophilic step and the second a-bond in a nucleophilic step. Electronic as well as steric factors may play a part. A novel type of thermal pericyclic reaction has been ann~unced.~’ The reaction of hex-1-yne and n-hexane (1 10) in a high-pressure/high-temperature flow reactor leads to alkenes as major products; these are thought to have risen according to Scheme 12.This new reaction may have importance for vinylation and for the fragmentation of alkanes to alkenes. Scheme 12 By using a labelled ortho-ally1 substituent it has been possible to examine the first step of the carbon analogue of the Claisen rearrangement quite separately from the second The results suggest that the first step is rate-determining. Above 350 “C a high-yield ene cyclization to form nine-membered rings occurs and it can be attributed to a steric acceleration arising from loss of degrees of freedom on placement of the ene components in ortho-related side-chains on a benzene ring A theoretical study has been made94 of the thermal interconversion of tetra-t- butyltetrahedrane and tetra-t-butylcyclobutadiene.The transition state is found to be early on the reaction co-ordinate and the activation energy has been estimated to be 84 kJ mol-’.89 R. Sustmann M. Bohm and J. Sauer Chem. Ber. 1979,112,883. 90 J. von Jouanne H. Kelm and R. Huisgen J. Amer. Chem. SOC.,1979,101 151. 91 D. I. Rawson B. K. Carpenter and H. M. R. Hoffmann J. Amer. Chem. SOC.,1979,101 1786. 92 J. Metzger and P. KO11,Angew. Chem. Internat. Edn. 1979 18 71. 93 J. B. Lambeit D. M. Fabricius and J. J. Napoli J. Amer. Chem. SOC.,1979 101 1793. 94 A. Schweig and W. Thiel J. Amer. Chem. SOC.,1979,101,4742.

ISSN:0069-3030    

DOI:10.1039/OC9797600163

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

10 Aromatic Compounds By R. BOLTON Department of Chemistry Bedford College (University of London ) London NW14NS 1 General and Theoretical Considerations The criteria of homoaromatic character have been calculated using ab initio STO-2G methods giving results similar to those obtained using MIND0/3 and frontier orbital methods.' A MIND0/3 study of nitrobenzene reproduced the geometry of the nitro-group adequately but failed to reflect the structure of the aryl system so eff ectively.2 Other calculations using both CND0/2 and MIND0/3 methods have been applied to the 'H n.m.r. shifts associated with annulenes. Good agreement with experimental values is found only if [14]annulene is assumed to be a buckled structure and if [18lannulene is nearly planar.3 An interesting example of a lor-aromatic system is 1,4-dihydro-1,4-diacine (1).The parent molecule together with some of the simpler derivatives shows both chemical behaviour and spectroscopic properties consistent with a delocalized aromatic structure; however when electron-withdrawing substituents (-C02Me -COPh -S02Me) are attached to the nitrogen atoms the resulting ten-membered ring does not show aromatic proper tie^.^ H I An analogue to the Claisen rearrangement has been suggested' in the reaction of (trifluoromethy1)cyclopentadienewith potassium hydroxide and allyl alcohol when the observed product allyl l-allylcyclopenta-2,4-dienoate, was suggested to result via the fulvene (2). Other similar processes having their analogy in conventional R.C. Haddon J. Org. Chem. 1979,44,3608. L. P. Davis and R. M. Guidry Austral. J. Chem. 1979,32 1369. ' H. Vogler J. Mol. Struct. 1979 51 289. (a) H.-J. Altenbach H. Stegelmeier M. Wilhelm B. Voss J. Lex and E. Vogel Angew. Chem. Internat. Edn. 1979,18,962;(b) M. Breuninger B. Gallenkamp K.-H. Miiller H. Fritz H. Prinzbach J. J. Daly and P. Schonholzer ibid. p. 964. T. Olsson and 0.Wennerstroem Actu Chem. Scand. 1979 B33 256. 186 R. Bolton benzene chemistry were also reported. Both 'H and I3Cn.m.r. spectroscopy studies have been applied to some 6-(para-~ubstituted-phenyl)-fulvenes.~ The problems associated with the transmission of electronic effects across aryl systems linked in various ways have received study by semi-empirical HMO and LCAO MO SCF methods and the results were compared with experimental measurements of the properties of amines and phenols corresponding to the structure YC6&MC6H4X in which M is the linkage through which the electronic perturbations are transmitted from the substituent X to the amino- or hydroxyl group (Y = NH2 or OH).7 Both calculation methods were held to be effective; not surprisingly the degree and character of the various conjugative interactions were found important.2 Benzene Derivatives Electrophilic Substitution.-A mechanistic problem inherent in each mode of substitution and satisfactorily solved in none of them is the reality of the T-complex as a discrete intermediate in reaction. The relative roles of both u-and T-complexes in the structure C6H7f an intermediate in proton-exchange reactions has been examined by MIND0/3 and ab initio calculation methods.Two possible routes appear to be available so that the .rr-complex is found not to be a necessary intermediate in the formation of the u-complex.' Calculation therefore offers only equivocal support to theories suggesting the essential intermediacy of T-complexes in aromatic substitution. The first synthesis of a phenyl carbo-cation has been reported. The formation of this ion from the products of solvolysis of (2a) was demonstrated by the isolation of between 1 and 10% of phenol and phenolic ethers derived from 2,3,6-tri- methylphenol and showing therefore the intermediacy of the 2,3,6-trimethylphenyl carbo-cation.*" Nitration.Two types of anomalous product may result from ipso-attack and throughout the year a number of interesting advances have been made in studies of the chemis6y of such products. Suzuki and his colleagues have continued their investigations of the side-chain attack which characterizes attempted nitration processes in fully substituted benzene systems. Thus the reaction of hexamethyl- benzene with nitric acid in acetic acid at low temperatures provides four derivatives of pentamethylbenzyl alcohol (Scheme 1). The same four derivatives are also formed from (3) a possible intermediate; but although they are formed at the same A. Otter H. Muehle M. Neuenschwander and H. P. Kellerhals Helv. Chim. Actu 1979,62 1626. 'V. A. Dadali T. M. Prokep'eva and Yu.B.Vysotskii Zhur.Org. Khim. 1979,15,1129. T. Sordo J. Bertrh and E. Canadell J.C.S. Perkin ZZ 1979 1486. M. Hanack and U. Michel Angew. Chem. Znternut. Edn. 1979,18 870. Aromatic Compounds HNO,* M~ HOAc MeGz Me Me Meo: Me NO (3) 1 CH,NO CH,OAc CH,OH MeoMe + MeoMe +Meoe Me Me /Me Me /Me Me /Me Me Me Me Me Scheme 1 rate in each total reaction the product distribution differs in the two proce~ses.~ The corresponding reaction of derivatives of pentamethylacetophenone and of 4,6-diacetyl-l,2,3,5-tetramethylbenzeneshowed an interesting trend towards attack at the most crowded methyl groups in the system. This negative steric effect might arise from a contribution by the adjacent carbonyl system in structures such as (4) in a sequence such as Scheme 2 demonstrates and occurs even when trihalogenomethyl ketones [e.g.C13CC(0)C6MeS] undergo nitration. lo The problems associated with these reactions have been discussed. -Me MQ:" Me Me MeooR -/Me Me Me NO Me (4) Scheme2 Another facet of ipso-substitution is shown by the isolation of adducts such as 4-methyl-4-nitrocyclohexa-2,5-dienone(5) from the nitration of phenols. Myhre and his colleagues have made a study of adducts such as (5)and in particular their synthetic uses and their rearrangement under acidic conditions to products involving formal nitrodeprotonation.'* Although both the dienones and their reduction H. Suzuki T. Mishina and T. Hanafusa Bull. Chem. SOC.Japan. 1979,52,191 (Chem.Abs. 1979,90 203 107w).lo H. Suzuki M. Hashihama T. Mishina and T. Hanafusa J.C.S. Chem. Comm. 1979,69. '' H. Suzuki Yuki Gosei Kagaku Kyokaishi 1979,37 290 (Chem.Abs. 1979,91 55 649c). K.S. Feldman A. McDermott and P. C. Myhre J. Amer. Chem. SOC.,1979,101 505. 188 R. Bolton products are labile the acetate and chloride of the dienol formed by reduction (NaBH,-MeOH -15 "C)were relatively more stable and could be used13 to supply a number of benzene derivatives whose synthesis would otherwise be difficult. Scheme 3 provides an example. Preparative methodsI4 for the isolation of these adducts by the nitration of a number of para-substituted phenyl acetates have been reported. 0 H OH ..*-.. Me NO2 Me-NO Scheme 3 The nitration of phenol and cresols in sulphuric acid (58-80%) is a quantitative process which involves attack by the nitronium ion at near the encounter-controlled rate.The ipso-attack which had earlier been identified15 in the nitration of p-cresol also accounts for the formation of quantities of 2-methyl-6-nitrophenol in the nitration of o-methylanisole.16 While there has been much evidence to suggest that such cyclohexadiene derivatives are formed in heterolytic nitration reactions polar mechanisms are not essential. 2,6-Di-t-butyl-4-methylphenol gives 2,6-di-t-butyl- 4-methyl-4-nitrocyclohexa-2,4-dienone (6) and the further product of addition (7) on treatment with dinitrogen Letroxide at room temperature for 2 h; the conditions suggest a radical mechanism." Me NO2 Me NO An original nitration mechanism observed under conditions in which a classical nitration process might confidently have been expected was found by Giffney and Ridd" in the reaction of nitric acid with NN-dimethylaniline in 85% sulphuric acid.The process was catalysed by nitrous acid when NNN'N'-tetramethylbenzidine and its nitration products were identified along with the expected 3-and 4-nitro-NN- dimethylaniline. A radical nitration sequence (Scheme 4) was suggested; the isolation of the tetramethylbenzidine structures gave strong circumstantial evidence for the intermediate PhNMe,tNO-. The classical nitration mechanism underwent more detailed analysis when Schofield's school used the nitration of anisole and of toluene under encounter- l3 K. s.Feldman and P.C. Myhre J. Amer. Chem. SOC., 1979,101,4768. l4 C. E. Barnes K. S. Feldman M. W. Johnson H. W. H. Lee and P. C. Myhre J. Org Chem. 1979,44 3925. l5 R. G. Coombes and J. G. Golding Tetrahedron Letters 1978 3583. l6 R. G. Coombes J. G. Golding and P. Hadjigeorgiu J.C.S. Perkin 11 1979 1451. '' G. Brunton H. W. Cruse K. M. Riches and A. Whittle Tetrahedron Letters 1979 1093. l8 J. C. Giffney and J. H. Ridd J.C.S. Perkin 11 1979 618. Aromatic Compounds $HMe NMe I 6 NMez Scheme 4 controlled rates to measure the rate of formation of nitronium ions in aqueous acid media.19 Other studies of more conventional nitration reactions include the conclusion that the formation of picramide from 2,4-dinitroaniline involved the intermediacy of the N-nitro-derivative since the rate of formation of picramide from N-nitro-2,4-dinitroaniline under acid conditions was similar to that from nitric acid and 2,4-dinitroaniline under the same conditions.20 The mercury(I1)-catalysed nitration of arenes21 was shown to involve mercuration as its essential rate-determining step; the orientation of nitration paralleled that of mercuration and differed from that observed in the absence of mercury salt.The nitration of phenanthrene in acetic anhydride was reported2* to give substan- tial quantities of 10-acetoxy-10’-nitro-9,9’-biphenanthryl. The identification of this product together with the apparently ubiquitous observation of ipso-attack in such reaction media may make it desirable to re-examine the earlier work on the electrophilic substitution of polyannular systems which took nitration in acetic anhydride or acetic acid as the archetypal process.Sulphonation. The details of the sulphonation of 2-methylnaphthalene and of all ten dimethyl-naphthalenes have been carefully Steric factors appear to be unusually important and appreciable amounts of disulphonation occurred in the same ring. Directing effects appear to be unusually weak in these systems compared with those in the benzene system and suggest that it is an over-simplification to regard the naphthalene system as just an extended benzene system. A number of substituted biphenyls have also been Halogenation. Since the early work of de la Mare’s group the concept of addition occurring in parallel with heterolytic substitution by chlorine2’ in aromatic systems has been well documented.The identification of much 2,4-dichlorodiphenyl ether l9 R. B. Moodie K. Schofield and P. G. Taylor J.C.S. Perkin II 1979 133. 2o G. F. Burya and L. R. Andreeva Zzuest. Akad. Nauk SSSR,Ser. Khim. 1979,1464 (Chem. Abs. 1979 91 156 941x). ” L:M. Stock and T. L. Wright J. Org. Chem. 1979 44 3467. ’’ D. M. D. Lane K. E. Richards G. J. Wright and A. Fischer Austral. J. Chem. 1978,31 2737. 23 K. Lammertsma and H. Cerfontain J.C.S. Perkin II 1979 673. 24 T. A. Kortekaas and H. Cerfontain J.C.S. Perkin II 1979 224. ” P. B. D. de la Mare ‘Electrophilic Halogenation’ Cambridge University Press 1976. 190 R. Bolton among the products of chlorination of diphenyl ether was explained by postulating the formation of 3,4,5,6-tetrachlorophenoxycyclohexene;supporting evidence was found in spectroscopic studies and from the chemical reactions of the crude reaction product.26 Aversa Cum and their colleagues have continued their studies of the formation and properties of such adducts in the chlorination of substituted and have identified new tetrachloro-derivatives of l-methyl-lY2,3,4-tetrahydronaphthalenefrom the homolytic chlorination of l-methyl-naphthalene .28 Bromination of 3,4-dimethylphenol has been shown’’ to produce not only the expected tribromo-derivative but also the product of ipso- attack at the para-position [2,4,6-tribromo-3,4-dimethylcyclohexa-2,5-dienone(S)].Analogously with the similar products of ipso-attack of phenols during nitration (8)rearranges in acid to give the main product 2,5,6-tribromo-3,4-dimethylphenol; however in light the re-aromatization product is 2,6-dibromo-4-bromomethyl-3-methylphenol (9).Side-chain bromination by N-bromosuccinimide in tetrachloromethane to give the mono-bromination product does not show a clear preference towards cr or u+in reflecting the variation of yield with the nature of the substituent in fifteen derivatives of toluene; however the corresponding formation of benzal bromides from the ring-substituted benzyl bromides showed a better agreement with the Brown- Okamoto parameters (p+ -0.88).30 The preparative chlorination of polyfluoroaromatic amines by t-butyl hypo- chlorite proceeds by two distinct stages.The initially formed N-chloroaniline derivative may be rearranged to the stable ring-substituted derivative after treat- ment with catalytic quantities of molecular iodine.31 Other Electrophilic Processes. Friedel-Crafts acylation of some polybenzenoid systems has shown interesting results. The electrophilic attack of substituted fluorenes may show orientation effects in which the directing effect of the substituent within one benzene ring acts in opposition to that commonly seen through the stabilizing effect of the second aromatic system upon attack at the 2-position of the fluorene moiety. Earlier reports of such substitution reactions have not been systematic (e.g. attack upon 1,4-difl~orofluorene~~) or have not allowed such a competition of effect (e.g.l-methylfl~orene),~~ but a beginning has been made34 of 26 W. D. Watson and H. E. Henries J. Org. Chem. 1979 44 1155. 27 M. C. Aversa G. Cum P. Giannetto and G. Romeo J. Chem. Res. 1978 (S) 292; (M)3629. 28 M. C. Aversa G. Cum P. Giannetto and G. Romeo J. Chem. Res. 1979 (S) 338; (M)3979. 29 J. M. Brittain P. B. D. de la Mare N. S. Isaacs and P. D. McIntyre J.C.S. Perkin IZ,1979 933. 30 W. Offermann and F. Voegtle J. Org. Chem. 1979,44 710. 31 R. E. Banks M. G. Barlow J. C. Hornby and T. J. Noakes J. Fluorine Chem. 1979,13,179. 32 M. J. Namkung and T. L. Fletcher Cunad.J. Chem. 1967,45 2569. 33 E. 0.Arene and D. A. H. Taylor J. Chem. Soc. (C),1966,481. 191 Aroma tic Compounds a systematic study of such behaviour. For example 1-methoxyfluorene (10) pro- vides a complex mixture of partially demethylated products of which 45% is 4,7-diacetyl-1-hydroxyfluorene or its methylated or acetylated derivatives; a small amount of 2,4-diacetyl- 1-hydroxyfluorene was also detected.Apparently the strong para-directing properties of the methoxy-substituent override the tendency of the fluorene system towards 2-substitution although at least part of this behaviour may result from steric factors. 33*34 However the selection of substituted fluorenes was not exhaustive and there is still room for a more systematic study of substituent effects in this system. Gore and his co-workers have recently turned their attention to the acylation of naphthalene derivatives with some unexpected results.The acetylation of acenaphthene provides products of both 3-and 5-attack the relative amounts of which may be altered by changing the effective bulk of the attacking agent either by increasing the size of the acyl fragment or by changing to a more complexing solvent nitrobenzene assists attack at the less hindered position as it does in the acylation of naphthalene itself.35 In contrast 3- 4- and 5-acyl derivatives are identified in the corresponding reaction of 1$-dimethylnaphthalene and in addition some evidence was found of rearrangement to derivatives of 1,7-dimeth~lnaphthalene.’~ The Perrier method in which the complex between acyl halide and aluminium halide is pre-formed and dissolved in the reaction solvent before addition of the aromatic substrate was used in a study of the complicated products of acetylation of 1-chloronaphthalene.All seven isomers were detected; the major product (ca. 80%) was 4-acetyl-1-chloronaphthaleneunless the reaction solvent was nitroben- zene when approximately equal amounts of the 4-,6- and 7-acetyl-1-chloro- naphthalenes were obtained. The 1-chloro-substituent was also found to activate attack at the 4-position by a factor of ca. 5 a result at variance with expectation both from studies of the Friedel-Crafts acylation of chlorobenzene and from measure- ments of the attack of chlorobenzene by other electrophiles. Some indications that the yields of product in the acetylation of some naphthalene derivatives depend upon time suggest that the unexpected effect may arise from idiosyncracies of this particular reaction rather than from a general property of 1-~hloronaphthalene.~’ Rearrangements already noted in the acenaphthene work as well as in the attack of l,8-dimethylnaphthalene,36may be involved.Thallation [TI(OCOCF3)3-CF3C02H,at 25 “C]has been shown to be more selective than mercuration (1 1) but otherwise appears to involve a conventional electrophilic (p 4) s~bstitution.~~ 34 D. R. Buckle N. J. Morgan and R. G. Alexander J.C.S. Perkin I 1979 3004. ” e.g. H. Luther and G. Wachter Chem. Ber. 1949,82 161 and refs. therein. 36 P. H. Gore and M.Jehangir J.C.S. Perkin I 1979,3007. 37 P. H. Gore and I. M. Khan J.C.S. Perkin I 1979,2779. 38 P. Y. Kwok L. M. Stock andT. L. Wright J. Org. Chem. 1979,44,2309.192 R. Bolton Nucleophilic Substitution.-The SNAr Mechanism. The classic mechanism of aromatic nucleophilic substitution continues to receive much attention. Tiecco and his co-workers have reported the displacement of halogen from otherwise unactivated aromatic systems by thiolate nucleophiles in hexamethylphosphoramide at 80 "C; the order of ease of displacement was reported to be I >F> Br >C1 and this together with the lack of influence of azobenzene (expected to inhibit the SRN1 mechanism) was advocated as evidence for the suggested displacement mechanism. However the differences of rate between iodobenzene fluorobenzene and bromo- benzene were only a factor of two in the rate constant; chlorobenzene was only one-eighth as rapidly attacked as bromobenzene and this contributed to the apparently wide spread of rate constants in the attack of the monohalogeno- benzenes.39 It seems still probable that more than one mechanism might prevail in these reaction conditions for although confirmation of the order of displacement was found by studying dihalogeno-benzenes of the structure XC6H4Y such studies are complicated by the different effects that the X and the Y substituents must have upon the attack which displaces the other substituent.A very different situation has been found in studies of the effect of complexation of metal upon the reactivity of aryl halides. Early work4' demonstrated the large activation which complexation with chromium as in (12) might bring about. Knipe ML n (12) a; ML = CI-(CO)~ b; ML =Mo(C0)3 McGuinness and Watts4' have reported rather more detailed studies of the effect of complexing upon the ease of displacement of fluorine and of chlorine in phenyl halides complexed with various metal ligands.Considerable differences were found by changing the nature of the metal and also the ease of displacement of the halogen atom [F>>C1; kF/kc,ca. 500 in (12b)l paralleled much more closely that found in 'conventional' processes such as the methoxydehalogenation of pentachloro-halo- genobenzenes or of 2,4-dinitro-halogenobenzenes in Another important demonstration of the effect of complexing by metals was shown in the 39 P. Cogolli F. Maiolo L. Testaferri M. Tingoli and M. Tiecco J. Org. Chem. 1979,44,2642.40 B. Nicholls and M. C. Whiting J. Chem. Suc. 1959,551; J. F. Bunnett and H. Hermann J. Org. Chem. 1971,36,4081. 41 A. C. Knipe S. J. McGuinness and W. E. Watts J.C.S. Chem. Comm. 1979 842. 42 e.g. J. Miller 'Aromatic Nucleophilic Substitution,' Elsevier Amsterdam 1968. Aromatic Compounds methoxydechlorination of 5-chloro-l,l0-phenanthroline in 89.8% DMSO-10.2% MeOH mixture. The rate of this process was ac~elerated~~' by the presence of a number of transition metals the effect appearing to be linked with the formal charge associated with the complex. In the preceding paper dealing with the displacement reaction of the uncomplexed chlorophenanthroline the kinetic behaviour suggested a somewhat more complicated mechanism which was reported as the coexistence of terms that are first-order and second-order in methoxide ion [equation (I)]:"'" d[Cl-]/dt =k[ArCl][OMe-] +k'[ArCl][OMe-]* (1) Although the point was not given detailed study it is possible that the second term in the kinetic equation may represent catalysis by sodium ion.Variations of the observed rate constant caused by changes in the concentration of reagent salts have been well known for some time but detailed measurement of the effect of changes in the gegenion upon rate have only recently been reported."" The rates of ethoxy- dehalogenation of iodo- and chloro-2,4-dinitrobenzene in anhydrous ethanol by lithium sodium potassium or caesium ethoxides were measured at 25 "C,and were compared with the results of a similar study with ethyl iodide as substrate.The major salt effects that were found were consistent with two effective reagents; 'free' ethoxide ion and 'paired' ethoxide ion. Conductimetric measurement was used to determine the contribution of each type of reagent in the solutions and the variations which were observed could be interpreted in terms of the different degrees of association of the different metal ethoxides. Kinetic complications were caused partly because of the difficulty of assessing the contribution by the metal halide that is produced upon the initial pre-equilibrium between ion-pairs and free ethoxide ion and at higher concentrations because of a general divergence which might have reflected the inadequacy of the kinetic form to cope with relatively high concen- trations of species in solution.Another approach to the problem was made by Gold and To~llec,"~ who took the pragmatic approach to define a term JE [equation (2)] which reflected the ability of solutions of sodium ethoxide in ethanol to donate OEt- to 2,4-dinitrophenetole JE =pK +pKE +log([Adduct]/[2,4-Dinitrophenetole]) (2) dissolved in them. The ion produced (13),was detected spectroscopically and the apparent equilibrium constant Kappwas corrected for changes in ionic strength to give K which along with the autoprotolysis constant of ethanol (KE),provided the N+ /\ -0 0-43 (a) K. Jackson J. H. Ridd and M. L. Tobe J.C.S. Perkin ZI 1979 607; (b) ibid. p. 611. 44 P.Jones R. Harrison and Lord Wynne-Jones J.C.S.Perkin ZZ,1979 1679."V.Gold and J. Toullec J.C.S. Perkin ZZ 1979 596. 194 R. Bolton parameters necessary for the new function. A similar function applied to methanol already The formation of Meisenheimer complexes of which (13)is an example remains a source of Gibson and C~ampton~~ used spectroscopic kinetic and equilibrium measurements to demonstrate that the reaction between hydroxide ion in aqueous media and picryl derivatives (1-X-2,4,6-trinitrobenzenes)is a process which first involves attack at C-3 and that the subsequent rearrangement of hydroxide from the 3-position to the 1-position then provides the conventionally formulated anion. It was felt although on less rigid evidence that the corresponding process was less likely in the analogous 2,4-dinitrophenyl systems.Low-tempera- ture flow methods were used in an n.m.r. study of Meisenheimer complexes between aliphatic amines and 2,4,6-trinitroanisole in DMSO-MeOH (1:l).” Surprisingly the products of the two reactions were different and apparently reflected different stabilities of the two Meisenheimer intermediates. With n-butylamine the fast formation of (14) was followed by the expected displacement of methoxide ion to give N-(n-buty1)picramide. Di-n-butylamine however rapidly provided the cor- responding complex which did not then lose OMe- but instead underwent methanolysis to give 1,l -dimethoxy-2,4,6-trinitrocyclopentadiene anion (15). Stabilities of Meisenheimer complexes have also been measured in the nucleo- philic attack of pyridinium ions by nu~leophiles*~*~~ and in the attack of (po1y)nitro- cyano-thiophens and -selenophens.In the latter case addition of methoxide ion occurred more readily with the nitro-group ortho and para to the site of attack the order being 2,4-dinitro > 2-nitro-4-cyano > 2-cyano-4-nitr0 in describing the ease of attack of carbon bearing hydrogen in either heterocyclic system. The selenophen derivatives perhaps expectedly were better able to stabilize such structures than their thiophen analogues.53 Bernasconi has revised and extended his earlier work on similar complexes between 1,3,5-trinitrobenzene and amine~.~~ One of the earliest compelling pieces of evidence for the two-stage mechanism of nucleophilic displacement was the observation of base catalysis.Hirst and his 46 F. Terrier Ann. Chim. (France) 1969,4 153. 47 C. H. Rochester J. Chem. SOC.,1965,2404. 48 S. Sekiguchi Yuki Gosei Kagaku Kyokaishi 1978,36,633 (Chem. Abs. l979,90,71243a). 49 B. Gibson and M. R. Crampton J.C.S. Perkin 11 1979 648. ’* C. A. Fyfe S. W. H. Damji and A. Koll J. Amer. Chem. SOC.,1979 101,951. 51 S. W. H. Damji and C. A. Fyfe J. Org. Chem. 1979,44 1757. 52 S. W. H. Damji C. A. Fyfe D. Smith and F. J. Sharom J. Org. Chem. 1979,44 1761. 53 F. Terrier. A.-P. Chatrousse and C. Paulmier J. Org. Chem. 1979.44 1634. 54 C. F. Bernasconi M. C. Muller and P. Schmid J. Org. Chem. 1979 44,3189. Aroma tic Compounds c011eagues~~ have observed that such catalysis apparently occurs in the reaction between aniline and l-fluoro-2,4-dinitrobenzene in dimethylformamide in acetonitrile or in nitromethane but not in dimethyl sulphoxide (DMSO).1-Chloro-2,4-dinitrobenzene showed no such effect under any of these conditions. The evidence for catalysis however was a kinetic dependence upon the aniline concen- tration. The order with respect to aniline was greater than unity. The results allow a number of interpretations one of which might be the instability of the solvents towards aniline. Catalysis by piperidine was shown in the aminodemethoxylation of 2-methoxy-3-nitrothiophenin benzene by piperidine at 10-30 “C. The evidence was again the incursion of a term involving a higher order with respect to the base than that expected in the simple bimolecular process and the interpretation of the mechanism by which this catalysis occurred draws attention to the Meisenheimer intermediate.56 A similar observation of catalysis by methoxide ion has already been noted.56b In an attempt to quantify the effects of ortho-substituents in similar displacement reactions the rates of aminodebromination of 2-bromo-3,5-dinitro- thiophen in methanol by a number of ortho-substituted anilines were measured.A multi-parameter equation was used to link the observed rates with steric and electronic properties of the ~ubstituents.~~ Aminodenitration has been reported as a preparative method in the synthesis of acridones from polynitro-benzophenones the displacement being assisted by the nitro-substituents as well as by the acyl group (Scheme 5).58 However the attack by piperidine upon 2,3-dinitrophenol is reported59 to give 6-piperidino-3-nitrophenol by a sequence (Scheme 6)which involves initially a remote attack meta to the group that is ultimately displaced.Ph 02NfJyJ II NO2 0 Scheme 5 Among novel systems showing nucleophilic displacement reactions attack by methoxide ion upon pyrylium ions continues to attract attention. The rates of the rapid reactions so far as generalizations may be made are consistent with the substituent effects expected.60 ” T. 0.Bamkole J. Hirst and I. Onyido J.C.S.Perkin 11 1979 1317. 56 G. Consiglio R. Noto and D. Spinelli J.C.S.Perkin 11 1979 222; J. Org. Chem. 1978,43,4038. ’’ G. Consiglio R. Noto D. Spinelli and C. Arnone J.C.S. Perkin II 1979 219.58 J. H. Gorvin and D. P. Whalley J.C.S. Perkin I 1979 1364. 59 R. E. Maxwell J.C.S. Chem. Comm. 1979,428. 6o G. Doddi S. Fornarini G. Illuminati and F. Stegel J. Org. Chem. 1979,44,4496. 196 R. Bolton 0- Scheme 6 Other variations in the conditions used for displacing chlorine by hydroxide in the 1-chloro-2,4-dinitro-benzeneand -naphthalene systems include a study of micellar catalysis which suggests the reaction to be somewhat more complex than the simple kinetic model would imply.61 Such processes seem to be a rich source of kinetic study. The SRNl Mechanism. Since the SNAr mechanism a number of more recent mechanisms have been advanced for the displacement of halogen from aryl halides by nucleophiles. Of these the SRNl mechanism is at present commanding consider- able interest.Relatively unactivated aryl iodides may show such a mechanism of nucleophilic displacement; the best but by no means the only reaction conditions seem to need liquid ammonia as solvent and the presence of dissolving alkali metals or light to initiate the reaction (Scheme 7).62Within this general mechanism however there are a number of sub-divisions; in some systems light is essential for the displacement to occur whereas in others light merely speeds the process but is ArX + e-+[ArX] [ArX]-+Ar. + X-Are + Y-+[ArY] [ArY] + ArX+ArY + [ArX]; Scheme 7 C. A. Bunton L. S. Romsted and G. Savelli J. Amer. Chem. Soc. 1979,101,1253. 62 J. F. Bunnett Accounts Chem. Res. 1978 11 413. Aromatic Compounds 197 not essential.Thus Pierini and Rod3 found that the displacement of halogen from halogeno-naphthalenes -phenanthrenes and -quinolines by PhSe- and PhTe- required light catalysis and would not proceed in the dark whereas Swartz and Bunnetf4 noticed that the phenylation of phosphanions by such a mechanism is accelerated by light but that a slower reaction could be discerned in the dark; this presumably reflected the presence of adventitious amounts of radical sources. After the identification of the SRNl mechanism a systematic study of the requirements and limitations of the mechanism has been begun. Thus Galli and Bunnett6' have compared the rates of phenylation of diethylphosphite anion [(Et0)2PO-] and pinacolone enolate [Me,CC(O)CH;] by six different mono-substituted benzenes PhX where X = F C1 Br I SPh or NMei in liquid ammonia at the boiling point.The ratio of relative rates of attack upon the two anionic nucleophiles was 1.36f 0.08; this indicated that the important reactant could be Ph- (or a common reagent made from each PhX) but not the anion radical PhX;. This study followed earlier work with S~amehorn~~.~~ in which the apparent selectivity between nucleophiles or the apparent differences in reactivity of iodobenzene and bromobenzene is not found in competition reactions and such selectivity would therefore seem to arise from different standing concentrations of radicals under the different reaction conditions. In addition to these studies of the mechanism of the reaction a number of report^^^-^' have dealt with the synthetic applications of the reactions.Perhaps one of the most compelling pieces of evidence in favour of the SRNl mechanism in the form suggested by Bunnett is the electrochemical induction of the same processes in which the electrodes act as sources or sinks of electrons. The application of cyclic v~ltammetry~~ to such reactions suggests that the loss of halogen from 2-halogeno- quinolines (as the radical anion) increases in the order C1< Br < I and provides rate constants for these carbon-halogen bond fissions [10-4k/s 1.7 (Cl) 13 (Br) 300 (I) in liquid ammonia at -40 "C] consistent with such processes. Rate constants of the order of 10' 1 mol-' s-' were deduced for the reactions of resulting phenyl radical with various nucleophiles and values of between 6 and 45 x lo61 mol-' s-' for the exchange reaction which serves to re-initiate the chain process.Another contribution to the systematic study of these reactions came from Moon and W01fe,~* who took the reaction of potassium acetone enolate with 2-chloro- quinoline as the standard reaction and attempted to determine the effects of various solvents upon the course and rate of the reaction. Perhaps predictably in view of the complex interactions between free-radical and heterolytic processes the experi- mentally observed effect was not simply linked to the expected solvent properties derived from studies of wholly heterolytic or wholly homolytic reactions. Thus " A. B. Pierini and R.A. Rossi J. Org. Chem. 1979,444667. " J. E. Swartz and J. F. Bunnett J. Org. Chem. 1979 44,4673. '' C. Galli and J. F. Bunnett J. Amer. Chem. Soc. 1979 101 6137. '' R. G. Scamehorn and J. F. Bunnett J. Org. Chem. 1977,42,1449,1457. '' R. G. Scamehorn and J. F. Bunnett J. Org. Chem. 1979,44,2604. " A. B. Pierini and R. A. Rossi J. Organometallic Chem. 1979 168 163. 69 R. A. Rossi R. H. de Rossi and A. B. Pierini J. Org. Chem. 1979 44 2662. 'O J. E. Swartz and J. F. Bunnett J. Org. Chem.. 1979 44 340. " C. Amatore J. Chaussard,J. Pinson J. M. Saveant and A. Thiebault J. Amer. Chem. Soc. 1979,101 602. 72 M. P. Moon and J. F. Wolfe J. Org. Chem. 1979,44,4081. 198 R. Bolton dimethylformamide or tetrahydrofuran sustained the photochemical process while 1,2-dimethoxyethane diethyl ether benzene and dimethyl sulphoxide were less satisfactory although all solvents showed a 'dark' (thermal) reaction concurrent with any light-catalysed process.In tetrahydrofuran under photochemical conditions potassioacetone displaced bromine less rapidly than chlorine from the appropriate 2-halogeno-quinoline and had very little effect upon iodobenzene whereas lithioacetone or potassioacetophenone had no appreciable effect upon 2-chloro- quinoline. Evidently the gegenion is important in these processes and also there is a subtle interplay between reactivity and the charge distribution in the carbanion. Diazonium-ion Processes.-Important contributions have been made both to the mechanisms of formation of aryldiazonium ions and to their modes of decompo-sition.D. L. H. Williams and his co-worker~~~ have reported the halide-ion- catalysed reaction between para-substituted anilines and nitrous acid in mineral acid media; the reaction seems to involve nitrosyl halides as the true electrophiles and is also characterized by reversibility of the nitrosation step [equation (3)] as well as by PhNH2 + NOX -P Ph&H2N0 X- (31 the incursion of encounter control in the attack of the more activated amines. Challis following the nitrosation reactions has observed the reaction of nitrosyl chloride with a number of primary aromatic amines and secondary alkylamines in alkaline (0.1M-NaOH) or substantially neutral (phosphate buffer; pH 6.85) solution. While both primary and secondary amine attack could generally be described by the kinetic form of equation (4) d[ArNl]/dt (or d[R2NNO]/dt) = k[Amine][NOCl] (4) Amines which were more basic than N-methyl-4-nitroaniline showed a rate of nitrosation substantially proportionate to the rate of the competing hydrolysis with water and independent of their basicity.This was interpreted as evidence of an encounter-controlled process in which the relative rates of attack upon NOCl by the two possible nucleophiles was determined by concentration considerations Challis and Shuker have also identified an interesting and specific effect by poly- hydroxylic species such as glycols which through the corresponding nitrite mono- esters can bring about nitrosation of amines in alkaline media; this applied to sugars may have a significant bearing upon mechanisms of carcinogenesis in V~VO.'~ Among studies of the reactions of aryldiazonium cations with nucleophiles a report of the incorporation of radioactive iodine and of 211At has that some considerable selection must occur before the displacement of nitrogen and the formation of the carbon-halogen bond to account for the degree of incorporation of astatine at very low concentrations (ca.mol I-' 10-35'/0 incorporation). Scheme 8 shows the suggested sequence. ArN2' + X-$ [ArN2',X-] $ [ArN2.X.] -P ArX + N2 Scheme 8 73 M. R. Crampton J. T. Thompson and D. L. H. Williams J.C.S. Perkin ZI 1979 18. '* B. C. Challis and D. E. G. Shuker J.C.S. Perkin IZ 1979 1020. 75 B. C. Challis and D. E.G. Shuker J.C.S. Chem. Comm. 1979,315. 76 G.J. Meyer K. Roessler and G. Stoecklin J. Amer. Chem. SOC.,1979,101 3121. Aromatic Compounds 199 A considerable contribution appears in a paper by Maurer Szele and Z~llinger~~" in which the contributions of kinetic studies to the assessment of various mechanisms are discussed. An unusually clear-sighted analysis of the consistency of kinetic forms with the various mechanistic ideas was applied to the dediazoniation process; the argument deserves perusal even by physical organic chemists who are not directly concerned with such reactions. Scheme 9 shows the process consistent with experi- mental fact including the incorporation of nitrogen into the diazonium ion through the reverse reaction (Ar' + N2 ArN2+).kl k2 ArN2+ [Ar+.N2] Ar+ + N2 k-1 k-2 k 1ROH k 1ROH ArOR ArOR + H+ + N2 + Hi Scheme 9 A second communication77b dealt with a kinetic isotope effect which unexpectedly increases with temperature. The diazo-coupling reactions of NN-dimethylaniline and m-toluidine apparently show this behaviour as a result of two reactions of the same kinetic order which both involve molecular complexing between the diazonium ion and the nitrogen atom of the amine; partitioning between the two processes explains this temperature dependence. 3 Preparative Aspects Benzene Derivatives.-The use of arene complexes in organic synthesis has been reviewed.78 Oxidation in various guises has become popular in studies of synthetic methods. The most fundamental use of dehydrogenation reactions is in the formation of aromatic systems from cyclohexyl compounds and the use of thionyl chloride and zinc chloride as such an aromatization mixture has been reported although the abstract gives little idea of the generality or limitations of this reagent mixt~re.'~ Benzyltriethylammonium permanganate has been advocated as an effective oxidiz- ing agent for the conversion of ethers into esters by oxidation at the a-carbon atom.*' Dibenzyl ether provides benzyl benzoate in 80% yield and the order of ease of attack of radicals attached to oxygen was shown to fall in the sequence PhCH2> Ph-Alkyl >RCHz>RR'CH >Me >Ph.A radical mechanism would be consistent with these observations. 77 (a) W. Maurer I.Szele and H. Zollinger Helu. Chim. Acta 1979 62 1079; (b)J. R. Penton and H. Zollinger J.C.S. Chem. Comm. 1979 819. 78 G. Jaouen Org. Chem. (New York),1978,33(Transition Met. Organomet. Org Synth. Part2) 65 (Chem. Abs. 1979 91 73 717c). " J. Knabe W. Schmitt and W. Simon,Arch. Pharm. (Weinheim) 1979,312,445 (Chem.Ah.,1979,91 107 723u). See also M. Albeck and T. Tamary J. Organometuflic Chem. '1978 164 C23 for the corresponding use of tellurium(1v) halides. H. J. Schmidt and H. J. Schaefer Angew. Chem; 1979,91,78. 200 R. Bolton Metal-catalysed processes also were reported; thus palladium(I1) trifluoroacetate oxidizes PhX to a mixture of biaryl and teraryls.81 Acetoxymethylation has also been brought about by using a mixture of lithium bromide tellurium(1v) oxide and acetic acid at temperatures near the boiling point of the mixture.The simpler and less reactive aromatic hydrocarbons such as benzene toluene and 0-and p-xylene were attacked only at the ring under these conditions. At higher temperatures however coupling occurred to give the appropriate diarylmethane (ArCH2Ar) and the more reactive substrates gave more complex products. Mesitylene (1,3,5- trimethylbenzene) for example gave (16),suggesting that the original products are themselves unstable in the reaction conditions and tend to alkylate the unreacted starting material. Acetoxycarbene was invoked as an intermediate in the original acetoxylation but the process would benefit from extensions both of mechanistic study and of the preparative uses.g2o A somewhat similar process involves the use of trifluoroacetic acid (ca.9%) and potassium peroxydisulphate in acetic acid solution Methylbenzene derivatives are acyloxylated by this mixture both the ring and the side-chain being vulnerable; copper(I1) acetate represses nuclear attack.82 Oxidative methods are also involved in the coupling of arenes by a mixture of copper(I1) chloride and aluminium chloride; in this way 1-(2',4',6'-tri-methylpheny1)naphthalene was prepared from mesitylene and naphthalene.The reaction was held to involve radical-cation intermediatesg3 The oxidation of sterically hindered phenols by periodic acid (HIO,) also was and periodic acid was the oxidizing agent in a selective conversion of unsaturated alcohols into ketones.2,3-Dichloro-5,6-dicyanobenzoquinoneand periodic acid were treated with the allylic alcohol in a mixture of benzene and aqueous hydrochloric acid (0.lM) when a number of compounds of the general formula PhCH=CHCH(R)OH were oxidized to the corresponding ketone in 80-90% yields.85 Reduction of carbonyl groups to methylene systems was also achieved under unusually mild conditions for 0-acyl-phenols where the ethyl carbonate derivative gave high yields of the corresponding 0-alkyl-phenol on treatment with sodium borohydride (3 molecular equivalents).86 Photochemical reduction apart from the photo-stimulated SRNlprocesses already reported has been applied to the tri- chloroben~enes.~~ Irradiation of solutions of each trichlorobenzene in methanol or in acetone provides all the dichlorobenzenes and monochlorobenzene suggesting 81 M.N. Vargaftik and I. I. Moiseev Izvest. Akad. Nauk SSSR,Ser. Khim. 1979,242. 82 (a) J. Bergman and L. Engman Tetrahedron Letters 1978 3279; (b) L. Jonsson and L. G. Wistrand J.C.S.Perkin I 1979,669. a3 L.-S. Wen and P. Kovacic Tetrahedron 1978 34 2723. 84 H. D. Becker and K. Gustafsson,J. Org. Chem. 1979,44,428. 85 S. Cacchi F. La Torre and G. Paolucci Synthesis 1978 848. 86 N. Minami and S. Kijima Chem. and Pharm. Bull. (Japan) 1979 27 1490 (Chem. Abs. 1979 91 174 937e). 87 G. G. Choudry A. A. M. Roof and 0.Hutzinger Tetrahedron Letters 1979,2059. Aromatic Compounds 201 some scrambling process and also tetra- and penta-chlorobiphenyls.The mechanism of formation of these coupling products deserves further study of the process whereby two aryl fragments apparently unite rather than abstract hydrogen from the protic solvent. Light-induced decomposition of the intermediates in the well-known and valuable synthesis of biaryls from the decomposition of aromatic amines by nitrite esters in aromatic is reported to cause a more selective attack of the aryl radical upon the aromatic substrate without appreciable loss of yield (17-60°/~).89 Demethylation has been brought about most selectively in two special cases. Trimethyliodosilane gives ca. 70%yields of the demethylation product in its reaction with (17) or (18);90also 2,3,4,6-tetramethoxybenzaldehydeloses specifically the methyl group attached to oxygen at C-2 on treatment with aluminium chloride in benzene.91 Amongst other preparative reactions involving diazonium intermediates the decompositions of triazenes derived from the coupling of a diazotized aniline with piperidine were successfully used to provide aryl fluorides containing 18F.Caesium fluoride was the source of the labelled halogen and the decomposition was carried out in tetrahydrofuran containing methanesulphonic acid when up to 50% of the radioisotope was incorporated in the derived aryl fl~oride.~' The synthesis of aryl fluorides by the decomposition of p-methyl-or p- t-butylbenzenediazonium borofluoride in solvents was studied in some detail. The main products were the expected aryl fluoride and the solvolysis product (e.g.phenol from water); these were obtained in relative amounts which reflected the ratio KD/a, where KDwas the dissociation constant and a was the degree of dissociation of the ion pairs.93 The use of titanium(m)-phenol complexes to promote phenylation by decompo- sing aryldiazonium ions at the ortho- positions has also been advanced.94 The synthesis of aryl fluorides by ion-exchange processes using dipolar aprotic solvents and activated nitro-chloro-benzenes (e.g. 0-chloronitrobenzene) was extended by a number of German patents in which the use of caesium fluoride was claimed to assist the action of potassium fluoride as a source of fluoride ion in these nucleophilic displacements to the extent that meta- nitro- or -cyano-chlorobenzenes were sufficiently rapidly attacked to make the process commercially viable.Coupled with this was the observation that 18-crown-6 ether aided the displacement to such Huang Shu Acta Chim. Sinica 1959,25,171; J. I. G. Cadogan J. Chem. SOC. 1962,4257. 89 M. Julliard C. Siv G. Vernin and J. Metzger Helv. Chim. Acta 1978 61 2941. 90 J. Minamikawa and A. Brossi Tetrahedron Letters 1978 3085. 91 E. G. Paul and P. S.-C. Wang J. Org. Chem. 1979,44,2307. 92 T. J. Tewson and M. J. Welch J.C.S. Chem. Comm. 1979,1149. 93 H. G. 0.Becker and G. Israel J. Prakt. Chem. 1979,321,579 (Chem. Ah. 1979,91,192 627h). 94 T. Caronna F. Ferrario and S. Semi Tetrahedron Letters 1979 657. 202 R. Bolton an extent that dimethylformamide was a satisfactory solvent although in the absence of such catalysts the lower boiling point and thermal instability makes this solvent less useful than tetramethylene ~ulphone.~~-~~ A number of specific processes now follow.The earlier use of the t-butyl group as a blocking group in the synthesis of ortho-substituted benzene derivatives (e.g. the preparation of 2,2',6,6'-tetramethylbenzophenone by the de-t-butylation of the corresponding 4,4'-di-t-butyl ketone itself obtained from 5-t-butyl-1,3-dimethyl- benzene)98 has been used to obtain 1,2- and 1,2,3-polysubstituted benzenes." The corresponding use of derivatives of p-t-butyliodobenzene in the Ullmann synthesis of biaryls followed by the de-t-butylation of the resulting materials also offers a straightforward route to ortho-substituted biphenyls."' Doubtless other processes may be employed to obtain biaryls or similar species containing a removable t-butyl group and this synthetic route has much value where the appropriate starting materials are only available as the result of substitution reactions blocked by a t-butyl group and directed to an unusual orientation.Another synthesis of biaryl systems involves the ready attack upon m-dinitroben- zene by aryl iodides under the influence of copper t-butoxide."' This variant of the Ullmann syntheses offers very ready access to a variety of derivatives of 2,6-dinitrobiphenyl in adequate to excellent yield (10-9670) [equation (5)]. + CuOBu' + ArI -+ NO* NO2 Polychlorobiphenyls have also been prepared by the reaction of o-chloranil and alkynes or benzynes102 in a method reminiscent of the similar reactions in polyfluoroaromatic chemistry.Stilbenes may also be obtained by a coupling process involving an olefinic system with extended conjugation either to a carbonyl group or to a benzene ring an aryl iodide palladium(I1) acetate and triethylamine. Styrene acrylic acid or methyl acrylate each provide the appropriate aryl derivative [equa- tion (6)]very effectively; nitro- and bromo-substituents may be present in the aromatic ring.'03 Pd(OAc),. Et3N ArI + CH2=CHX b ArCH=CHX (6) Friedel-Crafts reactions of optically active 3-chlorobutan-l-ol the corresponding acid or its esters with aluminium chloride and benzene gave optically specific products which arose from inversion of configuration at the attacking carbon atom and therefore contributed to a knowledge of the stereochemistry of attack in this 95 H.G. Oeser K. H. Koenig and D. Mangold Ger. Offen. 2 724 366 (Chem. Abs. l979,90,71891k). 96 H. G. Oeser K. H. Koenig and D. Mangold Ger. Offen. 2 724 367 (Chem.Abs.,1979,90 103 599g). 97 H. G. Oeser K. H. Koenig and D. Mangold Ger. Offen. 2 803 259 (Chem.Abs. 1979,91 157 418u). 98 K. Maruyama R. Tanikaga and R. Goto Nippon Kagaku Zasshi 1963,84,75 (Chem.Abs. 1964,60 144b). 99 M. Tashiro and T. Yamato J.C.S. Perkin I 1979 176. loo M. Tashiro and T. Yamato J. Org. Chem. 1979,44 3037. lo' J. Cornforth and T. W. Wallace J.C.S. Chem. Comm. 1979 294. lo' J. L. Pyle R. A. Lunsford and J. S. Cantrell J. Org. Chem. 1979,44,2391. lo3 J. E. Plevyak J.E. Dickerson and R. F. Heck J. Org. Chem. 1979,44,4078. Aromatic Compounds Me + MeCH=CHCO,H Me0 \ (7) %""w 0 reaction.lo4 Derivatives of 1,2-dialkoxy-benzenes were reported to give 5,6-substi- tuted indanones [equation (7)] upon treatment with polyphosphoric acid (PPA) and crotonic acid in a reaction with evident parallels to the Friedel-Crafts acylation process,1o5 and Suzuki's interest in crowded aromatic ketones led to the synthesis of a number of such species by the further methylation ('pivaloylation') of propionoyl residues already present in the system using potassium t-butoxide to generate the carbanion methyl iodide as the alkylating agent and t-butyl alcohol-benzene mixture as solvent [equation (8)].'06 KOBut Me1 ArCOCH2Me -ArCOCMe3 Other reports of the synthesis of such ketones point to a less predictable influence of the order of addition of reagents upon the yields of tetramethyldiacyl-benzenes.Di-acylation can be achieved if any of the tetramethylbenzenes are treated with three molecular proportions of acetyl or propionoyl chloride and six molecular propor- tions of aluminium chloride -apparently without any of the migration of methyl group that has been noted earlier-but the yield of diacetodurene is 85% if a solution of the hydrocarbon in carbon disulphide is added to the other reagents but falls to 10% if a mixture of acyl chloride and hydrocarbon in carbon disulphide is added to a suspension of aluminium chloride in the same solvent. 107*cf.108 Polyfluoroaromatic chemistry is exemplified by a study of photosubstitution in which hexafluorobenzetle with benzophenone in methanol provided 2,3,4,5,6- pentafluorobenzyl alcohol and benzpinacol; pentafluoropyridine reacted analo- gously to give the 4-substituted product only suggesting some nucleophilic character to the radi~a1.l'~ Nucleophilic reactions of decafluoropyrene were also reported.'" Methoxydefluorination occurred at the 1- 3- 6- and 8-positions in agreement with the modified I concept,"' but also with resonance theory and other theoretical calculations.Polychloroaromatic chemistry was advanced by a careful and detailed synthesis of the isomeric monobromo- and -iodo-tetrachloropyridines by unam- biguous methods. 'l2 A warning on the use of aryl-cadmiums as reagents in the synthesis of aryl ketones was sounded.rneta-Substituted aryl-cadmiums gave para-substituted ketones.l13 The effect was greatest with the methoxy-substituent but was also evident with the lo4 S. Nakashima T. Kondo Y. Nakamoto and S. Suga Bull. Chem. SOC. Japan. 1979,52,2377. lo' H. G. Grant Z. Naturforsch. 1979 34b,728. lo' H. Suuki Y. Aomori T. Mishina and T. Hanafusa Bull. Chem. SOC. Japan 1978,51 3393. lo' A. G. Pinkus and N. Kalyanam Org. Prep. Proced. Int. 1978,10,255 (Chem. Abs. 1979,90,86 938e). lo* H. Galenkamp and A. C. Faber Rec. Trav. chim. 1958,77 850. lo9 M. Zupan B. Sket and B. Pahor Proc. IUPACSymp. Photochem. 7th. 1978,398 (Chem. Abs. 1979 90,121 098e). J. Burdon I. W. Parsons and H. S. Gill J.C.S. Perkin I 1979 1351.J. Burdon and I. W. Parsons J. Amer. Chem. Soc. 1977,99,7445. '12 A. G. Mack H. Suschitzky and B. J. Wakefield J.C.S. Perkin I 1979 1472. P. R. Jones and J. G. Shelnut J. Org. Chem. 1979,44,696. 204 R. Bolton thiomethoxy-substituent although small for methyl trifluoromethyl and fluorine substituents at the meta-position. 4 Polybenzenoid Systems Fhoranthene chemistry has been re~iewed,"~ and a study of selectivity relations in naphthalene biphenyl and benzothiophen has contributed considerably to this pr~blem."~ 9-Phenanthryne has been indicted as the intermediate involved in the reaction of 9-bromophenanthrene with ketone enolate anions in tetrahydrofuran under the influence of sodium amide. The reaction conditions however are strofigly reminiscent of those in SRNlprocesses and such an alternative mechanism deserves consideration.Newman has reported a new synthesis of fluoro-methylbenz[a]anthracenes,the key process of which is the treatment of a dihydro-dihydroxy-derivativewith diethylaminosulphur trifluoride (Et2NSF3)."' Correspondingly trans- 7,8-dihy- droxy-7,8,9,10-tetrahydrobenz[a]pyrene can be converted into 7-fluorobenz-[alpyrene. Unexpectedly the product of reaction of the dihydroxytetrahydro- compound (19) with Et2NSF is a product of ring-contraction the fluorine atoms occurring in a difluoromethyl substituent outside the ring; aromatization of this product with dichlorodicyanobenzoquinone reverses the ring-contraction to produce the six-membered (aromatic) ring (Scheme lo)."* \/ oH (19) CHF F Scheme 10 The present attention which carcinogenic hydrocarbons have commanded has made the synthesis of substituted polyannular hydrocarbons most important.The ob~ervation"~ that all the isomeric hydroxybenz[ alanthracenes may be prepared by hydrogenation of the aromatic system regioselectively shows the value of providing structures in which the various sites of attack are activated by the hydro-aromatic fragment of the partially reduced benzanthracene system. Among work on chemical carcinogens the present emphasis is upon the bay region of such hydrocarbons. Epoxides such as (20) are held to undergo nucleophilic attack forming a bond between C-1 and an exocyclic amino-group of a guanine fragment in the DNA structure.Thus 15,16-dihydro-1 l-methylcyclopenta- [a]phenanthren-17-one (21; R =Me) is carcinogenic whereas the 11-ethyl N. Campbell and N. H. Wilson Commun.-R. SOC. Edinburgh Phys. Sci. 1979 15 193 (Chem.Abs. 1979,91,157 4798). A. A. Hamffray and R. L. Bruce J. Org. Chem. 1979,44724. M.-L. Viriot J. Chem. Res.. 1979 (S) 324; (M)3686. M. S. Newman and J. M. Khanna J. Org. Chem. 1979,44866. M. S. Newman V. S. Khanna and K. Kanakarajan,J. Amer. Chem. SOC. 1979,101,6788. '19 P. P. Fu C. Cortez K. B. Sukumaran and R. G. Harvey J. Org. Chem. 1979,44,4265. Aromatic Compounds analogue (21 ; R = Et) is less effective and the corresponding butyl derivative is inert. However the bridged analogue 15,16-dihydro-l,l l-methanocyclo- penta[a]phenanthren-17-one (22) was prepared by conventional methods from 1,10-methano-1,2,3,4-tetrahydrophenanthren-4-oneuia a Stobbe condensation with diethyl succinate and found to be carcinogenic.120 While such emphasis on the bay region is justified empirically and molecular studies of the dihydro-diols and diol epoxides derived from the carcinogenic hydrocarbons show that a covalent bond if formed between a macromolecule and the appropriate carbon atoms of the poly- annular hydrocarbon must be axial to minimize steric effects,121 there is no cor- relation between either SN1or SN2 reactivity of the epoxides of carcinogenic and non-carcinogenic hydrocarbons and their mutagenic properties.122 Perhaps this problem comes from the real difficulties of providing a nucleophile comparable in both chemical reactivity and steric properties to the macromolecule with which it is compared.A polyannular system has also been used to demonstrate the mechanism of reaction of trifluoromethyl hypofluorite (CF,OF). 4-Acetoxypyrene (23) readily gave 4-acetoxy-5 -fluoro-4-trifluoromethoxy-4,5-dihydropyrene(24) at -78 "Cin dichloromethane; the adduct was unstable at room temperatures and over a few days it provided 4-acetoxy-5 -fluoropyrene. 2-Acetamidopyrene (25) did not despite the large activating effect of the ortho-acetamido-group undergo an elec- trophilic attack upon the 1-position. It was therefore deduced that unlike difluorination attack by trifluoromethyl hypofluorite is not an electrophilic process.123 The synthesis and properties of kekulene (26) were reported in the previous Annual Report [Vol.75 p. 2361; however studies of the system now suggest Scheme 11 120 T. S. Bhatt M. C. Coombs A.-M. Kissonerghis A. F. D. Clayton and M. McPartlin J.C.S. Chem. Comm. 1979,433. 12' D. E. Zacharias J. P. Glusker P. P. Fu and R. G. Harvey J. Amer. Chem. Soc. 1979,101,4043. 122 T. Okamoto K. Shudo N. Miyata Y. Kitahara and S. Nagata Chem. andPham. Bull. (Japan),1978 26,2014. lZ3 T.B.Patrick G. L. Cantrell and C.-Y. Chang J. Amer. Chem. Soc. 1979,101 7434. 206 R. Bolton similarities to phenanthrene. Only every other ring is aromatic according to the bond lengths deduced from crystallographic studies so that kekulene should not be regarded as a dodecabenzo-annulene system but more as a type of extended stilbene system.124 5 Non-benzenoid Systems and Cyclophanes Cyc1ophanes.-A number of new and important cyclophanes have been reported many of them synthesized by classical routes that usually involve extrusion of groups (photo-extrusion of sulphur dioxide is a frequent method of linking the two aliphatic chains to make the cyclophane or classical methods of ring-closure common to alicyclic chemistry.[2.2](2,7)Naphthalenoparacyclophane has been reported,126 and the interesting quinhydrone derivative of [2.2.2.2]( 1,2,4,5)cyclo- phane (27) is the subject of a second paper.12’ The first preparation of [2.2.2.2]- (1,2,3,4)cyclophane (28) involves building up the third and fourth ring linkages by a Friedel-Crafts reaction of monochlorodimethyl ether (ClCH20Me) upon a paracyclophane structure the cyclization finally being achieved through a dibromide structure in the same way that 9,lO-dihydrophenanthrenewas much earlier obtained from 2,2’-bis(bromomethyl)biphenyl.’28 [S.l]Metacyclophane also has been pre- pared,’29 and the synthesis of some derivatives of biphenyl linked by a poly- methylene chain has produced a new type of strained non-planar biaryl structure.(27) (28) C. Krieger F. Diederich D. Schweitzer and H. A. Staab Angew. Chem. Internat. Edn. 1979,18,699. e.g.,G.D. Ewing and V.Boekelheide J.C.S. Chem. Comm. 1979,207;R. S. Givens R. J. Olsen and P. L. Wylie J. Org. Chem. 1979,44 1608. 126 J. R. Davy M. N. Iskander and J. A. Reiss Tetrahedron Letters 1978 4085.12’ H.A. Staab and V. M. Schwendemann Annalen 1979 1258. ’’* J. Kleinschroth and H. Hopf Angew. Chem. Internat. Edn. 1979,18 329. 129 N. Finch and C. W. Gemenden J. Org. Chem. 1979,442804. Aromatic Compounds 207 The essential step is the ring-closure of derivatives of biphenyl with chains attached to the 2-and #-position by the Prelog-Stoll acyloin conden~ation.~~’ The synthesis of [1.1.l.l]metacyclophane-7,14,21,28-tetraolderivatives (29) properly falls together with the new interest in even larger polyphenol The trivial name ‘calixarene’ has been advanced”* for such systems which are exemplified by (30); this is formally a derivative of [1.1,1.l.1.l.l.l]metacyclophane-7,14,21,28,35,42,49,56-octaol and it undergoes attack by chloro-2,4-dinitroben- zene or by camphorsulphonyl chloride to give products in which up to six of the eight hydroxyl groups have been substituted.The photochemistry of cyclophanes also presents some interesting aspects; [6 +61 reversions have been observed in the photolysis of paracyclophanes and the derived [2.2.23( 1,2,4) -and [2.2.2.2]( 1,2,3,5)-cyclophanes (Scheme 12). 33 gl Scheme 12 Annu1enes.-Two reviews of annulene chemistry have appeared. 134~135 Interesting annuleno-annulenes have recently been prepared; examples are trisdehydro-[18.10.2][14]annulen0[22]annulene’~~derivatives which appear to show indepen- dent ring currents and a number of structures described in a paper which reviews the main synthetic methods available to produce these Considerable argument has been directed towards the relative stabilities of benzocyclobutene systerns and radialene (1,2,3,4,5,6-hexamethylenecyclo hexane) M.Nakazaki K. Yamamoto S. Isoe and M. Kobayashi J. Org. Chem. 1979,442160. 131 H. Kaemmerer G. Happel V. Boehmer and D. Rathay Monatsh. 1978,109,767. R. Muthukrishnan and C. D. Gutsche J. Org. Chem. 1979,44,3962. G. Kaupp E. Teufel and H. Hopf Angew. Chem. Internat. Edn. 1979,18,215. 134 P. J. Garratt in ‘Comprehensive Organic Chemistry’ ed. J. F. Stoddart Pergamon Oxford 1979 vol. 1 p. 361. 135 M. Iyoda Kagaku No Ryoiki 1978,32,907 (Chem. Abs. 1979,91,56484g). 136 S. Akiyama and M. Nakagawa Tetrahedron Letters 1978 1483. M. Nakagawa Angew. Chem. Internat. Edn. 1979 18,202. 208 R.Bolton structures without a definite result.Thus maleic anhydride was successfully used to identify the equilibrium between benzocyclobutene (31) and 1,2-bis(methylene)- cyclohexa-3,s-diene (32) .I3* Despite the earlier tricyclobutabenzene (3 3) is reported to be stable with respect to decomposition to 1-adia1ene.I~' Naphtharadialene [1,2,3,4,5,6,7,8-octakis(methy1ene)-Ag-octalin]has been described as an intermediate in the production of (34). This structure is obtained in ca. 15% yield by the pyrolysis of either 1,4,5,8-tetrakis(chloromethyl)-2,3,6,7-tetramethylnaphthalene or 1,4,5,8-tetramethyl-2,3,6,7-tetrakis(chloromethyl)-naphthalene. 14' XCH2 CHZX X=H,Y=Cl X = C1 Y = H Scheme 13 5,5'-Bisazulenyl has been prepared by a Ziegler-Hafner reaction of the pentamethinium salt (35),142 and bearing in mind the poor yields associated with many azulene syntheses the synthesis of [2.2.2.2]( 1,3)azulenophane represents a considerable triumph.Zinc dust in dimethylformamide provides 1,2-bis-( 1-azu-lenyl)ethane which undergoes attack under Mannich reaction conditions at C-3 of the azulene residues to give the precursor to the azulenophane obtained in 0.1% yield by high-dilution cyclization methods (Scheme 14).143 Me,N (35) 13' W. R. Roth M. Biermann H. Darm R. Jochem C. Mosselman and H. Hermann Chem. Ber. 1978 111,3892. 139 L.G.Harruf M. Brown and V. Boekelheide J. Amer. Chem. SOC.,1978 100 2893; P.Schiess and M.Heitzmann Helv. Chim. Acta. 1978,61 844. 14* W. Nutakul R. P. Thummel and A.D. Taggart J. Amer Chem. Soc. 1979 101 770. 14' H. Hart M. Jeffares A. Teuerstein and D. L. Ward J. Amer. Chem. Soc. 1978,100,8012. '42 M.Hanke and Ch. Jutz Angew. Chem. Internat. Edn. 1979,18,214. 143 M. Fujimura T. Nakazawa and I. Murata Tetrahedron Letters 1979,825. Aromatic Compounds 209 CH .. ... CH, I I *[2.2.2.2](1 .,3)azulenophane CH,yMe Reagents i Zn DMF; ii HCHO (Me2N),CH2; iii Me1 Scheme 14 Probably the most spectacular of the structures prepared this year is (36),which is evidently the ne plus ultra of cyclopropenium ionic structures. The synthetic methods employed'44 are displayed in Scheme 15. R2NhNR2 CI Reagents i Me,SiOSO,CF,; ii KF THF; iii K: HC104 (36) CI Scheme 15 6 Free-radical Aromatic Chemistry Much of the present interest is directed towards ipso-attack.The phenomenon was well known in homolytic chemistry before its observation in electrophilic aromatic substitution but a revival of interest is demonstrated by the that the benzyl radical displaces chlorine from 0-dichlorobenzene and a more detailed investigation of alkyldenitration or alkyldeacetylation caused by the attack upon C-2 by adaman- tyl radicals of the heterocyclic species (37).146 Tiecco extended this interest in ipso-attack of heterocyclic systems to an elegant demonstration of the various (37)X = COCH3or NO2 (38) 144 R. Weiss M. Hertel and H. Wolf Angew. Chem. Zntemat. Edn. 1979,18,473. 14' R. Henriquez W. M. MacKenzie N. McPhail and D. C. Nonhebel Colloq. Znt. C.N.R.S. 1977 (publ.1978).No. 278 (RadicauxLibres Org.)p. 313 (Chem.Abs. 1979,91 192 439y). M. Tiecco in ref. 145,p. 423 (Chem.Abs.. 1979,91 192 44211). 210 R. Bolton consequences of this form of reaction. 5-Nitro-2-acyl-furans undergo attack by l-adamantyl radicals at both C-2 and C-5. Attack at C-5 causes loss of the nitro-group and the formation of 5-( l'-adamanty1)-2-acyl-furans; attack at C-2 does not cause the displacement of the acyl group but instead gives dihydrofuran derivatives (38) and (39).147 The deductions of the effects of chlorine substituents made from an earlier and incomplete study of the polychlorophenylation of simple aromatic were confirmed in a more detailed Other discussions on the meaning of polarity applied to the phenyl radi~al,'~' and experimental measurements of the reactivity of the~e,'~~*'~* have substantiated earlier beliefs.14' P. Cogolli L. Testaferri M. Tiecco and M. Tingoli J.C.S. Chem. Comm. 1979 800. 14' R. Bolton E. P. Mitchell and G. H. Williams J. Chem. Res. 1977 (S) 223; (M) 2618. 149 G. Vernin L. Bouscasse J. Metzger and C. Piirkinyi I. Chem. Res. 1979 (S) 26; (M)0228. lS0 A. A. Zavitsas G. Hanna A. Arafat J. Ogunwole and L. R. Zavitsas Colloq. Inr. C.N.R.S. 1977 (publ. 1978) No. 278 (RadicauxLibres Org.) p. 479 (Chem. Abs. 1979 91 174 49811). J. P. Lorand R. G. Kryger and N. R. Herron in ref. 150 p. 463 (Chem.Abs. 1979,91 174497m). T. Migita K. Takayama Y. Abe and M. Kosugi J.C.S. Perkin I 1979 1137.

ISSN:0069-3030    

DOI:10.1039/OC9797600185

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

11 Heterocyclic Compounds By A. J. BOULTON and M. J. COOK School of Chemical Sciences University of East Anglia Norwich NR4 7TJ 1 Heterocycles in Transformations of Functional Groups 1,4-Dihydropyridines have received considerable attention as reducing agents in a number of laboratories. The role of metal ions as catalysts has been discussed,’ and the specific effect of zinc ions in the reduction of pyridine-2-carbaldehyde by 1-benzyl- 1,4-dihydronicotinic acid diethylamide has been described.2 A chiral 1,4-dihydropyridine that has been worked into a crown ether system (1) delivers hydride in an asymmetric red~ction.~These reactions are not confined to unsaturated carbon sulphonium salts are also atta~ked.~ Me ,H \ H2NYo2H Me R (4) (2) R=H (3) R=alkyl Me (1) Asymmetric induction using proline derivatives has been described by two Japanese groups.In one approach the basic nitrogen forms the first attachment to the substrate and the carboxy-group delivers the substituent which forms the new asymmetric centre.’ In the other the amino-acid is converted into a range of chiral amine ligands to complex Grignard reagents and organo-lithium compounds during addition to aldehydes6 The lactim ether (2) derived from L-alanine can be lithiated and the C-alkylated product (3) then used to form amino-acids (4) in good optical yield.’ An N-(camphorsulphony1)-oxaziridine has been proposed as a chiral oxidiz- ing ageote8 R. A. Gase and U. K. Pandit J. Amer. Chem. Suc. 1979,101,7059.R. A. Hood and R. H.Prince J.C.S. Chem. Comm. 1979,163. J. G. de Vries and R. M. Kellogg J. Amer. Chem. SUC.,1979,101 2759. T. J. van Bergen D. M. Hedstrand W. H. Kruizinger and R. M. Kellogg J. Org. Chem. 1979,44,4953. ’ S. S. Jew S. Terashima and K. Koga Tetrahedron 1979,35,2337 2345. T. Mukaiyama K. Soai T. Sato H. Shimizu and K. Suzuki J. Amer. Chem. Suc. 1979,101 1455. ’U.Schiillkopf W. Hartwig and U. Groth Angew. Chem. Internat. Edn. 1979,18,863. F. A. Davis R. Jenkins S. Q. A. Rizvi and T. W. Panunto J.C.S. Chem. Cumm. 1979,600. A. J. Boulton and M. J. Cook The use of pyrylium salts for converting primary amines into other functionalities by nucleophilic displacement of a pyridine ring from the derived pyridinium salts [cf. Ann. Reports (B) 1977 74 2511 has led to a number of further preliminary communications and some full papers.Particularly noteworthy transformations not hitherto mentioned in these Reports include the preparation of a wide variety of alkyl aryl and heteroaryl iodides from the corresponding amines,' of aryl" and alkyl" thiocyanates and of alkyl fluorides,'* and the C-alkylation of nitronate anions.I3 Steric acceleration to nucleophilic displacement apparently gives the fused pyrylium salts (5) an advantage over the 2,4,6-triphenyl compounds in these amine-substitution reactions.10 A 'reductive deamination' procedure which had earlier been applied to benzylic pyridinium salts by reduction with borohydride to the 1,2-dihydropyridine (6) and thermal decomposition 14~15was found to proceed more readily and with a wider range of substrates (R = alkyl or aryl) when the 1,4-dihydropyridine (7) was heated.l6 The mechanism of the decomposition of 1,2-dihydropyridine (6) was shown by labelling experiments not to involve a retro-ene reaction (cf ref. 14) and probably to be free-radical in nature.16 Ph &Ph NH Ph NH lrk~~~~,~~~2 Me Me R 0' R' N R2 (9) Isoxazoles have long been employed as protective and directive groups usually with advantage being taken of the ready reductive cleavage of the N-0 bond to generate the reactive enamino-ketone function at an appropriate stage in the sequence. A typical example of this type was reported recently in the synthesis of the 1,2,6-thiadiazine 1,l-dioxide (9) from (8).17 Now 2-isoxazolines are found to be perhaps even more versatile being able to undergo reactions not open to the isoxazoles.'* Metalation of 2,3,4-trimethylisoxazolin-5-one(lo) and its bromina- tion with N-bromosuccinimide followed by reaction with triphenylphosphine both A.R. Katritzky N. F. Eweiss and P.-L. Nie J.C.S. Perkin Z 1979,433. lo A. R. Katritzky and S. S. Thind J.C.S. Chem. Comm. 1979 138. A. R. Katritzky U. Gruntz N. Mongelli and M. C. Rezende J.C.S. Perkin I,1979 1953. l2 A. R. Katritzky A. Chermprapai and R. C. Patel J.C.S.Chem. Comm. 1979,238. l3 A. R. Katritzky. G. De Ville and R. C. Patel J.C.S. Chem. Comm. 1979 602. l4 A. J. Boulton J. Epsztajn A. R. Katritzky and P.-L. Nie Tetrahedron Letters 1976 2689. l5 A. R. Katritzky J.Lewis and P.-L. Nie J.C.S. Perkin Z 1979 442. l6 A. R. Katritzky K. Horvath and B. Plau J.C.S. Chem. Comm. 1979 300. l7 H. A. Albrecht J. F. Blount F. M. Konzelmann and J. T. Plati J. Org. Chem. 1979,44,4191. V. Jager and W. Schwab Tetrahedron Letters 1978,3129;V. Jager H. Grund and W. Schwab Angew. Chem. Znternat. Edn. 1979,18,78. Heterocyclic Compounds activate the methyl group at the 3-position and the intermediates show potential for future construction work.lg The anion derived from 1,3-dihydrobenzo[c]thiophendioxide has been used by two research groups in the synthesis of polycyclic compounds.20-21 The principle is that thermal decomposition of the alkenylated product (1 1) generates an inter- mediate (12) which can undergo an intramolecular Diels-Alder reaction in the same way as that earlier described [Ann.Reports (B) 1974 71,3451 for similar inter- mediates from dihydrobenzocyclobutenes. HO II HO II HO I I Ph,;O I(13) I II OH 'i' I- I I+OPPh I I I- I 'PPh,(13) I- \/ ,c=c Os,OPh N A mixture of imidazole triphenylphosphine and iodine is recommended as a reagent for the reduction of vicinal diols to olefins.22 It is suggested that the intermediate (13) is formed which converts a hydroxy-group into an iodo-group as indicated; the other hydroxy-group is activated and iodide ion completes the reduction. Another heterocyclic reagent which is conveniently prepared in situ is the water-soluble benzoylating agent (14).23 2 General Synthetic Methods Reaction Types and Physicochemical Studies In this Section we discuss some aspects of heterocyclic chemistry which are not conveniently categorized by ring size as in the following Sections.l9 S.A. Tischler and L. Weiler Tetrahedron Lerters 1979,4903. K. C. Nicolaou and W. E. Barnette J.C.S. Chem. Comm. 1979 1119. ''W. Oppolzer D. A. Roberts and T. G. C. Bird Helv. Chim. Acra 1979,62,2017. '* P.J. Garegg and B. Samuelsson Synthesis 1979,469. 23 M. Yamada. Y. Watabe. T. Sakakibara and R. Sudoh J.C.S. Chem. Comm. 1979 179. A. J. Boulton and M. J. Cook Synthesis.-o-Formyl-N-alkyl-anilines (19,important intermediates for the pre- paration of many heterocyclic systems can be prepared by the action of BCI and an isocyanide on the alkyl-aniline; this is an interesting variant on the o-acyl-aniline synthesis using nitriles reported last year [Ann.Reports (B) 1978 75 2411. The intermediate benzoborazoline derivatives (16) can be i~olated.’~ + PhNHOH NaBH,CN ++4 1 CH2CH0 I CH,C=CCO,Et (18) 1 H ?OMe 1 CO,EtQ (17) (21) A number of heterocyclic syntheses were noted which use a hetero-Cope re- arrangement at some stage. The important pyrrolo[l,2-a]indole system (17) was prepared from phenylhydroxylamine and an acetylenic aldehyde (18) in a multi-step sequence in which the 1,2-oxazine (19) was rearranged to the benzazocine (20). None of the intermediates was i~olated.’~ A Diels-Alder addition and Cope rearrangement are concerned in the conversion of a dihydropyridine through an isoquinuclidine into a hexahydroisoquinoline in which the key step is the re- arrangement of the (un-isolated) intermediates (2 1)and (22).26Also relevant here are new syntheses of 3-a~yl-pyrrolidines,’~ of 3,3’-bi(pyrrolidin-2-0ne),’~and of 5,6,7,8-tetrahydroq~inoline.’~ Cyc1oaddition.-A reaction which was at first incorrectly interpreted3’ has now been straightened out and some interesting chemistry of azoalkenes (23) has emerged.24 T. Sugasawa H. Hamana T. Toyoda and M. Adachi Synthesis 1979,99. ” R. M. Coates and C. W. Hutchings,J. Org. Chem. 1979,444742. 26 P. S. Mariano D. Dunaway-Mariano and P. L. Huesmann J. Org. Chem. 1979,44 124. ” L. E. Overman and M. Kakimoto J. Amer. Chem. SOC.,1979,101 1310. ’* Y. Tamaru T. Harada and Z. Yoshida J. Amer. Chem.SOC.,1978,100 1923. 29 T. Kusumi K. Yoneda and H. Kakisawa Synthesis 1979,221. 30 S. Sommer Chem. Letters 1977 583. Heterocyclic Compounds Enamines do not undergo [4+21 but rather [3 +21 cycloaddition giving initial azomethine-imines (24). Proton transfer [to form (25)] and loss of the secondary amine produces N-amino-pyrroles (26). One group31 reports the isolation of the intermediate (24); another3* that of (25) probably both are correct as the sub- tituents chosen by the two sets of workers were quite different. The N-amino- pyrroles were found to undergo cycloadditions to form benzenes with loss of an amino-nitrene when acetylenic esters are used and reversibly to form adducts of type (27) with N-phen~lrnaleimide.~~ Cyclo-adducts of (24) were also prepared.31 On the other hand dimethyl azodicarboxylate forms the six-membered [4 +21 cyclo-adduct (28)with phenylazocyclohexene.34 R'N- R'NH R'NH (24) (25) (26) NNHR' n 0 (27) S II Sulphur trioxide and cyanogen form the 'criss-cross' cyclo-adduct (29).35An interesting cycloaddition mode is shown by ally1 and propargyl dithioesters e.g.(30) which with dimethyl acetylenedicarboxylate forms (3l).36 The reaction between dimethyl diazomalonate and an ynamine is HOMO (ynamine)-/LUMO (dipole)-~ontrolled.~~ The product (32) undergoes an interesting example of a 'conducted tour' migration of one of the methoxycarbonyl 31 S. Sommer Angew. Chem. Internat. Edn. 1979 18 695. 32 A. G. Schultz W. K. Hagmann and Ming Shen Tetrahedron Letters 1979,2965.33 A. G. Schultz and Ming Shen Tetrahedron Letters 1979,2969. 34 S. Sommer and U. Schubert Angew. Chem. Internat. Edn. 1979,18,696. " H. W. Roesky N. Amin G.Remmer A. Gieren U. Riemann and B. Dederer Angew. Chem. Internat. Edn. 1979,18,223. 36 V. Drozd and 0.A. Popova Tetrahedron Letters 1979,4491. 37 R. Huisgen H.-U. Reissig and H. Huber J. Amer. Chem. SOC., 1979,101 3647. A. J. Boulton and M. J. Cook groups guided in this instance by diphenylketen. The intermediate (33) can be i~olated.~’ The same group have published an interesting short note on the [2 +21 and [3 + 21 cyclo-adducts formed from methyl 3,3-dimethyl-3H-pyrazole-5-car-b~xylate.~’ The reactivity of 3,4-dimethoxyfuran in [4 + 21 cycloadditions (Diels- Alder reactions) has been reported extensively in two papers from Eugster’s group.4o I Me02Co \I Et2N Me (33) 1 Nitrogen Extrusion and Other Extrusions.-Interest in the elimination of nitrogen from cyclic azo-compounds has been maintained at a high level.The question of the intermediacy of benzothiirens (35) in the thermal and photochemical de-compositions of 1,2,3-benzothiadiazoles (34) has received further attention [cf. Ann. Reports (B) 1977 74 2531. The earlier work considered evidence from the structures of the thianthrene dimers here4* the decomposition is conducted in tetralin and the authors look at the orientation of the thiols produced. In all cases 6-substituted benzothiadiazoles form the unrearranged (3-substituted) thiols (36) predominantly.However appreciable migration occurred in the photochemical decomposition except when R was OMe and when R was C02Me some re- arrangement was also found in the thermal reaction. The evidence does not require the benzothiiren to occupy an energy minimum on the reaction profile. The de- composition of benzothiadiazole (34; R = H) has also been studied by variable- temperature photoelectron spectroscopy which is claimed to be a useful technique 38 H.-U. Reissig and R. Huisgen J. Amer. Chem. Soc. 1979,101,3648. 39 R. Huisgen and H.-U. Reissig J.C.S. Chem. Comm. 1979,’568. 40 P. X. Iten A. A. Hofmann and C. H. Eugster Helu. Chim. Acru 1979 62 2202; A. A. Hofmann I. Wyrsch-Walraf P. X. Iten and C. H. Eugster ibid. p. 2211. R.C. White J. Scoby and T. D. Roberts Tetrahedron Lerrers 1979 2785. Heterocyclic Compounds for the detection of transient species at elevated temperatures. However here no benzothiiren was observed only the rearrangement product i.e. the thioketen (37).42 Nitrogen is eliminated at high temperatures from the fused cinnoline (38) to give the unstable biphenylene analogue (39).43 Naphth[ 1,8-bc]azete (40) is formed quantitatively on irradiation of (41) and oxidation of (41) with m-chloroperbenzoic acid gives the sulphoxide of (40) directly.44 Stereochemical aspects of the thermal4’ and practical aspects of the photo~hemical~~ decomposition of cyclic azo-compounds have been reported and ab initio calculations on the reaction have been per- formed.47 (42) X=O (45) (43) x=s Elimination of carbon monoxide (at 600 “C) from benzofuran-2,3-dione (42) initially forms the keten (44) but under similar conditions thioisatin (43) gives benzothiet-2-one (49 according to the photoelectron spe~tra.~’ Irradiation of (46) at 77 K forms the monothio-o- quinone (47) which undergoes photo-equilibration with its cyclic isomer (48).Both products proved to be too unstable to be isolated.48 The primary products of thermal elimination of CO,from (49) i.e. the thiocarbonyl ylides cyclized to episulphides before they could be dete~ted.~’ 42 R. Schulz and A. Schweig Tetrahedron Letters 1979,59. 43 J. W. Barton and D. J. Lapham Tetrahedron Letters 1979 3571. 44 J. Nakayama T. Fukushima E. Seki and M.Hoshimo J. Amer. Chem. SOC.,1979,101,7684. 4s P. B. Dervan T. Uyehara and D. S. Santilli J. Amer. Chem. SOC.,1979,101,2069; P. B. Dervan and T. Uyehara ibid. p. 2076; D. S. Santilli and P. B. Dervan ibid. p. 3663. 46 P. S. Engel C. J. Nalepa R. A. Leckonby and W. K. Chae J. Amer. Chem. SOC.,1979,101,6435. 47 P. C. Hiberly and Y. Jean J. Amer. Chem. SOC.,1979 101 2538. 48 P. de Mayo A. C. Weedon and G. S. K. Wong J. Org. Chem. 1979,44,1977. 49 T. B. Cameron and H. W. Pinnick J. Amer. Chem. SOC.,1979,101,4755. A. J. Boulton and M. J. Cook Physicochemical Properties and Structural Studies.-The basicities of bis-annelated pyridines (50)fall regularly with decreasing ring size.” For n =4,the pK is 8.09 but the novel highly strained compound with n = 2 prepared by two groups this year,50*s1 has pKa =4.40.From data for pyridine (pK = 5.3) and compound (51) (pK =4.85) it appears that the effects of the annelated four-membered rings are additive there being a lowering of 0.45 pK units per ring However the quinoline (52) has a pKa of 3.99 which is 1.07 units lower than quinoline itself.s2 The origin of the low basicity of 2,6-di-t-butylpyridine in the aqueous phase has been taken up again by two groups. A study of the rate of protonation by H30+ supports the view that the low basicity is due to steric hindrance of solvation (rather than steric compression of the N-H bond of the conjugate This theory is also supported by a complete analysis of the thermodynamics of hydration which also demonstrates that the hydration properties of both the cation and the free base are at variance with trends in other pyridine~.’~ A systematic study of the proton affinities of some eighteen nitrogen heterocycles shows that in the gas phase the basicity increases progressively on benzoannelation (in contrast with the trend in the solution phase) but decreases with increasing number of nitrogen atoms in the ring.” The basicities of phosphorin and arsenin both in solution and in the gas phase are unexpectedly low a comparison of proton affinities and core ionization data for the two rings with those for phosphines and arsines is consistent with the theory that the low basicities arise from the compounds’ inability to accommodate appropriate changes in geometry on protonation.s6 Studies in a quite different area show that the site of protonation of the fused triazines (53) and (54) is N-6,” and the involvement of the zwitterionic tautomer (55) in isotopic exchange at C-8 of various purines has been verified.s8 n so R.P. Thummel and D. K. Kohli Tetrahedron Letters 1979 143. 51 A. Naimann and K. P. C. Vollhardt Angew. Chem. Znternat. Edn. 1979,18,411. 52 J. H. Markgraf J. H. Antin F. J. Walker and R. A. Blatchly J. Org. Chem. 1979 44 3261. 53 1979,101 2707. C. F. Bernasconi and D. J. CarrC J. Amer. Chem. SOC. 54 E. M. Arnett and B. Chawla J. Amer. Chem. Soc. 1979,101,7141. 55 M. Meot-Ner J. Amer. Chem. SOC., 1979,101,2396. 56 A. J. Ashe M. K. Bahl K. D. Bomben W.-T. Chan J. K. Gimzewski P.G. Sitton and T. D. Thomas J. Amer. Chem. SOC., 1979,101 1764. 57 J. P. Riley F. Heatley I. H. Hillier P. Murray-Rust and J. Murray-Rust J.C.S. Perkin 11 1979 1327. S8 J. R. Jones and S. E. Taylor J.C.S. Perkin ZZ 1979 1253 1587. Heterocyclic Compounds 219 Three examples of the use of nitrogen n.m.r. illustrate its potential value in heterocyclic chemistry. In the imidazole series I5N shifts provide information about the active sites in the molecule demonstrating a degree of charge transfer between the cation and the anion of (56)in CHC13.59 Chemical shifts of 14N are superior to 13C shifts for studying tautomeric equilibria of pyridine-2-thione and various 2-amino- pyridines because of the very large difference in chemical shifts between nitrogen atoms in the alternative environments.60 Coupling constants "N-'H and 15N-13C have been used as a sensitive probe for studying the tautomerism of the uracil anion; the two forms (57) and (58)are very evenly balanced.61 A new mass spectrometric technique has been devised for investigating gas-phase tautomerism.It involves comparison of the collision-induced dissociation-mass- analysed ion kinetic energy (CID-MIKE) spectra of cations formed by ethylation (thermodynamically controlled) of the mobile system with those of the protonated forms of N-and 0-ethyl models. The results confirm that 2-hydroxypyridine predominates over 2-pyridone but that 2-quinolone is favoured over 2-hydr-oxyquinoline under these conditions.62 0 OH R R (59) Ph PhW a phg;h +;uph H Ph N Ph N H H There has been some activity in the hydroxy-pyrrole (pyrrolinone) area recently.A new route to pyrrolin-2-one has been described and the 3H/5H equilibrium investigated the SH-form predominate^.^^ In the 3-series C=O forms are report- ed to prevail in some cases e.g. (59;R = Ph or CH2Ph) but both tautomers (2-H and s9 I. I. Schuster and J. D. Roberts J. Org. Chem. 1979 44 3864; I. I. Schuster C. Dyllick-Brenzinger and J. D. Roberts ibid. p. 1765. 6o L. Stefaniak Org. Magn. Resonance 1979,12 379. 61 R. L. Lipnick and J. D. Fissekis J. Org. Chem. 1979 44 1627. 62 A. Maquestiau Y. van Haverbeke R. Flammang H. Mispreuve A. R. Katritzky J. Ellison J. Frank and Z. Mesziiros J.C.S. Chem. Comm. 1979,888. 63 J.T. Baker and S. Sifniades J. Org. Chem. 1979,44 2798. A. J. Boulton and M. J. Cook OH) are seen in others e.g. (59; R=Me). Various 4-carboxy-substituted 3-hydroxy-pyrroles favour the OH A compound which had earlier been reported to be 3-hydroxy-2,4,5-triphenylpyrrole has been found to have the dimeric structure (60) and to dissociate reversibly on heating to give the pyrrolone (61) and the hydroxy-pyrrole (62) or a tautomer A theoretical study (MIND0/3) of the tautomerism of 3-hydroxypyrrole had very limited success in predicting the experimental results.66 In the field of 'hypervalent' sulphur compounds n.m.r. measurements in the nematic phase add further evidence for the C2"symmetry (or at least fail to provide evidence for anything different) of compounds of type (63).67 However reports of equilibrations involving bond-switching at sulphur have appeared in several journal^.^^-^' Perhaps the simplest example to illustrate here is that between the two amines (64) and (65) which is observed directly by n.m.r.When the sulphur is replaced by oxygen the equilibration does not An X-ray study of the system (66) appears to indicate that there is little or no bonding between the S and X Hypervalent sulphur (or hypovalent nitrogen) is evident in the persistent radicals formed by photolysis of S4N4-olefin adducts to which structures (67) have been assigned. The unsaturated analogue (68) was also prepared.72 R' Ph,N ~ y ~ R 2 L S x (66) Y=NorCH X=OorS (67) 3 (68) 1,4-Dihydro-1-methylpyridine is deprotonated by trimethylsilylmethylpotassium to yield an organometallic 8n-electron system.The species is moderately stable (at -50 "C), and is expected to exist with all the ring atoms except the nitrogen coplanar with the pentadienyl moiety serving as a ligand for the potassium as shown in (69).73 Phosphole anions isoelectronic with thiophens are predicted to possess a de- localized Ir-electron system and evidence for considerable n character in the C-P 64 T. Momose T. Tanaka and T. Yokota Heterocycles 1977,6,1827; T. Momose T. Tanaka T. Yokota N. Nagamoto and K. Yameda Chem. Pharm. Bull. 1979,27,1448. " J. P. Freeman and M. J. Haddadin Tetrahedron Letters 1979,4813. 66 A. Karpfen P. Schuster and H. Berner J. Org. Chem. 1979,44 374.67 J. P. Jacobsen J. Hansen C. T. Pedersen and T. Pedersen J.C.S. Perkin ZZ 1979 1521. 6a K. Akiba S. Arai and F. Iwasaki Tetrahedron Letters 1978,4117. 69 K. Akiba S. Arai T. Tsuchiya Y. Yamamoto and F. Iwasaki Angew. Chem. Internat. Edn. 1979,18 166. 'O K. Akiba T. Kobayashi and S. Arai J. Amer. Chem. SOC. 1979 101 5857. 71 R. J. S. Beer D. McMonagle M. S. S. Siddiqui A. Hordvik and K. Jynge Tetrahedron 1979,35,1199. '* S. Rolfe D. Griller K. U. Ingold and L. H. Sutcliffe J. Org. Chem. 1979,44 3515. 73 M.Schlosser and P. Schneider Angew. Chem. Internat. Edn. 1979,18,489. Heterocyclic Compounds 22 1 bonds has been obtained using 31Pn.m.r. The anions e.g. (70) are formed by cleavage of the P-phenyl derivatives with potassium and are sufficiently stable to be unquenched by added ethanol (contrast dialkyl-phosphines pKca.35).74 The novel bis-1,2,6-selenadiazine (7l),the sulphur analogue of which was reported last year [Ann. Reports (B),1978,75,244]shows its proton chemical shift at S 5.9;cf.4.74for the thiadiazine. The difference in the magnitudes of the induced paramagnetic ring currents is determined by the HOMO-LUMO energy gap.75 K+ N Me (70) In the area of conformational analysis the controversy alluded to last year [Ann. Reports (B) 1978 75 2661 concerning the effect of a second heteroatom on the barrier to inversion of an N-methyl group in six-membered rings is now resolved. Apparently conflicting standpoints have been reconciled with the statement that a p-heteroatom increases the 'ax-ts half-barrier' but decreases the 'eq-ts half-barrier'.76 Another controversial question has been that of the orientation of the N-H bond in piperidines.The weight of evidence is now heavily in favour of the predominance of the NH-equatorial form but some loose ends remain. The difference in chemical shifts of geminal protons a to the nitrogen was used by some as a criterion for assigning an NH-axial preference; now however the chemical shifts of the a-protons in (72)and (73),drawn here as their predominant conformers have been found not to be significantly different.77 An X-ray crystal structure confirms the axial t-butyl group on the chair ring in (72) with a small degree of torsion to relieve the train.'^ A study on bicyclic sulphonium salts has shown that the equilibrium for isomerization of cisltruns ring fusion in (74)favours the trans-fused isomer.However the ring fusion is predominantly cis in the ester (75),and also in Bu' M HH2' 2 aN%H2 H 2' + (72) (73) (74) R=H (75) R=C02Me 74 L. D. Quin and W. L. Orton J.C.S. Chem. Comm. 1979,401. 7s M. L. Kaplan R. C. Haddon F. C. Schilling J. H. Marshall and F. B. Bramwell J. Amer. Chem. Soc. 1979,101,3306. 76 A. R. Katritzky R. C. Patel and F. G. Riddell J.C.S. Chem. Comm. 1979 674. 77 F. W. Vierhapper and E. L. Eliel J. Org. Chem. 1979,44 1081. A. J. Boulton and M. J. Cook the ylide derived from the ion (74).78 Among phosphorus heterocycles twist conformers are adopted by the following (76) in both the solid state and solution (77) in the solid state but not in ~olution,~' and (78)80 and (79),81 both in solution.In 1-methyl-silacyclohexane the methyl group is mainly axial according to the 'H n.m. r . spectrum.82 pf'R' H OAr (76) R' = NMe2 R2 is =O (78) (79) (77) R1is =0,R2 = NMe2 3 Three-memberedRings A novel approach to the synthesis of l-azirines via oxazaphospholines has been described as summarized in Scheme 1. The scheme provides access to azirines not Reagents i Me,C(OMe), H'; ii PPh,; iii H,O'; iv Et,N Scheme 1 readily accessible by the vinyl azide route.83 N-Sulphenyl-aziridines can be pre- pared by oxidation of sulphenamides in the presence of olefins and the sulphenyl groups are readily removed by b~rohydride.~~ The products of two earlier reported ring syntheses have now been shown to be wrongly assigned.Thus alkyl- diazoacetates and NN'-di-isopropylcarbodi-imide,in the presence of copper triflate or rhodium(I1) acetate give (82) rather than (83)85[cf.Ann. Reports (B) 1976,73 2411 and the problems encountered in separating the supposed phosphiren (84) [cf. Ann. Reports (B) 1972 69 4251 from 1,5-diazabicyclo[4.3.0]non-5-enehydro-bromide have now been explained the product is in fact (85)!86 78 D. M. Roush E. M.Price L. K. Templeton D. H. Templeton and C. H. Heathcock J. Amer. Chem. Soc. 1979,101 2971. 79 G. S. Bajwa W. G. Bentrude N. S. Pantaleo M. G. Newton and J. H. Hargis J. Amer. Chem. SOC. 1979,101,1602. R. 0.Hutchins B. E. Maryanoff M. J. Castillo,K.D. Hargrave and A. T. McPhail J.Amer. Chem. SOC. 1979.101.1600. D. G. Gorenstein and R. Rowell J. Amer. Chem. SOC., 1979,101,4925. 82 R. Carleer and M. J. 0.Anteunis Org. Magn. Resonance 1979,12 673. 83 A Hassner and V. Alexanian J. Org. Chem. 1979 44 3861. 84 R. S. Atkinson and B. D. Judkins J.C.S. Chem. Comm. 1979,832,833. J. Drapier A. Feron R. Warin A. J. Hubert and P. TeyssiC Tetrahedron Letters 1979 559. H. Quast and M. Heuschmann J.C.S. Chem. Comm. 1979,390. Heterocyclic Compounds 223 A strong theme in the year’s organic literature has been the investigation of ring-cleavage reactions and a number of theoretical treatments have been reported. The Dewar 12-complex theory was described in detail nearly 30 years ago and now a new series of calculations supports a detailed restatement of the relationship between 12-complexes and three-membered rings containing 0,S NH PH SiH2 OH’ SH’ NH2+,etc.In particular the direction of nucleophilic ring-opening of unsymmetrically substituted compounds which it is argued is a criterion for dis- tinguishing between the 12-complex type and a classical ring species is found to be generally consistent with the MIND0 scale of 12-complex character. According to the theory significant 12-complex character can be attributed to the protonated ring The photochemical ring-opening of oxirang8 and of aziridine diaziridine and ~xaziridine,~~ and the rearrangements of the last have been the subject of ab initio calculations as also have the oxidation of imines to ~xaziridines~~ and the acid-catalysed hydrolysis of benzene An empirical investigation of the mechanism of hydrolysis of oxaziridine has provided evidence for both 0-and N-protonation of this Some new ring-cleavage reactions have been described some of possible synthetic use.The ring-opening of aryl-oxirans under certain conditions (CuS04-C5H5N phosphate buffer at pH 7) gives cis-diols. The stereochemistry of the cleavage is reproduced by nucleophiles other than water which enter at the benzylic po~ition.~’ Ylides are obtained in a novel ring-opening of 2-aryl-3,3-dicyano-oxirans,using pyridine [to give (86)] sulphides or triphenylph~sphine.’~ 1,3-Di-t-butyl- aziridinone a particularly stable a-lactam reacts very readily with m-chloro- perbenzoic acid to give the oxaziridine and CO; N-oxidation is postulated to be the first The oxaziridine (87) with phenylmagnesium bromide gives biphenyl but with phenyl-lithium phenol is produced and also the adduct (88).The analogue (89) follows the latter pathway with both organometallic reagents.98 AryCOCN OPh I 0 (i) PhM iAph% RN-LHPh + RN=CHPh (ii)H30+* RNH-CHPh2 R‘ H (88) (87) R=Bu‘ (86) (89) R=PhS02 (M = Li or MgBr) 87 M. J. S. Dewar and G. P. Ford J. Amer. Chem. SOC.,1979,101 783. B. Bigot A. Sevin and A. Devaquet J. Amer. Chem. SOC.,1979,101 1095 1101. 89 J. Sauer Tetrahedron 1979,35 2109. 90 B.Bigot D. Roux A. Sevin and A Devaquet J. Amer. Chem. Soc. 1979,101,2560. 91 E.Oliveros M. Riviere J. P. Malrieu and C. Teichteil J.Amer. Chem. SOC.,1979 101 318. 92 A. Aiman J. Koller and B. PlesniEar J. Amer. Chem. SOC.,1979 101 1107. 93 J. E.Ferrell and G. H. Loew J. Amer. Chem. SOC.,1979,101,1385. 94 A.R.Butler B. C. Challis and A. M. Lobo J.C.S. Perkin ZI 1979 1035; A. R.Butler J. G. White B. C. Challis and A. M. Lobo ibid. p. 1039. 9s M. Imuta and H. Ziffer J. Amer. Chem. SOC., 1979 101 3990. 96 A. Robert M. T. Thomas and A. Foucaud J.C.S. Chem. Comm. 1979 1048. 97 T. Hata and M. Watanabe J. Amer. Chem. SOC., 1979 101 1323. 98 F. A.Davis P. A. Mancinelli K. Balasubramanian and U. K. Nadir J. Amer. Chem. SOC.,1979 101 1044. A. J. Boulton and M. J. Cook Another burst of papers from Zurich on the apparently inexhaustible chemistry of 3-dimethylamino-2,2-dimethyl-2H-[see Ann.Reports azirine has appea~ed.~~-"~ (B) 1977 74 2551. A feature of its reaction with heterocumulenes is that alter- native pathways are followed as indicated depending upon the nucleophilicity of the atoms or groups X and Y in the intermediates (9O).lo1However among thiocyanates the reaction of the phenyl compound is anomalous giving (91).993-Phenyl-2H-azirines undergo addition of CO with rhodium catalysts to give vinyl i~ocyanafes.~~~ N4cR1R2 Me,N%b (x= O,Y = CR'R~)/ Y S x (90) Thiiran-imines (92) show three different modes of addition to different doubly- or triply-bonded reactants (see Scheme 2). The reactions (a)and (c) find analogies in the chemistry of diaziridine-imines and a-lactams respectively. The successive Me Ph Ph (93) (94) Me N R 1 ArSO,N\I(Ph, Et2N CHZSO~AI Ph2 m QPhNS0,Ar S Nws CHPh Ph (95) Reagents i Et,NCECMe; ii RCHO; iii NMe Scheme 2 99 U.Schmid H. Heimgartner and H. Schmid Helv. Chim. Actu 1979,62 160. loo G. Mukherjee-Miiller S. Chaloupka H. Heimgartner H. Schmid H. Link K. Bernauer P. Schonholzer and J. J. Daly Helv. Chim. Acta 1979,62 768. lo' J. LuklE and H. Heimgartner Helv. Chim. Actu 1979,62 1236. lo2 G. Mukherjee-Miiller H. Heimgartner and H. Schmid Helv. Chim. Actu 1979 62 1429. '03 T. Sakakibara and H. Alper J.C.S. Chem. Comm. 1979,458. Heterocyclic Compounds 225 rearrangements (93) -+ (94)+(95) of the ynamine adduct are note~orthy.'~~ Di-t-butyldiaziridinone (96) does not form the expected thione with the sulphurizing agent (97); instead the five-membered heterocycle (98) is produced which report- edly exists in two stereoisomeric -NBu' 4 Four-membered Rings General.-The sodium salt of dimethyl N-(toluene-p-sulphonyl)sulphoximine a nucleophilic methylene-transfer reagent is known to react with dialkyl ketones to give oxirans.It has now been found that excess of the reagent leads to oxetans so providing a particularly convenient route to this ring system. lo6 Azetidinq-2,4-diones (malonimides) result from the photochemical ring-contraction of suc-cinimides in yields of up to 50% ,lo' and stable four-membered-ring nitrones (azetine 1-oxides) (99) have been obtained from the reaction of nitro-alkenes with ynarnines.'O* A series of reactions involving isocyanides have been reported giving imino-azetidines from N-phthalimido-aziridines bearing electron-withdrawing groups in a (3+ 1) cheletropic reaction with the valence-isomeric azomethine ylides,"' 2,4-bis(imino)thietans from arylsulphonylimino-thiirans (92),ll0 and tris(irnino)thietans (100) from arylsulphonyl isothiocyanates."' The tris-imine (100)reacts at C-2 with methanol diethylamine and ethanethiol to give open-chain products but at C-4 with hydrazoic acid finally forming the tetrazole (101)."* R'kk' 0-R2,*R' H CONR; (99) G.L'abbC J.-P. Dekerk S. Toppet J.-P. Declercq G. Germain and M. Van Meerssche Tetrahedron Letters 1979 1819. lo' G. L'abbC J. Fltmal J.-P.Declercq G. Germain and M. Van Meerssche Buff.SOC. chim. belges 1979 88,737. lo' S. C. Welch and A. S. C. Prakasa Rao J. Amer. Chem. SOC. 1979 101 6135. K. Maruyama T. Ishitoku and Y.Kubo J. Amer. Chem. SOC. 1979,101,3670. lo* A. D. de Wit M. L. M. Pennings W. P. Trompenaars D. N. Reinhoudt S.Harkema and 0.Nevestveit J.C.S. Chem. Comm. 1979,993. J. Charrier H. Person and A. Foucaud Tetrahedron Letters 1979 1381. G. L'abbC and J.-P. Dekerk Tetrahedron Letters 1979 3213. G. L'abbC L. Huybrechts J.-P. Declercq G. Germain and M. Van Meerssche J.C.S. Chem. Comm. 1979,160. 112 G. L'abbC L. Huybrechts S. Toppet J.-P. Declercq G. Germain and M. Van Meerssche Buff. SOC. chim. befges 1979 88 291. A. J. Boulton and M. J. Cook The first authentic stable bisdioxetan (102) has been reported.On thermolysis it forms benzoic anhydride q~antitatively."~ The indole dioxetan (103) has been found to be sufficiently stable to allow its spectroscopic and chemical investigation. '14 A 1,2-disilacyclobutane (104) has been prepared; it undergoes some unusual and interesting thermal and photochemical rearrangements.' l5 A further intriguing reaction is that between phenylbis(trimethylsily1)phosphine and phosgene which gives as a secondary product the tetraphosphabicyclo[2.2.O]hexane (1O5).ll6 Me Ph Me,Si SiMe 0 Me3SiwSiMe3 Ph Ph Me Ph,Si-SiPh PhtN ___) Bu"C 0 I CONHBu' = phthaloyl) (109) P-Lactams.-Routes to p-lactams attract attention because of their application to the synthesis of pharmacologically active materials. Base-catalysed cyclization of y-bromopropionamides suffers from a competing elimination reaction but condi- tions have been described which minimize the latter,"' and an alternative solution to the same problem exploits the acidity of the N-H bond of 0-acyl and 0-alkyl hydroxamic acid derivatives.In this approach cyclization (with base) gives substi- tuted N-hydroxy-compounds and an elegant extension of the method uses diethyl azodiformate and PPh to cyclize hydroxamic derivatives (106) of commercially available N-protected L-serine. This affords the cyclic compound (107)with reten- tion of chirality."' A further P-lactam-forming reaction converts the thiazoline (108) into the penicillin (log) using t-butyl i~ocyanide."~ The first direct introduction of a substituent at C-6 in cephalosporins and at C-5 in penicillins has been reported.The benzoyloxy-group enters the bridgehead position '13 W. Adam C.-C. Cheng 0.Cueto I. Erden and K. Zinner J. Amer. Chem. SOC.,1979,101,4735. '14 I. Saito S. Matsugo andT. Matsuura J. Amer. Chem. SOC.,1979 101,4757,7332. ''' M. Ishikawa T. Fuchikami M. Kumada T. Higuchi and S. Miyamoto J. Amer. Chem. Sac. 1979,101 1348. '16 R. Appel V. Barth M. Halstenberg G. Huttner and J. von Seyerl Angew. Chem. Internat. Edn. 1979. 18 872. H. H. Wasserman D. J. Hlasta A. W. Tremper and J. S. Wu Tetrahedron Letters 1979 549. P. G. Mattingly J. F. Kerwin and M. J. Miller J. Amer. Chem. SOC.,1979,101 3983. '19 A. Schutz and I. Ugi J. Chem. Res. 1979 (S) 157 (M)2064. Heterocyclic Compounds 227 in the a-configuration if one uses t-butyl perbenzoate and catalytic cuprous chloride in refluxing benzene.120 Stereoselective synthesis of 6p- alkyl-penicillanates is achieved by reduction of the known 6a-alkyl-6~-isocyano-derivative with tri-n-but- yltin hydride,12' and the stereocontrolled synthesis of 7a-methoxy-1-oxa-cephems has also been described. In this the methoxy-group is introduced at the 3a-position of the precursor (1lo) obtained from the appropriate 6-epi-peni~i1lin.l~~ There has been a spate of reports on the preparation and properties of further examples in the penem series. The derivatives (111),unsubstituted at the 6-position have dominated the scene with syntheses being described that use clavulanic and 6-aminopenicillanic a~id'~~,'~' as precursors or with structures such as (112)126 and (113)12' as intermediates.A penem sulphoxide is produced on S-oxidation of a thia-analogue of clavulanic acid.128 The acids (111)prove more stable than their 6-acylamino-substituted derivatives and in marked contrast to penicillanic and cephalosporanic acids (which are also unsubstituted on the p-lactam ring) they show antibiotic activity towards a broad spectrum of bacteria. lZ6 RCONH R'CONH 0n-3 m:"' OY (117) 'OZH (118) 'OZH An unusual Cu'-mediated addition process merits special attention. The reaction of (114) with base in the presence of CuI and PBr was claimed to give the 2-alkylthio-penem (115),12'but a report in the early 1980 literature has revised this structure in favour of the unexpected isopenem (116).Details of the preparation of authentic (115) are Other 'non-classical' p-lactam structures include 120 H. Matsumura T. Yano M. Ueyama K. Tori and W. Nagato J.C.S. Chem. Comm. 1979,485. 12' D. I. John E. J. Thomas and N. D. Tyrrell J.C.S. Chem. Comm. 1979 345. S. Uyeo I. Kikkawa Y. Hamashima H. Ona Y. Nishitani K. Okada T. Kubota K. Ishikura Y. Ide K. Nakano and W. Nagata J. Amer. Chem. Spc, 1979,101,4403. lZ3 P. C. Cherry C. E. Newall and N. S. Watson J.C.S. Chem. Comm. 1979,663. 124 C. M. D. Beels M. S. Abu-Rabie P. Murray-Rust and J. Murray-Rust J.C.S. Chem. Comm. 1979,665. 125 I. Ernest J. Gosteli and R. B. Woodward J. Amer. Chem. SOC.,1979 101 6301. 126 M. Lang K. Prasad W. Holick J. Gosteli I.Ernest and R. B. Woodward J. Amer. Chem. SOC.,1979 101,6296. H. R. Pfaendler J. Gosteli and R. B. Woodward J. Amer. Chem. SOC.,1979,101,6306. 12* P. Lombardi G. Franceschi and F. Arcamone Tetrahedron Letters 1979,3777. 129 F. DiNinno E. V. Linek and B. G. Christensen J. Amer. Chem. Soc. 1979,101 2210. 130 S. Oida A. Yoshida T. Hayashi E. Nakayama S. Sato and E. Ohki Tetrahedron Letters 1980,21,619. 228 A. J. Boulton and M. J. Cook the 2-oxocephem system (117). Unfortunately expectations that increased con- jugation to the 2-0x0-group would increase the reactivity of the p-lactam carbonyl thereby enhancing antibacterial activity were not fully realized. 131~132 Compounds based on (118) represent the first examples of p-lactams fused to a saturated six-membered ring that have potent antibacterial a~tivity.'~~ 5 Five-membered Rings Synthetic modifications of five-membered-ring heterocycles using lithiation reac- tions have been extended in scope by several groups.Lithium 3-furoate may be lithiated at the 2-position to give promising intermediate^.'^^ 2-Furyl- 135*136 1-methyl-2-pyrr0lyl-,'~~ react with a trialkylborane and 1-methyl-2-indolyl-lithi~rn'~~ to form the (heterocyc1yl)trialkylborate anions (119) (9-R-9-BBN will serve instead of R3B135.137). The ions (119) may be decomposed (by I2 or N-chlorosuccinimide) to give (120) or first be treated with an electrophilic alkylating agent (e.g. MeI or an &unsaturated ketone) then decomposed (by H202 and NaOH) to give a 2,3- dialkyl derivative e.g.(121).'37 The 1979 literature is replete with indole syntheses including the photochemical formation of the pyrrole ring using o-iodoaniline in an SRNlreaction with an en~late,'~' acid-catalysed cyclization of the pyrrole (122) to the indole (123),13' and too numerous to detail. 3-(Indol-2-yl)pyri- dinium salts with base undergo cleavage of the pyridine ring and subsequent re-cyclization of the chain at the indole 3-position giving 1-formyl-carbazoles (124).14' New syntheses of furans in particular of 3-and 2,4-di-substituted compounds have been reported starting from propargyl tetrahydropyranyl ether in a 'one-pot' sequence which involves the preparation and regiospecific alkylation of the carbanion (125).146A synthesis of 3-acyl-furans using sulphur techniques has been reported.147 13' C. U. Kim P. F. Misco and D. N. McGregor J. Medicin. Chem. 1979,22,743. 13' I. Ernest Helv. Chim. Acta 1979,62,2681. 133 J. G. Gleason T. F. Buckley K. G. Holden D. B. Bryan and P. Siler J.Amer. Chem. SOC.,1979,101 4730. 13' D. W. Knight Tetrahedron Letters 1979 469. 13' E. R. Marinelli and A. B. Levy Tetrahedron Letters 1979 2313. I. Akimoto and A. Suzuki Synthesis 1979 146. 137 A. B. Levy,Tetrahedron Letters 1979,4021. R. Beugelmans and G. Roussi J.C.S. Chem. Cumm. 1979,950. 139 M. Natsume and H. Muratake Tetrahedron Letters 1979 3477. "O I. Fleming and M. Woolias J.C.S. Perkin I 1979,829. "' M. Somei F. Yamada and C. Kaneko Chem. Letters 1979,943. 14' G. S. Ponticello and J. J.Baldwin J. Org. Chem. 1979,44,4003; U. Hengartner D. Valentine K. K. Johnson M. E. Larscheid F. Pigott F. Scheidl J. W. Scott R. C. Sun J. M. Townsend and T. H. Williams ibid. p. 3741. 14' Y. Ito K. Kobayashi N. Seko and T. Saegusa Chem. Letters 1979,1273. 14' R. Beugelmans H. Ginsburg M. Le Goff A. Lecas J. Pusset and G. Roussi Heterocycles 1979 12 811. ldS A. N. Kost T. V. Stupnikova R. S. Sagitullin B. P. Zemskii and A. K. Sheinkman Doklady Akad. NaukS.S.S.R 1979 244 103 [Pruc. Acad. Sci. (U.S.S.R.),1979 244 141. 146 M. Stahle and M. Schlosser. Angew. Chem. Internat. Edn. 1979,18 875. K. Inomata M. Sumita and H. Kotake Chem. Letters 1979,709. Heterocyclic Compounds Work in several laboratories has been directed towards the synthesis of thiophen- 3-acetic and -3-malonic acids one approach to which involves the thiophenium S-ylides [cf.Ann. Reports (B) 1978 75 2541. The dichloro-compound (126) thermally cyclizes with loss of HCl to the thienofuran (127),'48 and with copper catalysis it liberates dicarbomethoxycarbene which can be trapped.'49 A full paper'5o describes a wide range of these ylides and also the preparation of the ester (128) and its rearrangement to (129). Another approach to thiophen-3-acetic esters involves cyclization of the dihalogeno-diene (130). + Me2NYxYNMe2 Me,N N /\ Me Me (133) (131) + Me2NYxTNMe2 RCH2S CH,S RI (134) (132) (X =CH or N; R =H or Me) In an extremely compressed pair of papers Gompper and Schneider15* have described the cyclization of ylides generated by the action of strong base on cations of type (131)and (132).The reaction proceeds with elimination of a molecule of amine lo* R. J. Gillespie J. Murray-Rust P. Murray-Rust and A. E. A. Porter J.C.S. Chem. Comm. 1979,366. lo9 R. J. Gillespie and A. E. A. Porter J.C.S. Chem. Comm. 1979 50. lS0 R. J. Gillespie and A. E. A. Porter J.C.S. Perkin I 1979,2624. P. J. Clayton A. W. Guest A. W. Taylor and R. Ramage J.C.S. Chem. Comm. 1979 500. R. Gompper and C. S. Schneider Synthesis 1979,213,215. A. J. Boulton and M. J. Cook or thiol and results (in some cases) in satisfactory yields of heterocyclic products (133) and (134). An alternative mode of reaction of the compounds where Xis CH is deprotonation from this central position to form allenes.Aza-anti-aromatics such as azete and aza-pentalenes have long been known to be stabilized by dialkylamino- substitution [cf.Ann. Reports (B),1973,70,479,491]. Asimilar effect applies to the highly coloured aza-cyclopentadienium cations (135) and (136) which are made from tetrachloro-2H- imidazole and 1,1,3-trichloro- 1H-isoindole re~pectively.'~~ Techniques for controlling high-temperature reactions which avoid the con- version of the majority of the organic material into unpromising charcoals have been developed to a fine art over the past few years. Flash vacuum pyrolysis (FVP) of 4,5,6,7-tetrahydrobenzofuranat 920-950 "C forms the unstable dimethylenedi- hydrofuran (137)' which can be trapped by dienophiles and the generation of the 'furanoradialene' (138) in a similar reaction is re~0rted.l~~ Pyrolysis of isox- azolinones reported in brief last year [Ann.Reports (B) 1978,75 2581 has been found to produce formonitrile oxide (HCNO) when applied to 4-isonitroso-5- isoxazolinones.'55 Other nitrile oxides are obtained in good yields by FVP of f~roxans.'~~ A series of papers describes in detail the co-pyrolysis of heterocycles with chloroform. Pyrroles and indoles form 2-and 3-chloro-pyridine~'~~ and -quin~lines,'~* while pyrazoles and indazoles give good yields of 2-chloro-pyri- midines and -quinazolines. 15' The reports of recent years on the 'nitrogen-walk' process of photo-rearrange- ment of cyano-pyrroles have been followed up by some equally elegant studies on the cyano-thiophens and one of the episulphide intermediates (139) has been iso- lated.I6' An extension of a well-known isoxazole synthesis provides a useful route to 1,2,4-0xadiazoles (140) from acyl-amidines including the interesting and rather R.Gompper and K. Bichlmayer Angew. Chem. Internat. Edn. 1979,18,156. lS4 J. Jullien J. M. Pechine F. Perez and J. J. Piade Tetrahedron Letters (a) 1979,3079; (6)1980,21,611. lS5 C. Wentrup Angew. Chem. Internat. Edn. 1979 18,467. lS6 W. R. Mitchell and R. M. Paton Tetrahedron Letters 1979 2443. "'R. E.Busby M. Iqbal M. A. Khan J. Parrick and C. J. G. Shaw J.C.S. Perkin I 1979 1958. 15* R. E. Busby S. M. Hussain M. Iqbal M. A. Khan J. Parrick and C. J. G. Shaw J.C.S. Perkin I 1979 2782. R. E. Busby J.Parrick S. M. H. Rizvi and C. J. G. Shaw J.C.S. Perkin I 1979 2786. J. A. Barltrop A. C. Day and E. Irving J.C.S. Chem. Comm. 1979,881,966. Heterocyclic Compounds 231 unstable cases where R=H. Replacing the hydroxylamine in Scheme 3 by a hydrazine leads to 1,2,4-triazole~.~~~ More details have been published of a novel synthesis of imidazoles from N-chloro-amidines and a further study of the chemical behaviour of the imidazoline intermediates has been made.162 4-Methylene-4,s- dihydro-oxazoles (14 l) intermediates in a synthesis of oxazoles from acetylenic imino-ethers have been isolated and can be transformed by electrophilic reagents into oxazoles with a 4-(substituted methyl) group.'63 ArCONH2 A ArCON=CRNMe2 % ArCONHCR=NOH 5 Reagents i (MeO),CRNMe,; ii NH,OH,AcOH Scheme 3 Although the desire to patent it seems to be slackening novel aspects of the evergreen Beirut reaction are still uncovered.Unsubstituted quinoxaline di-N- oxide is from time to time reported as being produced by the diethylamine-catalysed reaction of benzofuroxan with a variety of unlikely compounds; now the Lebanese groups have shown that this is produced amongst other things simply from the amine and the benzof~roxan.~~~ With 1-diethylaminobutadiene the enamine (142) is forrned.l6' 0- I 0' An interesting synthesis of 2-aryl-benzotriazoles has been described. Starting from precursors such as (143) it is suggested that o-nitrophenyl-carbodi-imidesare formed. Subsequent rearrangements involving the nitro-group result in the loss of C02,with formation of the benzotriazole (144).166A nitro-group is again involved in the base-induced cyclization of N-phenacyl-o-nitro-N-tosylaniline(145).The 16' Y.-I. Lin S. A. Lang M. F. Lovell and N. A. Perkinson J. Org. Chem. 1979,44,4160. 162 L. Citerio D. Pocar R. Stradi and B. Gioia J.C.S. Perkin I 1978 309; L. Citerio D. Pocar M. L. Saccarello and R. Stradi Tetrahedron 1979 35 2375 2453. 163 L. E. Overman S. Tsuboi and S. Angle J. Org. Chem. 1979,44,2323. 164 M. Z. Nazer C. H. Issidorides and M. J. Haddadin Tetrahedron 1979.35 681. P. Devi J. S. Sandhu and G. Thyagarajan J.C.S. Chem. Comm. 1979,710. 166 P. G. Houghton D. F. Pipe and C. W. Rees J.C.S. Chem. Comm. 1979,771. A. J. Boulton and M. J.Cook benzoyl and tosyl fragments are lost and 2-ethoxy-1 -hydroxybenzimidazole is formed (Scheme 4).167 I L 0-ti,iii OH Reagents i NaOEt EtOH; ii EtO-; iii H’ Scheme 4 A number of complex azide-tetrazole equilibria have been studied. 3-Azido-5- phenyl-s- triazole (146) is favoured over the cyclized triazolotetrazole forms (147) and (148) but the (slow) equilibrium of the anion is more finely balanced in DMSO the cyclized ion (149) is preferred at low temperatures while the azide [anion of (146)] predominates at high temperatures. An interesting range of isomeric N-methylated derivatives of the ring system was prepared.’68 The preference for cyclization in the anion rather than in the neutral molecule has been supported by theoretical calculations.169 The tautomerism of 3-azido-1,2,4-benzotriazine,which has two alternative ring nitrogens for cyclization has been studied the open-chain and both cyclic forms are ob~erved.”~ The equilibrium between tetrazole and azide in the system (150) S (151) shows a linear dependence between the Hammett substituent constant for R i.e.o,and the equilibrium constant K (rather than (146) (147) 16’ J. Machin and D. M. Smith J.C.S. Perkin I 1979 1371. 16’ R. N. Butler T. McEvoy E. Alcalde R. M. Claramunt and J. Elguero J.C.S. Perkin I 1979 2886. lC9 S. Olivella and J. Vilarrasa J. Heterocyclic Chem. 1979 16 685. A. Messmer G. Hajos J. Tamas and A. Neszmelyi,J. Org. Chern. 1979 44 1823. Heterocyclic Compounds logK).171 This is a curious result and it would be interesting to see whether it is found in other systems or with a wider range ofsubstituents.The structures (152) of the reaction products from S-alkylated thioamides (153) and azide ion have been corrected the acyclic triaza-dienes (154) are formed,17* as was predicted by Variable-temperature photoelectron spectroscopy has been referred to earlier (Section 2). The claim174 to have observed 1,2,3-benzoxadiazole (155) as the major component of the gas-phase equilibrium with the diazo-phenol (156) by this method is particularly interesting and confirmation by other physicochemical techniques would be very welcome. Carbon atoms formed in the decomposition of diazotetrazole (157) insert into furan with ring-cleavage to give the acetylenic aldehyde (158).The fate of the carbon was followed by labelling experiments; both C=C addition and C-2-H insertion seem to occur.175 Ring-cleavage is a common fate of five-membered heterocyclic rings adjacent to which a carbene or nitrene centre is generated and the literature of 1979 contains a number of examples of this. Thermolysis of the oxazolyldiazomethane (159) gives an acyl-imide (160) [with an obvious structural relationship to (158)] which readily rearranges to the acyl-enamine (161). Under N2 (157) A. Konnecke R. Dorre E. Kleinpeter and E. Lippmann Tetrahedron 1979.35 1957. 172 G. L’abbC A. Willocx J.-P. Declercq G. Germain and M. Van Meerssche Bull. SOC. chim. belges 1979 88 107. A. Holm Adv. Heterocyclic Chem. 1976 20 173. 17‘ R.Schulz and A. Schweig Angew. Chem. Internat. Edn. 1979,18,692. ’’’ S. F. Dyer and P. B. Shevlin J. Amer. Chem. SOC.,1979 101 1303. A. J. Boulton and M. J. Cook more vigorous conditions fragmentation occurs to the nitrile R'CN and an acety- lenic ketone and similar products are formed from the isoxazolyldiazomethane (162). For these reactions intermediate dehydro-oxazines are The 4-azido-isoxazole (163) on heating fragments to give the two cyanides (164) and (165) and nit~0gen.l~~ Me N N7CH=CHPh 4 MeCN + N2 + NCCOCH=CHPh (164) (165) (163) Although o-azido-benzanilides do not form either arylamino-anthranils or indazolinones on thermolysis their anions (1 66) form the 2-aryl-indazolin-3 -ones (167) in fair to good ~ie1ds.l~~ With thionyl chloride they give 3-chloro-2-aryl- indaz01es.l~~These two results suggest that cyclization requires a lone pair of electrons in the molecular plane on the nitrogen atom which cyclizes to the azide.However anions of o-azidoacetophenones (168) apparently isoelectronic with the neutral amides do form the C-N bond to give the indoxyls (169).l8' Whatever the mechanisms may be the reactions are useful ones. Photochemical reactions of anthranils,'81*'82 indoxazenes,18* inda~oles,'~~ and 2,l -benzisothiazoles'84 have been reported extensively. Ring-cleavage products are generally observed often with concomitant nucleophilic substitution in the benzene Ph H \Ph (?. H (171) On decomposition in a substituted benzene 2,5-diphenyl-3-diazopyrroleforms either the cyclo-octapyrrole (170) (when R is H CN or NO2) or a 3-aryl-pyrrole 176 S.-I.Hayashi M. Nair D. J. Houser and H. Shechter Tetrahedron Letters 1979 2961. G. Kumar K. Rajagopalan S. Swaminathan and K. K. Balasubramanian Tetrahedron Letters 1979 4685. M. A. Ardakani and R. K. Smalley Tetrahedron Letters 1979,4765. 179 M. A. Ardakani R. K. Smalley and R. H. Smith,.Synthesis 1979 308. '" M. A. Ardakani and R. K. Smalley Tetrahedron Letters 1979,4769. "' E. Giovannini and B. F. S. E. de Sousa Helv. Chim. Acta 1979,62 185 198. T. Doppler H. Schmid and H.-J. Hansen Helv. Chim. Acta 1979,62,271,304,314. E. Georgarakis H. Schmid and H.-J. Hansen Helv. Chim. Actu 1979,62 234. B. Jackson H. Schmid and H.-J. Hansen Helu. Chim. Actu 1979 62 391.Heterocyclic Compounds (171) (when R is Me or OMe). An intermediate spiro-norcaradiene (172) is suggested for the formation of both Cycloaddition reactions of diazo-pyrazoles have been studied widely and recent work in this area has included the reactions of 3-diazo-pyrazoles and -indazoles and of 4-diazo-1,2,3-triazoles with various ylides186" and with isocyanates,'86b to form a wide variety of condensed heterocyclic systems usually in good yield. 1-Chlorobenzotriazole has been reported to be a shelf-stable oxidizing agent but the unfused analogue (173) decomposes very easily. The first step is probably migration of C1 to form the 4H-isomer (174) which can either lose nitrogen to form the chloro-azirene (179 or cleave to benzonitrile and phenylchlorodiazomethane; the observed products are derived from these.187 x-Y Ycp X X,Y The spiro-pyrazolinone (176) has been prepared and in solution it shows an interesting rapid temperature-dependent equilibrium with the isomer (177).188 A synthesis of 4-amino-isothiazoles (178) from a-tosyloximino-nitriles has been reported (Scheme 9 and the products were shown to be flexible synthons for a variety of ring systems containing the fused isothiazole n~c1eus.l~~ NC NC H,N X RCH,SH + ,>x -% ,px% TsO-N RCH,S-N S' Scheme 5 Nucleophilic attack at the sulphur atom of heteroaromatic rings is nothing new but novel aspects continue to be discovered.Isothiazolium and 1,2,5-thiadiazolium M. Nagarajan and H. Shechter J. Amer. Chem. SOC.,1979,101,2198.G. Ege and K. Gilbert Tetrahedron Letters 1979,(a) 1567;(b)4253. 187 T. C.Gallagher M. J. Sasse and R. C. Storr J.C.S. Chem. Comrn. 1979,419. G. Mann L.Hennig H. Wilde S. Hauptmann S. Behrendt and M. Kretschmer Tetrahedron Letters 188 1979,4645. 189 K. Gewald and P. Bellmann Annalen 1979,1534. 236 A. J. Boulton and M. J. Cook salts (179) incorporate cyanide and methylpropiolate anions with ring expansion the product (180; X = CH Z =N) slowly decomposes to the starting material^.'^^ The selenophen (18 1)is ring-cleaved by organolithium reagents. lgl X-X-_Cd,JNHMe F= s' -))-NHMe *s."->,Me cw I N &NMe 111 Me c Me HZ Z 111 (179) Z = N or C-C02Me z (180) X = CH or N MeOOOMe ___* MeOaOMe BuLi Se Li SeBu R'N S ,N Potts continues to reap the fertile field of bicyclic meso-ionic heterocycles.The imidazo[2,1 -b]thiazole and thiazolo[3,2-b][ 1,2,4]triazole systems (182) add dipolarophiles across the sulphur atoms to form adducts which can lose S or H,S to form fused pyridones (183).lg2 The preparation and properties of a number of novel monocyclic meso-ionic systems which were reported in preliminary notes in 1976 [Ann. Reports (B),1976,73,252] are published in full detail in an extensive series of papers from the Sheffield group.'93 Meso-ionic derivatives (184) of the 1,2,5- thiadiazole system have been prepared.lg4 More work on the photochemistry of meso-ionic monocycles (185) has been reported. Two important types of reaction which have been postulated are the ring-opening [to (186)] and the further cyclization [to (187)] with decomposition via an anti-aromatic intermediate (188) (Scheme 6).In the case of the meso-ionic x=c=o 1 (186) 'Y-z (a) R = Me X =CPh Y = CH Z= S (b) R=Ph X = Y =N Z=O (c) R = Ar X = CR' Y = N Z= 0 Scheme 6 J. Rokach P. Hamel Y. Girard and G. Reader TetrahedronLetters 1979 1281. 19' S. Gronowitz A. Hallberg and T. Frejd Tetrahedron 1979,35 2607. lg2 K. T. Potts and S. Kanemasa I. Org. Chem. 1979,44,3803,3808. 193 E. Cawkill R. N. Hanley G. P. Rowson I. S. Smith W. D. OlIis and C. A. Ramsden J.C.S. Perkin I 1979,724 and five succeeding papers. Ig4 K. Masuda J. Adachi and K. Nomura J.C.S. Chem. Comm. 1979 331. Heterocyclic Compounds 237 thiazoles (Ma) the heterocumulene (186a) can be trapped but it has not yet been detected spectroscopically.195 The oxatriazole (185b) on photolysis forms phenyl azide and also phenyl isocyanate. The azide was at one time thought to arise through the ‘cyclic azide’ (188b) but Danish have shown that such a symmetrical intermediate cannot be on the main pathway to the azide by irradiating the labelled compound (185b; Y=15N) the phenyl azide was found to carry the marker practically exclusively on the terminal nitrogen. The formation of the isocyanate also suggests that the phenyl group with or without its attached nitrogen moves closer to the ring carbon atom before cleavage. 196 The cyclization-fragmentation (lower route of Scheme 6) is also found in (185a) as shown by the production of carbonyl sulphide the authors apparently accept the intermediate (188a) here.’95 The thiazole (185a) reacts with singlet oxygen to form (189) presumably uiu the intermediate (190).’95 Sydnones (185c) which hitherto have been reported only to form charge-transfer complexes with tetracyanoethylene react with it under more forcing conditions with loss of C02 giving the open-chain hydrazones (191).19’ Ph \ c=o CR’=C(CN)Z / -B MeN + cos ArN / \ \ c=o N=C(CN)* (192) X = CO R = OH (193) X = CMe2 R = OH z (194) X=CMe,,R=H X = CO Y = NCHZCHzCl Z = C1 X= CMe2 Y = 0,Z = Br X = CMe2 Y = O,Z= ORF Martin Granoth and co-workers have continued their studies on spiro-phos- phoranes and three notes record the synthesis of (192),19’ the pK,+ of (193),’99 and the spectral effects of deprotonation of (194)”’ [cf.Ann. Reports (B),1978 75 2641. The same group have also turned their attention to hypervalent iodine compounds an X-ray structure determination of a benziodazole (195) has been made,201 and the I-bromobenziodoxole (196) was prepared.’” The iodoxole (197) exchanges its perfluoroalkoxy-group very rapidly with a perfluoroalkoxide anion. In these compounds the iodine has approximately trigonal-bipyramidal geometry with two equatorial electron pairs; the exchange intermediate probably has a square-planar arrangement of groups about the iodine atom.202 19’ N. H. Toubro B. Hansen N. Harrit A. Holm and K. T. Potts Tetrahedron 1979,35 229. 196 C. Bjerre C.Christophersen B. Hansen N. Harrit F. M. Nicolaisen and A. Holm Tetrahedron 1979 35,409. 19’ H. C. Berk and J. E. Franz J. Org. Chem. 1979,44 2395. 19’ Y. Segall and I. Granoth J. Amer. Chem. SOC.,1979 101 3687. 199 I. Granoth and J. C. Martin J. Amer. Chem. SOC.,1979 101,4618. ’00 I. Granoth and J. C. Martin J. Amer. Chem. SOC.,1979,101,4623. ’O’ T. M. Balthazor D. E. Godar and B. R. Stults J. Org. Chem. 1979 44 1447. ’O’ R. L. Amey and J. C. Martin J. Org. Chem. 1979 44 1779. 238 A. J. Boulton and M. J. Cook Dico-ordinate phosphorus has also attracted much attention recently. Ketonic hydrazones have been known for some years to form diazaphospholes; e.g. (198) from acetone methylhydrazone and PC13.203 Now it has been found that the isomeric system (199) is also produced in this reaction.It is not known just how this happens and the authors were not able to cause the isomers to inter~onvert.~'~ Russian workers have shown that the diazaphosphole (200) reacts with diphenyl-diazomethane at room temperature in ether to give the fused phosphiran (201) which ring-opens in methanol to form the six-membered ring (202). These results were confirmed by X-ray cry~tallography.~~~ The benzodiazaphospholes (203) prepared as indicated exist as monomer dimer and trimer in solution the propor- tion of monomer being ca. 30% in xylene at 140"C and 100% in nitrobenzene. With BF two species were observed which the authors suggest are the adducts of the monomer in which one or the other nitrogen atom is co-ordinated to the boron.206 Ph \-Me (198) R=Me (200) R=Ph A novel compound containing boron is the very curious species (204) prepared from diphenylbromoborane and di-isopropylcarbamoyl-lithium.207 Metal sandwich compounds are becoming more of a mouthful every year.2o8 Four molecules of the thiadiborolen (205) form the bread of a black centrosymmetric (by X-ray) 'tetra-decker' sandwich complex containing two atoms of cobalt and one of iron between the rings.2o9 6 Six-membered Rings A number of significant advances during the year have added to the heterocyclic chemist's already well-stocked armoury.2-Chloro-3-substituted quinolines and hence the 3-substituted quinolines (by reduction) are easily prepared from acyl- anilides under Vilsmeier formylation conditions.Quinoxalines are produced in the 203 J. Luber and A. Schmidpeter Angew. Chem. Znternat. Edn. 1976,15 111. 204 J. H. Weinmaier J. Luber A. Schmidpeter and S. Pohl Angew. Chem. Internat. Edn. 1979 18,412. *05 B. A. Arbuzov E. N. Dianova and Yu. Yu. Samitov Doklady Akad. Nauk S.S.S.R.,1979 244 1117 [Proc. Acad. Sci.(U.S.S.R.),1979 244,591. 206 C. Malavaud M. T. Boisdon Y. Charbonnel and J. Barrans Tetrahedron Letters 1979,447. '07 A. S. Fletcher W. E. Paget K. Smith K. Swaminathan J. H. Beynon R. P. Morgan M. Bozorgzadeh and M. J. Haley J.C.S. Chem. Comm. 1979 347. cf. W. Shakespeare 'As You Like It' Act 111 Scene 2 line 239. 209 W. Siebert W. Rothermel C. Bohle C. Kruger and D. J. Brauer Angew. Chem. Znternat. Edn. 1979 18.949.Heterocyclic Compounds 239 corresponding reaction using dimethylnitrosamine instead of the formamide.210 Quinoline derivatives are also accessible by photochemical cyclization of thioamides (206); the synthesis is adaptable to a range of 2-and 3-substit~ents.~~~ A general method for c-fused pyridines uses the thermal decomposition of appropriate ortho-methyl vinyl azides e.g. (207) -+(208),212 and a synthesis of pyrimidin-4-ones has been described in which diphenylcyclopropenone reacts with amid~ximes.~~~ The versatility of p-imino-enamines as heterocyclic precursors is demonstrated by their reactions with ethyl chloroformate carbon disulphide aldehydes and ketones to give pyrimidin-2-ones and p~rimidine-2-thiones~~~ and 1,2-dihydropyrimidine~,~~~ while with thionyl chloride they produce the thiadiazine oxides (209) at low temperatures; these lose SO to form the pyrazoles at high temperatures.*16 Two rhodium-catalysed reactions convert aniline into quinaldine; using ethylene under pressure,217 and with acetaldehyde in the presence of nitrobenzene.218 /C02Et -$02Et N N Me (207) A new method for the introduction of substituents at the 4-position of pyridine uses the sequence of Scheme 7.The precursor is prepared from pyridine in two steps. The N-substituent is designed to shield the 2-position and to activate the 4-position towards nucleophilic attack. The conversion is successful with a fairly wide range of Scheme 7 21D B. Narine and 0. Meth-Cohn Tetrahedron Letters 1978 2045; 0.Meth-Cohn B. Narine and B. Tarnowski ibid. 1979 31 11; 0.Meth-Cohn S. Rhouati and B. Tarnowski ibid. p. 4885. 'I' P. de Mayo L. K. Sydnes and G. Wenska J.C.S. Chem. Comm. 1979,499. "'T. L. Gilchrist C. W. Rees and J. A. R. Rodrigues J.C.S. Chem. Comm. 1979,627. 'I3 M. Takahashi and S. Watanabe Chem. Letters 1979 1213. 214 J. Barluenga M. Tomas V. Rubio and V. Gotor J.C.S. Chem. Comm. 1979 675. 'I5 J. Barluenga M. Tomas S. Fustero and V. Gotor Synthesis 1979 346. J. Barluenga J. F. L6pez-Ortiz and V. Gotor J.C.S. Chem. Comm. 1979 891. S. E. Diamond A. Szalkiewicz and F. Mares J. Amer. Chem. SOC.,1979,101,4902. 'la Y. Watanabe M. Yamamoto and S. C. Shim Chem. Letters 1979 1025. A. J. Boulton and M. J. Cook nucleophiles A more familiar route to 4-substituted pyridines is via nitra-tion of the N-oxide.The corresponding bromination has seldom proved satisfactory but in difficult cases the use of thallium(rr1) acetate and bromine may be effective.220 Deoxygenation of nitropyridine oxides with phosphorus reagents can also be temperamental and irradiation of a dilute solution of the N-oxide with trimethyl phosphite is an alternative to the thermal reaction.221 Picoline 1-oxides and N-phenylbenzimidoyl chloride with base give side-chain acyl-aminated (2 10) and acylamino-arylated (21 1)products by rearrangement of the anhydro-bases of type (212).222 In a related series photochemical rearrangement of (213) gives (214) together with the 5-substituted isomer. The corresponding 1-0ctyloxy-pyridone gives the 3-octyloxy-isomer but the 1-phenethoxy-analogue gives the 3-benzyl derivative with loss of CH20.223Rearrangement to the 3-position of pyridine has also been observed in the reaction of N-(ary1oxy)-pyridinium ions with azide (and some other) ions.The products 3-(0- hydroxypheny1)-pyridines,contrast with the 2-substituted isomers obtained by other base-catalysed rearrangement^.^^^ Pentachloropyridine 1-oxide and cyclic enamines afford the expected products (215) and in some cases the far-from-expected ring-contracted compounds (216).225 (210) R = N(Ph)COPh (211) R =C6H4N(H)COPh Ph OCH, I 219 A. R. Katritzky H. Beltrami J. G. Keay D. N. Rogers M. P. Sammes C. W. F. Leung and C. M. Lee Angew. Chem. Internat. Edn. 1979 18 792; A.R. Katritzky H. Beltrami and M. P. Sarnrnes J.C.S. Chem. Comm. 1979 137. 220 H. Saito and M. Hamana Heterocycles 1979,12,475. 221 C. Kaneko A. Yarnamoto and M. Gomi Heterocycles 1979 12,227. 222 R. A. Abramovitch D. A. Abramovitch and P. Tomasik J.C.S. Chem. Comm. 1979,956. 223 A. R. Katritzky A. V. Chapman M. J. Cook and G. H. Millet J.C.S. Chem. Comm. 1979 395. 224 R. A. Abramovitch A. L. Miller T. A. Radzikowska and P. Tornasik J. Org. Chem. 1979,44,464. 225 H. Suschitzky B. J. Wakefield and J. P. Whitten J.C.S. Chem. Comm. 1979 183. Heterocyclic Compounds 241 Novel ring transformations include two conversions of pyrimidine-diones into pyridones. i.e. (217) +(218)226 and (219) +(220).227 In the former the N-C-N unit is replaced by the C-C-N of an a-substituted amide while the latter conversion involves a dianion with rearrangement and extrusion of cyanate ion.Thermolysis of dihydro-triazines (22 1)and -pyrimidines (222) involves ring-open- ing 1,7-hydrogen transfer re-cyclization [cf.Ann. Reports (B),1978,75,267] and loss of ammonia to form pyrimidines (223; X = N) and pyridines (223; X = CH) respectively.228 With alkaline hydrogen peroxide the pyridinium betaine (224) gives (225) and (226) via a 2,3-dihydro-2,3-dihydroxypyridinium betaine intermediate. In contrast 2,4,6-triaryl-pyridinium salts give p-amino- and P-aroylamino-chal- cones.229 0-R’ (i) -2H+ -0I’J-R2 (ii) rearrangement’ N /R3 H (219) Ph CH2R Ph (221) X=N (222) X=CH R A Some interesting pyridinium betaines (227) and (228) are formed reversibly from the pyridines with diethoxycarbonylketen tetraethoxycarbonylallene or their pre- cursors.The allene adducts (228) may be prepared by the reaction of (227) with the free keten.230 226 K. Hirota Y. Kitade S. Senda M. J. Halat K. A. Watanabe and J. J. Fox J. Amer. Chem. SOC.,1979 101,4423. 227 R. N. Comber J. S. Swenton and A. J. Wexler J. Amer. Chem. SOC.,1979,101 5411. 228 L. S. Cook and B. J. Wakefield Tetrahedron Letters 1979 1241. 229 A. R. Katritzky C. A. Ramsden Z. Zakaria R. L. Harlow and S. H. Simonsen J.C.S. Chem. Comm. 1979,363. 230 R. Gompper and U. Wolf Annalen 1979,1388,1406. A. J. Boulton and M. J. Cook An unusual product (229) of reaction between the mesomeric betaine (230) and o-chloranil was verified by X-ray analysis.231 Elimination of C02 from the intramolecular Diels-Alder reaction product of the coumarin esters (23 1)provides the benzo-phthalides (232).232 Other intramolecular cycloaddition reactions to pyrimidine rings [cf.Ann.Reports (B),1977,74,272] have been Loss of C02from the adduct formed between the oxazinone (233) and maleimide gives the pyridine (234). In contrast the reaction of (233) with an ynamine forms (235) and (236) presumably by addition to the valence isomer (237) the former by a [4+2] cycloaddition the latter by a [2+2] cycloaddition to give (238) as an intermediate.234 R 0 NKO -+N Ra:\/ uNR2 Ph Ph (234) 0 c0nr2 1 NEt The Diels-Alder reaction of 4-cyano-1-methyl-2-pyridonewith 2,3-dimethyl- butadiene offers a novel entry into the isocarbostyril series,235 and further investiga- 231 W.Friedrichsen C. Kruger E. Kujath G. Liebezeit and S. Mohr Tetrahedron Letters 1979,237. 232 G. A. Kraus J. 0.Pezzanite and H. Sugimoto Tetrahedron Letters 1979 853. 233 T. Jojima H. Takeshiba and T. Kinoto Heterocycles 1979,12 665. 234 A. E. Baydar G. V. Boyd P. F. Lindley and F. Watson J.C.S. Chem. Comm. 1979 178. 235 H.Kato R. Fujita H. Hongo and H. Tomisawa Heterocycles 1979,12 1. Heterocyclic Compounds 243 tions of 2-pyridones in the role of dienes reveal that the reaction with dimethyl acetylenedicarboxylate is favoured by the presence of a 6-methyl and by high Different types of product arise from Diels-Alder reactions of the triazines (239) and (240).After loss of nitrogen the intermediate (241; X = C1) decomposes via a 1,5-shift and loss of HC1 to a 2,6-dichloropyridine but the fluoro-analogue under- goes a further [4 +21 cycloaddition with another molecule of a1kene.238 X x\L"N +/!HR (ii) -N X XR (239) X=C1 (240) X=F (241) tj/\ But BulQ-.BuIBut (242) But C1 The hitherto unknown 1-arsanaphthalene (242) has been prepared by addition of benzyne to arsenin (arsabenzene) and then removing one of the etheno-bridges by standard tetrazine methods. It is very air-sensiti~e.~~~ Dehydrochlorination of the silacyclohexadiene (243) affords the dimer (244) via the monomeric 1,4-di-t- butylsilabenzene which could be trapped by diene~.~~' 7 Seven-membered and Larger Rings Thiepins are notoriously unstable extruding sulphur via a benzene episulphide intermediate.A remarkably stable example is (245) which has ti 7.1 h at 131 "Cin [2H8]toluene. The t-butyl groups are believed to provide steric hindrance to the cyclization in the decomposition pathway and their effectiveness is well shown by the contrast provided by the di-isopropyl analogue which loses sulphur at -70 0C.241 236 G. P. Gisby S. E. Royall and P. G. Sammes J.C.S. Chem. Comm. 1979,501. 237 K. Matsumoto Y. Ikemi-Kono T. Uchida and R. M. Acheson J.C.S. Chem. Comm. 1979 1091. 238 M. G.Barlow R. N. Haszeldine and D. J. Simpkin J.C.S. Chem. Comm. 1979,658. 239 A.J. Ashe D. J. Bellville and H. S. Friedman J.C.S. Chem. Comm. 1979,880.240 G. Mark1 and P.Hofmeister Angew. Chem. Internat. Edn. 1979,18,789. 241 K. Nishino S. Yano Y. Kohashi K. Yamamoto and I. Murata J. Amer. Chem. SOC., 1979,101,5058. A. J. Boulton and M. J. Cook The thiepin (246) could not be isolated but a sulphur-containing species could be trapped the thiol derivative (247) being amongst the products ___ E (E = C02Me) s >C=CHE E H (249) R = CN or COzMe (248) 1 O-YAc H (252) (E = C02Me) (254) R' =Me R2= H (256) R' =Me R2= H (255) R'= H R2=Me (257) R' = H R2=Me The 1H-and 3H-1,2-benzodiazepines are already known and now the first 5H-compounds (248) have been obtained by oxidation of the 1H-derivatives (249) with lead(1v) acetate. The reaction also forms the indazoles (250) presumably via the unstable 3H-isomers (251).On photolysis (248) gives the indole (252) through a tricyclic valence isomer.243 4H- Benzodiazepines e.g. (253) are valence isomers of cyclopropa-cinnolines (254) and (255) which are formed by cyclization of styryl-nitrilimines obtained by dehydrochlorination of the chloro-hydrazones (256) and "'D. N. Reinhoudt G. Okay W. P. Trompenaars S. Harkema D. M. W. van der Ham and G. J. van Hummel Tetrahedron Letters 1979 1529. 243 T. Tsuchiya and J. Kurita J.C.S. Chem. Comm. 1979 803. Heterocyclic Compounds 245 (257). However (253) is not an intermediate in their formation since it has been found that the cis- and trans-isomers (256) and (257) fo’rm the endo- and exo-isomers (254) and (25 5) stereospecifically.Compound (253) is undoubtedly an intermediate in the thermal interconversion of (254) and (255) which takes place spontaneously in solution and also in their slower transformation into the 1H-isomers (258).244 (259) oCHPr” PhfiPh \ N -N R2 (263) R’ = Bu”,R2= H (269) R = OMe n = 1 (264) R’ = H R2= Bun (270) R=H,n=l (267) R’ = H R2 = Ph (271) R=H,n=3 Photolysis of the N-imide (259) leads to the lH-1,3-benzodiazepine (260) in a reaction which finds analogies in the N-oxide series. Further irradiation of the product gives the indole (261);245 cf. (248) -+(252). In the monocyclic diazepine series it is found that the anions generated by deprotonation of (262) can be used to prepare 4-substituted derivatives of this Thermolysis of the cyclopropanes (263) and (264) gives the (E)-and (2)-isomers of the dihydro-oxepins (265) and (266) respectively.In contrast (267) gives 4-phenylphenol via the unstable compound 4-phenyloxepin. The cyclic allenes (268) have been postulated as intermediates in the two pathwaysz4’ [cf.Ann. Reports (B) 1977 74 2541. The crystal structure of the bicyclic dihydro-oxepin (269) has been reported the double bonds though having normal bond lengths are twisted and the bridgehead carbons approach pyramidal The parent (270) is found not to undergo the Cope rearrangement unlike its homologue (271). The lack of reactivity of (270) has been attributed to its inability to be converted from the structure with transoid oxygen atoms (shown here) into the cisoid isomer.249 244 A.Padwa and S. Nahm J. Org. Chem. 1979,444746. ”’ T. Tsuchiya M. Enkaku J. Kurita and H. Sawanishi J.C.S. Chem. Comm. 1979 534. 246 L. Bemi M. T. Thomas and V. Snieckus Synthesis 1979 130. 247 F. Bourelle-Wargnier M. Vincent and J. Chuche J.C.S. Chem. Comm. 1979,584. 248 W. H. Rastetter T. J. Richard J. Bordner and G. L. A. Hennessee J. Org. Chem. 1979 44 999. 249 W. H. Rastetter and T. J. Richard J. Amer. Chem. Soc. 1979 101 3893. A. J. Boulton and M. J. Cook In the sulphur series the cis- and trans-2,3-divinylthiirans have been thermo- lysed. The cis-isomer gives the product of Cope rearrangement but the trans- isomer forms (272) and (273) presumably via initial C-S bond cleavage and subsequent reactions of the biradi~al.~’~ Two groups have reported the synthesis of the parent 10welectron system 1,4-dihydro- 1,4-diazocine (274) derivatives of which have been reported earlier.The compound is sensitive to air in solution but can be sublimed in uacuo and is stable to acid and basic media. In contrast to derivatives bearing electron-withdraw- ing groups at nitrogen the ring is practically planar and X-ray and spectral data are indicative of aromatic chara~ter.~” The green aza[ 18lannulene (275) the first monocyclic pyridine analogue of this type has been prepared and its n.m.r. spectrun reveals that the N atom occupies an internal position as shown. On protonation the ratio of NH-outside to NH-inside cations is ca. 4 :1.2’2 A correction should be noted to last year’s Report on polycyclic medium rings.3,ll -Dimethy1-1,5,9,13-tetra-azatricyclo[9.5.1.1 3*9]octadecane shown as the (chiral) cis-isomer [Ann. Reports (B),1978 75 274; structure (274)] is in fact the rneso-trans-i~omer.~~~ The diaza-bicyclotetradecane (276) is mono- (pK = 6.5)and di-protonated (pK = -3.25) from the outside but the inside-protonated ion is formed on standing in strong acid for a week. However it appears that this does not arise by simple proton transfer but via an aminium cation radical. Support for this comes from its accelerated production in the presence of a one-electron There are now so many apparently well-funded groups working on crowns and cryptands that it is inevitable that many more interesting and significant papers in this 250 M.P. Schneider and M. Schnaithmann J. Amer. Chem. SOC.,1979 101 255. 251 H.-J. Altenbach H. Stegelmeier M. Wilhelm B. Voss J. Lex and E. Vogel Angew. Chem. Internat. Edn. 1979 18 962; M. Breuninger B. Gallenkamp K.-H. Muller H. Fritz H. Prinzbach J. J. Daly and P. Schonholzer ibid. p. 964. *” W. Gilb and G. Schroder Angew. Chem. Internat. Edn.,1979 18 312. 253 D. S. Kemp R. V. Punzar and J. C. Chabala Tetrahedron Letters 1979,4240. 254 R. W. Alder and R. B. Sessions J. Arner. Chem. Soc. 1979 101 3651; R. W. Alder A. Casson and R. B. Sessions ibid. p. 3652. Heterocyclic Compounds area of feverish publication have to be omitted than can be chosen for mention here. Fortunately detailed reviews of the subject have begun to appear see the following section.The photochemical reduction of the metal in N-crown-complexed silver(1) to the zerovalent and the complexation of alkali metals256 as (M’-crown) M- are two less usual aspects of their chemistry. Multi-looped polyether systems have been developed both ~piro-f~~ed~~~~~~~ and with other arrangement^,^^^ and an amusing exploitation of bullvalene isomerization has led to the production of ‘breathing crown ethers’ i.e. crowns which within limits can adapt their ring size according to wearer. Thus the ring of (277) varies from eleven to thirteen members and similarly the bullvaleno-[20-22]-crown-6 can change within the limits indicated.260 Bis-monoaza-crown ethers (278) form 1 1complexes with the bis-salt (279) each ring acting as host to one cationic moiety,261 and a [27]-crown-9- hexacarboxylate forms complexes with guanidinium and imidazolium ions which are stable and also selective even in aqueous (277) (278) n = 2 X = (CH,) or (CH,) 8 Monographs and Reviews In ‘The Chemistry of Heterocyclic Compounds’ (Weissberger-Taylor series) three volumes on a major ring system (thia~ole),,~~ and one a third on another (ind~le),~~~ covering the condensed py~azines~~~ have been published.A seven-volume mono- graph on the porphyrins has appeared,266 and B. D. Tilak’s 60th birthday is ”’ R. Humphry-Baker M. Gratzel P. Tundo and E. Pelizzetti Angew. Chem. Internat. Edn. 1979 18 630. 2s6 J. L. Dye Angew. Chem. Internat. Edn. 1979 18 587. ”’ E. Weber Angew. Chem. Internat. Edn. 1979 18 219.V. Prelog and D. Bedekovic Helv. Chim. Acta 1979 62 2285. 2s9 R. C. Helgeson T. L. Tarnowski and D. J. Cram J. Org. Chem. 1979 44,2538. 260 G. Schroder and W. Witt Angew. Chem. Internat. Edn. 1979 18,311. 261 M. R. Johnson I. 0.Sutherland and R. J. Newton J.C.S. Chem. Comm. 1979,306. 262 J. M. Lehn P. Vierling and R. C. Hayward J.C.S. Chem. Comm. 1979,296. ‘Thiazole and its Derivatives’ ed. J. V. Metzger (Weissberger and Taylor’s ‘The Chemistry of Hetero-cyclic Compounds’) Wiley-Interscience New York 1979 Vol. 34 Parts 1-3. 264 ‘Chemistryof Indoles’ ed. W. J. Houlihan (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley-Interscience New York 1979 Vol. 25 Part 3. ‘Condensed Pyrazines’ ed. G. W. H. Cheeseman and R. F. Cookson (Weissberger and Taylor’s ‘The Chemistry of Heterocyclic Compounds’) Wiley-Interscience New York 1979 Vol.35. 266 ‘The Porphyrins’ Vols. I and 11 ‘Structure and Synthesis’; Vols. III-V ‘Physical Chemistry’; Vols. VI and VII ‘Biochemistry’ ed. D. Dolphin Academic Press New York 1978-9. 248 A. J. Boulton and M. J. Cook commemorated in a volume of reviews267 on a variety of interesting short topics 1-hydroxy-indoles,“ naphtho-indolizines,b 3,5-disubstituted pyridines and related pyridinophanes,‘ phospholes and benzophospholes (‘phosphindoles’),d 3-oxido- pyridinium betaines,‘ dibenzoxazepines,’ and benzazetes;R also covered are some aspects of cycloaddition to azoles,h azirine chemistry’ and aziridine stereochemistry,’ pyryliumk and thiiranium salts,’ the reaction of azides with indoles,” synthesis of benzo[b]thiophens the use of thiophens in the synthesis of optically active quater- nary hydrocarbons,” the photochemical construction of heterocyclic compounds,P and quantum-chemical aspects of electrophilic substitution in five-membered rings.4 Crowns cryptands and other multidentate macrocycles are the subject of a monograph,268 and three other reviews deal with certain aspects of this area describes the stabilization of derivatives of alkali-metal anions in which crown ethers play an important role; another269 covers cyclic di- and tetra-esters of polyether systems and a third,270 entitled ‘From Carbohydrates to Enzyme Analo- gues’ covers a lot of ground (including a section extolling the virtues of dreaming271).1,SDipolar cyclizati~ns~~~ are discussed in and 1,3-dipolar cyclo-rever~ions~~~ two long articles that are full of interest. Other reactions to be reviewed include the photo-oxygenation of the cyclotrimerization of cyano-compounds to 1,3,5-triazine~,~~~ condensations of alkyl groups in pyrylium salts 276 acid-catalysed transformations of 1,3-dioxans and 1,3-diox01ans,~~~ the reactions of heterocycles which involve the catalytic use of cyanide and the reactions of nitrones with ketens (including an interesting account of Staudinger’s ‘nitrene~’).~~~ More modern nitrenes are also reviewed,280 and other areas of interest to hetero- cyclic synthesis are the diazenium28’ and 3-chloro-2-propeniminium salts,282 and he~amethylenetetramine.~~~ The ‘imino-Diels-Alder’ synthesis of N-heterocycles (particularly 3-piperideines) has been and also the synthesis of hetero- 267 (a) R.M.. Acheson; (b) N. R. Ayyangar and A. G. Lugade; (c) K. Deuchert and S. Hunig; (d)A. N. Hughes; (e) A. R. Katritzky and N. Dennis; cf) K. Nagaragan; (g)C. W. Rees; (h)R. B. Mitra G. H. Kulkarni G. S. Shirwaikar and R. S. Jagtap; (i)A. Hassner and V. Alexanian; 0’)P. Tarburton C. A. Kingsbury and N. H. Cromwell; (k)A. T. Balaban; (I) V. N. Gogte and H. M. Modak; (m)J. M. Peach and A. S. Bailey; (n)B. Iddon; (0)L. A. Hulshof and H. Wynberg; (p)A. Padwa P. H. J. Carlsen and N. Kamigata; (4)I. A. Abronin L. I. Balen’kii and Ya. L. Gol’dfarb in ‘New Trends in Heterocyclic Chemistry’ ed. R. B. Mitra N. R. Ayyangar V. N. Gogte R.M. Acheson and N. H. Cromwell Elsevier Amsterdam Oxford and New York 1979. 268 ‘Synthetic Multidentate Macrocyclic Compounds’ ed. R. M. Izatt and J. J. Christensen Academic Press New York 1978. 269 J. S. Bradshaw G. E. Maas R. M. Izatt and J. J. Christensen Chem. Rev. 1979 79 37. 270 J. F. Stoddart Chem. SOC.Rev. 1979 8 85. 271 cf. W. Shakespeare ‘Julius Caesar’ Act I Scene 2 line 24. For more on dreams and their place in chemistry see A. KekulC quoted by K. Hafner Angew. Chem. Internat. Edn. 1979,18,641. 272 E. C. Taylor and I. J. Turchi Chem. Rev. 1979 79 181. 273 G. Bianchi C. De Micheli and R. Gandolfi Angew. Chem. Internat. Edn. 1979 18 721. 274 M. V. George and V. Bhat Chem. Rev. 1979,79,447. 27s D. Martin M. Bauer and V. A. Pankratov Russ.Chem. Rev. 1978,47 975. 276 V. V. Mezheritskii A. L. Wasserman and G. N. Dorofeenko Heterocycles 1979,12 51. 277 D. L. Rakhmankulov E. A. Kantor and R. A. Karakanov Heterocycles 1979 12 1039. 278 E. Hayashi and T. Higashino Heterocycles 1979 12,837. 279 M. A. Abou-Gharbia and M. M. Joullie‘ Heterocycles 1979 12 819. 280 B. Iddon 0.Meth-Cohn E. F. V. Scriven H. Suschitzky and P. T. Gallagher Angew. Chem. Internat. Edn. 1979,18,900. M. A Kuznetsov Russ.Chem. Rev. 1979 48 563. 282 L. Liebscher and H. Hartmann Synthesis 1979 241. 283 N. Blazevic D. Kolbah B. Berlin V. Sunjic and F. Kajfez Synthesis 1979 161. 284 S. M. Weinreb and J. I. Levin Heterocycles 1979,12 949. Heterocyclic Compounds 249 cycles using heterocum~lenes.~~~ The uses of isoxazoles in synthesis have been collected.286 Specific ring systems which have been covered during the year include besides those mentioned above the azetidine~,~~’ pyrida~ines,~~~ benzo[c]~innolines,~~~ pyrro10[3,2-c]quinolines;~~~ 1,lO-phenanthroline~~~~ pyrroli~idines,~~’ and other polyaza-phenanthrene~,~~~ 1,4-thia~ines,’~~ quina~olines,~~~ and thiirenium ions.296 Other reviews of special areas deal with Reissert 1,2-azoles (isoxa- zoles pyrazoles and isothia~oles),~~~ selenium-nitrogen heterocycles,299 three- membered rings with two heteroatom~,~~~ physicochemical aspects of purine^,^" the ‘H n.m~.~O* spectroscopy of phytoxanthones and the stereochemistry of and u.v.~’~ quinolizidines indolizidines and pyrrolizidine~.~~~ The application of photoelectron spectroscopy to conformational analysis is illustrated with many heterocyclic exam- ple~,~~~ and a review by Kauffmann on ‘areno-analogy’ while stopping short of a clear definition of the term is certainly packed with plenty of interesting heterocyclic The latest volume of the Specialist Periodical Reports on sulphur selenium and tellurium seems to give excellent value more than half of the chapters deal with heterocyclic ring systems and there is also a section on the p-lactam antibiotic^.^'^ 285 0.Tsuge Heterocycles 1979 12 1067.286 C. Kashima Heterocycles 1979,12 1343. 287 N. H. Cromwell and B. Phillips Chem. Rev, 1979,79 331. 288 J. W. Barton Adu. Heterocyclic Chem. 1979 24 151. 289 M. Tiiler and B. Stanovnik Adv.Heterocyclic Chem. 1979 24 363. 290 M. A. Khan and J. F. da Rocha Heterocycles 1979 12 857. 291 D. J. Robins Adu. Heterocyclic Chem. 1979 24 247. 292 W. Sliwa Heterocycles 1979 12 1207. 293 W. Sliwa and H. Zamarlik Heterocycles 1979 12 529. 294 W. L. F. Armarego Adv. Heterocyclic Chem. 1979 24 1. 295 R. J. Stoodley Adv. Heterocyclic Chem. 1979 24 293. 296 G. Capozzi V. Lucchini and G. Modena Rev. Chem. Intermediates 1979,2 347. 297 F. D. Popp Adv. Heterocyclic Chem. 1979 24 187. 298 S. D. Sokolov Russ. Chem. Rev. 1979,48 289. 299 I. Lalezari A. Shafiee and M. Yalpani Adv. Heterocyclic Chem. 1979 24 109. 300 E. Schmitz Adu. Heterocyclic Chem. 1979 24 63. ”” J. H. Lister Ado. Heterocyclic Chem. 1979 24 215. ’02 M. Afzal and J. M. Al-Hassan Heterocycles 1979 12 421.303 M. Afzal J. M. Al-Hassan and F. N. Al-Masad Heterocycles 1979 12 269. 304 I. M. Skvortsov Russ. Chem. Rev. 1979 48 262. 305 M. Klessinger and P. Rademacher Angew. Chem. Internat. Edn. 1979 18 826. 306 T. Kauffmann Angew. Chem. Internat. Edn. 1979 18 1. 307 L Organic Compounds of Sulphur Selenium and Tellurium’ ed. D. R. Hogg (Specialist Periodical Reports) The Chemical Society London 1979 Vol. 5.

ISSN:0069-3030    

DOI:10.1039/OC9797600211

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (i) The Transition Elements By H. M. COLQUHOUN and J. HOLTON ICI Corporate Laboratory The Heath Runcorn Cheshire WA7 4QE and M. V. TWlGG ICI Agricultural Division Billingham Cleveland TS23 1LD 1 Introduction In this Report the emphasis is on the application of organo-transition-metal species in organic synthesis and during 1979 the high level of interest in this area continued. Although there has been considerable discussion on mechanistic aspects of catalytic olefin metathesis no major practical advances have been reported and accordingly the section dealing with this topic has been omitted. New sections deal with carboxylation and synthetic procedures involving phase-transfer catalysis -areas in which useful developments are being made.Relevant reviews include those dealing with palladium-catalysed reactions of olefins with aryl halides,’ syntheses involving polybromo-ketones/iron carbonyl reactions,* and heterogenized catalyst^.^ Reduction of organic compounds with low-valent transition-metal specie^,^ cobalt-catalysed reactions of hydrosilanes and carbon monoxide with unsaturated organic compound^,^ and catalytic hydro- genation of arenes6 have also been reviewed. A book concerned with Ziegler-Natta catalysts and polymerizations’ has been published and a volume of Advances in Organornerallic Chemistry was devoted to the synthesis of organic compounds.8 The growing acceptance of transition-metal reagents in synthesis is reflected by the appearance of several books concerned with this topic.’ ’ R.F. Heck Accounts Chem. Res. 1979,12 146. R. Noyori Accounts Chem. Res. 1979,12,61. A. Y. Yuffa and G. V. Lisichkin Russ. Chem. Rev. 1978,47,751. T. L. Ho Synthesis 1971 1. S. Murai and N. Sonoda Angew. Chem. Internat. Edn. 1979 18 837. E. L. Muetterties and J. R. Bleeke Accounts Chem. Res. 1979 12 324. ’J. Boor ‘Ziegler-Natta Catalysts and Polymerisations’ Academic Press London 1978. ‘Advances in Organometallic Chemistry’ Vol. 17 ed. F. G. A. Stone and R. West Academic Press London 1979. R. P. Houghton ‘Metal Complexes in Organic Chemistry’ Cambridge University Press 1979; M. Freidfelder ‘Catalytic Hydrogenation in Organic Synthesis Procedures and Commentary’ John Wiley New York 1979; J. K. Kochi ‘Organometallic Mechanisms and Catalysis’ Academic Press London 1978; ‘Transition Metal Organics in Organic Synthesis’ Vol.11 ed. H. Alper Academic Press London 1978; ‘Fundamental Research in Homogeneous Catalysis 11’ ed. Y. Ishii and M. Tsutsui Plenum Press London 1979. H. M. Colquhoun J. Holton and M. V. Twigg 2 Hydrogenation The scope of reductions by sodium borohydride has been extended by several reports this year of transition-metal-promoted reductions by sodium borohydride. The reduction of a ketone in the presence of an aldehyde usually necessitates a three-step process uiz. protection of the aldehyde reduction of the ketone and finally liberation of the aldehyde. This lengthy procedure is often poorly selective and leads to separation problems and low yields.A simple one-step route has now been devised using NaBH4 and CeC13.6H20 (in molar ratio 1.5 :l)." It is known that in aqueous solution non-conjugated aldehydes form hydrates to a greater extent than ketones while conjugated ones are not hydrated. Protection of a non-conjugated aldehyde is achieved by formation of a gem-diol which is stabilized by its co- ordination to a cerium(II1) ion. The presence of Ce'" is sufficient to ensure adequate protection during reduction but does not hamper recovery of the aldehyde during work-up. Thus in an equimolar mixture of hexanal and cyclohexanone only 2% of the aldehyde is reduced compared to 100°/~of the ketone; similarly (1)is obtained in 75% isolated yield as shown in Scheme 1. Selective reduction cannot be achieved with conjugated aldehydes (e.g.benzaldehyde) which are readily reduced. This however allows selective reduction of conjugated aldehydes in the presence of non-conjugated aldehydes so that for example benzaldehyde is reduced to the alcohol (85%) while cyclohexanecarboxaldehyde is not reduced. H 0 ? wC02Me CHO CHO (1) Reagents i NaBH, CeCl,.6H20 Scheme 1 The complex formed by a cobalt(I1) salt and sodium borohydride reduces alkenes in high yield with high steric selectivity (mono- > di-> tri- and tetra-substituted olefins)." In limonene only the disubstituted exocyclic double bond is reduced and not the trisubstituted endocyclic double bond. Alkynes undergo facile reduction to alkanes but partial reduction to alkenes is not controllable.Aryl bromides are not readily reduced by sodium borohydride but in the presence of a catalytic amount of [Ni(PPh&] substantial debromination occurs in NN-dimethylformamide (DMF) at 70 "C over 3-20 hours.12 Aryl chlorides also react but more slowly. Reduction of certain functional groups e.g. nitro-or cyano-groups occurs in preference to dehalogenation and hydroxy and amino functions hinder the reaction. lo J. Luche and A L. Gemal J. Amer. Chem. Soc.,1979,101,5848. '' S. Chung J. Org. Chem. 1979,444 1014. l2 S. Lin and J. A. Roth J. Org. Chem. 1979 44 309. Organometallic Chemistry-Part (i) The Transition Elements Aromatic nitro-compounds are not reduced by sodium borohydride alone. However in the presence of copper(I1) a~etylacetonate,'~ reduction to the cor- responding amine occurs.The chromium(I1)-amine complex formed by rapid addition of an aqueous solution of chromium(I1) perchlorate to a cold solution of ethylenediamine (or triethylamine) in DMF reduces terminal and alkyl-phenylacetylenes to the cor- responding olefin with a high selectivity for the ~is-isorner.'~ Dialkyl-acetylenes are not reduced by this reagent. Propargyl alcohols undergo facile reduction but with low stereoselectivity the [Cr"-ethylenediamine] complex favouring trans-addition whereas [Cr"(NEt,)] favours cis-addition. trans-Addition is the exclusive pathway in the absence of amine. In the presence of amines reduction of (2) occurs quantitatively with cis :trans selectivities of 55 :45 and 10:90 for ethylenediamine and triethylamine respectively.Thus the relative proportions of cis- and trans- isomers depend on both the nature of the acetylene and the amine. Pr" H Pr" CH20H \/ \/ Pr"CrCCH20H + H/c=c \CH20H+ H/c=c\ H (2) trans cis The rhodium hydride [RhH(PPr',),] and to a lesser extent [Rh2H2( p-N2)-{P(cyclohexyl)3}4] are active homogeneous catalysts for the hydrogenation of nitriles." Aliphatic and aromatic nitriles are hydrogenated under ambient condi- tions in the presence of these hydrides to the corresponding primary amine. Using unsaturated nitriles hydrogenation of the olefinic group proceeds more readily than that of the nitrile function. It is interesting to compare [RhH(PPr',),] with the well-known hydrogenation catalyst [RhCl(PPh,)J which reduces only the olefinic group under similar conditions.The selective hydrogenation of a nitro-group in the presence of an acetylenic function may be achieved using ruthenium supported on carbon or alumina.16 Results with various acetylenic compounds show the reactivity sequence RCECH > ArC=CH >ArCGCR. Although selective reduction occurs with monosubstituted acetylenes catalyst turnover is poor owing to strong absorption of the terminal acetylene onto the catalyst. However the use of a blocking group such as dimethyl- carbinol to increase steric crowding around the triple bond maintains a high rate of hydrogenation of a nitro-group by protecting the catalyst from deactivation. Hence 2-methyl-4-(3-nitrophenyl)-3-butyn-2-01 is selectively reduced to the correspond- ing amine in 100°/~yield (50°C 504Opsi of H2).The blocking group is easily removed by a catalytic amount of sodium hydroxide. The bidentate ligand anthranilic acid has been anchored to polystyrene beads to form (3); its reaction with [RhCl3-3H2O] followed by reduction with sodium borohydride produces a polymer-supported rhodium(1) species.17 This is a useful hydrogenation catalyst of high activity with long-term stability and a considerable l3 K. Hanaya T. Muramatsu H. Kudo and Y. L. Chow J.C.S. Perkin I,1979 2409. l4 J. K. Crandall and W. R. Heitmann J. Org. Chem. 1979 44 3471. *' T. Yoshida T. Okano and S. Otsuka J.C.S. Chem. Comm. 1979,870. l6 A. Onopchenko E. T. Sabourin and C. M. Selwitz J.Org. Chem. 1979,441233. " N. L. Holy J. Org. Chem. 1979 44 239. H.M. Colquhoun J. Holton and M. V. Twigg (3) Cb,H PPh2 [ (R) -(S)-BPPFOH] (4) tolerance to poisons (e.g. air). Using this catalyst a variety of olefinic and aromatic hydrocarbons may be reduced as well as carbonyl nitrile and nitro functional groups. A new asymmetric synthesis of 2-amino-1 -aryl-ethanols has been developed based on the reduction of prochiral ketones.'' Using a chiral rhodium complex of the hydroxyalkyl-ferrocenylphosphine(4),catalytic hydrogenation of aminomethyl aryl ketones can be achieved in high optical and chemical yields [reaction(l)]. Con-ventional chiral hydride agents are not very effective with these prochiral carbonyl compounds because of the presence of active hydrogens on the starting ketones and the instability of the latter under basic conditions.\I H A remarkable effect of pressure on stereoselectivity has been described for the asymmetric hydrogenation of a -acylaminocinnamic acids. l9 Using neutral or cationic rhodium complexes with for instance DIOP to catalyse the hydrogenation of (2)-a-benzamidocinnamic acid it was found that (R)-N-benzoylphenylalanine was the preferred product at atmospheric pressure. However the (S)-isomer pre- dominated at high pressure (50-100 atm of HJ. This result may be explained in terms of two competing mechanisms; at low pressure co-ordination of the olefin is followed by addition of hydrogen whereas at high pressure the addition of hydrogen precedes complexation of the olefin.The stereochemistries of [Rh*] and [Rh*H2] dictate the orientation of the olefin upon co-ordination and in this example lead to inversion in the configuration of the product. Triethylamine is often added to such rhodium catalysts to improve optical yields. It is of interest to note that here the base supresses the pressure effect i.e. prevents pre-co-ordination of H2 at high pressures as well as improving optical yields. 3 Dimerization Oligomerization and Polymerization Interest in oligomerization and telomerization of butadiene has continued. The reaction of butadiene with an aldehyde (acetaldehyde benzaldehyde or acrolein) in the presence of [Ni(cod),] and PPh gives2' predominantly (> 70%)the linear 2 1 T. Hayashi A.Katsumura M. Konishi and M. Kumada Tetrahedron Letters 1979 425. l9 I. Ojima T. Kogure and N. Yoda Chem. Letters 1979,495. 2o R. Baker and M. J. Crimmin J.C.S. Perkin I 1979 1264. Organometallic Chemistry-Part (i) The Transition Elements 255 R + RCHO -(2) OH R =Me Ph or CH2=CHCH2 telomer i.e. 1-substituted 3,6,8-nonatrien-l-o1 [see reaction (2)]. With tri-cyclohexylphosphine the linear product is no longer preferred and up to 85% of branched product is obtained. A similar reaction between isoprene and acetalde- hyde does not occur in the presence of [Ni(cod),] but using nickel cyclo- dodecatriene and triphenylphosphine the 2 :1adduct is obtained in which isoprene is dimerized in a head-to-tail manner. The two major products are 3,7-dimethyl-3- vinyloct-7-en-2-01 and its isomer 3,7-dimethyl-3-vinyloct-6-en-2-ol.The effect of changing the phosphorus ligand on the distribution of products21 has been studied by Heimbach et al. who have also examined the effect of ligand concentration.22 A study of the system nickel(0)-triphenylphosphine-butadiene has shown that at low nickel to phosphorus ratios the formation of cyclo-trimers predominates but at higher ratios cyclo-dimers are favoured. ‘Partial control’ graphs of product yield against ligand :metal ratio were drawn and they allowed the optimization of the catalysed process as well as a better analysis of the mechanism. The linear dimerization of butadiene produces octatrienes but to obtain octadienes a hydrogen-donating source (such as a Grignard reagent alcohol or formic acid) is required.It has been shown that nickel(0) complexes together with morpholine and formaldehyde catalytically convert butadiene into ~ctadienes.~~ The predominant products are the dihydro-dimers trans,trans-octa-2,6-diene and trans-octa-l,6-diene. N-Hydroxymethyl-morpholine which is the product of the reaction between morpholine and formaldehyde is an efficient hydrogen-donor molecule for this catalytic hydrodimerization. The reaction is thought to proceed in one step and not through the intermediate formation of an octatriene. The selective dimerization of ethylene to 1-butene by [Ta(CH2CMe3),(CHCMe3)] and PMe3 has prompted the proposal of a new mechanism for the oligomerization of ethylene.24 It has been suggested that the C4 chain does not form by insertion of ethylene into a metal-ethyl bond but via a metallocyclopentane intermediate (see Scheme 2).For metals in a low oxidation state (the metal is formally oxidized upon Scheme 2 ” A. Busch P. Heimbach R. Meyer and H. Schenkluhn J. Chem. Res. (S) 1979,228. ’’F. Brille P. Heimbach J. Kluth and H. Schenkluhn Angew. Chem. Znrernar. Edn. 1979 18,400. 23 J. Thivolle-Cazat and I. Tkatchenko J.C.S. Chem. Comm. 1979 377. 24 J. D. Fellmann G. A. Rupprecht and R. R. Schrock J. Amer. Chem. SOC.,1979,101,5099. H. M. Colquhoun,J. Holton andM. V. Twigg formation of a metallocycle) and where the insertion of ethylene into a metal-alkyl bond is not expected to be fast this represents a plausible alternative mechanism.If but-l-ene is not displaced by ethylene then higher oligomers can be formed and in the extreme polyethylene. The proposal of a novel mechanism for olefin polymerization via a! -elimination to form a transient carbene species has led workers to re-examine the established views on Ziegler-Natta catalysis25 (i.e.insertion into a metal-alkyl bond). Model systems have shown that the a-elimination step is possible,26 and during the year the proposed mechanism has undergone subtle changes,” making it simpler and there- fore perhaps more plausible. On the other hand evidence for the Cosse mechanism has been found in the cobalt system [Co(q5-C5HS)(PPh3)Me2] where deuterium- labelling studies demonstrate that ethylene inserts into the metal-methyl bond.28 The question of the mechanism has yet to be resolved indeed each mechanism may operate in different systems but lively interest and debate has been aroused in the field of Ziegler-Natta catalysis and further reports are likely.4 Carbon Monoxide Chemistry Carbony1ation.-Cobalt-catalysed carbonylation of aldehydes in the presence of trialkyl-silanes affords moderate yields (ca.50%) of a! -siloxy-aldehydes (Scheme 3) which are useful intermediates in organic synthesis and are otherwise difficult to prepare.29 A silyl-cobalt carbonyl [R,SiCo(CO),L] (L = CO or PPh3) is suggested to be the active species (see also Section 6). + HSiEt,Me + CO rco,(co),l RxH 0 A study of the Wakamatsu synthesis in which an aldehyde is catalytically carbonylated in the presence of an amide giving N-acyl-amino-acids (Scheme 4) shows that the reaction proceeds with high selectivity in virtually quantitative yield.Attempts to obtain asymmetric induction by incorporating chiral ligands into the system were however U~SUCC~SS~U~.~~ [CO,(CO)!31 ),0 + R’CONH +CO H, R’ H R’ NHCOR2 Scheme 4 25 G. Ghiotti E. Garrone S. Coluccia C. Monterra and A. Zecchina J.C.S. Chem. Comm. 1979 1032. 26 C. D. Wood S.3. McLsin and R. R. Schrock J. Amer. Chem. Soc. 1979,101,3210;N. J. Cooper and M. L. H. Green J.C.S. Dalron 1979 1121. 27 R. J. Al-essa and R. J. Puddephatt J.C .S. Chem. Comm. 1980,45. E. R. Evitt and R. G. Bergman J. Amer. Chem. SOC.,1979,101 3973. 29 S. Murai T. Kato N. Sonoda Y.Seki and K. Kawamoto Angew.Chem. Internat. Edn. 1979,18,393. 30 J. J. Parnaud G. Campari and P. Pino J. Mol. Catalysis 1979,6 341. Organometallic Chemistry-Part (i) The Transition blements 257 A novel catalyst which allows carbonylation of aryl halides at atmospheric pressure is prepared by addition of cobalt(@ acetate to a suspension of sodium hydride and sodium alkoxide in THF under carbon monoxide.31 Carbonyl- ation of iodobenzene in the presence of sodium neopentoxide for example gave a 70%yield of benzoic acid and neopentyl benzoate in the ratio 9 :1. The mechanism of this reaction is unknown but the formation of 2-aryl-tetrahydrofurans as by- products (up to lo"/") suggests that free radicals may well be involved. The rhodium-induced carbonylation of 2-aryl-azirines under ambient conditions affords highly reactive vinyl isocyanates in good yield (Scheme 5).A somewhat speculative mechanism proposes that carbon monoxide adds to an intermediate vinylnitrene-rhodium complex followed by decomplexation of the resulting iso- ~yanate.~' N [Rh(C0)2Cl] OCN >=( R Ar/QyR+CO,,r Ar R Scheme 5 The complex obtained by the reaction of bis(cyc10-octa- 1,5diene)nickel with methacrylamide in the presence of tricyclohexylphosphine reacts instantly with carbon monoxide at room temperaf~re,~~ to give a quantitative yield of 3-methyl- succinimide (Scheme 6). It is suggested that an analogous cobaltacyclic amide may be an intermediate in the known catalytic synthesis of 3-methylsuccinimide from methacrylamide and carbon monoxide.H cy3P-N(XO +co-+o Me Scheme 6 Chemistry of Synthesis Gas.-The first reported Fischer-Tropsch-type chain growth on a soluble mononuclear catalyst results in formation of alkyl-benzenes Ph(CH2),H (n = 1-5) when a solution of [W(CO),] and AlC13 in benzene is treated with carbon monoxide and hydrogen at 200 "C(20-100 atm). Turnover numbers > 200 (CO :W) may be achieved in this which appears to involve an initial arylation of tungsten followed by successive insertion/reduction steps as proposed for the corresponding heterogeneous reaction. The high-pressure Union Carbide synthesis of ethane-1,2-diol from carbon monoxide and hydrogen continues to provide a stimulus for research into possible mechanisms whereby two molecules of carbon monoxide may be reductively coupled.Wood and Schro~k~~ have described the rapid reaction between [Ta(q 5-C5Me5)Me4] and carbon monoxide to give an q2-acetone complex which 31 J. J. Brunet C. Sidot B. Loubinoux and P. CaubGre J. Org. Chem. 1979 44 2199. 32 T. Sakakibara and H. Alper J.C.S. Chem. Comm. 1979,458. 33 T. Yamamoto K. Igarishi J. Ishizu and A. Yamamoto J.C.S. Chem. Comm. 1979 554. 34 G. Henrici-OlivC and S. OlivC Angew. Chem. Irtiernat. Edn. 1979,18 77. 35 C. D. Wood and R. R. Schrock J. Amer. Chem. SOC., 1979,101,5421. H. M. Colquhoun J. Holton andM. V. Twigg Me Me * [(C,Me,)Ta-Of; +-(CsMe5)x7Me I I 0 I 0 Me H Me L Reagents i CO Et,O at -78 "C; ii CO at 25 "C; iii HzO Scheme 7 then takes up a second molecule of carbon monoxide more slowly.Hydrolysis of the final product yields one equivalent of methyl isopropyl ketone (Scheme 7). A more conventional scheme for coupling of carbon monoxide envisages the reduction of co-ordinated carbon monoxide to a hydroxymethyl ligand insertion of carbon monoxide into the metal-carbon c-bond and hydrogenolysis of the resulting hydroxyacetyl complex. This scheme is now supported by isolation and charac- terization of the first stable low-valent transition-metal hydroxymethyl complex36 (Scheme 8). Moreover thermolysis of the acyloxymethyl complex [Mn(CO),CH20R] (R = ButCO) under hydrogen (7 atm) results in rearrangement to [Mn(CO),COCH,OR] which is then hydrogenolysed to give the mono-ester of ethane-1,2-diol in good yield.37 n -MeOH + Scheme 8 Yet a third route to coupled products of carbon monoxide has been described by Bercaw and ~o-workers,~~ who found that [(q5-CsMe5)2ZrH2] reacts with [(qS-C5Me5)Zr(C0)2]under hydrogen to give a quantitative yield of complex (5) which contains a bridging ethene-l,2-diolate ligand.When [(q'-CsHs)2WCO] replaces the zirconium carbonyl in this reaction however a 'zirconoxy-carbene' complex of tungsten (6) is 36 C. P. Casey M. A. Andrews and D. R. McAllister J. Amer. Chem. SOC.,1979,101,3371. 37 B. D. Dombek J. Amer. Chem. Soc. 1979,101,6466. 38 J. M. Manriquez D. R. McAllister R. D. Sanner and J. E. Bercaw J. Amer. Chem. SOC.,1978,100,2716. 39 P. T. Wolczanski R. S. Threlkel and J. E. Bercaw J. Amer. Chem.SOC.,1979,101,218. Organometallic Chemistry-Part (i) The Transition Elements 5 Carboxylation The palladium(0)-catalysed reaction of carbon dioxide with iso-propylidenecyclopropane gives a mixture of two-five-membered lactones in pro- portions which depend on the nature of the catalyst (Scheme 9). Thus using PPh and [Pd(diben~ylideneacetone)~], a 69% yield of (7) was obtained with only 8% of (8)whereas with [Pd(Ph2PCH2CH2PPh2),] the lactone (8)was formed in 48% yield with only a trace of (7). Other methylene-substituted methylenecyclopropanes reacted similarly but when ring-substituted analogues were used only starting materials could be recovered. A mechanism involving addition of carbon dioxide to a trimethylenemethane-palladium complex was propo~ed.~' palIadium(0) + CO -The addition of carbon dioxide to the cyanomethyl complex [Fe(H)CHzCN(Ph2PCHzCH2PPh2)z] (formed from the reaction of acetonitrile with the corresponding naphthyl iron hydride) gives a cyanoacetate complex which liberates cyanoacetic acid on heating in a~etonitrile.~~ It is not clear from this paper whether the original cyanomethyl complex is re-formed but if so this would seem to provide a simple catalytic route to cyanoacetic acid.The paramagnetic titanium aryl [Ti(q5-C5H5)(C6H4-o-CH2NMe2)2] eliminates NN-dimethylbenzylamine on heating in toluene and the resulting species (possibly a benzyne complex) incorporates carbon dioxide to give a terdentate amino-aryl- carboxylate ligand (Scheme lo)."' Toluene + CO -PhCH2NMe2 74 "C Scheme 10 40 Y.Inoue T. Hibi M. Satake and H. Hashimoto J.C.S. Chem. Comm. 1979,982. 41 S. D. Ittel C. A. Tolman A. D. English and J. P.Jesson J. Amer. Chem. SOC.,1978 100,7577. 42 L. E. Manzer J. Amer. Chem. SOC.,1978,100,8068. H. M. Colquhoun J. Holton and M. V. Twigg 6 Reactions of Co-ordinated Ligands Condensation of an alcohol with a nitrile in strong acid (the Ritter reaction) proceeds via a carbenium ion and is therefore often limited to tertiary alcohols. This limitation may however be overcome in some instances by utilizing the enhanced stability of secondary and even primary carbenium ions adjacent to transition metals. Thus generation of the complexed benzyl cation [Cr(q'-PhCH,)(CO),]+ from the corresponding alcohol by treatment with sulphuric acid followed by addition of excess nitrile allows the ready preparation of amide complexes [Cr(q'-PhCH,NHCOR)(CO)3](R = Me Ph Pr" etc.) in very high yield.The ~~~~~~ alkyne-cobalt complex [ ~ o ~ ( ~ behaves similarly and acid- ~ catalysed rearrangements characteristic of the uncomplexed alcohol are avoided.43 A potentially valuable methylene-transfer reagent i.e. [Fe(q5-C5H5)(CO),-CH2SMe2]' BF4- is obtained by the methylation of [Fe(q'-C5Hs)-(C0)2CH2SMe] with Me30' BF4-. This reagent is an air-stable crystalline solid which when refluxed with olefins in di~xan,~~ affords cyclopropanes in high yield. Considerable interest is currently being shown in the coupling of unsaturated ligands as induced by transition metals.For example [Ti(q5-C5H5),(CO),] reacts readily with dialkyl ketomalonates (Scheme 11)or with carbodi-imides (Scheme 12) to give coupled ligand~.~~ Scheme 11 RR 2[Cp2Ti(C0)2] + 2RN=C=NR -P' Cp2TidNxI'iCp2 + 4CO \ N RR Scheme 12 The anionic diazabutadiene complex (9) may be oxidized by a variety of reagent^,^' including [Mn(CO)5Br] and Hg2+-H+ to yield a dimeric complex (lo) which contains a metal-metal bond and a bridging ligand (X-ray) that is derived from the coupling of two diazabutadiene moieties. Reductive coupling of benzaldehyde may be achieved via an 'insertion' reaction into the silicon-manganese bond of [Mn(CO)5SiMe3] giving the siloxybenzyl com- plex [Mn(C0),CHPh(OSiMe3)] which decomposes at room temperat~re~~ to [PhCH(OSiMe,)] and [Mn,(CO)lo].Insertion of an aldehyde into a silicon-trans- 43 S. Top and G. Jaouen J.C.S. Chem. Comm. 1979,224. 4.1 S. Brandt and P. Helquist J. Amer. Chem. SOC.,1979 101,6473. 45 M. Pasquali C. Floriani A. Chiesi-Villa and C. Guastini J. Amer. Chem. SOC.,1979,101,4740. 46 L. H. Staal A. Oskam K. Vrieze E. Roosendaal and H. Schenk Inorg Chem. 1979,18,1634. 47 D. L. Johnson and J. A. Gladysz J. Amer. Chem. SOC., 1979,101 6433. Organometallic Chemistry-Part (i) The Transition Elements 26 1 ition-metal bond has been proposed as a key step in Murai’s carbonylation/hydro- silylation ~ynthesis,~ but this has not been previously demonstrated. The spiro[4,5]decane derivative (11)may be obtained via a tricarbonyldienylium iron complex (Scheme 13) and the corresponding spiro[5S]decane system is accessible by a similar r OMe l+ i ii ~ OMeR iii.iv OMe C02Me IMe02C C02Me Me02C Reagents i cH(CO,Me),; ii Me,NO; iii NH,OAc; iv NaH THF Scheme 13 7 Asymmetric Synthesis Catalytic hydrocyanation of norbornene in the presence of [Pd{( + )-DIOP}] gives 2-exo-cyanonorbornene(80%yield). The (1S,2S,4R)-( +)-enantiomer is present in ca. 30% enantiomeric excess and the reaction of norbornadiene under similar conditions gives 2-exo -cyanonorborn-5-ene with ca. 17% enantiomeric excess of the (lR,2R,4S)-enantiomer. 7,7-Dimethylnorbornene does not react however suggesting that the reaction is very susceptible to steric hindrance.49 l-(NN-Dimethylaminomethyl)-2-formylcymantrene (AFCMT) when resolved into its enantiomers is a useful reagent for the asymmetric synthesis of amino- acids.” For example condensation of diglycine with ( + )-AFCMT in the presence of a copper(I1) salt yields an optically active complex.Hydroxyethylation of this complex with acetaldehyde followed by acid hydrolysis gives (R)-threonine (Thr) and (R)-allothreonine (aThr) in 92-98’/0 enantiomeric excess (Scheme 14). Hydroformylation using polymer-supported asymmetric diphosphine-rhodium catalysts5’ is reported to give unique selectivity and optical yields (ca. 30%) comparable to those of homogeneous catalysts. The supported catalysts may be re-used after filtration without loss of activity or selectivity. ‘* A. J. Pearson J.C.S. Perkin I 1979 1255.49 P. S. Elmes and W. R. Jackson J. Amer. Chem. SOC.,1979,101 6128. Yu. N. Belokon I. E. Zel’tzer N. M. Loim V. A. Tsiryapkin Z. N. Parnes D. N. Kursanov and V. M. Belikov J. C. S. Chem. Comm. 1979 789. 51 S. i.Fritschel J. J. H. Ackerman T. Keyser and J. K. Stille J. Org. Chem. 1979 44 3152. H. M. Colquhoun J. Holton and M. V.Twigg (CO3)Mn CH2NMe2 Thr + aThr + Gly HzNCH~CONHCH~CO~H + CU" NMe2 I +.O HC\.,2Cu \ MeCOH \\ 0\\ H o Reagents i MeCHO NaOMe Scheme 14 Asymmetric epoxidation of unactivated alkenes may be achieved by using t-butyl hydroperoxide in the presence of Mo"' catalysts containing optically active diol~,~'" but optical yields are poor (7-14%). Development of this technique may be slow owing to the difficulty of designing suitable chiral ligands that are stable to oxidation.In view of this limitation it is of interest that asymmetric epoxidation has been achieved indirectly via the cyclization of propylene chlorohydrins in the presence of an optically active cobalt complex.52b Optical yields of up to 35% were achieved by a mechanism that apparently involves hydroxyalkyl-cobalt intermediates. 8 Isomerization Examples of rhodium-catalysed migration of a double bond include the clean rapid conversion of (12) into the more substituted isomer (13) by refluxing it in 95% 4 4 ethanol with a small quantity of rhodium tri~hloride.'~ That nickel acetylacetonate (1mole YO)at 165 "Ccatalyses the isomerization of the substituted 2,s-dienone (14) to the fully conjugated 2,4-isomer (15) with high selectivity is of interest since it has economic attraction^.^^ Moreover the catalyst may be recycled without loss of activity." (a)K.Tani M. Hanafusa and S. Otsuka Tetrahedron.Lerters,1979 3017; (6)T. Takeichi M. Ishimori and T. Tsuruta Bull. Chem. SOC.Japan 1979,52,2614. s3 D.F.Taber and B. P. Gunn 3. Org. Chem. 1979,44450. "T.Onishi Y. Fujita and T. Nishida Chem. Letters 1979,765. Organometallic Chemistry-Part (i) The Transition Elements In contrast to the previous use of iron pentacarbonyl for the conversion of trans -steroidal dienes into cis -isomers chromium hexacarbonyl brings about highly regioselective isomerization of steroidal cis-dienes to the trans-isomers. For instance the smooth conversion of ergosterol acetate (16) into ergosteryl B2 acetate (17)is accomplished by refluxing with chromium hexacarbonyl in n-octane.Unlike the cis-diene the trans-diene once formed presumably does not function as a four-electron donor to the chromium centre and so under appropriate conditions the isomerization is effectively irre~ersible.~~ The reaction of allylic acetates with catalytic quantities of [Pd(PPh,),] in refluxing THF can result in rapid positional and stereochemical isomerization. The proposed mechanism involves co-ordination of freed acetate ion to the metal centre followed by stereo-controlled migration to carbon (Scheme 15). Prolonged reaction affords complete conversion into a 1,3-diene with no aromatization. This reaction thus provides a route to 1,3-dienes from allylic acetates.56 In principle two enantiomers could have different reactivities towards chiral isomerization catalysts resulting in selective isomerization of one enantiomer.The COMe I Scheme 15 ” D. H. R. Barton S. G. Davies and W. B. Motherwell Synthesis 1979,265. 56 B. M. Trost T. R. Verhoeven and J. M. Fortunak Tetrahedron Letters 1979,2301. H.M. Colquhoun J. Holton and M. V. Twigg isomerization of racemic 1-olefins to 2-olefins by the homogeneous catalyst (R)-"-dime t hyl- 1-p henyle t hylamine-AIB u',-[Ni(N -me t hyl~alicylideneamine)~] is reporteds7 to constitute just such a reaction. Both the unchanged 1-olefin (e.g. 4-methylhex-1-ene) and the product isomeric (E)-2-olefin are optically active demonstrating that isomerization in the presence of the chiral amine is stereoselec- tive.Although optical purities are low this reaction is an interesting example of the kinetic resolution of a racemic mixture. 9 Metal Clusters In Catalysis There has been much interest in the use of soluble transition-metal cluster compounds as potential models for catalysis on metal surfaces and as possible selective catalysts for organic reactions. X-Ray and n.m.r. studies of the bonding between organic molecules and clusters have provided results relevant to inter- actions at metal surfaces but the tendency of many cluster compounds to fragment in solution means that catalysis by a cluster compound need not be due to the cluster itself. This is particularly true of the more labile cluster compounds of the first-row transition metals.However a rare exampleSs of unambiguous catalysis by such a compound involves [Fe( 77 5-CsH5)(p3-C0)]4(18). This catalyses the selective hydro- genation of terminal acetylenes to olefins (in the presence of olefin or internal acetylene) and of aryl-nitro-compounds to anilines and the hydrogenation of activated terminal olefins. The bridging carbonyl groups in (18) are thought to be responsible for its marked reluctance to fragment. Under reaction conditions the related dimer [Fe(q s-C5Hs)(CO)z]z is converted into inactive [Fe(q5-CSH5)(CO),H] so the cluster (18)itself must be responsible for the observed catalysis. Several anionic nickel carbonyl clusters e.g. [Ni1z(C0)21H]3- are efficient cata- lysts for the linear polymerization of acetylene in a~etone.~' Related platinum clusters are inactive and perhaps nickel-carbonyl fragments are the true active species.Last year several supported-cluster catalyst systems were reported but the activities of supported mixed-metal clusters have only just been described.60 " G. Giacomelli L. Lardicci R. Menicagli and L. Bertero J.C.S. Chem. Comm. 1979,633. '* C. U. Pittman R. C. Ryan J. McGee and J. P. O'Connor J. Organometallic Chem. 1979,178 C48. 59 S.Ceriotti G. Longoni and P. Chini J. Organometallic Chem. 1979,174 C27. 6o R. Pierantozzi K. J. McQuade B. C. Gates M. Wolf H. Knozinger and W. Ruhmann J. Amer. Chem. SOC.,1979 101 5436. Organometallic Chemistry-Part (i) The Transition Elements Phosphinated poly(styrene-divinylbenzene) supports containing [Fe2Pt(CO)8(PhzP-@)2] or [RuPt,(CO),(Ph,P-@),] are long-lived catalysts for hydrogenation of ethylene.Silica-supported [H20s,(CO),(Ph2P-sil)] and [HAu0s3(C0),,(Ph2P-si1)] where sil is silica are inactive for hydrogenation of propylene but they do catalyse the isomerization of but-1-ene. No doubt further reports on supported mixed-metal cluster catalysts will appear. 10 Phase-transfer Catalysis Phase-transfer catalysis using a quaternary ammonium salt or a crown ether as transfer agent is now a much used technique in organic chemistry.61 Recently stoicheiometric and catalytic phase-transfer methods have been successfully exten- ded to reactions of organometallic compounds. Examples include an exceptionally facile synthesis of ferrocene derivatives,62a as well as preparative procedures for ?r-allylcobalt tricarbonyl,62b alkylidynetricobalt nonacarbony1,62b and acyl-cobalt tetracarbonyls.62‘ Phase transfer of hydroxide ion catalyses carbonyl-substitution reactions of metal carbonyls,62d and facilitates the preparation of hydroplatinum compounds.62e More importantly phase-transfer methods allow convenient generation of reactive organometallic species in situ in the synthesis of organic compounds.Fulvenes are obtained by the novel desulphurization and coupling (Scheme 16) of thiobenzophenones with [Fe(q’-C,H,)(CO),]-. The reactive carbonyl may be generated in situ via phase transfer of hydroxide ion a thioketone is treated with [Fe( q5-C5H5)(C0)2]2 aqueous sodium hydroxide benzene and a phase-transfer catalyst.After stirring the mixture overnight at room temperature followed by simple work-up better yields of fulvenes are obtained than when the carbonyl anion is produced by conventional methods.63 Scheme 16 Tetracarbonylferrates are versatile reagents in organic chemistry but their pre- paration from iron pentacarbonyl is time-consuming and care is needed in their manipulation. They can however be conveniently generated in an organic solvent directly from iron pentacarbonyl and aqueous sodium hydroxide under phase-61 C.M. Starks and C. Liotta ‘Phase Transfer Catalysis -Principles and Techniques’ Academic Press London 1978;W. E. Keller ‘Compendium of Phase Transfer Reactions and Related Synthetic Methods’ Fluka AG CH-9470Buchs Switzerland 1979;W.P. Weber and G. W. Gokel ‘Phase Transfer in Organic Synthesis’ Springer-Verlag Berlin 1977. 62 (a)M. Salisova and H.Alper Angew. Chem. Internat. Edn. 1979,18,792; (b)H.Alper H.des Abbayes and D. des Roches J. Organometallic Chem. 1976,121 C31; H.des Abbayes and A. Buloup ibid. 1979 179 C21; (d)K.-Y. Hui and B. L. Shaw ibid. 1977,124,262;(e) M.E.Fakley and A. Pidcock J.C.S. Dalton 1977 1444. 63 H.Alper and H.-N. Paik J. Amer. Chem. Soc. 1978,100,508. 266 H. M. Colquhoun J. Holton and M. V. Twigg transfer conditions. This forms the basis of an efficient synthesis of symmetrical and unsymmetrical ketones from halides.64 Stirring a mixture of benzyl bromide iron pentacarbonyl aqueous sodium hydroxide benzene and transfer agent (tetra- butylammonium bromide) for three hours at room temperatures under an inert atmosphere affords dibenzyl ketone in 94% yield.Similar results were obtained with several substituted benzyl bromides but not with less reactive halides such as benzyl chloride or alkyl bromides. These react with [Fe(CO),] to form the inter- mediate alkyl-iron complex; further reaction with a second molecule of the halide does not take place. The intermediate will however react with a more reactive halide to give an unsymmetrical ketone. Practically this sequential reaction of two halides is an attractive route to unsymmetrical ketones. Catalytic carbonylation involving [Co(CO),]- is the basis of several synthetically useful reactions that are normally carried out using relatively high pressures of carbon monoxide.It has been demonstrated that [Co(CO),]- can be generated from [Co,(CO),] and hydroxide ion under phase-transfer conditions allowing the smooth conversion of benzyl halides into carboxylic acids in good yield at atmospheric pressure and room tempera- t~re.~’ A variety of conjugated dienes and trienes undergo regiospecific acylation66 with methyl iodide carbon monoxide and a catalytic amount of [Co(CO),]- (generated via phase transfer). Analogous reactions with alkynes afford hydroxy- b~tenolides.~’ For instance 1-vinylcyclohexene is acylated only at the least substi- tuted carbon of the diene to give the (E)(trans)-isomer (19) in 60% isolated yield; l-phenylbuta-1,3-diene is acylated at the 4-position to give the (E)-product (20) (86%).It is thought that this reaction proceeds via 1,2-addition of [MeCOCo(CO),] to the least substituted double-bond of the diene (or triene). Loss of carbon monoxide from the metal then leads to formation of a P-keto r-ally1 complex e.g. (21). Subsequent deprotonation of the acidic methylene and removal of the cobalt carbonyl fragment in the presence of carbon monoxide gives the thermodynamically stable (E)-isomer with regeneration of [Co(CO),]-. %COMe ph+COMe H (CO)~CO H The inexpensive hydrogenation catalyst K,[Co(CN),H] has not found widespread application owing to its insolubility in organic solvents. However the use of K,[Co(CN),H] under phase-transfer conditions allows a variety of conjugated carbon-carbon bonds to be selectively hydrogenated.68 Only trans-pent-2-ene (80% yield) was obtained from penta-1,3-diene and hydrogenation of 2,3-dimethylbuta-1,3-diene afforded a mixture of 2,3-dimethylbut-2-ene (80%) and 2,3-dimethylbut-1 -ene (20%).ap-Unsaturated ketones react less rapidly but with 64 Y. Kimura Y. Tomita S. Nakanishi and Y. Otsuji Chem. Letters 1979 321. 65 L. Cassar and M. Foa J. Organometallic Chem. 1977,134 C15; H. Alper and H. des Abbayes ibid. 1977,134 C11. 66 H. Alper and J. K. Currie Tetrahedron Letters 1979,2665. ” H. Alper J. K. Currie and H. des Abbayes J.C.S. Chem. Comm. 1978,311. D. L. Reger M. M. Habib and D. J. Fauth Tetrahedron Letters 1979 115. Organometallic Chemistry-Part (i) The Transition Elements high selectivity.The conjugated carbon-carbon double bond in 1-carvone (22) is hydrogenated almost quantitatively. Miscellaneous uses of phase-transfer catalysis in synthesis via organometallics include the nickel(0)-catalysed cyanation of aromatic halides.69 It is claimed that phase-transfer conditions are more convenient and produce better yields than conventional methods. It may be expected that more examples of this technique will be reported in the future and that continued progress (e.g. in the selection of an appropriate organic solvent and transfer catalyst to optimize yields) will be made in this growth area. 11 Miscellaneous A novel ketone synthesis involving the formal addition of an aldehyde C-H bond to an alkene has been described by Suggs." The aldehyde is first converted into an aldimine which adds readily to [Rh(PPh3)3Cl] yielding an iminoacyl-rhodium(II1) hydride complex.The reaction of the latter with an alkene followed by hydrolysis affords a ketone in up to 80% yield. The reaction can be catalytic in rhodium (Scheme 17). Cycloaddition of butadiene and dialkyl-ynamines is catalysed by the iron(o) complex [Fe(cycl~-octatetraene)~], and affords cyclohexa-l,4-dienaminesin up to 80% yield. Other catalysts such as CuCl or PdC12 cause dimerization of the Scheme 17 69 L. Cassar M. Foa F. Montanari and G. P. Marinelli J. Organometallic Chem. 1979,173,335. 'O J. W.Suggs J. Amer. Chem. SOC. 1979,101,489. 268 H. M. Colquhoun,J. Holton andM.V. Twigg ynamine while [RuH2(PPh3),] results in polymerization of the latter under the same condition^.^^ The cyclization of pent-4-enylamines occurs regiospecifically in the presence of [PtCl4I2- giving pyrrolidine derivatives in good yield. The proposed mechanism involves intramolecular nucleophilic attack on a co-ordinated double bond followed by cleavage of the resulting metal alkyl by acid." Synthesis involving Iron Carbony1s.-Iron carbonyl species have many potential uses in organic synthesis and being readily available at moderate cost they can be attractive reagents. Two reports illustrate their practical utility. The final stage of one to the synthesis of aphidicolin (a diterpenoid tetraol with strong activity against Herpes virus) was accomplished by direct carbonylation/ring expan- sion of the tosylate derivative (23) with [Na2Fe(C0)4].This procedure afforded the desired cyclohexanone (24) which had previously been transformed into aphidi- Colin. The trapping of reactive 2-oxyallyliron(11) intermediates (derived from bromo-ketones and an iron carbonyl) with monoenes or 1,3-dienes is an efficient route to cyclopentanones and cycloheptenones respectively (for a review see ref. 2). This procedure has been extended74 to intramolecular reactions and provides a new route to polycyclic terpenes. This ring-closure is illustrated by the formation of a 2 :1 mixture of (*)-campherenone (26) and (&)-epicampherenone (27) in 58% yield from the dibromo-ketone (25) in the presence of one mole equivalent of [Fe(C0)5] at 100 "C (Scheme 18).xo (25) Scheme 18 71 J. P. Genet and J. Ficini Tetrahedron Letters 1979 1499. '* J. Ambuehl P. S. Pregosin L. M. Venanzi G. Consiglio F. Bachechi and L. Zambonelli J. Organo-metallic Chem. 1979 181 255. 73 J. E. McMurry A. Andrus G. M. Ksander J. H. Musser and M. A. Johnson J. Amer. Chem. SOC., 1979 101,1330. 74 R.Noyori M. Nishizawa F. Shimizu Y. Hayakawa K. Maruoka S. Hashimoto H. Yamamoto and H. Nozaki J. Amer. Chem. Sac. 1979,101,220. Organometallic Chemistry-Part (i) The Transition Elements This intramolecular [3 +41 reaction (i.e. employing a dibromo-keto-diene) also permits direct synthesis of the oxidoperhydroazulene skeleton. Although yields from these intramolecular reactions are not very high it may be expected that in some instances the approach will be of value.The cluster hydride [Et,N]'[HFe,(CO) is readily prepared7' from iron pentacarbonyl but unlike tetracarbonylferrate salts it has the advantage of being stable in air and can be stored indefinitely at room temperature. Treatment of a range of aromatic nitro-compounds with this reagent produces anilines in excellent yield; aldehydes are not reduced and ring dechlorination is not important. Double bonds in cup -unsaturated carbonyl compounds are selectively reduced. Palladium Chemistry.-Palladium complexes are versatile reagents in organic synthesis and this is clearly demonstrated in a simple synthesis of (&)-pyre- thr~lone,~~ which is a component of naturally occurring pyrethroids.Three different palladium-catalysed reactions (see Scheme 19) are used to produce the key inter- mediate octa-5,7-dien-2-one (28) from butadiene and phenol. The mixture of the isomers of (28) is then readily converted into (E)-and (2)-pyrethrolone which can easily be separated. 0 A@-' OPh Reagents i [Pd(PPh,),CI,] PhONa; ii PdCl, CuCl; iii [Pd(OAc),] PPh3 Scheme 19 Simple organo-palladium chemistry (oxidative addition and insertion of carbon monoxide) has been used to advantage in developing a new route to butenolides from acetylenic alcohol^.'^ The acetylene alcohol is first converted into the corresponding vinyl iodo-alcohol (29) which is then catalytically converted into the butenolide (25 "C;3 atm; 2 days); see Scheme 20.Good overall yields are generally achieved and because of the mild conditions a wide variety of functional groups can be tolerated. 75 G. P. Boldrini A. Umani-Ronchi and M. Panunzio J. Organometallic Chem. 1979,171,85. 76 J. Tsuji T. Yamakawa and T. Mandai Tetrahedron Letters 1979 3741. 77 A. Cowell and J. K. Stille Tetrahedron Letters 1979,133. H. M. Colquhoun J. Holton and M. V. Twigg R' \ R' R' HO HO R2 (29) H R2 H J Pdo lbase I-Pd-H + I The synthon 2-acetoxymethyl-3-trimethylsilylprop-1-enereacts with olefins bearing electron-withdrawing in the presence of a palladium(0) catalyst to produce cyclopentane systems (Scheme 21). Yields of 50-85% are achieved with olefins bearing ester nitrile ketone or sulphone substituents but simple alkyl- substituted or electron-rich olefins fail to react.This reaction is equivalent to the addition of trimethylenemethane to olefins and may be compared with the cyclo- addition of methylenecyclopropane or metal-trimethylenemethane complexes to olefins -reactions which are synthetically unattractive. This simple one-step approach to cyclopentane annulation should prove more useful. Scheme 21 Another route to five-membered rings has been reported uia palladium (11)--promoted intramolecular cyclization of silyl enol Using the silyl enol ether of an alkenyl methyl ketone the cyclic ap-unsaturated ketone may be prepared. For example 2-trimethylsilyloxy-hexa-1,5-dieneis converted into 3-methyl-2-cyclo- pentenone (87%)by an equimolar amount of [Pd(OAc),] in acetonitrile.A variety of silyl enol ethers were successfully used but attempts to prepare six-membered rings or larger gave poor yields. '* B. M. Trost and D. M. T. Chan J. Amer. Chem. SOC.,1979,101,6429. 79 Y. Ito H. Aoyama T. Hirao A. Mochizuki and T. Saegusa I Amer. Chem. SOC.,1979 101,494.

ISSN:0069-3030    

DOI:10.1039/OC9797600251

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

12 Organometallic Chemistry Part (ii) Main-Group Elements By J. L. WARDELL Department of Chemistry University of Aberdeen Meston Walk Old Aberdeen A59 2UE 1 Introduction An authoritative review of the synthetic uses of a-metallated isocyanides has appeared.' A comprehensive survey of the preparation of aryl- and heteroaryl- trimethylsilanes was made topics covered the direct C-Si coupling cycloaddition modification of silyl-aromatics by incorporation of further functional groups and conversion of existing substituents.2" Another useful review on organosilanes was concerned with electrophilic substitution.26 Among the points covered in a review on the stereochemistry of organo-arsenic compounds were configurational stability and the energy barriers to inversion of asymmetric amine~.~ Several methods of direct synthesis were also reported with direct electrochemical synthesis being re~iewed.~ This method has been successfully used for Cd Zn Hg Al In and Sn derivatives.The low-temperature co-deposition of metal vapours with solvents in high excess followed by warming and subsequent partial re-clustering of metal atoms allows preparations of very active metal atoms in the form of slurries to be made; organometallic derivatives of Cd Zn Al In Sn and Pb were readily obtained from these slurries and organic halides.' Another synthesis is the co- condensation of reactive free radicals [e.g.CH3* and CF3-; produced from C2H6 and C2FG by radio-frequency glow discharge] with metals at -196 "C; derivatives of Cd Hg Bi Ge and Sn were so prepared.6 2 Group1 Ab initiu M.O.calculations (STO-3G) were made on pentaco-ordinate cations CH3M2'(M = Li and Na as well as BeH and MgH). The structures (l),of symmetry C, can be envisaged as models for electrophilic substitutions occurring with reten- tion while the D3hstructure (2) is a model for processes that occur with inversion. The DJh form was calculated to be the more stable for CH3Li2+ a species that is U. Schollkopf Pure Appl. Chem. 1979,51 1347. (a) D. Habich and F. Effenberger Synthesis 1979,841;(6) T. H. Chan and I. Fleming ibid. p. 761. F. D. Yambushev and V. I. Savin Russ. Chem. Rev. 1979,48,582. D. G. Tuck PureAppl. Chem. 1979,51,2005. K. J. Klabunde and T. 0.Murd0ck.J. Org. Chem.1979,44,3901. T. J. Juhlke R. W. Braun T. R. Bierschenk and R. J. Lagow J. Amer. Chem. Soc. 1979,101,3229. 272 J. L. Wardell known in the gas phase. The results suggest (i) that three-centre two-electron bonds may favour linear over cyclic arrangements and (ii) electrophilic aliphatic substitu- tion may proceed either with retention or inversion of configuration depending on the circ~mstances.~" It was also pointed out that a second-row substituent e.g. M =Na stabilizes methyl cations CHzM' more effectively than does its first-row counterpart .7 H M-C-MI+ H H-..I MC+' H' 'M (2) D3h The stabilizing influence of Li substituents on strained or unsaturated molecules such as ethylene cyclopropane acetylene and various bi- and poly-cyclic species was calculated (STO-3G basis sets) to be significant; e.g.the strain in tetra- lithiotetrahedrane (3) was calculated to be less than one-fourth of that in tetra- hedrane itself.' The compound Li& (3) reported last year9 to be produced by photolysis of Li2C2 reacts with Me1 to give a species having all the properties expected of tetramethyltetrahedrane." von Schleyer" also looked at the structures energies and bonding of lithium-substituted allenes propynes and cyclopropenes by ab initio methods. The most stable arrangements involve acetylidic and bridging lithium atoms; e.g. allenyl-lithium has a bent carbon skeleton which accommodates simultaneous bonding of Li to C-1 and to C-3 as shown in (4) but not to the nearest atom C-2; for C,Li4 (5) H there are two such bridging lithium atoms and two acetylide-type lithium atoms.The carbenoid CHF,Li is suggested (from ab initio calculations) to exist in three isomeric forms (i) a CHF2- Li' ion-pair (ii) a CHFLi' F-ion-pair (6) and (iii) (the least stable) a CHF.LiF complex; i.e. none has a classical structure that contains tetra- hedral carbon." The 13C n.m.r. spectra of carbenoids (7) CBr3Li and MeCBr,Li all labelled with 13C at the carbenoid centre were recorded at -100°C in THF solution. From the CBr3Li spectrum three compounds could be dete~ted;'~ these ' (a) E. D. Jemmis J. Chandrasekhar and P. von R. Schleyer J. Amer. Chem. SOC.,1979 101 527; (6) T. Clark and P. von. R. Schleyer Tetrahedron Letters 1979,4641. J. D. Dill A.Greenberg and J. F. Liebman J. Amer. Chem. SOC.,1979,101,6814. M. G. Hutchins Ann. Reports (B),1978 75 120. lo N. S. Zefirov V. N. Kirin N. M. Yur'eva A. S. Koz'min N. S. Kulikov and Yu. N. Luzikov Tetrahedron Letters 1979 1925. E. D. Jemmis J. Chandrasekhar and P. von R. Schleyer J. Amer. Chem. SOC.,1979,101,2848. T. Clark and P. von R. Schleyer Tetrahedron Letters 1979,4963. l3 D. Seebach H. Siegel K. Mullen and K. Hiltbrunner Angew. Chem. Internat. Edn. 1979 18 784; H. Siegel K. Hiltbrunner and D. Seebach ibid. p. 785. Organ om eta llic Chemistry-Pa rt (ii ) Main -Group Elements Br Br-.. I Br.. ,C-Li ,CLLi,Br- Br Br Br (7) n=4or6 (8) (9) were the carbene :CBr2 and two CBr,Li species one having tetrahedral carbon and the other (more stable) either like (8) or (9),i.e.analogous to (6). All carbenoids exhibit large downfield shifts of the carbenoid carbons. Previously a preparation of primary alkyl-lithiums from olefins (Scheme 1)was reported; now a complement to it -the preparation of secondary or tertiary alkyl-lithium from the same olefins (Scheme 2) -has been p~b1ished.l~ R'R2C=CH2 + PhSH i,R'R2CHCH2SPh R'R2CHCH2Li Reagents i Radical initiator; ii Li THF Scheme 1 R'R~C=CH~+ PhSH 4R'R2C(SPh)CH2 R'R2CL,CH2 Reagents i HCIO,; ii Li THF Scheme 2 The relative ortho-directing ability of groups Y in aromatic lithiations has been further studied," both intramolecularly using YC6H4CONEt2 (1O) and inter- molecularly involving competition between phenyloxazoline and PhY for BuLi.After suitable trapping the metallation of (10) by Bu"Li and tetramethylethyl- enediamine in THF at -100°C indicated CONEt2 to be superior to S02NEt2 oxazoline MeO Me2NCH2 C1 C02H and Me in directing lithiation to an ortho-position. In the intermolecular reactions a sequence of ortho-directing ability was established as Me2NS02 >CONEt >oxazoline>CH,NMe anion crossover was detected e.g. between the compound o-LiC6H4C=NCMe2CH2 and PhS02NMe2. d Metallation of the acetal (H-2) protons in 1,3-dioxolans,l,3-dioxans,and open- chain acetals is only possible if the proton can occupy an equatorial-like con- formation; i.e. a preferred equatorial deprotonation even in the case of a carbanion a to oxygen.16 A hydroxyl substituent activates cyclopropanes towards metallation by Pr'Li; the major product of reaction of cyclo-C3H5CHR(OH) after carboxyl- ation,17 was cis-1-RCH(0H)-2-HO2C-cyclo-C3H4 the other products being the trans-isomer and l-RCH(OH)-l-H02C-cyclo-C3~.Lithiation of (E)-R'SCH=CHCH2XR2 (11; X = 0 or S) by BuLi occurs18 at the sp3 carbon; in contrast lithiation of (11;R'=Ph XR2=NMe2) happens as shown in Scheme 3. l4 C. G. Screttas and M. Micha-Screttas J. Org. Chem. 1979,44713. l5 (a) P.Beak and R. A. Brown J. Org. Chem. 1979,44,4463; (b) A. I. Meyers and K. Lutomski ibid.,p. 4464. l6 A. I. Meyers A. L. Campbell A. G. Abatjoglou and E. L. Eliel Tetrahedron Letters 1979,4159. G.W.Klumpp M. Kool,M. Schakel R. F. Schmitz and C. Boutkan J. Amer. Chem. SOC.,1979,101 7065. '* J.J. Fitt and H. W. Gschwend J. Org. Chem. 1979,44303. '"n J. L. Wardell PhS H BuLi H/-CNMe __* Li ---NMe Scheme 3 R'CH~ CHR2R3 H \/ i ii \C=N H/C=N R1R4C/H \CHR2R3 Reagents i LiNPr',; ii R4X Scheme 4 The lithiation and alkylation (Scheme 4) of aliphatic aldimines has been shown to give a ratio of syn-to anti-products of 96:4. This is interpreted as representing a minimum value for the syn :anti ratio of the lithiated aldimine intermediates." The factor responsible for the preferential syn stabilization though not yet identified is determined to be >18 kJ mol-'. Complete regiochemical control2' pertains in the generation of alkenyl-lithiums from arenesulphonylhydrazones(e.g. Scheme 5). Me Me Li \C=N-NHS02Ar & \C=N -5 \c=c / H / /\ C5HllCH2 CSHIlC/H \NS02Ar Me C5H1I I I Ar =~,~,~-PI-'~C~H~ Li Li Reagents i Bu'Li at -78 "C,THF; ii 0 "C Scheme 5 Transmetallation of allyl-tin and -lead compounds by organolithiums continues to be a most useful source of unsymmetrically substituted allyl-lithiums; the utility of the method is enhanced by development of new allylic-tin species uia Wittig-style reactions.21 Another source of allyl-lithiums i.e.the conrotatory ring-opening of cyclopropyl-lithiums (e.g. see Scheme 6) has also attracted further attention. The ring-opening of (12; X =CN) to endu,endo-and exu,exo-(13) proceeds at a slower rate than the isomerization of the latter to the thermodynamically more stable isomer exo endo-(13). Percentages of equilibrium conformations and rotational barriers in X 'H H\ 4c.y / -C -C + exo,exo-(13) H Ph / \ Ph Li+ Ph (12) endo,endo-(13) X =H alkyl aryl or CN Scheme 6 l9 R.R. Fraser and J. Banville J.C.S. Chem. Comm. 1979 47. *O A.R.Chamberlin and F. T. Bond Synthesis 1979,44. 21 D.Seyferth and R. E. Mammarella J. Organometallic Chem. 1979 177 53; D.Seyferth and K. R. Wursthorn ibid. 1979,182,455;B. Mauze ibid. 1979 170,265. Organometallic Chemistry-Part (ii) Main-Group Elements these and other allyl-alkali-metal compounds were determined. The potential steric congestion in the endo,endo-isomers is not realized as the rings adopt a cyclophane- like conformation; in addition an expansion of the angles at sp2carbon atoms of ally1 occurs." The dynamic behaviour and structure of propyl-lithium enriched with I3C and 6Li was studied by n.m.r.spectroscopy. An advantage of using 6Li is that its quadrupole relaxation is too slow (unlike that of 7Li) to perturb the spectra. The hexamer undergoes fast intra-aggregate C-Li bond exchange to at least -80 "C and inter- aggregate exchange at higher temperatures. Evidence was also gained for different species at lower temperature^.^^ 3 Group2 Interestz4 in (cyclopentadienyl)zberylliumremains high. New electron-diff raction data at 120" were interpreted as being compatible with a C, symmetry and in particular with a slipped sandwich (or pentahapto trihapto) model e.g. (14) -a angle between C5H5 planes = -.4(3)" (14) structure similar to that obtained by X-ray diffraction in which d3was shown to be 1.2 A but not compatible with D5dsymmetry or [v-C5H5 a-C,H5] structures.The potential energy of the molecule was found not to alter much as d3changes between 0 and 1.2 A. Ab initio calculations with a double-5 basis were also carried out. Lower energies are obtained for the [?r-C5H5 a-C5H5] and D5dmodels in keeping with various earlier calculations but clearly in conflict with the electron-diffraction data. Ionization potentials obtained from the He (I) photoelectron spectrum were compared with the calculated orbital energies satisfactory agreement being found for the slipped sandwich structure. The Raman spectra of solid (at -100 and 25 "C) and liquid [(C5H=J2Be](at 65 "C)also suggested the presence of 'IT-bonded rings -one pentahapto and the other polyhapto.Allylic magnesium compounds and benzyne generated in situ undergo three competing reactions (a)nucleophilic addition (b) ('IT' + T') and (C) (7r4+'IT') cycloadditions (Scheme 7). With cyclohexyne only nucleophilic additions result.* While the addition of R'MgX (R1= alkyl or aryl) to [BrMgC_CCHR20MgBr] (Rz=H or Me) in the presence of Cu'X provides 22 G. Boche K. Buckl D. Martens D. R. Schneider and H. U. Wagner Chem. Ber. 1979 112 2961; G. Boche K. Buckl D. Martens and D. R. Schneider Tetrahedron Letters 1979,4967;T. B. Thompson and W. T. Ford J. Amer. Chem. Soc. 1979,101 5459. 23 G. Fraenkel A. M. Fraenkel M. J. Geckle and F. Schloss J. Amer. Chem. SOC.,1979,101,4745. 24 A. Almenningen A.Haaland and J. Lusztyk J. Organometallic Chem. 1979,170,271; R. Gleiter M. C. Bohm A. Haaland R. Johansen and J. Lusztyk ibid. p. 285; J. Lusztyk and K. B. Starowieyski ibid. p. 293. 25 J. G. Duboudin B. Jousseaume and M. Pinet-Vallier J. Organometallic Chem. 1979,172 1. 276 J. L. Wardell Scheme 7 [(BrMg),C=CR1CHR20MgBr] allylmagnesiurn bromide26 produces the cyclized material (15). The carbomagnesiation of the unsaturated alcohols. Ph2(HO)C(CH2),CH=CHz (16; n = 0 1 2 or 4) and of cycloalkenols e.g. (2-cyclohexenyl)diphenylcarbinol(17) occurs using RMgX (R = alkyl PhCHz or But) and [(allyl)2Mg] but not with primary alkyl- or aryl-magnesium~.~~ The reaction is catalysed by Ni but is retarded in THF or if amines are present. The order of reactivity ofcompounds (16) was established as n = 1> 0 >> 2 >> 4.The mechanism of the uncatalysed reaction of (17) with [(CH2=CHCH2)MgX] is shown in Scheme 8,in OH OMgCH2CH=CH2 / Ph'Cb4 & Ph,,cI^ / -Ph,C /&CH ,CH=CH Reagents i CH,=CH2MgX. Scheme 8 which a unirnolecular cisaddition (with respect to the OH group) occurs.z7 The Grignard reagent (1 8) from MeCHCICHzCHMeCH=CHz cyclizes reversibly in ethereal solutions to stereoisomers of (19); at 100 "C,in THF the equilibrium constant K(= [(19)]/[(18)]) is 3.4 with a forward rate constant of 6.8 x s; these values comparez8 with those for the unsubstituted cyclobutylmethylmagnesiurn & &CH2MgCl BrMgb CHR20MgBr Me MgCl Me (15) (18) (19) 26 J.G. Duboudin and B. Jousseaume Synth. Comm. 1979,9,53. " J. J. Eisch and J. H. Merkley,J. Amer. Chem. SOC.,1979,101 1148; J. J. Eisch J. H. Merkley and J. E. Galle J. Org. Chem. 1979,44,587. E.A.Hill and M. M. Myers J. Organometallic Chem. 1979,173 1. Organ ome tallic Chemistry -Part (ii) Ma in -Group Elements 277 system of 0.94 x and 2 x s. Compounds R1MgOR2 (20) as well as the zinc and aluminium analogues decompose on heating to an alkane R'H an olefin R2H and the metal oxide,29 in a process involving a cyclic six-centred transition state; e.g. methylmagnesium-threo- 1,2-diphenyl-1 -propoxide produces exclusively (2)-diphenylpropene. As (20) is produced from R12Mg and an alcohol the process is in essence a useful method of dehydrating alcohols.29 OMgX R'MgX + R'R'CHCO Scheme 9 The reactivity of R'MgX in the enolization of ketones e.g.as shown in Scheme 9 was established as R' = Et >Pr' >Me >> But and is a consequence of both steric and electronic factors. The reaction involved co-ordination of R'MgX to the ketone and subsequent rate-determining removal of hydrogen from the a-carbon in a six-membered transition Results from a detailed study of the reaction of PhCH2MgCl with H2C0 indicate that it is not the paradox as often stated but has many features in common with other aldehyde-benzyl-Grignard reactions; the products in yields that are dependent on the condition^,^' are o-Me2C6H4CH20H 0-HOCH2CH2C6H4CH20H,and PhCH2CH20H. Several T-arene complexes of cadmium@) and zinc(@ i.e.[M2+(ArH)] have been isolated from solutions of [Cd(AsF,),] [Cd(SbF6),] and [Zn(SbF6),] with methylbenzenes in liquid SO2. Related species [Hg2+(ArH),] (n = 1or 2) have also been prepared. Such complexes are sensitive to water and organic solvents. Stability constants for the complexes [Cd(AsF&.ArH] are smaller than those of [Hg2(ArH)]" and [Hg(ArH)]" and are in the range 0.5-2.1 1 mol-'. Localized bonding of the arene to the metal is indicated from 'H and 13C n.m.r. data; complexation generally produces deshielding of the '13Cd resonance.32 The first well-characterized organo-mercury(1) derivatives (21) have been described33 (Scheme 10). The corresponding Hg" ketenides (22) are similarly AcOHg-Hg H+ \ 2Hg2X2 + Ac20 3 /c=c=o XHg-Hg (21) AcOHg H+ \ 2HgX2+Ac20 -/ c=c=o X = OAc NO3 or C104 Scheme 10 29 E.C. Ashby G. F. Willard and A. B. Goel J. Org. Chem. 1979 44 1221. 30 A. G. Pinkus and W. C. Servoss J.C.S. Perkin ZZ 1979 1600. 31 R. A. Benkeser W. DeTalvo and D. Darling J. Org. Chem. 1979,44 225. 32 L. C. Damude and P. A. W. Dean J. Organometallic Chem. 1979,168,123; 1979,181 1. 33 E. T. Blues D. Bryce-Smith and H. Karimpour J.C.S. Chem. Comm. 1979 1043. 278 J. L. Wardell prepared (Scheme 10). Complexes (21) and (22) [i.r. v(CC0) ca. 2070(s) v(HgC) 276(m) and v (CCO) 62O(w)] are probably polymeric being involatile infusible and insoluble species and (happily) non-explosive except for X = C104. Reactions with dilute hydrochloric acid [providing Hg"' (n = 1 or 2) from (22) or (21)] with hydrogen chloride gas [producing keten and AcCl] and with bromine {giving [(XHg,)(AcOHg,)CBrCOBr];X = c104,n = 1 or 2 from (22) or (21)} as well as thermolysis (to C20) all support the proposed formulae.The secondary deuterium isotope effects in the intramolecularly competing methoxymercuriation of CH2=CD2 (23) (Scheme 11)and cis-MeCH=CDMe were CH2=CD2 -+ [MeOCH2CD2HgC1] + [MeOCD2CH2HgCl] (23) CY P Reagents i [Hg(OAc),] MeOH; ii NaCl Scheme 11 determined from the isomer ratios a :p to be 1.12 and 1.06 respectively. These values indicate that the transition states do not have symmetrical structures as do mercurinium ions but have appreciable C-0 bonding.34 4-Alkyl-cyclohexenes undergo oxymercuriation-demercuriation in a remarkedly stereoselective but non- regioselective manner; for 3-alkyl-cyclohexanes both a stereo- and regio-selectivity results.35 Organomercury complexes of guanosine (24) (GLH,; R = NH2) and related species including inosine (24; R = H) were amongst those Infrared (24) R = ribosyl spectra of solids prepared from MeHgNO or PhHgOH (R'HgX) at an appropriate pH as well as n.m.r.spectra in (CD,),SO solutions indicated that the binding sites were at N-1 for [RIHg(LH)] at N-7 for [R1Hg(LH2)]N03 and at both N-1 and N-7 for [(R'Hg)2(LH)]N03. In addition to these 1 1and 2 1species a 3 1complex i.e. [(MeHg),L]N03 (binding at N-1 N-7 and C-8) can be obtained either on heatingor on prolonged standing of solutions at pH 7 containing ratios of MeHgNO to LH2 of 3 1.The hydrogen attached to C-8has enhanced acidity owing to the co-ordination of MeHg at the adjacent N-7. The following conclusions were obtained from a study of the reduction of organo-mercury(I1) compounds by sodium dithionite (i) for simple alkyls the predominant reaction is a one-electron reduction to give an alkyl radical with the loss of any enantiomeric resolution possessed by prochiral substrates (ii) for aryl substrates symmetrization results and (iii) for oxymercurials reversion to an alkene 34 S. Shinoda M. Isemura and Y. Saito Bull. Chem. SOC.Japan 1979 52 1855. 35 H. C. Brown G. J. Lynch W. J. Hammar and L. C. Liu J. Org. Chem. 1979,44 1910. 36 E. Buncel A. R. Norris W. J. Racz and S. E. Taylor J.C.S. Chem. Comm. 1979,562; A.J. Canty and R. S. Tobias Inorg. Chem. 1979,18 413. Orga nom eta 11ic Chemistry -Part (ii) Main -Group Elements occurs.37 The reaction of oxymercurials with H2C=CHR (R = CN CO,Et or Ph) in the presence of [NaBH(OMe)J leads38 to the replacement of HgX by CHzCH2R (Scheme 12). + H2C=CHR + [NaBH(OMe),] -Scheme 12 4 Group3 A theoretical study using double-l basis sets was made on the complex between an aluminium atom and acetylene whose e.s.r. spectrum had previously been obtained at liquid-helium temperatures and interpreted as arising from a CT-bound complex. However the most stable of the bound isomers was calculated to be the vinylidene structure (25) (binding energy ca. 20 kcal mol-') while the cis-(and trans-)- AlCH=CH species (26) had a binding energy of only ca.8 kcal mol-'. A resolution of this apparent conflict was suggested3' to be that at the temperature of liquid helium there is insufficient energy to overcome the barrier of the 1,2-hydrogen shift required for conversion of (26) into (25). Matrix-isolation techniques were used to obtain the complex between an aluminium atom and benzene.40 It was deduced that A1 complexes with one of the C=C units of the ring. H A1'\c=c. AI-C=CH~ \H (25) (26) Hydroalumination of alkynes by [HA1(NR2)J in the presence of [Cp2TiC12] as catalyst in benzene occurs stereospecifically with cis- addition; e.g. from PhC=CMe,(E)-[PhCH=CMeA1(NR2),] (10%)and (E)-[(R2N),A1(Ph)C=CHMe] (90%) were obtained. The regiochemistry of the product(s) is determined by that of the intermediate alkynyl-titanium Carbometallation of certain alkynols can be accomplished under mild conditions with transition-metal-organo-aluminiumsystems; e.g.[Et2AlCl] [Cp2TiC12] and HC=CCH2CH20H at 0 "C provides after hydrolysis trans-EtCH=CHCH2CH20H and CHz=CEtCH2CH20H in a 1:1ratio. Changing the catalyst to the more bulky and less readily reduced [(q5-MeC6H4)2TiC12] increases the overall yields but without having much effect on the regio~electivity.~~ Organo-zirconium(1v) complexes have been as precursors of organo- aluminiums (Scheme 13). The transmetallations occur more readily for alkenyl than 37 L. M. Sayre and F. R. Jensen,J. Org. Chem. 1979,48 228. 38 B. Giese and K. Heuck Chem. Ber. 1979,112,3759,3766.39 M. Trenary M. E. Casida B. R. Brooks and H. F. Schaefer J. Amer. Chem. SOC.,1979,101 1638. 40 P. H. Kasai and D. McLeod J. Amer. Chem. Soc. 1979,101 5860. 41 E. C. Ashby and S. R. Noding J. Organometallic Chem. 1979,177,117;see also J. Org. Chem. 1979,44 4364. 42 D. C. Brown S. A. Nicholas A. B. Gilpin and D. W. Thompson J. Org. Chem. 1979,44 3457. 43 D. B. Carr and J. Schwartz J. Amer. Chem. Soc. 1979,101 3521. 280 J. L. Wardell c1 [CpzZr(H)ClI__* CpzZr' -% [CpzZrClz]+ (RAICl2) 'R Reagents i alkene or alkyne; ii AlCl Scheme 13 alkyl substituents and proceed predominantly with retention of configuration at carbon. Acyl groups can also be transferrred. Silica-supported titanium chloride and polystyrene-supported titanocene dichloride have been to catalyse the hydroalumination of alkanes and dienes by LiA1H4.Racemic l-olefins are iso- merized by the homogeneous catalytic system (R)-NN-dimethyl- l-phenyl- ethylamine-A1Bu'3-nickel(N-methylsalicylideneamine)z:both the unchanged 1-olefins and the (E)-2-olefins that are formed are optically active indicating that the reaction is stereoselective; e.g. EtCPhHCHzCH=CHz is 35% isomerized to (-)-(R)- (E)-EtCPhHCH=CHCH3 (0.24% optical purity) with the unchanged l-olefin having a (+)-(S)config~ration~~ (0.12% optical purity). Cyclopropylmethyl allylic and benzylic acetates are alkylated by trialkyl-aluminiums in CHzCl2 solution at room temperature; carbo-cationic intermediates have been detected.46 Esters may be converted into amides by treatment with R'zA1NR2z; thus m-N02C6H4C02Me and [EtzA1NH2] from [Et,Al] and NH3 produced rn-NozC6H4CONH2 in 91'/o yield.47 Thallium(II1) tris(trifluoromethylsu1phonate)is much more effective in aromatic thallati~ns~~ than is [Tl(OCOCF,),]; mono-thallation of polyfluoro-benzenes readily occurs using [Tl(OSO,CF,),] in CF3CO2H.Oxythallation of norbornene deriva- tives using [Tl(OAc),] in MeOH provides cis-exo-acetoxythallated adducts (27),in contrast to the analogous reaction of the mercury compound which leads to the methoxy-derivatives. Treatment of the adducts (27) with NaBH4 provides olefins and some exo-al~ohols.~~ 5 Group4 The preparation and spectroscopic characterization of the elusive species dimethyl- silylene MezSi (28) has been achieved.Irradiation at 254 nm of (MezSi)6 in rigid hydrocarbon glasses at 77K produces singlet silylene (28) (Y= 1220cm-' A, =453 nm). Trapping of (28) by various agents including hexene but not MezSi(OMe)* was possible. Irradiation of (28)with visible light led to the formation of 2-silapr0pene.~' As well as the usual traps for silylenes e.g. P-diketones and alkene~,~' a silylene such as (28) can be trapped as its dimer MezSi=SiMez by anth~acene;~~ thus heating 2,3-dibenzo-7,7-dimethyl-1,4,5,6-tetraphenyl-7-.UF. Sato H. Ishikawa Y. Takahashi M. Miura and M. Sato Tetrahedron Letters 1979 3745. 45 G. Giacomelli L. Lardicci R. Menicagli and L. Bertero J.C.S. Chem. Comm. 1979,633. 46 A. Itoh K. Oshima S. Sasaki H. Yamamoto T. Hiyama and H. Nozaki Tetrahedron Letters 1979,4751.47 J. L. Wood N. A. Khatri and S. M. Weinreb Tetrahedron Letters 1979,4907. 48 G. B. Deacon and D. Tunaley Austral. J. Chem. 1979,32,737. 49 S. Uemura H. Miyoshi M. Okano I. Morishima andT. Inubushi J. Organometallic Chem. 1979,165,9. T. J. Drahnak J. Michl and R. West J. Amer. Chem. SOC.,1979,101,5427. W. Ando and M. Ikeno J.C.S. Chem. Comm. 1979,655;M. Ishikawa K. I. Nakagawa and M. Kumada J. Organometallic Chem. 1979 178 105. 52 Y. Nakadaira T. Kobayashi T. Otsuka and H. Sakurai J. Amer. Chem. SOC. 1979,101,486. Organometallic Chemistry-Part (ii) Main-Group Elements 281 . D1 Si=Si, / Me Ph RR3 (29) R3 (301 silanorbornadienein the presence of anthracene at 350 "C provides (29; R' =R2= Me R3-R3 = -CH=CHCH=CH-).Geometric isomerism in Si=Si bonded species e.g. (30); has been Thermolysis of (29; R' = Me R2 = Ph R3 =H) in the presence of anthracene at 300°C provides (29; R'=Me R2=Ph R3-R3= -CH=CHCH=CH) via trans-(30). In a similar fashion the cis-isomer also reacts stereospecifically. The use of higher temperatures and less reactive enophiles than anthracene lead to a reduced stereoselectivity. These results clearly show the Si=Si to be a true double bond with slow (E)",(2)isomerism at the temperatures used. 53 During an ab initio study using non-empirical pseudopotential methods on various C2H4Si isomers it was calculateds4 that the stability sequence is silylacetylene<silacyclopropene (3 1)=silacyclopropylidene (32) <2-sila-allene < 2-silapropyne.Particularly noteworthy was the stability of singlet (32) and the non-aromatic character of (3 1).Photolysis of HC_CSiRl2SiRz3 provides silylethyl- enes silacyclopropene and silapropadiene derivatives (e.g.as in Scheme 14). These PhMeSi=CH2 + HC-CSiMe2Ph hu HCGCSiMezSiMezPh __* + 'She2 PhMe2SiCH=C=SiMe2 Scheme 14 Reagents i LiNPr', C5HI2 0 "C Scheme 15 were trapped" by MeOH. Successful attempts have been made56 to generate and trap the silylbenzene derivative (33). Compound (34) was generated from 1 l-di-n- butyl-4-t-butyl-4-methoxy-l,4-dihydrostannin. To contrast with Scheme 15 only substitution at silicon occurs when the less hindered (34; R =Me X = C1) is treated with LiNEt, to give initially (34; R=Me X=NEt,). Trapping of (33) by con- jugated dienes provides (7'+ 7') cyclo-adducts." H. Sakurai Y. Nakadaira and T. Kobayashi J. Amer. Chem. SOC.,1979,101,487. 54 J. C. Barthelat G. Trinquier and G. Bertrand J. Amer. Chem. Soc. 1979,101,3785. 55 M. Ishikawa H. Sugisawa K. Yamamoto and M. Kumada J. Organometallic Chem. 1979,179 377. 56 G. Mark1 and P. Hofmeister Angew. Chem. Internat. Edn. 1979 18 789. 282 J. L. Wardell Interest has been maintained in research on silaethylenes A direct experimental determination of AH for Me2Si=CH2 was made using ion cyclotron resonance The method employed was to determine the minimum base strength required for the formation and detection of BH' by ion cyclotron resonance via deprotonation of Me3Si' (Scheme 16) and then from the known B + Me3SiCI 5Me3Si+ 2Me2Si=CH2 + BH+ Scheme 16 enthalpy of proton transfer to the base B a value for AHf (ca.20.5 kcal mol-*) was obtained.A T-bond energy of 34 kcal mol-' was also calculated. Lower values were reported for these properties from calculations based on the thermodynamic cycle involving the thermal decomposition and dissociative ionization processes for 1,l-dimethyl-1-silacyclobutane.57b Photolysis of acyl-p~lysilanes~~ at 360 nm gives rise to carbenes and/or silaethyl- enes of enhanced stability (Schemes 17 and 18). While the trapping (by alcohols and OSiR R:SiSiR;C(0)R3 -% R:SiSiR&O-CR2 + RiSi=C / \R3 Scheme 17 0 (Me3Si)3Si-C-Bu'II hv ,0SiMe3 (Me3Si)2Si=C - (Me3Si)2Si-1 /OSiMe3C /\But \But (Me3Si)2Si- C-OSiMe3IBut Scheme 18 (35) unsaturated compounds) and dimerization of these silaethylenes were generally studied (Me3Si)2Si=C(OSiMe3)But was shown to have a moderate lifetime at ambient temperature and to be in equilibrium with its head-to-head dimer (35).Spectral characterizations were made by U.V. and by 'H I3C and 29Si n.m.r. The enhanced stability was attributed to both steric and electronic factors particularly of the Me3Si groups. The X-ray structure of (35) and another head-to-head dimer of a silylethylene i.e. (Me3Si)2C=C=SiPh2 were reported.59 Other silicon-carbon double-bonded intermediates were formed in the photolysis of 1-and 2-naphthyl- SiR2SiR3. From the 1-naphthyl derivatives,60 even in the presence of a trapping 57 (a) W. J. Pietro S.K. Pollack and W. J. Hehre J. Amer. Chem. Soc. 1979 101 7126; (b)L. E. Gusel'nikov and N. S. Nametkin J. Orgunometallic Chem. 1979 169 155. '13 A. G. Brook J. W. Harris J. Lemon and M. El-Sheikh J. Amer. Chem. SOC.,1979 101 83; A. G. Brook S. C. Nyburg W. F. Reynolds Y. C. Poon Y. M. Chang J. S. Lee and J. P. Picard ibid.,p. 6750. " M. Ishikawa T. Fuchikami M. Kumada T. Higuchi and S. Miyamoto J. Amer. Chem. SOC.,1979,101 1348. 60 M. Ishikawa M. Oda N. Miyoshi L. Fabry M. Kumada Y. Yamabe K. Akagi and K. Fukui J. Amer. Chem. SOC.,1979,101,4612. Organometallic Chemistry-Part (ii) Main-Group Elements 283 agent 1-HR2Si-2-R3Si-naphthaleneswere obtained uia 1,3-hydrogen shifts in the intermediate Si=C-bonded species. Claisen sigmatropic rearrangements of PhOSiMezCH=CHz (36) and related species were reported;61 (36) gave on heating at 350 "C l-oxa-5,6-benzo-2,2- dimethyl-2-silacyclohexane.Photolysis of Me3SiC( =N2)C02R1 in R20H yields products (i) Me3SiCHOR2C02R' from insertion of the corresponding carbene into the 0-H bond of R20H (ii) Me3SiC(OR3)HC02R2 (R3 = R' or R') by Wolff rearrangement and (iii) Me2Si0R2CMeCO2R' (37) apparently from the silene Me2Si=CMeC02R1. However in the gas phase,62 the precursor to (37) was shown to be the keten Me,Si(OR')C(Me)=C=O. A method of preparation of tri- substituted ethylenes stereoselectively is based on the reaction of R'COCR2HSiR33 with R4Li and on the subsequent highly discriminative elimination of R33Si and the oxide group from the adducts.syn-Elimination occurs under basic conditions whereas anti-elimination proceeds with Two preparations of that most useful reagent Me3SiI in situ have been published by Olah;64 these are the reactions of (Me& with I and of Me3SiCl with NaI in MeCN. The addition of Me3SiI to @-unsaturated ketones is a new use of this reagent.65 Gielen continued his work66 on chiral tin compounds with details of the synthesis optical stability and stereo-reactions of hydrides such as [(PhMe,CCH,)R(Ph)SnH] (R=Me or Bu'). The chiral hydrides obtained by asymmetric reduction of the corresponding racemic halides by chiral [HA1(OC6H3Me2-2,6)-(OCHPhCHMeNMe,)]- Li' only slowly racemize in benzene solution at room temperature (t+17days). The H-D exchange with [Ph3SnD] occurs with retention of configuration at tin.In contrast to the structure of [Ph3SnOSnPh3] those of O[(PhCH2)3M]2 (M = Ge or Sn) have linear M-0-M fragment^.^^ The synthesis and structure of the nido-cluster (38) was reported;68 compound (38) is sensitive to air and to moisture. As well as the fast intramolecular exchanges in [C5H5SnMe3] and [(cyclo-nonatetraenyl)SnMe,] (by 1,9-sigmatropic shifts) in solvents such as THF or DME [(MesCs)zSnll]+HBF4 Ph CN (39) 61 J. Ancelle G. Bertrand M. Joanny and P. Mazerolles Tetrahedron Letters 1979 3153. 62 W. Ando A. Sekiguchi T. Hagiwara T. Migata V. Chowdhry F. H. Westheimer S. L. Kammula M. Green and M. Jones J. Amer. Chem. SOC.,1979,101,6393. 63 M. Obayashi K. Utimoto and H. Nozaki Bull. Chem. SOC.Japan 1979,52 1760.64 G.A. 0lah.S. C. Narang B. G. B. Gupta andR. Malhotra J. Org. Chem. l979,44,1247;Angew. Chem. Internat. Edn. 1979,18 612. 65 R. D. Miller and D. R. McKean Tetrahedron Letters 1979 2305. M. Gielen and Y. Tondeur J. Organometallic Chem. 1979 169 265. 67 C. Glidewell and D. C. Liles J.C.S. Chem. Comm. 1979,93; Acta Cryst. 1979,35B 1689. 6a P. Jutzi F. Kohl and C. Kriiger Angew. Chem. Internat. Edn. 1979,18 59. 284 J. L. Wardell intermolecular exchanges via ion-pairs in the presence of HMPT have been recog- ni~ed.~' The 7-stannanorbornane derivative (39) from 1,l-dimethyl-2,3,4,5-tetraphenyl-stannacyclopentadieneand (CN),C=C(CN), is stable below -30 "C; at higher temperatures (39) decomposes (at -10 "C ti = 17 min) to 5,5,6,6-tetracyano- 1,2,3,4-tetraphenyl-1,3-cyclohexadieneand Me2Sn which can be trapped or allowed to p~lymerize.~' The insertion of (CN),C=C(CN) into C-Sn bonds proceeds uia charge-transfer complexes under both photochemical and thermal activation.The activation step is transfer of an electron from the charge-transfer complex the same paramagnetic and intermediate species being formed in both the thermal and photochemical reaction^.^' A similar study was concerned7* with the insertion of (CH)2C=C(CN)2 into H-M bonds (M = Si Ge or Sn). The sequence of events is given in Scheme 19 in which tcne is tetracyanoethylene (40) is a charge-transfer complex and ke,t.is the rate constant for electron transfer. R3MH + tcne -+ [HMR3-tcne] 5[HMR3' tcne'] (40) J [(CN)2HC(CN)2CMR3]e [H' MR; tcne'] Scheme 19 Palladium complexes in particular [PhCH2Pd(PPh3),C1] catalyse the coupling of %Sn with PhCH2X and ArX.Various functional groups are tolerated in this high-yielding synthesis. a-Deuteriobenzyl bromide and Me4Sn provide the inverted PhCHDMe Compounds [ArPb(OCOR),] prepared by plumbylation and by transmetallation of mercury and silicon derivatives are useful phenylating reagents towards ArH phenols and p-dike tone^.^^ 6 Group5 It has been variously established that correlations exist between core-ionization energies and proton affinities. The data for arsabenzene however fall well off the correlation line for arsines and it was considered that the low basicity is due to the inability to undergo the necessary geometric rearrangement on pr~tonation.~~ It was deduced76 from the n.m.r.spectrum of 4-methylstibabenzene in a nematic phase that there is no large C-C bond alternation within the ring and that the length of C-a-C-p is only slightly greater than that of C-p-C-7. The thermally labile 69 (a) G. Boche F. Heidenhain and B. Staudig Angew. Chem. Internat. Edn. 1979,18,218;(b)A. Bonny and S. R. Stobart J.C.S. Dalton 1979,786. 70 C. Grugel W. P. Neumann and M. Schriewer Angew. Chem. Internat. Edn. 1979,18 543. 71 S. Fukuzumi K. Mochida and J. K. Kochi J.Amer. Chem. SOC., 1979,101,5961;see also 0.A. Reutov V. 1. Rozenberg G. V. Gavrilova and V. A. Nikanorov J. Organometallic Chem. 1979,177,101. 72 R. J. Klinger K. Mochida and J. K. Kochi J Amer. Chem. SOC.,1979,101,6626.73 D. Milstein and J. K. Stille J. Amer. Chem. SOC., 1979,101 4992. " H. C. Bell J. R. Kalman J.T. Pinhey andS. Sternhel1,Austral. J.Chem. 1979,32,1521;H. C. Bell J. R. Kalman G. L. May J. T. May J. T. Pinhey and S. Sternhell ibid. p. 1531; H. C. Bell J. T. Pinhey and S. Sternhell ibid. p. 1551; J. T. Pinhey and B. A. Rowe ibid. p. 1561. 75 A. J. Ashe M. K. Bahl K. D. Bomben W. T. Chan J. K. Gimzewski P. G. Sitton and T. D. Thomas J. Amer. Chem. SOC.,1979,101 1764. 76 T. C. Wong M. G. Ferguson and A. J. Ashe J. Mol. Structure 1979 52 231. Organometallic Chemistry-Part (ii) Main-Group Elements arsanaphthalene (41) previously unknown was prepared77 as shown in Scheme 20. The 13C n.m.r. spectrum of (41) was obtained despite its slow decomposition in solution.Treatment of (41) with CF3C~CCF provides (42; R =CF3). R R (42)R= H (41) y4y Reagents i (R = 2-pyridyl) NdN R Scheme 20 Mesityl(diphenylmethylene)arsane [2,4,6-Me3C6HzAs=CPh2] which is a compound with an isolated double bond is stable at ambient temperature in the absence of air and shows little tendency to oxidize.” It was synthesized from [2,4,6-Me3C6HzAs(C1)CHPh2] and diazabicycloundecene. A. J. Ashe D. J. Bellville and H. S. Friedman J.C.S. Chem. Comm. 1979 880. 78 T. C. Klebach H. van Dongen and F. Bickelhaupt Angew. Chem. Internat. Edn. 1979,18 395.

ISSN:0069-3030    

DOI:10.1039/OC9797600271

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

13 Organoboron Chemistry By K. SMITH and W. E. PAGET Department of Chemistry University College of Swansea Singleton Park Swansea SA2 8PP This Report is concerned with major advances in organoboron chemistry over the past five years. It is perhaps appropriate that in 1979 the importance of the field and the unparallelled contributions of H. C. Brown were recognized by the award of a Nobel Prize. H. C. Brown has himself recently reflected upon forty years of hydride reductions.' There have been many recent reviews covering individual aspects of organoboron chemistry but we cite only one book2" and a review2' because together they contain key references to all areas of organoboron chemistry that are likely to be of interest to organic chemists. 1 Reductions using Organoboron Compounds Alkali-metal trialkylhydridoborates (trialkylborohydrides) are increasingly being recognized as useful reducing agents and detailed studies of their preparations from trialkylboranes and a variety of simple and complex hydrides have a~peared.~ The sterically hindered compounds are particularly useful for stereoselective reduction of carbonyl compounds (e.g.Scheme l).4Some trialkylborohydrides are now com- mercially available. Reagents i Li[Me,CHCH(Me)],BH at -78 "C Scheme 1 cup-Enones which are not encumbered at the p-position generally undergo conjugate reduction to give enolates which can be directly alkylated in situ if required (Scheme 2).' On the other hand branching at the &position generally leads to direct reduction of the carbonyl gro~p.~*~ H.C. Brown and S. Krishnamurthy Tetrahedron 1979,35 567. (a) H. C. Brown 'Organic Synthesis oia Boranes,' Wiley-Interscience New York,1975; (6) A. Pelter and K. Smith in 'Comprehensive Organic Chemistry' ed. D. H. R. Barton and W. D. Ollis Pergamon Oxford 1978 Vol. 3 pp. 689-940. (a) C. A. Brown and S. Krishnamurthy J. Organometaal. Chem. 1978,156,111; (b) C. A. Brown and J. L. Hubbard J. Am. Chem. Soc. 1979 101 3964; (c) H. C. Brown. S. Krishnamurthy and J. L. Hubbard ibid. 1978 100 3343; J. Organometal. Chem. 1979 166 271. S. Krishnamurthy and H. C. Brown J. Am. Chem. SOC.,1976,98,3383. J. M. Fortunato and B. Ganem J. Org. Chem. 1976,41,2194. W. G. Dauben and J. W. Ashmore Tetrahedron Lett.1978,4487. K. Smith and W.E. Paget Reagents i LiBus3BH; ii IACO,Et \ Scheme 2 Trialkylborohydrides are extremely powerful reducing agents and as such are useful for the deoxygenation of alcohols by reduction of their tosylates7 or oxy- phosphonium salts (applied particularly to glycosyl derivatives),8 and for the demethylation of quaternary ammonium salts.’ They also react with elemental sulphur and selenium to give active anhydrous lithium sulphides (Li2S or Li2S2 depending upon the stoicheiometry) and selenides which are useful reagents for introduction of sulphur and selenium into organic molecules. lo Metal carbonyls may be converted into metal formyl complexes,” and dimeric carbonyl compounds cleaved to metal carbonyl anions,” by the action of lithium triethylborohydride.9-Alkyl-9-borabicyclo[3.3. llnonanes (9-alkyl-9-BBN’s) and their 23-alkyl ate- complexes are interesting new types of reducing agents. The boranes (9-alkyl-9- BBN’s) eliminate alkene on treatment with an aldehyde and there is concomitant reduction of the aldehyde. B-Siamyl-9-BBN (siamyl = 1,2-dimethylpropyI) appears to be particularly promising for selective reduction of aldehydes in the presence of ket~nes,’~ whilst optically active B-isopinocampheyl-9-BBN (formed by hydro- boration of a-pinene using 9-BBN) is capable of producing primary alcohols RCHDOH of very high optical purity (>go%) from deuterio-aldehydes RCD0.14 Lithium 9,9-dibutyl-9-boratabicyclo[3.3, llnonane donates a hydride ion from one of the bridging positions and itself undergoes rearrangement (Scheme 3).” However it shows considerable discrimination in the facility with which it gives up its hydride.Thus for example it reacts with 4-methylcyclohexanone (cf.Scheme 1) to give the cis-alcohol (84%) in the presence of methanol or the trans-isomer (90%) in the presence of lithium meth0~ide.l’~ It can also be used for selective Bu Bu Bu Bu \-/ \/ B +EX EH + LiX + Lib4 Scheme 3 7 S. Krishnamurthy and H. C. Brown J. Org. Chem. 1976,41,3064; S. Krishnamurthy J. Organometal. Chem. 1978,156 171. 8 P. Simon J.-C. Ziegler and B. Gross Synthesis 1979 951. 9 M. P. Cooke and R. M. Parlman J. Org. Chem. 1975,40,531. 10 (a) J. A. Gladysz V. K. Wong and B. S. Jick J. Chem.SOC.,Chem. Commun. 1978,838; Tetrahedron 1979,35,2329; (b) J. A. Gladysz J. L. Hornby and J. E. Garbe J. Org. Chem. 1978,43 1204. It J. A. Gladysz and J. C. Selover Tetrahedron Lett. 1978,319; R. L. Pruett R. C. Schoening J. L. Vidal and R. A. Fiato J. Organometal. Chem. 1979,182 C57. 12 J. A. Gladysz G. M. Williams W. Tam D. L. Johnson D. W. Parker and J. C. Selover Inorg. Chem. 1979,18 553. 13 M. M. Midland and A. Tramontano J. Org. Chem. 1978 43 1470. 14 M. M. Midland S. Greer A. Tramontano and S.A. Zderic J. Am. Chem. SOC.,1979,101,2352. 1s (a) G. W. Kramer and H. C. Brown J.Am. Chem. SOC.,1976,98,1964; (b) Y. Yamamoto H. Toi A. Sonoda and S.-I. Murahashi ibid. p. 1965. Organoboron Chemistry 289 dehalogenation of reactive (tertiary alkyl allyl or benzyl) halides,16 or for regio- selective cleavage of epoxides in a manner opposite to that usually enc0~ntered.l~ Acyloxy-borohydrides have also been recommended as novel types of reducing agents," whilst new applications of the established reagents 9-BBN (e.g.reduction of enones to allylic and catecholborane (unsaturated tosylhydrazones to alkenes or allenes)20 have also been reported. 2 Hydroboration Details of the hydroboration of alkenes ard alkynes and of the cyclic hydroboration of dienes using monochloroborane diethyl etherate21 or the more stable and convenient adducts of dimethyl sulphide with monohalogeno-boranes,22 have appeared. The dimethyl sulphide adducts in particular promise to be amongst the more important hydroborating agents in future years.1,3,2-Dithiab0rolan~~ is another new hydroborating agent. In some respects 9-BBN is an unusual hydroborating reagent. For example the rate of its hydroboration of many alkenes is independent of the nature or concentration of the alkene because the rate-limiting step is dissociation of the 9-BBN dimer into monomer.24 Also B-cyclo-octyl-9-BBN derivatives do not undergo the isomerization of other B-cyclo-octyl and 9-BBN unlike other dialkyl-boranes hydroborates most alkenes faster than the corresponding alkynes.26 Details of the general applications of 9-BBN have appea~ed,~' and the preparation of a B-deuterio-derivative has also been reported.28 Much effort has been devoted to the development of a convenient procedure for preparation of monoisopinocampheylborane a relatively unhindered asymmetric hydroborating agent.29 One method involves displacement of a-pinene from di-isopinocampheylborane using tetramethylethylenediamine (TMEDA) and results in a product of very high optical purity much higher than that of the original a-pinene used in the preparation of the di-isopino~ampheylborane.~~~ The TMEDA complex of thexylborane (1,l72-trirnethylpropylborane)reacts with l6 Y.Yamamoto H. Toi S.-I. Murahashi and I. Moritani J. Am. Chem. SOC.,1975 97 2558. 17 Y. Yamamoto H. Toi A. Sonoda and S.-I. Murahashi J. Chem. SOC.,Chem. Commun. 1976 672. " N. Umino T. Iwakuma and N. Itoh Tetrahedron Left. 1976,763,2875; G. W. Gribble W. J. Kelly and S. E. Emery Synthesis 1978 763.l9 S. Krishnamurthy and H. C. Brown J. Org. Chem. 1975,40,1864;H. C. Brown S. Krishnamurthy and N. M. Yoon ibid. 1976 41 1778. 2o G. W. Kabalka D. T. C. Yang and J. D. Baker J. Org. Chem. 1976,41 574; G. W. Kabalka R. J. Newton J. H. Chandler and D. T. C. Yang J. Chem. SOC.,Chem. Commun. 1978,726. H. C. Brown and N. Ravindran J.Am. Chem. SOC.,1976 98 1785 1798 H. C. Brown and M. Zaidlewicz ibid. p. 4917. 22 H. C. Brown N. Ravindran and S. U. Kulkarni J. Org. Chem. 1979,44,2417 H. C. Brown and S. U. Kulkarni ibid. p. 2422. 23 S. Thaisrivongs and J. D. Wuest J. Org. Chem. 1977 42 3243. 24 H. C. Brown C. G. Scouten and K. K. Wang J. Org. Chem. 1979,44,2589. 25 H. Taniguchi L. Brener and H. C. Brown J. Am. Chem. SOC., 1976,98,7107. 26 C.A. Brown and R. A. Coleman J. Org. Chem. 1979,44,2328. 27 H. C.Brown R. Liotta and G. W. Kramer J. Org. Chem. 1978,43,1058;H. C. Brown C. G. Scouten and R. Liotta J. Am. Chem. SOC., 1979,101,96;J. C.-S. Chen J. Organometal. Chem. 1978,156,213. 28 M. M. Midland and S. Greer Synthesis 1978 845. *' (a) H. C. Brown and A. K. Mandal Synthesis 1978 146 (b) H. C. Brown J. R. Schwier and B. Singaram J. Org. Chem. 1978,43,4395;(c) A. Pelter D. J. Ryder J. H. Sheppard C. Subrahmanyam H. C. Brown and A. K. Mandal Tetrahedron Lett. 1979,4777. 290 K. Smith and W. E. Paget alkenes to give complexes of monoalkyl-boranes from which the free borane can easily be liberated.30 Diphenylborane another potentially useful reagent for prep- aration of 'mixed' organoboranes has also been prepared in high yield.31 Hydroboration of allene~~~ is very dependent upon the nature of the hydro- borating agent and reaction with 9-BBN is especially useful for the preparation of allyl-b~ranes.~~"~~ Hydroboration-oxidation of an allene was used as a key step in a total synthesis of isocaryophyllene (Scheme 4).33 Reagents i BH, THF at 160"C for 3 h; ii CrO Scheme 4 Vinylsilanes are hydroborated regioselectively with dialkyl-boranes to give over 95OiCl of the P-dialkylboryl-silane whereas borane-THF favours the formation of the ~u-isomer.~~ Borane converts p-enamino-esters into the corresponding a& unsaturated and vinyl-aziridines into allyl-amine~.~~ Hydroboration of 1-bromo-alkynes with a dialkyl-borane followed by treatment with t-butyl-lithium or with lithium triethylborohydride provides a method of synthesizing cis-alkenyl- boranes i.e.alkenyl-boranes with stereochemistry opposite to that obtained by simple hydroboration of a terminal alk~ne.~' It has finally been proved that hydroboration occurs in a cis manner even in acyclic cases3* 3 Synthetic Applications of Organoboranes Potassium tri-isopropoxyborohydride is a superior reagent for hydride-induced carbonylation of organoboranes a reaction which gives an aldehyde after oxidative work-~p.~~ The reaction occurs only under conditions which allow the existence of a small amount of free trialkylb~rane;~' if acid is added subsequent to the car- bonylation step a second rearrangement occurs giving rise to a secondary alcohol upon work-~p.~~ The carbonylation reaction has been applied in the synthesis of benzaldehyde from triphenylb~rane,~~ 14C-labelled aldehydes ketones and of tertiary and of juvabione and its epimer (Scheme 5).44 30 H.C. Brown J. R. Schwier and B. Singaram J. Org. Chem. 1979,44,465. 31 P. Jacob J. Organometal. Chem. 1978,156 101. 32 (a) L. Chevolot J. Soulit and P. Cadiot Tetrahedron Lett. 1974,3435;(b) H. C. Brown R. Liotta and G. W. Kramer J. Am. Chem. SOC.,1979 101 2966; (c) V. V. Ramana Rao S. K. Agarwal D. Devaprabhakara and S. Chandrasekaran Synth. Commun. 1979,9,437. 33 A. Kumar A. Singh and D. Devaprabhakara Tetrahedron Lett. 1976,2177. 34 J. A. Soderquist and A. Hassner J. Organometal. Chem. 1978 156 C12. 35 J.Froburg G. Magnusson and S. ThorBn Tetrahedron Lett. 1975 1621. 36 R. Chaabouni A. Laurent and B. Marquet Tetrahedron Left. 1976,757. 37 E. Negishi R. M. Williams G. Lew and T. Yoshida J. Organometal. Chem. 1975 92 C4; J. B. Campbell and G. A. Molander ibid. 1978 156 71. 38 G. W. Gabalka R. J. Newton and J. Jacobus J. Org. Chem. 1978,43 1567. 39 H. C. Brown J. L. Hubbard and K. Smith Synthesis 1979,701. 40 H. C. Brown and J. L. Hubbard J. Org. Chem. 1979 44,467. 41 J. L. Hubbard and H. C. Brown Synthesis 1978 676. 42 G. W. Kabalka and J. W. Fernell Synth. Commun. 1979,9,443. 43 G.W. Kabalka E. E. Gooch C. J. Collins and V. F. Raaen J. Chem. SOC.,Chem. Commun. 1979,607. 44 E. Negishi M. Sabanski J.-J. Katz and H. C. Brown Tetrahedron 1976 32 925. Organoboron Chemistry 291 C0,Me 53% overall yield Reagents i (Me,CHCMe,)BHBu’; ii CO 70 atm 50 “C; iii [O] Scheme 5 A number of new reagents for oxidation of organoboranes have been reported of which the most notable are trimethylamine oxide dihydrate4’ and pyridinium chlorochr~mate.~~ The latter oxidizes organoboranes and alkoxyboranes directly to aldehydes and ketones.The reagent PhI(OAc)2 converts alkyl- and vinyl-boron compounds into the corresponding alkyl or vinyl The first quantitative conversion of trialkylboranes into chloro-alkanes utilizes nitrogen trichloride as the reagent.48 Methoxide ion is a superior base to hydroxide ion for the base-induced iodinolysis of organoboranes allowing all three alkyl groups of a primary trialkylborane to be converted into iodo-alkane (two for secondary alkyl groups).49 Base-induced iodinolysis and brominolysis of organoboranes both involve inversion of stereochemistry at the displaced centre.” Iodinolysis of a vinyl-catecholborane has been applied in the synthesis of some substituted prosta- glandins.’ Iron(II1) salts have been used to convert organoboranes into alkyl seleno- cyan ate^'^ and a~ides,’~ whilst Chloramine-T reacts with trialkylboranes to give the corresponding alkyl toluenes~lphonamide.’~ The direct transfer of two alkyl groups from a trialkylborane to a single nitrogen atom (‘nitrogen stitching’) has been accomplished in one case as part of a synthesis of the perhydroazaphenalene ring system which is found in alkaloids of the Coccinellidae (Scheme 6).” Trialkylboranes react with the Grignard reagent derived from 1,5-dibromopen- tane to give a spiroborate complex and the alkyl Grignard ~eagent.’~ Alkenyl groups of alkenyl-boranes may be hydrolysed under the influence of palladium(I1) acetate in THF,57 or coupled to give (E,E)-dienes using a reagent composed of 45 G.W. Kabalka and H. C. Hedgecock J. Org. Chem. 1975.40 1776. 46 V. V. Ramana Rao D. Devaprabhakara and S. Chandrasekaran J. Organometal. Chem. 1978,162 C9; C. Gundu Rao S. U. Kulkami and H. C. Brown ibid. 1979,172,C20; H. C. Brown S. U. Kulkami and C. Gundu Rao Synthesis 1979,702,704. 47 Y. Masuda and A. Arase Bull. Chem. SOC.Jpn. 1978,31,901; Y. Masuda A. Arase and A. Suzuki Chem. Lett. 1978 665. 48 H.C. Brown and N. R. De Lue J. Orgunomeful. Chem. 1977,135 C57. 49 N. R. De Lue and H. C. Brown Synthesis 1976 114. ” H. C. Brown N. R. De Lue G. W. Kabalka and H. C. Hedgecock J. Am. Chem. SOC.,1976,98,1290; D. E. Bergbreiter and D. P. Rainville J. Orgunometul. Chem. 1976,121 19. 51 P. W. Collins E. Z. Dajani M. S. Bruhn C. H.Brown J. R.Palmer and R. Pappo Tetrahedron Lett. 1975,4217. ’* A. Arase and Y. Masuda Chem. Lett. 1976,785. 53 A. Suzuki M. Ishidoya and M. Tabata Synthesis 1976 687. ” V. B. Jigajinni A. Pelter and K. Smith Tetrahedron Lett. 1978 181. 55 R. H. Mueller Tetrahedron Lett. 1976 2925. ” K. Kondo and S.-I. Murahashi Tetrahedron Lett. 1979 1237. 57 H. Yatagai Y.Yamamoto and K. Maruyama J. Chem. SOC.,Chem. Commun. 1978,702. K.Smith and W. E. Paget Reagents i [CINHOC,H,(NO,),]; ii H202, OH-; iii heat Scheme 6 palladium(@ chloride lithium chloride and trieth~lamine.’~ On the other hand they can be coupled with aryl or vinyl halides under the influence of palladium(0) and a base.59 Diboryl-alkanes react with silver nitrate to give substantial amounts of cycloalkanes6’ or (E)-alkenes (from 1,2-dibor~l-alkanes).~~ The previously discovered oxygen-induced conjugate addition of trialkylboranes to enones and similar compounds has been extended to 1-acyl-2-vinyl-cyclo-propanes giving y8-unsaturated ketones (Scheme 7).62 B-Alkenyl-9-BBN deriva- R:B + H,C=CH A COR2 i,ii ,R ‘CH2CH=CHCH,CH2COR2 Reagents i 0,; ii H,O Scheme 7 tives undergo conjugate addition of the alkenyl-boron unit to enones apparently by a non-radical mechanism providing another approach to y8-unsaturated ketones.63 Electrolysis of trialkylboranes in the presence of 2-alkylacrylates is an alternative way of inducing conjugate addition.64 Diethylborylpivalate (or triethylborane in the presence of derivatives of pivalic acid) reacts with hydroxylic compounds relatively readily liberating ethane.Such systems have been extensively utilized for the selective protection of sugars and other polyhydroxy-compounds.65 Inversion occurs at the migration terminus during base-induced rearrangement of a-halogenoalkyl-boranes and during the formation of cyclopropanes from y- chloroalkyl-boranes.66 Kinetic and competition experiments provide evidence for a dehydroboration-rehydroborationprocess in the alkene-alkyl exchange reactions of B-alkyl-9-BBN and by implication also in the isomerization of alkyl-boranes.A potentially useful procedure for selective elimination of the secondary alkyl groups present in a typical tri-n-alkylborane prepared by hydro- boration of a terminal alkene involves heating the borane first with anisole and then with a small amount of DMS0.68 V. V. Ramana Rao C. V. Kumar and D. Devaprabhakara J. Organometal. Chem. 1979,179 C7. s9 N. Miyaura and A. Suzuki J. Chem. Soc. Chem. Commun. 1979,866 N. Miyaura K. Yamada and A. Suzuki Tetrahedron Lett. 1979 3437. 6o R. Murphy and R. H. Prager Tetrahedron Lett. 1976,463. 61 K. Avasthi S. S. Ghosh and D. Devaprabhakara Tetranedron Lett. 1976,4871.62 N. Miyaura M.Itoh N. Sasaki and A. Suzuki Synthesis 1975 317. 63 P. Jacob and H. C. Brown J. Am. Chem. SOC.,1976,98,7832. 64 Y. Takahashi K. Yuasa M. Tokuda M. Itoh and A. Suzuki Bull. Chem. Soc. Jpn. 1978,51,339. 6s W. V. Dahloff and R. Koster J. Org. Chem. 1976,41 2316; and references cited therein. 66 M. M. Midland A. R. Zolopa and R. L. Halterman J. Am. Chem. Soc. 1979,101,248; H. L. Goering and S. L. Trenbeath ibid. 1976 98 5016. 67 M. M. Midland J. E. Petre and S. A. Zderic J. Organometal. Chem. 1979,182 C53. 68 Y. Masuda M. Hoshi and A. Arase Bull Chem. SOC.Jpn. 1979,52,271. Organoboron Chemistry 293 4 Synthetic Applications of Organoborates Probably the most significant development in organoborane chemistry over the past decade has been the realization of the synthetic importance of the reactions of four-co-ordinate borate salts with electrophiles.Full details of the reactions of cyanoborates with electrophiles the first reactions to demonstrate the synthetic importance of organoborates were published at the start of the current review period.69 The most useful processes involve acylation of the cyanoborates with reagents such as trifluoroacetic anhydride leading ultimately to ketones or tertiary alcohols (Scheme 8). The adducts of the cyclic intermediates with water have been characterized by X-ray ~rystallography,~' and the reaction has been applied in the annulation of terpenoid polyenes." R2 R3 'n' .. R'R2R3B -b Na+ [R'R2R3BCN]- 4RIYAL\ N J fCF3 R'R2R3COH & R'R2R3CB < R2COR3 Reagents i NaCN; ii (CF,CO),O; iii HzOz OH-; iv excess (CF,CO),O.Scheme 8 The formation of a tertiary alcohol from cis,cis-perhydro-9b-boraphenaleneis interesting in that it gives the trans,trans,trans-alcohol, in contrast to the cis,cis,cis-alcohol obtained by carbonylation (see Scheme 9).72 Alkynylborates react with acids or alkylating agents to give intermediate vinyl- boranes which may be oxidized to ketones or hydrolysed to alkene~.~~ The reactions with a-nitro-alkenes are Michael-type addition With simple alkylating -HQH iv,v,iii* HQH H Reagents i CO pressure; ii heat; iii HzOZ, OH-; iv KCN; v (CF,CO),O warm Scheme 9 69 A. Pelter K. Smith M. G. Hutchings and K. Rowe J. Chem. SOC.,Perkin Trans.1 1975 129 138; A. Pelter M. G. Hutchings and K. Smith ibid.,p. 142; A. Pelter M. G. Hutchings K. Smith and D. J. Williams ibid.,p. 145. 70 P. R. Mallinson D. N. J. White A. Pelter K. Rowe and K. Smith J. Chem. Res. 1978 (S)234 (M) 3101. 71 R. Murphy and R. H. Prager Aust. J. Chem. 1976,29 617; J. Organometal. Chem. 1978,156 133. " A. Pelter P. J. Maddocks and K. Smith J. Chem. SOC.,Chem. Commun. 1978,805. 73 (a) H. C. Brown A. B. Levy and M. M. Midland J. Am. Chem. SOC.,1975 97 5017; (b) M. M. Midland and H. C. Brown J. Org. Chem. 1975 40 2845; (c) A. Pelter, C. R. Harrison C. Subrahamanyam and D. Kirkpatrick J. Chem. SOC.,Perkin Trans. 1,1976,2435;(d) A. Pelter T. W. Bentley C. R. Harrison C. Subrahmanyam and R. J. Laub ibid. p. 2419; (e) A. Pelter C.Subrah- manyam R. J. Laub K. J. Gould and C. R. Harrison Tetrahedron Lett. 1975,1633; (f A. Pelter and L. Hughes J. Chem. SOC.,Chem. Commun. 1977,913. 294 K. Smith and W.E. Paget agents mixtures of the (E)-and (2)-isomers of the vinylboranes are obtained but with more complex ones (e.g. propargyl halides a-halogenocarbonyl compounds and the like) the reaction is stereospecific giving rise to (2)-alkenyl derivatives on hydrolysis (Scheme The intermediate vinylboranes can also be worked up in other ways; for example by application of the Zweifel alkene synthesis using iodine and base.75 R:B R2 H R2 \/ ii \ / Li' [R:BCrCR2]-c=c _.+ c=c (-LiBr) R' ' R'' 'CH2X 'CH2X Reagents i BrCH,X; ii MeC0,H Scheme 10 The stereoselectivity of production of disubstituted ethenes can be greatly improved by use of Bu;SnCl as the electrophile instead of This gives a stannyl-vinylborane stereospecifically; on subsequent hydrolysis this gives a (2)-alkene.Similar reactions occur on reaction of trialkylboranes directly with 1-trialkylstannyl-alkyne~,'~ whereas the use of dialkynyl-stannanes gives rise to bora- stanna- heterocycle^.^^ Other electrophiles which give rise to useful products include iodine (gives alkyne~)~~ and ethylene oxide (gives alkenylethanol derivatives).80 Substituents in the original alkyne also affect the course of the reaction. Thus (tri-methylsily1)ethynyl-borates give overwhelmingly one geometrical isomer of the vinylborane even on &action with simple alkylating agenk8' The lithiated deriva- tives of lithium ethynyltrialkylborates can be alkylated by alkyl halide and then treated with iodine to give unsymmetrical internal alkynesE2 Lithiated propargyl chlorides and acetates react with trialkylboranes to give allenyl-boranes which equilibrate with the corresponding propargyi-boranes at ambient temperature (Scheme 1l).83The reaction of these species with aldehydes gives homopropargyl and homoallenyl alcohols respectively; these reactions are typical of &-unsaturated organoboranes (see Section 5).R -78°C I 20°C Lif [R3BC=CCH2X]-(-LiX) R2B-C=C=CH2 RzBCHzCrCR ____t Scheme 11 74 A. Pelter K. J. Gould and C. R. Harrison J. Chem. SOC.,Perkin Trans. 1 1976 2428. 75 G. Zweifel and R. P. Fisher Synthesis 1975 376.76 J. Hooz and R.Mortimer Tetrahedron Lett. 1976 805. 77 B. Wrackmeyer and R. Zentgraf J. Chem. SOC.,Chem. Commun. 1978,402. 78 L. Killian and B. Wrackmeyer J. Organometal. Chem. 1978,153 153; and references cited therein. 79 A. Suzuki N. Miyaura S. Abiko M. Itoh H. C. Brown J. A. Sinclair and M. M. Midland J. Am. Chem. Soc. 1973,95 3080. K. Utimoto T. Furubayashi and H. Nozaki Chem. Lett. 1975,397. K. Utimoto M. Kitai M. Naruse and H. Nozaki Tetrahedron Lett. 1975 4233; R.Koster and L. A. Hagelee Synthesis 1976 118. K. Utimoto Y.Yabuki K. Okada and H. Nozaki Tetrahedron Lett. 1976,3969. 83 (a) G. Zweifel S. J. Backlund and T. Leung J.Am. Chem. SOC.,1978,100,5561;(6) M. M. Midland and D. C. McDowell J. Organometal. Chem. 1978,156 C5.Organoboron Chemistry 295 Dialkyl(alkenyl)(alkynyl)borates undergo reactions with electrophiles in the same way as trialkyl(alkynyl)borates except that the products are conjugated dienes rather than mono-enes and so omg4Similarly dialkyl(dialkyny1)boratesreact with iodine to give conjugated di-yne~.~' If the method of preparation of the dialkynyl- borate is chosen so as to allow the synthesis of derivatives with two different alkynyl groups on a single boron atom the conjugated di-ynes are also unsymmetrical thus providing a more convenient alternative to the Cadiot-Chodkiewicz rea~tion.~'~*~ Alkenyl(trialky1)borates undergo the same types of reactions as alkynyl-borates for example with iodine to give alkenes,86 but in general they have been less widely studied.The alkene synthesis works well on alkenyl(alkyl)dimethoxyborates allowing better utilization of alkyl groups and this approach has been applied in the synthesis of prostaglandin model Alkenyl-boranes can be hydrolysed under basic conditions if they are first converted into the corresponding borates by treatment with butyl-lithium.88 Alkenyl-borates are also intermediates in the synthetically useful reactions of trialkylboranes with methoxyvinyl-lithium (Scheme 12).89 iii R2C=CH2 Li+12BiRJ -RCOCH~ Reagents i I, at -80 "C;ii H,O'; iii H20z HO-; iv BF Et20;V 12 HO-Scheme 12 Allyl-borates are formed with considerable regioselectivity and then react very selectively with electrophiles which attack at the position y-to boron.This allows head-to-tail coupling of allylic borates with ally1 halides for e~ample.~' Propargyl-borates are intermediates in the formation of alkynyl- and allenyl-silanes from lithiated 3-phenoxy-1 -trimethylsilylpropyne and trialkylborane~.~' Ate-complexes formed from trialkylboranes and 2-lithiated furan thiophen N-methylpyrrole and N-methylindole undergo reaction with iodine to give the 2-alkylated heterocycle^.^^ Other electrophiles can also be used to induce 84 G. Zweifel and S. J. Backlund J. Organometal. Chem. 1978,156 159. 85 (a) A. Pelter K. Smith and M. Tabata J. Chem. SOC.,Chem. Commun. 1975,857; (b) J. A. Sinclair and H. C. Brown J. Org. Chem. 1976,41,1078; (c) A. Pelter R. J. Hughes K. Smith and M. Tabata Tetrahedron Lett. 1976 4385. 86 N.J. Lalima and A. B. Levy J. Org. Chem. 1978,43,1279. D. A. Evans T. C. Crawford R. C. Thomas and J. A. Walker J. Org. Chem. 1976,41 3947. 88 E. Negishi and K.-W. Chiu J. Org. Chem. 1976 41 3484. 89 A. B. Levy S. J. Schwartz N. Wilson and B. Christie J. Organometal. Chem. 1978 156 123. 90 Y. Yamamoto and K. Maruyama J. Am. Chem. SOC.,1978,100,6282; Y. Yamamoto H. Yatagai and K. Maruyama J. Chem. SOC.,Chem. Commun. 1979,157; Chem. Lett. 1979,385. 91 T. Yogo J. Koshino and A. Suzuki Tetrahedron Lett. 1979 1781. 92 I. Akimoto and A. Suzuki Synthesis 1979,146; T. Sotoyama S. Hara and A. Suzuki Bull. Chem. SOC. Jpn. 1979,52 1865; E. R. Marinelli and A. B. Levy Tetrahedron Lett. 1979,2313; A. B. Levy J. Org. Chem. 1978,43,4684. 296 K.Smith and W.E. Paget rearrangement and in the case of N-methylindole this has been used to prepare 2,3-disubstituted indoles (Scheme 13; EX = e.g. ICH2CN ICH2CONH2 CH2=CHCH2Br et~.).~~ Two heteroaromatic units can be coupled by the reaction of the cyclic ethanolamine-borates of di(heteroary1)borinic acids with bromine or N-bromosuccinimide,94 whilst the presence of the bromine substituent in 6-bromo- 2-lithiopyridine causes rearrangement of its initially formed trialkylborate salts leading ultimately to unsaturated nit rile^.^' Reagents i R,B; ii EX; iii [O] Scheme 13 Addition of CuI to lithium trialkylmethylborates gives uncharacterized species assumed to be Cu'[R,BMe]- which undergo conjugate addition of the alkyl group to a@-unsaturated nitriles esters et~.,'~ and can also be used to alkylate reactive halide^.^' A modification of the latter reaction gives a stereoselective synthesis of ~inylsilanes.~~ Copper(1) species though perhaps not the corresponding borates are also intermediates in the preparation of conjugated (E,E)-dienes from dialkenyl- chloroborane and methyl~opper.~~ Lithium tetra-alkyl- and trialkylaryl-borates transfer an alkyl (or aryl) group to acid chlorides giving ketones as products.100 Thus the trialkylborane acts to moderate the reactivity of the organolithium reagent preventing further alkylation.Reactions of trialkylboranes with 1,l-bis(pheny1thio)alkanes give borates which spontaneously rearrange to give compounds that are oxidizable to ketones. Addi- tion of an electrophile such as HgC12 prior to oxidation results in the formation of tertiary alcohols (Scheme 14)."' If 2-alkylbenzo-1,3-dithioles are used instead of 1,l-bis(phenylthio)alkanes this allows the reactions to be applied to hindered organoboranes.lo2 The reaction of the ate-complex from a trialkylborane and methylthiomethyl-lithium with methyl iodide gives the homologated organoborane R2BCH2R.lo3 93 A. B. Levy Tetrahedron Lett. 1979,4021. 94 G. M. Davies P. S. Davies W. E. Paget and J. M. Wardleworth Tetrahedron Lett 1976 795. 95 K. Utimoto N. Sakai M. Obayashi and H. Nozaki Tetrahedron 1976 32 769. 96 N. Miyaura M. Itoh and A. Suzuki Tetrahedron Lett. 1976,255;K. Yamada N. Miyaura M. Itoh and A. Suzuki Bull. Chem. SOC. Jpn. 1977,50,3431;Y.Yamamoto H. Yatagai and K. Maruyama J. Org. Chem. 1979,44,1744. " K. Yamada T. Yano N. Miyaura and A. Suzuki Bull. Chem. SOC.Jpn. 1979,52,275. 98 K. Uchida K. Utimoto and H. Nozaki J. Org. Chem. 1976 41 2941. 99 Y. Yamamoto H. Yatagai and I. Moritani J. Am. Chem. SOC., 1975 97 5606; Y. Yamamoto H. Yatagai K. Maruyama A. Sonoda and S. Murahashi Bull. Chem. SOC., Jpn. 1977 50 3427. loo E. Negishi K.-W. Chiu and T. Yosida J. Org. Chem. 1975,40,1676; E. Negishi A. Abrarnovitch and R. E. Merrill J. Chem. SOC.,Chem. Commun. 1975 138. lo' R. J. Hughes S. Ncube A. Pelter K. Smith E. Negishi and T. Yoshida J. Chem. SOC., Perkin Trans. 1 1977,1172. lo' S. Ncube A. Pelter and K. Smith Tetrahedron Lett. 1979 1883 1895. lo3 E. Negishi T. Yoshida A. Silveira and B.L. Chiou J. Org. Chem. 1975 40 814. Organ o boron Chemistry HgCIz R:R'COH 1[01 \,B-CR:R2 c--R;BCR'R2SPh X' Scheme 14 R'COR' The reactions of lithium aldimines with dialkyl-chloroboranes followed by treatment with electrophiles offer an alternative method for the synthesis of ketones and tertiary alcohols.104 5 Applications of fly-Unsaturated Organoboron Compounds Allyl-boranes have been extensively studied by Mikhailov's group for many years. In particular their reactions with alkynes allenes and reactive alkenes resulting in addition of the allyl-boron unit (with rearrangement of the ally1 group) across the multiple bond have led to interesting novel boron-containing Reactions of allyl-boron compounds with aldehydes and ketones also involve rearrangement and provide syntheses of homoallylic alcohols,lo6 sometimes with considerable diastereoselectivity .106c*d Propargyl-and allenyl-boron compounds react with carbonyl compounds to give homoallenyl and homopropargyl alcohols respectively.83a*107 Following Mukaiyama's demonstration of crossed aldol reactions between boron enolates (vinyloxy-boranes) and carbonyl compounds,108 much effort has been devoted to studying such reactions.Methods for the synthesis of vinyloxy-boranes include addition of boron compounds to a& unsaturated carbonyl compounds '08*'09 or ketens,*1° reactions of trialkylboranes with a-diazocarbonyl compounds,'" and boron-compound-promoted enolysis of ketones."' By careful choice of method it is often possible to obtain either the (2)-or the (E)-isomer of the vinylborane with considerable ~electivity,"~~"~ and it has been shown that a given geometrical isomer Y.Yamamoto K. Konda and I. Moritani Bull. Chem. SOC.Jpn. 1975,48,3682; J. Org. Chem. 1975 40 3644. B. M. Mikhailov T. K. Kozminskaya and B. I. Bryantsev Zh. Obshch. Khim. 1976 46 87; Yu. N. Bubnov B. A. Kazanskii 0.A. Nesmeyanova T. Yu. Rudashevskaya and B. M. Mikhailov Zzv. Akad. Nauk SSSR,Ser. Khim. 1977,2545. (a) G. W. Krarner and H. C. Brown J. Org. Chem. 1977 42 2292; (b) B. M. Mikhailov Yu. N. Bubnov and A. V. Tsyban J. Organometal. Chem. 1978,154,113; (c)T. Herold and R. W. Hoffmann Angew. Chem. Znt. Ed. Engl. 1978,17 768; (d)R. W. Hoffrnann and H.-J. Zeiss ibid. 1979 18 306. lo' 8.Favre and M.Gaudemar J. Organometal. Chem. 1975,92 17. lo* M. Muraki K. Inomata and T. Mukaiyama Bull. Chem.SOC. Jpn. 1975,48,3200;T. Mukaiyama and T. Inoue Chem. Lett. 1976,559 Io9 W. Fenzl R. Koster and H. J. Zimmermann Justus Liebigs Ann. Chem. 1975 2201; 1976 1116. P. Paetzold and M. Lasch Chem. Ber. 1979 112 663. 'I1 S. Masamune S. Mori D. Van Horn and D. W. Brooks Tetrahedron Lett. 1979 1665. 'I2 W. Fenzl and R. Koster Justus Liebigs Ann. Chem. 1975 1322; W. Fenzl H. Kosfeld and R. Koster ibid. 1976 1370. (a) M. Hirama and S. Masamune Tetrahedron Lett. 1979,2225; (b) D. E. Van Horn and S. Masamune ibid. p. 2229; (c) M. Hirama D. S.Garvey L. D.-L. Lu and S. Masamune ibid. p. 3937. 'I4 D. A. Evans E. Vogel and J. V. Nelson J. Am. Chem. SOC., 1979,101,6120.K. Smith and W.E. Paget reacts in a highly diastereoselective manner with a given carbonyl compound thus allowing the synthesis of diastereoisomers with relative ease (e.g.Scheme 15).113~"4 This approach has allowed a simplified synthesis of the Prelog-Djerassi lactonic acid. '3c (>97%this isomer) (385% this isomer) Reagents i c,BOSO,CF +EtNPr',; ii RCHO; iii BOS02CF + EtNPr' Scheme 15 Potassium trialkyl(vinyloxy)borates formed by addition of potassium enolates to trialkylboranes react more selectively with alkyl halides than do the potassium enolates Vinylamino-boranes also undergo aldol condensation reac- tions,"6 whilst the related reactions of phenylamino-boron compounds allow specific ortha-substitution of aniline derivative~."~ Particularly useful is the formation of ortho-formyl derivatives from the reactions with isocyanides (Scheme 16)."* Related reactions have been used to prepare indoles' l9 and acridines.I2' 6 Novel Types of Organoboron Compound Attempts to synthesize highly hindered tri-t-butylborane have now been success- ful.12' A number of bora-adamantane compounds have been prepared including l-bora-adamantane,122 2-b0ra-adamantane,'~~ the dibora-compound (1),124and the E.Negishi M. J. Idacavage F. DiPasquale and A. Silveira Tetrahedron Lett. 1979 845. T. Sugasawa T. Toyoda and K. Sasakura Synth. Commun. 1979,9,515; T. Sugasawa and T. Toyoda ibid. p. 553 Tetrahedron Lett. 1979 1423. T. Sugasawa T. Toyoda M. Adachi and K. Sasakura J. Am. Chem.SOC.,1978,100,4842. "* T. Sugasawa H. Hamana T. Toyoda and M. Adachi Synthesis 1979 99. T. Sugasawa M.Adachi K. Sasakura and A. Kitagawa J. Org. Chem. 1979,44,578. 120-B. M. Mikhailov V. A. Dorokhov and 0. G. Boldyreva Izu. Akad. Nauk SSSR,Ser. Khim. 1978 2574. H. Noth and T. Taeger J. Organometal. Chem. 1977,142,281. B. M. Mikhailov and T. K. Baryshnikova Dokl. Akad. Nauk SSSR,1978 243 929. 123 B. M. Mikhailov T. A. Shchegoleva E. M. Shashkova and V. G. Kiselev Izu. Akad. Nauk SSSR,Ser. Khim. 1977,894. 124 S. U. Kulkarni and H. C. Brown J. Org. Chem. 1979 44 1747. 12' Organoboron Chemistry R' R' liii R' NHR' X \ Reagents i BCI,; ii RZN=C; iii Et3N; iv aq. AcOH; v aq. HCI NR~ Scheme 16 hexabora-adamantane (2).lZ5Such compounds form extremely strong complexes with donor molecules.122*124 A bora-adamantane with a betaine structure has also been prepared. The reactions of dialkyl-chloroboranes with di-iso-propylcarbamoyl-lithium give rise to other novel types of organoboron betaines with interesting properties. lZ7 For example compound (3) apparently forms stable addition compounds with simple amides. 127a (1) (2) (3) A plethora of transition-metal complexes of boron compounds has been synthesized. Of particular interest are complexes of borabenzene derivatives,"* including a new class of stable twenty-electron sandwich complexes (4),lZ9and multi-decker sandwiches in which cyclic boron compounds such as (5),l3' (6),13'and (7)13' are the ligands. The current multi-decker record holder rivalling the 'Big Mac@' in terms of number of layers is a trinuclear tetra-decker sandwich of (5)with consecutive Co Fe and Co atoms as the n~c1ei.l~~ M.P. Brown A. K. Holliday and G. M. Way J. Chem. Soc. Dalton Trans. 1975 148; I. Rayment and H. M. M. Shearer ibid. 1977 136. W. Kliegel and E. Ahlenstiel Chem. Ber. 1976 109 3547. 127 (a) A. S. Fletcher W. E. Paget K. Smith K. Swaminathan J. H. Beynon R. P. Morgan M. Bozorgzadeh and M. J. Haley J. Chem. SOC..Chem. Commun. 1979 347; (b) A. S. Fletcher W. E. Paget K. Smith K. Swaminathan and M. J. Haley ibid.. p. 573. 12' G. E. Herberich H. J. Becker and G. Engelke J. Organometal. Chem. 1978,153,265; and references cited therein; G. E. Herberich G. Engelke and W. Pahlmann Chem.Ber. 1979,112,607;A. J. Ashe W. Butler and H. F. Sandford J. Amer. Chem. SOC.,1979,101 7066. 129 G. E. Herberich W. Koch and H. Lueken J. Organometal. Chem. 1978,160 17. 130 W. Siebert and W. Rothermel Angew. Chem. Znt. Ed. Engl. 1977 16 333. 131 G. E. Herberich J. Hengesbach U. Kolle G. Huttner and A. Frank Angew. Chem. Int. Ed. Engl. 1976 15,433. 13' W. Siebert and M.Bochmann Angew. Chem. Znt. Ed. Engl. 1977,16,857; W. Siebert J. Edwin and M. Bochmann. ibid.. 1978,17.868. 133 W. Siebert,'W. Rotherme1,C. Bohle C. Kriiger and D. J. Brauer Angew. Chem. Int. Ed. Engl. 1979 18,949. K. Smith and W.E. Paget Et Et Et Et Na+ do MeB\ ,BMe S Ph Cyclopentadien ylboron and 7-borabicyc10[2.2.1]heptadienes'~~ are fluxional molecules.Reactions of polyborylmethyl anions with carbonyl compounds give rise to alkenyl-boron compounds with one less boron unit on the B-attached carbon atom.'36 This type of approach has been applied in the synthesis of homologated aldehyde^,'^^" methyl ketones,'36b borazaroquinolines,'36' and keten dithioacetal~.'~~~ In the last case the reagent is an a-phenylthio-boron compound other examples of which have been used in the synthesis of acetals and mon~thioacetals'~~ and of iodomethaneboronic Several other (a-halo- geno-alky1)boronic acid derivatives have been prepared by various procedures. 139 Amine adducts of cyano- carbamoyl- and carboxy-boranes e.g. (8),are interest- ing as boron-containing analogues of a-amino-acid~.'~~ An isocyanide (9)has also been ~btained.'~' A number of other potentially interesting new compound types have not been so well characterized however.For example the previously claimed Bu2BCOPh has now been shown not to be the product of reaction of 'Bu2BK' with benzoyl chloride and indeed 'Bu2BK' is not even an approximate representation of the species in solution after treatment of Bu2BCl with sodium-potassium alloy.'42 The product is in fact some type of borohydride. However highly interesting cyclic products such as (10)and (1 1) have been claimed without substantial evidence to be produced from the reactions of cyclohexene with the MeBC12-potassium and with the photolysis products of tri-l-naphthylb~rane.'~~ The danger of making assumptions about these latter reactions has been pointed 134 P.Jutzi and A. Seufert J. Organometal. Chem. 1979,169,327 357 373; Chem. Ber. 1979,112,2481; H. D. Johnson T. W. Hartford and C. W. Spangler J. Chem. SOC., Chem. Commun. 1978,242. 135 J. J. Eisch and J. E. Galle J. Organometal. Chem. 1977 127 C9. 136 (a) D. S. Matteson R. J. Moody and P.K. Jesthi J.Am. Chem. SOC., 1975,97,5608;(b) R. J. Moody and D. S. Matteson J. Organometal. Chem. 1978,152,265,(c) D. S. Matteson M. S. Biernbaum R. A. Bechtold J. D. Campbell and R. J. Wilcsek J. Org. Chem. 1978,43,950;(d) A. Mendoza and D. S. Matteson ibid. 1979,44 1352. 137 A. Mendoza and D. S. Matteson J. Chem. SOC., Chem. Commun. 1978,357;J. Organometal. Chem. 1978,156.149. 138 D. S. Matteson and D. Majumdar J. Organometal.Chem. 1979 170 259. 139 M. W. Rathke E. Chao and G.Wu J. Organometal. Chem. 1976,122,145; D. S. Matteson and P. K. Jesthi ibid. 1976,114,l;H. C. Brown N. R. De Lue Y. Yamamoto and K. Maruyama J. Org. Chem. 1977,42,3252. 140 B. F. Spielvogel F. Harchelroad and P. Wisian-Nielson J. Inorg. Nucl. Chem. 1979 41 1223; and references cited therein. 141 J. L. Vidal and G. E. Ryschkewitsch,J. Chem. SOC.,Chem. Commun. 1976,192. 142 K. Smith and K. Swaminathan J. Chem SOC.,Dalton Trans. 1976,2297. 143 S. M. van der Kerk J. Boersma and G. J. M. van der Kerk Tetrahedron Lett. 1976,4765. 144 B. G. Ramsey and D. M. Anjo J. Am. Chem. Soc. 1977,99,3182. 145 J. J. Eisch and H. P. Becker J. Organometal. Chem. 1979,171,141;see also K. Smith Ann.Reports (B) 1976 73 122. Organoboron Chemistry 301 Me $I-BH2C02H Me3$-BH2NC O R a 7 Miscellaneous Organoboron Chemistry Tris(organylthio)boranes,(RS)3B react with carboxylic or ester~'~' to give thioesters and their established application for the synthesis of thioketals has been e~tended.'~~ They are also useful for synthesis of 1,3-bis(organylthio)alkenes from enones,14' and for the formation of 2-hydroxyalkyl sulphides by ring-opening of epoxides.150 The corresponding selenoboron compounds are applicable to selenoketal Dialkyl(methylthio)boranes RiBSMe give dialkyl-bromoboranes on reaction with bromine,1s2 and dialkyl-bromoboranes can be converted into 'mixed' tri- alkylboranes RlR2B by treatment with sodium hydride in the presence of an a1kex1e.l~~9-Bromo-9-BBN is a convenient and selective reagent for cleavage of and catecholborane has been used in the formation of amides and macrocyclic lactones from carboxylic acids.155 146 A. Pelter T. E. Levitt K. Smith and A. Jones J. Chem. SOC.,Perkin Trans. 1 1977 1672. 147 T. Cohen and R. E. Gapinski. Tetrahedron Lett. 1978,4319. 14* D. R.Morton and S.J. Hobbs J. Org. Chem. 1979,44,656; H. A. Klein 2.Naturforsch. Teil B 1979 34,999. 149 T. Cohen D. A. Bennett and A. J. Mura J. Org. Chem. 1976,41 2506. Is' H. A. Klein Chem. Ber. 1979,112 3037. D. L. J. Clive and S. M. Menchen J. Chem. SOC., Chem. Commun. 1978,356; J. Org. Chem. 1979,44 1883. Is' A. Pelter K. Rowe D. N. Sharrocks K. Smith and C. Subrahmanyam J.Chem. SOC.,Dalton Trans. 1976,2087. A. Pelter K. Rowe and K. Smith J. Chem. SOC., Chem. Commun. 1975 532. lS4 M. V. Bhatt J. Organometal. Chem. 1978,156 221. 15' D. B. Collum S.-C. Chen and B. Ganem J. Org. Chem. 1978,43,4393.

ISSN:0069-3030    

DOI:10.1039/OC9797600287

出版商:RSC    

年代:1979

数据来源: RSC

摘要:

14 Organophosphorus Chemistry By C. D.HALL Department of Chemistry King's College (University of London) Strand London WC2R 2LS During the six years since the last review,' more than ten thousand papers have been published in the field of organophosphorus chemistry; in consequence it is inevitable that this report will be highly selective. In particular lack of space has led to the omission of a section on phosphorus biochemistry. To a large extent the period has been one of consolidation with the major advances arising from the study of penta- and hexa-co-ordinate phosphorus compounds many of which are now available as stable isolable compounds. Interest in highly reactive phosphorus species (phos- phorus radicals methylenephosphines and metaphosphates) has also flourished and as synthetic and instrumental techniques improve one may envisage further growth in these areas.The period has seen the publication of all seven volumes of the invaluable book by Kosolapoff,2 and several useful texts or monographs have a~peared.~ In addition the Specialist Periodical report^,^ now up to Volume 10 continue to provide excellent abstract coverage annually. 1 Pentaco-ordinate Phosphorus Compounds Structure.-Phosphoranes vary in structure from trigonal-bipyramidal (tbp) e.g. (1)5and (2) to square-pyramidal (sqp) e.g. (3;X= 0,Y =H Z = Me) with the vast S. Trippett Ann.Reports (B),1973,70 Ch. 8 p. 268. 'Organic Phosphorus Compounds' ed. G. M. Kosolapoff and L. Maier Wiley-Interscience New York 1973 VO~S. 1-7.J. W.Emsley and C. D. Hall 'The Chemistry of Phosphorus' Harper and Row London 1976; D. E. C. Corbridge 'Phosphorus -An Outline of its Chemistry Biochemistry and Technology' Elsevier Amsterdam 1978; R. Luckenbach 'Dynamic Stereochemistry of Pentaco-ordinated Phosphorus and Related Elements' G. Thieme Stuttgart 1973. 'Organophosphorus Chemistry' ed. S. Trippett and D. W. Hutchinson (Specialist Periodical Reports) The Chemical Society London 1970-78 Vols. 1-10. R. Sarma F. Ramirez B. McKeever J. F. Maracek and S. Lee J. Amer. Chem. Soc.. 1976,98,581. 304 C. D. Hall majority of spirophosphoranes falling into the category of distorted tbp e.g. (3; X = 0,Y =H Z =F).6 Analysis of the distortions from ideal tbp in compounds of type (3)shows that these are towards sqp i.e.along the pathway followed in a Berry pseudorotation,’ and calculations reveal that the sqp is favoured by enhanced electronegativity in X and Y and an enhanced electropositive character for Z.* Ligand Reorganization. -Interest in ligand reorganization (‘permutational iso- merization’ or ‘polytopal rearrangement’) within phosphoranes has continued at a high level especially with regard to the energy barriers for such rearrangements.’ Dynamic n.m.r. spectroscopy remains the principal technique in this area and studies of acyclic phosphoranes containing trifluoromethyl groups e.g. (4) by ”F n.m.r. and 13C n.m.r. have revealed apicophilicities that decrease in the order X = F >CI >OMe >SMe >NMe2>Me.” Likewise ‘H and ”F n.m.r.studies of monocyclic e.g. (9,and bicyclic phosphoranes e.g. (6),have extended the range 1 :,Ph Ph-P qCF CF3 (5) shown above and placed it on a more quantitative A combination of the available data results in a range of semi-quantitative relative values of apicophilicity (Table 1).These energy differences must be treated with caution but may be a useful guide to assessing the energetics of displaceinent ‘reactions at phosphorus via pentaco-ordinate intermediates. Table 1 Relative apicophilicities for a variety of groups Group F CN Ph0,PhS CI,NCO,NCS H N OMe SMe NMe Me Pr’ Ph A(AGl)/kJrnol-’ 0 1 4 5 -8* 11 12 20 27 31 34 50 * Values range from 4 to 12. Similar methods have been used to determine the barriers facing the diequatorial disposition of small rings [e.g.in (7) (8) and (9)]and in this context the importance of maintaining lone pairs on heteroatoms attached to phosphorus in the equatorial plane has been evaluated.’ In addition it is now obvious that one cannot ignore steric factor~,’”~ and the small size of the hydrogen atom may well account for its 6 H.Wunderlich D. Mootz R. Schmutzler and M. Wieber 2.Naturforsch. 1974,29b 32. 7 R. R. Holrnes and J. A. Deiters J. Amer. Chem. SOC.,1977 99,3318. 8 R.R. Holmes J. Amer. Chem. SOC.,1975,97 5379. 9 S. Trippett Phosphorus Sulfur 1976 1,89. 10 K. I. The and R. G. Cavell Znorg. Chem. 1977 16 2887; ibid. 1976 15,2518; R. G. Cavell J. A. Gibson and K. I. The ibid. 1978 17 2880. 11 R. K. Oram and S.Trippett J.C.S. Perkin I 1973 1300; J. Brierley J. I. Dickstein and S. Trippett Phosphorus Sulfur 1979 7 167. 12 1. Szele S.J. Kubisen jnr. and F. H. Westheimer J. Amer. Chem. SOC.,1976,98 3533. Organophosphorus Chemistry unexpectedly high apicophilicity. On the theoretical side Holmes has developed a model which predicts the free energies of activation for Berry pseudorotations; the agreement with experiment over a wide range of phosphoranes is g00d.l~ Ph OPh OMe (7) (8) (9) The Berry process is now widely accepted as the most likely mechanism for ligand reorganization. Ab initio calculations on PHSreveal AG' =8 kJ mo1-I (for Berry) versus 42 kJ mol-' for the turnstile (TR) me~hanism,'~ and compounds such as (lo) with every incentive to adopt a 0" (2+3) conformation turn out to be distorted tbp but apparently still capable of undergoing rapid reorganization of ligands." Furthermore compounds such as (11)do not undergo ligand reorganization when according to the TR mechanism they should.16 Preparation and Chemistry of Phosphoranes.-Reviews have appeared on the synthetic applications of oxyphosphoranes" and on the penta-alkyl derivatives of l3 R. R. Holmes J. Amer. Chem. SOC. 1978 100 433. 14. J. A. Altmann K. Yates and I. G. Csizmadia J. Amer. Chem. SOC. 1976,98 1450. Is D. Hellwinkel W. Blaicher W. Krapp and W. S. Sheldrick Chem. Be?. 1980,113,1406. l6 D. B. Denney personal communication. F. Ramirez and I. Ugi Bull. SOC. chim. France 1974,453. H. Schmidbaur Adv. Organometallic Chem.1976,14,205. l9 L. L. Chang. D. B. Denney D. Z. Denney and R. J. Kazior J. Amer. Chem. Soc. 1977,99,2293; D. A. Bowman D. B. Denney and D. Z. Denney Phosphorus Sulfur 1978,4229. 2o N. J. De'ath and D. B. Denney Phosphorus Sulfur 1977 3 51. 306 C.D. Hall elements of Group 5.18 The reaction of sulphenate esters (12) with trico-ordinate phosphorus compounds (see Scheme 1) is now the method of choice for the preparation of acyclic alkoxyphosphoranes which in some cases may be distilled or obtained crystalline.” The peroxide route has also received further attention,20 and kinetic evidence has been marshalled to support the contention that the reaction of trico-ordinate phosphorus with diethyl peroxide” or dioxetan22 is a concerted (biphilic) process.Difluorophosphoranes are obtained from phosphines or phos- phites with CF30F (CF30), or (CF3S)2,the first being the reagent of [reaction (l)] and details of the dynamic n.m.r. of difluorophosphetans (13) have appeared.24 R’OSPh + R:P -* [RiP(OR’)SPh] RlOSPh RzP(OR’)2 + PhSSPh (12) (R2=alkyl aryl or alkoxy) Scheme 1 CF30F + R3P -* R3PF2 + COF2 (13) a; R=H b; R=Me 0 R3P + HO(CH2),0H + Pri2NC1-B R3P/ ‘(CH2), + Pri&H2Cl-(2) ‘O/ Diols and 0-amino-phenols react with a wide range of trico-ordinate phosphorus compounds in the presence of N-chlorodi-isopropylamine to yield phosphoranes [reaction (2)],” and Kabachnik has shown that spirophosphoranes (15) may be obtained from (14) and o-aminophenol.26 0y; + (Ph0)2PC13 + N 0:N:.:n (14) HH (15) ” G.Scott P. J. Hammond C. D. Hall and J. D. Bramblett J.C.S. Perkin ZZ 1977 882. *’ P. D. Bartlett A. L.Baumstark M. E. Landis and C. L. Lerman J. Amer. Chem. Soc. 1974,% 5267. 23 N. J. De’ath D. Z. Denney D. B. Denney and C. D. Hall Phosphorus 1974,3 205. 24 N. J. De’ath D. B. Denney D. Z. Denney and Y. F. Hsu,J. Amer. Chem. SOC., 1976,98,768. *’ S. Antczak S. A. Bone J. Brierley and S. Trippett J.C.S. Perkin I 1977 278. 26 N. A. Tikhonina V. A. Gilyarov and M. P. Kabachnik Zzvest. Akad. NaukS.S.S.R. Ser. khim. 1976 2442. Organophosphorus Chemistry The condensations of trico-ordinate phosphorus compounds with dienes ( 16a),27 @-unsaturated carbonyl compounds ( 16b),28 and a-dicarbonyls or monothiocar- bonyls (16~)~' continue to offer useful routes to a variety of mono- and bi-cyclic phosphoranes [reaction(3)].Numerous stable phosphoranes containing the P-H bond have been ~repared,~' and the positions of equilibria with the corresponding tervalent phosphorus compounds [reaction(4)] have been shown to depend to a large (16) a; X Y = CH2 b; X=O;Y=CH c; X=OorS;Y=O 00 (4) X Y x HY (X,Y = 0or NMe) extent on symmetry." Furthermore the first stable hydroxyphosphorane (18a) was obtained recently by the action of dry HCI in CHzC12 on its trimethylsilyl ester ( 17).32 Equilibrium to the phosphate (18b) was slow on the n.m.r. time-scale below 10"C,in MeCN. OSiMe (17) (184 R'P(OR2) + R3CH=C(R4)NO2--.* R1(R20)zP'~o-R4 (19) R3= Pr' or Ar R4 = H or Ph (20) High yields of monocyclic phosphoranes (20) are obtainable from phosphonites and nitro-olefins (19),33 and activated olefins (21) have been shown to give good 27 N.A. Razumova N. A. Kurshakova Z. L. Evtikhov and A. A. Petrov J. Gen. Chem. (U.S.S.R.) 1974 44 1834. 28 V. V. Vasil'ev N. A. Razumova and L. V. Dogadaeva J. Gen. Chem. (U.S.S.R.),1976,46,461. 29 B. A. Arbuzov N. A. Polezhaeva V. V. Smirnov and A. A. Musina Bull. Acad. Sci. U.S.S.R.,1975,24 1548; D. Bernard and R. Burgada Tetrahedron 1975,31,797. 30 D. Houalla M. Sanchez D. Gonbeau and G. Pfister-Guillouzo Nouueau. J. Chem. 1979 3 507; M. Koenig A. Munoz. B. Garigues and R. Wolf Phosphorus Sulfur 1979,6 435. 3' R. Burgada and C. Laurenco J. Organometallic Chem.1974,66 255. 32 F. Ramirez M. Nowakowski and J. F. Marecek J. Amer. Chem. SOC. 1977,99,4515. 33 R. D. Gareev G. M. Loginova and A. N. Pudovik J. Gen. Chem. (U.S.S.R.) 1976,46 1843; J. I. G. Cadogan R. A. North,and A. G. Rowley J. Chem. Res.(S). 1978 1. 308 C. D. Hall yields of acyclic monocyclic and bicyclic phosphoranes with phosphinites or phos- phonites in the presence of alcohols diols or catechol~~~ [reaction(5)]. PhzPOEt + CH2=CHX + EtOH + Ph2P(OEt)2CH2CH2X (5) (21) (X =CN or C02Et) Some bicyclic phosphoranes e.g. (22) are remarkably stable,3s and general routes to analogous phosphoranes (23)have been de~eloped.~~ Finally although the routes from phosphonium salts or the phosphoryl group remain relative rarities careful control of the conditions gives spirophosphoranes [rea~tion(6)],~' and Trippett has developed a method from alkylated phosphine oxides or sulphides by treatment with catechols in the presence of di-isopropylamine [rea~tion(7)].~~ (23) Y = CH2 NH or 0 2 = CH2 or NH Me Phosphoranes have been detected by low-temperature n.m.r.as intermediates in the Arbusov reaction,39 and conductivity measurements in acetonitrile have allowed the calculation of equilibrium constants for the dissociation of both pentaco-ordinate and hexaco-ordinate phosphorus [reactions (8) and (9)].""On the other hand a kinetic study of the hydrolysis of phosphoranes has shown that the reaction proceeds through a hexaco-ordinate intermediate (or transition state) rather than through a 34 P.D. Beer R. C. Edwards C. D. Hall J. R. Jennings and R. J. Cozens J.C.S. Chem. Comm.,1980,351. " D.Hellwinkel and W. Krapp Chem. Ber. 1978,111,13. 36 A.Schmidpeter J. H. Weinmaier and E. Glaser Angew. Chem. Znrernar. Edn. 1977,16 549,865. 37 H. Schmidbaur P. Holl and F. H. Kohler Angew. Chem. Internat. Edn. 1977 16 722. 38 S.Antczak and S. Trippett J.C.S.Perkin Z 1978 1326. 39 J. Michalski J. Mikolajczak M. Pakulski and A. Skowronska Phosphoms Sulfur,1978.4 233; D.B. Denney D. Z. Denney and G. Di Miele ibid. p. 125. 40 I. S. Sigal and F. H. Westheimer J. Amer. Chem. SOC.,1979,101 5329 5334. Organophosphorus Chemistry dissociative me~hanism.~~ By analogy with orthoesters alkoxyphosphoranes are powerful alkylating agents,42 and those containing a P-H bond will add to aldehydes or imines to form phosphoranes [reaction H PhCH-ZH (':I!:) XY +PhCH=Z --* (>?I (X,Y = 0or NMe) (Z= 0,NMe or NPh) A trioxaphosphetan (24)has been recognized as a convenient source of singlet oxygen,44 and pure isomers of 1,3,2-oxazaphospholidines,e.g.(25),have been prepared by asymmetric induction and their isomerization followed polarimetric- 2 Hexaco-ordinatePhosphorus Compounds Interest in the preparation of hexaco-ordinate phosphorus compounds has expanded from the cyclic phosphonite method (Scheme 2)46through a facile synthesis from R (R= Me or Ph) H Scheme 2 HOW Reagents i POCl or PCI,; ii Et,N Scheme3 41 W. C. Archie jun. and F. H. Westheimer J. Amer. Chern. SOC.,1973,95 5955.42 W. G. Voncken and H. M. Buck Rec. Trau. chirn. 1974,93,210. 43 C. Laurenco and R. Burgada Tetrahedron 1976,32,2089. 44 A. P. Schaap K. Kees and A. L. Thayer J. Org. Chem. 1975,40 1185. " (a) A. Klaibi A. Cachapuz Carrelhas J.-F. Brazier and R. Wolf J.C.S. Perkin ZZ 1974 1668; (b) A. KlaCbB 14. Koenig R. Wolf and P. Ahlberg J.C.S. Dalton 1977 570. 46 M. Wieber K. Foroughi and H. Klingl Chem. Ber. 1974 107,639. 310 C.D. Hall phosphorus oxychloride (Scheme 3)47 to a simple preparation of hexamethoxy- phosphate anion (Scheme 4).48 (MeO)5P + MeOK (excess) T(Me0)6P Kf Scheme 4 The chirality of the six-co-ordinate anion of (26) has been demonstrated by the diastereotopic nature of the methyl groups,49 and one form of the salt (27) has been obtained pure again by asymmetric indu~tion.'~ Equilibration of the diastereomers can be followed as with the pentaco-ordinate systems by an n.m.r.or a polarimetric temperature jump method .456 Nucleophilic substitution at pentaco-ordinate phosphorus e.g. in (28),occurs via hexaco-ordinate structures with inversion and/or retention at phosphoru~.'~ Although the stable configuration of spiro-bicyclic six-co-ordinate phosphorus is apparently cis,52it appears that under certain conditions nucleophilic attack at Pv is under kinetic control and gives initially the less stable trans structure (29) before isomerization to the cis form (30).53This is probably an example of stereoelectronic control by lone pairs on heteroatoms within the substrate which give in the case of the trans compound a more effective overlap with the developing u-bond between phosphorus and the incoming nucleophile.3 Tetraco-ordinate Phosphorus Compounds Phosphorus(v) Esters.-The kinetics and mechanism of nucleophilic displacement especially hydrolysis at the tetraco-ordinate phosphorus of phosphorus(v) esters 47 M. Gallagher A. Munoz G. Gence and M. Koenig J.C.S. Chem. Comm. 1976,321. 48 D. B. Denney D. Z. Denney and C.-F. Ling J. Amer. Chem. SOC.,1976,98,6755. 49 D. Hellwinkel and W. Krapp Phosphorus 1976,6,91. 50 M. Koenig A. KlaCbk A. Munoz,and R. Wolf J.C.S. Perkin 11 1976,955. S. Trippett and R. E. L. Waddling Tetrahedron Letters 1979 193. 52 R. Sarma F. Ramirez B. McKeever J. F. Maracek and V. A. V. Prasad Phosphorus Sulfur 1979,5 323." J. H. M. Font Freide and S. Trippett J.C.S. Chem. Comm. 1980,157. Organophosphorus Chemistry have continued to receive considerable attention,54 and among the more unusual aspects are reports of micellar catalysis,55 an a-effect with hydro-peroxide as nu~leophile,~~ and the effects of heterocyclic groups on the alkaline hydrolysis of phosphinates e.g. (31) and phosphonates (32).57 A large proportion of (31) X=O or S (32) X=O,S or NMe the work however has concentrated on the stereochemistry of nucleophilic dis- placement and much has been documented on the synthesis resolution and determination of enantiomeric purity of tetraco-ordinate organophosphorus esters" and acids.59 In this respect the star prize must go to the synthesis of the chiral (1R)-['60,'70,'80]phospho-(S)-propane-l,2-diol (34) by the reaction of (33) which originates from ephedrine with the 0-benzyl ether of (S)-propane-1,2-dio16' (see Scheme 5).Me #' (331 Me Me 0 H* Ph (34) Reagents i H3180+,CF3C02H;ii H2 Pd/C Scheme 5 Derivatives of the anti-cancer drug cyclophosphamide continue to attract atten- tion,61 and optically active forms of the drug have been reported.62 Within a welter s4 V. E. BelSkii Russ. Chem. Rev. 1977,46,1578; F. fI. Westheimer Pure Appl. Chem. 1977,49,1059. " C. A. Bunton S. Diaz G. M. Van Fleteren and C. Park J. Org. Chem. 1978,43,258. " L. Horner and A. Parg Annalen 1977,61. " D. W. Allen B. G. Hutley and M. T. J. Mellor J.C.S. Perkin ZI 1977 1705,789.'13 C. R. Hall and T. D. Inch Phosphorus Sulfur 1979,7,171. 59 M. Mikolajczyk and M. Leitloff Russ. Chem. Rev. 1975,44 670. " S. J. Abbott S. R. Jones S. A. Weinman F. M. Bockhoff F. W. McLafferty and J. R. Knowles J. Amer. Chem. SOC., 1979,101,4323. 61 H. J. Hohurst G. Peter and R. F. Struck Cancer Res. 1976,36 2278. 62 Ger. Offen. 2 644 905,1977 (Chem. Abs. 1977,87,53 401); T. Kawashima R. D. Kroshefsky R. A. Kok and J. G. Verkade J. Org. Chem. 1978,43 11 11. 312 C. D. Hall of good reviews those on phosphorus-selenium phosphorus esters from oxypho~phoranes,~~ and phosphorylation6’ are perhaps of widest appeal. Phosphonium Salts.-Among the many syntheses of phosphonium salts one of the most useful is the acid-catalysed cyclization of hydroxy-phosphines (35)to give good yields of phospholanium (36) or phosphorinanium salts (37),66 as shown in Scheme 6.R2=alkyl or Ph (37) n=lor2 Reagents i HBr; ii NaHCO Scheme6 Since the early reports of enormously enhanced rates of hydrolysis of phos-phonium salts in media of low p~larity,~’ much has been learned about the effects of salt solvent and substituents on the decomposition of phosphonium salts promoted by hydroxide or alkoxide anions.68 In alkaline hydrolysis the vital intermediates are believed to be pentaco-ordinate e.g. (38) and (39) with loss of the phenyl anion occurring from the ionized phosphorane (see Scheme 7). The alkoxide reactions are Ph Ph I ,.-Ph HO-I...Ph Ph-P -Ph-P +Ph,PO +Ph-‘7 I Ph I’Ph OH 0-(38) (39) Ph OMe I =-Ph Ph-P I Ph Me0 OMe (41) OMe Me0 Ph,PO + MeOMe t-+I -MeO-Ph-P I /.Ph L MeOOpi.Ph ’ I Ph Ph Me0 MeO-Scheme 7 63 J.Michalski Chemicu Scriptu (A) 1975 8 58. 64 F. Ramirez and I. Ugi Phosphorus Sulfur 1976,1,231. 6J L. A. Slotin Synthesis 1977 737. 66 W. R. Purdum and K.D. Berlin J. Org. Chem. 1975 40 2801. 67 A. Schnell J. G. Dawber and J. C. Tebby J.C.S. Perkin ZZ,1976 633; F. Y. Khalil and G. Aksnes 2. phys. Chem. (Frunkfurr) 1975 97 179. 68 G. Aksnes PhosphorusSulfur 1977 3 227; G. Aksnes F. Y. Khalil and P. J. Majewski ibid. p. 157. Organophosphorus Chemistry 313 however thought to proceed via hexaco-ordinate intermediates (41)and (42),thus avoiding a route involving de-alkylation of a methoxyphosphorane (40).68 Notice the suggestion of trans attack on (40)to form (41)followed by rearrangement to cis before loss of the phenyl anion (cf.ref. 53). Not unexpectedly the hydrolysis of optically active phosphonium salts in media of low polarity gives rucemic oxide presumably due to the extended lifetimes of the pentaco-ordinate intermediate^."^ A thorough investigation confirms that the presence of bulky substituents at phosphorus [e.g. R=Bu' in (43)] leads to alkaline hydrolysis with retention of configuration at phosphorus whereas smaller groups (e.g. R = Pr" or Pr') give rise to almost complete in~ersion.~' Allen has added to his study of the hydrolysis of heteroarylphosphonium salts (44),71 and alkoxyphosphonium salts (45) which are intermediates in the Arbusov reaction have been isolated and characterized .72 6CH2Ph Br-R1\+,Me Me\+ Ph'y .P-CH,Ph Br-P FSO,-[d3 R2' \OR R (45) R' R2 = Et Ph OMe or OPh (43) (44) X=O or S 5 1O/O 49% The excellent work with cyclic phosphonium salts has been continued by Marsi with the observation of inversion in phosphocanium salts (46)73and alkoxyphos- phorinanium salts (47),74retention in a totally resolved phospholanium salt (48),75 but a non-stereospecific reaction with an alkoxyphospholanium salt (49),74all of 69 A.Schnell and J. C. Tebby J.C.S. Perkin I 1977 1883. 70 R.Luckenbach,2.Naturforsch. 1976,31b 1127. 71 D.W.Allen and B. G. Hutley J.C.S. Perkin I 1978,675. 72 K.S.Colle and E. S. Lewis J. Org.Chem. 1978,43,571. 73 K.L. Marsi and F. B. Burns Phosphorus 1974,4,211. 74 K.L.Marsi and J. L. Jasperse J. Org. Chem. 1978,43,760;K.L. Marsi ibid. 1975.40 1779. '' K.L. Marsi and A. Tuinstra J. Org. Chem. 1975,40 1843. 314 C. D. Hall which can be rationalized in terms of ring strain versus apicophilicity. The stereo- chemical properties of the 1-chlorophospholenium chloride (50)and its hydrolysis to a mixture of oxides have been and the isomerization of cis- phospholen (52) to the trans-compound (53)in the presence of traces of phosgene (present in CDCl,) has been the mechanism of isomerization probably involves (51). Finally a useful review has appeared on the synthesis of heterocyclic compoupds from vinylphosphonium and it may be of interest to note that phosphonium salts of type (54) have been shown to possess anti-leukaemic a~tivity.~’ RazCH2CH26Ph3Br-\ 0 \ Ph (54) (53) Phosphorus Ylides.-Work on the synthetic utility of the Wittig reaction has been so extensive that there is space only to mention some of the major reviews; these include historical aspects,80 the Horner-Wadsworth-Emmons modification,” carotenoids,82 insect pheromone^,^^ heterocyclic non-benzenoid cy~lophanes,~~ and syntheses employing phosphacumulenes and phospha-allene ylidesg6 Phosphazene and derivatives (R3P=NX) have also been reviewed.87 Interest in the mechanism of the Wittig reaction has been maintained especially with respect to the elucidation of factors controlling the stereochemistry of the resultant olefin.The original hypothesis of formation of the betaine (55)as the initial step followed by collapse to an oxaphosphetan (56),which subsequently rearranges to product^,^'^ has been superseded by the idea that (56) is formed directly in the 76 L. D. Quin and R. C. Stocks Phosphorus Sulfur,1977 3 151. ” P. J. Hammond and C. D. Hall Phosphorus Sulfur 1977,3,351. 78 E. Zbiral Synthesis 1974 775. 79 R. J. Dubois C.-C. Lin and J. A. Beisler J. Medicin. Chem. 1978 21 303. G. Wittig Accounts Chem. Res. 1974,7 6. J. Boutagy and R. Thomas Chem. Rev. 1974,14 87. 82 H. Pommer Angew. Chem. Znternut. Edn. 1977,16,423;B. C. L. Weedon Pure Appl. Chem. 1976,47 161. 83 R. Rossi Synthesis 1977 817. 84 K. P. C. Vollhardt Synthesis 1975,765. *’ B.Thulin 0.Wennerstrom and I. Somfai Actu. Chem. Scand. (B),1978 32 109. 86 H. J. Bestmann Angew. Chem. Internat. Edn. 1977 16 349. 87 R. A. Shaw Phosphorus Sulfur 1979 5,363. Organophosphorus Chemistry rate-limiting and then decomposes by cleavage of the phosphorus-carbon bond to form (57) which undergoes a rapid &elimination of phosphine oxide to generate the olefin (see Scheme 8). BestmannS9= suggests that (56) is formed with the cis-configuration (58) (see Scheme 9) and that when R is electron-donating (i.e. the ylide is ‘reactive’) the carbanion (59) eliminates phosphine oxide very rapidly with retention of stereochemistry to form the cis-(2)-olefin (60). If R is electron- withdrawing however the carbanion is stable enough for rotation about the C-C bond to compete with the elimination rate and the trans-(E)-olefin (62) results.Incidentally it may be necessary for (58) to pseudorotate to (61) before the phosphorus-carbon bond can cleave from an apical position. In contrast a Ar,P=CHR + Ar‘CHO + Ar,h-CHR Ar 3P0 I 6-CHAr‘ + RCH=CHAr’ \ (ir /” T Ar,P-CHR Ar,P CHR -II I1 0-CHAr’ .-0-CHAr’ (56) (57) Scheme 8 (Ris electron-withdrawing) Ar3P0 R + 1 Ar Scheme 9 B. Giese J. Schoch and G. Riichardt Chern. Ber. 1978,111 1395. 89 (a) H. J. Bestmann Pure Appl. Chem. 1979 51 515; (6) J. D. Thacker M.-H.Whangbo and J. Bordner J.C.S. Chem. Cornrn. 1979 1072. 316 C. D. Hall subsequent view89* suggests that there is initial formation of the trans-oxaphos- phetan (63),which ionizes to (64) and if R is electron-donating,in thepresence of salt then gives syn-elimination to form trans-olefin (cf.certain E 1cB elimination^).^^ In salt-free media however (64) is alleged to rotate about the C-C bond to give (65) which allows anti-elimination to form the cis-olefin as shown in Scheme 10. If R is electron-withdrawing (e.g. C02Et) the carbanion would be planar e.g. (66) and would tend to form the trans-olefin. Ar,PO + + R.. D + Ar,P 'C H 1 H'I -.Ar H\ c=c/ H 0-c-/\ 'H R Ar (65) Scheme 10 4 Trico-ordinate Phosphorus Compounds Phosphines.-Considerable emphasis has been placed on the synthesis and resolu- tion of chiral phosphines e.g. (67),91and their use in stereochemical reaction cycles has been reviewed.92 The synthesis configuration and conformation of phosphorus heterocycles such as (68) has been described9 and the chemistry of A 3-phosphorins [i.e.phosphabenzenes (69)] has been One of the most remarkable \ Rl--p- (68) X = 0,S or NR2 (67) X = H o-NMe2, R2/ o-OMe or p-OMe R' =Me Et or CH2Ph \ @:XI R2 = Me Pr" Pr' CH2Ph o-tolyl,or Et2N (70) 90 D. H. Hunter and D. J. Shearing J. Amer. Chem. SOC. 1971,93,2348. 91 L. Horner and M. Jordan Phosphorus Sulfur 1979,6,491. 92 R.Luckenbach,N. Muller and W. Endres Chem.-Ztg. 1976,100,320. 93 S. Samaan Phosphorus Sulfur 1979,7,89. 94 A. J. Ashe 111 Accounts Chem. Res. 1978,11 153; G. Markl Phosphorus Sulfur 1977,3,77. Organophosphorus Chemistry reports in this area is of the synthesis of the diphosphine (70)from white phosphorus and 0-dichl~robenzene.~~ The quaternization of phosphines with alkyl halides proceeds through a transition state which is rea~tant-like,~~ and the rate data correlate with the ionization potentials of the lone pairs on pho~phoranes.~~ The reaction of triphenylphosphine with CC1 may be controlled to give any one of three products (71)-(73) and (71) is a convenient source of the dichloro-ylide (74).98 Ph3P + CC4 3 Ph3kC13 C1- or Ph3kHCI2 C1- or Ph3kH2CI C1- (71)1(Me2NM' (72) (73) Ph3P=CC12 + (Me2N)3PC12 (74) The synthesis and use of optically active phosphines as co-catalysts for hydrogenation is still actively and the co-ordination properties of acyclic and constrained (bicyclic) amino-phosphines have been discussed.loo Nucleophilic displacement at acyclic phosphines e.g. (73 proceeds to form (76) or (77) with inversion.1o1 Finally one should mention a useful conversion of acid chlorides into aromatic aldehydes using A2-p hosp holens (78). Ph But .. Me Me0-0P P H20* Me0+ ArCHO P PhI Ph' 'COAr R/ $0 (78) Phosphorus(II1) Esters.-Trialkyl phosphites are now available from white phos- phorus carbon tetrachloride and alkoxide ion,'O3 and the first chiral trico-ordinate 95 K. G. Weinberg J. Org. Chem. 1975.40 3586. 96 W. E. McEwan J. E. Fountaine D. N. Schulz and W.-I. Shiau J. Org. Chem. 1976 41 1684; T. Thorstenson and J. Songstad Actu. Chem. Scund. (A),1976,30,781,724. 97 0.Dahl and L. Henriksen Actu.Chem. Scund. (B),1977 31,427. 98 R. Appel and W. Morbach Synthesis 1977,699. 99 L. Horner and B. Schlotthauer Phosphorus Sulfur 1978,4 155. loo R. D. Kroshefsky J. G. Verkade and J. R. Pipal Phosphorus Sulfur 1979,7,377. lo' E. P. Kyba J. Amer. Chem. SOC.,1976,98,4805. lo* C. A. Scott D. G. Smith and D. J. H. Smith Synth. Comm. 1976,6 135. lo' C. Brown R. F. Hudson G. A. Wartew and H. Coates. J.C.S. Chem. Comm. 1978,7. 318 C.D. Hall ester (79) albeit in low optical purity has been prepared by Mik~lajczyk.''~ A study of the synthesis and stereochemistry of a range of 2-substituted-4-methyl-l,3,2-dioxaphospholans (80)revealed that in contrast to the 1,3-dioxans the trans-isomer was The pure pans-isomer of (81) was obtained by fractional dis- tillation from a mixture of (-)-ephedrine and PC13.106 OMe Me I The reaction of cyclic phosphorus esters e.g.(82),or cyclic phosphate anions (83) with methyl iodide is stereospecific and occurs with retention at pho~phor~~.~'~ Likewise the reactions of cyclic phosphites with sulphenyl chlorides1o8 and oxygen sulphur or selenium1og proceed with retention at phosphorus. Conversely reaction with N-chloro-dialkylamines is not stereospecific."' The mechanism of the Perkow reaction has been questioned yet again and kinetic evidence using a-bromo- or a-iodo-acetophenones as substrate suggests attack on halogen (see Scheme 11)as the initial common step for both the Perkow and the Arbusov reaction."' (R0)2P(0)CH2COAr (R0)3P+ XCHzCOAr -+ [(R0)3$X CH2COAr] -B or (X = Br or I (RO)2P(0)OC(Ar) =CH2 Scheme 11 In harmony with the phosphine picture nucleophilic displacement at tervalent phosphorus esters (84)occurs with predominant inversion.'12 The interesting displacement by oxime nucleophiles is followed by a rearrangement which has been shown by CIDNP techniques to proceed through a radical-cage mechanism (see lo4 M.Mikolajczk J. Drabowicz J. Ornelanczuk and E. Fluck J.C.S. Chem. Comm. 1975 382. lo' W. G. Bentrude and H. W. Tun J. Amer. Chem. SOC.,1976,98 1850. lo6 C. R. Hall and T. D. Inch Tetrahedron Letters 1976 3645. lo' R. A. Adamcik L. L. Chang and D. B. Denney J.C.S. Chem. Comm. 1974 986; K. Lesiak B. Uznanski and W. Stec Phosphorus 1975,6,65. D. B. Denney and M. Moskal Phosphorus 1974,477.Io9 W. J. Stec Khim. Primen. FosfororgSoedin. Tr.Konf. 5th 1972,351 (Chem. Abs. 1976,84 17 295). 'lo L. L. Chang and D. B. Denney J. Org. Chem. 1977,42,782. L. Toke I. Petriehazy and G. Szakal J. Chem. Res. (S),1978 155. J. Ornelanczuk and M. Mikolajczyk J.C.S. Chem. Comm. 1976 1025. OrganophosphorusChemistry Scheme 12).l13 Optically active alcohols can be converted into optically active halides using the well-known reaction with PC13 but an initial temperature of -25 "C followed by prolonged stirring at 4 "C is cru~ial."~ R:PX + -P R:PON=CR [R;PO-*N=CR:] 0II -P R:PN=CR; R:C=NOH Scheme 12 It has been shown that protonation or alkylation of the bicyclic phosphite (85) leads to a tricyclic structure (86)with a P-N bond;115 bicyclic phosphites such as (87) are now known to be very toxic."6 5 Dico-ordinate Phosphorus For many years the existence of methylenephosphines (=C=P-) was thought to be extremely unlikely because of 'poor 2p-3p overlap'.The synthesis of a stable methylenephosphine (88)'" by the sequence shown in Scheme 13 has effectively undermined this idea and this must be regarded as one.of the major advances of the period. 0 BU' ButCOCl 11 / RP(SiMe& -Bu'C-P(SiMe3)R + RP=C \ OSiMe3 (R = Me3% Me But cyclohexyl or Ph) (88) Scheme 13 6 Phosphorus Radicals and Reactive Species Mono-and Di-co-ordinate .Phosphorus Radicals.-A comprehensive review covering phosphinidenes (RP :) and phosphinidene oxides/sulphides RP=X (X = 0 or S) has appeared.'" Typical reactions in which phosphinidene oxides are 11' C.Brown R.V.Hudson A. Maron and K. A. F. Record J.C.S. Chern. Cornrn. 1976,663. R. 0.Hutchins D. Masilamani and C. A. Maryanoff J. Org. Chern. 1976,41 1071. '15 D. S.Milbrath and J. G. Verkade J. Arner. Chern. SOC.,1977,99,6607. '16 D.S.Milbrath J. P.Springer J. C. Clardy and J. G. Verkade J. Amer. Chern. SOC.,1976,98 5493. 11' G.Becker Z. anorg. Chern. 1976,423,242;ibid. 1977 430 66. U. Schmidt Angew. Chem. Internat. Edn.,1975 14 523. 320 C.D. Hall postulated as intermediates are shown in reactions (11) and (12),119 and the e.s.r. spectrum of the dico-ordinate phosphorus radical cation (89) has been reported. 120 base 2(MeO)P(0)H2-[MeOP=O] + H3P0 + MeOH (12) Trico-ordinate Phosphorus Radicals.-Phosphinium radical cations (90),which may be produced by y-irradiation of phosphines'21 or anodic oxidation of trico-ordinate phosphorus,lZ2 are also mentioned as intermediates in the reactions of trico-ordinate phosphorus with p-benzoq~inones.'~~ The e.s.r.spectrum of the triphenylphosphine radical anion (91)has also been rec~rded."~ But (89) Tetraco-ordinate Phosphorus Radicals.-A review on phosphoranyl radicals with particular reference to the interpretation of their e.s.r. spectra covers the literature to mid-1979.'25 The majority of phosphoranyl radicals have structures which approximate to tbp (92),with the unpaired electron (shown in an equatorial position) distributed between phosphorus and the apical ligands. This is revealed by theoreti- cal calculations and by e.s.r.spectra in which the hyperfine splitting constant to phosphorus Q (P) is in the region of 600-1200 G.lZ5 Furthermore since hyper- fine splitting with substituents in the apical position is different to that with equatorial substituents e.g. (93)-(95) it is possible to establish a scale of apicophilicity by e.s.r. spectroscopy; in general the more electronegative substituents prefer the apical (92) A B C D =F C1 CF30 (93) (94) (95) RO,alkyl or H 'I9 T. H. Chan and K. T. Nwe Tetrahedron 1975,31 2537; C. J. R. Fookes and M. J. Gallagher J.C.S. Perkin I 1975 1876. lZo D. Griller K. Dimroth T. M. Fyles and K. U. Ingold J. Amer. Chem. Sac. 1975 97 5526. 12' G. W. Eastland and M. C. R. Symons J.C.S. Perkin 11 1977 833.lZ2 H. Ohmori S. Nakai and M. Masui J.C.S. Perkin I 1979 2023. '23 G. Boekestein and H. M. Buck Phosphorus Sulfur 1978 5,61. 124 R. Nasirov S. P. Solodovnikov and M. I. Kabachnik Bull. Acad. Sci. U.S.S.R., 1976 2230. 12' B. P. Roberts in 'Advances in Free Radical Chemistry' en. G. H. Williams Heyden and Sons,London 1980 Vol. 6 Ch. 5. Organophosphorus Chemistry 321 position. Thus the apicophilicity in XPF3 may be shown to increase in the order X= H <Bu'O <F< OCF,. Recent work has revealed however that if one ligand bond provides a much deeper 'electron trap' than the others the phosphoranyl radical is better described as a distorted tetrahedral structure e.g. (96) with local C,,symmetry at phosphorus and with the unpaired electron confined to a (+* antibonding P-Cl orbital as Furthermore low values of a (P) (10-20 G) demonstrate that some phosphoranyl radicals e.g.(97) have almost all the unpaired electron density in the phenyl ring and are essentially tetrahedral.'28 Ligand exchange in tetra-alkoxyphosphoranylradicals is now known to be rapid,129.130 and a clear distinction has been made between the mode of ligand exchange in phosphoranyl radicals and the mechunism of the proce~s.'~' There is good evidence to suggest that the latter involves a discrete (+* phosphoranyl intermediate (99),which avoids the 'pairwise' (Berry) mode and may apply to acyclic and monocyclic phosphoranyl radicals e.g. (101)'30 A k D/!+ C OR (98) (99) (100) (101) (A B C D =F,C1 CF30 RO alkyl or H) Phosphoranyl radicals may undergo a-or p-scission [reactions (13a) and (13b)] and the evidence points strongly to a-scission occurring from the apical position? a-scission Bun*+ Bu"2POBu' Bu'OPBu" -( \ p-scission ~ 20% Bu"3PO + But* t Hence radical attack on phosphorus(n1) compounds must give entry into an apical position.T. Berclaz M. Geoffroy and E. A. C. Lucken Chem. Phys. Letters 1975 36,677. G. W. Eastland and M. C. R. Symons J.C.S. Perkin IZ 1977 833. 12' G. Boekestein E. H. J. M. Jansen and H. M. Buck J.C.S. Chem. Comm. 1974 118. lZ9 A. Nakanishi K. Mishibida and W. G. Bentrude J. Amer. Chem. SOC.,1978,100,6403. 130 R. S. Hay and B. P. Roberts J.C.S. Perkin IZ 1978 770. /-' 322 C.D.Hall and (less strongly) to p-scission occurrirfg preferentially from an equatorial posi- tion.'*' There is no evidence however for p-scission occurring before ligand exchang; in alkoxyphosphoranyl radicals and no evidence for the existence of a 'memory effect' i.e. the ability of a phosphoranyl radical to retain a 'memory' of its origin in terms of the relative concentrations of (102) and (103).'29*'30 + R'OO erc 7 Pentaco-ordinate Phosphorus Radicals. -Recent very elegant work by Kaba~hnik'~' has demonstrated that radicals of type (104) exhibit 'wandering valency' with the unpaired electron located on six four three or two oxygen atoms depending on the substituents in the phenyl rings. In the totally symmetrical structure shown migration occurred over all six oxygen atoms but migration ceased on decreasing the temperature and the electron was localized on a single ligand.13' A. I. Prokof'ev A. A. Khodak M. A. Malysheva P. V. Petrovsky N. N. Bubnov S. P. Solodovnikov and M. I. Kabachnik Doklady Akad. Nauk. S.S.S.R.,1978,240,92.

ISSN:0069-3030    

DOI:10.1039/OC9797600303

出版商:RSC    

年代:1979

数据来源: RSC