9 Alicyclic Chemistry By J. M. MELLOR Department of Chemistry The University Southampton SO9 5NH 1Introduction A number of areas are the subjects of reviews. Those not discussed further in this Report include the chemistry of benzocyclobutene and related compounds;' trans-cycloalkenes and [a,b]betweenanenes;* polyep~xides;~ the uses in organic synthesis of oxycycl~propanes,~ 3-methylcyclohex-2-enonederivatives,' and azoalkanes;6 the use of the intramolecular Diels-Alder reaction' in the synthesis of natural products; and the application of bicyclic and tricyclic intermediates' to the stereocontrolled synthesis of prostaglandins. The following topics have also been reviewed but aspects are discussed further in this article cycl~butadiene,~ the dynamic stereochemistry of five- six- and seven-membered rings," and the concept of sigma-assistance and the discussion" of the importance of through-bond interac- tions.2 Synthesis Monocyclic Compounds.-A general method for synthesis of cyclopropane deriva- tives'* proceeds by the reaction of dibromomalonic esters with copper in DMSO. Addition to a variety of alkenes including acrylonitrile 1-octene and styrenes occurs in high yield but the reaction is non-stereospecific. An alternative four-stage sequence13 to similar products (Scheme 1) has the advantage of high stereo-specificity. 2-Alkoxy-cyclopropanecarboxylateshave been used as precursors of 1,4-dicarbonyI compounds. Their potential has been increased by the effective cycl~propanation'~of silyl-enol ethers with methyl diazoacetate.Tetrachloro- cy~lopropene'~ adds to alkenes with high stereospecificity suggesting that there is R. P. Thummel Acc. Chem. Res. 1980,13 70. ' J. A. Marshall Acc. Chem. Res. 1980 13 213. W. Adam and M. Balci Tetrahedron,1980 36 833. E. Wenkert Acc. Chem. Res. 1980,13,27. ' J. K. Sutherland Chem. SOC.Rev. 1980,9 265. W. Adam and 0.De Lucchi Angew. Chem. Int. Ed. Engl. 1980 19 762. ' G. Brieger and J. N. Bennett Chem. Rev. 1980 80 63; R. L. Funk and K. P. C. Vollhardt Chem. SOC.Rev. 1980,9,41. R. F. Newton and S. M. Roberts Tetrahedron,1980,36 2163. T. Bally and S. Masamune Tetrahedron,1980 36 343. lo E. Toromanoff Tetrahedron 1980,36 2809. J. W. Verhoeven Recl. Trav. Chim. Pays-Bas 1980 99 369. N. Kawabata and M.Tanimoto Tetrahedron,1980,36 3517. l3 J. Ohishi Synthesis 1980 690. l4 H-U. Reissig and E. Hirsch Angew. Chem. Int. Ed. Engl. 1980 19 813. l5 W. Weber and A. de Meijere Angew Chem. Int. Ed. Engl. 1980 19 138. 139 140 J. M. Mellor Reagents i MeSSMe SOZCl2 CH2C12 at -50 "C; ii CH,(CO,Et), EtOH EtONa; iii Me2S0,; iv EtOH EtONa Scheme 1 a carbene intermediate. The products e.g. (l),which are obtained in high yield can be dehalogenated to afford vinylcyclopropanes. Access to simple cyclobutane derivatives is still difficult. A useful two-step method16 from commercially available tosylmethyl isocyanide makes cyclobutanone available by initial alkylation with 1,3-dibromopropane and subsequent hydrolysis. Two routes to hydroxy-cyclobutenediones (derivatives of semisquaric acid) have been described.These compounds which are related to the mycotoxin moniliformin are available by [2 + 21 cycloaddition of tetraethoxyethylene to trimethylsilyl- keten17 or to methylketen,18 or by photoaddition18 of dichlorovinylene carbonate with 1,l -dichloroprop- 1-ene. Cyclobutanetetraone is unknown but the tetra-imine (3) is obtained" by the surprisingly simple experimental procedure of the reaction of (2) with nitrosobenzene in benzene. The product (3) which is a tetramer of phenyl isocyanide is a strong oxidizing agent; in the conversion of alcohols into aldehydes (4) is obtained. The intensive effort to find improved methods for the preparation of five- membered rings continues. General annelation procedures are described elsewhere.Transition-metal-catalysed intramolecular hydroacylation of unsaturated aldehydes to give cyclopentanones has attracted much attention. Full details2' of a catalytic method based on rhodium complexes have been given. The method is limited to mono- or di-substituted alkenes. Rhodium complexes2' are effective in promoting the cyclization of 1,6-dienes to give methylenecyclopentanes in high yield but again the further substitution of the double-bonds prevents cyclization. The use of alkyne-cobalt carbonyl complexes to give 2-substituted cyclopentenones has been described. The method has now been used22 to transform the alkynes (5) and (6) into the prostaglandin synthons (7a) and (7b) respectively by reaction with ethylene.Two methods relying on rearrangements (Schemes 223 and 324) provide simple routes to key synthons. l6 D. van Leusen and A. M. van Leusen Synthesis 1980 325. W. T. Brady and K. Saidi J. Org. Chem. 1980.45 727. '* D. Bellus P. Martin H. Sauter and T. Winkler Helv. Chim. Acfa 1980 63 1130. H. J. Bestmann G. Schmid and E. Wilhelm Angew. Chem. Inf. Ed. Engl. 1980,19 136. 2o R. C. Larock K. Oertle and G. F. Potter J. Am. Chem. Soc. 1980 102 190. R. Grigg T. R. B. Mitchell and A. Ramasubbu J. Chem. SOC.,Chem. Commun. 1980,27. 22 R. F. Newton P. L. Pauson and R. G. Taylor J. Chem. Res. (S),1980,277. 23 L. A. Paquette G. D. Crouse and A. K. Sharma J. Am. Chem. SOC.,1980,102 3972. 24 B. M. Trost T. A. Runge and L. N. Jungheim J. Am. Chem. Soc. 1980,102,2840.Alicyclic Chemistry 0 (7a) R = (CH2)&O2Me (7b) R = CH2CH=CH(CH2)3C02Me CHO Reagents i KH THF at room temperature Scheme 2 OCH,Ph Reagents i dioxan (Ph2PCHzCH2PPhz)zPd Scheme 3 The retro-Diels-Alder reaction has been used with great success to generate a number of interesting unstable compounds. By thermolysis2' of bridged ketones at 800°C and trapping of the products at -196"C a number of ketones e.g. (8) which are tautomers of phenols have been spectroscopically characterized. The formation of six-membered rings via initial [2 + 21 photocycloadditions has been used in a number of syntheses of natural products. Addition of cyclohexenones to methyl cyclobutenecarboxylate and subsequent thermolysis is a useful route26 to derivatives of trans-decalin.A very efficient procedure2' leading to cyclohexenones is shown in Scheme 4. The method promises to have a wide applicability to substituted alkenes and to vinyl ethers. Although an understanding of the observed regiochemistry is not yet developed a regioselectivity that is of synthetic importance has been found. Thus 1-methylcyclohexene gives predominantly (9) but 3,3-dimethylbut-1 -ene gives mainly (10). An alternative decalone synthesis2' proceeds 0 (8) (9) (10) 25 M-C. Lasne and J-L. Ripoll Tetrahedron Lett. 1980,21,463. 26 P. A. Wender and J. C. Hubbs J. Org. Chem. 1980 45 365; P. A. Wender and L. J. Letendre ibid. p. 367. S. W. Baldwin and J. M. Wilkinson J. Am. Chem. SOC.,1980,102,3634. ** R.Scheffold M. Dike S. Dike T. Herold and L. Walder J. Am. Chem. SOC., 1980,102 3642. 2' 142 J. M. Mellor 0 0 1ii Reagents i hv;ii Bu',AIH; iii base Scheme 4 Scheme 5 by a chemically catalysed [using aquocobalamine or other cobalt(II1) complexes] controlled-potential electrolysis resulting in reductive coupling of an alkyl halide with an ap-unsaturated ketone. Examples of intramolecular coupling are shown in Scheme 5. The versatility of the well-established [4 + 31 cycloaddition of allyl cations to dienes has been extended29 by the use of allyl alcohols as precursors (Scheme 6). In contrast to previous methods vinyl ethers and not ketones are directly isolated. Reagents i C,H, ZnCI, EtNPr', MeCN at room temperature Scheme 6 A procedure3' for ring expansion by three carbons is based on coupling of a P-keto-sulphone with an allyl ester.The method has been adapted inter alia for the synthesis of eight-membered rings (Scheme 7) and for a further synthesis of muscone (Scheme 8).A very simple synthesis of muscone is achieved3' by regioselec- tive aldol cyclization of hexadecane-2,15-dione. The selectivity is observed by use of the combination of a tertiary amine with a dialkylaluminium aryloxide. A metathesis reaction of a linear unsaturated ester followed by a Dieckmann con- densation of the diester product has for some time appeared to be a potential route to macrocyclic ketones. The method using W0C4 and [(Cp),TiMe2] as catalyst has been successfully applied3 to ethyl oleate in a synthesis of civetone (11).29 H. M. R. Hoffmann and J. Matthei Chem. Ber. 1980,113,3837. 30 B. M.Trost and J. E. Vincent J. Am. Chem. SOC.,1980 102,5680. 31 J. Tsuji T. Yamada M. Kaito and T. Mandai Bull. Chem. Soc. Jpn 1980,53,1417. 32 J. Tsuji and S. Hashiguchi Tetrahedron Lett. 1980 21 2955. 143 Alicyclic Chemistry CH2 cy" + Me,Si&OSO,Me S0,Ph SiMe S0,Ph OH SOzPh Reagents i NaH NaI DMF; ii Bu,NF THF; iii KH 18-crown-6 DME Scheme7 6-d iii,iv S0,Ph Reagents i NaH NaI DMF; ii Bu,NF THF; iii Hz Pd; iv Na(Hg) Na,HPO, MeOH Scheme 8 The chemistry of three interesting fluorocarbons has been reported. 1rradiatio1-1~~ of hexafluorobenzenein the presence of oxygen gives not only hexafluoro-Dewar- benzene but also the oxide (12).Thermolysis of (12) at 50°C gives mainly the dienone (13). Thermolysis of (14) at 585°C and trapping of the products at -196 "C results in the of perfluorocyclopentadienone (15). Photolysis of (15) gives perfluorocyclo-octatetraene possibly via the intermediacy of perfluorocyclobutadiene. On warming (15) gives an expected [4 + 21 dimer but interestingly the dimer appears to have an em configuration. The pyrazoline (16) has been prepared3' uia addition of perfluorotetramethyl-Dewarthiophen to trifluorodiazoethane. Thermolysis of (16) at -600 "C gives perfluoropentamethyl- cyclopentadiene (17) in 11% yield. The product (17) can be isolated by g.1.c. but is a strong acid of pK < -2 i.e. stronger than nitric acid and it is a volatile liquid that readily attacks glassware.33 M. G. Barlow R. N. Haszeldine and C. J. Peck J. Chem. Soc. Chem. Commun. 1980 158. 34 M. W. Grayston W. D. Saunders and D. M. Lemal J. Am. Chem. Soc. 1980,102,413. 35 E. D. Laganis and D. M. Lemal J. Am. Chem. Soc. 1980,102,6633. 144 J. M. Mellor F F&Jb FF F (13) Bicyclic Compounds.-A general procedure has been described36 for the prepar- ation of bicyclo[x. y.O]alkane skeletons by the dialkylation of dilithium salts of vicinal dialkyl cycloalkanedicarboxylates with cyw -dihalides. The method is a satis- factory entry to the bicyclo[3.3.0]octane skeleton. This skeleton has been the target of intensive synthetic studies. An efficient synthesis3' of a potential intermediate for synthesis of natural products is shown in Scheme 9.Using chiral phosphines modest enantioselectivity is observed in the Wittig reaction. 0 0 Reagents i [(Ph,P),Pd] DBU toluene at 80 "C;ii N-bromosuccinimide DMSO H,O; iii Ph,P; iv K&O Scheme 9 The conversion of the ethylene (18)into the doubly bridged ethylene (19) requires the conversion of an achiral system into the chiral product. Irradiati~n~~ of achiral (20) in ( + )-diethy1 tartrate afforded an intermediate ketone which was reduced to give (19) with low enantioselectivity. Alternative synthetic routes to these doubly bridged alkenes called betweenanenes by Marshall proceed by direct photo- is~merization~~ or by [2,3] sigmatropic rearrangement of a spirocyclic ylide pre- 36 K.G. Bilyard P. J. Garratt and R. Zahler Synthesis 1980 389. 37 B. M. Trost and D. P. Curran J. Am. Chem. SOC.,1980,102,5699. 38 M. Nakazaki K. Yamamoto and M. Maeda J. Chem. SOC.,Chem. Commun. 1980,294. 39 A. Nickon and P. St. J. Zurer Tetrahedron Lett. 1980,21,3527. 40 V. Cere C. Paolucci S. Pollicino E. Sandri and A. Fava J. Chem. SOC.,Chem. Cornmun. 1980 755. Alicyclic Chemistry 145 The highly unstable spiropentene (21)has been prepared41 by elimination of hydrogen bromide from (22).Polymerization occurs in the condensed phase at -78“C but (21)is moderately stable in solution (in CHCl,) at -30“C. The problems of stereo-controlled synthesis of spirocyclic natural products have stimu- lated the investigation of further approaches. The use4’ of a p -dicarbonyl system (Scheme 10) is efficient in generating a spirocycle but is untested for demanding 06N-phenylselenophthalimide opseph b Scheme 10 cases that require stereoselectivity.Semmelhack’s group43 have extended their studies by devising a synthesis of acorenone and acorenone B which relies on the key transformation of the chromium complex (23)to give (24).However the cyclization is not very efficient. Pearson’s use of cyclohexadienylium-Fe(C0)3 complexes to construct spirocyclic systems e.g. the conversion44 of (25)into (26) again has little steric control but the approach has now been extended to the synthesis of other interesting skeletons with good stereocontrol; e.g. tricothecane derivative^^^ and cis-hydrindene~.~~ 0 CN CN CN Polycyclic Compounds.-Following the development of intermolecular additions of alkenes to diynes catalysed by [(C~)CO(CO)~] Vollhardt and co-workers have now extended the method to the synthesis of tricyclic systems from acyclic precur- sors.Cyclization4’ of (27)gave (28)in 85% yield and the uncomplexed silylated diene could readily be obtained from (28).Such methods have considerable promise for the synthesis of natural products. The trachylobane series of diterpenes incorpor- ates a tricyclo[3.2.1.02~7]octanemoiety and this feature is the greatest obstacle to synthesis. Alternative strategies4* for a simple synthesis of this skeleton are shown in Scheme 11 one of the methods was used in the synthesis of trachylobane derivatives. The use of the intramolecular Wittig reaction in the construction of 41 R.Bloch and J-M. Denis Angew. Chem. Znt. Ed. Engl. 1980,19,928. 42 W. P. Jackson S. V. Ley and J. A. Morton J. Chem. SOC.,Chem. Commun. 1980 1028. 43 M. F. Semmelhack and A. Yamashita J. Am. Chem. Soc. 1980,102 5924. 44 A. J. Pearson P. Ham and D. C. Rees Tetrahedron Lett. 1980 21,4637. 45 A. J. Pearson and C. W. Ong Tetrahedron Lett. 1980,21,4641. 46 A. J. Pearson and M. Chandler Tetrahedron Lett. 1980 21 3933. 47 E. D. Sternberg and K. P. C. Vollhardt J. Am. Chem. Soc. 1980,102,4839. 48 R. M. Cory and R. M. Renneboog J. Chem. SOC.,Chem. Commun. 1980 1081; R. M. Cory D. M. T. Chan Y. M. A. Naguib M. H. Rastall and R. M. Renneboog J. Org. Chem. 1980,45,1852. 146 J. M.Mellor Reagents i H,C=CHSO,Ph THF HMPT; ii H2C=C(Me)$Ph3 X-Scheme 11 0 (unstable intermediate) [ref. 511 C’ -[ref. 521 [ref. 531 Reagents i KOBu‘; ii Et3N Scheme 12 anti-Bredt alkene~~~ has been reviewed. Such compounds are still the target of intensive synthetic studies. Recent examples are collected in Scheme 12.50-53 Syn-theses of propellanes which are another category of highly strained compounds are collected in Schemes 1354-56and 14.57 49 K. B. Becker Tetrahedron 1980 36 1717. H. Gerdes S. Javeri and H. Marschall Chem. Ber. 1980,113 1907. K. B. Becker and J. L. Chappuis Helu. Chim. Actu 1980,63,1812. ” H. 0.House M. B. DeTar R. F. Sieloff and D. Van Derveer J. Org. Chem. 1980,45,3545. 53 L.A. M.Turkenburg J. W. van Straten W.H. de Wolf and F. Bickelhaupt J. Am. Chem. SOC.,1980 102,3256 54 R. Bishop and A. E. Landers Aust. J. Chem. 1979,32,2675. ” W. F.Carroll and D. G. Peters J. Am. Chem. SOC.,1980,102,4127. 56 P. G.Gassman and G. S. Proehl J. Am. Chem. Sac. 1980,102,6862. 57 T. Tsuji Z. Komiya and S. Nishida Tetrahedron Lett. 1980,21,3583. Alicyclic Chemistry [ref. 561 Reagents i hv; ii cathode DMF; iii Na Scheme 13 The optical activity of fluxional molecules has never been examined. 2-Methyl- semibullvalene (29) has been ~ynthesized~~ in higher enantiomeric purity the absolute configuration has been determined and the observed c.d. spectrum com- pared with predictions. Access to substituted semibullvalenes is difficult but a one-pot synthesis5' (Scheme 15) has been successfully developed.Bridged [14]annulenes were first synthesized from anthracene by building in the bridging unit. This route was lengthy and not very efficient. The alternative method developed by Vogel's group based on the development of the perimeter by using the dialdehyde (30) had many improvements but was limited by the inaccessibility of (30).A much improved method of preparation of (30)has now been described,60 based on the diacylation of cycloheptatriene. The dialdehyde (30)has been conver- ted into (3l) which suffers considerable deformation from planarity. Spectroscopic data (u.v. and n.m.r.) indicated that (31) is a polyolefin and not an aromatic molecule. However X-ray data appear initially to conflict with this conclusion.In the absence of a low-temperature X-ray structure to resolve the question the view61 that (31) is a polyolefin that undergoes a fluxional valence-tautomeric '13 L. A. Paquette R. F. Doehner J. A. Jenkins and J. F. Blount J. Am. Chem. SOC.,1980 102 1188. 59 D. Paske R. Ringshandl I. Sellner H. Sichert and J. Sauer Angew. Chem. Int. Ed. Engl. 1980,19 456. 60 E.Vogel H. M. Deger J. Sombroek J. Palm A. Wagner and J. Lex Angew. Chem. Int. Ed. Engl. 1980,19,41. 61 E.Vogel H. M. Deger P. Hebel and J. Lex Angew. Chem. Int. Ed. Engl. 1980,19,919; H. Gunther H.von Puttkamer H. M. Deger P. Hebel and E. Vogel ibid.,p. 921. 148 J. M. Mellor equilibrium in the crystal at room temperature remains an unproven but attractive hypothesis.Titanium-catalysed dimerization of cycloheptatriene aff ords6* the dimers (32) and (33) which are probably obtained by an initial [6 + 21 addition to give (34) followed by [4 + 21 additions to give either (32) or (33). CHO es;QCHO (29) (30) (31) (32) (33) (34) Access to the larger diamondoid hydrocarbons has been significantly advanced. The subject has been reviewed63 by McKervey and full details have been published64 of the synthesis of triamantane (35),in five steps from norbornadiene. [8]Tritwis- tane (36) a member of a rare family of molecules of the chiral point group D3 has been synthesized6' in several steps from the photo-adduct of the p-benzoquinone-cyclohexa-1,3-dieneDiels-Alder product (37). 3 Stereochemical Consequences of Through-Bond Interactions Verhoeven" has presented a timely review of 'sigma-assistance' and described both the earlier spectroscopic observations of through-bond interactions and examples of the more recently discovered consequences of such interactions on reactivity.Although these effects can be observed in the chemistry of acyclic systems they are most dramatically exposed in reactions of rigid bridged systems. The following discussion is focussed on a limited number of topics illustrating the control of reaction pathways by through-bond interactions. [4 + 21 Cyc1oadditions.-In Table 1are collected recent examples illustrating the stereochemical control of through-bond interactions. Two important conclusions emerge from these results with dienes (38) (39) and (41)-(43)' endo-addition is 62 K.Mach H. Antropiusova F. Turecek V. Hanus and P. Sedmera Tetrahedron Lett. 1980,21 4879. 63 M. A. McKervey Tetrahedron 1980 36 971. 64 F. S. Hollowood M. A. McKervey R. Hamilton and J. J. Rooney J. Org. Chem. 1980 45,4954. 6J K. Hirao and 0.Yonemitsu J. Chem. Soc. Chem. Commun. 1980,423. A licyclic Chemistry Table 1 Stereoselectivity in [4 + 21 cycloadditions Diene Dienophile Product stereochemistry Reference N-Methyltriazolinedione Exclusively endo a N-Methyltriazolinedione Exclusively endo a N-Meth yltriazolinedione Exclusively endo a Maleic anhydride Exclusively endo b Maleic anhydride Exclusively endo b Methyl propiolate Exclusively endo b Methyl propiolate Mainly exo b Dimethyl acetylenedicarboxylate Mainly exo b Singlet oxygen Mainly endo C Singlet oxygen Mainly endo C TCNE Mainly endo d TCNE Mainly endo d Singlet oxygen Mainly endo e Singlet oxygen Mainly exo e \ / / oqcl* a OMe OMe Cl (42) (43) (44) (a) L.A. Paquette R. V. C. Can P. Charumilind and J. F. Blount J. Org. Chem. 1980 45 4922; (6) L. A. Paquette R. V. C. Carr M. C. Bohm and R. Gleiter J. Am. Chem. Soc. 1980 102 1186; M. C. Bohm R. V. C. Carr R. Gleiter and L. A. Paquette ibid. p. 7218; (c) L. A. Paquette R. V. C. Carr E. Arnold and J. Clardy J. Org. Chem. 1980 45 4907; (d) M. Avenati J-P. Hagenbuch C. Mahaim and P. Vogel Tetrahedron Left. 1980 21 3167; (e) L. A. Paquette F. Bellamy M. C. Bohm and R. Gleiter J.Org. Chem. 1980,45 4913. either observed exclusively or dominantly whereas the dienes (40) and (44) nor-mally undergo em-addition. This stereospecificity is explained not by steric factors but by orbital interactions of the bridged systems which lead to unequal availability of electrons on the two faces of the reacting diene. The second important feature is best illustrated by the behaviour of (40) with N-methyltriazolinedione. It has been concluded that the exceptionally high reactivity of this dienophile is character- ized by an unusually early transition state in which the importance of these electronic effects is magnified. Hence only with the more reactive N-methyltriazolinedione does (40) give an endo product. In (39) and other dienes the orbital interaction is always sufficiently important to control the formation of an endo product.A similar FMO analysis has been applied66 to the case of [4 + 21 additions to propellanes. In the additions of triazolinedione to (45) and to (46) the preference is for addition of the dienophile from the syn face for (45) but from the anti face for (46). 66 M. C. Bohm and R. Gleiter Tetrahedron 1980 36 3209. 150 J. M. Mellor .O (45) (46) Other Cyc1oadditions.-In cycloaddition reactions norbornene shows both an exceptional reactivity relative to other alkenes and a high preference for exo- addition. exo-Addition has been attributed in the past to torsional effects or to there being steric hindrance to endo-addition and the exceptional rates to relief of ring strain.The inadequacy of these views has been nicely exposed by measure- menf7 of the relative rates of reaction of nitrile oxides azides diazomethane a nitrone and a diene with norbornene and with the alkenes (47)-(49). When suitable allowance has been made for the relative contributions of strain relief the results show that norbornene is unusually reactive. The full explanation of this rate increase is not clear -it has been called6’ factor ‘x’,but some orbital interaction that leads to an enhanced availability of electrons from the exo-face is probable. Ab initio calculations lend support68 to this view. b (47) (49) Additions69 to 7-substituted norbornadienes have been extensively investigated. Four modes of addition (anti-exo syn-em anti-endo and syn-endo) are possible.Relative rates of addition of hexachlorocyclopentadiene to a series of dienes are shown in Table 2. The data indicate that rates of syn-endo- and anti-endo-addition Table 2 Rates and partial rate factors for the reaction of hexachlorocyclopentadiene with norbornadienes Partial rate factors Diene Overall rate 1O5k2/s-’ anti-endo syn-endo anti-exo Norbornadiene 39.8 1 1 16.9 (5O;X = OMe) 10.1 1.13 0.74 7.23 (5O;X = H) 9.85 0.85 0.97 7.05 (50;X= F) 8.26 0.86 0.63 5.95 7-Chloronorbornadiene 1.32 0.40 0.40 0.35 (50) 67 R. Huisgen P. H. J. Ooms M. Mingin and N. L. Allinger J. Am. Chem. SOC.,1980 102 3951. 68 G.Wipff Tetrahedron Lett. 1980,21,4445. 69 P.H.Mazzochi B. Stahly J. Dodd N. G. Rondan L.N. Domelsmith M. D. Rozeboom P. Caramella and K. N. Houk J. Am. Chem. SOC.,1980,102,6482. Alicyclic Chemistry are essentially identical and decrease slightly as the electronegativity of the 7- substituent increases. In contrast the rate of the anti-em mode of addition is markedly affected by the nature of the 7-substituent. Again steric factors must be unimportant but the nature of the orbital interaction that leads to these results is not clear. Electrophilic Substitution.-The suggestion that long-range orbital interactions might control reactivity in a series of bridged aromatic compounds (51)-(55) has been made by a group of Australian chemists. Relative rates of nitr?tion7' of these acenaphthylenes are shown. At this stage it appears premature to explain these results by orbital interactions.Other explanations such as the formation of a complex with the substituent in (54) leading to the observed enhanced reactivity cannot be ignored. A similar study of br~mination~' of a series of bridged aromatics e.g. (56),was interpreted on the basis of there being substantial long-range orbital interactions. (51) Relative rate of nitration is 1.00 Relative rate of nitration (52) R' = R2 = H 0.69 (53) R1 = OMe R2 = H 0.70 (54) R' = H,R2 = OMe 9.91 (55) R'R~= o 0.31 Birch Reductions.-Both product and rate studies of the reduction (by Li NH3 and Bu'OH) of a series of bridged aromatic compounds show the importance of orbital interactions. For example the double-bond in (57) is reduced much more readily (by a factor of 141) than that in n~rbornene.~' The remarkable distance over which such effects operate is shown in compounds (58)-(60).It has been c~ncluded'~ that the reduction of the double-bond in (58) is markedly accelerated 70 M. J. Oliver H. K. Patney and M. N. Paddon-Row Am. J. Chem. 1980,33,795. 71 M. N. Paddon-Row B. V. Lap H. K. Patney and R. N. Warrener Aust. J. Chem. 1980,33,1493. 72 M.N.Paddon-Row and R. Hartcher J. Am. Chem. SOC.,1980,102,662. 73 M.N.Paddon-Row and R. Hartcher J. Am. Chem. SOC.,1980,102,671. 152 J. M. Mellor by through-bond (i.e.four-bond) interactions. No acceleration is observed in (59) but the pathway (through five bonds) may be unfavourable. In (60) the modest enhancement of reactivity of the double-bond has tentatively been attributed to through-bond (i.e.six-bond) interactions.Radical Cyc1izations.-Verhoeven" has summarized the kinetically favoured modes of cyclization of alkenyl radicals and related the favoured pathways to the import- ance of through-bond interactions. Thus the preferential cyclization of hex-5-enyl radicals to give a five-membered ring and not a six-membered ring may partly be attributed to through-bond interactions. The more traditional explanation of prefer-ence for an ex0 mode of cyclization rather than an endo mode has been This analysis based on steric effects has been extended7' to rationalize the observed stereoselectivity of closure of substituted hex-5-enyl radicals.The present evidence suggests that both through-bond effects and steric effects contribute to determine the products of cyclization. In photocyclization of hexadienone~~~ it is observed that product formation via cyclization to a five-membered ring is favoured over the alternative mode to a six-membered ring. The factors controlling the mode of cyclization in the excited state are not clear. 4 Conformational Analysis of Six-Membered Rings The search continues for better methods of determination of structure in the solution phase and for more accurate methods of determination of the difference in energy between conformers. Careful analysis of lanthanide-induced shifts now permits the determination of energy difference^^^ for the conformers of 2-methyl 3-methyl- and 4-methyl-cyclohexanone.This study was based on a two-site binding model and was even effective for 2-chlorocyclohexanone. The merit of the study is that conformer energies are determined directly. However less rigorous analyses based on lanthanide-induced shifts can be unreliable and a study7' of cis-3,4-dialkyl-cyclohexanones warns of the dangers of such analyses. Full details have been published of the determinati~n~~ of the thermodynamic parameters relating to conformers of methylcyclohexane isopropylcyclohexane and some cis-1,4-dialkyl-cyclohexanes. The results were obtained by I3C n.m.r. analysis of compounds that were enriched with 13C at a single carbon atom. N.m.r. analysis of (61) shows a preference" for the trideuteriomethyl group to occupy the axial position a result which warns of possible conformational changes as a consequence of isotopic substitution.74 A. L. J. Beckwith C. J. Easton and A. K.Serelis J. Chem. SOC.,Chem. Commun. 1980,482. 75 A. L. J. Beckwith T. Lawrence and A. K. Serelis J. Chem. SOC.,Chem. Commun. 1980,484. 76 W. C. Agosta and S. Wolff J. Org. Chem. 1980,45 3139. " R. J. Abraham D. J. Chadwick L. Griffiths and F. Sancassan J. Am. Chem. SOC.,1980,102 5128. 78 A. Pons and J. P. Chapat Tetrahedron 1980,36,2297. 79 H. Booth and J. R. Everett J. Chem. SOC.,Perkin Trans. 2 1980 255. F. A. L. Anet V. J. Basus A. P. W. Hewett and M. Saunders J. Am. Chem. SOC. 1980 102 3945. 153 Alic yclic Chemistry 5 Other Stereochemical Aspects Craze and Watt have determined8* the energy barrier to hydride transfer in the ketols (62)-(64).It was observed that transfer of hydride is slowest in (62) and fastest in (64),and it is known that the two reacting centres are held closest together in (64). Hence the compounds of the series effectively represent a progression towards a transition state for hydride transfer. Reaction in (64) is fastest because the ground state is closer to the optimum geometry for transfer of hydride. The concept of 'orbital steering' was originally invoked with the implication that a misalignment of reacting groups (of the order of 10")might have profound effects upon reaction rates. The hypothesis has been effectively testeds2 for the lactonization of the hydroxy-acids (65)-(68) and for this series there is no evidence to support orbital steering.A small angular displacement is not kinetically significant. 6 Structural Aspects Neutral Species.-The X-ray structure of tetra-t-butylcyclobutadiene (69)has been Unexpectedly it is non-planar. This result both raises the question of the spin multiplicity of (69) and explains its ready conversion into tetra-t-butyl- tetrahedrane. Photoelectron spectrag4 of the diene and of a tetrahedrane have been reported. An elegant series" of experiments help to clarify the structure of cyclobu-tadiene. Deuteriated cyclobutadienes were generated by the decomposition of (70) and (71) and the products were trapped as adducts of acrylic derivatives. In the case of (71) decomposition is anticipated to give both (72) and (73).However (70) is expected to give only (72). The nature of the adducts that are trapped then depends upon the competitive rates of the trapping reaction and the equilibra- tion of (72) with (73). Experiment has established that in the decomposition of (70) there is a preferential trapping of (72). It must be concluded that cyclobu- tadiene does not have a D4,,equilibrium geometry in solution. Further experiment shows that the rate of trapping is comparable with the rate of equilibration of (72) and (73). D xc D s (73) (74) G-A. Craze and I. Watt J. Chem. SOC., Chem. Commun. 1980,147. F. M. Menger and L. E. Glass J. Am. Chem. SOC.,1980,102,5404. 83 H. Irngartinger N. Riegler K-D.Malsch K-A. Schneider and G. Maier Angew. Chem.Inr. Ed. Engl. 1980,19 211. 84 E. Heilbronner T. B. Jones A. Krebs G. Maier K-D. Malsch J. Pocklington and A. Schmelzer J. Am. Chem. SOC.,1980,102,564. 85 D. W. Whitman and B. K. Carpenter J. Am. Chem. SOC.,1980,102,4272. 154 J. M. Mellor Determinations of the microwave spectrum and dipole moment of (74) provide86 strong evidence for spiroconjugation. The observed dipole moment (p = 0.95 D) is very high for a hydrocarbon. Carbenium Ions. The study of deuterium isotope effects on the I3Cchemical shifts in the spectra of carbenium ions is an established method of structural analysis. Application to the problem of the norbornyl cation8’ indicates that this ion has a symmetrical structure. In contrast the cyclobutylcyclopropylcarbinylcation under- goesg8 a complex set of rearrangements; it has been argued89 that the 2-methyl-2- norbornyl cation has some non-classical character and again the 2-bicyclo[2.1.llhexyl cation” has non-classical character. All these results have been obtained by the powerful method of Saunders and they emphasize the need to recognize a continuum of carbenium ion behaviour ranging between classical ions through partially bridged structures that are characterized by unequal bonding to cases that are characterized by equal bonding in a symmetrical bridge. Radical Species.-Cyclopropyl radicals have been generated by the reaction of sodium naphthalene with cyclopropyl halides in tetrahydrofuran. The radicals that are generated can then undergo electron transfer to give cyclopropyl anions and hence products.It has now been established” that for both secondary and tertiary cyclopropyl radicals inversion is faster than the electron transfer. The unusual photolytic cleavage of a carbon-hydrogen bond in a hydrocarbon has been ob- in the photolysis of pentamethylcyclopentadiene to give (79 which was shown by e.s.r. spectroscopy to have D5hsymmetry. A series of cyclopentadienyl radicals have been generated93 by attack of t-butoxyl radicals on alkyl-substituted cyclopentadienyltrimethylstannanes;on the e.s.r. timescale the parent cyclopen- tadienyl radical also has DShsymmetry. Irradiation of (76) with X-rays leads to the formation of (77) in a matrix. On warming (77) is transformed into a new radical which it has been argued94 is (78).Under similar conditions the 7-norbor- nadienyl radical9’ rearranges to the tropylium radical. Jy I --a (75) (76) (77) (78) Carbanions.-A careful examination of 7-phenylnorborn-7-yl carbanions shows that the effective geometry of the carbanion depends on the counter-ion. Thus at -68 “C the lithium salt is pyramidal,96 with the major barrier to inversion being attributed to ionic dissociation. In contrast the potassium salt is effectively planar. S. W. Staley A. E. Howard M. D. Harmony S. N. Mathur M. Kattija-Ari J-I. Choe and G. Lind J. Am. Chem. SOC.,1980,102,3639. M. Saunders and M. R. Kates J. Am. Chem. SOC.,1980,102,6867. M. Saunders and H-U. Siehl J. Am. Chem. SOC.,1980,102,6868. a9 K. L. Servis and F-F. Shue J.Am. Chem. SOC.,1980,102,7233. L. R. Schmitz and T. S. Sorensen J. Am. Chem. SOC.,1980,102 1645. 91 G.Boche D. R. Schneider and H. Wintermayr J. Am. Chem. SOC.,1980,102 5697. 92 A. G.Davies and J. Lusztyk J. Chem. SOC., Chem. Commun. 1980 554. 93 M. Kira M. Watanabe and H. Sakurai J. Am. Chem. SOC.,1980,102,5202. D.Brandes F. Lange and R. Sustmann Tetrahedron Lett. 1980 21 261. ” D.Brandes F. Lange and R. Sustmann Tetrahedron Letf. 1980,21,265. 96 P. R.Peoples and J. B. Grutzner J. Am. Chem. SOC.,1980,102,4709. Alicyclic Chemistry Two related papers have established the existence of cu,a'-dianion~~~ and a-keto-dianion~~~ as intermediates. The former can be generated by treatment of a ketone with first potassium hydride (to give a monoanion) and then n-butyl-lithium and tetramethylenediamine.The latter can be prepared from a-bromo-ketones (Scheme 16). OLi -&L& ii& OLi Br Br Li Reagents i lithium hexamethyldisilazide; ii Bu'Li Scheme 16 '' J. S. Hubbard and T. M. Harris J. Am. Chem. SOC.,1980,102,2110. 9a C.J. Kowalski M. L. O'Dowd M. C. Burke and K. W. Fields J. Am. Chem. SOC.,1980,102,5411.