18 Alicyclic Chemistry By J. M. MELLOR Department of Chemistry University of Southampton Southampton SO9 5NH Traditionally this Report has attempted to highlight important contributions throughout the area of alicyclic chemistry. In view of the publication of the Chemi- cal Society Specialist Periodical Reports’ giving comprehensive coverage of this area and of the difficulty of containing an effective critique of the notable con- tributions within the required length this Report is not in accordance with tradi- tion. Two topics synthesis and methods ofannelation and the study of structural properties and orbital interactions are discussed in detail. This discussion is preceded by a list of reviews concerning contributions outside those areas re- viewed in more detail.New texts on alicyclic chemistry are available.2 Reviews concern various aspects of organometallic synthesis3 written by different members of Wilke’s group the nature of protonated cyclopropane intermediate^,^ Brown’s view of a-bridging in norbornyl system^,^ valence isomerization in bullvalene and related systems,6 an analysis of stereochemical control in concerted processes,’ and a further discussion of the uses of photoelectron spectroscopy.8 A reappraisal of Bredt’s Rule has appeared’ and the nature of bridgehead olefins has been further examined.lo ‘Aliphatic Alicyclic and Saturated Heterocyclic Chemistry’ ed. W. Parker (Specialist Periodical Reports) The Chemical Society London Vol. 1 1973; Vol. 2 1974. * L. N. Ferguson ‘Highlights of Alicyclic Chemistry’ Franklin 1973.’ K. Fischer K. Jonas P. Misbach R. Stabba and G. Wilke Angew. Chem. Infernaf. Edn. 1973 12 943; B. Bogdanovic ibid. p. 954 H. Bonnemann ibid. p. 964; P. Heimbach ibid. p. 975. ‘M. Saunders P. Vogel E. L. Hagen and J. Rosenfeld Accounts Chem. Res. 1973,6 53. H. C. Brown Accounts Chem. Res. 1973,6 377. B. Decock B. Le Reverend and P. Goudmand Bull. SOC.chim. France II 1973 389. ’ J. Mathieu Bull. SOC.chim. France II 1973 807. H. Bock and B. G. Ramsey Angew. Chem. Internat. Edn. 1973 12 734. G. Kobrich Angew. Chem. Internat. Edn. 1973 12 464. lo H. H. Grootveld C. Blomberg and F. Bickelhaupt J.C.S. Chem. Comm. 1973 542 C. Batich 0.Ermer E. Heilbronner and J. R. Wiseman Angew. Chem. Internar. Edn. 1973 12 312; J.E. Gano and L. Eizenberg J. Amer. Chem. SOC.,1973,95 972; A. H. Alberts H. Wynberg and J. Strating Tetrahedron Letters 1973 543 3047; C. B. Quinn J. R. Wiseman and J. C. Calabrese J. Amer. Chem. SOC. 1973 95 6121; B. L. Adams and P.Kovacic ibid. p. 8206; M. Farcasiu D. Farcasiu R. T. Conlin M. Jones and P.von R. Schleyer ibid. p. 8207; A. D. Wolf and M. Jones ibid. p. 8209. 57 1 572 J. M. Mellor 1 Synthesis Three-and Four-memberedRings.-An outstanding series of papers has elabora- ted upon the preparation and uses of cyclopropyldiphenyl sulphonium fluoro- borates. The preparation" of the ylide (1) can be effected in high overall yield in situ (Scheme 1) but (1) readily undergoes thermal decomposition to give Reagents i Ph,S-MeN02-AgBF,; ii NaH-THF; iii LiNPr' Scheme 1 cyclopropyl phenyl sulphide.However under suitable conditions (1) may be trapped and affords an excellent synthesis of oxaspiropentanes,' spiropentanes,' and cyclobutanones' and hence y-butyrolactones' by subsequent peroxidative attack (Scheme 2). The synthetic procedures are appropriate to substituted Rif R2 R2 R' Reagents i KOH-DMSO->O; ii KOH-DMSO-PhCH =CHCOPh; RZ R' iii KOH-DMSO->O ;iv H'; v Na0,H. R2 Scheme 2 B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1973,95 5298. " B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1973,954 531 1. l3 B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1973,95 5307. l4 B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1973,95 5321 ; M.J. Bog-danowicz T. Ambelang and B. M. Trost Tetrahedron Letters 1973 923. A 1icyclic Chemistry ylides thus (2) is transformed into (3) on reaction with acetone indicating a re- tention of configuration at the carbanion followed by inversion of configuration in the displacement. Both the oxaspiropentanes and cyclobutanones are valuable synthetic intermediates. Although acid-catalysed rearrangement of the oxaspiropentanes gives cyclo- butanones in high yield rearrangement under basic conditions e.g.lithium diethyl- amide gives allyl alcohols. From (4) derived from cyclopentanone two allyl alcohols (5)and (6)might be formed but work-up of the reaction with trimethyl- chlorosilane affords12.' (7) in 94 % yield. Thermolysis of (7) at 330 "C gives (8) and this sequence is an important method of general applicability for the prepa- ration of cyclopentanones.The group of Conia have noted16 the opening of oxaspiropentanes by trimethylchlorosilane to give intermediates readily trans- formed into cyclobutanones (Scheme 3). The ready synthesis of cyclobutanones CISiMe KosiMe3 ~ lOO% ao ~ CH,CI,. 20°C CH2CI Scheme 3 has led to a studyI7 of their subsequent transformations to afford an efficient method of geminal alkylation [see synthesis of methyl desoxypodocarpate (9) (Scheme 4)]. Is B. M. Trost and M. J. Bogdanowicz J. Amer. Chem. SOC.,1973,95,289. l6 J. P. Barnier B. Garnier C. Girard J. M. Denis J. Salaun and J. M. Conia Tetra-hedron Letters 1973 1747. " B. M. Trost and M.J. Bogdanowicz J. Amer. Chem. SOC.,1973,95,2038; B. M. Trost and M. Preckel ibid. p. 7862. 574 J. M. Mellor 1iii-v 90% Reagents i ;Ph,BF,-KOH-DMSO; ii LiBF,-PhH; iii (Me,N),CHOCMe,; iv TsS(CH,),STs; v NaOMe-MeOH; vi MeI-MeCN-H,O 50 "C; vii (Ph P)3RhCI-MeCN. Scheme 4 Of the above reactions of diphenylsulphonium cyclopropylides only the addition to ap-unsaturated carbonyl compounds to give spiropentanes and addition to highly hindered saturated ketones are inefficient with respect to attack at the carbonyl centre. However the alternative approach'* shown in Scheme 5 leads Scheme 5 to an efficient formation of a cyclopropylmethanol and hence by acid-catalysed rearrangement to a cyclobutanone. Either spiropentanes or oxaspiropentanes can be prepared from conjugated ketones by suitable choice of reagent.These reagents are also easier to prepare than cyclopropylides of sulphoximines the use of which has now been reviewed. B. M. Trost D. Keeley and M. J. Bogdanowicz J. Amer. Chem. Soc. 1973.95 3068. l9 C. R. Johnson. Accounts Chem. Res. 1973 6 341. Alicyclic Chemistry A full report” gives the preparation of (10) (43 % yield 97 % purity) (1 1) (70% yield 99 % purity) and (12)(30% yield 99% purity) by treatment of the appro- priate methallylchloride with an alkali amide. A novel pyrolysis2’ converts furfuryl benzoate at 700°C into (13) (40%yield). A more lengthy route22 by retro-Diels-Alder reaction gives the substituted analogue (14) by pyrolysis of (15) at 400°C.Full details23 are now published of the photocyclization of a-methylene-ketones proceeding viaType I1 biradicals to give either cyclobutanones or cyclopropanones (Scheme 6) but yields are rather low. .O .O Scheme 6 Following the syntheses of cyclobutadienes reported last year the first tri- alkylcyclobutadiene (16) stable at room temperature has been prepared.24 The absence of a band in the U.V. spectrum above 300 nm was used to conclude a singlet ground state with rapid valence isomerization between (16a) and (16b). In contrast further st~dy~’,~~ of the i.r. spectrum of cyclobutadiene obtained in a low-temperature matrix suggests D, symmetry and a triplet ground state is suggested and supported by new ab initio calculations. 2o R. Koster S.Arora and P. Binger Annalen 1973 1219. *’ W. S. Trahanovsky J. Amer. Chem. SOC.,1973,95 5412. 22 R. C. De Selms and F. Delay J. Amer. Chem. SOC.,1973,95 274. 23 R. A. Cormier W. L. Schreiber and W. C. Agosta. J. Amer. Chem. SOC.,1973,95,4873. 24 G. Maier and A. Alzerreca Angew. Chem. Internat. Edn. 1973,12 1015; S. Masamune N. Nakamura M. Suda and H. Ona J. Amer. Chem. SOC.,1973,95 8481. ’’ 0. L. Chapman C. L. McIntosh and J. Pacansky J. Amer. Chem. SOC.,1973,95,614. 26 A. Krantz C. Y. Lin and M. D. Newton J. Amer. Chem. SOC.,1973,95,2744. 576 J.M. Mellor The synthesis of faur-membered rings by [2 + 2]cycloadditions continues to be a subject of great interest but few procedures of synthetic importance have been recently developed.Ethylene adds to acrylonitrile to give cyclobutyl cyanide27 but not under conditions that suggest a useful laboratory preparation. Weak catalysis of this addition by nickel(0) is suggested but is not clearly established to be of importance. Further cycloadditions of ketones to olefins28 and to acety- lene~~’ are shown in Scheme 7. Scheme 7 Five-membered Rings.-Methods of synthesis of five-membered rings have for long been overshadowed by the greater interest in developing methods for six- membered rings. Now the stimulus of attempted synthesis of prostaglandins has led to considerable success. The epoxide (17) is converted3’ into the lactone (18) with boron trifluoride. As the mode of cyclization in the biosynthesis of prostaglandins is still not clarified it is too early to call this a ‘biogenetically patterned synthesis’.However the above example (yield 15%) suggests an im- portant route to cyclopentenyl cations from dienyl cations. The synthesis of cyclopentenones has been re~iewed,~ of cyclo- and an effective ~reparation~~ pentenones from 1,3-dienes is described in Scheme 8. An alternative route to cyclopentanones is afforded by the ring c~ntraction~~ of boracyclanes on bro- ’’ H. K. Hall C. D. Smith and D. E. Plorde J. Org. Chem. 1973 38 2084. P. W. Jeffs and G. Molina J.C.S. Chem. Comm. 1973 3. 29 H. H. Wasserman J. U. Piper and E. V. Dehmlow J. Org. Chem. 1973 38 1451. 30 E. J. Corey G. W. J. Fleet and M. Kato Tetrahedron Letters 1973 3963. 31 R. A. Ellison Synthesis 1973 397. 32 E.J. Corey and S. W. Walinsky J Amer. Chem. SOC.,1972 94 8932. 33 Y. Yamamoto and H. C. Brown J.C.S. Chem. Cornm. 1973 801. Alicyclic Chemistry Scheme 8 mination (Scheme 9) but this route has less general applicability. A limitation is posed by the required formation of the boracyclane from the appropriate diene. a) Brz:: H,O,-NaOH ' OH I 0 OMe Scheme 9 An elegant synthesis34 of /?-vetivone (19) (Scheme 10) depends upon the preferred site of alkylation of the enolate anion of the enol ether of a 1,3-diketone. CH,Cl (19) Reagents i n -HMPA-THF-LiNPr', -78 "C; ii MeLi; iii H' CH ,CH ,C1 Scheme 10 G. Stork R. L. Danheiser and B. Ganem J. Amer. Chem. Soc. 1973,95 3414. 578 J. M. Mellor The stereochemistry is controlled by the preference of the methyl group for a pseudo-axial orientation.As a method of spiroannelation this route would appear to have considerable versatility. Since the early days of steroid synthesis the construction of trans-fused hydrin- danes has proved difficult. Typically on hydrogenation (20; R = H) gives the thermodynamically preferred cis-product. However the ether (20; R = But) on catalytic hydr~genation,~’ because of steric hindrance on the p-face gave a higher percentage of trans-product (21). Using this approach with further sub- stitution at C-4 a synthesis of 19-nor-steroids is described. Novel ~yntheses~~,~’ of cis-hydrindanones are described in Scheme 11 but neither has a likely utility. The formation of five-membered rings by cycloaddition reactions has been extended.Last year [Ann. Reports (B) 1972 69 4121 the allowed [,2 + .4,] H ko Ac,O-ZnCI,-CH,CI Ref. 36 30% Br Br Br Br H H Ref. 37 0 H o Scheme 11 thermal cycloaddition of olefins to allyl carbanions was reported. Now the effective thermal cycloaddition of allyl carbonium ions to olefins which is not symmetry-allowed has been achieved.38 Addition of [Fe,(CO),] to aa’-dibromo- ketones generates oxyallyl cationic intermediates which undergo cycloaddition with aryl-substituted olefins in a stereospecific manner in high yield (Scheme 12). ’’ Z. G. Hajos and D. R. Parrish J. Org. Chem. 1973,38 3239 3244. 36 L. W. Boyle and J. K. Sutherland Tetrahedron Letters 1973 839. ” H. J. Liu and T.Ogino Tetrahedron Letters 1973 4937. R. Noyori K. Yokoyama and Y.Hftyakawa J. Amer. Chem. SOC.,1973,95 2722. Alicyclic Chemistry Ar Me Scheme 12 Simple aliphatic olefins cannot be used. The use of ally1 cations in the synthesis of seven-membered rings has been discussed in detail,39 and their application to the synthesis of cyclopentanes noted. Last year the application of thermal cyclization of unsaturated ketones to give cyclohexanones was noted. The above work is fully discussed4' and Conia's group now report4' the use of the ene reac- tion in the construction of five-membered rings (Scheme 13). Scheme 13 Six-memberedRings.-Both outstanding modifications of well known processes such as the Robinson annelation procedure and the Johnson cationic cyclizations and also the development of novel cyclization procedures are reported.The use of a-hal~geno-acetals~~ in cyclization processes is considerable. Halogeno-acetals are available from the halogeno-ketones prepared either from carboxylic acids by diazomethane addition or by addition to terminal olefins. Subsequent cycli- zations are illustrated in Scheme 14. A number of interesting points stem from this study. Cyclization to give either (22) or (23) is controlled by the nature of the cation. Study of a number of systems shows that in the absence of special con- straints cyclization with an axially held halogeno-acetal chain is preferred and hence this constitutes an important new synthesis of cis-decalins. When a tight ion pair is involved as with the lithium salt in benzene an equatorial conforma- 39 H.M. R. Hoffmann Angew. Chem. Internat. Edn. 1973 12 819. 40 J. Brocard G. Moinet and J. M. Conia Bull. SOC.chim. France II 1973 1711. 41 G. Mandville F. Leyendecker and J. M. Conia Bull. SOC. chim. France II 1973 963; M. Bortolussi R. Bloch and J. M. Conia Tetrahedron Letters 1973 2499. 42 G. Stork J. 0. Gardner R. K. Boeckman and K. A. Parker J. Amer. Chem. SOC. 1973 95 2014; G. Stork and R. K. Boeckman ibid. p. 2016. 580 J.M. Mellor n n i 70-85 % + OyO ___) NCg NCm 92 % 8% Br OJ 70-85% ~ “62 Reagents i sodium hexamethyldisilazane ;ii potassium hexamethyldisilazane ;iii lithium hexamethyldisilazane. Scheme 14 tion is adopted and hence a trans-decalin results.trans-9-Cyano-2-decalones are available by addition to o~talones.~~ The Robinson annelation of 2-alkylcyclohexanones with methyl vinyl ketone is limited in application by the extensive competing polymerization of the vinyl W. Nagata M. Yoshioka and T. Teresawa J. Amer. Chem. SOC.,1972,94 4612. Alicyclic Chemistry 58 1 ketone and by the formation of products from both enolate anions of the cyclo- hexanone. Two important developments have overcome these limitations and suggest many uses for this modified annelation. With methyl vinyl ketone the base strength and reactivity of the enolate anion is comparable to that of the cyclohexanone. Use44 of or-silylated enones (Scheme 15)overcomes this problem. OLi n Reagents i SiEt3 ;ii 5 % NaOMe-MeOH; iii SiEt 0 Scheme 15 Addition of a cyclohexenone to lithium dimethylcuprate gives45 an organo-copper enolate which fails to equilibrate by proton transfer from the vinyl ketone.Hence in contrast to the lithium enolates highly regiospecific addition with a kinetically stable organo-copper enolate is possible. Even direct annelation of cyclopen- tanones is possible (Scheme 16). 0 ocu nA j$120y)+o~ 97 % 3 76 Reagents i. LiCuMe,-Et,O; ii SiMe Scheme 16 44 G. Stork and B. Ganem J. Amer. Chem. SOC.,1973.95 6152. 45 R. K. Boeckman J. Amer. Chem. SOC.,1973,95,6867. 582 J. M. Mellor The use of the Lansbury chloro-olefin annelation procedure has been further adapted to the synthesis of hydroa~ulenones~~ and of cycloalkanecarboxylic acids4’ (Scheme 17).Construction of bridged systems by ad-bisalkylation of 03- C02H CI Reagents i ; ii CH =CHMgBr; iii HCO,H A 40 ”/’,. dc, Br Scheme 17 enamines is not an efficient process. However the use of palladium complexes48 leads to catalysis by reversible formation of n-ally1 complexes and a moderately efficient annelation(Scheme 18).Thead-annelation ofenamines by ap-unsaturated 0 0 Q AcOCH ,CH=CHCH .OAc &+ $,. 30 % 34 % Scheme 18 acid chlorides has previously proved an efficient method of synthesis of bridged bicyclic diketones. Now the reaction is adapted4’ to the synthesis of polyfunc- tional adamantanones (Scheme 19). Dauben and Ipaktschi’’ have developed n 29 % Scheme 19 46 P.T. Lansbury P. M. Wovkulich and P. E. Gallagher Tetrahedron Letters 1973 65. ‘’ P. T. Lansbury and R. C. Stewart Tetrahedron Letters 1973 1569. 48 H. Onoue I. Moritani and S.I. Murahashi Tetrahedron Letters 1973 121. 49 P. W. Hickmott H. Suschitzky and R. Urbani J.C.S. Perkin I 1973 2063. W. G. Dauben and J. Ipaktschi. J. Amer. Chem. SOC.,1973,95 5088. Alicyclic Chemistry an elegant and efficient synthesis of bridged olefins (Scheme 20). In spite of the strain imposed by cyclization the efficient loss of triphenylphosphine oxide in-duces closure. Even closure to give a bicyclo[3,3,l]nona-1,3-diene(trapped but 6 + 0 PhCH=CH-CH=PPh, / Ph I Ph 57 % Scheme 20 not isolated) is possible. The reaction is generally applicable to the synthesis of cyclohexa-1,3-dienes from acyclic ketones" and to the annelation of cyclic ketones e.g.synthesis of occidol(24) from (25) in three steps. "OWMe02C,o-e Useful developments of the Diels-Alder reaction still continue (see Scheme 21).53-56 Synthesis of the fragrant a-dama~cone~~ (26) and of P-damascenoneS4 (27)shows that catalysis of the cycloaddition may proceed by effective activation of either dienophile or diene. Control of the stereochemistry has been clarified both by experimental observation^^^ concerning the relative importance of secondary orbital overlap and steric effects and by PMO calculation^^^ con-cerning regiospecificity and syn-anti specificity. W. G. Dauben D. J. Hart J. Ipaktschi and A. P. Kozikowski Tetrahedron Lerters 1973,4425.s2 E. Sonveaux and L. Ghosez J. Amer. Chem. SOC.,1973,95 5417. 53 P.G. Sammes and T. W. Wallace J.C.S. Chem. Comm. 1973 524. 54 K. S.Ayyar R. C. Cookson and D. A. Kagi J.C.S. Chem. Comm. 1973 161. 55 R.C. Cookson and R.M. Tuddenham J.C.S. Chem. Comm. 1973,742. 56 E. J. Corey and R. L. Danheiser Tetrahedron Letters 1973 4477. " D. W. Jones and G. Kneen J.C.S. Chem. Comm. 1973,420; D. W. Jones and R.L. Wife ibid. p. 421; H. Takeshita M. Shima and S. Ito Bull. Chem. SOC. Japan 1973 46. 2915 C. K. Bradsher F. H. Day A. T. McPhail and P. Wong J.C.S. Chem. Comm. 1973 156; E. T. McBee. M. J. Keogh R.P.Levek and E. P.Wesseler J. Org. Chem. 1973 38 632; K. Seguchi A. Sera and K. Maruyama Tetrahedron Letters 1973 1585; B.M. Jacobson J. Amer. Chem. SOC. 1973,95,2579. K. N. Houk J. Amer. Chem. SOC. 1973 95 4092; K. N. Houk and R. W. Strozier ibid. p. 4094; N. D. Epiotis ibid. p. 5624; P. V. Alston R. M. Ottenbrite and D. D. Shillady J. Org. Chem. 1973 38 4075; 0.Eisenstein and N. T. Anh Bull. SOC. chim. France II 1973 2721 2723; N. T. Anh Tetrahedron 1973 29 3227; M. N. Paddon-Row P. L. Watson and R. N. Warrener Tetrahedron Letters 1973 1033. 584 J. M. Mellor H'-H,O/ 95 % Ref. 52 Ph 0-Mf Me0 OH \ Ref.53 0+ Meek + a% ;1''( -6 AlCl,-CH,CI Ref. 55 \ "y* 9 Ac20.135"C Ref. 56 70 % o, 0 The potential of cationic cyclizations in the synthesis of steroids has been shown by Johnson's group. Now they show the flexibility of the approach by total syntheses of oestrone," optically active progesterone,60 17-hydroxy-5fl-pregnan- 59 P.A. Bartlett and W. S. Johnson J. Amer. Chem. Soc. 1973 95 7501. 6o R. L. Markezich W. E. Willy B. E. McCarry and W. S. Johnson J. Amer. Chem. SOC. 1973 95 4414; B. E. McCarry R. L. Markezich and W. S. Johnson ibid. p. 4416. Alic-vclic Chemistry gg \ (26) (27) 20-0ne,~' and testosterone benzoate.62 Details are given elsewhere in this volume but two general points may be noted here. The novel use of nitro-alkanes permits the trapping of vinyl cations to give derivatives of a-hydroxy-ketones (Scheme 22). Studies related to the synthesis of oestrone that in the cyclization of H / OH +AH-J/ Scheme 22 (28)to give (29)and (30)the ratio (29):(30)depends upon the nature of the leaving group X.This result is best interpreted as evidence for a concerted mode of (28) (29) (30) 6' D. R. Morton M. B. Gravestock R. J. Parry and W. S. Johnson J. Amer. Chem. SOC. 1973 95 441 7. 62 D. R. Morton and W. S. Johnson J. Amer. Chem. SOC.,1973,95,4419. 63 P. A. Bartlett J. I. Brauman W. S. Johnson and R. A. Volkmann J. Amer. Chem. SOC. 1973,95 7502. 586 J. M. Mellor cyclization. Full details are given of the cyclization of unsaturated acetal~,~~ the use of allene participation6' to give six-membered rings and the influence of substitution upon the stereochemistry of the ring junction. Cyclization of (31) give#' the cis-decalin (32). Cationic cyclizations are of greater synthetic im- portance than their radical analogues.Nevertheless impressive stereospecificity is observed67 in the radical cyclization of(33) which gives (34)(12 % yield) as the only tetracyclic product. (33) (34) Seven-memberedRings.-Problems in the synthesis of sesquiterpenoids particu- larly highly functionalized lactones have exposed a lack of methods. Successful syntheses of bulnesol and guaioP8 depend upon cationic cyclization [(35) --* (36)]. Two fresh approaches have promise. &Unsaturated ketones typically undergo 1,3-rearrangement from the first excited singlet state. Ph~torearrangement~' of (37) efficiently gives (38). The easily prepared and stable ylide (39) can be trans- formed7' via a vinylcyclopropane into a cycloheptadiene (Scheme 23).A route 64 A. van der Gen K. Wiedhaup J. J. Swoboda H. C. Dunathan and W. S. Johnson J. Amer. Chem. SOC.,1973 95 2656. '' M. H. Sekera B. Weissman and R. G. Bergman J.C.S. Chem. Comm. 1973 679. 66 K. E. Harding R. C. Ligon C. Tseng and T. Wu J. Org. Chem. 1973 38 3478. '' J. Y. Lallemand M. Julia and D. Mansuy Tetrahedron Letters 1973 4461. 68 N. H. Anderson and H. Uh Tetrahedron Letters 1973 2079. 69 R. G. Carlson R. L. Coffin W. W. Cox and R. S. Givens J.C.S. Chem. Comm. 1973 501. 'O J. P. Marino and T. Kaneko. Tetrahedron Letters 1973 3971 3975. Alicyclic Chemistry (37) H,C=PPh, 1 0 0 Scheme 23 more appropriate to the synthesis of azulenes concerns' the catalysed decompo- sition of diazoketones (Scheme 24).Routes based upon addition of ally1 cations to dienes have been reviewed3' and further studied72 and cyclizations using chloro-olefins described.73 CuCl PhH Scheme 24 71 L. T. Scott J.C.S. Chem. Comm. 1973 882. l2 S. Ito M. Ohtani and S. Amiya Tetrahedron Letters 1973 1737; R.Noyori Y. Baba S. Makino and H. Takaya ibid. p. 1741; A. E. Hill G. Greenwood and H. M. R. Hoffmann J. Amer. Chem. SOC.,1973,95 1338. 73 P. T. Lansbury Accounts Chem. Res. 1972 5 31 1. 588 J. M. Mellor Miscellaneous Syntheses.-A novel synthesis74 of macrocycles proceeds in quantitative yield by the ene reaction of (40)to give (41) and (42). Photore-arrangement7’ of By-epoxy-ketones leads to iactones and thereby affords a novel macrolide synthesis. \ Ref.76 I (43) Ref. 77 I Br i. Hi Ref. 78 ii p-TsC1-py I (45) ‘OTs AICI,-CH,CI,-MeNO ~ 4% 00 i AIH ii. SOCI,1 Scheme 25 74 J. B. Lambert and J. J. Napoli J. Amer. Chem. SOC.,1973 95 294. ’’ R. G. Carlson J. H. Huber and D. E. Henton J.C.S. Chem. Cumm. 1973 223. Alicyclic Chemistry 589 Collected in Scheme 25 are the ~yntheses~~-~~ of different spirocyclic systems the properties of which are discussed in the next section. Further attempts have been made to synthesize ~entalene,~' and spectroscopic observation of the mono- mer generated at -196 "C was possible. However the highly substituted pentalene (47)was stable" at room temperature (synthesis in Scheme 26). Scheme 26 The first [2,2,2]propellane (48) has been prepared" by successive ring con- tractions of a-diazoketones.The final keten is trapped as the amide (48) which has t+ -28 min at 25 "C. A compound of surprising thermal stability is prismane (48) (?+ -11 h at 90°C). Synthesis82 from the now readily available benzvalene proceeds in three steps (Scheme 27). Following last year's report of the synthesis of the trioxides of benzene [Ann. Reports (B),1973,69,416]more recent work has concerned a study of their reactivity to nucleophilic a preparati~n~~ of anti-benzene dioxide (49),and the synthesis85 of the cis-benzene tri-imine (50). 76 H. Durr B. Ruge and H. Schmitz Angew. Chem. Internat. Edn. 1973 12 577. 77 A. de Meijere and L. Meyer Angew. Chem. Internat. Edn. 1973,12 858; R. D.Miller M. Schneider and D. L. Dolce J. Amer. Chem. SOC.,1973 95 8468. '' M. F. Semmelhack J. S. Foos and S. Katz J. Amer. Chem. SOC.,1973 95 7325. 79 K. Hafner R. Donges E. Goedecke and R. Kaiser Angew. Chem. Internat. Edn. 1973 12 337. 'O K. Hafner and M. U. Suss Angew. Chem. Internat. Edn. 1973,12 575. P. E. Eaton and G. H. Temme J. Amer. Chem. SOC.,1973,95 7508. 82 T. J. Katz and N. Acton J. Amer. Chem. SOC.,1973 95 2738. 83 R. Schwesinger H. Fritz and H. Prinzbach Angew. Chem. Internat. Edn. 1973 12 993 994. 84 E. Vogel H. J. Altenbach and E. Schmidbauer Angew. Chem. Internat. Edn. 1973,12 838. 85 R. Schwesinger and H. Prinzbach Angew. Chem. Internat. Edn. 1973 12 989. 590 J. M. Mellor Ph i KOH 65 7’ ii C~CI,-OH I N=N Scheme 27 0 (49) 2 Structural Properties and Orbital Interactions The early discussions of the consequences of orbital interactions either through bonds or through space emphasized the effects upon spectral properties.These theoretical analyses have received ample experimental verification from photo- electron spectroscopy particularly from the work of Heilbronner’s group. Recently such studies have been made on for example the spirocyclic systems whose syntheses are discussed above and hence spiroconjugation has been es- tablished. It is now clear that orbital interactions can have profound consequences upon the chemical reactivity of both ground and excited states. Accordingly we discuss the consequences of such interactions in spiroconjugated homoconjugated antiaromatic and hyperconjugated systems.Spiroconjugatiom-Spiroconjugation has recently been examined in three types of system (a)systems having a cyclopropyl or cyclobutyl ring fused to a cyclic n-system having either (4n + 2) or 4n n-electrons; (b) systems having a cyclic mystem of a polyene fused to another n-system of an olefin or polyene ;and (c) systems having a cyclic n-system of a polyene fused by the spiro-centre to an acetal. In case (a) interaction might be expected between the appropriate MO of the n-electron system and the Walsh orbitals of the cycloalkyl ring. In 4n n-electron systems this would imply interaction with the LUMO and with (4n + 2) Alicyclic Chemistry 59 1 n-electron systems with HOMO.Conflicting results have been obtained in searching for experimental verification in case (a). Electron-diffraction resultse6 with (51) suggest that there is little interaction between the three- and five-membered rings in contrast to earlier conclusions made from n.m.r.87 and photoelectron spectra." Conjugative interaction in (44)is expected to be less and this view is supported by a preliminary of chemical and spectral properties but it is suggested that the photoelectron spec- trum indicates a little interaction. Staley has probed the concepts of homoaromaticity and spiroaromaticity by examining the properties of carbanions. Anion (52) has a (4n + 2) n-electron system and should therefore undergo charge donation from the HOMO to the cyclopropyl ring.Anion (52)cannot be isolated" and even at -65 "Cis converted into the carbanion of ethylbenzene. In contrast anion (53) with a 4n n-electron 8 system is more table'^*^^ and n.m.r. evidence suggests a ring current in the n-system attributable to spiroconjugation with charge donation from the cyclo- propyl group. Spiroconjugation of type (b)has been explored in the olefins (43) and (46) and in the anion (54). Neither polarography nor measurements of acidityg1 indicated that anion (54)was more stable than analogues of type (55). Anion (54)is therefore c1 (54) not spiroaromatic but this may be due to an alternative and preferred mode of stabilization by the chlorines. The related olefin (43) can spiroconjugate by interaction of the 4n-system either with the 2n-system or with the Walsh orbitals.The observed U.V. spectrum [I,, 239nm for (43) and I,, 257nm for (Sl)] is inter~reted~~ as evidence for spiroconjugation. The magnitude of this spiro- 86 J. F. Chiang and C. F. Wilcox J. Amer. Chem. SOC.,1973,95 2885. R. A. Clark and R. A. Fiato J. Amer. Chem. SOC.,1970,92,4736. R. Gleiter E. Heilbronner and A. de Meijere Helu. Chim. Acla 1971,54 1029. 89 S. W. Staley G. M. Cramer and W. G. Kingsley J. Amer. Chem. SOC.,1973,95 5052. 90 S. W. Staley and W. G. Kingsley J. Amer. Chem. SOC.,1973.95 5804. 91 M. F. Semmelhack R. J. Defranco Z. Margolin and J. Stock J. Amer. Chem. SOC. 1973 95 426. 592 J. M. Mellor conjugation will be better assessed by photoelectron spectroscopy. The tetraene (46)has two bands in the U.V.spectrum at A,, 218 and 276 nm whereas the triene (45) has a single band at 254 nm. The conclusion78 of a spiroconjugative inter- action is confirmed92 by photoelectron spectroscopy which also reveals spiro- conjugation in (56),93 (57),94 and (58).95 The third type of spiroconjugation (c) requires interaction of the p-orbitals of the acetal oxygens with a nsystem and has previously been recognized in acetals of cyclopentadienone. The rate of Diels-Alder dimerization and the U.V. spectrum of (59) indicate96 a further case of spiroconjugation. Ph Ph Homoconjugated and Antiaromatic Species.-Not only has the cyclopentadienyl cation (C5H5+) been shown97 to be highly destabilized as expected of an anti- aromatic species but the cation prepared by treatment of the bromide with SbF gives an e.s.r.spectrum establishing that the ground state is a triplet and not a singlet species. The novel homoaromatic systems (60),98 (61),99*'00 and (62)99*'00 have been prepared. It is agreed that both (61) and (62) are stabilized by homoconjugative 92 C. Batich E. Heilbronner and M. F.Semmelhack Helv. Chim. Acta 1973 56 21 10. 93 A. Schweig U. Weidner J. G. Berger and W. Grahn Tetrahedron Lefters 1973 557. 94 A. Schweig U. Weidner D. Hellwinkel and W. Krapp Angew. Chem. Internat. Edn. 1973 12 310. 95 A. Schweig U. Weidner R. K. Hill and D. A. Cullison J. Amer. Chem. SOC.,1973 95 5426. 96 J. M. Holland and D. W. Jones J.C.S. Perkin I 1973 927. 9' R.Breslow and S. Mazur J. Amer.Chem. SOC.,1973,95 584; M. Saunders R. Berger A. Jaffe J. M. McBride J. O'Neill R. Breslow J. M. Hoffman C. Perchonock E. Wasserman R. S. Hutton andV. J. Kuck ibid. p. 3017. 98 G. B. Trimitsis E. W. Crowe G. Slomp and T. L. Helle J. Amer. Chem. SOC.,1973 95 4333. 99 M. V.Moncur and J. B. Grutzner J. Amer. Chem. SOC.,1973,95 6449. loo M. J. Goldstein and S. Natowsky J. Amer. Chem. SOC.,1973 95 6451. Alicyclic Chemistry interactions but there is disagreement in the assessment of the importance of laticyclic stabilization in (62). Analysis"' of the anion (63) further implies the lack of bishomoantiaromatic character in the 7-norbornenyl anion but preparationlo2 of the anion (64) has not indicated whether it has significant homoantiaromatic character.Observation oftheions(65)lo3 and(66)'04shows that by bond fixationin(65)andconformational twisting in (66) the destabilizing antiaromaticity of a 4n-system is minimized. Anion (67) has a (4n + 1)n-electron system is defined as an atropic system and observation by n.m.r. indicates'05 that it supports at best only a minor ring current in contrast to the above diatropic or paratropic species. A further novelty is the organic sandwich species (68) obtainedlo6 from (69) in FS0,H. The n.m.r. spectrum is best interpreted on the basis of a species with degeneracy atrributed to a double rotation and not on the basis of equilibrating species. The diol(70) in FS0,H gives a dication to which the structure (71) has been assigned,lo7 and solution of (72) or (73) in superacid media"* gave the cation (74).lo' D. D. Davis and W. B. Bigelow Tetrahedron Letters 1973 149. lo' S. W. Staley and N. J. Pearl J. Amer. Chem. SOC.,1973 95 2731. '03 S. W. Staley and A. W. Orvedal J. Amer. Chem. SOC.,1973,95 3382. lo' S. W. Staley and A. W. Orvedal J. Amer. Chem. SOC.,1973 95 3384. lo' S. W. Staley and G. M. Cramer J. Amer. Chem. SOC.,1973,95 5051. Io6 M. J. Goldstein and S. A. Kline J. Amer. Chem. SOC., 1973 95 935. lo' H. Hogeveen and P. W. Kwant Tetrahedron Letters 1973 1665. lo' S. Masamune M. Sakai A. V. Kemp-Jones H. Ona A. Venot and T. Nakashima Angew. Chem. Znternaf. Edn. 1973 12 769. 594 J. M. Mellor H OH H I Cl (74) (73) Hyperconjugation.-The expectation [Ann.Reports (B) 1972 68 4041 that a study of orbital interactions through bonds and through space would lead to a recognition of their great importance in controlling chemical reactivity is being realized. Interactions which lead to a reversal in ordering of n-levels will determine reactivity in symmetry-controlled cycloadditions. In (75) a dominant through- bond intera~tion"~ through the strained a-system places the symmetric 7~ combination above the antisymmetric n combination in energy. Hence a photo- chemical closure of (75) to cubane is not expected. Less drastic interactions which lead not to an actual reversal of energy levels but only to more minor displacements control the reactivity in for example log R. Gleiter E. Heilbronner M. Hekman and H.D. Martin Gem. Ber. 1973 106 28. Alicyclic Chemistry Diels-Alder additions. With electron-rich dienes rate is largely determined by interaction of the HOMO of the diene with the LUMO of the dienophile. This interaction will be increased by any increase in energy of the HOMO of the diene. Experimental rate studies havebeen made withdienes for which the HOMOenergy is modified by spiroconj~gation,~~*~~ and by other orbital interactions."' Orbital interactions between a functional group and the a-framework modify reactivity conformation and control of stereochemistry by an attacking reagent. Carbonium ion stability is increased by a conjugative interaction in simple acycliccases. The7-norbornylcationisabnormallyunstable :anew explanation' ' attributes the lack of stability to a lack of interaction between the highest occupied a-orbital of the cyclohexane framework and the cationic centre [see (76)].Similar symmetry constraints stabilize the no-and %-orbitals in the ether (77)' and the sulphide (78)' ' relative to acyclic examples. Solution of 1,4-dichlorobicyclo- [2,2,2]octane in superacid generates' ' the dication (79). The unusual stability of this dication is due to the symmetry-allowed hyperconjugative interaction with the three carbon bridges. Cation (80) is stabilized by extensive cyclopropane a-participation''4 and preliminary results suggest that (81) may also be stable. H (76) (78) X = S The anomeric effect,' l5 the preference of methyl groups for adopting an eclipsed rather than staggered conformation with respect to a vinylic group,'16 and the concept of steric attraction by a remote group in a transition state'17 have all 110 W.L. Jorgensenand W. T. Borden J. Amer. Chem. SOC.,1973,956649; M. N. Paddon-Row Tetrahedron Letters 1972 1409. 111 R. Hoffmann P. D. Mollere and E. Heilbronner J. Amer. Chem. SOC.,1973,95,4860. 112 J. C. Bunzli D. C. Frost and L. Weiler J. Amer. Chem. SOC.,1973 95 7880. 113 G. A. Olah G. Liang P. von R. Schleyer E. M. Engler M. J. S. Dewar and R. C. Bingham J. Amer. Chem. SOC.,1973,95 6829. 114 A. de Meijere and 0.Schallner Angew. Chem. Internat. Edn. 1973 12 399. 115 S. David 0.Eisenstein W. J. Hehre L. Salem and R. Hoffmann J. Amer. Chem. SOC. 1973,95 3806. 116 W. J. Hehre and L. Salem J.C.S.Chem. Comm. 1973 754. 111 N. D. Epiotis and W. Cherry J.C.S. Chem. Comm. 1973 278; N. D. Epiotis J. Amer. Chem. SOC.,1973 95 3087; R. Hoffmann C. C. Levin and R. A. Moss ibid. p. 629. 596 J. M. Mellor been attributed to hyperconjugative interactions. Such interactions can induce a dissymmetry in for example the n-cloud of a carbonyl group. A fresh inter- pretation"* of Cram's Rule argues that the preferred face for nucleophilic attack is determined by such an interaction and new light is cast upon the vexed problem of the control of stereochemistry in reductions of cyclohexanones by the view' l9 that interaction of the o-framework with the carbonyl group induces dissymmetry in the n-system. A more detailed analysis is required of recent experimental results concerning nucleophilic attack at cyclohexanones' 2o before the importance of hyperconjugative interactions can be fully assessed but results12' shown in Scheme28 might be explained by such effects.Both '3C-H coupling constants' 22 R R R R = Et R = Ph R = Me R= Pr' 50 % 68 % 72% 5% 50 % 32 % 28 % 95 % Scheme 28 and 13C chemical shifts'23 have been used to establish the magnitude and pre- ferred pathways for hyperconjugative effects. The contribution of through-bond effects to the phenomenon of 'conformational transmission' is still unresolved and recent solvolytic studies' 24 and calculations' 25 are indeterminate. l8 N. T. Anh 0.Eisenstein J.-M. Lefour and M.-E. Tran Huu Dau J. Amer. Chem. SOC. 1973,95 6146. l9 J.Klein Tetrahedron Letters 1973 4307. 120 J. Laemmle E. C. Ashby and P. V. Roling J. Org. Chem. 1973,38,2526;E. C. Ashby J. R. Boone and J. P. Oliver J. Amer. Chem. SOC.,1973,95 5427; E. Volpi G. Biggi and F. Pietra J.C.S. Perkin 11 1973 571. D. Varech and J. Jacques Tetrahedron Letters 1973 4443. IZ* N. H. Werstiuk R. Taillefer R. A. Bell and B. Sayer Cunad. J. Chem. 1973,51 3010. * 23 I. Morishima K. Yoshikawa K. Okada T. Uonezawa and K. Goto J. Amer. Chem. SOC.,1973 95 165. 124 H. Tanida S. Yamamoto and K. Takeda J. Org. Chem. 1973 38 2077. P. A. Kollman D. D. Giannini W. L. Duax S. Rothenberg and M. E. Wolff J. Amer. Chem. SOC.,1973,95 2869.