9 Alicyclic Chemistry By J. M. MELLOR Department of Chemistry The University Southampton SO9 5NH 1 Introduction The pace of discovery of new carbocyclic skeletons in Nature is only matched by the ever increasing efficiency of their total synthesis in the laboratory. The state of the art is indicated by the remarkable number of reports of total synthesis of complex natural products in which only two Authors are named. Pride of place must go to Gibbons for his lone effort on the first efficiently stereoselective synthesis' of pleuromutilin (1). However the new level of skill in synthetic design and execution is witnessed by synthesis from readily prepared intermediates of khusimone (2)*(9 synthetic steps; 11%overall yield) modhephene (3)3(7 steps; 8% yield) silphinene (4)4 (15 steps; 10% yield) vetispirene (5)5 (5 steps; 38% yield) mycorrhizin A (6),6hibiscone C(7),7 confertin (8),8aromatin (9),9hirsutene I E.G. Gibbons J. Am. Chem. SOC.,1982,104,1767. W..Oppolzer and R. Pitteloud I. Am. Chem. Soc.. 1982,104,6478. P. A. Wender and G. B. Dreyer J. Am. Chem. SOC.,1982,104 5805. A. Leone-Bay and L. A. Paquette J. Org. Chem. 1982,47,4173. T.-H. Yan and L. A. Paquette TetrahedronLett. 1982 23,3227. E. R. Koft and A. B. Smith J. Am. Chem. SOC.,1982,104,2659. E. R. Koft and A. B. Smith J. Am. Chem. SOC.,1982,104,5568. A. G. Schultz and L. A. Motyka J. Am. Chem. SOC.,1982,104 5800. P. T. Lansbury and J. P. Vacca Tetrahedron 1982.38 2797. 172 J.M. Mellor (lo)," capnellenediol (ll)," the complement inhibitor K-76 (12)12 (a fungal meta- bolite which inhibits a step contributing to the inflammatory process in rheumatoid arthritis) a chiralI3 and a racemic14 synthesis of compactin (13) synthesis of the aglycone phyllanthocin (14)," and two syntheses of verrucarol (15).16 Many other CHO syntheses merit discussion but space prohibits such luxury.However synthesis of cyclopentanoids has been reviewed" and the discussion of many other fascinating structures may be found in a symposium on Animal Defence Mechanisms." The importance of cyclopentanoid targets is emphasized by the review of prostacyc- lins" and of the development of methodologies based on cyclopentenones20 and '(I S. V. Ley and P. J. Murray J. Chem. SOC.,Chem. Commun. 1982 1252. '' G.Pattenden and S. J. Teague Tetrahedron Lett. 1982 5471. E. J. Corey and J. Das J. Am. Chem. SOC.,1982,104 5551. l3 M. Hirama and M. Uei J. Am. Chem. SOC.,1982,104,4251. l4 N. N. Girotra and N. L. Wendler Tetrahedron Lett. 1982 5501. P. R. McGuirk and D. B. Collum J. Am. Chem. SOC.,1982,104,4496. l6 R. H. Schlessinger and R. A. Nugent J. Am. Chem. SOC.,1982 104 1116; B. M. Trost and P. G. McDougal ibid. p. 6110. l7 B. M. Trost Chem. SOC.Reu. 1982,11 141. Tetrahedron 1982 38 1855. l9 W. Bartmann and G. Beck Angew. Chern. Int. Ed. Engl. 1982,21,751. 2n M. Harre P. Raddatz R. Walenta and E. Winterfeldt Angew. Chem. Int. Ed. Engl. 1982 21,480. Alicyclic Chemistry 173 on photochemical routes to cyclopentanoids.21 Examples of the importance of intramolecular [2 + 21 photoadditions in synthesis are discussed below but the subject has been reviewed2’ and similarly the use of siloxydienes in the Diels-Alder reaction has been reviewed by Dani~hefsky~~ and further examples are given below.A further Symposium in print concerns various aspects of the chemistry of biradi~als’~ and the norbornyl cation is the subject of a review by summariz-ing his view that there is still no definitive evidence which requires the nonclassical structure for the 2-norbornyl cation. A balanced viewz6 by Grob incorporating many recent results from Basle suggests that the original nonclassical/classical argument has lost most of its meaning. A gradation of bridging behaviour is to be observed in differently substituted 2-norbornyl cations.The applications of molecular mechanics in alicyclic chemistry” have been reviewed and the extent to which orbital interactions through several bonds affect physical and chemical properties2* has been analysed. Again further recent examples are discussed below. The full impact of exciting new methods of obtaining structural information by n.m.r. techniques has yet to be experienced. An insight into the future is given by the determination of ~tructure’~ of the photoproduct (16) obtained from (17).The structure of (16) is assigned using two-dimensional correlated spectra. Again 2D 0 0 (16) (17) techniques are used to prove the structure of (18) a steroid photodimer. Here the analysis is based3’ on 13C-13C couplings at a natural abundance level which required a large sample weight (0.84g).Structures of other steroids have been estab1ished3l by related methods but again with present spectrometers gram quantities are required. The first structural determination of a natural product using these double quantum coherence methods is reportedj2 for velloziolide (19); the sample weight was 500 mg. 2‘ M. Demuth and K. Schaffner Angew. Chem. Int. Ed. Engl. 1982,21 820. 22 W. Oppolzer Acc. Chem. Res. 1982 15 135. 23 S. Danishefsky Acc. Chem. Res. 1981 14 400. 24 Tetrahedron 1982 38 735. 25 H. C. Brown Pure Appl. Chem. 1982 54 1783. 2h C. A. Grob Angew. Chem.. Int. Ed. Engl. 1982 21 87. *’ E. Osawa and H. Musso Top. Stereochem. 1982 13 117. 28 M. N. Paddon-Row Acc.Chem. Res. 1982,15 245. 29 D. Leibfritz E. Haupt M. Feigel W. E. Hull and W.-D. Weber Annalen 1982 1971. ’’ R. Freeman T. Frenkiel and M. B.Rubin J. Am. Chem. SOC.,1982,104 5545. 31 R. Jacquesy C. Narbonne W. E. Hull A. Neszmelyi and G. Lukacs J. Chem. Soc. Chem. Commun. 1982,409. 32 A. C. Pinto M. L. A. Goncalves R. B. Filho A. Neszmelyi and G. Lukacs J. Chem. SOC.,Chem. Commun. 1982,293. 174 J. M. Mellor 0dP @@ OH -0 0 2 Synthesis Monocyclic Compounds.-The stimulus of the insecticidal activity of the derivatives of the chrysanthemic acids -particularly the unnatural cis-series -has resulted in further synthetic studies. Russian chemists describe33 an improved route to 3,3- dimethylcyclopropene and subsequent formation in 70%yield of cis-chrysanthemic acid (20) by reaction with 2-methylpropenyl magnesium bromide and then carbon dioxide.A later report however a lower yield (39%). A very attractive alternative proceeding with intermediacy of a cyclopropene concerns forma- tion of a 3H-pyrazole (21) by hydrazine addition to an @-unsaturated ketone and subsequent MnO oxidation of the intermediate pyrazoline. Photolysis of (21) and stereospecific hydrogenation gives (22) in 94% yield for the two steps. Enantioselec- tive rqute~~~ towards synthesis of the chrysanthemic acids are noted. 33 0. A. Nesmeyanova T. Y.Rudashevskaya A. I. Dyachenko S. F. Savilova and 0.M. Nefedov Synthesis 1982 296. 34 H. Lehmkuhl and K. Mehler Annalen 1982 2244. 35 M. Franck-Neumann and M.Miesch Tetrahedron Lett. 1982 23 1409. 36 M. Franck-Neumann D. Martina and M. P. Heitz Tetrahedron Lett. 1982 23 3493; M.4. De VOS and A. Krief J. Am. Chem. Soc. 1982,104,4282. Alicyclic Chemistry 175 Me0,C ArS0,fS OH * Acow (22) (24) 0 1-Arylsulphonylbicyclo[1.1.O]butanes [e.g. (23)] are easily prepared from 76-epoxysulphones and provide surprising intermediates in the synthesis of some natural products [e.g. the pheromone (24),37 and mc-junionone (25)38]. Progress in the understanding of cyclobutadiene chemistry has centred on the carbene route (Scheme l) which can give either cyclobutadiene~~~ [e.g. (26)] or acetylenes by fragmentation It is suggested4' that (26) is formed from a singlet carbene but the triplet carbene leads to fragmentation.+=+ $-C02 Bu' CO Bu' Scheme 1 Reductive cyclization of ao-dihalides has been of little importance other than for formation of cyclopropanes. Now by careful definition of conditions excellent yields are obtained41 in the formation of both four- and five membered rings. The of rhodium(I1) catalysed decompo~ition~~ a-diazo-@-keto-esters leads very efficiently to the formation of cyclopentane derivatives by intramolecular C-H insertion (Scheme 2). A number of palladium(0) catalysed processes for construction Scheme 2 37 Y. Gaoni Tetrahedron Lett. 1982,23,5215. 38 Y.Gaoni Tetrahedron Lett. 1982,23,5219. 39 P.Eisenbarth and M. Regitz Chem. Ber. 1982 115 3796. 40 P. Eisenbarth and M. Regitz Angew. Chem. Int. Ed. Engl. 1982,21,913.41 W.F.Bailey and R. P. Gagnier Tetrahedron Lett. 1982,23,5123. 42 D.F.Taber and E. H. Petty J. Org. Chem. 1982.47.4808. 176 J. M. Mellor of five-membered rings are reported. Trost and Runge describe43 full details of their synthesis of cyclopentanones by isomerization of tetrahydrofurans (Scheme 3). Palladium(0) catalysis permits efficient ~earrangement~~ of cyclopropane deriva- tives to give five-membered rings (Scheme 4). The method is applicable to construc- tion of spirocycles. An intramolecular [3 + 21 cy~loaddition~~ leads to formation Scheme 3 Pd" &CO2Me C0,Me 4 C0,Me C0,Me Scheme 4 of a five-membered ring and construction of a bicyclic system from acyclic precursors (Scheme 5). The Grignard reagent (27) can be used in alternative methods of construction of carbocycles.Thus 1,4-addition to cyclohex-2-enone followed by a SiMe H i ii / SOzPh ,6 0 OAc liii SiMe (27) @ PhSO Reagents i (27);ii AcCl; iii Pd(dppe),; 65% Scheme 5 43 B. M. Trost and T. A. Runge I. Am. Chem. SOC.,1981 103,7559. 44 Y.Morizawa K. Oshima and H. Nozaki Tetrahedron Lett. 1982,23,2871. 4s B.M. Trost and D. M. T. Chan J. Am. Chem. Soc. 1982,104,3733. Alicyclic Chemistry Lewis acid promoted cyclization leads46 to (28)in -80% overall yield. The acylation of acetylenes with py-unsaturated acid chlorides4’ promoted by Lewis acids leads to cyclopent-2-enones. The method is particularly efficient for formation of spirocycles. Thus from (29) and propyne by rearrangement (30) is obtained in 65% yield.Two important new procedures for construction of five-membered rings have been developed by Stork’s group. In one case trans-hydrindanes are constructed by an intramolecular Michael addition4’ with high stereoselectivity. In a further procedure cyclization is via intramolecular addition of a vinyl radical to a double bond. Irradiati~n~~ of a vinyl halide with excess tri-n-butylstannane generally leads to efficient cyclization (see Scheme 6). A quite different reductive cyclizationS0 proceeds via an organomercury intermediate (Scheme 7). eN Scheme 6 Reagents i Hg(OAc), AcOH; ii NaBH(OMe),; iii KOH H20 MeCN; iv CrO Scheme 7 The recent interest in the ene-reaction as a method of ring synthesis has been extended by the intermolecular reaction of cup-unsaturated carbonyl corn pound^^' with alkenes (Scheme 8) and by the use of organomagnesium compounds in intramolecular ene reactions.The known ‘metallo-ene’ reaction has been adapted5* 46 B. M. Trost and B. P. Coppola J. Am. Chem. Soc. 1982,104,6879. 47 M. Karpf Tetrahedron Lett. 1982 23 4923. 48 G. Stork C. S. Shiner and J. D. Winkler J. Am. Chem. SOC.,1982,104 310. 49 G. Stork and N. H. Baine J. Am. Chem. SOC.,1982,104 2321. ” S. Danishefsky S.Chackalamannil and B.-J. Wang J. Org. Chem. 1982 47 2231. ” B. B. Snider and E. A. Deutsch J. Org. Chem. 1982,47,745. ’* W. Oppolzer E. P. Kundig P. M.Bishop and C. Perret Tetrahedron Len. 1982 23 3901; W. Oppolzer R. Pitteloud and H. F. Strauss J.Am. Chem. SOC.,1982,104 6476. 178 J. M. Mellor Reagents i methyl vinyl ketone Me,AlCl Scheme 8 by efficient generation of the allylic Grignard reagents using a procedure requiring fresh magnesium obtained by distillation. Subsequent heating of the allylic Grignard reagents leads to effective ring synthesis by intramolecular cyclization. Khusimone (2) and ~apnellene~~ (Scheme 9) have been synthesized by such procedures. 1iv H vii iv-vi HH 1 t Reagents Mg powder Et,O; ii 60T 23h; iii acrolein; iv SOCl,; v Mg powder Et,O; vi r.t. 20h; vii several steps Scheme 9 Later we note the improved methods for construction of six-membered rings in steroids. Few real innovations in the synthesis of six-membered rings are to be reported.However enantioselectivity in the Diels-Alder reaction of cyclopen- tadiene with acrylate has reached the point that asymmetric induction is described as ‘virtually quantitative’. The great problem in construction of macrocycles is avoidance of conditions requiring high dilution. Use of polymer-supported palladium catalysts55 enables isomerization to give macrocycles to be effected in concentrated solutions (0.5 M) [e.g. formation of (31)and (32) from (33)]. High dilution is required in the coupling of dicarbonyl compounds by titanium. A testimony to the importance of the method however is the stereospecific con~ersion~~ of (34) into humulene (35)in 60%yield. Three photochemical procedures lead to important bicyclic systems. Irradiation of phenol57 in CF3S03H-SbF5 gives (36) in 20% yield.Full details are reported of ’3 W. Oppolzer and K. Battig Tetrahedron Lett. 1982 23,4669. 54 W. Oppolzer C. Chapuis G. M. Dao D. Reichlin and T. Godel Tetrahedron Lett. 1982 23,4781. ” B. M. Trost and R. W. Warner J. Am. Chem. SOC.,1982,104 6112. 56 J. E. McMurray and J. R. Matz Tetrahedron Lett. 1982 23 2723. ’’ R. F. Childs G. S. Shaw and A. Varadarajan Synthesis 1982 198. Alicyclic Chemistry 502ph procedures58 permitting copper(1) promoted photocyclization of alkenylallyl alcohols [e.g.conversion of (37) into (38) (83% yield)]. Although further examples are reported5’ of observation of norcaradienes in equilibrium with cyclohep- tatrienes the first observation of the parent norcaradiene (39) has been achieved6’ by low temperature photolysis of (40).& e&o& (37) (38) (39) (40) (36) Bridged and Polycyclic Compounds.-Examples of [4.1.1] and [3.1.1] propellanes have previously been prepared and are known to be highly unstable because of the ease with which the strained central carbon-carbon bond can be cleaved to give radicals. In contrast Wiberg’s group have calculated61 that in [1.1.13propellane (41) a higher bond dissociation energy may be expected because of the greater strain energy in the products relative to those formed from for example [4.1.1] propellane. Preparation of (41) by the reaction of (42) with t-butyl-lithium permits R. G. Salomon D. J. Coughlin S. Ghosh and M. G. Zagorski J. Am. Chem. Soc. 1982 104 998; R.G. Salomon S. Ghosh M. G. Zagorski and M. Reitz J. Org. Chem. 1982 47 829. 59 K. Takeuchi T. Kitagawa T. Toyama and K. Okamoto J. Chem. Soc. Chem. Commun. 1982 313; W. Bauer J. Daub G. Maas M. Michna K. M. Rapp and J. J. Stezowski Chem. Ber. 1982,115 99. M. B. Rubin J. Am. Chem. Soc. 1981,103,7791. 61 K. B. Wiberg and F. H. Walker J. Am. Chem. Soc. 1982,104,5239. 180 J. M. Mellor the remarkable thermal stability of (41) to be confirmed (ti 114"C-5 min). In sharp contrast [2.2.llpropellane (43)has only been observed6* using matrix-isola- tion techniques. A related cyclization from the dibromide (44)permits the first synthesis63 of octavalene (49,which only at 80°C slowly isomerizes to cyclo- octatetraene Lack of product stability is not the difficulty in synthesis of dodecahedrane (46) (no evidence of melting even at 450°C),which has at last been ~ynthesized~~ in 23 steps from the cyclopentadienide anion.The detailed studies of Paquette's group in this area have resulted in the synthesis of both m~nomethyl-~~ and a dimethyl- dodecahedrane.66 The proposal by Australian chemisd7 that the biogenetic pathway to the series of endiandric acids (A B C and D) having unusual structures might proceed by a series of non-enzymatic electrocyclizations has been confirmed6* by the group of Nicolaou in an outstanding study. A retro-synthetic analysis in Scheme 10shows the possible origin of the known acids which occur in Nature as racemates from an achiral diacetylene precursor. In one of the more remarkable parts of the synthetic study hydrogenation of (47)and subsequent electrocyclization leads directly to the methyl esters of endiandric acids B and C.Developments in steroid synthesis have centred on new methods of construction of six-membered rings leading to racemic products and on improvements to estab- lished methods permitting induction of chirality. Sternberg and Vollhardt6' have used a cobalt mediated [2 + 2 + 2lcyclo-addition in a short route to the Torgov intermediate (Scheme 11).Stork and Sherman7' have based a new route to 11-ketoprogesterone on synthesis and elaboration of the acid (48).The value of the 62 F. H. Walker K. B. Wiberg and J. Michl J. Am. Chem. SOC.,1982,104,2056. 63 M. Christ1 and R. Lang J. Am. Chem. Soc. 1982,104,4494.64 R. J. Ternansky D. W. Balogh and L. A. Paquette J. Am. Chem. Soc. 1982,104,4503. 65 L. A. Paquette R. J. Ternansky and D. W. Balogh J. Am. Chem. SOC., 1982,104,4502. 66 L. A. Paquette and D. W. Balogh J. Am. Chem. Soc. 1982,104,774. '' W. M. Bandaranayake J. E. Banfield and D. St. C. Black J. Chem. Sac. Chem. Commun.,1980,902. 68 K. C. Nicolaou N. A. Petasis R. E. Zipkin and J. Uenishi J. Am. Chem. Sac. 1982 104 5555; ibid.,p. 5557; K. C. Nicolaou R. E. Zipkin and N. A. Petasis ibid.,p. 5558; ibid.,p. 556U. 69 E. D. Sternberg and K. P. C. Vollhardt J. Org. Chem. 1982,47 3447. '' G. Stork and D. H. Sherman J. Am. Chem. SOC.,1982,104,3758. Alicyclic Chemistry 181 n = 0 Endiandric acid A Endiandric acid C Endiandric acid D n = 1 Endiandric acid B R1 RZ Q c‘=-=> C0,Me Ph (47) R’ RZ Scheme 10 Johnson biomimetic polyene cyclization as a route to a variety of steroids is well recognized.Now it is established71 that a benzyloxy-substituent at a chiral centre (pro-C-7) induces considerable diastereoselection. Using racemic sub~trates,’~ the 71 W. S. Johnson D. Berner D. J. Dumas P. J. R. Nederlof and J. Welch J. Am. Chem. SOC.,1982 104,3508. 72 W. S. Johnson D. J. Dumas and D. Berner J. Am. Chem. SOC.,1982 104 3510. 182 J. M. Mellor 1ii 0 n Reagents i CpCo(CO) ,A; ii FeCI, MeCN; iii pTsOH Scheme 11 methodology is used in a synthesis of the important aldosterone blocking agent spironolactone(49). A simple and efficient method of elaboration of 17-ketosteroids to obtain a corticosteroid side-chain via ethylenediamine-catalysed condensation with nitromethane to give an intermediate nitroalkene which is then treated with formaldehyde.3 Chemistry Neutral Species Strained Alkenes and A1kynes.-Recent studies have concerned not only a continuation of the many reports of the chemistry of bridgehead alkenes and of cyclic allenes but also the limiting ring size embracing a trans-alkene linkage and an acytylenic group. Photoisornerizati~n~~ of cis-cycloheptene using photo-sensitizers has permitted the first observation of the kinetics of the conversion of trans-cycloheptene into cis-cycloheptene. Truns-cycloheptene is stable at -78 “C. 73 D. H. R. Barton W. B. Motherwell and S. Z.Zard J. Chem. SOC.,Chem. Commun. 1982 551. 74 Y. Inoue T. Ueoka T. Kuroda and T. Hakushi J. Chem. SOC.,Chem. Commun.,1981,1031. Alicyclic Chemistry 183 Cyclopentyne is highly reactive and in fresh trapping it has been shown that reaction of (50) with phenyl-lithium provides a new route to cyclopentyne. Photoelectron spectroscopy has an established importance in determination of ionization potentials. A satisfactory experimental method for determination of electron affinities has been slower in development. Now the electron affinities of cis-and trans-cyclo-octene have been measured using electron transmission measurernent~:~~ the difference (0.14eV) is less than the observed difference in ionization potentials (0.29eV). Br The earlier investigations of the chemistry of (51) and (52) (Annu.Rep. Bog. Chem.,Sect. B 1981,78,199)have been extended by matrix isolation experiment~~~ that have permitted the recording of the i.r. spectrum of (52). Trapping provide further evidence for the intermediacy of both (51) and (52). Further studies of both a Wittig route7' to strained bridgehead alkenones and the use of intramolecular Diels-Alder reactions in construction of bridgehead alkenes" are reported. Direct irradiation" of the bridgehead alkene (53) leads to cis-trans-isomerization and trapping studies suggest formation of the more reactive (54). The sterically hindered bridgehead alkene (55) isso stabilized to the anticipated [2 + 21 mode of dimerization that it survives unchanged8* at 185 "Cover 24 h.75 L. Fitjer U. Kliebisch D. Wehle and S. Modaressi Tetrahedron Lett. 1982 23 1661. " M. Allan E. Haselbach M. von Buren and H.-J. Hansen Helo. Chim. Acta 1982,65 2133. 77 P. R. West 0.L. Chapman and J.-P. LeRoux J. Am. Chem. SOC., 1982,104 1779. 78 M. Balci W. R. Winchester and W. M. Jones J. Org. Chem. 1982 47 5180; J. W. Harris and W. M. Jones J. Am. Chem. SOC., 1982,104,7329. 79 H. J. Bestmann and G. Schade Tetrahedron Lett. 1982 23 3543. *" K. J. Shea S. Wise L. D. Burke P. D. Davis J. W. Gilman and A. C. Greeley J. Am. Chem. SOC. 1982,104 5708. J. R. Wiseman and J. E. Kipp J. Am. Chem. SOC.,1982,104,4688. ** S. F. Sellers T. C. Klebach F. Hollowood and M. Jones J. Am. Chem. SOC., 1982,104 5492. 184 J. M. Mellor Other Neutral Species.-The distinction between valence isomerization and mesomeric interaction in cyclobutadienes has been probed by two very different techniques.I3CN.m.r. analysisB3 at -82°C suggests the existence of a dynamic equilibrium between the valence isomers (56a) and (56b). A kinetic analysis84 of [1,2-2H2]cyclobutadiene using trapping experiments confirms a low activation energy for the valence isomerization and excludes the possibility of a delocalized T-sys tem. Structures (57) and (58)are related as an aromatic phenol and a ketone tautomer. Both spectroscopic observationE5 and calculationsB6 indicate that (58) is the more stable showing that the aromaticity of (57) is inadequate to compensate for the greater strain relative to the non-aromatic but less strained ketone (58).Carbenium 10ns,-'~C N.m.r. spectra of the norbornyl cation have probedB7 the nature of this cation at very low temperatures. Useful spectra have been obtained at 5 K which establish that in super acid media if equilibration between structures having a localized charge is occurring then the activation energy for such a process cannot be more than 0.2 kcal mol-I. Hence a delocalized structure seems probable. Both solvolytic studies proceeding with ionizationE8 and SN2 displacement^^^ at norbornyl derivatives indicate that some earlier views overemphasize the import- ance of steric effects in controlling exolendo rate ratios. Radical Species.-Electrochemical studies establishg0 the rapid cycloreversion of the radical anion of tetraphenylcyclobutane by a [u2,+ u2,]process.It is suggested that this cycloreversion has considerable generality in the chemistry of substituted cyclo bu t anes. 83 G. Maier. H.-D. Kalinowski and K. Euler Angew. Chem. Int. Ed. Engl. 1982 21 693. 84 D.W. Whitman and B. K. Carpenter J. Am. Chem. SOC., 1982,104,6473. 85 R. McCague C. J. Moody and C. W. Rees J. Chem. SOC.,Chem. Commun. 1982,622. 86 H. S.Rzepa J. Chem. Res. 1982 324. 87 C. S.Yannoni V. Macho and P. C. Myhre J. Am. Chem. SOC.,1982 104 907;*C. S.Yannoni V. Macho and P. C. Myhre ibid. p. 7380. 88 C. A.Grob B. Gunther and R. Hanreich Helu. Chim. Acta 1982,65,2110. 89 K.Banert and W. Kirmse J. Am. Chem. SOC.,1982,104,3766. 90 M.Homer and S. Hunig Liebigs Ann. Chem. 1982 1409.Alicyclic Chemistry There are reports of attempted observations of a variety of important radicals. E.s.r. studies have failed again to give evidence of the parent cyclopropenyl radical. However both (59) and (60) have been observed. It is interesting that the structure of (60) is as represented" and that no evidence for a tertiary radical centre was obtained. Picosecond fluorescence has been used by excitation of (61) to observe the singlet biradical (62). An attempt93 to prove that sensitized photolysis of (63) might proceed via in part the tetraradical (64) is inconclusive but a failure to observe products indicating the intermediacy of radicals strongly that the mechanism of oxidation of (65) and hence by implication other alcohols by NAD(H) and alcohol dehydrogenase does not involve radical inter- mediates.Carbanions.-Redu~tion~~ of (66) gives the dianion (67) which has been character- ized spectroscopically and chemically. Both the 'H and 13Cn.m.r. spectra of (67) show a characteristic symmetry and there is strong evidence that (67) is a bis- homoconjugatively stabilized species. Electrochemical reduction of (66) suggests that the second electron transfer to the radical anion is relatively facilitated; this behaviour is well known with cyclo-octatetraene. Further calculation^^^ contradict 91 R. Sutcliffe D. A. Lindsey D. Griller J. C. Walton and K. U. Ingold J. Am. Chem. SOC.,1982 104,4674. 92 D. F. Kelley P. M. Rentzepis M. R. Mazur and J. A. Berson J. Am. Chem. SOC., 1982 104 3764.93 L. McElwee-White and D. A. Dougherty J. Am. Chem. SOC., 1982,104,4722. 94 1. MacInnes D. C. Nonhebel S. T. Orszulik and C. J. Suckling J. Chem. SOC., Chem. Commun. 1982,121. W. Huber K. Mullen R. Busch W. Grimme and J. Heinze Angew. Chem. Inr. Ed. EngI. 1982 21 301. 96 J. M. Brown R. J. Elliott and W. G. Richards J. Chem. SOC. Perkin 2 1982 485. '.5 186 J. M. Mellor the views expressed last year (see Annu. Rep. Prog. Chem. Sect. B 1981 78 202) of the lack of homoaromatic character in the anions of bridged hydrocarbons. In particular the homoaromaticity of (68) is again supported. 4 Stereochemical Aspects The interest in long range substituted effects has led to their observation by new techniques that are responsive to subtle effects which are dependent on both distance and stereochemical pathways.Thus analysis9' of I3C chemical shifts by n.m.r. of steroids shows the importance of through-space field-eff ects of electronegative substituents over six bonds. Ob~ervation~~ of fluorescence using single photon counting methods proves that intramolecular quenching by electron transfer of excited states can occur over large distances for example in (69). Electron trans- mission spectroscopy has been to measure the electron affinities and hence to observe the interactions of T orbitals in some dienes. A large through-space interaction is observed in (70)but a substantial through-bond interaction is observed in (71); the chemical consequences of such interactions have recently been dis- cussed.28A continued focus of attention in the chemistry of norbornyl derivatives has been the differential reactivity at exo- and endo-sites and the view that such differences are electronic rather than steric in origin.Both 2H and I3Cn.m.r. results show"' the importance of electronic factors [see the relative chemical shifts in (72)]. Further studies of Diels-Alder additions to dienes closely related to (72) show that subtle factors are controlling the preferred face of addition. Huisgen in examining both the abnormally fast reactivity of norbornene in cycloaddition reactions and the preference for reaction at the exo-face coined the phrase 'factor 97 H.-J. Schneider and W. Gschwendtner J. Org. Chem. 1982 47 4216. 9R P. Pasman N.W. Koper and J. W. Verhoeven Red. Trav. Chim. Pays.-Bas 1982 101 363; P. Pasman F. Rob and J. W. Verhoeven J. Am. Chem. SOC., 1982,104,5127. 99 V. Balaji K. D. Jordan P. D. Burrow M. N. Paddon-Row and H. K. Patney J. Am. Chem. SOC. 1982,104,6849. IfloL. A. Paquette and P. Charumilind J. Am. Chem. SOC.,1982 104 3749. Alicyclic Chemistry x’ as the key for the observed phenomena (Annu. Rep. Prog. Chem. Sect. B 1980 77 150). Further explanations of ‘factor x’ have appeared. Extended Huckel calculations”’ indicate that a bending of the double bond in norbornene in an endu-direction (corresponding to the result of an exo-addition) is energetically more favourable than a bending in an exo-direction (corresponding to the result of an endo-addition).This analysis explains the preference for endu-bending by hypercon- jugative effects. A different viewlo2 re-emphasizes the importance of ‘non-equivalent orbital extension’ a factor originating from hybridization changes by ‘orbital tilting’. A third view’03 rejects the importance of factors originating either from ‘non-equivalent orbital extension’ or hyperconjugative interactions. Instead a preference for allylic groups to adopt a staggered conformation with respect to partially formed bonds in the transition state of addition to alkenes.is restated. In addition to norbornene em-attack leads to a relatively staggered arrangement of partially formed bonds with respect to the allylic bonds but endo-attack leads to larger eclipsing interactions.These proposals close to the original Schleyer analysis of torsional strain receive some support from the experimental result that (73) undergoes cycloaddition reactions at comparable rates to norbornene. In the more strained norbornene hyperconjugative effects might have been expected to lead to faster rates. lo’ J. Spanget-Larsen and R. Gleiter Tetrahedron Leff. 1982 23 2435. . lo* S. Ito and A. Kakehi Bull. Chem. SOC.Jpn. 1982 55 1869. N. G. Rondan M. N. Paddon-Row P. Caramella J. Mareda P. H. Mueller and K. N. Houk J. Am. Chem.SOC.,1982,104,4974.