5 Aliphatic and Alicyclic Chemistry By P. QUAYLE Department of Chemistry University of Manchester Manchester M 13 9PL UK 1 Introduction The year started off in contemplative mood. Berson’s narrative lo ‘Discoveries missed discoveries made’ provides an interesting insight into how reactions are discovered lost and sometimes rediscovered under different names. Equally thought provoking were two articles by Eschenmoser one concerned with the origins of pre-biological natural products,2 and an account of the synthetic efforts directed towards the synthesis of homo-DNA oligonucleotides. As noted previ~usly,~ the current resurgence in interest in the chemistry of molecules of ‘theoretical interest’ (or non-natural products) has been manifested in the number of reviews appearing in this area.Interest in the chemistry of C, (Buckminsterfullerene) continues ~nabated.~ Related areas of chemistry have received exhaustive coverage and include an introduction to ‘Molecular Lego’,6 overviews of supermolecular chemistry,’ cycloalkadiyne chemistry,8 polymeric carbon allotrope^,^ ‘radialenes’,’’ oxocarbons,’ ’cyclobutanes,’ 2a cubanes,’ 2b and dendritic macromolecules.’ Numer-ous reviews and appraisals of current synthetic methodology have appeared. A most interesting c~mpilation’~ entitled ‘New Synthetic Methods’ provides a useful forum for emerging synthetic methodology. In a similar vein a collection of papers’ concerning (a) J.A. Berson Tetrahedron 1992 48 3; (b) For a personal account on how to invent a reaction see D.H.R.Barton and D. Doller Acc. Chem. Res. 1992 25 504. A. Eschenrnoser and E. Loewenthal Chem. SOC.Rev. 1992 21 1. A. Eschenrnoser and M. Dobler Helu. Chim. Acta. 1992 75 218. P. Quayle Ann. Rep. Sect. B 1991 88 103. H. W. Kroto Angew. Chem. Int. Ed. Engl. 1992,31,11;F. W. McLafferty (Ed.) Acc. Chem. Res. 1992,25 98. J. P. Mathias and J. F. Stoddart Chem. Soc. Rev. 1992 21 215. ’ C. See1 and F. Vogtle Angew. Chem. Int. Ed. Engl. 1992,31 528; E. Constable Tetrahedron 1992,48 10013. R. Gleiter Angew. Chem. Int. Ed. Engl. 1992,31 1;K. C. Nicolaou and A. L. Smith,Acc. Chem. Res. 1992 25 497. F. Diederich and Y. Rubin Angew. Chem. Int. Ed. Engl. 1992,31 1101. lo H. Hopf and G. Maas Angew. Chem. Int. Ed. Engl. 1992 31 931.P. Seitze and P. Imming Chem. Reu. 1992 92 1227. l2 (a)T. Tada and P. Garratt Chem. Rev. 1992,92 1685; (b)P. E. Eaton Angew. Chem. Int. Ed. Engl. 1992 31 1421. l3 G. R. Newkome C. N. Moorfield and G. R. Baker Aldrichimica Acta 1992 25 33. l4 S. E. Denmark (guest editor) Tetrahedron 1992 48 1959. I5 M.T. Reetz (guest editor) Tetrahedron 1992 48 5557. 107 108 P. Quayle the use of titanium reagents in organic synthesis provides much useful information. Cascade reactions,I6 enantioselective Rh” catalysed reactions,’ desymmeterization of meso-epoxides,’ transition metal catalysed reactions of organozinc reagents ’ fluorinated organometallics,20 asymmetric carbonyl reductions,21 chromium(11) re- agents,22 palladium catalysed reactions of organometallic~,~~ asymmetric-ene reac- tion~,~~ rhodium catalysed asymmetric hydrogenation^,^^ intramolecular carbenoid reactions in organic synthesis,26 asymmetric Michael reaction^,^ and asymmetric dihydroxylation reactions2 have been reviewed.A critical discussion of palladium- catalysed allylic substitution reactions29 has appeared as has an update on the anomeric effect.30 It is fitting some twenty-five years after the promulgation3’ of the Wood- ward-Hoffmann rules that a reappraisal of pericyclic reactions be published.32 Two comprehensive reviews on stereocontrolled organic synthesis have a~peared;~ the use of enzymes in this particular endeavour continues to expand.34 Of particular note are the use in multi-step synthesis of highly functionalized but readily available homochiral substrates such as cyclohexa-3,5-diene- 1,2-diok3’ Exploitation of sulfox- ides in asymmetric synthesis continues to produce much new synthetic meth~dology.~~ Similarly target-orientated synthesis by necessity generates new synthetic methodol- ogy as demonstrated by the variety of routes now available for the synthesis of forskolin and its analogues37 and C-glyco~ides.~~ The quest for carbocyclic nucleosides has generated much new chemistry,39 as has the search for reliable methods for the preparation of g-40 and ‘unusual’41 amino acids.Sugars remain popular as chiral auxiliarie~.~’ Overviews of contemporary organic synthesis and metal-assisted organic synthesis are to be found in articles edited by Richer43” and van K~ten~~~ respectively.l6 H. M.R. Hoffmann Angew. Chem. Int. Ed. Enyl. 1992 31 1332. l7 H. Brunner Angew. Chem. Int. Ed. Engl. 1992 31 1183. l8 (a) I. Patterson and D. J. Berrisford Angew. Chem. Int. Ed. Engl. 1992 31 1178; (b)W. A. Nugent J. Am. Chem. Soc. 1992 114 2768. l9 E. Erdik Tetrahedron 1992 48 9577. ’O D. J. Burton and Z.-Y. Yang Tetrahedron 1992 48 189. ” V. K. Singh Synthesis 1992 605; S. Wallbaum and J. Martens Tetrahedron Asymmetry 1992 3 1475. 22 P. Cintas Synthesis 1992 248. 23 T. N. Mitchell Synthesis 1992 803. 24 E. Mikami M. Tereda S. Narisawa and T. Nakai SYNLETT 1992 255. 25 K. Inoguchi S. Sakarabu and K. Achiwa SYNLETT 1992 169. 26 A. Padwa and K. E. Krumpe Tetrahedron 1992 48 5385. ” J. d’Angelo D. Desmaele F.Dumas and A. Guingent Tetrahedron Asjwmetry 1992 3 459. ” B.B. Lohray Tetrahedron Asymmetry 1992 3 1317. 29 C. G. Frost J. Howarth and J. M. J. Williams Tetrahedron Asymmetry 1992 3 1089. 30 E. Juarista and G. Cueras Tetrahedron 1992 48 5019. 31 R. B. Woodward Chemical Society Special Publn. 1967 21 217. 32 K.N. Houk Y. Li J.D. Evanseck Anyew. Chem. Int. Ed. Engl. 1992 31 681. 33 J. A. Gladysz and J. Michl (eds.) Chem. Rev. 1992,92,741; D. J. Ager and M. B. East Tetrahedron 1992 48 2803. 34 V. S. Parmar (ed.) Pure and Applied Chem. 1992 64 1055. 35 H. A. Carless Tetrahedron Asymmetry 1992 3 795. 36 A. J. Walker Tetrahedron Asymmetry 1992 3 961. 37 M. I. Colombo J. Zinczuk and E.A. Ruveda Tetrahedron 1992 48 963. 38 M. H. D. Postena Tetrahedron 1992 48 8545.39 A.D. Borthwick and K. Biggadike Tetrahedron 1992 48 571. 40 R. M. Williams Aldrich Chim. Acta 1992 25 11. 41 Y. Ohfume Acc. Chem. Res. 1992 25. 360. 42 H.-U. Reissig Anyew. Chem. Int. Ed. Enyl. 1992 32 288. 43 (a) J.-C. Richer Pure Appl. Chem. 1992 64 1809; (6) G. van Koten Pure Appl. Chem. 1992 64 315. Aliphatic and Alicyclic Chemistry 109 Overman has reviewed the concept of charge in organic synthesis.44 Finally in a most revealing article Collum dispels some of the myths associated with the use of TMEDA in fundamentally important processes such as metalation reaction^.^' 2 Aliphatic Chemistry The synthesis and reactivity of alkynyl- and allenyl-(pheny1)iodonium compounds46 and vinyl-pho~phonates~~ have been reviewed.A much-needed compilation of copper-mediated coupling reactions has appeared.48 Once again palladium-mediated ‘Heck’ and ‘Stille’ coupling reactions have been used extensively for the synthesis of functionalized olefins and arenes. In this context the use of novel C,-symmetric ligand systems for asymmetric alkylations has enjoyed a major breakthrough this year.490 Heck reaction of aryl halides and 4H-1,3-dioxin provides ready access to functionalized cinnamaldehydes (Scheme 1). In addition Reagents i Pd(OAc), P(Ph,), Ag,CO, DMF 60°C; ii H30’ (1 1 Reagents i Ag,CO, DMF Pd(OAc), (R)-BINAP; ii H,-Pd/C; iii H,O+ Scheme 1 reaction of 4H- 1,3-dioxin with iodobenzene in the presence of Pd(OAc),-(R)-BINAP using Ag,CO, as base afforded the product (1) in 62% yield with 43% e.e.49b Stille coupling (Scheme 2) of the bis-stannane (2) provides rapid access to polyenes of defined Me3Sn SnMe3 1 Reagents i Pdo Scheme 2 44 L.E. Overman Acc. Chem. Res. 1992 25 352. 45 D. B. Collum Acc. Chem. Res. 1992 25 448. 46 P. J. Stang Angew. Chem. Int. Ed. Engi. 1992 31 274. 47 T. Minami and J. Motoyoshiya Synthesis 1992 332. 48 B.H. Lipshutz and S. Sengupta Org. React. 1992 41 135. 49 (a)B. M. Trost D. L. Van Vranken and C. Bingel J. Am. Chem.Soc. 1992,114,9327;F. Ozawa. A. Kubo and T. Hayashi Tetrahedron Lett. 1992,33,1485;U. Leutenegger G. Umbricht C. F. Matt and A. Pfaltz Tetrahedron 1992,48,2143; (b)T.Sakamoto Y. Kondo. and H. Yamanaka Tetrahedron Lett. 1992,33 6845. 110 P.Quayle stereochemistry ." Moriarty' has described a versatile coupling reaction between alkenyl-iodonium salts and a variety of organotin substrates Scheme 3. Vinyl-zinc R' = vinyl alyl ally1 53-8096 Reagents i Pd(CH,CN),CI (cat.) Scheme 3 reagentss2 in many cases prove to be superior to the corresponding stannanes in Stille reactions Scheme 4. Vinyl and aryl triflates are often used in palladium catalysed 0 Bzov -Bzov 70% BzO BzO Reagents i CF,y ZnC1; ii Pd(PPh3) (cat.) Scheme 4 coupling reactions. corn in^'^ has demonstrated that the pyridine-derived triflating agents (3) are superior to N-phenyltriflimide which is commonly used in the preparation of these substrates Scheme 5. SoderquistS4 has amply demonstrated the 0 OTf Reagents i L-Selectride; ii (3) Scheme 5 50 A.Kiehl A. Eberhardt M. Adam V. Enkelmann and K. Mullen Angew. Chem. Int. Ed. Engl. 1992,31 1588. 51 R. M. Moriarty and W. R. Epa Tetrahedron Lett. 1992 33 4095. 52 B. Jiang and Y. Xu Tetrahedron Lett. 1992 33 511; A. Pimm P. Kocienski and S. D. A. Street SYNLETT 1992 886. 53 D. L. Comins and A. Dehghani Tetrahedron Lett. 1992 33 6299. 54 I Rivera J. C. Colberg and J. A. Soderquist Tetrahedron Lett. 1992 33 6919. Aliphatic and Alicyclic Chemistry viability of alkyl- and alkenyl-boranes in Suzuki coupling reactions as exemplified in his synthesis of (k)-ibuprofen Scheme 6. A fundamental ob~ervation~~ is that the Y Reagents i Bu'-9-BBN Pd' NaOH (94%); ii Tf,O/py (87%); iii B Pd' K,PO (68%) Q Scheme 6 rate of migration of alkyl groups from tin to palladium in such coupling reactions is enhanced via intramolecular coordination with a proximal amino residue.Also of note is Grigg'~~~ observation that the rate of tandem cyclization-carbonylation reactions can be enhanced by the addition of thallium acetate Scheme 7. ___) Ph 0 Ph 0 Reagents i CO (1 atm.) MeOH PdCI,(PPh,) (5mol.%) TlOAc Scheme 7 Homoenolates derived from gly~ine~~" have been coupled with a variety of electrophiles without the requirement for full protection of the amino moiety Scheme 8. A 'three component coupling' in a related sequence nicely demonstrates the synthetic utility of such processes Scheme 9.57b NHBoc E+* IZn-EYNHBOC C02Bn k02Bn Scheme 8 55 E.Vedejs A. R. Haight and W. 0.Moss J. Am. Chem. Soc. 1992 114,6556; J. M. Brown M. Pearson T. B. H. Jastrzebski and G. van Koten J. Chem. SOC. Chem. Commun. 1992 1440. 56 R. Grigg P. Kennewell and A. J. Teasdale Tetrahedron Lett. 1992 33 7789. 57 (a)R. F.W. Jackson N. W. Stuart A. Wood K. Jarnesw and M. J. Wythes J. Org. Chem.,1992.57,3397; (6)Y. Tamura K. Yasui H. Takanabe S. Tanaka and K. Fugami Angew. Chem..Int. Ed. Engl. 1992,31 645. 112 P. Quayfe Reagents i Pd(PPh3), CO HMPA 25 "C Scheme 9 Hydrosilylation-oxidation of mew olefins affords a rapid entry to the bicyclic alcohols in a near optically pure state Scheme lo.'* The synthesis of the vinyLS9 89% (95% e.e.) Reagents i HSiCI, [PdCI(n-C,H,)], (R)-MOP; ii KF KHCO, H,O Scheme 10 and allyl-stannanes6' continues to attract much attention.A number of novel transformations of these substrates has been documented this year including a synthesis of vinyl-silanes via a 1,2-migration-destannylationsequence6' (Scheme 11) SiMe3 Me3Si 0 ___c UR1 R'COCl Reagents i AlCI, -78"C CH,Cl Scheme 11 and a stereoselective stannyl-Pummerer reaction.62 Thomas63 has developed a remarkably efficient 1,5-asyrnmetric induction strategy for the synthesis of olefinic diols Scheme 12. LCHO -BnOL C H BnO + Bu3Sn-OBn OBIl 70% (> 96%d.e.) Reagents i SnCl, CH,CI, -78 "C Scheme 12 58 (a)Y.Uozumi S.-y. Lee and T. Hayashi Tetrahedron Lett. 1992,33,7185;(b)1. Matsuda J. Sakakibara H. Inoue and H. Nagashima Tetrahedron Lett.1992 33 5799. s9 J. P. Marino M. V. M. Emonds P. J. Stengel A. R. M. Oliveira F. Simonelli and J. T. B. Ferreira Tetrahedron Lett. 1992 33 49; D. M. Hodgson Tetrahedron Lett. 1992 33 5603. 6o Y. Tsuji and T. Kakehi J. Chem. SOC. Chem. Commun. 1992 1OOO. 61 K.-T. Kang J.C. Lee and J. S. U.. Tetrahedron Lett. 1992 33 4953. 62 R. L. Beddoes D. McLeod D. Moorcroft P. Quayle and Y. Zhao. Tetrahedron Lett. 1992 33 417. 63 A. H. McNeill and E. J. Thomas Tetrahedron Lett. 1992 33 1369. Aliphatic and Alicyclic Chemistry The use of N-lithioimidazole as a dummy ligand in cuprate reactions has been described.64 The preparation of functionalized vinylic lithiocyanocuprates should prove to be a useful de~elopment,~’ Scheme 13. Complementary approaches to I 0 0 Reagents i Cp,Zr(H)CI; ii Me,Cu(CN)Li,; iii BF,.OEt Scheme 13 functionalized copper66 and bimetallic reagents67 have been described providing ready access to a variety of reactive intermediates.The synthesis of polyenes continues as an area of much interest. Jeffery6* has described a facile route to skipped polyenes and Trod9 has developed a general synthesis of buta-l,3-dienes from readily available acetylenic ketones Scheme 14. Palladium7’ and ruthenium7 catalysed acetylene and olefin isomerization reactions provide rapid access to a variety of synthetically useful intermediates Scheme 15. The use of silanes as masked OH groups continues to gain acceptance in synthetic Scheme 16. A facile synthesis of the synthetically useful (E)-1-iodoalkenes from aldehydes has been de~eloped.’~ Hypervalent alkenyliodonium salts are emerging as useful synthetic intermediates.Stang74 has for example demonstrated that readily available bis-iodonium salts undergo displacement reactions under mild conditions to afford the vinyl-cyanides (4),Scheme 17. New methods have appeared for 64 B. H. Lipshutz P. Fatheree W. Hagen. and K. L. Stevens Terrahedron Lett. 1992 33 1041. 65 B. Lipshutz and R. Keil J. Am. Chem. Soc. 1992. 114 7919. 66 F.C. Tucci. A. Chieffi and J.V. Cornasseto Tetrahedron Lett. 1992 33. 5721; A.R. Sidduri and P. Knochel J. Am. Chem. SOC.,1992,114.7579; D. E. Stack and R. D. Rieke. Tetrahedron Lett. 1992,114 6575. 67 J. R. Waas A. R. Sidduri and P. Knochel Tetrahedron Lett..1992,33,3717 B. H. Lipshutz. R. Kell. and J.C. Barton Tetrahedron Lett. 1992 33 5860. 68 T. JetTery S. Gueugnot and G. Linstrumelle Tetrahedron Lett. 1992 33 5757. 69 B. M. Trost and U. Kazrnaier J. Am. Chem. Soc. 1992 114 7933. 70 B. M. Trost and C. Pedregal J. Am. Chem. SOC. 1992 114. 7292. 71 B. M. Trost and J. A. Flygare J. Am. Chem. SOC. 1992 114 5476. 72 J. Legeune and J. Y. Lallernand Tetrahedron Lett. 1992,33,2977;T. Harada S.Imanaka. Y. Ohyama Y. Matsuda and A. Oku Tetrahedron Lett. 1992 33 5807. 73 A. G. Martinez R. M. Alvarez S. M. Gonzalez L. R. Subramanian. and M. Conrad Tetrahedron Lett.. 1992,33 2043. 74 P. J. Stang A. Schwartz T. Blurne. and V.V. Zhdankin. Tetrahedron Lett.. 1992 33. 6759. 114 P. Quayle M%Si =--(Ref.68) 83% --0 --0 (Ref. 69) Reagents i CuI/DMF/Na,CO,/Bu:NCI; ii Ni(OAc),.4H2O EtOH NH,(CH,),NH, H,; iii Ph,P/Tol-uene/llO "C Scheme 14 OMe (Ref. 70) OMe (Ref. 71) 57% + -OH Reagents:i Pd,(dba), CHCI, TPP; ii Cp(Ph,P),RuCI (O.leq.) NH,PF (0.2eq.) 100 "C;iii RhCI, THF 100 "C Scheme 15 Aliphatic and Alicyclic Chemistry -*Lp i ii OH Reagents i Bu,SnH AIBN; ii H,O, NaHCO, MeOH Scheme 16 IPh CN (4) Reagents NaCN CuCN CH,CN Scheme 17 the synthesis of vinyl-sulfides7 and -~ilanes.~~ Davis77 has developed a 'super silylating' agent (Me,SiB(OTf),) for use in allylation reactions of aldehydes with allylsilanes. The Motherwell reaction78 has been reinvestigated resulting in the realization of a general carbonyl coupling reaction Scheme 18.A highly efficient Reagents Zn Scheme 18 functionalization of acetylenes leading to the generation of tetrasubstituted olefins has been described,79 Scheme 19. The first asymmetric selenoxide elimination" reaction R-CO,Et -RT:: I HO Reagents i TaCI, Zn; ii THF Py; iii R'CHO; iv I Scheme 19 7s N. A. Petasis and I. Akritopolou SYNLETT 1992 665. 76 S. Takano Y. Sugihara and K. Ogasawara SYNLETT 1992 668. l7 A. P. Davis and M. Jaspars Angew. Chem. Int. Ed. Engl. 1992 31 470. 78 C.A. M. Afonso W. B. Motherwell D. M. O'Shea and L. R. Roberts Tetrahedron Lett. 1992,33 3899. 79 Y. Katuoka J. Miyai M. Tezuka K. Takai and K. Utimoto J. Org. Chem. 1992 57 6796. 8o N. Komatsu Y. Nishibayashi T.Sugita and S. Urmura J. Chem. SOC..Chem. Commun. 1992 46. 116 P. Quayle has been reported affording allenes with modest levels of optical purity (2-21 % e.e.). Gree" has developed a highly efficient method for the preparation of allenes in a nearly optically pure state based upon the efficient transfer of chirality from metal to 'ligand' in optically pure (irontricarbony1)diene complexes (Scheme 20). A facile synthesis of Et I (> 95% d.s.) R (major) Reagents 1 ClC(O)OPh Py; ii (EtCuBr)MgBr; iii CAN/MeOH Scheme 20 internal acetylenes from readily available 1,1-dibromoallene should prove to be of some synthetic utility.82 The use of sulfoxides as chiral auxiliaries continues to be an area ofintense Full details concerning the preparation of diastereomerically pure sugar-derived sulfoxides have appeared.84 Caution must be exercised when the Anderson procedure is adopted for the preparation of optically enriched sulfoxides; in one case at least when using a sterically hindered alkyl-lithium reagent retention at sulfur rather than inversion has been observed.85 Phenylsulfonyl- 1,3-86 and 1,4-dieness7 are an interesting class of polyfunctionalized dienes.Recent studies by Backvall have further extended their synthetic utility Scheme 21. The sulfone group continues to find use both as an activating and stereocontrolling element.88 2 dR1 j-iii R\ R\ \ Reagents i R'CH,NO, DBU; ii KMnO,; iii Bu'OK THF Reagents i 0, PhSH; ii Oxone; iii PhSCI Et,N; iv Et,N; v H,O, HOAc Scheme 21 K.Nunn P. Mosest R. Gree K. Pelem R.W. Saadfrank and H.G. von Schering Angew. Chem. Int. Ed. Engl. 1992 31 224. 82 M. Kunishima K. Hioki T. Ohara and S. Tani J. Chern. SOC. Chem. Commun. 1992 219. 83 M. Casey I. Mukhurgee and H. Trabsa Tetrahedron Lett. 1992 33 127; G. Solladie N. Maugein I. Morreno A. Almario M. Marino and 5. L. Garcia-Ruano Tetrahedron Lett. 1992,33,4561;D. Barros M. Carmen Carreno J. L. Garcia-Ruano and M. C. Maestro Tetrahedron Lett. 1992 33 2733. 84 1. Fernandez N. Khiar J. M. Llera and F. Alcudia J. Org. Chem. 1992 57 6789. R5 J. Draowicz B. Budzinski and M. Mikolajczyk J. Chem. SOC..Chem. Commun. 1992 1500. J.-E. Backvall A.M. Ericsson N.A. Plobeck and S. K. Juntunen Tetrahedron Lett. 1992 33 131. *' Z. Ni X. Wang A. Rodriguez and A.Padwa Tetrahedron Lett. 1992 33 7303. 88 H.-J. Gais and G. Hellman J. Am. Chem. SOC.,1992,114,4439;C. M. Rodriguez M. A. Ramirez and V. S. Martin Tetrahedron Lett. 1992 33 3039. Aliphatic and Alicyclic Chemistry The diastereoselective synthesis of 2,3-epo~y-sulfoxides,~~ -silanesgO and -phos- phines’l has been reported. NugentI8’ has developed a chiral Lewis acid catalyst which enables the facile desymmeterization of meso-epoxides Scheme 22. Asymmetric 78% (88% e.e.) Reagents 1 [(Zr(OBu‘),) 31-TMSN3. 0 C N t)3 Scheme 22 dihydroxylation of olefins continues to be a focus of much methodological attenti~n.’~ A practical demonstration of this powerful process is outlined in a three-step synthesis of (-)-or ( +)-muricatacin Scheme 23.93 (Camphory1)sulfonyl oxaziridines are versatile epoxidizing agents and the publication of a method suitable for their large H’M~B~-92% HO C12H25 0 HO‘ a (+)-Muricatacin Reagents i.CH3(0Et), EtC0,H (cat.) A; ii AD-mix-x Scheme 23 89 C. M. Rayner and A. D. Westwell Tetruhedron Lett.. 1992,33. 2409; C. M. Rayner. M. S. Sin and A. D. Westwell Tetrahedron Lett. 1992 33. 7237. 90 P. Mohr Tetrahedron Lett. 1992 33 2455. 91 J. Clayden E. W. Collington and S. Warren Tetrahedron Lett. 1992 33 7043. 92 K.-S. Jeong P. Sjo and K. B. Sharpless Tetrahedron Lett. 1992. 33 3833; G. A. Crispino and K. B. Sharpless Tetrahedron Lett. 1992 33 4273; J. A. Turpin and L. 0.Weigel Tetruhrdron Lett.. 1991. 33 6563; L. Wang and K. B. Sharpless J.Am. Chem. Soc. 1992 114 7568; D. Xu G.A. Cripino and K. B. Sharpless J. Am. Chem. Soc. 1992. 114,7570; K. Fuji K. Tanaka and H. Miyarnoto. Tetruhedron Lett. 1992,33 402 1. 93 Z.-M.Wang X.-L. Zhang. K. B. Sharpless S. C. Sinha A. Sinha-Bagchi and E. Keinan. Trtruhedrnn Lrtt.. 1992. 33 6407. 118 P. Quayle scale preparation is most welcome.94 Ley95 has developed a new protecting group strategy for use in carbohydrate chemistry in which selective protection of diequatorial vicinal diols with the diene (5) is observed. Selective removal of the protecting group can be achieved without the disruption of other acid sensitive functionality Scheme 24. Clearly this represents a major methodological advance. Reagents i CSA CHCl, A Scheme 24 The introduction of amino groups into highly functionalized molecules is sometimes difficult to achieve using standard polar functional group manipulations.In a recurrent theme but with a novel twist Barton96 has developed a radical amination reaction sequence in which a carbon-centred radical prepared by one of several routes is efficiently trapped (ca. 100%)with a diazirene to afford upon work-up high yields of the requisite primary amine Scheme 25. The asymmetric synthesis of amines has been i-iii I Reagents i F3cx[ ; ,hv 95%; ii B(OH), EtOH H,O 87%; iii Ac,O Py 90% Ph NS I Scheme 25 OAc 94 I. Mergelsberg D. Gala D. Scherer D. DiBenedetto and M. Tanner Tetrahedron Lett. 1992 33 161. 9s S.V. Ley R. Leslie P.D. Tiffin and M. Woods Tetrahedron Lett.1992 33 161. 96 D. H. R. Barton J. Cs. Jaszberenyi and E.A. Theodorakis J. Am. Chem. Sac. 1992 114 5904. Aliphatic and Alicyclic Chemistry achieved uia the diastereoselective conjugate addition reactions of amide anions to en~lates,~' and by the dia- by catalytic asymmetric hydrogenation of imine~,~~ stereoselective addition of carbon nucleophiles to oximes and related corn pound^.^^ Oppolzer has reported two complementary routes to the asymmetric synthesis of p-amino alcohols either uia reaction of an achiral zinc enolate with homochiral or-chloronitroso reagents'"" or by reaction of a homochiral enolate with an achiral aminating agent.*'Ob Both routes proceed with excellent levels of induction (~96% e.e.). Hoppe'" has shown that carbamates of B-aminoalcohols undergo highly enantioselective deprotonation-alkylation reactions in the presence of sparteine Scheme 26.Clearly methodological advances in this area rely upon the identification Reagents i Bu"Li-sparteine(3 eq.) Et,O -78°C; ii E' Scheme 26 of other complexing agents which will ensure that this sequence has greater generality. The asymmetric synthesis of alcohols has taken on a new dimension since the development of other methodology (e.g.diastereoselective allylic alcohol epoxidation reactions) which use alcohols as starting materials. In recent years a most significant advance appears to be the use of homochiral oxazaborolidines for the asymmetric reduction of ketones. Again this year this method has gained prominence resulting in a wealth'02u of examples as exemplified in Scheme 27.The structure of the catalyst employed in these reductions has been determined by X-ray crystallography' OZb enabling the definition of a mechanistic model for the reduction sequence. A variety of 97 Y. Yamamoto N. Asao and T. Uyehara J. Am. Chem. Sue. 1992 114 5427. 98 C. A. Willoughby and S. L. Buchwald J. Am. Chem. Sue. 1992,114,7562;M. J. Burk and'J. E. Feaster J. Am. Chem. Soc. 1992,114,6266;see also D. R. Williams and M. H. Osterhout J. Am. Chem. Soc. 1992 114 8750. 99 K. Higashiyama H. Inoue and H. Takagashi Tetrahedron Lett. 1992,33,235:K. Soai T. Hatouaka and T. Miyazawa J. Chem. Soc.. Chem. Commun. 1992 1097. loo (a)W. Oppolzer 0.Tamura G. Sundarababu and M. Signer J.Am. Chem. Sue. 1992 114,5900; (b)W. Oppolzer 0.Tamura and J. Deerburg Helo. Chim. Acta 1992 75 1965. lo' J. Schwerdtfeger and D. Hoppe Angew. Chem. Int. Ed. Engl. 1992 31 1505; For a mini-review see P. Knochel Angew. Chem. Int. Ed. Engl. 1992 31 1459. lo* (a)E. J. Corey K. Y. Yi and P. T. Matsuda Tetrahedron Lett.. 1992,33,2319;E. J. Corey J. 0.Link and R. B. Bakshi Tetrahedron Lett. 1992,33,7107; E. J. Corey and K. A. Cimprich Tetrahedron Lett. 1992 33,4099; E. J. Corey and J.O. Link Tetrahedron Lett. 1992,33,4141; E. J. Corey and J. 0.Link J. Am. Chem. Soc. 1992 1-14 1906; (b)E. J. Corey M. Azimioara and S. Sarshar Tetrahedron Lett. 1992 33 3429. 120 P. Quuyle i ii 92%e.e. squalene epoxide H Ph Ph eo Reagents i ; o>BH ,88% (92% e.e.); ii Pr'ONa Pr'OH 3h A 91% (92% e.e.) \.Bu' Scheme 27 novel reducing agents have been reported this year some of which [(6) to (S)] appear to have some synthetic ~tility.'~~-~~~ OMe details concerning the use of the modified Noyori asymmetric hydrogenation system have appeared together with a representative synthetic application Scheme 28. The nucleophilic addition of C-centred anions to a carbonyl group is a fundamental synthetic operation. Reactions of aldehydes possessing an a-stereogenic centre with Grignard reagents affords the 'Cram' product usually with modest levels of 1,2-induction. However by merely changing the counter-ion associated with the lo3 R. Rawson and A.I. Meyers J. Chem. SOC.,Chem. Commun. 1992 494. lo4 N. Srivatava A.Mital and A. Kuma J. Chem. SOC..Chem. Commun. 1992 493. J.-M. Brunel 0.Pardigan B. Faure and G. Buono J. Chem. Soc. Chem. Commun. 1992 281 lo6 D.F. Taber P. B. Deker and L. J. Silverberg J. Org. Chern. 1992 57 5990. Aliphatic and Alicyclic Chemistry Indolizidine 223 AB Reagents i [(R)-Ru(BINAP)CI,], NEt, 0.1 mol. YOHCI/MeOH. 5Opsi H, 90% (98% ex.) Scheme 28 Grignard reagent high levels of induction may be observed,"' Scheme 29. The direct conversion of vinyl-boranes into vinyl-zinc reagents has been achieved. These nucleophilic organometallic reagents generated in situ undergo enantioselective alkylation reactions with aldehydes in the presence of a suitable homochiral catalyst. lo* A variety of chirally modified organometallics have been observed to undergo similar reactions with aldehydes with high levels of asymmetric induction.Io9 Mechanistic evidence has been presented which implies the existence of chelated intermediates in the nucleophilic addition of organometallics to a-alkoxy ketones' lo (i.e. validation of the Cram 'cyclic model' of induction some 30 years after its OH ?H PhyCHO N~-~ F'h* + P h p CHO "Cram" Nu-= MeMgCl 70 30 Nu-= MeMg 94 6 Scheme 29 lo' M.T. Reetz N. Harmat and R. Marchwald Angew. Chem. Int. Ed. Enyl. 1992 31 342. lo' W. Oppolzer and R.N. Radinov Helv. Chim. Actu 1992 75 170. lo9 A. Hafner R.O. Duthbaler R. Marti G. Rihs P. Rothe-streit. and F. Schwarzenbach J. Am. Chem. Soc. 1992,114,2321; B. Weber and D. Seebach Angew. Chem. In[.Ed. Enyl. 1992,31,85; D. Seebach D. A. Plattner A. K. Beck Y. M. Wang and D. Hunziker. Helv. Chim. Actu 1992 75 2171. 'lo X. Chen E.R. Hortelano. E. E. Eliel and S.V. Frye J. Am. Chem. Soc. 1992 114 1778. 122 P. Quayle introduction). In other systems the presence of a polar functional group may effect 'coordinated delivery' of a nucleophilic species to a carbonyl group,' '' Scheme 30. Clearly our understanding of such reactions remains to some extent empirical. SYn Anti 6 1 Reagents i ZnC1 Et,O -78 "C Scheme 30 The aldol reaction continues to be investigated as a vehicle for the asymmetric synthesis of P-hydroxy propionates and related systems."* A major theme this year has been concerned with the development of enantioselective catalyst systems for the Mukaiyama crossed-aldol reaction.' l3 In a rather interesting development Davis' l4 has shown that intramolecular hydrosilylation of these P-hydroxy esters followed by intermolecular allylation afforded the corresponding diols with useful levels of asymmetric induction (trans:cis = 20 :l) Scheme 31.The chemistry of 'zirconecene' continues to generate much interest. For example reaction of zirconecene with allylic or propargylic ether derivatives generates the corresponding allylic or allenic organometallics respectively which then undergo clean alkylation reactions with a variety of aldehydes,' ' Scheme 32. Unexpected-'" R. S. Coleman and A. Carpenter Tetrahedron Lett. 1992 33 1697. '" E. J. Corey D.-H. Lee and S. Choi Tetrahedron Lett.1992 33 6735 I. Paterson and R. D. Tillyer Tetrahedron Lett. 1992 33 4233; W. Oppolzer and C. Starkemann Tetrahedron Lett. 1992 33 2439; A. G. Myers S. E. Kephart and H. Chen J. Am. Chem. SOC.,1992,114,7923;A. K. Ghosh T.T. Duong and S. P. McKee J. Chem. SOC.. Chem. Commun. 1992 1673; see P.G. Willard Q.-Y. Liu and L. Lochmann J. Am. Chem. SOC.,1992 114 348 for X-ray structure of a LHMDS-ester complex. l3 e.g. W. Odenkirk J. Whelan and B. Bosnich Tetrahedron Lett. 1992,33,5729; S.4. Kiyooka Y. Kaneko and K.4. Kume Tetrahedron Lett. 1992,33,4927;E. Parmee Y. Hong 0.Tempkin and S. Masamune Tetrahedron Lett. 1992,33 1729; E. J. Corey C. L. Cywin and T. D. Roper Tetrahedron Lett. 1992,33 6907; R. C. Corcorran and J. Ma J. Am. Chem. SOC.,1992,114,4536; V. Sharma M.Sirnard and J. D. Wuest J. Am. Chem. SOC.,1992 114 7931. A.P. Davis and S.C. Hegarty J. Am. Chem. SOC. 1992 114 2745; For an example of a catalytic asymmetric ketone hydrosilylation see M.J. Burk and J. E. Feaster J. Am. Chem. SOC. 1992 114 2099. 'I5 H. Ito T. Nakamura T. Taguchi and Y. Hanzawa Tetrahedron Lett. 1992 33 3769. Aliphatic and Alicyclic Chemistry (major) Reagents i F- 0°C; ii SnCI Scheme 31 CP /cP OTBDMS ?h-( -OTBDMS 73% ii I OH OH > 98 2 Reagents i ‘Cp,Zr’; ii C,H ,CHO BF,.OEt, 50“ Scheme 32 ly,’ a-allenyl ketones undergo kinetically controlled deprotonation to afford the cumulenolates (9),which may be trapped with a variety of electrophiles producing the functionalized allenes (lo) Scheme 33.0 0 !r,H3 - R A,’ 3544% LRlR Reagents i LHMDS or LDA THF -78°C Scheme 33 ’I6 N.A. Petasis and K.A. Teets J. Am. Chem. Soc. 1992 114 10328. 124 P. Quayle The use of radical processes in organic synthesis continues to generate much interest especially for the construction of five-membered rings and polycyclic ring systems. ' ' 7a Latterly attention has also focused upon the control of relative stereochemistry in radical-mediated C-C bond formation and related reactions.' '7b Toru' * has described a three-component coupling reaction more usually associated with cuprate chemistry for the vicinal dialkylation of unsaturated ketones Scheme 34. SiMe3 70% Scheme 34 The Cieplak effect"' has come under much scrutiny and a unified model for the conjugate addition reactions of cuprates to y-alkoxyenoates has been proposed.' 2o 3 Alicyclic Chemistry Introduction.-The Birch reduction' 2' of aromatic compounds and the divinylcyclo- propane-cyclopentadiene rearrangement' 22 have been reviewed.An in-depth survey of the intramolecular S,' reaction contains much useful information relating to ring forming processes.'23 Cyc1opropanes.-Olah' 24 has described the preparation of the 1-ferrocenyl- 1-cyclo-propyl cation the first long-lived cyclopropyl cation. Doyle and Mul1e1-I~~ have 'I' (a) For an overview see W. B. Motherwell and D. Crich in 'Free-Radical Chain Reactions in Organic Synthesis'. Academic Press London 1992; (h)W. Smadja M. Zahouily and M. Malacria Tetrahedron Lett.1992,33,5511;A. Naim G. Mills and P. B. Shelvin Tetrahedron Lett. 1992,33,6779; D. P. Curran and G. Thoma J. Am. Chem. SOC.,1992,114,4436;W. Damrn B. Giese J. Hartung T. Hasskerl K. N. Houk 0.Hutler and H. Zipse J. Am. Chem.SOC.,1992,114,4067; D. P. Curran and B. Yoo Tetrahedron Lett. 1992 33 6931; N. A. Porter I. J. Rosenstein R.A. Breyer J. D. Bruhnke W.-X. Wu and A.T. McPhail J. Am. Chem. SOC. 1992 114 7664; J.G. Stack D.P. Curran S. V. Geib J. Rebek and P. Ballester J. Am. Chem. Soc. 1992 114 7007; Y.-D. Wu and K.N. Houk J. Am. Chem. Soc. 1992 114 1656; P. Erdrnan J. Schafer R. Springer H.-G. Zeitz and B. Giese Helu. Chim. Acta 1992 75 638; B. Giese W. Damm M. Roth and M. Zehnder SYNLETT 1992,441;see also D. P. Curran T. L. Fevig and M. J. Totleben SYNLETT 1992 943 for an appraisal of samarium-promoted Barbier reactions.T. Toru Y. Watanabe M. Tsuaka R. K. Gautam K. Tazawa M. Bakouetila T. Yoneda and Y. Ueno Tetrahedron Lett. 1992 33 4037. J. M. Coxon and D. Q. McDonald Tetrahedron Lett. 1992,33,651;M. N. Paddon-Row Y.-D. Wu and K. N. Houk J. Am. Chem. Soc. 1992,114 10638; A. Mukherjee E. M.M. Venter W. J. le Noble W. A. Watson and R. P. Kashap Tetrahedron Lett. 1992,33 3837; V. Vinkovic K. Mlinaric-Majerski and Z. Marinic Tetrahedron Lett. 1992,33 7441 ;see also C. Beeson N. Pham and T. A. Dix Tetrahedron Lett. 1992 33 2955; G. Mehta F. A. Khan and K. A. Laskshrni Tetrahedron Lett. 1992 33 7977. Y. Yamamoto Y. Chounan S. Nishii T. Ibuka and H. Kitahara J. Am. Chem. Soc. 1992 114 7652. P. W. Rabideau and Z.Marcinow Ory. React. 1992 42 Ch. 3. 122 T. Hudlicky R. Fan J. W. Reed and K.G. Gadamastti Org. React. 1992 41. Ch. 1. L. A. Paquette and C. J. M. Stirling Tetrahedron 1992 48 7383. G. K. S. Prakash H. Buchholz V. P. Reddy A. de Meijere and G. A. Olah J. Am. Chem. Soc. 1992,114 1097. M.N. Protopopova M. P. Doyle P. Muller and D. Ene J. Am. Chem. Soc. 1992 114 2755. Aliphatic and Alicyclic Chemistry I25 reported that the intermolecular cyclopropenation of alkynes with diazo esters catalysed by Rh,[(SR)-MEPY] can proceed with high levels of induction (98% e.e.). Padwa and Doyle’26 have studied the effect of ligand upon the chemoselectivity of catalytic carbenoid reactions. These workers concluded that cyclopropanation of a C-C double bond can be achieved with high levels of chemoselectivity when Rh,(cap) is employed as the catalyst rather than Rh,(OAc) or Rh,(pfb), Scheme 35.catalyst (A) (B) Rh*(OAc)? 52 48 Rh,@fb) 100 0 Rh2(cap) 0 100 Scheme 35 Martin’ 27 has developed an intramolecular cyclopropanation strategy for the preparation of oxabicyclo[4.1 .O]heptanes (1 1 ),which are valuable synthetic intermedi- ates. Hence reaction of the diazo-olefin (12) with Rh,[(SS)-MEPY] afforded the cyclopropanes (11) in good chemical yields (55-80%) and in up to 92% optical purity Scheme 36. KobayashiI2* has reported the first catalytic enantioselective Sim- mons-Smith cyclopropanation reactions of allylic alcohols in which a Reagents i Rh2[(SS)-MEPY],. CH2C12 Scheme 36 C2-symmetric bis-sulfonamide (13) was employed as the chiral auxiliary.To date chemical yields for this sequence are good but the optical purities are variable (13-82% e.e.) Scheme 37. M~therwell’~~ has shown that zinc carbenoids (14) may be generated from aldehydes using Zn/ClSi( Me),CH,.CH .Si(Me),Cl and trapped in situ 126 A. Padwa. D. J. Austin S. F. Hornbuckle. M. A. Semones. M. P. Doyle. and M. N. Protopopava J. Am. Chem. Soc. 1992 114. 1874. 12’ S. F. Martin C. J. Oalmann. and S. Liras Trtruhrdrori Lerr.. 1992. 33 6727. IZxH. Takahashi M. Yoshioka. M. Ohno. and S. Kobayashi Tetruhcdron Lett.. 1992 33. 2575. W. R. Motherwell and L. R. Roberts J. Chrm. SOL...Chum. Commun. 1992 1582. 126 P.Quayle Ph OH iPh A O H / 100% (80% e.e.) NHSqR Reagents i Et,Zn (2eq.) CH,I (3.0eq.) "NHS4R (13) Scheme 37 with olefins to afford the corresponding cyclopropanes in good yields.Treatment of the readily available a-(a1koxy)methyliron compounds (15) with a Lewis acid in the presence of an electron-rich olefin affords the cyclopropanes (16) in moderate to good yields'30 (44-68%) Scheme 38. De~xygenation'~'of the tertiary amide (17) with R I 1 P X Reagents i TMSOTf CH,CI, -78 "C Scheme 38 Sm/SmI generates the bicyclic species (18),in moderate overall yield. Presumably this sequence proceeds via the intermediacy of an a-amino carbene Scheme 39. Burgess'32 Reagents i SrnIJSrn THF reflux Scheme 39 I3O W. J. Seitz A. K. Saha D. Casper and M. Hossain Tetrahedron Lett.1992,33,7755;R. M. Vargas R. D. Theys and M. Mahum Hossain J. Am. Chem. SOC. 1992 114 777. 13' A. Ogawa N. Takarni M. Sekiguchi I. Ryu N. Karnbe and N. Sonada J. Am. Chem. SOC. 1992,114 8729. 13' K. Burgess and K.-K. Ho Tetrahedron Lett. 1992 33 5677. Aliphatic and Alicyclic Chemistry 127 has described an asymmetric synthesis of ornithine- and arginine-2,3-methanologues starting from the homochiral epoxy-tosylate (19) Scheme 40. Brinke~-'~~ has ri BOC-CJT~O-OXTI-O B Reagents i NaH C,H, 15-crown-5 25 "C Scheme 40 developed a facile method for the functionalization of bicyclo[n. 1 .O] systems which relies upon the activating effect of the cyclopropane ring on vicinal C-H bonds. Note that this particular C-H bond activation does not extend to the homologous bicyclo[n.2.0] system Scheme 41.81 19 Reagents i CHCI, NaOH TEBA Scheme 41 Cyc1obutanes.-Ikegami' 34 has demonstrated that by judicious choice of ligand Rh" catalysed C-H insertion reactions may be directed towards the formation of spirocyclobutanones rather than to the isomeric bicyclo[n.3.0] system Scheme 42. An asymmetric [2 +21-photocycloaddition reaction has been employed by Smith135 in the total synthesis of (-)-echinosporin. In the crucial reaction inter- molecular photocyloaddition of the enol ether (20) with cyclopent-2-enone afforded the (predicted) tetracyclic intermediate (21) as the major product in 50% isolated yield Scheme 43. An intramolecular [2 +21-cycloaddition strategy has been put to good effect by Crimmins' 36 in his total synthesis of (&)-bilobalide Scheme 44.Fleming 37 has used a silicon tether to control the regio- and stereochemical outcome of similar photocycloaddition reactions. Narasaka' 38 has developed a highly enantioselective (>80% e.e.) cyclobutane synthesis via a thermal cycloaddition reaction between electron-rich olefin and acrylamide derivatives catalysed by a homochiral titanium catalyst. Cycloaddition' 39 of the keteniminium salt (22) generated in situ 133 L. Xu W. B. Smith and U.H. Brinker J. Am. Chem. SOC. 1992 114 783. 134 S.4. Hashimoto N. Watanabe and S. Ikegami Tetrahedron Lett. 1992 33 2709. A. B. Smith G.A. Sulikowski M.M. Sulikowski and K. Fujimoto J. Am. Chem. SOC.. 1992 114 2567. M.T. Crimmins D. K. Jung and J.L. Gray J. Am. Chem. SOC.,1992 114 5445. S.A. Fleming and S.C. Ward Tetrahedron Lett. 1992 33 1013. 138 K. Narasaka Y. Hayashi H. Shimadzu and S. Niihata J. Am. Chem. SOC. 1992 114 8869. 139 C. Genicot and L. Ghosez Tetrahedron Lett. 1992 33 7357. 128 P. Quayle n O# C02Me 0 C02Me (A) (B) Reagents (i) Rhz(OAc)2 37 63 Rh2(02CCF3)4 56 44 ~~(HNAc)~ 14 86 Scheme 42 Scheme 43 Scheme 44 Aliphatic and Alicyclic Chemistry from the amide (23) with a variety of olefins affords cyclobutanones with moderate to excellent asymmetric induction (48-98% ex.) Scheme 45. 0 93% (93% e.e.) Reagents i Tf,O Base -10 'C CH,Cl,; ii H,O Scheme 45 The synthesis of C4.5.5.5lfenestrenesvia an intramolecular enone-alkyne photocyclo- addition reaction (a little-used variant) has been reported.140 Cyclobutanones serve as useful intermediates for the synthesis of y-butyrola~tones.'~~ The torquoselectivity observed in the electrocyclic conversion of cyclobutenes to their open-chain isomers has again come under in~estigation.'~' Eat~n'~~ has further investigated the nature of the cubyl cation. Della and Walt~n'~~ have generated cubyl radicals and studied their subsequent chemical functionalization. Cyc1opentanes.-A variety of organometallic approaches to cyclopentanes have been reported this year. Herndon 145 has discovered that cyclopropyl chromium carbene complex (24) unexpectedly underwent a metathesis-type reaction upon reaction with hepta-1,6-diyne to afford the phenol (25) in 51% isolated yield Scheme 46.A OMe (24) Scheme 46 molybdenum equivalent '46 of the Pauson-Khand reaction has been developed which appears to proceed in marginally higher yields than its cobalt counterpart. The Pauson-Khand 14' reaction itself has been utilized in the construction of polycyclic and 140 P. Gerber and R. Keese Tetrahedron Lett.. 1992 33. 3987 see also M. L. Graziano M. R. lesce F. Cermola and G. Cimminiello J. Chem. SOC..Perkin Trans. I 1992. 1269. 14' K. Tsushima and A. Murai Tetrahedron Lett. 1992 33 4345. 14' S. Niwayama and K. N. Houk Tetrahedron Lett. 1992,33,883; C. W. Jefford G. Bernardinelli. Y. Wang D.C. Spellmeyer A. Buda and K. N. Houk J. Am. Chem. SOC.. 1992 114. 1157. 143 P.E.Eaton and J. P. Zhou J. Am. Chem. SOC.,1992 114 3118. 144 E. W. Della N. J. Head P. Mallon and J. C. Walton. J. Am. Chem. Soc. 1992 114 10 730. 145 S.V. Tumer J. W. Herndon and L.A. McMullen J. Am. Chem. SOC.,1992 114 8394. C. Mukai M. Uchiyama and M. Hanaoka. J. Chem. Soc.,Chem. Commun. 1992 614. 14' M. E. Kraft I. L. Scott and R. H. Romero Tetrahedron Lett. 1992,33.3829; A. S. Gybin W. A. Smit R. Caple A.L. Veretenov A.S. Shashkov L.G. Vorontsova M.G. Kurella V.S. Chertkov A.A. Carapetyan A. Y. Kosnikov M. S. Alexanyan S. V. Lindeman,V. N. Panov A. V. Maleev Y. T. Strchkov. and S.M. Sharpe J. Am. Chem. Soc.. 1992. 114 5555. 14' 130 P. Quayle fused heterocyclic systems. Eat~n'~~ has reported the first catalytic iron-mediated [4+ 11 cyclopentenone synthesis Scheme 47.Fused bicyclic and spirocyclic cyclopen- ten one^'^^ are readily available by way of a Ni(CO) promoted carbonylative cycloaddition reaction of acetylenes with ally1 halides Scheme 48.Of note in this 7678% R1y?y: R' 0 Reagents i Fe(CO), 10 mol. YO,CO 25 "C Scheme 47 0 Reagents i Ni(CO), MeOH 25 "C Scheme 48 reaction sequence is the regiochemical control apparent in the incorporation of the acetylene into the product. Buchwald' 50a has demonstrated that cyclopentenones bearing reactive functionality may be prepared using Negishi-type ene-yne carbonyla- tion chemistry. Negishi'50b himself has utilized the same sequence in the preparation of ( + )-iridomyremycin (26) from the ene-yne (27). Vinyl rhodium carbenoids (28) undergo regioselective [3 + 21 annulation reac-tion~~ ' with electron-rich olefins to afford the functionalized cyclopentenes (29) in good overall yields.FSiMe3 14' B.E. Eaton B. Rollman and J.A. Kaduk J. Am. Chem. SOC. 1992 114 6245. L. Pages A. Llebaria F. Camps E. Molins,C. Miravitilles,and J. M. Moreto,J. Am.Chem.SOC.,1992,114 10449; F. Camps A. Llebaria J. M. Moreto and L. Pages Tetrahedron Lett. 1992 33 109. (a)R. B. Grossman and S. L. Buchwald J. Org. Chem. 1992,57 5804; (b)G. Agnel Z. Owczarczyk and E.4. Negishi Tetrahedron Lett. 1992 33 1543. H. M. L. Davies and B. Hu,Tetrahedron Lett. 1992 33 453. Aliphatic and Alicyclic Chemistry Suzuki’52 palladium-catalysed coupling of alkyl boranes (30)with the vinyl halides (31) has been applied in an intramolecular sense for the synthesis of carbocycles (32) possessing exocyclic alkene vinylidene groups of defined stereochemistry .A variety of palladium-catalysed cascade reactions’ 53 have been employed in the synthesis of cyclopentanes Scheme 49. Fu~hs’~~ has developed a “4 + 11’ strategy whereby sulfone dianions (33) are alkylated with o bis-electrophiles (34) to afford cyclopen- tenylsulfones (35) in a one-pot reaction. X OAc I (Ref. 153a) 0 +A(.& E+A E E / Me0 2-P EE (7 Br (Ref. 153b) E E Reagents i Pd(OAc), PPh, HCO,H CH,CN A; ii Pd(OAc), PPh, Ag,CO (2eq.) CH,CN 80°C Scheme 49 Herndon’ 55 has demonstrated that a variety of 5-hexenyltributylstannane deriva-tives undergo high yielding 5-em-cyclization upon reaction with the’modified ‘PhSe+’ reagent N-phenylselenophthalimide/tintetrachloride at -78 “C Scheme 50.Radical N. Miyayura M. Ishikawa and A. Suzuki Tetrahedron Lett. 1992 33 2571. (a)B. Burns R. Grigg V. Santhakumar V. Sridharan P. Stevenson and T. Warakua Tetrahedron 1992 48,7297; (b)F. E. Meyer J. Brandenburg P. J. Parsons and A. de Meijere J.Chem.Soc.. Chem. Commun. 1992 390. S. S. Magar and P. L. Fuchs Tetrahedron Lett. 1992 33 745. *’’J. W. Herndon and J. J. Harp Tetrahedron Lett. 1992 33 6243. 132 P. Quayle R Reagents i NSP-SnCI,. CH,Cl, -78 'C Scheme 50 processes' 56 have again been used extensively for the construction of cyclopentanes. A particularly useful development has been reported by Hanessian,' 56d who used trimethyltin radicals to initiate a cascade process and then removed the tin moiety oxidatively generating an acetal at the end of the sequence Scheme 51.Grigg' 57 has Reagents i Me,SnCl NaCNBH, AIBN Bu'OH A; ii MeOH CAN Scheme 51 shown that polycyclic systems can be rapidly constructed from simple acyclic precursors using a nitrone-based cascade process Scheme 52. Reagents i Hg(OAc),; ii A; iii I Scheme 52 Cyc1ohexanes.-The Diels-Alder reaction continues to be the premier method for the stereoselective construction of functionalized cyclohexane derivatives. Transition' 58 state structures for the JMDA reaction have been modelled using Allingers MM2 force field. Chou' 59 has evaluated the relative directing effects of 2,3-disubstituted buta- 1,3-dienes in the Diels-Alder reaction.A bewildering variety of dienes and dienophiles have again been utilized in the Diels-Alder reaction this year Figures l(a)and l(b). The development of Lewis acid catalysts such as (36) and (37)for use in the Diels-Alder 156 (a)J. S. Yadav K. T. K. Kumar and V. R. Gadgil Tetrahedron Lett. 1992,33,3687; (b)V.H. Rawal and S. Iwasa. Tetrahedron Lett.. 1992 33 4687; (c)J. M. Contelles P. R. Riiz B. Sanchez and M. L. Jimeno Tetrahedron Lett.. 1992 33. 5261; (d) S. Hanessian and R. Leger J. Am. Chem. SOC. 1992 114 3115. 151 R. Grigg M. Hadjisoteriou P. Kennewell J. Markandu and M. Thornton-Pett J. Chem. SOC.. Chem. Commun. 1992. 1308. 158 L. Raimondi F. K. Brown J. Gonzalez. and K.N.Houk J. Am. Chem. SOC.,1992 114 4796. 159 T.-S. Chou C.-Y. Chang. M.-C. Wu S.-H. Hung. H.-M. Liu and W.-Y. Yeh J. Chem. Soc. Chem. Cornmun. 1992 1643. Aliphatic and Alicyclic Chemistry 0 Ph Ph Bz0 0 (Ref. 160) (Ref. 161) (Ref. 162) R'THoyoY:e I / 0 OL '-_. (Ref. 163) (Ref. 164) (Ref. 165) (Ref. 166) n 4 0 B00 1 "I Ph (Ref. 167) (Ref. 168) (Ref. 169) NTs s^ KBR2 R*07? 0 (Ref. 170) (Ref. 171) (Ref. 172) (Ref. 173) Figure l(a) Ih0 D. Craig and J.C. Reader. Tetrahedron Lett.. 1992 33 4073. Y 161 M. Toyota. T. Seishi. M. Yokoyama K. Fukumoto and C. Kabuto Tetrahedron Lett. 1992 33 4581. 162 T. K. M. Shing and Y. Tang J. Chem. SOL... Chem. Commun. 1992 341. I63 B. Alcaide C. Biurru J. Plumet and E.Borredon. Tetrahedron 1992 48 9719. I64 A. Razaname P. Vogel and F. Claret Hek. Chim. Acta 1992 75 1087. 165 S.R. Desai V. K. Gore T. Mayelvaganan R. Padmakumar and S.V. Bhat. Tetrahedron 1992. 48 481. 166 G.H. Posner T.-C. Carry T. E. N. Anjeh and A. N. French J. Org. Chem. 1992 57 7012. I67 I. E. Mark0 and A. Chesney SYNLETT 1992 275. 168 S. Horne and R. Rodrigo J. Chem. Soc.. Chem. Commun. 1992 164. 169 K. C. Nicolaou C.-K. Hwang E. J. Sorenson and C. F. Clairborne J. Chem. Soc..Chem. Commun.. 1992 1117. 170 M.-H. Cheng G.-M. Yang J.-F. Chow G.-H. Lee and S.-M. Peng J. Chem. Soc.. Chem. Commun. 1992. 934. 171 K. Narasaka and 1. Yamamoto. Tetrahedron 1992. 48. 5743. 172 D. A. Singleton J. P. Martinez J. Watson and G. M.Nidip Tetrrihedron. 1992. 48. 5831. 173 P. Hamley G. Helmchen A. B. Holmes D. R. Marshall J. W. M. MacKinnan D. F. Smith and J. W. Ziller J. Chem. Soc.. Chem. Commun.. 1992 786. 134 P. Quayle (Ref. 174) (Ref. 175) Figure l(b) reaction have figured pr~rninently."~ An X-ray crystal of the Corey catalyst (38) has been obtained. In conjunction with NMR data the structure of one catalyst dienophile complex (39)has been formulated as shown in Figure 2. This model correctly predicts the absolute sense of induction observed in the Diels-Alder reactions of this dienophile-catalyst system. Fe ArS02/ N,~/o I Bun (36) (37) L J Figure 2 174 M. Chini P. Crotti F. Macchia M. Pineschi and L. A. Flippin Tetrahedron 1992,48 539. A.Defin A. Brouillard-Poichet and J. Streith Helv. Chim. Acta 1992 75 109. 176 E. J. Corey T.-P. Loh T. D. Roper M. D. Azimiora and M. C. Noe J. Am. Chem. SOC.,1992,114,8290; T.K. Hollis N.P. Robinson and B. Bosnich J. Am. Chem. SOC. 1992 114 5464; E.J. Corey and K. Ishihara Tetrahedron Lett. 1992 33 6807; S. Kobayashi I. Hachiya T. Takahori M. Araki and H. Ishitani Tetrahedron Lett. 1992,33,6815; W.Odenkirk A. L. Rheingold and B. Bosnich J. Am. Chem. SOC. 1992 114 6392; K. Maruoka S. Saito and H. Yamamoto J. Am. Chem. Soc. 1992 114 1089. '" E. J. Corey S. Sarshar and J. Bordner J. Am. Chem. SOC.,1992 114 7938. Aliphatic and Alicyclic Chemistry Other methods of synthesis reported this year include a manganese(III)-promoted oxidative free radical cyclization ''I3 of p-ketoimides (Scheme 53) double Michael Reagents i.Mn(OAc),.2H20 Cu(OAc),.H,O HOAc 25 "C Scheme 53 addition reactions,' 79 and a polyene cyclization sequence leading to ( & )-taxodione,' go Scheme 54. Tietze' '' utilized a tandem Sakurai carbonyl-ene sequence OMe I i -83% Reagents i BF3-CH3N02 25 "C Scheme 54 for the construction of steroidal-like tricyclic systems Scheme 55. 'Heck',' 82 'Trost',' 83 and radical' 84 cyclization reactions nicely compliment each other as SiMe Reagents i TMSOTf 1.1 eq. -78°C to -30°C Scheme 55 178 P.A. Zoretic X.Weng C. K. Biggers M. S. Biggers M. L. Caspar and D. G. Davis Tetrahedron Lett. 1992 33 2637. 179 H. Hagwara K.Kon-No and H. Uda J. Chem. SOC.,Chem. Commun. 1992 866.180 S.R.Harring and T. Livinghouse J. Chem. Soc.. Chem. Commun. 1992 502. 181 L. F. Tietze and M.Rischer Angew. Chem. fnt. Ed. Engl. 1992 31 1221. 182 J. L. Mascarenas A.M. Garcia L. Castedo and A. Mourino Tetrahedron Lett. 1992 33 4365. I63 B. M. Trost and J. Dumas J. Am. Chem. SOC.,1992 114 1924. 184 C. Chen and D. Crich Tetrahedron Lett. 1992 33 1945. 136 P. Quayle illustrated in Scheme 56 for the approaches developed to the synthesis of the A-ring of vitamin D metabolites. Ref. 184 U Scheme 56 Cycloheptanes and Cyc1ooctanes.-The chemistry of cyclooctanes has been re-viewed.*85 Smithlg6 has prepared the first trans-homotropone and studied its rearrangement chemistry. Dowdlg7 has developed a novel route to the synthesis of cycloheptenes/cyclooctenes based upon a radical cyclization-fragmentation stragegy Scheme 57.Crich’ 88 has developed a radical-based route to bicyclo[5.3.0]decan- 2-ones utilizing the intramolecular capture of acyl radicals which are generated from Reagents i Bu,SnH. AIBN 80°C; ii TMSI ZnI,; iii DBU Scheme 57 acylselenides. The intramolecular nitrile oxide cycloaddition reactions of sugar-derived nitrones have been extended by Dureau1tlg9 to the synthesis of poly- hydroxylated cycloheptane derivatives Scheme 58. The frenzied interest in taxane Is’ N. Pestasis and M. A. Patani Tetrahedron 1992 48 5755. J.L. Wood and A.B. Smith J. Am. Chem. SOL..,1992 114 10075. ‘” P. Dowd and W. Zhang J. Am. Chem. SOC.,1992 114. 10084; Tetrahedron Lett. 1992 33 3285.D. Batty and D. Crich Tetrahedron Lett. 1992 33 875. 189 0.Duclos A. Dureault and J. C. Depezay Tetrahedron Lett. 1992 33 1059. Aliphatic and Alicyclic Chemistry OBn OBn OBn HO OBn (major) Reagents i NaOCl (eq.).CH,CI, 20 C Scheme 58 chemistry has again culminated in many ‘approaches’ to the basic ring system. Wender’” has presented an elegant and viable approach to the synthesis of the basic tricyclic core starting from a-pinene Scheme 59. Fetizon”’ has also described li c &l3R RO-Reagents i htl (85%) Scheme 59 a photochemical route to the taxane skeleton whereby irradiation of the ketone (40) resulted in a Norrish type I1 cleavage generating the [5.2.1] system (41). 19’ P.A. Wender and T. P. Mucciaro.J. Am. Chem. Soc.. 1992 114. 5878. I91 M. B. le-Hocine D. D. Khac M. Fetizon. F. Guir. Y. Guo and T. Prange 7krruhedroii Lrtr.. 1992 33. 1443. 138 P. Quayle Medium and large ring~.-White'~~ has completed a total synthesis of (&)-byssochlamic acid which utilizes an intramolecular [2 +23-photocycloaddition reaction in the key C-C bond forming step Scheme 60. Marshalllg3 has developed a 0 00 0 A0 i Scheme 60 highly efficient synthesis of large ring-containing acetylenes via intramolecular alkylation of an aldehyde with an allenyl stannane Scheme 61. Numerous publications RO eH 1 - 5%93 RO Reagents i BF,.OEt, -78 "C Scheme 61 this year have again been concerned with the synthesis of ene-diynes as exemplified by the first asymmetric synthesis'94 of the ten-membered ring system (42) related to the neocarzinostatin chromophore Scheme 62.In terms of simple elegance the synthesis of cyclacenes' 95 such as Kohnkene (43) via repetitive Diels-Alder reactions is perhaps one of the most aesthetically pleasing results of the year. 19' J. D. White M. P. Dillon and R. J. Butlin J. Am. Chem. SOC. 1992 114 9673. 193 J.A. Marshall and X.-J. Wang J. Org. Chem. 1992 57 3387. 194 K. Natatani K Arai and S. Terashima J. Chem. SOC. Chem. Commun. 1992 289. 195 P. R. Ashton G.R. Brown N. S. Issacs D. Giuffrida F. H. Kohnke J.P. Mathias A.M.Z. Slawin D. R. Smith J. F. Stoddart and D.J. Williams J. Am. Chem. SOC. 1992 114 6330. Aliphatic and Alicyclic Chemistry Reagents i LiN(SiMe,), THF -78 "C BF,.OEt,; ii Ac,O Scheme 62