5 Aliphatic and Alicyclic Chemistry By P. QUAYLE Department of Chemistry The Victoria University of Manchester Manchester M 139PL 1 Introduction Reports concerning the chemistry of molecules of 'theoretical interest' have featured heavily this year. Pride of place must surely go to the generation and spectroscopic characterization of cyclobutadiene encapsulated in the cavity of a hemicarcerand.' The ability to prepare2" in relatively high yield (up to 44%) pure samples of C60 (Buckminsterfullerene) has enabled many groups to study the chemical reactivity of this unusual caged compound.2b Similarly the chemistry of enediynes has continued to attract much attention since the isolation and potential therapeutic properties of the neocarzinostatins and calicheamicins were dis~overed.~ A timely personal account of rational synthetic design chronicles advances over the last two decades? Other areas of intense activity have also been extensively reviewed including an overview of enantiocontrolled cycloaddition processes,' catalytic asymmetric synthesis,6 the use of radical reactions in organic synthesis,' organocopper reagents in organic synthesis,* enzymes in organic synthesis,' syn-thetic applications of carbonyl ylides and related systems," enantioselective alkyla- tion reactions," and the use of non-racemic starting materials such as amino acids'* D.J. Cram M. E. Turner and R. Thomas Angew. Chem. Int. Engl. 1991 30 1024. (a) D. H. Parker P. Wurz W. J. Pellin J. C. Hemminger D. M. Gruen and L. M. Stock J. Am.Chem. SOC.,1991,113,7492; (b)F. Diederich and R. L. Wheller Angew. Chem. Znt. Edn. Engl. 1991,30,678; J. W. Bausch G. K. Prakash G. A. Olah D. S. Tse D. C. Lorents Y. K. Bae and R. Malhortra J. Am. Chem. Soc. 1991 113 3205; G. A. Olah I. Bum C. Lambed R. Aniszfeld N. J. Trivedi D. K. Sensharman and G. K. Prakash J. Am. Chem. SOC.,1991 113,9385; A. Penicaud J. Hsu C. A. Reed A. Koch K. C. Khemani P-M. Allemand and F. Wudl. J. Am. Chem. SOC.,1991 113 6698; H.W. Kroto A. W. Allaf and S. P. Balm Chem. Rev. 1991 91 1213. K. C. Nicolaou and W. M. Dai Angew. Chem. Znt. Edn. Engl. 1991 30 1387; I. H. Goldberg ACC. Chem Res. 1991,24; 191; M. D. Lee G. A. Ellstad and D. B. Borden Acc. Chem. Rex 1991,24,235. E. J. Corey Angew. Chem Zrit. Edn. Engl. 1991 30 435. L.M. Haewood Tetrahedron Asmmmetry 1991,2 1173. K. Narasaka Synthesis 1991 1; K. Burgess and M. J. Ohmeyer Chem. Rev. 1991 91 1179; J. M. Brown Tetrahedron Asyymetry 1991 2 487; P. J. Cox and N. S. Simpkins Tetrahedron Asymmetry 1991 2 1; C. Bolm Angew. Chem. Int. Edn. Engl. 1991 30 542. 'T. V. Rajan Babu Acc. Chem. Res. 1991 24 139; D. P. Curran SYNLEm 1991 63; C. P. Jaspere D. P. Curran and T. L. Fevig Chem. Rev. 1991 91 1231. E. Nakamura SYNLEm 1991 53. R. Csuk and B. I. Glanzer Chem. Rev. 1991 91 49; Z-F. Xie Tetrahedron Asymmetry 1991 2 733; W. Boland C. Frossl and M. Lorenz Synthesis 1991 1049. lo A. Padwa Acc. Chem Res. 1991 24 22; A. Padwa and S. F. Horbuckle Chem. Rev. 1991 91 263. R. Noyori and M. Kitamura Angew. Chem Int. Edn. Engl. 1991,30 49.M. T. Reetz Angew. Chem Int. Edn Engl. 1991 30,1531. 103 104 P. Quayle and epoxy alcohol^'^ in organic synthesis. Recent developments in natural product synthesis have also been re~iewed.’~ 2 Aliphatic Chemistry -Functional Group Chemistry Recent advances in the Peterson olefination reacti~n’~ and palladium catalysed cross-coupling reactions16 have been reviewed. Stang has reviewed the chemistry of ynol esters and related Synthetic applications of di-anion chemistry and rhodium-mediated transformations have also been extensively discussed.18 Most transition metal catalysed coupling reactions between sp3-hybridized alkyl halides and ‘organometallic’ reagents have limited scope due to unwanted p-elimina- tion reactions. However Suzuki” has shown that 9-alkyl-9-BBN derivatives undergo efficient carbonylation reactions with a variety of alkyl halides using Pd(PPh,) as catalyst.The reaction is also promoted by irradiation (Scheme 1). Scheme 1 The synthesis of dienes via a palladium catalysed cross-coupling reaction between a vinyl organometallic reagent and vinyl halide is now a routine operation. In a critical survey Negishi has shown that2’ optimal coupling (in terms of yield and stereospecificity) is obtained when the vinyl zinc reagent is employed as the nucleophilic partner. Using vitamin A (3) as an example (Scheme 2) the crucial I (2) Reagents i Pd’ (2); ii THF TBAF Scheme 2 13 R. M. Hanson Chem. Reu. 1991,91,437. 14 A. Hassner Isr. J. Chem. 1991 31 p.3.15 A. G. M. Barrett J. M. Hill E. M. Wallace and J. A. Flygate SYNLETT; 1991 764. 16 Y. Hatanaka and T. Hiyama SYNLETT 1991 845. 17 P. J. Stang Acc. Chem. Rex 1991 24 304. 18 J. Adams and D. M. Spero. Tetrahedron,1991,47,1765; C. M. Thompson and D. L. C Green Tetrahedron 1991,47 4223. 19 T. Ishiyama N. Miyausa and A. Suzuki Tetrahedron Lett. 1991 32 6923. 2o E.4. Negishi and Z. Owczarczyk Tetrahedron Lett. 1991 32 6683. Aliphatic and Alicyclic Chemistry coupling reaction between the zinc reagent (1)and the iodide (2) proceeded in high yield (87%) with >98% stereospecificity. These coupling reactions2' can be carried out in the presence of unprotected hydroxyl functionality and of electrophilic functional groups (e.g. esters) as illustrated in Scheme 3.OH 92%(E 2). Reagents i 2Bu'Li; ii ZnBr2; iii Me02C.(CH2)3 OH Scheme 3 / =\]/OH R Ar-I 2-Pd(0Ac) /NaHCO, B~:N&I/DMF 1 Pd(0Ac)J PPh,(cat)/ AgOAc/ DMF Ar Scheme 4 The synthesis of allylic alcohols can be achieved in high yields using the Heck reaction in the presence of silver acetate or silver carbonate22 (Scheme 4). Brown23 has published an alternative diene synthesis from vinyl boronic acid derivatives (Scheme 5). Kn~chel~~ has also published a novel diene synthesis from acetylenic R Br i,ii \ 0 R' Reagents i ;ii H+-70% Li Scheme 5 21 J.-M. Duffault J. Einhorn and A. Alexakis Tetrahedron Lett. 1991 32,3701. 22 T. Jeffrey Tetrahedron Lett. 1991 32 2121. 23 H.C. Brown N. G. Bhat and R. R. Iyer Tetrahedron Lett. 1991 32,3655. 24 P.Knochel and M. J. Rzeman Tetrahedron Lett. 1991 32 1855. 106 P. Quayle . .. 1,11 Cu(CN)Li Qo* I\ OH Reagents i ICH2ZnI (excess); ii Scheme 6 copper reagents (Scheme 6). Alternati~ely,~~ palladium catalysed coupling of a vinyl triflate and an allene in the presence of a P-diketone leads to the isolation of functionalized dienes in high yields (Scheme 7). Lipshutz26 has developed a general method for the preparation of buta-l,3-dienes starting from the bis-stannane (4) (Scheme 8). 76% Scheme 7 0 64% Reagents i Me2Cu(CN)Li2; ii / ,-78 "C b Scheme 8 25 V.Gauthier B. Cazes and J. Gore Tetrahedron Lett. 1991 32 915. 26 B. H. Lipshutz and J.I. Lee Tetrahedron Lett. 1991 32 7211. Aliphatic and Alicyclic Chemistry The chemistry of high oxidation state iodine compounds has been the subject of much recent interest. For example Stang2' has developed a novel route to difunc- tionalized acetylenes from the iodonium salt (9,Scheme 9. Alternatively:' the salt (6) can be readily transformed into the tri-substituted olefips (7) in near quantitative yields Scheme 10. The synthesis and coupling reactions of vinyl cup rate^^^ prepared in situ from acetylenes has been the subject of a number of reports. [ Ph-1-= H62 Nu--I-Ph]*+*2 x TfO-NU-? -NU (5) Scheme 9 [R-EE-1-Ph]' BFL i,ii b R)=\ (6) PhSO1 X (7) X = C1 Br I 83-100% Reagents i PhSO,H/MeOH; ii Bu,NX Scheme 10 3 Acyclic Stereoselection A major advance has been the development of an in situ method30a for the prepar- ation of [BINAP.RuC12],-Et3N for use in asymmetric reductions.Hence reaction of (RuCl,.COD), with triethylamine generates a very active catalyst which in the presence of BINAP reduces P-keto esters to the P-hydroxy esters with excellent enantioselectivities (~97% ee). Of particular significance is the observation that this catalyst systems enables reduction to occur at relatively low pressures of hydrogen (50 psig) compared to the high pressurz; (ca. 1500 psig) usually associated with this reduction procedure. A second group have shown that related catalyst systems ( RuC12[ SbPh3I3/BINAP) has a similar reactivity profile reducing P-keto esters to the respective P-hydroxy esters with marginally improved enantioselectivities (>98% ee) (4-5 atmospheres of hydrogen).Sharple~s~~ has reported 'a catalyst system (OsO modified by a dihydroquinidine auxiliary) which enables the dihydroxylation of a variety of olefins to occur in high chemical (75-905'40) and optical yields (up to 99% ee). Corey's oxazaborolidine methodology for the enationselective reduction of has been employed on numerous occasions this year and has been the subject of theoretical in~estigations.~~ 27 P.J. Stang and V. V. Zhdankia J. Am. Chem. SOC.,1991 113 4571. 28 M. Ochai K. Oshima and Y. Masaki Tetrahedron Lett. 1991 32 7711. 29 B. H. Lipshutz and K. Kato Tetrahedron Lett. 1991 32 5647. 30 (a) D. F.Taber and L. J. Silverberg Tetrahedron Lett. 1991,32 4227; (b)M. Kitamura M. Tokunaga T. Ohkuma and R. Noyori Tetrahedron Lett. 1991,32 4163. 31 Y. Ogino H. Chen E. Manoury T. Shibata M. Beller D. Lubben and K. B. Sharpless Tetrahedron Lett. 1991 32 5761. 32 E. J. Corey X.-M. Cheng K. A. Cimprich and S. Sarshar Tetrahedron Lett. 1991 32 6835 C.-P. Chen K. Prasad and 0.Repic Tetrahedron Lett. 1991,32,7175 E. J. Corey and H. Kigoshi Tetrahedron Lett. 1991 32 5025. 33 V.Nevalainen Tetrahedron Assym. 1991 2 827. 108 P.Quayle (9) anti syn = 1:8.6 Scheme 11 M~therwell~~ has described a new method for the generation of enolates. For example reaction of the alkoxide (8) with benzaldehyde in the presence of suitable catalyst afforded the aldol product (9) in 84% isolated yield (anti:syn = 1:8.6) Scheme 11.Japanese workers3' have shown that the potassium enolate generated from the ketone (10) undergoes alkylation to afford an optically active product -hence the intermediate enolate possesses 'memory of chirality' Scheme 12. Gener-ati~n~~ of the enolate from the N-acyl aziridine (1 1) and reaction with benzaldehyde *'"' -aoEt KH 18-C-6 \ ' 'OEt Me1 / OEt 93%ee 66%ee (10) Scheme 12 BnO/''\<OBn i LHMDS; -78 "C ii F'hCHO Ph":"I;OBn 73% OBn afforded the syn-aldol product (12) in 73% yield as the sole product. A number of workers37 have shown that titanium enolates afford syn-selective aldol products (ds > 90 10). Curiously,38 reaction of the prolinal derivative (13) with the amide (14) in the presence of a slight excess of Bu;BOTf afforded the contra-Evans 34 G.L. Edwards W. B. Motherwell D. M. Powell and D. A. Sandheum 1. Chem. SOC.,Chem. Commun. 1991 1399. 35 T. Kawabata K. Yahiro and K. Fuji J. Am. Chem. Soc. 1991 113 9694. 36 D. Tanner and C. Birgeson Tetrahedron Lett. 1991 32 2533. 37 M. D. Bonner and E. R. Thornton J. Am. Chem. SOC,1991,113,1299; D. A. Evans D. L. Eieger M. T. Bioldean and F. Urpi J. Am. Chem. SOC 1991 113 1047. 38 K. Hayashi Y. Hamada and T. Shiori Tetrahedron Lett. 1991 32 7287. Aliphatic and Alicyclic Chemistry Et,N; Bu,"BOTf H b w CH2C120"C Ph Boc OH Ph OCHO I Boc anti (15) Et3N:Bu;BOTf (2 1.8) Syn:anti (1OO:O); Et,N:Bu;BOTf (1.08 1.15) Syn:anti (0 100) Scheme 13 anti-aldol product (15) (100 :1 anti :syn) presumably via an 'open' transition state Scheme 13.Opp0lzer~~ has developed a general strategy for the synthesis of anti-aldol products using chiral sultam methodology.The thianone (16) undergoes kinetic aldol reactions with high anti-selectivities (-96 :4) and serves as a useful surrogate for pentan-3-one in such reactionN (Scheme 14). a-Epoxy aldehydes undergo kinetic aldol reaction41 to afford the anti-aldol products (Felkin- Anh transition state). I-'" .. +Ph 0 OH OH (16) Reagents i LDA -78 "C; ii PhCHO; iii NaBH4/EtOH; iv Raney Ni Scheme 14 F3C -98% ee (17) Reagents i Et3N -78 "C(17); ii RCHO -18 "C Scheme 15 39 W.Oppolzer C. Starkemann I. Rodriguez and G. Bernadinelli Tetrahedron Lett. 1991 32,61. 40 T.Hayashi Tetrahedron Lett. 1991 32,5369. 41 R. C. Peller G. Jimarauel D. G. Powers and C.-T. Chang Tetrahedron Lett. 1991 32 449; J. M. Escudier M. Baltas and L. Gorrichon Tetrahedron Lett. 1991 32,5345. 110 P. Quayle Corey4’ has described the first highly enantioselective ‘Darzens’ reaction Scheme 15. Reet~~~ has described a stereocomplementary approach to the preparation of 1,2-diamines. Conjugate addition to 8-functionalized a$-unsaturated carbonyl and nitro-groups has been the subject of a number of investigations.& The use of binaphthol as a chiral auxiliary in a number of alkylation reactions has been also been reported?’ A number of workers& have remarked upon the stereoselective alkylation reactions of carbon-centred radicals as exemplified by Scheme 16.This area of chemistry promises to be highly fruitful. gH& AIBN/A Hexane 73 :1 (erythro :threo) 67% Scbeme 16 Hydroxy-enones such as (18) undergo highly stereoselective epoxidation reactions using the Sharpless protoc01:~ Scheme 17. OH 0 OH 0 OH 0 @p=(y$+@y CH,CI (18) -15°C >99:1 82% Scbeme 17 4 Alicyclic Chemistry The use of aromatic compounds as synthons in natural product synthesis has been reviewed.48 Experimental validation of the Cieplak model governing the facial 42 E. J. Corey and S. Choi Tetrahedron Lett. 1991 32 2857. 43 M. T. Reetz R. Jaeger R. Drewlies and M.Hubel Angew. Chem. Znt. Edn. Engl 1991 30,103. 44 M. T. Reetz F. Wang and K. Harms J. Chem. SOC.,Chem. Commun. 1991 1309; S. Hanessian and K. Sumi Synthesis 1991 1083;A. G. M. Barrett P. D. Weipert D. Dhanak R.K. Husa and S. A! Lebold J. Am. Chem. SOC.,1991 113 9820. 45 K. Fuji K. Tanaka M. Mizuchi and S. Hosoi Tetrahedron Lett. 1991 32 7277; Y. Tami S. Koike A. Ogura and S. Miyano J. Chem. SOC.,Chem. Commun. 1991 799. 46 N. A. Porter B. Giese and D. P. Curran Acc. Chem. Rex 1991 24 296; P. Renaud Helv. Chim. Acta 1991 74 1305; D. P. G. Hamon P. Razzino and R. Massy-Westropp 1.Chem. SOC.,Chem. Commun. 1991 332; A. L. J. Beckwith R. Hersperger and J. M. White J. Chem Soc. Chem. Commun. 1991 1151; B. Giese W. Damn J. Dickhaut F. Wetterich S. Sun and D.P. Curran Tetrahedron Lett. 1991 32 6097; B. Giese M. Bulli and H.-G. Zeitz SYNLETT 1991 425; N. A. Porter W.-X.Wu and T. McPhail Tetrahedron Lett. 1991 32 707; N. A. Porter R. Breyer E. Swann J. Nally J. Prahan T. Allen and A. T. McPhail J. Am. Chem. SOC. 1991 113 7002; J. G. Stack D. P. Curran J. Rebeck and P. Ballester J. Am. Chem. SOC.,1991 113 5918; W. Smadja M. Zahouily M. Journet and M. Malacria Tetrahedron Lett. 1991 32 3683; Y. Guindon J. F. Lavallee M. L. Brunet G. Homer and J. Rancourt J. Am. Chem. SOC.,1991 113,9701. 47 M. Bailey I. E. Marko and W. D. Ollis Tetrahedron Lett. 1991 32 2687. 48 L. N. Mander SYNLEm 1991 134. Aliphatic and Alicyclic Chemistry 111 selectivity of olefin functionalization has appeared.49 The factors governing the stereoselectivity in nucleophilic addition to cyclic ketones is still the cause for some debate.50 5 Cyclopropanes The use of chiral catalyst systems in olefin cyclopropanation reactions has been the subject of a number of reports.Evanss1 and Ma~arnune~~ have described the use of copper catalysts containing C,-symmetric ligands for effecting highly enantioselec- tive cyclopropanation of olefins. Typically enantioselectivities for these reactions fall into the range of 94-99’/0 ee (Scheme 18). A Rhodium (III)-porphyrin catalyst Ph CO2R COZR N2J CuOTf ; R02CAN C02R Ph-’ ph-p -ph-P 0.1 mol% OH 99% ee (Ref. 51) ‘R2 5 (Ref. 53) Scheme 18 system53 has been reported to be syn-selective in the cyclopronation of styrene with ethyl diazoacetate; unfortunately the reaction proceeded with only modest asym- metric induction (ca.10% ee). Doyle54 has developed a highly effective rhodium- based system for the corresponding intramolecular cyclopropanation reactions (Scheme 18). Reaction” of the homochiral diazoester (19) with styrene in the 49 G. Metha and F. A. Khan J. Chem. SOC.,Chem. Commun. 1991 18. 50 Y. D. Wu A. Tucker and K. N. Houk J. Am. Chem. SOC.,1991 113 5018; G. Frenking K. F. Kohler and M. T. Reetz Angew. Chem. Zntl. Edn. Engl. 1991 30,1146. 51 D. A. Evans K. A. Woerpel M. M. Hinman and M. M. Faul J. Am. Chem. Soc. 1991 113 726. 52 R. E. Lowenthal and S. Masarnune Tetrahedron Lett. 1991 32 7273. 53 S. O’Malley and T. Kodakek Tetrahedron Lett.1991 32 2445. 54 M. P. Doyle R. J. Pieter S. F. Martin R. E. Austin C. J. Oalmann and P. Muller J. Am. Chem. SOC. 1991 113 1423. 55 H. M. Davies and W. R. Cantrell Terrahedron Lett. 1991 32 6509. 112 P. Quayle presence of Rh,(octanoate) afforded the cyclopropane (20) in 67% yield (>98% d.e.) Scheme 19. Alternati~ely,'~ Simmonds-Smith cyclopropanation of the glucose- derivative (21) and removal of the auxiliary afforded the alcohol (22) in a near optically pure state. 1 . B BnO 0 OH6 O-Ph (22) (21) Reagents i Et2Zn/Cu212 Toluene -35 "C +0 "C; ii Tf20; iii H20/Py/DMF Scheme 19 CyclopropanationS7of the allylic alcohol (23) afforded the product (24) in 90% d.e. alternatively direct cyclopropanation of the homochiral cyclopentenol (25) afforded (26) as the sole product in 77% isolated yield (Scheme 20).Harvey5* has shown that unactivated buta-l,3-dienes undergo cyclopropanation rections with the OH .OH 90%ee (24) Scheme 20 56 A. B. Charelle B. Cote and J. F. Maroux J. Am. Chem. Soc. 1991 113,8166. 57 M. Kabat J. Kiegel N. Cohen K. Toth P.M. Wovkulich and M. R. Uskovic Tetrahedron Lett. 1991 32,2343. 58 D.F. Harvey and K. P. Lund J. Am. Chem. SOC.,1991 113,8916. Aliphatic and Alicyclic Chemistry (Ref.58) Me0 71% ?Yo"' (ref. 59a) 0 52% (Ref. 596) Scheme 21 labile molybdenum carbene complex (27) Scheme 21. Intramolecular variantd9" of this process have also been realised (Scheme 21). An intramolecular cyclopropana- tion sequence was utilized in a synthesis of (1)-thaspane (Scheme 22)59b.An efficient6' OH Scheme 22 Thaspane -Me3Si7 0 S i B u ' Ph2 S02Ph OSozMe LDA -78 "C 89% PhS02 SiMe3 a -x TBAF ''.pOH 9& ".fiOSiBu' Ph2 (27) Scheme 23 (a) D. F. Harvey K. P. Lund and D. A. Neil Tetrahedron Lett. 1991,32,6311; (b)A. Snikuishna and K. Rrishnan J. Chem. Soc. Chem. Commun. 1991 1693. 6o M. M. Kabat and J. Wicha Tetrahedron Lett. 1991 32 531. 114 P. Quayle synthesis of the cyclopropene (27) has been reported in which the crucial olefination step involved a fluoride mediated desilylation sequence Scheme 23. A similar6' elimination sequence was employed in the synthesis of the spiropentadiene (28). 6 Cyclobutanes Vollhardt6* employed a [2 + 2 + 21 cycloaddition strategy in the synthesis of illudol (30).The key reaction in this sequence secured the 5-6-4 ring system (29) in 92% yield Scheme 24. Reaction of dichloroketene with the glucal (31) afforded,63 after dehalogenation the optically pure cyclobutanone (32). The cyclobutane (32) was further transformed into the lactone (33) by standard methodology. OTBDMS OTBDMS (29) (92%) I Reagents i CpCo(CO), PhCH3 llO"C hv 6 h. Scheme 24 OMe (33) 61 A. Srikrishna and K. Krishnan J. Chem. SOC.,Chem. Commun. 1991 1693. 62 E. P. Johnson and K. P. C. Vollhardt J. Am. Chem. SOC.,1991 113 381. 63 J. Pan I. Hanna and J.-Y. Lallemand Tetrahedron Lett. 1991 32 7543. Aliphatic and Alicyclic Chemistry 115 Photbcy~loaddition~~ of cyclopentenone with the olefin (34) afforded the adduct (35) in 63% isolated yield.Ketone (35) proved to be a useful intermediate in the synthesis of the spatane ditertepenes. Phot~lysis~~ of the carbene complexes (36) in the presence of the enamide (37) afforded the adducts (38) in moderate yields (50-60% 94-97% de). OTMS 0 RIO-Ph g3, Ph 0 (37) (38) 7 Cyclopentanes Organometallic Approaches.-The Smit modification of the Pauson-Khand reaction has been used with good effect in the synthesis of a variety of cyclopentanone~~~*~~ (Scheme 25). silica 0 85 "C/ 12 hr 53% (Ref. 66) (Ref. 67) Reagents i TsNH-; ii BF,.OEt, -18 "C; iii Me,NO 02 CH2C12 Scheme 25 64 R.G. Salomon N. D. Sachinauala S. Roy B. Basu S. R. Raychaudhuri D. B. Miller and R. R. Sharma J. Am. Chern. Soc. 1991 113 3085. 65 L. S. Hegedus R. W. Bates and B. Soderberg J. Am. Chem. Soc. 1991 113 923. 66 A. L. Veretnov W. A. Srnit L. G. Voronstova M. G. Kurella R. Caple and A. S. Gibin Tetruhderon Lett. 1991 32 2109. 67 N. Jeong S. E. Yoo S. J. Lee and Y. K. Chung Tetrahedron Lett. 1991 32 2137. 116 P. Quayle =aft6* has demonstrated that the intermolecular Pauson-Khand reaction pro- ceeds with enhanced regiocontrol when the reacting partners possess pendent co-ordinating groups (Scheme 26). A remarkable69 rate enhancement in these cycliz- ation processes was observed when the reactions were carried out on the analogous acetylenic carbene complexes (Scheme 27).Pearson7' has developed a carbonylation rection of di-ynes and ene-ynes affording the cy+opentanone derivatives in good yields upon thermolysis with iron pentacarbonyl in toluene. CO,(CO), ~ + Ph-G -Me2NwPh c"" + 72% 4 51 Ph Me2N Scheme 26 Scheme 27 Intramolecular hydroacylation of the alkene (38) afforded the bicyclic system (39) in good yield (60%) (Scheme 28).78 In a rather interesting development Lieb~kind~~ has shown that the readily available molybdenum complex (40)under-went nucleophilic addition at Ca -a reversal of the normal polarity of enones. Hence reaction of (40) with acetophenone enolate and subsequent elaboration and removal of the metal afforded the bicyclic system (41) in excellent overall yield (75%) Scheme 29.Kn~chel~~ has developed an intramolecular carbocupration sequence whereby formation of the organocuprate (42) led upon warming to room temperature and quenching with a suitable electrophile to the isolation of the cyclopentanes (43)in moderate to good yields (55-70%). 68 M. E. Kraft C. A. Juliano I. L. Scott C. Wright and M. D. McEachin J. Am. Chem. SOC.,1991 113 1693. 69 F. Cumps J. M. Moreto S. Ricart and J. M. Vinas Angew. Chem. Inti. Edn. Engl. 1991 30,1470. 70 A. J. Pearson and R. A. Dubbert J. Chem. Soc, Chem. Commun. 1991 202. 71 K. P. Gable and G. A. Benz Tetrahedron Lett. 1991 32 3473. 72 L S. Liebskind and A. Bombrun J. Am. Chem. SOC.,1991 113 8736. 73 S. A. Rao and P. Knochel J. Am.Chem. SOC.,1991 113 5745. Aliphatic and Alicyclic Chemistry [(Ph,P),RhCI], & CP4 "0 ''* CDC1,/6 60% BnO 'o+ (38) (39) Scheme 28 ,,co .. I-IV b-=y Mo d Ph 1 co PF; "0 CP via (40) Reagents i PhCOCH,Li; ii I iii NH:CF,CO,; iv FeCl, Scheme 29 In a related sequence N~rmant'~ has shown that the organozinc reagents (44) readily undergo cyclization to afford the cis-substituted cyclopentanes (45) upon quenching with a suitable electrophile. R' Cu(CN)LiZnMe i 25 "C;2-15 hrs ii E+ c* R R (42) (43) i -70 "C.+ 20 "C c; ii E+ X-Zn OMe Ill I SiMe3 (45) Negishi7' has employed his bi-cyclization-carbonylationmethodology to the syn- thesis of pentalenic acid Scheme 30. 74 G.Courtemanche and J. F. Normant Tetrahedron Lett. 1991 32 5317. 75 G. Agnel and E.4. Negishi J. Am. Chem. SOC.,1991 113 7424. 118 P. Quayle SiMe (84%) \ HO Reagents i ‘Cp,Zr’; ii CO (1 atm) Scheme 30 A number of Pdo-mediated cyclization reactions have appeared a selection of which are presented in Scheme 31. 72% 73% OMe Pd,(dba) XHCl Ph ib 40-35 “C HOAc _____ + phso22 PhSOz (Ref. 78) r SOzPh 86% 76 G. J. Engelbrecht and C. W. Holsapfel Tetrahedron Lett. 1991 32 216). 77 B. M. Trost M. Lautens C. Chan D. J. Jebaratnam and T. Mueller J. Am. Chem. SOC.,1991,113,636. 78 B. M. Trost and Y. Shi J. Am Chem. Soc. 1991 113 701. 119 Aliphatic and Alicyclic Chemistry 0 ? -‘I,,, 61% ‘“1 1 (Ref.80) - Pdo (Ref. 81) 62% 0°c02cH3 S02Ph SO2R Scheme 31 Radical Cyc1ization.-Radical approaches to cyclopentanes are legion a representa- tive selection of the procedures recently discussed are presented in Scheme 32. 0 0 SmI ___ (Ref. 82) TH F DMPU TMS 79% 79 B. M. Trost A. S. Tasker and A.Brande J. Am. Chem. SOC.,1991 113,670. 8o D. Bouyssi G. Balme and J. Gore Tetrahedron. Lett. 1991 32 6541. 81 B. M.Trost T. A. Gresse and D. M. T. Chan J. Am. Chem. SOC.,1991 113 7350. 82 R.A. Batey and W. B. Motherwell Tetrahedron Lett. 1991 32 6649. 120 I? Quayle Qe ZxSMI ____ (Ref. 83) Bu3SnH AIBN A 0 Et0,C-75% Bu,SnH WPh (Ref. 84) AIBN/PhH A -Ph H -C02Me Bu3SnH C02Me (Ref.86) 0,.Toluene 0 "C \ 68% I (Ref. 87) 'SnBu3 86% I 85% Scheme 32 83 S. E. Booth and P. R. Jenkins and C. J. S. Swain J. Chem. SOC.,Chem. Commun. 1991 248. 84 S. Kim S. Lee and J. S. Koh J. Am. Chem. SOC.,1991 113 5106. 85 Y. M. Tsai and C.-D. Cherng Tetrahedron Lett. 1991 32 3515. 86 E. Nakamura T. Innubushi S. Aoki and D. Machi J. Am. Chem. SOC.,1991 113 8982. S. Kim I. S. Kee and S. Lee J. Am. Chem. SOC.,1991 113 9882. G. A. Molander and C. C. Kenny J. Org. Chem. 1991 56 1439. Aliphatic and Alicyclic Chemistry 121 Miscellaneous.-Reaction of the optically pure ep~xide~~ (46) with potassium hydride afforded the trans-functionalized cyclopentane (47) a key intermediate in the synthesis of brefeldin A Scheme 33.?H OBn KH MEMO-___* MEMO-THF 65% 0 0 (44) (47) 1 1 Scheme 33 Me0 Me0 OMe OMe (48) (p :a =29:33) \ OMe (49) Scheme 34 89 D. F. Taber L. J. Siverberg and E. D. Robinson J. Am. Chem. SOC.,1991 113 6639. 122 P. Quayle Taylo?’ has utilized a samarium iodide promoted pinnacol-type coupling reaction in a synthesis of rocaglamide. Hence in the key reaction treatment of the di-carbonyl compound (48) with samarium iodide afforded a 1:l mixture of the diols (49) Scheme 34. Hoye has developed a rhodium catalysed carbene addition-rearrangement sequence for the preparation of fused cyclopentan~nes.~~ Hence reactions of the diazoketone (50) with rhodium acetate in the presence of 2-butyne ultimately afforded the bicyclic system (51) in 51% overall yield.A more ‘traditional’ rhodium catalysed process involved the metal promoted insertion reaction of the ‘carbenoid’ generated from the diazo ketone (52) into a proximal C-H bond to afford the ketone (53) in excellent yield9* (85%). RhJOAc), A Me-=-Me N2 0 25°C 51% 0 Finally treatment of the vinyl iodonium salt (54) with triethylamine in benzene afforded the cyclopentene (59 pesumably oia the intermediates of the alkylidene carbene (56)?3 H (54) (55) 8 Cyclohexanes Diels-Alder Reactions.-As always many synthetic schemes leading to functional- ized six membered rings rely upon Diels-Alder methodology to control regio- and stereochemistry. During the past year a number of catalysts have been developed in order to promote asymmetric Diels- Alder reactions.Of the examples selected for this review the Corey catalyst (57) appears to achieve the highest enantiomeric excess in the Diels-Alder adduct (Table 1). 90 A. E. Davey M. J. Schaeffer and R. J. Taylor J. Chem. Soc. Chem. Commtm. 1991 1137. 91 T. R. Hoye and C. J. Dinsmore Tetrahedron Lett. 1991 32 3755. 92 H. R. Sonawane H. S. Bellier J. R. Ahuja and D. J. Kulkami J. Org. Chem 1991 56 1434. 93 M. Ochai M. Kubiushima S. Tani and Y. Nagao J. Am. Chem. Soc. 1991 113 3135. Aliphatic and Alicyclic Chemistry phh#ph I. CF,SOZN NSOICF3 A< I 48% (Ref. 96) MeS02N ,O Me B (57) I R 95% ee (Ref. 95) 99% ee (Ref.94) 94% ee (Ref. 97) 86% ee (Ref. 98) Table 1 Kea~~~ has reported that furans undergoes a high yielding intramolecular Diels- Alder reaction in the presence of MeAlCl (0.1 eq.) at low temperatures (-65 "C) with high endo :exo ratios. It is suggested that this catalyst regime is complementary to high pressure techniques otherwise used for such reactions (Scheme 35). A 0 .Q7 HO endo :exo =91 :9 Reagents O.leq MeAlCl, CH2C12 -65 "C 2h 91% Scheme 35 Scheme 36 94 E. J. Corey and T.-P. Loh J. Am. Chem. Soc. 1991 113 8966. 95 E. J. Corey N. Imai and S. Pikul Tetrahedron. Lett. 1991 32 7517. 96 P. N. Devine and T. Oh Tetrahedron I+. 1991 32 883. 97 E. J. Corey and Y. Matsumura Tetrahedron Lett. 1991 32 6289. 98 E. J. Corey N.Imai and H.-Y. Zhang J. Am. Chem. Soc. 1991 113 728. 99 C. Rogers and B. A. Keay Tetrahedron Lett. 1991 32 6477. 124 P. Quayle X 0W-com (Ref. 100) C02Me (Ref. 102) (Ref. 101) 0 \ (Ref. 105) (Ref. 103) (Ref. 104) 0&OMe I (Ref. 106) (Ref. 107) (Ref. 108) I Ph (Ref. 109) (Ref. 110) (Ref. 111) 100 T. Hudlicky and H. F. Olivo Tetrahedron Lett. 1991 32 6077. 101 H. C.Kolb and S. V. Ley Tetrahedron Lett. 1991 32 6187. 102 S. F. Martin T. Rein and Y. Liao Tetrahedron Lett. 1991 32 6481. K. Ando N. Akadegawa and H. Takagawa J. Chem. SOC.,Chem. Commun. 1991 1765. 104 E. P. Kundig G. Bernadelli and J. Leresche J. Chem. SOC.,Chem. Commun. 1991 1713. 10s X. Wang J. Chem. SOC.,Chem. Commun.1991 1515. 106 M. Ohkita T. Tsuji and S. Nishida J. Chem SOC. Chem. Commun. 1991 37. lo' S. Hatakeydima K. Sugawara and S. Takano 1 Chem. SOC.,Chem. Commun. 1991 1533. 108 H.-J.Kang C. S. Ra and L. A. Paquette J. Am. Chem. Soc. 1991 113,9384. N.Kitagiri M. Yamoto T. Iwaoka and C. Kaneko J. Chem. SOC.,Chem. Commun. 1991 1429. 'lo D. A. Singleton and J. R. Martinez Tetrahedron Lett. 1991 32 7365. 111 G. H. Posner T. D. Nelson C. M. Kinter and K. Afarinkia Tetrahedron Lett. 1991 32 5295. Aliphatic and Alicyclic Chemistry OMe SiMe, I (Ref. 112) (Ref. 113) (Ref. 114) Table 2 representative list of dienes/dienophiles is tabulated in Table 2. Of interest is the development introduced by Shea' l5 which has been termed 'Pericyclic Umpolung'.In this work a disposable tether was introduced in a link between the diene and dienophile in order to control the regioselectivity of the Diels-Alder process (Scheme 36). Other Methods of Construction.-Radical reactions'16 have been utilized for the synthesis of heavily oxygenated and polycyclic cyclohexane derivatives. Double Michae1117 reactions have been employed in the construction of fused systems e.g. Scheme 37. Wulffl'* has developed a particularly rapid entry into steroidal system based upon carbene cycloaddition chemistry Scheme 38. OTBDMS I Hi COzMe 63% Scheme 37 OTBS Reagents i hOMe, CH,CN CO; ii 120 "C Scheme 38 112 N. K. Bhamare T. Granger C. R.John and P. Yates Tetrahedron Lett. 991 32 4 39.113 J. J. Pegram and C. B. Anderso Tetrahedron Lett. 1991 32 2197. 114 A. Barco S. Benetti G. P. Pollini G. Spalluto and V. Zanirato Tetrahedron Lett. 1991 32 2517. K. J. Shea A. J. Staab and K. S. Zandi Tetrahedron Lett. 1991 32 2715. 116 J. Marco-Contelles L. Martinez A. Martinez-Grau C. Pozuelo and M.L. Jimeno Tetrahedron Lett. 1991,32 6437. I17 N. Ihara S. Suzuki N. Taniguchi F. Fukumoto and C. Kabuto J. Chem. Soc. Chem. Commun. 1991 1168. 118 J. Bao V. Dragisich S. Wenglowsky and W. D. Wulff J. Am. Chem. Soc. 1991 113 9873. 126 P. Quayle A particularly expedient"' approach to shikimic acid relies upon an intramolecular Wittig reaction Scheme 39. 00 Scheme 39 Functionalization.-Davis12' has reported that the enolate generated from the p -keto ester (58) can be oxidized using the oxaziridine (60) to afford the alcohol (59) a pivotal intermediate for the synthesis of anthracyclinones in 70% yield with an optical purity in excess of 95% ee.V M\ wOMe M\ eHOMe Me0 Me0 0 Magnus'*' has developed a concise synthesis of the benzo-morphanone skeleton (62) from the tri-isopropysilyl ether (61). 9 Cycloheptanes Decomposition'22 of the diazo compound (63) in the presence of rhodium acetate dimer and the diene (64) affords the fused cycloheptadiene (65) in 94% yield. Alternati~ely,'~~ ring expansion of the cyclobutanone (66) to the cycloheptanone (67) was accomplished in good yield (68%) upon reaction with Bu3SnH/AIBN. 119 S. Mirza and J. Harvey Tetrahedron Lett.1991 32 4111. 120 F. A. Davis A. Kumar and B. C. Chen Tetrahedron Lett. 1991 32 867. 121 P. Magnus and I. Coldham J. Am. Chem. SOC.,1991 113,672. 122 W. R. Cantrell and H. M. L. Davies J. Org. Chem. 1991 56 723. 123 P. M. Dowd and W. Zhang J. Am. Chem. SOC,1991 113 9875. Aliphatic and Alicyclic Chemistry C02Me rOTBDMS 0 Me (64) (65) H H Clavukerin A'24 (68) has been prepared from the cyclobutanone (69) by way of a Grob-type fragmentation (Scheme 40). Har~ood'~~ has published a modified route to phorbol esters utilizing IMDA reactions of functionalized furans. Banwe11'26 has developed a concise approach' to functionalized tropolones from i ,2-dihydroxy-cyclo hexa-3,Sdienes. n . .. 4 -"'8 -Q 0 0 (49) n a; ii MsCI EQN Reagents i BrMg Scheme 40 10 Cyclooctanes Paq~ette'~~ has developed a double Tebbe-Claisen sequence for the synthesis of functionalized cyclooctanones Scheme 41.Synthetic approaches to the taxanes have been extensively reviewed.12* An intramolecular Diels- Alder- Wittig rearrangement sequence has been developed for the construction of the taxane skeletone Scheme 42.'29 124 S. K. Kim and C.S. Pak J. Org. Chem 1991 56 6829. 125 L. M. Harwood T. Ishikawa H. Phillips and D. Watkin J. Chem. Soc. Chem. Commun. 1991 527. 126 M. G. Banwell and M. P. Collis J. Chem. Soc. Chem. Commun. 1991 1343. 127 C. M. G. Phillipo N. H. Vo and L. A. Paquette J. Am. Chem SOC.,1991 113,2762; C. M. G. Phillipo N. H. Vo and L. A. Paquette J.Am. Chem. Soc. 1991 113 2762. 128 C. S. Swindell Org. Prep. Proc. Int. 1991 23 465. 129 J. S. Yadav and R. Ravishankar Tetrahedron Lett. 1991 32 2629. 128 P. Quayle A 36% < OQ -_ Scheme 41 H OR V " 0 Reagents i. NaBH,; ii BuLi THF -78 "C to r.t. Scheme 42 11 Medium-Large Rings Synthetic approaches to ene-diyne systems related to calicheamycin have been extensively re~iewed.~ Further efforts in this area have recently been reported by MagnusI3' and Nic~laou.'~' Tius has 132 developed a strategy for the synthesis of cembranes utilizing an intramolecular alkylation sequence Scheme 43. Diastereo-LiN(TMS) - THF 55 "C (74%) Scheme 43 130 P. Magnus and M. Davies J. Chem. SOC.,Chem.Commun. 1991 1522. See also M. E. Maier and T. Brandstetter Tetrahedron Lett. 1991 32 3679; M. Hirarna T. Gomibuchi K. Fujiwara Y. Sugiura and M. Vesugi J. Am. Chem. SOC.,1991 113 9851; A. G. Myers P. M. Harrington and E. Y. Kuo J. Am. Chem. Soc. 1991 113 694. 131 K. C. Nicolaou Y.-P. Hong Y. Toisawa S.-C. Tsay and W.-M. Dai J. Am. Chem. SOC.,1991 113 9878; K. C. Nicolaou A. C. Smith S. V. Wenderborn and C.-K. Hwang J. Am. Chem. SOC.,1991,113 3106. 132 M. A. Tius and N. K. Reddy Tetrahedron Lett. 1991 32 3605. Aliphatic and Alicyclic Chemistry cuprate addition to the macrocyle (70) and subsequent Dieckman con- densation and decarboxylation afforded (R)-muscone in -50% overall yield (85% ee) Scheme 44. --+-50% 85% ee H Me2CuLi (70) Scheme 44 12 Total Synthesis IMDA approaches to cytochalasin synthesis have been reviewed.134 Synthetic high- lights this year include approaches to the ginkg~lides,'~~ the total synthesis of (+)-eremantholide A,136calichaernicin~ne,~~~ and onamide A.138 133 T.Ogawa C.-L. Fang H. Suemune and K. Sakai J. Chem. SOC.,Chem. Commun. 1991 1438. 134 E. J. Thomas Acc. Chem. Res. 1991 24 229. 135 E. J. Corey and K. S. Rao Tetrahedron Lett. 1991 32 4623. 136 R. K. Boeckman S. K. Yoon and D. K. Heckendom J. Am. Chem. Soc. 1991 113 9682. 137 J. N. Haselline M. P. Cabal N. B. Mantlo N. Iwasawa D. S. Yamashita R. S. Coleman S. J. Danishefsky and G. K. Schulle J. Am. Gem. Soc. 1991 113 3850. '38 C. Y. Hong and Y. Kishi J. Am.Chem. SOC.,1991 113 9694.