6 Alicyclic Chemistry By N. S. SlMPKlNS Department of Chemistry University of Nottingham Nottingham NG7 2RD 1 General Several reports have appeared describing ring expansion methods which give access to various ring sizes; some examples are shown in Scheme 1. Addition of doubly deprotonated phenylthionitromethane to cycloalkanones gives adducts such as (1) which are converted into the desired ring-expanded products using A1Cl3.' The method in general works satisfactorily except that cyclopentanone gives a poor yield of the initial adduct and the adducts have proved susceptible to unwanted dehydration and retro-aldol reactions. The eight-membered ring product (2) is obtained via an aldol-retro-aldol process which uses Bu'OK in DMSO at room temperature.2 Nine- and ten-membered products are obtained similarly.A less SPh (1) 92% 68Yo (2) 62% AIMeCI SiMe (4) 77% (5) trace Scheme 1 ' S. Kim and J. H. Park Chem. Lett. 1988 1323. * Z.-F. Xie H. Suemune and K. Sakai J. Chem. SOC.,Chem. Commun. 1988 612. 139 140 N. S. Simpkins familiar process involves treatment of cyclic trimethylsilylmethylaldehydes such as (3) with Lewis acids.3 In the example shown (4) is the major ring-enlarged product resulting from sequential carbon and hydrogen migrations. This reaction can be tuned to give products of type (4) or (5) with high selectivity primarily by changing the Lewis acid. A further report deals with the ring expansion method highlighted last year in which cyclic diketones are treated with ethylene glycol-BF,-OEt .4 This new variant produces cycloheptenes from suitably substituted cyclopentanones and is illustrated with a synthesis of ( * )-bulnesol (6) (Scheme 2).&-< HOCH,CH,OH BF,.OEt H HO (6) Scheme 2 Treatment of various halogenoepoxides with activated copper in THF or toluene gives the expected cycl~alkenols.~ 2 Three-membered Rings The cyclopropenone ketal (7) reacts smoothly with organocuprates to produce a cuprio-cyclopropane intermediate which can then be quenched with electrophiles to give cis-disubstituted products (e.g. Scheme 3).6 fi-fi -fi OM0 Mex (7) CuMe \ Reagents i MezCuLi EtzO-THF; ii MepSiC1 MeN qo n Me KNMe 0 Scheme 3 A number of different cuprates and electrophilic quenchers have been explored including an interesting divinylation procedure which involves in situ rearrangement to give a seuen-membered ring products.Cyclopropane products are also produced uia 1,3-elimination from y-iodo-ketones and -esters.’ Cohen has described a new K. Tanino T. Katoh and I. Kuwajima Tetrahedron Lett. 1988 29 1815 1819. M. Tanaka H.Suemune and K. Sakai Tetrahedron Lett. 1988,29 1733. ’ T.-C. Wu and R. D. Rieke Tetrahedron Lett. 1988 29 6753. E.Nakamura M. Isaka and S. Matsuzawa J. Am. Chem. SOC.,1988,110,1297. ’ M. Mori N. Kanda Y. Ban and K. Aoe J. Chem. SOC.,Chem. Commun. 1988 12. Alicyclic Chemistry variant for cyclopropanation of enones which involves conjugate addition of a suitable phenylthio-stabilized organolithium followed by internal displacement of a phenylthio group activated by copper (I) trifluoromethanesulphonate (Scheme 4).* s -,ph,j,:i"^ I cu+ &SiMe3 -18 "C SiMe3 SPh PhS SPh Scheme 4 Vinylcyclopropanes are also prepared using this method by employing suitable sulphur-stabilized allylic carbanions.Fischer carbene complexes react with both 1,3-dienes and enynes to give useful products including cyclopr~panes.~ Reaction of dibromomalonate derivatives with electron-poor olefins in the pres- ence of Bu3Sb gives cyclopropanes having three electron-withdrawing groups (Scheme 5)." The products have potential use in nucleophilic cyclopropane-opening reactions. NC ,CO,Et 88% / Scheme 5 Krief has described further studies of the little-used selenones and their derived carbanions." The cyclopropanation reaction using selenones follows along the lines of the sulphone analogue but appears somewhat more general (e.g.Scheme 6). Scheme 6 Other recent cyclopropane preparations include cyclopropylacylsilanes,'* 1-chloro-l-fluorocyclopropanes,'3and substituted cyclopropylamines prepared using a Favorskii-type pr~cedure.'~ Phase transfer conditions can be used for displacement of halogens from readily available gern-dichlorocyclopropanes.'5 T. Cohen and M. Myers J. Org. Chem. 1988 53,457; K. Ramig M. Bhupathy and T. Cohen J. Am. Chem. SOC.,1988 110 2678. P. F. Korkowski T. R. Hoye and D. B. Rydberg J. Am. Chem. SOC.,1988 110 2676; W. D. Wulff D. C. Yang and C. K. Murray ibid.p. 2653. 10 C. Chen Y.-Z. Huang and Y. Shen Tetrahedron Lett. 1988 29 1033. '' A. Krief W. Dumont and A. F. De Mahieu Tetrahedron Lett. 1988 29 3269; A. Krief W. Dumont and J. L. Laboureur ibid. p. 3265. 12 J. S. Nowick and R. L. Danheiser Tetrahedron 1988 44 4113. 13 W. R. Dolbier jun. and C. R. Burkholder Tetrahedron Lett. 1988 29 6749. 14 N. De Kimpe P. Brunet R. Verhe and N. Schamp J. Chem. SOC.,Chem. Commun. 1988 825. M. Fedorynski A. Dybowska and A. Jonczyk Synthesis 1988 549. N. S. Sirnpkins Several reports describe new preparations and reactions of unsaturated cyclopro- panes particularly alkylidenecyclopropanes. McMurry has shown that the trouble- some reactions of phosphorane (8) can be carried out efficiently using tris-[2-(2- methoxyethoxy)ethyl]amine as a phase-transfer catalyst (Scheme 7).16 The method gives vastly superior results to the standard conditions and works well even with enolizable substrates.75'/o I B n O d (Bn = benzyl) \ 83 O/o Reagents i Ph3Pd (8) N\ \OnOM,) Scheme 7 Another very general procedure which gives good results is a modification of Cohen's Peterson approach (Scheme 8).17 By refluxing the initial Peterson adduct with excess Bu'OK the need to isolate the unstable /3-silylcarbinol intermediate is avoided and better overall results are achieved. R'b:2e3 lRbY:ej 5IRK;;] -Rb R3 R2 R2 R2 OLi R2 Reagents i LDMAN -45"C THF; ii R3CHO; iii Bu'OK Scheme 8 A third very interesting route to these products involves the reaction of alkenes with 3-phenylselenoalk- 1 -enylidene carbenes (e.g.Scheme 9).'* The example shown proved particularly interesting in that rearrangement of (9) to either (10) or (11) is possible. Vinylcyclopropanes and alkylidenecyclopropanes have been utilized recently by Motherwell in studies dealing with ring opening by TolS021 and Pd"-catalysed [3 + 2]cycloadditions respectively.'' Two groups have described asymmetric routes to the vinyl cyclopropane (12) (Scheme 10). Preparation of (S) -(12) using the now familiar chiral lactams of 16 J. A. Stafford and J. E. McMurry Tetrahedron Lett. 1988 29 2531. 17 T. Cohen S.-H. Jung M. L. Romberger and D. W. McCullough Tetrahedron Lett. 1988 29 25. 16 R. T. Lewis and W. B. Motherwell J. Chem.SOC.,Chern. Commun. 1988 751. l9 R. T. Lewis W. B. Motherwell and M. Shipman J. Chern. Soc. Chern. Commun. 1988,948; M. C. M. de C. Alpoim A. D. Morris W. B. Motherwell and D. M. O'Shea Tetrahedron Lett. 1988 29 4173. A1icyclic Chemistry I-lX -4 H202 (10) X = OH H SePh (11) X = SePh Scheme 9 0 -+ $N$~~~~~-C02Me C02Me 0 0 99% d.e. J J MeOz Cqr02M e CH,(CO,Me), Bu'OCO~_/-71 COzMe Me02C4-oC02Bu' pd,(ciba);CHCI chiral catalyst (R)-(12) 70% e.e. H i ,Me Chiral catalyst = PPhz Scheme 10 Meyers gives the final product in >99% e.e. although a four-step sequence is required.20 The more direct catalytic asymmetric route using palladium so far gives only 70% e.e.2' Other chiral cyclopropanes have been synthesized using camphor-derived chiral auxiliaries,22 and also starting with a chiral oxa~olidine.~~ Finally a chiral iron acyl 20 A.I. Meyers J. L. Romine and J. A. Fleming J. Am. Chem. SOC.,1988 110 7245. 21 T. Hayashi A. Yamamoto and Y. Ito Tetrahedron Lett. 1988 29 669. 22 K. Tanaka I. Funaki A. Kaji K. Minami M. Sawada andT. Tanaka J. Am. Chem. SOC.,1988,110,7185. 23 D. J. Aitken J. Royer and H.-P. Husson Tetrahedron Lett. 1988 29. 3315. N. S. Simpkins auxiliary enables asymmetric synthesis of either cis-or trans-substituted cyclopro- panecarboxylic acids,24 whereas an alternative strategy employs tartrates as chiral starting materials2' (e.g. Scheme 11). co PPh3 yo ,PPh3 I' I i-iii iv v + -02" major diastereoisomer C02Me C02Me 1 1 Reagents i 4 eq.ZnCI,; ii 1.5 eq. Et,Zn; iii 4 eq. CH,I,; iv Br,; v HxMe Ph NH Scheme 11 3 Four-membered Rings A review dealing with the topic of cyclobutanones and cyclobutenones in nature and in synthesis has been published.26 A number of simple 1,3-disubstituted cyclo- butanes are available using a straightforward malonate alkylation pr~cedure.~' As in previous years intramolecular [2 + 2]cycloadditions have proved a popular entry to cyclobutane-containing skeletons.** Two reports indicate the utility of ring expansion of cyclopropanes as an entry to cyclobutanes (Scheme 12). The BF,.OEt,-mediated rearrangement of optically active cyclopropane (13) occurred with high stereoselectivity with the minor isomer 24 P.W. Ambler and S. G. Davies Tetrahedron Lett. 1988 29 6979 6983. 25 A. Krief W. Dumont and P. Pasau Tetrahedron Lett. 1988 29 1079; A. Krief and W. Dumont ibid. p. 1083; see also A. Krief D. Surleraux and H. Frauenrath ibid. 6157. 26 D. Bellus and B. Emst Angew. Chem. Int. Ed. Engl. 1988 27 797. 27 P. E. Pigou and C. H. Schiesser J. Org. Chem. 1988 53 3841. 28 A. G. Schultz M. Plummer A. G. Taveras and R. K. Kullnig J. Am. Chem. Soc. 1988 110 5547; A. De Mesmaeker S. J. Veenstra and B. Ernst Tetrahedron Lett. 1988 29 459; R. L. Funk P. M. Novak and M. M. Abelman ibid. p. 1493. Alicyclic Chemistry OH (13) 95 5% A Scheme 12 possibly arising from an isomer of (13) carried through from previous steps.29 The pinacol-type rearrangement of the epoxide derived from (14) occurs in situ presum-ably catalysed by m-chlorobenzoic acid.30 A selection of other substrates behave similarly and the intermediate oxaspiropentanes are isolable in certain cases.Silyloxyacetylenes have proved effective in cycloadditions with ketenes to give cyclobutenone products (e.g. Scheme 13).31Cyclobutenone products themselves can also be combined with silyloxyacetylenes in an efficient aromatic annulation pro- ~edure.~~ Addition of an organolithium to dialkyl squarates followed by acidic treatment constitutes an efficient route to substituted cyclobutenediones (Scheme 14).33 Replacement of the second R'O group with a different organolithium is also possible OSiPr; CH* P r ASi 0, I I1 85 % Scheme 13 ,"'"uo R'O (i)RLi ___,IZN-HCI Oxo (ii) H20 R CHIC12 R'O R'o OH R'O R (15) Scheme 14 29 J.Salaun and B. Karkour Tetrahedron Lett. 1988 29 1537. 30 D. W. McCullough and T. Cohen Tetrahedron Lett. 1988 29 27. 31 C. J. Kowalski and G. S. Lal J. Am. Chem. Soc. 1988 110 3693. 32 R. L. Danheiser A. Nishida S. Savariar and M.P. Trova Tetrahedron Lett. 1988 29 4917. 33 M. W. Reed D. J. Pollart S. T. Perri L. D. Foland and H. W. Moore J. Org. Chem. 1988 53 2477; L. S. Liebeskind R. W. Fengl K. R. Wirtz and T. T. Shawe ibid. p. 2482. 146 N. S. Simpkins and the intermediates (15) find an alternative application in a preparation of b~tenolides.~~ In contrast to the cyclopropanation process mentioned above,9 alkynyl chromium and tungsten carbene complexes give [2 + 2Jcycloaddition products with a range of enol ethers.35 The resulting adducts e.g.(16) appear to have some potential for cyclobutanoid synthesis (Scheme 15). OMe (16) M = Cr or W -Me H Scheme 15 In another 12 + 2]cycloaddition process cyclobutylamines are prepared following trapping of keteniminium ions with alkenes and in situ reduction using cyanoboro- h~dride.~~ Finally two groups have described syntheses of naturally occurring cyclobutane amino acids.37 4 Five-membered Rings A number of interesting and varied constructions of cyclopentanoids have appeared this year. Functionalized cyclopentenes can be prepared via base-induced ring contraction of thiocarbonyl Diels- Alder adducts (Scheme 16).38 Excellent yields are obtained although the conditions for the second step need to be tailored to each particular substrate.The method is particularly attractive in that simple dienes rather than carbonyl partners are employed in the annulation. OTBS OTBS OTBS 82'/o 92Yo Scheme 16 34 S. T. Perri L. D. Foland and H. W. Moore Tetrahedron Lett. 1988 29 3529. 35 K. L. Faron and W. D. Wulff J. Am. Chem. SOC.,1988 110 8727. 36 C. J. Urch and G. C. Walter Tetrahedron Lett. 1988 29 4309. 37 Y. Gaoni Tetrahedron Lett. 1988 29 1591; G. W. J. Fleet J. A. Seijas and M. P. Vasquez Tato Tetrahedron 1988 44,2011. 38 S. D. Larson J. Am. Chem. SOC.,1988 110 5932. AIicyclic Chemistry Me A,toluene 4-t-butylcatechol LMe (17) 81% 0 Scheme 17 Three reactions which afford cyclopentenones are outlined in Scheme 17.Forma- tion of the spirocyclic methylenecyclopentenone (17) is thought to occur uia an oxy-Cope rearrangement followed by cyclization of an enol intermediate.39 Cyclo- pentanones such as (18) are prepared stereoselectively in 40-70% yield presumably uia an allene oxide.40 The formation of (19) in large excess over its regioisomer (20) illustrates the utility of the SMe group in controlling the intermolecular Pauson reaction by ~helation.~~ Chains bearing a pendant NMe group exhibit a similar effect although oxygen groups do not work. Cyclopentenones are also available by photochemical rearrangement of quinone-derived starting materials such as ethers (21)42or ketals (22)43 (Scheme 18).0 hv hv & __* __. 0U R OMe Scheme 18 39 P. A. Jacobi L. M. Armacost J. I. Kravitz M. J. Martinelli and H. G. Selnick Tetrahedron Lett. 1988 29 6865; P. A. Jacobi L. M. Armacost J. I. Kravitz and M. J. Martinelli ibid. p. 6869; P. A. Jacobi and J. I. Kravitz ibid. p. 6873. 49 S. J. Kim and J. K. Cha Tetrahedron Lett. 1988 29 5613. 41 M. E. Krafft J. Am. Chem. Soc. 1988 110,968. 42 A. G. Taveras jun. Tetrahedron Lett. 1988 29 1103. 43 M. C. Pirrung and D. S. Nunn Tetrahedron Lett. 1988 29 163. N. S. Simpkins A cyclization/ring-contraction reaction initiated by an oxonium cation generated from an acetal allows the synthesis of cis-hydroindenes (Scheme 19).44 Similar products are also prepared using another annulation procedure (Scheme 20);45here the ketone is converted into the corresponding thermodynamic enolate which is then reacted with (23)to give an intermediate cyclopropanol that rearranges smoothly to the cyclopentanone.The yields for the first step proved somewhat disappointing and it was found to be important that R # H for the subsequent rearrangement step to give the desired cyclopentanone. Aromatic substituted cyclopentanones are also available by a method involving ring expansion starting with a substituted cyclopropyl ketone.46 a" SnCl CH,CI, -78 "C RO OR Scheme 19 OH Scheme 20 Scheme 21 shows two epoxide-based cyclizations which lead to highly functional- ized cyclopentanoid products.The first reaction is a modification of the hydrostanny- lation-cyclization procedure reported previously with the product radical opening the ep~xide.~~ The second process is also thought to be essentially a radical reaction and appears especially attractive due to its tolerance of other functionality mild reaction conditions and the fact that epoxides act as the radical initiator.48 Trost has again added significantly to the repertoire of transition metal catalysed cyclizations-Scheme 22 shows representative examples involving 1,6-diyne~,~~ dienyl allylic acetates," and enallenes." The preparation of (24) in stereoselective fashion is a particularly impressive feat. A notable feature of the method is that suitable precursors such as (25) are easily available from simple starting materials as shown- also using Pdo chemistry.44 M. Sworin and W. L. Neurnann J. Org. Chem. 1988 53 4894. 45 J. T. Carey and P. Helquist Tetrahedron Lett. 1988 29 1243. 46 B. Deb C. V. Asokan H. Ila and H. Junjappa Tetrahedron Lett. 1988 29 2111. 47 Y. Ichinose K. Oshima and K. Utimoto Chem. Lett. 1988 1437. 48 W. A. Nugent and T. V. RajanBabu J. Am. Chem. SOC.,1988 110 8561. 49 B. M. Trost and D. C. Lee J. Am. Chem. SOC.,1988 110 7255. 50 B. M. Trost and J. I. Luengo J. Am. Chem. SOC.,1988 110 8239. 51 B. M. Trost and J. M. Tour J. Am. Chem. SOC.,1988,110,5231; B. M. Trost and K. Matsuda ibid. p. 5233. Alicyclic Chemistry SnPh3 SnPh3 [Ref. 471 70% [Ref.481 Scheme 21 TBDMSO TBDMSO (dba),Pd,.CHCI Tol,P Et,SiH *< R 89% fOAc ,Pd' PhSOz (i) OC02Et Pdo -6 PhSO2 then > 00 SOzPh PhO2S SO2Ph (ii) acetylation SOzPh (25) 49% (24) 56% polymer-supported NiCIJCrCI Ed E 80'/o Scheme 22 Transition metal catalysed carbonylation-cyclization is perhaps even more syn- thetically attractive since more highly oxygenated products are produced. Two new variants which yield cyclopentenone products are highlighted in Scheme 23. In the preparation of (26) and related products two successive carbonylations occur with concomitant cyclization double-bond isomerization and ester formation.52 The E.Negishi G. Wu and J. M.Tour Tetrahedron Lett. 1988 29 6745.N. S. Simpkins n-Hex n-Hept CO(600psi.) C02Me NEt, MeOH CI,Pd(PPh,) 'T H 0 X = CI Br OAc OSO,Me efc. (26) 42-94% TBDMSO TBDMSO ArNC,Ni(cod),Bu;P Ph DMF 100°C H Ar = 2,6-dimethylphenyl (27) 83% Scheme 23 usual variety of allylic leaving groups can be usefully employed in the reaction as indicated above. The second reaction uses an aryl isocyanide in place of the more usual isoelectronic counterpart CO the products [e.g. (27)] being hydrolysable to the corresponding cyclopentenone~.~~ Enzymic methods allow the efficient enantioselective preparation of various hydroxycyclopentyl carboxylatess4 and the popular building block 4-hydroxy-2- cyclopentenyl acetate.55 Three chemical methodss6-s8 which allow the preparation of hydroxylated cyclopentanoids in high optical purity are illustrated in Scheme 24.Each of these methods is essentially a resolution and relies on the separation of diastereomeric products. 5 Six-membered Rings Treatment of suitable unsaturated substrates with I(py),BF4-HBF4 at low tem- perature results in cyclization to give six-membered ring iodides.59 A number of cyclohexane products having a 1,3-disposition of exo-cyclic alkene groups have been prepared using a palladium ene-type process (e.g. Scheme 25).60 The particular example shown is highly regio- and stereoselective with only the indicated product being obtained. Another palladium-mediated process converts a sugar-derived enol ether into the corresponding carbocycle.61 Various 2,5-cyclohexadien- 1-ones can be prepared from the corresponding dienes in higher yield than previously possible by adopting the Bu'OOH-PDC oxidation procedure used previously for allylic and benzylic oxidation (Scheme 26).62 53 K.Tarnao K. Kobayashi and Y. Ito J. Am. Chem. SOC., 1988 110 1286. 54 T. Sato H. Maeno T. Noro and F. Fujisawa Chem. Lett. 1988 1739. 55 T. Sugai and K. Mori Synthesis 1988 19; F. Theil S. Ballschuh H. Schick M. Haupt B. Hafner and S. Schwarz ibid. p. 540. 56 B. M. Eschler R.K. Haynes S. Krernmydas and D. D. Ridley J. Chem. SOC.,Chem. Commun. 1988 137. 57 E. A. Mash and S. B. Hemperly Tetrahedron Lett. 1988 29 4035. 58 F. Toda and K. Tanaka Tetrahedron Lett. 1988 29 1807. 59 J. Barluenga J. M. Gonzalez P.J. Carnpos and G. Asensio Angew. Chem. Int. Ed. Engf. 1988,27,1546. 60 W. Oppolzet R.E. Swenson and J.-M. Gaudin Tetrahedron Lett. 1988 29 5529. 6' S. Adam Tetrahedron Lett. 1988 29 6589. 62 A. G. Schultz A. G. Taveras and R. E. Harrington Tetrahedron Lett. 1988 29 3907; see also A. G. Schultz and A. G. Taveras ibid. p. 6881. Alicyclic Chemistry (ii) MCPBA Bu'O Bu'O Bu'O' 0 [Ref. 561 (and diastereomer) + '&OH HO8 &OH -+ [Ref. 571 ( -1429) recrystallize A[( -)-(29) ( -)-(28)] A vacuum ( -)(28) crystalline 100% e.e. AcO complex [Ref. 581 (28) /\/ \/\ (29) = Scheme 24 I 87% OAc Scheme 25 0 .:#' 73yo Scheme 26 N. S. Simpkins An attractive two-stage procedure converts quinones through to functionalized cyclohexenones in stereoselective fashion (Scheme 27).63Addition of the second nucleophile (either R-or H-)is controlled by the lithium alkoxide function intro- duced in the first step.The two new groups thus end up trans. The chiral monoester (30)-available in large quantities by pig-liver esterase hydro- lysis of the corresponding diester-has been effectively manipulated to give lactones (31) and (32) or their enantiomers (Scheme 28).64 The important step here is the () (ii) BrMg-=-Ph 0 63Yo MeLi TMEDA THF 0 OH 90% Scheme 27 eO2I-l -e02H ';Io -a. H C02Me ! C02Me I Me Me (31) I 1 enantiomers of (31) and (32) Scheme 28 63 M. Solomon W. C. L. Jamison M.McCormick D. Liotta D. A. Cherry J. E. Mills R. D. Shah J. D. Rodgers and C. A. Maryanoff J. Am. Chem. SOC.,1988 110 3702. 64 M. Shimada S. Kobayashi and M. Ohno Tetrahedron Lett. 1988. 29 6961. Alicyclic Chemistry alkylation of (30) [or (33)] using LDA (2.1 equivalents) and MeI which proves highly stereoselective giving essentially only the cis-isomer shown. The desired lactones are then obtained by standard chemistry. (R)-( -)-5-Trimethylsilyl-2-cyclohexenone, highlighted last year as a useful chiral synthon for cyclohexanes has been transformed into several natural products.6s As always numerous studies relating to the Diels-Alder reaction have appeared. 2-Benzoyloxynitroethylenereacts smoothly with a number of dienes to give nitro- cyclohexenes which can be reduced to the corresponding amines using LiAlH4 .66 The diene (34) gives the expected adducts in Diels-Alder reactions which can then be oxidized and treated with Bu4NF to give cyclohexadienes as products (Scheme 29).67 <SPh PhSO2-(i) 'CO,Me ABu,NF ozMe \ (ii) MCPBA SiMe3 SiMe3 (34) Scheme 29 A CONH2 (35) (36) Reagents i MeO,CCH=CHCO2Me; ii Bu,NF THF-15% H,O Scheme 30 The intriguing cyclic azadiene (35) also gives Diels-Alder adducts such as (36) which are perfectly set up to give substituted cyclohexanones (C2-C3 bond cleavage) on fluoride treatment (Scheme 30).68The reaction proved to be exo-selective and interestingly fluoride treatment of some adducts results in cleavage of the Cl-C2 bond to give substituted glutarimides.A detailed account of the asymmetric Diels- Alder reaction of @-unsaturated N-acyloxazolidinones has been published.69 Dienes bearing sulphide sulphoxide or sulphone groups are effective in Diels- Alder reaction^.^' Sulphones are useful activating groups for dienophiles as empha- 65 M. Asaoka K. Takenouchi and H. Takei Tetrahedron Lett. 1988,29,325; M. Asaoka K. Takenouchi and H. Takei Chem. Lett. 1988 1225; M. Asaoka N. Fujii and H. Takei ibid. 1655. 66 G. A. Kraus J. Thurston P. J. Thomas R. A. Jacobson and Y. Su Tetrahedron Lett. 1988 29 1879. 67 J. J. Pegram and C. B. Anderson Tetrahedron Lett. 1988 29 6719. 60 M. Rivera H. Lamy-Schelkens F. Sainte K. Mbiya and L. Ghosez Tetrahedron Lett. 1988 29 4573. 69 D.A. Evans K. T. Chapman and J. Bisaha J. Am. Chem. Soc. 1988 110 1238. 70 S.-S. P. Chou and D.-J. Sun J. Chem. SOC.,Chem. Commun. 1988 1176. N. S. Simpkins H / SO,Ph PhMe 172 “C,96h IH Ph02S 92% [Ref. 711 (OTBDMS . -. R R SOzPh PhO2S [Ref. 721 Scheme 31 sized by two recent examples of intramolecular Diels- Alder (IMDA) processes (Scheme 31).71972 Substantial interest seems to have focused on the IMDA reactions of substituted furans and some more notable example^^^-^^ are therefore highlighted in Scheme 32. These reactions illustrate the varied dienophiles and the disparate reaction conditions that have proved effective in furan Diels-Alder reactions. One other related report deals with the high-pressure induced Diels- Alder cycloadditions of butenolides using electron-rich diene~.~~ Finally Diels- Alder-type products have also been obtained in reactions involving propargyl cations78 and aryl chromium carbene complexes.79 6 Larger Rings Lee has shown that bifunctional reagents having allylsilane and acetal functions can give seven-membered ring products (Scheme 33).80 Another reaction which uses a functionalized allylsilane gives similar products via an intramolecular [3 + 41 cycloaddition process.81 Certain seven-membered rings functionalized with carboxylate groups can be prepared via a tandem a-hydroxycyclobutane rearrangement-retro-aldol cleavage process (Scheme 34).82A 71 D.Craig D. A. Fischer 0. Kemal and T. Plessner Tetrahedron Lett. 1988 29 6369.72 M. E. Jung and V. C. Truc Tetrahedron Lett. 1988 29 6059. 73 L. M. Harwood G. Jones J. Pickard R. M. Thomas and D. Watkin Tetrahedron Lett. 1988,29 5825. 74 S. G. Cauwberghs and P.J. DeClercq Tetrahedron Lett. 1988 29 6501. 75 W. H. Darlington and J. Szmuszkovicz Tetrahedron Lett. 1988 29 1883. 76 J. A. Cooper P. Cornwall C. P. Dell and D. W. Knight Tetrahedron Lett. 1988 29 2107. 77 R. M. Ortuno A. Guingant and J. d’Angelo Tetrahedron Lett. 1988 29 6989. ” P. G.Gassman and S. P. Chavan Tetrahedron Lett. 1988 29 3407. 79 A. Yamashita J. M. Timko and W. Watt Tetrahedron Lett. 1988 29 2513. 8o T. V. Lee R. J. Boucher and C. J. M. Rockell Tetrahedron Lett. 1988,29,689; T. V. Lee R. J. Boucher K. L. Ellis and K. A. Richardson ibid. p.685. R. J. Giguere S. M. Duncan J. M. Bean and L. Purvis Tetrahedron Lett. 1988 29 6071. 82 B. C. Ranu and D. C. Sarkar J. Chem. Soc. Chem. Commun. 1988 245. Alicyclic Chemistry 19 Kbar H, Pd-BaSO, ch H 9-155 I w -AO0 .H -CP 24 h 20 "C A.'U [Ref. 731 [Ref. 751 COzMe 280"C 16h ~ Scheme 32 TMSOTf-TiCI SiMe,(YoSiMe'5 H 63% [Ref. 761a H:OMe Me0 OMe H& Scheme 33 ST) * @Me HgO HBF, aq.THF n * COZH Jones reagent-GMe Me COzH Scheme 34 N. S. Simpkins fused system was also synthesized using the same method and conveniently com- bined the two rearrangements in one pot. Both tropone and 2-chlorotropone undergo nucleophilic attack at the 2-position using various nucleophiles including en01ates.~~ The products are useful in natural product synthesis especially in cycloaddition reactions highlighted in previous years.Two interesting examples of seven-membered ring formation using the divinyl- cyclopropane rearrangement are shown in Scheme 35. In the first example the highly functionalized divinylcyclopropane is produced in situ by enolization of the acidic P-keto ester function.84 Other conditions can be used to produce the opposite epimer at C4. In the preparation of (37) it is the cyclopropane group that is formed in situ -again the reaction is highly ~tereocontrolled.~~ M e 0 9 Et,N TMSCl TMSO eH Bu'0,C DMF,50 "C MeO.. -Bu'O~C OBn OBn 87% (Bn = benzyl) [Ref. 841 0 (37) 67% [Ref. 851 Scheme 35 Several other syntheses of seven-membered rings have been aimed at natural products of the guaianolide or pseudoguaianolide family (Scheme 36).86-88Both intermediates (38) and (39) are converted into known precursors of the natural product ( f )-confertin.An unsuccessful approach to the lathrane diterpenes incorporated the conversion of (40) into (41) as the key ring-forming reaction (Scheme 37).89 Similar ring-closure processes also worked on a number of simple model compounds in each case using silyl enol ethers as nucleophiles. Further details of the rearrangement of divinylcyclobutanes to cyclooctenones have been published." Intramolecular coupling reactions involving aldehydes have 83 J. H. Rigby C. H. Senanayake and S. Rege J. Org. Chem. 1988,53 4596. 84 P.A. Wender and K. Brighty Tetrahedron Lett. 1988 29 6741. 85 H. M. L. Davies C. E. M. Oldenburg M. J. McAfee J. G. Nordahl J. P. Henretta and K. R. Romines Tetrahedron Lett. 1988 29 975. 86 M. Kennedy and M. A. McKervey J. Chem. SOC. Chem. Commun. 1988 1028; H. Duddeck M. Kennedy M. A. McKervey and F. M. Twohig ibid. p. 1586. P. T. Lansbury J. P. Galbo and J. P. Springer Tetrahedron Lett. 1988 29 147. 88 M. C. Welch and T. A. Bryson Tetrahedron Lett. 1988 29 521. 89 T. F. Braish J. C. Saddler and P. L. Fuchs J. Org. Chem. 1988 53 3647. 9u S. A. Miller and R. C. Gadwood J. Org. Chem. 1988 53 2214. Alicyclic Chemistry (i)(ii) mandelate (Bu'O),AIH @Me\AcO OH (38) [Ref. 861 Bu'OK SU Go [Ref. 871 0 NaOH,H,O, TBDMSO TBDMSO (39) [Ref.881 Scheme 36 TBDMSO 0 T a - MeS-S+Me BF,-q&yMeS MeS SMe (40) (41) 77% Scheme 37 been used in assembling the cyclooctene ring present in the tricyclic framework of ophiobolins and ceroplastols (Scheme 38).91*92 The intermediate (42) was taken on to the natural products albolic acid and ceroplastol 11. Other methods for eight-membered ring formation include ring expansions using cycl~butanes,~~ and the very elegant [4 + 41 cycloaddition procedure highlighted last year.94 Finally; Marshall has further expanded his studies of cembranolide synthesis utilizing methods such as the [2,3]-Wittig ring contraction and allyltin reaction^.'^ 91 M. Rowley and Y. Kishi Tetrahedron Lett. 1988 29 4909.92 N. Kato H. Kataoka S. Ohbuchi S. Tanaka and H. Takeshita J. Chem. SOC.,Chem. Commun. 1988 354. 93 T. Fujiwara T. Ohsaka T. Inoue and T. Takeda Tetrahedron Lett. 1988 29 6283; H. Suginome M. Itoh and K. Kobayashi J. Chem. SOC.,Perkin Trans. 1 1988 491. 94 P. A. Wender N. C. Ihle and C. R. D. Correia J. Am. Chem. SOC.,1988 110 5904. 95 J. A. Marshall and W. Y. Gung Tetrahedron Lett. 1988 29 1657; J. A. Marshall and J. A. Markwalder ibid. p. 4811; J. A. Marshall E. D. Robinson and J. Lebreton ibid. p. 3547. 158 N. S. Simpkins Bu'Ph,SiO OH I? Y [Ref.91] TiCI, Zn,THF b \ \ [Ref. 921 Scheme 38 (42) 7 Bicyclics and Polycyclics Certain bridged ketones can be substituted at the bridgehead position by means of a cuprate/alkoxide mixture the reaction apparently proceeding via in situ formation of the bridgehead en one^.^^ A number of interesting hydrindanone derivatives can be prepared using a hetero- Claisen rearrangement (e.g.Scheme 39).97 Other electron-deficient allenes also participate in the reaction and the products can be further transformed e.g. (43) to (44) using HJPd followed by A1,03. An extension of previous studies has shown that Friedel-Crafts acylation of cycloalkenes can lead to useful polycyclic products.98 The polycyclization method described by Deslongchamps can be used to synthesize a steroidal skeleton in a single step (Scheme 40).99 The result is accompanied by a detailed analysis of the stereochemical aspects involved in formation of rings C and D.Another application of the rearrangement chemistry illustrated in Scheme 2 is in the preparation of spiro-fused ring systems. loo The preparation of variously sub- + =C=/SozPh-q+ Po -pdh NH SOzPh COMe COMe (44) (43) 85% Scheme 39 96 G. A. Kraus and P. Yi Synth. Commun. 1988 473. 97 A. Bosum and S. Blechert Angew. Chem. Znt. Ed. Engl. 1988 27 558. 98 A. Tubul and M. Santelli J. Chem. SOC. Chem. Commun. 1988 191. 99 J.-F. Lavallee and P. Deslongchamps Tetrahedron Lett. 1988 29 6033. I00 S. Nagumo H. Suemune and K. Sakai Tetrahedron Lett. 1988 29 6927. Alicyclic Chemistry C02Me cs,co ___, &+p CHCI C02Bu' Scheme 40 NHTs NHTs pyJ-TsNSO BF,.OEt d+Cb Me [Ref.1011 Me Me N,CHC02Et b H (45) [Ref. 1021 Me3Si02C Me (i) LDA THF Me,SiCI -78 "C (ii) PhMe reflux OSiMe (46) [Ref. 1031 Me Scheme 41 stituted decalin systems remains an important topic as indicated by chemistry highlighted in Scheme 41.'0'-'03Compounds (45) and (46) are potentially useful precursors in syntheses of compactin or mevinolin. Rearrangement of ketones bearing silylacetylenic side chains gives bicyclic products containing an allylsilane function (Scheme 42).'04 Several ketones having a methyl group in the 2-position [e.g. (47; R = Me)] give products analogous to (48). Interestingly if R = H the intermediate vinylsilane undergoes alternative rearrangement to give (49). 101 M. J. Melnick A. J. Freyer and S.M. Weinreb Tetrahedron Lett. 1988 29 3891. I02 J. P. Marino and J. K. Long J. Am. Chem. SOC.,1988 110 7916. 103 S. J. Danishefsky and J. E. Audia Tetrahedron Lett. 1988 29 1371. 104 A. S. Kende P. Hebeisen and R. C. Newbold J. Am. Chem. SOC.,1988 110 3315. N. S. Simpkins (47) Trost has described the use of vinylcyclopropanols as terminators in some remark- able cyclizations leading to polycyclic systems of several types (Scheme 43).'05 In each case products are obtained stereoselectively in high yield and without recourse to high-dilution methods. Me,SiOSO,CF H OMe 91 O/O Scheme 43 Finally two cyclization methods which utilize palladium catalysis to furnish polycyclic products from aryl (or vinyl) iodides are shown in (Scheme 44).'06*'07 8 Natural Product Synthesis Funk has applied the Claisen rearrangement-ring contraction of macrocyclic lactone (50) to prepare the tricyclic product (51) which is well suited for elaboration to ingenol (52) (Scheme 45).*08 105 B.M. Trost and D. C. Lee J. Am. Chem. SOC.,1988 110 6556. 106 M. M. Abelman and L. E. Overman J. Am. Chem. SOC.,1988 110 2328. 107 R. C. Larock H. Song B. E. Baker and W. H. Gong Tefrahedron Lett. 1988 29 2919. 108 R. L. Funk T. A. Olmstead and M. Parvez J. Am. Chem. SOC.,1988 110 3298. Alicyclic Chemistry 161 I + \ H [Ref. 1061 Et Pd(OAc) ____+ Ph,P AOP \ [Ref. 1071 Scheme 44 Scheme 45 Total syntheses of ( i)-laurenene,"' taxusin,"' ginkgolides A"' and B,'" and two independent syntheses of forskolin have been reported.' l3 Most notable this year has been the focus of synthetic attention on compounds of the esperamicin/calicheamicin family.This is hardly surprising considering their novel and challenging structural features combined with their potent biological profiles. Particularly impressive is the DNA cleavage ability of compounds such as calicheamicin yln (53),which is ascribed to the sequence of events in Scheme 46 leading to the benzenoid biradical (54). Nucleophilic addition to the Cl-C2 double bond which brings C6 and C11 closer together is thought to be R prerequisite for I09 P. A. Wender T. W. von Geldern and B. H. Levine J. Am. Chern. SOC.,1988 110 4858. 110 R. A. Holton R.R. Juo H. B. Kim A. D. Williams S. Harusawa R. E. Lowenthal and S. Yogai J. Am. Chern. SOC.,1988 110 6558. 'I' E. J. Corey and A. K. Ghosh Tetrahedron Lett. 1988 29 3205. 112 E. J. Corey M.-C. Kang M. C. Desai A. K. Ghosh and I. N. Houpis J. Am. Chern. Soc. 1988 110 649; E. J. Corey and A. V. Gavai Tetru:'tedronLett. 1988 29 3201. 113 S. Hashimoto S. Sakata M. Sonegawa and S. Ikegami J. Am. Chern. SOC.,1988 110,3670; E. J. Corey P. Da Silva Jardine and J. C. Rohloff ibid. p. 3672. 162 N. S. Simpkins 0 0 s\ SMe (54) (53) Scheme 46 the cyclization. Synthetic studies have prepared suitable model systems capable of probing this hypothesis e.g. (55),'14 (56),'15 and (57).lI6 Finally more advanced synthetic intermediates have been obtained by both Schreiber and Danishefsky e.g.(58)'" and (59).'18 0 0 Meo2c&H H H \\\ /// OTBDMS \=/ 114 K. C. Nicolaou Y. Ogawa G. Zuccarello and H. Kataoka 1.Am. Chem. SOC.,1988 110 7247; K. C. Nicolaou G. Zuccarello Y. Ogawa E. J. Schweiger and T. Kumazawa ibid. p. 4866. 115 P. Magnus R. T. Lewis and J. C. Huffman J. Am. Chem. Soc. 1988 110 6921; P. Magnus and P. A. Carter ibid. p. 1626. A. S. Kende and C. A. Smith Tetrahedron Lett. 1988 29 4217; see also P. A. Wender M. Harmata D. Jeffrey C. Mukai and J. Suffert Tetrahedron Lett. 1988 29 909. 117 S. L. Schreiber and L. L. Keissling J. Am. Chem. Soc. 1988 110 631. 118 S. J. Danishefsky N. B. Mantlo D. S. Yamashita and G. Schulte J. Am. Chem. Soc. 1988 110 6890.