J. CHEM. soc. PERKIN TRANS. 1 1993 265 1 Bicycloannulation of a-Bromo a,p-Unsaturated Esters; Synthesis of the Tricycl04.4.0.0~~~decaneFramework and its Congeners Hisashiro Hagiwara," Futoshi Abe and Hisashi Uda Institute for Chemical Reaction Science, Tohoku University, Katahira, Aoba-ku, Sendai 980, Japan Reactions of the kinetic enolates 6 of 1-acetylcyclohexenes 5 with a-bromo a,S-unsaturated esters 7 proceed via a successive Michael-Michael-substitution pathway to give methyl 2-oxotricyclo- 4.4.0.0'.5decane-5-carboxylates 8 in a one-pot operation. It is well recognised that there is a plethora of highly condensed carbocyclic frameworks, particularly in terpenoids. Among such carbocyclic architectures, the tricyclo4.4.0.0'~sdecane framework 1, which is contained in cubebene 2 and related compounds,2 is unique and unusual, because five- and six- membered rings are fused by forming a three-membered ring.This tricyclo C4.4 .O .O '1 5decane framework has attracted much attention from synthetic organic chemists and has been synthesized so far by intramolecular addition of a keto carbenoid function in the synthesis of cubebene 23or photo- induced rearrangement of a cross-conjugated cyclohexadienone in the synthesis of (-)-9-anastreptone 4.4 In the course of our cs, n TricycI04.4.0.0'~5decane1 aCubebene 2 3 (-)-Anatreptone 4 synthetic efforts directed towards annulation by successive Michael reactions, we disclose herein an alternative reaction for the synthesis of tricyc104.4.0.0~~~decanes8 and their congeners by successive Michael-Michael-substitution of 1-acetylcycloalkenes5 and a-bromo a$-unsaturated esters 7a and 7b (Scheme 1).6 In this particular reaction, three carbon-carbon 0 0-0 I *RR R' C02Me 5a R'=H 6 8aR=Hb R'= 4,4-OCHamp;H,O 7a R=H 8bR=Me c R' = 3-OTBDMS 7b R=Me Scheme 1 bonds are formed successively, at first intermolecularly and then intramolecularly, twice, thereby making two rings (bicyclo- annulation) in a one-pot operation.Results and Discussion Methyl a-bromoacrylate 7a was easily prepared by bromination of methyl acrylate 9a in carbon tetrachloride followed by distillation from quinoline and stored with a small amount of hydroquinone in a freezer. Methyl a-bromocrotonate 7b * was also prepared in the same manner to give a mixture of E and 2 isomers in a 1 :2 ratio (NMR) which were separable by medium- pressure liquid chromatography (MPLC).The (,!?)-isomer of ester 7b was quantitatively isomerised into the thermodynamic- ally more stable (2)-isomer (A-value, C0,Me = 1.27, Br = 0.38 kcal m~l-')~,? by heating in ethanol. Since the presence of ethanol is essential for rapid isomerisation,80,c the process probably proceeds via a Michael-type addition4imination pathway, though the intermediary adduct of ethanol was not detected by monitoring of the isomerisation by NMR spectro- scopy (Scheme 2). The geometries of the E and 2 bromo-R+ i kBr-RYBrC0,MeC02Me * Br C02Me ji 9aR=H 1Oa 7a 9bR=Me 10b 7b FtBr 111 Me/ 'C0,Me .7 C02Me (07b (Z)-7b Scheme 2 Reagents and conditions: i, Brz, CCl,; ii, quinoline, distil-lation; iii, ethanol, reflux crotonates 7b were assigned by comparison of the chemical- shift-values of the olefinic protons 8c*10 (see Experimental section).The requisite 1-acetylcycloalkenes and their trimethylsilyl enol ethers 11,13,15,17and 19 were prepared according to the known procedures." Reaction of the kinetic enolate 6a of 1-acetylcyclohexene 5a, generated from the trimethylsilyl enol ether 11 by reaction with methyllithium in tetrahydrofuran (THF), with methyl a-bromoacrylate 7a gave methyl 2-oxotri- cyclo~4.4.0.0'~5decane-5-carboxylate12a in 51yield (Scheme 1 and Table 1, entry 1). The reaction with methyl (Z)-a- bromocrotonate 7b afforded methyl 4-methyl-2-oxotricyclo- 4.4.0.0'~5decane-5-carboxylate 12b in 62 yield (Table 1, entry 2).The kinetic enolate 6 (R' = H), generated directly from 1 -acetylcyclohexene 5a by treatment with lithium diiso- propylamide (LDA), resulted in the recovery of the starting enone 5, probably because the extra diisopropylamide initiated polymerisation of the a-bromo a,P-unsaturated esters 7a and t 1 cal = 4.184 J. Table 1 Bicycloannulation of 1-acetylcycloalkene with a-bromo a$-unsaturated ester Entry Starting material Product I C0,Me 11 1 12a R=H 51 2 12bR=Me 62 (76)' 3 6WOb 4 62' OTMS 0 13 5 14aR=H 37 6 14bR=Me 20 (28)a 7 18ob OTMS R TBDMSO TBDMSO C0,Me 15 8 16aR=H 38 9 16bR=Me 33 (41)" 10 33b OTMS 0 17 C0,Me 11 18aR=H 52 12 18bR=Me 51 ?TMS om 19 C0,Me 13 20aR=H 37 14 20bR=Me 38 Yield calculated from consumed 1-acetylcyclohexene.Yield from the reaction in the presence of HMPA. 'Yield from the reaction in the presence of cyclohexene. 7b. Similarly, the trimethylsilyl enol ethers 13 and 15 from substrates 5b and 5c gave the corresponding tricyclic com- J. CHEM. soc. PERKIN TRANS. I 1993 pounds 14 and 16 in 20-38 yield (Table 1, entries 5-10). Addition of hexamethylphosphoric triamide (HMPA) did not improve the yield (Table 1, entries 3,7 and 10). The major by- product in these reactions was the recovered l-acetylcyclo- hexene (Table 1, entries 2, 6 and 9).The cyclopentene 17 and cycloheptene derivatives 19 also underwent the bicyclo-annulation to give the tricyclic analogues 18 and 20 in 37-52 yield, respectively . Determinationof Stereochemistry.-The tricyclic compounds thus obtained were spectroscopically and chromatographically homogeneous. A phase-sensitive NOESY experiment on compound 16b (400 MHz) showed nuclear Overhauser effects (NOE) between the methyl group and the protons as indicated by arrows (Fig. 1). Especially diagnostic for determination of n 16b "d Fig. 1 Result of phase-sensitiveNOESY of compound 16b the relative stereochemistry from C-1 to C-6 are the NOES between the methyl group at C-4 and the proton at C-6, establishing the syn relationship between these two groups.The relative stereochemistry at C-7, however, was ambiguous from its coupling constant of the proton at C-7 (unresolved broad multiplet, w3 12 Hz), probably because of distortion of the six- membered ring which fused with a cyclopropane ring. Then, treatment of compound 16b with lithium in liquid ammonia cleaved the cyclopropane ring to afford two known decalones 22 and 23 l2 in 59 yield (ratio 1 :1.2) (Scheme 3). The less polar decalone 22 isomerised, by treatment with sodium methoxide in methanol, to the more polar compound 23 in 94 yield. Both decalones 22 and 23 exhibited clear coupling patterns of triplets of doublets at 6 3.47 (1 H, td, J 10.1 and 3.5 Hz) and 6 3.81 (1 H, td, J 9.8 and 4.3 Hz), respectively, indicating that the protons on the carbons bearing the tert- butyldimethylsiloxy groups at C-8 are axial.Stereochemical aspects of the reductive ring opening with lithium in liquid ammonia are explained as follows. Successive transfers of an electron to the tricyclic compound 16 provided the dienolate 21 whose tert-butyldimethylsiloxy group occupied an equatorial position. A proton approached the ester enolate of the dienolate 21 from the amp;face of the molecule, thereby avoiding steric hindrance due to the tert-butyldimethylsiloxy group. Axial protonation occurred at the ketone enolate of the dienolate 21. As a result, the decalone 22 having a cis-steroidal conformation was formed as a primary product. Since both decalones 22 and 23 are starting materials for the synthesis of (+)-dihydro- compactin, and since the relative stereochemistry of the more stable decalone 22 was fully assigned from the 600 MHz NMR spectrum,' the relative stereochemistry of the tricyclic compound 16 was determined as depicted in Fig. 1.Even after prolonged heating with sodium methoxide, the methoxy- carbonyl group at C-5 kept its axial orientation. Other tricyclic compounds 12, 14, 16, 18 and 20 seem to have the same stereostructures, deduced from the narrow distribution of chemical-shift-values of the secondary methyl (6 1.16 k 0.02) and the methoxy (S 3.73 amp; 0.02) groups. Reaction Pathway.-The reaction of the kinetic enolate, generated from the trimethylsilyl enol ether 24, with a-bromo J.CHEM. soc. PERKIN TRANS. 1 1993 -____) HIMe TBDMSO C02Me Me02C 0-Si-Me Bu' 16b 16b 21 ii H n Me IH 22 23 Scheme 3 Reagents: i, Li, liq. NH,; ii, MeONa, MeOH 25a R = H 2624 25b R = Me -0-2-* CQ2Me rJ C02Me C02Me 11 12b 27 28 Scheme 4 Reagents: i, MeLi, a-bromo a$-unsaturated ester 7;ii, MeLi, cyclohexene, methyl (Z)-bromocrotonate 7b a,P-unsaturated esters 7a and 7b gave only the single Michael adduct 25a and 25b in 20 and 11 yield, respectively. Also, the 2:l adduct 26 of 1-acetylcyclohexene 5a and methyl a-bromocrotonate 7b was isolated as a minor constituent. The formation of adduct 26 is explained by the Michael addition of the enolate 27 to 1-acetylcyclohexene 5a followed by intra- molecular aldol condensation.There are two alternative pathways for the formation of a cyclopropane ring, the Michael- substitution or a carbenoid addition pathway 27 +28 --* 12b (Scheme 4). However, the latter pathway was denied by the following experiment. The addition of one mole equivalent of cyclohexene (Table 1, entry 4) provided only the tricyclic compound 12b in 62 yield. No adduct with cyclohexene was isolated. These results indicate that the present reaction was initiated at first by Michael addition of the kinetic enolate of l-acetyl- cycloalkene to an a-bromo a,amp;unsaturated ester 7 and the formation of the cyclopropane ring proceeded via the successive Michael-substitution reaction pathway. The stereochemical course of the reaction drawn from these results is as follows.Methyl 2-a-bromocrotonate 7b approaches the enolate 29 from the opposite face of the tert-butyldimethylsiloxy group. After intermolecular chelation of the lithium cation on the kinetic enolate 29 with the methoxycarbonyl group of compound 7b, the first Michael addition occurred via the s-cis conformation of ester 7b. It is noteworthy that 1,6 remote stereocontrol was realised in this particular process, since the configuration of the secondary methyl group of adduct 30was controlled by the stereochemistry at C-3 of the enolate 29. Then the intra- molecular second Michael addition proceeded from the a-face of the a,P-unsaturated carbonyl moiety of adduct 30by keeping intramolecular chelation between the lithium cation on the ester enolate and carbonyl group to give bicycle 31.Finally, an intramolecular substitution completed the tricyclo-4.4.0.01*5decane framework (Scheme 5).In the case when methyl (E)-a-bromocrotonate 7bwas used for the reaction with the kinetic enolate 6c, the products isolated were l-acetyl-3- (tert-butyldimethylsi1oxy)cyclohexene 5c and a small amount of methyl (2)-a-bromocrotonate 7b.Supposing that the present reaction proceeds via the s-cis conformation of the (E)-crotonate 7b, the steric interference between the olefinic methyl group of (E)-7b and the enolate moiety of compound 29 might disturb the formation of a cyclic and closed chelated structure in the initial intermolecular Michael reaction, which proceeded via an open non-chelated transition state.Consequently, the enolate of the single Michael adduct with methyl (E)-a-bromocrotonate 7b could not proceed to the second intra- molecular Michael addition, and the retro-Michael reaction Li it, n TBDMSO TBDMSO 29 Me Br Me 7b 30 Li,H 0 IH Me0,C 16b 31 Scheme 5 resulted in isomerisation of the E isomer to the thermo- dynamically more stable 2 isomer. In summary, the present reaction offers easy access to tri- cycl04.4.0.0' 9'ldecane and related frameworks, making two rings stereoselectively by three successive bond-forming reac- tions (bicycloannulation) in a one-pot operation. Experimental IR spectra were recorded on a JASCO A-3 spectrophotometer for solutions in carbon tetrachloride.'H NMR spectra were obtained for solutions in deuteriochlorofonn with Bruker AM- 400 (400 MHz), CXP-300 (300 MHz), AC-250 (250 MHz) and JEOL PMX-60 (60 MHz) instruments with tetramethylsilane as internal standard. '3C NMR spectra were obtained for solutions in deuteriochloroform with the AC-250 spectrometer. J Values are given in Hz. Mass spectra were run on a JEOL JMS-DX300 spectrometer with a JMA-3500 data system. Gas chromato- graphy (GLC) was performed with an OV-1 column (l, 1 m) with the mass spectrometer as a detector. Medium-pressure liquid chromatography (MPLC) was carried out on a JASCO PRC-50 instrument with a silica gel-packed column. Micro- analysis was carried out in the microanalytical laboratory of this Institute.Anhydrous sodium sulfate was used for drying organic extracts. THF was distilled from LiAlH, before use. Upon typical work-up, product was extracted with solvent (2 x 20 cm3 for 1-10 mmol-scale reaction). The organic layer was washed successively with water once and brine once. After being dried over sodium sulfate, the extracts were evaporated under reduced pressure. Methyl (Z)-a-Bromocrotonate 7b.-To a stirred solution of methyl crotonate 9b (13.9 g, 139 mmol) in carbon tetrachloride (15 cm3) was added bromine (7.55 cm3, 147 mmol, 1.05 mol equiv.) at 0 "C. After the mixture had been stirred for 30 min at that temperature, the solvent was evaporated off under reduced pressure. Addition of quinoline (18.0 g, 1 mol equiv.) followed by repeated distillation (2 x 106 OC/65 mmHg) afforded a mixture of the geometrical isomers (13.3 g, 74.3 mmol, 53.3 in two steps) which were separable by MPLC eluent hexane- ethyl acetate (4: l).Methyl (E)-a-bromocrotonate 7b has d(60 MHz) 2.04 (3 H, d, J7.8), 3.81 (3 H, s) and 6.75 (1 H, q, J 7.8). Methyl (2)-a-bromocrotonate 7b has d(60 MHz) 1.93 (3 H, d, J6.8), 3.79 (3 H, s) and 7.32 (1 H, q, J6.8). A solution of methyl (E)-a-bromocrotonate (96.2 mg, 0.54 mmol) in ethanol (4 cm3) was heated under reflux for 2 h under nitrogen. Evaporation of the solvent followed by MPLC J. CHEM. SOC. PERKIN TRANS. I 1993 purification gave recovered methyl (2)-a-bromocrotonate 7b quantitatively. General Procedure for the Reaction of the Kinetic Enolate of a 1-Acetylcycloalkene with a-Bromo a,p-Unsaturated Ester 7.-To a stirred solution of the trimethylsilyl enol ether of 1-acetylcyclohexene5 in THF (1 mol dm3) was added MeLi (1.1 mol dm3 solution in diethyl ether) at -78 "C under nitrogen.After being stirred at that temperature for 20 min and then at 0 "C for 20 min, the mixture was treated with a solution of a-bromo a,P-unsaturated ester 7 (2 mol equiv.) in THF (1.3 mol dm3). In the experiments in entries 3, 7 and 10, HMPA (4 mol equiv.) was also added. The resulting solution was allowed to warm to room temperature for 3-5 h. The reaction was quenched by the addition of aq. ammonium chloride and the product was extracted with diethyl ether. Purification by MPLC afforded the tricyclic compound. Methyl 2-oxotricyc1o4.4.0.0'~'decane-5-carboxy1ate 12a (51.3); v,,,/cm-' 1740, 1725, 1440, 1200 and 1120; dH(60 MHz) 0.97-2.9 (13 H, m) and 3.73 (3 H, s); dc(62.5 MHz) 212.6, 170.6, 51.6,41.4,41.1, 31.6,28.2,24.5,20.3,20, 19.4 and 16.4; m/z 208 (M+, 31), 180 (Mf -CO, loo), 166 (42), 149 (36), 134 (39), 107 (51), 106 (42), 105 (31), 91 (52) and 79 (51) (Found: M', 208.1099. C12H,,0, requires M, 208.1099).Methyl 4-methy1-2-oxotricyc1o4.4.0.0'~'decane-5-carboxy1-ate 12b (62.2); v,,,/cm-' 1735, 1140, 1220 and 1120; 6,(60 MHz) 1.15 (3 H, d, J6), 1.25-3.06 (12 H, m) and 3.75 (3 H, s); dc(62.5 MHz) 212, 170.2, 51.6,45.8,42.7, 39.7, 31.3, 24.8,20.5, 20.2, 19.6, 16.7 and 16.6; m/z 222 (M', 31), 194 (M+ -CO, loo), 180 (65), 163 (43), 148 (82), 121 (76), 120 (67), 119 (44),105 (69), 93 (69), 92 (40), 91 (92), 81 (32), 79 (78), 77 (65), 67 (32), 65 (39), 59 (33), 55 (44), 53 (42), 41 (84) and 39 (68) (Found: M+, 222.1256.C13H,,03 requires M, 222.1256). Methyl 8,8-ethylenedioxy-2-0xotricycloC4.4.0.0 9 'ldecane-5 -carboxylate 14a (36.7); v,,,/cm-' 1745, 1735, 1445, 1360, 1300, 1200 and 1080; d(60 MHz) 0.73-3.23 (11 H, m), 3.74 (3 H, s) and 4.88 (4 H, s) (Found: C, 63.0; H, 6.8. C14H1805 requires C, 63.0; H, 6.8). Methyl 8,8-ethylenedioxy-4-methyl-2-oxotricyclo4.4.O.O1~'-decane-5-carboxylate 14b, an inseparable mixture of 1-acetyl-4,4-ethylenedioxycyclohexene5b and compound 14b. The ratio was determined to be 3:2 by analytical GLC (19.6 yield; v,,,/cm-' 1740, 1735, 1680, 1650, 1440, 1370, 11 50 and 1130; d(60 MHz) 1.18 (d, J6, Me of 14b),2.29 (Ac of 5b),3.1-1.4 (m), 3.75 (s), 3.9 (s), 3.99 (s) and 6.9-6.67 (m, olefinic H of 5b); m/z 280 (M+, 16.7), 221 (M+ -CO,Me, 100) and 86 (47) (Found: M+, 280.1311. C15H2005 requires M, 280.1311).Methyl 7-(tert-butyldimethylsiloxy)-2-oxotricyclo4.4.0.-01~'decane-5-carboxylate 16a (37.7); v,,,/cm-' 1740, 1735, 1440, 1260, 1200 and 900; d(60 MHz) 0.05 (6 H, s, Me,Si), 0.86 (9 H, s, Bu'), 1.162.76 (11 H, m), 3.7 (3 H, s, OMe) and 3.92 (1 H, m, 7-H); m/z 282 (24), 281 (M+ -C4Hg, loo), 249 (33), 239 (49), 89 (31), 75 (62) and 73 (45). Methyl 7-(tert-butyldimethylsiloxy)-4-methyl-2-oxotricyclo-4.4.0.01.5decane-5-carboxylate16b (33); v,,,/crn-' 1740, 1730, 1440, 1300 and 1200; dH(250 MHz) 0.079 (3 H, s, MeSi), 0.099(3H,s,MeSi),0.92(9H,s,But),1.19(3H,d,J6.5,4-Me), 1.2-1.4 (2 H, m), 1.56 (1 H, d, J2.5, 6-H), 1.45-1.65 (3 H, m), 1.82(1 H,dd, Jl8.5and9.9,3P-H),2.31(1H,dd, J18.4and9.2, 3a-H), 2.41 (1 H, m, 8a-H), 3.08 (1 H, ddq, J9.9, 9.1 and 6.5, 4a-H), 3.75 (3 H, s, MeO) and 4.15 (1 H, m, w+ 16, 7a-H); dc(62.5 MHz) 211.3, 170.2, 65.3, 51.9, 44.6, 44.0, 39.8, 34.7, 31.4, 31.1, 25.8, 18.1, 17.8, 17, 16.3, -4.81 and -4.85;m/z295 (M+ -C4Hg, loo), 263 (39, 253 (33), 89 (32), 75 (59) and 73 (46).Methyl 2-oxotricyclo4.3-0.0' ,5nonane-5-carboxylate 18a (52.3); v,,,/cm-' 1730, 1440, 1340, 1300, 1240 and 1060; d(60 MHz) 0.97-2.81 (11 H, m) and 3.74 (3 H, s); m/z 194 J.CHEM. SOC. PERKIN TRANS. 1 1993 (M', 3773, 166 (88), 152 (54), 135 (34), 120 (67), 107 (41), 93 (loo), 92 (61), 91 (78), 79 (47), 77 (50),41 (32) and 39 (40) (Found: M+, 194.0943. Cl1H1,O3 requires M, 194.0943). Methyl 4-methyl-2-oxotricyclo4.3.0.O1~5nonane-5-carboxyl-ate 18b (50.6); vmax/cm-' 1730, 1440, 1235, 1220 and 1055; d(60 MHz) 1.14 (3 H, d, J 6.2), 1.24-3.04 (10 H, m) and 3.72 (3 H, s); m/z 208 (M', 38), 180 (73), 166 (70), 134 (loo), 107 (76), 106 (39), 105 (41), 91 (56), 79 (54), 77 (37), 41 (36) and 39 (32) (Found: M+, 208.1098. C,ZH,,O3 requires M, 208.1099). Methyl 1 1 -oxotricyclo5.4.0.0'~8undecane-8-carboxylate 20a (37.4); vmax/cm-' 1730, 1440, 1290, 1240 and 1155; 6(60 MHz) 0.7-2.77 (15 H, m) and 3.73 (3 H, s); m/z 222 (M', 23), 194 (M' -CO, loo), 163 (32), 91 (30) and 79 (32) (Found: M', 222.1255.Cl3H1,O, requires M, 222.1256). Methyl 9-methyl- 1 1 -oxotricyclo 5.4 .O .O' *8undecane-8-carb-oxylate 20b (38.3); v,,,/cm-' 1730, 1440, 1285, 1240 and 1150;6(60 MHz) 1.14 (3 H, d, J6.4), 0.78-3.13 (14 H, m) and 3.72 (3 H, s); m/z 236 (M', 19) and 208 (M' -CO, 100) (Found: M+, 236.1412. C,,HZoO3 requires M, 236.1412). Cleavage of the Cyclopropane Ring of Tricycle 16b by Lithium in Liquid Ammonia.-To stirred liquid NH, ( -10 cm3; distilled from Na) was added Li (5.9 mg, 0.84 mmol) at -78 "C. After this had been stirred for 10 min, a solution of tricycle 16b (6 1 mg, 0.17 mmol) and water (6 mm3, 0.34 mmol) in THF (3 cm3) was added and the mixture was stirred at -78 "C for 3 min.The reaction was quenched by careful addition of aq. ammonium chloride. Extraction with diethyl ether followed by MPLC separation afforded methyl (1S*, 2R*, 4aS*, 8S*, SaR*)-S-(tert-butyldimethylsiloxy)-2-methyl-2-oxoperhydronaphthalene-1-carboxylate 22 (16.4 mg, 26.7); 6(300 MHz) 0.05 (6 H, s, Me2Si), 0.86 (9 H, s, Bu'), 1.17 (3 H, d, J 5.5, 2-Me), 1.20-1.33 (2 H, m), 1.49-1.65 (2 H, m), 1.84-3.01 (2 H, m), 2.08-2.19 (2 H, m),2.33-2.73(4H,m),3.47(1H,td,J10.1 and3.5,8-H)and3.67 (3 H, s, OMe), and methyl (1S*, 2R*, 4aR*, 8S*, SaR*)-S-(tert-butyldimethylsiloxy)-2-methyl-4-oxoperhydronaphthalene-1-carboxylate 23 (19.8 mg, 32.3); 6(300 MHz) 0.04 (6 H, s, Me2Si), 0.89 (9 H, s, But), 1.06 (3 H, d, J 7.14, 2-Me), 1.1 1-1.4 (3 H, m), 1.58-1.83 (2 H, m), 1.88-2.01 (2 H, m), 2.07-2.17 (1 H, m,3P-H),2.57-2.68(1H,m),2.71(1H,dd,J13.5and5.9,3a-H), 2.92-3.05 (2 H, m, 4a- and 1-H), 3.71 (3 H, s, OMe) and 3.81 (1 H, td, J 9.8 and 4.3, 8-H).To a stirred solution of sodium methoxide prepared from sodium hydride (50; 9.2 mg, 0.2 mmol) in anhydrous methanol (1 cm3) was added a solution of the decalone 22 (16.4 mg, 0.046 mmol) in methanol (1 cm3). The resulting solution was heated under reflux for 2.5 h. The reaction was quenched by addition of dil. HCI. Extraction with diethyl ether followed by treatment of the extract with diazomethane gave an oil (21.8 mg), which was purified by MPLC to give the decalone 23 (1 5.4 mg, 94).The spectral data were identical with those obtained in the previous experiment. Methyl 2- Bromo-5-(3-isopropyl-6-methylcyclohex-1 -enyl)-5- oxopentanoate 25a.-According to the general procedure, the reaction of the trimethylsilyl enol ether 24 (253.3 mg, 1 mmol) with methyl a-bromoacrylate 7a (334 mg, 2 mmol) gave the 2655 single Michael adduct 25a (1 54.1 mg, 58); v,,,/cm-' 1749, 1672, 1629, 1437, 1243 and 1216; 6(60 MHz) 0.66-3.04 (21 H, m), 3.79 (3 H, s) and 6.53-6.69 (1 H, m). Methyl 2-Bromo-5-(3-isopropyl-6-methylcyclohex-l-enyl)-3-methyl-5-oxopentanoate 25b.-According to the general pro- cedure, the reaction of the trimethylsilyl enol ether 24 (253.3 mg, 1 mmol) with methyl a-bromocrotonate 7b (0.24 cm3, 2 mmol) gave the single Michael adduct 25b (55.7 mg, 20); v,,,/cm-' 1750, 1675, 1630, 1465, 1275 and 1155; 6(60 MHz) 0.76-3.33 (23 H, m), 3.77 (3 H, s) and 6.63-6.8 (1 H, m).Methyl 4-(cyclohex-1-enyl)-4-hydroxy-6-methyl-2-oxotri-cyclo5.5.0.0'~8dodecane-7-carboxylate 26 (5); v,,,/cm-' 3481, 1727, 1655 and 1194; 6(300 MHz) 0.98 (3 H, d, J 6.4), 1.03-2.42 (20 H, m), 2.77 (1 H, dd, B part of AB-type q, J 16.6 and 2,3-H), 3.04 (1 H, d, A part of AB-type q, J 16.6,3-H), 3.72 (3 H, s), 4.76 (1 H, br s;intensity was decreased by D20addition) and 6.99 (1 H, m, W+ 10, olefinic H); m/z 346 (M', 373, 328 (M' -H,O, 2), 314 (4), 180 (14), 109 (100) and 81 (61). References 1 For example, J. D. Connolly and R. A. Hill, Dictionary of Terpenoids, Chapman and Hall, London, 1991.2 Isolation of some terpenoids having the tricycl04.4.0.0'*~decane framework: Y. Ohta, T. Sakai and Y. Hirose, Tetrahedron Lett., 1966, 6365;F. Bohlmann, J. Jakupovic, M. Ahmed, M. Wallmeyer, H. Robinson and R. M. King, Phytochemistry, 1981, 20, 2383; F. Bohlmann, J. Jakupovic and W. Vogel, Phytochemistry, 1982,21, 1153;R. Takeda and K. Katoh, Bull. Chem. Soc. Jpn., 1983,56,1265; J. C. Coll and B. F. Bowden, Bull. Soc. Chim. Belg., 1986,, 815; K. Kurata, K.Shiraishi, T. Takato, K. Taniguchi and M. Suzuki, Chem. Lett., 1988,1629;H.-y. He, J. Salva, R. F. Catalos and D. J. Faulkner, J. Org. Chem., 1992,57,3191. 3 A.Tanaka, H.Uda and A. Yoshikoshi, Chem. Commun., 1969,308; A. Tanaka, R.Tanaka, H. Uda and A. Yoshikoshi, J. Chem. Soc., Perkin Trans. I, 1972, 1721; E.Piers, R.W. Britton and W. de Waal, Tetrahedron Lett., 1969, 125 1. 4 K. Massone, Diplomarbeit Universitat des Saarlandes, 1987. 5 H. Hagiwara, J. Synth. Org. Chem. Jpn., 1992,50,713. 6 Preliminary communication: H.Hagiwara, F. Abe and H. Uda, J. Chem. Soc., Chem. Commun., 1991, 1070. 7 C. S.Marvel and J. C. Cowen, J. Am. Chem. Soc., 1939,61,3156. 8 (a) J. Klein and S. Zitrin, J. Org. Chem., 1970,35, 666;(b) V. L. Heasley,D. W. Spaite and D. F. Shellhamer, J. Org. Chem., 1979,44, 2608;(c) For a recent application, see L. Duhamel, 0.Peschard and G. PIC, Tetrahedron Lett., 1991,32, 4695. 9 J. A. Hirsch, Top, Stereochem., 1967,1, 199. 10 L. M. Jackman and R. H. Wiley, J. Chem. Soc., 1960,2886;J. Martin and L. Martin, J. Chim. Phys., 1964,61, 1222. 1 1 For 5a,acetylcyclopentene and acetylcycloheptene: N. Jones and H. T. Taylor, J. Chem. Soc., 1959,4017;for 5b: S.Danishefsky, T. Kitahara, C. F. Yan and J. Morris, J. Am. Chem. SOC.,1979, 101, 6996;for 5c: G.A. Kraus and M. E. Krolski, Synth. Commun., 1982, 12, 521. 12 H.Hagiwara, M. Kon-no and H. Uda, J. Chem. SOC.,Chem. Commun., 1992, 866. Paper 3/0241 OE Received 27th April 1993 Accepted 8th June 1993
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