Stereoselective construction ofcis-transoid-cis-tricyclo7.3.0.0dodecanes by an intramolecular Dielsndash;Alder reaction: a formal total synthesis of (plusmn;)-Delta;9(12)-capnellene

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1992 Stereoselective Construct ion of cis-fransoid-cis-Tricyclo7.3.0.~7dodecanes by an Intramolecular Diels-Alder Reaction: a Formal Total Synthesis of ( )-As('2)-Capnetlene Masataka Ihara, Takayuki Suzuki, Mamoru Katogi, Nobuaki Taniguchi and Keiichiro Fukumoto Pharmaceutical institute, Tohoku University, Aoba yarna, Sendai 980,Japan (1R',2S*) -2- (2-Oxobut-3-enyl) -1-(1-oxoprop-2-enyl) -1,3,3-trimethylcyclopentane 5 was prepared stereoselectively from 4,4-dimethylcyclopent-2-en-l -one 6 and then converted into the conjugated silyl enol ether 17. Intramolecular cycloaddition of 17, followed by base-catalysed equilibration, provided (1S*,2R",7R',9R') -3-tert-butyldimethylsiloxy-9,12,12-trimethyltricyclo7.3.0.02~7dodec-3-en-8-one 18a, which was transformed, after contraction of the cyclohexene ring, into the synthetic intermediate 32for ( _+ )-A9('2)-capnellene1. 6'" 2)-Capnellene 1," isolated from the soft coral Capnelfa imbricata, is believed to be the biogenetic precursor to the capnellene family of linear triquinane-type sesquiterpenes 2a-f.These compounds show biological activities similar to those of the hilstane family, which possesses antibacterial and anti- tumour properties.lb The capnellane family seems to act as 1 chemical defence agents in the coral reef biomass to inhibit the growth of microorganisms and the settlement of larvae.2 Thus, synthesis of the cis- transoid-cis- tricycl06.3.0.0~.~ undecane skeleton has presented a challenge which has attracted the attention of synthetic chemist^.^.^ We have planned a new synthetic approach aiming at A9('2)-capnelIene 1 and A9(l2)-capnellene-,8P, l0a-trio1 2a via the cis-transoid-cis-tricyclo-7.3.0.02.7dodecane derivative 3, which would be created by an intramolecular Diels-Alder reaction of the triene 4.It was further expected that the triene 4 could be provided from the bis-enone 5 derived from the known cyclopentenone (Scheme 1). We describe here in full a formal total synthesis of (amp;)-Ag(l ')-capnellene 1 according to this ~trategy.~ Concurrent introduction of two kinds of carbon units at the C-2 and C-3 positions of the cyclopent-2-enone 66 was successfully carried out by conjugate addition of vinyl-magnesium bromide in the presence of copper() iodide and N,N,N',N'-tetramethylethylenediamine (TMEDA),? followed by trapping of the resulting enolate with Mander's reagent * in t The following abbreviations have been used throughout for re-agents: N,N,N ',N',-tetramethyle thylenediamine (TM EDA), hexa-methylphosphoric triamide (HMPA), camphorsulfonic acid (CSA), bsol;ithiurn diisopropylamide (LDA), diisobutylaluminium hydride (DIBAL), tetrahydrofuran (THF), triacetoxyperiodinane (TAPI), fert- butyldimethylsilyl chloride (TBDMSCI),terr-butyldimethylsilyl tri-fluoromethanesulfonate (TBDMSOTf) and 1,8-diazabicycl05.4.0-undec-7-ene (DBU).- 1 and2.* 0 3U 0 - @0 4 0b 6 scheme 1 the presence of hexamethylphosphoric triamide (HMPA) (Scheme 2).In order to remove the carbonyl group of the keto ester 7,obtained in 89 yield as a single stereoisomer, 7 was converted, using ethane- 1,2-dithiol in the presence of boron trifluoride-diethyl ether, into the thioacetal8 in 93 yield. Since dethioacetalization of 8 utilizing Raney nickel accompanied hydrogenation of the vinyl group, the olefin 8 was subjected to hydroboration-oxidation prior to the dethioacetalization. Selective transformation into the primary alcohol 9 was achieved by the action of dicycl~hexylborane,~ followed by oxidation with hydrogen peroxide in the presence of sodium hydroxide. The thioacetal group of 9, formed in 88 yield, was reduced on heating together with W-2 Raney nickel in hot methanol. On the treatment of the ester 10, quantitatively produced, with a catalytic amount of (+)-camphor-lO-sulfonic acid (CSA) in hot benzene provided the lactones lla and llb as a mixture of trans and cis compounds in a 1.6: 1 ratio.Two isomers 1 la and 1lb were separated by high performance liquid chromatography (HPLC). In its 500 MHz 'H NMR spectrum, the angular hydrogen at the C-1 position of the trans-isomer 1la resonated at 2.51 ppm as a double double doublet (J7.8,9.8 and 13.2 Hz), while the hydrogen of the cis-isomer was observed at 2.96 ppm as double triplet (J6.8 and 10.5 Hz). Deprotonation of 866 the mixture lla and llb with lithium di-isopropylamide (LDA), followed by the reaction of the lithium enolate with methyl iodide at -78 "C to room temperature, gave the methylated compound 12 in 74 yield as a single stereoisomer.The cis structure of 12 was determined by the 8.2 nuclear Overhauser effect (NOE) between the methyl group at the C-1 position and the angular hydrogen at the C-6 position (Scheme 2). Thus, the I le 0 -*=0lf 7 81 iii 10 9 IV t lla trans 12 llb cis Scheme 2 Reugenrs: i, CH,=CHMgBr, CuI, TMEDA then NCC0,- Me, HMPA; ii, HSCH,CH,SH, BF,*Et,O; iii, dicyclohexylborane then H,O,, NaOH; iv, Raney Ni; v, CSA; vi, LDA; Me1 requisite stereochemistry on the A ring was stereoselectively constructed by the above methylation step. For the purpose of the conversion of the cis fused lactone 12 into the bis-enone 5 (Scheme 3), 12 was first reduced with an 13 14 1 iii t HO.ivorv5 OH 15 Scheme 3 Reugenrs: i, DIBAL; ii, DMSO, (COCl), then Et,N; iii, CH,=CHMgBr; iv, TAPI; v, Ph,BiCO, excess of diisobutylaluminium hydride (DIBAL) in tetrahydro- furan (THF) at 0 "C to afford quantitatively the diol 13,m.p. 64-66 "C. Swern oxidation of 13, followed by the reaction of the resulting dial 14 with vinylmagnesium bromide, produced the bis-ally1 alcohols 15 in 96 overall yield as a stereoisomeric mixture. Oxidation of 15 using manganese dioxide, pyridinium dichromate, tetrapropylammonium perruthenate or Swern J. CHEM. SOC. PERKIN TRANS. 1 1992 oxidation gave complex mixtures. Transformation of 15 to the bis-enone 5 was accomplished by the use of the Dess-Martin triacetoxyperiodinane (TAPI) lo or triphenylbismuth carbon- ate.' ' Thus, 5 was prepared in 75 yield by the former reagent and in 62yield by the latter respectively.In order to transform the bis-enone 5 into the correspond- ing conjugated silyl enol ether 17 (Scheme 4),5 was treated 5 + OTBDMS 0 0 16 TBDMS = SiMepBu' OTf = OSO2CF3ii or iii l7 18a 18b t ht I Scheme 4 Reagents: i, TBDMSCI, KOBu'; ii, AI,O,; iii, heat; iv, DBU with lithium hexamethyldisilazide and tert-butyldimethylsilyl chloride (TBDMSCI) but intractable polar products formed. Reaction of5 with trimethylsilyl chloride, zinc chloride and tri- ethylamine l2 was carried out at various temperatures, but none of the required product was obtained. Treatment of 6with tert-butyldimethylsilyl trifluoromethanesulfonate (TBDMSOTf) in the presence of triethylamine l3 gave only a polar product, the structure of which was tentatively assigned to the salt 16. After a number of trials, the production of the desired triene 17 was achieved by a modification of Levy's proced~re.'~ Thus, a solution ofpotassium tert-butoxide in THF was slowly added to a stirred mixture of 5 and TBDMSC1 in THF at -78 "C.The silyl enol ether 17 formed was isolated after treatment with silica gel. Reverse addition of the mixture of 5 and TBDMSCI to the solution of potassium terf-butoxide in THF resulted in a rather low yield. The triene 17,thus obtained, was subjected to the intramolecular Diels-Alder reaction without further purifi- cation.Two stereoisomers 18a and 18b were obtained in 55 overall yield from 5 in 1:2 ratio on heating 17 in refluxing benzene for 2 h. The cycloaddition of 17 carried out in the presence of neutral alumina as Lewis acid l5 at room tem- perature for 20 h produced two isomers 18a and 18b in 26 yield in 1O:l ratio. Treatment of the mixture of 18a and 18b with 1,8-diazabicycl05.4.0undec-7-ene (DBU) in hot benzene caused epimerization of 18b into 18a so that after 4 h, 18a was quantitatively obtained as the sole stereoisomer from the mix- ture (Scheme 4).Thus, 18a was stereoselectively synthesized in 55 overall yield from 5 by the following successive processes; triene formation, intramolecular cycloaddition, performed by heating 17 in hot benzene, and base treatment.It is considered that the cis-transoid-clsisomer 18a must more stable than the cis-transoid-transisomer 18b,the former arising Via the endo form 19a, and the latter via the ex0 form 19b-It is ah expected that, in the conformations 19c and 19d J. CHEM. SOC. PERKIN TRANS. 1 1992 leading to the cisoid isomers 1 and 18d, there is considerable repulsion between one of the methyl groups at the C-3 position and the oxygen of the doxy group (Scheme 5). It is, therefore, OTBDMS OTBDMS 019r 18a OTBDMS OTBDMS 0 19b 18b 0 OTBDMS 5 OTBDMS 0 19C 10CI 19d 18d Scbeme 5 deduced that the product 18a, obtained by the above treatment, would be the desired cis-transoid-cis-isomer.The structure was supported by the 13.3 NOE between one of the methyl groups at the C-12 position and the hydrogen at the C-2 position as well as the 8.4 NOE between the same methyl group and the hydrogen at the C-7 position.Reduction of the carbonyl group of 18a with sodium oms q$)1 or il iii ___c18a -for 2oa R OH 2h R=OH(P) 21 2Ob R=OH(a) 1" 0+R X vi -OH OH 24a R = COamp;le(P) 22 X=CHOH 24b R = COamp;le(a) 'E23 X=N2 Scheme 6 Reagents: i, NaBH,; ii, Li, liq. NH,, MeOH; iii, Bu,NF; iv, HCO,Et, NaOMe; v, TsN,, Et,N, vi, hv, MeOH borohydride gave the single stereoisomer 20a in 92 yield, while the other stereoisomer 20b was exclusively obtained in 90 yield by reduction with metallic lithium in the presence of methanol in liquid ammonia (Scheme 6).The former com- pound, 20a, is, therefore, a kinetically controlled product, while the latter, 20b, is a thermodynamically controlled product. The TBDMS group of 20a was removed by the action of tetrabutylammonium fluoride to afford the ketone 21 in 100 yield. The contraction of the C ring was achieved by Wolff rearrangement.' 20.16 Thus, 21 was transformed into the diazo ketone 23 in two steps: hydroxymethylenation (84 yield) followed by diazo exchange reaction of the resulting 22 with toluene-p-sulfonyl azide in the presence of triethylamine (80 yield). Irradiation of 23 in methanol furnished a 3 :1 mixture of the rearranged products 24a and 24b in 71 yield. Both stereoisomers 24a, m.p.101-102 "C and 24b, m.p. 90-93 "C, were readily separated by silica gel chromatography. The stereochemistry of the methoxycarbonyl group of the major isomer 24a was tentatively assigned as 01, since the C-methyl groups of 24a were observed at lower fields (6 0.95, 1.02 and 1.23) in the 'H NMR spectrum compared with those of the minor one 24b (6 0.89,0.91 and 1.15 ppm). Transformation of the diol 25, obtained by reduction of 24a with DIBAL, into the corresponding methylene compound utilizing several methods failed. Therefore, the hydroxy group of 24a was first protected. Treatment of 24a with TBDMSOTf in the presence of 2,6-dimethylpyridine and 4-N,N-dimethyl- aminopyridine (DMAP) afforded the TBDMS ether 26a in 98 yield. Reduction of 26a with DIBAL at 0 "C formed the primary alcohol 27a in 95 yield.Attempted transformation of 27a into the 2-nitrophenylseleno compound 29a using 2-nitrophenyl R (OH for? _. HOH H OH 24a R = C02Me(~) 24b R = C02Me(p)1 ii-cI-p i * 25 q$ OTBS OTBS 26a R = C02Me(a) iii ~27aR = CH20H(a) 26b R = C02Me(j3) 28a R = CH2OMs(a) iv c29a R = CH2SeCamp;I4NO2(a) . 27b R=CH20H(P) c28b R = CH20AAs(B) iv K29b R = CH2SeCamp;i.,N02@) Iv 32 30 R=TBDMS 'K31 R=HI 1 Scheme 7 Reagents: i, DIBAL; ii, TBDMSOTf, 2,6-dimethylpyridine, DMAP iii, MsCI, Et,N; iv, 2-N0,C,H4SeCN, NaBH,; v, H,O,; vi, Bu,NF; vii, TAP1 selenocyanate and triphenylphosphine ''failed. Therefore, by the Sharpless procedure,'* the alcohol 27a was converted quantitatively into the mesylate 28a, which was then treated with 2-nitrophenyl selenide anion, prepared by the reaction of 2-nitrophenyl selenocyanate with sodium borohydride.Oxi- dation of the seieno compound 29a,obtained in 98 yield, with 30 hydrogen peroxide, followed by the spontaneous elimin- ation of the selenoxide, produced the olefin 30in 70 yield. The same olefin 30 was further synthesized from the isomer 24b possessing the amp;orientated methoxycarbonyl group uia 26b-29b,according to the same procedures as above. Substitution of the mesylate 28b with 2-nitrophenyl selenocyanate proceeded more slowly due to the sterically hindered functionality. The TBDMS group of 30 was cleaved with tetrabutylammo- nium fluoride to give, in 90 yield, the secondary alcohol 31, which was oxidized using TAP1 loto the ketone 32 in 91 yield.The IR (neat), 'H and 13C NMR and MS spectra of the product 32 were consistent with those of the authentic compo~nd.~' Since 32 had been converted into (+)-A9('2)-capnellene the formal total synthesis was accomplished (Scheme 7). Experimental General Methods.-M.p.s were determined on a Yanako micromelting point apparatus and are uncorrected. IR spectra were recorded on a JASCO IR-Report-100 spectrophotometer. NMR spectra were measured on a JEOL-FX-90A or a JNM- GX-500 spectrometer. Chemical shifts are reported relative to internal SiMe,, and J values are given in Hz. Mass spectra were measured on a JEOL-JMS-OlSG-2, JEOL-DX-300 or JEOL- DX-303 spectrometer. All reactions except hydrogenation were run under dry N, or Ar.Solvents were freshly distilled prior to use: THF and Et,O were distilled from Na-benzophenone; CH,Cl, was distilled from P205. Unless otherwise noted, all reaction mixtures were dried, after work-up, over anhydrous Na,SO,. Silica gel column chromatography was carried out with Merck Kieselgel 60 (70-230 mesh). TLC was carried out on Merck Kieselgel 60 Fz54 (0.25 mm). HPLC was performed with a Gilson HPLC system Model 302/303 and monitored by UV absorption and refractive-index measurements. (2R*,3R*)-2-Methoxycarbonyl-4,4-dimethyl-3-vinylcyclo-pentanone 7.-To a suspension of copper(1) iodide (360 mg, 1.9 mmol) in dry THF (30 cm3) was added at ambient tem- perature TMEDA (4.9 cm', 32.5 mmol) and the mixture was stirred for 5 min at the same temperature.To the resulting mixture was slowly added at -78 "C a solution of vinyl- magnesium bromide in dry THF (1 mol drn-,; 35 cm3, 35 mmol). After the mixture had been stirred for 1 h at -78 "C, a solution of the enone ti6 (2.00 g, 18.2 mmol) in dry THF (13 cm3) was added dropwise to it during 1.5 h; the whole was then stirred for 4 h at -78 "C. To the stirred solution were added at -78 "C, HMPA (3.1 cm3, 17.8 mmol) and methyl cyanoformate (4.2 cm3, 52.9 mmol), and stirring was continued for 8 h. The mixture was then allowed to warm slowly to ambient temperature. After addition of saturated aqueous NH,Cl, the resulting mixture was extracted with hexane ( x 2) and Et,O.The combined extracts were washed with brine, dried and evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel. Elution with hexane-AcOEt (19 :1 v/v) afforded the title compound 7 (3.16 g, 89) as an oil (Found: C, 67.05; H, 8.3. Cl 1H1603 requires C, 67.3; H, 8.2); v,,,(CHCl,)/cm-' 1755 (C=O), 1728 (GO), 1640 (C=C) and 1152 (C-0); 6,(90 MHz; CDCl,) 0.92 (3 H, s, Me), 1.20 (3 H, s, Me), 2.30 (2 H, s, 5-H2), 2.97 (1 H, dd, J 7.2 and 11.9, 3-H), 3.30 (1 H, d, J 11.9, 2-H), 3.76 (3 H, s, OMe), 5.W 5.30 (2 H, m, CH=CH2) and 5.83 (1 H, ddd, J 7.2, 10.8 and 18.6, CHXH,); m/z 196 (M+). J. CHEM. SOC. PERKIN TRANS. 1 1992 (2S*,3R*)- 1, 1 -(1,2-Ethylenedithio)-2-methoxycarbonyl-4,4-dimethyl-3-vinylcyclopentane8.-To a stirred solution of the keto ester 7 (5.20 g, 26.5 mmol) in CH,Cl, (32 cm3) were added at ambient temperature ethane-1,2-dithiol(3.36 cm3, 40.0 mmol) and boron trifluoride-diethyl ether (3.36 cm3, 27.3 mmol), and the mixture was stirred for 36 h at the same tem- perature.After addition of water, the mixture was thoroughly extracted with Et,O. The extract was washed with saturated aqueous NaHCO, and brine, dried and evaporated under reduced pressure to afford a residue, which was chromato- graphed on silica gel eluting with hexane-AcOEt (9: 1 v/v) to give the title compound8 (6.74 g, 93) as an oil (Found: C, 57.25; H, 7.5; S, 23.35. C,3H2002S2 requires C, 57.3; H, 7.4; S, 23.55); v,,,(CHCl,)/cm-' 1740 (C=O), 1640 (M)and 1160 (C-0); dH(90 MHz; CDC1,) 0.98 (3 H, s, Me), 1.04 (3 H, s, Me), 2.34 (2 H, s, 5-H2), 2.73 (1 H, dd, J7.6 and 12.3,3-H), 2.80-3.50 (5 H, m), 3.71 (3 H, s, OMe), 4.90-5.20 (2 H, m, CH=CH2) and 5.74 (1 H, ddd, J7.6,9.2 and 17.7, CH=CH,); m/z 272 (M').(2S*,3R*)- 1,l -(1,2-Ethylenedithio)-3-(2-hydroxyethyl)-2-methoxycarbonyl-4,4-dimethylcyclopentane 9.-Dicyclohexyl-borane' was prepared by reaction of cyclohexene (7.08 cm3) with boranAimethy1 sulfide complex (10 mol drn-,, 3.33 cm3) in dry THF (33.3 cm3). To a stirred solution of the olefin 8(3.0 g, 11.1 mmol) in dry THF (5.0 cm3) was slowly added, with ice cooling, the above mixture of dicyclohexylborane in THF (20.1 cm3). The mixture was stirred for 1 h with ice cooling after which MeOH (5.0 cm3), aqueous NaOH (3 mol dm-,, 3.7 cm3) and 30 hydrogen peroxide (1.26 cm3) were added to it. The resulting mixture was stirred for 30 min and then neutralized with 10 hydrochloric acid with ice cooling.After concentration under reduced pressure, the resulting residue was taken up in Et20. The extract was washed with saturated aqueous NaHCO, and brine, dried and evaporated under reduced pressure. The residue was chromatographed on silica gel with hexane-AcOEt (3 :2 v/v) as eluent to give the title compound 9 (2.8 g, 88) as plates, m.p. 76-77 "C (Et,O-hexane) (Found: C, 54.1; H, 7.6; S, 21.95. Cl,H2z03S, requires C, 53.75; H, 7.65; S, 22.1); v,,,(CHCl,)/cm-' 3550 (OH), 1730 (GO) and 1163 (C-0); dH(9O MHz; CDCl,) 0.96 (3 H, s, Me), 1.06 (3 H, s, Me), 1.60-1.85 (1 H, m, 3-H), 2.10 (1 H, br s, OH), 2.00-2.40 (2 H, m, CH,CH,OH), 2.30 (2 H, s, 5-H2), 2.90-3.68 (7 H, m) and 3.75 (3 H,s, OMe);m/z 290(M+).(1S*,2R*)-2-(2-Hydroxyethyl)-1-methoxycarbonyl-3,3-dimethylcyclopentane 10.-A mixture of the thioketal9 (483 mg, 1.67 mmol) and Raney Ni (W-2) (10.0 g) in MeOH (18 cm3) was heated for 24 h under reflux and a H, (1 atm) atmosphere. After having been cooled, the mixture was filtered through Celite and washed with MeOH and CHCl,. Evaporation of the combined filtrate and washings under reduced pressure gave a residue, which was acidified by addition of 10hydrochloric acid with ice cooling after addition of Et,O. The aqueous layer was extracted thoroughly with Et20 and the extract was washed with brine, dried and evaporated under reduced pressure.Chromatography of the residue on silica gel with hexane- AcOEt (3: 2 v/v) as eluent afforded the title compound 10 (333 mg, 100) as an oil; v,,,(CHCl,)/cm-' 3600 (OH) and 1730 (GO); 6H(500 MHz; CDC13) 0.79 (3 H, S, Me), 1.04 (3 H, S, Me), 1.25-2.08 (7 H, m), 2.21 (1 H, br s, OH), 2.57 (1 H, dt, J5.3 and 10.1, 1-H), 3.51 (1 H, ddd, J 5.3, 8.0 and 10.7, CHHOH), 3.64 (1 H, ddd, J4.8, 5.9 and 10.7, CHHOH) and 3.72 (3 H, s, OMe); m/z 200 (M'). 7,7-Dimethyl-3-oxabicyclo4.3.0nonan-2-ones1la and 11b.-A stirred solution of the hydroxy ester 10 (403 mg, 2.01 mmol) and CSA (36.0 mg, 0.16 mmol) in dry benzene (14 cm3) was heated for 24 h at 80 "C.After dilution with benzene, the J. CHEM. SOC. PERKIN TRANS. 1 1992 resulting mixture was washed with saturated aqueous NaHCO, and brine, dried and evaporated under reduced pressure. The residue was purified by silica gel column chromatography eluting with hexane-AcOEt (4:l v/v) to afford a mixture of two lactones (329.8 mg, 97) as an oil in a ratio of 1.6:l. Separation of two isomers was carried out by HPLC on Si 80-199-C5 with hexane-AcOEt (17:3 v/v) as eluent to give the trans-lactone lla (203 mg, 60) as an oil; ~,(CHCl,)/crn-~ 1740 (CdI); 6H(500 MHz; CDCl,) 0.88 (3 H, S, Me), 1.06 (3 H, S, Me), 1.50-1.75 (4 H, m), 1.84-1.95 (3 H, m), 2.51 (1 H, ddd, J7.8, 9.8 and 13.2, 1-H), 4.33 (1 H, dd, J 7.8 and 11.9,4-H) and 4.38 (1 H, dd, J 7.8 and 11.9, 4-H); m/z 168 (M+) (Found: M+, 168.1 142.CloH1602 requires M, 168.1 150). The second eluate gave the cis-lactone llb (126 mg, 37) as an oil; v,,,(CHC1,)/cm-' 1730 (GO); 6,(500 MHz; CDCl,) 0.81 (3 H, s, Me), 1.02 (3 H, s, Me), 1.41 (1 H, ddd, J8.5,9.8 and 12.6), 1.50-1.59 (2 H, m), 1.82-1.88 (1 H, m), 2.04-2.20 (3 H, m), 2.96 (1 H, dt, J6.8 and 10.5, 1-H), 4.14 (1 H, ddd, J 1.9, 10.9 and 12.5,4-H) and 4.38 (1 H, ddd, J2.4,4.0 and 10.9,4-H); m/z 168 (M+) (Found: M+, 168.1139). (1R*,6S*)- 1,7,7- Trimethyl-3-oxabicyclo4.3.0nonan-2-one 12.-To a stirred solution of LDA, prepared from butyllithium- hexane (1.54 mol drn-,; 5.2 cm3, 8.01 mmol) and di-isopropyl- amine (1.35 cm3, 9.63 mmol) in dry THF (10 cm3), was added dropwise at -78 "C a solution of the mixture of lactones lla and llb (193 mg, 1.15 mmol) in dry THF (Loan3).After having been stirred for 1 h at -78 to -20 "C, to the stirred mixture was added at -78 "C methyl iodide (1.29 an3,20.7 mmol); the mixture was then stirred for 1.5 h at -78 "C-ambient temperature. After addition of saturated aqueous NH4Cl, the mixture was thoroughly extracted with Et20. The extract was washed with aqueous Na2S203 (0.1 mol drn-,) and brine, dried and evaporated under reduced pressure to afford a residue, which was chromatographed on silica gel. Elution with hexane- AcOEt (9: 1 v/v) gave the title compound 12 (154.9 mg, 74) as a pale yellowish oil; vmax(CHC13)/cm-' 1730 (M);6H(500 MHz; CDC1,) 0.82 (3 H, s, 7-Me), 1.07 (3 H, s, 7-Me), 1.40 (3 H, s, 1-Me), 1.441.49 (2 H, m), 1.60 (1 H, ddt, J4.0, 12.0 and 13.9, 5-H), 1.66 (1 H, ddd, J3.8,6.1 and 13.8,9-H), 1.71 (1 H,dd, J6.8 and 12.0,6-H), 1.88 (1 H, dddd, J 1.4,2.5,6.8 and 13.9,5-H), 2.35 (1 H, ddd, J7.6, 10.3 and 13.8, 9-H), 4.24 (1 H, ddd, J 1.4, 11.1 and 13.9,4-H) and 4.38 (1 H, ddd, J 2.5,4.0 and 11.1,4-H); m/z 182 (M+).(1R*,2S*)-2-(2-Hydroxyethyl)-1-hydroxymethyl- 1,3,3-tri- rnethylcyclopentane 13.-To a stirred solution of the trimethyl lactone 12 (240 mg, 1.10 mmol) in dry THF (20 cm3) was slowly added at 0 "C a solution of DIBAL in hexane (1 mol drn-,; 6.6 cm3, 6.6 mmol), and the mixture was stirred for 30 rnin at 0 "C and for 1 h at ambient temperature. After addition of water (2.5 cm3), the mixture was stirred for 30 rnin at ambient temperature and then filtered through Celite.The filtrate and washings with Et20 were dried and evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel. Elution with hexane-AcOEt (1:l v/v) afforded the title compound 13 (244 mg, 100) as plates, m.p. 64-66 "C (Et20- hexane) (Found: C, 70.6; H, 11.9. C1 'Hz202 requires C, 70.9; H, 11.9); v,,,(CHC13)/cm-' 3630 (OH) and 3435 (OH); dH(90 MHz; CDCl,) 0.83 (3 H, s, Me), 0.98 (3 H, s, Me), 1.09 (3 H, s, Me), 1.10-1.80 (7 H, m), 2.50 (2 H, br s, 2 x OH), 3.42 (1 H, d, J 10.5, CHHOH), 3.55-3.86 (2 H, m, CH20H) and 3.56 (1 H, d, J 10.5, CHHOH); m/z 168 (M+ -H20) (Found: M+ -H20, 168.1471.C, 1H200 requires m/z, 168.1513). (1R*,2R*)-2-(2-Hydroxybut-3-enyl)-1-(1-hydroxyprop-2-eny1)-1,3,3-trirnethylcyclopentane15.-To a stirred solution of oxalyl chloride (1.9 cm3, 21.5 mmol) in dry CH,C12 (5.0 cm3) was slowly added at -78 "C a solution of dimethyl sulfoxide (DMSO) (3.1 cm3, 43.0 mmol) in dry CH2C12 (5.0 cm'). After having been stirred for 5 rnin at -78 "C, to the mixture was added at -78 "C a solution of the dioll3 (0.966 g, 5.2 mmol) in dry CH2Cl, (10 cm3). After having been stirred for 10 min, followed by addition of Et,N (9.0 cm3, 64.5 mmol), the mix- ture was stirred for 15 rnin at -78 "C and for 30 rnin at ambient temperature. After addition of water, the mixture was thoroughly extracted with hexane.The extract was washed with brine, dried and evaporated under reduced pressure to give the dial 14 as an oil, which was used for the next reaction without purification. A solution of the above dial 14 in dry THF (23.6 cm3) was slowly added into a stirred solution of vinylmagnesium bromide in dry THF (1 mol drn-,; 50.0 cm3,50.0 mmol), and the mixture was stirred for 12 h at ambient temperature. After addition of saturated aqueous NH4Cl with ice cooling, the resulting mixture was thoroughly extracted with Et20. The extract was washed with brine, dried and evaporated under reduced pressure. The residue was chromatographed on silica gel with hexane-AcOEt (7:3 v/v) as eluent to give the title compounds 15 (1.19 g, 96 from 13) as a stereoisomeric mixture (Found C, 75.75; H, 11.1.C15H2602 requires C, 75.6; H, 11.0); v,,,(CHCl,)/cm-' 3600 (OH) and 3400 (OH); aH(9O MHz; CDC1,) 0.77 (3 H, s, 2 x Me), 0.91 (3/2 H, s, Me), 0.96 (3/2 H, s, Me), 1.07 (3/2 H, s, Me), 1-10 (3/2 H, s, Me), 1.15-2.30 (7 H, m), 2.70-3.20 (2 H, br s, 2 x OH), 5.03-5.44 (4 H, m, olefinic H) and 5.67-5.68 (2 H, m, olefinic H); m/z 205 (M+ -Me -H20). (1R*,2S*)-2-(2-0xobut-3-enyl)-1-(l-oxoprop-2-enyl)-l,3,3-trimethylcyclopentane 5.-Method A. To a stirred solution of TAPI" (179 mg, 0.423 mmol) in dry CH2C12 (2.0 cm3) was added at ambient temperature a solution of the bisallyl alcohols 15 (15.2 mg, 0.064 mmol) in dry CH2C12 (2.0 an3),and the mixture was stirred for 2 h at the same temperature. After addition of Et20 and saturated aqueous NaHCO, containing Na2S203 (10 mg) with ice cooling, the mixture was stirred for 10 min at ambient temperature.The mixture was thoroughly extracted with Et20. The extract was washed with saturated aqueous NaHCO, and water, dried and evaporated under reduced pressure. Chromatography of the residue on silica gel with hexane-AcOEt (19: 1 v/v) as eluent gave the title compound 5 (11.2 mg, 75) as an oil (Found: C, 76.8; H, 9.3. C15H2202 requires C, 76.9; H, 9.45); v,,,(CHCl,)/cm-' 1690 (M); S,(500 MHz; CDCl,) 0.87 (3 H, s, Me), 0.97 (3 H, s, Me), 1.22- 1.62(3 H, m), 1.41 (3 H, s, Me), 2.13 (1 H, dd, J6.0 and 8.0,2-H), 2.23-2.32 (1 H, m), 2.66 (1 H, dd, J6.0 and 17.5, CHHCO), 2.71 (1 H,dd, J8.0and 17.5,CHHCO),5.56(1 H,dd, J2.0and 10.0, MHH),5.77 (1 H, dd, J 1.6 and 10.5, MHH),6.22 (1 H, dd, J 1.6 and 17.8, C=CHH), 6.23 (1 H, dd, J2.0 and 16.5, GCHH), 6.35 (1 H, dd, J 10.5 and 17.8, CH=CH2) and 6.72 (1 H, dd, J 10.0and 16.5, CH=CH2); m/z 234 (M+) (Found: M+, 234.1613.C1,H2,O2 requires M, 234.1619). Method B. A solution of the bisallyl alcohols 15 (24.9 mg, 0.105 mmol) and triphenylbismuth carbonate '' (160 mg, 0.32 mmol) in dry CH2C12 (4.0 cm3) was stirred for 24 h at 40 "C and then filtered through Celite. The filtrate was evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel. Elution with hexane-AcOEt (19: 1 v/v) afforded the bis-enone 5 (15.2 mg, 62) as an oil, whose IR, 'H NMR and MS spectra were identical with those of compound 5, prepared by the Method A.(lS*,2R*,7R*,9R*)-18aand(1S*,2R*,7S*,9R*)-3-tert-Butyldi-methylsiloxy-9,l2,l2-trimethyltricyclo7.3.O.O2~7dodec-3-en-8-one 18b.---To a stirred solution of the bis-enone 5 (46.0 mg, 0.154 mmol) and TBDMSCl(27.8 mg, 0.185 mmol) in dry THF (2.0 cm3) was slowly added during 2 h at -78 "Ca solution of 870 freshly prepared potassium tert-butoxide (19.0 mg, 0.169 mmol) in dry THF (17 cm3), and the mixture was stirred for 1 h at -78 "C. The mixture was poured onto silica gel (ca.5.0 g) under ice cooling. The resulting mixture was filtered through glass filter using AcOEt as eluent. The combined filtrate and washings were evaporated under reduced pressure to give a residue, which was chromatographed on silica gel with hexane- AcOEt (1 :1 v/v) to afford the siloxy diene 17 as an oil, which was immediately subjected to the intramolecular Diels-Alder reaction.Method A. A solution of the above product 17 in dry benzene (5.0 cm3) was heated for 2 h under reflux. Evaporation of the resulting mixture under reduced pressure provided a residue, which was purified by column chromatography on silica gel. Elution with hexane-AcOEt (19: 1 v/v) gave the mixture (1 :2) of the title compounds 18a and 18b (37.4 mg, 55) as an oil; v,,,(CHC13)/cm-' 1730 (Go);hH(500 MHz; CDCI,) 0.1 2,O. 14, 0.18 and 0.19 6 H (1 :1 :2 :2), each s, SiMe,, 0.92 and 0.95 9 H (1:2), each s, Bu', 0.94, 1.05, 1.06, 1.11 and 1.26 9 H (1:4:1:1:2), each s, 3 x Me, 1.25-1.31 (1/3 H, m), 1.38-1.62 (3 H, m), 1.80-1.87 (1 H, m), 1.88-1.92 (2/3 H, m), 1.96-2.19 (13/3 H, m), 2.20 (1/3 H, br s), 2.51 (2/3 H, ddd, J6.0, 11.5 and 14.0, 7-H), 2.56 (1/3 H, ddd, J3.5, 5.0 and 8.5, 7-H), 2.64 (1/3, br d, J8.5,2-H), 4.62-4.64 (2/3 H, m, 4-H) and 4.744.77 (1/3 H, m, 4-H); mi: 348 (M') (Found: M+, 348.2490.C21H3602Si requires M, 348.2483). Method B. A mixture of the above siloxy diene 17 and neutral alumina (2.0 g) in hexane-AcOEt (7: 3 v/v; 7.0 cm3) was stirred for 20 h at room temperature. The mixture was filtered through Celite. The combined filtrate and washings with Et20 were dried and evaporated under reduced pressure. Silica gel chromatography of the residue eluating with hexane-AcOEt (49: 1 v/v) gave the mixture (10: 1) of tricyclic compounds 18a and 18b (1 2.1 mg, 26) as an oil; v,,,(CHCl,)/cm-' 1730(W); 6,(500 MHz; CDCl,) 0.12,0.14,0.18 and 0.19 6 H (10: 10: 1: l), each s, SiMe,, 0.92 and 0.95 9 H (10: l), each s, Bu', 0.94, 1.05, 1.06, 1.1 1 and 1.26 9 H (10: 2: 10: 10: l), each s, 3 x Me, 1.25-1.31 (10/11 H, m), 1.38-1.62 (3/11 H, m), 1.80-1.87 (30/11 H,m), 1.88-1.92(1/11 H,m), 1.9amp;2.19(16/11 H,m),2.20(10/11 H, br s), 2.51 (3/11 H, ddd.J6.0, 11.5 and 14.0,7-H), 2.56 (10/11 H, ddd, J 3.5, 5.0 and 8.5, 7-H), 2.64 (10/11 H, br d, J 8.5, 2-H), 4.624.64 (1/11 H, m, 4-H) and 4.74-4.77 (10/11 H, m, 4-H); m/z 348 (M+) (Found: Mf, 348.2493). (1S*,2R*,7R*,9R*)-3-tert-Butyfdimethyl.sifoxy-9,12,12-tri-methyftricycf07.3.0.O~~~dodec-3-en-8-one18a.-A solution of the above mixture of tricyclic compounds 18a and 18b (4.0 mg, 0.0115 mmol) and DBU (0.17 cm3, 0.1 15 mmol) in dry benzene (3.0 cm3) was heated for 4 h under reflux.After dilution with hexane, the mixture was washed with 5 aqueous KHSO, and brine, and dried. Evaporation of the mixture, followed by chromatography of the residue on silica gel with hexane-AcOEt (19: 1 v/v), gave the cis-transoid-cis-isomer 18a (4.0 mg, 100) as a powder, m.p. 52-56deg;C; v,,,(CHCl,)/cm-' 1730 (W); 6H(500 MHz; CDCl,) 0.12 (3 H, s, SiMe), 0.14 (3 H, s, SiMe), 0.92 (9 H, s, Bu'), 0.94 (3 H, s, Me), 1.06 (3 H, s, Me), 1.1 1 (3 H, s, Me), 1.25-1.31 (1 H, m), 1.41-1.52 (2 H, m), 1.56-1.62 (2 H, m), 1.8CL1.87 (3 H, m), 2.01-2.07 (1 H, m, 6P-H), 2.20 (1 H, br s), 2.56 (1 H, ddd, J3.5,5.0 and 8.5,7-H), 2.64 (1 H, br d, J8.5,2-H) and 4.744.77 (1 H, m, 4-H); 6,( 125 MHz; CDCl,) -4.485 (q), -4.376 (q), 18.101 (s), 20.325 (t), 20.574 (t), 24.976 (q), 25.349 (q), 25.847 (q), 30.840 (q), 37.435 (t), 39.582 (d), 41.386 (t), 43.066 (s), 49.1 17 (d), 56.661 (s), 58.870 (d), 103.823 (d), 151.716 (s) and 227.173 (s).(1S*,2R*,7R*,8R*,9R*)-3-tert-Butyfdimethylsif~~~y-8-h~~d~oxy-9,12,12-trimethyftricycfo7.3.0.02~7dodec-3-ene20a.-To a stirred solution of the siloxy ketone 18a (40.5 mg, 0.116 J. CHEM. SOC. PERKIN TRANS. 1 1992 mmol) in anhydrous MeOH (3.0 cm3) was added portionwise at 0 "C sodium borohydride (17.7 mg, 0.466 mmol), and the mixture was stirred for 12 h at 0 "C.Removal of the solvent under reduced pressure provided a residue, which was par- titioned between Et20 and brine. The combined ethereal extracts were dried and evaporated under reduced pressure to give a residue, which was chromatographed on silica gel. Elution with hexane-AcOEt (9:l v/v) afforded the title com- pound 20a (37.3 mg, 92) as an oil; v,,,(neat)/cm-' 3470 (OH); 6H(500 MHz; CDCl,) 0.49 (3 H, s, SiMe), 0.53 (3 H, s, SiMe), 0.93 (9 H, s, Bur), 1.02 (3 H, s, Me), 1.04 (3 H, s, Me), 1.18 (3 H, s, Me), 1.22-1.59 (5 H, m), 1.63-1.75 (1 H, m), 1.85-1.89 (1 H, m), 1.91-2.02 (2 H, m), 2.15-2.24 (1 H, m), 2.26-2.34 (2 H, m), 3.77 (1 H, br s, 8-H) and 4.78 (1 H, m, 4-H); m/z 350 (M') (Found: M +,350.2626. C2 1H3802Si requires M, 350.2639).(1S*,2R *,7R *,8 R *,9 R*)-8-Hydroxy-9,12,12- t rimethyftri- cycl07.3.0.0~*~dodecan-3-one21.-To a stirred solution of the siloxy alcohol 20 (99.0 mg, 0.257 mmol) in THF (4.5 cm3) was slowly added at 0 "C a solution of tetrabutylammonium fluoride in THF (1 mol dm-,; 0.8 cm', 0.8 mmol) containing water (5 w/v), and the mixture was stirred for 30 min at ambient temperature. After evaporation under reduced pressure, the residue was taken up into Et20. The extract was washed with brine, dried and evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel. Elution with hexane-AcOEt (9:l v/v) provided the title compound 21 (60.6 mg, 100) as an oil; v,,,(neat)/cm-' 3460 (OH) and 1700 (C=O); dH(500 MHz; CDCl,) 0.95 (3 H, S, Me), 1.06(3 H, s, Me), 1.26 (3 H, s, Me), 1.42-1.58 (5 H, m), 1.72-1.83 (2H,m), 1.87-1.94(1 H,m),2.10-2.19(1 H,m),2.27-2.34(2H, m), 2.41 (1 H, ddd, J 5.0,9.8 and 15.0,4-H), 2.49 (1 H, dd, J 6.0 and 8.3, 2-H), 2.55 (1 H, ddd, J 5.0, 7.0 and 15.0,4-H) and 3.65 (1 H, d, J 4.3, 8-H); m/z 236 (M') (Found: M+, 236.1788.C,,H,,O, requires M, 236.1775). (1S*,2R *,7R *,8R*,9R*)-8-Hydroxy-4-hydroxymethyfene-9,12,12-trimethyltricyclo7.3.0.02*7dodecan-3-one22.-After addition of anhydrous MeOH (0.11 cm3, 2.79 mmol) to a mixture of NaH (60 oily suspension; 90.0 mg, 2.34 mmol) in dry Et,O (2.0 cm3) with ice cooling, to the resulting mixture were added a solution of the hydroxy ketone 21 (82.1 mg, 0.390 mmol) in dry Et,O (1.0 cm3) and ethy formate (0.63 cm3, 7.81 mmol).After having been stirred for 4 h at ambient temperature, followed by dilution with saturated aqueous NH,Cl, the mix- ture was thoroughly extracted with Et20. The extract was washed with water and brine, dried and evaporated under reduced pressure to give a residue, which was chromatographed on silica gel. Elution with hexane-AcOEt (4: 1 v/v) afforded the title compound 22 (77.4 mg, 84) as an oil; v,,,(neat)/cm-' 3440 (OH) and 1690 (M);hH(500 MHz; CDCl,) 1.10 (6 H, S, 2 x Me), 1.22 (3 H, s, Me), 1.27-1.55 (5 H, m), 1.93-1.99 (1 H, m), 2.10 (1 H, d, J7.4, 1-H), 2.22 (1 H, ddd, J4.6, 12.8 and 14.7, 5-H), 2.40 (1 H, dt, J 3.7 and 14.7,5-H), 2.42-2.46 (1 H, m, 7-H), 2.58 (1 H, t, J7.4,2-H), 3.80 (1 H, d, J5.5,8-H), 8.59 (1 H, br d, J 4.0, =CH) and 14.35 (1 H, br d, J4.0, SHOH); m/z 264 (M') (Found: M +,264.1700. C16H240, requires M, 264.1724).(lS*,2R*,3R*,6R*,7R*$R*)-24aand (1 S*,2R*,3S*,6R*,7R*,- 8R*)-7-Hydroxy-3-methoxycarbonyf-8,11,11-trimethyltricyclo-6.3.0.02,6undecane 24b.-To a stirred solution of the hydroxy- methylene derivative 22 (41.0 mg, 0.155 mmol) in dry CH,Cl, (2.0 cm3) were added under ice cooling Et,N (0.10 cm3, 0.758 mmol) and a solution of toluene-p-sulfonyl azide (1 12.0 mg, 0.568 mmol) in dry CH,Cl, (0.5 cm3), and the mixture was stirred for 3 h at ambient temperature. After evaporation of the solvent under reduced pressure, the residue was chromato-graphed on silica gel with hexane-AcOEt (3:2 v/v) to afford the J.CHEM. SOC. PERKIN TRANS. 1 1992 diazo ketone 23 (32.5 mg, 80) as an oil; v,,,(neat)/cm-' 2080 (C=N+=N-) and 171O(C=O); 6H(500 MHz; CDCl,) 1.08 (3 H, S, Me), 1.12 (3 H, s, Me), 1.21 (3 H, s, Me), 1.40-1.48 (1 H, m), 1.50-1.58 (2 H, m), 1.63-1.77 (2 H, m), 2.01-2.10 (2 H, m), 2.4amp; 2.49 (2 H, m), 2.57 (1 H, t, J7.4,2-H), 2.67 (1 H, ddd, J4.6, 11.0 and 14.3, 5-H), 2.81 (1 H, dt, J 5.0 and 14.3, 5-H) and 3.79 (1 H, d, J 5.5, 8-H). An ice-cooled solution of the above diazo ketone 23 in anhydrous MeOH (20 cm3) was irradiated for 2 h through a Pyrex filter with a 400-W high-pressure mercury lamp. Evaporation of the solvent under reduced pressure afforded a residue which was purified by chromatography on silica gel.Elution with hexane-AcOEt (4:l v/v) provided the title compound 24a (17.6 mg, 53) as plates, m.p. 101-102 "C; v,,,(CHC13)/cm-' 1734(GO),1145 (C-0) and 1041 (C-04); dH(500 MHZ; CDCI,) 0.95 (3 H, S, Me), 1.02 (3 H, S, Me), 1.23 (3 H, s, Me), 1.41-1.48 (2 H, m), 1.49-1.62 (3 H, m), 1.75-1.90 (3 H,m), 2.04-2.12 (1 H, m), 2.40-2.46 (1 H, m), 2.63-2.73 (2 H, m), 3.66 (3 H, s, OMe) and 3.80 (1 H, d, J 6.8, 7-H); m/z 266 (M') (Found: M+, 266.1864. C16H2603 requires M, 266.1 88 1). Elution with hexane-AcOEt (4:l v/v) gave the isomer 24b (5.9 mg, 18) as plates, m.p. 90-93 "C; v,,,(CHCI~)/C~-~ 1730 (C=O), 1150 (C-0) and 1041 (C-O-C); 6H(500 MHz; CDCl3) 0.89 (3 H, s, Me), 0.91 (3 H, s, Me), 1.15 (3 H, s, Me), 1.21-1.32 (2 H, m), 1.38-1.51 (3 H, m), 1.66-1.73 (1 H, m), 1.80-1.87 (1 H, m), 1.88-1.95 (1 H, m), 1.97-2.07 (1 H, m), 2.56-2.62 (1 H, m), 2.70-2.78 (1 H, m), 2.82-2.88 (1 H, m), 3.66 (3 H, s, OMe) and 3.83-3.89 (1 H, m, 7-H); m/z 266 (M+) (Found: M+, 266.1858).( 1S*,2R*,3R*,6R*,7R*,8R*)-7-Hydroxy-3-hydroxymethyf-8,11,1 l-rrimethyfrri~ycfo6.3.0.0~~~undecune25.-To a stirred solution of the hydroxy ester 24a (2.0 mg, 0.091 mmol) in dry THF (0.4 cm3) was added at 0deg;C a solution of DIBAL in hexane (1 mol drn-,; 0.06 cm3, 0.06 mmol), and the mixture was stirred for 30 min at the same temperature and for 1 h at ambient temperature. After addition of water (0.1 cm3), followed by stirring for 30 min at ambient temperature, the resulting mixture was filtered through Celite using Et,O.The combined filtrate and washings were dried and evaporated under reduced pressure to give a residue, which was subjected to silica gel chromatography. Elution with hexane-AcOEt (3: 2 v/v) afforded the title compound 25 (1.8 mg, 100) as plates, m.p. 101-102 "C; v,,,(CHCl3)/crn-' 3360 (OH); dH(500 MHz; CDCl,) 0.96 (3 H, s, Me), 1.11 (3 H, s, Me), 1.21 (3 H, s, Me), 1.28-1.64 (4 H, m), 1.65-1.78 (2 H, m), 1.91-2.02 (2 H, m), 2.61 (1 H, quint., J 7.8,6-H), 3.44 (1 H, dd, J6.0 and 11.5, CHHOH), 3.62 (1 H, dd, J 5.5 and 11.5, CHHOH) and 3.86 (1 H, d, J 7.0, 7-H); m/z 238 (M') (Found: M', 238.1938. C15H2,02 requires M, 238.1931). ( 1S*,2R*,3R*,6R*,7R*,8R*)-7-tert-Butyldimethyf~ifoxy-3-metho.xycarbonyf-8,ll,1l-trimethyftricycfo6.3.O.O2~6unde~une 26a.-To a stirred solution of the hydroxy ester 24a (51.8 mg, 0.195 mmol), DMAP (12.0 mg, 0.098 mmol) and 2,6-di-methylpyridine (0.18 cm3, 1.52 mmol) in CH2C12 (1.5 cm3) was added at 0deg;C TBDMSOTf (0.23 cm', 1.02 mmol) and the mixture was stirred for 4 h at ambient temperature. After dilution with CH2C12, the mixture was washed with saturated aqueous NH,Cl and brine, and dried.Evaporation of the solvent under reduced pressure gave a residue, which was chromatographed on silica gel. Elution with hexane-AcOEt ( 17:3 v/v) afforded the title compound 26a (72.4 mg, 98) as an oil; v,,,(neat)/cm-' 1730 (C=O); S"(500 MHz; CDC1,) 0.01 (6 H, s, SiMe,), 0.86 (9 H, s, Bu'), 0.92 (3 H, s, Me), 0.97 (3 H, s, Me), 1.12 (3 H, s, Me), 1.34-1.55 (5 H, m), 1.63-1.70 (1 H, m), 1.75-1.85 (2 H, m), 2.00-2.07 (1 H, m), 2.35 (1 H, dt, J5.0 and 8.5), 2.56-2.65 (2 H, m), 3.65 (3 H, s, OMe) and 3.85 (1 H, d, J 8.0, 7-H); m/z 323 (M' -Bur)(Found: M+ -Bur, 323.2031.C18H3103Si requires m/z, 323.2041). (1 S*,2S*,3R*,6R *,7R *,8R *)-7- tert-Butyfdimethyfsifoxy-3-hydroxymerhyl-8,11,11-trimethyftri~ycfo6.3.0.0~~~undecane 27a.-To a stirred solution of the siloxy ester 26a (72 mg, 0.189 mmol) in dry THF (3 cm3) was added at 0deg;C a solution of DIBAL in hexane (0.95 mol dm-3; 2.0 cm3, 1.9 mmol), and the mixture was stirred for 30 min at 0deg;C and for 1 h at ambient temperature. After addition of water (2.0 cm3), the mixture was stirred for 30 min and filtered through Celite using Et,O.The combined filtrate and washings were dried and evaporated under reduced pressure to give a residue, which was chromatographed on silica gel with hexane-AcOEt (9 : 1 v/v) as eluent to afford the title compound 27a (63.4 mg, 95) as an oil; v,,,(neat)/cm-' 3340 (OH) and 1092 (OSi); 6H(500 MHz; CDC1,) 0.020 and 0.024 (each 3 H, each s, SiMe,), 0.89 (9 H, s, Bu'), 0.94 (3 H, s, Me), 0.97 (3 H, s, Me), 1.1 1 (3 H, s, Me), 1.24- 1.46 (5 H, m), 1.47-1.60 (3 H, m), 1.76-1.97 (4 H, m), 2.48 (1 H, quint., J 8.2,6-H), 3.42 (1 H, dd, J 7.4 and 10.8, CHHOH), 3.57 (1 H,dd,J6.0and 10.8,CHHOH)and3.86(1 H,d,J7.6,7-H); m/z 352 (M') and 295 (M+ -Bu') (Found: M+ -Bur, 295.2088.C17H3 ,O,Si requires m/z, 295.2093). (1S*,2S*,3R*,6R*,7R*,8R*)-7-tert-Butyfdimethyf~~foxy-3-(2-nitrophenylseleno)merhyf-8,11,11-trimethyftri~ycfo6.3.0.0~~~-undecune 29a.-To a solution of the siloxy alcohol 27a (45.1 mg, 0.128 mmol) in dry CH2CI2 (1.0 cm3) was added Et,N (0.096 cm3, 0.641 mmol).After the mixture had been stirred for 5 min, methanesulfonyl chloride (0.044 cm3, 0.384 mmol) was added to it at 0deg;C. The mixture was then stirred for 30 min at 0 "C, diluted with benzene, washed with 5 aqueous KHS04 and water, dried and evaporated under reduced pressure. Chromatography of the residue on silica gel with hexane- AcOEt (17:3 v/v) as eluent gave the mesylate 28a (50.5 mg, 100) as an oil; v,,,(neat)/cm-' 1354 and 1174 (SO,) and 1091 (OSi); 6,(90 MHz; CDCl,) 0.03 (6 H, s, SiMe,), 0.90 (9 H, s, Bu'), 0.94 (3 H, s, Me), 0.99 (3 H, s, Me), 1.12 (3 H, s, Me), 1.25-2.60(12H,rn),3.00(3H,s,SO2Me)and3.85(1 H,d,J7.4, 7-H); m/z 415 (M' -Me) (Found: M+ -Me, 415.2322.C2 H3904SSi requires m/z,41 5.2336). To a stirred solution of the mesylate 28a (55.8 mg, 0.128 mmol) in dry THF (1.0 cm3) was added at ambient temperature during 3 days the freshly prepared reagent; this was in the form of six batches separately prepared by the reaction of 2-nitrophenyl selenocyanate (37 mg, 0.187 mmol) with sodium borohydride (7.5 mg, 0.195 mmol) in anhydrous EtOH (0.5 cm3) at 0 "C. After the reaction, the mixture was diluted with saturated aqueous NH4Cl and thoroughly extracted with CH2C12. The extract was washed with brine, dried and evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel.Elution with hexane-AcOEt (9: 1 v/v) afforded the title compound 29a (66.8 mg, 98) as a pale yellowish oil; v,,,(neat)/cm-' 1525 and 1350 (NO,), 1093 (OSi) and 870 (C-N); 6"(500 MHz; CDCl,) 0.024 and 0.026 (each 3 H, each s, SiMe,), 0.88 (9 H, s, Bu'), 0.95 (3 H, s, Me), 0.99 (3 H, s, Me), 1.09 (3 H, s, Me), 1.24-1.47 (4 H, m), 1.48-1.65 (3 H, m), 1.87 (1 H, dt, J 7.8 and 22.1), 1.92-2.13 (3 H, m), 2.56-2.65 (1 H, m, 6-H), 2.77 (1 H, dd, J 8.4 and 10.8, CHHSe), 3.01 (1 H, dd, J 6.0 and 10.8, CHHSe), 3.84 (1 H, d, J 7.2,7-H), 7.30 (1 H, ddd, J 1.8,6.2 and 8.2, ArH), 7.46-7.55 (2 H, m, 2 x ArH) and 8.28 (1 H, dd, J 1.8 and 8.2, ArH); m/z 480 (M' -Bu') (Found: M' -Bu', 480.1460.C2,H,,NO3SeSi requires m/z,480.147 1). (1S*,2R*,6R*,7R*,8R*)-7-tert-Buryfdimerhyfsifoxy-3-merhyfene-8,11,11-trimerhyftri~ycfo6.3.0.0~~~undecune30.- Method A. To a stirred solution of the seleno compound 29a (4.0 mg, 0.0077 mmol) in dry THF (0.5 cm3) was added at 0 "C 30 H202 (0.01 cm3, 0.077 mmol), and the mixture was stirred for 2.5 h at ambient temperature. After addition of saturated aqueous NaHCO,, the resulting mixture was thoroughly extracted with mixtures of benzene and hexane (1 :1 v/v). The organic layer was washed with saturated aqueous NaHCO, and brine, dried and evaporated under reduced pressure to afford a residue which was chromatographed on silica gel with hexane-AcOEt (19: 1 v/v) as eluent to provide the title com-pound 30(1.8 mg, 70) as an oil; v,,,(neat)/cm-' 1640 (=); 6H(500 MHz; CDCl3) 0.03 (6 H, S, SiMe,), 0.90 (9 H, S, Bu'), 1.00 (3 H, s, Me), 1.01 (3 H, s, Me), 1.10 (3 H, s, Me), 1.37-1.45 (3 H, m), 1.48-1.63 (3 H, m), 1.83 (1 H, ddd, J8.7, 13.2 and 16.6), 2.23 (1 H, dtt, J2.0,9.0and 16.2), 2.41-2.49 (1 H, m), 2.54-2.62 (2 H, m), 3.90 (1 H, d, J6.7,7-H) and 4.73 and 4.78 (each 1 H, each br s, =CH,); m/z319 (M+ -Me) (Found: M+ -Me, 319.2463.C20H350Si requires m/z, 319.2457). Method B.According to the above procedure, the isomer 29b (3.9 mg, 0.0075 mmol) was converted into the olefin 30(1.6 mg, 64) as an oil, which was identical in all respects with the above sample, prepared by Method A. (lS*,2S*,3S*,6R*,7R*,8R*)-7-tert-ButyldimethyZsiZoxy-3-methoxycarbonyl-8,11,11-trimethyZtricycI06.3.0.0~~~undecane 26b.-According to the same procedure for the production of 26a, the hydroxy ester 24b (5.8 mg, 0.02 mmol) was converted, using TBDMSOTf (0.02 cm3, 0.08 mmol), DMAP (1.0 mg, 0.008 mmol) and 2,6-dimethylpyridine (0.02 cm', 0.12 mmol) in CH,Cl, (1.0 cm3), into the title compound 26b (7.7 mg, 93) as an oil; v,,,(neat)/cm-' 1740 (C==O);6,(500 MHz; CDC1,) 0.01 and 0.02 (each 3 H, each s, SiMe,), 0.86 (6 H, s, 2 x Me), 0.89 (9 H, s, Bu'), 1.07 (3 H, s, Me), 1.20-1.61 (5 H, m), 1.62-2.09 (4 H, m), 2.35-2.94 (3 H, m), 3.65 (3 H, s, OMe) and 3.81 (1 H, d, J 6.8, 7-H); m/z 380 (M+) (Found: M+, 380.2705.C22H4003Si requires M, 380.2746). (1S*,2S*,3S*,6R*,7R*,8R*)-7-tert-ButyldimethylsiZoxy-3-hydroxymethyZ-8,11,11-trimethyltricycl06.3.0.0~~~undec~ne 27b.-According to the same procedure for the production of 27a, the ester 26b (7.7 mg, 0.019 mmol) was reduced with DIBAL-hexane (1.0 mmol dm-,; 0.2 cm3, 0.2 mmol) in dry THF (0.5 cm3) to give the title compound 27b (6.0 mg, 84) as an oil; v,,(neat)/cm-' 3340 (OH); 6,(500 MHz; CDC1,) 0.01 and 0.02 (each 3 H, each s, SiMe,), 0.89 (9 H, s, Bu'), 0.94 (3 H, s, Me), 0.95 (3 H, s, Me), 1.03 (3 H, s, Me), 1.23-1.52 (7 H, m), 1.59 (1 H, br s, OH), 1.72 (1 H, dt, J 7.2 and 12.8), 1.94 (1 H, ddd, J 4.0,9.2and 13.9),2.11 (1 H,ddd, J6.2, 12.0and 18.3),2.26(1 H, dd, J6.6 and 12.8), 2.53-2.61 (1 H, m), 3.56 (1 H, dd, J7.2 and 10.2,CHHOH),3.70(1H,dd,J7.1and10.2,CHHOH)and3.80 (1 H, d, J 7.2, 7-H); m/z295 (M+ -But) (Found: M+ -Bur, 295.21 15).(1S*,2S*,3S*,6R*,7R*,8R*)-7-tert-~utyIdimethyZsiZoxy-3-methy/sulfonyIoxyme~hyZ-8,11,1l-trimethy/tricycI06.3.0.0~*~-undecane 29b.-According to the same procedure for the production of 28a, the alcohol 27b (4.0 mg, 0.011 mmol) was transformed, using methanesulfonyl chloride (0.003 cm3, 0.035 mmol) and Et,N (0.008 cm3, 0.057 mmol) in dry CH2C12 (1.0 cm3), into the mesylate 28b (4.0 mg, 82) as an oil; v,,,(neat)/cm-' 1360 and 1181 (SO,); 6,(90 MHz; CDCl,) 0.03 (6 H, s, SiMe,), 0.89 (9 H, s, Bu'), 0.94 (6 H, s, 2 x Me), 1.04 (3 H, s, Me), 3.00 (3 H, s, SO,Me), 3.81 (1 H, d, J 7.1, 7-H) and 4.10-4.30 (2 H, m, CH,OMs); m/z415 (M' -Me) (Found: M+ -Me, 415.2330). According to the same procedure for the production of 29b, the mesylate 28b (4.0 mg, 0.0093 mmol) was converted, using 2-nitrophenyl selenocyanate (53 mg, 0.23 mmol) and sodium J.CHEM.SOC. PERKIN TRANS.1 1992 borohydride (10.5 mg, 0.28 mmol), into the title compound 29b (3.9 mg, 80) as an oil; v,,,(neat)/cm-' 1514 and 1332 (NO,), 1099 (0) and 839 (C-N); 6H(500 MHz; CDCl,) 0.01 and 0.03 (each 3 H, each s, SiMe,), 0.89 (9 H, s, Bu'), 1.02 (6 H, s, 2 x Me), 1.05 (3 H, s, Me), 1.20-1.45 (6 H, m), 1.68 (1 H, dt, J 6.2 and 12.1), 1.85-2.05 (2 H, m), 2.20-2.30 (1 H, m), 2.35 (1 H, dd, J 6.0 and 13.5), 2.57-2.63 (1 H, m), 2.85 (1 H, t, J 10.6, CHHSe), 3.01 (1 H, dd, J 5.4 and 10.6, CHHSe), 3.83 (1 H, d, J 7.8, 7-H), 7.30 (1 H, ddd, J 1.4, 7.2 and 8.4, ArH), 7.467.55 (2 H, m, 2 x ArH) and 8.26 (1 H, dd, J 1.4 and 8.1, ArH); m/z 522 (M' -Me) and 480 (M' -Bur) (Found: M' -Bu', 480.1491).(1S*,2R*,6R*,7R*,8R*)-7-Hydroxy-3-methyZene-8,ll,ll-tri-rnethyltricycl06.3.0.0~~~undecane31.-To a stirred solution of the siloxymethylene derivative 30 (10.0 mg, 0.0299 mmol) in THF (0.5 cm3) was added at 0deg;C a solution of tetrabutyl-ammonium fluoride in THF (1 mol drn-,; 0.12 cm3, 0.12 mmol) containing water (5 w/v), and the mixture was heated for 4 h at 60". After evaporation of the solvent, the residue was chromatographed on silica gel eluting with hexane-AcOEt (9: 1 v/v) to afford the title compound 31 (5.9 mg, 90) as an oil; v,,,(neat)/cm-' 3430 (OH) and 1651 (CS); 6H(500 MHz; CDCl,) 1.03 (3 H, s, Me), 1.06 (3 H, s, Me), 1.20 (3 H, s, Me), 1.25-1.30 (1 H, m), 1.41-1.52 (4 H, m), 1.661.69 (1 H, m), 1.71- 1.79 (1 H, m), 1.80-1.87 (1 H, m), 2.33-2.41 (1 H, m), 2.46-2.54 (1 H, m), 2.62-2.70 (2 H, m), 3.78 (1 H, br t, J6.4,7-H) and 4.78 and 4.84 (each 1 H, each s, =CH,); m/z 220 (M+) (Found: M+, 220.1839.C, sH240 requires M, 220.1854). (lS*,2R*,6R*,8R*)-3-MethyIene-8,1l,ll-trimethyltricycZo-6.3.0.02*6undecan-7-one32.-To a stirred solution of TAP1 lo (33.5 mg, 0.079 mmol) in dry CH2Cl, (1.0 cm3) was added a solution of the alcohol 31 (5.8 mg, 0.0264 mmol) in dry CH,Cl, (1.0 cm3), and the mixture was stirred for 30 min at ambient temperature. After addition of Et,O and saturated aqueous NaHCO, containing Na2S20, (5 mg) with ice cooling, the mixture was stirred for 10 min at ambient temperature.The re- sulting mixture was thoroughly extracted with Et,O and the ex- tract was washed with saturated aqueous NaHCO, and water, dried and evaporated under reduced pressure. Chromatography of the residue on silica gel with hexane-AcOEt (19:l v/v) as eluent gave the ketone 32 (5.2 mg, 91) as an oil, whose IR, 'H NMR (100 MHz; CDCl,), ' NMR (50 MHz; CDCl,) and MS spectra agreed well with those reported for the authentic compound.30 (1S*,2R*,7R*,8S*,9R*)-3-tert-ButyZdimethyZsiIoxy-8-hy-droxy-9,12,12-trimethyltricycZo7.3.0.02~'dodec-3-ene2Ob.-To a mixture of liquid NH, (4.0 cm3) and anhydrous MeOH (0.5 cm3) were added at -33 "C a solution of the ketone 18a (2.0 mg, 0.0057 mmol) in dry THF (2.0 cm3), followed by metallic Li (90.0 mg, 13.0 mmol), and the resulting mixture was stirred for 1 h at the same temperature.After addition of saturated aqueous NH,Cl, followed by evaporation of NH,, the residue was acidified with 5 aqueous KHSO,. The mixture was extracted with CH2Cl, and the extract was washed with brine, dried and evaporated under reduced pressure to give a residue, which was subjected to chromatography on silica gel. Elution with hexane-AcOEt (19: 1 v/v) afforded the title compound 20b (1.8 mg, 90) as an oil; v,,,(neat)/cm-' 3370 (OH), 1660 (W) and 1061 (OSi);6,(500 MHz; CDCl,) 0.10 (3 H, s, SiMe), 0.12 (3 H, s, SiMe), 0.91 (9 H, s, Bur), 0.97 (3 H, s, Me), 1.06 (3 H, s, Me), 1.18 (3 H, s, Me), 1.20-1.27 (2 H, m), 1.34-1.40 (1 H, m), 1.47-1.55 (3 H, m), 1.68-1.74 (1 H, m), 1.83-1.90 (2 H, m), 1.94- 1.99 (1 H, m), 2.30-2.34 (1 H, m), 3.63 (1 H, s, J 11.0, 8-H) and 4.62-4.64 (1 H, m, 4-H); m/z350 (M') (Found: M+, 350.2648.C2,H,,02Si requires M, 350.2639). J. CHEM. SOC. PERKIN TRANS. 1 1992 Acknowledgements We thank Professors Y. Yamamoto and T. Uyehara of Tohoku University for their generous gift of the spectral data of 32. We also thank Professor L. N. Mander of the Australian National University for the kind information about methyl cyanoformate. We are indebted to Mr. K. Kawamura, Miss K. Mushiake, Miss M. Inada, Mrs. A. Satoh and Miss N. 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Cornmun., 1980,lO, 273. 7 A part of this work has been published as a preliminary communication: M. Ihara, T. Suzuki, M. Katogi, N. Taniguchi and K. Fukumoto, J. Chem. SOC., Chem. Commun., 1991,646. 8 L. N. Mander and S. P. Sethi, Tetrahedron Lett., 1983,24,5425. 9 H. C. Brown, Organic Synthesis via Boranes, Wiley-Interscience, New York, 1975,p. 28. 10 D. B.Dess and J. C. Martin, J. Org. Chem., 1983,48, 4155;J. Am. Chem. SOC., 1991,113,7277. 11 D. H. R. Barton, J. P. Kitchin, D. J. Lester, W.B. Motherwell and M. T. B. Papoula, Tetrahedron,1981,37,73. 12 (a) S. Danishefsky and T. Kitahara, J. Am. Chem. SOC., 1974,96, 7805;(b) M. Ihara, M. Katogi, K. Fukumoto and T. Kametani, J. Chem.Soc., Perkin Trans. I, 1988,2963. 13 (a) H. Emde, A. Gotz, K. Hofmann and G. Simchen, Liebigs Ann. Chem., 1981, 1643; (b) L. N. Mander and S. P. Sethi, Tetrahedron Lett., 1984,2!5,5953;(c)M. Ihara, Y.Ishida, M. Abe, M. Toyota, K. Fukumoto and T. Kametani, J. Chem. SOC., Perkin Trans. 1, 1988, 1155. 14 J. Jkvy, J.-Y. Laronze and J. Sapi, Tetrahedron Lett., 1988,29,3303. 15 M. Koreeda, D. J. Ricca and J. I. Luengo, J. Org. Chem., 1988,53, 5586. 16 K. B. Wiberg, R. L. Furtek and K. L. Olli, J. Am. Chem. Soc., 1979, 101,7675. 17 P. A. Grieco, S. Gilman and M. Nishizawa, J. Org. Chem., 1976,41, 1485. 18 K. B. Sharpless and M. W. Young, J. Org. Chem., 1975,40,947. Paper 1/05754E Received 13th November 1991 Accepted 13th January 1992