Synthesis based on cyclohexadienes. Part 17. Total synthesis of the sesquiterpenes ofEremophila georgeidiels

摘要

J. CHEM. SOC. PERKIN TRANS. I 1995 Synthesis based on cyclohexadienes. Part 17.' Total synthesis of the sesquiterpenes of Eremophila georgei Diels Natesan Selvakumar, Seenivasaga N. Janaki, Kakumanu Pramod and G. S. R. Subba Rao * Department of Organic Chemistry, Indian Institute of Science, Bangalore-560012, India The first stereoselective total synthesis of the novel sesquiterpenes 1 and 2 is described. The preparation of the key intermediate 27 involved a rearrangement of a bicyclo3.2.loctane framework to an isomeric bicycle3.2.1) octene skeleton via a bicyclo2.2.2octane derivative. A number of natural products possess the novel bicyclo- C3.2.1)octane framework with a bridgehead methyl group. These are represented by the complex tricyclic sesquiterpenes 1 and 2, isolated from Eremophila georgei Diels,2 and the tetracyclic diterpenes scopadulciol3 and scopadulcic acids A 4 and B 5, reported from Scoparia d~fcis.~ The presence of a unique tricyclic ring system in conjunction with the bridgehead methyl group in these molecules makes them synthetically challenging targets.1 R'=H,R2=OH 3 R' = Me, R2= CHZOH 2 R'R~=O 4 R' = COpH, I?= CHpOH 5 R' = Me,R2= C02H The structures of the sesquiterpenes 1 and 2 were established by chemical and spectral methods and confirmed by X-ray crystal studies by Ghisalberti and co-workers. The biogenetic origin of these sesquiterpenes was also proposed by these workers. We describe herein our results in the construction of this unique tricyclic ring system using a Diels-Alder strategy which culminated in the first stereoselective total synthesis of the sesquiterpenes 1 and 15" Results and discussion Birch reduction of the indane 65bafforded the diene 7 in quantitative yield (Scheme 1).Treatment of the diene 7 with KNH,-NH, gave the conjugated diene 8. Regiospecific cycloaddition of the diene 8 with or-chloroacrylonitrile afforded a mixture of the adducts 9 and 10, which were inseparable by column chromatography. However, hydrolysis of the adducts 9 and 10 with aq. KOH in dimethyl sulfoxide (DMS0)6 at 55 "C for 48 h furnished the tricyclic ketone 11 (mixture of methyl epimers) in 50 yield. Reduction of the tricyclic ketone 11 with NaBH, gave a 2: 1 mixture of endo and exo alcohols 12 and 13 respectively, which were separable by column chromatography.Solvolysis of the endo alcohol 12 with BF,-OEt, afforded the enone 14. The exo alcohol 13 yielded the ketone 15 under identical conditions. The IR spectrum of the enone 14 had absorptions at 1680 and 1630 cm-', while the 'H NMR spectrum showed signals atd 0.94 and 1.O (3 H, 2 d, J6.5) for the secondary methyl group, indicating that the tricyclic enone 14 is a mixture of diastereoisomers at C-2. On the other hand, the ketone 15 had IR absorptions at 1715 and 1625 cm-' for the saturated 4 12 9 R'=CI,#=CN 10 R'=CN,#=CI 11 R'#=O 12 R' =H,amp;OH 13 R' = OH, R2= H 16 R' = Me, R2= OH 17 R' =OH, R2 = Me0 13 15 18 19 1 R'=H,R~=OH 2 R'R~=O Scheme 1 Reugentsandconditions: (a) Na, liq.NH,; (b) KNH,, NH,; (c) CH,=C(CI)CN, 90 "C, 48 h; (d) aq. KOH, DMSO, 55 OC, 48 h; (e) NaBH,, EtOH; (f) BF,-OEt,, PhH, 48 h, reflux; (g) MeMgI, 0 "C to reflux; (h) H,, 10 Pd/C, EtOH; (i) NaH, MeI, DME, room temp. to 60 OC carbonyl group and the double bond, respectively. The second- ary methyl group appeared as two doublets at 6 0.93 and 0.94 in its 'H NMR spectrum. The enone 14 has the basic tricyclic ring system present in the sesquiterpenes 1 and 2 except for the bridgehead methyl group, and is accessible in six steps from the indane 6. A similar methodology for the preparation of the analogous enone 18, which has the bridgehead methyl group (and can therefore be transformed into the natural sesqui- terpenes 1 and 2) was then examined.Since the endo alcohol 12 was rearranged to the enone 14 under acidic conditions, similar treatment of the tertiary alcohol 16, available from the ketone 11, should lead to the enone 18 upon exposure to acid. Reaction of the ketone 11 with MeMgI afforded a 2: 1 mixture of the endo and ex0 alcohols 16 and 17, respectively. The skeletal rearrangement was carried out under mild conditions. Thus, exposure of the endo alcohol 16 to a catalytic amount of BF,-Et,O in dry benzene at room temp. afforded the enone 18in good yield. Under identical conditions, the ex0 alcohol 17 also gave the enone 18 in good yield. The 'H NMR spectrum of the enone 18 showed a pair of doublets at 6 0.92 and 1.04 integrating for the three protons of the C-2 methyl group, indicating the epimeric nature of that centre.Attempted separation of these epimers was not successful. Catalytic hydrogenation of the enone 18 over 10 Pd/C afforded the saturated ketone 19. The appearance of only two singlets, at 6 1.1 and 1.14, for the bridgehead methyl group and the presence of two doublets at 60.91 and 0.94 for the secondary methyl group in its 'H NMR spectrum clearly established that the hydrogenation had taken place stereoselectively, presumably from the a face of the molecule as the p face is blocked by the ethano bridge. Alkylation of the ketone 19 with NaH and excess of Me17 yielded the sesquiterpene ketone 2, which upon reduction with NaBH, gave the sesquiterpene alcohol 1in good yield.The spectral and analytical data of the synthetic compounds 1 and 2 were in agreement with the data reported for the natural products, thus establishing their gross structure. Although the above synthesis of the tricyclic compounds 1 and 2 was achieved by a short (eight steps), efficient and straightforward route, the stereochemistry of the C-2 methyl group could not be controlled by this method. Hence an alternative strategy for the stereoselective synthesis of the natural products 1 and 2, involving a stereoselective introduction of the C-2 methyl group, was conceived. The method envisaged is similar to the synthesis * of norprezizanone 24 prepared from the enone 23, which was readily available from the alcohol 22 by an acid-catalysed skeletal rearrangement. The alcohol 22 was obtained from 6-methoxytetralin 20 through the ketone 21.The key step in these transformations is the stereoselective introduction of the C-2 methyl group. Similar transformations on the alcohol 25, also available from the ketone 21, should result in the stereoselective total synthesis of the sesquiterpenes 1 and 2 and hence the preparation of the enone 25 was undertaken. 20 21 laorb 22 R~=H,R*=OH 25 R' = Me, R2 = OH 26 R'=OH,R2=Me 23 R=H 24 R=H 27 R=Me 2 R-Me Scheme 2 Reagents and conditions: (a) NaBH,, EtOH; (b) MeLi, Et,O, -78 "C to room temp.; (c) BF,-OEt,, PhH, room temp.;(d) BF,-OEt,, PhMe, reflux Preparation of the enone 27 Treatment of the ketone 21 * with MeLi afforded a 1 :1 mixture of the tertiary alcohols 25 and 26, which was easily separated J.CHEM. SOC. PERKIN TRANS. 1 1995 by column chromatography (Scheme 2). Examination of the 'H NMR spectrum of these alcohols revealed that the methyl protons appeared at 6 1.04 in the less polar alcohol while in the more polar alcohol they appeared at 6 1.24. The shielding of the methyl protons in the less polar alcohol is attributed to the double-bond anisotropy and hence its structure is assigned to be that of the ex0 alcohol 26. Reaction of the ex0 alcohol 26 with BF,-OEt, in benzene at room temp. for 30 min afforded a mixture of the ketone 28 and the enone 27 in the ratio 4 :1. Under identical conditions, the endo alcohol 25 also rearranged to a mixture of the enone 27 and the ketone 28in the ratio 4 :1.The IR spectrum of the enone 27 showed absorptions at 1677 and 1614 cm-' due to the a,P-unsaturated carbonyl group. The appearance of the olefinic proton at 6 5.64 as a broad singlet in the 'H NMR spectrum confirmed its structure. The ketone 28 showed a carbonyl absorption at 1700 cm-' and the olefinic proton appeared at 6 5.2, in accord with the structure. It is interesting to note that the generation of a stable tertiary carbocation appears to be the rationale behind the formation of the mixture of compounds 27 and 28. Since the enone 27 is required for the synthesis of the sesquiterpenes 1 and 2, and is predominantly formed upon rearrangement of the endo alcohol 25, several experiments were carried out to obtain the endo alcohol 25 exclusively from the ketone 21.Reaction of the ketone 21 with MeLi-LiClO,,' Me,CuLi lo and Me,CuLi, l1 was investigated. With reagents MeLi-LiC10, and Me,CuLi,, only a mixture of the alcohols was obtained, with the ex0 alcohol 26 predominating. In the case of Me,CuLi, reaction occurred only partially, even after a prolonged period. Since all our efforts to increase the yield of the endo alcohol 25 from the ketone 21 were in vain, the acid-catalysed rearrangement of the alcohols 25 and 26 was examined in detail with a view to improving the yield of the enone 27. Upon changing the acid from BF,*OEt, to either HClO,, toluene-p- sulfonic acid (PTSA) or formic acid, no improvement in the yield was observed.However, when the rearrangement was performed in refluxing benzene, a significant change was noticed in the ratio of the ketone 28 to the enone 27. When the ex0 alcohol 26 was refluxed with BF,eOEt, in benzene for 16 h, the ratio of the ketone 28 to enone 27 was found to be 11 :9 (unlike the 4: 1 mixture formed during the reaction at room temp.) due to the equilibration of the ketone 28 to the enone 27 under refluxing conditions. To confirm this equilibration process, the ketone 28 was refluxed in benzene in the presence of BF,-OEt, (cat.) and at various intervals of time an aliquot of the reaction mixture was analysed. After 10 h of reflux, a 4 :1 mixture of the ketone 28and the enone 27 was obtained. The transformation was consider- ably faster for the first 24 h as the ratio reached a 1 :1 mixture, but slowed down after 24 h.After a prolonged period (68 h) the ratio became 1 : 19, thus the ketone 28 isomerizes to the enone 27 in 92 yield. A probable mechanism of the conversion of the ketone 28 into the enone 27 is depicted in Scheme 3. The enone appears to be thermodynamically more stable than the ketone. When the rearrangement of the alcohols 25 and 26 was carried out at room temp., the kinetic product 28 was also observed. However, under refluxing conditions, it isomerizes to the enone 27, wherein formation of the stable tertiary carbocation 29 appears to be the driving force for this rearrangement. Since the energy to overcome the activation barrier is supplied in the form of heat, the rearrangement should be faster if carried out in a higher boiling solvent.This was indeed the case, since a 19: 1 ratio of the enone 27 to the ketone 28 was obtained in refluxing toluene. Having achieved the preparation of the enone 27 in good J. CHEM. SOC. PERKIN TRANS. I 1995 84 1 26 25 28 27 20 Scheme 3 Probable mechanism for the conversion 28 -27 yield, total synthesis of the natural sesquiterpenes 1 and 2 was undertaken by adopting essentially our earlier strategy 'with slight modifications as outlined in Scheme 4. Synthesis of the sesquiterpenes 1 and 2 The enone 27 was treated with KOBu' in Bu'OH and Me1 to obtain the ketone 30 in good yield. The ketone displayed the carbonyl absorption at 1700 cm-' in its IR spectrum and the 'H NMR spectrum exhibited the olefinic proton at 6 5.48 as a triplet.The carbonyl group in compound 30 was protected as the benzyl ether of the corresponding alcohol since the final deprotection of the benzyl ether would regenerate the alcohol functionality leading to the natural products. Reduction of the ketone 30 was found to be sluggish when NaBH, and lithium aluminium hydride (LAH) were used, presumably due to the steric hindrance. However, the keto group was smoothly reduced to the alcohol 31 with diisobutylaluminium hydride (DIBALH), where the stereochemistry of the OH group was assumed to be 'P' equatorial. Benzylation of the alcohol 31 was sluggish with NaH and benzyl bromide in tetrahydrofuran (THF) with a catalytic amount of tetrabutylammonium iodide (TBAI), even under refluxing conditions.However, the benzyl ether 32 was obtained in quantitative yield when 1,2-dimethoxyethane (DME) was used in place of THF. The 'H NMR spectrum of the benzyl ether exhibited peaks corresponding to the benzylic protons at 6 4.72 as a singlet and at 6 7.3 for the aromatic protons. Hydroboration of the ether 32 with BH,-THF complex furnished the alcohol, which was oxidized to the ketone 33 with pyridinium chlorochromate (PCC) in good yield. Aldol condensation of the ketone 33 with furfural afforded the furfurylidene derivative 34,which was subjected to ozonolysis followed by oxidative work-up to the corresponding diacid.'' The diacid was esterified with diazomethane to the diester 35, whose IR spectrum showed an absorption at 1725 crr-' for the ester groups, and the methoxycarbonyl protons appeared as two singlets at 6 3.70 and 3.72 in the 'H NMR spectrum. Dieckmann condensation of diester 35 with 1.2 mol equiv. KOBu' resulted in the P-keto ester 36 in good yield. The P-keto ester showed two absorptions in the IR spectrum at 1740 and 1720 cm-' for the keto and the ester groups, respectively. In 30 P 31 32 BnO 33 34 If 35 36 38 37 b/ 39 40 Scheme 4 Reagents and conditions: (a) KOBu', MeI, PhH, reflux; (b) DIBALH, THF, -78 "C to room temp.; (c) NaH, PhCH,Br, Bu,NI, DME, reflux; (d) (i) BH,*THF, THF, 0deg;C to room temp., then aq.NaOH, 30 H,O,; (ii) PCC, CH,CI,; (e) NaOH, furfural (Zfur- aldehyde), EtOH, 0 "C to room temp.; (f) (i) 0,, EtOAc, -78 "C; then 30 H,02, AcOH; (ii) CH,N,, Et,O; (g) KOBu', PhH, reflux; (h) (i) NaH, PhSeC1, aq. H,O,; (ii) Me,CuLi, -100 "C;(i) DABCO, o-xylene, 85 OC; (j) (i) NaH, CS,, MeI, THF, reflux; (ii) TBTH, AIBN, PhMe, reflux; (k) H,, 10 Pd/C, EtOH; (1) PDC, CH,CI, addition, the 'H NMR spectrum exhibited only one peak for the methoxycarbonyl group, at S 3.76, and a peak for the C-3 proton at 6 3.26 as a doublet of doublets. The P-keto ester 36 possesses the basic tricycloC6.2.1 .O '.'undecane skeleton with a bridgehead methyl group which is required for the natural products 1 and 2. Treatment of the keto ester 36 with NaH and PhSeCl followed by oxidation of the resultant phenylseleno com-pound gave the unstable unsaturated keto ester, which was immediately treated with 1 mol equiv.of Me,CuLi at -100 "C affording the P-keto ester 37 as a mixture of diastereoisomers. Based on our earlier experience,' the conjugate addition reaction was assumed to have taken place stereoselectively, resulting in an epimeric mixture only at C-3 having the methoxycarbonyl group. This was confirmed by decarboxyl- ation of the keto ester 37 with 1,4-diazabicyclo2.2.2octane (DABCO) in o-xylene', which afforded the ketone 38 as a single isomer, as evidenced from its 'H NMR spectrum which showed a lone doublet at 6 0.96 for the C-2 methyl group. Having prepared the ketone 38 as a single isomer, the deoxygenation at C-4 was achieved by the use of Barton's protocol.' Reduction of the ketone 38 to the alcohol 39 was accomplished with excess of DIBALH. The xanthate of the resultant alcohol 39 was obtained in nearly quantitative yield with NaH-CS,-Me1 in refluxing THF, which was reduced by successive addition of tributyltin hydride (TBTH) in refluxing toluene to afford the benzyl ether 40 as a single diastereoisomer as evidenced from its 'H NMR spectrum which exhibited peaks at 6 1.01, 1.05 and 1.13 for the protons of the three methyl groups, and the C-2 methyl protons appeared at 6 0.86 as a doublet. Hydrogenolysis of the benzyl ether 40 with 10 Pd on charcoal afforded the sesquiterpene alcohol 1, which upon oxidation with pyridinium dichromate (PDC) furnished the sesquiterpene ketone 2 in high yield.The IR and 'H NMR spectra of the synthetic ketone 2 and the alcohol 1 were identical with those of an authentic sample provided by Professor Ghisalberti. This constitutes the first total synthesis of these complex tricyclic sesquiterpenes. In conclusion, the first stereoselective total synthesis of the sesquiterpenes 1 and 2 is reported from a readily available cyclohexadiene based on a new and general methodology for the construction of a tricycloC6.2.1 .O ',5undecane skeleton. The synthesis involved a novel rearrangement of a bicyclo- C3.2. lloctene derivative 28 to an isomeric bicycloC3.2. lloctene derivative 27 through the intermediacy of a bicyclo2.2.2system 29.The enone 27 formed the BCD ring core present in the tetracyclic diterpenes scopadulcic acids 3-5. With proper appendages, this new methodology can be extended to their total synthesis. Experimental Mps were measured on a Mettler FP1 instrument and are uncorrected. IR spectra were recorded on a Perkin-Elmer 781 spectrometer as either neat samples or solutions in CHCl, . 'H NMR and 13C NMR spectra were recorded as solutions in CDCl, (unless otherwise stated) with SiMe, as internal standard using Hitachi R-1500 FT 60, JEOL FX-90Q, Bruker ACF-200, Bruker WH-270 and Bruker AMX 400 spectro- meters. Chemical shifts are reported in amp;units, and J-values are in Hz. The usual work-up involved dilution of the reaction mixture with water, extraction with diethyl ether, washing of the organic extract with (successively) water and brine, followed by drying over Na,SO,, and evaporation at aspirator pressure.Column chromatography was performed on silica gel (60-120 mesh) by elution with a light petroleum (distillation range 60-80 OC)-ethyl acetate mixture (9 :1). Liquid ammonia was distilled over sodium amide. Sodium hydride was 60 in oil, and was used after being washed with light petroleum. 5-Methoxy-l-methyl-4,7-dihydroindane7 A solution of 5-methoxy-I-methylindane65b(8.1 g, 50 mmol) in dry THF (10 cm3)-tert-butyl alcohol (20 cm3) was added to stirred distilled ammonia (350 cm3). Sodium (2.3 g, 0.1 mol) was added and the resulting blue solution was stirred for 3 h.Excess of sodium was destroyed by adding solid NH,Cl. Ammonia was allowed to evaporate off, and the residue was extracted with light petroleum. The organic layer was washed with water and dried. Removal of the solvent gave the diene 7 as a liquid, v,,,/cm-' 1690 and 1660; 6,(60 MHz; CCI,) 1.0 J. CHEM. SOC. PERKIN TRANS. 1 1995 (3 H, d, J 7, Me), 1.65 (2 H, m), 2.2 (3 H, br m, allylic), 2.65 (4 H, br s, doubly allylic), 3.5 (3 H, s, OMe) and 4.6 (1 H, br s, olefinic). 5-Methoxy-1-methyl-6,7-dihydroindane8 To a solution of potassium amide formed by the addition of potassium (1 g) to distilled ammonia (250 cm3) followed by FeCl, (cat.) in ammonia was added a solution of the above diene 7 in dry diethyl ether (10 cm3).The resultant dark red solution was stirred for 45 min before being quenched with solid NH,Cl until the red colour disappeared. Ammonia was allowed to evaporate off and the reaction mixture was worked up with light petroleum to give the diene 8, which was used immediately in the next step, v,,,/cm~' 1660 and 1610. 8-Chloro-7-methoxy-2-methy1tricyclo5.2.2.0 1.5~ndec-5-ene-8- carbonitrile 9 and 10 A mixture of the above diene 8, a-chloroacrylonitrile (I I .8 cm3, 0.15 mol) and hydroquinone (10 mg) was sealed in a tube under nitrogen and heated at 90deg;C for 48 h. All the volatiles were removed under reduced pressure and the residue obtained was purified by chromatography to furnish a mixture of adducts 9 and 10 (8.05 g, 64),v,,,/cm-' 2220; 6,(60 MHz; CCl,) 0.95 (3 H, d, J 7, Me), 1.1-2.6 (11 H, m), 3.45 (3 H, s, OMe), 5.81 and 5.98 (1 H, two br s, olefinic) (Found: C, 66.6; H, 7.1. C,,H,,ClNO requires C, 66.8, H, 7.15).7-Methoxy-2-methyltricyclo5.2.2.0 undec-5-en-S-one 11 A solution of the adducts 9 and 10 (6.29 g, 25 mmol), 50 aq. KOH (5.6 cm3, 50 mmol) in DMSO (25 cm3) was stirred at 55 "C for 48 h. The residue obtained after the usual work-up was chromatographed to give the ketone 11 (2.58 g, 50), v,,,/cm-' 1725; 6,(270 MHz) 0.98 and 1.05 (3 H, 2 d, J 6.6, Me), 1.3-2.55 (1 1 H, m), 3.50 and 3.52 (3 H, 2 s, OMe) and 5.88 (1 H, br s, olefinic) (Found: C, 75.6; H, 8.9. C13H18O2 requires C, 75.7; H, 8.8). 7-Methoxy-2-methyltricyclo5.2.2.0 undec-5-en-8-0112 and 13 To a stirred solution of the ketone 11 (I .03 g, 5 mmol) in methyl alcohol (25 cm3) was added NaBH, (95 mg, 2.5 mmol) at room temp.After 2 h, methyl alcohol was removed under reduced pressure from the reaction mixture and the residue was worked up to afford a viscous liquid which showed two closely separated spots on TLC. The mixture was chromatographed: elution with light petroleum-ethyl acetate (9: 1) gave the ex0 alcohol 13 (322 mg), v,,,/cm-' 3440; 6,(90 MHz) 0.94 (3 H, d,J6.2,Me),1.0-2.45(12H,m),3.36(3H,s,OMe),3.84(lH, br m, CHOH) and 5.84 (1 H, br s, olefinic). Further elution with light petroleum-ethyl acetate (4: 1) afforded the endo alcohol 12 (645 mg, 93 total yield, exo: endo ratio 1 :2), v,,,/cm-' 3460; 6,(90 MHz) 0.94 (3 H, d, J6.2, Me), 1.0-2.45 (12 H, m), 3.39 (3 H, s, OMe), 3.87 (1 H, br m, CHOH) and 5.76 (1 H, br s, olefinic) (Found: C, 74.9; H, 9.8.C13H2*02 requires C, 75.0; H, 9.7). 2-Methyltricyclo6.2.1 .O15undec-5-en-7-one 14 A solution of the endo alcohol 12 (416 mg, 2 mmol) in dry benzene (20 cm3) with BF,-OEt, (0.5 cm3) was stirred under reflux for 48 h. The reaction mixture was diluted with benzene, washed successively with water, aq. NaHCO,, and water, and dried. The crude product obtained was purified by chroma- tography to furnish the enone 14 (253 mg, 72), vmax/cm-' 1680 and 1630; 6,(270 MHz) 0.94 and 1.O (3 H, 2 d, J 6.5, Me), 1.1-2.3 (9 H, m), 2.6 (2 H, m, allylic protons), 2.9 (1 H, m, bridgehead proton) and 5.74 (1 H, m, olefinic) (Found: C, 81.6; H, 9.0.C,,H,,O requires C, 81.8; H, 9.15). J. CHEM. SOC. PERKIN TRANS. I 1995 2-Methyltricyclo5.3.1.01~undec-5-en-amp;one 15 When the exo alcohol 13 (208 mg, 1 mmol) in dry benzene (15 cm3) was treated with BF3-OEt, (cat.) as described above, the ketone 15 was obtained (120 mg, 6873, v,,,/cm-' 1715 and 1625; 6,(270 MHz) 0.93 and 0.94 (3 H, 2 d, J 6.8, Me), 1.1-2.4 (11 H, m), 2.72 (1 H, m, bridgehead proton) and 5.42 (1 H, m, olefinic) (Found: C, 81.6; H, 9.1). 7-Methox y -8-methyltricyclo5.2.2.01Jundec-5-en-8-01 16 and 17 A solution of the ketone 11 (1.24 g, 6 mmol) in dry diethyl ether (10 cm3) was added during 10 min to a solution of MeMgI prepared from magnesium (292 mg, 12 mmol) in diethyl ether (10 cm') at 0 "C under nitrogen.The reaction mixture was warmed to room temp. and refluxed for 6 h before being worked up. The residue obtained was chromatographed as above for the compounds 12 and 13 to give the exo alcohol 17 (390 mg), v,,,/cm-' 3460; amp;(90 MHz) 0.93 (3 H, d, J 6.6, Me), 1.10 (3 H, s, Me), 1.25-2.45 (12 H, m), 3.35 (3 H, s, OMe), 5.89 (1 H, br, olefinic) and endo alcohol 16 (78 1 mg, 88 total yield, exo: endo ratio 1 :2), vmax/cm-' 3500; 6,(90 MHz) 0.94 (3 H, d, J6.6, Me), 1.21 (3 H, s, Me), 1.26-2.40 (12 H, m), 3.42 (3 H, s, OMe) and 5.96 (1 H, br, olefinic). 2,8-Dimethyltricyclo6.2.1.O 1q5undec-5-en-7-one 18 A solution of the endo alcohol 16 (488 mg, 2.2 mmol) in dry benzene (30 cm3) was treated with BF,-OEt, (0.5 cm3) as mentioned above for the compound 14 to furnish the pure enone 18 (284 mg, 6879, vmax/cm-' 1680 and 1450; 6,(90 MHz) 0.92 and 1.04 (3 H, 2 d, J 7, Me), 1.23 (3 H, s, Me), 1.6 2.1 (9 H, m), 2.56 (2 H, m, allylic protons) and 5.75 (1 H, m, olefinic) (Found: C, 82.0; H, 9.4.CI3Hl8O requires C, 82.1; H, 9.5). Similar treatment of the exo alcohol 17 also gave the enone 18. 2,amp;Dimethyltricyclo6.2.1 .O 'p5undecan-7-one 19 A solution of the enone 18 (209 mg, 1.1 mmol) in absolute ethyl alcohol (10 cm3) was stirred with 10 Pd/C (10 mg) under H, .After 4 h the catalyst was filtered off on a pad of Celite and silica gel, and the filtrate was chromatographed to furnish the ketone 19 (207 mg, 98), v,,,/cm-' 1710; 6,(270 MHz) 0.91 and 0.94 (3 H, 2 d, J 6.6, Me), 1.1 and 1.14 (3 H, 2 s, Me) and 1.3-2.6 (14 H, m) (Found: C, 81.1; H, 10.5. CI3H2,O requires C, 81.2; H, 10.5).2,6,6,amp;Tetramethyltricyclo6.2.1.O undecan-7-one 2 To a stirred suspension of NaH (120 mg, 3 mmol) in dry DME (16 cm3) at room temp. was added a solution of the ketone 19 (192 mg, 1 mmol) and Me1 (0.6 cm3, 9.6 mmol) in DME (3 cm3). The reaction mixture was heated to 60 "C for 2 h before being quenched with water (1 cm3). The residue obtained after the usual work-up was chromatographed to give compound 2 as a liquid (143 mg, 65), vmax/cm-l 1705; 6,(90 MHz) 0.90 and 0.94 (3H,2d,J6.5,Me),l.l2(3H,s,Me),l.l6(6H,s,2Me)andx 1.4-2.0 (12 H, m) (Found: C, 81.8; H, 10.9. CI5H2,O requires C, 81 3;H, 11.Ox)lit.,, v,,,/cm-' 1700; 6,(90 MHz) 0.92 (3 H, d, J7, Me), 1.12(6H,s,2 x Me), 1.16(3H,s,Me).2,6,6,amp;Tetramethyltricyclo6.2.1.O undecan-7-011 To a solution of the ketone 2 (88 mg, 0.4 mmol) in ethyl alcohol (10 cm3) was added NaBH, (15 mg, 0.4 mmol) at room temp. After being stirred for 2 h, the reaction mixture was concen- trated under reduced pressure and was poured into aq. NH,Cl (25 cm'). The usual work-up followed by chromatography furnished the aIcohoI 1 (83 mg, 93) as a viscous liquid, v,,,/cm~' 3460; 6,(90 MHz) 0.88 and 0.90 (3 H, 2 d, J 6.8, Me), 0.98 (3 H, s, Me), 1.03 (3 H, s, Me), 1.06 (3 H, s, Me), 1.24-2.08 (13 H, m) and 3.23 and 3.26 (1 H, 2 br s, CHOH) (Found: M', 222.1989. C,,H,,O requires M, 222.1984) lit.,2 v,,,/cm-' 3640; amp;(90 MHz) 0.86 (3 H, J 7, d, Me), 0.92, 1.03, 1.07 (s, 3 x Me), 3.18 (1 H, s, 7a-H).amp;Methoxy-9-methyltricyclo 6.2.2.0 dodec-6-en-9-01 25 and 26 Reaction of the ketone 21 with MeLi at -78 "C. A 1.O mol dm-3 solution of MeLi in diethyl ether (12 cm3, 12 mmol) was added to a solution of ketone 218 (2.06 g, 10 mmol) in dry diethyl ether (100 cm3) dropwise over a period of 5 rnin at -78 "C under argon. After 1 h, the reaction mixture was warmed to room temp. over a period of 15 rnin for 2 h. The product mixture was added into aq. NH,Cl and extracted with diethyl ether. The organic layer was washed successively with water, aq. sodium thiosulfate, water and brine, and dried. The residue obtained after the removal of solvent showed two well separable components on TLC.The mixture was chromato- graphed as mentioned above for compounds 12 and 13 to afford the exo alcohol 26 (910 mg), vmax/crrp' 3466; 6,(60 MHz; CCl,) 1.04 (3 H, s, Me), 1.20-2.50 (15 H, m), 3.33 (3 H, s, OMe) and 5.80 (1 H, br s, olefinic); 6,(22.5 MHz) 19.0 (t), 21.2 (t), 22.8 (t), 26.8 (t), 27.3 (q), 31.8 (t), 32.2 (t), 37.0 (t), 49.1 (t), 51.1 (q), 76.5 (t), 83.0 (s), 123.0 (d) and 145.0 (s) and the endo alcohol 25 (910 mg, 82 total yield, exo :endo ratio 1 :l), vma,/cm-' 3472; 6,(60 MHz; CCl,) 1.24 (3 H, s, Me), 1.28-2.54 (15 H, m), 3.40 (3 H, s, OMe) and 5.85 (1 H, br s, olefinic); amp;-(22.5 MHz) 18.5 (t), 21.0 (t), 24.2 (t), 25.0 (q), 26.3 (t), 31.5 (t, 2 x C), 37.0 (s), 51.0 (q), 51.8 (t), 75.8 (s), 82.0 (s), 122.1 (d) and 145.0(s). Reaction of the ketone 21 with various reagents.(a) With LiClO, and MeLi.-Lithium perchlorate (321 mg, 2 mmol) was heated to 100 "C under reduced pressure (0.1 mmHg) for 6 h to obtain a fine powder of anhydrous LiCIO,, which was dissolved in anhydrous diethyl ether (10 cm3) and the temper- ature was brought to -78 "Cunder argon, To this homogeneous solution were added successively a solution of the ketone 21 (4 12 mg, 2 mmol) in dry diethyl ether (1 0 cm3) and a 1 mol dmp3 solution of MeLi (4 cm3, 4 mmol) in diethyl ether, and the reaction mixture was warmed to room temp. after 1 h. After 30 rnin at room temp., the reaction mixture was worked up and chromatographed as above to afford the exo alcohol 26 (229 mg) and endo alcohol 25 (108 mg) (76 total yield, exo:endo ratio 68 :32).(b) With excess of Me,CuLi.-To a stirred suspension of CuI (2.285 g, 12 mmol) in anhydrous diethyl ether (20 cm3) at 0 "C under argon was added dropwise a 1 mol dm-3 solution of MeLi (24 cm3, 24 mmol) in diethyl ether. After 5 min, a solution of the ketone 21 (618 mg, 3 mmol) in dry diethyl ether (10 cm3) was added and the resultant mixture was brought to room temp. and stirred overnight. The reaction mixture was worked up and chromatographed as above. The first component was the ex0 alcohol 26 (107 mg) followed by the unchanged starting material 21 (371 mg, 60 recovered). The last component was the endo alcohol 25 (71 mg) (72 on the basis of consumed starting material, exo :endo ratio 60 :40).(c) With Me,CuLi,.-To a suspension of CuI (1.714 g, 9 mmol) in anhydrous diethyl ether (20 cm3) at 0deg;C under argon was added a 1 mol dmP3 solution of MeLi (27 cm3, 27 mmol) in diethyl ether slowly over a period of 5 min. After the mixture had been stirred for 5 min, a solution of ketone 21 (618 mg, 3 mmol) in dry diethyl ether (10 cm3) was added at the same temperature. The resultant mixture was left to warm to room temp. after 1 h and was stirred for a further 3 h. The reaction mixture was worked up and chromatographed as above to afford the ex0 alcohol 26 (359 mg) and the endo alcohol 25 (220 mg) (87 total yield, exo: endo ratio 62 :38). 9-Methyltricycl07.2.1.0'~6dodec-6-en-amp;one27 and 8-methyltricyclo6.3.1.O J dodec-tkn-9-one 28 (R = Me) Reactions of various substrates with BF3*OEt,.(a) exo Alcohol 26 at room temp.-A solution of the exo alcohol 26 (1.11 g, 5 mmol) in dry benzene (35 cm3) with BF3-OEt2 (cat.) was stirred at room temp. for 30 min. The reaction mixture showed two spots different from starting material on TLC. The reaction mixture was worked up with diethyl ether and the residue obtained was chromatographed. Elution with light petroleum-ethyl acetate (9 :1) afforded the ketone 28 (R = Me) (700 mg), vmax/cm-l 1700; 6,(90 MHz) 1.12 (3 H, s, Me), 1.20-2.64 (14 H, m) and 5.2 (1 H, d, J 2, olefinic); 6,(22.5 MHz) 17.30 (q), 22.37 (t), 26.01 (t), 26.66 (t), 29.26 (t), 34.86 (t), 36.81 (t), 46.43 (s), 55.79 (t), 56.58 (s), 127.59 (d), 149.96 (s) and 211.60 (s) (Found: M+, 190.1352.CI3Hl8O requires M, 190.1358). Further elution with light petroleum+thyl acetate (4 :1) gave the enone 27 (1 74 mg, 92 total yield, ketone :enone ratio 4: l), vma,/cm--' 1677 and 1614; 6,(90 MHz) 1.23 (3 H, s, Me), 1.36-1.96 (12 H, m), 2.4 (2 H, br, C-5) and 5.64 (1 H, br s, olefinic); 6,(22.5 MHz) 19.32 (q), 22.32 (t), 24.27 (t), 30.38 (t), 34.54(t, 2 x C), 35.97(t),47.16(~), 50.93(s), 52.62(t), 122.20(d), 169.41 (s) and 203.49 (s) (Found: M+, 190.1370). (b) endo Alcohol 25 at room temp.-When endo alcohol 25 (888 mg, 4 mmol) was subjected to the rearrangement in benzene (30 cm3) as described above, there were obtained the ketone 28 (1 34 mg) and the enone 27 (553 mg, 88 total yield, ketone :enone ratio 1 :4).(c) exo Alcohol 26 in refluxing benzene.-A solution of the exo alcohol 26 (1.465 g, 6.6 mmol) in benzene (40 cm3) with BF3*OEt2 (cat.) was refluxed for 16 h. The reaction mixture was worked up as above to afford the ketone 28 (276 mg) and the enone 27 (225 mg, ketone :enone ratio 1 1 :9). (d) Ketone 28 in refluxing benzene.-A mixture of the ketone 28 (1.90 g, 10 mmol), benzene (50 cm3) and BF3-OEt2 (cat.) was refluxed. An aliquot was removed at different intervals of time and worked up as described above. After 10 h of reflux, the ratio of ketone 28 to enone 27 was 4: 1, while the same was a 1 :1 mixture after 24 h. After 68 h of reflux, the ratio of ketone to enone reached 1 :19.(e) Ketone 28 in refluxing toluene.-When the ketone 28 (444 mg, 2 mmol) was refluxed with BF3.0Et2 (cat.) for 7 h in toluene (20 cm3) as above, there were obtained the ketone 28 (14 mg) and the enone 27 (336 mg) (92, ketone:enone ratio 1 :19). 7,7,9-Trimethyltricyclo7.2.1.0 '*6dodec-5-en-8-one 30 To a stirred slurry of KOBu' in tert-butyl alcohol, prepared from potassium (1.17 g, 30 mmol) and dry tert-butyl alcohol (25 cm3), was added a solution of the enone 27 (1.90 g, 10 mmol) in dry benzene (50 cm3). After 30 min, Me1 (6.22 cm3, 0.1 mol) was added rapidly and the mixture was refluxed for 2 h. The reaction mixture was brought to room temp. and a further quantity of Me1 (2 cm3) was added.The resulting solution was stirred for 6 h and the usual work-up followed by chro- matography afforded the ketone 30 (1.679 g, 77), vmaX/cm-' 1700; SH(60 MHz) 1.18 (3 H, s, Me), 1.22 (3 H, s, Me), 1.28 (3 H, s, Me), 1.4C2.40 (12 H, m) and 5.48 (1 H, t, J 4, olefinic); 6,(22.5 MHz) 19.87 (t), 20.78 (t), 25.34 (t), 30.54 (q), 31.71 (q), 35.61 (t), 36.13 (q), 38.21 (t), 44.59 (s), 46.54 (s), 46.93 (t), 52.52 (s), 118.59 (d), 149.28 (s) and 218.21 (s) (Found: M', 218.1671. C,,H,,O requires M, 218.1642). amp;Benzyloxy-7,7,9-trhethyltricyclo7.2.1.01*6dodec-5ene 32 A 20 solution of DIBALH (13.2 cm3, 12.25 mmol) in hexane was added to a solution of the ketone 30 (1.526 g, 7 mmol) in dry THF (50 cm3) under Ar at -78 "C.After being stirred for 1 h, the reaction mixture was warmed to room temp. for 2 h. J. CHEM. SOC. PERKIN TRANS. 1 1995 The resultant solution was quenched with MeOH (4 cm3) and poured into saturated aq. sodium potassium tartrate (1 25 cm3). The clear solution obtained was worked up, and this was followed by chromatography to afford the alcohol 31, vmaX/cm-' 3420; amp;(60 MHz) 1.12 (3 H, s, Me), 1.14 (3 H, s, Me), 1.19 (3 H, s, Me), 1.20-2.12 (13 H, m), 3.22 (1 H, br d, CHOH, becomes singlet with D20) and 5.46 (1 H, t, J 3.6, olefinic). A solution of the above alcohol 31 and benzyl bromide (0.83 cm3, 7 mmol) in dry DME (20 cm3) was added to a suspension of NaH (560 mg, 14 mmol) and TBAI (cat.) in dry DME (30 cm3) at room temp. under argon.The reaction mixture was refluxed for 24 h followed by the usual work-up and chromatography (light petroleum) to yield the ether 32 as an oil (2.04 g, 9473, v,,,/cm-' 1450; 6,(60 MHz) I .16 (3 H, s, Me), 1.20 (6 H, s, 2 x Me), 1.24-2.24 (12 H, m), 3.08 (1 H, s, 8-H), 4.72 (2 H, s, OCH,Ph), 5.44 (1 H, t, J 3.6, olefinic) and 7.247.48 (5 H, m, Ph); 6,(50 MHz) 20.64, 25.63, 26.19, 27.80, 30.29,31.60,37.49,38.62,41.40,44.90,46.33,51.67,76.44,93.69, 116.85,126.88and 128.00(5 x Arc), 139.45and 151.77(Found: M+, 310.2283. CZ2H3,-,O requires M, 310.2297). 8-BenzyIoxy-7,7,9-trimethyltricyclo7.2.1 .0'96 dodecan- 5-one 33 To a stirred solution of the ether 32 (1.86 g, 6 mmol), in dry THF (50 cm3) was added 0.6 mol dmP3 BH,*THF (22.6 cm3, 12 mmol) dropwise at 0 "C under argon.The resultant mixture was' brought to room temp. and stirred for a further 5 h. The reaction mixture was quenched with water and was treated successively with 20 aq. NaOH (1.8 cm3, 9 mmol) and 30 aq. H202 (1.4 cm3, 18 mmol). After 3 h, the usual work-up and chromatography afforded the corresponding C-5 alcohol (1.614 g, 82), vmax/cm-' 3440; 6,(60 MHz) 1.10 (3 H, s, Me), 1.20 (3 H, s, Me), 1.32 (3 H, s, Me), 1.20-2.20 (14 H, m), 3.02 (1 H, s, 8-H), 3.80 (1 H, br, 5-H), 4.72 (2 H, s, OCH,Ph) and 7.22-7.46 (5 H, m, Ph). A mixture of the above alcohol (1.574 g, 4.8 mmol), PCC (1 -293 g, 6 mmol) and silica gel (1.5 g) in dry CH2C12 (40 cm3) was stirred at room temp. for 30 min. The solvent was removed, the resultant powder was dissolved in diethyl ether, and the solution was filtered through a pad of Celite.The filtrate was evaporated and the residue was purified by chromatography to afford the ketone 33 (1.471 g, 94). An analytical sample was obtained by recrystallization in light petroleum, mp 78 "C; vmax/cm-l 1700; 6,(60 MHz) 1.16 (3 H, s, Me), 1.28 (3 H, s, Me), 1.32 (3 H, s, Me), 1.30-2.40 (13 H, m), 2.96 (1 H, s, 8-H), 4.70 (2 H, s, OCH,Ph) and 7.24-7.50 (5 H, m, Ph); 6,(22.5 MHz) 16.26(q), 22.63 (t), 24.97 (q), 31.73 (q), 32.90 (t), 33.42 (t), 38.76 (t), 39.67 (s), 43.05 (t), 46.04 (s), 48.90 (s), 55.01 (t), 65.16 (d), 76.60 (t), 93.90 (d), 127.07 and 128.11 (2 d, 5 x Arc), 139.29 (s) and 209.78 (s) (Found: C, 81.0; H, 9.5; M', 326.2232.C22H3OO2 requires C, 80.9; H, 9.3; M, 326.2245). Methyl 4-benzyloxy-1- 2-(methoxycarbonyl)ethyl -3,3,5-trimethylbicyclo 3.2.1 octane-2-carboxylate 35 To a stirred solution of the ketone 33 (1.467 g, 4.5 mmol) in ethyl alcohol (40 cm3) at 0 "C under argon was added dropwise 20 aq. NaOH (0.9 cm3, 4.5 mmol). After 30 min a solution of furfural (2-furaldehyde) (0.37 cm3, 4.5 mmol) in ethyl alcohol (1 cm3)was added, and the reaction mixture was warmed to room temp. After 7 h, the usual work-up gave the furfurylidene derivative 34 as a yellow solid which was used directly in the next step without purification. A solution of compound 34 in ethyl acetate (50 cm3) was ozonized at -78 "C until TLC indicated the disappearance of starting material.The solvent was evaporated off and the residue was treated with acetic acid (30 cm3), 30 aq. H202 (10 cm3) and dil. H2S04 (0.5 cm3). The mixture was stirred overnight and concentrated at 40 *C under reduced pressure. J. CHEM. SOC. PERKIN TRANS. I 1995 The residue was dissolved in diethyl ether (300 cm3), the solution was washed with brine, and the solvent was evaporated off to give the corresponding dicarboxylic acid. A solution of the above acid in dry diethyl ether (100 cm3) was esterified with ethereal diazomethane. The residue ob- tained after removal of the solvent was purified by chroma- tography to obtain the diester 35 (1.23 g, 6873, which was recrystallized from light petroleum, mp 63 "C; vmax/cm-' 1725; 6,(60 MHz) 1.12 (3 H, s, Me), 1.16 (3 H, s, Me), 1.20 (3 H, s, Me), 1.20-2.60 (11 H, m), 3.06 (1 H, s, 4-H), 3.70 (3 H, s, CO,Me), 3.72 (3 H, s, C02Me), 4.70 (2 H, s, OCH2Ph) and 7.28-7.48 (5 H, m, Ph); 6,(22.5 MHz) 19.45 (q), 25.41 (q), 30.06 (t),31.26(t),31.91 (q),33.75(t,2 x C),39.17(s),46.21 (s),46.64 (s), 50.33 (q), 50.76 (q), 51.52 (t), 59.54 (d), 76.76 (t), 93.01 (d), 127.14 and 128.23 (2 d, 5 x Arc), 139.06 (s), 172.87 (s) and 174.06 (s) (Found: C, 72.0; H, 8.7; M', 402.2387.C24H340, requires C, 7 1.6; H, 8.5; M, 402.2406). Methyl 7-benzyloxy-6,6,amp;trimethyl-4-oxotricyclo6.2.1.0'w5-undecane-karboxylate 36 To a solution of KOBu' in tert-butyl alcohol prepared from potassium (1 1 1 mg, 3 mmol) and dry tert-butyl alcohol (5cm3) was added a solution of the diester 35 (1.005 g, 2.5 mmol) in dry benzene (50 cm3) under argon.The reaction mixture was refluxed for 6 h and then added to aq. NH4C1. Work-up with ethyl acetate followed by chromatography afforded the P-keto ester 36 as an oil (722 mg, 78), vmax/cm-l 1740 and 1720; amp;-(90 MHz) 1.20 (6 H, s, 2 x Me), 1.30 (3 H, s, Me), 1.32-2.44 (9H,m),3.04(1 H,s,7-H),3.26(1 H,dd, J9and 10.8,3-H), 3.76 (3 H, s, CO,Me), 4.70 (2 H, s, OCH,Ph) and 7.28-7.48 (5 H, m, Ph); 6,(22.5 MHz) 15.97 (q), 24.94 (q), 30.80 (q), 32.75 (t), 33.01 (t), 35.48 (t), 38.60 (s), 44.58 (s), 47.06 (s), 50.70 (d), 52.26 (q), 54.99 (d), 66.57 (d), 76.71 (t), 93.61 (d), 127.04 and 128.08 (2 d, 5 x Arc), 139.01 (s), 169.76(s) and 208.33 (s) (Found: C, 74.6; H, 8.35.C23H3004 requires C, 74.7; H, 8.2). 7-Benzyloxy-2,6,6,8-tetramethyltricyclo6.2.1.0'*5undecan-4one 38 A solution of the 0-keto ester 36 (370 mg, 1 mmol) in dry THF (3 cm3) was added to a stirred suspension of NaH (44 mg, 1.1 mmol) in dry THF (7 em3) over a period of 10 min at 0 "C under argon. After 15 min, PhSeCl(2 1 1 mg, 1.1 mmol) in THF (3 cm3) was added rapidly. The reaction mixture was poured into a mixture of diethyl ether (50 cm3) and saturated aq. NaHCO, (50 cm3), and worked up as usual to obtain the selenide. To a stirred solution of the above crude selenide in CH2C1, (8 cm3) was added 30 aq. H20, (0.22 cm3, 1.95 mmol) dropwise at 5 "C. After 10min, the reaction mixture was diluted with CH,Cl,, washed with water and dried to give a residue, which was chromatographed to afford the corresponding unsaturated keto ester as an unstable oil (331 mg, 90), vmaX/cm-' 1719.A solution of the above unsaturated keto ester (331 mg, 0.9 mmol) in dry diethyl ether (10 cm3) was added to a solution of Me,CuLi prepared by the addition of a 1 mol dm-3 solution of MeLi (1.8 cm3, 1.8 mmol) in diethyl ether into a suspension of Cul (171 mg, 0.9 mmol) in dry diethyl ether (10 em3) at 0 "C under argon at -100 "C. The reaction mixture was stirred for 30 min and quenched with aq. NH4C1. The usual work-up followed by chromatography yielded the P-keto ester 37 as an oil (304 mg, 88), vm,,/cmp' 1725; 6amp;00 MHz) 1.00 (3 H, d, J 7, 2-Me), 1.12-2.48 (20 H, m), 2.95-3.01 and 3.38-3.42 (2 H, m), 3.71 and 3.73 (3 H, 2 s, CO,Me), 4.68 (2 H, br, OCH,Ph) and 7.26-7.40 (5 H, m, Ph).A mixture of the P-keto ester 37 (288 mg, 0.75 mmol), DABCO (841 mg, 7.5 mmol) and o-xylene (5 em3) was heated to 85 0C under argon for 7 h. The reaction mixture was acidified with 0.5 mol dmP3 HC1 and worked up to obtain the ketone 38 (200 mg, 82) after chromatography. An analytical sample was obtained by recrystallization from light petroleum, mp 116 "C; vmaX/cm-' 1735; 6,(90 MHz) 0.96 (3 H, d, J 7.2, 2-Me), 1.10 (6 H, s, 2 x Me), 1.24 (3 H, s, Me), 1.28-2.60 (10 H, m), 2.92 (1 H, s, 7-H), 4.60 (2 H, s, OCH2Ph) and 7.26 (5 H, br s, Ph); amp;(75 MHz) 16.26, 17.57, 25.07, 30.67, 33.41, 35.18, 35.88, 38.22, 46.40, 47.59 (2 x C), 52.13, 61.03, 76.54, 93.81, 126.98 and 128.04 (5 x ArC), 139.06 and 216.57 (Found: C, 80.65; H, 9.2.C22H30O2 requires C, 80.9; H, 9.3). 7-Benzyloxy-2,6,6,amp;tetramethyltricyclo 6.2.1 undecane.0135 40 A 20 solution of DIBALH in hexane (1.08 cm3, 1 mmol) was added to a stirred mixture of ketone 38(163 mg, 0.50 mmol) in dry THF (6 cm3) under argon at -78 "C. After 1 h, a further quantity of DIBALH (1.08 cm3, 1 mmol) was added and the mixture was stirred for a further 1 h before being warmed to room temp. for another 1 h. The mixture was worked up as for the compound 31 and chromatography afforded the alcohol 39 (148 mg, 90), v,,,/cm-' 3442; amp;(90 MHz) 0.92 (3 H, d, J 7, 2-Me), 1.20 (6 H, s, 2 x Me), 1.36 (3 H, s, Me), 1.36-2.60 (10 H, m), 3.00 (1 H, br, 7-H), 4.40 (1 H, t, J 3.6, 4-H), 4.70 (2 H, br, OCH2Ph) and 7.26-7.48 (5 H, m, Ph); 6,(22.5 MHz) 18.5, 19.0,26.0,30.5,34.0,37.5,38.0,40.5,46.0,48.0,50.0,52.0, 60.8, 73.5, 76.5,94.0, 127.0 and 128.0 (5 x Arc) and 139.5.To a suspension of NaH (64 mg, 1.6 mmol) and imidazole (cat.) in dry THF (3 cm3) was added a solution of the alcohol 39 (131 mg, 0.4 mmol) in dry THF (2 em3) under argon, and the mixture was refluxed for 2 h. It was then cooled, a solution of CS2 (0.24 cm3, 4 mmol) in THF (1 cm3) was added, and reflux was resumed for a further 45 min. The reaction mixture was cooled, a solution of Me1 (0.25 cm3, 4 mmol) in THF (1 cm3) was added, and the mixture was refluxed for 30 min. After the usual work-up, the residue obtained upon filtration through a column of silica gel (light petroleum) was worked up to yield the corresponding xanthate as a yellow oil (1 57 mg, 94).A mixture of the above xanthate (1 54 mg, 0.37 mmol) and azoisobutyronitrile (AIBN) (cat.) in dry toluene (2 cm3) was added to a refluxing solution of TBTH (0.20 cm3, 0.74 mmol) in toluene (5 cm3) under argon. After 6 h, a further quantity of TBTH (0.20 cm3, 0.74 mmol) with AIBN (cat.) in toluene (1 cm3) was added during reflux. Reflux was continued for an additional 5 h and all volatiles were then removed under reduced pressure. The residue obtained upon chromatography on neutral alumina (light petroleum) yielded the benzyl ether 40 (108 mg, 94), vma,/cm-' 1452; 6,(200 MHz) 0.86 (3 H, d, J7,2-Me), 1.01 (3 H, s, Me), 1.05 (3 H, s, Me), 1.13 (3 H, s, Me), 1.07-2.00 (1 2 H, m), 3.03 (1 euro;5, s, 7-H), 4.68 (2 H, dd, OCH2Ph) and 7.26-7.41 (5 H, m, Ph); 6,(100 MHz) 17.48, 19.83, 23.01, 25.65,30.38,32.15,34.32,34.83,38.90,40.36,47.35,47.92,53.67, 54.10,76.53,94.44,127.11,127.19, 128.17(5 x ArC)and139.71 (Found: C, 84.6; H, 10.4.C22H3,0 requires C, 84.6; H, 10.3). 2,6,6,amp;Tetramethyltricyclo6.2.1.0'Jundecan-7-01 1 A solution of the benzyl ether 40 (94 mg, 0.3 mmol) in absolute ethyl alcohol (6 em3) was stirred with 10 Pd/C (10 mg) under H,. After 2 h, the reaction mixture was worked up as for compound 19 to give the alcohol 1 (63 mg, 9473, vmax/cm-l 3440; 6amp;00 MHz) 0.85 (3 H, d, J 7.1, 2-Me), 0.91 (3 H, s, Me), 1.03(3 H, s, Me), 1.06 (3 H, s, Me), 1.1 1-1.92 (13 H, m) and 3.18 (1 H, S, 7-H); 6,(100 MHz) 16.22, 19.82, 23.31, 24.98, 29.29, 32.22, 33.59, 34.74, 37.85, 40.43, 46.25, 47.79, 53.71, 54.14 and 85.41.2,6,6,8-Tetrarnethyltricyclo6.2.1.O1q undecan-7-one 2 A mixture of the alcohol 1 (44 mg, 0.2 mmol), PDC (150 mg, 0.4 mmol) and silica gel (200 mg) in dry CH,C12 (5 em3) was stirred for 2 Ik. The reaction mixture was worked up as for compound 33 to obtain the ketone 2 (41 mg, 9373, v,,,/cm-' 1698; 6,(200 MHz) 0.W (3 H, d, J 7.2, 2-Me), 1.10 (6 H, s), 1.13(3H,s)and 1.162.15(12H,m);6,(75MHz)19.62,21.49, 22.64,24.46,29.17,31.39,33.22,35.00,40.06,45.04,45.41,53.19, 53.71, 54.01 and 219.64. Acknowledgements We thank Professor E. L.Ghisalberti of University of Western Australia for kindly providing the spectra of sesquiterpenes 1 and 2. We thank the CSIR and the UGC, New Delhi for the award of fellowships (S. N. J., K. P. and N. S.). The Sophisticated Instrumental Facility (SIF) at the IISc campus is acknowledged for recording the high-field NMR spectra. References 1 For Part 16 of the series, see P. S. Shanker and G. S. R. Subba Rao, Ind. J. Chem.,accepted for publication. 2 P. J. Carrol, E. L. Ghisalberti and D. E. Ralph, Phytochemistry, 1976, 15, 777; E. L. Ghisalberti, A. H. White and A. C. Willis, J. Chem. SOC.,Perkin Trans. 2, 1975, 1300. 3 T. Hayashi, M. Kishi, M. Kawasaki, M. Arisawa, M. Shimuzu, S. Suzuki, M. Yoshizaki, N. Morita, Y. Tezuka, T. Kikuchi, L. H. Berganza, E. Ferro and I. Bassualdo, Tetrahedron Lett., 1987,28,3693. J. CHEM. SOC. PERKIN TRANS. I 1995 4 K. Pramod and G. S. R. Subba Rao, J. Chem. Soc., Chem. Commun., 1982,762. 5 (a) The preliminary account of the work has been reported: N. 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Paper 4/06192F Received 1 1th October 1994 Accepted 3rd November 1994