OAc H H O H O H H (–)-1 (–)-2 3 C O CH2Cl CHO H CHO H H 4 5 6 CHO CHO OH OH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 i ii H 6 OH OH 1 2 3 4 5 6 7 8 9 10 11 12 15 i H 7 OH OH O OH H 8 OH OH OH ii iii H O R H O H OH H OAc vi v iv 10 (–)-2 9 R = a-CH2OH 11 R = b-CH2OH (–)-1 36 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 36–37† Partial Synthesis of (µ)-11,12-Dinordriman-8-one and the (µ)-Enantiomer of Polywood† Manuel Cort�es,* Luis Moreno and Jos�e L�opez Facultad de Qu�ýmica, Pontifica Universidad Cat�olica de Chile, Casilla 306, Correo 22, Santiago, Chile A chiral sequiterpene diol 6, readily available from the natural product polygodial (4), has been used for the first partial synthesis of the title compounds.In a study of the odour evaluation of trans-decalins, the secondary acetate (�)-1 and the ketone (�)-2 have been reported to possess a woody tonality.1,2 Racemic 1 (known as Polywood) and 2 have been previously synthesized by acid-catalysed cyclization of acyclic or monocyclic precursors.3,4 Later, the acetate (µ)-1 and ketone (µ)-2 were prepared using enzyme-catalysed kinetic resolution of (�)-3.5 Pursuing our interest in the synthesis of terpenoids and related products from naturally chiral compounds, 6–8 we report here the first partial syntheses of (µ)-1 and (µ)-2, using readily available starting material and cheap reagents.The starting material was the chiral diol 69–10 derived from isopolygodial (5) which in turn was obtained by basic isomerization of polygodial (4), available from various natural sources11–13 (Scheme 1).The synthetic sequence is shown in Scheme 2. Epoxidation of 6 with m-chloroperbenzoic acid produced a single epoxide (7) in 75% yield. the a-stereochemistry of the epoxide was determined by means of both 1H and 13C NMR spectroscopy. Comparison of the 7-H signal in the 1H NMR spectrum of 7 (d 3.3, dd, W1/2 5.2 Hz) with that of 11-acetoxy- 7a,8-epoxydrimane (d 3.04, dd, W1/2 4.6 Hz)14 indicated that both compounds have the same epoxide stereochemistry. On the other hand the signal for C-5, appearing at a field of 15.2 ppm higher than that corresponding to 6 in the 13C NMR spectrum, confirmed the a configuration of the epoxide as reported for similar compounds.15 This stereochemistry is explained by considering that the hydrogen bonding between the hydroxy group at C-11 and the peracid directs the epoxidation reactions.16 The epoxide 7 was refluxed with LiAlH4 in tetrahydrofuran (THF) to afford the triol 8 in 85% yield.Oxidative degradation of 8 with sodium periodate gave the ketol 9 in 75% yield. Transformation of 9 into (µ)-2 was carried out by treatment with Jones reagent. The carboxylic acid could not be isolated because decarboxylation was spontaneous. The retro-aldol process was discarded because when the ketol 9 was treated with a mixture of sulfuric acid, water and acetone (Jones reagent without CrO3), the starting material was recovered exclusively.The physical constants and spectral data of (µ)-2 were in accord with the values described by Gautier et al.5 Compound (µ)-2 was reduced with DIBALH to give the b-alcohol 10 in 80% yield. Finally, acetylation of 10 with Ac2O in pyridine gave (µ)-1 in 97% yield. It is important to note that attempted oxidation of the epimeric ketol 11 (prepared by the same sequence starting with the diol derived from polygodial) gave a large number of products, none of which could be identified. We have no explanation for the difference in reactivity between the two epimers. Experimental Melting points were determined on a Kofler hot-stage apparatus and are uncorrected.Optical rotations were obtained for solutions in chloroform (g/100 mL) on a Perkin Elmer 241 polarimeter. 1H and 13C NMR spectra were recorded on a Bruker AM 200 spectrometer. Chemical shifts are reported in ppm downfield relative to tetramethylsilane (d scale) in CDCl3 solutions.Carbon substitution degrees were established by DEPT pulse sequence. For analytical TLC, Merck silica gel 60G in 0.25 mm thick layers was used. Chromatographic separations were carried out by conventional column on Merck silica gel 60 (70–230 mesh) using hexane– EtOAc mixtures of increasing polarity. All organic extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure, below 65 °C. (µ)-Polygodial (4) was purified from a light petroleum extract of the bark of Drimys winteri.11 7a,8-epoxy-(9b-H)-drimane-11,12-diol (7).·To a solution of the diol 6 (1 g, 4.2 mmol) in CH2Cl2 (30 mL) m-chloroperbenzoic acid *To receive any correspondence (e-mail: rmeza@lascar.puc.cl).†This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Scheme 1 Reagents: i, KOH, MeOH (50%); ii, NaBH4, MeOH (80%) Scheme 2 Reagents: i, m-chloroperbenzoic acid, CH2Cl2, 15 °C (75%); ii, LiAlH4, THF (85%); iii, NaIO4, MeOH (75%); iv, CrO3, H2SO4, acetone (72%); v, DIBALH, THF (80%); vi, Ac2O, Py (97%)1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 J.CHEM. RESEARCH (S), 1998 37 (0.94 g, 5.4 mmol) was added in small portions at room temperature during 10 min. Stirring was continued at room temperature for 35 min. The reaction mixture was washed with NaHCO3 and water, dried and concentrated.The residue was chromatographed over silica gel to afford the (unstable) epoxide 7 (0.79 g, 75%), mp 105–107 °C (from acetone–hexane); [a]D 25 µ69.2 (1.01, CHCl3) dH 0.84 (s, 3 H), 0.87 (s, 3 H), 0.94 (s, 3 H) and 3.3 (dd, W1/2 5.2 Hz) (Found: C, 69.90; H, 10.60. C15H26O3 requires C, 70.83; H, 10.30%). (8R)-(9b-H)-Drimane-8,11,12-triol (8).·To a stirred mixture of LiAlH4 (0.6 g, 16 mmol) in dry THF (50 mL) a solution of the epoxide 7 (1.15 g, 4.5 mmol) in dry THF (30 mL) was added and the mixture was heated at reflux temperature under nitrogen for 4 h.The excess of reagent was decomposed by the addition of EtOAc and an aqueous solution of HCl (10%). The mixture was extracted with EtOAc and the organic phase was washed with NaHCO3 and water, dried and concentrated to give the triol 8 (0.99 g, 85%) mp 117–120 °C (from EtOAc); [a]D 25 µ41.6 (c, 1.12), dH 0.75 (s, 3 H), 0.82 (s, 3 H) 1.01 (s, 3 H) and 3.5–4.0 (m, 4 H) (Found: C, 69.90; H, 11.09.C15H28O3 requires C, 70.27; H, 11.01%). 11-Hydroxy-(9b-H)-12-nordriman-8-one (9).·To a stirred solution of NaIO4 (0.76 g, 3.53 mmol) in water (15 mL) a solution of the triol 8 (0.86 g, 2.54 mmol) in MeOH (10 mL) was added at room temperature during 1.5 h. The reaction solution was extracted with EtOAc and the organic phase was washed with NaHCO3, water and dried. The crude product was purified by column chromatography to provide compound 9 (0.5 g, 75%), mp 111–112 °C (from acetone–hexane); [a]D 25 µ22.1 (c, 0.68 in CHCl3); dH 0.92 (s, 3 H), 0.94 (s, 3 H), 0.94 (s, 3 H), 2.1–2.4 (m, 2 H) and 3.93 (m, 2 H) (Found: C, 74.80; H, 10.80.C14H24O2 requires C, 74.95; H, 10.78%). 11,12-Dinordriman-8-one [(µ)-2].·To compound 9 (3.2 g, 15.4 mmol) in acetone (50 mL) Jones reagent (11.5 mL, 2.6 M; 30.8 mmol) was added while swirling and the reaction was monitored by TLC. Usual work-up gave the ketone (µ)-2 (2.2 g, 72%), mp 90–92 °C (from hexane) (lit.,5 88–90 °C); [a]D 25 µ81.8 (c, 1.1 in CHCL3) {lit.,5 [a]20 D µ81.6 (c, 1.23 in CHCl3)}.For spectroscopic data see ref. 5. 11,12-Dinordriman-8b-ol (10).·To a solution of the ketone (µ)-2 (0.5 g, 0.52 mmol) in dry THF (20 ml) at 0.1 M solution of diisobutylaluminium hydride in hexane (5 mL, 5 mmol) was added dropwise at room temperature. The reaction mixture was stirred for 2 h at room temperature. EtOAc (5 mL) and water (5 mL) were then successively added and the organic phase was separated.The aqueous layer was extracted with EtOAc. The combined organic phases were washed with brine, dried and concentrated. The residue was purified bography to afford the b-alcohol 10 (0.43 g, 80%), mp 89–91 °C (from hexane) (lit.,5 89–90 °C), [a]D 25 µ18.8 (c, 0.32 in CHCl3) [lit.,5 µ19.6 (c, 1.2 in CHCl3)]. For spectral data, see ref. 5. 8b-Acetoxy-11,12-dinordrimane (µ)-2 (Polywood).·Acetylation of 10 (0.06 g, 0.31 mmol) under normal conditions with Ac2O– pyridine gave the acetate (µ)-1 (0.07 g, 97%) as an oily product; [a]D 25µ15.60 (c, 0.52 in CHCl3) (lit.,5 [a]D 20µ16.47).The 1H and 13C NMR spectra were in accord with those kindly sent to us by Dr N�af (ref. 5). We gratefully acknowledge the Consejo Nacional de Ciencia y Tecnolog�ýa (Research Grant 1960451) for financial support. We also thank Dr F. N�af (Firmenich SA, Research Lab. Switzerland) for 1H and 13C NMR spectra of compounds (µ)-2 and (µ)-1 and Professor S.Alegr�ýa for helpful discussions. Received, 22nd April 1997; Accepted, 29th September 1997 Paper E/7/02743E References 1 G. Ohloff, The Fragrance of Ambergris, in Fragrance Chemistry, ed. E. T. Theimer, Academic Press, New York, 1982, p. 553. 2 G. Ohloff, Experientia, 1986, 42, 271. 3 G. Ohloff, F. N�af, R. Decorzant, W. Thommen and E. Sundt, Helv. Chim. Acta, 1973, 56, 1414. 4 S. M. Linder, D. Reichlin and R. L. Snowden, Tetrahedron Lett., 1993, 34, 4789. 5 A. Gautier, C. Vial, C. Morel, M. Lander and N. N�af, Helv. Chim. Acta, 1987, 70, 2039. 6 M. Cort�es and J. L�opez, Nat. Prod. Lett., 1994, 5, 183. 7 V. Armstrong, M. Cort�es and J. L�opez, Nat. Prod. Lett., 1996, 8, 225. 8 M. E. Reyes, V. Armstrong, E. Madriaga, M. Cort�es and J. L�opez, Synth. Commun., 1996, 26, 1995. 9 A. J. Aasen, T. Nishida, C. R. Enzell and H. Appel, Acta Chem. Scand., Ser. B, 1997, 31, 51. 10 G. Aranda, I. Facon, J. I. Lallemand, M. Leclaire, R. Azerad, M.Cort�es, J. L�opez and H. Ramirez, Tetrahedron. Lett., 1992, 51, 7845. 11 M. Cort�es and M. L. Oyarz�un, Fitoterapia, 1981, 52, 33. 12 C. S. Barnes and J. W. Loder, Aust. J. Chem., 1962, 15, 322. 13 Y. Fukuyama, T. Sato, Y. Asakawa and T. Takemoto, Phytochemistry, 1982, 21, 2895. 14 D. M. X. Donelly, J. O’Reilly, A. Chiaroni and J. Polonsky, J. Chem. Soc., Perkin Trans 1, 1980, 2196. 15 M. G. Sierra, M. I. Colombo, M. E. Zudenigo and E. A. Ruveda, Phytochemistry, 1984, 23, 1685. 16 M. Mousseron-Canet, B. Labeeuw and J. C. Lane, Bull. Soc. Chim. Fr., 1968, 2125. Table 1 13C NMR data (CDCl3, 50.3 MHz) Compound Carbon 6 7 8 9 (µ)-2 10 (µ)-1 C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 C-10 C-11 C-12 C-13 C-14 C-15 COCH3 COCH3 36.5 18.8 42.7 33.1 54.1 24.3 127.5 137.2 43.3 36.0 63.1 67.7 21.7 22.0 33.0 36.3 18.3 42.4 32.8 38.9 22.8 56.9 61.9 48.4 34.8 60.3 66.7 22.1 22.8 32.9 37.4 20.1 42.2 33.4 56.7 18.8 33.1 76.5 48.5 37.6 60.9 69.4 21.8 23.7 33.1 39.3 18.5 42.2 33.4 46.0 23.2 36.8 214.7 67.1 40.0 60.7 · 22.0 22.0 33.5 42.0 18.8 42.3 33.2 52.2 23.1 42.0 211.7 59.6 38.4 —— 19.4 21.4 33.3 42.4 18.3 42.5 33.0 54.3 17.0 35.2 67.9 51.3 34.2 —— 21.4 21.4 33.1 42.1 18.3 42.4 33.0 53.9 17.6 32.2 70.6 47.8 34.2 —&