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Synlett 2002(10): 1712-1714
DOI: 10.1055/s-2002-34211
LETTER
© Georg Thieme Verlag Stuttgart · New York

‘One-pot’ Reactions: Total Synthesis of the Spirocyclic Marine Sesquiterpene, (+)-Axenol

Kai Oesterreich, Iris Klein, Dietrich Spitzner*
Institut für Chemie, Abt. Bioorganische Chemie, Universität Hohenheim, Garbenstr. 30 70599 Stuttgart, Germany
Fax: +49(711)4593703; e-Mail: spitzner@uni-hohenheim.de;
Further Information

Publication History

Received 19 June 2002
Publication Date:
23 September 2002 (online)

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Abstract

The marine sesquiterpene alcohol (+) axenol was prepared in a very short way from (+)-menthone using a one-pot olefination-ring closing metathesis.

Key words

domino reaction - methylenation - metathesis - organometallic - natural products

    References

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13

Domino reaction: To a stirring solution of 5.01 g (13.8 mmol) MoOCl3(THF)2(5) in THF (30 mL) under Ar at
-80 °C was added 15.8 mL of a solution of 1.6 M MeLi in diethyl ether. Stirring was continued at -80 °C for 10 min after which a solution of 1.07 g (4.2 mmol) of the ketone 2a (2:1) in THF (5 mL) was added slowly using a syringe. The reaction mixture was slowly warmed to r.t. over night. To the brown reaction mixture was added 179 mg (0.2 mmol) of the catalyst {[MesIm][(Cy)3P]RuCl2CHPh}(6) and stirring was continued at r.t. for additional 24 h (monitoring by GC). The reaction mixture was diluted with petrol ether/diethyl ether, (10 + 1) and the suspension filtered through silica gel. The concentrated filtrate was distilled. Kugelrohr (110-120 °C/0.06 Torr); yield (3 + 4, as 2:1-mixture): 0.510 g (60%), colorless oil. The mixture was chromatographed on silica gel/10% AgNO3, eluent CH2Cl2. IR (Film): ν = 2956, 2930, 2955, 2870 (CH), 1704 (C=O), 1652 (C=C), 1460, 1376, 1130 cm-1. C15H24O: HRMS: Calcd 220.1827. Found: 220.1821. 3: 1H NMR (CDCl3): δ = 0.89 (d, J = 8.4 Hz, 3 H, CH 3), 0.92 (d, J = 6.6 Hz, 6 H, CH 3), 1.37 (ddd, J = 12.8 Hz, J = 12.8 Hz, J = 3.8 Hz, 1 H, 8-H), 1.50-1.75 (m, 4 H, 10-H, 9-H,
4-H), 1.75 (br s, 3 H, allylic-CH 3), 2.05-2.40 [m, 5 H, 3-H, 8-H, 7-H, CH(CH3)2], 2.84 (ddd, J = 13.4 Hz, J = 9.4 Hz, J = 5.2 Hz, 1 H, 4-H), 5.35 (s, 1 H, 1-H). 13C NMR (CDCl3): δ = 16.9 (q, CH3), 17.2 (q, CH3), 19.0 (q, CH3), 21.7 (q, CH3), 26.5 [d, CH(CH3)2], 28.4 (t, C-4), 28.8 (t, C-8), 32.0 (t, C-9), 36.3 (t, C-3), 43.8 (d, C-10), 53.6 (d, C-7), 69.9 (s, C-5), 123.3 (d, C-1), 145.1 (s, C-2), 212.8 (s, CO). GC-EI-MS: m/z (%) = 220 (25) [M+], 192 (14) 149 (12), 121 (100), 108 (62). CD (methanol): λmax(Θ/Δε) = 296 nm (+4.56 × 103/+1.38). 4: 1H NMR (CDCl3): δ = 0.86-0.91 (3 × d, 9 H, 3 Me), 1.54-1.6 (m, 1 H), 1.61-1.68 (m, 1 H), 1.76 (d, J = 1.1 Hz, 3 H, allyl. CH 3 ), 1.84-1.91 (m, 1 H), 1.96-2.07 (m, 3 H), 2.08-2.15 (m, 2 H), 2.16-2.24 (m, 2 H), 2.25-2.34 (1 H), 5.50 (s, 1 H, 1-H). 13C NMR (CDCl3): δ = 15.9 (q), 16.8 (q), 19.1 (q), 21.3 (q), 24.6 (t, C-8), 26.1 (d, C-10), 29.2 (t, C-4), 34.5 (t, C-9), 35.5 (t, C-3), 41.4 [d, CH(CH3)2] 53.9 (d, C-7), 68.0 (s, C-5), 126.4 (d, C-1), 141.3 (s, C-2), 215.7 (s, CO). GC-EI-MS: m/z (%) = 220 (20) [M+], 192 (10) 149 (10), 121 (100), 108 (60). CD (methanol): λmax(Θ/Δε) = 296 nm (-3.48 × 103/-1.05).
(+)-1: A solution of 88 mg (0.4 mmol) of ketone 3 in THF (10 mL) at r.t. was added 2 mL (2 mmol) of l-Selectride
[1.0 M LiBH(s-Bu)3 in THF] with stirring. Stirring was continued over night. After this time 0.5 g of solid pyridine-1-oxide was added and stirring was continued for another
1 h. The solution was concentrated and the remaining oil dissolved in diethyl ether (50 mL), the etheral solution washed with 2 N HCl (15 mL), water (3 × 10 mL), dried (MgSO4), concentrated, and the residue purified on silica gel (petroleum ether/diethyl ether, 10 +1). Yield 75 mg (84%). IR(film): ν = 3470 (OH), 2950 (CH) cm-1. 1H NMR (CDCl3): δ = 0.73 (d, J = 6.7 Hz, 3 H, CH 3), 0.92 [d, J = 6.6 Hz, 3 H, CH(CH)3], 0.93 [d, J = 6.6 Hz, 3 H, CH(CH)3], 1.05 (dddd, J = 3.7 Hz, J = 12.8 Hz, J = 12.8 Hz, J = 12.8 Hz, 1 H, 9-H), 1.15 (m, 1 H, 7-H), 1.26 (dddd, J = 3.7 Hz, J = 12.8 Hz, J = 12.8 Hz, J = 12.8 Hz, 1 H, 8-H), 1.45 (m, 1 H, 9-H), 1.55 [m, 1 H, CH(CH3)2], 1.65 (m, 1 H, 8-H), 1.70 (m, 1 H, 10-H), 1.75 (q, J = 1.5 Hz, 3 H, allylic-CH 3), 1.78 (ddd, J = 12.5 Hz, J = 8.0, J = 8.0 Hz, 1 H, 4-H), 1.88 (ddd, J = 12.5 Hz, J = 8.0, J = 8.0 Hz, 1 H, 4-H), 2.21 (m, 2 H,
3-H), 3.52 (br s, 1 H, 6-H), 5.18 (m, 1 H, 1-H). 13C NMR (CDCl3): δ = 16.2 (q, CH3), 16.9 (q, allylic-CH3), 20.7 and 21.2 [q, CH(CH3)2], 24.4 (t, C-8), 29.3 [d, CH(CH3)2], 31.7 (t, C-4), 33.9 (t, C-9), 34.0 (d, C-10), 36.3 (t, C-3), 45.3 (d, C-7), 58.9 (s, C-5), 76.4 (d, C-6), 125.5 (d, C-1), 142.8 (s,
C-2). GC-MS (70 eV): m/z (%) = 222 (70), 204 (20), 121 (100). [α]D 25 +23 (c 0.6, CHCl3). [Lit. [15] : +1.3 (c 0.6, CHCl3, 589 nm); lit. [5b] : [α]D 32 -17 (c 0.5, CHCl3) for (-)-1].