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Synlett 2002(2): 0340-0342
DOI: 10.1055/s-2002-19750
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Ring Closing Metathesis-Based Approach to (±)-Herbertene, (±)-α-Herbertenol, (±)-β-Herbertenol and (±)-Herbertenediol

A. Srikrishna*, M. Srinivasa Rao
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
e-Mail: ask@orgchem.iisc.ernet.in;
Further Information

Publication History

Received 30 November 2001
Publication Date:
02 February 2007 (online)

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Abstract

An efficient methodology for the synthesis of the aromatic sesquiterpenes (±)-herbertene, (±)-α-herbertenol, (±)-β-herbertenol (±)-herbertenediol and (±)-α-cuparenone, employing a combination of Claisen rearrangement and ring closing metathesis reactions, is described.

Key words

herbertane - aromatic sesquiterpenes - Claisen rearrangement - ring closing metathesis

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Typical Procedure for Claisen Rearrangement: A solution of the cinnamyl alcohol 18a (300 mg, 1.85 mmol), ethyl vinyl ether (532 mg, 7.4 mmol) and a catalytic amount of mercury (II) acetate (≈ 50 mg) was heated to180 °C in a Carius tube under nitrogen atmosphere for 48 h. The reaction mixture was then cooled, diluted with ether, washed with aq. NaHCO3 solution and brine, and dried (Na2SO4). Evaporation of the solvent and purification of the product on a silica gel column using ethyl acetate-hexane (1:20) as eluent furnished the aldehyde 19a (226 mg, 65%) as an oil. Typical Procedure for RCM Rreaction: A solution of the dienol 20a (50 mg, 0.23 mmol) in CH2Cl2 (4 mL) was added to a solution of Grubbs" catalyst (15 mg, 8 mol%) in CH2Cl2 (4 mL) under nitrogen atmosphere and stirred for 4 h at room temperature. Evaporation of the solvent and purification of the residue on a silica gel column furnished the cyclopentenol 21a (42 mg, 97%) as a 1:1 diastereomeric mixture.

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All the compounds exhibited spectral data consistent with their structures. Yields refer to isolated and chromatographically pure compounds. Selected spectral data for the aldehyde 19a: IR (neat, cm-1): 2737, 1721, 1636, 1604, 919. 1H NMR (300 MHz, CDCl3 + CCl4): δ 9.55 (1 H, br s), 7.30-6.90 (4 H, m), 6.08 (1 H, dd, J = 17.4 and 10.5 Hz), 5.19 (1 H, d, J = 10.3 Hz), 5.10 (1 H, d, J = 17.4Hz.), 2.79 and 2.70 (2 H, 2 × d, J = 12.9 Hz.), 2.35 (3 H, s), 1.51 (3 H, s). 13C NMR (75 MHz, CDCl3 + CCl4): δ 201.9 (CH), 145.4 (C), 145.3 (CH), 138.0 (C), 128.5 (CH), 127.4 (CH), 127.1 (CH), 123.4 (CH), 113.0 (CH2), 53.3 (CH2), 42.9 (C), 26.2 (CH3), 21.8 (CH3). For a 1:1 diastereomeric mixture of the dienol 20a: IR (neat, cm-1): 3398, 1635, 917. 1H NMR (300 MHz, CDCl3 + CCl4): δ 7.24-6.90 (4 H, m), 6.20-6.00 (1 H, m), 5.85-5.75 (1 H, m), 5.15-4.95 (4 H, m), 4.13 (1 H, br s), 2.34 (3 H, s), 2.05-1.90 (2 H, m), 1.50 (1 H, br s), 1.48 and 1.46 (3 H, CH3). 13C NMR (75 MHz, CDCl3 + CCl4): δ 147.4 and 147.0 (CH), 146.9 (C), 142.1 and 142.0 (CH), 137.7 and 137.6 (C), 128.3 and 128.2 (CH), 127.4 and 127.3 (CH), 127.0 and 126.9 (CH), 123.8 and 123.7 (CH), 113.5 (CH2), 112.1 and 112.0 (CH2), 70.5 and 70.4 (CH), 48.4 (CH2), 43.8 (C), 25.8 and 25.6 (CH3), 21.8 (CH3). For a 1:1 diastereomeric mixture of the cyclopentenol 21a: IR (neat, cm-1): 3346, 1605. 1H NMR (300 MHz, CDCl3 + CCl4): δ 7.30-6.90 (4 H, m), 6.02 (1 H, d, J = 5.1Hz.), 5.88-5.80 (1 H, m), 4.90 (1 H, br s), 2.55-2.35 (1 H, m), 2.34 and 2.32 (3 H, s), 1.95-1.60 (2 H, m), 1.54 and 1.40 (3 H, s, CH3). 13C NMR (75 MHz, CDCl3 + CCl4): δ 149.2 and 148.6 (C), 143.1 and 142.6 (CH), 137.5 and 137.4 (C), 132.2 and 132.1 (CH), 128.2 and 128.1 (CH), 126.6 and 126.5 (CH), 126.4 and 126.3 (CH), 122.7 and 122.6 (CH), 77.2 (CH), 53.1 and 52.1 (C), 51.3 and 50.8 (CH2), 30.1 and 28.5 (CH3), 21.6 (CH3). For the cyclopentenone 22a: IR (neat, cm-1): 1716, 1586. 1H NMR (300 MHz, CDCl3 + CCl4): δ 7.65 (1 H, d, J = 5.7 Hz.), 7.20 (1 H, t, J = 7.5 Hz.), 7.10-6.95 (3 H, m), 6.19 (1 H, d, J = 5.7 Hz.), 2.63 and 2.51 (2 H, 2 × d, J = 18.7 Hz.), 2.35 (3 H, s), 1.63 (3 H, s). 13C NMR (75 MHz, CDCl3 + CCl4): δ 209.2 (C), 171.1 (CH), 145.2 (C), 138.3 (C), 131.6 (CH), 128.7 (CH), 127.6 (CH), 126.5 (CH), 122.7 (CH), 51.9 (CH2), 48.1 (C), 27.3 (CH3), 21.7 (CH3). For the cyclopentenone 23a: IR (neat, cm-1): 1712, 1606, 1594. 1H NMR (300 MHz, CDCl3 + CCl4): δ 7.73 (1 H, d, J = 5.7 Hz.), 7.19 (1 H, t, J = 7.6 Hz.), 7.10-6.90 (3 H, m), 6.20 (1 H, d, J = 5.7Hz.), 2.35 (3 H, s), 1.46 (3 H, s), 1.19 (3 H, s), 0.52 (3 H, s). 13C NMR (75 MHz, CDCl3 + CCl4): δ 213.8 (C), 168.2 (CH), 143.4 (C), 137.7 (C), 129.4 (CH), 128.3 (CH), 127.6 (2 C, CH), 124.0 (CH), 54.7 (C), 51.5 (C), 26.4 (CH3), 26.0 (CH3), 21.8 (CH3), 20.1 (CH3).

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Alternately, the aldehydes 19a-d were also obtained (65-70%) via the orthoester Claisen rearrangement [MeC(OEt)3; EtCOOH; Δ] of the alcohols 18a-d followed by conversion of the resultant esters into aldehydes by reduction (LAH)-oxidation (PCC) sequence.