Synlett 2006(3): 0403-0406  
DOI: 10.1055/s-2006-926258
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioconvergent Access to the Enantiomerically Pure Building Blocks (+)- or (-)-4-Hydroxy-3-methyl-2-cyclohexenone Using a Chemoenzymatic Process

Elie Palombo, Gérard Audran*, Honoré Monti*
Laboratoire de Réactivité Organique Sélective, U.M.R. 6180 ‘Chirotechnologies: catalyse et biocatalyse’, Université Paul Cézanne, Aix-Marseille III, 13397 Marseille Cedex 20, France
Fax: +33(4)91288862; e-Mail: g.audran@univ.u-3mrs.fr; e-Mail: honore.monti@univ.u-3mrs.fr;
Further Information

Publication History

Received 7 December 2005
Publication Date:
06 February 2006 (online)

Abstract

A convenient chemoenzymatic enantioconvergent access to enantiomerically pure (+)- or (-)-4-hydroxy-3-methyl-2-cyclohexenone is described using a one-pot two-step kinetic resolution-stereoinversion protocol followed by hydrolysis. The key step of the sequence is the spontaneous elimination of an undesired stereocenter. The choice between enzymatic acyl transfer or ester alcoholysis of the corresponding racemic starting material, together with the selectivity of a lipase, determines the absolute configuration of the desired single enantiomer.

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Characterization of Compound 2: white solid; mp 62 °C. IR (KBr): ν = 3412, 1728, 1211, 1159 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.80 (dd, J = 7.2, 3.6 Hz, 1 H), 3.07 (s, 2 OH), 2.66 and 2.35 (ABX, J = 14.0, 1.5 Hz, 2 H), 2.49 (dddd, J = 14.2, 7.9, 6.2, 1.7 Hz, 1 H), 2.25 (dddd, J = 14.2, 7.2, 6.0, 1.1 Hz, 1 H), 2.05 (dtd, J = 13.6, 7.2, 6.2 Hz, 1 H), 1.93 (dddd, J = 13.6, 7.9, 6.0, 3.6 Hz, 1 H), 1.24 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 209.8 (C), 75.0 (C), 72.8 (CH), 51.3 (CH2), 36.8 (CH2), 28.1 (CH2), 26.1 (CH3). Anal. Calcd for C7H12O3: C, 58.32; H, 8.39. Found: C, 58.21; H, 8.43.
Characterization of Compound 3: white solid; mp 106 °C. IR (KBr): ν = 3391, 1757, 1723, 1148 cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.00 (dd, J = 8.8, 4.1 Hz, 1 H), 2.54 and 2.40 (ABX, J = 14.6, 1.7 Hz, 2 H), 2.36 (m, 2 H), 2.18-2.05 (partially overlapped m, 1 H), 2.08 (s, 3 H), 1.97 (m, 1 H), 1.20 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 207.7 (C), 170.4 (C), 75.0 (CH), 73.7 (C), 51.7 (CH2), 37.4 (CH2), 26.3 (CH3), 25.3 (CH2), 20.9 (CH3). Anal. Calcd for C9H14O4: C, 58.05; H, 7.58. Found: C, 57.89; H, 7.60.

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CAL-B and RML lipases also showed high enantio-selectivity, but with a slightly lower ee.