A new route to protected acyloins and their enzymatic resolution with lipases

A series of 16 different 3-acyloxy methyl ketones, the acyloin acetates and butyrates (±)-5, was synthesised by a straight-forward new method through alkylation of tert-butyl 2-acyloxyacetoacetates 3, followed by chemoselective dealkoxy-carbonylation of the tert-butyloxycarbonyl group in the presence of other ester groups. Subsequent hydrolysis of (±)-5 can be achieved with base to give racemic acyloins 6, or with lipase catalysis to afford the corresponding non-racemic acyloins (S)-6. The remaining (R)-acyloin esters 5 can be racemised and resubjected to the procedure, or hydrolysed chemically. The kinetic resolution with two of the six tested enzymes, CAL-B and BCL (PS) lipase, proceeded selectively [enantiomeric ratio (E) values between 50 and > 200] and most of the acyloins (S)-6 were obtained in very high enantiomeric excesses (up to > 99% ee). © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.