Amano PS-catalysed enantioselective acylation of (±)-α-methyl-1,3-benzodioxole-5-ethanol:: an efficient resolution of chiral intermediates of the remarkable antiepileptic drug candidate, (-)-talampanel

(S)-(+)-alpha-Methyl-1,3-benzodioxole-5-ethanoI 5 is a chiral building block in the synthesis of the future drug (-)-talam-panel 1. Amano PS-induced enantioselective acylation of (+/-)-3 at 50degreesC using vinyl acetate as acyl donor furnished (+)-5 in 53% yield and 80% e.e., and the corresponding acetyl derivative (-)-(R)-alpha-methyl-1,3-benzodioxole-5-ethyl acetate 6 in 44% yield and 96% e.e. The base-catalysed methanolysis of (-)-6 followed by Mitsunobu inversion and subsequent methanolysis of the product, (+)-8 also gave the desired (+)-5 in 38% overall yield (four steps) and 96% e.e. (C) 2003 Elsevier Science Ltd. All rights reserved.