Lipase-catalyzed kinetic resolution of 4-aryl- and 4-heteroarylbut-3-en-2-ols

Several 4-aryl-and 4-heteroarylbut-3-en-2-ones [2a-c, bearing 4-phenyl-, 4-(furan-2-yl)-and 4-(1-benzyl-1H-indol-3yl)-substituents, respectively] were prepared by condensation reaction of acetone with the corresponding aldehydes (1a-c). Reduction of the ketones (2a, b) with NaBH4 resulted in the formation of the corresponding racemic secondary alcohols (rac-3a, b). On the other hand, reduction of the ketone bearing indole moiety (2c) gave an unstable product. The lipase-catalyzed enantiomer selective acetylation of the alcohols (rac-3a, b) by vinyl acetate has been investigated with a crude lipase from submerged fermentation (SmF) of a thermophilic fungus, with several crude enzyme preparations from solid state fermentation (SSF) of selected mesophilic fungi and with several commercially available lipases. The commercial and SmF lipases and the majority of SSF preparations exhibited high but usual enantiomer selectivities and resulted in the formation of (R)-acetates [(R)-4a, b] according to the Kazlauskas' rule. Several SSF preparations, however, behaved as selective anti-Kazlauskas catalysts.