Synthesis and lipase-catalyzed asymmetric acetylation of 3-hydroxy-2-hydroxymethylpropanal acetals

Prochiral dialkylacetal derivatives of 3-hydroxy-2-hydroxymethylpropanal 6a-e were synthesized from the corresponding 2-substituted diethyl malonates 5a-e and subjected to asymmetric enzymatic acetylation. The diethyl malonates 5a-f were prepared from diethyl chloromethylenemalonate 3 by using either a one- or a two-step process. Asymmetric acetylation of 3-hydroxy-2-hydroxymethylpropanal diethyl acetal 6b with several enzymes was studied first, showing the highest enantiotopic selectivity with lipase from Pseudomonas fluorescens (PfL). Solvent effect was also investigated: the best selectivity was obtained in a mixture of hexane and diethyl ether. Furthermore, several other acetals 6a-e were also tested under the optimal acetylation conditions. (C) 1997 Elsevier Science Ltd.