ONE-POT SYNTHESIS OF OPTICALLY-ACTIVE CYANOHYDRIN ACETATES FROM ALDEHYDES VIA LIPASE-CATALYZED KINETIC RESOLUTION COUPLED WITH INSITU FORMATION AND RACEMIZATION OF CYANOHYDRINS

A novel one-pot synthesis of optically active cyanohydrin acetates from aldehydes has been accomplished by lipase-catalyzed kinetic resolution coupled with in situ formation and racemization of cyanohydrins in an organic solvent. Racemic cyanohydrins 2, generated from aldehydes 1 and acetone cyanohydrin in diisopropyl ether under the catalysis of basic anion-exchange resin (OH- form), were acetylated stereoselectively by a lipase from Pseudomonas cepacia (Amano) with isopropenyl acetate as an acylating reagent. The (S)-isomer of 2 was preferentially acetylated by the lipase, while the unreacted (R)-isomer was continuously racemized through reversible transhydrocyanation catalyzed by the resin. These processes thus enabled one-stage conversion of various aldehydes 1a-n into the corresponding (S)-cyanohydrin acetates 3a-n with up to 94% ee in 63-100% conversion yields. The racemization of the optically active cyanohydrin 2e by Amberlite IRA-904 (OH- form) was found to be much faster than the enzymatic acetylation, confirming the effective second-order asymmetric transformation. Enzymatic deacetylation of (S)-cyanohydrin acetates in an organic solvent and the synthesis of optically active pyrethroids are also described.