CAL-B Catalyzed Enantioselective Synthesis of Cyanohydrins - A Facile Route to Versatile Building Blocks

Abstract

A straightforward process for the preparation of optically active cyanohydrins, important building blocks for the synthesis of drugs and agrochemicals, has been established. Lipase B from Candida antarctica (CAL-B) catalyzes the kinetic resolution of racemic cyanohydrin acetates under mild conditions: optimization of the process led to a user-friendly synthesis of (S)-and (R)-cyanohydrins.

Pyrethroid insecticides. Chapter III: Synthesis of 3-phenoxy mandelonitrile

“…For example several lipases such as Arthrobacter lipase, 52 Pseudomonas sp. lipase, 53 lipase P (Amano), 56 and Candida antartica lipase, 55 hydrolyse efficiently (S)-3-phenoxymandelonitrile acetate (S)-1c to the corresponding (S)-3-phenoxymandelonitrile (S)-(3a) directly transformed to enantiopure deltamethrin (S,1R,3R)-(1a) on reaction with (1R,3R)-deltamethrinic acid chloride (2aCl) while Candida cylindracea lipase hydrolyses its enantiomer (R)-1c instead of leading to (R)-3-phenoxymandelonitrile (R)-(3a) and acetyl (S)-3-phenoxymandelonitrile (S)-(1c) that cannot be conveniently use to produce enantiopure deltamethrin. 52 Enantioselective hydrolysis by Arthrobacter lipase gave the optically pure (S)-3-phenoxymandelonitrile (S)-(3a) at a particularly suitable pH of 4.0.…”

“…26,27,60 Ester hydrolysis in acidic media proved unsatisfactory because hydrolysis of the cyano group takes place faster than that of the ester. 60 Best results have been obtained performing a transesterification using lipases and an alcohol 27,55,56 such as ethanol in large excess, which is able to deprotect 1c to produce smoothly 3-phenoxymandelonitrile (S)-(3a) (Scheme 16, third step). 27 The process is highly stereoselective and therefore only applies to a single enantiomer of the racemate.…”

“…27 The process is highly stereoselective and therefore only applies to a single enantiomer of the racemate. 27,55,56 A different solution to such a problem is depicted below (Scheme 32). Scheme 16.…”