Chemo‐ and Stereoselective Synthesis of Fluorinated Amino Alcohols through One‐pot Reactions using Alcohol Dehydrogenases and Amine Transaminases

Abstract

A series of amino alcohols have been prepared in a chemo-, diastereo- and enantioselective fashion starting from the corresponding (het)aryl diketones, avoiding tedious chemical protection and deprotection steps. Different alcohol dehydrogenases have been able to selectively reduce the more reactive trifluoroacetyl groups under optimized conditions, while amine transaminases catalyzed the biotransamination of the less hindered acetyl groups. Based on the different reactivity of the acetyl and trifluoroacetyl groups, the design of sequential and concurrent cascades was investigated. The proper selection of the enzymes permits the synthesis of amino alcohol stereoisomers in high to excellent yields (86->99% conversion) and remarkable stereocontrol (up to >99% de and >99% ee) using an aqueous medium and mild reaction conditions.