Parallel Antisense Concurrent One‐Pot/Two‐Step Cascade for the Asymmetric Biocatalytic Amination of Racemic sec ‐Alcohols

We report the development of a concurrent one‐pot/two‐step biocatalytic cascade for the asymmetric synthesis of enantiomerically enriched α‐chiral primary amines from racemic aryl‐ring‐containing secondary alcohols via alcohol oxidation employing a non‐enantioselective alcohol dehydrogenase, followed by asymmetric reductive amination using a stereoselective transaminase. The amine donor 2‐propylamine served, on the one hand, as the nitrogen source for the amination step and, on the other hand, its deaminated/oxidized form (acetone) acted as the oxidant for the first step. The elaborated protocol employed lyophilized Escherichia coli whole cells containing a heterologously expressed ambidextrous alcohol dehydrogenase deduced from Lactobacillus kefir ( E. coli / Lk ADH‐Prince) in combination with stereocomplementary recombinant transaminases ( E. coli /TAs) that simultaneously converted the in situ‐generated carbonyl intermediates into the corresponding optically active amines with high‐to‐excellent stereocontrol. The developed cascade enables the efficient preparation of nonracemic amines with high conversions (up to 94%), very good isolated yields (up to 85%), and excellent enantiomeric excesses (up to >99%), providing access to both enantiomers under mild, nontoxic, and exclusively aqueous reaction conditions.