Sequential Two‐Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases

Abstract A sequential two‐step chemoenzymatic methodology for the stereoselective synthesis of (3 E )‐4‐(het)arylbut‐3‐en‐2‐amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy‐radical TEMPO, followed by the asymmetric reductive bio‐transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio‐transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.