Sequential two-step stereoselective amination of allylic alcohols through combination of laccases and amine transaminases

Abstract

A sequential two-step chemoenzymatic methodology has been described for the stereoselective synthesis of (3E)-4- (het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions. The approach consists in the oxidation of the corresponding alcohol precursors using the catalytic system composed by the laccase from Trametes versicolor and the oxyradical TEMPO, followed by the asymmetric biotransamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the biotransaminations and the compatibility of both enzymatic reactions have been deeply studied, searching for the design of a compatible sequential cascade. This synthetic strategy has been successfully achieved, the combination of enzymes displaying a broad substrate scope as 16 chiral amines have been obtained in moderate to good isolated yields (29-75% isolated yield) and excellent enantiomeric excess (94->99). Interestingly, both amine enantiomers can be achieved depending on the selectivity of the amine transaminase employed in the system.