Biocatalytic aminohydroxylation of styrenes for efficient synthesis of enantiopure β-amino alcohols

Abstract

A general biocatalytic process of intermolecular aminohydroxylation of styrenes with aniline has been achieved for efficient one-pot preparation of enantiopure β-amino alcohols. The reaction involves first asymmetric epoxidation of alkene substrates by a heme-dependent monooxygenase (P450) or the FAD-dependent styrene monooxygenase, followed by the aminolysis of nascent epoxide intermediates with aniline in water solution. Hybrid cluster-continuum (HCC) model calculations reveal the mechanism of the aminolysis of epoxide with aniline as well as the critical role of the water in mediating such a reaction. In addition, the combined experiments with simulations demonstrate that the chirality of amino alcohol is determined by the absolute configuration of the epoxide formed in the enzymatic reaction. In conclusion, the developed biocatalytic process provides an efficient, environmentally friendly approach for production of high value-added enantiopure β-amino alcohols, starting from cheap and readily available alkenes.