Expanding Biocatalysis for Organosilane Functionalization: Enantioselective Nitrene Transfer to Benzylic Si-C-H Bonds

Abstract

Directed evolution has the potential to enable abiological chemistry by engineering natural enzymes to function on non-natural substrates. In this study, we expanded the repertoire of enzymatic functionalization of organosilicon compounds by evolving a cytochrome P450 variant for the selective amidation of organosilanes, resulting in the production of functionalized α-aminosilanes with remarkable enantioselectivities (up to 333 TTN and >99% ee). The evolved enzyme catalyzes this nitrene transfer reaction on benzylic Si-C-H bonds under aerobic conditions with up to 125-fold higher yield compared to its progenitor, evolved previously for amidation of unactivated C-H bonds in carbon-based molecules.