Expanding Biocatalysis for Organosilane Functionalization: Enantioselective Nitrene Transfer to Benzylic Si–C–H Bonds
Anuvab Das, Yueming Long, Ryan R. Maar, John M. Roberts, Frances H. Arnold
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.