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

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.