A comprehensive mechanistic investigation of sustainable carbene N-H insertion catalyzed by engineered His-ligated heme proteins.

Engineered heme proteins possess excellent biocatalytic carbene N-H insertion abilities for sustainable synthesis, and most of them have His as the Fe axial ligand. However, information on the basic reaction mechanisms is limited, and ground states of heme carbenes involved in the prior computational mechanistic studies are under debate. A comprehensive quantum chemical reaction pathway study was performed for the heme model with a His analogue as the axial ligand and carbene from the widely used precursor ethyl diazoacetate with aniline as the substrate.