LAUSR

Recent studies reported the development of biocatalytic heme carbenoid Si−H insertions for the selective formation of carbon‐silicon bonds, but many mechanistic questions remain unaddressed. To this end, a DFT mechanistic investigation was performed which reveals an FeII‐based concerted hydride transfer mechanism with early transition state feature. The results from these computational analyses are consistent with experimental data of radical trapping, kinetic isotope effects, and structure‐reactivity data using engineered variants of hemoproteins. Detailed geometric and electronic profiles along the heme catalyzed Si−H insertion pathways were provided to help understand the origin of experimental reactivity trends. Quantitative relationships between reaction barriers and some properties such as charge transfer from substrate to heme carbene and Si−H bond length change from reactant to transition state were found. Results suggest catalyst modifications to facilitate the charge transfer from the silane substrate to the carbene, which was determined to be a major electronic driving force of this reaction, should enable the development of improved biocatalysts for Si−H carbene insertion reactions.