Enzyme-Catalyzed Stereoselective C(sp ³ )–S Bond Formation via a Dichotomic Carbene Transfer Mechanism

)-S bonds via both a S-H carbene insertion (up to >99% ee) and a [2,3]-sigmatropic rearrangement reaction by harnessing engineered myoglobin catalysts in combination with pyridotriazole-based carbene precursors. These transformations enable the synthesis of valuable α-pyridyl sulfides with broad substrate scope, high yields, and good to excellent stereocontrol. Intriguingly, mechanistic studies show that the S-H insertion reaction proceeds via a radical pathway, while a polar, two-electron mechanism is exploited by the enzyme for mediating [2,3]-sigmatropic rearrangement reaction, thus revealing a remarkable versatility of the hemoprotein toward operating via both a radical and nonradical pathway. This methodology provides an efficient and sustainable route to valuable pyridine-containing chiral sulfides while unveiling a dual-reactivity mode of a hemoprotein catalyst in an abiological carbene transfer reaction.