Kinetic Hydrolysis of Sulfinamides toward S(IV) Chirality Enabled by Visible-Light-Excited Ene-Reductases

Previously reported enzymatic approaches to chiral S(IV) stereogenic compounds were limited to the natural enzyme reactivity. Herein, we report a photoenzymatic kinetic resolution strategy by repurposing ene-reductases as unnatural photohydrolases, synthesizing enantioenriched arylsulfinamides (up to 99.5:0.5 er). Mechanistic investigations and computational studies suggest an excited ene-reductase-triggered nitrogen-centered radical (NCR) pathway. This work further demonstrates the potential for reprogramming enzyme functionality through direct visible-light excitation and provides an alternative biocatalytic route to chiral sulfinamides.