Synthesis of Chiral Sulfinamides Enabled by Polycyclic Ketone Monooxygenase Catalyzed Asymmetric Oxidation of Sulfenamides

Chiral sulfinamides find broad applications in bioactive compounds, chiral auxiliaries, chiral ligands, and organocatalysts. However, biocatalytic approaches for their enantioselective synthesis have rarely been explored. Herein, an efficient biocatalytic strategy for the synthesis of chiral sulfinamides via polycyclic ketone monooxygenase (PockeMO) catalyzed asymmetric oxidation of sulfenamides was reported. A diverse array of chiral sulfinamides can be readily accessed with high yields (up to >99%) and enantioselectivities (>99:1 er). Additionally, this biocatalytic platform was scalable, and the resulting synthetic chiral sulfinamides could be easily derivatized to various chiral S-stereogenic compounds. Molecular dynamics simulation studies revealed that hydrogen bonding interactions between the sulfenamides and key residues were essential for enantioselectivity control. This work unlocks a biocatalytic avenue to access chiral sulfinamides for synthetic chemistry and drug discovery.