Asymmetric synthesis of stereogenic-at-sulfur compounds via biocatalytic oxidation with Unspecific Peroxygenases

Abstract Stereogenic-at-sulfur compounds are vitally important biologically active small molecules, with many drugs featuring chiral sulfur(IV) atoms. Methods for the asymmetric synthesis of sulfoxide centres are well established, but methods that produce enantiomerically enriched sulfoximines and sulfinimines are far less well developed, with no known biocatalytic methods based on oxygenation. In this study, we demonstrate that Unspecific Peroxygenases (UPOs) catalyze the biocatalytic oxygenation of sulfilimines and sulfenimines to form enantiomerically enriched sulfoximines and sulfinimines respectively, on preparative scale. In the sulfenimine series, sulfoximines are generated in up to 99% ee via a kinetic resolution approach. In the sulfilimine series, the selective, stereodivergent synthesis of either of the enantiomeric sulfinimine products (both up to 99% ee) can be achieved, with different UPOs affording products with opposite enantioselectivity. Both series represent novel applications of UPO technology to an ever-growing list of selective, practical and industrially relevant biotransformations.