Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.

ABSTRACT

Functionalized sulfides are important in many areas of science, ranging from chemical biology through drug discovery to organic materials chemistry. Sulfides bearing pendant reactive groups in the α-position are particularly useful; however, methods for the selective valorization of simple sulfides or the late-stage functionalization of complex sulfides by the convenient addition of valuable functionality are underexplored. Here we exemplify a general reaction platform for sulfide functionalization by showcasing three modes of α-sulfur C-H functionalization; cyanation, alkenylation, and alkynylation. Using inexpensive and commercially available riboflavin tetraacetate and visible light, decoration of both feedstock and complex sulfides proceeds in a good yield and with high selectivity. Methionine-containing peptides can also be selectively functionalized and a tolerance screen using amino-acid dopants suggests that the platform is compatible with most amino-acid side chains and thus is a potential tool for bioconjugation.