Palladium-Catalyzed Carbene Se-H Insertion Reaction for C-Se Bond Formation.

Organoselenium compounds represent an important class of molecules with broad applications in medicinal chemistry, materials chemistry and biochemistry. Current methods for C-Se bond formation often suffer from harsh reaction conditions and limited substrate compatibility. Thus, the development of efficient C-Se bond construction strategies is of great significance. In this work, we first report an efficient palladium-catalyzed Se-H insertion reaction by employing diazo compounds, which provides a robust approach for C-Se bond formation. Mechanistic insights were obtained through deuterium-labeling experiments and control experiments. This method demonstrates excellent features including broad substrate scope, remarkable functional group tolerance, and mild reaction conditions. In addition, initial antifungal activity assays revealed that several target compounds exhibited promising activity against Candida albicans and Cryptococcus neoformans, affording a novel family of hit compounds for the development of antifungal agents.