C−H Alkylation of Heterocycles via Light‐Mediated Palladium Catalysis

Abstract Methods enabling direct C−H alkylation of heterocycles are of fundamental importance in the late‐stage modification of natural products, bioactive molecules, and medicinally relevant compounds. However, there is a scarcity of a general strategy for the direct C−H alkylation of a variety of heterocycles using commercially available alkyl surrogates. We report an operationally simple palladium‐catalyzed direct C−H alkylation of heterocycles using alkyl halides under the visible light irradiation with good scalability and functional group tolerance. Our studies suggest that the photoinduced alkylation proceeds through a cascade of events comprising, site‐selective alkyl radical addition, base‐assisted deprotonation, and oxidation. A combination of experiments and computations was employed for the generalization of this strategy, which was successfully translated towards the modification of natural products and pharmaceuticals.