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Updated: Jun 9, 2025
A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
C-H Alkylation of Heterocycles via Light-Mediated Palladium Catalysis
Sudip Senapati1, Sudhir Kumar Hota2, Lennard Kloene1
1RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, D-52074, Aachen, Germany.
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.
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