Work

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

Year: 2024

Type: article

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.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202417107

Authors: Sudip Senapati, Sudhir Kumar Hota, Lennard Kloene, Claire Empel, Sandip Murarka, Rene M. Koenigs

Institutions: RWTH Aachen University, Indian Institute of Technology Jodhpur

Language: English

Topic: Catalytic C–H Functionalization Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $5,510

Funders: Deutsche Forschungsgemeinschaft, Science and Engineering Research Board