Photoinduced Palladium‐Catalyzed Site‐Selective <i>Meta</i> ‐Alkylation of Pyridines

Abstract

ABSTRACT Achieving regioselective meta ‐C–H alkylation of pyridines remains a long‐standing challenge due to their intrinsic electronic bias and the lack of general strategies compatible with simple alkyl electrophiles. In contrast to Minisci‐type alkylations, which preferentially functionalize electron‐deficient positions, meta ‐alkylation of unbiased pyridines using alkyl bromides has remained elusive. Herein, we report a photoinduced palladium‐catalyzed strategy that enables regioselective meta ‐alkylation of pyridines with commercially available alkyl bromides via a redox‐neutral dearomatization pathway. Visible‐light excitation of palladium generates a hybrid alkyl–Pd(I) radical species that undergoes regioselective addition to oxazino‐pyridine intermediates despite inherent polarity mismatch, forming a stabilized π ‐allyl Pd(I) radical prior to rearomatization. The method exhibits a broad substrate scope encompassing diverse pyridines, quinolines, and alkyl bromides, and enables one‐pot and sequential meta ‐functionalization strategies. DFT calculations support an outer‐sphere radical addition mechanism and rationalize the observed regioselectivity. This work establishes a new paradigm for Pd‐catalyzed meta ‐C–H alkylation of azines, a complementary conceptual approach to conventional and important Minisci chemistry.