Photoinduced Palladium-Catalyzed Site-Selective Meta-Alkylation of Pyridines.

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.