Organocatalytic Cascade Synthesis of 2,4,6‐Trisubstituted Pyridines via Nucleophilic Activation of α ‐Chlorothioester

Two complementary organocatalytic strategies for the synthesis of polysubstituted pyridines from α‐chlorothioesters and unsaturated imines have been developed. The DBU‐mediated protocol proceeds via nitrogen ylide intermediates, while the NHC‐catalyzed approach involves acyl azolium species. These metal‐free methods exhibit complementary substrate scopes: DBU favors electron‐donating substituents, whereas NHC catalysis demonstrates broad functional group tolerance. Mechanistic studies confirm an intramolecular N → O sulfonyl migration pathway. Gram‐scale reactions and product derivatization to a bipyridine ligand highlight the practical utility of these protocols.