Electrophilic C3−H Alkenylation of 2,6‐Dialkoxypyridine Derivatives via Pd(II)/Tl(III) Reaction System

Abstract Herein, we report the reaction system based on Pd(II) catalyst and Tl(OCOCF 3 ) 3 for the electrophilic C3−H alkenylation of 2,6‐dialkokypyridines with alkenes. Synergistic action of the Pd/thioether ligand catalytic system and Tl(III) results in efficient C−H alkenylation of various nitrogen heteroaromatics with complete regioselectivity. Remarkably, the use of a sterically hindered thioether ligand and the Pd(II)/Tl(III) system enables mono‐selective C3(5)−H alkenylation of 2,6‐dialkoxypyridines, and subsequent introduction of a second, different alkene affords unsymmetrical, multi‐substituted pyridine derivatives. Mechanistic studies indicate that the reaction proceeds via electrophilic thallation of heteroarenes followed by Pd‐catalyzed Heck‐type reaction. The utility of this method is showcased by its application to the late‐stage functionalization of structurally complex bioactive molecules having 2,6‐dialkoxypyridine as a core structure.