Grignard Reagent Addition to Pyridinium Salts: A Catalytic Approach to Chiral 1,4-Dihydropyridines

Catalytic dearomatization of pyridinium salts is a powerful technique for constructing chiral <i>N</i>-heterocycles, which are crucial in alkaloid natural products and drugs. Despite its potential, progress in metal-catalyzed asymmetric dearomatization of pyridinium derivatives has been limited. Here, we present the enantioselective 1,4-dearomatization of pyridinium salts using Grignard reagents and chiral copper catalysis. This approach yields enantioenriched functionalized 1,4-dihydropyridines. Experimental kinetic isotope effects and density functional theory calculations provide insights into the reaction mechanism, regio- and enantioselectivity, and the rate-limiting step.