Grignard Reagent\nAddition to Pyridinium Salts: A Catalytic\nApproach to Chiral 1,4-Dihydropyridines

Catalytic dearomatization of pyridinium salts is a powerful\ntechnique\nfor constructing chiral <i>N</i>-heterocycles, which are\ncrucial in alkaloid natural products and drugs. Despite its potential,\nprogress in metal-catalyzed asymmetric dearomatization of pyridinium\nderivatives has been limited. Here, we present the enantioselective\n1,4-dearomatization of pyridinium salts using Grignard reagents and\nchiral copper catalysis. This approach yields enantioenriched functionalized\n1,4-dihydropyridines. Experimental kinetic isotope effects and density\nfunctional theory calculations provide insights into the reaction\nmechanism, regio- and enantioselectivity, and the rate-limiting step.