Manganese-Catalyzed Kumada Cross-Coupling Reactions of Aliphatic Grignard Reagents with N-Heterocyclic Chlorides

Abstract

Herein we report the use of manganese(II) chloride for the catalytic generation of C(sp2)–C(sp3) bonds via Kumada cross-coupling. Rapid and selective formation of 2-alkylated N-heterocyclic complexes were observed in high yields with use of 3 mol% MnCl2THF1.6 and under ambient reaction conditions (21 °C, 15 min to 20 h). Manganese-catalyzed cross-coupling is tolerant toward both electron-donating and electron-withdrawing functional groups in the 5-position of the pyridine ring, with the latter resulting in an increased reaction rate and a decrease in the amount of nucleophile required. The use of this biologically and environmentally benign metal salt as a catalyst for C–C bond formation highlights its potential as a catalyst for the late-stage functionalization of pharmaceutically active N-heterocyclic molecules (e.g., pyridine, pyrazine).