Suzuki–Miyaura Cross-Coupling of 2-Pyridyl Trimethylammonium Salts by N–C Activation Catalyzed by Air- and Moisture-Stable Pd–NHC Precatalysts: Application to the Discovery of Agrochemicals

Abstract

We report the first Suzuki–Miyaura cross-coupling of 2-pyridyl ammonium salts by highly selective N–C activation catalyzed by air- and moisture-stable Pd(II)–NHC (NHC = N -heterocyclic carbene) precatalysts. The use of well-defined and highly reactive [Pd(IPr)(3-CF 3 -An)Cl 2 ] (An = aniline) or [Pd(IPr)(cin)Cl] (cin = cinnamyl) Pd(II)–NHC catalysts permits an exceptionally broad scope of the cross-coupling to furnish valuable biaryl and heterobiarylpyridines that are ubiquitous in medicinal chemistry and agrochemistry research. The overall process leverages the Chichibabin C–H amination of pyridines with N–C activation to enable an attractive strategy to the 2-pyridyl problem. The utility of the method to the discovery of potent agrochemicals is presented. Considering the importance of 2-pyridines and the versatility of N–C activation methods, we envision that this new C–H/N–C activation strategy will find broad application.