Yuge Hu#, Yanqing Gao, Jiuhui Ye, Zhiqing Ma, Juntao Feng, Xili Liu, Peng Lei*,and Michal Szostak*. Suzuki−Miyaura Cross-Coupling of 2‑Pyridyl Trimethylammonium Salts by N−C Activation Catalyzed by Air- and Moisture-StablePd−NHC Precatalysts: Application to the Discovery of Agrochemicals. Organic Letters. doi: 10.1021/acs.orglett.3c00741.
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-CF3-An)Cl2] (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.