Arylation, Alkenylation, and Alkylation of 2-Halopyridine <i>N</i>-Oxides with Grignard Reagents: A Solution to the Problem of C2/C6 Regioselective Functionalization of Pyridine Derivatives

Abstract

A facile arylation, alkenylation, and alkylation of functionalized 2-halopyridine N-oxides with various Grignard reagents was developed. It represented a highly efficient and selective C-H bond functionalization of pyridine derivatives in the presence of reactive C-Cl or C-Br bonds. Using Cl or Br as a blocking group, C2/C6 site-controllable functionalization of pyridine derivatives has been achieved. Various pyridine compounds can be prepared as illustrated in the total syntheses of Onychine, dielsine, and PARP-1 inhibitor GPI 16539.