Palladium catalyzed oxidative Suzuki coupling reaction of indolizine at the 3-position using oxygen gas as the only oxidant

Abstract

Stoichiometric metal oxidant applied in the functionalization of indolizine at the 3-position through C–H activation in a previous report was found to increase the cost of the synthesis and worsen the environmental pollution. In this paper, we developed a Pd(OAc)₂/O₂ catalytic system with or without ligands for an oxidative Suzuki coupling reaction of indolizine at the 3-position through C–H activation. As reported in the literature, some indolizines dimerized when catalyzed by palladium acetate under ligand-free conditions. However, we found that the dimerization of 2,3-unsubstituted indolizines was inhibited by the addition of ligands. Based on this finding, the arylation of these indolizines can be successfully achieved via a Pd(OAc)/O₂ system using picolinic acid as a ligand. 1,2-disubstituted indolizines that do not easily dimerize can react smoothly with arylboronic acids under ligand-free conditions. Furthermore, broad group tolerance was shown in both indolizine and arylboronic acid. Finally, this method has the advantages of mild conditions, a broad array of starting materials and the use of a green oxidant.