Cobalt-catalyzed reductive carboxylation of pyridines with CO2 via pyridylphosphonium salts

Abstract

Reports on late-stage C–H bond carboxylation reactions using CO₂ are very limited. In this work, a cobalt-catalyzed carboxylation reaction of pyridylphosphonium salts with CO2 has been developed. The catalyst system, consisting of Co(acac)2 and Mn, is convenient and practical. When combined with triphenylphosphonation of C4−H bond of pyridines, the formal C4−H carboxylation of pyridines with CO2 can be achieved via a one-pot, two-step procedure. This method was further applied to the late-stage C−H bond carboxylation modifications of pyridine-containing drug molecules, such as loratadine.