Sustainable Strategy for the Synthesis of C5-Modified Pyrimidine Nucleosides Utilizing Chloroform–COware Chemistry

Abstract CO gas has been a versatile C1 source for carbonylation, amino-carbonylation, and alkoxy-carbonylation. We report an efficient and safer protocol for alkoxy-carbonylation of C5-iodo-derivatives of nucleosides and nucleobases. The modified nucleosides have various applications in chemical biology, medicinal chemistry, and drug discovery. We utilized chloroform and KOH as CO-surrogate for ex situ palladium-catalyzed alkoxy-carbonylation. We explored our protocol for pyrimidine-based nucleosides/nucleobases, which offered good to moderate yields at 80 °C for 24 h. We converted esters to other functional groups such as acids and amides.