Continuous Flow Synthesis of Carbonylated Heterocycles via Pd-Catalyzed Oxidative Carbonylation Using CO and O₂ at Elevated Temperatures and Pressures

A continuous-flow Pd-catalyzed oxidative carbonylation protocol utilizing CO and O 2 gas for the synthesis of carbonylated heterocycles is described. The optimization of temperature, pressure, CO/O 2 ratio, catalyst loading, and reaction time resulted in process intensified conditions for this transformation. The optimized continuous flow conditions (120 °C, 20 bar pressure, 24 min residence time) were used to prepare a number of benzoxazolone, 2-benzoxazolidinone, and other biologically and synthetically important five- and six-membered carbonylated heterocycles in good overall yield and purity (14 examples). The continuous-flow process enables the safe and scalable oxidative carbonylation using CO/O 2 under elevated pressures and temperatures.