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

• Published in: Organic process research & development Vol. 21; no. 7; pp. 1080 - 1087
• Main Authors: Chen, Yuesu, Hone, Christopher A, Gutmann, Bernhard, Kappe, C. Oliver
• Format: Journal Article Web Resource
• Language: English
• Published: American Chemical Society 21.07.2017
• Subjects: Catalyst loadings; Chemistry; Chimie; Continuous flows; Continuous-flow process; Continuous-flow synthesis; Elevated pressure; Elevated temperature; Organic Chemistry; Oxidative carbonylation; Physical and Theoretical Chemistry; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; Residence time
• ISSN: 1083-6160; 1520-586X; 1520-586X
• DOI: 10.1021/acs.oprd.7b00217

A continuous-flow Pd-catalyzed oxidative carbonylation protocol utilizing CO and O2 gas for the synthesis of carbonylated heterocycles is described. The optimization of temperature, pressure, CO/O2 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/O2 under elevated pressures and temperatures.