Continuous flow processing of bismuth-photocatalyzed atom transfer radical addition reactions using an oscillatory flow reactor

Abstract

Metal oxides represent an abundant and non-toxic class of photocatalysts for organic transformations. However, their use in larger scale processes is complicated by incompatibilities with continuous flow processing – a proven scale-up route for photochemistry. We detail the development of an efficient atom transfer radical addition protocol using a sustainable solvent system (acetone : PEG 400) and a low loading (2 mol%) of Bi₂O₃, which can be handled in an oscillatory flow reactor. Optimization of the reaction and oscillatory parameters led to high throughput (36 g in 4 h, 89% yield, 599 g L⁻¹ h⁻¹), with a process mass intensity (PMI) of just 8.5. The process also facilitates high recyclability (3 cycles with no loss of yield), and was demonstrated to be applicable to a range of other substrates on multigram scale, in moderate to excellent yields.