High-throughput optimization of the C-H arylation of oxetanes via Ni/aldehyde photocatalysis

Oxetanes are under-explored in medicinal chemistry, despite their favorable physicochemical properties, in part, because of the challenges associated with their syntheses. High-throughput experimentation (HTE) enables the rapid screening of reaction variables, accelerating the reaction development process. Herein we report the use of HTE in the optimization of a mild C-H arylation reaction of oxetanes, and other ethers, using p-cyanobenzaldehyde as a cheap and effective photoexcited hydrogen-atom transfer catalyst, in conjunction with a Ni catalyst. Our optimized conditions enable the use of a modern, reproducible light source as well as sub-solvent quantity oxetane, while eliminating the need for toxic co-solvents and dangerous sources of UV light.