Development of Photoredox Cross-Electrophile Coupling of Strained Heterocycles with Aryl Bromides Using High-Throughput Experimentation for Library Construction

Microscale high-throughput experimentation was used to develop a photoredox-assisted reductive cross-coupling reaction of aryl halides with strained aliphatic heterocycles facilitated via a ring-opening reaction. This methodology was found to be applicable to medicinally relevant substrates including Boc-protected strained aliphatic heterocycles and (hetero)­aryl bromides and was used for compound library construction via parallel medicinal chemistry. Furthermore, the coupling reactions were shown to be scalable to the gram scale by continuous flow reaction. A possible reaction mechanism is also discussed.