Work

Reductive radical chain initiation through the thermal generation of carbon dioxide radical anion

Year: 2025

Type: article

Abstract: Radical chain initiation strategies are fundamental to the synthesis of small molecule drugs and macromolecular materials. Modern methods for initiation through one-electron reduction are largely dominated by photo- and electrochemistry but the large-scale industrial application of these methods is often hampered by scalability challenges. Here we report a general, thermally driven and scalable method for the reductive initiation of radical chains that involves reacting an inexpensive azo initiator with a formate salt to form a carbon dioxide radical anion. Substoichiometric quantities of this initiator system were used to form C( sp 2 )–C( sp 3 ), C( sp 2 )–S, C( sp 2 )–H, C( sp 2 )–B and C( sp 2 )–P bonds from complex (hetero)aryl halides, with high chemoselectivity and under transition-metal-free conditions. The developed initiator system was also used to probe the mechanism of other radical reactions.

Source: Nature Synthesis

DOI: 10.1038/s44160-025-00919-z