Radical cascade synthesis of γ-amino acids or γ-lactams via carboxyl-mediated intramolecular C–H amination†

Abstract

The γ C–H amination of carboxylic acid presents a promising and sustainable strategy for synthesizing high-value pharmaceutical chemicals. Radical reaction pathways initiated by aroyloxy radical-involved hydrogen atom transfer (HAT) provide diverse but challenging opportunities for remote C–H functionalization. In this report, the first example of intramolecular γ C–H amination of carboxylic acids using a commercially available oxime auxiliary has been achieved. This innovative approach employs a radical relay chaperone, facilitating selective C–H functionalization via 1,5-HAT/radical cross-coupling and enabling the net incorporation of ammonia at the γ carbon of carboxylic acids. In addition, this protocol enables the recycling of the by-product benzophenone, and both product isolation and by-product recycling are silica gel-free. The reactions offer high chemo- and regio-selectivities, operate under mild reaction conditions, boast a broad substrate scope, exhibit good functional group compatibility, and are easily scalable.