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

• Published in: Green chemistry : an international journal and green chemistry resource : GC Vol. 26; no. 18; pp. 9859 - 9868
• Main Authors: Huang, Tao, Liu, Can, Yuan, Pan-Feng, Wang, Tao, Yang, Biao, Ma, Yao, Liu, Qiang
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 01.01.2024
• Subjects: Amination; Amino acids; Ammonia; Benzophenone; Byproducts; Carboxylic acids; Chemical synthesis; Cross coupling; Functional groups; Hydrogen atoms; Recycling; Silica; Silica gel; Substrates
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/D4GC03057E

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.