Selective α‐Oxyamination and Hydroxylation of Aliphatic Amides

• Published in: Angewandte Chemie International Edition Vol. 56; no. 40; pp. 12307 - 12311
• Main Authors: Li, Xinwei, Lin, Fengguirong, Huang, Kaimeng, Wei, Jialiang, Li, Xinyao, Wang, Xiaoyang, Geng, Xiaoyu, Jiao, Ning
• Format: Journal Article
• Language: English
• Published: Germany 25.09.2017
• Subjects: amides; C−H functionalization; oxidations; radicals; synthetic methods; C−H functionalization; amides; oxidations; radicals; synthetic methods
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.201706963

Compared to the α‐functionalization of aldehydes, ketones, even esters, the direct α‐modification of amides is still a challenge because of the low acidity of α‐CH groups. The α‐functionalization of N−H (primary and secondary) amides, containing both an unactived α‐C−H bond and a competitively active N−H bond, remains elusive. Shown herein is the general and efficient oxidative α‐oxyamination and hydroxylation of aliphatic amides including secondary N−H amides. This transition‐metal‐free chemistry with high chemoselectivity provides an efficient approach to α‐hydroxy amides. This oxidative protocol significantly enables the selective functionalization of inert α‐C−H bonds with the complete preservation of active N−H bond. Active duty: A general and efficient oxidative α‐oxyamination of aliphatic amides, including secondary N−H amides, was developed. This transition‐metal‐free chemistry, with high chemoselectivity, provides an efficient approach to α‐hydroxy amides. This oxidative route enables the selective functionalization of inert α‐C−H bonds with complete preservation of the active N−H bond.