DOI: 10.1055/a-1677-6619

Site-selective C(sp3)-H Functionalizations Mediated by Hydrogen Atom Transfer Reactions via α-Amino/α-Amido Radicals

Jaspreet Kaur
1  Fakultät für Chemie und Pharmazie, Universitat Regensburg, Regensburg, Germany (Ringgold ID: RIN9147)
2  Fakultät für Chemie und Pharmazie, Universitat Regensburg, Regensburg, Germany (Ringgold ID: RIN9147)
› Author Affiliations
Supported by: Alexander von Humboldt-Stiftung Sofja Kovalevskaja Award

Amines and amides, as N-containing compounds, are ubiquitous in pharmaceutically active scaffolds, natural products, agrochemicals and peptides. Amides in nature bear key responsibility for three-dimensional structure, such as in proteins. Structural modifications to amines and amides, especially at their positions α- to N, bring about profound changes in biological activity oftentimes leading to more desirable pharmacological profiles of small molecule drugs. A number of recent developments in synthetic methodology for the functionalizations of amines and amides omit the need of directing groups or pre-functionalizations, achieving direct activation of the otherwise benign C(sp3)-H bond. Among these, hydrogen atom transfer (HAT) has proven a very powerful platform for the selective activation of amines and amides to their α-amino and α-amido radicals, which can then be employed to furnish C-C and C-X (X=heteroatom) bonds. The ability to both form these radicals and control their reactivity in a site-selective manner is of utmost importance for such chemistries to witness applications in late-stage functionalization. Therefore, this review captures contemporary HAT strategies to realize chemo- and regioselective amine and amide α-C(sp3)-H functionalization, based on bond strength, bond polarity, reversible HAT equilibria, traceless electrostatic directing auxiliaries and steric effects of in situ-generated HAT agents.

Publication History

Received: 20 September 2021

Accepted after revision: 25 October 2021

Publication Date:
25 October 2021 (online)

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany