Complementary Strategies for Directed C(sp3)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

• Published in: Angewandte Chemie International Edition 2018-01, Vol.57 (1), p.62-101
• Main Authors: Chu, John C. K., Rovis, Tomislav
• Format: Article
• Language: English
• Subjects: Activation; carbenes; Chemical bonds; Chemical synthesis; C−H functionalization; hydrogen atom transfer; Metals; nitrenes; transition metals
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201703743

The functionalization of C(sp3)−H bonds streamlines chemical synthesis by allowing the use of simple molecules and providing novel synthetic disconnections. Intensive recent efforts in the development of new reactions based on C−H functionalization have led to its wider adoption across a range of research areas. This Review discusses the strengths and weaknesses of three main approaches: transition‐metal‐catalyzed C−H activation, 1,n‐hydrogen atom transfer, and transition‐metal‐catalyzed carbene/nitrene transfer, for the directed functionalization of unactivated C(sp3)−H bonds. For each strategy, the scope, the reactivity of different C−H bonds, the position of the reacting C−H bonds relative to the directing group, and stereochemical outcomes are illustrated with examples in the literature. The aim of this Review is to provide guidance for the use of C−H functionalization reactions and inspire future research in this area. The targeted functionalization of C(sp3)−H bonds streamlines chemical synthesis and allows the use of simple starting materials. This Review discusses the strength and weakness of the three main approaches: transition‐metal‐catalyzed C−H activation, 1,n‐hydrogen atom transfer, and transition‐metal‐catalyzed carbene/nitrene transfer.