Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer

Abstract

The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple synthetic equivalents for synthons. Hydrogen atom transfer (HAT) is a key method for forming alkyl radicals from C–H substrates. Classic reactions, including the Barton nitrite ester reaction and Hofmann–Löffler–Freytag reaction, among others, provided early examples of HAT. However, recent developments in photoredox catalysis and electrochemistry have made HAT a powerful synthetic tool capable of introducing a wide range of functional groups into C–H bonds. Moreover, greater mechanistic insights into HAT have stimulated the development of increasingly site-selective protocols. Site-selectivity can be achieved through the tuning of electron density at certain C–H bonds using additives, a judicious choice of HAT reagent, and a solvent system. Herein, we describe the latest methods for functionalizing C–H/Si–H/Ge–H bonds using indirect HAT between 2018–2023, as well as a critical discussion of new HAT reagents, mechanistic aspects, substrate scopes, and background contexts of the protocols.

Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis

“…Hydrogen atom transfer (HAT) is an elementary step in radical chemistry and also a fundamental step involved in many biological systems . Thanks to the rapid development of photocatalysis in the past decade, HAT reactions have found widespread applications in organic synthesis and material science.…”

Electrochemical C(sp3)−H Functionalization Using Acetic Acid as a Hydrogen Atom Transfer Reagent

“…The HAT process involves the abstraction of a hydrogen atom from a substrate using a hydrogen atom abstractor, which is typically a radical species. [27] The choice of a hydrogen atom abstractor has a definitive influence on the efficiency and selectivity of the process. [28][29][30] Thus, the development of a novel hydrogen atom abstractor could provide a dramatic expansion in synthetic organic chemistry.…”

Efficient Photolytic Breakdown of Waste Polystyrene Foam Using an “All-in-One” Photo-HAT Reagent at Ambient Conditions

“…Light-induced methods to degrade waste polymers are sustainable alternatives to thermal methods. , Photochemical treatment of synthetic and natural waste polymers has recently become the main focus of scientists because of the lower energy requirements and greener nature, which meet the criteria of sustainability. , Although hydrogen atom transfer (HAT) reactions have always been a versatile tool for C–H bond chemistry, exploitation of light-induced HAT reactions for the degradation/valorization of waste polymers through oxidative C–C bond breakages has recently proved to be an effective and sustainable strategy. − Moreover, recent photochemical studies have also demonstrated that halogen radicals can act as the HAT reagent and selectively abstract benzylic hydrogens under mild reaction conditions. , …”