Copper-catalyzed radical relay in C(sp³)–H functionalization

Abstract

In this review, we summarize the recent advances in the field of copper-catalyzed C–H functionalization via a radical relay process, with a critical focus on the asymmetrical versions.

Copper-Catalyzed Three-Component Photo-ATRA-Type Reaction for Asymmetric Intermolecular C–O Coupling

“…With the evolution of transition-metal-catalyzed radical cross-coupling chemistry, many catalytic asymmetric three-component ATRA-type reactions have recently been invented under thermal or light-driven conditions and have allowed construction of various C–C and C–N bonds in a highly enantioselective manner . In sharp contrast, there has been little progress in the corresponding intermolecular C–O coupling-involved three-component ATRA-type reactions, mainly due to the weak coordinating ability of oxygen nucleophiles toward metal as well as the difficult trap of the oxidatively sensitive incipient carbon radicals by catalyst . To overcome these issues, a few exceptional examples of intramolecular C–O radical coupling were developed by enantioselective two-component ATRA-type reactions.…”

Direct Benzylic C(sp3)–O Coupling with Alcohol via Site-Selective C(sp3)–H Cleavage at Room Temperature through a Remote Directing Group-Enabled Radical Relay Strategy

“…Herein, as an advancement of our continuing efforts in NCR-involved methodologies, we would like to disclose our recent study on room-temperature benzylic C­(sp 3 )–H direct alkoxylation via the synergistic remote DG-enabled radical relay strategy, in which electroneutral methine cyclohexadienyl imine G was proposed as the crucial electrophilic intermediate to stabilize benzyl radical H (Scheme c). This reaction is not only ligand-free and additive-free but also realized with a minimized loading of the terminal oxidant NFSI (1.2 equiv), compared to most previously reported reactions in which excessive amounts (2–3 equiv) of NFSI were necessary as the terminal oxidant , or the imide donor, ,− while reactions achieved with 1.5 equiv or even lower loadings ,,, of NFSI were relatively rare. To the best of our knowledge, this work employs the lowest loading of NFSI as the terminal oxidant in radical relay reactions.…”

“…Among diverse types of C­(sp 3 )–H bonds, functionalization on benzylic C­(sp 3 )–H bonds, owing to the intrinsic discrepancy between the bond dissociation energies of them and other types of C­(sp 3 )–H bonds, is one of the most significant extensively studied site-selective C­(sp 3 )–H coupling reactions . In the past few years, Liu and Stahl , reported a variety of pioneering and influential studies on site-selective benzylic C–H couplings via copper-catalyzed radical relay , using N -fluorobenzenesulfonimide (NFSI) as a terminal oxidant. Most of these reactions required certain ligands to promote the N–F activation that initiates the radical relay process.…”

C-centered radical-initiated cyclization by directed C(sp3)–H oxidative functionalization

“…Hydrogen atom transfer from the C(sp 3 )–H bond position to C-, N-, or O-centered radicals occurs firstly, and thus achieve the installation of functional groups at the C(sp 3 )–H position (Scheme 1c). 14 However, because the translocated and initial radicals are similar in nature, the premature coupling process cannot be avoided, 15 but this issue is not discussed in this review.…”