C–H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material sciences, crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these C–H functionalizations required precious 4d or 5d transition metal catalysts. Given the cost-effective and sustainable nature of earth-abundant first row transition metals, the development of less toxic, inexpensive 3d metal catalysts for C–H activation has gained considerable recent momentum as a significantly more environmentally-benign and economically-attractive alternative. Herein, we provide a comprehensive overview on first row transition metal catalysts for C–H activation until summer 2018.

3d Transition Metals for C-H Activation.

Organic reactions that involve the direct functionalization of non-activated C–H bonds represent an attractive class of transformations which maximize atom- and step-economy, and simplify chemical synthesis. Due to the high stability of C–H bonds, these processes, however, have most often required harsh reaction conditions, which has drastically limited their use as tools for the synthesis of complex organic molecules. Following the increased understanding of mechanistic aspects of C–H activation gained over recent years, great strides have been taken to design and develop new protocols that proceed efficiently under mild conditions and duly benefit from improved functional group tolerance and selectivity. In this review, we present the current state of the art in this field and detail C–H activation transformations reported since 2011 that proceed either at or below ambient temperature, in the absence of strongly acidic or basic additives or without strong oxidants. Furthermore, by identifying and discussing the major strategies that have led to these improvements, we hope that this review will serve as a useful conceptual overview and inspire the next generation of mild C–H transformations.

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Mild metal-catalyzed C–H activation: examples and concepts

Research and industrial interest in radical C–H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C–H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M–R groups, and coupling of radical cations with nucleophiles (Nu).

Recent Advances in Radical C-H Activation/Radical Cross-Coupling.

Transition metal-mediated C–H bond activation and functionalization represent one of the most straightforward and powerful tools in modern organic synthetic chemistry. Bi(hetero)aryls are privileged π-conjugated structural cores in biologically active molecules, organic functional materials, ligands, and organic synthetic intermediates. The oxidative C–H/C–H coupling reactions between two (hetero)arenes through 2-fold C–H activation offer a valuable opportunity for rapid assembly of diverse bi(hetero)aryls and further exploitation of their applications in pharmaceutical and material sciences. This review provides a comprehensive overview of the fundamentals and applications of transition metal-mediated/catalyzed oxidative C–H/C–H coupling reactions between two (hetero)arenes. The substrate scope, limitation, reaction mechanism, regioselectivity, and chemoselectivity, as well as related control strategies of these reactions are discussed. Additionally, the applications of these established methods in the s...

Oxidative C-H/C-H Coupling Reactions between Two (Hetero)arenes.

Conventional methods for carrying out carbon–hydrogen functionalization and carbon–nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon–carbon and carbon–heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon–hydrogen functionalization and carbon–nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

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Wu Li

Papers

Oxidative Coupling between Two Hydrocarbons: An Update of Recent C–H Functionalizations