Catalytic transformation of ubiquitous C–H bonds into valuable C–N bonds offers an efficient synthetic approach to construct N-functionalized molecules. Over the last few decades, transition metal catalysis has been repeatedly proven to be a powerful tool for the direct conversion of cheap hydrocarbons to synthetically versatile amino-containing compounds. This Review comprehensively highlights recent advances in intra- and intermolecular C–H amination reactions utilizing late transition metal-based catalysts. Initial discovery, mechanistic study, and additional applications were categorized on the basis of the mechanistic scaffolds and types of reactions. Reactivity and selectivity of novel systems are discussed in three sections, with each being defined by a proposed working mode.

Transition Metal-Catalyzed C–H Amination: Scope, Mechanism, and Applications

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.

This Review summarizes the advancements in Pd-catalyzed C(sp3)–H activation via various redox manifolds, including Pd(0)/Pd(II), Pd(II)/Pd(IV), and Pd(II)/Pd(0). While few examples have been reported in the activation of alkane C–H bonds, many C(sp3)–H activation/C–C and C–heteroatom bond forming reactions have been developed by the use of directing group strategies to control regioselectivity and build structural patterns for synthetic chemistry. A number of mono- and bidentate ligands have also proven to be effective for accelerating C(sp3)–H activation directed by weakly coordinating auxiliaries, which provides great opportunities to control reactivity and selectivity (including enantioselectivity) in Pd-catalyzed C–H functionalization reactions.

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Palladium-Catalyzed Transformations of Alkyl C-H Bonds.

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

Transition metal-catalyzed direct functionalization of C–H bonds is one of the key emerging strategies that is currently attracting tremendous attention with the aim to provide alternative environmentally friendly and efficient ways for the construction of C–C and C–hetero bonds. In particular, the strategy involving regioselective C–H activation assisted by various functional groups shows high potential, and significant achievements have been made in both the development of novel reactions and the mechanistic study. In this review, we attempt to give an overview of the development of utilizing the functionalities as directing groups. The discussion is directed towards the use of different functional groups as directing groups for the construction of C–C and C–hetero bonds via C–H activation using various transition metal catalysts. The synthetic applications and mechanistic features of these transformations will be discussed, and the review is organized on the basis of the type of directing groups and the type of bond being formed or the catalyst.

Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups

Nickel-catalyzed direct amination of arenes with alkylamines

Nickel-Catalyzed Direct Thioetherification of β-C(sp3)–H Bonds of Aliphatic Amides

Cobalt(III)-catalyzed annulation of esters and alkynes: a facile route to indenones

Cp*Co(III)-catalyzed direct allylation of enamides has been accomplished with the exclusive formation of allylated Z-enamides with high efficiency. In addition, the employment of maleimides as the reaction partner under the same catalytic conditions provides a series of succinimide-substituted Z-enamides.

Wenlong Yu

Papers

Transition metal-catalyzed C–H bond functionalizations by the use of diverse directing groups

Nickel-catalyzed direct amination of arenes with alkylamines

Nickel-Catalyzed Direct Thioetherification of β-C(sp3)–H Bonds of Aliphatic Amides

Cobalt(III)-catalyzed annulation of esters and alkynes: a facile route to indenones

Cobalt(III)-catalyzed cross-coupling of enamides with allyl acetates/maleimides