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.

The present review is devoted to summarizing the recent advances (2015-2017) in the field of metal-catalysed group-directed C-H functionalisation In order to clearly showcase the molecular diversity that can now be accessed by means of directed C-H functionalisation, the whole is organized following the directing groups installed on a substrate Its aim is to be a comprehensive reference work, where a specific directing group can be easily found, together with the transformations which have been carried out with it Hence, the primary format of this review is schemes accompanied with a concise explanatory text, in which the directing groups are ordered in sections according to their chemical structure The schemes feature typical substrates used, the products obtained as well as the required reaction conditions Importantly, each example is commented on with respect to the most important positive features and drawbacks, on aspects such as selectivity, substrate scope, reaction conditions, directing group removal, and greenness The targeted readership are both experts in the field of C-H functionalisation chemistry (to provide a comprehensive overview of the progress made in the last years) and, even more so, all organic chemists who want to introduce the C-H functionalisation way of thinking for a design of straightforward, efficient and step-economic synthetic routes towards molecules of interest to them Accordingly, this review should be of particular interest also for scientists from industrial R&D sector Hence, the overall goal of this review is to promote the application of C-H functionalisation reactions outside the research groups dedicated to method development and establishing it as a valuable reaction archetype in contemporary R&D, comparable to the role cross-coupling reactions play to date

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A comprehensive overview of directing groups applied in metal-catalysed C-H functionalisation chemistry.

The effective use of ring strain has been applied to considerable advantage for the construction of complex systems. The focus here is directed towards cyclopropanes as building blocks for organic synthesis. Although thermodynamics should take the side of synthetic chemists, only a specific substitution pattern at the cyclopropane ring allows for particularly mild, efficient, and selective transformations. The required decrease in the activation barrier is achieved by the combined effects of vicinal electron-donating and electron-accepting moieties. This Review highlights the appropriate tools for successfully employing donor–acceptor cyclopropanes in ring-opening reactions, cycloadditions, and rearrangements.

A new golden age for donor-acceptor cyclopropanes.

C–H activation has emerged as a transformative tool in molecular synthesis, but until recently oxidative C–H activations have largely involved the use of stoichiometric amounts of expensive and toxic metal oxidants, compromising the overall sustainable nature of C–H activation chemistry. In sharp contrast, electrochemical C–H activation has been identified as a more efficient strategy that exploits storable electricity in place of byproduct-generating chemical reagents. Thus, transition-metal catalysts were shown to enable versatile C–H activation reactions in a sustainable manner. While palladium catalysis set the stage for C(sp2)–H and C(sp3)–H functionalizations by N-containing directing groups, rhodium and ruthenium catalysts allowed the use of weakly coordinating amides and acids. In contrast to these precious 4d transition metals, the recent year has witnessed the emergence of versatile cobalt catalysts for C–H oxygenations, C–H nitrogenations, and C–C-forming [4+2] alkyne annulations. Thereby, the ...

Electrocatalytic C–H Activation

Molecular syntheses largely rely on time- and labour-intensive prefunctionalization strategies. In contrast, C-H activation represents an increasingly powerful approach that avoids lengthy syntheses of prefunctionalized substrates, with great potential for drug discovery, the pharmaceutical industry, material sciences, and crop protection, among others. The enantioselective functionalization of omnipresent C-H bonds has emerged as a transformative tool for the step- and atom-economical generation of chiral molecular complexity. However, this rapidly growing research area remains dominated by noble transition metals, prominently featuring toxic palladium, iridium and rhodium catalysts. Indeed, despite significant achievements, the use of inexpensive and sustainable 3d metals in asymmetric C-H activations is still clearly in its infancy. Herein, we discuss the remarkable recent progress in enantioselective transformations via organometallic C-H activation by 3d base metals up to April 2019.

Enantioselective C-H Activation with Earth-Abundant 3d Transition Metals.

Cobalt-catalyzed C–H activation by means of oxazolinyl assistance set the stage for versatile direct amidations with ample substrate scope. Thus, a high-valent cobalt(III) catalyst enabled C–H amidations with excellent levels of positional and chemo-selectivities. Mechanistic studies provided strong support for a kinetically relevant C–H functionalization.

Oxazolinyl-Assisted C–H Amidation by Cobalt(III) Catalysis

Catalytic Friedel–Crafts Reaction of Aminocyclopropanes

Highly enantioselective iron-catalyzed C-H alkylations by inner-sphere C-H activation were accomplished with ample scope. High levels of enantiocontrol proved viable through a novel ligand design that exploits a remote meta-substitution on N-heterocyclic carbenes within a facile ligand-to-ligand H-transfer C-H cleavage.

Joachim Loup

Papers

Enantioselective C-H Activation with Earth-Abundant 3d Transition Metals.

Oxazolinyl-Assisted C–H Amidation by Cobalt(III) Catalysis

Catalytic Friedel–Crafts Reaction of Aminocyclopropanes

Asymmetric Iron-Catalyzed C−H Alkylation Enabled by Remote Ligand meta-Substitution

Enantioselektive C-H-Aktivierung mit natürlich vorkommenden 3d-Übergangsmetallen