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.

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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Electrochemical strategies for C-H functionalization and C-N bond formation.

During the past decades, synthetic organic chemistry discovered that directing group assisted C–H activation is a key tool for the expedient and siteselective construction of C–C bonds. Among the v...

Bidentate Directing Groups: An Efficient Tool in C-H Bond Functionalization Chemistry for the Expedient Construction of C-C Bonds.

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

Electrochemistry enabled C-H/N-H functionalizations at room temperature by external oxidant-free cobalt catalysis. Thus, the sustainable cobalt electrocatalysis manifold proceeds with excellent levels of chemoselectivity and positional selectivity, and with ample scope, thus allowing electrochemical C-H activation under exceedingly mild reaction conditions at room temperature in water.

Electrochemical C−H/N−H Activation by Water‐Tolerant Cobalt Catalysis at Room Temperature

Electrocatalysis has been identified as a powerful strategy for organometallic catalysis, and yet electrocatalytic C-H activation is restricted to strongly N-coordinating directing groups. The first example of electrocatalytic C-H activation by weak O-coordination is presented, in which a versatile ruthenium(II) carboxylate catalyst enables electrooxidative C-H/O-H functionalization for alkyne annulations in the absence of metal oxidants; thereby exploiting sustainable electricity as the sole oxidant. Mechanistic insights provide strong support for a facile organometallic C-H ruthenation and an effective electrochemical reoxidation of the key ruthenium(0) intermediate.

Electrooxidative Ruthenium-Catalyzed C-H/O-H Annulation by Weak O-Coordination.

The catalytic generation of hypervalent iodine(III) reagents by anodic electrooxidation was orchestrated towards an unprecedented electrocatalytic C-H oxygenation of weakly coordinating aromatic amides and ketones. Thus, catalytic quantities of iodoarenes in concert with catalytic amounts of ruthenium(II) complexes set the stage for versatile C-H activations with ample scope and high functional group tolerance. Detailed mechanistic studies by experiment and computation substantiate the role of the iodoarene as the electrochemically relevant species towards C-H oxygenations with electricity as a sustainable oxidant and molecular hydrogen as the sole by-product. para-Selective C-H oxygenations likewise proved viable in the absence of directing groups.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.201914226

C-H Oxygenation Reactions Enabled by Dual Catalysis with Electrogenerated Hypervalent Iodine Species and Ruthenium Complexes.

Expedient hydroarylations of C=Het bonds (Het=heteroatom) were accomplished by user-friendly organometallic C-H activation in a positional-selective manner. The broadly applicable C-H functionalization platform enabled the step-economical transformation of aldehydes, ketones, and imines under additive-free reaction conditions. In contrast to palladium, rhodium, ruthenium, rhenium, iridium, nickel, and cobalt catalysis, solely manganese(I) complexes outcompeted the innate substrate control, clearly highlighting the unique power of manganese(I) C-H activation catalysis.

Catalyst-Guided C=Het Hydroarylations by Manganese-Catalyzed Additive-Free C-H Activation.

Despite major advances, organometallic C-H transformations are dominated by precious 5d and 4d transition metals, such as iridium, palladium and rhodium. In contrast, the unique potential of less toxic Earth-abundant 3d metals has been underexplored. While iron is the most naturally abundant transition metal, its use in oxidative, organometallic C-H activation has faced major limitations due to the need for superstoichiometric amounts of corrosive, cost-intensive DCIB as the sacrificial oxidant. To fully address these restrictions, we describe herein the unprecedented merger of electrosynthesis with iron-catalyzed C-H activation through oxidation-induced reductive elimination. Thus, ferra- and manganaelectro-catalyzed C-H arylations were accomplished at mild reaction temperatures with ample scope by the action of sustainable iron catalysts, employing electricity as a benign oxidant.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/chem.201904018

Leonardo Massignan

Papers

Electrochemical C−H/N−H Activation by Water‐Tolerant Cobalt Catalysis at Room Temperature

Electrooxidative Ruthenium-Catalyzed C-H/O-H Annulation by Weak O-Coordination.

C-H Oxygenation Reactions Enabled by Dual Catalysis with Electrogenerated Hypervalent Iodine Species and Ruthenium Complexes.

Catalyst-Guided C=Het Hydroarylations by Manganese-Catalyzed Additive-Free C-H Activation.

Iron-Electrocatalyzed C-H Arylations: Mechanistic Insights into Oxidation-Induced Reductive Elimination for Ferraelectrocatalysis.