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.

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.

Arylated products are found in various fields of chemistry and represent essential entities for many applications. Therefore, the formation of this structural feature represents a central issue of contemporary organic synthesis. By the action of electricity the necessity of leaving groups, metal catalysts, stoichiometric oxidizers, or reducing agents can be omitted in part or even completely. The replacement of conventional reagents by sustainable electricity not only will be environmentally benign but also allows significant short cuts in electrochemical synthesis. In addition, this methodology can be considered as inherently safe. The current survey is organized in cathodic and anodic conversions as well as by the number of leaving groups being involved. In some electroconversions the reagents used are regenerated at the electrode, whereas in other electrotransformations free radical sequences are exploited to afford a highly sustainable process. The electrochemical formation of the aryl–substrate bond ...

Electrochemical Arylation Reaction.

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

Electrochemical cobalt-catalyzed C-H functionalizations were achieved in terms of C-H oxygenation under mild conditions at 23 °C. The robust electrochemical C-H functionalization was characterized by ample substrate scope, whereas mechanistic studies provided support for a facile C-H cleavage. The electrochemical cobalt-catalyzed C-H oxygenation proved viable on arenes and alkenes with excellent levels of positional and diastereo-selectivity, avoiding the use of stoichiometric silver(I) oxidants under ambient conditions.

Electrochemical Cobalt-Catalyzed C–H Oxygenation at Room Temperature

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

Powering the Future: How Can Electrochemistry Make a Difference in Organic Synthesis?

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.

Asymmetric pallada-electrocatalyzed C-H olefinations were achieved through the synergistic cooperation with transient directing groups. The electrochemical, atroposelective C-H activations were realized with high position-, diastereo-, and enantio-control under mild reaction conditions to obtain highly enantiomerically-enriched biaryls and fluorinated N-C axially chiral scaffolds. Our strategy provided expedient access to, among others, novel chiral BINOLs, dicarboxylic acids and helicenes of value to asymmetric catalysis. Mechanistic studies by experiments and computation provided key insights into the catalyst's mode of action.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.202003826

Cong Tian

Papers

Electrochemical Cobalt-Catalyzed C–H Oxygenation at Room Temperature

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

Powering the Future: How Can Electrochemistry Make a Difference in Organic Synthesis?

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

Enantioselective Pallada-Electrocatalyzed C-H Activation by Transient Directing Groups: Expedient Access to Helicenes.