Efficient and selective molecular syntheses are paramount to inter alia biomolecular chemistry and material sciences as well as for practitioners in chemical, agrochemical, and pharmaceutical industries. Organic electrosynthesis has undergone a considerable renaissance and has thus in recent years emerged as an increasingly viable platform for the sustainable molecular assembly. In stark contrast to early strategies by innate reactivity, electrochemistry was recently merged with modern concepts of organic synthesis, such as transition-metal-catalyzed transformations for inter alia C-H functionalization and asymmetric catalysis. Herein, we highlight the unique potential of organic electrosynthesis for sustainable synthesis and catalysis, showcasing key aspects of exceptional selectivities, the synergism with photocatalysis, or dual electrocatalysis, and novel mechanisms in metallaelectrocatalysis until February of 2021.

Organic Electrochemistry: Molecular Syntheses with Potential.

Transition metal-catalysed C–H activation has emerged as an increasingly powerful platform for molecular syntheses, enabling applications to natural product syntheses, late-stage modification, pharmaceutical industries and material sciences, among others. This Primer summarizes representative best practices for the experimental set-up and data deposition for C–H activation, as well as discussing key developments including recent advances in asymmetric, photoinduced and electrocatalytic C–H activation. Likewise, strategies for applications of C–H activation towards the assembly of structurally complex (bio)polymers and drugs in academia and industry are discussed. In addition, current limitations in C–H activation and possible approaches for overcoming these shortcomings are reviewed. This Primer provides an overview of the best practices for C–H activation as well as key advances in asymmetric, photoinduced and electrocatalytic-mediated catalysis for this synthetic platform. An overview of how C–H activation facilitates the synthesis of molecules such as structurally complex (bio)polymers and drugs is provided along with the current challenges and priorities for the next decade.

C–H activation

Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized.

Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

A flow-metallaelectro-catalyzed C-H activation was realized in terms of robust rhodaelectro-catalyzed alkyne annulations. To this end, a modular electro-flow cell with a porous graphite felt anode was designed to ensure efficient turnover. Thereby, a variety of C-H/N-H functionalizations proved amenable for alkyne annulations with high levels of regioselectivity and functional group tolerance, viable in both an inter- or intramolecular manner. The electro-flow C-H activation allowed easy scale up, while in-operando kinetic analysis was accomplished by online flow-NMR spectroscopy. Mechanistic studies suggest an oxidatively induced reductive elimination pathway on rhodium(III) in an electrocatalytic regime.

Flow Rhodaelectro-Catalyzed Alkyne Annulations by Versatile C–H Activation: Mechanistic Support for Rhodium(III/IV)

Transition metal catalyzed C-H phosphorylation remains an unsolved challenge. Reported methods are generally limited in scope and require stoichiometric silver salts as oxidants. Reported here is an electrochemically driven RhIII -catalyzed aryl C-H phosphorylation reaction that proceeds through H2 evolution, obviating the need for stoichiometric metal oxidants. The method is compatible with a variety of aryl C-H and P-H coupling partners and particularly useful for synthesizing triarylphosphine oxides from diarylphosphine oxides, which are often difficult coupling partners for transition metal catalyzed C-H phosphorylation reactions. Experimental results suggest that the mechanism responsible for the C-P bond formation involves an oxidation-induced reductive elimination process.

Scalable Rhodium(III)‐Catalyzed Aryl C−H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination

Direct conversion of C–H bonds into C–C bonds is a promising alternative to the conventional cross-coupling reactions, thus giving rise to a wide range of efficient catalytic C–H functionalization ...

Oxidatively Induced Reductive Elimination: Exploring the Scope and Catalyst Systems with Ir, Rh, and Ru Complexes

Alkanes are an abundant and inexpensive source of hydrocarbons; thus, development of new methods to convert the hydrocarbon feedstocks to value-added chemicals is of high interest. However, it is challenging to achieve such transformation in a direct and selective manner mainly due to the intrinsic inertness of their C-H bonds. We herein report a tailored Cp*Co(III)(LX)-catalyzed efficient and site-selective intermolecular amidation of unactivated hydrocarbons including light alkanes. Electronic modulation of the cobalt complexes led to the enhanced amidation efficiency, and these effects were theoretically rationalized by the FMO analysis of presupposed cobalt nitrenoid species. Under the current cobalt protocol, a secondary C-H bond selectivity was observed in various nonactivated alkanes to reverse the intrinsic tertiary preference, which is attributed to the steric demands of the cobalt system that imposes difficulties in accessing tertiary C-H bonds. Experimental and computational studies suggested that the putative triplet Co nitrenoids are transferred to the C-H bonds of alkanes via a radical-like hydrogen abstraction pathway.

Cobalt-Catalyzed Intermolecular C-H Amidation of Unactivated Alkanes.

Electrolytic C‒H Oxygenation via Oxidatively Induced Reductive Elimination in Rh Catalysis

Ionic conjugated polymer, poly(2-ethynyl-N-propargylpyridinium bromide), was prepared by the cyclopolymerization of 2-ethynyl-N-propargylpyridinium bromide on using various transition metal catalysts, or by thermal methods without adding catalyst. The polymerization of 2-ethynyl-N-propargylpyridinium bromide catalyzed by PdCl2 gave the resulting polymers in relatively high yields. The polymer structure was characterized by various instrumental methods to confirm the conjugated polymer backbone structure carrying cumulated pyridine moiety. The polymers prepared by PdCl2 in DMSO or m-cresol were completely soluble in DMF, DMSO, and formic acid. The inherent viscosities of the resulting polymers were in the range of 0.07-0.19 dL/g. Thermal properties of the polymers were also discussed.

Seongho Jin

Papers

Oxidatively Induced Reductive Elimination: Exploring the Scope and Catalyst Systems with Ir, Rh, and Ru Complexes

Cobalt-Catalyzed Intermolecular C-H Amidation of Unactivated Alkanes.

Electrolytic C‒H Oxygenation via Oxidatively Induced Reductive Elimination in Rh Catalysis

Synthesis and Properties of Poly(2-ethynyl-N-propargylpyridinium bromide)

Oxidatively Induced Reductive Elimination for Methyl Group Transfer via Isolable Transmetalation Complexes