Bifurcated Rhodaelectro-catalyzed C-H Activation for the Synthesis of Pyrroles and Lactones.

While electrocatalyzed alkyne annulations of arenes represent a powerful strategy for the assembly of heteroaromatic motives, electrochemical C(sp2)-H activations of alkenes remain scarce. Herein, a strategy for the rhodaelectro-catalyzed functionalization of enamides is presented for the efficient construction of pyrroles using electricity as a sustainable oxidant. Moreover, the tuning of the solvent system allowed a fascinating switch in chemoselectivity, which is not possible with traditionally used chemical oxidants, giving rise to lactone architectures. The rhoda-electrocatalysis features a broad scope as well as high regio- and chemoselectivities.

Chemo- and Site-Selective Electro-Oxidative Alkane Fluorination by C(sp3 )-H Cleavage.

Electrochemical fluorinations of C(sp3 )-H bonds with a nucleophilic fluoride source have been accomplished in a chemo- and site-selective fashion, avoiding the use of electrophilic F+ sources and stoichiometric oxidants. The introduced metal-free strategy exhibits high functional group tolerance, setting the stage for late-stage fluorinations of biorelevant motifs. The synthetic utility of the C(sp3 )-H fluorination was reflected by subsequent one-pot arylation of the generated benzylic fluorides.

Rhodaelectro-catalyzed access to chromones via formyl C-H activation towards peptide electro-labeling.

Chromones represent a privileged scaffold in medicinal chemistry and are an omnipresent structural motif in natural products. Chemically encoded non-natural peptidomimetics feature improved stability towards enzymatic degradation, cell permeability and binding affinity, translating into a considerable impact on pharmaceutical industry. Herein, a strategy for the sustainable assembly of chromones via electro-formyl C-H activation is presented. The rational design of the rhodaelectro-catalysis is guided by detailed mechanistic insights and provides versatile access to tyrosine-based fluorogenic peptidomimetics.

Cobaltaelectro-catalyzed C-H activation for resource-economical molecular syntheses.

The direct cleavage of otherwise inert C-H bonds has emerged as a sustainable approach for organic synthesis; in contrast to other approaches, these reactions result in the formation of fewer undesired by-products and do not require pre-functionalization steps. In recent years, oxidative C-H/N-H alkyne annulations and C-H oxygenations were realized by 3d metals. Unfortunately, most of these reactions require stoichiometric amounts of often toxic chemical oxidants. This protocol provides a general method for cobaltaelectro-catalyzed C-H activations of benzamides. Here, anodic oxidation obviates the need for a chemical oxidant and uses 10-20% of a more environmentally benign, inexpensive catalyst. We outline a detailed and precise description of the designed electrolytic cell for metallaelectrocatalysis, including readily available electrode materials and electrode holders. The custom-made device is further compared with the commercially available and standardized ElectraSyn 2.0 electrochemistry kit. As example applications of this approach, we describe cobaltaelectro-catalyzed C-H activation protocols for the direct C-H oxygenation of benzamides and resource-economical synthesis of isoquinolones. The cobaltaelectrocatalysis setup and reaction take about 17 h, while an additional 5 h have to be anticipated for workup and chromatographic purification. The methods described herein feature broad functional group tolerance, operational simplicity, low waste-product formation and an overall exceptional level of resource economy.

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

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.

Iridium-Catalyzed Electrooxidative C-H Activation by Chemoselective Redox-Catalyst Cooperation.

Iridium-catalyzed electrochemical C-H activation was accomplished within a cooperative catalysis manifold, setting the stage for electrooxidative C-H alkenylations through weak O-coordination. The iridium-electrocatalyzed C-H activation featured high functional-group tolerance through assistance of a metal-free redox mediator through indirect electrolysis. Detailed mechanistic insights provided strong support for an organometallic C-H cleavage and a synergistic iridium(III/I)/redox catalyst regime, enabling the use of sustainable electricity as the terminal oxidant with improved selectivity features.