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. Electrocatalysis is now being used for many oxidation reactions in organic synthesis. This protocol describes how to set up an electrolytic cell for use in cobalt-catalyzed C–H/N–H alkyne annulations and C–H oxygenations.