Electrochemical Homo‐ and Crossannulation of Alkynes and Nitriles for the Regio‐ and Chemoselective Synthesis of 3,6‐Diarylpyridines

We disclose a mediated electrochemical [2+2+2] annulation of alkynes with nitriles, forming substituted pyridines in a single step from low‐cost, readily available starting materials. The combination of electrochemistry and a triarylamine redox mediator obviates the requirements of transition metals and additional oxidants. Besides the formation of diarylpyridine moieties via the homocoupling of two identical alkynes, the heterocoupling of two different alkynes depending on their electronic nature is possible, highlighting the unprecedented control of chemoselectivity in this catalytic [2+2+2] process. Mechanistic investigations like cyclic voltammetry and crossover experiments combined with DFT calculations indicate the initial oxidation of an alkyne as the key step leading to the formation of a vinyl radical cation intermediate. The utilization of continuous flow technology proved instrumental for an efficient process scale‐up. The utility of the products is exemplified by the synthesis of π‐extended molecules, being relevant for material or drug synthesis. Intermolecular Homo‐couplings, but especially Cross‐couplings are challenging! We reported an electrochemical [2+2+2] annulation of alkynes with nitriles using triarylamine as a redox mediator to form substituted pyridines. Our process demonstrates unprecedented control of chemoselectivity, allowing both homo‐ and heterocouplings of alkynes and nitriles. A mechanistic rationale is proposed, supported by CV, EPR, NMR, and computational studies.