Developed electrochemical cyclotrimerization demonstrates regioselectivity in polysubstituted aromatics, indicating nickel's potential in synthetic pathways.
Transition metal catalyzed [2+2+2] cycloaddition reactions between three alkynes, a diyne and an alkyne, or a triyne offer a straightforward and typical protocol toward all kinds of polysubstituted benzens. Herein, the synthesis of polysubstituted aromatics through electrochemical nickel catalyzed cyclotrimerization of alkynes is developed. The regio‐divergent cyclotrimerization of terminal alkynes is achieved by judicious choice of ligands, and tributylphosphine, sterically hindered bipyridine, or β‐diketone ligands delivered 1,2,4‐ and 1,3,5‐substituted aromatics with high regioselectivities, respectively. Besides, the semi‐intermolecular [2+2+2] cycloaddition between diynes and alkynes are also amenable under this catalytic system. This approach operates without metal reductant, exhibits wide functional groups tolerance, ease of scalability, and furnishes 75 examples with moderate to good yields, including some biorelevant compounds. Mechanistic experiments and density functional theory calculation reveal the catalytic pathways of 1,3,5‐ and 1,2,4‐cyclotrimerizations, and the origin of the ligand controlled regioselectivity.
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Ma et al. (2025) studied this question.
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