Ni-Catalyzed Cyclotrimerization of Unactivated Internal Alkynes: Ligand-Dependent Regioselectivity.

A nickel-catalyzed [2 + 2 + 2] cyclotrimerization of unactivated internal alkynes is presented, enabling regioselective access to fully substituted benzene derivatives through ligand control. The transformation proceeds under additive-free conditions and tolerates a wide range of aryl, heteroaryl, and aliphatic alkynes. Regioselectivity is governed by the ligand framework, in which trialkylphosphine ligands promote the exclusive formation of 1,2,4-substituted benzenes, whereas the N-heterocyclic carbene ligand IPr favors the formation of 1,3,5-isomers as the major product, although the selectivity remains moderate. The reaction is operationally simple, scalable, and broadly applicable, offering a practical strategy for the synthesis of aromatic frameworks from simple unactivated alkynes.