Regioselectivity in the Iridium-Catalyzed [2 + 2 + 2] Cycloaddition of Unsymmetrical α,ω-Diynes with Nitrile: A DFT Study

The high regioselectivity of the iridium-catalyzed [2 + 2 + 2] cycloaddition of unsymmetrical α,ω-diynes with nitriles was experimentally determined by Takeuchi and co-workers. In the present study, the regioselectivity in the iridium-catalyzed [2 + 2 + 2] cycloadditions of phenyl- and trimethylsilyl-substituted α,ω-diynes with acetonitrile was examined using PBE-D2-level DFT calculations. The obtained results show that the pathways that produce the pyridine substituted with a phenyl group at the α-position are preferred in the case of a phenyl-substituted diyne, while the pathways that yield the pyridine substituted with a trimethylsilyl group at the β-position are favored in the reaction of a trimethylsilyl-substituted diyne. The obtained results agree with experimentally observed regioselectivities. The structural configuration around the iridium atom affects the energetically preferred pathway beyond the formation of the end-on complex between acetonitrile and iridacyclopentadiene. In addition, both the steric and electronic effects of the substituents on the α-carbon atom play important roles in determining the regioselectivity.