Investigations via Kinetics and Multivariate Linear\nRegression Models of the Mechanism and Origins of Regioselectivity\nin a Palladium-Catalyzed Aryne Annulation

The\nsynthetic potential of unsymmetrically substituted arynes is\nnot yet fully realized due to regioselectivity issues. Although many\nmodels exist to predict the regioselectivity of arynes, these models\ndo not hold for metal-mediated reactions. Previously, we reported\na way to induce regioselectivity in a metal-catalyzed aryne annulation\nreaction by using bulky monodentate phosphine ligands. Reported herein\nis a mechanistic investigation into the operative catalytic cycle\nwithin this transformation. Additionally, the molecular parameters\nresponsible for regioselectivity have been examined via linear free\nenergy relationships and multivariate linear regression. This model\nshows the interdependence on both the steric and electronic properties\nof the aryne and the size of the phosphine ligand for regioselectivity.