Investigations via Kinetics and Multivariate Linear Regression Models of the Mechanism and Origins of Regioselectivity in a Palladium-Catalyzed Aryne Annulation

The synthetic potential of unsymmetrically substituted arynes is not yet fully realized due to regioselectivity issues. Although many models exist to predict the regioselectivity of arynes, these models do not hold for metal-mediated re-actions. Previously, we reported a way to induce regioselectivity of a metal-catalyzed aryne annulation reaction by using bulky monodentate phosphine ligands. Reported herein is a mechanistic investigation into the operative catalytic cycle within this transformation. Additionally, the molecular parameters responsible for regioselectivity have been examined via LFERs and multivariate linear regression to create a predictive model for regioselectivity. This model shows the interdependence on both the steric and electronic properties of the aryne and the size of the phosphine ligand.