Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd-3(OAc)(6): The Coexistence of Multinuclear Pd- n Reaction Pathways Highlights the Importance of Pd Speciation in C-H Bond Activation

Abstract

Palladacycles are key intermediates in catalytic C-Hbondfunctionalization reactions and important precatalysts for cross-couplings.It is commonly believed that palladacycle formation occurs throughthe reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically,mononuclear "Pd(OAc)(2)" species, with cyclopalladationliberating acetic acid as the side product. In this study, we showthat N,N-dimethyl-fluoro-benzylamines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd-3(OAc)(6), proceeding via higher-order cyclopalladated intermediates.Regioselectivity is altered subtly depending on the ratio of substrate:Pd-3(OAc)(6) and the solvent used. Our findings are importantwhen considering mechanisms of Pd-mediated reactions involving theintermediacy of palladacycles, of particular relevance in catalyticC-H bond functionalization chemistry.