Regio- and Stereoselective 1,2-Oxyhalogenation of Non-Conjugated Alkynes via Directed Nucleopalladation: Catalytic Access to Tetrasubstituted Alkenes**

Abstract

A catalytic 1,2-oxyhalogenation method that converts non-conjugated internal alkynes into tetrasubstituted alkenes with high regio- and stereoselectivity is described. Mechanistically, the reaction involves a PdII/PdIV catalytic cycle that begins with a directed oxypalladation step. The origin of regioselectivity is the preference for formation of a six-membered palladacycle intermediate, which is facilitated by an N,N-bidentate 2-(pyridin-2-yl)isopropyl (PIP) amide directing group. Selectivity for C(alkenyl)−X versus −N (X=halide) reductive elimination from the PdIV center depends on the identity of the halide anion; bromide and iodide engage in C(alkenyl)−X formation, while intramolecular C(alkenyl)−N reductive elimination occurs with chloride to furnish a lactam product. DFT calculations shed light on the origins of this phenomenon.