Concerted Switching of Regio- and Stereochemistry in Reductive Hydroarylation of Phenylpropiolic Acid Derivatives: Unraveling a Dual Selectivity Inversion

Nickel-catalyzed reductive hydroarylation of phenylpropiolic esters with aryl halides overrides conventional electronic and stereochemical preferences delivering anti -α-hydroarylation products with high selectivity. The method tolerates aryl iodides and bromides, with chemoselective discrimination of iodides vs bromides by tuning reaction conditions. Mechanistic studies reveal a synergistic control mode: steric repulsion governs regioselectivity, while ester carbonyl coordination enables postinsertion Z / E isomerization. A Ni(0)/Ni(II)/Ni(I) manifold and protic solvent as hydrogen donor are supported by deuterium labeling and HRMS-ESI.