Asymmetric radical type 1,2-aryloxy-phosphinolylation of vinylarenes catalyzed by chiral vanadyl complexes

Enantioselective 1,2-difunctionalization of olefins by radical type aryloxylation at the benzylic or propargylic position is challenging. Here we show high enantioselective three-component, 1,2-aryloxy-phosphinoylation of vinylarenes with various phenol derivatives catalyzed by chiral vanadyl(V) complexes derived from 3,5-disubstituted-N-salicylidene-L-t-leucinate. The optimal scenario with solvent screening for 4-methylstyrene and phenol as a model system was in 1:1 mixture of acetonitrile/dichloromethane with 3-(2,5-dimethylphenyl)-5-bromo-substituted catalyst that led to the corresponding (R)-product in 74% ee. The interventions of the regio-isomeric 1,2- phosphinoyl-aroxylation, phenolic o-C-attack, and direct two-component homo- and/or cross-coupling between phenol and 4-methyl-styrene were minimized. Exclusive regio-selective and chemoselective phenolic O-trapping products were further attained with up to 88% yield and 93 ± 3% ee. Four best m-styrenes (i.e., bromo, acetoxy, 1-pyrazolyl, and cyano), two-best p-styrenes (i.e., trifluoromethyl and acetyl) and one-enyne were selected to combine with 3-t-butyl-phenol with high asymmetric induction of 87-94% ee. Preliminary calculations for the catalytic reaction between 3-chloro-styrene and phenol by the best catalyst were performed to rationalize the origin and extent of enantio-controls.