Enantioselective Radical-Type 1,2-Alkoxy-Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes

A series of vanadyl complexes bearing 3-t-butyl-5-bromo, 3-aryl-5-bromo, 3,5-dihalo-, and benzo-fused N-salicylidene-tert-leucinates was examined as catalysts for 1,2-alkoxy-phosphinoylation of 4-, 3-, 3,4-, and 3,5-substituted styrene derivatives (including Me/t-Bu, Ph, OR, Cl/Br, OAc, NO2, C(O)Me, CO2Me, CN, and benzo-fused) with HP(O)Ph-2 in the presence of t-BuOOH (TBHP) in a given alcohol or cosolvent with MeOH. The best scenario involved the use of 5 mol % 3-(2,5-dimethylphenyl)-5-Br (i.e., 3-DMP-5-Br) catalyst at 0 degrees C in MeOH. The desired catalytic cross coupling reactions proceeded smoothly with enantioselectivities of up to 95 % ee of (R)-configuration as confirmed by X-ray crystallographic analysis of several recrystallized products. The origin of enantiocontrol and homolytic substitution of the benzylic intermediates by vanadyl-bound methoxide and radical type catalytic mechanism were proposed.

Automated summary

A series of vanadyl complexes were tested as catalysts for the 1,2-alkoxy-phosphinoylation of styrene derivatives. The best catalytic conditions involved the use of 5 mol% of a 3-(2,5-dimethylphenyl)-5-Br catalyst at 0 °C in MeOH, resulting in enantioselectivities of up to 95%. The proposed mechanism involves the homolytic substitution of the benzylic intermediates by vanadyl-bound methoxide and radical-type catalytic mechanism.