Asymmetric Cross-Coupling of Racemic α-Bromo Esters with Aryl Grignard Reagents Catalyzed by Cyclopropane-Based Bisoxazolines Cobalt Complexes.

Abstract Four new cyclopropane-based bisoxazolines were synthesized and applied to cobalt-catalyzed cross-coupling reactions between racemic α-bromo esters and aryl Grignard reagents. The reaction afforded a series of chiral α-arylalkanoic esters with high yields and good enantioselectivities (up to 93% yield, 92:8 er). This research focuses on the cross-coupling between racemic α-bromopropanoate and p-isobutylphenyl Grignard reagent’s which provides ibuprofen ester efficiently. Furthermore, ibuprofen ester 7e was transformed into (S)-ibuprofen (99:1 er) via hydrolysis and recrystallization.