Asymmetric Kumada Couplings of α-Bromo Ketones

Abstract

Kumada reactions (metal-catalyzed couplings of organic electrophiles with Grignard reagents) were among the first studied cross-­coupling reactions. Despite the early success of Kumada reactions with alkyl electrophiles, no examples of the enantioselective version have been reported. The authors described a novel asymmetric Kumada coupling of racemic α-bromo ­ketones with aryl Grignard reagents. The scope of the reaction is quite broad, exploiting Knochel’s methods for synthesizing functionalized Grignard reagents. High yields and ee values can be obtained, even with dialkyl ketones using modified bis(oxazoline) ligand 2. Furthermore, the cross-coupling products can be derivatized with good diastereoselectivity without racemization.