Cobalt-Catalyzed Enantioconvergent Negishi Cross-Coupling of α-Bromoketones

Abstract

Cobalt-catalyzed enantioconvergent cross-coupling of α-bromoketones with aryl zinc reagents is achieved to access chiral ketones bearing α-tertiary stereogenic centers with high enantioselectivities. The more challenging and sterically hindered α-bromoketones bearing a 2-fluorophenyl group or β-secondary and tertiary alkyl chains could also be well-tolerated. Adjusting the electronic effect of chiral unsymmetric N,N,N-tridentate ligands is critical for improving the reactivity and selectivity of this transformation, which is beneficial for further studies of asymmetric 3d metal catalysis via ligand modification. The control experiments and kinetic studies illustrated that the reaction involved radical intermediates and the reductive elimination was a rate-determining step.

Synthesis of Chiral α-Aryl Ketones by Photoredox/Nickel-Catalyzed Enantioconvergent Acyl Cross-Coupling with Organotrifluoroborate

“…Transition-metal-catalyzed enantioconvergent transformation provides a practical strategy to assemble this type of chiral carbonyl compounds . After transition-metal-catalyzed enantioconvergent cross-coupling of racemic α-bromoketones with organometallic reagents at remarkably low temperature was established, more transition-metal-catalyzed enantioconvergent acylative approaches from readily available carboxylic acid derivatives to α-chiral ketones with racemic reagents have emerged (Scheme a) . More than pallidum-catalyzed enantioconvergent Fukuyama cross-coupling of thioesters with racemic benzylic organozinc reagents, both organometallic reagent- and noble-metal catalyst-free enantioconvergent methods with better functional group tolerance are receiving increased attention.…”