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Catalytic Asymmetric α-Alkylation of Ketones with Unactivated Alkyl Halides

Peigen Wang, Liangwei Zhu, Jingwen Wang, Zhong‐Lin Tao

2023Journal of the American Chemical Society25 citationsDOI

Abstract

A catalytic, enantioselective method for direct α-alkylation of ketones with unactivated alkyl halides is realized by employing an α-enolizable ketone in a nickel-catalyzed C(sp 3 )–C(sp 3 ) cross-coupling reaction. The key to the success is attributed to a unique bimetallic ligand. A variety of acyclic ketones and unactivated alkyl iodides can serve as suitable substrates under mild conditions to generate chiral ketones with α-quaternary carbon stereocenters in high yields with good enantioselectivities. A range of transformations based on the ketone moiety are also demonstrated to show the potential application of this method. Preliminary mechanistic studies support a dinickel-catalyzed cross-coupling mechanism.

Topics & Concepts

ChemistryAlkylAlkylationKetoneStereocenterHalideEnantioselective synthesisCatalysisLigand (biochemistry)MoietyCoupling reactionOrganic chemistryCombinatorial chemistryOxazolineBiochemistryReceptorCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisAsymmetric Synthesis and Catalysis
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