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Updated: Mar 2, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
α-Halo Amides as Competent Latent Enolates: Direct Catalytic Asymmetric Mannich-Type Reaction
Bo Sun1, Pandur Venkatesan Balaji1, Naoya Kumagai1
1Institute of Microbial Chemistry (BIKAKEN), Tokyo , 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Abstract:
α-Halogenated carbonyl compounds are susceptible to dehalogenation and thus largely neglected as enolate precursors in catalytic enantioselective C-C bond-forming reactions. By merging the increased stability of the α-C-halogen bond of amides and the direct enolization methodology of the designed amide, we explored a direct catalytic asymmetric Mannich-type reaction of α-halo 7-azaindoline amides with N-carbamoyl imines. All α-halo substituents, α-F, -Cl, -Br, -I amides, were tolerated to provide the Mannich-adducts in a highly stereoselective manner without undesirable dehalogenation. The diastereoselectivity switched intriguingly depending on the substitution pattern of the aromatic imines, which is ascribed to stereochemical differentiation based on the open transition-state model. Functional group interconversion of the 7-azaindoline amide moiety of the Mannich-adducts and further elaboration into a diamide without dehalogenation highlight the synthetic utility of the present protocol for accessing enantioenriched halogenated chemical entities.
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