α-Halo Amides as Competent Latent Enolates: Direct Catalytic Asymmetric Mannich-Type Reaction

Bo Sun, Pandur Venkatesan Balaji, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8295-8301
Number of pages7
JournalJournal of the American Chemical Society
Volume139
Issue number24
DOIs
Publication statusPublished - 2017 Jun 21
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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