TY - JOUR
T1 - α-Halo Amides as Competent Latent Enolates
T2 - Direct Catalytic Asymmetric Mannich-Type Reaction
AU - Sun, Bo
AU - Balaji, Pandur Venkatesan
AU - Kumagai, Naoya
AU - Shibasaki, Masakatsu
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/6/21
Y1 - 2017/6/21
N2 - 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.
AB - 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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U2 - 10.1021/jacs.7b03291
DO - 10.1021/jacs.7b03291
M3 - Article
C2 - 28530808
AN - SCOPUS:85021069964
SN - 0002-7863
VL - 139
SP - 8295
EP - 8301
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 24
ER -