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

Journal of the American Chemical Society
Bo SunMasakatsu Shibasaki

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.

References

May 10, 2003·Chemosphere·Gordon W Gribble
Mar 17, 2005·Angewandte Chemie·Hisashi Yamamoto, Kentaro Futatsugi
Dec 13, 2005·Angewandte Chemie·Maria Manuel B Marques
Jan 17, 2008·Chemical Society Reviews·Jorge M M VerkadeFloris P J T Rutjes
Apr 12, 2008·Accounts of Chemical Research·Daniel H PaullThomas Lectka
Jun 25, 2009·Chemical Society Reviews·Ramón Gómez Arrayás, Juan C Carretero
Apr 22, 2010·Angewandte Chemie·Manabu HatanoKazuaki Ishihara
Oct 22, 2010·Chemical Communications : Chem Comm·Julianne M YostDon M Coltart
Mar 9, 2011·The Journal of Organic Chemistry·Filip ColpaertNorbert De Kimpe
Apr 27, 2011·Angewandte Chemie·Naoya Kumagai, Masakatsu Shibasaki
Oct 29, 2013·Journal of the American Chemical Society·Wen-Bo LiuBrian M Stoltz
Jan 23, 2014·Organic & Biomolecular Chemistry·Suckchang HongHyeung-geun Park
May 3, 2014·Angewandte Chemie·Karin WeidnerMasakatsu Shibasaki
Dec 9, 2014·Chemical Science·B M TrostY Zhang
Dec 17, 2014·Journal of the American Chemical Society·Liang YinMasakatsu Shibasaki
Dec 18, 2014·Angewandte Chemie·Hong-Yu WangGang Zhao
Apr 1, 2015·Angewandte Chemie·Karin WeidnerMasakatsu Shibasaki
Dec 15, 2015·Journal of the American Chemical Society·Lennart BrewitzMasakatsu Shibasaki
Feb 3, 2016·Angewandte Chemie·Won-jin Chung, Christopher D Vanderwal
May 14, 2016·Organic Letters·Fernando Arteaga ArteagaMasakatsu Shibasaki

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Citations

Jan 18, 2019·Angewandte Chemie·Roman PlutaMasakatsu Shibasaki
Feb 7, 2020·ChemistryOpen·Anna FantinatiClaudio Trapella
Aug 26, 2020·Chemistry : a European Journal·Thomas R PuleoJeffrey S Bandar
Apr 7, 2021·Journal of the American Chemical Society·Yasuhiro YamashitaShu Kobayashi
Apr 24, 2018·The Journal of Organic Chemistry·Toshifumi TakeuchiMasakatsu Shibasaki
Jan 11, 2018·Journal of the American Chemical Society·Xingyu JiangJohn F Hartwig

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