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Brewitz L, Arteaga FA, Yin L, et al. Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides. J Am Chem Soc. 2015;137(50):15929-39doi: 10.1021/jacs.5b11064.
Brewitz, L., Arteaga, F. A., Yin, L., Alagiri, K., Kumagai, N., & Shibasaki, M. (2015). Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides. Journal of the American Chemical Society, 137(50), 15929-39. https://doi.org/10.1021/jacs.5b11064
Brewitz, Lennart, et al. "Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides." Journal of the American Chemical Society vol. 137,50 (2015): 15929-39. doi: https://doi.org/10.1021/jacs.5b11064
Brewitz L, Arteaga FA, Yin L, Alagiri K, Kumagai N, Shibasaki M. Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides. J Am Chem Soc. 2015 Dec 23;137(50):15929-39. doi: 10.1021/jacs.5b11064. Epub 2015 Dec 10. PMID: 26652911.
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J Am Chem Soc. 2015 Dec 23;137(50):15929-39. doi: 10.1021/jacs.5b11064. Epub 2015 Dec 10.

Direct Catalytic Asymmetric Mannich-Type Reaction of α- and β-Fluorinated Amides.

Journal of the American Chemical Society

Lennart Brewitz, Fernando Arteaga Arteaga, Liang Yin, Kaliyamoorthy Alagiri, Naoya Kumagai, Masakatsu Shibasaki

Affiliations

  1. Institute of Microbial Chemistry (BIKAKEN) , Tokyo, Kamiosaki 3-14-23, Shinagawa-ku, Tokyo 141-0021, Japan.

PMID: 26652911 DOI: 10.1021/jacs.5b11064

Abstract

The last two decades have witnessed the emergence of direct enolization protocols providing atom-economical and operationally simple methods to use enolates for stereoselective C-C bond-forming reactions, eliminating the inherent drawback of the preformation of enolates using stoichiometric amounts of reagents. In its infancy, direct enolization relied heavily on the intrinsic acidity of the latent enolates, and the reaction scope was limited to readily enolizable ketones and aldehydes. Recent advances in this field enabled the exploitation of carboxylic acid derivatives for direct enolization, offering expeditious access to synthetically versatile chiral building blocks. Despite the growing demand for enantioenriched fluorine-containing small molecules, α- and β-fluorinated carbonyl compounds have been neglected in direct enolization chemistry because of the competing and dominating defluorination pathway. Herein we present a comprehensive study on direct and highly stereoselective Mannich-type reactions of α- and β-fluorine-functionalized 7-azaindoline amides that rely on a soft Lewis acid/hard Brønsted base cooperative catalytic system to guarantee an efficient enolization while suppressing undesired defluorination. This protocol contributes to provide a series of fluorinated analogs of enantioenriched β-amino acids for medicinal chemistry.

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