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The Proline-Catalyzed Direct Asymmetric Three-Component Mannich Reaction:  Scope, Optimization, and Application to the Highly Enantioselective Synthesis of 1,2-Amino Alcohols | Journal of the American Chemical Society
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The Proline-Catalyzed Direct Asymmetric Three-Component Mannich Reaction:  Scope, Optimization, and Application to the Highly Enantioselective Synthesis of 1,2-Amino Alcohols
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    The Proline-Catalyzed Direct Asymmetric Three-Component Mannich Reaction:  Scope, Optimization, and Application to the Highly Enantioselective Synthesis of 1,2-Amino Alcohols
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    Contribution from the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2002, 124, 5, 827–833
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    https://doi.org/10.1021/ja0174231
    Published January 10, 2002
    Copyright © 2002 American Chemical Society

    Abstract

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    We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide β-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.

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     To whom correspondence should be addressed. E-mail:  blist@ scripps.edu.

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    Cite this: J. Am. Chem. Soc. 2002, 124, 5, 827–833
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    Published January 10, 2002
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