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Kendall N. Houk - One of the best experts on this subject based on the ideXlab platform.

  • Cinchona urea catalyzed asymmetric sulfa michael reactions the bronsted acid hydrogen bonding model
    Journal of the American Chemical Society, 2016
    Co-Authors: Matthew N Grayson, Kendall N. Houk
    Abstract:

    The Cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Bronsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Bronsted acid−hydrogen bonding transition state (TS) model for Cinchona alkaloid catalysis that we recently showed to be favored over Wynberg’s widely accepted ion pair−hydrogen bonding model and represent the first detailed mechanistic study of a Cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by Cinchona alkaloids.

  • Cinchona alkaloid catalyzed asymmetric conjugate additions the bifunctional bronsted acid hydrogen bonding model
    Journal of the American Chemical Society, 2016
    Co-Authors: Matthew N Grayson, Kendall N. Houk
    Abstract:

    Wynberg's report from 1977 that natural Cinchona alkaloids catalyze the asymmetric conjugate addition of aromatic thiols to cycloalkenones is a landmark discovery in hydrogen bonding organocatalysis. Wynberg proposed that this reaction proceeded via the formation of a thiolate-alkylammonium tight ion pair and activation of the enone electrophile by a hydrogen bond from the catalyst's hydroxyl group. This reaction model provided the mechanistic basis for understanding Wynberg's reaction and many other asymmetric transformations since. Our quantum mechanical calculations reveal a different model should be used to explain the results: the alkylammonium ion activates the enone by Bronsted acid catalysis, and the catalyst's hydroxyl group orients the thiolate nucleophile. The new model rationalizes the stereoselective outcome of Wynberg's reaction and provides a new, general model for asymmetric Cinchona organocatalysis.

Matthew N Grayson - One of the best experts on this subject based on the ideXlab platform.

  • Cinchona urea catalyzed asymmetric sulfa michael reactions the bronsted acid hydrogen bonding model
    Journal of the American Chemical Society, 2016
    Co-Authors: Matthew N Grayson, Kendall N. Houk
    Abstract:

    The Cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Bronsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Bronsted acid−hydrogen bonding transition state (TS) model for Cinchona alkaloid catalysis that we recently showed to be favored over Wynberg’s widely accepted ion pair−hydrogen bonding model and represent the first detailed mechanistic study of a Cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by Cinchona alkaloids.

  • Cinchona alkaloid catalyzed asymmetric conjugate additions the bifunctional bronsted acid hydrogen bonding model
    Journal of the American Chemical Society, 2016
    Co-Authors: Matthew N Grayson, Kendall N. Houk
    Abstract:

    Wynberg's report from 1977 that natural Cinchona alkaloids catalyze the asymmetric conjugate addition of aromatic thiols to cycloalkenones is a landmark discovery in hydrogen bonding organocatalysis. Wynberg proposed that this reaction proceeded via the formation of a thiolate-alkylammonium tight ion pair and activation of the enone electrophile by a hydrogen bond from the catalyst's hydroxyl group. This reaction model provided the mechanistic basis for understanding Wynberg's reaction and many other asymmetric transformations since. Our quantum mechanical calculations reveal a different model should be used to explain the results: the alkylammonium ion activates the enone by Bronsted acid catalysis, and the catalyst's hydroxyl group orients the thiolate nucleophile. The new model rationalizes the stereoselective outcome of Wynberg's reaction and provides a new, general model for asymmetric Cinchona organocatalysis.

Wei Wang - One of the best experts on this subject based on the ideXlab platform.

Wenhu Duan - One of the best experts on this subject based on the ideXlab platform.

Yongjun Chen - One of the best experts on this subject based on the ideXlab platform.