Cinchona Alkaloid-Catalyzed Asymmetric Conjugate Additions: The Bifunctional Brønsted Acid-Hydrogen Bonding Model

Journal of the American Chemical Society
Matthew N Grayson, K 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 Brønsted 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.

References

Dec 7, 2006·Journal of the American Chemical Society·Ryan A OlsenFrancisco Zaera
Dec 13, 2007·Chemical Reviews·Abigail G Doyle, Eric N Jacobsen
May 29, 2008·Chemical Communications : Chem Comm·Stephen J Connon
Jun 6, 2009·Chemistry : a European Journal·Clotilde S CucinottaFrancesco L Gervasio
Aug 20, 2009·The Journal of Organic Chemistry·Nihan Celebi-OlçümK N Houk
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hongming LiLi Deng
Oct 27, 2010·Organic & Biomolecular Chemistry·Luis Simón, Jonathan M Goodman
Jul 24, 2012·The Journal of Organic Chemistry·Wenguo YangZhiyong Jiang
Aug 21, 2013·The Journal of Organic Chemistry·Matthew N Grayson, Jonathan M Goodman
Jun 27, 2014·Journal of the American Chemical Society·Yu-hong Lam, K N Houk
Jan 30, 2015·The Journal of Organic Chemistry·Matthew N Grayson, Jonathan M Goodman
Jan 30, 2015·Journal of the American Chemical Society·Yu-Hong Lam, K N Houk
Feb 6, 2015·The Journal of Organic Chemistry·Lois M OvervoordeJonathan M Goodman

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Citations

Jun 3, 2016·Accounts of Chemical Research·Gamze TanriverViktorya Aviyente
Jul 12, 2016·Journal of the American Chemical Society·Matthew N Grayson, K N Houk
Feb 24, 2017·Organic Letters·Matthew ReesLouise Male
Jul 25, 2017·Chemical Communications : Chem Comm·Cristina TrujilloStephen J Connon
Oct 13, 2017·Organic & Biomolecular Chemistry·Artur PrzydaczŁukasz Albrecht
Jun 1, 2018·Organic & Biomolecular Chemistry·Agnieszka CholewiakPiotr Kwiatkowski
Jul 24, 2018·Chemistry : a European Journal·Arkajyoti SenguptaKrishnan Raghavachari
Jun 5, 2019·Organic & Biomolecular Chemistry·Mateusz DygudaŁukasz Albrecht
Feb 6, 2020·Chemistry : a European Journal·Isaac G SonsonaRaquel P Herrera
Dec 20, 2018·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Dongdong ZhengAlbert M Brouwer
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Albert Granados, Adelina Vallribera
Nov 13, 2020·Journal of the American Chemical Society·Nastaran Salehi MarzijaraniYining Ji
Apr 29, 2021·Organic & Biomolecular Chemistry·Bruno N Falcone, Matthew N Grayson
Mar 29, 2018·The Journal of Physical Chemistry. a·Mojgan Heshmat, Timofei Privalov
Mar 6, 2018·ACS Omega·Tatu KumpulainenAlbert M Brouwer

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