Keto-Enol Thermodynamics of Breslow Intermediates

Journal of the American Chemical Society
Mathias PaulAlbrecht Berkessel

Abstract

Breslow intermediates, first postulated in 1958, are pivotal intermediates in carbene-catalyzed umpolung. Attempts to isolate and characterize these fleeting amino enol species first met with success in 2012 when we found that saturated bis-Dipp/Mes imidazolidinylidenes readily form isolable, though reactive diamino enols with aldehydes and enals. In contrast, triazolylidenes, upon stoichiometric reaction with aldehydes, gave exclusively the keto tautomer, and no isolable enol. Herein, we present the synthesis of the "missing" keto tautomers of imidazolidinylidene-derived diamino enols, and computational thermodynamic data for 15 enol-ketone pairs derived from various carbenes/aldehydes. Electron-withdrawing substituents on the aldehyde favor enol formation, the same holds for N,N'-Dipp [2,6-di(2-propyl)phenyl] and N,N'-Mes [2,4,6-trimethylphenyl] substitution on the carbene component. The latter effect rests on stabilization of the diamino enol tautomer by Dipp substitution, and could be attributed to dispersive interaction of the 2-propyl groups with the enol moiety. For three enol-ketone pairs, equilibration of the thermodynamically disfavored tautomer was attempted with acids and bases but could not be effected, indicating ...Continue Reading

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Citations

Aug 25, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shuang Ma, Patrick H Toy
Dec 15, 2016·The Journal of Organic Chemistry·Olga BortoliniChristian Silvio Pomelli
May 5, 2018·Chembiochem : a European Journal of Chemical Biology·Zhihong GuoWan Chan
Feb 26, 2020·Organic & Biomolecular Chemistry·Nicholas KonstandarasJason B Harper
Nov 21, 2018·The Journal of Organic Chemistry·Ming-Hsiu HsiehJen-Shiang K Yu
Sep 10, 2020·The Journal of Organic Chemistry·Zengyu ZhangXiaoyu Yan
Jan 7, 2020·Organic Letters·Wacharee HarnyingAlbrecht Berkessel
Dec 3, 2021·Physical Chemistry Chemical Physics : PCCP·Ming-Hsiu Hsieh, Jen-Shiang K Yu
Jan 15, 2022·The Journal of Organic Chemistry·Gou-Tao HuangJen-Shiang K Yu

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