Department of Chemistry (Organic Chemistry), University of Cologne , Greinstrasse 4, 50939 Cologne, Germany.
Department of Chemistry, Indian Institute of Technology Bombay , Powai, Mumbai 400076, India.
J Am Chem Soc. 2016 Apr 20;138(15):5044-51. doi: 10.1021/jacs.5b13236. Epub 2016 Apr 6.
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 kinetic inhibition of proton transfer.
Breslow 中间体于 1958 年首次提出，是卡宾催化反转中至关重要的中间体。首次尝试分离和表征这些短暂的氨基烯醇物种是在 2012 年取得成功的，当时我们发现饱和双二异丙基甲硅烷基/甲硅烷基咪唑啉亚基与醛和烯醛很容易形成可分离的、尽管反应性的二氨基烯醇。相比之下，三唑啉亚基与醛进行化学计量反应时，仅给出酮式互变异构体，没有可分离的烯醇。在此，我们提出了咪唑啉亚基衍生的二氨基烯醇的“缺失”酮式互变异构体的合成方法，以及源自各种卡宾/醛的 15 个烯醇-酮对的计算热力学数据。醛上的吸电子取代基有利于烯醇的形成，卡宾部分上的 N,N'-二异丙基[2,6-二(2-丙基)苯基]和 N,N'-甲硅烷基[2,4,6-三甲基苯基]取代基也是如此。后一种效应取决于二异丙基取代对二氨基烯醇互变异构体的稳定作用，并且可以归因于 2-丙基基团与烯醇部分之间的分散相互作用。对于三个烯醇-酮对，尝试用酸和碱使热力学不利的互变异构体达到平衡，但无法实现，这表明质子转移的动力学受到抑制。
