The Stability of Imidazolidinones is the Primary Influence on the Catalytic Activity of Proline Amides and Proline Sulfonamides in Enamine Catalysis Using Alkyl Aldehyde Substrates
The Stability of Imidazolidinones is the Primary Influence on the Catalytic Activity of Proline Amides and Proline Sulfonamides in Enamine Catalysis Using Alkyl Aldehyde Substrates
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DOI：
10.1002/ejoc.201201174
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发表时间：
2013
影响因子：
2.8
通讯作者：
S. Tin;J. Fuentes;T. Lebl;M. Clarke
中科院分区：
文献类型：
--
作者：
S. Tin;J. Fuentes;T. Lebl;M. Clarke
一些N-取代的脯氨酸衍生物催化烷基醛与亲电伙伴的反应，而另一些则产生可忽略不计的产物。醛和脯氨酸衍生物之间的关键反应进行了研究，并观察到的反应性的基本原理。衍生自芳香胺（弱催化剂）的简单脯氨酸酰胺以牺牲烯胺为代价相当迅速地形成稳定的咪唑烷酮，如果有的话，后者在不到一个小时的时间内就被检测到。碱性较低的脯氨酸酰胺形成咪唑烷酮的动力学非对映异构体，其非常缓慢地反转其立体化学以得到最终的热力学产物。这些非对映体的立体化学通过1H NMR、NOE和TOCSY实验完全归属。衍生自烷基胺的脯氨酸酰胺（良好的催化剂）形成高浓度的烯胺，其仅缓慢（数天）转化为惰性咪唑烷酮的单一非对映异构体。相比之下，另一种好的催化剂，脯氨酸磺酰胺，立即形成反应性咪唑啉酮，迅速开环并与其他醛交换。这可能是滴加给亚胺离子和烯胺进入催化循环。因此，有两个完全不同的机制制度，导致有效的催化。这些机制的见解，现在应该允许一些元素的合理设计脯氨酰胺烯胺反应使用醛。
Some N-substituted proline derivatives catalyse the reactions of alkyl aldehydes with electrophilic partners, and others give negligible amounts of product. The key reaction between the aldehyde and the proline derivative has been studied, and a rationale for the reactivity observed is presented. Simple proline amides derived from aromatic amines (poor catalysts) form stable imidazolidinones quite rapidly at the expense of enamines, the latter being detected, if at all, for less than an hour. Less basic proline amides form a kinetic diastereomer of an imidazolidinone that very slowly inverts its stereochemistry to give a final thermodynamic product. The stereochemistry of these diastereomers was fully assigned by 1H NMR, NOE, and TOCSY experiments. A proline amide derived from an alkylamine (good catalyst) forms high concentrations of enamine that is only slowly (days) converted into a single diastereomer of an inert imidazolidinone. In contrast, another good catalyst, a proline sulfonamide, immediately forms a reactive imidazolidinone, that rapidly ring-opens and exchanges with other aldehydes. This presumably drip-feeds iminium ions and enamines into the catalytic cycle. Thus, there are two quite different mechanistic regimes that lead to efficient catalysis. These mechanistic insights should now allow some element of rational design of prolinamides for enamine reactions using aldehydes.