ION PAIR ALDOL ADDITION REACTIONS

描述：首席研究员注意到Aldol加成 反应是最重要的碳-碳键形成之一 在合成有机化学中的反应，它被广泛应用于 药物和其他生物活性分子的合成 反应现在最常在非极性溶剂中进行，例如 四氢呋喃(THF)，经常与羰基锂盐一起使用 化合物(烯醇酸锂)。他报告说，这些元素的聚合 通过溶液性质、核磁共振和X射线对化合物进行了表征 结晶学和这种聚集体已经被提出为 与其他羰基的羟醛加成反应中的活性物种 但对金融衍生品的实际作用研究很少 这样的聚集体在反应中。他接着指出，通过组合 一些化合物的UV-Vis光谱和质子转移平衡研究 锂的烯醇酸盐，聚集常数已获得，即使在 稀溶液和作为浓度函数光谱是 通过“奇异值分解”分析来确定数量 不同的物种存在，并允许去卷积，从而使 每种成分的光谱。为此，手套箱-光谱仪 已经开发出一种装置，在该装置中，样品舱内置于 手套盒用光缆与光谱仪相连。 需要注意的是，该装置允许溶液的光谱 在手套盒的惰性气氛下准备和学习。这个 到目前为止的结果据说表明，单体离子对可能 在反应中起着重要的动力学作用。 建议将这种研究扩大到其他感兴趣的资产。 并测量了它们的羟醛加成反应动力学 醛、酮及其与不饱和物质的Michael加成反应 羰基化合物。这表明，动力学研究将表明 烯醇化活性物种的聚集状态和 了解离子对单体和聚集体的相对作用将 导致更完整的反应机理和更好的 了解复杂的综合设计所需的知识。校长 研究者特别注意到，溶剂加成物的作用， 例如锂盐、六甲基磷三胺和双氰胺 三胺将在严格控制的条件下进行研究，以 确定锂的配位在立体化学中的作用 加成反应。 还建议应用相同的光谱研究技术， Aldol和Michael的质子转移平衡和反应动力学 与羧酸二锂盐的加成反应 二酮。值得注意的是，这些二锂盐也在使用 在有机合成中越来越多，但反应机理是 几乎没有人研究过。据报道，这些盐也是聚集在一起的 但对单体和单体的相对反应性知之甚少 集合体。拟议的研究旨在提供独特的信息 关于这些反应，这在任何其他地方都是很难获得的 道路。建议随后推广到其他碱盐 和碱土金属、早过渡金属和晚过渡金属以及 由于其中许多盐已被发现有用途，因此也建议使用镧系元素。 在一些立体定向合成中。

DESCRIPTION: The principal investigator notes that the Aldol addition reaction is one of the most important carbon-carbon bond forming reactions in synthetic organic chemistry, that it is widely used in the synthesis of drugs and other biologically active molecules and that the reaction is now most often run in non-polar solvents, such as tetrahydrofuran (THF), frequently with lithium salts of carbonyl compounds (lithium enolates). He reports that the aggregation of these compounds has been characterized by solution properties, NMR and by X-ray crystallography and that such aggregates have been proposed as the reactive species in the Aldol-type additions with other carbonyl derivatives but there have been very few studies on the actual role of such aggregates in reactions. He goes on to note that by a combination of UV-vis spectroscopic and proton transfer equilibrium studies of some lithium enolates, aggregation constants have been obtained even in dilute solution and that spectra as a function of concentration are analyzed by "Singular Value Decomposition" to determine the number of different species present and to permit deconvolution to give the spectrum of each component. For this purpose a glovebox-spectrometer apparatus has been developed in which the sample compartment built into the glovebox is connected with a spectrometer with fiber-optic cables. It is noted that the apparatus permits spectroscopy of solutions prepared and studied under the inert atmosphere of the glovebox. The results thus far are said to suggest that the monomeric ion pairs might play an important kinetic role in reactions. It is proposed to extend such studies to additional enolates of interest and to measure the reaction kinetics of their Aldol additions to aldehydes and ketones and of Michael addition reactions with unsaturated carbonyl compounds. It is indicated that the kinetic studies will show the state of aggregation of the enolate reactive species and that knowledge of the relative roles of ion pair monomers and aggregates will lead to more complete reaction mechanisms and to the better understanding required for sophisticated synthesis design. The principal investigator notes that in particular, the roles of solvent addends, such as lithium salts, hexamethylphosphoric triamide, and di- and triamines will be studied under carefully controlled conditions to determine the role of coordination of lithium in the stereochemistry of the addition reactions. It is also proposed to apply the same techniques of spectroscopic study, proton transfer equilibria and reaction kinetics of Aldol and Michael addition reactions to the dilithium salts of carboxylic acids and beta- diketones. It is noted that these dilithium salts are also being used increasingly in organic synthesis but that the reaction mechanisms are virtually unstudied. It is reported that these salts are also aggregated but nothing is known about the relative reactivities of monomers and aggregates. The proposed studies are to provide unique information about these reactions, which would be difficult to obtain in any other way. It is suggested that subsequent extension to other salts of alkali and alkaline earth metals, early and late transition metals and lanthanides is also proposed since many of these salts have found use in some stereospecific syntheses.