Stereoselective Reactions of Oxocarbenium Ions and Related Intermediates

项目摘要/摘要 尽管含氧碳正离子的立体选择性成键反应是 碳水化合物化学和有机合成，这些反应往往不能按预期进行 立体化学。例如，在许多情况下，立体化学也无法预测，因为没有 理解立体选择性的模型(如中环氧碳正离子的情况)，或者这些模型 未能适应与预期选择性的偏差(如观察到的邻组参与)。至 解决我们对这些立体化学模型的理解上的差距，以下是具体目标 追求：(1)我们将考察邻基参与环状化合物的立体选择性反应 (2)我们将把邻基参与的概念扩展到包括体系 与碳水化合物无关，包括解决非循环立体控制的问题；以及(3)我们将 确定七元环亲电体(氧卡宾离子)和亲核试剂(烯醇酸盐)可以反应 立体选择性地。在第一个目标中，我们将使用与碳水化合物具有相同结构特征的系统 为了解释为什么邻群效应没有预期的那么强，我们提出了一个事实 初步研究。我们还将扩展我们的初步研究，这些研究表明唾液酸中的CO2R基团 对氧碳正离子的稳定性及其反应的立体化学性质影响不大。这个 第二个目标将使用与碳水化合物关系不密切的系统来解决 碳水化合物化学。第三个目标将采用立体化学模型来理解所涉及的反应。 在七元环糖中，我们将扩大初步研究，涉及七个- 与六元环烯醇酸盐的类似反应相比，成员环烯醇酸盐具有更高的选择性。这些 研究将与理论化学家Jeffery Evanseck教授(Duqune)合作进行 他擅长使用计算方法来研究反应机理。建议数 这项研究意义重大，因为它将使研究人员能够预测键形成的立体化学 通常用于合成碳水化合物、天然产物和其他生物活性的反应 化合物。这项拟议的研究具有创新性，因为我们使用非碳水化合物的系统来 发展立体选择性反应，可用于碳水化合物化学、药物化学和天然 产品合成。这些研究与人类健康有关，因为它们将帮助药物化学家计划 并通过精确控制执行生物活性化合物的合成，如碳水化合物 三维结构。

Project Summary/Abstract Although stereoselective bond-forming reactions involving oxocarbenium ions are important methods in carbohydrate chemistry and organic synthesis, these reactions often do not proceed with the expected stereochemistry. For example, in many cases stereochemistry cannot be predicted either because there are no models to understand stereoselectivity (as in the case of medium-ring oxocarbenium ions) or that these models fail to accommodate deviations from expected selectivity (as observed for neighboring-group participation). To address the gaps in our understanding of these stereochemical models, the following specific aims will be pursued: (1) we will examine neighboring-group participation in stereoselective reactions of cyclic oxocarbenium ions; (2) we will extend the concept of neighboring-group participation to encompass systems that are not related to carbohydrates, including to solve problems in acyclic stereocontrol; and (3) we will establish that seven-membered ring electrophiles (oxocarbenium ions) and nucleophiles (enolates) can react stereoselectively. In the first Aim, we will use systems that share structural characteristics with carbohydrates to explain why neighboring group effects are not as strong as may be anticipated, a fact suggested by our preliminary studies. We will also extend our preliminary studies that suggest the CO2R group of sialic acids exerts little influence on the stability of oxocarbenium ions and the stereochemistry of their reactions. The second Aim will use systems that are not closely related to carbohydrates to address mechanistic questions in carbohydrate chemistry. The third Aim will pursue a stereochemical model to understand the reactions involved in seven-membered ring sugars, and we will expand preliminary studies that reactions involving seven- membered ring enolates are more selective than analogous reactions of six-membered ring enolates. These studies will be performed in collaboration with a theoretical chemist, Professor Jeffery Evanseck (Duquesne University), who is skilled in using computational methods to investigate reaction mechanisms. The proposed research is significant because it will enable researchers to predict the stereochemistry of bond-forming reactions commonly used for the synthesis of carbohydrates, natural products, and other biologically active compounds. The proposed research is innovative because we use systems that are not carbohydrates to develop stereoselective reactions that can be used in carbohydrate chemistry, medicinal chemistry, and natural product synthesis. These studies are relevant to human health because they will help medicinal chemists plan and execute the synthesis of biologically active compounds such as carbohydrates with precise control of three-dimensional structures.