Stereoselective Reactions of Oxocarbenium Ions and Related Intermediates

氧碳鎓离子及相关中间体的立体选择性反应

基本信息

批准号：
10198948
负责人：
KEITH ALLEN WOERPEL
金额：
$ 26.2万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-06-30
项目状态：
已结题

项目摘要

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.

项目摘要/摘要尽管涉及氧化碳离子的立体选择性键形成反应是重要方法碳水化合物化学和有机合成，这些反应通常不会进行预期立体化学。例如，在许多情况下，立体化学不能预测，因为没有了解立体选择性的模型（如中环核酸离子）或这些模型无法适应与预期选择性的偏差（如相邻群体参与所观察到的）。到解决我们对这些立体化学模型的理解中的差距，以下具体目标将是追捕：（1）我们将检查邻近组的参与循环的立体选择反应氧化离子；（2）我们将扩展邻近参与的概念涵盖系统与碳水化合物无关的，包括解决无环立体控制中的问题；（3）我们将确定七元的环电钻（氧化核离子）和亲核者（烯醇）可以反应立体选择性。在第一个目标中，我们将使用与碳水化合物共享结构特征的系统解释为什么邻近的群体影响不像预期的那样强大，这一事实是我们的初步研究。我们还将扩展我们的初步研究，该研究表明唾液酸的二氧化碳基团对氧化离子离子的稳定性及其反应的立体化学作用几乎没有影响。这第二目的将使用与碳水化合物无密切相关的系统来解决机械问题碳水化合物化学。第三个目标将追求立体化学模型以了解所涉及的反应在七元的环糖中，我们将扩大初步研究，涉及七个的反应构件的环烯醇比六元环烯醇的类似反应更具选择性。这些研究将与理论化学家Jeffery Evanseck教授合作进行研究（Duquesne 大学），他擅长使用计算方法研究反应机制。提议研究很重要，因为它将使研究人员能够预测形成键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。拟议的研究具有创新性，因为我们使用不是碳水化合物的系统开发可用于碳水化合物化学，药物化学和天然的立体选择反应产品合成。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执行具有生物活性化合物的合成，例如碳水化合物，以精确控制三维结构。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Diastereoselective Substitution Reactions of Acyclic β-Alkoxy Acetals via Electrostatically Stabilized Oxocarbenium Ion Intermediates.

DOI：
10.1021/acs.orglett.2c01004
发表时间：
2022-05-06
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Ramdular, Amanda;Woerpel, K. A.
通讯作者：
Woerpel, K. A.

Halogen Atom Participation in Guiding the Stereochemical Outcomes of Acetal Substitution Reactions.

DOI：
10.1002/anie.202209401
发表时间：
2022-10-17
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
影响因子：
16.6
作者：
Demkiw, Krystyna M.;Remmerswaal, Wouter A.;Hansen, Thomas;van der Marel, Gijsbert A.;Codee, Jeroen D. C.;Woerpel, K. A.
通讯作者：
Woerpel, K. A.

Mechanistic Studies on the 1,2-Spin-Center Shift in Carbohydrate Systems with a Fluorenylcyclopropyl Radical Clock.