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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.

项目总结/摘要尽管涉及氧碳正离子的立体选择性成键反应是制备手性化合物的重要方法，但在制备手性化合物中，碳水化合物化学和有机合成，这些反应往往不进行预期的立体化学例如，在许多情况下，立体化学也不能预测，因为没有立体化学。模型来理解立体选择性（如在中环氧碳正离子的情况下），或者这些模型不能适应与预期选择性的偏差（如相邻组参与所观察到的）。到为了解决我们对这些立体化学模型的理解方面的差距，将实现以下具体目标追求：（1）我们将研究邻基参与环状立体选择性反应氧代碳正离子;（2）我们将扩展相邻基团参与的概念，以涵盖系统与碳水化合物无关，包括解决非循环立体控制问题;（3）我们将确定七元环亲电体（氧碳正离子）和亲核体（烯醇化物）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为了解释为什么邻组效应不像预期的那么强，我们的研究表明了这一事实。初步研究。我们还将扩展我们的初步研究，表明唾液酸的CO2 R基团对氧代碳正离子的稳定性及其反应的立体化学几乎没有影响。的第二个目标将使用与碳水化合物不密切相关的系统来解决机械问题，糖类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环糖，我们将扩大初步研究，涉及七- 元环烯醇化物比六元环烯醇化物的类似反应更具选择性。这些研究将与理论化学家Jeffery Evanseck（迪克讷）教授合作进行他擅长使用计算方法研究反应机理。拟议这项研究意义重大，因为它将使研究人员能够预测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物质的反应。化合物.这项研究是创新的，因为我们使用的系统不是碳水化合物，开发可用于碳水化合物化学、药物化学和天然药物化学的立体选择性反应产物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精确控制碳水化合物等生物活性化合物的合成，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.