New Methods for Nitrogen and Oxygen Heterocycle Synthesis

氮氧杂环合成新方法

基本信息

批准号：
8912659
负责人：
Sherry R Chemler
金额：
$ 32.46万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2019-06-30
项目状态：
已结题

项目摘要

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. New reactions for the synthesis of saturated oxygen and nitrogen heterocycles based on copper-catalyzed additions to readily available alkenes are being developed. The use of chiral copper complexes for stereocontrolled Csp3-O and Csp3-N bond formation is being explored. Based on our mechanistic work in this area, we have found that both polar and radical reaction mechanisms are involved, and judicious selection of substrate and reaction conditions can enable the concise and enantioselective synthesis of otherwise challenging complex molecules from simple alkenol and alkenylamine substrates. In this project, an enantioselective alkene carboetherification scope is expanded to useful oxygen heterocycles such as phthalans, compounds that have shown activity as 1 receptor ligands (relevant to CNS disorder therapy). The first highly enantioselective hydroalkoxylation of unactivated alkenes for the synthesis of chiral oxygen heterocycles is being developed. A diverse collection of novel chiral spirocyclic compounds is accessible from 1,1-disubstituted alkenes using a suite of copper-catalyzed intramolecular alkene difunctionalization reactions. In this context new copper-catalyzed enantioselective alkene dioxygenation and oxyamination reactions will be explored. Potentially powerful aerobic alkene oxidative difunctionalizations are also being explored. Copper-catalyzed intermolecular couplings between vinylarenes and alkyl radicals, formed in situ, are being explored for the synthesis of oxygen and nitrogen heterocycles. Lastly, an elusive catalytic enantioselective Mannich reaction with phenols is being pursued. The concise, enantioselective synthesis of bioactive saturated oxygen and nitrogen heterocyclic small molecules will be performed as a demonstration of the biomedical relevance of these reactions.

在此处输入作为您的申请的新摘要信息的文本。此部分必须为否。文本长度超过 30 行。合成饱和氧氮杂环的新反应基于铜催化加成到容易获得的烯烃的基础上开发了手性铜配合物用于立体控制的 Csp3-O 和基于我们在此方面的机械工作，正在探索 Csp3-N 键的形成。区域，我们发现极性反应机制和自由基反应机制都是涉及，并明智地选择底物和反应条件可以使具有挑战性的复杂化合物的简洁和对映选择性合成在这个项目中，来自简单的烯醇和烯基胺底物的分子。对映选择性烯烃碳醚化范围扩大至有用氧杂环化合物，例如酞烷类化合物，具有 α1 活性的化合物受体配体（与中枢神经系统疾病治疗相关）。未活化烯烃的对映选择性加氢烷氧基化用于合成正在开发多种新颖的手性氧杂环。手性螺环化合物可以从 1,1-二取代烯烃中使用一系列铜催化的分子内烯烃双官能化反应。在此背景下，新的铜催化的对映选择性烯烃双加氧反应和将探索潜在的强需氧烯烃反应。铜催化的氧化双官能化也在探索中。原位形成的乙烯基芳烃和烷基之间的分子间偶联，最后，正在探索氧和氮杂环的合成。与酚类发生难以捉摸的催化对映选择性曼尼希反应追求生物活性饱和氧的简洁、对映选择性合成。并进行氮杂环小分子示范这些反应的生物医学相关性。