Radical redox catalysis by Ti complexes

Ti配合物的自由基氧化还原催化

基本信息

批准号：
9974150
负责人：
Song Lin
金额：
$ 30.94万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

Project Summary This proposal focuses on uncovering new radical-based catalytic methodologies that facilitate the synthesis of bioactive compounds. Organic radicals are highly reactive species with unique chemoselectivities that complement canonical two-electron chemistry. Recently, the emergence of new catalytic strategies that leverage single-electron redox events and harness radical intermediates for the selective functionalization of organic molecules has provided chemists with useful tools for solving contemporary synthetic problems. However, the highly reactive nature of many organic radicals has made it difficult to impart catalyst-control over the selectivity of these fleeting intermediates, especially when complex reaction systems are concerned. In particular, catalytic stereoselective reactions involving free radical intermediates remain limited, and the discovery of such processes is highly desirable. To provide new radical-based platforms for reaction discovery and synthetic innovation, we recently developed a novel catalytic approach that exploits the unique redox features of Ti complexes. Specifically, we advanced a new strategy—radical redox-relay catalysis—for the development of redox- neutral reactions that combines single-electron oxidation and reduction events in the same catalytic cycle. This strategy was successfully implemented in the stereoselective Ti-catalyzed cycloaddition of N-acylaziridines or cyclopropyl ketones with alkenes as well as Ti/Co co-catalyzed rearrangement of epoxides to allylic alcohols. On the strength of these promising results, we anticipate that such radical catalysis strategies will ultimately emerge as powerful tools for solving a wide range of long-standing synthetic problems. Each project in this proposal applies our general strategy of Ti redox catalysis to address a prominent challenge in organic synthesis. Specifically, we aim to develop reactions that achieve enantioselective [3+2] cycloaddition, enantioselective epoxide isomerization, synthesis of skipped enones, and isomerization of aziridines to allylic amines. These transformations are either currently unknown or have significant limitations in reaction scope, efficiency, or selectivity. We will also carry out in-depth studies using canonical physical organic and electrochemical techniques to gain insights into the mechanisms of these reactions. The development and mechanistic understanding of these proposed transformations will represent significant advances for the field of organic synthesis.

项目摘要该提案着重于发现新的基于激进的催化方法，以促进生物活性化合物的合成。有机自由基是高反应性的物种，具有独特的补充规范两电子化学的化学选择性。最近，新的出现利用单电子氧化还原事件的催化策略和利用激进的中间体的催化策略有机分子的选择性功能化为化学家提供了解决的有用工具来解决当代合成问题。但是，许多有机自由基的高反应性具有使催化剂控制在这些短暂的中间体的选择性上很难，尤其是当涉及复杂的反应系统时。特别是，催化立体选择反应涉及自由基中间体仍然有限，并且这种过程的发现很高理想。为了为反应发现和合成创新提供新的基于激进的平台，我们最近开发了一种新型的催化方法，可利用Ti复合物的独特氧化还原特征。具体而言，我们采取了一种新的策略 - 激进的氧化还原 - 列雷催化 - 用于发展氧化还原。在同一催化中结合了单电子氧化和还原事件的中性反应循环。该策略成功实施了 N-酰胺二嘧啶或环丙基酮，带有烷烃以及Ti/Co共排列的重排赤醇的环氧化物。关于这些承诺结果的实力，我们预计如此激进催化策略最终将成为解决各种长期存在的强大工具合成问题。本提案中的每个项目都将我们的Ti氧化还原催化的一般策略应用于应对有机综合中的一个巨大挑战。具体而言，我们旨在发展反应成就对映选择性[3+2]环加成，对映选择性环氧异构化，合成跳过烯烃，以及将氮岛氨基化的异构化与全能胺的异构化。这些转变是目前未知或在反应范围，效率或选择性方面有显着局限性。我们也会使用规范的物理有机和电化学技术进行深入的研究以获得洞悉这些反应的机制。对的发展和机械理解这些提出的转化将代表有机合成领域的重大进展。