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.

项目概要该提案的重点是发现新的基于自由基的催化方法，以促进有机自由基是具有独特活性的高活性物质。最近，出现了新的化学选择性，补充了规范的双电子化学。利用单电子氧化还原事件并利用自由基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问题的有用工具然而，许多有机自由基的高反应性已经成为当代的合成问题。使得很难对这些短暂的中间体的选择性进行催化剂控制，特别是当涉及复杂的反应体系时，特别是催化立体选择性反应。涉及自由基中间体的方法仍然有限，并且此类过程的发现非常重要为了提供新的基于自由基的反应发现和合成创新平台，我们希望。最近开发了一种新型催化方法，利用钛配合物独特的氧化还原特性。具体来说，我们提出了一种新策略——自由基氧化还原中继催化——用于开发氧化还原- 在同一催化反应中结合单电子氧化和还原事件的中性反应该策略在 Ti 催化的立体选择性环加成反应中得到了成功实施。 N-酰基氮丙啶或环丙基酮与烯烃以及 Ti/Co 共催化重排凭借这些有希望的结果，我们预计会有如此激进的结果。催化策略最终将成为解决一系列长期存在的问题的强大工具该提案中的每个项目都应用了我们的 Ti 氧化还原催化的一般策略。具体来说，我们的目标是开发能够解决有机合成中的突出挑战的反应。实现对映选择性[3+2]环加成、对映选择性环氧化物异构化、合成跳过烯酮，以及氮丙啶异构化为烯丙胺。目前未知或在反应范围、效率或选择性方面有重大限制。使用典型的物理有机和电化学技术进行深入研究以获得深入了解这些反应的发展和机制。这些拟议的转变将代表有机合成领域的重大进步。