Radical redox catalysis by Ti complexes

项目摘要 这项提案的重点是发现新的基于自由基的催化方法，以促进 生物活性化合物的合成。有机自由基是一种高度活性的物种，具有独特的 化学选择性是对经典双电子化学的补充。最近，出现了新的 利用单电子氧化还原事件和利用自由基中间体进行催化反应的策略 有机分子的选择性官能化为化学家提供了解决 当代的合成问题。然而，许多有机自由基的高活性性质具有 使催化剂难以控制这些转瞬即逝的中间体的选择性，特别是 当涉及复杂的反应系统时。特别是催化立体选择性反应 涉及自由基中间体的情况仍然有限，而且这种过程的发现很少。 令人向往。为了为反应发现和合成创新提供新的基于自由基的平台，我们 最近开发了一种新的催化方法，利用了钛配合物独特的氧化还原特性。 具体地说，我们提出了一种新的策略-自由基氧化还原-继电催化-用于开发氧化还原- 在同一催化剂中结合单电子氧化和还原事件的中性反应 周而复始。该策略在钛催化的立体选择性环加成反应中得到了成功的应用 N-酰氮杂环丙酮与烯烃以及钛/钴共催化的重排反应 从环氧化物到烯丙醇。基于这些有希望的结果，我们预计这种激进的 催化策略最终将成为解决一系列长期存在的 合成问题。本提案中的每个项目都将我们的钛氧化还原催化总体策略应用于 解决有机合成中的一个突出挑战。具体地说，我们的目标是开发出 实现对映体选择性[3 2]环加成，对映体选择性环氧化物异构化，合成 跳过的烯酮，以及氮杂环丙烷异构化为烯丙基胺。这些转换要么是 目前在反应范围、效率或选择性方面未知或有很大限制。我们还将 使用规范的物理、有机和电化学技术进行深入研究，以获得 对这些反应的机制的洞察。网络技术的发展及其机理认识 这些拟议的转化将代表着有机合成领域的重大进展。

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.