Radical redox catalysis by Ti complexes

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 生物活性化合物的合成。有机自由基是具有独特性质的高活性物质 化学选择性补充了规范的双电子化学。最近，新的出现 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 当代综合问题。然而，许多有机自由基的高反应性使得 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 当涉及复杂的反应系统时。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 理想的。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 循环。该策略已成功应用于Ti催化的立体选择性环加成反应中 N-酰基氮丙啶或环丙基酮与烯烃以及 Ti/Co 共催化重排 环氧化物转化为烯丙醇。凭借这些有希望的结果，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问题的强大工具 综合问题。本提案中的每个项目都应用了我们的 Ti 氧化还原催化的总体策略 解决有机合成中的突出挑战。具体来说，我们的目标是开发出以下反应： 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。这些转变要么是 目前未知或在反应范围、效率或选择性方面有重大限制。我们还将 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机制。的发展和机理认识 这些拟议的转变将代表有机合成领域的重大进步。

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.