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方法，以促进合成 生物活性化合物。有机自由基是高活性物种，具有独特的化学选择性， 补充正则双电子化学。最近，新的反应策略的出现 利用单电子氧化还原事件和利用自由基中间体 有机分子的官能化为化学家提供了解决当代 合成问题。然而，许多有机自由基的高活性性质使其很难 给予催化剂对这些转瞬即逝的中间体的区域和立体选择性的控制，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 开发了利用低价钛络合物独特的氧化还原特性的催化策略 实现氧化还原中性和净还原转化，通过催化剂创新，我们 证明了自由基介导的反应可以使反应具有高度的对映选择性。这些 有希望的结果促使我们继续发明新的催化和反应策略，这些策略可以 有效地利用激进中间体并提供强大的工具来解决广泛的 长期存在的合成问题。在母公司的提案中，我们的目标是在以前成功的基础上再接再厉，但 把我们的研究转移到新的领域。在这里的每个目标项目中，我们的目标是提出一个新的 使用基于自由基的催化剂或试剂来解决有机中的突出挑战的方法 综合。此授权中的目标转换要么是当前未知的，要么是显著的 反应范围或选择性的限制。在我们旨在发展的具体反应中 这项授权的背景是：对映体选择性环加成，对映体选择性环氧化物异构化， 醇的氧化去对称化、酰胺的对映选择性⍺氧化和位置选择性 脂肪族C-H键的官能化。此外，深入研究使用规范的物理有机 电分析技术将提供对反应机理的见解。最新进展 机械地理解这些拟议的转型将是重大的进步 在有机合成领域。

Project Summary This proposal focuses on uncovering new radical-based 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 reaction 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 regio- and stereoselectivity 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 developed catalytic strategies that leverage the unique redox features of low-valent Ti complexes to achieve redox-neutral and net-reductive transformations, and through catalyst innovation, we demonstrated that free-radical-mediated reactions can be made highly enantioselective. These promising results prompted us to continue to invent novel catalytic and reaction strategies that can effectively harness radical intermediates and provide powerful tools for solving a wide range of longstanding synthetic problems. In the parent proposal, we aim to build upon our previous success but move our research into new grounds. In each of the projects targeted herein, we aim to advance a new approach that employ radical-based catalysts or reagents to address a prominent challenge in organic synthesis. The transformations targeted in this grant are either currently unknown or display salient limitations in reaction scope or selectivity. Among the specific reactions that we aim to develop in the context of this grant are: enantioselective cycloadditions, enantioselective epoxide isomerizations, oxidative desymmetrization of alcohols, enantioselective ⍺-oxidation of amides, and site-selective functionalization of aliphatic C–H bonds. In addition, in-depth studies using canonical physical organic and electroanalytical techniques will provide insights into the reaction mechanisms. The development and mechanistic understanding of these proposed transformations will represent significant advances for the field of organic synthesis.