New Synthetic Methods Enabled by Excited-State Redox Chemistry

项目摘要 本提案中描述的工作旨在开发由激发态氧化还原实现的新型合成方法 这些活动旨在解决催化和合成有机化学领域的长期挑战。其中一个主要焦点是 一项建议是继续发展质子耦合电子转移（PCET）技术， 合成.特别是，我们专注于开发基于PCET的方法，用于催化官能化 脂肪族C-C键，包括环状醇的氧化还原中性异构化反应，以形成直链羰基 化合物，以及用于碳环醇的催化扩环和缩环的新方法。 我们还讨论了努力开发一类新的手性酰胺基催化剂，可以激活的PCET 以产生瞬时酰胺基，其然后可以介导对映选择性和位点选择性官能化， 脂肪族C-H键。这项工作的第二个目标是发展非平衡合成方法 通过激发态氧化还原事件实现。这些技术提供了利用光子吸收的机会 事件来驱动逆着热化学梯度的反应，但不需要产生激发态 印刷受体.重要的是，这些方法提供了新的方法来实现非玻尔兹曼产品 分布和反应结果，根据定义，不可能获得使用常规地面- 状态方法。应用于光驱动的去外消旋反应的发展。第三 目标是推进我们在开发烯烃加氢胺化光催化方法方面的努力， 加氢醚化我们建议开发第一个通用的分子间抗- 未活化的烯烃与伯烷基胺之间的马尔可夫尼科夫加氢胺化反应， 仲胺产物，选择性地，基于铵自由基阳离子的化学性质。基于PCET 还提出了用磺酰胺进行对映选择性氢胺化的方法，其中不对称 诱导被认为是由手性氢键供体和手性氢键供体之间的直接非共价相互作用引起的。 中性N中心自由基中间体。我们还提出了开发类似的分子间 加氢醚化方法及其对映选择性变体。如果成功，这些努力将提供宝贵的 新的反应和概念的化学社区从事发现，合成， 制造药物和其他具有生物功能的小分子探针，从而创造一种 对人体健康有重大益处。

Project Summary The work described in this proposal aims to develop novel synthetic methods enabled by excited-state redox events to address longstanding challenges in catalysis and synthetic organic chemistry. A primary focus of this proposal is the continued development of proton-coupled electron transfer (PCET) technologies in organic synthesis. In particular we focus on developing PCET-based methods for the catalytic functionalization of aliphatic C-C bonds, including redox-neutral isomerization reactions of cyclic alcohols to form linear carbonyl compounds, and novel methods for the catalytic ring-expansion and ring-contraction of carbocyclic alcohols. We also discuss efforts to develop a new class of chiral amide-based catalysts that can be activated by PCET to generate transient amidyls, which can then mediate enantioselective and site-selective functionalization of aliphatic C-H bonds. A second goal of this work is the development of out-of-equilibrium synthetic methods enabled by excited-state redox events. These technologies provide opportunities to use photon absorption events to drive reaction against a thermochemical gradient, but without requiring generation of excited state substrates. Importantly, these methods provide novel approaches to achieve non-Boltzmann product distributions and reaction outcomes that are not, by definition, possible to obtain using conventional ground- state methods. Applications to the development of light-driven deracemization reactions are presented. A third goal is to advance our efforts in developing photocatalytic methods for olefin hydroamination and hydroetherification. We propose to develop the first general catalytic protocol for intermolecular anti- Markovnikov hydroamination reactions between unactivated olefins with primary alkyl amines to yield secondary amine products, selectively, based on the chemistry of aminium radical cations. PCET-based methods for enantioselective hydroaminations with sulfonamides are also proposed, wherein the asymmetric induction is proposed to arise from direct non-covalent interactions between a chiral H-bond donor and a neutral N-centered radical intermediate. We also present plans to develop analogous intermolecular hydroetherification methods and their enantioselective variants. If successful, these efforts will provide valuable new reactions and concepts for the chemistry communities engaged in the discovery, synthesis, and manufacture of pharmaceuticals and other small-molecule probes of biological function, and thus create a significant benefit to human health.