Organobismuth Compounds As Universal Precursors for Oxidative and Reductive Radical Group Transfer via Photoredox Catalysis

有机铋化合物作为通过光氧化还原催化进行氧化和还原基团转移的通用前体

• 批准号: 10463570
• 负责人: Nicholas D Chiappini
• 金额: $ 2.2万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463570
• 关键词: Agrochemicals; Alkanesulfonates; Alkenes; Alkylation; Antifungal Agents; Bismuth; Boronic Acids; Carbon; Catalysis; Cations; Chemicals; Chemistry; Coupling; Development; Energy Transfer; Esters; Ethers; Free Radicals; Future; Generations; Goals; Health; Human; Imines; Investigation; Iridium; Ligands; Literature; Lithium; Mediating; Methodology; Methods; Mission; Modernization; Nature; Oxidants; Oxidation-Reduction; Pathway interactions; Periodicity; Pharmaceutical Chemistry; Pharmacologic Substance; Preparation; Protocols documentation; Reaction; Reagent; Research; Research Project Grants; Salts; Science; System; Training; Transition Elements; Triplet Multiple Birth; United States National Institutes of Health; Ursidae Family; Variant; Work; design; drug discovery; insight; materials science; migration; novel; novel strategies; oxidation; scaffold; tool; tool development

PROJECT SUMMARY/ABSTRACT This research project will develop organobismuth compounds (bismines) as universal reactive precursors for the generation, transfer, and functionalization of carbon and heteroatom-centered radicals. Taking advantage of the wide, tunable nature of photochemical oxidants, initial efforts will identify oxidants capable of efficient oxidation of bismines to their corresponding radical cations. Following potentially reversible mesolytic cleavage, these radical cations would afford carbon- or heteroatom centered radicals which would then add to a range of radical acceptors (olefins, arenes, imines, azodicarboxylates) to yield functionalized products. Although early investigations will focus on group transfer from stoichiometric amounts of bismine, the longer term goal of this endeavor is a dual catalytic photoredox and bismuth- mediated platform for generation of radicals from stable feedstock precursors (organosilanes, boronic acids, silyl ethers). In parallel to investigations of oxidative radical generation from bismines, we will explore addition of photoreductively generated alkyl radicals to bismines to generate transient bismuthanyl radicals. Inspired by literature precedent of ligand abstraction from bismuth by radical species, in addition to reversibility of radical additions to earlier pnictogens, we will develop bismines as reagents for the functionalization of alkyl radicals for form C(sp2)–C(sp3), C(sp3)–C(sp3), C–O, and C–N bonds. Although this would also initially be pursued in a stoichiometric fashion, insights gained from bismine turnover from oxidative functionalization would inform design of a catalytic variant of this transformation in the longer term. After developing both oxidative and reductive radical generation and transfer reactions using bismines, we will use mechanistic and reactivity insights gained to develop bismines as a platform for the difunctionalization of olefins via convergent carbobismuthinated intermediates. This intermediate could be accessed through three distinct mechanistic pathways followed by intramolecular ligand migration: (1) trapping of an bismine radical cation by an olefin (2) trapping of a bismine by an olefin radical cation (3) trapping of a bismine by a triplet sensitized olefin. Intermediate bismines could then engage in the functionalization modes developed in both oxidative and reductive radical reactivity to afford large range of possible difunctionalized products. In the longer term, this would also be developed into a catalytic protocol. Taken together the three proposed aims will develop bismines as novel, unified entry points to canonical reactive intermediates for radical generation, functionalization and transfer. All three methods will advance the mission of the NIH by enabling the swift, modular synthesis of medicinally relevant building blocks and compounds for drug discovery and tool development. Additionally, the fundamental organobismuth chemistry developed in pursuit of these aims will prove enabling to others utilizing organobismuth reagents in catalysis, development of antifungal compounds, and materials science by greatly increasing the variety of available scaffolds and synthetic approaches thereto.

项目概要/摘要 该研究项目将开发有机铋化合物（双胺）作为通用反应前体 利用广泛、可调的碳和杂原子中心自由基的生成、转移和功能化。 根据光化学氧化剂的性质，初步努力将确定能够有效地将双胺氧化为其光化学氧化剂的氧化剂。 在潜在可逆的内消解裂解之后，这些自由基阳离子将提供碳- 或以杂原子为中心的自由基，然后添加到一系列自由基受体（烯烃、芳烃、亚胺、 尽管早期的研究将集中于基团转移。 化学计量的铋胺，这项努力的长期目标是双重催化光氧化还原和铋- 从稳定的原料前体（有机硅烷、硼酸、甲硅烷基醚）产生自由基的介导平台。 在研究双胺产生氧化自由基的同时，我们将探索光还原添加 受配体文献先例的启发，将烷基自由基转化为双胺，以产生瞬时的铋基自由基。 通过自由基物种从铋中提取，除了早期磷元素自由基加成的可逆性之外，我们将 开发双胺作为烷基自由基功能化的试剂，形成 C(sp2)–C(sp3)、C(sp3)–C(sp3)、C–O 和 C–N 尽管这最初也将以化学计量的方式进行，但从双矿营业额中获得的见解。 从长远来看，氧化功能化将为这种转化的催化变体的设计提供信息。 在使用双胺开发氧化和还原自由基生成和转移反应后，我们将使用 获得了开发双胺作为烯烃双官能化平台的机理和反应性见解 该中间体可以通过三种不同的机制获得。 分子内配体迁移遵循的途径： (1) 烯烃捕获双胺自由基阳离子 (2) 捕获 通过烯烃自由基阳离子捕获双胺 (3) 然后可以通过三线态敏化烯烃捕获双胺。 参与在氧化和还原自由基反应中开发的功能化模式，以提供大范围的 从长远来看，这也将发展成为一种催化方案。 综合起来，这三个拟议目标将把双胺开发为规范反应的新颖、统一的切入点 自由基生成、功能化和转移的中间体，这三种方法都将推进 NIH 的使命。 通过快速、模块化地合成用于药物发现和工具的医学相关构建模块和化合物 此外，为实现这些目标而开发的基本有机铋化学将证明是可行的。 向其他人利用有机铋试剂进行催化、抗真菌化合物的开发和材料科学 极大地增加了可用支架及其合成方法的多样性。

项目成果

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis.

质子耦合电子转移在有机合成中的光化学和电化学应用。

• 发表时间: 2022-01-26
• 影响因子: 62.1
• 作者: Murray, Philip R D;Cox, James H;Chiappini, Nicholas D;Roos, Casey B;McLoughlin, Elizabeth A;Hejna, Benjamin G;Nguyen, Suong T;Ripberger, Hunter H;Ganley, Jacob M;Tsui, Elaine;Shin, Nick Y;Koronkiewicz, Brian;Qiu, Guanqi;Knowles, Robert R
• 通讯作者: Knowles, Robert R