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.

项目摘要/摘要 该研究项目将开发有机物化合物（Bismines）作为普遍反应性前体 以碳和杂原子为中心的自由基的产生，转移和功能化。利用宽阔的可调 光化学氧化的性质，最初的努力将确定能够有效氧化偶然的氧化剂 相应的自由基阳离子。遵循潜在可逆的中溶性裂解，这些激进的阳离子将提供碳 - 或杂原子中心的自由基，然后将其添加到一系列自由基受体（烯烃，竞技场，亚胺， 偶氮羧酸盐）以产生功能化的产品。尽管早期调查将集中于从 化学计量量的bismine，这项工作的长期目标是双重催化光毒素和bismuth- 介导的平台，用于从稳定的原料前体（有机硅，硼酸，甲硅烷基醚）产生自由基的平台。 与对偶然产生氧化自由基产生的研究并行，我们将探索添加光减少的 产生的烷基自由基到bismines产生瞬态的bismuthanyl自由基。受配体先例的启发 除了对早期pnictogen的根治性添加的可逆性外，从根本物种中抽象出来，我们还将 开发bismines作为C（SP2）–C（SP3），C（SP3）–C（SP3），C – O和C – N的烷基自由基的功能化的试剂 债券。尽管最初也将以化学计量的方式追求这一点 从长远来看，氧化功能化将为这种转化的催化变体提供信息。 在使用Bismines开发了氧化和减少的自由基产生和转移反应之后，我们将使用 获得的机械性和反应性见解获得了开发bismines作为通过 收敛的Carbobsuthined中间体。可以通过三种不同的机制访问此中级 途径随后是分子内配体迁移：（1）烯烃（2）捕获丁香自由基阳离子（2） 烯烃自由基阳离子（3）三胞胎敏感烯烃捕获偶然的bismine。然后，中间的bismines可以 参与以氧化和降低的自由基反应性开发的功能化模式，以提供大量 可能的实函数化产品。从长远来看，这也将发展为催化方案。 综上 激进产生，功能化和转移的中间体。这三种方法将推进NIH的任务 通过启用迅速的，模块化的合成药物相关的构件和药物发现和工具的化合物 发展。此外，为追求这些目标而开发的基本有机物化学将证明 对于其他使用有机抗物试剂进行催化，抗真菌化合物的开发和材料科学的人来说 大大增加了各种可用的脚手架和合成方法。

项目成果

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

• DOI: 10.1021/acs.chemrev.1c00374
• 发表时间: 2022-01-26
• 期刊: Chemical reviews
• 影响因子: 62.1
• 作者: Murray PRD;Cox JH;Chiappini ND;Roos CB;McLoughlin EA;Hejna BG;Nguyen ST;Ripberger HH;Ganley JM;Tsui E;Shin NY;Koronkiewicz B;Qiu G;Knowles RR
• 通讯作者: Knowles RR