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 这项研究项目将开发有机铋化合物(双胺)作为通用的活性前体 碳和杂原子中心自由基的产生、转移和官能化。利用宽广的、可调的 光化学氧化剂的性质，初步的努力将确定能够有效地将双胺氧化为其 相应的自由基阳离子。在潜在的可逆介孔裂解之后，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， 偶氮二羧酸盐)以产生官能化产品。尽管早期的调查将集中在从 化学计量比的铋，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、硅醚)生成自由基的中介平台。 在研究双胺产生氧化自由基的同时，我们将探索光还原加成反应。 生成双胺的烷基自由基，生成瞬时的铋自由基。受到配体文献先例的启发 自由基物种从铋中提取，除了自由基加成对早期致癌物质的可逆性外，我们还将 开发双胺作为烷基C(Sp2)-C(Sp3)、C(Sp3)-C(Sp3)、C-O和C-N的官能化试剂 债券。虽然这最初也将以化学计量的方式进行，但从双胺的周转中获得的见解 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。 在开发了使用双胺的氧化和还原自由基生成和转移反应之后，我们将使用 开发双胺作为烯烃去功能化平台的机理和反应性见解 收敛的碳铋中间体。这种中间体可以通过三种不同的机制来访问 分子内配体迁移的途径：(1)烯烃对双胺自由基阳离子的捕获(2) 双胺被烯烃自由基阳离子捕获(3)用三重态敏化的烯烃捕获双胺。到那时，中级双矿可以 参与在氧化和还原自由基反应性方面开发的功能化模式，以提供广泛的 可能是功能不全的产品。从长远来看，这也将发展为一项催化议定书。 这三个提议的目标加在一起，将使双胺成为通向规范反应的新的、统一的切入点。 自由基产生、官能化和转移的中间体。这三种方法都将推进美国国立卫生研究院的任务 通过实现用于药物发现和工具的医学相关构件和化合物的快速、模块化合成 发展。此外，为追求这些目标而开发的基础有机铋化学将被证明是可能的 在催化、抗真菌化合物的开发和材料科学中使用有机铋试剂的其他人 极大地增加了可用支架的种类和合成方法。

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