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: 10231424
• 负责人: Nicholas D Chiappini
• 金额: $ 6.6万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231424
• 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.

项目总结/摘要 该研究项目将开发有机铋化合物（铋矿）作为通用反应前体，用于 以碳和杂原子为中心的自由基的产生、转移和官能化。利用宽，可调 光化学氧化剂的性质，初步的努力将确定氧化剂能够有效氧化铋，以其 相应的自由基阳离子。在潜在可逆的介晶裂解之后，这些自由基阳离子将提供碳- 或杂原子中心的自由基，其随后将加成到一系列自由基受体（烯烃，芳烃，亚胺， 偶氮二羧酸酯）以产生官能化产物。虽然早期的调查将集中在集团转移从 化学计量量的铋，这种奋进的长期目标是双重催化光氧化还原和铋- 介导的平台，用于从稳定的原料前体（有机硅烷、硼酸、甲硅烷基醚）产生自由基。 在平行的研究氧化自由基的产生从铋，我们将探讨除了光还原 生成的烷基自由基转化为铋，从而生成瞬时的铋基自由基。受配体文献先例启发 通过自由基物种从铋中提取，除了自由基添加到早期氮族元素的可逆性之外，我们将 开发二亚胺作为烷基官能化的试剂，形成C（sp2）-C（sp3）、C（sp3）-C（sp3）、C-O和C-N 债券虽然这最初也将以化学计量的方式进行，但从铋的周转中获得的见解， 氧化官能化将在更长的时间内为这种转化的催化变体的设计提供信息。 在开发了使用铋的氧化和还原自由基生成和转移反应之后，我们将使用 获得了机理和反应性的见解，以开发二亚胺作为烯烃双官能化的平台， 收敛型碳铋化中间体。这种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）烯烃捕获二亚胺自由基阳离子（2） 二亚胺被烯烃自由基阳离子捕获（3）二亚胺被三重态敏化烯烃捕获。然后，中间体铋可以 参与在氧化和还原自由基反应性中开发的官能化模式，以提供大范围的 可能的双官能化产物。从长远来看，这也将发展成为一项催化议定书。 这三个目标将使铋矿成为规范反应的新的、统一的切入点。 用于自由基生成、官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、模块化地合成与医学相关的结构单元和化合物， 发展此外，在追求这些目标的过程中发展起来的基本有机双金属化学将证明是可行的。 在催化、抗真菌化合物的开发和材料科学中利用有机铋试剂， 大大增加了可用支架及其合成方法的种类。