Iron-Catalyzed Cross-Coupling

铁催化交叉偶联

• 批准号: 9111982
• 负责人: Michael L Neidig
• 金额: $ 35.17万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-05 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111982
• 关键词: Benzene; Catalysis; Cations; Chemicals; Chemistry; Coupling; Data; Development; Foundations; Goals; Grant; Health; Health Sciences; Human; In Situ; Iron; Ligands; Metals; Methodology; Methods; Mission; Molecular; Molecular Biology; Molecular Probes; Outcome; Palladium; Performance; Pharmaceutical Chemistry; Pharmacologic Substance; Pharmacology; Platinum; Procedures; Production; Protocols documentation; Public Health; Quinolones; Reaction; Reagent; Research; Route; Salts; Solvents; Spectrum Analysis; Structure; Sustainable Development; System; Systems Development; Transition Elements; United States National Institutes of Health; Work; base; carbene; catalyst; cost; density; design; electronic structure; improved; innovation; insight; next generation; novel; oxidation; quinoline; solid state; success; theories

DESCRIPTION (provided by applicant): Catalytic cross-coupling reactions have solved countless problems in total synthesis, pharmaceutical chemistry, and the production of fine chemicals. While these reactions have traditionally been carried out with platinum group metals (PGMs), there has been a recent push to develop methods that circumvent the need for expensive and toxic precious metal catalysts. A growing body of research has demonstrated that iron can be an excellent catalyst, effecting cross-couplings that have proven difficult for PGMs such as the coupling of alkyl halides and Grignard reagents with both high activity and selectivity. While iron-catalyzed C-C cross-coupling chemistry offers tremendous potential for sustainable, low-cost methodologies for selective C-C bond formation across the spectrum of available nucleophiles and electrophiles, a detailed molecular level understanding of these systems has remained elusive. In fact, at present there remains no single iron-catalyzed cross-coupling reaction for which a broadly accepted mechanism has been determined, hindering rational catalyst development. This limitation is in stark contrast to palladium chemistry, where detailed studies of active catalyst structure and mechanism have provided the foundation for the continued design and development of catalysts with novel and/or improved catalytic performance. Our long-term goal is to develop iron-catalyzed C-C cross-coupling to the level of understanding currently present for palladium, thus permitting the rational development of iron chemistry across the spectrum of desired C-C bond forming reactions. In the proposed grant, a novel experimental approach combining inorganic spectroscopies, density functional theory and synthesis will be utilized to develop molecular-level insight into active catalyst structure and th mechanisms involved in current leading edge iron-catalyzed C-C cross-coupling reactions, and to utilize this insight to develop new catalysts and reaction methodologies with improved catalytic performance. Following up on strong preliminary data, the specific aims of the proposal are to: (1) develop molecular-level understanding of the active iron catalysts and reaction mechanisms present in iron-bisphosphine catalyzed C-C cross-coupling, (2) develop molecular-level understanding of the active iron catalysts and reaction mechanisms present in C-C cross-coupling catalyzed by simple ferric salts, and (3) develop novel iron-based C-C cross-coupling methods driven by fundamental insight into active catalyst structure and mechanism. The research is innovative because it involves a novel physical-inorganic approach to study iron cross-coupling catalysis, advances our understanding of the active catalysts and mechanisms involved in this catalysis and leverages this fundamental insight to the design and development of new iron catalysts and reaction methodologies for cross-coupling. The proposed research is significant because it is expected to expand the number of molecules that can be made using low-cost, sustainable iron cross-coupling methods. Long term, this expansion of synthetic methods will enable discoveries in molecular biology and pharmacology of direct impact to human health.

描述（由申请人提供）：催化交叉偶联反应已解决了无数的问题，在总合成，药物化学和精细化学物质的产生中。尽管这些反应传统上是使用铂金属金属（PGM）进行的，但最近一直在推动开发方法来规避昂贵和有毒的贵金属催化剂的需求。越来越多的研究表明，铁可以是一种极好的催化剂，可实现交叉耦合，这对于PGM来说很难，例如具有高活性和选择性的烷基卤化物和grignard试剂的偶联。虽然催化的C-C交叉偶联化学为可持续的低成本方法论提供了巨大的潜力，可用于在可用的可用亲核和电力群中选择性C-C键形成，但对这些系统的详细分子水平的理解仍然难以捉摸。实际上，目前尚无单一铁催化的交叉偶联反应，已经确定了广泛接受的机制，从而阻碍了理性催化剂的发展。这种局限性与钯化学形成鲜明对比，在该化学中，有关活性催化剂结构和机制的详细研究为催化剂的持续设计和开发提供了新颖和/或改善催化性能的基础。我们的长期目标是将铁催化的C-C交叉偶联发展为当前对钯的理解水平，从而允许在所需的C-C键形成反应的各种范围内铁化学的合理发展。在拟议的赠款中，一种结合无机光谱的新型实验方法，将利用密度功能理论和合成来发展分子水平对主动催化剂结构和参与当前前端铁催化的C-C交叉耦合反应的机制，并利用这种洞察力，以发展新的表现能力，并改善了养分型养分型，并改善了养分型养分型。遵循强大的初步数据，该提案的具体目的是：（1）在铁生膦催化C-C交叉偶联中，对活性铁催化剂和反应机制的分子水平理解，（2）通过在C-C-C跨核酸盐中发展出对铁的新颖机制的分子水平的理解，从C-C交叉偶联方法是由对主动催化剂结构和机制的基本见解驱动的。这项研究具有创新性，因为它涉及一种新型的物理无机方法来研究铁交叉偶联催化，促进了我们对涉及该催化的活性催化剂和机制的理解，并利用了这种基本的洞察力，对新的铁催化剂的设计和开发以及反应方法的设计和开发。拟议的研究很重要，因为预计它将扩大可以使用低成本，可持续的铁交叉偶联方法制成的分子数量。长期，这种合成方法的扩展将使分子生物学和对人类健康的直接影响的药理学发现。