Iron-Catalyzed Carbon-Carbon and Carbon-Heteroatom Bond Forming Reactions

铁催化碳-碳和碳-杂原子键形成反应

• 批准号: 9816315
• 负责人: Michael L Neidig
• 金额: $ 30.8万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9816315
• 关键词: Alkenes; Amines; Carbon; Catalysis; Cations; Chemicals; Chemistry; Coupling; Development; Foundations; Future; Goals; Grant; Health; Health Sciences; Human; In Situ; Iron; Kinetics; Ligands; Metals; Methodology; Methods; Mission; Molecular; Molecular Biology; Molecular Probes; Natural Products; Nature; Nitrogen; Organic Synthesis; Outcome; Palladium; Pathway interactions; Performance; Pharmaceutical Chemistry; Pharmacologic Substance; Pharmacology; Platinum; Process; Production; Public Health; Reaction; Reagent; Research; Role; Route; Salts; Spectrum Analysis; Structure; Sustainable Development; System; TMEDA; Transition Elements; United States National Institutes of Health; Work; base; catalyst; cost; density; design; improved; innovation; insight; method development; next generation; novel; quinoline; success; theories

Transition metal catalysis has solved countless problems in total synthesis, pharmaceutical chemistry, and the production of fine chemicals. While these reactions have traditionally been performed using 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 across a wide variety of organic transformations, including reactions that have proven difficult for PGMs, such as the cross-coupling of alkyl halides and Grignard reagents with both high activity and selectivity. While iron-catalyzed C-C cross-couplings and olefin aminofunctionalizations offer tremendous potential for sustainable, low-cost methods for selective C-C and C-N bond formation in organic synthesis, a detailed molecular-level understanding of these systems has remained elusive, thus, 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 carbon-carbon and carbon-heteroatom bond forming reactions to the level of understanding currently present for palladium, thus permitting the rational development of iron chemistry across the spectrum of desired C-C, C-N and C-X (X = B, F, etc.) bond forming reactions.! In the proposed grant, a novel experimental approach combining inorganic spectroscopies, density functional theory, synthesis and kinetic studies will be utilized to provide molecular-level insight into the active iron catalysts and reaction mechanisms involved in iron- catalyzed C-C cross-coupling and olefin aminofunctionalization. These insights can be utilized to inspire and facilitate the development of new catalysts and reaction methodologies with improved catalytic performance. Following our successful work in the prior grant period, the specific aims of the proposal are to: (1) expand molecular-level understanding of the active iron catalysts and reaction mechanisms present in iron-ligand catalyzed C-C cross-coupling, (2) expand molecular-level understanding of the active iron catalysts and reaction mechanisms present in C-C cross-couplings with simple ferric salts, and (3) develop molecular-level understanding of the active iron catalysts and reaction mechanisms present in iron-catalyzed olefin aminofunctionalizations. The research is innovative because it involves a novel physical-inorganic approach to study iron-catalyzed organic reactions and advances our understanding of the active iron species and mechanisms involved in catalysis to inspire and facilitate the development of improved methodologies. The proposed research is significant because it is expected to expand the number of molecules that can be made using low-cost, sustainable iron catalysis. Long term, this expansion of synthetic methods will enable discoveries in molecular biology and pharmacology of direct impact to human health. !

过渡金属催化已经解决了全合成，药物化学， 精细化学品的生产。虽然这些反应传统上使用铂进行， 族金属（PGM），最近一直在推动开发方法，避免需要 昂贵且有毒的贵金属催化剂。越来越多的研究表明，铁可以 一种出色的催化剂，适用于各种有机转化，包括已被证明 对于铂族化合物来说，这是困难的，例如具有高活性和高选择性的烷基卤和格氏试剂的交叉偶联， 选择性虽然铁催化的C-C交叉偶联和烯烃氨基官能化提供了巨大的优势， 有机合成中选择性C-C和C-N键形成的可持续、低成本方法的潜力， 对这些系统的详细分子水平的理解仍然难以捉摸，因此，阻碍了合理的催化剂 发展这一限制与钯化学形成鲜明对比，在钯化学中，对活性金属的详细研究表明， 催化剂的结构和机理为继续设计和开发 具有新的和/或改进的催化性能的催化剂。我们的长期目标是开发铁催化 碳-碳和碳-杂原子键形成反应的理解水平 对于钯，从而允许在所需C-C范围内合理开发铁化学， C-N和C-X（X = B、F等）键形成反应！在拟议的拨款中，一种新的实验方法 结合无机光谱学、密度泛函理论、合成和动力学研究， 提供分子水平的洞察到活性铁催化剂和反应机制涉及铁- 催化的C-C交叉偶联和烯烃氨基官能化。这些见解可以用来激励和 促进具有改进的催化性能的新催化剂和反应方法的开发。 根据我们在前一个赠款期的成功工作，该提案的具体目标是：（1）扩大 从分子水平理解铁配体中存在的活性铁催化剂和反应机理 催化的C-C交叉偶联，（2）扩展对活性铁催化剂的分子水平理解， 反应机制存在于C-C交叉偶联与简单的铁盐，和（3）发展分子水平 对铁催化烯烃中存在的活性铁催化剂和反应机理的理解 氨基官能化。这项研究是创新的，因为它涉及一种新的物理-无机方法， 研究铁催化的有机反应，促进我们对活性铁物种的理解， 催化作用所涉及的机制，以激励和促进改进方法的发展。的 一项拟议中的研究意义重大，因为它有望扩大可以制造的分子数量。 使用低成本、可持续的铁催化剂。从长远来看，这种合成方法的扩展将使 分子生物学和药理学的发现对人类健康有直接影响。 !