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

基本信息

批准号：
10454402
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
项目类别：
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

项目摘要

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. !

过渡金属催化解决了无数的总合成，药物化学和精细化学物质的产生。传统上使用白金进行了这些反应集团金属（PGMS），最近有一个努力开发方法来规避需求昂贵且有毒的贵金属催化剂。越来越多的研究表明铁可以是跨多种有机转化的出色催化剂，包括已证明的反应对于PGM来说，很难，例如烷基卤化物和具有较高活性和高活性的Grignard试剂的交叉偶联选择性。铁催化的C-C交叉耦合和烯烃氨基官能化提供了巨大的有机合成中选择性C-C和C-N键形成的可持续低成本方法的潜力，A 对这些系统的详细分子级别的理解仍然难以捉摸，因此阻碍了理性催化剂发展。这种局限性与钯化学形成鲜明对比，其中有效研究催化剂结构和机制为持续设计和开发的基础具有新颖和/或改善催化性能的催化剂。我们的长期目标是开发铁催化碳碳和碳杂质键键对当前存在的理解水平形成反应对于钯，因此允许铁化学在所需的C-C频谱中的合理发展， C-N和C-X（X = B，F等）键形成反应。在拟议的赠款中，一种新型的实验方法结合无机光谱，密度功能理论，合成和动力学研究将用于提供分子水平的洞察力，以了解参与铁的活性铁催化剂和反应机制催化的C-C交叉偶联和烯烃氨基功能化。这些见解可用于激发和促进新的催化剂和反应方法的发展，并改善催化性能。遵循上一批赠款期间的成功工作，该提案的具体目的是：（1）扩展分子水平对铁 - 配体中存在的活性铁催化剂和反应机制的理解催化的C-C交叉偶联，（2）扩展了对活性铁催化剂和 C-C交叉偶联中存在与简单铁盐的反应机制，（3）发展分子级了解铁催化的烯烃中存在的活性铁催化剂和反应机制功能化。这项研究具有创新性，因为它涉及一种新颖的物理无机方法研究铁催化的有机反应，并提高了我们对活性铁物种的理解和催化涉及的机制激发和促进改进方法的发展。这拟议的研究很重要，因为有望扩大可以制作的分子数量使用低成本的可持续铁催化。长期，这种合成方法的扩展将启用分子生物学和药理学对人类健康的直接影响的发现。呢

项目成果

期刊论文数量（31）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

C-Term magnetic circular dichroism (MCD) spectroscopy in paramagnetic transition metal and f-element organometallic chemistry.

DOI：
10.1039/d0dt03730c
发表时间：
2021-01-14
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
0
作者：
Wolford NJ ;Radovic A ;Neidig ML
通讯作者：
Neidig ML

Iron(II) Active Species in Iron-Bisphosphine Catalyzed Kumada and Suzuki-Miyaura Cross-Couplings of Phenyl Nucleophiles and Secondary Alkyl Halides.

DOI：
10.1021/jacs.5b06648
发表时间：
2015-09-09
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Daifuku SL;Kneebone JL;Snyder BE;Neidig ML
通讯作者：
Neidig ML

NHC and nucleophile chelation effects on reactive iron(ii) species in alkyl-alkyl cross-coupling.

DOI：
10.1039/c7sc04750a
发表时间：
2018-02-21
期刊：
Chemical science
影响因子：
8.4
作者：
Fleischauer VE;Muñoz Iii SB;Neate PGN;Brennessel WW;Neidig ML
通讯作者：
Neidig ML

Electronic Structure and Bonding in Iron(II) and Iron(I) Complexes Bearing Bisphosphine Ligands of Relevance to Iron-Catalyzed C-C Cross-Coupling.

DOI：
10.1021/acs.inorgchem.5b02263
发表时间：
2016-01-04
期刊：
Inorganic chemistry
影响因子：
4.6
作者：
Kneebone JL;Fleischauer VE;Daifuku SL;Shaps AA;Bailey JM;Iannuzzi TE;Neidig ML
通讯作者：
Neidig ML

Additive and Counterion Effects in Iron-Catalyzed Reactions Relevant to C-C Bond Formation.