Iron-Based Olefin Metathesis Catalysts

铁基烯烃复分解催化剂

• 批准号: 8084435
• 负责人: Vincent Lavallo
• 金额: $ 5.05万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8084435
• 关键词: Alkenes; Back; Benign; Binding; Carbon; Chloride Ion; Chlorides; Communities; Complex; Development; Dissociation; Electrons; Environment; Exhibits; Fellowship; Generations; Goals; Investigation; Iron; Iron Compounds; Ligands; Mediating; Medicine; Metals; Methodology; Methods; Modeling; Modification; Mono-S; Organic Iron Compounds; Pharmacologic Substance; Phosphines; Preparation; Problem Solving; Process; Property; Radial; Reaction; Research; Research Proposals; Route; Ruthenium; Site; Skeleton; Solutions; Synthesis Chemistry; System; Technology; Therapeutic; Toxic effect; Transition Elements; Work; base; carbene; catalyst; complex R; cost effective; design; functional group; metal complex; preference; public health relevance; success

DESCRIPTION (provided by applicant): The preparation of therapeutics relies largely on the ability of chemists to construct a wide range of organic molecules. Since many pharmaceuticals contain a sophisticated carbon skeleton, processes that selectively couple two carbon moieties are of paramount importance. One of the most efficient and selective carbon-carbon bond forming methods is the ruthenium-catalyzed olefin metathesis reaction. Since iron is inexpensive and has a low toxicity, a significant technological advance would be to design iron-based olefin metathesis catalysts. Preparing such catalysts will require the synthesis of hitherto unknown low-coordinate iron alkylidenes. As a starting point, neutral iron(ll) alkylidenes of the formula CI2(L)Fe=C(H)R, where L is a cyclic amino carbene ligand, will be prepared. In contrast to ruthenium alkylidenes that are typically low-spin, iron complexes CI2(L)Fe=C(H)R may exist in a high-spin state. Due to the presence of at least one electron in all of the d-orbitals of the transition metal center, high-spin CI2(L)Fe=C(H)R complexes may resist olefin coordination, consequently retarding metathesis activity. A solution to this potential problem would be to synthesize XCI(L)Fe=C(H)R and X2(L)Fe=C(H)R complexes, where X is a CN- or C6F5- group. Replacement of the CI- groups of CI2(L)Fe=C(H)R by these stronger field ligands will increase the ligand field splitting parameter in the system, which should promote a lower-spin state more favorable for olefin coordination. Another approach to providing accessible coordination sites for substrate binding would be to render CI2(L)Fe=C(H)R complexes cationic by chloride abstraction. The resultant XCI(L)Fe=C(H)R and X2(L)Fe=C(H)R, where X is an extremely non-coordinating counterion such as B(C6F5)4- or HBC11Cl11-, should dissociate in solution to form the formally 12 and 10 electron iron mono and dications CI(L)Fe=C(H)R+ and (L)Fe=C(H)R2+, respectively. A different approach would be to prepare neutral iron(O) alkylidenes. An ideal iron(0) species that may display metathesis activity would be (R3P)LFe=(H)R. Complexes of this class should be capable of dissociating the phosphine ligand in solution, to afford LFe=(H)R fragments with at least two vacant coordination sites, independent of the spin state of the metal. The ultimate goal of this research proposal is to provide the synthetic community with inexpensive, environmentally benign, highly active and selective olefin metathesis catalysts. PUBLIC HEALTH RELEVANCE The proposed research plan intends to use iron compounds to provide methods that allow pharmaceuticals to be produced in a more environmentally friendly and cost effective manner. Thus, this work may ultimately provide clean methods to produce cheaper medicines.

描述（由申请人提供）：治疗剂的制备很大程度上取决于化学家构建各种有机分子的能力。由于许多药物包含一个复杂的碳骨架，因此有选择地搭配两个碳部分的过程至关重要。最有效和选择性的碳碳键形成方法之一是氟塞酸烯烃的烯烃分解反应。由于铁很便宜并且毒性低，因此技术进步将是设计基于铁的烯烃元理解催化剂。制备这种催化剂将需要迄今未知的低坐标铁烷基烯烯的合成。作为起点，将制备配方ci2（l）fe = c（h）r的中性铁（LL）烷基德烯，其中L是环状氨基碳纤维配体。与通常是低自旋的氟球酮相比，铁配合物CI2（L）Fe = C（H）R可能存在于高旋转状态。由于在过渡金属中心的所有D轨道中至少存在一个电子，因此高旋转CI2（L）Fe = C（H）R复合物可以抵抗烯烃的配位，从而阻碍了遗传活性。解决该潜在问题的解决方案是合成XCI（L）Fe = C（H）R和X2（L）Fe = C（H）R复合物，其中X是CN-或C6F5-组。用这些较强的场配体替换CI2（L）Fe = C（H）R的CI群将增加系统中配体场分裂参数，这应该促进较低的旋转状态更有利于烯烃协调。提供用于底物结合的可访问配位位点的另一种方法是通过氯化物抽象来渲染CI2（L）Fe = C（H）R复合物。所得的XCI（L）Fe = C（H）R和X2（L）Fe = C（H）R，其中X是极其非协调的柜台，例如B（C6F5）4-或HBC11Cl11-，应在溶液中解离以形成正式的12和10电子铁和DICICANIT MONO和DICICATICS CI（L）Fe2+ = C（H）R+（H）R+（l）另一种方法是制备中性铁（O）烷基丙烯。可能表现出归化活性的理想铁（0）物种将为（r3p）lfe =（h）r。该类别的复合物应能够分离溶液中的磷酸配体，以提供至少两个空缺配位位点的LFE =（H）R片段，与金属的自旋状态无关。该研究建议的最终目标是为合成界提供廉价，环境良性，高度活跃和选择性的烯烃分解催化剂。公共卫生相关性拟议的研究计划打算使用铁化合物提供允许以更环保和成本效益的方式生产药品的方法。因此，这项工作最终可能提供干净的方法来生产更便宜的药物。