Correlation of electronic structure to iron catalyzed C-H bond functionalization

电子结构与铁催化C-H键功能化的相关性

• 批准号: 9115643
• 负责人: Theodore A Betley
• 金额: $ 32.4万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9115643
• 关键词: Address; Alkenes; Amination; Amines; Anions; Azides; Carbon; Catalysis; Chemicals; Chloride Ion; Chlorides; Complex; Cytochrome P450; Development; Enzymes; Funding; Generations; Goals; Health; Heterocyclic Compounds; Hydrocarbons; Hydrogen Bonding; Hydroxylation; Iron; Ligands; Masks; Mediating; Metals; Methods; Mixed Function Oxygenases; Modeling; Modification; Nature; Nitrogen; Oxidants; Oxygen; Pharmacologic Substance; Porphyrins; Process; Protocols documentation; Pyrrolidines; Reaction; Reporting; Research; Route; Scheme; Structure; Variant; Waste Products; Work; analog; base; catalyst; chemical synthesis; electronic structure; feeding; functional group; improved; nitrene; novel; piperidine; wasting

 DESCRIPTION (provided by applicant): Correlation of electronic structure to iron catalyzed C-H bond functionalization In the field of homogenous catalysis, few reports have appeared offering general, chemically mild methods for the introduction of nitrogen- or oxygen-containing functional groups into simple hydrocarbon substrates. The ability to selectively incorporate functionality into unactivated C-H bonds represents a significant advance in converting inexpensive chemical feed stocks (e.g. hydrocarbons) to value-added functional molecules. However, the oxidative substitution of C-H bonds with amines or other functional groups often requires preoxidation of substrate or employs strong chemical oxidants in concert with atom or group transfer processes. A streamlined synthesis for functionalized products (e.g. N-heterocycles) with minimal or complete absence of waste generation would have tremendous impact on the synthesis of fine chemicals and pharmaceuticals. Towards this end, we have synthesized a class of electrophilic complexes featuring transiently-formed, or metastable metal-ligand multiple bonds capable of mediating C-H bond functionalization. Using dipyrrin ligand platforms as truncated models of the porphyrin platform found in P450 hydroxylase enzymes, we have observed reactivity from the ferrous-ligand constructs mirrors their porphyrin analogues. Catalytic C-H bond amination and olefin aziridination have been observed from the reaction of organic azides with simple iron(II) and iron(I) coordination complexes. The iron-catalyzed amination reaction is tolerant to a variety of organic azide precursors and has shown reactivity with a range of organic substrates to form N- heterocyclic products: linear azides can be intramolecularly aminated to form both pyrrolidine and piperidine structures, bearing an array of a-functional groups. The broader scientific impact of the proposed research can be summarized as the following: we will improve our understanding of factors contributing to the promotion of productive C-H bond activation and functionalization, further developing new classes of inorganic/organometallic catalysts to synthesize value-added commodity chemicals via clean reaction routes with minimal waste product.

 描述（由申请人提供）：电子结构与铁催化的C-H键官能化的相关性在均相催化领域中，很少有报道提供将含氮或含氧官能团引入简单的氢底物碳中的通用的、化学温和的方法。将功能选择性地结合到未活化的 C-H 键中的能力代表了将廉价化学原料（例如碳氢化合物）转化为增值功能分子的重大进步。 C-H 键与胺或其他官能团的氧化取代通常需要底物的预氧化或采用强化学氧化剂与原子或基团转移过程相结合，以最小或完全不产生废物的方式简化功能化产品（例如 N-杂环）的合成。为此，我们合成了一类具有瞬时形成或亚稳态的亲电配合物。使用二吡啉配体平台作为 P450 羟化酶中发现的卟啉平台的截短模型，我们观察到亚铁配体结构的反应性反映了它们的催化 C-H 键胺化和烯烃。从有机叠氮化物与简单铁(II)和铁(I)配位的反应中观察到氮丙啶化铁催化的胺化反应对多种有机叠氮化物前体具有耐受性，并且与一系列有机底物表现出反应性，可形成 N-杂环产物：直链叠氮化物可进行分子内胺化，形成吡咯烷和哌啶结构，并带有所提出的研究的更广泛的科学影响可概括如下：我们将提高对促进高效 C-H 键激活和促进​​的因素的理解。功能化，进一步开发新型无机/有机金属催化剂，通过开发废物最少的清洁反应路线来合成增值的商品化学品。