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，很少有报道提供将含氮或含氧官能团引入简单烃底物中的一般的、化学上温和的方法。选择性地将官能性结合到未活化的C-H键中的能力代表了将廉价的化学原料（例如烃）转化为增值的官能分子的显著进步。然而，用胺或其他官能团氧化取代C-H键通常需要预氧化底物或使用强化学氧化剂与原子或基团转移过程相配合。具有最小或完全不产生废物的功能化产物（例如N-杂环）的流线型合成将对精细化学品和药物的合成产生巨大影响。为此，我们合成了一类具有瞬时形成的或亚稳态的金属-配体多重键的亲电配合物，其能够介导C-H键官能化。使用二吡咯配体平台作为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构建体的反应性反映了它们的卟啉类似物。研究了有机叠氮化合物与简单铁（Ⅱ）和铁（Ⅰ）配合物的反应，发现了催化C-H键胺化和烯烃氮丙啶化反应。铁催化的胺化反应耐受各种有机叠氮化物前体，并且已经显示出与一系列有机底物的反应性以形成N-杂环产物：线性叠氮化物可以分子内胺化以形成吡咯烷和哌啶结构，其带有α-官能团阵列。拟议研究的更广泛的科学影响可以总结如下：我们将提高对促进生产性C-H键活化和功能化的因素的理解，进一步开发新型无机/有机金属催化剂，通过清洁的反应路线以最少的废物合成增值商品化学品。