Catalytic Functionalization of C-H Bonds with Main Group Reagents

主族试剂对 C-H 键的催化官能化

• 批准号: 8946206
• 负责人: John F Hartwig
• 金额: $ 34.92万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8946206
• 关键词: Affect; Alcohols; Alkylation; Amines; Aromatic Amines; Boranes; Carbon; Complex; Cyclic Ethers; Cyclopropanes; Data; Development; Electronics; Ethers; Felis catus; Generations; Goals; Grant; Health; Human; Hydrocarbons; Hydrogen Bonding; Individual; Intercept; Iridium; Ketones; Ligands; Metals; Methods; N.I.H. Research Support; Nature; Nitrogen; Pharmaceutical Chemistry; Pharmacologic Substance; Phenanthrolines; Phosphines; Phosphorus; Process; Property; Publishing; Reaction; Reagent; Relative (related person); Research; Rest; Rhodium; Science; Silanes; Silicon; Siloxanes; Site; Structure; System; Time; Transition Elements; base; catalyst; cyclopropane; design; drug discovery; functional group; improved; innovation; public health relevance; silane; success; unpublished works

 DESCRIPTION (provided by applicant): Methods for the catalytic functionalization of C-H bonds are widely considered to possess the potential to revolutionize the synthesis of complex molecules, but the realization of this potential requires the selective functionalization of a singe C-H bond in compounds containing many other C-H bonds and functional groups that are typically more reactive than the C-H bond. The PI is developing an unusual strategy for the functionalization of C-H bonds involving the reactions of boranes and, more recently, of silanes with aryl, heteroaryl, and alkyl C-H bonds. The products from these reactions are valuable synthetic intermediates that can be converted to diverse final products containing new C-C, C-N, C-O, and C-S bonds. The fundamental innovation underlying the C-H bond functionalization in this proposal is the higher reactivity of complexes containing covalent transition metal-main group bonds toward C-H bond functionalization than those containing typical organometallic ligands. During the past several years, the PI's group has discovered a new class of catalyst for the silylation of aryl C-H bonds; silylmetal complexes that are catalytically competent and react with arenes to form arylsilanes; iridium-catalyzed borylations of aliphatic C-H bonds of cyclopropanes, amines and cyclic ethers; borylations of secondary alkyl and benzyl C-H bonds directed by alcohols and amines; a catalyst for broadly applicable borylations of heteroarenes; and one-pot combinations of borylation and subsequent functionalization to create sterically controlled functionalizations of arenes, alkylations of arenes, and mild access to unstable arylboronate intermediates. The proposed research will build upon these studies and additional preliminary data. The PI's group will prepare new ligand structures that enable metal-catalyzed borylations of primary C-H bonds with limiting substrate, increase the reactivity of the catalysts toward basic heteroarenes, and create practical methods for the silylation of functionalized arenes. In addition, they will use these catalysts to achieve directed borylations and silylations of alkyl C-H bonds and methods for the generation and characterization of intermediates in the iridium-catalyzed borylations and silylations. To achieve these goals, seven major aims are proposed: 1) to design new ligands for the borylation and silylation of aryl and alkyl C-H bonds by iridium and rhodium catalysts; 2) To discover new borylations of aliphatic C-H bonds enabled by the ligands of Aim 1; 3) To gain a mechanistic understanding of the relationships between iridium catalyst structure and activity for C-H borylation; 4) To broaden the scope of directed silylations of aliphatic C-H Bonds; 5) To create intermolecular silylations of aromatic C-H bonds that occur with remote steric effects and high functional group compatibility; 6) To reveal the mechanism of these intermolecular silylations of arenes, and 7) To develop new functionalizations of the main group products of the C-H bond functionalizations.

 说明书(申请人提供)：C-H键的催化功能化方法被广泛认为具有革新复杂分子合成的潜力，但这种潜力的实现需要在包含许多其他C-H键和通常比C-H键更活跃的官能团的化合物中选择性地对单个C-H键进行官能化。PI正在为C-H键的官能化开发一种不同寻常的策略，涉及到硼烷和最近硅烷与芳基、杂芳基和烷基C-H键的反应。这些反应的产物是有价值的合成中间体，可以转化为含有新的C-C、C-N、C-O和C-S键的各种最终产品。这一提议中C-H键功能化的根本创新在于，与含有典型有机金属配体的化合物相比，含有共价过渡金属-主基键的配合物对C-H键功能化的反应活性更高。在过去的几年里，Pi的团队发现了一类新的催化剂，用于芳基C-H键的硅烷化反应；具有催化活性并与芳烃反应生成芳基硅烷的硅基金属络合物；Ir催化的环丙烷、胺和环醚的脂肪族C-H键的硼化反应；醇和胺直接的仲烷基和苯基C-H键的硼化反应；用于广泛应用的杂环芳烃的硼化反应；以及一锅硼化和随后的官能化的组合，以创建空间受控的芳烃官能化、芳烃的烷基化反应和温和地获得不稳定的芳基硼酸盐中间体。拟议的研究将建立在这些研究和其他初步数据的基础上。PI基团将制备新的配体结构，使金属催化的伯基C-H键与极限底物发生硼化反应，提高催化剂对碱性杂芳烃的反应活性，并为官能化芳烃的硅基化反应创造实用的方法。此外，他们还将使用这些催化剂来实现烷基C-H键的直接硼化和硅化，以及在Ir催化的硼化和硅化反应中中间体的生成和表征方法。为了实现这些目标，提出了七个主要目标：1)设计用于芳基和烷基C-H键的硼化和硅基化的新配体；2)发现由AIM 1的配体实现的新的脂肪族C-H键的硼化反应；3)从机理上了解Ir催化剂结构与C-H硼化反应活性之间的关系；4)拓宽脂肪族C-H键的定向硅基化反应的范围；5)创建具有远程空间效应和高官能团相容性的芳香族C-H键的分子间硅基化反应；6)揭示芳烃分子间硅化反应的机理；7)开发C-H键官能化主要基团产物的新官能化。