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cyclopropane; design; drug discovery; functional group; improved; innovation; public health relevance; silane; success; unpublished works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.

 描述（由申请人提供）：C-H 键的催化功能化方法被广泛认为具有彻底改变复杂分子合成的潜力，但实现这一潜力需要对含有许多其他化合物的化合物中的单个 C-H 键进行选择性功能化。 C-H 键和官能团通常比 C-H 键更具反应性 PI 正在开发一种不寻常的策略，用于硼烷反应以及最近的硼烷反应的 C-H 键官能化。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 C-C、C-N、C-O 和 C-S 键的各种最终产品。建议是含有共价过渡金属主基键的配合物对 C-H 键官能化的反应性比含有典型有机金属配体的配合物更高。 PI的研究小组发现了一种用于芳基C-H键甲硅烷基化的新型催化剂，该络合物具有催化能力，可与芳烃反应形成芳基硅烷；环丙烷、胺和仲醚的脂肪族C-H键的硼基化；由醇和胺引导的烷基和苄基C-H键；广泛适用的杂芳烃硼基化的催化剂；以及硼基化和随后的官能化的一锅组合，以产生芳烃的空间控制官能化、芳烃的烷基化以及温和地获得不稳定的芳基硼酸酯中间体。 PI的小组将制备新的配体结构，使金属催化的伯C-H键与限制性底物发生硼化，提高催化剂对碱性的反应活性。此外，他们将使用这些催化剂实现烷基 C-H 键的直接硼基化和硅烷化，以及铱催化的硼基化和硅烷化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的硼基化和甲硅烷基化的新配体铱和铑催化剂的 C-H 键；2) 发现由目标 1 的配体实现的脂肪族 C-H 键的新硼化；3) 获得对铱催化剂结构和 C-H 硼化活性之间关系的机械理解；脂肪族C-H键的定向硅烷化的范围； 5) 产生芳香族的分子间硅烷化；具有远程空间效应和高官能团相容性的C-H键；6）揭示芳烃分子间硅烷化的机制，7）开发C-H键功能化主族产物的新功能化。