New Methods for Direct Carbon-Hydrogen Bond Functionalization

直接碳氢键功能化的新方法

• 批准号: 8501892
• 负责人: Olafs Daugulis
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-05 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8501892
• 关键词: Alkanes; Alkylation; Amides; Amination; Amines; Amino Acids; Aminoquinolines; Benzoic Acids; Benzylamines; Carbon; Carboxylic Acids; Chemistry; Complement; Copper; Data; Development; Disulfides; Goals; Grant; Halogens; Hydrocarbons; Hydrogen Bonding; Lead; Methodology; Methods; Palladium; Pathway interactions; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Picolinic Acids; Price; Production; Reaction; Research; Transition Elements; base; cost; drug structure; improved; method development; next generation; public health relevance

DESCRIPTION (provided by applicant): The primary goal of the proposed research is to develop new and useful transformations using carbon-hydrogen bond activation reactions. While extensive synthetic methodology has been developed based on oxidative addition reactions of C-X bonds (X=halogen, heteroatom), catalytic C-C bond forming reactions arising from C-H bond activation are less common despite the wider availability, price, and environmental advantages of the starting hydrocarbons compared to functionalized compounds. The reactions arising from C-H bond activation will complement the current methods for C-C bond formation and will have a substantial impact on synthetic methodology. In this project, palladium-catalyzed arylation, alkylation, vinylation, and alkynylation of unactivated sp3 C-H bonds will be explored in context of synthesis of biologically relevant unnatural amino acid derivatives. Furthermore, we will explore palladium-catalyzed fluorination of unactivated sp3 C-H bonds. Additionally, we have obtained preliminary results showing that auxiliaries developed for the palladium-catalyzed C-H bond functionalization are effective for copper-catalyzed sp2 C-H bond arylation, sulfenylation, and amination. We have a substantial amount of preliminary data showing that proposed chemistry is viable and may lead to useful methodology. The specific aims of the research are as follows: 1. New auxiliary and reaction development for sp3 C-H bond conversion to C-C bonds, 2. Fluorination of unactivated sp3 C-H bonds, 3. Auxiliary assisted, copper-catalyzed C-H bond functionalization.

描述（由申请人提供）：拟议研究的主要目标是利用碳氢键活化反应开发新的有用的转化。虽然基于C-X键（X=卤素、杂原子）的氧化加成反应已经开发出广泛的合成方法，但尽管起始碳氢化合物具有更广泛的可用性、价格和环境优势，但由C-H键活化引起的催化C-C键形成反应并不常见与功能化化合物相比。 C-H键活化产生的反应将补充目前的C-C键形成方法，并对合成方法产生重大影响。在该项目中，将在合成生物学相关的非天然氨基酸衍生物的背景下探索未活化的 sp3 C-H 键的钯催化芳基化、烷基化、乙烯基化和炔基化。此外，我们将探索未活化的 sp3 C-H 键的钯催化氟化。此外，我们还获得了初步结果，表明为钯催化的 C-H 键功能化而开发的助剂对于铜催化的 sp2 C-H 键芳基化、磺基化和胺化是有效的。我们有大量的初步数据表明，所提出的化学方法是可行的，并且可能会产生有用的方法。研究的具体目标如下：1. sp3 C-H键转化为C-C键的新助剂和反应开发，2.未活化sp3 C-H键的氟化，3.助剂辅助的铜催化C-H键功能化。