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）：拟议的研究的主要目标是使用碳 - 氢键激活反应进行新的和有用的转换。尽管基于C-X键（X =卤素，杂原子）的氧化添加反应开发了广泛的合成方法，但尽管与功能化的化合物相比，催化C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-C-键反应反应形成了C-H键激活引起的反应。 C-H键激活引起的反应将补充当前C-C键形成的方法，并将对合成方法产生重大影响。在这个项目中，将在合成生物学上相关的非天然氨基酸衍生物的背景下探索钯催化的芳基化，烷基化，乙烯酸化和藻类化。此外，我们将探索未激活的SP3 C-H键的钯催化的氟化。此外，我们获得了初步结果，表明为钯催化的C-H键功能化而开发的辅助因素对于铜催化的SP2 C-H键芳基化，硫酰化和胺化有效。我们有大量的初步数据，表明拟议的化学是可行的，并且可能导致有用的方法。该研究的具体目的如下：1。SP3 C-H键转化为C-C键的新辅助和反应发展，2。未激活的SP3 C-H键的氟化，3。辅助辅助，铜催化的C-H键函数化。