New Methods for Direct Carbon-Hydrogen 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和有用的转化。虽然基于C-X键(X=卤素，杂原子)的氧化加成反应已开发出广泛的合成方法，但由C-H键活化引起的催化C-C键形成反应并不常见，尽管与官能化化合物相比，起始碳氢化合物具有更广泛的可获得性、价格和环境优势。由C-H键活化引起的反应将补充现有的C-C键形成方法，并将对合成方法学产生重大影响。在本项目中，将在合成生物相关的非天然氨基酸衍生物的背景下，探索钯催化的未活化的SP3C-H键的芳基化、烷基化、乙烯基化和炔基化。此外，我们还将探索钯催化的未活化的SP3C-H键的氟化反应。此外，我们还获得了初步的结果，表明为钯催化的C-H键功能化开发的助剂对铜催化的sp2 C-H键芳基化、亚磺化和胺化反应是有效的。我们有大量的初步数据表明，拟议的化学是可行的，并可能导致有用的方法学。本研究的具体目的如下：1.新的SP3 C-H键转化为C-C键的助剂及反应进展；2.未活化的SP3 C-H键的氟化；3.辅助铜催化的C-H键功能化。

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.