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使用碳-氢键活化反应开发新的有用的转化。虽然已经基于C-X键（X=卤素、杂原子）的氧化加成反应开发了广泛的合成方法，但是由C-H键活化引起的催化C-C键形成反应不太常见，尽管与官能化化合物相比，起始烃具有更广泛的可用性、价格和环境优势。由C-H键活化引起的反应将补充目前的C-C键形成方法，并将对合成方法产生重大影响。在这个项目中，钯催化的芳基化，烷基化，乙烯化，和炔基化的未活化的sp3 C-H键将在生物相关的非天然氨基酸衍生物的合成的背景下进行探索。此外，我们将探索钯催化的未活化的sp3 C-H键的重氮化。此外，我们已经获得的初步结果表明，开发的钯催化的C-H键官能化的助剂是有效的铜催化的sp2 C-H键芳基化，亚磺酰化，和胺化。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。具体研究目的如下：1. sp3 C-H键转化为C-C键的新助剂和反应开发，2。未活化的sp3 C-H键的氟化，3.辅助的铜催化的C-H键官能化。

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.