C-H Bond Functionalization in Organic Synthesis

有机合成中的C-H键官能化

基本信息

批准号：
7902275
负责人：
MELANIE S. SANFORD
金额：
$ 23.94万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-08-01 至 2011-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal describes the development of general and highly selective Pd-catalyzed methods for converting unactivated arene and alkane C-H bonds to new functional groups X, where X = acetate, ether, amine, halide, cyanide, arene, alkene, or alkyne. These transformations will find widespread application in SAR studies of pharmaceutical candidates as a result of their generality, functional group tolerance, and extremely high regio- and chemoselectivities. In addition, these methods provide versatile approaches to many other valuable structures, including alpha- and beta-functionalized ketones, 1,2- and 1,3-diols, diamines, and amino alcohols, and oxygen/nitrogen heterocycles, which all serve as important synthetic building blocks. Furthermore, many of these products represent key structural motifs of biologically active molecules, including polyketide natural products such as the epothilones (anti-cancer) and pseudomonic acid (antibacterial) and flavonoid (antibacterial, antioxidant, antimutagenic) derivatives. The proposed research will involve catalytically coupling alkane/arene C-H bond activation at Pd(ll) to subsequent functionalization with hypervalent iodine reagents or other oxidants. High reactivity and regioselectivity will be achieved by the use of organic substrates that contain appropriate chelating functional groups (for example oximes, heterocycles, ethers, amides and amines). The scope and functional group tolerance of these transformations will be explored, and asymmetric catalyst systems will be investigated. In addition, related tandem transformations will be developed in order to use the proposed methodology for the construction of structurally and stereochemically diverse molecules from simple building blocks such as arenes, alkanes, and olefins.

描述（由申请人提供）：该提案描述了将未活化芳烃和烷烃 C-H 键转化为新官能团 X 的通用和高选择性 Pd 催化方法的开发，其中 X = 乙酸酯、醚、胺、卤化物、氰化物、芳烃、烯烃或炔烃。由于其通用性、官能团耐受性以及极高的区域和化学选择性，这些转化将在候选药物的 SAR 研究中得到广泛应用。此外，这些方法为许多其他有价值的结构提供了通用的方法，包括α-和β-官能化酮、1,2-和1,3-二醇、二胺和氨基醇，以及氧/氮杂环，它们都用作重要的合成构件。此外，许多这些产品代表了生物活性分子的关键结构基序，包括聚酮化合物天然产物，例如埃坡霉素（抗癌）和假单胞菌酸（抗菌）以及类黄酮（抗菌、抗氧化、抗突变）衍生物。拟议的研究将涉及催化偶联 Pd(II) 处的烷烃/芳烃 C-H 键活化，以及随后用高价碘试剂或其他氧化剂进行的官能化。通过使用含有适当螯合官能团（例如肟、杂环、醚、酰胺和胺）的有机底物，可以实现高反应性和区域选择性。将探索这些转化的范围和官能团耐受性，并将研究不对称催化剂体系。此外，还将开发相关的串联转化，以便使用所提出的方法从芳烃、烷烃和烯烃等简单结构单元构建结构和立体化学不同的分子。