C-H Bond Functionalization in Organic Synthesis

该提案描述了一般的和高选择性的Pd催化方法的发展， 将未活化的芳烃和烷烃C-H键转化为新的官能团X，其中X =乙酸酯，醚， 胺、卤化物、氰化物、芳烃、烯烃或炔。这些转换将在以下领域得到广泛应用 候选药物的SAR研究，因为它们的一般性，官能团耐受性， 极高的区域和化学选择性。此外，这些方法提供了多种方法， 许多其它有价值的结构，包括α-和β-官能化的酮，1，2-和1，3-二醇， 二胺、氨基醇和氧/氮杂环，它们都是重要的合成试剂。 积木此外，许多这些产品代表了生物活性的关键结构基序， 分子，包括聚酮化合物天然产物，如埃博霉素（抗癌）和假单胞菌 酸（抗菌）和类黄酮（抗菌、抗氧化、抗突变）衍生物。 所提出的研究将涉及在Pd（II）处催化偶联烷烃/芳烃C-H键活化， 随后用高价碘试剂或其它氧化剂官能化。高反应性和 区域选择性将通过使用含有适当螯合官能团的有机底物来实现 基团（例如肟、杂环、醚、酰胺和胺）。范围和职能组 将探索这些转化的耐受性，并将研究不对称催化剂体系。在 此外，还将开发相关的串联转换，以便将拟议的方法用于 从简单的结构单元构建结构和立体化学上不同的分子， 芳烃、烷烃和烯烃。

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 transformationswill 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.