C-H Bond Functionalization in Organic Synthesis

本提案描述了开发通用的和高选择性的Pd催化的方法 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、乙醚、 胺、卤化物、氰化物、芳烃、烯烃或炔烃。这些变换将在以下方面得到广泛应用 候选药物的SAR研究作为其一般性、官能团耐受性的结果，以及 极高的区域和化学选择性。此外，这些方法还提供了多种方法来 许多其他有价值的结构，包括α-和β-官能化酮、1，2-和1，3-二醇， 二胺、氨基醇和氧/氮杂环，这些都是重要的合成 积木。此外，这些产品中的许多代表了生物活性的关键结构基元 分子，包括聚酮类天然产物，如Epothilone(抗癌)和假体 酸(抗菌)和类黄酮类(抗菌、抗氧化、抗突变)衍生物。 拟议的研究将涉及在Pd(11)上催化偶联烷烃/芳烃C-H键以 随后用高价碘试剂或其他氧化剂进行官能化。高反应性和 区域选择性将通过使用含有适当的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)。范围和功能组别 我们将探讨这些转化的耐受性，并研究不对称催化剂体系。在……里面 此外，将开发相关的串联变换，以便将拟议的方法用于 用简单的构造物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.