C-H Bond Functionalization in Organic Synthesis

描述（由申请人提供）：该提案描述了将未活化的芳烃和烷烃C-H键转化为新官能团X的一般和高选择性pd催化方法的发展，其中X =乙酸，醚，胺，卤化物，氰化物，芳烃，烯烃或炔。这些转化由于其通用性、官能团耐受性和极高的区域选择性和化学选择性，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功能化酮，1,2-和1,3-二醇，二胺和氨基醇，以及氧/氮杂环，它们都是重要的合成基石。此外，许多这些产品代表了生物活性分子的关键结构基序，包括聚酮类天然产物，如埃波霉素（抗癌）、假单酸（抗菌）和类黄酮（抗菌、抗氧化、抗诱变）衍生物。拟议的研究将涉及催化偶联Pd（ll）上的烷烃/芳烃C-H键活化，随后用高价碘试剂或其他氧化剂进行功能化。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，可以实现高反应活性和区域选择性。这些转化的范围和官能团耐受性将被探索，不对称催化剂系统将被研究。此外，将开发相关的串联转化，以便使用所提出的方法从简单的构建块（如芳烃、烷烃和烯烃）构建结构和立体化学不同的分子。

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.