C-H Bond Functionalization in Organic Synthesis

描述(由申请人提供)：本建议书描述了在钯催化下将未活化的芳烃和烷烃C-H键转化为新的官能团X的一般和高选择性方法的发展，其中X=醋酸酯、乙醚、胺、卤化物、氰化物、芳烃、烯烃或炔烃。由于它们的通用性、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，这些方法提供了许多其他有价值的结构的通用方法，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，这些都是重要的合成构件。此外，这些产品中的许多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Epothilone(抗癌)、假单酸(抗菌)和类黄酮(抗菌、抗氧化剂、抗突变)衍生物。拟议的研究将涉及催化偶联Pd(11)上的烷烃/芳烃C-H键，然后用高价碘试剂或其他氧化剂进行官能化。通过使用含有适当的螯合官能团(例如，肟、杂环、醚、酰胺和胺)的有机底物，将获得高的反应性和区域选择性。将探索这些转化的范围和官能团的耐受性，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、烷烃和烯烃等简单的构筑块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.