C-H Bond Functionalization in Organic Synthesis

描述(由申请人提供)：本提案描述了用于未活化芳烃和烷烃碳氢键在配体指导下转化为新官能团的一般和选择性Pd催化方法的发展。目标1和目标2的重点是探索C-H键氟化和三氟甲基化的新方法，利用容易获得和廉价的氟和三氟甲基起始材料。一个关键的目标是为Pd催化的有机分子引入氟化基团确定新的(并且可能广泛适用的)反应模式。目标3寻求开发使用容易获得的氧气作为末端氧化剂的方法，以将C-H键转化为不同的官能团。目的4致力于开发应用广泛的不对称催化C-H功能化反应。所有这些目标将通过利用桑福德集团在新反应开发/优化、详细的机理研究以及反应性有机钯中间体的合成/表征方面的专业知识来实现。本文开发的反应将在候选药物、天然产物、正电子发射断层成像(PET)显像剂和生物探针的合成/多样化中得到应用。

DESCRIPTION (provided by applicant): This proposal describes the development of general and selective Pd-catalyzed methods for the ligand-directed conversion of unactivated arene and alkane carbon-hydrogen bonds into new functional groups. Aims 1 and 2 focus on exploring new methods for C-H bond fluorination and trifluoromethylation, utilizing readily available and inexpensive fluoride and trifluoromethyl starting materials. A key objective is to identify novel (and potentially broadly applicable) reactivity modes for the Pd-catalyzed introduction of fluorinated groups into organic molecules. Aim 3 seeks to develop methods that use readily available dioxygen as the terminal oxidant for converting C-H bonds into diverse functional groups. Aim 4 focuses on developing widely applicable asymmetric catalytic C-H functionalization reactions. All of these aims will be tackled by taking advantage of the Sanford group's expertise in new reaction development/optimization, in detailed mechanistic investigations, and in the synthesis/characterization of reactive organopalladium intermediates. The reactions developed herein will find application in the synthesis/diversification of pharmaceutical candidates, natural products, positron emission tomography (PET) imaging agents, and biological probes.