融合C-H键官能化的串联催化新策略和新方法

Over the past few years, metal-catalyzed direct C-H functionalization has been demonstrated to be effective for various C-C and C-X bond formation reactions. On the other hand, cascade catalysis, where multiple catalytic reactions work cooperatively in one-pot, is a powerful but under-developed strategy for the fast and efficient assembly of complex molecules. The combination of C-H functionalization reaction with other catalytic reactions in a cooperative manner will greatly extend the application scope and enhance the efficiency of organic synthesis. We have recently developed several new C-H functionalization reactions which enable the direct and efficient incorporation of hydroxyl, amino, and activated methine-substituted allyl group into a molecule. Moreover, the reaction conditions applied are simple, mild, and the reactions are compatible with various solvents, additives and temperature. These advantageous features offer an unprecedented opportunity for cascade catalysis. In the current project, we aim at applying C-H functionalization reactions in cascade catalysis for the first time. A number of cascade catalysis reactions combining C-H functionalization with other types of catalytic reactions have been proposed. These catalytic reactions include: catalytic olefin isomerization, (asymmetric) allylic alkylation, (asymmetric) olefin epoxidation, (asymmetric) olefin dihydroxylation, Wacker oxidation, Wacker-type oxidation, olefin metathesis, heterogeneous hydrogenation, catalytic carbonylation-amination, click chemistry, Sonogashira coupling, etc.. The fulfillment of this project will offer a new stratagy for organic synthesis. Some exciting preparatnory results have been achieved.

C-H键官能化是最新发展的由C-H键直接引入各种官能团的合成方法。串联催化反应是串联多种催化反应于一锅的快速、高效地构建复杂分子的新技术。融合C-H键官能化与串联催化技术于一体将极大地提高合成的效率和应用范围。申请人近期发展了几类新型的C－H键活化反应，能高效地引入羟基、胺基或活化次甲基取代的烯丙基。这几类反应条件简单温和、对反应条件要求不高。这些特性为实现与串联催化融合提供了可能，并且已经在前期工作中得到了验证。本项目中，我们首次将C－H键活化应用于串联催化，设计和实现C－H键活化与其他催化反应有机串联的一锅合成法，从而实现从简单原料合成复杂有用的产物。这些催化反应包括：双键异构化、（不对称）烯丙基化、烯烃（不对称）环氧化/双羟化、Wacker（-Type）氧化、烯烃复分解、催化氢化、催化羰基化-胺化、点击化学、Sonogashira偶联等。本项目的实现将为有机合成提供一种新策略和方法。

C-H 键官能化是基于 C-H 键直接引入各种官能团的合成方法。串联催化反应是串联多种催化反应于一锅的快速、高效地构建复杂分子的新技术。融合 C-H 键官能化与串联催化技术于一体将极大地提高合成的效率和应用范围。本项目发展了系列融合Rh(III)催化C-H活化串联催化反应，应用于具有一定复杂度的杂环的合成及烯烃的双官能化反应。包括：发展了Rh(III)/H+催化的串联催化合成咔唑；Rh(III)与Pd(II)的共催化的二氢异喹啉酮的合成；Rh(III)与Cu(II)共催化的苯并杂环的合成；Rh（III)与Ag的串联催化合成五元杂环的合成并应用到天然物的全合成当中；Mn与Ag的串联催化合成多环体系；Rh(III)/H+催化的含氟杂环的构建；Rh(III)与Cu(II)的串联催化，用于烯烃的双官能化；Mn催化的串联C-H键活化/smiles 重排反应。并在此基础上，进行了其他新颖C-H键活化反应的探索。项目按照原计划书进行，进展顺利。在该基金的资助下，取得了一系列研究成果。 本项目的成功实施，为系列重要杂环骨架的绿色高效合成提供了新的思路，并有可能为串联催化在其他合成领域的应用提供参考。