基于Au(I)/Au(III)变价催化机制进行的C-C重键与C-H键的氧化交叉偶联反应研究

Traditional single Au(I) or Au(III) redox-neutral catalytic systems have no way to make full use of the comprehensive advantages of Au(I) and Au(III) in catalytic processes. In order to overcome this disadvantage, the project will aim at developing highly efficient and mild Au(I)/Au(III) redox catalytic systems and exploring the related mechanisms. In the project we will first try to design and synthesize a series of substrates containing carbon-carbon multiple bond (allenes, alkenes, alkynes) and C-H structural units, then focus on subjection of these substrates to the Au(I)/Au(III) redox catalytic systems with aim to make full use of the superiority of Au(I) or Au(III) in activating carbon-carbon multiple bonds, the high efficiency of Au(III) in activating C-H bonds and promoting oxidative cross-coupling reactions within the gold redox catalytic systems. Thus a novel oxidative cross-coupling reaction between carbon-carbon multiple bonds and C-H bonds catalyzed by gold is expected to be realized, which may provide new methodologies for the preparation of a series of carbo- or heterocylces with potential pharmacological or biological activities as well as potential usage in function materials. The methods introduced in this project will not only open ways to realize the oxidative difunctionalizations of carbon-carbon multiple bonds which are difficult to pursue via traditional single Au(I) or Au(III) redox-neutral catalytic systems, but also overcome some disadvantages associated with other transition-metal-catalyzed C-H activation reactions including the requirement of heteroatom directing groups, harsh reaction conditions, and susceptibility to beta-H eliminations upon addition to carbon-carbon multiple bonds.

针对传统单一Au(I)或Au(III)催化机制存在无法发挥Au(I)与Au(III)的综合催化优势的弊端，本项目拟发展高效及温和的Au(I)/Au(III)变价催化体系并探索其变价催化循环机理；设计和合成一系列具有C-C重键（联烯、烯、炔）及C-H结构的底物，将Au(I)或Au(III)高效活化C-C重键、Au(III)高效活化C-H键及促进氧化偶联几个独特的过程糅合在Au(I)/Au(III)变价催化体系内接力完成，有望实现一类新型的基于金催化的C-C重键与C-H键的氧化偶联反应，为一系列具有潜在生理、药理活性或功能材料应用价值的碳环或杂环的合成提供新方法。拟研方法不但可以实现传统单一Au(I)或Au(III)催化机制无法实现的C-C重键的氧化双官能化反应，而且还可以克服传统过渡金属催化C-H键活化通常需杂原子导向基团、苛刻的反应条件及对C-C重键加成易于发生beta-H消除反应之不足。

本项目立项的初衷是希望凭借Au(I)/Au(III)变价催化体系将Au(I)高效活化碳-碳重键和Au(III)高效活化碳-氢键的性能糅合在同一体系内完成，从而实现碳-碳重键与碳-氢键的氧化交叉偶联以构建具有重要应用价值的化合物。但在实际研究过程中意外地发现，在大多数情况下价廉易得的Cu(0)/Selectfluor体系比Au(I)/Au(III)变价催化前体Au(I)/Selectfluor体系具有更高的催化活性和选择性，这得益于现场产生了活性羟基铜试剂XCuOH (X = F or BF4)。由此，研究计划调整为重点开发Cu(0)/Selectfluor体系催化的氧化串联反应。通过项目组的共同努力，目前已取得了系列创新性结果：（1）实现了Cu(0)/Selectfluor体系催化1,5-烯炔构建了3-甲酰基茚酮；1,6-烯炔构建了苯并芴酮和氟代苯并芴酮类化合物；催化邻芳基查尔酮碳-碳双键与碳-氢键氧化偶联/C-C键切断反应，合成了9,10-菲醌类化合物；催化邻芳基苯甲醛和邻酚氧基苯甲醛碳-氧双键与碳-氢键偶联分别合成苯并吡喃酮和呫吨酮类化合物；催化邻芳基磺酰亚胺碳-氮双键与碳-氢键偶联合成菲碇；（2）实现了多例Cu(0)/Selectfluor体系催化的氧化串联反应，包括催化芳基环己醇、芳基(硫代)色酮叔醇选择性转化为beta-芳基-环己烯酮、联苯和（硫代）香豆素；芳基环丁醇转化为四氢萘酮；（3）基于相似原理，开发了CuI/Selectfluor、FeCl2/Selectfluor、Se/Selectfluor、phenol/Selectfluor体系，实现了由邻芳基苯磺酰胺、邻芳基苯乙酮、端炔和查尔酮分别转化为6-芳基菲啶、5,6-二氢菲啶、9,10-菲醌、1,4-丁烯二酮和1,2-二酮；（4）开发了Cu、Pd和Ag等过渡金属催化的其他反应，包括高效构建了1,4-萘醌、茚酮、异色满、官能化菲啶、喹喔啉、1,1-二氯代亚胺、alpha-硫甲基二硫缩烯酮和多官能化3-丁烯酮等化合物。本项目研究为一系列具有重要应用前景的化合物的合成提供了高效、便捷和原料简便易得的新方法。至项目结题时共发表各类学术论文18篇；申请国家发明专利32项，获得授权发明专利21项，培养研究生10名。