【作者】 王洁；

【导师】 朱进；

【作者基本信息】 南京大学 ， 高分子化学与物理， 2017， 博士

【摘要】 过渡金属催化C-H键活化构建C-C和C-杂键的发展,在推动新反应体系的发展和催化机理研究方面取得了显著的成就。这些研究将金属有机化学基元反应和催化体系的开发相结合,发展了一系列C-H键活化与官能化的新体系。本论文主要研究了铑(Ⅲ)催化的C-H键官能化在杂环化合物合成方面的应用。主要内容包括:第一章,简单介绍铑(Ⅲ)催化的C-H键活化构建杂环化合物的发展现状。第二章,研究了铑(Ⅲ)催化的N-亚硝基导向的C-H键活化后与α-重氮-β-酮酯化合物无痕化、原子经济性地构建吲哚衍生物的反应。相比较目前利用导向基团的亲核性作为无痕化反应的机理,本文首次实现了 N-亚硝基作为亲电性导向基团在环化/脱硝过程中进行无痕化去除。重要的是,N-亚硝基亲电性的发现和应用丰富了N-亚硝基的反应模式。第三章,我们发展了一种新的连续的C-C/C-N键形成方式,即在Rh(Ⅲ)催化体系下利用苯甲酰亚胺C-H键活化/分子内环化α-重氮-β-双酯制备3-羟基-异喹啉衍生物。其中重氮双酯偶联试剂提供两个碳源参与环化反应。另外,在该课题中我们一并研究了α-重氮-β-酮酯作为偶联底物在Rh(Ⅲ)催化苯甲酰亚胺C-H键活化/分子内环化合异喹啉衍生物的应用。第四章,我们发展了 Rh(Ⅲ)催化亚胺导向的C-H键活化/环化合成喹唑啉衍生物。在[Cp*RhCl2]2/AgBF4催化体系下使用苯甲亚胺底物和恶唑酮偶联试剂采用C-N连续形成的策略成功实现了喹唑啉的合成,其中苯甲亚胺底物即作为定位底物又提供一个氮源参与反应,而偶联试剂恶唑酮衍生物则即作为内部氧化剂保持催化循环持续性的同时又提供另一个氮源并环化最终形成喹唑啉衍生物。第五章,我们报告了N-叔丁基羰基酯(N-Boc)键断裂在C-H键活化反应中作为多样化反应模式的启动器实现了联级反应构建不同形式的氮杂环化合物。在Rh(Ⅲ)催化体系中,N-Boc腙/N-Boc肼底物与重氮双酯/重氮酮酯偶联生成了在合成和医学上重要的一类化合物N-氨基氮杂环化合物,包括N-氨基异喹啉-3-酮,N氨基吲哚和N-氨基异喹啉。此外,反应性中级联的分叉允许苯并二氮杂类化合物的合成。第六章,我们报道了在氧化还原中性条件下,Co(Ⅲ)催化的N-Boc苯乙酮腙与炔烃通过N-N键断裂和连续的C-C/C-N键偶联快速合成异喹啉衍生物。此外,反应在30min内即可完成反应得到产率高达85%的目标产物。更多还原

【Abstract】 Transition-metal-catalyzed C-H functionalization has been explored for building desired valuable C-C/C-hetero bonds or heterocycle skeletons and also has made remarkable achievements in promoting the development of new reaction system and the research of catalytic mechanism.These studies have combined a series of metal organic chemical radical reactions and catalytic systems to develop a series of new C-H functionalization system.In this paper,synthesis of heterocyclic structures via rhodium(Ⅲ)catalyzed C-H functionalization was studied.The main contents include:In the first chapter,we simply introduce the current development situation of Rh-catalyzed C-H bond activation.In the second chapter,Rh(Ⅲ)-catalyzed,N-nitrosodirected C-H activation allows the development of a traceless,atom-and step-economic,cascade approach for the synthesis of indole skeletons,starting from readily available N-nitroso and α-diazo-β-keto compounds.A distinct C-H activation-based traceless synthetic protocol via electrophilic removal of a directing group is reported,complementing the currently exclusively used nucleophilic strategy.Importantly,the cyclization/denitrosation reaction represents a hitherto unobserved reactivity pattern for the N-nitroso group.In the third chapter,we report synthesis of isoquinolines based on efficient C-C and C-N bond formation through Rh(Ⅲ)-catalyzed C-H activation and subsequent intramolecular cyclization is reported.Diazodiesters serving as a C2 source in the newly formed heterocycles are first demonstrated.Additionally,the Rh(Ⅲ)-catalyzed direct C-H activation/cyclization of benzimidates with diazoketoesters is also described.In the fourth chapter,we report an efficient double C-N bond formation sequence to prepare highly substituted quinazolines utilizing benzimidates and dioxazolones under the catalytic redox-neutral[Cp*RhCl2]2/AgBF4 system,where dioxazolones could work as an internal oxidant to maintain the catalytic cycle,is reported.N-unsubstituted imine not only acts as a directing group but also functions as a nucleophile in postcoupling cyclization,and dioxazolone acts as a coupling partner for access to heterocycle.In the fifth chapter,we report the discovery of N-tert-butyloxycarbonyl(N-Boc)cleavage as a versatile reactivity paradigm for diverse C-H activation-initiated reactivity relay cascades.Rh(Ⅲ)-catalyzed coupling of N-Boc hydrazone/N-Boc hydrazine with diazodiester/diazoketoester provides efficient access to a synthetically and medicinally important class of compounds,N-amino azaheterocycles,including N-amino isoquinolin-3-ones,N-amino indoles,and N-amino isoquinoliniums.In addition,bifurcation of reactivity relay cascades allows the synthesis of benzodiazepines.In the sixth chapter,we report herein a redox-neutral Cp*Co(Ⅲ)-catalyzed cyclization of acetophenone N-Boc hydrazones with alkynes for streamlined synthesis of isoquinolines,accomplished via formation of a C-C and a C-N bond along with N-N bond cleavage.Moreover,this rapid approach can be completed in 30 min with yields up to 85%.更多还原