调控芳基三氮烯作为偶氮化和芳基化试剂在不对称去芳构化中的应用

The catalytic asymmetric dearomatization (CADA) reaction is an efficient and simple strategy to convert simple planar aromatic compounds into three-dimensional chiral complex molecules, which provides convenient accesses to various natural products, pharmaceuticals, and their analogues. Although many dearomatization protocols have been developed, however, most of the reported dearomatization reactions are mainly focused on oxidative, allylative and alkylative dearomatization reactions, etc. Furthermore, to the best of our knowledge, no example of an asymmetric diazenylation dearomatization or intermolecular arylation dearomatization reaction has been reported. Although aryltriazenes have been widely used as diazotization and arylation reagents in organic synthesis due to their good stability, diverse transformations and mild reaction conditions, asymmetric synthesis with aryltriazenes have surprisingly not been reported so far. At the same time, by regulating aryltriazene to achieve diazenylation and arylation dearomatization reaction will make it to be a diverse building block, and also achieve its application in asymmetric synthesis. Catalyst plays a crucial role in regulation of aryltriazene for diverse transformations, BrØnsted/Lewis acids and transition metals were often used as catalyst for aryltriazene reaction. Therefore, this proposal is aimed to achieve asymmetric diazenylation and arylation dearomatization reaction of electron-rich aromatics with aryltriazene via chiral BrØnsted/Lewis acid and transition metal catalyst controlled switch. By using chiral BrØnsted acid as catalyst, the formation of chiral ion pair with chiral anion and aryl azo cation is the key step to realize asymmetric diazenylation dearomatization. On the other hand, arylative dearomatizated enantioenriched arylated product will be afforded via chiral ligand controlled Lewis acid or transition metal catalysis.

催化不对称去芳构化是一种将简单的平面芳香化合物转化为三维手性分子的简洁高效方法，为天然产物、药物等的合成提供了便利。但目前的报道主要集中于氧化、烯丙基化和烷基化去芳构化等反应，而偶氮化去芳构化和分子间芳基化去芳构化目前尚未见报道。芳基三氮烯因稳定性好、反应位点多及条件温和等优点在有机合成中常作为偶氮化和芳基化试剂，但在不对称合成中的应用尚未实现，特别是经有效调控同时实现不对称偶氮化和芳基化去芳构化反应，可使其成为多样化的“有机合成砌块”，同时填补其在不对称合成中的空白。质子酸、路易斯酸和过渡金属等常用催化剂是调控芳基三氮烯进行多样化转化的关键。基于此，本项目拟通过催化调控芳基三氮烯实现富电子芳烃的不对称偶氮化和芳基化去芳构化反应。以手性质子酸为催化剂，利用手性离子对策略实现不对称偶氮化去芳构化；过渡金属或路易斯酸催化时，利用手性配体诱导实现不对称芳基化去芳构化。

芳烃是人类从化石资源中获取的主要化工原料，也是新疆的优势化石资源下游产品，将其进行高附加值转化具有重要意义。本项目主要围绕芳烃的高值转化与利用，采用分子编辑策略，发展绿色催化与合成技术，深入探究反应机理，建立了有机小分子化合物的绿色精准合成方法，合成了系列包括有机染料和药物先导化合物等的高附加值产品。主要包括：1、以芳胺为原料合成了一系列芳基三氮烯，研究了芳基三氮烯的反应活性，发展了离子液体促进/催化和光促进等多种模式的三氮烯活化方式。将其作为多样化合成砌块，通过调控实现了吲哚、吲哚啉、萘酚、喹喔啉酮、N-苯基甲基丙烯酰胺、亚磺酸钠及乙腈等的选择性偶氮化和芳基化反应，还发展了可见光促进芳基三氮烯分子sp3碳氢键的氧化、烯丙基和苄基化反应，构建了芳基偶氮、联芳烃、芳基偶氮砜、内酰胺以及二芳基砜等化合物库。并将偶氮化方法用于磺胺药物的后修饰，修饰后的药物对于肿瘤细胞HeLa具有一定的选择性。为以后发展面向体内生物正交的芳基三氮烯点击化学奠定了基础。2、发展了过渡金属钯催化吲哚分子的立体选择性芳基化Heck去芳构化-硅烷化/偕二乙烯基化串联反应，以及电化学条件下色胺、色醇等芳烃的立体选择性胺化/叠氮化/醚化-环化去芳构化串联反应，高效和高立体选择性的合成了系列功能化吲哚啉衍生物。尽管并未实现对映选择性催化，但为后期电化学不对称催化去芳构化奠定了基础。3、新型纳米、核壳MOFs催化剂以及异质结催化剂的制备及其在有机催化中的应用。通过2-甲基咪唑调控经典MOFs的形貌和粒径，合成了一系列具有特殊形貌和尺寸的纳米HKUST-1和核壳ZIF-67@Co-MOF-74催化剂，并将其分别用于苯乙烯的可控氧化和水分解制氧反应中，催化效果与传统MOFs催化剂相比得到了显著提升。此外，还制备了Z型g-C3N4/rGO/BiVO4异质结光催化剂，并将其用于可见光催化甲醇为甲酰基源吲哚分子的C3选择性甲酰化反应。总之，该项目的实施为高值精细化学品的绿色制备与芳烃的高效催化转化提供了新思路。