过渡金属催化苯炔前体的合成及其应用的电化学研究

Ortho-(trimethylsilyl)aryl triflate is an important benzyne precursor in organic synthesis, which found widespread application in the construction of polysubstituted aromatic derivatives, heterocyclic compounds and natural products. Currently, the typical synthetic approach (kobayashi method) for this benzyne precursor usually involves low temperature and strong base n-Butyllithium, which is difficult to handle and shows poor functional group compatibility. In most cases, precursors with even slightly more complex or sensitive functional groups are difficult to access. In this context, this project plans to utilize electrochemical ruthenium catalyzed C–H functionalization to construct the important benzyne precursor-Ortho-(trimethylsilyl)aryl triflates. This methodology only employs electricity as the terminal oxidant; it will provide a convenient and versatile access for the synthesis of benzyne precursors. A series of sensitive functional groups will be tolerated well and the diversity of benzyne precursor library will also be greatly improved. Last but not least, this project will also investigate the first row transition metal cobalt catalyzed C–H/N–H electrochemical annulation reaction of the benzyne precursor which we obtained before. Again, electricity was used as the terminal oxidant, to effectively construct the synthetically meaningful 6(5H)-Phenanthridones scaffold. To further demonstrate the synthetic utility of our method, a set of natural products and bioactive molecules which contain the core of 6(5H)-Phenanthridones will be synthesised by utilizing the current methodology.

邻三甲硅基芳基三氟甲烷磺酸酯是有机合成中的一类重要的苯炔前体，在多取代芳香烃、杂环及天然产物合成中具有广泛应用。目前报道的其合成方法常需采用涉及低温及强碱正丁基锂试剂的kobayashi途径，操作繁琐且底物官能团兼容性差，含有复杂敏感取代基的苯炔前体合成困难。在此背景下，本项目拟采用过渡金属钌催化碳氢键官能团化与电化学有机合成结合的手段，来构建邻三甲硅基芳基三氟甲烷磺酸酯这一重要的苯炔前体。该方法仅使用电流作为氧化剂，将提供一种简便通用的的苯炔前体合成方法，使更多含敏感官能团的苯炔前体的合成成为可能，极大的丰富苯炔前体结构的多样性。最后，本课题还计划将合成的苯炔前体应用到廉价金属钴催化C−H/N−H活化及其与苯炔的关环反应电化学研究中。项目拟采用电流作为氧化剂，来高效的构建6(5H)-菲啶酮重要结构单元，在此基础上合成一系列含有该母核结构的药物分子及及天然产物，进一步说明此方法的实用性。

邻三甲硅基芳基三氟甲烷磺酸酯是有机合成中的一类重要的苯炔前体，在多取代芳香烃、杂环及天然产物合成中具有广泛应用。目前报道的其合成方法常需采用涉及低温及强碱正丁基锂试剂的kobayashi途径，操作繁琐且底物官能团兼容性差，含有复杂敏感取代基的苯炔前体合成困难。在此背景下，本项目拟采用过渡金属钌催化碳氢键官能团化与电化学有机合成结合的手段，来构建邻三甲硅基芳基三氟甲烷磺酸酯这一重要的苯炔前体。该方法仅使用电流作为氧化剂，将提供一种简便通用的的苯炔前体合成方法，使更多含敏感官能团的苯炔前体的合成成为可能，极大的丰富苯炔前体结构的多样性。最后，本课题还计划将合成的苯炔前体应用到廉价金属钴催化C−H/N−H活化及其与苯炔的关环反应电化学研究中。项目拟采用电流作为氧化剂，来高效的构建6(5H)-菲啶酮重要结构单元，在此基础上合成一系列含有该母核结构的药物分子及及天然产物，进一步说明此方法的实用性。