Divergent synthesis of N-heterocycles via controllable cyclization of azido-diynes catalyzed by copper and gold

炔烃是有机合成中一类非常重要的合成子，其原料易得、化学转化丰富，π酸活化的炔烃特别是末端炔烃可接受一系列亲核试剂的选择性进攻，从而实现CC键、CH键和CX键的高效构筑。但是，该类加成反应主要发生在末端炔烃的β位（即非末端）。究其原因，普遍认为是由炔烃的电性所决定，β位电正性更强，所以更易接受亲核试剂的进攻。叶龙武课题组致力于实现针对该类炔烃加成反应的区域选择性调控。该课题组研究发现，利用金属铜(II)可很好地催化同时连有炔基和叠氮基的杂原子取代炔烃的氧化反应，这是首例廉价金属催化的该类二炔氧化反应，同时也是首次报道的叠氮基捕获经炔烃氧化途径产生的金属卡宾。特别是，利用该方法实现了一系列多环含氮杂环分子（具有药物核心骨架）的高效构建。吕鑫教授课题组通过密度泛函理论(DFT)计算，很好地诠释了该类反应的机理，特别是明晰了反应化学选择性和区域选择性控制的根源。 该研究工作主要由叶龙武课题组2015级博士生申文波完成，博士生周波、李龙和本科生刘鑫协助完成。吕鑫教授课题组博士生孙青负责理论计算，郑南峰教授课题组博士生严娟珠协助单晶测试。【Abstract】Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules. However, these alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones. Interestingly, by employing the same starting materials, the gold-catalyzed cascade cyclization leads to the divergent formation of synthetically useful pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these cascade reactions is strongly supported by both control experiments and theoretical calculations.We are grateful for the financial support from the National Natural Science Foundation of China (21572186, 21622204, and 91545105), the Natural Science Foundation of Fujian Province for Distinguished Young Scholars (2015J06003), the President Research Funds from Xiamen University (20720150045), XMU Training Program of Innovation and Enterpreneurship for Undergraduates (2016G10384076), and NFFTBS (J1310024). 研究工作得到国家自然科学基金委优青项目、面上项目（21622204, 21572186, 91545105），福建省杰出青年科学基金（2015J06003），厦门大学校长基金（20720150045），厦门大学大学生创新创业训练计划项目（2016G10384076）和国家基础科学人才培养基金项目（J1310024）的资助