Wang Yi-Bo, Liu Wei, Li Ting, Lu Yazhu, Yu Yi-Tian, Liu Hai-Tao, Liu Meiwen, Li Pengfei, Qian Peng-Cheng, Tang Hao, Guan Jia, Ye Long-Wu, Li Long
College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, China.
Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, College of Science, Southern University of Science and Technology Guangming Advanced Research Institute Southern University of Science and Technology (SUSTech), Shenzhen, Guangdong 518055, China.
J Am Chem Soc. 2024 Dec 11;146(49):33804-33816. doi: 10.1021/jacs.4c12063. Epub 2024 Nov 30.
Due to the inherent challenges posed by the linear coordination of gold(I) complexes, asymmetric gold-catalyzed processes remain challenging, particularly in the atroposelective synthesis of axially chiral skeletons. Except for extremely few examples of intramolecular annulations, the construction of axial chirality via asymmetric gold-catalyzed intermolecular alkyne transformation is still undeveloped. Herein, a gold/HNTf-cocatalyzed asymmetric diazo-alkyne annulation is developed, allowing the atroposelective and divergent synthesis of chiral non--symmetric biaryls and arylquinones in generally good to excellent yield (up to 93% yield) and enantioselectivity (up to 99% ee), with broad substrate scope. Notably, this work represents the first gold-catalyzed atroposelective construction in an intermolecular manner. More interestingly, this strategy is successfully extended to the first asymmetric construction of seven-membered-ring atropisomers bearing one carbon-centered chirality in excellent diastereoselectivity and high enantioselectivity (up to 93% ee and 50:1 dr). Remarkably, the utility of this methodology is further illustrated by the successful application of a representative axially chiral ligand in a series of enantioselective reactions. Importantly, the Brønsted acid as a proton-shuttle cocatalyst significantly promotes this asymmetric annulation. Additionally, the origin of enantioselectivity of this annulation and the role of HNTf are disclosed by density functional calculations and control experiments.
由于金（I）配合物的线性配位带来的固有挑战，不对称金催化过程仍然具有挑战性，特别是在轴向手性骨架的对映选择性合成中。除了极少数分子内环化的例子外，通过不对称金催化的分子间炔烃转化构建轴向手性仍未得到充分发展。在此，开发了一种金/三氟甲磺酸（HNTf）共催化的不对称重氮-炔烃环化反应，可实现对映选择性和发散性合成手性非对称联芳基和芳基醌，产率一般良好至优异（高达93%），对映选择性高达99% ee，底物范围广泛。值得注意的是，这项工作代表了首次以分子间方式进行的金催化对映选择性构建。更有趣的是，该策略成功扩展到首次不对称构建具有一个碳中心手性的七元环阻转异构体，具有优异的非对映选择性和高对映选择性（高达93% ee和50:1 dr）。值得注意的是，该方法的实用性通过一种代表性的轴向手性配体在一系列对映选择性反应中的成功应用得到进一步说明。重要的是，布朗斯特酸作为质子穿梭共催化剂显著促进了这种不对称环化反应。此外，通过密度泛函计算和对照实验揭示了该环化反应对映选择性的起源以及HNTf的作用。
