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综述

不对称构筑二芳基次甲基立体中心的研究进展

尚阳, 肖检*, 王雅雯, 彭羽*   

  1. 西南交通大学生命科学与工程学院 四川省天然药物仿生合成工程研究中心 成都 610031
  • 通讯作者: * E-mail: xiaojian@swjtu.edu.cn; pengyu@swjtu.edu.cn
  • 作者简介:尚阳, 1995年出生于四川南充, 2018年在重庆邮电大学获得学士学位. 2018年至2021年, 在彭羽教授指导下攻读并获得硕士学位. 研究兴趣是木脂素天然产物的全合成.
    肖检, 1990年出生于四川巴中, 西南交通大学生命科学与工程学院助理研究员. 2018年在兰州大学功能有机分子化学国家重点实验室获得博士学位, 导师为彭羽教授. 2018年加入西南交通大学生命科学与工程学院化学系, 主要研究方向包括活性天然产物和药物分子的全合成、有机合成新方法发展等.
    王雅雯, 西南交通大学生命科学与工程学院教授. 2000、2005年在兰州大学分别获得学士和博士学位, 导师为刘伟生教授. 曾任兰州大学化学化工学院教授.主要研究领域为小分子荧光探针的合成及生物成像、超分子化学等.
    彭羽, 西南交通大学生命科学与工程学院教授. 2000、2005年在兰州大学分别获得学士和博士学位, 导师为李卫东教授. 2008年至2009年在美国内华达大学里诺分校和加州大学圣芭芭拉分校做博士后研究, 合作导师为Liming Zhang教授. 曾任兰州大学化学化工学院和功能有机分子化学国家重点实验室教授. 主要研究领域为活性天然产物和药物分子的全合成、镍催化的还原环化新方法发展等.
  • 基金资助:
    国家自然科学基金(Nos. 21772078 and 22071200), 四川省科技计划项目(No. 2020JDRC0021) 和中央高校基本科研业务费专项资金资助项目(Nos. 2682020CX55, 2682021ZTPY011 and XJ2021KJZK004).

Advances on Asymmetric Construction of Diarylmethine Stereocenters

Shang Yang, Xiao Jian*, Wang Yawen, Peng Yu*   

  1. School of Life Science and Engineering, Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, Southwest Jiaotong University, Chengdu 610031
  • Supported by:
    National Natural Science Foundation of China (Nos. 21772078 and 22071200), the Science and Technology Department of Sichuan Province (No. 2020JDRC0021) and the Fundamental Research Funds for the Central Universities (Nos. 2682020CX55, 2682021ZTPY011 and XJ2021KJZK004).

二芳基次甲基结构单元广泛存在于具有重要生理和药理活性的天然产物和药物当中. 同时, 该结构单元中所特有的二芳基次甲基立体中心的对映选择性构筑往往也是天然产物全合成的难点和挑战性所在. 因此, 引起了众多有机合成化学家的研究兴趣. 近年来, 该手性立体中心的构建方法发展迅速, 新方法和新反应的报道也层出不穷; 开发出来的一些高效催化剂, 展示出独特的催化活性和选择性. 本文根据反应类型的不同, 将其分为不对称共轭加成反应和不对称氢化反应等六类, 综述近十年来二芳基次甲基立体中心的不对称构建方法, 及相关方法在天然产物全合成中的应用. 最后, 我们从全合成的角度进一步总结和分析未来构建二芳基次甲基手性立体中心的发展趋势, 力求发展更加高效、避免贵金属的催化剂及环境友好型的新方法和新试剂.

关键词: 二芳基次甲基, 不对称合成, 天然产物, 共轭加成, 偶联反应

Diarylmethine structure units are widely present in natural products and pharmaceuticals with important physiological and pharmacological activities. The enantioselective control of its stereogenic center, which is the most unique in this structure unit, has often become a difficulty and challenge during the research of total synthesis of natural products. Therefore, this field has attracted great interest to many metal-organic chemists and synthetic organic chemists. In recent years, the construction methods of this stereocenter have developed rapidly, and new reactions and reagents have emerged one after another, and some highly efficient catalysts have been invented, exhibiting unique catalytic activity and selectivity. In this review, according to the difference of reaction types, these methods can be divided into six types, such as asymmetric conjugate addition reaction (asymmetric 1,4-addition reactions involving aryl boronic acids, asymmetric 1,4-addition reactions involving aryl borates, enantioselective organocatalytic 1,4-addition reactions, asymmetric 1,4-conjugate addition induced by Evans chiral imide and asymmetric 1,6-conjugate addition of para-quinone methides), asymmetric allylation or propargylation of aromatic rings, transition metal-catalyzed asymmetric cross-coupling reaction, transition metal-catalyzed asymmetric C-H bond activation and functionalization, three-component reactions for asymmetric synthesis of 1,1-diaryl alkanes, asymmetric hydrogenation reactions for 1,1-diaryl alkanes, etc. This review aims to collect and summarize the asymmetric construction methods of diarylmethine stereogenic centers, and their applications in the total synthesis natural products in the past decade. Finally, from the perspective of total synthesis, we further summarize and analyze the future development trend for the construction of diarylmethine chiral stereogenic centers, and encourage young generation to develop new methods and reagents that can avoid precious metals/catalysts and therefore are more efficient and environmentally friendly. More importantly, we hope that the developments of these practical methodologies can be further applied to asymmetric total synthesis of natural products and medicines, and eventually solve the source problem of these “useful molecules” with potential medicinal value.

Key words: diarylmethine, asymmetric synthesis, natural products, conjugate addition, coupling reaction