Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (11): 1345-1359.DOI: 10.6023/A21080391 Previous Articles     Next Articles



李翼b, 徐明华a,b,*()   

  1. a 南方科技大学 化学系/深圳格拉布斯研究院 广东省催化化学重点实验室 深圳 518055
    b 中国科学院上海药物研究所 新药研究国家重点实验室 上海 201203
  • 投稿日期:2021-08-21 发布日期:2021-09-24
  • 通讯作者: 徐明华
  • 作者简介:

    李翼, 2009年毕业于武汉大学, 获理学学士学位; 2014年毕业于中国科学院上海药物研究所, 获理学博士学位(导师: 徐明华研究员); 同年留所工作, 任助理研究员. 2016~2018年, 入选上海药明康德“青年人才计划”, 在国内新药研发部担任药物化学项目负责人, 主持创新药物研发项目, 全面负责小分子药物的临床前研究、开发及临床申报工作. 2018年至今, 在美国得克萨斯大学医学分部从事博士后研究. 主要研究兴趣包括不对称合成方法学, 以及针对肿瘤和糖尿病等重大疾病的创新药物研究.

    徐明华, 南方科技大学化学系教授. 1999年博士毕业于中国科学院上海有机化学研究所, 先后在美国弗吉尼亚大学和乔治敦大学医学研究中心从事博士后研究; 曾任中国科学院上海药物研究所研究员、课题组长、博士生导师. 主要从事有机不对称合成及手性药物方面的研究, 致力于以一些重要有机分子及药物分子合成为导向的手性化学和手性技术探索, 发展高效不对称催化方法. 中国科学院“百人计划”、国家杰出青年科学基金获得者, 2016年获国家自然科学二等奖.

  • 基金资助:
    项目受国家自然科学基金(21971103); 广东省催化化学重点实验室(2020B121201002)

Applications of Asymmetric Petasis Reaction in the Synthesis of Chiral Amines

Yi Lib, Ming-Hua Xua,b()   

  1. a Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China
    b State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • Received:2021-08-21 Published:2021-09-24
  • Contact: Ming-Hua Xu
  • Supported by:
    National Natural Science Foundation of China(21971103); Guangdong Provincial Key Laboratory of Catalysis(2020B121201002)

Chiral amines are valuable constituents of many natural products, pharmaceuticals and functional materials, they are also widely utilized as versatile building blocks and important chiral catalysts as well as chiral auxiliaries in organic synthesis. Therefore, it is of great scientific significance and application value to develop efficient methods for the synthesis of structurally diverse chiral amines and chiral amine scaffolds. In 1993, Petasis and co-workers reported an efficient synthesis of allylic amines through a Mannich-type reaction of vinylboronic acids with secondary amines and paraformaldehyde, where the organoboron reagents served as the nucleophilic component. Since then, this three-component Petasis reaction of organoboron reagents with amines and carbonyl derivatives has been developed as an appealing and concise method to access various amines. The asymmetric Petasis reaction provides a facile and efficient route to optically active amines and thus has attracted much attention over the past two decades. In this review, we summarize the recent progress achieved in the synthesis of chiral amines by asymmetric Petasis reaction and provide an overview on the methods applied for stereochemical control. The strategies that have been employed for accessing enantioenriched amines, including various chiral substrate-based diastereoselective induction approaches and several recent developments of enantioselective catalysis. In a large number of asymmetric Petasis reaction cases, good to high levels of stereoselectivities can be achieved relying on the utilization of chiral amine source, chiral carbonyl substrates, and chiral organoboron reagents. In particular, chiral amines such as α-methylbenzylamines and chiral α-hydroxy aldehyde analogues have emerged as a broadly applicable class of substrates for asymmetric Petasis reaction. The most promising advance has been the success of catalytic asymmetric Petasis reaction for enantioselective synthesis of chiral amines in the last few years. Chiral bifunctional thioureas and binaphthols have been demonstrated to be effective organocatalysts. Finally, the perspectives on the relevant challenges and future directions in this field are also discussed.

Key words: Petasis reaction, chiral amine, boronic acid, asymmetric synthesis, asymmetric catalysis