School of Pharmaceutical Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Nat Commun. 2019 Jul 11;10(1):3062. doi: 10.1038/s41467-019-10878-7.
Axially chiral biaryl amino-alcohols play a pivotal role in organic synthesis and drug discovery. However, only a very few enantioselective methods have been reported to synthesize chiral biaryl amino-alcohols. Therefore, the rapid enantioselective construction of optically active biaryl amino-alcohols still remains a formidable challenge. Here we report an N-heterocyclic carbene (NHC)-catalyzed atropoenantioselective acylation of biphenols triggered by a cooperative strategy consisting of desymmetrization followed by kinetic resolution. This protocol features broad substrate scope and good functional group tolerance, and allows for a rapid construction of axially chiral biaryl amino-alcohols in good to high yields and with excellent enantioselectivities. Furthermore, the structurally diverse axially chiral biaryl amino-alcohol derivatives provide multiple possibilities for chemists to develop catalysts or ligands for different chemical transformations.
轴手性联芳基氨基醇在有机合成和药物发现中起着至关重要的作用。然而，只有极少数对映选择性方法被报道用于合成手性联芳基氨基醇。因此，快速对映选择性构建光学活性联芳基氨基醇仍然是一个巨大的挑战。在这里，我们报道了一种 N-杂环卡宾 (NHC) 催化的在手性轴控制下的联苯酚的酰化反应，该反应是通过一个包含去对称化和动力学拆分的协同策略触发的。该方案具有广泛的底物范围和良好的官能团容忍性，可以快速构建具有良好到高收率和优异对映选择性的轴手性联芳基氨基醇。此外，结构多样的轴手性联芳基氨基醇衍生物为化学家们提供了多种可能性，可以开发用于不同化学转化的催化剂或配体。
