Yang Gongming, He Yi, Wang Tianyi, Li Zhipeng, Wang Jian
School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Angew Chem Int Ed Engl. 2024 Jan 15;63(3):e202316739. doi: 10.1002/anie.202316739. Epub 2023 Dec 8.
Indole-based planar-chiral macrocycles are widely found in natural products and bioactive molecules. However, in sharp contrast to the preparation of indole-based axially chiral structures, the enantioselective catalysis of indole-based planar-chiral macrocycles is still a formidable task so far. Here we report an N-heterocyclic carbene (NHC)-catalyzed intramolecular atroposelective macrocyclization of 3-carboxaldehyde indole/pyrroles, featuring with broad substrate scope and good functional group tolerance, and allowing for a rapid access to diverse indole/pyrrole-based planar-chiral macrocycles with various tether-lengths (10-16 members) in good yields and with excellent enantioselectivities. Importantly, the indole-based macrocyclic structures with both planar and axial chirality were directly and efficiently obtained through this protocol with excellent enantioselectivities and diastereoselectivities. In addition, these synthesized planar-chiral macrocycles offer many possibilities for chemists to develop new catalysts or ligands, as well as new reactions.
基于吲哚的平面手性大环化合物广泛存在于天然产物和生物活性分子中。然而，与基于吲哚的轴手性结构的制备形成鲜明对比的是，到目前为止，基于吲哚的平面手性大环化合物的对映选择性催化仍然是一项艰巨的任务。在此，我们报道了一种由N-杂环卡宾（NHC）催化的3-醛基吲哚/吡咯的分子内阻转选择性大环化反应，该反应具有广泛的底物范围和良好的官能团耐受性，能够快速获得各种不同链长（10-16元）的基于吲哚/吡咯的平面手性大环化合物，产率良好且对映选择性优异。重要的是，通过该方法可以直接高效地获得同时具有平面手性和轴手性的基于吲哚的大环结构，且对映选择性和非对映选择性都非常出色。此外，这些合成的平面手性大环化合物为化学家开发新的催化剂或配体以及新反应提供了许多可能性。
