Zhou Zhanyu, Kasten Kevin, McKay Aidan P, Cordes David B, Smith Andrew D
EaStCHEM, School of Chemistry, University of St Andrews, St Andrews, Fife, KY16 9ST, UK.
Angew Chem Int Ed Engl. 2025 Jul 28;64(31):e202507126. doi: 10.1002/anie.202507126. Epub 2025 Jun 23.
The development of synthetic methods for the catalytic enantioselective preparation of planar chiral paracyclophane derivatives is of considerable interest to the synthetic community. To date, relatively few successful and effective organocatalytic approaches to this molecular class have been reported. This manuscript describes effective isothiourea catalysed acylative kinetic (KR) and dynamic kinetic resolution (DKR) approaches to the generation of a range of planar chiral paracyclophane macrocycles with excellent levels of enantioselectivity. Effective KR of configurationally stable planar chiral paracyclophanols with 12- and 13-membered ansa-chains is demonstrated (6 examples, s = up to 50) using 5 mol% of the isothiourea (R)-BTM and isobutyric anhydride. Application to configurationally labile macrocyclic phenols with 14 to 18-membered ansa-chains allows their effective acylative DKR, generating the desired products with excellent enantioselectivity (25 examples, up to 95% yield and 98:2 er).
用于催化对映选择性制备平面手性对环芳烷衍生物的合成方法的开发，引起了合成界的广泛关注。迄今为止，针对这类分子的成功且有效的有机催化方法报道相对较少。本文描述了有效的异硫脲催化的酰化动力学拆分（KR）和动态动力学拆分（DKR）方法，用于生成一系列具有优异对映选择性水平的平面手性对环芳烷大环化合物。使用5 mol%的异硫脲（R）-BTM和异丁酸酐，证明了具有12和13元桥链的构型稳定的平面手性对环芳烷醇的有效KR（6个实例，s高达50）。将其应用于具有14至18元桥链的构型不稳定的大环酚，可实现其有效的酰化DKR，以优异的对映选择性生成所需产物（25个实例，产率高达95%，对映体比例为98:2）。
