对映选择合成
化学
动力学分辨率
杂原子
利乐
催化作用
基质(水族馆)
组合化学
有机化学
药物化学
戒指(化学)
海洋学
地质学
作者
Shubham Agrawal,Pankaj Kumar Majhi,Alister S. Goodfellow,Raj Kumar Tak,Haoxiang Zhu,Haoxiang Zhu,Haoxiang Zhu,Michæl Bühl,Andrew David Smith
标识
DOI:10.1002/anie.202402909
摘要
A general and highly enantioselective method for the preparation of tetra‐substituted 3‐hydroxyphthalide esters via isothiourea‐catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)‐HyperBTM (5 mol%) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99%, 99:1 er). Substitution of the aromatic core within the 3‐hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3)‐, is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computation, with a key substrate heteroatom donor O•••acyl‐isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination.
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