EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Chemistry. 2019 Feb 21;25(11):2816-2823. doi: 10.1002/chem.201805631. Epub 2019 Jan 28.
An operationally simple isothiourea-catalysed acylative kinetic resolution of unprotected 1,1'-biaryl-2,2'-diol derivatives has been developed to allow access to axially chiral compounds in highly enantioenriched form (s values up to 190). Investigation of the reaction scope and limitations provided three key observations: i) the diol motif of the substrate was essential for good conversion and high s values; ii) the use of an α,α-disubstituted mixed anhydride (2,2-diphenylacetic pivalic anhydride) was critical to minimize diacylation and give high selectivity; iii) the presence of substituents in the 3,3'-positions of the diol hindered effective acylation. This final observation was exploited for the highly regioselective acylative kinetic resolution of unsymmetrical biaryl diol substrates bearing a single 3-substituent. Based on the key observations identified, acylation transition state models have been proposed to explain the atropselectivity of this kinetic resolution.
已开发出一种操作简单的异硫脲催化的未保护 1,1'-联芳基-2,2'-二醇衍生物的酰基化动力学拆分方法，可用于以高度对映体富集的形式获得轴手性化合物（s 值高达 190）。对反应范围和限制的研究提供了三个关键观察结果：i）底物的二醇基序对于良好的转化率和高 s 值是必不可少的；ii）使用α,α-取代的混合酸酐（2,2-二苯基乙酸新戊酸酐）对于最小化二酰化并获得高选择性至关重要；iii）二醇中 3,3'-位的取代基的存在阻碍了有效酰化。最后一个观察结果被用于高度区域选择性酰化动力学拆分具有单个 3-取代基的不对称联芳基二醇底物。基于确定的关键观察结果，提出了酰化过渡态模型来解释这种动力学拆分的对映选择性。
