Catalytic enantioselective synthesis of perfluoroalkyl-substituted b-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study
Catalytic enantioselective synthesis of perfluoroalkyl-substituted b-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study
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DOI：
10.1039/c9sc00390h
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发表时间：
2019-06-28
期刊：
影响因子：
8.4
通讯作者：
Smith, Andrew D.
中科院分区：
文献类型：
--
作者：
Antunez, Diego-Javier Barrios;Greenhalgh, Mark D.;Smith, Andrew D.
报道了以对称酸酐为烯醇酸铵前体和全氟烷基酮（R-F = CF3, C2F5, C4F9）通过异硫脲（HyperBTM）催化反应制备一系列全氟烷基取代β -内酯的对映选择性反应。优化后，使用C2F5-和c4f9取代的酮在室温下形成β -内酯具有高的非映对和对映选择性（26个例子，最高可达bbb95: 5 dr和>99:1 er），而使用cf3取代的酮在-78℃下形成最佳dr和er（11个例子，最高可达bbb95: 5 dr和>99:1 er）是必要的。通过开环衍生-内酯，以及两步转化得到全氟烷基取代的氧乙烷，证明了在不损失立体化学完整性的情况下。密度泛函理论计算，以及C-13天然丰度KIE研究，已被用于探索协同异步[2 + 2]-环加成途径优于逐步醛缩-内酯化过程的反应机理。
The enantioselective preparation of a range of perfluoroalkyl-substituted beta-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (R-F = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivity was observed for beta-lactone formation using C2F5- and C4F9-substituted ketones at room temperature (26 examples, up to >95 : 5 dr and >99 : 1 er), whilst -78 degrees C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to >95 : 5 dr and >99 : 1 er). Derivatisation of the beta-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside C-13 natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.