School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Angew Chem Int Ed Engl. 2021 Nov 22;60(48):25313-25317. doi: 10.1002/anie.202112180. Epub 2021 Nov 2.
Benzothiophenes are valuable heterocycles that are widely used in medicines, agrochemicals, and materials science. Herein, we report a general method for the synthesis of enantioenriched 2,3-disubstituted benzothiophenes via a transition-metal-free C2-alkylation of benzothiophenes with boronic esters. The reactions utilize benzothiophene S-oxides in lithiation-borylations to generate intermediate arylboronate complexes, and subsequent Tf O-promoted S-O bond cleavage to trigger a Pummerer-type 1,2-metalate shift, which gives the coupled products with complete enantiospecificity. Primary, secondary and tertiary alkyl boronic esters and aryl boronic esters are successfully coupled with a range of C3-substituted benzothiophenes. Importantly, this transformation does not require the use of C3 directing groups, therefore it overcomes a major limitation of previously developed transition-metal-mediated C2 alkylations of benzothiophenes.
苯并噻吩是一类具有重要价值的杂环化合物，广泛应用于医药、农药和材料科学领域。在此，我们报告了一种通过无过渡金属催化的苯并噻吩与硼酸酯的 C2-烷基化反应来合成对映体富集的 2,3-二取代苯并噻吩的通用方法。该反应利用苯并噻吩 S-氧化物的锂化-硼化反应来生成芳基硼酸酯中间体，随后 TfO 促进 S-O 键断裂，引发 Pummerer 型 1,2-金属迁移，从而以完全对映选择性得到偶联产物。伯、仲和叔烷基硼酸酯以及芳基硼酸酯都能与一系列 C3-取代的苯并噻吩顺利偶联。重要的是，这种转化不需要使用 C3 导向基团，因此克服了先前开发的过渡金属介导的苯并噻吩 C2 烷基化反应的一个主要限制。
