Program on Chemical Biology , Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education , 54 Kamphaeng Phet 6, Laksi , Bangkok 10210 , Thailand.
J Org Chem. 2019 Dec 20;84(24):16222-16236. doi: 10.1021/acs.joc.9b02793. Epub 2019 Dec 4.
4-Chloroisocoumarins can be conveniently prepared from 2-alkynylaryloate esters via the activation of alkynes by electrophilic chlorine, generated in situ from -chlorosuccinimide (NCS) in the presence of 10 mol % trimethylsilyl chloride (TMSCl), which leads to 6--dig-selective chlorinative annulation to give the desired products in moderate to quantitative yields. The procedure employs readily available reagents and can be conveniently carried out on a wide scope of substrates under mild conditions (0 °C to rt). Furthermore, the reaction is scalable for gram-scale preparation of 4-chloroisocoumarins. Additionally, 4-bromo- and 4-iodoisocoumarins can be prepared in moderate to good yields by replacing NCS with -bromosuccinimide (NBS) and -iodosuccinimide (NIS), respectively.
4-氯异香豆素可通过炔烃的亲电氯活化，由-氯代琥珀酰亚胺（NCS）原位生成，在 10 mol%三甲基氯硅烷（TMSCl）存在下，从 2-炔基芳基酯方便地制备，这导致 6-二取代选择性氯化环化，以中等至定量收率得到所需产物。该方法采用易得的试剂，并可在温和条件下（0°C 至室温）方便地对广泛的底物进行。此外，该反应可用于克级规模制备 4-氯异香豆素。此外，用 -溴代琥珀酰亚胺（NBS）和 -碘代琥珀酰亚胺（NIS）分别代替 NCS，可以以中等至良好的收率制备 4-溴-和 4-碘异香豆素。
