Sc(Ⅲ)催化硫醇对邻亚甲基苯醌的亲核加成反应合成邻羟基苄硫醚衍生物

Sc(Ⅲ) Catalyzed Nucleophilic Addition of in situ Generated ortho-Quinone Methides with Thiols:an Efficient Access to ortho-Hydroxybenzyl Thioethers

以2-[羟基(苯基)甲基]苯酚类化合物和简单的硫醇为原料,1,2-二氯乙烷为溶剂,在Sc(Ⅲ)促进下原位生成邻亚甲基苯醌,并发生亲核加成反应构建邻羟基苄硫醚.该反应在50℃下搅拌2 h即可完成,目标产物产率82%～95%.反应可放大至克级规模.

Ortho-hydroxybenzyl thioethers play a vital role in chemical biology as they have anti-oxidant and anti-inflammatory properties.o-Quinone derivatives is not only a variety of active and important intermediate,but also widely used in the synthesis of natural products and medicinal chemistry.In the present study,the Sc(Ⅲ)catalyzed nucleophilic addition to o-quinone methides by thiols for the synthesis of ortho-hydroxybenzyl thioethers was developed.The reactions could be carried out with different primary thiols,secondary thiols and benzothiols.For 2-[hydroxyl(phenyl)methyl]phenols,electron-withdrawing groups and electron-donating groups on aromatic rings could react smoothly to obtain corresponding products.The structures of the products were characterized by infrared spectra,proton nuclear magnetic resonance,carbon nuclear magnetic resonance and high resolution mass spectra.The prominent features of the present strategy are wide substrate scope,mild reaction conditions and moderate to good yields.Furthermore,the reaction could be scaled up to multigram scale.A preliminary series of control experiments has been analyzed and the study on the extension to para-hydroxybenzyl alcohols for the synthesis of para-hydroxybenzyl thioethers has been achieved.