Pd-catalyzed direct S−C cross-coupling with glycosyl 1-thioacetates to synthesize thioglucoside analogues of gliflozins

In this study, we developed a green method for direct S−C cross-coupling between glycosyl 1-thioacetates and aryl iodides under mild conditions, affording S−C cross-coupling products in excellent yields. The cross-coupling reactions typically proceeded at 50 °C in DMF for 2–6 h, catalyzed by 2–8 mol% of PdG 3 -XantPhos with K 2 CO 3 as a base. We further demonstrated that the expensive Pd-catalyst and unreacted raw materials could be conveniently recycled through simple extraction and crystallization operations. The method was subsequently applied to the efficient synthesis of thioglucoside analogues of gliflozins, which are promising SGLT2 inhibitors with potential applications as antidiabetic drugs.