A new synthesis of C-β-d-glycopyranosylmethyl sulfides by metal-free coupling of anhydro-aldose tosylhydrazones with thiols

Abstract

Herein, cross coupling reactions of O-peracylated 2,6-anhydro-aldose tosylhydrazones with aliphatic, (hetero)aromatic, and sugar-derived thiols were studied under thermal conditions in the presence of K₃PO₄. The reactions with aliphatic thiols provided the corresponding C-β-D-glycopyranosylmethyl sulfides in 20–50% yields, whereas the reactions with thiophenols gave the corresponding sulfides in 50–80% yields. On the other hand, sugar-derived thiols failed to yield the expected compounds with acceptable selectivity. The transformations present a new access to these types of glycomimetic compounds. The method is complementary to thiol–ene additions of exo-glycals (also obtained from the abovementioned tosylhydrazones) that provide good yields of aliphatic and sugar-derived C-glycosylmethyl sulfides. Thus, anhydro-aldose tosylhydrazones serve as a common starting material towards any kind of C-glycosylmethyl sulfide type target compounds either in a direct coupling reaction or in thiol–ene additions of exo-glycals.