Selective Reductive Coupling of Formaldehyde into Carbohydrate Precursors.

Direct and highly selective conversion of formaldehyde to multicarbon (C2+) products is a highly desirable but challenging approach to synthesize carbohydrate precursors. In this study, we investigated the use of environmentally friendly imidazolium-based ionic liquids (ILs)-NHC to promote formaldehyde coupling under a base-free condition. The highly selective conversion of formaldehyde into glycolaldehyde precursor (GP) and dihydroxyacetone precursor was achieved through a one-pot, two-step process with [BHMIm][OAc] as a crucial intermediate. The maximum total yield of these two carbohydrate precursors reached 67.2% under optimized conditions. 1H-1H NOESY NMR experiments and DFT calculations revealed that hydrogen bonding between the acetate anion and the intermediate (or GP) plays a crucial role in substrate activation and conversion. Furthermore, NMR and mass spectrometry analyses demonstrated the formation of the intermediate, two carbohydrate precursors, and three carbohydrates, and thus, a potential reaction pathway was suggested. This study provides an appealing new route to stepwise construct C3 ∼ 4 products from C1 building blocks.