Synergistic solvent effect in 1,2-cis-glycoside formation

Construction of three continuous 1,2-cis-α-glucosidic linkages was achieved in optimized solvent system. High-throughput optimization was conducted, by using substrates protected by perdeuterated benzyl (Bn-d7) groups. It enabled facile evaluation of yield and stereoselectivity with 1H NMR and MALDI-TOF MS, respectively. We found that CHCl3 and ethereal solvent had a synergetic effect to enhance the α-selectivity. The optimized solvent systems in CHCl3/CPME and CHCl3/Et2O were applied to the linear synthesis of Glcα1→2Glcα1→3Glcα1→3Man (Glc3Man1), which was achieved in 86% overall stereoselectivity.