Improvement of the stereoselectivity of the glycosylation reaction with 2-azido-2-deoxy-1-thioglucoside donors

• A 6-O-chloroacetyl group on the thioglucopyranoside afforded higher α-selectivity.
• Several structural distinct acceptors were used.
• The nature of the acceptor was found to be critical to the stereoselectivity.

2-Azido-2-deoxy-1-thioglucoside donors with an electron withdrawing group at position 6 were employed to study the stereoselectivity of the glycosylation reaction with several acceptors, ranging from unhindered small primary alcohols to other sugars and steroids, using NIS/TfOH as promoter. p-Tolyl 2-azido-3,4-di-O-benzyl-6-O-chloroacetyl-2-deoxy-1-thio-α/β-D-glucopyranoside afforded the higher α-selectivity, showing that a stronger electron withdrawing ester at O-6 influenced the anomeric selectivity towards the 1,2-cis glucosides. The anomeric stereoselectivity was highly dependent on the acceptor.

Figure optionsDownload as PowerPoint slide