Efficient Synthesis of α-Glycosyl Chlorides Using 2-Chloro-1,3-dimethylimidazolinium Chloride: A Convenient Protocol for Quick One-Pot Glycosylation

A mild and convenient method for the synthesis of -glycosyl chlorides in high 80-96% yields within 15-30 min using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) is disclosed. The method has a wide substrate scope and is compatible with labile OH protecting groups, including benzyl, acetyl, benzoyl, isopropylidene, benzylidene, TBDMS (tert-butyldimethylsilyl), and TBDPS (tert-butyldiphenylsilyl) groups. The excellent selectivity obtained in this reaction is attributed to in-situ isomerization of -glycosyl chlorides to the more stable -glycosyl chlorides, as demonstrated by H-1 NMR spectroscopic studies. Disarmed sugars with OBz or OAc groups at C-2 were chlorinated at a faster rate but ismomerized () at a slower rate than armed sugars with an OBn group at C-2. More importantly, the method enables highly desirable one-pot glycosylation reactions to take place, thus allowing efficient syntheses of disaccharides and simple O-glycosylated sugars in high overall yields without the need for separation or purification of the -glycosyl chloride donors. This method will be especially useful for direct glycosylation reactions using glycosyl chloride donors that are unstable upon separation and purification.