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

Abstract

A mild and convenient method for the synthesis of α‐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 α selectivity obtained in this reaction is attributed to in‐situ isomerization of β‐glycosyl chlorides to the more stable α‐glycosyl chlorides, as demonstrated by 1H NMR spectroscopic studies. Disarmed sugars with OBz or OAc groups at C‐2 were chlorinated at a faster rate but ismomerized (β→α) 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 α‐glycosyl chloride donors. This method will be especially useful for direct glycosylation reactions using glycosyl chloride donors that are unstable upon separation and purification.

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