Efficient synthesis of α-glycosyl chlorides using 2-chloro-1,3-dimethylimidazolinium chloride : a convenient protocol for quick one-pot glycosylation

• Main Authors: Tatina, Madhu Babu, Khong, Duc Thinh, Judeh, Zaher M.A.
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Engineering::Chemical engineering::Biochemical engineering; Carbohydrates; Chlorine
• Online Access: https://hdl.handle.net/10356/139778
• Institution: Nanyang Technological University

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.