Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis. (30th August 2019)

• Record Type: Journal Article
• Authors: Nakatsuji, Yuya; Kobayashi, Yusuke; Takemoto, Yoshiji
• Is Part Of: Angewandte Chemie. Volume 131:Number 40(2019)
• Page Start: 14253
• Page End: 14257
• Publication Date: 2019-08-30
• Subjects: Brønsted-Säurekatalyse -- Glykosylierungen -- Kohlenhydrate -- Organokatalyse; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201907129
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The direct 2‐deoxyglycosylation of nucleophiles with glycals leads to biologically and pharmacologically important 2‐deoxysugar compounds. Although the direct addition of hydroxyl and sulfonamide groups have been well developed, the direct 2‐deoxyglycosylation of amide groups has not been reported to date. Herein, we show the first direct 2‐deoxyglycosylation of amide groups using a newly designed Brønsted acid catalyst under mild conditions. Through mechanistic investigations, we discovered that the amide group can inhibit acid catalysts, and the inhibition has made the 2‐deoxyglycosylation reaction difficult. Diffusion‐ordered two‐dimensional NMR spectroscopy analysis implied that the 2‐chloroazolium salt catalyst was less likely to form aggregates with amides in comparison to other acid catalysts. The chlorine atom and the extended π‐scaffold of the catalyst played a crucial role for this phenomenon. This relative insusceptibility to inhibition by amides is more responsible for the catalytic activity than the strength of the acidity. Abstract : Nicht sehr gesellig : Die direkte 2‐Desoxyglykosylierung von Amiden mit Glykalen gelang mithilfe eines neu entworfenen 2‐Chlorazolium‐Salzes als Brønsted‐Säurekatalysator, das eine geringere Wahrscheinlichkeit als andere Säurekatalysatoren zeigt, Aggregate mit Amiden zu bilden. Diese geringe Anfälligkeit für eine Inhibition durch Amide trägt wohl mehr zur katalytischen Aktivität bei als die Säurestärke.