Iterative Synthesis of 2‐Deoxyoligosaccharides Enabled by Stereoselective Visible‐Light‐Promoted Glycosylation

• Published in: Angewandte Chemie International Edition Vol. 61; no. 20; pp. e202114726 - n/a
• Main Authors: Liu, Kai‐Meng, Wang, Peng‐Yu, Guo, Zhen‐Yan, Xiong, De‐Cai, Qin, Xian‐Jin, Liu, Miao, Liu, Meng, Xue, Wan‐Ying, Ye, Xin‐Shan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 09-05-2022
• Edition: International ed. in English
• Subjects: 2-Deoxyglycosides; Alcohols; Alcohols - chemistry; Alkenes; Alkenes - chemistry; Bromine Radical; Digoxin; Glycosylation; Intermolecular Hydroetherification; Light; Linkages; Photoreaction; Stereoselectivity; Substrates; Synthesis; Stereoselectivity; 2-Deoxyglycosides; Intermolecular Hydroetherification; Bromine Radical; Photoreaction
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202114726

The photoinitiated intramolecular hydroetherification of alkenols has been used to form C−O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. We herein report the visible‐light‐promoted 2‐deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.6). This method was suitable for a wide array of substrates and displayed good reaction yields and excellent stereoselectivity. The value of this protocol was further demonstrated by the iterative synthesis of 2‐deoxyglycans with α‐2‐deoxyglycosidic linkages up to a 20‐mer in length and digoxin with β‐2‐deoxyglycosidic linkages. Mechanistic studies indicated that this reaction involved a glycosyl radical cation intermediate and a photoinitiated chain process.
A fast photoglycosylation is reported that proceeds through a bromide‐based hydrogen species and electron transfer process. The value of this protocol was well demonstrated by the iterative synthesis of oligosaccharides on a gram scale as well as digoxin and a 20‐mer deoxyglycan in good yields and with excellent stereoselectivity.