Stereoselective Assembly of 2-Deoxy-2-fluoroglycosides Enabled by Pyridinium Catalysis
Shi-Ang Zhai1, Zhiwei Ai1, Qinshuo Zhang1
1Key Laboratory of Advanced Carbon-Based Functional Materials (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou 350108, China.
Abstract:
2-Deoxy-2-fluoroglycosides are versatile chemical entities in glycoscience, functioning as enzyme probes, inhibitors, and valuable building blocks for bioactive glycomimetics. However, their efficient and stereoselective synthesis remains challenging. Herein, we report a pyridinium-salt-catalyzed highly stereoselective addition of an O-type glycosyl acceptor to 2-fluoroglycals, providing efficient access to a structurally diverse library of 2-fluoroglycosides. The excellent stereoselectivity favoring syn-addition and deuterated experimental results suggest a concerted mechanism. NMR titrations combined with DFT calculations demonstrate the presence of product inhibition and shed light on the reduced efficiency observed in the reactions involving electron-deficient phenols as well as alcoholic substrates.
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