C2‐(1 N/2 N‐Methyl‐tetrazole)methyl Ether (MeTetMe) as a Stereodirecting Group for 1,2‐trans‐β‐O‐Glycosylation

• Published in: European journal of organic chemistry 2021-11, Vol.2021 (41), p.5732-5745
• Main Authors: Rahaman Molla, Mosidur, Thakur, Rima
• Format: Article
• Language: English
• Subjects: Adducts; Carbohydrates; Cycloaddition; Directing groups; Ethers; Glycosides; Reagents; Selectivity; Stereoselective glycosylation; Stereoselectivity; Tetrazoles; trans-1,2-O-Glycosylation
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202100973

Development of stereoselective synthetic methods for O‐glycosides is of paramount importance in the field of glycochemistry. Therefore, we report herein (1 N/2 N)‐methylated tetrazole methyl (MeTetMe) ethers as a C2‐directing group for the formation of 1,2‐trans‐β‐O‐glycosides. The synthesis of the tetrazole moiety was readily achieved by a 3+2 cycloaddition reaction on nitrile functionality. The tethered thioglycoside donors were found to deliver the β‐O‐glycosides when activated by PIFA‐TfOH reagent system. The reactions were performed with six newly synthesized phenyl and ethyl thioglycosides to obtain the glycosylated adducts in moderate to high yields and excellent to exclusive β‐selectivity. The glycosylation method was easily scalable up to grams without affecting the yield and stereoselectivity. The MeTetMe group was efficiently removed under Birch reduction conditions without affecting the benzyl ethers or isopropylidene acetal protection. The C2‐(1 N/2 N)‐methylated tetrazole methyl (MeTetMe) ether directed stereoselective synthesis of 1,2‐trans‐β‐O‐glycosides is described. The strategy has been found successful for both gluco‐ and galacto‐ configured donors when glycosylated with a broad range of alcohols to yield adducts in high to exclusive stereoselectivity. The newly developed substituted methyl ether has been easily introduced from cyanomethyl ether precursor and efficiently removed under Birch reduction conditions.