C2‐Cyanomethyl (CNMe) Ether‐Protected Glycosyl Trichloroacetimidate Donors for Stereoselective β‐O‐Glycosylations

• Published in: European journal of organic chemistry 2023-04, Vol.26 (15), p.n/a
• Main Authors: Rahaman Molla, Mosidur, Thakur, Rima, Aghi, Anjali, Kumar, Amit
• Format: Article
• Language: English
• Subjects: 1,2-trans-β-O-glycoside; Alcohols; C2-participating group; cyanomethyl ether; Glycosides; Oligosaccharides; Orthogonality; stereoselective glycosylation; Stereoselectivity; Synthesis; trichloroacetimidate donors
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300079

Stereoselective construction of glycosidic linkages have emerged as one of the pivotal aspects for the synthesis of complex oligosaccharide assemblies. We herein report C2‐cyanomethyl (CNMe) ether as a strong stereodirecting group on trichloroacetimidate glycosyl donors for the synthesis of 1,2‐trans‐β‐O‐glycosides. The developed donors bearing various arming and disarming protections along with C2‐CNMe ether delivered the glycosides in short reaction time, moderate to good yields and high to excellent stereoselectivities. Gluco‐ and galacto‐ configured donors were found compatible with an array of alcohols having varied reactivities. The orthogonality of the CNMe ether protection with silyl ether group has been further explored for sequential glycosylations. Cyanomethyl (CNMe) ether group has been reported as a stereodirecting C2‐protecting group on glycosyl trichloroacetimidate donors. The synthesized donors were activated by TMSOTf catalyst to obtain the β‐O‐glycosides in excellent stereoselectivities. The stereoselectivity was achieved in the presence of both arming and disarming protections on the donor as well as the acceptor handles. The donors have been extended in the synthesis of saccharides bearing consecutive β‐O‐linkages.