Cyanomethyl (CNMe) ether: an orthogonal protecting group for saccharides.

Logical manipulation of protecting groups is one of the vital strategies involved in the synthesis of complex oligosachharides. As opposed to the robust permanent protecting groups, the chemoselective protection-deprotection processes on orthogonal protecting groups have facilitated the synthesis of the target molecules with higher effeciency. While the derivatives of benzyl ethers are the most popular orthogonal ether based protecting groups for hydroxyls, the exploration of methyl ethers for similar synthetic application is much limited. We herein report cyanomethyl (CNMe) ether as a readily synthesized orthogonal protecting group for saccharides. The ether moiety was rapidly removed under Na-naphthalenide conditions in good to excellent yields and was found to be compatible with other well-known benzyl/methyl/silyl ether and acetal protecting groups. Additionally, the CNMe group was observed to be tolerant to standard reagents used for the deprotection of ether, ester and acetal protecting groups. The protection and deprotection steps remained unaffected by the position of hydroxyl, the configuration of monosaccharides or the presence of olefins in the skeleton.

Cyanomethyl Ether as an Orthogonal Participating Group for Stereoselective Synthesis of 1,2-trans-ß-O-Glycosides.

Stereoselective formation of glycosidic linkages has been the prime focus for contemporary carbohydrate chemistry. Herein, we report cyanomethyl (CNMe) ether as an efficient and effective participating orthogonal protecting group for the stereoselective synthesis of 1,2-trans-ß-O-glycosides. The participating group facilitated good to high ß-selective glycosylation with a broad range of electron-rich and electron-deficient glycosyl acceptors. Detailed experimental and theoretical studies reveal the involvement of CNMe ether in the formation of a six-membered imine-type cyclic intermediate for the observed stereoselectivity. Rapid incorporation and selective removal of the CNMe ether group in the presence of benzyl ether and isopropylidene acetal protection have also been reported here. The nitrile group provided an opportunity for the glycodiversification through further derivatizations.