Oxidative Activation of C-S Bonds with an Electropositive Nitrogen Promoter Enables Orthogonal Glycosylation of Alkyl over Phenyl Thioglycosides.

A method for the selective activation of thioglycosides that uses the N ⁺ -thiophilic reagent O-mesitylenesulfonylhydroxylamine (MSH) as a promoter is presented. The reaction proceeds via anomeric mesitylensulfonate intermediates, which could be isolated and fully characterized by placing a fluorine atom at the C2 position. In the presence of a soft Lewis acid, glycosylation reaction proceeds at ambient temperature with good yields. It is further demonstrated that it is possible to orthogonally activate S-ethyl in the presence of S-phenyl donors, enabling the design of sequential glycosylation strategies.