Revisit of the phenol O-glycosylation with glycosyl imidates, BF3·OEt2 is a better catalyst than TMSOTf

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With BF3·OEt2 as the catalyst, the glycosylation of phenols with glycosyl trichloroacetimidates (or N-phenyl trifluoroacetimidates) bearing 2-O-participating groups leads to the desired 1,2-trans-O-glycosides in generally excellent yields without formation of the 1,2-cis-anomers. However, with TMSOTf as the catalyst, the outcomes of the corresponding phenol O-glycosylation are highly dependent on the nucleophilicity of the phenols; less nucleophilic is the phenol, higher amounts of the 1,2-cis-O-glycoside together with more side-products are generated. 1,2-Orthoesters have been found to be the major products at a low temperature (<−70°C) in all these phenol O-glycosylation reactions, which are transformed into the final products at a higher temperature. BF3·OEt2 is an effective catalyst to promote the conversion of 1,2-orthoesters into the corresponding 1,2-trans-O-glycosides. However, the 1,2-orthoesters could be converted into the dioxolenium triflate and glycosyl triflate in the presence of TMSOTf, these intermediates which might be in equilibrium with the glycosyl oxocarbenium related species lead to the final mixture of the α/β-O-glycosides and side-products.