Cu(I)-Catalyzed Stereoselective Glycosylation of “Electron-Deficient” Glycals

An efficient and
mild Cu­(I)-catalyzed Michael-type conjugate addition
for 2-nitro glycals to access O-, S-, and C-glycosides with high stereoselectivity is
reported. Under optimized conditions, nitrogalactals achieved high
α-selectivity, whereas nitroglucal predominantly gave β-selective
glycosides. The method is further demonstrated with other Michael-type
substrates, including 2-formyl glycals and 3-keto glycals. Initial
mechanistic investigations using NMR and supported by DFT calculations
suggest that the reaction proceeds via a preorganized complex that
positions the nucleophile close to the double bond to promote the
Michael-type addition, in a manner analogous to enzyme-catalyzed processes.
Moreover, the versatility of this synthetic approach was exemplified
in the stereoselective synthesis of a mucin-type glycopeptide and
the chemoselective one-pot synthesis of a trisaccharide.