Synthesis of iminosugars via 1,3-dipolar cycloaddition reactions of nitrones to α,β-unsaturated sugar aldonolactones

1,3-Dipolar cycloaddition reactions of nitrones to α,β-unsaturated γ- and δ-lactones are presented. The special emphasis is placed on cycloadditions involving five-membered nitrones. Contrary to the additions involving δ-lactones, where only the exo approach of reactants is observed providing in many cases a single product, γ-lactones can add five-membered ring nitrones in both exo and endo mode. Moreover, in the case of γ-lactones, upon heating and prolongation of the reaction time, visible reversibility of the reaction is observed and, as the consequence, the formation of more stable, thermodynamic products is noticed. The energies of the 1,3-dipolar cycloaddition of cyclic nitrones with α,β-unsaturated lactones have been investigated through molecular orbital calculations to reproduce well the observed experimental facts. The usefulness of adducts obtained via cycloaddition reactions to the iminosugars synthesis is demonstrated by a large number of examples, since both components usually offer good regio- and stereoselectivity with the introduction of convenient functionalities. The strategy involves hydrogenolysis of the N–O bond followed by the construction of the desired iminosugar skeleton via intramolecular alkylation of the nitrogen atom.