Multivalent Aminoseptanose Mimetics by Copper-Catalyzed (3+2) Cycloadditions of Azidomethyl-Substituted Bicyclic 1,2-Oxazines

Abstract

Starting from readily available enantiopure azidomethyl-substituted bicyclic 1,2-oxazine derivatives and mono-, di- or trialkynes, their copper-catalyzed (3+2) cycloadditions furnished a series of 1,2,3-triazolyl-linked compounds in good yields. These click reactions proceeded smoothly at room temperature when copper iodide as catalyst was used in the presence of triethylamine and tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine as ligand. Generally, the unprotected bicyclic 1,2-oxazine derivatives seemed to show slightly higher reactivity and provided better yields compared with their silyl-protected counterparts. Exhaustive hydrogenolysis with cleavage of the 1,2-oxazine N-O bonds in the presence of palladium on charcoal as promotor is feasible but was found to be capricious. Reasonable results were obtained when acetic acid employed as cosolvent. By applying these conditions, several of the bicyclic 1,2-oxazine derivatives were successfully converted into the expected mono- or divalent aminooxepine derivatives which can be regarded as aminoseptanose mimetics.