Intramolecular azide-alkene cycloaddition-elimination reaction in an aldohex-2-enonic acid derivative

A 6-azido-2-tosylenolate, obtained from D-glucono-1,5-lactone in six steps, underwent an intramolecular cycloaddition–elimination pathway under mild conditions, yielding a chiral, substituted 5,6-dihydro-4H-pyrrolo[1,2-c]-1,2,3-triazole. The conditions were optimized to give exclusive formation of the triazole. The mechanism appears to involve intramolecular ring closure via a 1,3-dipolar azide–alkene cycloaddition to give a 1,2,3-triazoline, followed by elimination of p-toluenesulfonic acid, leading to aromatization. Triazole products, obtained by chemical modification, are expected to display activity as enzyme inhibitors. Furthermore, partially protected derivatives of the 2-hexenoate were prepared as useful synthetic intermediates. [Display omitted] •Synthesis of a key intermediate methyl 2-hexenoate from d-gluconolactone.•Reaction of the 2,6-di-O-tosylhexenoate with azide gave a bicyclic triazole.•An intramolecular azide-alkene cycloaddition-elimination mechanism is proposed.•The bicyclic triazole and derivatives are potential enzyme inhibitors.•Derivatives prepared from the key 2-hexenoate are useful synthetic precursors.