Convenient synthesis of epimeric indolizidines by the intramolecular 1,3-dipolar cycloaddition of a sugar derived N-(3-alkenyl)nitrone

The stereoselective synthesis of two epimeric penta-hydroxylated indolizidines was accomplished from 2,3:5,6-di-O-isopropylidene-α-d-mannofuranose and N-(2-methylpent-4-en-2-yl)hydroxylamine. The transformation of these substrates into the corresponding 7-oxa-1-azabicyclo[2.2.1]heptane by the intramolecular 1,3-dipolar cycloaddition was the key step of the synthesis. The adduct was transformed into the tricyclic ammonium salt by intramolecular N-alkylation. The tricyclic ammonium salt was converted to the target compounds by: (route 1) the catalytic hydrogenation; or (route 2) the reaction with sodium azide, followed by the enantioselective reduction of the resulting indolizidinone.