Stereospecific Synthesis of Difunctionalized 2,5-Disubstituted cis-2,5-Dimethylpyrrolidine (Azetoxyl) Nitroxides by Oxidative Cleavage of Protected 8-Azabicyclooctane Precursors

Article abstract of DOI:10.1021/jo00213a028

Dimethylnortropinone nitroxide 6 was converted into bicyclic ketones 8-10.Rearrangement of the corresponding oxime derivatives 14 and 16 led, respectively, to lactams 18 and 19.Hydrolysis of 19 with concomitant oxidation gave the cis-azethoxyl nitroxide amino acid 20.Alternatively, reaction of 8 and 10 with BuLi followed by dehydration and ozonolysis of the resulting alkene mixture gave, respectively, cis-substituted pyrrolidines 26 and 29.From 29 the (somewhat unstable) cis-azetoxyl nitroxide diols 32 were prepared.A third method of cleavage of the bicyclic ring system was established by the route 10 -> 35 -> 36 -> 37.From 37 difunctionalized cis-azetoxyl nitroxides 40 and 41 were prepared.