A synthesis of 6-azabicyclo[3.2.1]octanes. The role of N-substitution

Article abstract of DOI:10.1021/jo702444c

(Chemical Equation Presented) The intramolecular cyclization reactions of aziridines with π-nucleophiles can be a useful route to a number of heterocyclic and carbocyclic ring systems. We were particularly interested in the use of this cyclization reaction for the synthesis of 6-azabicyclo[3.2.1] octanes. We report here the development of a new synthesis of the aziridine necessary for the aziridine-π-nucleophile cyclization. We also report on the cyclization of aziridines with three different substitutions on the aziridine nitrogen. We have found that N-diphenylphospinyl and N-H aziridines, while participating in the initial ring-opening reaction, do not lead to the desired bicyclic ring systems. In contrast, a nosyl group on the aziridine nitrogen leads efficiently to the bicyclic ring system and can be readily deprotected.