Synthesis of azabicycles via cascade aza-Prins reactions: accessing the indolizidine and quinolizidine cores

Abstract

The first detailed study of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access towards an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. Based upon our findings on the aza-Prins and aza-silyl-Prins cyclisations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclisation and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl- and amido- substituted azabicyclic products all being accessed through these highly diastereoselective processes