Proton Relay Catalysis Enables the Synthesis of 2-Oxa- and 2-Azabicyclo[2.2.1]heptanes

Abstract

An effective binary catalytic system enables the synthesis of oxa- and aza-bicyclo[2.2.1]heptanes from cyclic γ-epoxy-alcohols. A combination of an aminotriphenolate Al(III) complex and a bromide salt delivers a wide variety of target compounds in good to excellent yields, with high diastereo-control. The mechanism includes a double-nucleophilic displacement at a carbon center via a proton-relay step involving the Al(III) complex phenolate, as supported by control experiments. Med-chem inspired synthons could successfully be obtained with the aza-bicyclo[2.2.1]heptanes.