Building bridges from flatland: synthetic approaches and applications of 2-aza- and 2-oxa-bicyclo[2.1.1]hexanes

The 2-azabicyclo[2.1.1]hexane (2-aza-BCH) and 2-oxabicyclo[2.1.1]hexane (2-oxa-BCH) motifs are bridged, saturated heterocycles with vast utility in medicinal chemistry, including isosteric replacement of phenyl rings and rigid replacements of pyrrolidines and tetrahydrofurans. Over the past decades, chemists have explored numerous routes for their preparation, allowing access to a variety of substitution patterns and a number of applications in the pharmaceutical sciences. This review acts as a roadmap of the synthetic routes to access these heterocycles, allowing for comparisions of these two exciting classes of saturated heterocycles whilst hopefully inspiring new directions in the field.