Abstract n .1.1Propellanes are key precursors to bicyclo n .1.1alkanes, rigid small-ring hydrocarbons that have emerged as important building blocks in contemporary drug design as bioisosteres for disubstituted benzene rings. n .1.1Propellanes featuring heterocyclic rings could enable the direct synthesis of a wide diversity of bridged bicyclic heterocycles, which should exhibit superior physicochemical profiles compared to their established carbocyclic analogues. Here we report the unified synthesis of a family of heterocyclic 3.1.1propellanes featuring oxygen, nitrogen and sulfur heteroatoms in the three-carbon bridge. The approaches we have developed are necessarily distinct from the established routes to carbocyclic propellanes, and utilize a common precursor that is conveniently assembled on a multigram scale via rhodium-catalysed cyclopropanation. These hetero3.1.1propellanes undergo a range of radical ring-opening reactions, affording bridged heterocycles that are of high utility in drug-discovery programmes.
Revie et al. (Wed,) studied this question.