Hetero[3.1.1]propellanes.

[n.1.1]Propellanes are key precursors to bicyclo[n.1.1]alkanes, rigid small-ring hydrocarbons that have emerged as important building blocks in contemporary drug design as bioisosteres for disubstituted benzene rings. [n.1.1]Propellanes 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 [3.1.1]propellanes 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 hetero[3.1.1]propellanes undergo a range of radical ring-opening reactions, affording bridged heterocycles that are of high utility in drug-discovery programmes.