Hetero[3.1.1]propellanes

Journal article

Abstract[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.

Authors: Revie, RI; Dasgupta, A; Biddick, Y; Christensen, KE; Smith, RC

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Chemistry
• Pages: 1-7
• Publication date: 2026-02-25
• Acceptance date: 2026-01-14
• DOI: 10.1038/s41557-026-02072-2
• EISSN: 1755-4349
• ISSN: 1755-4330
• Language: English
• Keywords: Bicyclic molecule; Aromaticity; Heteroatom; Benzene; Sulfur