Nature Chemistry, Published online: 01 June 2026; doi:10.1038/s41557-026-02173-y A strategy is developed that merges triplet nitrene-mediated ring expansion with titanium-catalysed cyanylation for the diastereoselective synthesis of vicinal tetrasubstituted cyclobutane amino nitriles. This strategy unlocks highly functionalized and congested three-dimensional cyclobutanes that could provide scaffolds for drug discovery but have previously been difficult to access.