Merging pharmacophores. The merger of polar functional groups to new combined pharmacophores presents opportunities for new design options for medicinal chemists. We envisaged the mild functional group tolerant conditions of the deFS reaction would enable the installation of oxetanes to combinations of functional groups by employing a new range of nucleophiles to form attractive novel motifs. Moreover, the incorporation of oxetane with its similarity to the carbonyl functionality may provide further isosteres for acyl-derivatives of functional groups. Investigation of temperature and equivalents of nucleophiles allowed optimization for each nucleophile class (See SI for further details).