With the wide spread of the bioisosteric replacement approach in medicinal chemistry, the demand for new functional groups allowing fine-tuning of desirable properties of potential drugs has increased considerably. We propose 3,3-difluoroxetan-2-yl (3,3-diFOx) as a promising fluorinated substituent and non-classical isostere of numerous functional groups. We have shown that functionalized derivatives with 3,3-diFOx moiety mounted onto an aromatic or saturated heterocyclic ring can be prepared in multigram quantities (up to 64 g scale in a single run).