Aza‐Heterocyclic Building Blocks with In‐Ring CF2‐Fragment

Abstract Modern organic chemistry is a titan supporting and reinforcing pharmaceutical, agricultural, food and material science products. Over the past decades, the organic compounds market has been evolving to meet all the research demands. In this regard, medicinal chemistry is especially dependent on available chemical space as subtle tuning of the molecule structure is required to create a drug with relevant physicochemical properties and a remarkable activity profile. The recent rapid evolution of synthetic methodology to deploy fluorine has brought fluorinated compounds to the spotlight of MedChem community. And now unique properties of fluorine still keep fascinating more and more as its justified installation into a molecular framework has a beneficial impact on membrane permeability, lipophilicity, metabolic stability, pharmacokinetic properties, conformation, pKa, etc. The backward influence of medicinal chemistry on organic synthesis has also changed the landscape of the latter towards new fluorinated topologies as well. Such complex relationships create a flexible and ever‐changing ecosystem. Given that MedChem investigations strongly lean on the ability to reach suitable building blocks and the existence of reliable synthetic methods in this review we collected advances in the chemistry of respectful, but still enigmatic gem‐difluorinated aza‐heterocyclic building blocks.