Olifir O. Novel Fluorinated Cycloalkane Derivatives as Building Blocks for Bioorganic and Medicinal Chemistry

Fluorinated functionalized derivatives of cyclobutane, cyclopentane, and spiro[3.3]heptane The aim of this work was to develop efficient synthetic approaches to novel fluorinated alicyclic compounds, particularly derivatives of cyclobutane, cyclopentane, and spiro[3.3]heptane, and to determine their physicochemical properties for their rational application as fluorinated building blocks in medicinal chemistry. Organic synthesis, ¹H, ¹³C, and ¹⁹F NMR spectroscopy, mass spectrometry, chromatography, and X-ray diffraction analysis. The practical significance of the dissertation lies in the development of efficient approaches to the preparation of saturated fluorinated carbocyclic and spirocyclic building blocks with promising applications in medicinal chemistry. Of particular practical value are the determined physicochemical trends for a series of 6-(trifluoromethyl)spiro[3.3]heptane derivatives. Determination of pKₐ and logP values and comparison with the corresponding parameters of non-fluorinated, monofluorinated, and gem-difluorinated analogues made it possible not only to characterize the properties of individual compounds but also to formulate practical rules for substituent selection based on the desired physicochemical properties. The scientific novelty of the obtained results consists in the development of preparative methods for the synthesis of novel gem-difluorinated derivatives of cyclobutane, cyclopentane, and 6-(trifluoromethyl)spiro[3.3]heptane, determinations the influence of fluorinated substituents on the acid–base and lipophilic properties of the synthesized compounds and elucidated the structural features of selected representatives of the 6-(trifluoromethyl)spiro[3.3]heptane series. The work also provides valuable insights into the spatial and stereochemical characteristics of the obtained compounds. In particular, the feasibility of preparing enantiomerically pure 6-(trifluoromethyl)spiro[3.3]heptane derivatives possessing axial chirality was demonstrated, while the absolute configuration of the corresponding bromoanilide derivatives was unequivocally established by single-crystal X-ray diffraction analysis. Field of application: organic, bioorganic and medicinal chemistry.