A new generation of saturated benzene mimetics, 2‐oxabicyclo[2.1.1]hexanes, was developed. These compounds were designed as analogues of bicyclo[1.1.1]pentane with an improved water solubility. Crystallographic analysis of 2‐oxabicyclo[2.1.1]hexanes revealed that they occupy a novel chemical space, but, at the same time, resemble the motif of meta‐disubstituted benzenes.

A practical synthetic approach to the difluoro-substituted bicyclo[1.1.1]­pentanes was developed. The key step was an addition of difluorocarbene (:CF2) to electron-rich bicyclo[1.1.0]­butanes by the CF3TMS/NaI system. The obtained difluoro-bicyclo[1.1.1]­pentanes are suggested to be used as saturated bioisosteres of benzene rings for the purpose of drug discovery projects.

Difluorocyclopropane-containing building blocks for drug discovery were synthesized from the functionalized alkenes and TMSCF /NaI. Novel fluorinated acids, amines, amino acids, alcohols, ketones and sulfonyl chlorides were obtained.

A practical synthesis of 2,4-methanopyrrolidines was elaborated. The key synthetic step was an intramolecular photochemical [2 + 2]-cycloaddition of an acrylic acid derivative in flow. In spite of a higher molecular weight, 2,4-methanopyrrolidines were shown to have higher solubility in water and lower lipophilicity than pyrrolidines, important characteristics of bioactive molecules in drug design.

A series of GABA analogs and related mono‐ and bifunctional building blocks based on the monofluorinated 1,3‐disubstituted cyclobutane scaffold was designed and synthesized. The synthetic approaches included desilylative deoxyfluorination of TMS‐protected cyanohydrin and iodofluorination of methylenecyclobutane carboxylate as the key steps. Both approaches were highly efficient for the multigram synthesis of γ‐ and δ‐amino acids, monoprotected diamines, amino alcohols, and hydroxy acids. The first method was diastereoselective (dr 3:1) but it failed to produce the target products as pure, separable diastereomers. On the contrary, the second approach lacked diastereoselectivity but provided pure cis and trans isomers of the corresponding fluorocyclobutanes by separation of diastereomers; the products were obtained on up to 100 g scale in a single run. Moreover, the method was applied for the preparation of 3‐azabicyclo[3.1.1]heptane derivatives. X‐ray diffraction studies showed that the synthesized building blocks are appropriate analogs of GABA with either somewhat larger or smaller size as compared to the parent amino acid.