Shavrina O. Pyridinyl- and pyrimidinyldifluoroacetic acids derivatives.

The dissertation is devoted to the development of convenient fluorination methods of the methylene link of pyridinyl- and pyrimidinylacetic acids derivatives, and their phosphorus analogues, pyridinylmethylphosphonic acids; investigation of the obtained compounds synthetic potential in the design of biologically promising molecules combining heterocyclic core (pyridine, pyrimidine, piperidine), difluoromethyl group and modifiable amine, alcohol, acid, imine and other functions in one structure. The process of electrophilic fluorination of pyridinyl-, pyrimidinylacetic acid derivatives and their phosphorus analogues with N-fluorobenzenesulfonimide in the presence of a base was investigated. The influence of the base’s nature on electrophilic fluorination has been established and two general fluorination procedures have been developed. The procedures include the use of strong organometallic bases, lithium silylamide and tert-butyl lithium, or weak inorganic base – lithium carbonate, which allow obtaining fluorinated derivatives with high yields, including selective mono- and gem-difluorination. The influence of the base’s nature on electrophilic fluorination with N-fluorobenzenesulfonimide in the presence of lithium carbonate was established and its mechanism was proposed. The reactivity of isomeric pyridinyl-, pyrimidinylacetatesand corresponding nitriles in mono- and gem-difluorination under the action of N-fluorobenzenesulfonimide was studied. The synthetic potential of fluorinated pyridinyl, pyrimidinylacetic, and pyridinylmethylphosphonic acids derivatives was demonstrated, their reduction by various types of reducing systems (H2 on Ni/Ra, Rh/C; BH3 /SMe2 ; LiAlH4 ; NaBH4 ), interactions with O-, P-, N -, S-centered nucleophiles and the chemical behavior of the obtained building blocks in cyclocondensation reactions were investigated.