Publisher Summary This chapter deals with the chemistry of five-membered ring fluorinated heterocycles. Fluorine and perfluoroalkyl groups positioned strategically in target molecules can considerably modify the chemical properties, biological activity, and selectivity. Fluoro-containing compounds play a significant role in medicinal and agricultural chemistry, as well as in material science. A number of fluoro and perfluoroalkyl-substituted pharmaceuticals, agrochemicals, dyes, and polymers are largely commercialized. Important differences in chemical reactivity of fluorinated compounds are based on the difference in: (1) carbon–fluorine, (2) carbon–hydrogen bond energy, and (3) electronegativity between fluorine and hydrogen. It is observed that fluorine introduced into biologically active molecules can block metabolism. There are two fundamentally different strategies, by which fluorine and perfluoroalkyl groups can be introduced into target molecules: (1) direct introduction that occurs by direct substitution of hydrogen by fluorine and perfluoroalkyl groups in a late step of the reaction sequence, and (2) introduction of fluorine and perfluoroalkyl groups by the application of fluorine-containing building blocks, derived from the readily available starting materials.

Fluoro Heterocycles with Five-Membered Rings

Elemental tellurium mediated synthesis of 2-(trifluoromethyl)oxazoles using trifluoroacetic anhydride as reagent

1,1‐Bis(ethylsulfanyl)perfluorobut‐1‐ene as Starting Material for the Synthesis of Substituted 2‐Trifluoromethylfurans and ‐pyrroles

Rhodium-catalyzed transformation of N-fluoroalkyl-1,2,3-triazoles in the presence of tert-butyl carbamate or water provided an efficient route to 2-fluoroalkyl imidazoles and 2-fluoroalkyl oxazoles, respectively. The treatment of N-fluoroalkyl-1,2,3-triazoles with excess water gave fluoroalkylated ketamides which were cyclized in situ to 2-fluoroalkyl oxazoles or thiazoles. Trifluoromethyl- and other difluoroalkyl-substituted heterocycles were obtained by the present method. The mechanism of this cascade transformation involving carbene insertion, HF elimination and cyclization was proposed.

General approach to 2-fluoroalkyl 1,3-azoles via the tandem ring opening and defluorinative annulation of N-fluoroalkyl-1,2,3-triazoles

Nucleophilic addition to N-phosphinylimines by rare-earth-metal triflate/trifluoroacetic anhydride activation.

Defluorination of polyfluorinated acylimines by zinc on heating in dioxane gave polyfluorinated oxazoles. The behavior of polyfluorinated oxazoles in nucleophilic substitution was studied.

Synthesis and properties of polyfluorinated oxazoles

Synthesis of N-methyl-2,5-bis(Trifluoromethyl)pyrroles

Cycloaddition reactions of norbornadiene with fluorinated heteroaddends (hexafluoro-acetone, dichlorotetrafluoroacetone, trifluoroacetonitrile, and N-trifluoroacetylhexafluoro-propan-2-imine) were studied. As a rule, the reactions follow the concerted mechanism. The reaction with bis(trifluoromethyl)ketene gave a mixture of tricyclene [2+2]- and [2+2+2]-cyclo-adducts formed along different pathways.

T. D. Truskanova

Papers

Synthesis and properties of polyfluorinated oxazoles

Synthesis of N-methyl-2,5-bis(Trifluoromethyl)pyrroles

Cycloaddition of norbornadiene to fluorine-containing heteroaddends

Cycloaddition of Norbornadiene to Fluorine‐Containing Heteroaddends.

Synthesis and Properties of Polyfluorinated Oxazoles.