Synthesis of polyfluoroalkylphosphorylated dihydroquinolines and dihydroisoquinolines decorated with N-acylethenyl substituents by the reaction of bis(polyfluoroalkyl)phosphonates with electron-deficient acetylenes and quinolines

Abstract

Dihydroquinolines and dihydroisoquinolines decorated with 2- or 4-polyfluoroalkylphosphoryl groups and N-acylethenyl, cyanoethenylphenyl substituents were synthesized in up to 91% yield via straightforward strategy including simultaneous catalyst- and solvent-free mild (room temperature, 0.2–20 h) N-ethenylation/C-phosphorylation of quinolines and isoquinolines with electron-deficient acetylene / bis(polyfluoroalkyl)phosphonate pairs. The structural interplay between 2 and 4-regioisomers was studied. The reaction with terminal acylacetylenes afforded N-acylethenyl-2-phosphoryl-1,2-dihydroquinolines of the E-configuration relative to the double bond. On the contrary, with cyanophenylacetylene, under similar conditions, a mixture of 1,2- and 1,4-regioisomers was formed (the N-ethenyl substituents having both the E- and Z-configuration) along with double phosphorylated bisadducts, 2,4-bis(polyfluoroalkylphosphoryl)-1,2,3,4-tetrahydro(iso)quinolines. The 1,4-isomers prove to be the thermodynamic products since they can be exclusively obtained by heating (70–75 °С) a mixture of 2- and 4-regioisomers. The synthesized compounds represent a new family of possible drug precursors.