Simple Synthesis of Some Pentafluoropropenyl Derivatives of Pyrimidine and Purine Based on Addition−Elimination Reaction

Abstract

Various pentafluoropropenyl derivatives of pyrimidine and purine bases have been obtained in good to high yield. The procedure involves the reaction of appropriate lithium derivatives prepared from both electron-rich and electron-poor pyrimidines, with the hexafluoropropene at a low temperature, via an addition-elimination process. Organolithiums of pyrimidine and purine bases give addition-elimination products as E/Z mixtures, whereas the products of the reaction of lithium amide of protected inosine with hexafluoropropene contain traces of an addition product as well as the stable perfluoroenamine. The methodology proposed allows a series of perfluorovinyl nucleobases to be obtained quickly and conveniently.

Fluorinated enamines of nucleobases as precursors of nucleoside analogues. Synthesis, spectroscopic and structural studies

“…In order to examine the intramolecular hydrogen bonding and to evaluate the sensitivity of the 1 H and 19 F shift values on the conformations of molecules, the 1 H and 19 F NMR spectra of tetrafluoropropenyl enamines of nucleobases have been investigated. A scheme depicting the postulated hydrogen bond interactions and atom numbering for selected compounds 2b and 6b is given in Fig.…”

“…The 1 H and 19 F NMR experiments were carried out in CDCl 3 and DMSO-d 6 . The choice of the NMR solvents was based upon their hydrogen bond profile.…”

“…In aromatic perfluoroalkene systems, the distortion of the planar structure induces a strong deshielding effect on C a -F. It can be explained by the diamagnetic anisotropy appearing due to the aromatic p-electron system. 15 Thus, 19 F NMR spectroscopy can be a very effective tool in investigation of conformations of the systems in which the fluoroalkenyl substituent can assume a coplanar or out-of-plane conformation with respect to the other part of the molecule, depending on the intra-and intermolecular interactions. Table 1 gives 19 F NMR data for compounds 2b-7b and 9b in the above-mentioned solvents.…”

“…15 Thus, 19 F NMR spectroscopy can be a very effective tool in investigation of conformations of the systems in which the fluoroalkenyl substituent can assume a coplanar or out-of-plane conformation with respect to the other part of the molecule, depending on the intra-and intermolecular interactions. Table 1 gives 19 F NMR data for compounds 2b-7b and 9b in the above-mentioned solvents. As expected, there are some differences in the chemical shift of C a -F in the E and Z stereoisomers; the signal of C a -F in the E stereoisomer is usually more deshielded than in C a -F in the Z stereoisomer because of the stronger interaction of the E-CF 3 group with the heteroring, and thus stronger steric repulsion.…”

Synthesis and applications of fluorinated nucleoside analogues

“…Wó jtowicz-Rajchel et al [129] obtained in 2006 various pentafluoropropenyl derivatives of pyrimidine bases substituted at C-5 and C-6 (compounds 326 and 329). The procedure involved the reaction of appropriate lithium derivatives prepared from both electron-rich 325 and electron-poor 328 pyrimidines, with the hexafluoropropene at a low temperature, via an additionelimination process.…”