Fiorenza Viani

EPC synthesis of gem-difluorocyclopentane derivatives

Abstract gem-Difluorocyclopentane derivatives were obtained in optically pure form by thermal or photochemical radical cyclization of the coresponding haloalkenes. Reductive or thermal elimination of the chiral auxiliary and appropriate elaborations afforded some difluoromethyl-cyclopentanols and -cyclopentantriols. The structure of the compounds was elucidated on the basis of 1H, 13C and 19F NMR data and of NOE difference experiments.

Synthesis of optically pure α-methylene-γ-lactones from (+)-R-(4-methylphenyl)-alkylsulphoxides

Abstract Optically pure (+)-R-(4-methylphenyl)sulphoxides were lithiated and alkylated with lithium α-bromomethyl acrylate with medium to high diastereoselection; condensation products gave in two steps optically pure α-methylene-γ-lactones.

A new versatile fluorinated C4 chiron

Abstract Optically pure 2-(fluoromethyl)-2-[(4-methylphenylsulphinyl)methyl]oxirane has been obtained in good yield and with high d.e. by reacting diazomethane with optically pure 1-fluoro-3-(4-methylphenylsulphinyl)propan-2-one. Regio- and stereo-selective openings of oxirane ring performed with selected nucleophiles afforded several useful derivatives.

Intramolecular trapping of difluoroalkyl radicals by tethered olefin in the asymmetric synthesis of 2,4-disubstituted-3,3-difluorotetrahydrofurans

Abstract Optically pure propenyl ethers of 3-sulphenyl-, 3-sulphinyl-, and 3-sulphonyl-1-chloro-1,1-difluoropropan-2-ols were submitted to radical cyclization affording, with moderate to high diastereoselectivity. 3,3-difluorotetrahydrofurans containing in 2 and 4 positions various substituents. Detailed NMR analysis allowed to measure trans/cis ratios and to establish the structure of the products.

Synthesis of fluorinated chirons: Stereoselective oxirane formation by reaction of diazomethane on 1-fluoro-3-arylsulfinyl-2-propanone and ring opening by selected nucleophiles

Abstract (R)-1-fluoro-3-[(4-methylphenyl)sulfinyl]-2-propanone (1) reacts with diazomethane affording (S)-2-(fluoromethyl)-2-[(R)-(4-methylphenyl)sulfinyl]methyl oxirane (2) as the main product. The influence of reaction conditions (solvent, temperature) on the chemo-and stereoselectivity has been studied. Several elaborations of 2, including reactions on the chiral auxiliary and opening of the oxirane ring by carbon, nitrogen, oxygen, phosphorus and halogen nucleophiles, are described. Full structural elucidation of the products is provided.

Synthesis of optically pure fluoro- and gem-chlorofluoro-cyclohexane derivatives by intramolecular trapping of dihaloalkyl radicals.

Abstract gem -Chlorofluorocyclohexanols 8 bearing a methyl and a p-tolylsulphinyl substituent have been obtained in optically pure form by radical cyclization of the corresponding halo-alkenes 4 . Reductive dechlorination of both (6R)- and (6S)- 8 gave fluoroderivative (6R)- 9 , which through functional group elaborations gave the hydroxyfluoro- and trihydroxyfluoro-cyclohexane derivatives 12 and 15 .

Synthesis of optically pure difluoro- or chloro,fluoro-cyclohexanols and cyclopentanols

Abstract Starting from the secondary alcohols 1, cyclohexanols 2 having three (Xue5fbF) of four (Xue5fbCl) chiral centres on the ring can be obtained in optically pure form by intramolecular trapping of difluoroalkyl or chlorofluoroalkyl radicals (tributyltin hydride method). The diastereoselection of the process seems to be determined mainly by the stereochemistry at the carbons bearing the sulfinyl and the hydroxyl substituents. Optically pure difluoro- or chloro, fluoro-cyclopentanols can be obtained in the same way.

gem-Difluoro-cyclohexene and -cycloheptene derivatives through cyclization of gem-difluoroallyl radicals

Abstract 6-Alkoxy-7-chloro-7,7-difluoro-5-[( S )-(4-methylphenyl)sulfinyl]-1,5-heptadienes have been transformed, through chlorine atom abstraction by tributyltin radical, into the corresponding difluoroallyl radicals, which, via intramolecular trapping by the vinyl group and reduction of the cyclohexenylmethyl and cycloheptenyl radicals obtained, gave gem -difluoro-cyclohexene and -cycloheptene derivatives. Reduction of the intermediate difluoroallyl radical afforded the corresponding dechlorinated open-chain difluoro compounds as side-products.

Fast-atom bombardment mass spectrometry of some nucleoside analogs

A new series of thymine derivative acyclic nucleosides, with mono- or polyfluorosubstitution on the acyclic portion of the molecules have been studied by fast-atom bombardment mass spectrometry, with the aid of metastable ion studies and deuterium labelling experiments. The protonated molecules show four main metastable-supported fragmentation processes, consisting of loss of CX

Asymmetric synthesis of 3-chloro-3-fluoro- and 3-fluoro-2,4-disubstituted tetrahydrofurans by the “fluorinated sulfoxide chiron” route

Abstract An efficient procedure for the preparation of the title compounds in moderate to high enantiomeric purity has been realized starting from olefins tethered on the fluorinated sulfinyl chiron 6 , prepared from methyl 4-methylphenyl sulfoxide and ethyl dichlorofluoroacetate. Radical-promoted cyclization of intermediates 9 according to the tributyltin hydride method afforded 3-chloro-3-fluorotetrahydrofuran derivatives 12 , from which the corresponding 3-fluorotetrahydrofurans 15 were obtained by reductive dechlorination. Structural assignments have been done on the basis of 1 H, 13 C and 19 F NMR data and NOE difference experiments.