Experimental Section
General. Melting points were measured using a Reichert melting point apparatus and are uncorrected. Infra-Red spectra were recorded on a Perkin-Elmer 881 instrument. Nuclear magnetic resonance spectra were obtained using BRUKER AC 400 spectrometer (1H, 400 MHz, 13C, 100 MHz). Chemical shifts (• values) are expressed in parts per million (ppm) with solvents as internal standards and coupling constants (J) are expressed in Hertz. Mass spectra were recorded with a Hewlett Packard 5989B instrument and high resolution mass spectra (HRMS) were performed with a Q-TOF micromass. Chromatography was performed using silica gel 60 (230-400 mesh) and thin layer chromatography (TLC) was performed on silica gel 60PF254 plates. Compounds were identified using UV fluorescence (• = 254 nm) and/or staining with a 5% phosphomolybdic acid solution in ethanol following by heating. Commercially reagents were used as received from the manufacturers except for tetrahydrofuran (distilled from potassium/benzophenone) and dichloromethane (dried over calcium hydride prior to use).
General procedure for the preparation of iodides
To a stirred solution of the appropriate alcohol (1.02 mmol) in a 3/2 mixture of diethyl ether/acetonitrile (15 mL) at 0 °C or in toluene (15 mL) at 20 °C were successively added imidazole (2.25 mmol), iodine (2.45 mmol) and triphenylphosphine (2.04 mmol). The stirring was maintained for 1 h at 0 °C and then for 24 h at 20 °C or directly at 20 °C for 24 h when toluene was used. The reaction was quenched by addition of a 10% aqueous sodium thiosulfate solution (6 mL) followed by saturated aqueous ammonium chloride solution (3 mL). The organic layer was extracted with ether, washed with a 10% aqueous sodium thiosulfate solution until the solution became colourless. Then it was washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography using as solvents a mixture of ethyl acetate/cyclohexane to afford the corresponding iodide.
General procedure for reduction of esters: method A with LiBH4 in THF
To a stirred solution of the appropriate ester (1.04 mmol) in anhydrous tetrahydrofuran (20 mL), at 0 °C and under argon atmosphere, was dropwise added a 2.0 M lithium borohydride solution (1.56 mmol) in tetrahydrofuran. The resulting mixture was stirred for 12 h at 20 °C, quenched by addition of saturated aqueous ammonium chloride solution (1.0 mL). After extraction with ethyl acetate, the organic layer was washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was then purified by flash column chromatography (ethyl acetate/cyclohexane) to afford the corresponding alcohol.
General procedure for reduction of esters: method B with LiBH4 in THF/EtOH
To a stirred solution of ester (1.56 mmol) in tetrahydrofuran/ethanol (v/v 1/9), at 0 °C and under argon atmosphere was dropwise added a 2.0 M lithium borohydride solution (0.78 mmol) in tetrahydrofuran. The resulting mixture was stirred for 12 h at 20 °C, and the reaction was stopped
