diphenylphosphanylmethanethiol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Acetylglycine (1.90 g, 16.2 mmol) was dissolved in anhydrous DMF (75 mL). HOBt (2.48 g, 16.2 mmol) was added to the resulting solution followed by DCC (3.34 g, 16.2 mmol). Once precipitate (DCU) was observed, phosphinothiol 1b was added (3.77 g, 16.2 mmol). The reaction mixture was allowed to stir under Ar(g) for 3 h. The precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a white solid. This solid was dissolved in ethyl acetate and purified by flash chromatography (silica gel, ethyl acetate). Compound 51 was isolated in 96% yield. Spectral Data. As reported previously.4b The precipitate was removed by filtration the filtrate was concentrated under reduced pressure to give a white solid purified by flash chromatography (silica gel, ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Acetylglycine (1.90 g, 16.2 mmol) was dissolved in anhydrous DMF (75 mL). HOBt (2.48 g, 16.2 mmol) was added to the resulting solution followed by DCC (3.34 g, 16.2 mmol). Once precipitate (DCU) was observed, phosphinothiol 1b was added (3.77 g, 16.2 mmol). The reaction mixture was allowed to stir under Ar(g) for 3 h. The precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a white solid. This solid was dissolved in ethyl acetate and purified by flash chromatography (silica gel, ethyl acetate). Compound 51 was isolated in 96% yield. Spectral Data. As reported previously.4b The precipitate was removed by filtration the filtrate was concentrated under reduced pressure to give a white solid purified by flash chromatography (silica gel, ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 11b (17.27 g, 63.0 mmol) was dissolved in anhydrous methanol and Ar(g) was bubbled through the solution for 1 h. Sodium hydroxide (2.52 g, 63 mmol) was then added, and the mixture was stirred under Ar(g) for 2 h. Solvent was then removed under reduced pressure, and the residue was dissolved in methylene chloride. This solution was washed twice with 2 N HCl and once with brine. The organic layer was dried over MgSO4(s) and filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes) to afford 1b as a clear oil in 94% yield. Alternatively, phosphinothiol 1b can be used in its crude form for formation of phosphinothioesters. Spectral data. 1H NMR (CDCl3, 300 MHz) δ 7.41-7.38 (m, 4 H), 7.33-7.26 (m, 6 H), 3.02 (d, J=7.8 Hz, 2 H), 1.38 (t, J=7.5 Hz, 1 H) ppm; 13C NMR (CDCl3, 75 MHz) δ 132.54 (d, J=17.1 Hz), 128.86, 128.36, 128.14, 20.60 (d, J=21.7 Hz) ppm; 31P NMR (CDCl3, 121 MHz) δ—7/94 ppm; MS (EST) m/z 232.05 (MH+=233.0, fragments at 183.0, 155.0, 139.0, 91.2). Ar(g) was bubbled through the solution for 1 h Solvent was then removed under reduced pressure the residue was dissolved in methylene chloride This solution was washed twice with 2 N HCl and once with brine The organic layer was dried over MgSO4(s) filtered the solvent was removed under reduced pressure The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phosphinothiol 20 (100 mg, 0.43 mmol) and N-acetylglycine (55 mg, 0.47 mmol) were dissolved in DMF (3 mL) under Ar(g). DCC (98 mg, 0.47 mmol) was added, and the mixture was stirred for 12 h at room temperature. The DCU by-product was removed by filtration, solvent was removed under reduced pressure, and the residue was purified by chromatography as in Method A. AcGlyCH2PPh2 was isolated as a white solid in 67% yield. Spectral data. 1H NMR (CDCl3, 300 MHz) δ 7.46-7.39 (m, 4 H), 7.38-7.36 (m, 6 H), 6.44 (bs, 1 H), 4.15 (d, J=5/7 Hz, 2 H), 3.53 (d, J=3.6 Hz, 2 H), 2.02 (s, 3 H) ppm; 13C NMR (CDCl3, 75 MHz) δ 196.13, 170.29, 136.45 (d, J=13.6 HZ), 132.62 (d, J=19.1 Hz), 129.17, 128.54 (d, J=6.7 Hz), 48.98, 25.29 (d, J-24.2 Hz), 22.84 ppm; 31P NMR (CDCl3, 121 MHz) δ −15.20 ppm; MS (ESI) m/z 331.08 (MH+—332.2, MK+—370.0). The DCU by-product was removed by filtration, solvent was removed under reduced pressure the residue was purified by chromatography as in Method A

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Method B (DCC coupling). Compound 20 (500 mg, 2.15 mmol) and N-acetylphenylalanine (446 mg, 2.15 mmol) were dissolved in DMF (15 mL) under Ar(g). 1,3-Dicyclohexylcarbodiimide (DCC; 489 mg, 2.37 mmol) was then added, and the reaction mixture was stirred for 12 h at room temperature. The 1,3-dicyclohexylurea (CU) by-product was removed by filtration, solvent was removed under reduced pressure, and the residue was purified by chromatography as in Method A. AcPheSCH2PPh2 was isolated as a white solid in 84% yield. Spectral data. 1H NMR (CDCl3, 300 MHz) δ 7.44-7.39 (m, 4 H), 7.35-7.33 (m, 6 H), 7.26-7.21 (m, 3 H), 7.11-7.09 (m, 2 H), 6.29 (d, J=8.4 Hz, 1 H), 4.98-4.91 (m, 1 H), 3.57-3.44 (m, 2 H), 3.09 (dd, J=14.1, 5.4 Hz, 1 H), 2.93 (dd, J=14.1, 7.5 Hz, 1 H), 1.88 (s, 3 H) ppm; 13C NMR (CDCl3, 125 MHz) δ 198.901, 169.86, 135.50, 132.62 (d, J=19.4 Hz), 129.11 (d, J-9.8 Hz) 128.79 (d, J=35.9 Hz), 128.50, 128.45, 126.99, 59.56, 37.99, 25.61 (d, J=24.4 Hz), 22.88 ppm; 31P NMR (CDCl3, 121 MHz −44.55 ppm. The 1,3-dicyclohexylurea (CU) by-product was removed by filtration, solvent was removed under reduced pressure the residue was purified by chromatography as in Method A

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Method A (transthioesterification). Phosphinothiol 20 (500 mg, 2.2 mmol) was dissolved in dry TBF (5 mL). The solution was deoxygenated by bubbling Ar(g) for 0.5 h. To this solution was added NaH (51.6 mg, 2.2 mmol). The mixture formed a slurry to which was added DMF (2 mL0 to dissolve any precipitate. The N-methylmercaptoacetamide (NMA) thioester of N-acetylphenylalanine (63 mg, 0.22 mmol) was added, and the reaction mixture was stirred for 8 h. Unreacted Phosphinothiol 20 was removed by adding Merrifield resin (1.5 g, 1.26 mmol/g), stirring for 6 h, and removing the resin by filtration. The residue was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes). AcPheSCH2PPh2 was isolated as a white solid in 92% yield. The solution was deoxygenated by bubbling Ar(g) for 0.5 h The mixture formed a slurry to which to dissolve any precipitate Unreacted Phosphinothiol 20 was removed by adding Merrifield resin (1.5 g, 1.26 mmol/g) stirring for 6 h removing the resin by filtration The residue was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Method A (transthioesterification). Phosphinothiol 20 (500 mg, 2.2 mmol) was dissolved in dry TBF (5 mL). The solution was deoxygenated by bubbling Ar(g) for 0.5 h. To this solution was added NaH (51.6 mg, 2.2 mmol). The mixture formed a slurry to which was added DMF (2 mL0 to dissolve any precipitate. The N-methylmercaptoacetamide (NMA) thioester of N-acetylphenylalanine (63 mg, 0.22 mmol) was added, and the reaction mixture was stirred for 8 h. Unreacted Phosphinothiol 20 was removed by adding Merrifield resin (1.5 g, 1.26 mmol/g), stirring for 6 h, and removing the resin by filtration. The residue was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes). AcPheSCH2PPh2 was isolated as a white solid in 92% yield. The solution was deoxygenated by bubbling Ar(g) for 0.5 h The mixture formed a slurry to which to dissolve any precipitate Unreacted Phosphinothiol 20 was removed by adding Merrifield resin (1.5 g, 1.26 mmol/g) stirring for 6 h removing the resin by filtration The residue was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Acetylglycine (1.90 g, 16.2 mmol) was dissolved in anhydrous DMF (75 mL). HOBt (2.48 g, 16.2 mmol) was added to the resulting solution followed by DCC (3.34 g, 16.2 mmol). Once precipitate (DCU) was observed, phosphinothiol 1b was added (3.77 g, 16.2 mmol). The reaction mixture was allowed to stir under Ar(g) for 3 h. The precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a white solid. This solid was dissolved in ethyl acetate and purified by flash chromatography (silica gel, ethyl acetate). Compound 51 was isolated in 96% yield. Spectral Data. As reported previously.4b The precipitate was removed by filtration the filtrate was concentrated under reduced pressure to give a white solid purified by flash chromatography (silica gel, ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 11b (17.27 g, 63.0 mmol) was dissolved in anhydrous methanol and Ar(g) was bubbled through the solution for 1 h. Sodium hydroxide (2.52 g, 63 mmol) was then added, and the mixture was stirred under Ar(g) for 2 h. Solvent was then removed under reduced pressure, and the residue was dissolved in methylene chloride. This solution was washed twice with 2 N HCl and once with brine. The organic layer was dried over MgSO4(s) and filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes) to afford 1b as a clear oil in 94% yield. Alternatively, phosphinothiol 1b can be used in its crude form for formation of phosphinothioesters. Spectral data. 1H NMR (CDCl3, 300 MHz) δ 7.41-7.38 (m, 4 H), 7.33-7.26 (m, 6 H), 3.02 (d, J=7.8 Hz, 2 H), 1.38 (t, J=7.5 Hz, 1 H) ppm; 13C NMR (CDCl3, 75 MHz) δ 132.54 (d, J=17.1 Hz), 128.86, 128.36, 128.14, 20.60 (d, J=21.7 Hz) ppm; 31P NMR (CDCl3, 121 MHz) δ—7/94 ppm; MS (EST) m/z 232.05 (MH+=233.0, fragments at 183.0, 155.0, 139.0, 91.2). Ar(g) was bubbled through the solution for 1 h Solvent was then removed under reduced pressure the residue was dissolved in methylene chloride This solution was washed twice with 2 N HCl and once with brine The organic layer was dried over MgSO4(s) filtered the solvent was removed under reduced pressure The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Acetylglycine (1.90 g, 16.2 mmol) was dissolved in anhydrous DMF (75 mL). HOBt (2.48 g, 16.2 mmol) was added to the resulting solution followed by DCC (3.34 g, 16.2 mmol). Once precipitate (DCU) was observed, phosphinothiol 1b was added (3.77 g, 16.2 mmol). The reaction mixture was allowed to stir under Ar(g) for 3 h. The precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a white solid. This solid was dissolved in ethyl acetate and purified by flash chromatography (silica gel, ethyl acetate). Compound 51 was isolated in 96% yield. Spectral Data. As reported previously The precipitate was removed by filtration the filtrate was concentrated under reduced pressure to give a white solid purified by flash chromatography (silica gel, ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Acetylglycine (1.90 g, 16.2 mmol) was dissolved in anhydrous DMF (75 mL). HOBt (2.48 g, 16.2 mmol) was added to the resulting solution followed by DCC (3.34 g, 16.2 mmol). Once precipitate (DCU) was observed, phosphinothiol 1b was added (3.77 g, 16.2 mmol). The reaction mixture was allowed to stir under Ar(g) for 3 h. The precipitate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a white solid. This solid was dissolved in ethyl acetate and purified by flash chromatography (silica gel, ethyl acetate). Compound 51 was isolated in 96% yield. Spectral Data. As reported previously The precipitate was removed by filtration the filtrate was concentrated under reduced pressure to give a white solid purified by flash chromatography (silica gel, ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Compound 11b (17.27 g, 63.0 mmol) was dissolved in anhydrous methanol and Ar(g) was bubbled through the solution for 1 h. Sodium hydroxide (2.52 g, 63 mmol) was then added, and the mixture was stirred under Ar(g) for 2 h. Solvent was then removed under reduced pressure, and the residue was dissolved in methylene chloride. This solution was washed twice with 2 N HCl and once with brine. The organic layer was dried over MgSO4(s) and filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes) to afford 1b as a clear oil in 94% yield. Alternatively, phosphinothiol 1b can be used in its crude form for formation of phosphinothioesters. Spectral data. 1H NMR (CDCl3, 300 MHz) δ 7.41-7.38 (m, 4H), 7.33-7.26 (m, 6H), 3.02 (d, J=7.8 Hz, 2H), 1.38 (t, J=7.5 Hz, 1H) ppm; 13C NMR (CDCl3, 75 MHz) δ 132.54 (d, J=17.1 Hz), 128.86, 128.36, 128.14, 20.60 (d, J=21.7 Hz) ppm; 31P NMR (CDCl3, 121 MHz) 6-7/94 ppm; MS (ESI) m/z 232.05 (MH+=233.0, fragments at 183.0, 155.0, 139.0, 91.2). Ar(g) was bubbled through the solution for 1 h Solvent was then removed under reduced pressure the residue was dissolved in methylene chloride This solution was washed twice with 2 N HCl and once with brine The organic layer was dried over MgSO4(s) filtered the solvent was removed under reduced pressure The residue was purified by chromatography (alumina, 25% v/v ethyl acetateinhexanes)