(3S)-5-phenylpent-1-yn-3-ol

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following a procedure of Noyori (Suzuki, M. et al., J. Med. Chem. 41, 3084-3090 (1998)); Imidazole (919.1 mg, 13.5 mmol, 1.8 eq.) and t-butylchlorodimethylsilane (1.35 g, 9.0 mmol) were added to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (1.2 g, 7.5 mmol, 1 eq.) in CH2Cl2 (18 ml), cooled to 0° C. The reaction mixture was then stirred at room temperature for 14 h before being poured into 1 M HCl (50 ml). The mixture was extracted with 40/60 petroleum ether (3×50 ml). The combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (99:1), giving the title product 88 as a clear, colourless oil (1.77 g, 86%). Analytical data consistent with the literature (Kiyotsuka, Y. et al., Org. Lett. 10, 1719-1722 (2008); Sato, F. et al., EP 1211241 A1, Taisho Pharmaceutical co., LTD (2002)). The mixture was extracted with 40/60 petroleum ether (3×50 ml) The combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (99:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-butyllithium (2.5 M in hexanes, 474 μL, 1.18 mmol, 3 eq.) was added dropwise to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (63.3 mg, 0.39 mmol, 1 eq.) in THF (1 ml) at −78° C. The mixture was allowed to warm to 0° C. and stirred 30 min before being cooled to −78° C. TMSCl (148.2 μL, 1.18 mmol, 3 eq.) was added dropwise and the mixture was allowed to warm to r.t. and stirred for 2 h. Citric acid (65 mg) in methanol (0.7 ml) was added and the mixture stirred for 1 h. The mixture was poured into a mixture of brine (3 ml) and Et2O (5 ml). The aqueous layer was extracted with Et2O (3×10 ml) and the combined organic phases were washed with brine (10 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (9:1), giving the title product 87 as a clear, colourless oil (18.5 mg, 15.5%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)). before being cooled to −78° C to warm to r.t. stirred for 2 h the mixture stirred for 1 h The aqueous layer was extracted with Et2O (3×10 ml) the combined organic phases were washed with brine (10 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (9:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-butyllithium (2.5 M in hexanes, 474 μL, 1.18 mmol, 3 eq.) was added dropwise to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (63.3 mg, 0.39 mmol, 1 eq.) in THF (1 ml) at −78° C. The mixture was allowed to warm to 0° C. and stirred 30 min before being cooled to −78° C. TMSCl (148.2 μL, 1.18 mmol, 3 eq.) was added dropwise and the mixture was allowed to warm to r.t. and stirred for 2 h. Citric acid (65 mg) in methanol (0.7 ml) was added and the mixture stirred for 1 h. The mixture was poured into a mixture of brine (3 ml) and Et2O (5 ml). The aqueous layer was extracted with Et2O (3×10 ml) and the combined organic phases were washed with brine (10 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (9:1), giving the title product 87 as a clear, colourless oil (18.5 mg, 15.5%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)). before being cooled to −78° C to warm to r.t. stirred for 2 h the mixture stirred for 1 h The aqueous layer was extracted with Et2O (3×10 ml) the combined organic phases were washed with brine (10 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (9:1)

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

実験手順: Following a modified procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); Tetrabutylammonium fluoride (1.0 M in THF, 25 ml, 25 mmol, 2.5 eq.) was added to a solution of (S)-5-phenyl-1-(triisopropylsilyl)pent-1-yn-3-ol 85 (3.165 g, 10 mmol, 1 eq.) in THF (95 ml). The reaction mixture was stirred for 1 h at r.t. and then quenched by addition of saturated aq. NH4Cl (50 ml). The mixture was extracted with Et2O (3×40 ml), the combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (10:1 to 9:1), giving the title product 86 as a clear, colourless oil (1.6 g, 99%). quenched by addition of saturated aq. NH4Cl (50 ml) The mixture was extracted with Et2O (3×40 ml) the combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (10:1 to 9:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following a procedure of Noyori (Suzuki, M. et al., J. Med. Chem. 41, 3084-3090 (1998)); Imidazole (919.1 mg, 13.5 mmol, 1.8 eq.) and t-butylchlorodimethylsilane (1.35 g, 9.0 mmol) were added to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (1.2 g, 7.5 mmol, 1 eq.) in CH2Cl2 (18 ml), cooled to 0° C. The reaction mixture was then stirred at room temperature for 14 h before being poured into 1 M HCl (50 ml). The mixture was extracted with 40/60 petroleum ether (3×50 ml). The combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (99:1), giving the title product 88 as a clear, colourless oil (1.77 g, 86%). Analytical data consistent with the literature (Kiyotsuka, Y. et al., Org. Lett. 10, 1719-1722 (2008); Sato, F. et al., EP 1211241 A1, Taisho Pharmaceutical co., LTD (2002)). The mixture was extracted with 40/60 petroleum ether (3×50 ml) The combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (99:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); n-butyllithium (2.5 M in hexanes, 474 μL, 1.18 mmol, 3 eq.) was added dropwise to a solution of (S)-5-phenylpent-1-yn-3-ol 86 (63.3 mg, 0.39 mmol, 1 eq.) in THF (1 ml) at −78° C. The mixture was allowed to warm to 0° C. and stirred 30 min before being cooled to −78° C. TMSCl (148.2 μL, 1.18 mmol, 3 eq.) was added dropwise and the mixture was allowed to warm to r.t. and stirred for 2 h. Citric acid (65 mg) in methanol (0.7 ml) was added and the mixture stirred for 1 h. The mixture was poured into a mixture of brine (3 ml) and Et2O (5 ml). The aqueous layer was extracted with Et2O (3×10 ml) and the combined organic phases were washed with brine (10 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (9:1), giving the title product 87 as a clear, colourless oil (18.5 mg, 15.5%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)). before being cooled to −78° C to warm to r.t. stirred for 2 h the mixture stirred for 1 h The aqueous layer was extracted with Et2O (3×10 ml) the combined organic phases were washed with brine (10 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (9:1)

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

実験手順: Following a modified procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); Tetrabutylammonium fluoride (1.0 M in THF, 25 ml, 25 mmol, 2.5 eq.) was added to a solution of (S)-5-phenyl-1-(triisopropylsilyl)pent-1-yn-3-ol 85 (3.165 g, 10 mmol, 1 eq.) in THF (95 ml). The reaction mixture was stirred for 1 h at r.t. and then quenched by addition of saturated aq. NH4Cl (50 ml). The mixture was extracted with Et2O (3×40 ml), the combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/Et2O (10:1 to 9:1), giving the title product 86 as a clear, colourless oil (1.6 g, 99%). quenched by addition of saturated aq. NH4Cl (50 ml) The mixture was extracted with Et2O (3×40 ml) the combined organic phases were washed with brine (50 ml) before being dried (MgSO4) filtered concentrated to give the crude product This was purified by column chromatography on silica eluting with petrol/Et2O (10:1 to 9:1)