| 78% |
With chloro-trimethyl-silane; copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -78℃; for 3h; |
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| 76% |
With chloro-trimethyl-silane; copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -78℃; for 2h; |
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| 57% |
Stage #1: vinyl magnesium bromide With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78 - 0℃; for 0.333333h;
Stage #2: (3aR,6aR)-2,2-Dimethyl-3a,6a-dihydro-cyclopenta[1,3]dioxol-4-one With chloro-trimethyl-silane In tetrahydrofuran at -78℃; for 3h; |
2-3 COMPOUNDS 3 AND 4
TMEDA (5.65 g, 48.65 mmol, 7.34 mL, 1.5 eq.) was added to a mixture of Cul (339.73 mg, 1.78 mmol, 0.055 eq.) in THF (125 mL) at 0 °C. The mixture was stirred at 0 °C for 5 min, and then cooled to -78 °C. A solution of vinylmagnesium bromide (1 M in THF, 48.65 mL, 1.5 eq.) was added, and the mixture was stirred at -78 °C for 20 min. TMSC1 (4.23 g, 38.92 mmol, 4.94 mL, 1.2 eq.) was added, followed by a solution of 1C (5 g, 32.43 mmol, 1 eq.) in THF (35 mL). The mixture was stirred at -78 °C for 3 h. The reaction progress was monitored by TLC (PE:EA=5: 1). Upon completion, the reaction was quenched by NH4CI (sat., aq., 50 mL), and the mixture was extracted with EA (2 x 100 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over Na2SC>4, filtered and concentrated to give a residue. The residue was purified by column chromatography (S1O2, PE:EA=20: 1 to 10: 1) to afford 2C (3.8 g, 18.77 mmol, 57% yield) as a yellow oil. |
| 57% |
Stage #1: vinyl magnesium bromide With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78 - 0℃; for 0.416667h;
Stage #2: (3aR,6aR)-2,2-Dimethyl-3a,6a-dihydro-cyclopenta[1,3]dioxol-4-one With chloro-trimethyl-silane In tetrahydrofuran at -78℃; for 3h; |
2; 3 COMPOUNDS 3 AND 4
TMEDA (5.65 g, 48.65 mmol, 7.34 rnL, 1.5 eq.) was added to a mixture of Cu (339.73 mg, 1.78 mmol, 0.055 eq.) in Tf iF (125 ml,) at 0 °C. The mixture was stirred at 0 °C for 5 mm, and then cooled to -78 °C. A solution of vinylmagnesium bromide (1 M in TllF, 48.65 rnL, 1.5 eq.) was added, and the mixture was stirred at -78 °C for 20 min. TMSC1 (4.23 g, 38.92 mmol, 4.94 mL, 1.2 eq.) was added, followed by a solution of 1C (5 g, 32.43 mmol, 1 eq.) in THF (35 mL). The mixture was stirred at -78 °C for 3 h. The reaction progress was monitored by TLC (PE:EA=5:1). Upon completion, the reaction was quenched by NfitiCl (sat., aq., 50 mL), and the mixture was extracted with EA (2 x 100 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over NaaSOr, filtered and concentrated to give a residue. The residue was purified by column chromatography SICK PE:EA==20: 1 to 10:1) to afford 2C (3.8 g, 18.77 mmol, 57% yield) as a yellow oil. |
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Stage #1: vinyl magnesium bromide With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -78℃; for 1h;
Stage #2: (3aR,6aR)-2,2-Dimethyl-3a,6a-dihydro-cyclopenta[1,3]dioxol-4-one With chloro-trimethyl-silane In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at -78 - 20℃;
Stage #3: With ammonium chloride In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide Saturated solution; |
3.1.7. tert-Butyl((3aR,4S,6R,6aR)-2,2-dimethyl-6-vinyl-tetrahydro-3aH-cyclopenta-[d]-[1,3]dioxol-4-yloxy)dimethylsilane (15)
Vinylmagnesium bromide (25 mL, 1.0 M in THF, 25 mmol) was added to a suspension of CuBr·SMe2 (0.41 g, 2.0 mmol) in THF (30 mL) at -78 °C. The mixture was stirred at this temperature for 1 h. To this were added, dropwise, enone 14refPreviewPlaceHolder8 (3.0 g, 19 mmol), HMPA (10 mL), and TMSCl (3.2 mL, 25 mmol) at -78 °C. The resulting mixture was warmed to room temperature and stirred overnight. Saturated NH4Cl solution (30 mL) was then added to quench the reaction. The mixture was extracted with Et2O (3×100 mL). The combined organic phases were washed with brine (100 mL), dried (Na2SO4), and concentrated. The residue was dissolved in MeOH (100 mL) and CeCl3·7H2O (7.4 g, 20 mmol) added at 0 °C. This was followed by the portionwise addition of NaBH4 (0.74 g, 20 mmol). The resulting mixture was stirred at this temperature for 1 h. Saturated NH4Cl solution (20 mL) was added to quench the reaction. The mixture was filtered through Celite and the filtrate concentrated. The residue was extracted with Et2O (3×100 mL) and the combined organic phases dried (Na2SO4), and filtered through a short silica gel column (10 cm). The filtrate was concentrated and the residue dissolved in CH2Cl2 (100 mL). TBSCl (3.0 g, 20 mmol) and imidazole (2.0 g, 31 mmol) were then added to this solution at room temperature. The mixture was stirred for 3 h and H2O (10 mL) was added to quench the reaction. The organic layer was separated, washed with H2O (20 mL), dried (Na2SO4), and concentrated. The residue was purified by silica gel column chromatography (hexanes/EtOAc=20:1) to give 15 as a colorless oil (2.5 g, 43% in three steps). 1H NMR (CDCl3, 400 MHz) δ 5.76 (m, 1H), 5.02-5.08 (m, 2H), 4.37 (m, 2H), 4.07 (m, 1H), 2.66 (m, 1H), 2.03 (m, 1H), 1.73 (m, 1H), 1.49 (s, 3H), 1.31 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ 139.1, 114.7, 111.3, 84.1, 80.1, 72.5, 44.3, 35.6, 26.3, 25.7, 24.7 18.4, -4.4, -4.7. Calcd HRMS for C16H30O3Si (M+H): 299.2042; found: 299.2043. |
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With copper(l) iodide; chloro-trimethyl-silane; dimethylsulfide |
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