(E)-4-phenylbut-2-en-1-ol

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A quantity of CuCN, 2.43 g, was added to a solution of butadiene monooxide, 19 g, in 500 mL anhydrous tetrahydrofuran and the mixture was cooled to -78° C. Phenyl magnesium bromide solution in ether, 32 mmol, was added dropwise to this mixture. The reaction mixture was warmed to 0° C. and was stirred until the reaction became homogeneous. The reaction mixture was cooled to -78° C. and 0.29 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) followed by NH4OH (30 mL), saturated NH4Cl (200 mL) and H2O (100 mL). Aqueous layer was extracted with two 200 mL portions of ethyl acetate. Combined organic layers were dried and concentrated. The residue was distilled under vacuum (0.1 torr) at 100° C. to give trans-4-phenyl-2-butene-1-ol (38.9 g, 79% pure). The reaction mixture was warmed to 0° C. The reaction mixture was cooled to -78° C. to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) Aqueous layer was extracted with two 200 mL portions of ethyl acetate Combined organic layers were dried concentrated The residue was distilled under vacuum (0.1 torr) at 100° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A quantity of CuCN, 2.43 g, was added to a solution of butadiene monooxide, 19 g, in 500 mL anhydrous tetrahydrofuran and the mixture was cooled to -78° C. Phenyl magnesium bromide solution in ether, 32 mmol, was added dropwise to this mixture. The reaction mixture was warmed to 0° C. and was stirred until the reaction became homogeneous. The reaction mixture was cooled to -78° C. and 0.29 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) followed by NH4OH (30 mL), saturated NH4Cl (200 mL) and H2O (100 mL). Aqueous layer was extracted with two 200 mL portions of ethyl acetate. Combined organic layers were dried and concentrated. The residue was distilled under vacuum (0.1 torr) at 100° C. to give trans-4-phenyl-2-butene-1-ol (38.9 g, 79% pure). The reaction mixture was warmed to 0° C. The reaction mixture was cooled to -78° C. to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) Aqueous layer was extracted with two 200 mL portions of ethyl acetate Combined organic layers were dried concentrated The residue was distilled under vacuum (0.1 torr) at 100° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of allylic alcohol 7 (5.0 g, 33.7 mmol) in dry CH2Cl2 (60 mL) at 0° C. was added m-chloroperbenzoic acid (8.7 g, 50.6 mmol) in small portions. The resulting solution was stirred for 8 h until complete consumption of starting materials (the progress of the reaction was monitored by TLC). The reaction mixture was quenched with water and the aqueous layer was extracted with CH2Cl2 (3×30 mL). The organic layer was washed with aq. 10% solution of NaHCO3 (15 mL). The combined organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography over silica gel using petroleum ether/EtOAc (4:1) to give the corresponding epoxide 8 (4.8 g, 88%) as a viscous gum. IR: (CHCl3, cm−1): νmax 700, 991, 1028, 1055, 1106, 1452, 2921, 3404; 1H NMR (200 MHz, CDCl3): δ 2.88-2.99 (m, 3H), 3.17-3.23 (m, 1H), 3.57-3.72 (m, 1H), 3.85-3.95 (m, 1H), 7.18-7.34 (m, 5H); 13C NMR (50 MHz, CDCl3): δ 34.2, 67.1, 78.9, 87.5, 125.5, 127.5, 128.4, 140.8; Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.25; H, 7.47%. The reaction mixture was quenched with water the aqueous layer was extracted with CH2Cl2 (3×30 mL) The organic layer was washed with aq. 10% solution of NaHCO3 (15 mL) The combined organic layer was dried over anhydrous Na2SO4 the solvent was removed under reduced pressure The crude product was purified by column chromatography over silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of LiAlH4 (2.4 g, 63.1 mmol) in dry Et2O (60 mL) at 0° C. under nitrogen atmosphere was added dropwise a solution of anhydrous AlCl3 (1.7 g, 12.6 mmol) in dry Et2O (30 mL). The reaction mixture was stirred at the same temperature for 30 min. To this stirred suspension, ester obtained in example 1 (8.0 g, 42.1 mmol) in dry Et2O (30 mL) was added dropwise over a period of 15 min and the resulting mixture stirred at 0° C. for 1 h. Then it was quenched with ice-water and filtered through celite and the residue was washed with ethyl acetate (3×30 mL). The combined organic layer was dried over anhydrous Na2SO4, concentrated, and the crude product was purified by column chromatography using petroleum ether/EtOAc (4:1) to afford the pure allylic alcohol 7 (5.4 g, 87%) as a colorless oil. IR: (CHCl3, cm−1): νmax 694, 744, 966, 1049, 1107, 1364, 1454, 2857, 2932, 3385; 1H NMR (200 MHz, CDCl3): δ 1.22 (br s, 1H), 3.38 (d, J=6.4 Hz, 2H), 4.12 (t, J=4.8 Hz, 2H), 5.62-5.93 (m, 2H), 7.15-7.32 (m, 5H); 13C NMR (50 MHz, CDCl3): δ 36.4, 61.9, 126.0, 126.3, 127.2, 128.5, 132.7, 137.2; Anal. Calcd for C10H12O: C, 81.04; H, 8.16. Found: C, 81.02; H, 8.15%. the resulting mixture stirred at 0° C. for 1 h Then it was quenched with ice-water filtered through celite the residue was washed with ethyl acetate (3×30 mL) The combined organic layer was dried over anhydrous Na2SO4 concentrated the crude product was purified by column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of LiAlH4 (2.4 g, 63.1 mmol) in dry Et2O (60 mL) at 0° C. under nitrogen atmosphere was added dropwise a solution of anhydrous AlCl3 (1.7 g, 12.6 mmol) in dry Et2O (30 mL). The reaction mixture was stirred at the same temperature for 30 min. To this stirred suspension, ester obtained in example 1 (8.0 g, 42.1 mmol) in dry Et2O (30 mL) was added dropwise over a period of 15 min and the resulting mixture stirred at 0° C. for 1 h. Then it was quenched with ice-water and filtered through celite and the residue was washed with ethyl acetate (3×30 mL). The combined organic layer was dried over anhydrous Na2SO4, concentrated, and the crude product was purified by column chromatography using petroleum ether/EtOAc (4:1) to afford the pure allylic alcohol 7 (5.4 g, 87%) as a colorless oil. IR: (CHCl3, cm−1): νmax 694, 744, 966, 1049, 1107, 1364, 1454, 2857, 2932, 3385; 1H NMR (200 MHz, CDCl3): δ 1.22 (br s, 1H), 3.38 (d, J=6.4 Hz, 2H), 4.12 (t, J=4.8 Hz, 2H), 5.62-5.93 (m, 2H), 7.15-7.32 (m, 5H); 13C NMR (50 MHz, CDCl3): δ 36.4, 61.9, 126.0, 126.3, 127.2, 128.5, 132.7, 137.2; Anal. Calcd for C10H12O: C, 81.04; H, 8.16. Found: C, 81.02; H, 8.15%. the resulting mixture stirred at 0° C. for 1 h Then it was quenched with ice-water filtered through celite the residue was washed with ethyl acetate (3×30 mL) The combined organic layer was dried over anhydrous Na2SO4 concentrated the crude product was purified by column chromatography

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A quantity of CuCN, 2.43 g, was added to a solution of butadiene monooxide, 19 g, in 500 mL anhydrous tetrahydrofuran and the mixture was cooled to -78° C. Phenyl magnesium bromide solution in ether, 32 mmol, was added dropwise to this mixture. The reaction mixture was warmed to 0° C. and was stirred until the reaction became homogeneous. The reaction mixture was cooled to -78° C. and 0.29 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) followed by NH4OH (30 mL), saturated NH4Cl (200 mL) and H2O (100 mL). Aqueous layer was extracted with two 200 mL portions of ethyl acetate. Combined organic layers were dried and concentrated. The residue was distilled under vacuum (0.1 torr) at 100° C. to give trans-4-phenyl-2-butene-1-ol (38.9 g, 79% pure). The reaction mixture was warmed to 0° C. The reaction mixture was cooled to -78° C. to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) Aqueous layer was extracted with two 200 mL portions of ethyl acetate Combined organic layers were dried concentrated The residue was distilled under vacuum (0.1 torr) at 100° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous CuCN (4.86 g, 54 mmol) was added to a solution of butadiene monooxide (38 g, 540 mmol) in anhydrous tetrahydrofuran (1.2 L) and the resulting mixture was stirred at −78° C. Commercial phenyl magnesium bromide solution (Aldrich) in ether (65 mmol) was added dropwise over a period of 10 min. The resulting reaction mixture was then allowed to warm to 0° C. and it was continued to stir until the reaction mixture was homogeneous. After this period, the reaction mixture was cooled to −78° C. and 0.58 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to 23° C. for 1 h. The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) followed by NH4OH (70 mL), saturated NH4Cl (500 mL) and then H2O (300 mL). The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was distilled under vacuum (0.12 torr) at 95° C. to give trans-4-phenyl-2-butene-1-ol (75.6 g). The resulting reaction mixture to warm to 0° C. to stir until the reaction mixture After this period the reaction mixture was cooled to −78° C. to warm to 23° C. for 1 h The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL) The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was distilled under vacuum (0.12 torr) at 95° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous CuCN (4.86 g, 54 mmol) was added to a solution of butadiene monooxide (38 g, 540 mmol) in anhydrous tetrahydrofuran (1.2 L) and the resulting mixture was stirred at −78° C. Commercial phenyl magnesium bromide solution (Aldrich) in ether (65 mmol) was added dropwise over a period of 10 min. The resulting reaction mixture was then allowed to warm to 0° C. and it was continued to stir until the reaction mixture was homogeneous. After this period, the reaction mixture was cooled to −78° C. and 0.58 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to 23° C. for 1 h. The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) followed by NH4OH (70 mL), saturated NH4Cl (500 mL) and then H2O (300 mL). The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was distilled under vacuum (0.12 torr) at 95° C. to give trans-4-phenyl-2-butene-1-ol (75.6 g). The resulting reaction mixture to warm to 0° C. to stir until the reaction mixture After this period the reaction mixture was cooled to −78° C. to warm to 23° C. for 1 h The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL) The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was distilled under vacuum (0.12 torr) at 95° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous CuCN (4.86 g, 54 mmol) was added to a solution of butadiene monooxide (38 g, 540 mmol) in anhydrous tetrahydrofuran (1.2 L) and the resulting mixture was stirred at −78° C. Commercial phenyl magnesium bromide solution (Aldrich) in ether (65 mmol) was added dropwise over a period of 10 min. The resulting reaction mixture was then allowed to warm to 0° C. and it was continued to stir until the reaction mixture was homogeneous. After this period, the reaction mixture was cooled to −78° C. and 0.58 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to 23° C. for 1 h. The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) followed by NH4OH (70 mL), saturated NH4Cl (500 mL) and then H2O (300 mL). The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was distilled under vacuum (0.12 torr) at 95° C. to give trans-4-phenyl-2-butene-1-ol (75.6 g). The resulting reaction mixture to warm to 0° C. to stir until the reaction mixture After this period the reaction mixture was cooled to −78° C. to warm to 23° C. for 1 h The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL) The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was distilled under vacuum (0.12 torr) at 95° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Anhydrous CuCN (4.86 g, 54 mmol) was added to a solution of butadiene monooxide (38 g, 540 mmol) in anhydrous tetrahydrofuran (1.2 L) and the resulting mixture was stirred at −78° C. Commercial phenyl magnesium bromide solution (Aldrich) in ether (65 mmol) was added dropwise over a period of 10 min. The resulting reaction mixture was then allowed to warm to 0° C. and it was continued to stir until the reaction mixture was homogeneous. After this period, the reaction mixture was cooled to −78° C. and 0.58 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to 23° C. for 1 h. The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) followed by NH4OH (70 mL), saturated NH4Cl (500 mL) and then H2O (300 mL). The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was distilled under vacuum (0.12 torr) at 95° C. to give trans-4-phenyl-2-butene-1-ol (75.6 g). The resulting reaction mixture to warm to 0° C. to stir until the reaction mixture After this period the reaction mixture was cooled to −78° C. to warm to 23° C. for 1 h The reaction was quenched by slow addition of saturated aqueous NH4Cl (120 mL) The aqueous layer was thoroughly extracted with ethyl acetate (2×300 mL) The combined organic layers were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was distilled under vacuum (0.12 torr) at 95° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A quantity of CuCN, 2.43 g, was added to a solution of butadiene monooxide, 19 g, in 500 mL anhydrous tetrahydrofuran and the mixture was cooled to -78° C. Phenyl magnesium bromide solution in ether, 32 mmol, was added dropwise to this mixture. The reaction mixture was warmed to 0° C. and was stirred until the reaction became homogeneous. The reaction mixture was cooled to -78° C. and 0.29 mole of phenylmagnesium bromide solution in ether was added dropwise for 30 min. The reaction mixture was allowed to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) followed by NH4OH (30 mL), saturated NH4Cl (200 mL) and H2O (100 mL). Aqueous layer was extracted with two 200 mL portions of ethyl acetate. Combined organic layers were dried and concentrated. The residue was distilled under vacuum (0.1 torr) at 100° C. to give trans-4-phenyl-2 -butene-1-ol (38.9 g, 79% pure). The reaction mixture was warmed to 0° C. The reaction mixture was cooled to -78° C. to warm to room temperature with stirring then quenched by slow addition of saturated NH4Cl (50 mL) Aqueous layer was extracted with two 200 mL portions of ethyl acetate Combined organic layers were dried concentrated The residue was distilled under vacuum (0.1 torr) at 100° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of allylic alcohol 7 (5.0 g, 33.7 mmol) in dry CH2Cl2 (60 mL) at 0° C. was added m-chloroperbenzoic acid (8.7 g, 50.6 mmol) in small portions. The resulting solution was stirred for 8 h until complete consumption of starting materials (the progress of the reaction was monitored by TLC). The reaction mixture was quenched with water and the aqueous layer was extracted with CH2Cl2 (3×30 mL). The organic layer was washed with aq. 10% solution of NaHCO3 (15 mL). The combined organic layer was dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography over silica gel using petroleum ether/EtOAc (4:1) to give the corresponding epoxide 8 (4.8 g, 88%) as a viscous gum. IR: (CHCl3, cm−1): νmax 700, 991, 1028, 1055, 1106, 1452, 2921, 3404; 1H NMR (200 MHz, CDCl3): δ 2.88-2.99 (m, 3H), 3.17-3.23 (m, 1H), 3.57-3.72 (m, 1H), 3.85-3.95 (m, 1H), 7.18-7.34 (m, 5H); 13C NMR (50 MHz, CDCl3): δ 34.2, 67.1, 78.9, 87.5, 125.5, 127.5, 128.4, 140.8; Anal. Calcd for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.25; H, 7.47%. The reaction mixture was quenched with water the aqueous layer was extracted with CH2Cl2 (3×30 mL) The organic layer was washed with aq. 10% solution of NaHCO3 (15 mL) The combined organic layer was dried over anhydrous Na2SO4 the solvent was removed under reduced pressure The crude product was purified by column chromatography over silica gel