Benzaldehyde, 2-(2-propenyl)- (9CI)

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

Procedure: BuLi (1.55 M in hexane, 14.7 mL, 22.7 mmol) was added to a sol. of 1-bromo-2-(dimethoxymethyl)benzene (5.00 g, 21.6 mmol) in Et2O (50 mL). The mixture was stirred for 30 min at −78 ° C. and MgBr2.Et2O (5.87 g, 22.7 mmol) was added. The mixture was allowed to warm up to 0° C. over 15 min and CuI (420 mg, 2.16 mmol) was added. The mixture was stirred at 0° C. for 5 min and allyl bromide (1.92 mL, 22.7 mmol) was added. The mixture was stirred overnight while warming up to rt. Aq. 1M HCl (1 mL) was added and the mixture was diluted with Et2O, and washed with aq. 1M HCl (1×). The org. Extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was dissolved in acetone (20 mL) and water (10 mL), and TosOH (cat. amount) was added. The mixture was stirred for 5 h at rt, and the solvents were partially removed under reduced pressure. The residue was diluted with Et2O, and washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1) yielded 2-allylbenzaldehyde (1.06 g, 34%). This compound was transformed into the title compound following typical procedure J with cyclopropylamine. to warm up to 0° C. over 15 min The mixture was stirred at 0° C. for 5 min The mixture was stirred overnight while warming up to rt washed with aq. 1M HCl (1×) Extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure The residue was dissolved in acetone (20 mL) water (10 mL), and TosOH (cat. amount) was added The mixture was stirred for 5 h at rt the solvents were partially removed under reduced pressure The residue was diluted with Et2O washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1)

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

Procedure: BuLi (1.55 M in hexane, 14.7 mL, 22.7 mmol) was added to a sol. of 1-bromo-2-(dimethoxymethyl)benzene (5.00 g, 21.6 mmol) in Et2O (50 mL). The mixture was stirred for 30 min at −78 ° C. and MgBr2.Et2O (5.87 g, 22.7 mmol) was added. The mixture was allowed to warm up to 0° C. over 15 min and CuI (420 mg, 2.16 mmol) was added. The mixture was stirred at 0° C. for 5 min and allyl bromide (1.92 mL, 22.7 mmol) was added. The mixture was stirred overnight while warming up to rt. Aq. 1M HCl (1 mL) was added and the mixture was diluted with Et2O, and washed with aq. 1M HCl (1×). The org. Extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was dissolved in acetone (20 mL) and water (10 mL), and TosOH (cat. amount) was added. The mixture was stirred for 5 h at rt, and the solvents were partially removed under reduced pressure. The residue was diluted with Et2O, and washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1) yielded 2-allylbenzaldehyde (1.06 g, 34%). This compound was transformed into the title compound following typical procedure J with cyclopropylamine. to warm up to 0° C. over 15 min The mixture was stirred at 0° C. for 5 min The mixture was stirred overnight while warming up to rt washed with aq. 1M HCl (1×) Extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure The residue was dissolved in acetone (20 mL) water (10 mL), and TosOH (cat. amount) was added The mixture was stirred for 5 h at rt the solvents were partially removed under reduced pressure The residue was diluted with Et2O washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1)

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

Procedure: BuLi (1.55 M in hexane, 14.7 mL, 22.7 mmol) was added to a sol. of 1-bromo-2-(dimethoxymethyl)benzene (5.00 g, 21.6 mmol) in Et2O (50 mL). The mixture was stirred for 30 min at −78 ° C. and MgBr2.Et2O (5.87 g, 22.7 mmol) was added. The mixture was allowed to warm up to 0° C. over 15 min and CuI (420 mg, 2.16 mmol) was added. The mixture was stirred at 0° C. for 5 min and allyl bromide (1.92 mL, 22.7 mmol) was added. The mixture was stirred overnight while warming up to rt. Aq. 1M HCl (1 mL) was added and the mixture was diluted with Et2O, and washed with aq. 1M HCl (1×). The org. Extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The residue was dissolved in acetone (20 mL) and water (10 mL), and TosOH (cat. amount) was added. The mixture was stirred for 5 h at rt, and the solvents were partially removed under reduced pressure. The residue was diluted with Et2O, and washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1) yielded 2-allylbenzaldehyde (1.06 g, 34%). This compound was transformed into the title compound following typical procedure J with cyclopropylamine. to warm up to 0° C. over 15 min The mixture was stirred at 0° C. for 5 min The mixture was stirred overnight while warming up to rt washed with aq. 1M HCl (1×) Extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure The residue was dissolved in acetone (20 mL) water (10 mL), and TosOH (cat. amount) was added The mixture was stirred for 5 h at rt the solvents were partially removed under reduced pressure The residue was diluted with Et2O washed with aq. 1M HCl (1×), and aq. sat. NaHCO3 (1×) extracts were dried over MgSO4 filtered the solvents were removed under reduced pressure Purification of the residue by FC (Et2O/petroleum ether 1:49→24:1)

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 20.2 g (198.0mmol) of lithium trimethylethylenediamine in 500 ml of dry tetrahydrofuran (THF) under nitrogen at -30° C. was added 79 ml (198.0 mmol) of 2.5M butyllithium (nBuLi) in hexanes dropwise over 15 minutes. The solution became pale yellow and was stirred at -30° C. for 30 minutes. To this solution was added 20.0 g (188.5 mmol) of benzaldehyde dropwise over 30 minutes. The solution became cloudy as the complex was formed and was stirred 1 hour. To this slurry was added 113 ml (283 mmol) of 2.5M nBuLi hexanes dropwise over 1 hour. This slurry was stirred for 24 hours and gradually cleared. The solution was then transferred via cannula into a slurry of 50.6 g (565 mmol) of copper cyanide in 500 ml of dry tetrahydrofuran under nitrogen at -78° C. The mixture was allowed to warm to -30° C. and stirred for 30 minutes. To this slurry was added 49 ml (565 mmol) of allyl bromide. The mixture instantly darkened upon addition. The reaction was quenched after 30 minutes with 3% aqueous ammonium hydroxide and saturated ammonium chloride. This biphasic solution was stirred overnight to ensure complete copper removal. The aqueous layer was extracted repetitively with ether to remove all product. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The yellow oil was purified by distillation at 62° C. at 0.03 torr affording 15.32 g (56%) of o-allylbenzaldehyde. 1H NMR: ε3.82 (d; 2H, J=6.17 Hz, CH2CH=CH2), 4.99 (d; 1H, J=17.1 Hz, one of CH=CH2), 5.09 (d; 1H, J=10.2 Hz, one of CH=CH2), 6.04 (m, 1H CH=CH2), 7.3 (d; 1H, J=7.8 Hz, aryl H), 7.40 (dd; 1H, J=7.6 Hz, aryl H), 7.54 (dd; 1H, J=7.4 Hz, 7.8 Hz, aryl H), 7.86 (d; 1H, J=7.6 Hz, aryl H), 10.26 (s; 1H aldehyde H). was formed was stirred 1 hour This slurry was stirred for 24 hours to warm to -30° C. stirred for 30 minutes The mixture instantly darkened upon addition The reaction was quenched after 30 minutes with 3% aqueous ammonium hydroxide and saturated ammonium chloride This biphasic solution was stirred overnight copper removal The aqueous layer was extracted repetitively with ether to remove all product The combined organic layers were dried over sodium sulfate concentrated under reduced pressure The yellow oil was purified by distillation at 62° C. at 0.03 torr

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 20.2 g (198.0 mmol) of lithium trimethylethylenediamine in 500 ml of dry tetrahydrofuran (THF) under nitrogen at -30° C. was added 79 ml (198.0 mmol) of 2.5M butyllithium (nBuLi) in hexanes dropwise over 15 minutes. The solution became pale yellow and was stirred at -30° C. for 30 minutes. To this solution was added 20.0 g (188.5 mmol) of benzaldehyde dropwise over 30 minutes. The solution became cloudy as the complex was formed and was stirred 1 hour. To this slurry was added 113 ml (283 mmol) of 2.5M nBuLi hexanes dropwise over 1 hour. This slurry was stirred for 24 hours and gradually cleared. The solution was then transferred via cannula into a slurry of 50.6 g (565 mmol) of copper cyanide in 500 ml of dry tetrahydrofuran under nitrogen at -78° C. The mixture was allowed to warm to -30° C. and stirred for 30 minutes. To this slurry was added 49 ml (565 mmol) of allyl bromide. The mixture instantly darkened upon addition. The reaction was quenched after 30 minutes with 3% aqueous ammonium hydroxide and saturated ammonium chloride. This biphasic solution was stirred overnight to ensure complete copper removal. The aqueous layer was extracted repetitively with ether to remove all product. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. The yellow oil was purified by distillation at 62° C. at 0.03 torr affording 15.32 g (56%) of o-allylbenzaldehyde. 1H NMR: δ3.82 (d; 2H, J=6.17 Hz, CH2CH=CH2), 4.99 (d; 1H, J=17.1 Hz, one of CH=CH2), 5.09 (d; 1H, J=10.2 Hz, one of CH=CH2), 6.04 (m, 1H CH=CH2), 7.3 (d; 1H, J=7.8 Hz, aryl H), 7.40 (dd; 1H, J=7.6 Hz, aryl H), 7.54 (dd; 1H, J=7.4 Hz, 7.8 Hz, aryl H), 7.86 (d; 1H, J=7.6 Hz, aryl H), 10.26 (s; 1H aldehyde H). was formed was stirred 1 hour This slurry was stirred for 24 hours to warm to -30° C. stirred for 30 minutes The mixture instantly darkened upon addition The reaction was quenched after 30 minutes with 3% aqueous ammonium hydroxide and saturated ammonium chloride This biphasic solution was stirred overnight copper removal The aqueous layer was extracted repetitively with ether to remove all product The combined organic layers were dried over sodium sulfate concentrated under reduced pressure The yellow oil was purified by distillation at 62° C. at 0.03 torr