tert-butyl 3-phenylprop-2-enoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: (S)-N-cinnamyl-α-methylbenzylamine (4) (0.100 g, 0.42 mmol), 1.6M butyllithium (0.242 ml, 0.39 mmol) and t-butyl cinnamate (7) (0.072 g, 0.35 mmol) were reacted according to the procedure of Example 1. Flash chromatography of the product on silica gel [ethyl acetate/petroleum ether (1:49)] afforded the title compound (Rf 0.3) as a colourless oil (0.145 g, 78%). δH (300 MHz; CDCl3) 7.50-7.18 (15H, m, Ph), 6.42 (1H, d, J=16.0, PhCH=CH), 6.11 (1H, dt, J=16.0 and 6.2; CH=CHPh), 4.53 (1H, dd, J=8.7 and 6.4, PhCHCH2), 4.07 (1H, q, J=6.7, PhCHCH3), 3.32 (2H, dd, J=6.2 and 1.1, NCH2), 2.83 (1H, dd, J=14.6 and 6.4, CH2CO2), 2.62 (1H, dd, J=14.6 and 8.7, CH2CO2), 1.31 (9H, s, (CH3)3C), 1.27 (3H, d, J=6.7, PhCHCH3).

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of (1R)-N-benzyl-1-phenyl-1-ethanamine (16.6 g, 79 mmol) in tetrahydrofuran (200 ml) at −10° C. was added n-butyl lithium (46 ml of a 1.6M solution in hexane, 74 mmol) dropwise. The purple solution was stirred for 15 minutes, cooled to −78° C. and a solution of tert-butylcinnamate (10.0 g, 49 mmol) in tetrahydrofuran (100 ml) added dropwise. After stirring for 2 hours (−)-camphorsulphonyl oxaziridine (18 g, 79 mmol) was added portionwise and the reaction stirred at −78° C. for 1 hour. The reaction was warmed to room temperature and saturated aqueous ammonium chloride solution added and the solvent removed under reduced pressure. The remaining aqueous mixture was extracted with dichloromethane (x2) and the combined organic layers were dried (MgSO4), filtered and evaporated under reduced pressure. The residue was dissolved in diethyl ether, filtered and the filtrate washed with water, dried (MgSO4), filtered and evaporated under reduced pressure. The pale yellow oily residue was purified by column chromatography on silica gel using a gradient elution of diethyl ether:hexane (0:100 to 10:90) to afford the title compound as a colourless oil, 10.0 g. was added portionwise the reaction stirred at −78° C. for 1 hour The reaction was warmed to room temperature the solvent removed under reduced pressure The remaining aqueous mixture was extracted with dichloromethane (x2) the combined organic layers were dried (MgSO4) filtered evaporated under reduced pressure The residue was dissolved in diethyl ether filtered the filtrate washed with water dried (MgSO4) filtered evaporated under reduced pressure The pale yellow oily residue was purified by column chromatography on silica gel using a gradient elution of diethyl ether:hexane (0:100 to 10:90)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (S)-N-allyl-α-methylbenzylamine (2) (1.94 g, 12.1 mmol) in anhydrous tetrahydrofuran (25 ml) was cooled to -78° C. and 1.6M butyllithium (6.03 ml, 9.6 mmol) was added dropwise via a syringe. The resulting orange lithium amide solution was stirred at -78° C. for 1 hour. A solution of t-butyl cinnamate (7) (1.64 g, 8.1 mmol) in anhydrous tetrahydrofuran (15 ml) was then added via a cannula and the solution was stirred for a further 1 hour. The resulting yellow enolate solution was then diluted with anhydrous tetrahydrofuran (30 ml) and solid (+)-(camphorsulphonyl)-oxaziridine (2.76 g, 12.1 mmol) was added. After stirring for a further 6 hours at -78° C., the mixture was warmed to 0° C. (15 minutes) and quenched by the addition of saturated aqueous ammonium chloride solution. Ethyl acetate (50 ml) was added, followed by brine (10 ml). The organic layer was separated, dried (magnesium sulphate) and filtered and the solvent was evaporated under reduced pressure to afford an oily solid residue. Treatment of this with diethyl ether precipitated the oxaziridine/sulfonimine which was removed by filtration and the resulting oil was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:19)] affording the title compound (Rf 0.20) as a colourless oil (2.89 g, 95%). δH (300 MHz: CDCl3) 7.50-7.21 (10H, m, Ph), 5.89 (1H, m, NCH2CH=CH2), 5.12 (1H, app. dd, J=17.2 and 41.4, trans CH=CH2), 5.04 (1H, app. dd, J=17.2 and 1.4, cis CH=CH2), 4.53 (1H, d, J=3.8, CHOH), 4.23 (1H, d, J=3.8, NCHCH), 4.13 (1H, q, J=6.8, PhCHCH3), 3.47 (1H, app. dd, J=15.6 and 7.1, NCH2), 3.03 (1H, bs, OH), 1.29 (9H, s, (CH3)3CH), 1.21 (3H, d, J=6.8, PhCHCH3). was added After stirring for a further 6 hours at -78° C. quenched by the addition of saturated aqueous ammonium chloride solution Ethyl acetate (50 ml) was added The organic layer was separated dried (magnesium sulphate) filtered the solvent was evaporated under reduced pressure to afford an oily solid residue Treatment of this with diethyl ether precipitated the oxaziridine/sulfonimine which was removed by filtration the resulting oil was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:19)]

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

Procedure: Under an argon atmosphere, n-butyllithium (0.9 mL, 1.6 M in hexane solution, 1.5 mmol) was added to a solution of N-benzyltrimethylsilylamine (0.3 mL, 1.5 mmol) in toluene (4 mL) at −78° C. over 5 min. After stirring for 0.5 hr, a solution of (1R,2R)-1,2-dimethoxy-1,2-diphenylethane (436 mg, 1.8 mmol) in toluene (2 mL) was added, and the mixture was stirred at −78° C. for 0.5 hr. Thereto was added a solution of tert-butyl cinnamate (204 mg, 1.0 mmol) and chlorotrimethylsilane (0.63 mL, 5.0 mmol) in toluene (2 mL) over 5 min. The mixture was stirred at −78° C. for 5 hr, and quenched with saturated aqueous ammonium chloride solution (1.5 mL). After adding a saturated aqueous sodium hydrogen carbonate solution (20 mL), the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate, after which it was concentrated and subjected to silica gel column chromatography (ethyl acetate/hexane=1/25) to give the title compound (302 mg, yield 97%) as a colorless oil of [α]25D+32.5 (c 1.35, CHCl3). the mixture was stirred at −78° C. for 0.5 hr The mixture was stirred at −78° C. for 5 hr quenched with saturated aqueous ammonium chloride solution (1.5 mL) After adding a saturated aqueous sodium hydrogen carbonate solution (20 mL) the mixture was extracted with ethyl acetate The organic layer was washed with brine dried over sodium sulfate after which it was concentrated