diethyl (E)-hex-3-enedioate

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

Procedure: To a stirred solution of 5.0 g (25.0 mmol) trans-2-butene-1,4-dicarboxylic acid diethyl ester in 125 ml THF was added 6.35 g (150 mmol) anhydrous lithium chloride and the resulting suspension cooled to −78° C. 25.0 ml (50.0 mmol) of a 2 M solution of LDA in THF was added dropwise and stirring continued for 45 min. 7.4 ml (78.7 mmol) 2-methoxyethyl bromide was then added and stirring continued for 15 min at −78° C., then 1 h at 0° C., and then 2 h at room temperature. The reaction was quenched by addition of saturated ammonium chloride solution and the mixture extracted three times with ether. The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine, dried over sodium sulphate, and concentrated in vacuo. Flash chromatography (50% toluene in EtOAc) afforded 1.29 g (16%) of the title compound as a yellow oil. MS m/e (%): 334 ([M+NH4]+, 100). stirring continued for 15 min at −78° C. 1 h at 0° C. 2 h at room temperature The reaction was quenched by addition of saturated ammonium chloride solution the mixture extracted three times with ether The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine dried over sodium sulphate concentrated in vacuo

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

Procedure: To a stirred solution of 5.0 g (25.0 mmol) trans-2-butene-1,4dicarboxylic acid diethyl ester in 120 ml THf was added 6.35 g (150 mmol) anhydrous lithium chloride and the resulting suspension cooled to −78° C. 25.0 ml (50.0 mmol) of a 2 M solution of LDA in THF was added dropwise and stirring continued for 45 min. 4.7 ml (50 mmol) isopropyl bromide was then added and stirring continued for 15 min at −78° C., then 4 h at 0° C., and then 48 h at room temperature. The reaction was quenched by addition of saturated ammonium chloride solution and the mixture extracted three times with ether. The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine, dried over sodium sulphate, and concentrated in vacuo. Successive flash chromatography (20% EtOAc in hexane for first column; 5% EtOAc in hexane for second column; 10% EtOAc in hexane for third column) afforded 259 mg (4%) of the title compound as a yellow oil. MS m/e (%): 302 ([M+NH4]+, 100). stirring continued for 15 min at −78° C. 4 h at 0° C. 48 h at room temperature The reaction was quenched by addition of saturated ammonium chloride solution the mixture extracted three times with ether The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine dried over sodium sulphate concentrated in vacuo

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

Procedure: To a stirred solution of 2.0 g (9.99 mmol) trans-2-butene-1,4-dicarboxylic acid diethyl ester in 80 ml THF was added 2.54 g (59.9 mmol) anhydrous lithium chloride and the resulting suspension cooled to −78° C. 10.0 ml (20.0 mmol) of a 2 M solution of LDA in THF was added dropwise and stirring continued for 45 min. 2.2 ml (20.4 mmol) butyl bromide was then added and stirring continued for 15 min at −78° C., then 30 min at 0° C, and then 4 h at room temperature. The reaction was quenched by addition of saturated ammonium chloride solution and the mixture extracted three times with ether. The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine, dried over sodium sulphate, and concentrated in vacuo. Successive flash chromatography (10% EtOAc in hexane for first column; then gradient: 10-100% toluene in cyclohexane for second column) afforded 509 mg (16%) of the title compound as a yellow oil. MS m/e (%): 330 ([M+NH4]+, 100). stirring continued for 15 min at −78° C. 30 min at 0° C 4 h at room temperature The reaction was quenched by addition of saturated ammonium chloride solution the mixture extracted three times with ether The combined organic phases were washed successively with saturated ammonium chloride solution, water, and saturated brine dried over sodium sulphate concentrated in vacuo

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

Procedure: To a stirred solution 688 mg (3.44 mmol) trans-2-butene-1,4-dicarboxylic acid diethyl ester in 35 ml THF was added 1.46 g (34.4 mmol) anhydrous lithium chloride and the resulting suspension cooled to −78° C. 3.44 ml (6.88 mmol) of a 2 M solution of LDA in THF was added dropwise and stirring continued for 45 min. 0.82 ml (6.9 mmol) benzyl bromide was then added and stirring continued for 1 h at −78° C. and 10 min at 0° C. The reaction was quenched at this temperature by addition of saturated ammonium chloride solution and the mixture extracted three times with ether. The combined organic phases were washed with saturated brine, dried over sodium sulphate, and concentrated in vacuo. Flash chromatography (5% EtOAc in hexane) afforded 927 mg (71%) of the title compound as a yellow oil. MS m/e (%): 398 ([M+NH4]+, 100). stirring continued for 1 h at −78° C. and 10 min at 0° C The reaction was quenched at this temperature by addition of saturated ammonium chloride solution the mixture extracted three times with ether The combined organic phases were washed with saturated brine dried over sodium sulphate concentrated in vacuo