(E)-but-2-en-1-ol

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (E)-but-2-en-1-ol (50 g, 693 mmol) in 1,1,1-triethoxyethane (890 mL 4854 mmol) was added acetic acid (5 g, 83 mmol) at room temperature. The reaction was heated to 125° C. for 4 h. The by-product ethanol was distilled by normal distillation to get crude compound ethyl 3-methylpent-4-enoate (70 g, 71.0%) as color less oil. This was taken to next step without further purification; 1H NMR (DMSO-d6) δ ppm 5.82-5.73 (m, 1H), 5.03-4.92 (m, 2H), 4.08-4.02 (m, 2H), 2.50 (m, 1H), 2.31-2.26 (m, 2H), 1.17 (t, J=8 Hz, 3H), 1.00 (d, J=8 Hz, 3H). The by-product ethanol was distilled by normal distillation

Conditions: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (E)-but-2-en-1-ol (50 g, 693 mmol) in 1,1,1-triethoxyethane (890 mL 4854 mmol) was added acetic acid (5 g, 83 mmol) at room temperature. The reaction was heated to 125° C. for 4 h. The by-product ethanol was distilled by normal distillation to get crude compound ethyl 3-methylpent-4-enoate (70 g, 71.0%) as color less oil. This was taken to next step without further purification; 1H NMR (DMSO-d6) δ ppm 5.82-5.73 (m, 1H), 5.03-4.92 (m, 2H), 4.08-4.02 (m, 2H), 2.50 (m, 1H), 2.31-2.26 (m, 2H), 1.17 (t, J=8 Hz, 3H), 1.00 (d, J=8 Hz, 3H). The by-product ethanol was distilled by normal distillation

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)

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

Procedure: To a solution of 1-(tert-butoxycarbonyl)-3-piperidine carboxylic acid (50.0 g) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (45.8 g) in chloroform (500 ml) was added 4-dimethylaminopyridine (29.3 g), and the mixture was stirred for 50 minutes. To the mixture was added (E)-but-2-en-1-ol (22.1 ml), and the mixture was stirred at room temperature for 1.5 hours. To the reaction mixture was added 10% aqueous potassium bisulfate solution (500 ml), and the mixture was extracted with chloroform. The separated organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution (400 ml) and saturated aqueous sodium chloride solution (350 ml). The separated aqueous layer was extracted with chloroform (300 ml) again. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=7/1) to give the titled compound (57.1 g). the mixture was stirred at room temperature for 1.5 hours the mixture was extracted with chloroform The separated organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution (400 ml) and saturated aqueous sodium chloride solution (350 ml) The separated aqueous layer was extracted with chloroform (300 ml) again The combined organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=7/1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)

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

Procedure: A reaction similar to that described in Example 1 (1a) was conducted using methyl 4-hydroxybenzoate (5.00 g, 32.9 mmol) and trans-crotyl alcohol (manufactured by Fluka, 2.37 g, 32.9 mmol) to give 5.78 g of the title compound (white powder, yield: 91%). A reaction similar to

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), 1,10-phenanthroline (36 mg, 0.20 mmol, 0.20 equiv), Cs2CO3 (652 mg, 2.0 mmol, 2.0 equiv), 4-iodoanisole (234 mg, 1.0 mmol, 1.0 equiv), trans-2-buten-1-ol (171 μL, 2.0 mmol, 2.0 equiv) and toluene (0.5 mL). The test tube was sealed and the reaction mixture was stirred at 110° C. for 22 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with diethyl ether. The filtrate was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1) provided 153 mg (86% yield) of the title compound as a light yellow oil. The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with diethyl ether The filtrate was concentrated in vacuo Purification of the residue by flash chromatography on silica gel (2×20 cm; pentane:diethyl ether 30:1)