pent-4-ynoxymethylbenzene

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

Procedure: 15 ml of 4-pentin-1-ol is added in drops at 0° C. to a suspension of 17.4 g of sodium hydride (55%) in 200 ml of DMF, and it is stirred for 1 hour at 0° C. Then, 30 ml of benzyl bromide is added in drops at this temperature, and it is stirred for another 2 hours at 0° C. Then, the reaction is carefully neutralized with 1N hydrochloric acid. The phase separation is carried out between diethyl ether and water, and the aqueous phase is extracted several times with diethyl ether. The combined organic phases are washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution, dried on magnesium sulfate and concentrated by evaporation. The residue is distilled in an oil pump vacuum, and 22.7 g of 5-benzyloxypent-1-ine is obtained as a colorless oil. is stirred for another 2 hours at 0° C The phase separation the aqueous phase is extracted several times with diethyl ether The combined organic phases are washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution dried on magnesium sulfate concentrated by evaporation The residue is distilled in an oil pump vacuum

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

Procedure: 15 ml of 4-pentin-1-ol is added in drops at 0° C. to a suspension of 17.4 g of sodium hydride (55%) in 200 ml of DMF, and it is stirred for 1 hour at 0° C. Then, 30 ml of benzyl bromide is added in drops at this temperature, and it is stirred for another 2 hours at 0° C. Then, the reaction is carefully neutralized with 1N hydrochloric acid. The phase separation is carried out between diethyl ether and water, and the aqueous phase is extracted several times with diethyl ether. The combined organic phases are washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution, dried on magnesium sulfate and concentrated by evaporation. The residue is distilled in an oil pump vacuum, and 22.7 g of 5-benzyloxypent-1-ine is obtained as a colorless oil. is stirred for another 2 hours at 0° C The phase separation the aqueous phase is extracted several times with diethyl ether The combined organic phases are washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution dried on magnesium sulfate concentrated by evaporation The residue is distilled in an oil pump vacuum

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

Procedure: To a solution of 17 (0.21 g, 0.51 mmol) and 5-benzyloxy-1-pentyne (133 mg, 0.77 mmol) in N,N-diisopropylethylamine (1 mL, 5.7 mmol) and dry THF (5 mL) were added CuI (9.7 mg, 51 μmol) and tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 25.5 μmol) under nitrogen. The mixture was heated at reflux under nitrogen for one day, and then was cooled to room temperature and filtered through a short pad of silica gel to remove insoluble and very polar components in the mixture. The filtrate was concentrated and dissolved in CH2Cl2 (50 mL). The solution was washed with water (2×20 mL) and brine (2×20 mL), and dried over Na2SO4. The solvent was removed under vacuum and the residue was purified by column chromatography (hexanes/EtOAc 20:1 to 6:1) to give 18 (0.14 g, 53%). 1H NMR δ 7.43-7.19 (m, 4H), 6.49 (d, 1H, J=16.4 Hz), 6.21 (d, 1H, J=16.4 Hz), 5.43 (s, 1H), 4.50 (s, 2H), 3.98 (d, 2H, J=11.2 Hz), 3.87 (d, 2H, J=11.2 Hz), 3.59 (t, 2H, J=6.0 Hz), 2.53 (t, 2H, J=6.8 Hz), 1.89 (m, 2H), 1.45 (s, 15H); 13C NMR δ 154.4, 138.1, 135.5, 131.3, 129.3, 127.9, 127.2, 127.1, 125.9, 122.8, 97.8, 90.1, 80.6, 79.0, 72.5, 68.3, 65.6, 52.7, 28.5, 28.0, 27.1, 19.3, 15.9. HRMS m/z: calcd for C31H39NNaO5 (MNa+), 528.2720; found, 528.2727. The mixture was heated at reflux under nitrogen for one day filtered through a short pad of silica gel to remove insoluble The filtrate was concentrated dissolved in CH2Cl2 (50 mL) The solution was washed with water (2×20 mL) and brine (2×20 mL) dried over Na2SO4 The solvent was removed under vacuum the residue was purified by column chromatography (hexanes/EtOAc 20:1 to 6:1)

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

Procedure: A flame-dried 20 mL vial fitted with a screw-cap septa was charged with Pd(PPh3)2Cl2 (0.06 equiv., 0.12 mmol, 84 mg), Cut (0.12 equiv., 0.24 mmol, 45.6 mg), and 4,5-diiodo-1,2-phenylene bis(trifluoromethanesulfonate) (1 equiv., 2 mmol, 1.25 g). The vessel was evacuated and backfilled with nitrogen (3×), followed by the sequential addition of THF (4 mL), Et3N (3 equiv., 6 mmol, 0.85 mL), and ((pent-4-yn-1-yloxy)methyl)benzene (2.3 equiv., 4.6 mmol, 802 mg) in THF (1 mL). The reaction was stirred for 3 h at rt, filtered through a pad of silica and concentrated in vacuo. Purification by flash chromatography (step gradient from Hex to 10% EtOAc/Hex) afforded 4,5-bis(5-(benzyloxy)pent-1-yn-1-yl)-1,2-phenylene bis(trifluoromethanesulfonate) (1.14 g, 1.59 mmol, 79%). TLC Rf=0.27 (10% EtOAc/Hex); 1HNMR (600 MHz): δ 7.42 (s, 2H), 7.27-7.39 (10H), 4.56 (s, 4H), 3.65 (t, 4H, J=6.0 Hz), 2.62 (t, 4H, J=7.1 Hz), 1.92-1.98 (m, 4H); 13CNMR (150 MHz): δ 138.8, 138.3, 128.4, 128.2, 127.59, 127.56, 126.3, 121.7, 119.6, 117.5, 115.3, 98.1, 77.4, 73.0, 68.5, 28.6, 16.5; FTIR: 2859, 2230, 1489, 1433, 1210, 1178, 1135, 1080, 732 cm−1; HRMS-ESI: calc. for C32H28F6O8S2Na (M+Na)+: 741.1027. found: 741.1039. A flame-dried 20 mL vial fitted with a screw-cap septa The vessel was evacuated filtered through a pad of silica concentrated in vacuo Purification by flash chromatography (step gradient from Hex to 10% EtOAc/Hex)

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

Procedure: To a flame-dried round-bottomed flask was added NaH (2 equiv., 47.6 mmol, 1.9 g of a 60% dispersion in mineral oil). The solid was washed with hexanes (15 mL), THF (95 mL) was added and the suspension was cooled to 0° C. Pentynol (1 equiv., 23.8 mmol, 2.0 g) was added drop wise in THF (5 mL), followed by drop wise addition of BnBr (0.92 equiv., 21.9 mmol, 2.60 mL). The reaction was warmed to ambient temperature over 16 h, quenched with saturated aqueous NH4Cl (25 mL), and diluted with water (20 mL). The organic layer was extracted with EtOAc (2×40 mL), washed with brine (40 mL) and dried with Na2SO4. Product isolation was achieved by concentration in vacuo and purification by flash column chromatography to afford ((pent-4-yn-1-yloxy)methyl)benzene (3.60 g, 20.7 mmol, 94%). TLC Rf=0.41 (5% EtOAc/Hex); 1HNMR (300 MHz): δ 7.29-7.44 (5H), 4.55 (s, 2H), 3.61 (t, 2H, J=6.2 Hz), 2.36 (td, 2H, J=7.1, 2.6 Hz), 1.97 (t, 1H, J=2.6 Hz), 1.81-1.93 (m, 2H). 13CNMR (75 MHz): δ 138.5, 128.4, 127.63, 127.58, 84.0, 73.0, 68.7, 68.5, 28.7, 15.3. The solid was washed with hexanes (15 mL), THF (95 mL) was added The reaction was warmed to ambient temperature over 16 h quenched with saturated aqueous NH4Cl (25 mL) diluted with water (20 mL) The organic layer was extracted with EtOAc (2×40 mL) washed with brine (40 mL) dried with Na2SO4 Product isolation was achieved by concentration in vacuo and purification by flash column chromatography