(E)-but-2-ene-1,4-diol

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

Procedure: To a solution of trans-2-butene-1,4-diol (7.57 g, 85.9 mmole) and a catalytic quantity of p-toluenesulfonic acid in 700 ml of dry ether was added dihydropyran (6.73 ml, 71.6 mmole) at the rate of 1.5 ml/hour. After stirring for four days, the reaction mixture was washed with saturated sodium bicarbonate, and the organic layer was separated and dried over sodium sulfate and concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1) to provide the title compound (5.75 g). the reaction mixture was washed with saturated sodium bicarbonate the organic layer was separated dried over sodium sulfate concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1)

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

Procedure: To a solution of trans-2-butene-1,4-diol (7.57 g, 85.9 mmole) and a catalytic quantity of p-toluenesulfonic acid in 700 ml of dry ether was added dihydropyran (6.73 ml, 71.6 mmole) at the rate of 1.5 ml/hour. After stirring for four days, the reaction mixture was washed with saturated sodium bicarbonate, and the organic layer was separated and dried over sodium sulfate and concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1) to provide the title compound (5.75 g). the reaction mixture was washed with saturated sodium bicarbonate the organic layer was separated dried over sodium sulfate concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1)

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

Procedure: A solution of Trityl chloride (500 mg; 1.81 mmol), TEA (0.277 ml; 1.99 mmol) and DMAP (8.8 mg; 0.072 mmol) in dry DCM (5 ml) was added with a syringe to a solution of the diol (10) (800 mg; 9.07 mmol) in DCM (15 ml). The mixture was stirred at room temperature for 1 hour and 30 minutes, then other TrCl, TEA and DMAP (half quantities than before) were added. The reaction was stirred at the same temperature until TLC (Hexane/EtOAc 50:50) showed complete disappearance of Trityl chloride. After 1.5 hours water (20 ml) was added and the reaction was stirred for few minutes, then the phases were separated. The organic layer was washed with water (25 ml) and brine (25 ml). The solvent was dried over MgSO4 and evaporated to afford a crude oil which was purified by flash chromatography using Hexane/EtOAc 50:50 as eluent which gave the title compound as a colourless oil, 637 mg, 71%. Rf: 0.72 in Hexane/EtOAc 50:50 (UV/PMA). the reaction was stirred for few minutes the phases were separated The organic layer was washed with water (25 ml) and brine (25 ml) The solvent was dried over MgSO4 evaporated to afford a crude oil which was purified by flash chromatography

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

Procedure: A solution of Trityl chloride (500 mg; 1.81 mmol), TEA (0.277 ml; 1.99 mmol) and DMAP (8.8 mg; 0.072 mmol) in dry DCM (5 ml) was added with a syringe to a solution of the diol (10) (800 mg; 9.07 mmol) in DCM (15 ml). The mixture was stirred at room temperature for 1 hour and 30 minutes, then other TrCl, TEA and DMAP (half quantities than before) were added. The reaction was stirred at the same temperature until TLC (Hexane/EtOAc 50:50) showed complete disappearance of Trityl chloride. After 1.5 hours water (20 ml) was added and the reaction was stirred for few minutes, then the phases were separated. The organic layer was washed with water (25 ml) and brine (25 ml). The solvent was dried over MgSO4 and evaporated to afford a crude oil which was purified by flash chromatography using Hexane/EtOAc 50:50 as eluent which gave the title compound as a colourless oil, 637 mg, 71%. Rf: 0.72 in Hexane/EtOAc 50:50 (UV/PMA). the reaction was stirred for few minutes the phases were separated The organic layer was washed with water (25 ml) and brine (25 ml) The solvent was dried over MgSO4 evaporated to afford a crude oil which was purified by flash chromatography

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

Procedure: To a solution of (2E)-2-butene-1,4-diol (8.22 mL, 0.10 mol) and imidazole (8.50 g, 0.125 mol) in DMF (50 mL) at 0° C., was added tert-butyldimethylsilyl chloride (7.50 g, 0.050 mol) in several portions over 10 minutes. The resulting mixture was warmed to room temperature and stirred (2 h), then poured into H2O (200 mL) and extracted with EtOAc (2×150 mL). The organic layer was washed (brine), dried (Na2SO4) and purified by silica gel column chromatography (hexanes:EtOAc) to yield 5 as a colorless oil (9.0 g, 89% yield). 1H NMR (400 MHz, CDCl3) δ 5.60-5.50 (m, 2H), 4.18 (m, 2H), 4.09 (m, 2H), 2.76 (br, 1H), 0.83 (s, 9H), 0.01 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 136.3, 135.4, 64.8, 63.8, 31.1, 23.6. extracted with EtOAc (2×150 mL) The organic layer was washed (brine) dried (Na2SO4) purified by silica gel column chromatography (hexanes:EtOAc)

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

Procedure: A mixture of N-benzylhydroxylamine (4.4 g, 27.7 mmol) and anhydrous NaOAc (3.0 g, 36.7 mmol) in 35 ml EtOH was stirred at ambient temperature for 15 min, after which time formaldehyde (4.1 ml, 55.1 mmol) was added and the mixture stirred for another 30 min. A solution of (E)-but-2-ene-1,4-diol (1.63 g, 18.50 mmol) in ethanol (20 ml) was then introduced to the mixture in a single slug and the resulting solution refluxed for 18 hours. The mixture was cooled, concentrated and taken up in DCM and the solution washed sodium bicarbonate solution, dried and concentrated to an immobile oil (5.25 g). The crude product was fractionated by chromatography over silica eluting firstly with EtOAc and then with 5% MeOH/EtOAc and the title compound was isolated as an immobile syrup (1.95 g). The chromatography was repeated with only EtOAc as eluant and the compound isolated (1.46 g, 35%) as an homogeneous syrup. 1H NMR (CDCl3) δ 7.41-7.22 (m, 5H), 4.10-3.82 (m, 2H), 3.80-3.60 (m, 4H), 3.5-2.3 (m, 5H). 13C NMR 137.0, 129.3, 128.8, 128.0, 81.6, 64.1, 63.0, 58.7, 47.7. the mixture stirred for another 30 min the resulting solution refluxed for 18 hours The mixture was cooled concentrated the solution washed sodium bicarbonate solution dried concentrated to an immobile oil (5.25 g)

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

Procedure: To a solution of trans-2-butene-1,4-diol (7.57 g, 85.9 mmole) and a catalytic quantity of p-toluenesulfonic acid in 700 ml of dry ether was added dihydropyran (6.73 ml, 71.6 mmole) at the rate of 1.5 ml/hour. After stirring for four days, the reaction mixture was washed with saturated sodium bicarbonate, and the organic layer was separated and dried over sodium sulfate and concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1) to provide the title compound (5.75 g). the reaction mixture was washed with saturated sodium bicarbonate the organic layer was separated dried over sodium sulfate concentrated in vacuo to afford the crude product which was purified via flash chromatography (LPS-1 silica gel; ether-hexane 1:1)

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

Procedure: A solution of 11.8 g (133.4 mmol) of trans 2-butene-1,4-diol in 100 ml of DMF was treated with 6.4 g (147 mmol) of sodium hydride dispersion on oil (55%), stirred at 0° C. for 45 min., and treated dropwise with 25.1 g (160 mmol) of 4-methoxybenzylchloride. The mixture was stirred during 5 hrs at RT and then poured into a saturated aqueous solution of NaCl. Extraction with AcOEt, drying of the combined organic phases over Na2SO4, filtration, evaporation of the solvent and chromatography on silica gel with heptane/AcOEt 9:1 gave 5.7 g (21%) of trans 4-(4-methoxy-benzyloxy)-but-2-en-1-ol. Light yellow oil. MS: 207 (M−H)−. The mixture was stirred during 5 hrs at RT Extraction with AcOEt drying of the combined organic phases over Na2SO4, filtration, evaporation of the solvent and chromatography on silica gel with heptane/AcOEt 9:1

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

Procedure: A solution of Trityl chloride (500 mg; 1.81 mmol), TEA (0.277 ml; 1.99 mmol) and DMAP (8.8 mg; 0.072 mmol) in dry DCM (5 ml) was added with a syringe to a solution of the diol (10) (800 mg; 9.07 mmol) in DCM (15 ml). The mixture was stirred at room temperature for 1 hour and 30 minutes, then other TrCl, TEA and DMAP (half quantities than before) were added. The reaction was stirred at the same temperature until TLC (Hexane/EtOAc 50:50) showed complete disappearance of Trityl chloride. After 1.5 hours water (20 ml) was added and the reaction was stirred for few minutes, then the phases were separated. The organic layer was washed with water (25 ml) and brine (25 ml). The solvent was dried over MgSO4 and evaporated to afford a crude oil which was purified by flash chromatography using Hexane/EtOAc 50:50 as eluent which gave the title compound as a colourless oil, 637 mg, 71%. Rf: 0.72 in Hexane/EtOAc 50:50 (UV/PMA). the reaction was stirred for few minutes the phases were separated The organic layer was washed with water (25 ml) and brine (25 ml) The solvent was dried over MgSO4 evaporated to afford a crude oil which was purified by flash chromatography

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

Procedure: To a solution of (E)-2-buten-1,4-diol (326 mg, 3.7 mmol) and p-toluenesulfonyl chloride (1.76 g, 9.25 mmol) in 30 mL of THF was added portionwise sodium tert-butoxide (1.07 g, 11.1 mmol)) under stirring at 0° C. The mixture was then stirred overnight at rt. Water (100 mL) was added and the product was extracted with CH2CL2 (3×25 mL). The extract was dried with MgSO4, filtered, and evaporated. Purification by flash column chromatography with hexane:ether:CH2CH2/3:1:1 gave the product as a crystal (1.21 g, 182%), m.p. 90-91° C. 1H NMR (300 MHz, CDCl3) δ 7.77 (d, J=8.7 Hz, 4H), 7.35 (d, J−8.4 Hz, 4H), 5.75-5.73 (m, 2H), 4.49-4.47 (m, 4H), 2.46 (s, 6H; Anal. Calcd for C18H20O6S2: C, 54.53; H, 5,08,found C, 54.61; H, 5.07. The mixture was then stirred overnight at rt the product was extracted with CH2CL2 (3×25 mL) The extract was dried with MgSO4 filtered evaporated Purification by flash column chromatography with hexane

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

Procedure: A solution of Trityl chloride (500 mg; 1.81 mmol), TEA (0.277 ml; 1.99 mmol) and DMAP (8.8 mg; 0.072 mmol) in dry DCM (5 ml) was added with a syringe to a solution of the diol (10) (800 mg; 9.07 mmol) in DCM (15 ml). The mixture was stirred at room temperature for 1 hour and 30 minutes, then other TrCl, TEA and DMAP (half quantities than before) were added. The reaction was stirred at the same temperature until TLC (Hexane/EtOAc 50:50) showed complete disappearance of Trityl chloride. After 1.5 hours water (20 ml) was added and the reaction was stirred for few minutes, then the phases were separated. The organic layer was washed with water (25 ml) and brine (25 ml). The solvent was dried over MgSO4 and evaporated to afford a crude oil which was purified by flash chromatography using Hexane/EtOAc 50:50 as eluent which gave the title compound as a colourless oil, 637 mg, 71%. Rf: 0.72 in Hexane/EtOAc 50:50 (UV/PMA). the reaction was stirred for few minutes the phases were separated The organic layer was washed with water (25 ml) and brine (25 ml) The solvent was dried over MgSO4 evaporated to afford a crude oil which was purified by flash chromatography

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

Procedure: To a solution of (2E)-2-butene-1,4-diol (8.22 mL, 0.10 mol) and imidazole (8.50 g, 0.125 mol) in DMF (50 mL) at 0° C., was added tert-butyldimethylsilyl chloride (7.50 g, 0.050 mol) in several portions over 10 minutes. The resulting mixture was warmed to room temperature and stirred (2 h), then poured into H2O (200 mL) and extracted with EtOAc (2×150 mL). The organic layer was washed (brine), dried (Na2SO4) and purified by silica gel column chromatography (hexanes:EtOAc) to yield 5 as a colorless oil (9.0 g, 89% yield). 1H NMR (400 MHz, CDCl3) δ 5.60-5.50 (m, 2H), 4.18 (m, 2H), 4.09 (m, 2H), 2.76 (br, 1H), 0.83 (s, 9H), 0.01 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 136.3, 135.4, 64.8, 63.8, 31.1, 23.6. extracted with EtOAc (2×150 mL) The organic layer was washed (brine) dried (Na2SO4) purified by silica gel column chromatography (hexanes:EtOAc)