but-3-ene-1,2-diol

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of Pd (OAc)2 (75 mg, 0.34 mmol), nBu3P (136 mg, 0.67 mmol), and Et3N (442 mg, 4.37 mmol) in DMF (10 ml) was added 3-butene-1,2-diol (296 mg, 3.36 mmol) followed by methyl 3-bromophenylacetate (1.0 g, 4.37 mmol), and the reaction mixture was stirred at 100° C. for 5 h. The reaction mixture was poured into water (100 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate) and evaporated in vacuo. The residue was purified by silica gel (25 g) column chromatography eluting with toluene/ethyl acetate (20:1) to give methyl 3-(4-hydroxy-3-oxobutyl)phenylacetate (193 mg, 24.4%) as an oil. extracted with ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) evaporated in vacuo The residue was purified by silica gel (25 g) column chromatography eluting with toluene/ethyl acetate (20:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of Pd (OAc)2 (75 mg, 0.34 mmol), nBu3P (136 mg, 0.67 mmol), and Et3N (442 mg, 4.37 mmol) in DMF (10 ml) was added 3-butene-1,2-diol (296 mg, 3.36 mmol) followed by methyl 3-bromophenylacetate (1.0 g, 4.37 mmol), and the reaction mixture was stirred at 100° C. for 5 h. The reaction mixture was poured into water (100 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate) and evaporated in vacuo. The residue was purified by silica gel (25 g) column chromatography eluting with toluene/ethyl acetate (20:1) to give methyl 3-(4-hydroxy-3-oxobutyl)phenylacetate (193 mg, 24.4%) as an oil. extracted with ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) evaporated in vacuo The residue was purified by silica gel (25 g) column chromatography eluting with toluene/ethyl acetate (20:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of Pd (OAc)2 (40 mg, 0.18 mmol), nBu3P (71 mg, 0.35 mmol), and Et3N (232 mg, 2.29 mmol) in DMF (5 ml) was added 3-butene-1,2-diol (155 mg, 1.76 mmol) followed by 4-iodotoluene (500 mg, 2.29 mmol), and the reaction mixture was stirred at 100° C. for 1.5 h. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate) and evaporated in vacuo. The residue was purified by silica gel (10 g) column chromatography eluting with toluene/ethyl acetate (50:1) to give 1-hydroxy-4-(p-tolyl)butan-2-one (230 mg, 73.4%) as a pale yellow solid. extracted with ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) evaporated in vacuo The residue was purified by silica gel (10 g) column chromatography eluting with toluene/ethyl acetate (50:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of Pd (OAc)2 (40 mg, 0.18 mmol), nBu3P (71 mg, 0.35 mmol), and Et3N (232 mg, 2.29 mmol) in DMF (5 ml) was added 3-butene-1,2-diol (155 mg, 1.76 mmol) followed by 4-iodotoluene (500 mg, 2.29 mmol), and the reaction mixture was stirred at 100° C. for 1.5 h. The reaction mixture was poured into water (50 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate) and evaporated in vacuo. The residue was purified by silica gel (10 g) column chromatography eluting with toluene/ethyl acetate (50:1) to give 1-hydroxy-4-(p-tolyl)butan-2-one (230 mg, 73.4%) as a pale yellow solid. extracted with ethyl acetate The organic layer was washed with brine dried (magnesium sulfate) evaporated in vacuo The residue was purified by silica gel (10 g) column chromatography eluting with toluene/ethyl acetate (50:1)

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

Procedure: 1,2-Dihydroxy-3-butene (20.00 g; 0.227 mol; 1.05 equiv.) was dissolved in pyridine (200 mL). The reaction mixture was cooled in an ice bath and p-toluenesulfonyl chloride (p-TsCl) (41.11 g; 0.216 mol) was added in four portions over 30 min. After thorough mixing, the reaction mixture was placed at 4° C for 18 h, at which time tlc analysis indicated no p-TsCl. The mixture was concentrated to approximately half the original volume at reduced pressure from a 40° C. water bath and then diluted with ether (200 mL). The mixture was washed with water (100 mL), ice-cold 3N HCl until the washes remained acidic (2×100 mL), and saturated sodium bicarbonate (100 mL). After drying the organic solution (MgSO4), the solvent was removed to afford 41.73 g of a 91:9 mixture (1H nmr analysis) of 1i and the corresponding di-tosylate. The crude product solidified over several days at -20° C. It was recrystallized from methylene chloride (50 mL) by the addition of hexanes (100 mL) and chilling to -20° C. to afford two crops (total 33.33 g; 61%) of 1i which was pure by tlc analysis, mp 38°-44° C. 1H nmr (300 MHz, CDCl3): 7.800 (2H, d, J=8.25 Hz); 7.356 (2H, d, J=8.19 Hz); 5.751 (1H, ddd, J=5.38, 10.46, 16.55 Hz); 5.378 (1H, br d, J=17.05 Hz); 5.247 (1H, br d, J=10.48 Hz); 4.396 (1H, m); 4.066 (1H, dd, 2.451 (3H, s); 2.276 (1H, d, J=4.50 Hz). IR (KBr, cm-1): 3520 (s,b); 1650 (w); 1600 (s); 1350 (s); 1170 (s). Combustion Analysis: Calcd - C, 54.53; H, 5.82; N, 0. Found - C, 54.84; H, 5.86; N, <0.3. The reaction mixture was cooled in an ice bath The mixture was concentrated to approximately half the original volume at reduced pressure from a 40° C. water bath diluted with ether (200 mL) The mixture was washed with water (100 mL), ice-cold 3N HCl until the washes After drying the organic solution (MgSO4) the solvent was removed

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

Procedure: 1,2-Dihydroxy-3-butene (20.00 g; 0.227 mol; 1.05 equiv) was dissolved in pyridine (200 mL). The reaction mixture was cooled in an ice bath and p-toluenesulfonyl chloride (p-TsCl) (41.11 g; 0.216 mol) was added in four portions over 30 min. After thorough mixing, the reaction mixture was placed at 4° C. for 18 h, at which time thin layer chromotography (hereinafter TLC) analysis indicated no p-TsCl. The mixture was concentrated to about half the original volume at reduced pressure from a 40° C. water bath and then diluted with ether (200 mL). The mixture was washed with water (100 mL), ice-cold 3N HCl until the washes remained acidic (2×100 mL), and saturated sodium bicarbonate (100 mL). After drying the organic solution (MgSO4), the solvent was removed to afford 41.73 g of a 91:9 mixture (1H nmr analysis) of the desired compound and the corresponding di-tosylate. The crude product solidified over several days at -20° C. It was recrystallized from methylene chloride (50 mL) by the addition of hexanes (100 mL) and chilling to -20° C. to afford two crops (total 33.33 g; 61%) of the desired compound which was pure by TLC analysis, mp 38°-44° C. 1H nmr (300 MHz, CDCl3): 7.800 (2H, d, J=8.25 Hz); 7.356 (2H, d, J=8.19 Hz); 5.751 (1H, ddd, J=5.38, 10.46, 16.55 Hz); 5.378 (1H, br d, J=17.05 Hz); 5.247 (1H, br d, J=10.48 Hz); 4.396 (1H, m); 4.066 (1H, dd, J=3.39, 10.20 Hz); 3.906 (1H, dd, J=7.41, 10.22 Hz); 2.451 (3H, s); 2.276 (1H, d, J=4.50 Hz). IR (KBr, cm-1): 3520 (s,b); 1650 (w); 1600 (s); 1350 (s); 1170 (s). Combustion Analysis: Theor--C, 54.53; H,5.82;N, 0. Found--C, 54.84; H, 5.86;N, <0.3. The reaction mixture was cooled in an ice bath The mixture was concentrated to about half the original volume at reduced pressure from a 40° C. water bath diluted with ether (200 mL) The mixture was washed with water (100 mL), ice-cold 3N HCl until the washes After drying the organic solution (MgSO4) the solvent was removed

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

Procedure: The racemic acetate substrate was prepared by one of two methods. The diol route began with racemic 1,2-dihydroxy-3-butene which could be prepared by reacting EpB with water under neutral conditions or with acid catalysis. The diol was treated with p-toluenesulfonyl chloride (p-TsCl) in pyridine at 4° C. to afford the desired monotosylate contaminated with about 10% of the corresponding ditosylate. The monotosylate could be selectively crystallized to afford pure monotosylate in 61% yield. Hydroxytosylate was acetylated under normal conditions (Ac2O, Et3N, CH2Cl2) to provide the acetoxy-tosylate (the desired racemic acetate) in 93% yield. The diol route is illustrated as follows: ##STR3## could be prepared

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

Procedure: The racemic acetate substrate was prepared by one of two methods. The diol route began with racemic 1,2-dihydroxy-3-butene which could be prepared by reacting EpB with water under neutral conditions or with acid catalysis. The diol was treated with p-toluenesulfonyl chloride (p-TsCl) in pyridine at 4° C. to afford the desired monotosylate contaminated with about 10% of the corresponding ditosylate. The monotosylate could be selectively crystallized to afford pure monotosylate in 61% yield. Hydroxytosylate was acetylated under normal conditions (Ac20, Et3N, CH2C12) to provide the acetoxy-tosylate (the desired racemic acetate) in 93% yield. The diol route is illustrated as follows: ##STR3## could be prepared

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

Procedure: Self-metathesis of 1,2-dihydroxy-3-butene. 1,2-Dihydroxy-3-butene (158 mg, 1.8 mmol) and (PCy3)2Cl2Ru═CHPh (30 mg, 0.036 mmol, 2.0 mol %) were dissolved in dry dichloromethane (5 ml). The solution was degassed then heated to reflux. Gradually, the solution's purple color changed to red-brown and a white solid formed. After 21 h heating was stopped and the white solid was filtered and dried in vacuo to give 11 mg, (0.074 mmol, 8.2% yield) of 3,4-dideoxyhexitol. 1H NMR (D2O) δ 5.80 (s, 1H), 4.25 (br s, 1H), 3.62 (m, 1H), 3.52 (m, 1H). The solution was degassed then heated to reflux formed After 21 h heating the white solid was filtered dried in vacuo

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

Procedure: To a solution of triphenylmethyl chloride (3.31 kg, 11.87 mol, 0.99 equiv) in toluene (6.74 kg) at RT, was added but-3-ene-1,2-diol (1.06 kg, 12.02 mol, 1.0 equiv.). The reaction mixture was cooled down to 0° C. Triethylamine (2.72 kg, 26.91 mol, 2.24 equiv.) was slowly added to the reaction mixture while maintaining temperature below 5° C., followed by 4-dimethylaminopyridine (8.38 g, 0.068 mol, 5.71 mmol). The reaction mixture was allowed to warm up to 10° C. then heated to 40° C. The reaction mixture was stirred at 40° C. overnight. The reaction was followed by TLC (Rf 0.45 in Heptane/EtOAc 20%). The reaction mixture was cooled down to 26.5° C., filtered and the solids were rinsed with toluene (2.72 kg). The filtrate was successively washed with 28% aq. NH4Cl solution (3.38 kg) and saturated aq NaCl solution (1.26 kg). The organic phase was then concentrated under reduced pressure to afford an oil as a crude mixture 3.95 kg). 1H NMR (500 MHz, DMSO) δ ppm 7.42 (dd, J=8.3, 1.0 Hz, 6H), 7.33 (dd, J=10.5, 4.8 Hz, 6H), 7.30-7.19 (m, 3H), 5.94-5.83 (m, 1H), 5.25 (td, J=17.3, 1.8 Hz, 1H), 5.08 (td, J=10.9, 1.8 Hz, 1H), 2.99 (dd, J=8.9, 6.3 Hz, 1H), 2.84 (dd, J=8.9, 5.7 Hz, 1H); 13C NMR (125 MHz, DMSO) δ 144.35, 140.07, 128.78, 128.26, 127.39, 115.04, 86.25, 70.88, 68.27. while maintaining temperature below 5° C. to warm up to 10° C. then heated to 40° C The reaction mixture was cooled down to 26.5° C. filtered the solids were rinsed with toluene (2.72 kg) The filtrate was successively washed with 28% aq. NH4Cl solution (3.38 kg) and saturated aq NaCl solution (1.26 kg) The organic phase was then concentrated under reduced pressure