1-dibutylphosphorylbutane

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

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

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

Procedure: A toluene (10 ml) solution of 5.9 g of 4-chlorophenyl isocyanate and 3.3 ml of epichlorohydrin was added dropwise to a toluene (1 ml) solution of 0.2 g of lithium bromide and 0.42 g of tri-n-butylphosphine oxide at 100° C. The mixture was stirred at the same temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Ethanol was added to the obtained residue to collect the crystals by filtration. Thus, 8.9 g of the title compound was obtained (yield 93%). The reaction mixture was concentrated under reduced pressure Ethanol was added to the obtained residue to collect the crystals by filtration

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

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

Procedure: For the purpose of improving catalytic activity, regio and enantio selectivities, various additives other than water may be added to the reaction system. For example, presence of phosphorus compounds, e.g., triethylphosphine oxide, triphenylphosphine oxide, tributylphosphine oxide, triethyl phosphite, tributyl phosphite, and triphenyl phosphite; or carboxylic acids, e.g., acetic acid, propionic acid and pivalic acid, in the reaction system gives rise to no interference with the reaction. may be added to the reaction system

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

Procedure: For the purpose of improving catalytic activity, regio and enantio selectivities, various additives other than water may be added to the reaction system. For example, presence of phosphorus compounds, e.g., triethylphosphine oxide, triphenylphosphine oxide, tributylphosphine oxide, triethyl phosphite, tributyl phosphite, and triphenyl phosphite; or carboxylic acids, e.g., acetic acid, propionic acid and pivalic acid, in the reaction system gives rise to no interference with the reaction. may be added to the reaction system

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

Procedure: A solution of (5)-tert-butyl 2-((S)-1,2-bis(tert-butyldimethylsilyloxy)ethyl)aziridine-1-carboxylate (0.740 g, 1.7 mmol) and 1H-imidazole (0.35 g, 5.1 mmol) in 3 mL toluen was thoroughly degassed and treated with tributylphosphine (0.42 ml, 1.7 mmol). The reaction mixture was heated to reflux and allowed to stir for 3 hours. NaH (60% dispersion in mineral oil) (0.069 g, 2.9 mmol) was added and the reaction mixture was allowed to stir at 110° C. overnight. The reaction mixture was quenched with saturated NH4Cl solution and diluted with EtOAc. The reaction mixture was washed with water then brine. The organics were dried over MgSO4 and concentrated in vacuo. Purification of the crude residue by column chromatography gave tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-(1H-imidazol-1-yl)butan-2-ylcarbamate with tributylphosphine oxide as the major impurity. This material was used without further purification. The reaction mixture was heated to reflux to stir at 110° C. overnight The reaction mixture was quenched with saturated NH4Cl solution diluted with EtOAc The reaction mixture was washed with water The organics were dried over MgSO4 concentrated in vacuo Purification of the crude residue by column chromatography

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

Procedure: A solution of (5)-tert-butyl 2-((S)-1,2-bis(tert-butyldimethylsilyloxy)ethyl)aziridine-1-carboxylate (0.740 g, 1.7 mmol) and 1H-imidazole (0.35 g, 5.1 mmol) in 3 mL toluen was thoroughly degassed and treated with tributylphosphine (0.42 ml, 1.7 mmol). The reaction mixture was heated to reflux and allowed to stir for 3 hours. NaH (60% dispersion in mineral oil) (0.069 g, 2.9 mmol) was added and the reaction mixture was allowed to stir at 110° C. overnight. The reaction mixture was quenched with saturated NH4Cl solution and diluted with EtOAc. The reaction mixture was washed with water then brine. The organics were dried over MgSO4 and concentrated in vacuo. Purification of the crude residue by column chromatography gave tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-(1H-imidazol-1-yl)butan-2-ylcarbamate with tributylphosphine oxide as the major impurity. This material was used without further purification. The reaction mixture was heated to reflux to stir at 110° C. overnight The reaction mixture was quenched with saturated NH4Cl solution diluted with EtOAc The reaction mixture was washed with water The organics were dried over MgSO4 concentrated in vacuo Purification of the crude residue by column chromatography

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

Procedure: A mixture of lithium bromide (0.181 g, 2.08 mmol), tri-n-butylphosphine oxide (0.454 g, 2.08 mmol), and dry o-xylene (10 ml) is azeotropically dried for 1 hr. After cooling below the reflux point, a mixture of (R)-glycidyl butyrate (5.000 g, 34.68 mmol) and 3-fluorophenyl isocyanate (4.755 g or 3.96 ml, 34.68 mmol) in dry o-xylene (10 ml) is added over 10 min to the hot mixture (some refluxing observed during the addition). When the addition is complete, the mixture is heated to reflux for 2 hr and then allowed to cool to 20-25o. The solvent is removed under reduced pressure and the residue chromatographed over silica gel, eluting with hexane/ethyl acetate (6:1, 4:1, and then 2:1), to give the title compound, [α]25D -46.7° (c 1.0, CHCl3); IR (mineral oil mull) 1758, 1615, 1591, 1498, 1229, 1197, 1169 cm-1 ; NMR (CDCl3, 300 MHz) δ 7.44, 7.34, 7.23, 6.86, 4.88, 4.39, 4.32, 4.13, 3.82, 2.33, 1.63, 0.92; MS (m/z) 281, 193, 180, 150, 148, 137, 123, 95, 43; HRMS (m/z)281.1068 (calc'd for C14H16FNO4 =281.1063). is azeotropically dried for 1 hr After cooling below the reflux point is added over 10 min to the hot mixture (some refluxing observed during the addition) When the addition the mixture is heated to reflux for 2 hr to cool to 20-25o The solvent is removed under reduced pressure the residue chromatographed over silica gel eluting with hexane/ethyl acetate (6:1, 4:1

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

Procedure: A mixture of lithium bromide (0.181 g, 2.08 mmol), tri-n-butylphosphine oxide (0.454 g, 2.08 mmol), and dry o-xylene (10 ml) is azeotropically dried for 1 hr. After cooling below the reflux point, a mixture of (R)-glycidyl butyrate (5.000 g, 34.68 mmol) and 3-fluorophenyl isocyanate (4.755 g or 3.96 ml, 34.68 mmol) in dry o-xylene (10 ml) is added over 10 min to the hot mixture (some refluxing observed during the addition). When the addition is complete, the mixture is heated to reflux for 2 hr and then allowed to cool to 20-25°. The solvent is removed under reduced pressure and the residue chromatographed over silica gel, eluting with hexane/ethyl acetate (6:1, 4:1, and then 2:1), to give the title compound, [α]25D -46.7° (c 1.0, CHCl3); IR (mineral oil mull) 1758, 1615, 1591, 1498, 1229, 1197, 1169 cm-1 ; NMR (CDCl3, 300 MHz) δ 7.44, 7.34, 7.23, 6.86, 4.88, 4.39, 4.32, 4.13, 3.82, 2.33, 1.63, 0.92; MS (m/z) 281, 193, 180, 150, 148, 137, 123, 95, 43; HRMS (m/z) 281.1068 (calc'd for C14H16FNO4 =281.1063). is azeotropically dried for 1 hr After cooling below the reflux point is added over 10 min to the hot mixture (some refluxing observed during the addition) When the addition the mixture is heated to reflux for 2 hr to cool to 20-25° The solvent is removed under reduced pressure the residue chromatographed over silica gel eluting with hexane/ethyl acetate (6:1, 4:1

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

Procedure: A toluene (10 ml) solution of 5.9 g of 4-chlorophenyl isocyanate and 3.3 ml of epichlorohydrin was added dropwise to a toluene (1 ml) solution of 0.2 g of lithium bromide and 0.42 g of tri-n-butylphosphine oxide at 100° C. The mixture was stirred at the same temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. Ethanol was added to the obtained residue to collect the crystals by filtration. Thus, 8.9 g of the title compound was obtained (yield 93%). The reaction mixture was concentrated under reduced pressure Ethanol was added to the obtained residue to collect the crystals by filtration

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

Procedure: For the purpose of improving catalytic activity, regio and enantio selectivities, various additives other than water may be added to the reaction system. For example, presence of phosphorus compounds, e.g., triethylphosphine oxide, triphenylphosphine oxide, tributylphosphine oxide, triethyl phosphite, tributyl phosphite, and triphenyl phosphite; or carboxylic acids, e.g., acetic acid, propionic acid and pivalic acid, in the reaction system gives rise to no interference with the reaction. may be added to the reaction system