4-prop-2-enylazetidin-2-one

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

Procedure: The 2-oxodioxolane ring can be prepared e.g. by the introduction of 1,2-dioxyethyl into 4-allyl-2-azetidinone (5a: Y=allyl) described in J. Chemical Society, Chem. Comm., 1979, 236 and carbonate formation according to the above reaction scheme. Namely, treatment of Compound (5a) with organosilyl reagent e.g. t-butyldimethylsilyl chloride, t-butyldiphenylsilylchloride, trimethylsilyl chloride, hexamethyldisilazane in an inert solvent e.g. dimethyl formamide, acetonitrile, hexamethylphosphorotriamide, dioxane, in the presence of an acid scavenger e.g. diiosopropylamine, triethylamine, pyridine, lutidine, at -20° C. to 25° C. for 0.5 to 24 hours to obtain 1-protected allyl compound (5b) and then treated with a base e.g. lithium diisopropylamide, sodium hydride, phenyllithium, butyl lithium, in an inert solvent e.g. dioxane, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 5 hours to metalate to obtain 1-organosilyl-4-allyl-3-metalated-2-azetidinone (6). This is treated with 1,4-dioxaspiro[5,4]decan-2-one in an inert solvent e.g. ether, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 3 hours to give a 1-organosilyl-4-allyl-3-hydroxyacetyl-2-azetidinone (7). This compound can be reduced with e.g. sodium borohydride, in alcohol at -80° C. to 10° C. for 0.5 to 5 hours to give 3-(1,2-dioxyethyl) compound (8; A=H) or alternatively, carbonyl addition reagent e.g. Grignard reagent, alkyl alkali metal, in an inert solvent e.g. dichloromethane, ether, tetrahydrofuran, at -20° C. to 100° C. for 0.5 to 5 hours or other conventional method to give the dihydroxyalkyl compounds (8; A≠H). The same compounds can be prepared by treatment of the said metalated azetidinone compounds (6) with protected hydroxyacetyl compound ACOCH2OZ in an inert solvent e.g. tetrahydrofuran at -80° C. to 0° C. for 0.1 to 5 hours to add Compound (6) to the carbonyl of ACOCH2OZ. The diol compound (8) is treated with carbonating reagent e.g. phosgene, phosgene dimer, pyrocarbonate ester, or the like in the presence of an acid scavenger e.g. diisopropylamine, triethylamine, pyridine, in an inert solvent e.g. dichloromethane, chloroform, benzene, ethyl acetate, in a conventional manner at -80° C. to 0° C. for 1 to 5 hours to give a 3-(2-oxo-1,3-dioxolanyl)-2-azetidinone compound (9). The same compounds can be prepared by treatment of the at -80° C. to 0° C. for 0.1 to 5 hours

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

Procedure: A solution of 4-allylazetidin-2-one (0.25 g) in dry tetrahydrofuran (25 ml) was stirred at -5° C. under argon and treated with a 2.5 M solution of n-butyl-lithium in hexane (3.0 ml). A period of 1 hour was allowed for the dianion to form and dry acetone (1.0 ml) was then added. After a further 10 mins. water (5 ml) was added to the reaction mixture, which was then concentrated to about 10 ml in volume. This was extracted with methylene chloride (20 ml), and the organic phase was then dried over sodium sulphate and concentrated. The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products. The least polar isomer was cis-4-allyl-3-(2-hydroxy-2-propylazetidin)2-one (0.029 g); m.p. 144° (ethyl acetate/60°-80° petroleum ether). ν max (CHCl3) 3400, 2980, 2930, 1745 and 1640 cm-1 ; δ(CDCl3) 1.35 (3H, s), 1.51 (3H, s), 2.18 (1H, br), 2.5-2.9 (2H, m), 3.28 (1H, d, J 5 Hz), 3.85 (1H, td J 9 and 5 Hz), 4.9-6.1 (3H, m), and 7.20 (1H, br) (Found: C, 64.2; H, 9.0; N, 8.2%. C9H15NO2 requires C, 63.9; H, 8.9 and N, 8.3%). The more polar isomer was trans-4-allyl-3-(2-hydroxy-2-propyl)azetidin-2-one (0.042 g); νmax (CHCl3) 3400, 2980, 2930, 1750 and 1640 cm-1, δ(CDCl3) 1.29 (3H, s), 1.39 (3H, s), 2.41 (3H, br t J 6 Hz), 2.88 (1H, d, J 2 Hz), 3.69 (1, 6d J 6 and 2 Hz), 4.9-5.4 (2H, m), 5.89 (1H, ddt J 18, 9 and 6 Hz), and 6.50 (1H, br). A period of 1 hour to form was then concentrated to about 10 ml in volume This was extracted with methylene chloride (20 ml) the organic phase was then dried over sodium sulphate concentrated The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products

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

Procedure: A solution of 4-allylazetidin-2-one (0.25 g) in dry tetrahydrofuran (25 ml) was stirred at -5° C. under argon and treated with a 2.5 M solution of n-butyl-lithium in hexane (3.0 ml). A period of 1 hour was allowed for the dianion to form and dry acetone (1.0 ml) was then added. After a further 10 mins. water (5 ml) was added to the reaction mixture, which was then concentrated to about 10 ml in volume. This was extracted with methylene chloride (20 ml), and the organic phase was then dried over sodium sulphate and concentrated. The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products. The least polar isomer was cis-4-allyl-3-(2-hydroxy-2-propylazetidin)2-one (0.029 g); m.p. 144° (ethyl acetate/60°-80° petroleum ether). ν max (CHCl3) 3400, 2980, 2930, 1745 and 1640 cm-1 ; δ(CDCl3) 1.35 (3H, s), 1.51 (3H, s), 2.18 (1H, br), 2.5-2.9 (2H, m), 3.28 (1H, d, J 5 Hz), 3.85 (1H, td J 9 and 5 Hz), 4.9-6.1 (3H, m), and 7.20 (1H, br) (Found: C, 64.2; H, 9.0; N, 8.2%. C9H15NO2 requires C, 63.9; H, 8.9 and N, 8.3%). The more polar isomer was trans-4-allyl-3-(2-hydroxy-2-propyl)azetidin-2-one (0.042 g); νmax (CHCl3) 3400, 2980, 2930, 1750 and 1640 cm-1, δ(CDCl3) 1.29 (3H, s), 1.39 (3H, s), 2.41 (3H, br t J 6 Hz), 2.88 (1H, d, J 2 Hz), 3.69 (1, 6d J 6 and 2 Hz), 4.9-5.4 (2H, m), 5.89 (1H, ddt J 18, 9 and 6 Hz), and 6.50 (1H, br). A period of 1 hour to form was then concentrated to about 10 ml in volume This was extracted with methylene chloride (20 ml) the organic phase was then dried over sodium sulphate concentrated The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products

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

Procedure: The 2-oxodioxolane ring can be prepared e.g. by the introduction of 1,2-dioxyethyl into 4-allyl-2-azetidinone (5a: Y=allyl) described in J. Chemical Society, Chem. Comm., 1979, 236 and carbonate formation according to the above reaction scheme. Namely, treatment of Compound (5a) with organosilyl reagent e.g. t-butyldimethylsilyl chloride, t-butyldiphenylsilylchloride, trimethylsilyl chloride, hexamethyldisilazane in an inert solvent e.g. dimethyl formamide, acetonitrile, hexamethylphosphorotriamide, dioxane, in the presence of an acid scavenger e.g. diiosopropylamine, triethylamine, pyridine, lutidine, at -20° C. to 25° C. for 0.5 to 24 hours to obtain 1-protected allyl compound (5b) and then treated with a base e.g. lithium diisopropylamide, sodium hydride, phenyllithium, butyl lithium, in an inert solvent e.g. dioxane, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 5 hours to metalate to obtain 1-organosilyl-4-allyl-3-metalated-2-azetidinone (6). This is treated with 1,4-dioxaspiro[5,4]decan-2-one in an inert solvent e.g. ether, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 3 hours to give a 1-organosilyl-4-allyl-3-hydroxyacetyl-2-azetidinone (7). This compound can be reduced with e.g. sodium borohydride, in alcohol at -80° C. to 10° C. for 0.5 to 5 hours to give 3-(1,2-dioxyethyl) compound (8; A=H) or alternatively, carbonyl addition reagent e.g. Grignard reagent, alkyl alkali metal, in an inert solvent e.g. dichloromethane, ether, tetrahydrofuran, at -20° C. to 100° C. for 0.5 to 5 hours or other conventional method to give the dihydroxyalkyl compounds (8; A≠H). The same compounds can be prepared by treatment of the said metalated azetidinone compounds (6) with protected hydroxyacetyl compound ACOCH2OZ in an inert solvent e.g. tetrahydrofuran at -80° C. to 0° C. for 0.1 to 5 hours to add Compound (6) to the carbonyl of ACOCH2OZ. The diol compound (8) is treated with carbonating reagent e.g. phosgene, phosgene dimer, pyrocarbonate ester, or the like in the presence of an acid scavenger e.g. diisopropylamine, triethylamine, pyridine, in an inert solvent e.g. dichloromethane, chloroform, benzene, ethyl acetate, in a conventional manner at -80° C. to 0° C. for 1 to 5 hours to give a 3-(2-oxo-1,3-dioxolanyl)-2-azetidinone compound (9). The same compounds can be prepared by treatment of the at -80° C. to 0° C. for 0.1 to 5 hours

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

Procedure: A solution of 4-allylazetidin-2-one (0.25 g) in dry tetrahydrofuran (25 ml) was stirred at -5° C. under argon and treated with a 2.5 M solution of n-butyl-lithium in hexane (3.0 ml). A period of 1 hour was allowed for the dianion to form and dry acetone (1.0 ml) was then added. After a further 10 mins. water (5 ml) was added to the reaction mixture, which was then concentrated to about 10 ml in volume. This was extracted with methylene chloride (20 ml), and the organic phase was then dried over sodium sulphate and concentrated. The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products. The least polar isomer was cis-4-allyl-3-(2-hydroxy-2-propylazetidin)2-one (0.029 g); m.p. 144° (ethyl acetate/60°-80° petroleum ether). ν max (CHCl3) 3400, 2980, 2930, 1745 and 1640 cm-1 ; δ(CDCl3) 1.35 (3H, s), 1.51 (3H, s), 2.18 (1H, br), 2.5-2.9 (2H, m), 3.28 (1H, d, J 5 Hz), 3.85 (1H, td J 9 and 5 Hz), 4.9-6.1 (3H, m), and 7.20 (1H, br) (Found: C, 64.2; H, 9.0; N, 8.2%. C9H15NO2 requires C, 63.9; H, 8.9 and N, 8.3%). The more polar isomer was trans-4-allyl-3-(2-hydroxy-2-propyl)azetidin-2-one (0.042 g); νmax (CHCl3) 3400, 2980, 2930, 1750 and 1640 cm-1, δ(CDCl3) 1.29 (3H, s), 1.39 (3H, s), 2.41 (3H, br t J 6 Hz), 2.88 (1H, d, J 2 Hz), 3.69 (1, 6d J 6 and 2 Hz), 4.9-5.4 (2H, m), 5.89 (1H, ddt J 18, 9 and 6 Hz), and 6.50 (1H, br). A period of 1 hour to form was then concentrated to about 10 ml in volume This was extracted with methylene chloride (20 ml) the organic phase was then dried over sodium sulphate concentrated The residue was chromatographed on silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 1:1 grading to ethyl acetate to give the cis and trans aldol products

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

Procedure: The 2-oxodioxolane ring can be prepared e.g. by the introduction of 1,2-dioxyethyl into 4-allyl-2-azetidinone (5a: Y=allyl) described in J. Chemical Society, Chem. Comm., 1979, 236 and carbonate formation according to the above reaction scheme. Namely, treatment of Compound (5a) with organosilyl reagent e.g. t-butyldimethylsilyl chloride, t-butyldiphenylsilylchloride, trimethylsilyl chloride, hexamethyldisilazane in an inert solvent e.g. dimethyl formamide, acetonitrile, hexamethylphosphorotriamide, dioxane, in the presence of an acid scavenger e.g. diiosopropylamine, triethylamine, pyridine, lutidine, at -20° C. to 25° C. for 0.5 to 24 hours to obtain 1-protected allyl compound (5b) and then treated with a base e.g. lithium diisopropylamide, sodium hydride, phenyllithium, butyl lithium, in an inert solvent e.g. dioxane, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 5 hours to metalate to obtain 1-organosilyl-4-allyl-3-metalated-2-azetidinone (6). This is treated with 1,4-dioxaspiro[5,4]decan-2-one in an inert solvent e.g. ether, dimethoxyethane, tetrahydrofuran, at -80° C. to 0° C. for 1 to 3 hours to give a 1-organosilyl-4-allyl-3-hydroxyacetyl-2-azetidinone (7). This compound can be reduced with e.g. sodium borohydride, in alcohol at -80° C. to 10° C. for 0.5 to 5 hours to give 3-(1,2-dioxyethyl) compound (8; A=H) or alternatively, carbonyl addition reagent e.g. Grignard reagent, alkyl alkali metal, in an inert solvent e.g. dichloromethane, ether, tetrahydrofuran, at -20° C. to 100° C. for 0.5 to 5 hours or other conventional method to give the dihydroxyalkyl compounds (8; A≠H). The same compounds can be prepared by treatment of the said metalated azetidinone compounds (6) with protected hydroxyacetyl compound ACOCH2OZ in an inert solvent e.g. tetrahydrofuran at -80° C. to 0° C. for 0.1 to 5 hours to add Compound (6) to the carbonyl of ACOCH2OZ. The diol compound (8) is treated with carbonating reagent e.g. phosgene, phosgene dimer, pyrocarbonate ester, or the like in the presence of an acid scavenger e.g. diisopropylamine, triethylamine, pyridine, in an inert solvent e.g. dichloromethane, chloroform, benzene, ethyl acetate, in a conventional manner at -80° C. to 0° C. for 1 to 5 hours to give a 3-(2-oxo-1,3-dioxolanyl)-2-azetidinone compound (9). The same compounds can be prepared by treatment of the at -80° C. to 0° C. for 0.1 to 5 hours