2-prop-2-enylcyclopentan-1-one

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While under a nitrogen, a solution of 2-allylcyclopentanone (12.4 g, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to −70° C. and treated with 1 N lithium bis(tri-methylsilyl)amide/tetrahydrofuran (200 mL, 200 mmol) at a rate to keep pot temperature below −55° C. Once the addition was complete, the mixture was stirred at −60 to −70° C. for one additional hour. A second solution of phenylselenyl chloride (19.5 g, 102 mmol) in anhydrous tetrahydrofuran (50 mL) was added dropwise and the mixture stirred at −60 to −70° C. for 30 min, then allowed to warm to 0° C. The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL), and the organic layer was separated. The aqueous solution was extracted with ethyl acetate (2×100 mL) and the combined organic solution was washed with saturated aqueous sodium chloride (200 mL), dried (MgSO4), and concentrated in vacuo. The residue was dissolved in heptane and loaded onto a silica gel column (˜600 cc) and eluted with 2:1 heptane/dichloromethane, then with 1:1 heptane/dichloromethane to afford 2-allyl-5-(phenylselanyl)cyclopentanone (19.7 g, 71%) as a pale yellow oil. NMR (CDCl3): δ 7.40-7.50 (m, 2 H), 7.05-7.25 (m, 3 H), 5.50-5.70 (m, 1 H), 4.80-4.95 (m, 2 H), 3.45-3.75 (m, 1 H), 2.30-2.50 (m, 1 H), 1.80-2.25 (m, 5 H), 1.50-1.75 (m, 1 H). MS (M+1): 279.1/280.9 (for 2 major isotopes of Se). temperature below −55° C Once the addition the mixture stirred at −60 to −70° C. for 30 min to warm to 0° C The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL) the organic layer was separated The aqueous solution was extracted with ethyl acetate (2×100 mL) the combined organic solution was washed with saturated aqueous sodium chloride (200 mL) dried (MgSO4) concentrated in vacuo The residue was dissolved in heptane eluted with 2:1 heptane/dichloromethane

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

Procedure: A stirred solution of methyl 2-carboxycyclopentanone (35.5 g, 250 mmol) in acetone (500 mL) was treated with anhydrous potassium carbonate (138 g, 1.0 mol) and allyl bromide (100 mL, 1.15 mol) and refluxed for 5 h. The mixture was cooled and filtered through Celite® (rinse filter cake with acetone), and the filtrate was concentrated in vacuo. The residual oil was dissolved in methanol (450 mL), treated with 6 N HCl (250 mL), and refluxed for 40 h. The solution was cooled to room temperature, concentrated in vacuo to remove most methanol, and diluted with water (200 mL). The aqueous solution was extracted with dichloromethane (3×250 mL), and the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each), dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume. This solution was loaded onto a silica gel column (˜500 cc) and eluted with dichloromethane to afford (after gentle concentration of fractions) 2-allylcyclopentanone (27.3 g, 88%) as a colorless oil. NMR (CDCl3): δ 5.65-5.75 (m, 1 H), 4.90-5.05 (m, 2 H), 2.40-2.50 (m, 1 H), 2.20-2.30 (m, 1 H), 1.85-2.15 (m, 5 H), 1.65-1.75 (m, 1 H), 1.45-1.55 (m, 1 H). refluxed for 5 h The mixture was cooled filtered through Celite® (rinse filter cake with acetone) the filtrate was concentrated in vacuo The residual oil was dissolved in methanol (450 mL) treated with 6 N HCl (250 mL) refluxed for 40 h concentrated in vacuo to remove most methanol diluted with water (200 mL) The aqueous solution was extracted with dichloromethane (3×250 mL) the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each) dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume eluted with dichloromethane

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

Procedure: A stirred solution of methyl 2-carboxycyclopentanone (35.5 g, 250 mmol) in acetone (500 mL) was treated with anhydrous potassium carbonate (138 g, 1.0 mol) and allyl bromide (100 mL, 1.15 mol) and refluxed for 5 h. The mixture was cooled and filtered through Celite® (rinse filter cake with acetone), and the filtrate was concentrated in vacuo. The residual oil was dissolved in methanol (450 mL), treated with 6 N HCl (250 mL), and refluxed for 40 h. The solution was cooled to room temperature, concentrated in vacuo to remove most methanol, and diluted with water (200 mL). The aqueous solution was extracted with dichloromethane (3×250 mL), and the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each), dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume. This solution was loaded onto a silica gel column (˜500 cc) and eluted with dichloromethane to afford (after gentle concentration of fractions) 2-allylcyclopentanone (27.3 g, 88%) as a colorless oil. NMR (CDCl3): δ 5.65-5.75 (m, 1 H), 4.90-5.05 (m, 2 H), 2.40-2.50 (m, 1 H), 2.20-2.30 (m, 1 H), 1.85-2.15 (m, 5 H), 1.65-1.75 (m, 1 H), 1.45-1.55 (m, 1 H). refluxed for 5 h The mixture was cooled filtered through Celite® (rinse filter cake with acetone) the filtrate was concentrated in vacuo The residual oil was dissolved in methanol (450 mL) treated with 6 N HCl (250 mL) refluxed for 40 h concentrated in vacuo to remove most methanol diluted with water (200 mL) The aqueous solution was extracted with dichloromethane (3×250 mL) the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each) dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume eluted with dichloromethane

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

Procedure: A stirring mixture of 2-allylcyclopentanone (0.993 g, 8 mmol) and ammonium acetate (1.54 g, 20 mmol) in 2,2,2-trifluoroethanol (2.5 mL) was treated with t-butyl isocyanide (1.81 mL, 16 mmol). The reaction mixture was stirred at room temperature for 4 days, following which the mixture was dissolved in a minimum amount of dichloromethane and purified by flash column chromatography (silica gel, 60% ethyl acetate in heptane) to afford the anti-isomer of (1S,2S)-1-acetamido-2-allyl-N-tert-butylcyclopentane carboxamide (0.771 g, 36%) as a white solid. The later migrating syn-isomer is obtained as a white solid (0.851 g, 40%), by increasing the concentration of the polar solvent ethyl acetate to 80%. Anti-isomer: 1H NMR (CDCl3, 300 MHz) δ 7.26 (br s, NH, 1 H), 6.82 (br s, NH, 1 H), 5.88-5.72 (m, 1 H), 5.07 (br d, J=17 Hz, 1 H), 5.00 (br d, J=12 Hz, 1 H), 2.56-2.41 (m, 1 H), 2.36-2.17 (m, 3 H), 2.01 (s, 3 H), 1.97-1.81 (m, 2 H), 1.72-1.60 (m, 2 H), 1.32 (s, 9 H); MS (+CI): m/z for C15H26N2O2: expected 266.2; found 266.2 (M+H)+ purified by flash column chromatography (silica gel, 60% ethyl acetate in heptane)

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

Procedure: A stirring mixture of 2-allylcyclopentanone (0.993 g, 8 mmol) and ammonium acetate (1.54 g, 20 mmol) in 2,2,2-trifluoroethanol (2.5 mL) was treated with t-butyl isocyanide (1.81 mL, 16 mmol). The reaction mixture was stirred at room temperature for 4 days, following which the mixture was dissolved in a minimum amount of dichloromethane and purified by flash column chromatography (silica gel, 60% ethyl acetate in heptane) to afford the anti-isomer of (1S,2S)-1-acetamido-2-allyl-N-tert-butylcyclopentane carboxamide (0.771 g, 36%) as a white solid. The later migrating syn-isomer is obtained as a white solid (0.851 g, 40%), by increasing the concentration of the polar solvent ethyl acetate to 80%. Anti-isomer: 1H NMR (CDCl3, 300 MHz) δ 7.26 (br s, NH, 1 H), 6.82 (br s, NH, 1 H), 5.88-5.72 (m, 1 H), 5.07 (br d, J=17 Hz, 1 H), 5.00 (br d, J=12 Hz, 1 H), 2.56-2.41 (m, 1 H), 2.36-2.17 (m, 3 H), 2.01 (s, 3 H), 1.97-1.81 (m, 2 H), 1.72-1.60 (m, 2 H), 1.32 (s, 9 H); MS (+CI): m/z for C15H26N2O2: expected 266.2; found 266.2 (M+H)+ purified by flash column chromatography (silica gel, 60% ethyl acetate in heptane)

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While under a nitrogen, a solution of 2-allylcyclopentanone (12.4 g, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to −70° C. and treated with 1 N lithium bis(tri-methylsilyl)amide/tetrahydrofuran (200 mL, 200 mmol) at a rate to keep pot temperature below −55° C. Once the addition was complete, the mixture was stirred at −60 to −70° C. for one additional hour. A second solution of phenylselenyl chloride (19.5 g, 102 mmol) in anhydrous tetrahydrofuran (50 mL) was added dropwise and the mixture stirred at −60 to −70° C. for 30 min, then allowed to warm to 0° C. The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL), and the organic layer was separated. The aqueous solution was extracted with ethyl acetate (2×100 mL) and the combined organic solution was washed with saturated aqueous sodium chloride (200 mL), dried (MgSO4), and concentrated in vacuo. The residue was dissolved in heptane and loaded onto a silica gel column (˜600 cc) and eluted with 2:1 heptane/dichloromethane, then with 1:1 heptane/dichloromethane to afford 2-allyl-5-(phenylselanyl)cyclopentanone (19.7 g, 71%) as a pale yellow oil. NMR (CDCl3): δ 7.40-7.50 (m, 2 H), 7.05-7.25 (m, 3 H), 5.50-5.70 (m, 1 H), 4.80-4.95 (m, 2 H), 3.45-3.75 (m, 1 H), 2.30-2.50 (m, 1 H), 1.80-2.25 (m, 5 H), 1.50-1.75 (m, 1 H). MS (M+1): 279.1/280.9 (for 2 major isotopes of Se). temperature below −55° C Once the addition the mixture stirred at −60 to −70° C. for 30 min to warm to 0° C The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL) the organic layer was separated The aqueous solution was extracted with ethyl acetate (2×100 mL) the combined organic solution was washed with saturated aqueous sodium chloride (200 mL) dried (MgSO4) concentrated in vacuo The residue was dissolved in heptane eluted with 2:1 heptane/dichloromethane

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

Procedure: A stirred solution of methyl 2-carboxycyclopentanone (35.5 g, 250 mmol) in acetone (500 mL) was treated with anhydrous potassium carbonate (138 g, 1.0 mol) and allyl bromide (100 mL, 1.15 mol) and refluxed for 5 h. The mixture was cooled and filtered through Celite® (rinse filter cake with acetone), and the filtrate was concentrated in vacuo. The residual oil was dissolved in methanol (450 mL), treated with 6 N HCl (250 mL), and refluxed for 40 h. The solution was cooled to room temperature, concentrated in vacuo to remove most methanol, and diluted with water (200 mL). The aqueous solution was extracted with dichloromethane (3×250 mL), and the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each), dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume. This solution was loaded onto a silica gel column (˜500 cc) and eluted with dichloromethane to afford (after gentile concentration of fractions) 2-allylcyclopentanone (27.3 g, 88%) as a colorless oil. NMR (CDCl3): δ 5.65-5.75 (m, 1 H), 4.90-5.05 (m, 2 H), 2.40-2.50 (m, 1 H), 2.20-2.30 (m, 1 H), 1.85-2.15 (m, 5 H), 1.65-1.75 (m, 1 H), 1.45-1.55 (m, 1 H). refluxed for 5 h The mixture was cooled filtered through Celite® (rinse filter cake with acetone) the filtrate was concentrated in vacuo The residual oil was dissolved in methanol (450 mL) treated with 6 N HCl (250 mL) refluxed for 40 h concentrated in vacuo to remove most methanol diluted with water (200 mL) The aqueous solution was extracted with dichloromethane (3×250 mL) the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each) dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume eluted with dichloromethane

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: While under a nitrogen, a solution of 2-allylcyclopentanone (12.4 g, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to −70° C. and treated with 1 N lithium bis(tri-methylsilyl)amide/tetrahydrofuran (200 mL, 200 mmol) at a rate to keep pot temperature below −55° C. Once the addition was complete, the mixture was stirred at −60 to −70° C. for one additional hour. A second solution of phenylselenyl chloride (19.5 g, 102 mmol) in anhydrous tetrahydrofuran (50 mL) was added dropwise and the mixture stirred at −60 to −70° C. for 30 min, then allowed to warm to 0° C. The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL), and the organic layer was separated. The aqueous solution was extracted with ethyl acetate (2×100 mL) and the combined organic solution was washed with saturated aqueous sodium chloride (200 mL), dried (MgSO4), and concentrated in vacuo. The residue was dissolved in heptane and loaded onto a silica gel column (˜600 cc) and eluted with 2:1 heptane/dichloromethane, then with 1:1 heptane/dichloromethane to afford 2-allyl-5-(phenylselanyl)cyclopentanone (19.7 g, 71%) as a pale yellow oil. NMR (CDCl3): δ 7.40-7.50 (m, 2 H), 7.05-7.25 (m, 3 H), 5.50-5.70 (m, 1 H), 4.80-4.95 (m, 2 H), 3.45-3.75 (m, 1 H), 2.30-2.50 (m, 1 H), 1.80-2.25 (m, 5 H), 1.50-1.75 (m, 1 H). MS (M+1): 279.1/280.9 (for 2 major isotopes of Se). temperature below −55° C Once the addition the mixture stirred at −60 to −70° C. for 30 min to warm to 0° C The reaction was quenched by addition of the solution to a rapidly stirred mixture of ethyl acetate (500 mL) and 5% aqueous citric acid (200 mL) the organic layer was separated The aqueous solution was extracted with ethyl acetate (2×100 mL) the combined organic solution was washed with saturated aqueous sodium chloride (200 mL) dried (MgSO4) concentrated in vacuo The residue was dissolved in heptane eluted with 2:1 heptane/dichloromethane

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

Procedure: A stirred solution of methyl 2-carboxycyclopentanone (35.5 g, 250 mmol) in acetone (500 mL) was treated with anhydrous potassium carbonate (138 g, 1.0 mol) and allyl bromide (100 mL, 1.15 mol) and refluxed for 5 h. The mixture was cooled and filtered through Celite® (rinse filter cake with acetone), and the filtrate was concentrated in vacuo. The residual oil was dissolved in methanol (450 mL), treated with 6 N HCl (250 mL), and refluxed for 40 h. The solution was cooled to room temperature, concentrated in vacuo to remove most methanol, and diluted with water (200 mL). The aqueous solution was extracted with dichloromethane (3×250 mL), and the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each), dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume. This solution was loaded onto a silica gel column (˜500 cc) and eluted with dichloromethane to afford (after gentile concentration of fractions) 2-allylcyclopentanone (27.3 g, 88%) as a colorless oil. NMR (CDCl3): δ 5.65-5.75 (m, 1 H), 4.90-5.05 (m, 2 H), 2.40-2.50 (m, 1 H), 2.20-2.30 (m, 1 H), 1.85-2.15 (m, 5 H), 1.65-1.75 (m, 1 H), 1.45-1.55 (m, 1 H). refluxed for 5 h The mixture was cooled filtered through Celite® (rinse filter cake with acetone) the filtrate was concentrated in vacuo The residual oil was dissolved in methanol (450 mL) treated with 6 N HCl (250 mL) refluxed for 40 h concentrated in vacuo to remove most methanol diluted with water (200 mL) The aqueous solution was extracted with dichloromethane (3×250 mL) the combined organic solution was washed with water, saturated aqueous sodium bicarbonate, and saturated aqueous sodium chloride (200 mL each) dried (Na2SO4), and gently (volatile product) concentrated in vacuo to 75 mL volume eluted with dichloromethane

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

Procedure: Cyclopentanone is treated with potassium-t-butoxide and then with allyl bromide in the same manner and in the same proportions as described for cyclohexanone in Example 6a, yielding 2-allylcyclopentanone.

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

Procedure: Ex-30a) Cyclopentanone is treated with potassium-t-butoxide and then with allyl bromide in the same manner and in the same proportions as described for cyclohexanone in Example 6a, yielding 2-allylcyclopentanone.

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

Procedure: To a stirring solution of 2-(propene-3-yl)cyclopentanone (0.745 g, 6.0 mmol) in 2,2,2-trifluoroethanol (5 mL) under an atmosphere of nitrogen was added (S)-α-methylbenzylamine (3.1 mL, 24 mmol), glacial acetic acid (1.38 mL, 24 mmol), and t-butylisonitrile (2.04 mL, 18 mmol). After stirring at room temperature for five days and then at 60° C. for an additional 2 days, the mixture was concentrated in vacuo, taken up in water (50 mL) and extracted using ethyl acetate (75 mL, then 50 mL). The combined organic layer was washed with brine (75 mL), dried using MgSO4, and concentrated in vacuo. The residual oil was dissolved in minimum quantity of methylene chloride prior to loading of the crude onto a silica gel column (175 mL). The crude mixture was purified by eluting the column with 20% ethyl acetate/heptane and then using a solvent mixture comprising 30% ethyl acetate/heptane to afford the subject compound single enantiomer (0.341 g, 15%) as a pale yellow viscous oil. NMR (CDCl3): δ 7.46 (m, 2 H), 7.31 (m, 2 H), 7.19 (m, 1 H), 6.27 (m, 1 H), 5.67 (m, 1 H), 4.90 (m, 2 H), 4.80 (br s, 1 H), 2.88 (m, 1 H), 2.43 (m, 2 H), 1.87 (m, 2 H), 1.50-1.80 (m, 10 H), 1.30 (s, 9 H). MS (M+1): 371.1; MS (M+Na): 393.4. at 60° C. for an additional 2 days the mixture was concentrated in vacuo extracted The combined organic layer was washed with brine (75 mL) dried concentrated in vacuo The residual oil was dissolved in minimum quantity of methylene chloride The crude mixture was purified by eluting the column with 20% ethyl acetate/heptane to afford the subject compound single enantiomer (0.341 g, 15%) as a pale yellow viscous oil