4.1.2. Preparation of Alkynes 1–7

2-endo-Ethynyl-7-benzyl-7-azabicyclo [2.2.1]heptane (endo-1)

To a solution of endo-9 (118 mg, 0.535 mmol) in dichloromethane (4 mL) was added trifluoroacetic acid (0.5 mL) at 0 °C. After stirring at ambient temperature for 1 h, the mixture was concentrated under reduced pressure, and the excess trifluoroacetic acid was removed by repeated evaporation with toluene. The crude ammonium salt was used for the next reaction without further purification. To a suspension of the crude ammonium salt and potassium carbonate (355 mg, 2.57 mmol) in dry acetone (2 mL) was added benzyl bromide (89 µL, 0.75 mmol) at 0 °C. After stirring for 3 h at this temperature, water (30 mL) was added to the mixture. The mixture was then extracted with dichloromethane (30 mL × 3), and the combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Column chromatography (silica gel 5 g, n-hexane/ethyl acetate, 100:1 to 30:1) gave the title compound (107 mg, 0.506 mmol, 94.6%) as a colorless oil. ¹H NMR (CDCl₃, 400 MHz): δ = 1.28–1.31 (m, 1H), 1.38–1.46 (m, 1H), 1.68–1.79 (m, 1H), 1.80–1.90 (m, 1H), 2.05–2.06 (m, 1H), 2.08–2.15 (m, 1H), 2.18–2.26 (m, 1H), 2.86–2.98 (m, 1H), 3.25–3.29 (m, 1H), 3.30–3.34 (m, 1H), 3.56 (s, 2H), 7.21–7.27 (m, 1H), 7.28–7.36 (m, 4H) ppm; ¹³C NMR (CDCl₃, 100 MHz): δ = 22.9, 28.3, 30.8, 37.3, 51.8, 59.9, 62.9, 69.4, 86.7, 126.9, 128.3 (2C), 128.5 (2C), 139.8 ppm; IR (neat): ν~ = 3295, 2963, 1452, 1365, 1299, 1116, 875, 718, 696, 409 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₅H₁₇N + H⁺: 212.1439 [M + H]⁺; found: 212.1445.

2-exo-Ethynyl-7-benzyl-7-azabicyclo[2.2.1]heptane (exo-1)

This compound was prepared according to the similar procedure as endo-1, starting from exo-9. Purification of the crude product with column chromatography (silica gel 6g, n-hexane/ethyl acetate = 20:1) gave the title compound (83.8 mg, 0.397 mmol, 73.2%) as a colorless oil. ¹H NMR (CDCl₃, 400 MHz): δ = 1.22–1.35 (m, 2H), 1.70–1.90 (m, 3H), 1.95–2.20 (m, 1H), 2.13–2.14 (m, 1H), 2.38–2.44 (m, 1H), 3.36–3.39 (m, 1H), 3.39–3.43 (m, 1H), 3.64 (d, J = 13.8 Hz, 1H), 3.82 (d, J = 13.8 Hz, 1H), 7.19–7.27 (m, 1H), 7.28–7.35 (m, 2H), 7.40–7.47 (m, 2H) ppm; ¹³C NMR (CDCl₃, 100 MHz): δ = 27.4, 27.9, 33.7, 39.0, 52.0, 59.7, 65.2, 68.4, 89.4, 127.0, 128.5 (2C), 128.7 (2C), 140.5 ppm; IR (neat): ν~ = 3298, 2965, 1495, 1452, 1365, 1186, 1108, 1027, 721, 696 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₅H₁₇N + H⁺: 212.1439 [M + H]⁺; found: 212.1436.

(2-endo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-2-yl)methanone (endo-2)

To a solution of endo-9 (62.0 mg, 0.280 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.5 mL) at 0 °C. After stirring at ambient temperature for 1 h, the mixture was concentrated under reduced pressure, and the excess trifluoroacetic acid was removed by repeated evaporation with toluene. The crude ammonium salt was used for the next reaction without further purification. To a solution of the crude ammonium salt and triethylamine (122 µL, 0.879 mmol) in dichloromethane (2 mL) was added pyridine-2-carbonyl chloride hydrochloride (120 mg, 0.675 mmol) at 0 °C, and the mixture was stirred at ambient temperature for 1 h. Then saturated aqueous sodium hydrogen carbonate solution (18 mL) was added, and the mixture was extracted with dichloromethane (15 mL × 3). The combined organic layers were washed with brine (15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Column chromatography (silica gel 2g, n-hexane/ethyl acetate = 3:1) gave the title compound (59.6 mg, 0.263 mmol, 94.0%) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz): δ = 1.47–1.66 (m, 2H), 1.78–2.00 (m, 2H), 2.12–2.15 (m, 1H), 2.24–2.41 (m, 2H), 2.98–3.09 (m, 1H), 4.83–4.90 (m, 1H), 5.06–5.15 (m, 1H), 7.37 (dd, J = 7.4, 4.7 Hz, 1H), 7.79 (ddd, J = 7.8, 7.4, 1.7 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 8.59 (dd, J = 4.7, 1.7 Hz, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 23.3 (1C × 50/100), 25.3 (1C × 50/100), 28.8 (1C × 50/100), 30.7 (1C × 50/100), 30.9 (1C × 50/100), 32.7 (1C × 50/100), 36.9 (1C × 50/100), 38.9 (1C × 50/100), 55.1 (1C × 50/100), 57.5 (1C × 50/100), 58.4 (1C × 50/100), 60.5 (1C × 50/100), 70.3 (1C × 50/100), 70.4 (1C × 50/100), 84.7, 124.2, 125.2, 136.8, 148.1, 153.1, 164.1 (1C × 50/100), 164.4 (1C × 50/100) ppm; IR (neat): ν~ = 3240, 2954, 1633, 1416, 1147, 996, 870, 812, 748 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + Na⁺: 249.1004 [M + Na]⁺; found: 249.1007.

(2-exo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-2-yl)methanone (exo-2)

This compound was prepared according to the similar procedure as endo-2, starting from exo-9. Purification of the crude product with column chromatography (silica gel 5 g, chloroform: methanol = 10:1) gave the title compound (31.2 mg, 0.138 mmol, 33.7%) as a colorless solid. mp: 84.7–85.6 °C; ¹H NMR (CDCl₃, 400 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 1.43–1.59 (m, 2H), 1.86–2.15 (m, 5H), 2.54–2.60 (m, 1H × 70/100), 2.60–2.66 (m, 1H × 30/100), 4.89–4.95 (m, 1H × 70/100), 4.98–5.02 (m, 1H × 30/100), 5.03–5.09 (m, 1H × 70/100), 5.24–5.31 (m, 1H × 30/100), 7.36 (ddd, J = 7.5, 4.8, 1.1, 1H), 7.79 (ddd, J = 7.8, 7.5, 1.7, 1H), 7.95 (ddd, J = 7.8, 1.1, 0.9, 1H), 8.60 (ddd, J = 4.8, 1.7, 0.9 Hz, 1H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 28.1 (1C × 30/100), 28.6 (1C × 70/100), 29.6 (1C × 70/100), 30.2 (1C × 30/100), 32.9 (1C × 30/100), 34.7 (1C × 70/100), 38.3 (1C × 70/100), 40.3 (1C × 30/100), 54.6 (1C × 70/100), 57.6 (1C × 30/100), 60.4 (1C × 30/100), 63.5 (1C × 70/100), 72.4 (1C × 30/100), 73.2 (1C × 70/100), 87.9 (1C × 70/100), 88.3 (1C × 30/100), 124.7 (1C × 30/100), 125.1 (1C × 70/100), 126.4 (1C × 70/100), 126.5 (1C × 30/100), 138.0 (1C × 70/100), 138.3 (1C × 30/100), 149.0 (1C × 70/100), 149.2 (1C × 30/100), 154.0, 164.2 (1C × 30/100), 165.4 (1C × 70/100) ppm; IR (KBr): ν~ = 3265, 1630, 1568, 1442, 1407, 1132, 813, 749, 728, 690 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + Na⁺: 249.1004 [M + Na]⁺; found: 249.0995.

(2-endo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-3-yl)methanone (endo-3)

The title compound was prepared according to a similar procedure as endo-2, using pyridine-3-carbonyl chloride hydrochloride as the reagent. Purification of the crude product with column chromatography (silica gel 10 g, chloroform: methanol = 50:1) gave the title compound (44.3 mg, 0.196 mmol, 76.3%) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz): δ = 1.48–1.69 (m, 2H), 1.89 (br s, 2H), 2.13–2.15 (m, 1H), 2.21–2.39 (m, 2H), 2.81–3.16 (m, 1H), 4.14 (br s, 1H), 4.76 (br s, 1H), 7.37 (dd, J = 7.8, 4.9 Hz, 1H), 7.89 (ddd, J = 7.8, 1.7, 1.7 Hz, 1H), 8.70 (dd, J = 4.9, 1.7 Hz, 1H), 8.79 (d, J = 1.7 Hz, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 23.4 (1C × 50/100), 25.3 (1C × 50/100), 29.0 (1C × 50/100), 30.8, 32.9 (1C × 50/100), 36.8 (1C × 50/100), 38.8 (1C × 50/100), 55.1 (1C × 50/100), 57.3 (1C × 50/100), 59.7 (1C × 50/100), 61.8 (1C × 50/100), 70.8, 84.0, 123.4, 131.3, 135.5, 148.7, 151.7, 166.5 ppm; IR (neat): ν~ = 3243, 2954, 1633, 1589, 1395, 1145, 1025, 471 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + H⁺: 227.1184 [M + H]⁺; found: 227.1178.

(2-exo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-3-yl)methanone (exo-3)

This compound was prepared according to a similar procedure as endo-3, starting from exo-9. Purification of the crude product with column chromatography (silica gel 4 g, chloroform: methanol = 20:1) gave the title compound (85.3 mg, 0.377 mmol, 84.0%) as a colorless solid. mp: 83.1–85.4 °C; ¹H NMR (CDCl₃, 400 MHz): δ = 1.40–1.56 (m, 2H), 1.60–1.91 (m, 3H), 1.93–2.00 (m, 1H), 2.26–2.28 (m, 1H), 2.96–2.99 (m, 1H), 4.08 (br s, 1H), 4.62 (br s, 1H), 7.49 (dd, J = 7.9, 4.9 Hz, 1H), 7.96 (d, J = 7.9, 1.7 Hz, 1H), 8.69 (dd, J = 4.9, 1.7 Hz, 1H), 8.77 (br s, 1H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): δ = 28.4, 29.5, 34.7, 38.3, 54.4, 64.7, 73.8, 87.9, 124.4, 132.4, 136.7, 149.6, 152.2, 167.1 ppm; IR (KBr): ν~ = 3252, 2952, 1631, 1586, 1414, 1137, 856, 828, 719, 675 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + H⁺: 227.1184 [M + H]⁺; found: 227.1176.

(2-endo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-4-yl)methanone (endo-4)

The title compound was prepared according to a similar procedure as endo-2, using pyridine-4-carbonyl chloride hydrochloride as the reagent. Purification of the crude product with column chromatography (silica gel 2 g, chloroform: methanol = 50:1) gave the title compound (70.5 mg, 0.312 mmol, 98.2%) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 1.49–1.56 (m, 1H), 1.56–1.69 (m, 1H), 1.69–2.03 (m, 2H), 2.08–2.43 (m, 3H), 2.89 (br s, 1H × 50/100), 3.05 (br s, 1H × 50/100), 4.07 (br s, 1H), 4.78 (br s, 1H), 7.39 (d, J = 5.9 Hz, 2H), 8.71 (d, J = 5.9 Hz, 2H) ppm; ¹³C NMR (CDCl₃, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 23.5 (1C × 50/100), 25.4 (1C × 50/100), 28.9 (1C × 50/100), 30.6, 33.0 (1C × 50/100), 36.7 (1C × 50/100), 38.8 (1C × 50/100), 54.9 (1C × 50/100), 57.2 (1C × 50/100), 59.4 (1C × 50/100), 61.5 (1C × 50/100), 71.0, 83.7, 121.7 (2C), 142.9, 150.5 (2C), 166.4 ppm; IR (neat): ν~ = 3244, 2954, 1636, 1551, 1494, 1409, 1196, 1146, 833, 758, 677 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + H⁺: 227.1184 [M + H]⁺; found: 227.1181.

(2-exo-Ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)(pyridine-4-yl)methanone (exo-4)

This compound was prepared according to a similar procedure as endo-4, starting from exo-9. Purification of the crude product with column chromatography (silica gel 3 g, chloroform: methanol = 20:1) gave the title compound (70.8 mg, 0.313 mmol, 76.2%) as a colorless solid. mp: 86.4–89.7 °C; ¹H NMR (CDCl₃, 400 MHz): δ = 1.45–1.57 (m, 2H), 1.74–2.08 (m, 4H), 2.13–2.19 (m, 1H), 2.61(br s, 1H), 4.04–4.21 (m, 1H), 4.78–4.96 (m, 1H), 7.37–7.60 (m, 2H), 8.67–8.74 (m, 2H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 27.0 (1C × 40/100), 27.5 (1C × 60/100), 28.5 (1C × 60/100), 29.2 (1C × 40/100), 32.1 (1C × 40/100), 33.7 (1C × 60/100), 37.4, 53.4 (1C × 60/100), 57.5 (1C × 40/100), 59.1 (1C × 40/100), 63.4 (1C × 60/100), 71.7 (1C × 40/100), 72.9 (1C × 60/100), 86.9, 121.4 (1C × 40/100), 122.2 (1C × 60/100), 142.8 (2C), 150.0 (2C × 60/100), 150.2 (2C × 40/100), 165.8 ppm; IR (KBr): ν~ = 3212, 2983, 2956, 1627, 1554, 1422, 1215, 842, 726 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₄H₁₄N₂O + H⁺: 227.1184 [M + H]⁺; found: 227.1177.

2-endo-Ethynyl-7-benzoyl-7-azabicyclo[2.2.1]heptane (endo-5)

To a solution of endo-9 (112 mg, 0.508 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (0.5 mL) at 0 °C. After stirring at this temperature for 1 h, saturated aqueous sodium hydrogen carbonate solution (10 mL), dichloromethane (8 mL) and benzoyl chloride (118 µL, 1.02 mmol) were added at 0 °C, and the mixture was stirred at ambient temperature for 20 h. Then the mixture was diluted with saturated aqueous sodium hydrogen carbonate solution (15 mL), and extracted with dichloromethane (30 mL × 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Column chromatography (silica gel 4 g, n-hexane/ethyl acetate = 3:1) gave the title compound (103 mg, 0.458 mmol, 90.3%) as a colorless solid. mp: 111.5–113.0 °C; ¹H NMR (DMSO-d₆, 400 MHz): δ = 1.31–1.38 (m, 1H), 1.46–1.54 (m, 1H), 1.62–1.82 (m, 2H), 2.02–2.11 (m, 1H), 2.14–2.24 (m, 1H), 2.91–2.99 (m, 1H), 3.03–3.07 (m, 1H), 4.05 (br s, 1H), 4.49 (br s, 1H), 7.40–7.47 (m, 2H), 7.47–7.55 (m, 3H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 23.0 (1C × 50/100), 24.7 (1C × 50/100), 28.5 (1C × 50/100), 30.2, 31.9 (1C × 50/100), 36.3 (1C × 50/100), 38.0 (1C × 50/100), 54.1 (1C × 50/100), 56.6 (1C × 50/100), 59.1 (1C × 50/100), 61.1 (1C × 50/100), 73.2, 84.7, 127.7 (2C), 128.4 (2C), 130.8, 135.2, 168.2 ppm; IR (KBr): ν~ = 3195, 2950, 1633, 1578, 1406, 1024, 847, 727, 701, 541 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₅H₁₅NO + Na⁺: 248.1051 [M + Na]⁺; found: 248.1063.

2-exo-Ethynyl-7-benzoyl-7-azabicyclo[2.2.1]heptane (exo-5)

This compound was prepared according to the similar procedure as endo-5, starting from exo-9. Purification of the crude product with column chromatography (silica gel 3 g, n-hexane: ethyl acetate = 3:1) gave the title compound (70.8 mg, 0.314 mmol, 83.6%) as a colorless solid. mp: 92.7–94.6 °C; ¹H NMR (DMSO-d₆, 400 MHz): δ = 1.35–1.53 (m, 2H), 1.61–1.83 (m, 3H), 1.89–1.97 (m, 1H), 2.61–2.69 (m, 1H), 2.92–2.96 (m, 1H), 4.08 (br s, 1H), 4.55 (br s, 1H), 7.39–7.63 (m, 5H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): δ = 27.8, 28.7, 33.6, 37.6, 53.3, 63.6, 72.6, 87.1, 128.2 (3C), 130.6 (2C), 135.7, 168.3 ppm; IR (KBr): ν~ = 3215, 2949, 1615, 1427, 1131, 934, 852, 789, 705, 482 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₅H₁₅NO + Na⁺: 248.1051 [M + Na]⁺; found: 248.1044.

2-endo-Ethynyl-7-acetyl-7-azabicyclo[2.2.1]heptane (endo-6)

To a solution of endo-9 (79.6 mg, 0.360 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.3 mL) at 0 °C. After stirring at this temperature for 1 h, the mixture was concentrated under reduced pressure, and the excess trifluoroacetic acid was removed by repeated evaporation with toluene. The counter anion was then exchanged by chloride by repeated evaporation with 2 M hydrogen chloride solution in diethyl ether. To the crude ammonium salt were added pyridine (2.2 mL) and acetic anhydride (102 µL, 1.10 mmol), and the mixture was stirred at ambient temperature for 19 h. Then, the mixture was concentrated under reduced pressure, and the excess pyridine and acetic anhydride were removed by repeated evaporation with toluene. Column chromatography of the residue (silica gel 5 g, chloroform) gave the title compound (56.9 mg, 0.349 mmol, 96.9%) as a colorless solid. mp: 43.2–46.1 °C; ¹H NMR (CDCl₃, 400 MHz): δ = 1.39–1.87 (m, 4H), 1.99–2.05 (m, 3H), 2.07–2.32 (m, 3H), 2.83–2.92(m, 1H), 4.09–4.16 (m, 1H), 4.58–4.75 (m, 1H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 22.2, 24.2 (1C × 50/100), 25.7 (1C × 50/100), 29.7 (1C × 50/100), 31.2 (1C × 50/100), 31.4 (1C × 50/100), 33.0 (1C × 50/100), 37.6 (1C × 50/100), 39.1 (1C × 50/100), 54.1 (1C × 50/100), 56.6 (1C × 50/100), 57.5 (1C × 50/100), 59.7 (1C × 50/100), 73.8 (1C × 50/100), 73.9 (1C × 50/100), 85.9, 168.3 (1C × 50/100), 168.6 (1C × 50/100) ppm; IR (KBr): ν~ = 3753, 3651, 3217, 2956, 1626, 1441, 1172, 1023, 878, 708 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₀H₁₃NO + Na⁺: 186.0895 [M + Na]⁺; found: 186.0899.

2-exo-Ethynyl-7-acetyl-7-azabicyclo[2.2.1]heptane (exo-6)

This compound was prepared according to a similar procedure as endo-6, starting from exo-9. Purification of the crude product with column chromatography (silica gel 4 g, chloroform) gave the title compound (53.1 mg, 0.325 mmol, 84.4%) as a colorless solid. mp: 75.1–75.5 °C; ¹H NMR (CDCl₃, 400 MHz): δ = 1.34–1.62 (m, 2H), 1.69–1.99 (m, 4H), 2.13 (s, 3H), 2.07–2.13 (m, 1H), 2.51–2.63 (m, 1H), 4.18–4.23 (m, 1H), 4.71–4.77 (m, 1H) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 23.0 (1C × 50/100), 23.3 (1C × 50/100), 29.2 (1C × 50/100), 29.3 (1C × 50/100), 30.7 (1C × 50/100), 30.8 (1C × 50/100), 33.8 (1C × 50/100), 35.4 (1C × 50/100), 39.7 (1C × 50/100), 41.2 (1C × 50/100), 53.9 (1C × 50/100), 57.3 (1C × 50/100), 59.9 (1C × 50/100), 63.2 (1C × 50/100), 73.0 (1C × 50/100), 73.8 (1C × 50/100), 89.1 (1C × 50/100), 89.2 (1C × 50/100), 168.7 (1C × 50/100), 168.8 (1C × 50/100) ppm; IR (KBr): ν~ = 3855, 3753, 3678, 3651, 3224, 2979, 1618, 1459, 1059, 708 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₀H₁₃NO + H⁺: 164.1075 [M + H]⁺; found: 164.1082.

Cyclopropyl(2-endo-ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)methanone (endo-7)

This compound was prepared according to a similar procedure as endo-5, using cyclopropanecarbonyl chloride as the reagent. Purification of the crude product with column chromatography (silica gel 8 g, n-hexane: ethyl acetate = 10:1) gave the title compound (39.2 mg, 0.207 mmol, 88.9%) as a yellow oil. ¹H NMR (CDCl₃, 400 MHz): δ = 0.68–0.79 (m, 2H), 0.88–1.12 (m, 2H), 1.34–1.93 (m, 5H), 2.02–2.42 (m, 3H), 2.89 (br s, 1H), 4.40 (br s, 1H), 4.62 (br s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 5.7 (2C), 10.4, 21.8 (1C × 50/100), 23.8 (1C × 50/100), 27.3 (1C × 50/100), 29.2, 31.4 (1C × 50/100), 35.3 (1C × 50/100), 37.4 (1C × 50/100), 52.6 (1C × 50/100), 55.0 (1C × 50/100), 55.2 (1C × 50/100), 57.6 (1C × 50/100), 68.5 (1C × 50/100), 68.9 (1C × 50/100), 82.8 (1C × 50/100), 83.0 (1C × 50/100), 169.9 ppm; IR (neat): ν~ = 3584, 3303, 2952, 1643, 1434, 1322, 1031, 486, 469, 453, 439, 422, 408 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₂H₁₅NO + H⁺: 190.1232 [M + H]⁺; found: 190.1227.

Cyclopropyl(2-exo-ethynyl-7-azabicyclo[2.2.1]heptan-7-yl)methanone (exo-7)

This compound was prepared according to a similar procedure as endo-7, starting from exo-9. Purification of the crude product with column chromatography (silica gel 3 g, dichloromethane/methanol, 60:1) gave the title compound (71.8 mg, 0.379 mmol, 86.2%) as a colorless solid. mp: 95.8–96.4 °C; ¹H NMR (DMSO-d₆, 400 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 0.59–0.80 (m, 4H), 1.27–2.02 (m, 7H), 2.59 (br s, 1H × 30/100), 2.68 (br s, 1H × 70/100), 2.87 (br s, 1H × 30/100), 2.96 (br s, 1H × 70/100), 4.40 (br s, 1H × 30/100), 4.45 (br s, 1H × 70/100), 4.52–4.59 (m, 1H × 70/100), 4.63 (br s, 1H × 30/100) ppm; ¹³C NMR (DMSO-d₆, 100 MHz): Splits of some peaks were observed due to the existence of rotamers. δ = 7.6 (1C × 30/100), 7.9 (1C × 30/100), 8.4 (1C × 70/100), 8.6 (1C × 70/100) 12.4 (1C × 30/100), 12.9 (1C × 70/100), 28.1 (1C × 30/100), 28.3 (1C × 70/100), 30.1 (1C × 70/100), 30.3 (1C × 30/100), 32.8 (1C × 30/100), 32.9 (1C × 30/100), 34.7 (1C × 70/100), 38.7 (1C × 70/100), 53.7 (1C × 70/100), 56.0 (1C × 30/100), 59.7 (1C × 30/100), 62.0 (1C × 70/100), 72.2 (1C × 30/100), 72.9 (1C × 30/100), 73.0 (1C × 70/100), 88.3 (1C × 70/100), 171.8 (1C × 30/100), 171.9 (1C × 70/100) ppm; IR (KBr): ν~ = 3205, 2952, 1620, 1473, 1307, 1199, 1162, 1038, 888, 727 cm⁻¹; HR-MS (ESI): m/z calcd for C₁₂H₁₅NO + Na⁺: 212.1060 [M + Na]⁺; found: 212.1051.