M. Ishikura et al.
FULL PAPER
rel-(1S,4S,6R)-6-(3-Methoxyphenyl)-2-azabicyclo[2.2.1]heptan-3-
one (7h): Colorless crystals; m.p. 210–212 °C (hexane/CH2Cl2). H
121.8, 123.6, 125.3, 125.9, 126.4, 127.3, 129.1, 131.9, 134.0, 138.8,
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181.0 ppm. IR (CHCl ): ν = 3436, 3348, 1696, 1622 cm–1. HRMS
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NMR (500 MHz, CDCl3): δ = 1.79 (dd, J = 1.7, 9.7 Hz, 1 H), 1.96
(dt, J = 1.8, 9.7 Hz, 1 H), 2.06 (dt, J = 4.6, 13.2 Hz, 1 H), 2.16
(ddd, J = 2.3, 8.6, 13.2 Hz, 1 H), 2.83 (s, 1 H), 3.22 (dd, J = 5.2,
8.6 Hz, 1 H), 3.81 (s, 3 H), 3.89 (s, 1 H), 5.68 (br. s, 1 H), 6.76 (s,
1 H), 6.77 (m, 1 H), 6.81 (d, J = 7.5 Hz, 1 H), 7.25 (m, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 31.0, 38.6, 44.9, 48.7, 55.3, 60.5,
(EI): calcd. for C16H15NO [M]+ 237.1154; found 237.1134.
rel-(1S,4S,6R)-6-(2-Naphthyl)-2-azabicyclo[2.2.1]heptan-3-one (7k):
Colorless crystals; m.p. 140–142 °C (propan-2-ol). 1H NMR
(500 MHz, CDCl3): δ = 1.95 (dd, J = 1.7, 10.3 Hz, 1 H), 2.01 (dt,
J = 1.7, 10.3 Hz, 1 H), 2.19–2.28 (m, 2 H), 2.89 (s, 1 H), 3.42 (t, J
= 6.9 Hz, 1 H), 4.02 (s, 1 H), 5.64 (br. s, 1 H), 7.36 (dd, J = 1.7,
8.6 Hz, 1 H), 7.44–7.50 (m, 2 H), 7.63 (s, 1 H), 7.81 (t, J = 9.7 Hz,
3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 30.9, 38.5, 45.0, 48.9,
60.4, 124.9, 125.9, 126.4, 126.5, 127.6, 127.7, 128.5, 132.2, 133.4,
111.4, 113.8, 119.6, 129.7, 143.8, 159.9, 181.1 ppm. IR (CHCl ): ν
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= 3436, 1694 cm–1. HRMS (EI): calcd. for C13H15NO2 [M]+
217.1103; found 217.1104. C13H15NO2 (217.11): calcd. C 71.86, H
6.96, N 7.45; found C 71.67, H 7.05, N 7.33.
139.5, 181.1 ppm. IR (CHCl ): ν = 3436, 1696, 1652 cm–1. HRMS
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(EI): calcd. for C16H15NO [M]+ 237.1154; found 237.1079.
C16H15NO (237.10): calcd. C 80.98, H 6.37, N 5.90; found C 80.79,
H 6.44, N 5.81.
rel-(1S,4S,6R)-5-(3-Methoxyphenyl)-2-azabicyclo[2.2.1]heptan-3-
one (8h): Colorless oil. 1H NMR (CDCl3): δ = 1.81 (d, J = 10.3 Hz,
1 H), 1.97 (dt, J = 1.8, 10.3 Hz, 1 H), 2.04 (m, 1 H), 2.23 (ddd, J
= 2.3, 9.2, 12.0 Hz, 1 H), 2.86 (s, 1 H), 3.30 (dd, J = 5.2, 9.2 Hz, 1
H), 3.79 (s, 3 H), 4.01 (s, 1 H), 5.70 (br. s, 1 H), 6.76 (m, 1 H), 6.81
(d, J = 7.5 Hz, 1 H), 6.84 (d, J = 8.1 Hz, 1 H), 7.23 (m, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 38.7, 38.9, 41.5, 51.3, 55.3, 55.8,
rel-(1R,4R,5R)-5-(2-Naphthyl)-2-azabicyclo[2.2.1]heptan-3-one (8k):
Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.89 (d, J = 9.8 Hz,
1 H), 2.03 (m, 1 H), 2.18 (ddd, J = 2.3, 5.1, 12.5 Hz, 1 H), 2.32
(ddd, J = 2.3, 9.1, 11.3 Hz, 1 H), 2.99 (s, 1 H), 3.49 (dd, J = 5.1,
9.0 Hz, 1 H), 4.07 (s, 1 H), 5.55 (br. s, 1 H), 7.39 (dd, J = 1.7,
8.5 Hz, 1 H), 7.46 (dq, J = 1.7, 7.4 Hz, 2 H), 7.66 (s, 1 H), 7.80 (t,
J = 8.5 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 38.6,
38.9, 41.6, 53.5, 55.9, 124.58, 125.8, 126.3, 126.7, 127.6, 127.7,
111.5, 113.5, 119.5, 129.7, 144.5, 159.8, 180.9 ppm. IR (CHCl ): ν
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= 3432, 1698 cm–1. HRMS (EI): calcd. for C13H15NO2 [M]+
217.1103; found 217.1103.
rel-(1S,4S,6R)-6-(2-Methoxyphenyl)-2-azabicyclo[2.2.1]heptan-3-
1
one (7i): Colorless crystals; m.p. 80–81 °C (hexane/CH2Cl2). H
128.4, 132.2, 133.4, 140.2, 180.8 ppm. IR (CHCl ): ν = 3432,
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1698 cm–1. HRMS (EI): calcd. for C16H15NO [M]+ 237.1154; found
NMR (500 MHz, CDCl3): δ = 1.73 (dd, J = 1.7, 9.7 Hz, 1 H), 1.93–
1.98 (m, 2 H), 2.13 (ddd, J = 2.3, 9.2, 1 3.2 Hz, 1 H), 2.81 (d, J =
2.9 Hz, 1 H), 3.44 (dd, J = 6.3, 8.6 Hz, 1 H), 3.84 (s, 3 H), 3.89 (s,
1 H), 5.56 (br. s, 1 H), 6.88 (d, J = 8.1 Hz, 1 H), 6.93 (t, J = 8.0 Hz,
1 H), 7.11 (d, J = 7.5 Hz, 1 H), 7.23 (dd, J = 1.8, 8.1 Hz, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 30.1, 38.6, 42.3, 44.9, 55.4, 59.2,
237.1090.
rel-(1S,4S,6R)-6-(3-Thiophenyl)-2-azabicyclo[2.2.1]heptan-3-one
1
(7l): Colorless oil. H NMR (500 MHz, CDCl3): δ = 1.72 (dd, J =
1.1, 9.7 Hz, 1 H), 1.95 (dd, J = 1.7, 9.7 Hz, 1 H), 2.03 (dt, J = 4.6,
13.2 Hz, 1 H), 2.16 (ddd, J = 1.7, 8.6, 10.9 Hz, 1 H), 2.81 (d, J =
2.3 Hz, 1 H), 3.25 (dd, J = 5.2, 8.6 Hz, 1 H), 3.87 (s, 1 H), 6.07
(br. s, 1 H), 6.98 (d, J = 4.0 Hz, 2 H), 7.30 (t, J = 4.6 Hz, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 33.1, 38.9, 44.4, 44.6, 61.6,
110.3, 120.3, 125.8, 127.6, 130.6, 157.4, 181.4 ppm. IR (CHCl ): ν
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= 3436, 1694 cm–1. HRMS (EI): calcd. for C13H15NO2 [M]+
217.1103; found 217.1104. C13H15NO2: calcd. C 71.86, H 6.96, N
7.45; found C 71.96, H 6.77, N 7.23.
123.8, 124.1, 127.1, 146.3, 180.6 ppm. IR (CHCl ): ν = 3430,
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rel-(1R,4R,5R)-5-(2-Methoxyphenyl)-2-azabicyclo[2.2.1]heptan-3-
one (8i): Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.80–1.84
(m, 2 H), 2.00 (m, 1 H), 2.26 (ddd, J = 2.3, 9.2, 13.2 Hz, 1 H), 2.89
(s, 1 H), 3.50 (dd, J = 4.0, 8.6 Hz, 1 H), 3.84 (s, 3 H), 3.97 (s, 1 H),
5.44 (br. s, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 6.92 (t, J = 6.9 Hz, 1
H), 7.12 (dd, J = 1.2, 6.9 Hz, 1 H), 7.22 (td, J = 1.2, 8.1 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 35.5, 38.7, 39.3, 49.0,
55.4, 55.81, 110.3, 120.2, 125.2, 127.5, 131.4, 132.1, 181.3 ppm. IR
1695 cm–1. HRMS (EI): calcd. for C10H11NOS [M]+ 193.0561;
found 193.0566.
rel-(1R,4R,5R)-5-(3-Thiophenyl)-2-azabicyclo[2.2.1]heptan-3-one
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(8l): Colorless oil. H NMR (500 MHz, CDCl3): δ = 1.74 (dd, J =
1.2, 9.7 Hz, 1 H), 1.97 (d, J = 9.7 Hz, 1 H), 2.03 (ddd, J = 2.3, 4.6,
12.6 Hz, 1 H), 2.21 (ddd, J = 2.3, 9.2, 12.0 Hz, 1 H), 2.83 (s, 1 H),
3.33 (dd, J = 5.2, 9.2 Hz, 1 H), 4.00 (d, J = 1.2 Hz, 1 H), 5.60 (br.
s, 1 H), 7.00 (dd, J = 1.8, 2.9 Hz, 1 H), 7.01 (dd, J = 1.7, 5.2 Hz,
1 H), 7.30 (dd, J = 2.9, 5.2 Hz, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 37.5, 38.8, 39.0, 51.6, 55.7, 119.9, 126.2, 127.8, 143.9,
(CHCl ): ν = 3436, 3348, 1694 cm–1. HRMS (EI): calcd. for
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C13H15NO2 [M]+ 217.1103; found 217.1106.
rel-(1S,4S,6R)-6-(1-Naphthyl)-2-azabicyclo[2.2.1]heptan-3-one (7j):
Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.94 (m, 1 H), 2.06
(m, 1 H), 2.10 (m, 1 H), 2.46 (m, 1 H), 3.09 (s, 1 H), 3.96 (dd, J =
5.0, 13.7 Hz, 1 H), 4.06 (s, 1 H), 5.56 (br. s, 1 H), 7.32 (d, J =
7.5 Hz, 1 H), 7.43 (t, J = 7.4 Hz, 1 H), 7.50–7.58 (m, 2 H), 7.75 (d,
J = 8.6 Hz, 1 H), 7.87 (d, J = 8.6 Hz, 1 H), 8.08 (d, J = 8.0 Hz, 1
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 38.0, 39.4, 39.5, 49.9,
55.8, 121.6, 123.8, 125.3, 125.9, 126.4, 127.4, 128.9, 132.1, 134.1,
180.6 ppm. IR (CHCl ): ν = 3463, 1683 cm–1. HRMS (EI): calcd.
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for C10H11NOS [M]+ 193.0561; found 193.0557.
rel-(1S,4S,6R)-6-(2-Thiophenyl)-2-azabicyclo[2.2.1]heptan-3-one
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(7m): Colorless oil. H NMR (500 MHz, CDCl3): δ = 1.84 (dd, J
= 1.8, 11.5 Hz, 1 H), 1.99 (dt, J = 1.7, 10.3 Hz, 1 H), 2.08 (dt, J =
4.6, 13.2 Hz, 1 H), 2.25 (ddd, J = 2.3, 5.6, 13.2 Hz, 1 H), 2.83 (d,
J = 2.9 Hz, 1 H), 3.43 (dd, J = 4.6, 8.6 Hz, 1 H), 3.87 (s, 1 H), 5.74
(br. s, 1 H), 6.86 (m, 1 H), 6.96 (dd, J = 3.4, 5.2 Hz, 1 H), 7.18
(dd, J = 1.2, 5.2 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
33.1, 38.8, 44.4, 44.6, 61.6, 123.8, 124.1, 127.1, 146.3, 180.6 ppm.
138.5, 181.0 ppm. IR (CHCl ): ν = 3488, 3416, 1700 cm–1. HRMS
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(EI) m/z: calcd. for C16H15NO [M]+ 237.1154; found 237.1090.
rel-(1R,4R,5R)-5-(1-Naphthyl)-2-azabicyclo[2.2.1]heptan-3-one (8j):
Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.97 (d, J = 8.1 Hz,
1 H), 1.99 (dd, J = 5.2, 8.0 Hz, 1 H), 2.13 (dt, J = 1.8, 9.7 Hz, 1
H), 2.46 (ddd, J = 1.8, 9.7, 21.8 Hz, 1 H), 2.88 (d, J = 3.5 Hz, 1
IR (CHCl ): ν = 3467, 1690 cm–1. HRMS (EI): calcd. for
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C10H11NOS [M]+ 193.0561; found 193.0560.
rel-(1R,4R,5R)-5-(2-Thiophenyl)-2-azabicyclo[2.2.1]heptan-3-one
1
H), 3.82 (dd, J = 5.8, 8.6 Hz, 1 H), 4.21 (s, 1 H), 5.66 (br. s, 1 H), (8m): Colorless oil. H NMR (500 MHz, CDCl3): δ = 1.88 (dd, J
7.25 (m, 1 H), 7.43 (t, J = 8.6 Hz, 1 H), 7.50–7.57 (m, 2 H), 7.75
(d, J = 8.6 Hz, 1 H), 7.87 (d, J = 8.6 Hz, 1 H), 7.99 (d, J = 8.6 Hz,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 32.4, 39.4, 44.9, 59.0,
= 1.5, 10.0 Hz, 1 H), 2.02 (m, 1 H), 2.08 (ddd, J = 1.8, 4.6, 12.6 Hz,
1 H), 2.30 (ddd, J = 2.9, 9.2, 12.6 Hz, 1 H), 2.86 (s, 1 H), 3.53 (dd,
J = 5.2, 8.6 Hz, 1 H), 4.02 (d, J = 2.9 Hz, 1 H), 5.48 (br. s, 1 H),
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Eur. J. Org. Chem. 2010, 3281–3294