M. Jida, J. Ollivier
FULL PAPER
13C NMR (62.9 MHz, CDCl3): δ = 139.2, 128.7, 128.1, 126.8, 67.7,
1-Benzyl-2-methylpiperidin-3-one (8b): Yellow oil. Yield: 21%. 1H
NMR (250 MHz, CDCl3): δ = 7.46–7.23 (m, 5 H), 3.61 (AB system,
64.3, 57.0, 53.6, 40.4, 25.6, 24.6, 22.7, 22.2, 13.8 ppm. IR (neat): ν
˜
= 3340, 2955, 2798, 1603 cm–1. MS (EI): m/z (%) = 245 (4) [M]+·,
189 (16), 188 (100), 91 (52). HRMS (EI): calcd. for C16H23NO
245.17740; found 245.17717.
δναΒ = 47.5 Hz, J = 13.7 Hz, 2 H), 3.48 (q, J = 6.7 Hz, 1 H), 3.20
3
2
3
2
3
(td, J = 12.5 Hz, J = 4.4 Hz, 1 H), 2.72 (td, J = 15.1 Hz, J =
3
6.1 Hz, 1 H), 2.58–2.21 (m, 2 H), 2.39–2.01 (m, 2 H), 1.21 (d, J =
6.7 Hz, 3 H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 207.1, 139.9,
3-Benzyl-2-[(1S)-1-methylpropyl]-3-azabicyclo [3.1.0] hexan-1-ol
(1e): Inseparable mixture of cis and trans diastereomers. Deliques-
128.7, 128.4, 127.6, 61.9, 58.9, 49.2, 38.3, 23.3, 10.3 ppm. IR (neat):
ν = 3086, 3036, 2938, 1718, 1600 cm–1. MS (EI): m/z (%) = 203 (6)
˜
cent white solid. Yield: 79%; cis/trans, 71:29. IR (neat): ν = 3028,
˜
[M]+·, 194 (11), 104 (30), 92 (100), 65 (10). HRMS (EI): calcd. for
C13H17NO 203.13570; found 203.13558.
2927, 2793, 1603 cm–1. Data for (1S,2S,5R)-cis-1e: 1H NMR
(360 MHz, CDCl3): δ = 7.31–7.22 (m, 5 H), 3.79 (AB system, δνα
Β
cis- and trans-1-Benzyl-2-isopropyl-4-methylpyrrolidin-3-one (4c):
Inseparable mixture of cis and trans diastereomers. Colourless li-
2
3
= 50.4 Hz, J = 14.4 Hz, 2 H), 3.25 (dd, J = 10.5 Hz, J = 3.6 Hz,
3
2
1 H), 3.09 (d, J = 2.2 Hz, 1 H), 2.28 (d, J = 10.5 Hz, 1 H), 1.89–
1.85 (m, 1 H), 1.58–1.53 (m, 1 H), 1.45–1.39 (m, 2 H), 1.28 (br. s,
1 H), 1.10 (dd, 2J = 9.0 Hz, 3J = 4.7 Hz, 1 H), 1.05 (d, 3J = 6.8 Hz,
quid. Yield: 54%; cis/trans, 20:80. IR (neat): ν = 3081, 3031, 2934,
˜
1711 1603 cm–1. C15H21NO (231.33): calcd. C 77.88, H 9.15, N
6.05; found C 77.51, H 8.96, N 5.92. 1H NMR (360 MHz, CDCl3):
3
3 H), 0.97 (t, J = 7.2 Hz, 3 H), 0.45 (t, 2,3J = 4.7 Hz, 1 H) ppm.
δ = 7.39–7.28 (m, 10 H, cis + trans), 3.72 (AB system, δνAB
=
13C NMR (62.9 MHz, CDCl3): δ = 138.9, 128.2, 128.1, 126.7, 73.6,
64.5, 61.7, 55.1, 38.2, 28.0, 24.5, 19.9, 15.7, 12.6 ppm. MS (EI): m/z
(%) = 245 (3) [M]+·, 187 (22), 90 (100), 65 (10). HRMS (EI): calcd.
for C16H23NO 245.1852; found 245.1850. Data for (1R,2S,5S)-
trans-1e: 1H NMR (360 MHz, CDCl3): δ = 7.33–7.28 (m, 5 H),
292.0 Hz, J = 13.3 Hz, 2 H, cis), 3.71 (AB system, δναΒ = 304.6 Hz,
2
J = 13.3 Hz, 2 H, trans), 3.38–3.28 (m, 1 H, trans), 2.83 (dd, J =
10.1 Hz, 3J = 2.5 Hz, 1 H, cis), 2.66 (d, 3J = 2.9 Hz, 1 H, cis), 2.60–
2.55 (m, 2 H, trans), 2.35–2.26 (m, 2 H, cis + trans), 2.14–2.06 (m,
2
3
2 H, cis + trans), 1.97 (dd, J = 11.5 Hz, J = 9.0 Hz, 1 H, trans),
3
3.59 (AB system, δναΒ = 320.4 Hz, J = 13.3 Hz, 2 H), 2.82 (d, J
3
1.15 (d, J = 7.2 Hz, 3 H, trans), 1.14–1.07 (m, 9 H, cis), 1.03 (d,
2
2
= 2.9 Hz, 1 H), 2.69 (d, J = 9.0 Hz, 1 H), 2.39 (dd, J = 9.0 Hz,
3 H, 3J = 7.2 Hz, trans), 1.02 (d, 3J = 7.2 Hz, 3 H, trans) ppm. 13C
NMR (62.9 MHz, CDCl3): δ = 218.7 (cis), 218.1 (trans), 140.8 (cis),
138.3 (trans), 128.8 (cis + trans), 128.6 (cis), 128.3 (cis + trans),
127.2 (trans), 74.3 (cis), 74.0 (cis), 59.2 (trans), 57.0 (cis), 51.2
(trans), 49.4 (cis), 33.9 (cis), 31.7 (trans), 29.0 (cis), 27.2 (trans),
19.1 (trans), 18.9 (cis), 18.0 (trans), 17.8 (cis) ppm. MS (EI, cis),
m/z (%) = 231 (2) [M]+·, 203 (28), 188 (35), 91 (100). MS (EI, trans),
m/z (%) = 231 (2) [M]+·, 203 (17), 188 (32), 91 (100).
3J = 4.0 Hz, 1 H), 1.87–1.83 (m, 1 H), 1.65–1.55 (m, 2 H), 1.47–
1.43 (m, 1 H), 1.28 (br. s, 1 H), 1.12 (d, J = 8.7 Hz, 3 H), 1.05 (t,
3
3J = 8.6 Hz, 3 H), 0.89 (dd, J = 9.0 Hz, J = 5.0 Hz, 1 H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 137.8, 128.5, 127.9, 126.6, 69.6,
60.9, 57.1, 53.9, 36.0, 26.7, 19.6, 15.7, 14.6, 13.2 ppm. MS (EI) m/z
(%) = 245 (4) [M]+·, 206 (34), 187 (14), 160 (31), 90 (100), 65 (11),
40 (21). HRMS (EI): calcd. for C16H23NO 245.1852; found
245.1853.
2
3
1-Benzyl-2-isopropylpiperidin-3-one (8c): Yellow oil. Yield: 35%. 1H
NMR (300 MHz, CDCl3): δ = 7.33–7.28 (m, 5 H), 3.75 (AB system,
δναΒ = 27.0 Hz, J = 13.6 Hz, 2 H), 3.23 (td, 2J = 14.4 Hz, 3J =
Potassium Hydroxide Promoted Ring Cleavage: Dry potassium hy-
droxide (70 mg, 1.25 mmol) was added to a solution of azabicy-
clo[3.1.0]hexane-1-ols 1b–f (0.5 mmol) in anhydrous methanol
(5 mL), and the mixture was heated at reflux for 10 min. After cool-
ing, the solvent was evaporated and the residue was diluted with
diethyl ether (10 mL) and water (2 mL). After extraction of the
aqueous phase with diethyl ether (3ϫ5 mL), the combined organic
layer was washed with brine (3 mL), dried with magnesium sulfate
and concentrated. The residue was purified by flash chromatog-
raphy on silica gel (petroleum ether/diethyl ether, 90:10) to furnish
pyrrolidinones 4b–f as an inseparable mixture of diastereomers and
piperidinones 8b–f.
2
3
3.3 Hz, 1 H), 2.71 (dt, J = 15.3 Hz, J = 4.5 Hz, 1 H), 2.60–2.51
3
(m, 2 H), 2.50 (d, J = 9.3 Hz, 1 H), 2.40–2.29 (m, 2 H), 2.03–1.96
(m, 1 H), 1.04 (d, 3J = 6.6 Hz, 3 H), 0.79 (d, 3J = 6.6 Hz, 3 H)
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 214.8, 139.1, 128.7, 128.3,
127.1, 77.2, 57.3, 44.2, 38.6, 27.2, 25.6, 20.0, 19.2 ppm. IR (neat):
ν = 3086, 3028, 2935, 1711, 1603 cm–1. MS (EI): m/z (%) = 231 (5)
˜
[M]+·, 203 (14), 188 (35), 174 (14), 160 (70), 91 (100), 84 (11).
HRMS (EI): calcd. for C15H21NO 231.16960; found 231.16936.
cis- and trans-1-Benzyl-2-(2-methylpropyl)-4-methylpyrrolidin-3-one
(4d): Inseparable mixture of cis and trans diastereomers. Colourless
liquid. Yield: 55%; cis/trans, 18:82. IR (neat): ν = 3085, 3030, 2930,
˜
cis- and trans-1-Benzyl-2,4-dimethylpyrrolidin-3-one (4b): Insepa-
rable mixture of cis and trans diastereomers. Colourless liquid.
1713, 1603 cm–1. C16H23NO (245.36): calcd. C 78.32, H 9.45, N
5.71; found C 77.91, H 9.42, N 5.38. 1H NMR (360 MHz, CDCl3):
Yield: 55%; cis/trans, 24:76. IR (neat): ν = 3082, 3032, 2932, 1715,
˜
1604 cm–1. C13H17NO (203.28): calcd. C 76.81, H 8.43, N 6.89;
δ = 7.40–7.29 (m, 10 H, cis + trans), 3.76 (AB system, δνAB
=
1
201.2 Hz, J = 13.3 Hz, 2 H, cis), 3.71 (AB system, δναΒ = 235.2 Hz,
found C 76.45, H 8.34, N 6.71. H NMR (300 MHz, CDCl3): δ =
J = 13.3 Hz, 2 H, trans), 3.33 (t, 3J = 8.3 Hz, 1 H, trans), 2.85 (dd,
7.37–7.28 (m, 10 H, cis + trans), 3.75 (AB system, δναΒ = 197.4 Hz,
J = 13.2 Hz, 2 H, cis), 3.73 (AB system, δναΒ = 226.2 Hz, J =
12.9 Hz, 2 H, trans), 3.32 (dd, 2J = 9.0 Hz, 3J = 4.5 Hz, 1 H, trans),
3
3
2J = 9.8 Hz, J = 2.5 Hz, 1 H, cis), 2.74 (t, J = 5.5 Hz, 1 H, cis),
2.63–2.56 (m, 2 H, trans), 2.52–2.20 (m, 3 H, cis + trans), 2.06–
3
1.90 (m, 1 H, cis), 1.95 (dd, 2J = 11.3 Hz, J = 9.0 Hz, 1 H, trans),
2
3
3
2.81 (dd, J = 9.6 Hz, J = 2.1 Hz, 1 H, cis), 2.74 (q, J = 6.3 Hz,
3
1.78–1.49 (m, 4 H, cis + trans), 1.19 (m, 18 H, cis + trans) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 217.3 (cis), 216.2 (trans), 137.8
(cis), 137.6 (trans), 129.0 (trans), 128.7 (cis), 128.6 (trans), 128.4
(cis), 127.3 (trans), 127.2 (cis), 68.7 (cis), 68.5 (cis), 58.8 (trans),
58.7 (cis), 57.2 (trans), 56.1 (cis), 42.3 (trans), 40.8 (cis), 38.4 (trans),
37.2 (cis), 25.8 (cis), 25.2 (trans), 24.9 (trans), 23.7 (cis), 22.9 (cis),
22.7 (trans), 22.5 (cis) ppm. MS (EI, cis), m/z (%) = 245 (1) [M]+·,
176 (100), 91 (98). MS (EI, trans), m/z (%) = 245 (2) [M]+·, 217
(22), 202 (28), 174 (23), 160 (100), 146 (51), 91 (76).
1 H, cis), 2.64 (m, 1 H, cis), 2.59 (q, J = 6.6 Hz, 1 H, trans), 2.44–
2.36 (m, 2 H, cis + trans), 2.02 (dd, J = 10.8 Hz, J = 9.0 Hz, 1
H, trans), 1.29 (d, J = 6.6 Hz, 3 H, trans), 1.24 (d, J = 6.3 Hz, 3
H, cis), 1.17 (d, J = 7.5 Hz, 3 H, cis), 1.09 (d, J = 7.2 Hz, 3 H,
trans) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 211.9 (cis), 210.9
(trans), 137.7 (cis), 137.4 (trans), 129.2 (cis + trans), 128.4 (cis +
trans), 127.4 (trans), 127.2 (cis), 65.6 (trans), 65.1 (cis), 58.6 (trans),
57.9 (cis), 57.2 (trans), 56.1 (cis), 41.9 (trans), 40.9 (cis), 15.9 (cis),
14.8 (trans), 14.0 (cis), 11.9 (trans) ppm. MS (EI, cis), m/z (%) =
2
3
3
3
3
3
203 (2) [M]+·, 175 (53), 132 (11), 91 (100). MS (EI, trans), m/z (%) 1-Benzyl-2-(2-methylpropyl)piperidin-3-one (8d): Yellow oil. Yield:
1
= 203 (2) [M]+·, 175 (52), 132 (10), 91 (100).
28%. H NMR (300 MHz, CDCl3): δ = 7.33–7.27 (m, 5 H), 3.73
4046
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Eur. J. Org. Chem. 2008, 4041–4049