M. J. Johansson et al. / Tetrahedron: Asymmetry 15 (2004) 3531–3538
3535
organic phases were dried over Na2SO4 and concen-
trated under reduced pressure to give 7a as a colourless
solid.
4.75 (d, J = 14.0Hz, 1H), 3.47 (d, J = 17.2Hz, 1H),
3.44 (d, J = 3.2Hz, 1H), 3.04 (m, 2H), 2.95 (d,
J = 10.8Hz, 1H), 2.82 (d, J = 14.4Hz, 1H), 2.45 (d,
J = 17.2Hz, 1H), 2.32 (m, 2H), 2.02 (d, J = 18.4Hz,
1H), 1.97 (s, 1H), 1.76–1.72(m, 3H), 1.63–1.44 (m,
4H); 13C NMR (CDCl3, 100MHz): d 169.0, 139.2,
129.0, 128.2, 127.0, 63.6, 60.0, 59.2, 46.4, 34.1, 33.6,
4.2.1. Data for (ꢀ)-N-cyclopropylmethyl-1,2,3,4,5,6-
20
hexahydro-1,5-methano-pyrido[1,2a][1,5]diazocin-8-one
7a. Colourless solid, yield 2.23g (85%). ½a ¼ ꢀ172:4
D
1
(c 0.55 in CHCl3); mp 92.5–94.5ꢁC; H NMR (CDCl3,
400MHz): d 7.24 (m, 1H), 6.39 (d, J = 8.8Hz, 1H), 5.96
(d, J = 7.2Hz, 1H), 4.00 (d, J = 15.6Hz, 1H), 3.87 (dd,
J = 15.6, 6.8Hz, 1H), 3.04 (d, J = 10.8Hz, 1H), 2.97 (d,
J = 10.4Hz, 1H), 2.91 (s, 1H), 2.39 (br s, 1H), 2.29 (d,
J = 10.4Hz, 1H), 2.24 (d, J = 10.8Hz, 1H), 2.15–2.01
(m, 2H), 1.77 (dd, J = 12.8, 4.4Hz, 2H), 0.60 (m, 1H),
0.35 (d, J = 7.6Hz, 2H), ꢀ0.07 (d, J = 4.8Hz, 2H); 13C
NMR (CDCl3, 100MHz): d 163.9, 152.0, 138.9, 116.5,
104.9, 63.1, 60.6, 60.0, 35.7, 30.4, 28.1, 26.1, 8.1, 4.0,
3.7; IR 2934, 1648, 1546cmꢀ1. Anal. Calcd for
C15H20N2O: C, 73.74; H, 8.25. Found: C, 73.63; H, 8.20.
33.3, 30.3, 29.5, 28.0, 20.2; IR 2928, 1629, 1444cmꢀ1
.
Anal. Calcd for C18H24N2O: C, 76.02; H, 8.51. Found:
C, 75.88; H, 8.45.
4.3. General procedure for the reduction of the 2-pyridone
moiety with PtO2/H2
Compound 7a (700mg, 2.9mmol) was dissolved in ace-
tic acid (30mL). PtO2 (68mg, 0.29mmol) was added in
one portion under a stream of nitrogen. The flask was
evacuated and backfilled with H2; this procedure was re-
peated several times. Thereafter the reaction mixture
was stirred under an H2 atmosphere at atmospheric
pressure for 26h. The PtO2 was filtered off and the reac-
tion concentrated under reduced pressure (toluene was
added to ensure complete removal of acetic acid). The
residue was dissolved in CH2Cl2 (50mL) and the pH ad-
justed to ꢁ11 using NaOH (2M, aq). The organic phase
was washed with brine, dried using Na2SO4 and concen-
trated under reduced pressure to give 8a.
4.2.2. Data for (ꢀ)-N-isopropyl-1,2,3,4,5,6-hexahydro-
1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one 7b. Pre-
pared from (ꢀ)-cytisine and acetone according to the
general procedure for reductive amination. Colourless
20
oil, yield 1.67g (92%). ½a ¼ ꢀ144:4 (c 2.44 in CHCl3);
D
1H NMR (CDCl3, 400MHz): d 7.16 (m, 1H), 6.30 (d,
J = 8.8Hz, 1H), 5.87 (d, J = 6.8Hz, 1H), 3.86 (d,
J = 15.2Hz, 1H), 3.77 (dd, J = 15.6, 6.4Hz, 1H), 2.83
(br s, 1H), 2.72 (br t, J = 12.2Hz, 2H), 2.50–2.35 (m,
3H), 2.31 (br s, 1H), 1.75 (d, J = 12.8Hz, 1H), 1.65 (d,
J = 12.8Hz, 1H), 0.77 (d, J = 6.8Hz, 3H), 0.72(d,
J = 6.8Hz, 3H); 13C NMR (CDCl3, 100MHz): d 163.6,
152.0, 138.6, 116.1, 104.5, 55.8, 55.3, 53.8, 50.0, 35.6,
30.2, 28.0, 26.2, 17.8; IR 2962, 1651, 1547cmꢀ1. HRMS
(ECI) m/z (M+1)+ calcd for C14H21N2O: 233.1654.
Found: 233.1679. Anal. Calcd for C14H20N2O: C,
72.38; H, 8.68. Found: C, 72.46; H, 8.54.
4.3.1. Data for (ꢀ)-N-cyclopropylmethyl-decahydro-1,5-
20
methano-pyrido[1,2-a][1,5]diazocin-8-one 8a. White so-
lid, yield 706mg (98%). ½a ¼ ꢀ58:6 (c 1.1 in CHCl3);
D
1
mp 52.8–53.5ꢁC; H NMR (CDCl3, 400MHz): d 4.72
(d, J = 13.6Hz, 1H), 3.51 (m, 1H), 3.35 (d,
J = 12.0Hz, 1H), 3.00 (d, J = 10.4Hz, 1H), 2.80 (d,
J = 13.2Hz 1H), 2.43 (d, J = 16.8Hz, 1H), 2.32–2.18
(m, 3H), 2.08 (dd, J = 12.4, 6.4Hz, 2H), 2.00 (d,
J = 11.6Hz, 1H), 1.94–1.61 (m, 7H), 0.78 (m, 1H),
0.43 (m, 2H), 0.05 (d, J = 4.4Hz, 2H); 13C NMR
(CDCl3, 100MHz): d 168.8, 63.9, 59.6, 59.0, 54.2, 46.7,
34.3, 33.9, 33.4, 29.5, 28.3, 20.3, 9.08, 4.6, 3.5; IR
2922, 1613, 1462cmꢀ1. Anal. Calcd for C15H24N2O: C,
72.54; H, 9.74. Found: C, 72.62; H, 9.74.
4.2.3. Data for (ꢀ)-N-cyclohexyl-1,2,3,4,5,6-hexahydro-
1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one 7c. Pre-
pared from (ꢀ)-cytisine and cyclohexyl-carboxaldehyde
according to the general procedure for reductive amina-
20
tion. Colourless oil, yield 2.82g (98%). ½a ¼ ꢀ173:3 (c
D
1
0.45 in CHCl3); H NMR (CDCl3, 400MHz): d 7.26–
7.22 (m, 1H), 6.38 (d, J = 9.2Hz, 1H), 5.94 (d,
J = 6.4Hz, 1H), 3.94 (d, J = 15.2Hz, 1H), 3.85 (dd,
J = 15.2, 6.0Hz, 1H), 2.85 (dd, J = 25.2, 11.2Hz, 3H),
2.53 (t, J = 10.4Hz, 2H), 2.37 (br s, 1H), 2.06 (br s,
1H), 1.77 (dd, J = 44.4, 11.2Hz, 2H), 1.61–1.45 (m,
5H), 1.05 (m, 5H); 13C NMR (CDCl3, 100MHz): d
163.8, 152.3, 138.8, 116.5, 104.5, 63.1, 56.8, 56.3, 53.7,
50.3, 36.1, 28.7, 28.5, 26.6, 26.5, 25.9, 25.8; IR 2927,
1648, 1543cmꢀ1. HRMS (ECI) m/z (M+1)+ calcd for
C17H25N2O: 273.3920. Found: 273.3949. Anal. Calcd
for C17H24N2O: C, 74.96; H, 8.88. Found: C, 75.10;
H, 8.93.
4.3.2. Data for (ꢀ)-N-acetyl-decahydro-1,5-methano-pyr-
ido[1,2-a][1,5]diazocin-8-one 5.6 Prepared from 3 accor-
ding to the general procedure for the reduction with H2/
PtO2. Colourless oil, yield 492mg (99%). Spectroscopic
data are in accordance with published data for this
20
D
1
compound.6 ½a ¼ ꢀ214:3 (c 0.6 in CHCl3); H NMR
(CDCl3, 400MHz): d 5.04 (d, J = 12.8Hz, 1H), 4.88 (d,
J = 13.6Hz, 1H), 3.91 (d, J = 12.8Hz, 1H), 3.47 (br d,
J = 10.8Hz, 1H), 3.33 (d, J = 13.2Hz, 1H), 2.80
(d, J = 13.6Hz, 1H), 2.61 (d, J = 14.0Hz, 1H), 2.33 (m,
2H), 2.09–1.57 (m, 11H); 13C NMR (CDCl3, 100MHz)
d 170.2, 169.5, 59.4, 51.5, 45.9, 41.8, 33.6, 32.82, 32.78,
28.1, 27.9, 21.8, 19.9. Anal. Calcd for C13H20N2O2: C,
66.07; H, 8.53. Found: C, 65.88; H, 8.64.
4.2.4. Data for (ꢀ)-N-benzyl-decahydro-1,5-methano-
pyrido[1,2-a][1,5]diazocin-8-one 8d. Prepared from 6
and benzaldehyde according to the general procedure
4.3.3. Data for 1,2,3,4,5,6-hexahydro-1,5-methano-pyr-
ido[1,2-a][1,5]diazocin-8-one 6. Prepared from (ꢀ)-cyti-
sine according to the general procedure for the reduction
of the 2-pyridone moiety with H2/PtO2 (reaction time
36h in this case), yielding crude 6 as a white crystalline
for reductive amination. White solid, yield 2.20g
20
D
1
(75%). ½a ¼ ꢀ63:5 (c = 1.02in CHCl 3); mp 97.5–
98.5ꢁC; H NMR (CDCl3, 400MHz): d 7.24 (m, 5H),