I. P. Tsypysheva et al. / Tetrahedron: Asymmetry 24 (2013) 1318–1323
1321
Optical rotations were measured on Perkin Elmer 341 LC digital
polarimeter with a sodium lamp (D-line wavelength = 589 nm).
High-resolution electron ionization mass spectra were recorded
using an Thermo Finnigan MAT95XP mass spectrometer (EI, 70 eV).
IR spectra were recorded on IR Prestige-21 spectrophotometer
(Shimadzu).
2J = 13.1, 3J7 -8 = 0.9, 4J7 -15anti = 0.9, H -7); 3.48 (dd, 1H,
a a a
3
3
3J3a-12b = 8.1, J3a-4 = 3.2, H-3a); 3.69 (ddt, 1H, 2J = 12.6, J11 -12 = 2.6,
a
4
3
4J11
= 1.2, J11 -15syn = 1.2, H -11); 3.99 (d, 1H, J12b-3a = 8.1,
H-12b); 4.00 (ddd, 1H, J4-14 = 5.9, J4-3a = 3.2, J4-13 = 1.5, H-4);
a
-9a
a a
3
3
4
3
4
6.32 (dd, 1H, J13-14 = 7.5, J13-4 = 1.5, H-13); 6.44 (dd, 1H,
3J14-13 = 7.5, J14-4 = 5.9, H-14); 7.16 (m, 2H, H-20(60)); 7.38
3
NMR spectra were recorded in CDCl3 on a Bruker AVANCE-III
500 spectrometer (5 mm z-gradient PABBI) operating at
500.30 MHz (1H) and 125.75 MHz (13C). The 1H NMR spectra were
acquired with a spectral width of 5.6 kHz and 32 k data points and
8 scans, providing a digital resolution of ca. 0.5 Hz (1H 90° pulse
(m, 1H, H-40); 7.44 (m, 2H, H-30(50)). IR (KBr, cmꢀ1) = 2931, 2786,
1776, 1709, 1681, 1655, 1598, 1497, 1390, 1248, 1193, 1149,
755, 728, 692. HRMS (EI): m/z calculated for C22H23N3O3 [M+]
377.1734 found 377.1727.
width = 11.5
29.7 kHz was used with 64 k data points and 512 scans (13C 90°
pulse width = 9.7 s). Gradient selected HSQC spectra were re-
l a spectral width of
s). For 13C NMR spectra,
4.2.2. (3aR,4S,8S,12R,12aS,12bR)-10-Methyl-2-phenyloctahydro-
1H-4,12a-etheno-8,12-methanopyrrolo[30,40:3,4]pyrido[1,2-a]
[1,5]diazocine-1,3,5(4H)-trione 5b
l
White crystals, mp 134–135 °C (EtOAc), ½a D20
¼ ꢀ5:2 (c 0.8,
ꢃ
corded using the standard Bruker sequence (hsqcetgp). These data
were collected with 4096 ꢂ 256 data points with 2 scans for each
increment. The delay d4 was set to 1.72 ms. Gradient selected
HMBC spectra (hmbcgpndqf) were collected with 4096 ꢂ 256 data
points with 4 scans for each increment. The delay d6 was set to
71.4 ms. Spectral widths of 5.6 and 29.7 kHz were used in the F2
(1H) and F1 (13C) domains, respectively. HSQC and HMBC data were
processed using a sine window in the F2 and F1 dimensions.
Gs-COSY data were collected with 2 K ꢂ 2 K data points with 2
scans for each increment. For the 2D NOESY NMR experiments,
the solution was degassed to remove any dissolved oxygen. The
following parameters and procedures are commonly employed:
spectral width 5.6 kHz, 2 K ꢂ 2K data matrix and 256 time incre-
ments of 2 transients each. Fourier transformations were carried
out with zero-filling only in and using the shifted sine-bell F1,
apodization function in both dimensions.
CHCl3). 13C NMR (CDCl3, d ppm): 25.4 (C15); 26.2 (C8); 29.7
(C12); 42.8 (C3a); 45.2 (C4); 46.8 (C100); 47.8 (C7); 48.4 (C12b);
58.4 (C11); 62.2 (C9); 63.4 (C12a); 126.3 (C20(60)); 128.9 (C40);
129.2 (C30(50)); 129.6 (C14); 131.5 (C10); 134.3 (C13); 171.6 (C5);
174.3 (C1); 174.6 (C3). 1H NMR (CDCl3, d ppm, J Hz): 1.75 (dtd,
1H, 2J = 13.3, 3J15anti-12 = 3.6, 3J15anti-8 = 3.6, 4J15anti-7 = 1.8,
a
3
3
H
anti-15); 1.95 (dtt, 1H, 2J = 13.3, J15syn-12 = 3.4, J15syn-8 = 3.4,
4J15syn-9 = 1.7, J15syn-11 = 1.7, Hsyn-15); 2.15 (dd, 1H, 2J = 12.1,
4
a
a
3J11b-12 = 2.0, Hb-11); 2.16 (m, 1H, H-8); 2.17 (s, 3H, H-100); 2.80
(ddt, 1H, 2J = 11.4, 3J9 -8 = 3.5, 4J9
= 1.7, 4J9 -15syn = 1.7, H -9);
a
a
-11
a
a a
4
3
4
3.16 (ddt, 1H, 2J = 12.1, J11 -12 = 3.4, J11
= 1.7, J11 -15syn = 1.7,
a
a
a
-9a
3
3
H -11); 3.36 (dd, 1H, J3a-12b = 7.9, J3a-4 = 3.2, H-3a); 3.37 (ddd,
a
1H, 2J = 13.4, J7b-8 = 6.6, J7b-9b = 1.3, Hb-7); 3.47 (d, 1H,
3
4
3J12b-3a = 8.1, H-12b); 3.58 (dd, 1H, 2J = 13.4, 4J7 -15anti = 1.8,
a
3
3
4
H -7); 4.00 (ddd, 1H, J4-14 = 5.9, J4-3a = 3.2, J4-13 = 1.7, H-4);
a
3
3
Reflections for 5a were collected using a SMART APEX II diffrac-
6.48 (dd, 1H, J14-13 = 8.0, J14-4 = 5.9, H-14); 6.59 (dd, 1H,
3J13-14 = 8.0, J13-4 = 1.7, H-13); 7.14 (m, 2H, H-20(60)); 7.38
4
tometer [k (Mo
Ka) = 0.71073 Å, graphite monochromator,
(m, 1H, H-40); 7.44 (m, 2H, H-30(50)). IR (KBr, cmꢀ1) = 2934, 2785,
1774, 1704, 1660, 1653, 1598, 1497, 1384, 1248, 1192, 1148,
756, 728, 694. HRMS (EI): m/z calculated for C22H23N3O3 [M+]
377.1734 found 377.1739.
x
-scans] at 120 K. The structure was solved by direct methods
and refined by the full-matrix least-squares procedure against F2
in anisotropic approximation. X-ray analysis data of compound
5a have been deposited at the Cambridge Crystallographic Data
Centre and allocated the deposition number CCDC 838451.
4.2.3. (3aS,4R,8S,8aS,14S,14aR,14bS)-2-Phenyldecahydro-1H-4,
14a-etheno-8,14-methanopyrrolo[1,2-a]pyrrolo[30,40:3,4]pyrido
[1,2-e][1,5]diazocine-1,3,5(4H)-trione 6a
4.2. General procedure for the Diels–Alder reaction
Yellow crystals, mp 204–205 °C (EtOAc), ½a D20
¼ þ5:0 (c 1.0,
ꢃ
A solution of 2.5 mmol of N-methylcytisine 1 and 12.5 mmol N-
phenylmaleimide in 10 ml of toluene was heated at reflux under
AP until the starting reactant disappeared (monitoring by TLC).
Then solvent was then evaporated in vacuo. The crude product
was chromatographed on SiO2 with ethylacetate as the eluent to
afford 5a and 5b.
CHCl3). 13C NMR (CDCl3, d ppm): 25.4 (C15); 26.5 (C8); 29.7
(C12); 42.8 (C3a); 45.2 (C4); 46.8 (C100); 47.8 (C7); 48.4 (C12b);
58.4 (C11); 62.2 (C9); 63.4 (C12a); 126.3 (C20(60)); 128.9 (C40);
129.2 (C30(50)); 129.6 (C14); 131.5 (C10); 134.3 (C13); 171.6 (C5);
174.3 (C1); 174.6 (C3). 1H NMR (CDCl3, d ppm, J Hz): 1.64 (br d,
1H, 2J = 12.8, Hanti-17); 1.71 (m, 1H, Hb-9); 1.73 (m, 1H, Hb-10);
1.88 (m, 1H, H -9); 1.97 (m, 1H, H -10); 2.00 (br d, 1H, 2J = 12.8,
4.2.1. (3aS,4R,8S,12R,12aR,12bS)-10-Methyl-2-phenyloctahydro-
1H-4,12a-etheno-8,12-methanopyrrolo[30,40:3,4]pyrido[1,2-a]
[1,5]diazocine-1,3,5(4H)-trione 5a
a
a
H
syn-17); 2.24 (m, 1H, H-8); 2.51 (m, 1H, H-14); 2.64 (dd,
3
1H, 2J = 12.1, J13b-14 = 2.2, Hb-13); 2.82 (m, 1H, Hb-11); 2.87 (m,
White crystals, mp 191–192 °C (EtOAc), ½a D20
ꢃ
¼ þ41:2 (c 0.9,
3
3
3
1H, H -11); 3.01 (ddd, 1H, J8a-9 = 10.5, J8a-9b = 6.8, J8a-8 = 1.8,
a
a
CHCl3). 13C NMR (CDCl3, d ppm): 25.7 (C15); 26.9 (C8); 33.9
(C12); 41.8 (C3a); 45.5 (C4); 46.6 (C100); 47.4 (C12b); 47.7 (C7);
58.2 (C11); 62.4 (C9); 64.0 (C12a); 126.3 (C20(60)); 128.9 (C40);
129.1 (C30(50)); 130.1 (C14); 131.6 (C10); 140.2 (C13); 172.5 (C5);
174.5 (C3); 175.0 (C1). 1H NMR (CDCl3, d ppm, J Hz): 1.71 (br d,
1H, 2J = 12.8, Hanti-15); 1.76 (br d, 1H, 2J = 12.8, Hsyn-15); 2.15
H-8a); 3.23 (dd, 1H, 2J = 13.1, J7b-9 = 6.3, Hb-7); 3.48 (ddd, 1H,
3
2J = 12.1, J13 -14 = 2.1, J13 -17anti = 1.8, H -13); 3.52 (dd, 1H,
3
4
a
a
a
3J3a-14b = 8.1, J3a-4 = 3.2, H-3a); 3.65 (dt, 1H, 2J = 13.1, 3J7 -8 = 1.0,
3
a
4J7 -17anti = 1.0, H -7); 4.00 (ddd, 1H, J4-16 = 5.9, J4-11 = 3.2,
3
3
a
a
4J4-15 = 1.5, H-4); 4.32 (d, 1H, J14b-3a = 8.1, H-14b); 6.34 (dd, 1H,
3J15-4 = 7.5, 4J15-3 = 1.5, H-15); 6.43 (dd, 1H, 3J16-15 = 7.5,
3J16-4 = 5.9, H-16); 7.15 (m, 2H, H-20(60)); 7.37 (m, 1H, H-40); 7.44
(m, 2H, H-30(50)). IR (KBr, cmꢀ1) = 2936, 2722, 1772, 1709, 1660,
1651, 1596, 1494, 1390, 1256, 1190, 1177, 1065, 754, 727, 692.
HRMS (EI): m/z calculated for C24H25N3O3 [M+] 403.1890 found
403.1901.
3
3
(dd, 1H, 2J = 12.6, J11b-12 = 2.1, Hb-11); 2.16 (ddd, 1H, 2J = 10.8,
4
3J9b-8 = 2.5, J9b-7b = 1.1, Hb-9); 2.21 (m, 1H, H-8); 2.24 (s, 3H, H-
100); 2.24 (s, 3H, H-100); 2.51 (m, 1H, H-12); 2.80 (ddt, 1H,
2J = 10.8, 3J9 -8 = 2.4, 4J9
= 1.2, 4J9 -15syn = 1.2, H -9); 3.36
a a
a
a
-11
a
3
4
(ddd, 1H, 2J = 13.1, J7b-8 = 6.9, J7b-9b = 1.1, Hb-7); 3.44 (dt, 1H,