The Journal of Organic Chemistry
Page 8 of 13
28.6 (C(4’)), 24.6 (C(CH3)3), 23.5 (C(2’)); m/z (ESI+) 413.2 (MH+,
Data/restraints/parameters 4966/0/299, Rint=0.039, Flack
x=-0.07(12), Final R1=0.0313, wR2=0.0805 (I>2s(I)).
1
2
3
4
5
6
7
100%); HRMS (ESI+) m/z: [MH]+ Calcd for C23H29N2O5
413.2071; Found 413.2065. Single Crystal Data: C23H28N2O5,
Methyl (2'S,3R,4'R,4a'R,6R,7aR)-3-(tert-butyl)-2',4'-dimethyl-
5,7-dioxo-1',2',4',4a'-tetrahydro-1H,3H,5H,6'H-
spiro[pyrrolo[1,2-c]thiazole-6,5'-[1,4]oxazino[4,3-
a]quinoline]-7a(7H)-carboxylate (major isomer of 8e)
tetragonal,
I41,
a=16.4674(2),
Data/restraints/parameters
c=15.6590(4) Å,
V=4246.33(13) Å3,
4405/1/272,
Rint=0.030, Flack x=0.07(12), Final R1=0.0277, wR2=0.0706
(I>2s(I)).
General procedure B (8 h) from tetramate 5b (250 mg, 0.92 mmol)
and o-aminobenzaldehyde 6d (222 mg, 1.02 mmol) to give
spirocycle 8e (111 mg, 0.235 mmol, 23%) as an orange solid. m.p.
195 – 197 C; Rf (50% EtOAc in petrol) 0.76; νmax/cm-1 1773,
1746, 1715; 1H NMR (500 MHz, C6D6, 8:2 mixture of
diastereomers) major isomer 8e’’’’ 7.14 – 7.10 (1H, m, C(11’)H),
6.72 (1H, td, J 7.3, 0.9, C(10’)H), 6.68 (1H, d, J 7.3, C(9’)H), 6.59
(1H, d, J 8.4, C(12’)H), 5.46 (1H, s, C(3)H), 3.69 – 3.63 (1H, m,
C(4’)H), 3.63 (1H, d, J 11.4, C(1)HAHB), 3.53 – 3.47 (1H, m,
C(2’)H), 3.44 (1H, dd, J 12.1, 12.7, C(1’)HAHB), 3.35 (1H, d, J
9.4, C(5’)H), 3.30 (1H, d, J 16.4, C(7’)HAHB), 3.18 (3H, s, OCH3),
2.51 (1H, d, J 11.5, C(1)HAHB), 2.42 (1H, dd, J 12.1, 10.5,
C(1’)HAHB), 2.33 (1H, d, J 16.4, C(7’)HAHB), 1.68 (3H, d, J 6.0,
C(4’)CH3), 0.98 (9H, s, C(CH3)3), 1.00 – 0.97 (3H, m, C(2’)CH3);
13C{1H} NMR (125 MHz, C6D6) major isomer 8e’’’’ 198.5 (C(7)),
179.1 (C(5)), 167.4 (CO2CH3), 145.0 (C(13’)), 129.1 (C(9’)),
128.5 (C(11’)), 118.3 (C(10’)), 118.1 (C(8’)), 113.3 (C(12’)), 82.9
(C(7a)), 76.2 (C(3)), 73.8 (C(4’)), 71.2 (C(2’)), 63.7 (C(5’)), 53.2
(C(1’)), 53.0 (CO2CH3), 51.9 (C(6)), 39.1 (C(7’)), 37.4 (C(CH3)3),
36.3 (C(1)), 27.1 (C(CH3)3), 20.4 (C(4’)CH3), 19.1 (C(2’)CH3);
m/z (ESI+) 473.2 (MH+, 100%); HRMS (ESI+) m/z: [MH]+ Calcd
for C25H33N2O5S 473.2105; Found 473.2098. Single Crystal Data:
8
9
Methyl (3R,4a'S,6S,7aR)-3-(tert-butyl)-5,7-dioxo-1',2',4',4a'-
tetrahydro-1H,3H,5H,6'H-spiro[pyrrolo[1,2-c]oxazole-6,5'-
[1,4]oxazino[4,3-a]quinoline]-7a(7H)-carboxylate (major
isomer of 8c)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General procedure B (12 h) from tetramate 5a (500 mg, 1.96
mmol) and o-aminobenzaldehyde 6c (440 mg, 2.15 mmol) to give
spirocycle 8c (53 mg, 0.12 mmol, 7%) as a red solid. m.p. 172 –
175 C; Rf (25% EtOAc in petrol) 0.46; νmax/cm-1 1773, 1747,
1718; 1H NMR (500 MHz, C6D6) 7.09 (1H, t, J 7.8, C(11’)H), 6.80
(1H, d, J 7.4, C(9’)H), 6.70 (1H, t, J 7.0, C(10’)H), 6.57 (1H, d, J
8.3, C(12’)H), 4.95 (1H, s, C(3)H), 4.68 (1H, d, J 9.0, C(1)HAHB),
3.82 (1H, dd, J 10.1, 2.9, C(4’)HAHB), 3.63 (1H, dd, J 10.2, 3.0,
C(5’)H), 3.58 – 3.54 (1H, m, C(2’)HAHB), 3.37 (1H, d, J 16.2,
C(7’)HAHB), 3.34 (1H, td, J 11.5, 3.0, C(2’)HAHB), 3.22 (1H, d, J
16.2, C(7’)HAHB), 3.21 – 3.17 (1H, m, C(1’)HAHB), 3.08 (3H, s,
CO2CH3), 3.09 – 3.04 (2H, m, C(1)HAHB + C(4’)HAHB), 2.60 (1H,
td, J 11.9, 3.7, C(1’)HAHB), 1.00 (9H, s, C(CH3)3); 13C{1H} NMR
(125 MHz, C6D6) 199.6 (C(7)), 177.8 (C(5)), 167.5 (CO2CH3),
145.2 (C(13’)), 129.6 (C(9’)), 128.4 (C(11’)), 118.8 (C(10’)),
118.2 (C(8’)), 113.1 (C(12’)), 99.1 (C(3)), 78.6 (C(7a)), 68.4
(C(1)), 68.0 (C(4’)), 66.9 (C(2’)), 57.5 (C(5’)), 53.8 (C(6)), 53.0
(CO2CH3), 46.4 (C(1’)), 36.5 (C(7’)), 35.6 (C(CH3)3), 25.0
(C(CH3)3); m/z (ESI+) 429.2 (MH+, 100%); HRMS (ESI+) m/z:
[MH]+ Calcd for C23H29N2O6 429.2020; Found 429.2017. Single
Crystal Data: C23H28N2O6, tetragonal, I41, a=16.3993(2),
c=15.9819(3) Å, V=4298.12(13) Å3, Data/restraints/parameters
4195/1/281, Rint=0.017, Flack x=0.01(13), Final R1=0.0287,
wR2=0.0806 (I>2s(I)).55
C25H32N2O6S1,
b=12.1677(3),
orthorhombic,
c=21.5109(6) Å,
P212121,
V=
a=9.2640(2),
2424.74(10) Å3,
Data/restraints/parameters 5020/0/299, Rint=0.019, Flack
x=-0.015(14), Final R1=0.0320, wR2=0.0879 (I>2s(I)).
Methyl (2'S,3R,4'R,4a'R,6R,7aR)-3-(tert-butyl)-2',4'-dimethyl-
8'-nitro-5,7-dioxo-1',2',4',4a'-tetrahydro-1H,3H,5H,6'H-
spiro[pyrrolo[1,2-c]oxazole-6,5'-[1,4]oxazino[4,3-
a]quinoline]-7a(7H)-carboxylate (8f)
Methyl (2'S,3R,4'R,4a'R,6R,7aR)-3-(tert-butyl)-2',4'-dimethyl-
5,7-dioxo-1',2',4',4a'-tetrahydro-1H,3H,5H,6'H-
spiro[pyrrolo[1,2-c]oxazole-6,5'-[1,4]oxazino[4,3-
a]quinoline]-7a(7H)-carboxylate (major isomer of 8d)
General procedure B (15 h) from tetramate 5a (70 mg, 0.28 mmol)
and o-aminobenzaldehyde 6e (86 mg, 0.33 mmol) to give
spirocycle 8f (4 mg, 0.008 mmol, 3%) as an orange solid. m.p. 235
– 240 C; Rf (25% EtOAc in petrol) 0.24; νmax/cm-1 1745, 1674
and 1607; 1H NMR (500 MHz, C6D6, 9:1 mixture of
diastereomers) major isomer 8f’’’’ 8.02 (1H, dd, J 9.3, 2.7,
C(11’)H), 7.74 (1H, d, J 2.7, C(9’)H), 6.04 (1H, d, J 9.3, C(12’)H),
5.04 (1H, s, C(3)H), 4.61 (1H, d, J 8.9, C(1)HAHB), 3.56 (1H, dq,
J 9.6, 5.9, C(4’)H), 3.25 – 3.19 (1H, m, C(2’)H), 3.16 (3H, s,
CO2CH3), 3.18 – 3.14 (1H, m, C(5’)H), 3.09 (1H, dd, J 12.5, 2.7,
C(1’)HAHB), 2.96 (1H, d, J 9.0, C(1)HAHB), 2.86 (1H, d, J 16.5,
C(7’)HAHB), 2.21 (1H, dd, J 12.5, 10.8, C(1’)HAHB), 2.02 (1H, d,
J 16.7, C(7’)HAHB), 1.61 (3H, d, J 6.0, C(4’)CH3), 0.99 (9H, s,
C(CH3)3), 0.91 (3H, d, J 6.2, C(2’)CH3); 13C{1H} NMR (125 MHz,
C6D6) major isomer 8f’’’’ 198.9 (C(7)), 178.0 (C(5)), 167.3
(CO2CH3), 149.3 (C(13’)), 138.7 (C(10’)), 124.8 (C(9’)), 124.4
(C(11’)), 117.3 (C(8’)), 111.3 (C(12’)), 100.2 (C(3)), 78.4 (C(7a)),
73.0 (C(4’)), 70.3 (C(2’)), 69.8 (C(1)), 62.9 (C(5’)), 52.7
(CO2CH3), 51.8 (C(1’)), 51.8 (C(6)), 36.5 (C(7’)), 35.5 (C(CH3)3),
24.9 (C(CH3)3), 20.0 (C(4’)CH3), 18.6 (C(2’)CH3); m/z (ESI+)
502.3 (MH+, 73%); HRMS (ESI+) m/z: [MH]+ Calcd for
C25H32N3O8 502.2184; Found 502.2186.
General procedure B (8 h) from tetramate 5a (2.25 g, 8.82 mmol)
and o-aminobenzaldehyde 6d (2.13 g, 9.70 mmol) to give
spirocycle 8d (1.24 g, 2.72 mmol, 31%) as a pink solid. m.p. 190
C; Rf (50% EtOAc in petrol) 0.88; νmax/cm-1 1773, 1745, 1721; 1H
NMR (600 MHz, C6D6, 8:2 mixture of diastereomers) major
isomer 8d’’’’ 7.15 – 7.11 (1H, m, C(11’)H), 6.80 (1H, d, J 7.4, 1.8,
C(9’)H), 6.76 (1H, td, J 7.2, 0.9, C(10’)H), 6.61 (1H, d, J 8.4,
C(12’)H), 5.05 (1H, s, C(3)H), 4.65 (1H, d, J 8.9, C(1)HAHB), 3.72
(1H, dq, J 9.5, 6.0, C(4’)H), 3.48 (1H, dqd, J 12.4, 6.1, 2.7,
C(2’)H), 3.42 (1H, dd, J 12.0, 2.7, C(1’)HAHB), 3.31 (1H, d, J 16.5,
C(7’)HAHB), 3.30 (1H, d, J 9.5, C(5’)H), 3.18 (3H, s, CO2CH3),
3.02 (1H, d, J 8.9, C(1)HAHB), 2.40 (1H, t, J 11.2, C(1’)HAHB),
2.38 (1H, d, J 16.8, C(7’)HAHB), 1.69 (3H, d, J 6.0, C(4’)CH3),
1.01 (9H, s, C(CH3)3), 0.99 (3H, d, J 6.2, C(2’)CH3); 13C{1H}
NMR (125 MHz, C6D6) major isomer 8d’’’’ 198.9 (C(7)), 179.4
(C(5)), 167.7 (CO2CH3), 145.3 (C(13’)), 129.0 (C(9’)), 128.4
(C(11’)), 118.2 (C(10’)), 118.0 (C(8’)), 113.1 (C(12’)), 100.3
(C(3)), 78.7 (C(7a)), 73.6 (C(4’)), 70.9 (C(2’)), 70.1 (C(1)), 63.7
(C(5’)), 58.0 (C(6)), 52.8 (C(1’)), 52.7 (CO2CH3), 37.6 (C(7’)),
35.7 (C(CH3)3), 25.2 (C(CH3)3), 20.3 (C(4’)CH3), 19.0
(C(2’)CH3); m/z (ESI+) 457.2 (MH+, 100%); HRMS (ESI+) m/z:
[MH]+ Calcd for C25H33N2O6 457.2333; Found 457.2324. Single
Crystal Data: C25H32N2O6, orthorhombic, P212121, a=9.0534(1),
Methyl (2'S,3R,4'R,4a'R,6R,7aR)-3-(tert-butyl)-2',4'-dimethyl-
8'-nitro-5,7-dioxo-1',2',4',4a'-tetrahydro-1H,3H,5H,6'H-
spiro[pyrrolo[1,2-c]thiazole-6,5'-[1,4]oxazino[4,3-
a]quinoline]-7a(7H)-carboxylate (8g)
b=11.9701(2),
c=22.0969(3) Å,
V=2394.64(6) Å3,
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