7024
W.-Y. Han et al. / Tetrahedron 69 (2013) 7019e7025
92%; 68:32 dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
0.3H), 4.88 (s, 0.7H), 6.85e6.93 (m, 2H), 7.11e7.34 (m, 9H), 7.55 (d,
1.28e1.44 (m, 2H), 1.58e1.85 (m, 4H), 2.80e2.87 (m, 1.7H), 3.07 (s,
0.3H), 3.30e3.49 (m, 2H), 4.12e4.16 (m, 1H), 6.74e6.79 (m, 1H),
6.98e7.03 (m, 2H), 7.18e7.29 (m, 2H), 7.43e7.47 (m, 1H), 7.74e7.84
J¼7.5 Hz, 0.7H), 7.71 (d, J¼7.5 Hz, 0.3); 13C NMR (75 MHz, CDCl3),
d
(ppm): 21.1, 21.8, 29.9, 30.2, 36.4, 37.3, 43.0, 45.2, 62.0, 62.5, 71.1,
73.2, 112.6, 114.5, 117.8, 125.6, 125.8, 126.3, 127.2, 127.3, 127.4, 127.5,
127.6,128.0,128.8,129.0,129.6,129.7,131.2,131.4,131.5,137.5,138.8,
146.0, 161.0, 161.3, 176.6, 179.8. HRMS (ESI-TOF) calcd for
C26H23N2O2 [MþH]þ: 395.1754; found: 395.1729.
(m, 2H); 13C NMR (75 MHz, CDCl3),
d (ppm): 23.4, 23.8, 24.6, 25.1,
26.6, 26.9, 35.6, 37.2, 48.5, 48.9, 60.3, 60.7, 69.4, 70.8, 113.1, 113.8,
115.0, 115.1, 115.4, 118.1, 118.3, 119.2, 119.7, 120.0, 124.0, 124.1, 127.8,
128.0, 129.3, 129.4, 130.3, 130.4, 130.5, 144.9, 145.0, 160.1, 160.9,
164.1, 164.2, 175.5, 178.6. HRMS (ESI-TOF) calcd for C21H20FN2O2
[MþH]þ: 351.1503; found: 351.1508.
4.3.11. 20-p-Tolyl-6,7,11b,13-tetrahydro-50H-spiro [isoquinolino[2,1-a]
quinoline-12,40-oxazol]-50-one (2k). Colorless oil, yield 97%; 73:27
dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm): 2.37 (s,
4.3.6. 2-(4-Bromophenyl)-10,20,30,40,4a0,60-hexahydro-5H-spiro[ox-
2.1H), 2.45 (s, 0.9H), 2.67e2.72 (m, 1H), 3.01e3.07 (m, 0.8H),
3.22e3.25 (m, 1.5H), 3.28e3.29 (m, 0.7H), 3.40e4.02 (m, 2H), 4.80
(s, 0.3H), 4.84 (s, 0.7H), 6.82e6.85 (m, 1H), 6.90e7.02 (m, 2H),
7.12e7.30 (m, 7H), 7.66 (d, J¼8.1 Hz, 1.4H), 7.82 (d, J¼8.1 Hz, 0.6H);
azole-4,50-pyrido[1,2-a]quinolin]-5-one (2f). Colorless oil, yield 64%;
65:35 dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
1.33e1.38 (m, 2H), 1.55e1.83 (m, 4H), 2.77e2.85 (m, 2H), 3.28e3.35
(m,1.3H), 3.28e3.47 (m, 0.7H), 4.11e4.15 (m,1H), 6.72e6.77 (m,1H),
6.97e7.02 (m, 2H), 7.16e7.21 (m, 1H), 7.58e7.64 (m, 2H), 7.87e7.91
13C NMR (75 MHz, CDCl3),
d (ppm): 21.5, 21.6, 29.9, 30.2, 36.1, 37.2,
42.9, 45.6, 62.1, 62.6, 71.1, 72.9, 112.5, 114.5, 117.7, 118.2, 118.9, 122.6,
124.8,126.2,127.3,127.4,127.6,127.7,127.8,128.3,128.8,129.1,129.2,
129.4, 131.3, 137.4, 143.1, 143.3, 146.0, 160.4, 176.7, 179.6. HRMS (ESI-
TOF) calcd for C26H23N2O2 [MþH]þ: 395.1754; found: 395.1731.
(m, 2H); 13C NMR (75 MHz, CDCl3),
d (ppm): 23.4, 23.8, 24.5, 25.1,
26.6, 27.0, 35.6, 37.2, 48.5, 48.9, 60.3, 60.7, 69.3, 70.8, 113.1, 113.8,
117.9, 118.1, 118.3, 119.3, 124.4, 124.5, 127.7, 127.8, 127.9, 129.3, 129.4,
129.7, 131.9, 132.1, 144.9, 145.0, 160.4, 175.6, 178.7. HRMS (ESI-TOF)
calcd for C21H20BrN2O2 [MþH]þ: 411.0703; found: 411.0690.
4.3.12. 20-(4-Methoxyphenyl)-6,7,11b,13-tetrahydro-50H-spiro [isoqui-
nolino[2,1-a]quinoline-12,40-oxazol]-50-one (2l). Colorless oil, yield
4.3.7. 20-Phenyl-2,4,4a,6-tetrahydro-1H,50H-spiro[[1,4] oxazino[4,3-
94%; 73:27 dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
a]quinoline-5,40-oxazol]-50-one (2g). Colorless oil, yield 37%; 57:43
2.66e2.71 (m,1H), 3.00e3.06 (m, 0.7H), 3.24e3.78 (m, 3.3H), 3.81 (s,
2.1H), 3.87 (s, 0.9H), 3.99e4.01 (m, 1H), 4.77 (s, 0.3H), 4.82 (s, 0.71H),
6.81e7.02 (m, 8H), 7.11e7.27 (m, 2H), 7.70 (d, J¼8.7 Hz, 1.4H), 7.89 (d,
dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm): 2.83e3.06
(m, 2H), 3.25e3.37 (m,1H), 3.43e3.48 (m, 2H), 3.73e3.79 (m, 2.6H),
3.97e3.79 (m, 1.4H), 6.82e6.83 (m, 1H), 6.93e6.95 (m, 1H),
7.01e7.03 (m, 1H), 7.22e7.26 (m, 1H), 7.47e7.61 (m, 3H), 8.02e8.05
J¼8.7 Hz, 0.6H); 13C NMR (75 MHz, CDCl3),
d (ppm): 30.1, 30.2, 36.2,
37.2, 42.9, 45.6, 55.2, 55.3, 62.1, 62.6, 71.1, 72.8, 112.4, 113.9, 114.1,
114.5, 117.6, 118.2, 118.9, 126.2, 127.2, 127.3, 127.6, 127.7, 127.8, 128.3,
128.8, 129.2,129.3, 129.4,129.6, 137.5,146.0, 146.5, 160.0,162.8, 163.0,
176.8, 179.7. HRMS (ESI-TOF) calcd for C26H23N2O3 [MþH]þ:
411.1703; found: 411.1694.
(m, 2H); 13C NMR (75 MHz, CDCl3),
d (ppm): 36.3, 37.7, 46.3, 46.9,
58.0, 58.1, 66.6, 66.8, 67.0, 67.3, 68.2, 112.4, 113.0, 118.1, 119.2, 119.3,
119.4, 125.3, 125.4, 127.9, 128.0, 128.1, 128.4, 128.7, 128.9, 129.5,
129.6, 133.0, 133.1, 144.4, 144.7, 161.5, 161.9, 175.0, 178.3. HRMS (ESI-
TOF) calcd for C20H19N2O3 [MþH]þ: 335.1390; found: 335.1392.
4.3.13. 20-(3-Fluorophenyl)-6,7,11b,13-tetrahydro-50H-spiro [isoquino-
4.3.8. 20-(3-Fluorophenyl)-2,4,4a,6-tetrahydro-1H,50H-spiro[[1,4]ox-
lino[2,1-a]quinoline-12,40-oxazol]-50-one (2m). Colorless oil, yield
1
azino[4,3-a]quinoline-5,40-oxazol]-50-one (2h). Colorless oil, yield
99%; 69:31 dr; H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
78%; 63:37 dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
2.68e2.73 (m, 1H), 3.02e3.08 (m, 0.7H), 3.16e3.28 (m, 1.6H),
3.42e3.43 (m, 0.7H), 3.54e3.80 (m, 1H), 3.98e4.02 (m, 1H), 4.81 (s,
0.3H), 4.86 (s, 0.7H), 6.82e6.85 (m, 1H), 6.90e7.28 (m, 9H), 7.33e7.55
2.83e3.06 (m, 2H), 3.25e3.36 (m, 1H), 3.44e3.59 (m, 2H),
3.73e3.79 (m, 2.6H), 3.99 (s, 1.4H), 6.83e6.84 (m, 1H), 6.94e6.96
(m, 1H), 7.02e7.04 (m, 1H), 7.23e7.46 (m, 3H), 7.72e7.75 (m, 1H),
(m, 2H); 13C NMR (75 MHz, CDCl3),
d (ppm): 29.9, 30.2, 36.0, 37.1,
7.80e7.83 (m, 1H); 13C NMR (75 MHz, CDCl3),
d
(ppm): 36.1, 37.6,
42.9, 45.6, 62.3, 62.7, 71.3, 73.2, 112.6, 114.6, 114.7, 117.8, 118.3, 123.3,
123.4, 124.8, 126.4, 127.4, 127.5, 127.7, 127.8, 127.9, 128.5, 128.9, 129.2,
129.3, 130.4, 137.4, 145.9, 146.4, 160.8, 164.1, 164.2, 176.1, 179.1. HRMS
(ESI-TOF) calcd for C25H20FN2O2 [MþH]þ: 399.1503; found: 399.1501.
46.2, 46.8, 57.9, 58.0, 66.7, 66.9, 67.1, 68.3, 112.4, 113.0, 115.1, 115.4,
119.3, 119.4, 120.0, 120.2, 123.8, 123.9, 124.0, 124.1, 127.9, 128.0,
129.4, 129.6, 130.4, 130.5, 130.6, 144.3, 144.5, 160.9, 161.0, 164.2,
164.3, 174.5, 177.8. HRMS (ESI-TOF) calcd for C20H18FN2O3 [MþH]þ:
353.1296; found: 353.1298.
4.3.14. 20-(4-Bromophenyl)-6,7,11b,13-tetrahydro-50H-spiro [isoquino-
lino[2,1-a]quinoline-12,40-oxazol]-50-one (2n). Colorless oil, yield 99%;
4.3.9. 20-Phenyl-6,7,11b,13-tetrahydro-50H-spiro[isoquinolino [2,1-a]
quinoline-12,40-oxazol]-50-one (2i). Colorless oil, yield 97%; 70:30
70:30 dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm):
2.66e2.71 (m, 1H), 3.01e3.07 (m, 0.7H), 3.15e3.25 (m, 1.6H),
3.41e3.42 (m, 0.7H), 3.52e3.78 (m, 1H), 3.98e4.01 (m, 1H), 4.79 (s,
0.3H), 4.84 (s, 0.7H), 6.81e6.82 (m, 1H), 6.89e7.26 (m, 7H), 7.50 (d,
J¼8.7 Hz, 1.4H), 7.59e7.62 (m, 2H), 7.75 (d, J¼8.7 Hz, 0.6H); 13C NMR
dr; 1H NMR (300 MHz, CDCl3),
d
(majorþminor) (ppm): 2.67e2.72
(m, 1H), 3.02e3.08 (m, 0.8H), 3.22e3.28 (m, 1.5H), 3.40e3.44 (m,
0.7H), 3.54e3.80 (m, 1H), 3.98e4.02 (m, 1H), 4.81 (s, 0.3H), 4.86 (s,
0.7H), 6.83e7.03 (m, 3H), 7.13e7.23 (m, 5H), 7.28e7.48 (m, 3H), 7.77
(d, J¼7.5 Hz, 1.4H), 7.93 (d, J¼7.5 Hz, 0.6H); 13C NMR (75 MHz,
(75 MHz, CDCl3), d (ppm): 29.8, 30.1, 35.9, 37.0, 42.9, 45.5, 62.2, 62.6,
71.2, 73.1, 112.6, 114.5, 117.8, 118.2, 118.7, 124.8, 126.3, 127.4, 127.5,
127.7, 127.8, 128.4, 128.8, 128.9, 129.0, 129.1, 129.2, 131.9, 132.0, 137.3,
145.8, 146.3, 159.6, 159.7, 176.1, 179.1. HRMS (ESI-TOF) calcd for
C25H20BrN2O2 [MþH]þ: 459.0703; found: 459.0688.
CDCl3),
d (ppm): 29.9, 30.2, 36.1, 37.2, 42.9, 45.6, 62.2, 62.7, 71.2,
73.0, 112.5, 114.6, 117.7, 118.2, 124.8, 126.3, 127.3, 127.4, 127.6, 127.7,
127.8, 128.4, 128.5, 128.7, 128.8, 129.2, 129.3, 132.4, 132.6, 137.4,
146.0, 146.5, 160.4, 176.5, 179.5. HRMS (ESI-TOF) calcd for
C25H21N2O2 [MþH]þ: 381.1598; found: 381.1585.
4.4. Experimental procedure for the transformation of 2i, 2k,
and 2n to the corresponding ring opening compounds
4.3.10. 20-o-Tolyl-6,7,11b,13-tetrahydro-50H-spiro [isoquinolino[2,1-
a]quinoline-12,40-oxazol]-50-one (2j). Colorless oil, yield 99%; 71:29
A solution of compound 2i, 2k or 2m (0.2 mmol) in MeOH (3 mL)
was stirred at 0 ꢀC for 3 min, then MeONa (0.5 mmol) was added,
respectively. The mixture was allowed to warm to room tempera-
ture and stirred for 10 min. After cooling to 0 ꢀC, the reaction was
dr; 1H NMR (300 MHz, CDCl3),
2.1H), 2.58 (s, 0.9H), 2.69e2.74 (m, 1H), 3.04e3.10 (m, 0.7H),
3.18e3.28 (m, 2.3H), 3.39e3.80 (m, 1H), 3.99e4.02 (m, 1H), 4.83 (s,
d
(majorþminor) (ppm): 2.24 (s,