H. Mahmud et al. / Tetrahedron 57 *2001) 4095±4105
4103
cm21): 3029, 2951, 2784, 1477, 1350, 1161, 675; EIMS
8m/z): 498.0 813, M112), 496.0 811, M1), 498.0 8M1
2), 288.9 842), 155.0 837), 154.0 8100), 136.3 8100), 107.0
822), 91.0 832), 76.9 8100); Anal. Calcd. For
C25H25N2BrO2S: C, 60.31; H, 5.07; N, 5.63. Found: C,
60.66; H, 5.07; N, 5.25.
8500 MHz): d7.87 8dd, J8.7, 2.0 Hz, 1H), 7.84 8d,
J2.0 Hz, 1H), 7.79 8d, J8.7 Hz, 1H), 7.58 8d, J
8.3 Hz, 2H), 7.20 8d, J8.3 Hz, 1H), 4.02 8dd, J13.3,
5.0 Hz, 1H), 3.88 8s, 3H), 3.49 8dd, J13.3, 9.9 Hz, 1H),
2.99 8ddd, J8.9, 8.9, 2.3, 1H), 2.82 8d, J6.2 Hz, 1H), 2.36
8s, 3H), 2.29 8s, 3H), 2.24 8ddd, J8.9, 8.9, 8.9 Hz, 1H),
2.20-2.15 8m, 1H), 2.00 8dddd, J11.2, 8.9, 8.9, 2.3 Hz,
1H), 1.52 8dddd, J11.2, 8.9, 8.9, 3.8 Hz, 1H); 13C NMR
8125 MHz): d166.6, 143.8, 141.8, 136.9, 132.5, 129.7,
129.0, 127.9, 127.0, 125.0, 122.1, 64.0, 54.9, 52.1, 49.2,
40.1, 35.3, 26.7, 21.5; FT-IR 8KBr, cm21): 3092, 3053,
2942, 2832, 2787, 1711, 1441, 1353, 1165; 675; EIMS
8m/z): 399.9 81, M1), 245.2 8100), 214.2 870), 154.0 85),
115.0 811); Anal. Calcd. For C21H24N2O4S: C, 62.98; H,
6.02; N, 6.99. Found: C, 63.03; H, 6.04; N, 6.84.
1
1.2.7. .3aS*,9bS*)-8-Bromo-2,3,3a,4,5,9b-hexahydro-1-
.4-methoxybenzyl)-5-.4-toluenesulfonyl)-1H-pyrrolo-
[3,2-c]quinoline 27. A round-bottom ¯ask was charged
with benzaldehyde 24 8148 mg, 0.38 mmol), N-p-methoxy-
benzylglycine hydrochloride 8109 mg, 0.56 mmol), Et3N
857 mg, 0.56 mmol) and DMF 82 mL); the reaction mixture
was heated to re¯ux under an argon atmosphere for 1.5 h.
After work-up 8see preparation of 16), the crude product
was puri®ed by ¯ash chromatography 8hexane/EtOAc:
4/1) to afford 27 as colorless powder 8163 mg, 83%). mp:
1.3.2. .3aS*, 9bS*)-Methyl 1-benzyl-2,3,3a,4,5,9b-hexa-
hydro-5-.4-toluenesulfonyl)-1H-pyrrolo[3,2-c]quinoline-
8-carboxylate 29. Carbonylation of 26 8700 mg, 1.41
mmol) Pd8OAc)2 890 mg, 0.40 mmol), PPh3 8120 mg,
0.46 mmol), NaOAc 8155 mg, 1.89 mmol) in MeOH
89 mL) and DMF 89 mL) according to the general proce-
dure, followed by ¯ash chromatography 8hexane/EtOAc:
3.5/1) provided the title compound as colorless powder
8638 mg, 95%). mp: 126±1278C. 1H NMR 8500 MHz):
d7.88±7.82 8m, 3H), 7.64 8d, J8.3 Hz, 2H), 7.25-7.12
8m, 7H), 4.06 8d, J12.8 Hz, 1H), 4.00 8dd, J13.1, 5.2 Hz,
1H), 3.87 8s, 3H), 3.64 8dd, J13.1, 9.3 Hz, 1H), 3.19 8d,
J12.8 Hz, 1H), 3.14 8d, J6.8 Hz, 1H), 2.83 8ddd, J9.1,
9.0, 2.8 Hz, 1H), 2.39 8s, 3H), 2.42±2.26 8m, 1H), 2.16 8ddd,
J9.1, 9.0, 9.0 Hz, 1H), 1.99 8dddd, J11.7, 9.1, 9.0,
2.8 Hz, 1H), 1.51 8m, 1H); 13C NMR 8125 MHz, CDCl3):
d166.5, 144.0, 142.3, 139.4, 136.8, 132.7, 129.7, 129.1,
128.6, 128.4, 128.1, 127.2, 126.8, 125.0, 121.8, 62.9, 57.6,
52.0, 51.7, 49.4, 36.0, 27.0, 21.6; FT-IR 8KBr, cm21): 3063,
3026, 2949, 2819, 1717, 1496, 1350, 1166, 674; EIMS
8m/z): 475.9 85, M1), 385.0 84), 320.6 8100), 277.3 835),
263.0 830), 155.2 88). Anal. Calcd. For C27H28N2O4S: C,
68.05; H, 5.92; N, 5.48; Found: C, 68.07; H, 5.87; N, 5.79.
1
146±1478C; H NMR 8500 MHz): d7.60 8d, J8.7, 1H),
7.59 8d, J8.5 Hz, 2H), 7.37 8d, J2.3 Hz, 1H), 7.33 8dd,
J8.7, 2.3 Hz, 1H), 7.22 8d, J8.2 Hz, 2H), 7.09 8d,
J8.2 Hz, 2H), 6.80 8d, J8.5 Hz, 2H), 4.03 8dd, J13.6,
5.8 Hz, 2H), 3.90 8d, J12.5 Hz, 1H), 3.78 8s, 3H), 3.40 8dd,
J13.6, 9.4 Hz, 1H), 3.16 8d, J12.5 Hz, 1H), 2.92 8d,
J7.6 Hz, 1H), 2.78 8ddd, J10.4, 8.2, 3.4 Hz, 1H), 2.48
8m, 1H), 2.40 8s, 3H), 2.18 8ddd, J8.2, 8.2, 8.2 Hz, 1H),
1.94 8dddd, J12.0, 8.2, 8.2, 3.4 Hz, 1H), 1.41 8m, 1H). 13C
NMR 8125 MHz): d158.6, 143.8, 137.0, 136.8, 133.0,
132.8, 131.2, 130.5, 129.7, 129.6, 127.1, 125.0, 117.7,
113.6, 62.3, 57.9, 55.2, 51.8, 49.5, 36.8, 27.7, 21.6; FT-IR
8KBr, cm21): 2960, 2931, 2892, 2805, 1482, 1353, 1167,
664; EIMS 8m/z): 527.9 82, M1 1 2), 525.9 82, M1), 404.8
83), 372.8 843), 251.0 87), 155.0 85), 120.9 8100), 91.0 812),
77.0 86); Anal. Calcd. For C26H27N2BrO3S: C, 59.20; H,
5.16; N, 5.31. Found: C, 59.29; H, 4.89; N, 5.02.
1.3. Carbonylation of bromopyrroloquinolines .28-30)Ð
general procedure
The bromopyrroloquinoline, Pd8OAc)2, Ph3P, NaOAc,
MeOH, and DMF were added to a oven-dried high pressure
reaction tube which was capped with a septum. The reaction
mixture was ¯ushed with argon for several minutes. The
septum was then replaced with a Te¯on screw cap ®tted
with a pressure gauge. The reaction mixture was pressurized
with carbon monoxide 8CO), purged 2±3 times with CO and
then heated to 1108C for 24 h at 65 psi of CO. The mixture
was ®ltered though Celite and the Celite pad was washed
several times with CH2Cl2. The ®ltrate was washed 3±4
times with water to remove DMF. The organic phase was
dried with anhydrous Na2SO4 and evaporated to dryness.
The residue was puri®ed by ¯ash chromatography in the
indicated solvent mixture to afford the pure pyrroloquino-
line esters.
1.3.3. .3aS*, 9bS*)-Methyl 2,3,3a,4,5,9b-hexahydro-1-.4-
methoxybenzyl)-5-.4-toluenesulfonyl)-1H-pyrrolo[3,2-c]-
quinoline-8-carboxylate 30. Carbonylation of 27 8900 mg,
1.71 mmol) with Pd8OAc)2 8145 mg, 0.65 mmol), PPh3
8175 mg, 0.67 mmol), NaOAc 8215 mg, 2.62 mmol) in
MeOH 811 mL) and DMF 811 mL) according to the general
procedure followed by ¯ash chromatography 8hexane/
EtOAc: 2/1) afforded the title compound as colorless
powder 8838 mg, 97%). mp: 113±1158C. 1H NMR
8500 MHz): d7.91-7.86 8m, 2H), 7.64 8d, J8.4 Hz,
2H), 7.22 8d, J8.3 Hz, 2H), 7.05 8dd, J8.3 Hz, 2H),
6.76 8d, J8.4 Hz, 2H), 4.00-3.97 8m, 2H), 3.87 8s, 3H),
3.76 8s, 3H), 3.62 8dd, J13.3, 9.1 Hz, 1H), 3.13 8d, J
12.5 Hz, 1H), 3.11 8d, J7.0, 1H), 2.80 8ddd, J8.7, 8.7,
2.7 Hz, 1H), 2.39 8s, 3H), 2.39-2.28 8m, 1H), 2.14 8ddd,
J8.7, 8.7, 8.7 Hz, 1H), 1.98 8dddd, J12.4, 8.7, 8.7,
2.7 Hz, 1H), 1.49 8dddd, J12.4, 8.7, 8.7, 4.5 Hz, 1H);
13C NMR 8125 MHz): d166.6, 158.5, 143.9, 142.3,
136.8, 132.7, 131.4, 129.7, 129.5, 129.0, 128.8, 127.1,
125.0, 121.8, 113.5, 62.8, 57.0, 55.2, 52.0, 51.5, 49.4,
36.1, 27.0, 21.6; FT-IR 8KBr, cm21): 3064, 3037, 2951,
2848, 1718, 1511, 1352, 1164, 672; EIMS 8m/z): 506.5 86,
M1), 350.8 8100), 293.0 821), 278.0 838), 182.8 846), 155
1.3.1. .3aS*, 9bS*)-Methyl 2,3,3a,4,5,9b-hexahydro-1-
methyl-5-.4-toluenesulfonyl)-1H-pyrrolo [3,2-c]quino-
line-8-carboxylate 28. Carbonylation of 25 8115 mg,
0.27 mmol) with Pd8OAc)2 815 mg, 0.07 mmol), PPh3
820 mg, 0.08 mmol), NaOAc 828 mg, 0.34 mmol) in
MeOH 81.5 mL) and DMF 81.5 mL) according to general
procedure followed by ¯ash chromatography 8hexane/
EtOAc: 2/2.5) provided the title compound as pale-yellow
crystals 8105 mg, 96%). mp: 114±1158C. 1H NMR