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3.4.1. (E)-2-4-6-Tribromo-5-methoxy-b-nitrostyrene, 9b.
Compound 9b was synthesized from 8b (13.4 mmol,
5.00 g), using the same procedure described above for
9a. A brownish yellow solid was obtained (2.46 g, 44%);
(m, 5H), 6.85 (s, 1H), 5.15 (t, 1H, J=7.2 Hz), 3.80 (s,
3H), 3.30 (dd, 2H, J=7.2 and 3.2 Hz).
3.8. 2-(2,4,6-Tribromo-3-methoxyphenyl)-2-(thiophenyl)-
1-aminoethane, 11b
1
mp 93°C; IR (KBr) 3127, 2848, 1644, 1527 cm−1; H
NMR (200 MHz, CDCl3) l 7.98 (d, 1H, J=13.8 Hz),
7.89 (s, 1H), 7.56 (d, 1H, J=14.0 Hz), 3.91 (s, 3H)
ppm; MS (EI) m/z (%) 417 (M,+4 100), 413 (M,+ 34).
Anal. calcd for C9H6Br3NO3: C, 25.96; H, 1.44. Found:
C, 26.01; H, 1.49%.
Compound 11b was synthesized from 10b (0.95 mmol,
0.500 g), using the same procedure described for amine
11a. Compound 11b was obtained as atropoisomers:
Yellow liquid (0.284 g, 71%); IR (CH2Cl2) 3448, 3363,
1
2935, 1581 cm−1; H NMR (200 MHz, CDCl3) 7.79 (s,
3.5. 2-(2,4-Dibromo-5-methoxyphenyl)-2-(thiophenyl)-1-
nitroethane, 10a
1H), 7.75 (s, 1H), 7.50 (m, 5H), 7.30 (m, 5H), 5.43 (t,
1H, J=7.9 Hz), 5.43 (t, 1H, J=7.9 Hz), 3.89 (s, 3H),
3.81 (s, 3H).
Compound 9a (1.4 mmol, 0.47 g) was dissolved in
methylene chloride (20 mL) and to the solution was
added thiophenol (1.9 mmol, 0.20 mL) and 4 drops of
N-isopropylcyclohexylamine. The resulting solution
was stirred for 1 h at rt. The solution was concentrated
and the crude reaction mixture was poured on silica gel,
agitated to remove solvent and then was subjected to
flash chromatography on silica gel using methylene
chloride: hexane (20:80) as eluting solvent. Removal of
the solvent gave a dark yellow oil (0.60 g, 95%); IR
3.9. 2(S)-N-[2(2,4-Dibromo-5-methoxyphenyl)-2-(thio-
phenyl)ethane]-1-methyl-2-pyrrolinecarboxamide, 12a
To a stirred solution of (S)-N-methylproline (0.28
mmol, 0.036 g) in dry tetrahydrofuran (20 mL) was
added dicyclohexylcarbodiimide (0.28 mmol, 0.057 g),
1-hydroxybenzotriazole (0.28 mmol 0.0378 g) and 4-
N,N-dimethylaminopyridine in catalytic amounts. A
solution of amine 11a (0.28 mmol, 0.12 g) in dry THF
(10 mL) was added to the suspension. The suspension
was stirred for 18 h, filtered and the solvent removed in
vacuo. The residue was purified by circular chromatog-
raphy using methylene chloride as eluting solvent.
Removal of the solvent gave a yellow oil (0.078 g, 33%);
IR (CH2Cl2) 3327, 3058, 2937, 1668, 1580 cm−1; 1H
NMR (500 MHz, CDCl3) l 7.69 (s, 1H), 7.68 (s, 1H),
7.51 (bs, 2H), 7.36–7.32 (m, 4H), 7.28–7.24 (m, 6H),
6.87 (s, 1H), 6.85 (s, 1H), 4.84–4.78 (m, 2H), 3.92–3.82
(m, 2H), 3.80 (s, 3H), 3.79 (s, 3H), 3.68–3.60 (m, 2H),
3.06–2.98 (m, 2H), 2.86–2.76 (m, 2H), 2.32–2.24 (m,
2H), 2.26 (s, 3H), 2.16 (s, 3H), 2.20–2.02 (m, 4H),
1.84–1.4 (m, 4H); 13C NMR (125 MHz, CDCl3) l
155.64, 138.82, 136.33, 136.29, 133.27, 132.89, 132.85,
129.22, 128.15, 115.37, 115.30, 112.37, 112.33, 111.63,
111.60, 68.98, 56.84, 56.77, 56.66, 51.25, 51.16, 42.49,
42.43, 41.89, 41.69, 31.11, 31.06, 24.50, 24.43 ppm; MS
(EI) m/z (%) 526 (M,+ 23), 84 (100). Anal. calcd for
C21H24Br2N2O2S: C, 47.72; H, 4.55. Found: C, 47.76;
H, 4.59%.
1
(CH2Cl2) 3070, 2847, 2937, 1554 cm−1; H NMR (200
MHz, CDCl3) l 7.77 (s, 1H), 7.26–7.36 (m, 5H), 6.60 (s,
1H), 5.27–5.35 (m, 1H), 4.70–4.91 (m, 2H), 3.76 (s, 3H)
ppm; MS (EI) m/z (%) 443 (M,+ 4), 292 (100). Anal.
calcd for C15H13Br2NO3S: C, 40.27; H, 2.90. Found: C,
40.31; H, 2.93%.
3.6. 2-(2,4,6-Tribromo-3-methoxyphenyl)-2-(thiophenyl)-
1-nitroethane, 10b
Compound 10b was synthesized from 9b (1.00 g, 2.4
mmol), using the procedure for 10a. Light yellow liquid
1
(1.19 g, 92%); IR (KBr) 3070, 2935, 1554 cm−1; The H
NMR showed a mixture 1:1 of atropoisomers. 1H
NMR (400 MHz, CDCl3) l 7.81 (s, 1H), 7.78 (s, 1H),
7.52–7.32 (m, 10H) for two isomers, 5.86 (t, 1H, J=7.4
Hz), 5.72 (t, 1H, J=7.2 Hz), 5.36–5.26 (m, 2H), 5.12–
5.02 (m, 2H), 3.89 (s, 3H), 3.82 (s, 3H) ppm; MS (EI)
m/z (%) 523 (M,+ 10), 370 (100). Anal. calcd for
C15H12Br3NO3S: C, 34.22; H, 2.28. Found: C, 34.24; H,
2.29%.
3.10. (S)-N-[2(2,4,6-Tribromo-5-methoxyphenyl)-2-
(thiophenyl)ethane]-1-methyl-2-pyrrolinecarboxamide,
12b
3.7. Reduction of 2-(2,4-dibromo-5-methoxyphenyl)-2-
(thiophenyl)-1-nitroethane, 10a, with samarium diiodide
to give 11a
Compound 12b was synthesized from 11b (0.38 mmol,
0.200 g), using the same procedure described for amide
12a. Compound 12b was obtained as a yellow liquid
(0.069 g, 30% yield); IR (CH2Cl2) 3348, 2938, 2847,
2789, 1673, 1508, 1452 cm−1; 1H NMR (200 MHz,
CDCl3) l 7.80 (s, 1H), 7.74 (s, 1H), 7.6–7.2 (m, 10H)
for both isomers, 5.47–5.18 (m, 2H) for both isomers,
4.3–4.1 (m, 2H), 4.05–3.88 (m, 2H), 3.90 (s, 3H), 3.80
(s, 3H), 3.04–2.9 (m, 2H), 2.85–2.77 (m, 2H), 2.40–2.00
(m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 1.8–1.4 (m, 8H); 13C
NMR (50 MHz, CDCl3) l 155.07, 153.99, 139.74,
139.58, 137.65, 136.27, 135.99, 135.83, 132.24, 132.19,
132.12, 132.09, 129.27, 127.75, 127.71, 125.89, 124.06,
121.61, 121.29, 118.81, 117.43, 117.35, 77.48, 77.22,
To a solution of samarium diiodide (0.1N, 45.0 mL, 4.5
mmol) under argon at rt, was added 10a (0.44 mmol,
0.19 g) in dry methanol (0.25 mL). The solution was
stirred for 30 h and the reaction was quenched by
adding saturated sodium thiosulfate solution (3 mL)
and the mixture was concentrated in vacuo. The residue
was extracted into methylene chloride (50 mL), the
organic phase dried over anhydrous sodium sulfate and
the solvent was removed under reduced pressure to give
amine 11a as pale brown oil (0.12 g, 65%). The amine
11a was then used in the next step without further
purification. IR (CH2Cl2) 3361, 3175, 3004, 1581, 1469
1
cm−1; H NMR (200 MHz, CDCl3) l 7.69 (s, 1H), 7.25