The Journal of Organic Chemistry
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(d, 1H, J = 7.6 Hz), 7.24ꢀ7.42 (m, 12H), 7.16 (d, 2H, J = 3.6 Hz), 6.85
(s, 2H), 4.26 (t, 2H, J = 6.8 Hz), 3.92 (q, 2H, J = 6.4 Hz), 380ꢀ3.89 (m,
4H), 1.80ꢀ1.89 (m, 2H), 1.35ꢀ1.43 (m, 8H), 0.93 (t, 3H, J = 7.2 Hz);
TOF MS ESþ calcd for C42H43N3S2 ([M þ H]þ) 654.2977, found
654.2971.
3.5. R,R-12. The compound was prepared with the same method as
S,S-12: 64.6% yield; 1H NMR (CDCl3, 400 MHz, TMS) δ 8.27 (s, 2H),
7.68 (d, 1H, J = 8.4 Hz), 7.24ꢀ7.43 (m, 12H), 7.16 (d, 2H, J = 3.2 Hz),
6.87 (s, 2H), 4.23 (t, 2H, J = 7.2 Hz), 3.94 (q, 2H, J = 6.4 Hz), 3.79ꢀ3.90
(m, 4H), 1.80ꢀ1.87 (m, 2H), 1.34ꢀ1.45 (m, 8H), 0.92 (t, 3H,J =7.2 Hz);
TOF MS ESþ calcd for C42H43N3S2 ([M þ H]þ) 654.2977, found
654.2949.
3.6. S,S-1. S,S-12 (140.0 mg, 0.21 mmol), 2-(2-bromomethylphenyl)-
1,3,2-dioxaborinane (218.5 mg, 0.86 mmol), and K2CO3 (173.9 mg,
1.26 mmol) were mixed in dry MeCN (3.0 mL) and DCM (1 mL) and
then the mixture was refluxed for 10 h under N2. The reaction mixture was
cooledtoroom temperature, dilutedHCl was added, and then themixture
was stirred for a further 1 h. The solvent was removed under vacuum, and
DCM was added to take up the residue. The organic layer was washed
with water and dried over anhydrous MgSO4. The solvent was removed
under reduced pressure and the residue was purified by column chroma-
tography (silica gel, DCM/MeOH, 30/1, v/v), yielding 53.2 mg of light
yellow powder (27.5%): [R]2D0 = ꢀ36.1° ( 0.8° (c = 0.30 in CH2Cl2); 1H
NMR (CDCl3, 400 MHz, TMS) δ 8.34 (s, 2H), 7.88 (d, 2H, J = 6.8 Hz),
7.71 (d, 2H, J = 8.8 Hz), 7.19ꢀ7.43 (m, 20H), 6.79 (s, 2H), 4.31 (t, 2H,
J = 7.2 Hz), 4.21 (d, 2H, J = 6.8 Hz), 3.66ꢀ4.01 (m, 8H), 1.85ꢀ1.93 (m,
2H), 1.64 (d, 6H, J = 6.8 Hz), 1.36ꢀ1.46(m, 2H), 0.95 (t, 3H, J = 7.6Hz);
13C NMR (100 MHz, CDCl3/CD3OD) δ 145.6, 141.4, 140.4, 139.7,
137.2, 136.2, 134.7, 131.4, 130.0, 129.1, 128.9, 128.4, 127.7, 127.2, 125.8,
124.4, 123.2, 121.5, 117.8, 109.2, 58.6, 56.2, 53.4, 47.5, 43.0 31.2, 20.5,
17.7, 13.8; TOF MS ESþ calcd for C56H57B2N3O4S2 ([M þ 2MeOH ꢀ
2H2O þ 2H]2þ) 475.7223, found 475.7225.
7.39 (d, 1H, J = 8.0 Hz), 7.18ꢀ7.26 (m, 2H), 4.25 (t, 2H, J = 7.2 Hz),
1.80ꢀ1.87 (m, 2H), 1.33ꢀ1.43 (m, 2H), 0.93 (t, 3H, J = 7.2 Hz); TOF
MS EIþ calcd for C16H16NI 349.0328, found 349.0331.
3.10. 5-(9-Butylcarbazol-6-yl)thiophene-2-carbaldehyde
(15). To a degassed solution of 14 (0.80 g, 2.29 mmol) in THF
(5 mL) were successively added a solution of K2CO3 (0.55 g, 4.0 mmol)
in water (2 mL), Pd(PPh3)4 (52.9 mg, 0.046 mmol), and 5-
formylthiophene-2-boronic acid (536.0 mg, 3.44 mmol). The reaction
mixture was refluxed under N2 for 6 h. The solvents were removed under
reduced pressure. The residue was taken up with DCM and washed with
water. The organic layer was dried over Na2SO4. After the solvent was
removed, the residue was purified by column chromatography (silica gel,
DCM), yielding 396.7 mg of yellow solid (52.0%): 1H NMR (CDCl3,
400 MHz, TMS) δ 9.89 (s, 1H), 8.40 (s, 1H), 8.13 (d, 1H, J = 8.0 Hz),
7.56ꢀ7.79 (m, 2H), 7.49 (t, 1H, J = 7.2 Hz), 7.42ꢀ7.46 (m, 3H), 7.28
(d, 1H, J = 7.6 Hz), 4.31 (t, 2H, J = 7.2 Hz), 1.84ꢀ1.92 (m, 2H),
1.36ꢀ1.46 (m, 2H), 0.94 (t, 3H, J = 7.2 Hz); TOF MS EIþ calcd for
C21H19NOS 333.1187, found 333.1193.
3.11. R-16. To a solution of 15 (100.0 mg, 0.30 mmol) in DCM
(3 mL) and ethanol (3 mL) was added(R)-1-phenylethanamine (72.7 mg,
0.60 mmol). The reaction mixture was refluxed under nitrogen for 8 h.
After the solution was cooled to room temperature, NaBH4 (111.0 mg,
3 mmol) was added in several portions to the stirred solution and the
stirring was continued for 1 h. The mixture was evaporated to dryness.
The residual was purified by column chromatography (silica gel, DCM/
MeOH, 15/1, v/v), yielding 103.0 mg of yellow oil (78.4%): 1H NMR
(CDCl3, 400 MHz, TMS) δ 8.28 (s, 1H), 8.10 (d, 1H, J = 7.6 Hz), 7.67
(d, 1H, J = 8.4 Hz), 7.44 (d, 1H, J = 8.0 Hz),7.34ꢀ7.40 (m, 6H),
7.21ꢀ7.28 (m, 2H), 7.14 (s, 1H), 6.82 (s, 1H), 4.26 (t, 2H, J = 7.2 Hz),
3.90 (q, 1H, J = 6.4 Hz), 3.78ꢀ3.88 (m, 2H), 1.81ꢀ1.88 (m, 2H),
1.36ꢀ1.44 (m, 5H), 0.92 (t, 3H, J = 7.2 Hz); TOF MS ESþ calcd for
C29H31N2S ([M þ H]þ) 439.2208, found 439.2217.
3.7. R,R-1. This compound was prepared with the same method as S,
S-1: 31.2% yield; [R]D20 = þ34.8° ( 1.0° (c = 0.30 in CH2Cl2); 1H NMR
(CDCl3, 400 MHz, TMS) δ 8.34 (s, 2H), 7.89 (d, 2H, J = 8.4 Hz), 7.71
(d, 2H, J = 8.8 Hz), 7.19ꢀ7.43 (m, 20H), 6.80 (s, 2H), 4.30 (t, 2H, J =
6.8 Hz), 4.21 (d, 2H, J = 5.6 Hz), 3.66ꢀ4.01 (m, 8H), 1.84ꢀ1.92 (m,
2H), 1.64 (d, 6H, J = 6.4 Hz), 1.38ꢀ1.46(m, 2H), 0.94 (t, 3H, J = 7.6Hz);
13C NMR (100 MHz, CDCl3/CD3OD) δ 149.60, 144.3, 135.2, 133.9,
133.1, 132.9, 132.3, 131.6, 131.1, 129.7, 128.3, 127.0, 125.4, 121.7, 113.1,
62.6, 60.1, 51.4, 46.9, 35.1, 33.5, 24.4, 21.5, 17.7; TOF MS ESþ calcd for
C56H57B2N3O4S2 ([M þ 2MeOH ꢀ 2H2O þ 2H]2þ) 475.7223, found
475.7233.
3.12. S-16. To a solution of 15 (130.0 mg, 0.39 mmol) in DCM
(3 mL) andethanol(3 mL) wasadded(S)-1-phenylethanamine (94.3mg,
0.78 mmol). The reaction mixture was refluxed under nitrogen for 8 h.
After the solution was cooled to room temperature, NaBH4 (144.3 mg,
3.9 mmol) was added in several portions to the stirred solution and the
stirring was continued for 1 h. The resulting mixture was evaporated to
dryness. The residue was purified by column chromatography (silica gel,
DCM/MeOH, 15/1, v/v), yielding 121.6 mg of yellow oil (71.2%): 1H
NMR (CDCl3, 400 MHz, TMS) δ 8.26 (s, 1H), 8.09 (d, 1H, J = 7.6 Hz),
7.67 (d, 1H, J = 8.0 Hz), 7.44 (d, 1H, J = 8.0 Hz),7.14ꢀ7.48 (m, 9H),
6.82 (s, 1H), 4.25 (t, 2H, J = 7.2 Hz), 3.95 (q, 1H, J = 6.4 Hz), 3.79ꢀ3.91
(m, 2H), 1.82ꢀ1.86 (m, 2H), 1.46 (d, 3H, J = 6.4 Hz), 1.34ꢀ1.42 (m,
2H), 0.92 (t, 3H, J = 7.2 Hz); TOF MS ESþ calcd for C29H31N2S ([M þ
H]þ) 439.2208, found 439.2216.
3.8. 3-Iodocarbazole (13). Carbazole (16.7 g, 0.1 mol) was dis-
solved in boiling glacial acetic acid (260 mL), and potassium iodide (11.0 g,
0.066 mol) was added. The solution was cooled, finely powdered
potassium iodate (16.0 g, 0.075 mol) added, and the mixture then
boiled until it acquired a clear straw-colored tint (10 min). The hot
solution was decanted from the undissolved potassium iodate and
allowed to cool slowly to 45 °C. The precipitate were rapidly filtered
off and recrystallized from alcohol, the solution being allowed to cool to
3.13. S-2. S-16 (120.0 mg, 0.27 mmol), 2-(2-bromomethylphenyl)-
1,3,2-dioxaborinane (138.0 mg, 0.54 mmol), and K2CO3 (111.8 mg,
0.81 mmol) were mixed in dry MeCN (3.0 mL) and DCM (1 mL), and
then the mixture was refluxed for 10 h under N2. The reaction mixture
was cooled to room temperature and diluted HCl was added, and then
the mixture was stirred for a further 1 h. The solvent was removed under
reduced pressure, and DCM was added to take up the residue. The
organic layer was washed with water and dried over anhydrous MgSO4.
The solvent was removed under reduced pressure and the residue was
purified bycolumn chromatography (silica gel, DCM/MeOH, 30/1, v/v),
yielding 64.7 mg of light yellow powder (42.0%): [R]2D0 = ꢀ44.2° ( 0.6°
1
45 °C and filtered, yielding 11.7 g of white solid (40.0%): H NMR
(CDCl3, 400 MHz, TMS) δ 8.38 (s, 1H), 8.00 (d, 1H, J = 8.0 Hz), 7.64
(d, 1H, J = 8.0 Hz), 7.40ꢀ7.46 (m, 2H), 7.20ꢀ7.24 (m, 2H); TOF MS
EIþ calcd for C12H8NI 292.9702, found 292.9707.
3.9. 9-Butyl-3-iodocarbazole (14). NaH (60 wt % in mineral oil;
0.17 g, 4.25 mmol) and n-C4H9Br (0.59 g, 4.35 mmol) were added to a
solution of compound 13 (0.85 g, 2.9 mmol) in DMF (5 mL). The
mixture was stirred at room temperature until the reaction was complete,
as monitored by TLC. The mixture was poured into water (100 mL) and
the precipitate collected by filtration and purified by column chromato-
graphy (silica gel, DCM/petroleum ether, 1/1, v/v), yielding 0.91 g of
white solid (90.2%): 1H NMR (CDCl3, 400 MHz, TMS) δ 8.40 (s, 1H),
8.03 (d, 1H, J = 7.2 Hz), 7.69 (d, 1H, J = 8.0 Hz), 7.47 (t, 1H, J = 8.0 Hz),
1
(c = 0.30 in CH2Cl2); H NMR (CDCl3, 400 MHz, TMS) δ 8.30
(s, 1H), 8.14 (d, 1H, J = 7.6 Hz), 7.88 (s, 1H), 7.70 (d, 1H, J = 8.4 Hz),
7.16ꢀ7.50 (m, 13H), 6.78 (s, 1H), 4.30 (t, 2H, J = 7.2 Hz), 4.19 (d, 1H,
J = 6.8 Hz), 3.96 (d, 1H, J = 8.4), 3.64ꢀ3.87 (m, 3H), 1.83ꢀ1.90 (m,
2H), 1.62 (d, 3H, J = 6.8 Hz), 1.36ꢀ1.45 (m, 2H), 0.93 (t, 3H, J = 7.6 Hz);
13C NMR (100 MHz, CDCl3/CD3OD) δ 145.8, 141.4, 140.9, 140.0,
139.7, 137.0, 136.3, 131.4, 130.0, 129.0, 128.9, 128.4, 127.7, 127.2, 125.9,
5693
dx.doi.org/10.1021/jo200675j |J. Org. Chem. 2011, 76, 5685–5695