Full Paper
1-(4-Methylphenylsulfonyl)-5-(tetramethyl-1,3,2-dioxaborolan-
6-Bromo-1H-indole-3-carbaldehyde (6): The formylation and pu-
2-yl)-1H-indole (3b): The reaction conditions were similar to those rification was performed according to Lauchli et al.[27] Under an
reported for the preparation of 1-(4-methylphenylsulfonyl)-4-(tetra- inert atmosphere, 6-bromo-1H-indole (2.5 g,12.8 mmol) dissolved
methyl-1,3,2-dioxaborolan-2-yl)-1H-indole, but using a reaction time
of 16 h. For purification, the reaction was quenched with EA/Et2O
(1:1), filtered through silica, washed repeatedly with brine and the
combined organic layers were dried with Na2SO4. After evaporation
of the solvent, the crude product was dissolved in MeCN (5 mL)
in DMF (12 mL) was added dropwise to a stirred solution of POCl3
(2.67 mL, 16.4 mmol) in DMF (17 mL) at 0 °C. The reaction was
warmed to room temp. and stirred for ca. 1 h until a yellowish
precipitate appeared. The reaction was slowly quenched by adding
KOH (6.65 g) in water (20 mL) and kept just below boiling. After
cooling to room temp., saturated NaHCO3 was added and the aque-
and 2
N NaOH (5 mL) were added. The mixture was then stirred for
30 min at room temperature. After quenching with satd. aq NH4Cl ous phase was extracted repeatedly with ethyl acetate and washed
solution, the mixture was extracted repeatedly with EA/Et2O. The
organic layers were combined, washed with brine, dried with
Na2SO4, and the solvent was evaporated. The crude product was
dissolved in a small amount of dichloromethane (CH2Cl2)/PE and
given onto a flash chromatography column (gradient PE/CH2Cl2,
four times with brine. The combined organic phases were dried
with Na2SO4 and removal of solvent in vacuo gave the desired com-
pound (2.84 g, 12.7 mmol, 99 %) as an off-white solid. Rf = 0.08 (PE/
1
EA, 4:1); m.p. 195 °C. H NMR (600 MHz, [D6]DMSO): δ = 12.56 (s, 1
H), 10.68 (s, 1 H), 8.30 (s, 1 H), 7.57 (dd, J = 8.1, 0.7 Hz, 1 H), 7.46
80:20 to 50:50) to give the desired product (360 mg, 0.9 mmol, (dd, J = 7.6, 0.6 Hz, 1 H), 7.16 (t, J = 7.9 Hz, 1 H) ppm. 13C NMR
81 %) as a fine white foam. Rf = 0.21 (PE/EA, 95:5); 0.21 (PE/CH2Cl2,
3:2); m.p. 151 °C. H NMR (400 MHz, [D6]DMSO): δ = 7.98–7.94 (m, 124.25, 118.30, 112.91, 112.76 ppm. HRMS: m/z calcd. for C9H6BrNO
(151 MHz, [D6]DMSO): δ = 185.04, 138.71, 134.28, 126.44, 125.17,
1
2 H), 7.85 (d, J = 8.4 Hz, 2 H), 7.80 (d, J = 3.7 Hz, 1 H), 7.63 (dd, J =
9.3, 0.5 Hz, 1 H), 7.38 (d, J = 8.1 Hz, 2 H), 6.87 (dd, J = 3.7, 0.4 Hz, 1
H), 2.35–2.26 (m, 3 H), 1.29 (s, 12 H) ppm. 13C NMR (101 MHz,
[D6]DMSO): δ = 148.17, 138.75, 136.70, 133.02, 132.85 (2 C), 132.83,
131.16, 129.77, 129.27 (2 C), 125.85 (br), 115.30, 112.32, 86.27 (2 C),
27.29 (4 C), 23.62 ppm. HRMS: m/z calcd. for C21H24O4NBS [M+]
397.1513; found 397.1514. C21H24BNO4S (397.29): calcd. C 63.49, H
6.09, N 3.53; found C 63.64, H 6.19, N 3.53.
[M + H]+ 223.9705; found 223.9705, 225.9685 [81BrM]+. C9H6BrNO:
calcd. C 48.25, H 2.7, N 6.25; found C 48.44, H 2.81, N 6.29.
tert-Butyl 6-Bromo-3-formylindole-1H-carboxylate (7): The fol-
lowing reactions were performed as described by Konas et al.[26]
Boc2O (3.03 g,13.9 mmol) and 4-(dimethylamino)pyridine (16.05 mg,
130 μmol) were added to a stirred solution of 6-bromo-1H-indole-
3-carbaldehyde (2.8 g, 12.6 mmol) in THF (35 mL). After 30 min, the
reaction showed complete conversion on TLC and was stopped by
adding H2O. The aqueous phase was extracted repeatedly with
ethyl acetate. The organic phases were combined, washed with
brine and dried with Na2SO4. After removal of the organic solvent
in vacuo, the compound was purified by flash chromatography (PE/
EA, 8:1) to give the desired product (3.69 g, 11.3 mmol, 90 %) as a
colorless solid. Rf = 0.33 (PE/EA, 9:1); m.p. 142 °C. 1H NMR (600 MHz,
[D6]DMSO): δ = 10.07 (s, 1 H), 8.68 (s, 1 H), 8.27 (d, J = 1.7 Hz, 1 H),
8.08 (d, J = 8.4 Hz, 1 H), 7.57 (dd, J = 8.4, 1.8 Hz, 1 H), 1.67 (s, 9
H) ppm. 13C NMR (151 MHz, [D6]DMSO): δ = 185.52, 147.80, 136.61,
133.26, 128.37, 126.50, 125.92, 120.26, 114.59, 112.83, 86.25, 27.45
(3 C) ppm. HRMS: m/z calcd. for C14H14BrNO3 [81BrM + H]+ 326.0293;
found 326.02095. C14H14BrNO3 (324.17): calcd. C 51.87, H 4.35, N
4.32; found C 52.11, H 4.37, N 4.40.
1-(4-Methylphenylsulfonyl)-6-(tetramethyl-1,3,2-dioxaborolan-
2-yl)-1H-indole (3c): The compound was prepared as described for
3a. Flash chromatography was carried out with PE/EA (95:5) to give
the desired compound (81 %) as a white solid. Rf = 0.29 (PE/EA, 9:1);
1
m.p. 146 °C. H NMR (400 MHz, [D6]DMSO): δ = 8.25 (d, J = 0.6 Hz,
1 H), 7.88 (d, J = 3.7 Hz, 1 H), 7.77 (d, J = 8.4 Hz, 2 H), 7.58 (ddd,
J = 28.2, 7.9, 0.6 Hz, 2 H), 7.38 (d, J = 8.1 Hz, 2 H), 6.88 (dd, J = 3.7,
0.6 Hz, 1 H), 2.30 (s, 3 H), 1.33 (s, 12 H), 1.17 (s, 2 H) ppm. 13C NMR
(101 MHz, [D6]DMSO): δ = 145.51, 134.36, 134.02, 133.05, 130.28 (2
C), 129.07, 128.46, 126.32 (2 C), 124.52 (br), 121.16, 118.85, 109.59,
83.77 (2 C), 24.67 (4 C), 20.97 ppm. HRMS: m/z calcd. for
C
21H25O4NBS [M + H]+ 397.1513; found 397.1514. C21H24BNO4S
(397.29): calcd. C 63.49, H 6.09, N 3.53; found C 63.27, H 6.24, N
3.39.
tert-Butyl 6-Bromo-3-(hydroxymethyl)-1H-indole-1-carboxylate
(8): The reduction was performed by adding NaBH4 (626 mg,
16.6 mmol) to a stirred solution of 7 (3.6 g, 11.1 mmol) in THF/EtOH
(2:1) at 0 °C. The mixture was warmed to room temp. and stirred
for 30 min. NH4Cl was added and the mixture was extracted repeat-
edly with Et2O. After drying the combined organic phases over
Na2SO4 and removal of the solvent in vacuo the desired compound
(3.6 g, 11.1 mmol, quantitative) was obtained as a white solid. Rf =
0.11 (PE/EA, 9:1); m.p. 90 °C. 1H NMR (600 MHz, [D6]DMSO): δ = 8.20
(s, 1 H), 7.60 (d, J = 8.4 Hz, 1 H), 7.54 (s, 1 H), 7.39 (dd, J = 8.4,
1.8 Hz, 1 H), 5.12 (t, J = 5.5 Hz, 1 H), 4.61 (dd, J = 5.5, 0.9 Hz, 2 H),
1.61 (s, 9 H) ppm. 13C NMR (151 MHz, DMSO): δ = 148.75, 135.76,
128.25, 125.33, 123.56, 121.87, 121.59, 117.37, 117.12, 84.15, 54.92,
7-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (3d): In a dry
round-bottomed flask, 7-bromo-1H-indole (480 mg, 2.5 mmol), po-
tassium acetate (710 mg, 7.5 mmol), bis(pinacolato)diboron
(950 mg, 3.75 mmol) and PdCl2[R-bis(diphenylphosphanyl)ferro-
cene] (160 mg, 0.25 mmol) were dried by repeatedly application of
fine vacuum and flushed with dry argon. Anhydrous DMF (20 mL)
was added and the stirring reaction mixture was heated to 100 °C
for 4 h under argon. After cooling to room temp., the reaction was
quenched by adding Et2O and water. The mixture was filtered
through silica gel, extracted repeatedly with the Et2O, and the or-
ganic phases were combined. After washing the organic layer three
times with brine and drying over Na2SO4, the solvent was removed
in vacuo. The crude product was purified by flash chromatography
(PE/EA, 98:2 to 90:10) to give the desired compound (270 mg,
1.11 mmol, 44 %) as a white solid. Rf = 0.57 (PE/EA, 9:1); m.p. 88 °C.
1H NMR (600 MHz, [D6]DMSO): δ = 10.19 (s, 1 H), 7.67 (d, J = 7.8 Hz,
1 H), 7.43 (dd, J = 7.0, 0.9 Hz, 1 H), 7.32–7.31 (m, 1 H), 7.06–6.95 (m,
1 H), 6.43 (dd, J = 3.0, 2.0 Hz, 1 H), 1.33 (s, 12 H) ppm. 13C NMR
27.58 (3 C) ppm. HRMS: m/z calcd. for C14H16BrNO3 [
81BrM + Na]+
350.0187; found 350.0183. C14H16BrNO3: calcd. C 51.55, H 4.94, N
4.29; found C 51.87, H 4.92, N 4.32.
tert-Butyl 6-Bromo-3-(bromomethyl)-1H-indole-1-carboxylate
(9): For the Appel reaction,[28] at 0 °C, PPh3 (3.58 g, 15.0 mmol) and
(151 MHz, [D6]DMSO): δ = 139.90, 128.39, 127.04, 125.87, 123.78, CBr4 (5.09 g, 15.0 mmol) were added subsequently to a stirred solu-
118.50, 110.24 (br), 100.92, 83.49 (2 C), 24.67 (4 C) ppm. HRMS: m/z
calcd. for C14H19BNO2 [M + H]+ 244.1503; found 244.1503.
C14H18BNO2 (243.11): calcd. C 69.17, H 7.46, N 5.76; found C 68.89,
H 7.46, N 5.77.
tion of tert-butyl 6-bromo-3-(hydroxymethyl)-1H-indole-1-carboxyl-
ate (4.4 g, 13.6 mmol) in CH2Cl2 (40 mL). By monitoring the reaction
with TLC, no starting material was found after 30 min. After removal
of solvent at 0 °C partially in vacuo, the oily residue was applied on
Eur. J. Org. Chem. 0000, 0–0
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