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DOI: 10.1055/s-0029-1219923
An Efficient Synthesis of New Aza-Substituted Indoles via Michael-Type Addition
Publikationsverlauf
Publikationsdatum:
06. Mai 2010 (online)
Abstract
An efficient method has been developed for the synthesis of new aza-substituted indoles. The methodology involves a two-step synthesis. The first step involves the Michael addition of indoline with various Michael acceptors. The other includes the oxidation of the indoline ring in the Michael adducts to an indole
Key words
alkylation - indoline - Michael addition - oxidation - catalyst
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
Representative
Procedure - Synthesis of 3-(1
H
-Indol-1-yl)cyclohexanone (4)
To
a solution of indoline (500 mg, 4.19 mmol) and cyclohex-2-enone
(429 mg, 4.19 mmol) in MeCN (15 mL) was added DMAP (25 mg, 0.05
mmol). The mixture was stirred at r.t. for 24 h. After evaporation
of the solvent, the crude product 3-(indolin-1-yl)cyclohexanone
(3) was purified by crystalli-zation from
EtOAc-hexane (pale yellow crystals, 850 mg, 94%,
mp 235-236 ˚C).
¹H
NMR (400 MHz, CDCl3): δ = 7.08-7.03
(m, =CH, 2 H), 6.64 (t, J = 7.6
Hz, =CH, 1 H), 6.42 (d, J = 7.6
Hz, =CH, 1 H), 3.82-3.75 (m, CH, 1 H), 3.49-3.43
(m, CH2, 1 H), 3.38-3.31 (m, CH2,
1 H), 2.98 (t, J = 8.2
Hz, CH2, 2 H), 2.60-2.57 (m, CH2,
1 H), 2.56-2.50 (m, CH2, 1 H), 2.47-2.41
(m, CH2, 1 H), 2.33-2.25 (m, CH2,
1 H), 2.16-2.07 (m, CH2, 2 H), 1.86-1.70
(m, CH2, 1 H), 1.69-1.60 (m, CH2,
1 H). ¹³C NMR (100 MHz, CDCl3): δ = 210.0,
150.2, 130.1, 127.6, 124.8, 117.9, 107.3, 55.0, 46.7, 43.9, 41.3,
28.5, 28.4, 22.9.
To a solution of 3-(indolin-1-yl)cyclohexanone
(1.00 g, 4.65 mmol) in CH2Cl2 (10 mL) was
added activated MnO2 (869 mg, 10 mmol). The mixture was
then stirred at r.t. for 24 h. After filtration, the mixture was
evaporated in vacuo to give 3-(1H-indol-1-yl)cyclohexanone
(4) as yellow oil (890 mg, 90%). ¹H
NMR (400 MHz, CDCl3): δ = 7.65 (dd, J = 7.8, 2.0 Hz, =CH,
1 H), 7.35 (d, J = 8.4
Hz, =CH, 1 H), 7.26-7.20 (m, =CH, 2 H),
7.16-7.12 (m, =CH, 1 H), 6.57 (d, J = 2.9 Hz, =CH,
1 H), 4.72-4.66 (m, CH, 1 H), 2.94-2.91 (m, CH2, 1
H), 2.90-2.77 (m, CH2, 1 H), 2.56-2.40
(m, CH2, 2 H), 2.35-2.30 (m, CH2,
1 H), 2.25-2.10 (m, CH2, 2 H), 1.85-1.78
(m, CH2, 1 H). ¹³C NMR (100
MHz, CDCl3): δ = 208.2, 135.7, 128.9,
124.0, 122.0, 121.5, 120.1, 109.6, 102.6, 54.4, 48.4, 41.1, 31.6,
22.5.