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DOI: 10.1055/s-2006-944182
Novel α-Carboline Synthesis Using Tandem aza-Wittig-Electrocyclization Reaction of Indol-2-yl Phosphorane with Enone
Publication History
Publication Date:
12 June 2006 (online)
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Abstract
Mild thermal reaction of indol-2-yl triphenyl- and methyldiphenyl-phosphorane derived from 2-azido-1-methylindole with enones provides a novel entry to 9-methyl-9H-pyrido[2,3-b]indoles through a tandem aza-Wittig-electrocyclization process.
Key words
indolyl phosphoranes - enones - aza-Wittig - electrocyclization - α-carbolines
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References and Notes
Preparation of the 1-Methylindol-2-yl Phosphoranes 2a,b.
2-Azido-1-methylindole (1), freshly obtained after filtration through a Florisil® pad of the crude product from azido transfer reaction of 1-methylindole (1 mmol) with tosyl azide,
[4]
was dissolved in dry Et2O (2 mL) and then slowly added to an anhyd Et2O solution (2 mL) of PPh3 (1 mmol) at 0 °C under nitrogen. The reaction mixture was stirred at 0 °C for ca. 1 h after which the separated solid material was filtered off to give the triphenylphosphorane (2a, 0.7 mmol, 70%) as a dark-yellow powder, mp 90-92 °C. 1H NMR (300 MHz, CDCl3): δ = 7.90-7.33 (m, 15 H), 7.20-7.15 (m, 1 H), 7.10-6.95 (m, 1 H), 6.90-6.80 (m, 2 H), 5.15 (s, 1 H), 3.87 (s, 3 H). 13C NMR (50 MHz, CDCl3): δ = 149.5, 144.4, 137.0, 134.5, 132.4, 132.0, 131.1, 130.0, 129.3, 127.8, 127.0, 125.5, 125.0, 124.3, 121.5, 118.7, 117.5, 117.0, 114.0, 113.7, 111.0, 109.3, 39.0.
The methyldiphenylphosphorane (2b) was similarly pre-pared in 55% yield by azidation of 1-methylindole (1 mmol) followed by direct treatment with methyldiphenylphosphine (1 mmol). The compound 2b was obtained as a viscous oil which showed a tendency to decompose under work-up conditions and was thus employed without purification.
1H NMR (300 MHz, CDCl3): δ = 7.95-7.65 (m, 5 H), 7.58-7.40 (m, 5 H), 7.21-7.18 (m, 1 H), 7.15-7.10 (m, 1 H), 6.90-6.80 (m, 2 H), 5.20 (s, 1 H), 3.87 (s, 3 H), 2.23 (d, 3 H, 2
J
PH = 12.8 Hz). 13C NMR (50 MHz, CDCl3): δ = 143.6, 141.0, 134.6, 133.0, 132.3, 131.6, 131.5, 130.7, 129.5, 129.2, 129.2, 128.2, 126.1, 125.9, 118.8, 117.0, 116.5, 107.5, 37.0, 14.88.
Synthesis of the Carbolines 3a-e. Typical Procedure.
A mixture of the triphenylphosphorane (2a, 1 mmol) and trans-crotonaldehyde (1 mmol) in dry toluene (5 mL) was stirred at 70 °C for ca. 20 h under a stream of nitrogen. After cooling, the solvent was removed in vacuo and the resultant residue chromatographed on a silica gel column by progressive elution with PE-EtOAc mixtures to give 4,9-dimethyl-9H-pyrido[2,3-b]indole (3b,
[18]
80%) as an oil. 1H NMR (300 MHz, CDCl3): δ = 8.40-8.36 (m, 1 H), 8.20-8.15 (m, 1 H), 7.60-7.55 (m, 1 H), 7.40-7.35 (m, 1 H), 7.23 (s, 1 H), 7.15-7.00 (m, 1 H), 4.10 (s, 3 H), 2.94 (s, 3 H). 13C NMR (50 MHz, CDCl3): δ = 153.3, 150.6, 145.8,143.0, 129.4, 125.8, 125.0, 123.1, 117.3, 116.6, 108.3, 30.0, 27.8.
The carbolines 3a
[17b]
[17c]
and 3e
14 had physical and/or spectral data consistent with those previously reported. The hitherto unknown carbolines 3c,d were identified on the basis of NMR and MS data as well as elemental analysis.
Replacement of phenyl with methyl group(s) on phosphorus could enhance the reactivity of our previous benzothiophen-2-yl and, especially, benzothiophen-3-yl phosphoranes with enones, see ref. 3b,3c.