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Synlett 2006(10): 1574-1576  
DOI: 10.1055/s-2006-944182
LETTER
© Georg Thieme Verlag Stuttgart · New York

Novel α-Carboline Synthesis Using Tandem aza-Wittig-Electrocyclization Reaction of Indol-2-yl Phosphorane with Enone

Carlo Boninia, Maria Funicello*a, Piero Spagnolob
a Dipartimento di Chimica, Università della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy
Fax: +39(0971)202223; e-Mail: funicello@unibas.it;
b Dipartimento di Chimica Organica ‘A. Mangini’, Viale Risorgimento 4, 40136 Bologna, Italy
e-Mail: spagnolo@ms.fci.unibo.it;
Further Information

Publication History

Received 2 March 2006
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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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.

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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.

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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.