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Synlett 2010(10): 1481-1484  
DOI: 10.1055/s-0029-1219918
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Desulfonylation of Indoles and 7-Azaindoles Using Sodium tert-Butoxide

Charlotte Chauleta, Cécile Croixa, Joan Bassetb, Maria-Dolores Pujolb, Marie-Claude Viaud-Massuard*a
a UMR-CNRS 6239, Génétique-Immunothérapie-Chimie & Cancer, Equipe 5, Laboratoire de Chimie Organique et Thérapeutique, Université des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France
Fax: +33(2)47367229; e-Mail: marie-claude.viaud-massuard@univ-tours.fr;
b Laboratorio de Quimica Farmaceutica, Facultad de Farmacia, Universidad de Barcelona, Av. Diagonal, s/n, 08028 Barcelona, Spain
Further Information

Publication History

Received 30 November 2009
Publication Date:
06 May 2010 (online)

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Abstract

A mild method for the desulfonylation of N-indoles and N-azaindoles is described. Deprotection is carried out under basic conditions, using sodium tert-butoxide in dioxane. Several functionalized indoles and 7-azaindoles were efficiently deprotected by this method, which is mild enough to be used to deprotect compounds including functions that are known to be sensitive to acidic or basic conditions.

Key words

N-desulfonylation - indole - 1H-pyrrolo[2,3-b]pyridine - sodium tert-butoxide - sealed tube

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General Procedure
An oven-dried screw-cap test tube was charged, under an atmosphere of argon, with starting compound (1 equiv) and NaOt-Bu (1.5 equiv) and fitted with a septum. The tube was evacuated and backfilled with argon. The evacuation/backfill was repeated two additional times. Under an argon purge, dioxane (7.5 mL for 1 mmol) was added by syringe to rinse the side of the tube. The septum was replaced with a Teflon screw cap, the tube was sealed, and the mixture was stirred at 80 ˚C for the time indicated in Table 1 (checked by TLC). After cooling, the mixture was quenched with H2O (3 mL) and was extracted with EtOAc (2 × 10 mL). The organic phase was dried, and the solvent was removed in vacuo. The crude product obtained was purified by column chromatography (cyclohexane-EtOAc). The yields of the pure compounds are indicated in Table 1.

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1 H -pyrrolo[2,3- b ]pyridine-2-carboxylic acid (2) ¹H NMR (200 MHz, DMSO): δ = 7.17-7.09 (m, 2 H, H-5, H-3), 8.09 (dd, J = 8.0, 1.6 Hz, 1 H, H-4), 8.39 (dd, J = 3.4 Hz, 1 H, H-6), 12.37 (s, 1 H, NH), 13.14 (s, 1 H, CO2H) ppm.
1-Methyl-3-oxo-1 H -furo[3,4- b ]indole (18)
¹H NMR (200 MHz, CDCl3): δ = 1.71 (d, J = 6.6 Hz, 3 H, CH3), 5.85 (q, J = 6.6 Hz, 1 H, CH), 7.28 (m, 2 H, H-5, H-6), 7.54 (d, J = 8.0 Hz, 1 H, H-8), 8.05 (d, J = 8.0 Hz, 1 H, H-5), 9.42 (br s, 1 H, NH) ppm.
2-( N , N -Dimethylhydrazinecarbonyl) indole (26) ¹H NMR (200 MHz, CDCl3): δ = 2.75 (s, 6 H, CH3), 6.85 (br s, 1 H, NH), 7.14 (t, J = 7.8 Hz, 1 H, H-6), 7.30 (t, J = 8.0 Hz, 1 H, H-5), 7.41 (d, J = 8.2 Hz, 1 H, H-4), 7.67 (d, J = 8.2 Hz, 1H, H-7), 9.20 (br s, 1 H, NH) ppm.