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

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.

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

References and Notes

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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.

<A NAME="RD34509ST-33">33</A>

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.

<A NAME="RD34509ST-34">34</A> Romero M. Pujol MD. Synlett  2003,  173