LETTER
Desulfonylation of Indoles and 7-Azaindoles
1483
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We have tested this methodology on nonsensitive mole-
cules, and it is clear that the presence of substituents such
as I, Br, and Cl or carboxylic acid does not affect the de-
sulfonylation reaction (entries 2, 11, 12, and 5, respec-
tively). Similarly, N-phenyl-1-(phenylsulfonyl)-1H-
pyrrolo[2,3-b]pyridine-2-carboxamide (25) and
N¢,N¢-dimethyl-1-(phenylsulfonyl)-1H-indole-2-carbohy-
drazide (27) led to the expected N-deprotected com-
pounds 26 and 28 in good yields (entries 13 and 14).
Finally, the presence of electron-donating groups (benzy-
lamino) or electron-withdrawing (nitro), functional
groups, precursors to other useful substituents, does not
affect the N-desulfonylation (entries 15 and 16).
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To summarize, we have demonstrated that the N-desulfo-
nylation of a wide range of indoles, and 7-azaindoles
could be accomplished with sodium tert-butoxide in diox-
ane. This reagent is readily available, inexpensive, and
easy to handle. We have shown that this new method is
able to deprotect heterocycles without altering functional
groups, such as ester, amide, and lactone, which are nor-
mally attacked under basic conditions.
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Acknowledgment
The Laboratory of Organic and Therapeutic Chemistry acknow-
ledge the financial support provided by the Conseil Régional de la
Région Centre and in part by the Ministry of Science and Techno-
logy (CTQ2007-60614/BQU) of Spain, one of us (J.B.) thanks the
AGAUR for the predoctoral fellowship. Thanks also to Monika
Ghosh for the translation assistance.
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References and Notes
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Böhmer, F.-D.; Fiebig, H.-H.; Burger, A. M.; Baasner, S.;
Beckers, T. J. Med. Chem. 2001, 26, 4535.
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(32) General Procedure
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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.
(33) 1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid (2)
1H NMR (200 MHz, DMSO): d = 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-1H-furo[3,4-b]indole (18)
1H NMR (200 MHz, CDCl3): d = 1.71 (d, J = 6.6 Hz, 3 H,
Synlett 2010, No. 10, 1481–1484 © Thieme Stuttgart · New York