4050
M. Abid et al. / Tetrahedron Letters 48 (2007) 4047–4050
under acidic conditions to form 1,4-butanedial, which
immediately reacts with the sulfonamides and undergoes
Paal–Knorr cyclization to form pyrrole derivatives after
eliminating two water molecules. It is known that the
acid strength of TfOH is significantly modified by
Acknowledgements
The financial support provided by University of
Massachusetts Boston and NIH (R-15 AG025777-02)
is gratefully acknowledged.
8
H O. Due to the substantial amount of H O formed
2
2
(
2 mol of H O/1 mol of 2,5-dimethoxytetrahydrofuran)
2
Supplementary data
in the cyclialkylation, the acidity of the system signifi-
cantly drops. This low acidity is not able to catalyze fur-
ther reactions.
The acidity drop is still significant even after increasing
the amount of TfOH to 100 mol %. The higher amount
of TfOH, however, is able to maintain the necessary acid
strength of the reaction mixture, and initiates the anne-
References and notes
1
2
. (a) Robinson, B. The Fischer Indole Synthesis; John Wiley
& Sons: Chichester, 1982; (b) Gribble, G. W. J. Chem. Soc.,
Perkin Trans. 1 2000, 1045, and references cited therein; (c)
Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106,
lation on the pyrrole ring. The additional 2 mol of H O
2
formed in the annelation have a similar effect to that
mentioned above. A further increase in TfOH concen-
tration enables the system to catalyze the second annela-
tion as well, to give the corresponding carbazoles
virtually in one step. This analysis indicates that
although the TfOH amount exceeds the 1:1 stoichio-
metric ratio, it is only needed to maintain the necessary
acid strength of the reaction mixture. As such the reac-
2
875; (d) T o¨ r o¨ k, B.; Abid, M.; London, G.; Esquibel, J.;
T o¨ r o¨ k, M.; Mhadgut, S. C.; Yan, P.; Prakash, G. K. S.
Angew. Chem., Int. Ed. 2005, 44, 3086.
. (a) Somei, M.; Yamada, F. Nat. Prod. Rep. 2004, 21, 278;
(
b) Furstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J. Am.
Chem. Soc. 1998, 120, 8305; (c) Somei, M.; Yamada, F.
Nat. Prod. Rep. 2005, 22, 73; (d) T o¨ r o¨ k, M.; Abid, M.;
Mhadgut, S. C.; T o¨ r o¨ k, B. Biochemistry 2006, 45, 5377; (e)
Abid, M.; T o¨ r o¨ k, B. Tetrahedron: Asymmetry. 2005, 16,
1547.
9
tion is still catalytic. Based on our earlier studies, we
suggest that both cyclialkylation and subsequent annela-
tion occur in a stepwise manner. Under the highly polar
experimental conditions the occurrence of the concerted
process is improbable.
3. (a) Hodges, M. L.; Spera, M. L.; Moody, M. W.; Harman,
W. D. J. Am. Chem. Soc. 1996, 118, 7117; (b) Katritzky, A.
R.; Fali, C. N.; Li, J. J. Org. Chem. 1997, 62, 4148.
4
. (a) Bur, S. K.; Padwa, A. Chem. Rev. 2004, 104, 2401; (b)
Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem.
Soc. 2004, 126, 10546; (c) Nishibayashi, Y.; Yoshikawa, M.;
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R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260; (e)
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2005, 7, 3549.
In conclusion, a one-pot triflic acid controlled cycliza-
tion/annelation provides efficient protocol for preparing
a wide variety of N-sulfonyl pyrroles, indoles and
carbazoles from commercially available sulfonamides.
This attractive method provides the products in
excellent yields and selectivities in short reaction times.
The simplicity and wide variability of the method
makes it a novel alternative to the current synthetic
processes, which produce these products in multistep
reactions.
5
. (a) Zelikin, A.; Shastri, V. R.; Langer, R. J. Org. Chem.
1
999, 64, 3379; (b) Roy, S.; Gribble, G. W. Tetrahedron
Lett. 2005, 46, 1325.
6
. (a) Ekkati, A. R.; Bates, D. K. Synthesis 2003, 1959; (b)
Banik, B. K.; Samajdar, S.; Banik, I. J. Org. Chem. 2004,
A general experimental procedure for the synthesis of
N-sulfonyl pyrroles, indoles and carbazoles. Benzenesulfon-
amide (100 mg, 0.636 mmol) and 2,5-dimethoxytetrahy-
drofuran (420 mg, 3.18 mmol) were placed in a round
bottom flask with 2 ml of CH Cl . This mixture was
cooled to 0 °C for 10–15 min and TfOH (0.05 equiv
for pyrroles, 1.0 equiv for indoles and 3.5 equiv for
carbazoles) was added dropwise to the reactants. After
addition, the mixture was stirred at room temperature
for an additional 2 h. The acid was quenched with water
6
9, 213; (c) Abid, M.; Landge, S.; T o¨ r o¨ k, B. Org. Prep.
Proced. Int. 2006, 38, 495; (d) Abid, M.; Spaeth, A.; T o¨ r o¨ k,
B. Adv. Synth. Catal. 2006, 348, 2191.
2
2
7. (a) Olah, G. A.; Prakash, G. K. S.; Sommer, J. Superacids;
John Wiley & Sons: New York, 1985; (b) Puglici, A.; Lee,
A.-L.; Schrock, R. R.; Hoveyda, A. H. Org. Lett. 2006, 8,
1
871; (c) Bennasar, M.-L.; Zulaica, E.; Tummers, S.
Tetrahedron Lett. 2004, 45, 6283.
8
. (a) Saito, S.; Sato, Y.; Ohwada, T.; Shudo, K. J. Am. Chem.
Soc. 1994, 116, 2312; (b) Olah, G. A.; Batamack, P.;
and the product was extracted with CH Cl . The
2
2
´
Deffieux, D.; T o¨ r o¨ k, B.; Wang, Q.; Moln a´ r, A.; Prakash, G.
combined organic layers were dried over sodium sulfate.
The solvent was evaporated in vacuo and the residue
was subjected to flash chromatography. The pure
products were characterized by GC–MS and NMR
K. S. Appl. Catal. A 1996, 146, 107.
´
9
. (a) Moln a´ r, A.; T o¨ r o¨ k, B.; Bucsi, I.; F o¨ ldv a´ ri, A. Top.
Catal. 1998, 6, 9; (b) Prakash, G. K. S.; Yan, P.; T o¨ r o¨ k, B.;
Olah, G. A. Catal. Lett. 2003, 87, 109; (c) Abid, M.; T o¨ r o¨ k,
B. Adv. Synth. Catal. 2005, 347, 1797.
(
see Supplementary data).