Synthesis of Sultams by Intramolecular Heck Reaction
COMMUNICATIONS
and Et3N (1.2 mmol, 1.2 equivs.) in CH2Cl2 (10 mL) at ꢀ788C
under an argon atmosphere. After stirring for 1 h at ꢀ788C,
the reaction mixture was filtered through a plug of silica gel
and washed with additional diethyl ether. The filtrate was con-
centratedunder vacuum, and the crude product was purified by
flash chromatography.
References and Notes
[1] A. Scozzafava, T. Owa, A. Mastrolorenzo, C. T. Supuran,
Curr. Med. Chem. 2003, 10, 925–953 and references cited
therein.
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Acids, Esters and their Derivatives, (Eds.: S. Patai, Z.
Rappoport), Wiley, New York, 1991, pp. 789–878.
[3] a) S. Hanessian, H. Sailes, E. Therrien, Tetrahedron 2003,
59, 7047–7056; b) L. Zhuang, J. S. Wai, M. W. Embrey,
T. E. Fisher, M. S. Egbertson, L. S. Payne, J. P. Guare,
Jr., J. P. Vacca, D. J. Hazuda, P. J. Felock, A. L. Wolfe,
K. A. Stillmock, M. V. Witmer, G. Moyer, W. A. Schleif,
L. J. Gabryelski, Y. M. Leonard, J. J. Lynch, Jr., S. R. Mi-
chelson, S. D. Young, J. Med. Chem. 2003, 46, 453–456;
c) M. Inagaki, T. Tsuri, H. Jyoyama, T. Ono, K. Yamada,
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4753–4756; b) I. R. Greig, M. J. Tozer, P. T. Wright,
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Frçhlich, P. Metz, Tetrahedron 2000, 56, 873–879;
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Chem. Soc. 1999, 121, 700–709; e) P. Metz, D. Seng, R.
Frçhlich, B. Wibbeling, Synlett 1996, 741–742.
Heck Cyclization of 15 with Pd(PPh3)4 (Scheme 3,
Method A)
To a suspension of Pd(PPh3)4 (0.0125 mmol, 5 mol %) and Et3N
(0.5 mmol, 2 equivs.) in dry CH3CN (10 mL) was added the a-
bromovinylsulfonamide (0.25 mmol) under an argon atmos-
phere. After heating under reflux for 2 h, the mixture was fil-
tered through a plug of silica gel and washed with diethyl ether.
The filtrate was concentrated under vacuum, and the residual
brown oil was purified by flash chromatography on silica gel.
Heck Cyclization of 15 with Pd(OAc)2 (Scheme 3,
Method B)
The a-bromovinylsulfonamide (0.25 mmol) was added to a
suspension of Pd(OAc)2 (0.0125 mmol, 5 mol %), P(o-Tol)3
(0.0275 mmol, 11 mol %), Bu4NCl (0.5 mmol, 2 equivs.) and
Na2CO3 (0.5 mmol, 2 equivs.) in dry CH3CN (5 mL) under an
argon atmosphere. After refluxing for 1 h, the mixture was fil-
tered through a plug of silica gel. The filtrate was concentrated
under vacuum, and the oily residue was purified by flash chro-
matography on silica gel.
[5] J. Lee, Y.-L. Zhong, R. A. Reamer, D. Askin, Org. Lett.
2003, 5, 4175–4177.
[6] M. Ueda, H. Miyabe, A. Nishimura, O. Miyata, Y. Take-
moto, T. Naito, Org. Lett. 2003, 5, 3835–3838.
General Procedure for Heck Cyclization in the
Presence of a Silver or Thallium Salt
To a stirred suspension of Pd(OAc)2 (0.02 mmol, 10 mol %),
P(o-Tol)3 (0.022 mmol, 11 mol %), and a silver or thallium
salt (0.4 mmol, 2 equivs.) in dry CH3CN (2 mL) was added
the a-bromovinylsulfonamide (0.2 mmol) under an argon at-
mosphere. After refluxing for the time listed in Tables 1 and
2, the mixture was filtered through a plug of silica gel. Follow-
ing removal of the solvent under vacuum, the oily residue was
purified by flash chromatography on silica gel.
[7] a) For a review, see: M. D. McReynolds, J. M. Dougherty,
P. R. Hanson, Chem. Rev. 2004, 104, 2239–2258; b) S.
Karsch, D. Freitag, P. Schwab, P. Metz, Synthesis 2004,
1696–1712; c) D. Freitag, P. Schwab, P. Metz, Tetrahe-
dron Lett. 2004, 45, 3589–3592.
[8] For recent reviews on the intramolecular Heck reaktion,
see: a) L. F. Tietze, H. Ila, H. P. Bell, Chem. Rev. 2004,
104, 3453–3516; b) A. B. Dounay, L. E. Overman,
Chem. Rev. 2003, 103, 2945–2963.
[9] A literature search retrieved only a single a-methylene-
g-sultam (1-butene-2,4-sultam) and its N-benzenesulfon-
yl derivative: A. D. Bliss, W. K. Cline, O. J. Sweeting, J.
Org. Chem. 1964, 29, 2412–2416. A patent search re-
trieved one additional benzannulated a-methylene-g-sul-
tam: K. Widdowson, H. Nie, (SmithKline Beecham Cor-
poration), Patent WO 9911264, 1999.
General Procedure for Michael Addition of Thiols to
a-Methylene-g-sultams
To a solution of the a-methylene-g-sultam (0.15 mmol) in dry
MeOH (1 mL) was added the thiol (0.75 mmol, 5 equivs.) fol-
lowed by a dropwise addition of Et3N (0.3 mmol, 2 equivs.). Af-
ter stirring the mixture at room temperature for 8–24 h, the
solvent was removed under vacuum, and the crude product
was purified by flash chromatography.
[10] C. S. Rondestvedt, Jr., J. Am. Chem. Soc. 1954, 76, 1926–
1929.
[11] B. M. Trost, Z. T. Ball, T. Jçge, J. Am. Chem. Soc. 2002,
124, 7922–7923.
[12] P. Pinho, J. Minnaard, B. L. Feringa, Org. Lett. 2003, 5,
259–261.
Acknowledgements
[13] Crystallographic data (excluding structure factors) for
the structures 21 and 22 reported in this paper have
been deposited with the Cambridge Crystallographic
Financial support of this work by the Deutsche Forschungsge-
meinschaft (grants ME 776/15-1 and 436 RUS 17/90/04) and
the Fonds der Chemischen Industrie is gratefully acknowledged.
Adv. Synth. Catal. 2005, 347, 754–758
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