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7d was evaluated and found to react, but the product was
obtained in low yield (37%) (Entry 9). Nevertheless, the
enantioselectivity of the process was good (64% ee). Finally,
the sulfonate O-alkyl substituent (R2) was varied to deter-
mine its effect on the reaction. Replacement of the cyclo-
hexyl group in Michael acceptor 1a (R2 = c-Hex) with ethyl
or isopropyl did not lead to any significant change in yield
or enantioselectivity (Entries 10 and 11).
[2]
[3]
[4]
Conclusions
The activity of α,β-unsaturated sulfonates in organocata-
lyzed Michael additions has been investigated for the first
time, and a general procedure for their bifunctional-thio-
urea-catalyzed sulfa-Michael addition with aromatic thiols
has been developed. The sulfa-Michael adducts were ob-
tained in generally good yields (24–92%) and with moder-
ate enantiomeric excesses (31–64%). Current work is fo-
cused on converting the Michael adducts into β-sulfur-sub-
stituted sulfonic acids and exploring the use of α,β-unsatu-
rated sulfonates in other organocatalytic reactions.
[5]
Experimental Section
General Procedure for the Sulfa-Michael Additions: An oven-dried
flask was charged with catalyst 6 (0.12 mmol, 20 mol-%), 4-Å mo-
lecular sieves (20 mg) and toluene (2.5 mL). α,β-Unsaturated sul-
fonate 1[10] (0.6 mmol) and aromatic thiol 7 (0.5 mmol) were then
added sequentially to the flask. The flask was flushed with argon
and stoppered, and the mixture stirred at room temperature for 16–
142 h. Direct purification of the crude reaction mixture by
chromatography (silica gel, ether/pentane 1:6) afforded the desired
Michael adducts 8a–8k as colorless or pale-yellow oils. Data for
cyclohexyl 2-(phenylthio)propane-1-sulfonate (8a): Yield (0.134 g,
85%). IR (film): ν = 2938, 1449, 1354, 1163, 930, 871, 754 cm–1.
˜
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.30–7.44 (m, 5 H, Ph),
3
4.64 (quintet, JH,H = 5.0 Hz, 1 H, c-Hex), 3.70 (m, 1 H, CHSPh),
3
3
3.38 (dd, JH,H = 14.3, 3.0 Hz, 1 H, CHHSO3), 3.12 (dd, JH,H
=
3
14.3, 10.6 Hz, 1 H, CHHSO3), 1.55 (d, JH,H = 6.7 Hz, 3 H, CH3),
1.20–1.96 (m, 10 H, c-Hex) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ = 132.4, 131.6, 129.0, 128.1, 81.6, 57.5, 38.0, 32.6, 24.8,
23.5, 19.8 ppm. MS (EI): m/z (%) = 314 (39), 232 (100), 151 (29),
150 (54), 110 (17), 109 (15), 83 (6), 65 (5), 55 (9). C15H22O3S2
(314.47): calcd. C 57.29, H 7.05; found C 57.48, H 7.04.
[6]
For a review on the sulfa-Michael reaction, see: a) D. Enders,
K. Lüttgen, A. A. Narine, Synthesis 2007, 959–980; for recent
organocatalytic sulfa-Michael additions not cited in the review,
see: b) P. McDaid, Y. Chen, L. Deng, Angew. Chem. 2002, 114,
348–350; Angew. Chem. Int. Ed. 2002, 41, 338–340; c) P. Ricci,
A. Carlone, G. Bartoli, M. Bosco, L. Sambri, P. Melchiorre,
Adv. Synth. Catal. 2008, 350, 49–53.
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
(priority programme 1179 Organocatalysis) and the Fonds der
Chemischen Industrie. We thank BASF AG and Bayer AG for the
donation of chemicals and Prof. A. Berkessel, Köln, for a gift of
catalyst 5. The help of Dr. A. A. Narine during the preparation of
this manuscript is gratefully acknowledged.
[7]
[8]
The sulfa-Michael addition to α,β-unsaturated sulfonates has
rarely been studied, and no asymmetric variants exist: a) H.
Distler, Angew. Chem. 1965, 77, 291–302; Angew. Chem. Int.
Ed. Engl. 1965, 4, 300–311; b) A. Berkessel, M. Voges, Chem.
Ber. 1989, 122, 1147–1151; c) J. J. Reddick, J. Cheng, W. R.
Roush, Org. Lett. 2003, 5, 1967–1970.
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Chem. 2006, 4, 4319–4330.
[1] For general reviews on organocatalysis, see: a) P. I. Dalko,
Asymmetric Organocatalysis: Reactions and Experimental Pro-
cedures, Wiley-VCH, Weinheim, 2007; b) A. Dondoni, A.
Massi, Angew. Chem. 2008, 120, 4716–4739; Angew. Chem. Int.
Eur. J. Org. Chem. 2009, 1665–1668
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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