Y.-J. Cao et al. / Tetrahedron Letters 48 (2007) 21–24
23
In order to expand the generality of this catalytic sys-
Acknowledgments
tem, the Michael additions of other cyclic and acyclic
ketones to b-nitrostyrene (4a) were examined using 2e/
PhCOOH as catalyst. As shown in Table 3, the reaction
of acetone with b-nitrostyrene afforded the desired
product 5o in 65% isolated yield with 57% ee (Table 3,
entry 1). Heterocyclic ketones worked very well in this
reaction to exhibit moderate to good stereoselectivities
with the ee and dr up to 89% and 99/1, respectively
(Table 3, entries 2–4). In the case of tetrahydro-4H-
thiopyran-4-one and N-Boc-piperidone, the addition of
a small amount of CH2Cl2 (100 lL) to the reaction
system was necessary to make the reaction efficient,
because both substrates were solids and could not be
readily suspended in water.
We are grateful to the National Science Foundation of
China (20472021 and 20672040), the National Key Pro-
ject for Basic Research of China (2004CCA00100), the
program for new century excellent talents in university
(NCET-05-0672), and the Hubei Province Science Fund
for Distinguished Young Scholar (2004ABBC011), for
support of this research.
Supplementary data
Supplementary data associated with this article can be
In summary, we have successfully developed a series of
bifunctional pyrrolidine–thiourea organocatalysts, with
the catalytic activity being tuned easily by simply chang-
ing the thiourea scaffold. These catalysts have proven to
be robust and can be efficiently used in the direct
Michael additions of ketones to various nitroolefins in
water. High yields (up to 98%) and great stereoselectiv-
ities (up to 99:1 dr and 99% ee) make the current
research very valuable. Further studies focusing on the
full scope of these catalysts in asymmetric catalysis in
both aqueous and organic media are currently in pro-
gress in this laboratory.
References and notes
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O
Ph
10 mol %
O
2e / benzoic acid
NO2
NO2
+
R2 Ph
R1
H2O, 35 oC
R1
R2
5o-s
3b-f
4a
Entry Ketone Product Time Yieldb drc
eed
(syn:anti) (%)
(h)
64
(%)
65
O
O
1
5o
—
57
2
5p
5q
42
11
80
90
99:1
98:2
88
89
O
O
3e
S
O
´
´
Hafren, J.; Cordova, A. Org. Biomol. Chem. 2006, 4, 38;
(h) Zu, L.; Wang, J.; Li, H.; Wang, W. Org. Lett. 2006, 8,
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Cheng, C.; Sun, J.; Wang, C.; Zhang, Y.; Wei, S.; Jiang,
F.; Wu, Y. Chem. Commun. 2006, 215.
4e
5r
11
88
97:3
63
N
Boc
a Unless otherwise specified, the reaction was carried out with 10 equiv
of ketones (3b–f) and 0.5 mmol 4a in the presence of 0.05 mmol 2e
and 0.05 mmol benzoic acid at 35 °C in 1 mL H2O.
b Isolated yields.
c Determined by chiral HPLC analysis of the mixture of syn/anti
product.
d Determined by chiral HPLC analysis (chiralpak AS-H, AD-H).
e 100 lL of CH2Cl2 was added.
7. List, B.; Pojarlier, P.; Martin, H. J. Org. Lett. 2001, 3, 2423.
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Roder, H. Synthesis 2001, 171; (b) Berner, O. M.;
Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877;
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