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LETTER
Table 3 Asymmetric Addition of 5b–h to 4e with Catalyst 1a
References
O
O
(1) For reviews of asymmetric protonations: (a) Duhamel, L.;
Duhamel, P.; Plaquevent, J. C. Tetrahedron: Asymmetry
2004, 15, 3653. (b) Yanagisawa, A.; Ishihara, K.;
Yamamoto, H. Synlett 1997, 411. (c) Mohr, J. T.; Hong,
A. Y.; Stoltz, B. M. Nat. Chem. 2009, 1, 359.
O
O
1 (2 mol%)
+ RSH
Ph
N
RS
N
Ph
4 Å MS, CH2Cl2
–40 °C
H
H
Bn
Bn
6i–o
4e
5b: R = i-Pr
5c: R = cyclopentyl
5d: R = 4-t-BuC6H4CH2
5e: R = 4-MeOC6H4CH2
5f: R = 4-ClC6H4CH2
5g: R = Ph
(2) (a) Morita, M.; Drouin, L.; Motoki, R.; Kimura, Y.;
Fujimori, I.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
2009, 131, 3858. (b) Cheon, C. H.; Yamamoto, H. J. Am.
Chem. Soc. 2008, 130, 9246. (c) Poisson, T.; Dalla, V.;
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(e) Sugiura, M.; Nakai, T. Angew. Chem. Int. Ed. 1997, 36,
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(e) Hamashima, Y.; Tamura, T.; Suzuki, S.; Sodeoka, M.
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J. P.; de Vries, J. G.; Blackmond, D. G.; Hii, K. K. M. Chem.
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5h: R = Ac
Entry
Thiol
5b
Time (h) Product
Yield (%)b ee (%)c
1
72
72
40
40
24
24
24
24
24
6i
76
70
92
89
93
90
94
91
92
89
89
87
90
81
13
46
37
73
2
5c
5d
5e
5f
6j
3
6k
6l
4
5
6m
6n
6o
6n
6o
6
5g
5h
5g
5h
7
8d
9d
(4) Leow, D.; Lin, S.; Chittimalla, S. K.; Fu, X.; Tan, C. H.
Angew. Chem. Int. Ed. 2008, 47, 5641.
a Unless otherwise indicated, the reactions were carried out with 0.2
mmol of 4e and 0.3 mmol of 5 in 1 mL of CH2Cl2 under nitrogen
atmosphere.
(5) Selected reviews of bifunctional organocatalysis:
(a) Connon, S. J. Chem. Commun. 2008, 2499. (b) Dalko,
P. I.; Moisan, L. Angew. Chem. Int. Ed. 2004, 43, 5138.
(c) Pihko, P. M. Angew. Chem. Int. Ed. 2004, 43, 2062.
(d) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719.
Selected reviews of squaramide catalysis: (e) Alemán, J.;
Parra, A.; Jiang, H.; Jørgensen, K. A. Chem. Eur. J. 2011,
17, 6890. (f) Storer, R. I.; Aciro, C.; Jones, L. H. Chem. Soc.
Rev. 2011, 40, 2330.
b Isolated yields.
c Determined by HPLC analysis using a Chiracel OD-H or AD-H col-
umn.
d Compound 5g or 5h was added via syringe pump over 12 h and the
reactions were carried out at r.t.
In summary, we have demonstrated that chiral squaramide
1 worked well as a bifunctional organocatalyst in the tan-
dem Michael–protonation reaction of a-substituted
acrylimides and alkyl thiols and furnished the correspond-
ing products with moderate to good enantioselectivities.
These results significantly expanded the scope of the
asymmetric catalysis of bifunctional squaramide. Further
investigations to improve the enantioselectivity by using
assembled organocatalyst are ongoing in our laboratory.
(6) Berkessel, A.; Gröger, H. Asymmetric Organocatalysis:
From Biomimetic Concepts to Applications in Asymmetric
Synthesis; Wiley-VCH: Weinheim, 2004.
(7) (a) Li, B. J.; Jiang, L.; Liu, M.; Chen, Y. C.; Ding, L. S.; Wu,
Y. Synlett 2005, 603. (b) Emori, E.; Arai, T.; Sasai, H.;
Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 4043.
(8) For selected chiral squaramide catalysts promoted
asymmetric organic reactions, see: (a) Dai, L.; Wang, S. X.;
Chen, F. E. Adv. Synth. Catal. 2010, 352, 2137. (b) Dai, L.;
Yang, H. J.; Chen, F. E. Eur. J. Org. Chem. 2011, 26, 5071.
(c) Zhu, Y.; Malerich, J. P.; Rawal, V. H. Angew. Chem. Int.
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J. P.; Rawal, V. H. Org. Lett. 2010, 12, 2028. (e) Qian, Y.;
Ma, G.; Lv, A.; Zhu, H.-L.; Zhao, J.; Rawal, V. H. Chem.
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Zhang, W.; Luo, S.-P.; Zhong, A.-G.; Xia, A.-B.; Xu, Z.-Y.
Chem. Eur. J. 2010, 16, 4177. (g) Yang, W.; Du, D.-M.
Org. Lett. 2010, 12, 5450. (h) Lee, J. W.; Ryu, T. H.; Oh,
J. S.; Bae, H. Y.; Jang, H. B.; Song, C. E. Chem. Commun.
2009, 7224.
Supporting Information for this article is available online at
(9) Evans, D. A.; Mathre, D. J.; Scott, W. L. J. Org. Chem. 1985,
50, 1830.
Synlett 2012, 23, 314–316
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