4
238
Y.-C. Teo, G.-L. Chua / Tetrahedron Letters 49 (2008) 4235–4238
Table 3
Recycling studiesa of the siloxy-L-serine catalyzed direct aldol reaction in [bmim][BF
4
]
1
0 mol%
NH2
COOH
O
O
OH
O
TBDPSO
2
+
H
1'
+
syn isomer
NO2
BF -
NO2
+
4
N
N
1a
3
Cycle
T (h)
Yieldb (%)
anti/sync (%)
eed (%)
1
2
3
4
18
18
48
60
86
84
72
68
82:18
82:18
81:19
82:19
90
88
86
86
a
Unless otherwise noted, the reaction was performed with aldehyde (0.5 mmol), ketone (2.5 mmol), and siloxy serine organocatalyst (0.05 mmol) in [bmim][BF
at room temperature.
4
] (0.5 mL)
b
Combined yield of isolated diastereomers.
c
Diastereoselectivity was determined by 1H NMR analysis of the reaction mixture.
d
Enantiomeric excess refers to the anti isomer and was determined by HPLC analysis on a chiral phase.
2
002, 43, 8741; (c) Córdova, A. Tetrahedron Lett. 2004, 45, 3949; (d)
Acknowledgment
Miao, W.; Chan, T.-H. Adv. Synth. Catal. 2006, 348, 1711; (e) Ni, B.; Zhang, Q.;
Headley, A. D. Green Chem. 2007, 9, 737; (f) Zhou, L.; Wang, L. Chem. Lett. 2007,
36, 628.
We thank the National Institute of Education (Grant No. RP5/06
TYC), Nanyang Technological University, for their generous finan-
cial support.
5. (a) Córdova, A.; Zou, W.; Ibrahem, I.; Reyes, E.; Engqvist, M.; Liao, W.-W. Chem.
Commun. 2005, 3586; (b) Zou, W.; Ibrahem, I.; Dziedzic, P.; Sundén, H.;
Córdova, A. Chem. Commun. 2005, 4946; (c) Dziedzic, P.; Zou, W.; Hafrén, J.;
Córdova, A. Org. Biomol. Chem. 2006, 4, 38; (d) Córdova, A.; Zou, W.; Dziedzic,
P.; Ibrahem, I.; Reyes, E.; Xu, Y. Chem. Eur. J. 2006, 12, 5383; (e) Jiang, Z.; Liang,
Z.; Wu, X.; Lu, Y. Chem. Commun. 2006, 2801; (f) Limbach, M. Tetrahedron Lett.
Supplementary data
2
006, 47, 3843; (g) Deng, D.-S.; Cai, J. Helv. Chim. Acta 2007, 90, 119; (h) Wu, X.;
Jian, Z.; Shen, H.-M.; Lu, Y. Adv. Synth. Catal. 2007, 349, 812; (i) Ramasastry, S. S.
V.; Zhang, H.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2007, 129, 288; (j)
Ramasastry, S. S. V.; Albertshofer, K.; Utsumi, N.; Tanaka, F.; Barbas, C. F., III.
Angew. Chem., Int. Ed. 2007, 46, 5572; (k) Teo, Y.-C. Tetrahedron: Asymmetry
2007, 18, 1155.
(a) Otto, S.; Engberts, J. B. F. N. Org. Biomol. Chem. 2003, 1, 2809; (b) Breslow, R.
Acc. Chem. Res. 2004, 37, 471; (c) Lindstrom, U. M.; Anderson, F. Angew. Chem.,
Int. Ed. 2006, 45, 548.
Hayashi, Y.; Sumiya, T.; Takashi, J.; Gotoh, H.; Urushima, T.; Shoji, M. Angew.
Chem., Int. Ed. 2006, 45, 958.
General procedure for the asymmetric direct aldol reaction in ionic liquids.
Preparation of (2R,1 S)-2-[hydroxy-(4-nitrophenyl)-methyl]-cyclohexanone 1a: A
catalytic amount of siloxy serine catalyst (0.0172 g, 0.05 mmol, 0.1 equiv) was
added to a vial containing 4-nitrobenzaldehyde (0.0760 g, 0.5 mmol, 1.0 equiv),
References and notes
6
.
1
2
3
.
.
.
For recent reviews, see: (a) Alcaide, B.; Almendros, P. Eur. J. Org. Chem. 2002,
595; (b) Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem. Soc. Rev. 2004, 33, 65; (c)
Schetter, B.; Mahrwald, R. Angew. Chem., Int. Ed. 2006, 45, 7506; (d) Mukherjee,
S.; Yang, J.-W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471.
For a recent review, see: (a) Ranke, J.; Stolte, S.; Strömann, R.; Arning, J.; Jastorff,
B. Chem. Rev. 2007, 107, 2183; For examples, see: (b) Stolte, S.; Matzke, M.;
Arning, J.; Böschen, A.; Pitner, W. R.; Welz-Biermann, U.; Jastorff, B.; Ranke, R.
Green Chem. 2007, 9, 1170.
(a) Jacques, M. Adv. Synth. Catal. 2006, 348, 275; (b) Chen, S.-L.; Chua, G.-L.; Ji,
S.-J.; Loh, T.-P. Ionic Liquid: A Green Solvent for Organic Transformations I, in
Ionic Liquids in Organic Synthesis. In ACS Symposium Series 950; Malthotra, S. V.,
Ed.; American Chemical Society, 2007; p 161; (c) Chen, S.-L.; Chua, G.-L.; Ji, S.-J.;
Loh, T.-P. Ionic Liquid: A Green Solvent for Organic Transformations II, in Ionic
Liquids in Organic Synthesis. In ACS Symposium Series 950; Malthotra, S. V., Ed.;
American Chemical Society, 2007; p 177; (d) Parvulescu, V. I.; Hardacre, C. Chem.
Rev. 2007, 107, 2615; (e) Afonsa, C. A. M.; Branco, L. C.; Candeias, N. R.; Gois, P. M.
P.; Lourenco, N. M. T.; Mateus, N. M. M.; Rosa, J. N. Chem. Commun. 2007, 2669.
(a) Kotrusz, P.; Kimentova, I.; Gotov, B.; Toma, S.; Solcaniova, E. Chem. Commun.
1
7
8
.
.
0
cyclohexanone (0.26 mL, 2.5 mmol, 5 equiv), and [bmim][BF
in a closed system. The reaction mixture was stirred at room temperature for
8 h and subsequently extracted with diethyl ether (6 mL ꢁ 5). The combined
organic extracts were dried with anhydrous MgSO and the solvent removed
4
] (0.5 mL) under air
1
4
under reduced pressure. The crude aldol product was purified by silica gel
column chromatography (hexane/ethyl acetate 4:1) to afford 1a as a white solid
(
0.107 g, 86% yield). The diastereomeric anti–syn ratio was determined by 1
H
NMR analysis of the reaction mixture: d 5.48 (d, 1H, J = 1.8 Hz, syn, minor), 4.89
d, 1H, J = 8.8 Hz, anti, major). Enantiomeric excess was determined by HPLC
with a Chiralcel AD-H column (hexane/i-PrOH = 90/10, 1.0 mL/min, k = 254 nm,
0 °C): t = 26.3 min (minor) and 34.9 min (major).
(
4
.
2
R
2
002, 2510; (b) Loh, T. P.; Feng, L.-C.; Yang, H. Y.; Yang, J.-Y. Tetrahedron Lett.