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Q. Chen et al.
LETTER
(17) Under the same reaction conditions, Prof. Barbas’ group
3075. (c) Maltsev, O. V.; Kucherenko, A. S.; Zlotin, S. G.
Eur. J. Org. Chem. 2009, 5134. (d) Mager, I.; Zeitler, K.
Org. Lett. 2010, 12, 1480.
found that Michael addition of cyclohexanone to
nitrostyrene catalyzed by diamine A bearing long alkyl
chains (Figure 1) with TFA gave 54% yield of product 5a
with 89% ee and a syn/anti ratio of 95:5. See ref. 6a.
(18) Typical Procedure for the Asymmetric Michael Addition
To a solution of the amine catalyst 1e19 (8.5 mg, 0.04 mmol)
and ILS sulfonic acid 3a20 (16.4 mg, 0.04 mmol) in H2O (0.8
mL) was added ketone (2.0 mmol) at r.t. The reaction
mixture was stirred for 20 min, and then nitroolefin (0.4
mmol) was added. The reaction mixture was stirred until
complete conversion of the nitroolefin (monitored by TLC)
and then extracted with CH2Cl2 (2 × 2 mL). The combined
organic phase was concentrated under vacuum to give the
crude residue, which was purified by flash column
chromatography (silica gel, hexane–EtOAc) to afford the
Michael adduct 5. The syn/anti ratio was determined by 1H
NMR spectroscopy of the crude mixture and the ee was
determined by chiral HPLC.
(9) For some selected examples of aldol reactions in aqueous
media, see: (a) Hayashi, Y.; Aratake, S.; Okano, T.;
Takahashi, J.; Sumiya, T.; Shoji, M. Angew. Chem. Int. Ed.
2006, 45, 5527. (b) Font, D.; Jimeno, C.; Pericàs, M. A. Org.
Lett. 2006, 8, 4653. (c) Wu, Y.; Zhang, Y.; Yu, M.; Zhao, G.;
Wang, S. Org. Lett. 2006, 8, 4417. (d) Mase, N.; Nakai, Y.;
Ohara, N.; Yoda, H.; Takabe, K.; Tanaka, F.; Barbas, C. F.
III. J. Am. Chem. Soc. 2006, 128, 734.
(10) For recent reviews about organocatalysis in aqueous media,
see: (a) Brogan, A. P.; Dickerson, T. J.; Janda, K. D. Angew.
Chem. Int. Ed. 2006, 45, 8100. (b) Hayashi, Y. Angew.
Chem. Int. Ed. 2006, 45, 8103. (c) Mase, N.; Barbas, C. F.
III. Org. Biomol. Chem. 2010, 8, 4043.
(11) The results from Prof. Barbas’ group indicated that the Aldol
reaction could not proceed in water when catalyst did not
include hydrophobic group. See ref. 9d.
(12) (a) Wu, J.; Ni, B.; Headley, A. D. Org. Lett. 2009, 11, 3354.
(b) Zheng, Z.; Perkins, B. L.; Ni, B. J. Am. Chem. Soc. 2010,
132, 50. (c) Ghosh, S. K.; Zheng, Z.; Ni, B. Adv. Synth.
Catal. 2010, 352, 2378. (d) Sarkar, D.; Bhattarai, R.;
Headley, A. D.; Ni, B. Synthesis 2011, 1993.
(13) Akahane, Y.; Inomata, K.; Endo, Y. Heterocycles 2011, 82,
1727.
(14) Peschke, B.; Bak, S.; Hohlweg, R.; Pettersson, I.; Refsgaard,
H. H. F.; Viuff, D.; Rimvall, K. Bioorg. Med. Chem. 2004,
12, 2603.
(15) Gao, Q.; Liu, Y.; Lu, S.-M.; Li, J.; Li, C. Green Chem. 2011,
13, 1983.
(16) Chiral pyrrolidines 1c and 1d were found to be effective
organocatalysts for Michael addition of ketones to
nitroolefins with high selectivity in organic solvent DMF.
See ref. 4g.
Analytic Data of 5a
1H NMR (400 MHz, CDCl3): δ = 7.36–7.22 (m, 3 H), 7.17
(d, J = 7.2 Hz, 2 H), 4.95 (dd, J = 12.4, 4.4 Hz, 1 H), 4.64
(dd, J = 12.4, 10.0 Hz, 1 H), 3.77 (dt, J = 14.4, 4.8 Hz, 1 H),
2.74–2.64 (m, 1 H), 2.54–2.33 (m, 2 H), 2.14–2.04 (m, 1 H),
1.83–1.50 (m, 4 H), 1.30–1.18 (m, 1 H). 13C NMR (100
MHz, CDCl3): δ = 211.9, 137.7, 128.9, 128.2, 127.8, 78.9,
52.5, 43.9, 42.7, 33.2, 28.5, 25.0. HPLC (Chiralpak AD-H,
i-PrOH–hexane = 10:90, flow rate = 0.5 mL/min, λ = 254
nm): tR (minor) = 19.4 min; tR (major) = 24.7 min;
ee = 92%.
(19) Gao, Q.; Liu, Y.; Lu, S.-M.; Li, J.; Li, C. Green Chem. 2011,
13, 1983.
(20) Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver, K.
J.; Forbes, D. C.; Davis, J. H. Jr. J. Am. Chem. Soc. 2002,
124, 5962.
Synlett 2013, 24, 839–842
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