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Sumiya, T.; Takahashi, J.; Gotoh, H.; Urushima, T.; Shoji, M. Angew. Chem., Int.
Ed. 2006, 45, 958.
13. Some references on additives, see: (a) Yuan, Y.; Long, J.; Sun, J.; Ding, K. Chem.
Eur. J. 2002, 8, 5033; (b) Sibi, M. P.; Manyem, S.; Palencia, H. J. Am Chem. Soc.
2006, 128, 13660; (c) Gryko, D.; Zimnicka, M.; Lipin´ ski, R. J. Org. Chem. 2007, 72,
964; (d) Pihko, P. A.; Laurikainen, K. M.; Usano, A.; Nuberg, A. I.; Kaavi, J. A.
Tetrahedron 2006, 62, 317; (e) Zhou, Y.; Shan, Z. J. Org. Chem. 2006, 71, 9510; (f)
Luo, S.; Hu, H.; Li, J.; Zhang, L.; Mi, X.; Zheng, X.; Cheng, J.-P. Tetrahedron 2007,
63, 11307; (g) Chen, F.; Huang, S.; Zhang, H.; Liu, F.; Peng, Y. Tetrahedron 2008,
64, 9585; (h) Mun, S.; Lee, J.-E.; Yun, J. Org. Lett. 2006, 8, 4887; (i) Córdova, A.;
Notz, W.; Barbas, C. F., III Chem. Commun. 2002, 3024; (j) Wu, Y.-S.; Chen, Y.;
Deng, D.-S.; Cai, J. Synlett 2005, 16279.
14. Da, C.-S.; Che, L.-P.; Guo, Q.-P.; Wu, F.-C.; Ma, X.; Jia, Y.-N. J. Org. Chem. 2009, 74,
2541.
15. (a) Tang, Z.; Jiang, F.; Cui, F.; Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 5755; (b) Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.;
Gong, L.-Z.; Mi, A.-Q.; Jiang, Y.-Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003, 125, 5262.
11. Mitchell, J. M.; Finney, N. S. Tetrahedron Lett. 2000, 41, 8431.
12. (a) Compound 2a: White solid; mp 146–148 °C; ½a D20
ꢁ
+31 (c 2.13, CHCl3); 1H
NMR (400 MHz CDCl3) d 8.50 (br, 1H), 7.19–7.25 (m, 3H), 7.04–7.12 (m, 7H),
5.22–5.27 (dd, 1H, J = 10.8 Hz, J = 5.6 Hz), 3.75–3.78 (dd, 1H, J = 8.8 Hz,
J = 4.8 Hz), 3.72–3.75 (d, 1H, J = 10.4 Hz), 2.98–3.06 (m, 2H), 2.41 (br, 1H),
2.17 (s, 6H), 2.01–2.13 (m, 2H), 1.72–1.79 (m, 2H); 13C NMR (100 MHz CDCl3) d
174.5, 140.9, 133.6, 129.6, 127.9, 127.6, 127.4, 126.7, 73.6, 60.9, 53.7, 47.2,
41.1, 30.7, 26.0; HRMS exact mass calcd for C21H27N3O ([M+H]+) 338.2227,
found 338.2222; IR (KBr) 3323, 3030, 2920, 2852, 2780, 1637, 1500, 1453,
1105, 1014, 870, 749, 700, 615 cmꢀ1. (b) Compound 2b: White solid; mp 51–
52 °C; ½a 2D0
ꢁ
+13 (c 2.00, CHCl3); 1H NMR (400 MHz CDCl3) d 8.82 (br, 1H), 7.17–
7.23 (m, 3H), 7.01–7.09 (m, 7H), 5.09–5.12 (d, 1H, J = 10 Hz), 3.81–3.84 (d, 1H,
J = 10.8 Hz), 3.74–3.78 (dd, 1H, J = 9.2 Hz, J = 4.8 Hz), 3.01–3.09 (m, 2H), 2.53–
2.60 (m, 2H), 2.03–2.11 (m, 4H), 1.70–1.85 (m, 3H), 1.24–1.53 (m, 12H), 0.93 (t,
6H, J = 7.4 Hz); 13C NMR (100 MHz CDCl3) d 174.5, 141.7, 134.8, 129.6, 127.8,
127.6, 127.3, 127.2, 126.6, 126.5, 69.1, 60.9, 54.1, 49.7, 47.3, 30.5, 29.7, 28.3,
26.3, 22.7, 14.1; HRMS exact mass calcd for C29H43N3O ([M+H]+) 450.3479,
found 450.3482; IR (KBr) 3342, 3062, 3083, 3027, 2956, 2928, 2860, 2818,
16. Similar to 2b, we also synthesized another catalyst 2e starting from L-proline
and racemic diphenylethyl diamine. However, the diastereoselectivity of 2e
was not 1:1 but 2:1 with the ratio of (S,R,R)- to (S,S,S)-isomer, which was
determined by 1H NMR, because of the stereoselectivity of the chiral building
blocks in synthetic course. With 1% 2e in brine at room temperature, the
reaction of acetone with 4-nitrobenzaldehyde afforded aldol with 92% yield
and slightly lowered enantioselectivity (85%) within 20 h. It could be
concluded in combination of the asymmetric outcome of 2d that the catalyst
1661, 1490, 1457, 1378, 1296, 1158, 1103, 1074, 756, 701, 612 cmꢀ1
.
(c) Compound 2c: White ceraceous solid; mp 42–45 °C; ½a D20
ꢁ
+10 (c 1.81,
CHCl3); 1H NMR (400 MHz CDCl3) d 8.63–8.64 (d, 1H, J = 4.4 Hz), 7.15–7.25 (m,
3H), 7.00–7.08 (m, 7H), 5.11–5.15 (dd, 1H, J = 10.8 Hz, J = 4.8 Hz), 3.86–3.89 (d,
1H, J = 11.2 Hz), 3.68–3.72 (dd, 1H, J = 8.8 Hz, J = 6.0 Hz), 2.99–3.04 (m, 2H),
2.52–2.59 (m, 2H), 2.04–2.16 (m, 3H), 1.93–1.99 (m, 2H), 1.73–1.79 (m, 2H),
1.19–1.49 (m, 32H), 0.89 (t, 6H, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3) d 174.6,
141.7, 134.8, 129.6, 127.8, 127.6, 127.3, 127.2, 126.5, 69.0, 60.9, 54.1, 49.7,
47.4, 31.9, 30.5, 29.8, 29.7, 29.6, 29.3, 28.7, 27.5, 26.3, 22.7, 14.1; HRMS exact
mass calcd for C39H63N3O ([M+H]+) 590.5044, found 590.5048; IR (KBr) 3332,
3062, 3027, 2924, 2854, 1660, 1488, 1378, 1300, 1186, 1148, 1106, 1073, 1026,
from L-Pro and (R,R)-diphenylethyl diamine should be superior to that from L-
Pro and (S,S)-diphenylethyl diamine in consideration of the enantioselectivity
of the reaction. Compound 2e: (S,R,R): 1H NMR (400 MHz CDCl3) d 8.86 (br, 1H),
6.99–7.77 (m, 10H), 5.10–5.18 (m, 1H), 3.81–3.84 (m, 1H), 3.73–3.75 (m, 1H),
2.92–3.07 (m, 2H), 2.51–2.60 (m, 2H), 2.04–2.18 (m, 4H), 1.61–1.86 (m, 3H),
1.17–1.50 (m, 12H), 0.92 (t, 6H, J = 7.0 Hz); (S,S,S): 1H NMR (400 MHz CDCl3) d
8.67 (br, 1H), 6.99–7.77 (m, 10H), 5.26–5.33 (m, 1H), 3.87–3.93 (m, 1H), 3.65–
3.69 (m, 1H), 3.11–3.19 (m, 2H), 2.73–2.76 (m, 2H), 2.22–2.27 (m, 4H), 1.91–
2.05 (m, 3H), 1.17–1.50 (m, 12H), 0.92 (t, 6H, J = 7.0 Hz).
909, 880, 757, 700, 614 cmꢀ1. (d) Compound 2d: Colorless colloid solid; ½a 2D0
ꢁ
+87 (c 2.06, CHCl3); 1H NMR (400 MHz, CDCl3) d 8.82 (br, 1H), 7.16–7.22 (m,
3H), 6.99–7.08 (m, 7H), 5.09–5.13 (dd, 1H, J = 11 Hz, J = 3 Hz), 3.81–3.84 (d, 1H,
J = 11.2 Hz), 3.74–3.77 (dd, 1H, J = 8.8 Hz, J = 5.2 Hz), 3.01–3.08 (m, 2H), 2.53–
2.60 (m, 2H), 2.02–2.11 (m, 4H), 1.68–1.85 (m, 3H), 1.24–1.53 (m, 12H), 0.93 (t,
6H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) d 174.6, 142.0, 134.9, 129.6, 127.8,
127.6, 127.2, 127.1, 126.5, 69.2, 61.0, 54.1, 49.4, 47.4, 30.9, 29.6, 28.1, 26.2,
22.7, 14.1; HRMS exact mass calcd for C29H43N3O ([M+H]+) 450.3479, found
450.3469; IR (KBr) 3326, 3084, 3062, 3030, 2955, 2928, 2861, 1670, 1496,
17. General procedure for 2b-catalyzed aldol reaction in brine. A mixture of
ketone (2.0 mmol), DNP (0.37 mg), and the catalyst 2b (0.9 mg) in brine
(1.2 mL) was introduced with aldehyde (0.2 mmol). Then the reaction
mixture was stirred at room temperature until the reaction was complete
(determined by TLC). After addition of saturated aqueous NH4Cl (5 mL), the
mixture was extracted with ethyl acetate thrice. Then the combined organic
layers were dried over anhydrous Na2SO4, concentrated to dryness in vacuo,
and purified by preparative TLC to achieve the aldol products and the
recycled catalyst 2b.
1456, 1379, 1299, 1247, 1157, 1098, 757, 700, 625 cmꢀ1
.