480
Vol. 52, No. 4
room temperature for 2 h, and the resulting mixture was concentrated in search was also supported in part by a Grant-in Aid for Scientific Research
vacuo. The residue was purified by column chromatography on silica gel from the Ministry of Education, Culture, Sports, Science and Technology of
(chloroform/methanol, 40 : 1, 9 : 1) to give 10e (111.8 mg, 99%) as a color- Japan.
less solid. mpϭ185—187 °C (decomposition). [a]D23ϭϩ8.38° (cϭ1.00,
CH3OH). IR (KBr) 3284, 3093, 2940, 2863, 1671, 1570, 1475, 1439, 1389, References and Notes
1
1281, 1185, 1131, 1037 cmϪ1. H-NMR (500 MHz, CDCl3) d: 10.58 (br s,
1H), 8.66 (br s, 1H), 7.85 (s, 2H), 7.75 (s, 1H), 7.41 (s, 1H), 6.09 (br s, 1H),
4.17 (br s, 1H), 3.62 (br s, 2H), 3.41 (br s, 2H), 3.31 (br s, 1H), 2.17—1.77
(m, 8H), 1.27 (m, 4H). 13C-NMR (125 MHz, CD3OD) d: 169.57, 157.07,
143.40, 133.17 (JCFϭ33.1 Hz), 124.83 (JCFϭ273.1 Hz), 118.87 (br), 115.45
(JCFϭ4.1 Hz), 61.16, 54.99, 54.36, 47.37, 33.95, 33.06, 31.20, 25.84, 25.75,
25.06. HR-MS (FAB, MϩH) Calcd for C20H25F6N4O2 467.1882, Found
467.1885.
1) Pelmutter P., “Conjugate Addition Reactions in Organic Synthesis,”
Pergamon Press, Oxford, 1992.
2) For recent reviews see: Kanai M., Shibasaki M., “Catalytic Asymmet-
ric Synthesis,” 2nd ed., ed. by Ojima I., Wiley, New York, 2000.
3) For recent reviews see: Tomioka K., Nagaoka Y., “Comprehensive
Asymmetric Catalysis,” Vol. 3, Chap. 31.1, ed. by Jacobsen E. N.,
Pfaltz A., Yamamoto H., Springer Verlag, Berlin, 1999.
4) For recent reviews see: Dalko P. I., Moisan L., Angew. Chem. Int. Ed.,
40, 3726—3748 (2001).
5) For recent reviews see: Jarvo E. R., Miller S. J., Tetrahedron, 58,
2481—2495 (2002).
6) Nagasawa K., Georgieva A., Takahashi H., Nakata T., Tetrahedron, 56,
187—192 (2000).
7) Nagasawa K., Georgieva A., Takahashi H., Nakata T., Tetrahedron, 57,
8959—8964 (2001).
8) Kita T., Georgieva A., Hashimoto Y., Nakata T., Nagasawa K., Angew.
Chem. Int. Ed., 41, 2832—2834 (2002).
9) Nagasawa K., Hashimoto Y., Chem. Rec., 3, 201—211 (2003).
10) Kashman Y., Hirsh S., McConnell O. J., Ohtani I., Kusumi T., Kaki-
sawa H., J. Am. Chem. Soc., 111, 8925—8926 (1989).
Compound 10f As described for 10b, 10a (33.3 mg, 0.0902 mmol) and
imidazole-4-acetic acid monohydrochloride (28.6 mg, 0.176 mmol) were
allow to react to give 10f (33.3 mg, 60%) as a colorless solid. mpϭ228—
232 °C (decomposition). [a]D24ϭϩ43.1° (cϭ1.10, CH3OH). IR (KBr) 3341,
3129, 2936, 2862, 1703, 1638, 1561, 1475, 1442, 1393, 1274, 1227, 1179,
1141 cmϪ1. 1H-NMR (500 MHz, CD3OD) d: 7.95 (s, 2H), 7.52 (s, 1H), 7.46
(s, 1H), 6.87 (s, 1H), 3.65 (m, 1H), 3.53 (m, 1H), 3.47 (s, 2H), 2.05 (br d,
Jϭ11.1 Hz, 1H), 1.95 (br d, Jϭ6.4 Hz, 1H), 1.76 (br s, 2H) 1.35 (m, 4H).
13C-NMR (125 MHz, CD3OD) d: 173.04, 157.07, 143.45, 136.21, 133.10
(JCFϭ33.1 Hz), 133.03, 124.91 (JCFϭ273.1 Hz), 118.89 (br), 118.03, 115.40
(JCFϭ4.1 Hz), 54.96, 54.38, 49.86, 35.46, 34.05, 33.14, 25.87. HR-MS
(FAB, MϩH) Calcd for C20H22F6N5O2 478.1678, Found 478.1690.
Compound 10g To
a
mixture of 3,5-bis(trifluoromethyl)aniline 11) Ohtani I., Kusumi T., Kakisawa H., Kashman Y., Hirsh S., J. Am.
Chem. Soc., 114, 8472—8479 (1992).
(61.1 ml, 0.394 mmol) and pyridine (55 ml, 0.680 mmol) in dichloromethane
(2 ml) was added 4-nitrophenylchloroformate (90.3 mg, 0.448 mmol) at 12) Ohtani I., Kusumi T., Kakisawa H., Tetrahedron Lett., 33, 2525 (1992).
room temperature. The mixture was stirred for 5 min, the resulting mixture 13) Jares-Erijman E. A., Ingrum A. L., Carney J. R., Rinehart K. L., Sakai
was added to a solution of 10a (82.6 mg, 0.224 mmol) in dichloromethane
R., J. Org. Chem., 58, 4805—4808 (1993).
(1 ml). To this was added N,N-diisopropylethylamine (39 ml, 0.224 mmol), 14) Berlinck R. G. S., Braekman J. C., Daloze D., Bruno I., Riccio R.,
and the whole mixture was stirred for an additional 20 h at room tempera-
ture. Then saturated NaHCO3aq was added, followed by dilution with
Ferri S., Spampinato S., Speroni E., J. Nat. Prod., 56, 1007—1015
(1993).
dichloromethane. The organic layer was washed with brine, dried over 15) Curran D. P., Kuo L. H., Tetrahedron Lett., 36, 6647—6650 (1995).
MgSO4, filtered and concentrated in vacuo. The residue was purified by col- 16) Schreiner P. R., Wittkopp A., Org. Lett., 4, 217—220 (2002).
umn chromatography on silica gel (hexane/ethyl acetate, 3 : 1, 2 : 1) to give 17) Wittkopp A., Schreiner P. R., Chem. Eur. J., 9, 407—414 (2003).
10g (132.1 mg, 94%) as a yellow solid. mpϭ249—252 °C (decomposition). 18) Vachal P., Jacobsen E. N., Org. Lett., 2, 867—870 (2000).
[a]D23ϭϩ36.4° (cϭ1.00, CH3OH). IR (KBr) 3357, 1614, 1593, 1498, 1389, 19) Vachal P., Jacobsen E. N., J. Am. Chem. Soc., 124, 10012—10014
1
1336, 1289, 1183, 1128, 1113 cmϪ1. H-NMR (500 MHz, CD3OD) d: 7.82
(2002).
(s, 4H), 7.31 (s, 2H), 3.56 (br s, 2H), 2.01 (br s, 2H), 1.79 (br s, 2H), 1.37 (m, 20) Wenzel A. G., Jacobsen E. N., J. Am. Chem. Soc., 124, 12964—12965
4H). 13C-NMR (125 MHz, CD3OD) 157.55, 143.10, 132.92 (JCFϭ33.1 Hz),
(2002).
124.67 (JCFϭ273.0 Hz), 118.67 (br), 115.36 (br), 55.71, 33.65, 26.11. HR- 21) Okino T., Hoashi Y., Takemoto Y., Tetrahedron Lett., 44, 2817—2821
MS (FAB, MϩH) Calcd for C24H21F12N4O2 625.1473, Found 625.1470. (2003).
Typical Procedure for the Asymmetric Hetero-Michael Reaction To 22) Okino T., Hoashi Y., Takemoto Y., J. Am. Chem. Soc., 125, 12672—
a mixture of g-crotonolactone (1) (9.6 ml, 0.131 mmol) and 10f (6.3 mg, 12673 (2003).
0.0132 mmol) in toluene (1.3 ml) was added pyrrolidine (2) (33.1 ml, 23) Alcazar V., Moran J. R., de Mendoza J., Tetrahedron Lett., 36, 3941—
0.397 mmol) at Ϫ40 °C. The resulting mixture was stirred vigorously at 3944 (1995).
Ϫ40 °C for 7 h. Then saturated NH4Claq was added, and the organic layer 24) Howard-Jone A., Murphy P. J., Thomas D. A., J. Org. Chem., 64,
was extracted with chroloform/methanol (ϭ40 : 1) solution. The extracts 1039—1041 (1999).
were dried over MgSO4, filtered and concentrated in vacuo, and the residue 25) Martin-Portugues M., Alcazar V., Prados P., de Mendoza J., Tetrahe-
was purified by column chromatography on silica gel (chroloform/methanol, dron, 58, 2951—2955 (2002).
1 : 0, 40 : 1) to give 3 (10.7 mg, 52%). The enantiomeric excess of 3 was de- 26) Allingham M. T., Howard-Jones A., Murphy P. J., Thomas D. A.,
termined by the use of chiral HPLC analysis (Chiralpak AD-H column, Caulkett P. W. R., Tetrahedron Lett., 44, 8677—8680 (2003).
0.46 cm (f)ϫ25 cm (L), n-hexane/2-propanol 95 : 5, flow rateϭ1.0 ml/min, 27) Quite recently, Takemoto and co-workers also reported a very similar
minor; 15.1 min (t1), major; 18.1 min (t2).
type of chiral thiourea catalyst for the Michael reaction of malonates
to nitroolefins.22)
Acknowledgements We are grateful for financial support in the form of 28) The ee values of 4 were determined by HPLC using a Chiralpak AD-H
an Award in Synthetic Organic Chemistry from Toray Co., Ltd., Japan and a
grant from the Pharmacy Research Encouragement Foundation. This re-
column. The absolute configuration of 4 is under investigation.