J. You and K. Ma
(
2
S)-4-Isopropyl-2-[3-((S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-imidazol-
-yl)phenyl]-1-phenyl-4,5-dihydro-1H-imidazole [(S)-1 f]: A solution of
isophthaloyl dichloride (4.06 g, 20 mmol) in CH Cl (40 mL) was added
dropwise at 08C to a stirred solution of l-valinol (4.12 g, 40 mmol) and
triethylamine (5.5 mL, 40 mmol) in CH Cl (70 mL). The reaction mix-
phy on silica gel with elution with ethyl acetate/petrol ether to afford the
racemic nitroaldol adduct.
2
2
General procedure for the catalytic enantioselective Henry reaction: Cu-
A
H
R
U
G
2
(OTf) (18.1 mg, 0.05 mmol), ligand (S)-1 (0.0525 mmol), and ethanol
2
2
(1.5 mL) were placed in a Schlenk tube fitted with a magnetic stirrer
under N2 at room temperature. After the mixture had been allowed to
stir for 2 h, aldehyde (0.5 mmol) was added, and this was followed by the
addition of dry freshly distilled nitromethane (0.26 mL, 5 mmol) and tri-
ture was then allowed to warm to room temperature, stirring was contin-
ued for 12 h, and then water (100 mL) was added. The layers were sepa-
rated, the organic layer was dried over Na SO , and the removal of the
2 4
solvent in vacuo gave a white solid, which was recrystallized from CH
2
Cl
2
A
H
R
U
G
to afford 3 f as white crystals (6.4 g, 95%).
same temperature for 24 h, volatiles were then removed in vacuo, and
the residue was purified by column chromatography on silica gel with
elution with ethyl acetate/hexane to afford the nitroaldol adduct.
A solution of 3 f (3.67 g, 10.9 mmol) in SOCl
for 5 h, excess thionyl chloride was then removed under reduced pressure
to afford 4 f, and CH Cl (60 mL), Et N (9.0 mL, 66 mmol), and aniline
2.2 mL, 24 mmol) were added to the residue at 08C. The mixture was
2
(5 mL) was stirred at reflux
The reported yields of asymmetric Henry reactions are isolated yields
and are the averages of at least two runs. The Henry reaction products
2
2
3
(
1
13
then allowed to warm to room temperature and stirred for 24 h and then
washed with NaOH (10%, 50 mL), and the aqueous fraction was extract-
are known and their H and C NMR spectra agreed with those in the
[
6d,9]
literature cited below.
Enantiomeric excesses were determined by
HPLC (LabTech 600 series) with Chiracel OD-H, OD, OJ, or AD-H col-
umns. The absolute configurations of nitroaldol adducts were assigned by
comparison with literature compounds.
ed with CH
over Mg SO
2
Cl
2
(350 mL). The combined organic layers were dried
2
4
and the solvent was removed in vacuo to give a brown
[
6d,9]
solid, which could be purified by column chromatography on silica gel
with elution with ethyl acetate/methanol (9:1) to afford (S)-1 f as a pale
2
D
5
yellow semi-solid (4.07 g, 83%). [a]
3
= 91.5 (c = 0.55 in CHCl );
1
3
H NMR (600 MHz, CDCl ): d = 0.91 (d, J = 6.6 Hz, 6H), 0.99 (d, J =
Acknowledgements
6
4
6
2
1
1
.6 Hz, 6H), 1.86–1.91 (m, 2H), 3.57 (dd, J = 7.2 Hz, 9.6 Hz, 2H), 4.02–
.06 (m, 2H), 3.59 (dd, J = 7.2 Hz, 9.6 Hz, 2H), 6.71–6.72, (m, 4H),
.94–6.97 (m, 2H), 7.09–7.14 (m, 5H), 7.35 (2d, J = 1.8 Hz, 1.8 Hz,
H), 7.89 ppm (t, J = 1.2 Hz, 1H); C NMR (150 MHz, CDCl ): d =
3
7.76, 18.73, 32.94, 56.11, 70.03, 122.59, 123.18, 127.71, 128.55, 129.18,
This work was supported by grants from the National Natural Science
Foundation of China (no. 20572074), the Program for New Century Ex-
cellent Talents in University (NCET-04-0881), the Outstanding Young
Scientist Award of Sichuan Province, the Setup Foundation of Sichuan
University, and the Foundation of the Education Ministry of China for
Returnees.
1
3
30.00, 131.59, 142.91, 160.67 ppm; HRMS (FAB) calcd for
+
[
C
30
H
34
N
4
+H] : 451.2862; found: 451.2852; elemental analysis calcd (%)
for C30
34 4
H N : C 79.96, H 7.61, N 12.43; found: C 79.85, H 7.74, N 12.23.
(
S)-4-Benzyl-2-[3-((S)-4-benzyl-1-phenyl-4,5-dihydro-1H-imidazol-2-yl)-
phenyl]-1-phenyl-4,5-dihydro-1H-imidazole [(S)-1g]: This compound was
prepared by the same procedure as described above ((S)-1 f). Starting
materials were (S)-2-amino-3-phenylpropan-1-ol and aniline. Compound
[
[
1] T. P. Yoon, E. N. Jacobsen, Science 2003, 299, 1691–1693.
2] For recent reviews, see: a) M. P. Sibi, S. Manyem, J. Zimmerman,
Chem. Rev. 2004, 104, 3263–3295; b) G. Desimoni, G. Faita, P.
Quadrelli, Chem. Rev. 2003, 103, 3119–3154; c) P. Braunstein, F.
Naud, Angew. Chem. 2001, 113, 702–722; Angew. Chem. Int. Ed.
2001, 40, 680–699; d) K. A. Jørgensen, M. Johannsen, S. Yao, H.
Audrain, J. Thornauge, Acc. Chem. Res. 1999, 32, 605–613; e) A. K.
Ghosh, P. Mathivanan, J. Cappiello, Tetrahedron: Asymmetry 1998,
9, 1–45.
(
S)-1g was obtained in 90% yield as a pale yellow powder after purifica-
tion by column chromatography on silica gel with elution with ethyl ace-
2
D
5
tate/methanol (9:1). m.p. 49–518C; [a] = 164.4 (c = 0.5 in CHCl
3
);
1
H NMR (600 MHz, CDCl
dd, J = 9.0 Hz, 4.8 Hz, 2H), 3.64 (dd, J = 6.6 Hz, 9.6 Hz, 2H), 3.65 (dd,
J = 6.6 Hz, 9.6 Hz, 2H), 4.48–4.53 (m, 2H), 6.57 (2d, J = 0.6 Hz,
3
): d = 2.77 (dd, J = 9.0 Hz, 5.4 Hz, 2H), 2.79
(
1
2
.2 Hz, 4H), 6.93 (t, J = 7.2 Hz, 2H), 7.08–7.13 (m, 5H), 7.17–7.20 (m,
H), 7.22–7.26 (m, 8H), 7.33 (2d, J = 1.2 Hz, 1.2 Hz, 2H), 7.90 ppm (t,
[3] For imidazolines as ligands in catalytic reactions, see: a) B. C¸ etin-
kaya, B. Alici, I. Özdemir, C. Bruneau, P. H. Dixneuf, J. Organomet.
Chem. 1999, 575, 187–192; b) B. C¸ etinkaya, E. C¸ etinkaya, P. B.
Hitchcock, M. F. Lappert, I. Özdemir, J. Chem. Soc. Dalton Trans.
1997, 1359–1362; c) A. Bastero, A. Ruiz, C. Claver, S. Castillón,
Eur. J. Inorg. Chem. 2001, 3009–3011; d) A. A. Ruiz, C. Claver, Or-
ganometallics 2002, 21, 5820–5829; e) A. Bastero, C. Claver, A. Rui,
S. Castillón, E. Daura, C. Bo, E. Zangrando, Chem. Eur. J. 2004, 10,
1
3
J = 1.2 Hz, 1H); C NMR (150 MHz, CDCl
3
): d = 42.12, 57.96, 65.14,
22.40, 123.33, 126.27, 127.81, 128.28, 128.55, 129.10, 129.35, 130.10,
31.39, 138.03, 142.44, 161.05 ppm; HRMS (FAB) calcd for
1
1
+
[
C
38
H
34
N
4
+H] : 547.2862; found: 547.2865; elemental analysis calcd (%)
: C 83.48, H 6.27, N 10.25; found: C 83.32, H 6.37, N 10.07.
R)-2-[3-((R)-1,4-Diphenyl-4,5-dihydro-1H-imidazol-2-yl)phenyl]-1,4-di-
for C38
34 4
H N
(
3
747–3760.
phenyl-4,5-dihydro-1H-imidazole [(R)-1h]: This compound was prepared
by the same procedure as described above ((S)-1 f). Starting materials
were (R)-2-amino-2-phenylethanol and aniline. Compound (R)-1h was
obtained in 78% yield as a pale yellow powder after purification by
column chromatography on silica gel with elution with ethyl acetate/
[
4] For imidazolines as ligands in enantioselective catalysis, see: a) C.
Botteghi, A. Schionato, G. Chelucci, H. Brunner, A. Kürzinger, U.
Obermann, J. Organomet. Chem. 1989, 370, 17–31; b) A. J. Davin-
port, D. L. Davies, J. Fawcett, D. R. Russell, J. Chem. Soc. Perkin
Trans. 1 2001, 1500–1503; c) J. Dupont, G. Ebeling, M. R. Delgado,
C. S. Consorti, R. Burrow, D. H. Farrar, A. J. Lough, Inorg. Chem.
Commun. 2001, 4, 471–474; d) C. A. Busacca, US Patent 6316620,
2
D
5
petrol ether (2:1). m.p. 83–858C; [a] = À42.0 (c = 0.5 in CHCl
3
);
1
3
H NMR (600 MHz, CDCl ): d = 3.83 (dd, J = 7.8 Hz, 9.6 Hz, 2H), 3.84
(
dd, J = 7.8 Hz, 9.6 Hz, 2H), 5.29 (2d, J = 8.4 Hz, 7.8 Hz, 2H), 6.77–
2
001; e) F. Menges, M. Neuburger, A. Pfaltz, Org. Lett. 2002, 4,
6
.79 (m, 4H), 6.99 (t, J = 7.2 Hz, 2H), 7.15–7.17 (m, 5H), 7.24–7.34 (m,
0H), 7.46 (2d, J = 1.2 Hz, 1.2 Hz, 2H), 8.06 ppm (t, J = 1.8 Hz, 1H);
4
713–4716.
1
[
5] For an excellent short review, see: C. Palomo, M. Oiarbide, A.
Mielgo, Angew. Chem. 2004, 116, 5558–5560; Angew. Chem. Int.
Ed. 2004, 43, 5442–5444.
1
3
C NMR (150 MHz, CDCl
3
): d = 61.58, 67.57, 122.84, 123.65, 126.67,
1
1
5
1
27.18, 127.84, 128.57, 128.70, 129.48, 130.37, 131.31, 142.56, 143.55,
61.77 ppm; HRMS (FAB) calcd for [C36
19.2538; elemental analysis calcd (%) for C36
0.80; found: C 83.11, H 6.01, N 10.59.
+
H
30
N
H
4
+H] : 519.2549; found:
: C 83.37, H 5.83, N
[
6] a) C. Christensen, K. Juhl, K. A. Jørgensen, Chem. Commun. 2001,
30 4
N
2
222–2223; b) C. Christensen, K. Juhl, R. G. Hazell, K. A. Jørgen-
sen, J. Org. Chem. 2002, 67, 4875–4881; c) D.-M. Du, S.-F. Lu, T.
Fang, J. Xu, J. Org. Chem. 2005, 70, 3712–3715; d) B. M. Choudary,
K. V. S. Ranganath, U. Pal, M. L. Kantam, B. Sreedhar, J. Am.
Chem. Soc. 2005, 127, 13167–13171; e) T. Purkarthofer, K. Gruber,
M. G. Khadjawi, K. Waich, W. Skranc, D. Mink, H. Griengl, Angew.
[
24]
Preparation of the racemic nitroaldols:
A
mixture of aldehyde
(
1.0 mmol), MeNO
2
(2.0 mmol), and Et N (3 drops) in ethanol
3
(
2.0 mmoL) was stirred at room temperature for 10 h. Volatiles were re-
moved in vacuo and the residue was purification by column chromatogra-
1870
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1863 – 1871