Asymmetric henry reaction catalyzed by chiral schiff base

Article abstract of DOI:10.1134/S1070428013060080

Four chiral Schiff bases were synthesized conveniently from chiral amino alcohol and 2-hydroxynaphthalene-1-carbaldehyde. These ligands were used to catalyze the addition of nitroalkanes to aldehydes under ambient conditions in good yields with up to 91%

Full text of DOI:10.1134/S1070428013060080

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 6, pp. 849–852. © Pleiades Publishing, Ltd., 2013.
Published in Russian in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 6, pp. 866–869.
Asymmetric Henry Reaction Catalyzed by Chiral Schiff Base*
De-qiang Ran, Tian-hua Shen, Xiao-cong Zhou, Jun-qi Li, Fu-na Cui,
Chun-an Ma, and Qing-bao Song
College of Chemical Engineering and Materials Science, Zhejiang University of Technology,
Hangzhou, 18# Chaowang Road, 310032, P.R.China
e-mail: qbsong@zjut.edu.cn
Received January 20, 2011
Abstract— Four chiral Schiff bases were synthesized conveniently from chiral amino alcohol and 2-hydroxy-
naphthalene-1-carbaldehyde. These ligands were used to catalyze the addition of nitroalkanes to aldehydes
under ambient conditions in good yields with up to 91% ee.
DOI: 10.1134/S1070428013060080
Since the first asymmetric Henry reaction reported
by Shibasaki in 1992 [1], various efficient metal-based
asymmetric catalysts were developed, such as bis-
oxazolines [2–6], cinchona alkaloid [7], dinuclear zinc
complexes [8, 9], salen–Co complexes [10–12], and
amino alcohols [13, 14]. After the first asymmetric
Henry reaction catalyzed by chiral copper–Schiff base
complexes was reported [15], a series of novel Schiff
base catalysts were developed [16–22]. Most of these
ligands were easily prepared from natural amino acids
and salicylaldehyde. Schiff bases containing a naph-
thol fragment were seldom reported.
carbaldehyde (III); Schiff bases Ia–Id were anticipat-
ed to be efficient catalysts for asymmetric Henry reac-
tion. Amino alcohols IIa–IId were prepared according
to known procedure [23–25], and their condensation
with aldehyde III in ethanol afforded Schiff bases Ia–
Id (Scheme 1). Taking into account the data of [21],
we selected copper(II) salts as Lewis acids to catalyze
asymmetric Henry reaction.
First, compounds Ia–Id were tested in the reaction
of 4-nitrobenzaldehyde with nitromethane in the
presence of Cu(OAc)2 ·2H2O at room temperature
(Scheme 2). 2-Nitro-1-(4-nitrophenyl)ethanol formed
in the reaction catalyzed by Schiff base Id was isolated
in 65% yield (ee 76%; Table 1, run no. 4). Having
selected the catalyst, we examined the effects of sol-
In this paper we report on the synthesis of four
simple Schiff base ligands Ia–Id by reaction of chiral
amino alcohols IIa–IId with 2-hydroxynaphthalene-1-
Scheme 1.
HO
CHO
R2
R1
R2
N
OH
EtOH
R2
HO
R1
+
H
OH
Ia–Id
R2
NH2
IIa–IId
III
R1 = Ph, R2 = H (a); R1 = R2 = Ph (b); R1 = PhCH2, R2 = H (c); R1 = PhCH2, R2 = Ph (d).
Scheme 2.
O
OH
MeNO2, Cu(OAc)2·2H2O
NO2
Ia–Id, EtOH, room temperature
Me
O2N
O2N
* The text was submitted by the authors in English.
849

DE-QIANG RAN et al.
850
Table 1. Asymmetric Henry reaction in the presence of
Schiff base ligands Ia–Ida
alcohols (Table 2). Enhanced enantioselectivity (85%)
was observed using butan-1-ol as solvent (run no. 5).
A number of copper(II) salts were also tested (Table 3),
and Cu(OAc)2 · 2 H2O turned out to be the most
efficient (run no. 1).
Run no.
Ligand
Yield,b %
ee, % (S)c
1
2
3
4
Ia
Ib
Ic
Id
43
68
65
65
< 5
37
19
76
The amount of nitromethane was also important
(Table 4). The yield and ee values were considerably
improved when the amount of nitromethane was in-
creased from 0.1 ml (1.8 mmol) to 0.4 ml (7.5 mmol).
No appreciable improvement was achieved by further
raising the amount of nitromethane.
a
All reactions were carried out with 0.3 mmol of 4-nitrobenzalde-
hyde and 0.2 ml of nitromethane in 3 ml EtOH in the presence of
10 mol % of ligand and 10 mol % of Cu(OAc)2 ·2H2O at room
temperature; hereinafter, reaction time 72 h.
Thus the optimal conditions are as follows: Schiff
base Id and Cu(OAc)2·2H2O as catalyst, butan-1-ol as
solvent, and excess of nitromethane (25 equiv, 0.4 ml,
7.5 mmol). To extend the scope of the reaction under
study, various aldehydes were brought into reaction
with nitromethane under the optimal conditions. The
corresponding products were obtained in moderate to
good yields with high ee values (Table 5). For ex-
ample, the reaction of nitromethane with 3-nitrobenz-
aldehyde afforded the corresponding adduct in 95%
yield with ee 91% (run no. 8).
b
c
Hereinafter, the yield of isolated product is given.
Hereinafter, the fraction of the S isomer was determined by
HPLC on a chiral column (AD-H); the absolute configuration
was determined by comparing the order of elution with
an authentic sample according to [2, 8, 9]; conditions of HPLC
analyses for adducts of 4-nitrobenzaldehyde with nitromethane:
eluent hexane–i-PrOH (65: 35), flow rate 1.0 ml/min; λ 254 nm;
tminor = 6.9 min, tmajor = 8.7 min.
Table 2. Effect of solvent on the enantioselectivity of asym-
metric Henry reactiona
Run no.
Solvent
Yield, %
ee, % (S)
EXPERIMENTAL
1
2
3
4
5
EtOH
65
60
58
50
69
76
67
78
71
85
MeOH
PrOH
The H and 13C NMR spectra were recorded from
1
solutions in CDCl3 on a Bruker Avance III spectrom-
eter operating at 500 and 125 MHz, respectively;
tetramethylsilane was used as internal reference. Chiral
HPLC analyses were performed on a Shimadzu LC-
20AT instrument equipped with a Shimadzu SPD-20A
detector and a Chiralcel AD-H column (Daicel Co.).
The melting points were determined using an X-4
micro-melting point apparatus and were not corrected.
All reactions were monitored by TLC. Silica gel (100–
200 mesh) was used for column chromatography. All
solvents were dried by standard methods. Commer-
cially available reagents were used without additional
purification, unless otherwise stated.
i-PrOH
BuOH
a
All reactions were carried out with 0.3 mmol of 4-nitrobenzalde-
hyde and 0.2 ml of nitromethane in the presence of 10 mol % of
ligand Id and 10 mol % of Cu(OAc)2 ·2H2O at room temperature
using 3 ml of solvent.
Table 3. Effect of copper salts on the enantioselectivity of
asymmetric Henry reactiona
Run no.
Copper salt
Yield, %
ee, % (S)
1
2
3
4
Cu(OAc)2·2H2O
CuSO2·5H2O
CuCl2·2H2O
Cu(OTf)2
69
23
30
15
81
31
59
31
Amino alcohols IIa, IIb [23], IIc [24], and IId [25]
were synthesized by known methods from L-phenyl-
glycine methyl ester hydrochloride or L-phenylalanine
methyl ester hydrochloride.
a
All reactions were carried out with 0.3 mmol of 4-nitrobenzalde-
hyde and 0.2 ml of nitromethane in the presence of 10 mol % of
ligand Id and 10 mol % of copper salt in 3 ml of BuOH at room
temperature.
Schiff bases Ia–Id (general procedure). A mixture
of 5 mmol of aldehyde III and 5 mmol of (S)-amino
alcohol IIa–IId in 30 ml of ethanol was stirred for
12 h at room temperature. The solvent was removed,
and the residue was purified by column chromatog-
raphy on silica gel using ethyl acetate–petroleum ether
(1:10) as eluent or by recrystallization from ethanol.
vent, copper salt, and amount of nitromethane on the
asymmetric Henry reaction with 4-nitrobenzaldehyde.
Insofar as protic solvents are superior to aprotic ones
[18, 26], the reaction was carried out in different
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

ASYMMETRIC HENRY REACTION CATALYZED BY CHIRAL SCHIFF BASE
851
Table 4. Effect of the amount of nitromethane on the enan-
(S)-1-{[(2-Hydroxy-1-phenylethyl)imino]methyl}-
naphthalen-2-ol (Ia) was purified by recrystallization
from ethanol. Yield 1.07 g (85%), yellow crystals,
mp 187°C. The NMR spectrum of Ia coincided with
that reported in [27].
tioselectivity of asymmetric Henry reactiona
Run no. MeNO2, mol (ml)
Yield, %
ee, % (S)
1
2
3
4
5
6
01.8 (0.1)
03.7 (0.2)
07.5 (0.4)
11.0 (0.4)
15.0 (0.8)
18.0 (1.0)
40
69
83
82
83
83
65
82
83
85
86
82
(S)-1-{[(2-Hydroxy-1,2,2-triphenylethyl)imino]-
methyl}naphthalen-2-ol (Ib) was purified by column
chromatography on silica gel. Yield 1.75 g (77%),
yellow crystals, mp 128–130°C. The NMR spectrum
of Ib coincided with that given in [23].
(S)-1-{[(1-Hydroxy-3-phenylpropan-2-yl)imino]-
methyl}naphthalen-2-ol (Ic) was purified by recrys-
tallization from ethanol. Yield 1.3 g (85%), yellow
a
All reactions were carried out with 0.3 mmol of 4-nitrobenzalde-
hyde in the presence of 10 mol % of ligand Id and 10 mol % of
Cu(OAc)2 ·2H2O in 3 ml of BuOH at room temperature.
1
crystals, mp 178–180°C. H NMR spectrum, δ, ppm:
2.92 d.d (1H, PhCH2, J = 13.78, 7.62 Hz), 3.02 d.d
(1H, PhCH2, J = 13.79, 4.23 Hz), 3.72 m (2H,
HOCH2), 3.92 d.d (1H, NCH), 5.11 br (1H, CH2OH),
6.62–7.50 m (11H, Harom), 8.37 s (1H, N=CH),
14.13 br (1H, 2-OH). 13C NMR spectrum, δC, ppm:
175.62, 158.59, 137.19, 136.99, 133.56, 129.43,
129.10, 128.75, 127.71, 126.91, 126.07, 123.96,
122.51, 117.90, 106.36, 68.24, 65.23, 38.64. Found, %:
C 78.56; H 6.26; N 4.57. C20H19NO2. Calculated, %:
C 78.66; H 6.27; N 4.59.
Table 5. Asymmetric Henry reaction of nitromethane with
various aldehydes under the optimal conditionsa
Run
no.
Yield, ee, Configura-
Aldehyde
%
%
tion
1
2
Benzaldehyde
73
68
59b
66c
S
Naphthalene-2-carbal-
dehyde
S
3
4
5
6
2,4-Dichlorobenz-
aldehyde
87
54
82
83
89d
69e
77f
70g
ND
S
(4-Formylphenyl)-
acetyl fluoride
(S)-1-{[(1-Hydroxy-1,3,3-triphenylpropan-2-yl)-
imino]methyl}naphthalen-2-ol (Id) was purified by
column chromatography on silica gel. Yield 2.1 g
(92%) (cf. [28], no analytical data were given), yellow
4-Bromothiophene-
2-carbaldehyde
ND
S
1
2,5-Dimethoxybenz-
aldehyde
solid, mp 159–160°C. H NMR spectrum, δ, ppm:
3.03 d.d (1H, PhCH2, J = 13.98, 10.63 Hz), 3.18 d.d
(1H, PhCH2, J = 13.92, 1.35 Hz), 4.00 br (1H,
CH2OH), 4.48 d.d (1H, NCH, J = 10.75, 1.37 Hz),
6.85–7.75 m (21H, Harom), 7.97 s (1H, N=CH),
14.31 br (1H, 2-OH). 13C NMR spectrum, δC, ppm:
37.75, 74.60, 80.08, 106.60, 118.07, 122.58, 124.01,
126.16, 126.24, 126.32, 126.68, 127.22, 127.40,
127.58, 128.40, 128.66, 128.67, 128.98, 129.64,
136.67, 133.65, 138.55, 144.28, 144.63, 158.99,
173.84. Found, %: C 83.92; H 5.94; N 3.04.
C32H27NO2. Calculated, %: C 84.00; H 5.95; N 3.06.
7
8
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
93
95
90h
91i
S
S
a
All reactions were carried out with 0.3 mmol of aldehyde and
0.4 ml of nitromethane in the presence of 10 mol % of ligand Id
and 10 mol % of Cu(OAc)2 ·2H2O in 3 ml of BuOH at room
temperature.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 0.5 ml/min,
λ 254 nm, tmajor = 37.2 min, tminor = 39.5 min.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 1.0 ml/min,
λ 254 nm, tmajor = 33.7 min, tminor = 36.4 min.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 1.0 ml/min,
λ 254 nm, tminor = 14.1 min, tmajor = 17.8 min.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 1.0 ml/min,
λ 254 nm, tmajor = 18.2 min, tminor = 29.4 min.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 1.0 ml/min,
λ 230 nm, tmajor = 22.1 min, tminor = 27.2 min.
HPLC conditions: hexane–i-PrOH, 95:5, flow rate 0.8 ml/min,
λ 215 nm, tmajor = 49.5 min, tminor = 51.5 min.
HPLC conditions: hexane–i-PrOH, 85:15, flow rate 1.0 ml/min,
λ 254 nm, tmajor = 11.3 min, tminor = 12.2 min.
b
c
d
e
f
Asymmetric Henry reaction (typical procedure).
A 10-ml round-bottom flask was charged with a mix-
ture of 0.03 mmol of chiral ligand I and 0.03 mol of
copper(II) salt, 3 ml of the corresponding solvent was
added, and the mixture was stirred for 3 h at room
temperature. Aldehyde, 0.3 mmol, and nitromethane
were then added, and the mixture was stirred until the
reaction was complete (TLC). Volatile components
were removed under reduced pressure, and the crude
product was purified by preparative TLC using petro-
g
h
i
HPLC conditions: hexane–i-PrOH, 85:15, flow rate 1.0 ml/min,
λ 254 nm, tmajor = 11.9 min, tminor = 14.1 min.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

DE-QIANG RAN et al.
852
10. Yamada, T., Synthesis, 2004, no 12, p. 1947.
leum ether–ethyl acetate as eluent. Enantiomeric ex-
cess (ee) was determined by HPLC using a Chiralpak
AD-H column.
11. Kogami, Y., Nakajima, T., Ashizawa, T., Kezuka, S.,
Ikeno, T., and Yamada, T., Chem. Lett., 2004, vol. 33,
p. 614.
Preparation of racemic Henry reaction products
(general procedure). A 10-ml round-bottom flask was
charged with 1 mmol of aldehyde, 5 ml of ethanol was
added at room temperature, and 0.16 ml (3 mmol) of
nitromethane and 5 drops of triethylamine were then
injected via a syringe. The mixture was stirred until
complete conversion was achieved (8 h, TLC). Volatile
components were removed under reduced pressure,
and the crude product was purified by preparative TLC
using petroleum ether–ethyl acetate as eluent. The
retention times of racemic β-nitro alcohols were deter-
mined by HPLC using a Chiralpak AD-H column.
12. Xiong, Y., Wang, F., Huang, X., Wen, Y.-H., and
Feng, X.-M., Chem. Eur. J., 2007, vol. 13, p. 829.
13. Palomo, C., Oiarbide, M., and Laso, A., Angew. Chem.,
Int. Ed., 2005, vol. 44, p. 3881.
14. Palomo, C., Oiarbide, M., and Mielgo, A., Angew.
Chem., Int. Ed., 2004, vol. 43, p. 5442.
15. Gan, C.-S., Lai, G.-Y., Zhang, Z.-H., Wang, Z.-Y., and
Zhou, M.-M., Tetrahedron: Asymmetry, 2006, vol. 17,
p. 725.
16. Guo, J. and Mao, J.-C., Chirality, 2009, vol. 21, p. 619.
17. Çolak, M. and Demirel, N., Tetrahedron: Asymmetry,
2008, vol. 19, p. 635.
This work was supported by the project of the state
key laboratory breeding base of green chemistry–syn-
thesis technology, Zhejiang University of Technology,
China.
18. Lai, G.-Y., Wang, S.-J., and Wang, Z.-Y., Tetrahedron:
Asymmetry, 2008, vol. 19, p. 1813.
19. Jammi, S., Saha, P., Sanyashi, S., Sakthivel, S., and
Punniyamurthy, T., Tetrahedron, 2008, vol. 64,
p. 11724.
REFERENCES
20. Blay, G., Climent, E., Fernández, I., Hernández-
Olmos, V., and Pedro, J.R., Tetrahedron: Asymmetry,
2007, vol. 18, p. 1603.
1. Sasai, H., Suzuki, T., Arai, S., and Shibasaki, M., J. Am.
Chem. Soc., 1992, vol. 114, p. 4418.
21. Çolak, M., Aral, T., Hoşgőren, H., and Demirel, N.,
Tetrahedron: Asymmetry, 2007, vol. 18, p. 1129.
2. Evans, D.A., Seidel, D., Rueping, M., Lam, H.W.,
Shaw, J.T., and Downey, C.W., J. Am. Chem. Soc., 2003,
vol. 125, p. 12692.
22. Gao, Y.-G., Chen, N., Wu, H.-J., and Li, X.-S., Russ. J.
Org. Chem., 2007, vol. 43, p. 1754.
3. Christensen, C., Juhl, K., Hazell, R.G., and Jørgen-
23. Poornachandran, M. and Raghunathan, R., Tetrahedron:
Asymmetry, 2008, vol. 19, p. 2177.
sen, K.A., J. Org. Chem., 2002, vol. 67, p. 4875.
4. Christensen, C., Juhl, K., and Jørgensen, K.A., Chem.
Commun., 2001, p. 2222.
5. Lu, S.-F., Du, D.-M., Zhang, S.-W., and Xu, J., Tetra-
hedron: Asymmetry, 2004, vol. 15, p. 3433.
24. Fleischer, R., Wunderlich, H., and Braun, M., Eur. J.
Org. Chem., 1998, p. 1063.
25. O’Hagan, D. and Tavasli, M., Tetrahedron: Asymmetry,
1999, vol. 10, p. 1189.
6. Du, D.-M., Lu, S.-F., Fang, T., and Xu, J., J. Org. Chem.,
2005, vol. 70, p. 3712.
26. Ginotra, S.K. and Singh, V.K., Org. Biomol. Chem.,
2007, vol. 5, p. 3932.
7. Corey, E.J. and Zhang, F.-Y., Angew. Chem., Int. Ed.,
1999, vol. 38, p. 1931.
8. Trost, B.M. and Yeh, V.S.C., Angew. Chem., Int. Ed.,
27. Schlecht, S., Frank, W., and Braun, M., Eur. J. Org.
Chem., 2010, p. 3721.
2002, vol. 41, p. 861.
9. Trost, B.M., Yeh, V.S.C., Ito, H., and Bremeyer, N., Org.
Lett., 2002, vol. 4, p. 2621.
28. Prechtl, F., Haremz, S., Parker, R., Kurschner, K.,
Braun, M., Hahn, A., and Fleisher, R., US Patent Appl.
Publ. no. 20030066984 A1, 2003.
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