Asymmetric Henry reaction catalyzed by a copper tridentate chiral schiff-base complex

Article abstract of DOI:10.1016/j.tetasy.2008.06.036

A series of copper-tridentate chiral Schiff-base complexes were prepared and employed in an asymmetric Henry reaction, affording the corresponding adducts in good yields and with high enantioselectivities (up to 96% ee).

Full text of DOI:10.1016/j.tetasy.2008.06.036

Tetrahedron: Asymmetry 19 (2008) 1813–1819
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric Henry reaction catalyzed by a copper tridentate
chiral schiff-base complex
*
Guoyin Lai, Sujing Wang, Zhiyong Wang
Hefei National Laboratory for Physical Science at Microscale, Joint-Lab of Green Synthetic Chemistry and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of copper-tridentate chiral Schiff-base complexes were prepared and employed in an asymmetric
Henry reaction, affording the corresponding adducts in good yields and with high enantioselectivities (up
to 96% ee).
Received 4 June 2008
Accepted 30 June 2008
Available online 9 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
prepared from a natural amino acid, can catalyze asymmetric
Henry reactions under mild conditions. However, both the yields
The Henry reaction1 (or nitroaldol reaction) is one of the most
important C–C bond forming reactions in organic synthesis. The
resulting products of this reaction, a coupling between nitroalk-
anes and carbonyl groups, can be converted into many valuable
building blocks depending on the different requirements in the
synthesis of natural products and other useful compounds.2 Recent
efforts have been focused on the development of various metal-
based catalysts by the groups of Shibasaki,3 Trost,4 Evans,5 Palo-
mo,6 Jørgensen,7 and others,8,12 and organocatalysts9 for the asym-
metric Henry reaction.10
(43–90%) and the enantioselectivities (45–86%) need to be im-
proved.12 In order to promote these results and acquire some infor-
mation on the relationship between the structure of a complex and
its enantioselectivity in the Henry reaction, we have been making
continuous efforts to modify the ligands for the Henry reaction.
2. Results and discussion
Initial studies have been focused on the reaction using different
complexes 1a–1l (Fig. 1). In our former work,12 two types of cata-
lysts 1k and 1l were employed in the asymmetric Henry reaction,
which contained 3,5-di-tert-butylated substituents 1l and without
any substituent on the phenol ring 1k. The experimental results
(Table 1, entries 11 and 12) showed that the substituents on the
phenol ring had a great influence on the enantioselectivity but
little influence on the reaction yield. On the other hand, nitro-
methane did not react with the imine group of the ligand in this
complex 1. Intrigued by this result, a variety of catalysts with
different substituents on the phenol rings were then prepared
and screened by the asymmetric Henry reaction. In this reaction,
ethanol was chosen as a solvent since we had employed it as the
reaction solvent previously.12 All the experimental results are
listed in Table 1. From Table 1, it was found that the steric hin-
drance of the substituent on the phenol ring of the ligand affected
the enantioselectivity. For instance, when the substituent was a
methyl group (Fig. 1, 1a and 1b), both the yields and enantioselec-
tivities were enhanced (Table 1, entries 1 and 2). Especially, when
the methyl group was located at the ortho position of phenol ring,
the highest ee value 92% can be obtained, which showed that sub-
stitution on the ortho-position (R1) would affect the reaction to a
greater extent than on the para-position (R2). Slightly increasing
the volume of the R1 substituent from methyl group to ethyl group
(Fig. 1, 1c) resulted in a little decrease both in the yield and ee
Chiral Schiff-bases have frequently been used in catalytic asym-
metric synthesis.11 Recently, we have reported that novel copper
Schiff-base complexes 1k and 1l (Fig. 1),12 which could be easily
1
2
1a:
=
,
R
Me R =H
1b: 1= ,
2
R
R
R
H R =Me
1
1
2
1c:
1d:
1e:
=
,
Et R =H
2
=
,
i-Pr R =H
1
2
=
,
R
t-Bu R =H
O
1f: 1= ,
2
R1 H R =t-Bu
N
Cu
1g: R =MeO, R2=H
1h: 1= ,
2
O
R
H R =MeO
Cl R =H
H R =Cl
1
2
2
1i:
=
,
R
R
1j: 1= ,
R1
1
1
2
1k:
1l:
=
=
R
R =H
2
R
R =t-Bu
R2
1
Figure 1. The structure of the catalytic complexes.
* Corresponding author. Tel.: +86 551 3603185; fax: +86 551 3631760.
E-mail address: zwang3@ustc.edu.cn (Z. Wang).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.06.036

1814
G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
Table 1
Table 2
The optimization of the catalytic complexesa
Effects of solvent and temperature on the asymmetric Henry reaction under the
catalysis of complex 1aa
OH
O
OH
O
Complex 1
NO2
Complex 1a
H
CH3NO2
NO2
H
CH3NO2
Ethanol, r.t.
solvent
O2N
O2N
O2N
O2N
2a
3
4a
eec (%)
2a
3
4a
Yieldb (%)
Entry
Complex
Yieldb (%)
Configd
Entry
Solvent
T (°C)
Time (h)
eec (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
86
81
83
86
82
87
99
82
88
86
85
85
92
84
70
88
72
70
54
74
88
83
78
64
S
S
S
S
S
S
S
S
S
S
S
S
1
2
3
4
5
6
7
8
9
10
11
12d
13
14
15e
16f
Ethanol
Toluene
CH2Cl2
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
ꢀ5
50
rt
rt
24
24
24
24
24
24
24
24
24
24
24
10
48
6
86
37
43
41
50
60
87
79
81
84
88
99
49
90
78
81
92
72
38
62
46
68
62
36
72
88
84
4
CH3CN
THF
Et2O
n-Hexane
CH3OH
t-Butanol
n-Propanol
i-Propanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
10
11e
12e
1j
1k
1l
a
All reactions were performed with 0.5 mmol of 4-nitro-benzaldehyde and
2.5 mmol nitromethane in the presence of 2.5 mmol % of complex 1 at room
temperature.
92
84
86
86
24
24
b
Isolated yields.
Determined by chiral HPLC using a OD–H column.
The absolute configurations of products were determined by comparison with
c
a
d
All reactions were performed with 0.5 mmol of 4-nitro-benzaldehyde and
2.5 mmol of nitromethane in the presence of 2.5 mol % of complex 1a in 2 mL of
solvent at the appointed temperature.
the literature5 values.
e
Refer to our previous work.12
b
Isolated yields by the column chromatography.
Determined by HPLC on a OD-H column.
100 mg of 4 Å sieve was added.
1.25 mol % of complex 1a was added.
c
d
(Table 1, entry 3). Increasing the steric hindrance further (Fig. 1, 1d,
1e, and 1f) led to lower yields and ee values (Table 1, entries 4–6).
For the tert-butyl substitution, the ee value decreased in spite of
the substitution at the para position because of the great hindrance
of the tert-butyl group. Thus, these studies indicated that a suitable
steric hindrance was necessary for obtaining both high yield and
ee; the methyl group meets this requirement. On the other hand,
the electronic effect also has an influence on the reaction. For in-
stance, the substitution of a strong electron-donating methoxyl
group on the phenol ring (Fig. 1, 1g and 1h) led to a obvious de-
crease in the ee values although this substitution had little influ-
ence on the reaction yields (Table 1, entries 7 and 8). When the
R1 or R2 group was an electron-withdrawing group, such as a
chloro group (Fig. 1, 1i and 1j), a slight electronic effect was ob-
served in this situation and a normal reaction yield was obtained
(Table 1, entries 9 and 10). After optimization for different substi-
tutions, complex 1a was seen to be the best catalyst among those
screened in this reaction.
e
f
5 mol % of complex 1a was added.
Table 3
Enantioselective Henry reaction of nitromethane with various aldehydes catalyzed by
complex 1aa
OH
O
2.5% mol 1a
ethanol, rt
CH3NO2
NO2
R
R
H
4
2
3
b: R = 2-NO2Ph
d: R = 3-ClPh
f: R = Ph
h: R = 2-MePh
j: R = 2-MeOPh
l: R = PhCH2
n: R = Pr
a: R = 4-NO2Ph
c: R = 4-ClPh
e: R = 2-ClPh
g: R = 4-MePh
i: R = 4-MeOPh
k: R = 1-Naphthyl
m: R = i-Bu
Entry
Product
Time (h)
Yieldb (%)
eec (%)
Configd
After the selection of the catalyst, solvents, additives, tempera-
tures, and the catalyst loading were tested in the asymmetric
Henry reaction between 4-nitro-benzaldehyde and nitromethane.
Generally, the protonic solvents were superior to the non-protonic
ones (Table 2, entries 1–11). Moreover, among different protonic
solvents, ethanol was established as the best for this reaction sys-
tem (Table 2, entry 1, 86% yield, 92% ee). When 10 mg of 4 Å sieves
was added, the reaction rate accelerated while the corresponding
product was obtained in high yield but with very low ee (Table
2, entry 12). When the reaction temperature was decreased from
room temperature to ꢀ5 °C, the reaction took longer time and gave
the corresponding product in a lower yield with almost the same
ee value (Table 2, entry 13). In contrast, increasing the reaction
temperature accelerated the reaction rate, but reduced the ee value
(Table 2, entry 14). Therefore, room temperature is an optimal
reaction temperature. Afterwards, different catalyst loadings were
tested, and the results showed that 2.5 mol % catalyst loading was
the best quantity for this reaction (entries 1, 15, and 16). Overall,
the optimized conditions include catalyst complex 1a, the reaction
1
2
3
4
5
6
7
8
9
10
11
12
13
14
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
24
24
24
24
24
24
48
24
36
24
48
48
72
96
86
87
81
82
85
76
67
81
72
83
80
71
76
70
92
92
90
91
96
91
91
95
84
93
91
81
85
85
S
S
S
S
S
S
S
S
S
S
S
e
—
S
S
a
Reactions were performed with 0.5 mmol of aldehyde and 2.5 mmol of nitro-
methane in the presence of 2.5 mol % of complex 1a in 2 mL of ethanol at room
temperature.
b
Isolated yields after the column chromatography purifications.
Determined by HPLC using chiral OD-H or OJ-H column.
The absolute configurations of products were determined by comparison with
c
d
the literature5,6,8a,8q values.
e
The absolute configuration is not determined.

G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
1815
Table 5
Bond lengths and angles
Bond lengths and angles
Cu(1)–O(1)
Cu(1)–N(1)
Cu(1)–O(2)
Cu(1)–O(2)
O(1)–Cu(1)–N(1)
O(1)–Cu(1)–O(2)
N(1)–Cu(1)–O(2)
O(1)–Cu(1)–O(2)
N(1)–Cu(1)–O(2)
O(2)–Cu(1)–O(2)
1.881(7)
1.898(8)
1.944(6)
1.944(6)
95.0(3)
172.1(3)
83.7(3)
103.5(3)
159.3(3)
79.3(3)
well and give the corresponding products with the yields of 71–
76% and ee values of 81–85% regardless of the branch on the chain
(Table 3, entries 12–14).
We also prepared a single crystal of complex 1c and measured
its X-ray structure (Fig. 2, Tables 4 and 5). Complex 1c crystallized
in the chiral space group P43212,13 as shown in Figure 2. The asym-
metric unit comprises a copper atom and a chiral Schiff-base mol-
ecule. Each Cu(II) is bounded to an N atom, two O atoms from one
Schiff-base and another O atom from another Schiff-base, complet-
ing a distorted square planar coordination geometry. Two adjacent
Cu atoms are linked together via two O toms from two adjacent
Schiff-bases, forming a dimer.
Figure 2. The crystal structure of complex 1c, selected bond lengths: Cu1–
N1 = 1.897 Å, Cu1–O1 = 1.881 Å, Cu1–O2 = 1.943 Å, Cu1–O21 = 1.944 Å.
carried out at room temperature and the reaction solvent being
ethanol.
With the optimized conditions in hand, the scope of the sub-
strate was extended. A variety of aldehydes were employed as sub-
strates to react with nitromethane, giving the corresponding
products with high yields and ee values, as shown in Table 3.
The data clearly showed that complex 1a and the optimized reac-
tion conditions can be applied in a wide scope of substrates,
including different kinds of aromatic and aliphatic aldehydes. The
aromatic aldehydes could undergo an asymmetric Henry reaction
smoothly with good yields and ee values. The steric hindrance
had little influence on this reaction (Table 3, entries 1–11). The
ones with electron-withdrawing group gave higher yields (entries
1–5 vs entries 7–10). The substrates with ortho-substituent (en-
tries 2, 5, 8, and 10) gave higher enantioselectivities than other
ones. The aliphatic aldehydes could also react with nitromethane
3. Conclusion
In conclusion, the efficiency of an asymmetric Henry reaction
was enhanced by the modification of the catalytic ligands on the
basis of natural a-amino acids. To the best of our knowledge, this
is the first time that the substituents on the phenol ring have been
reported to have a great influence on the yield and enantioselectiv-
ity of the Henry reaction. However, these substituents are far from
the stereogenic carbon atom of our Schiff-base ligands. The struc-
ture of the single crystal of catalyst 1c has been measured, which
could be useful for the design of new catalysts for asymmetric
Henry reactions. Further studies on asymmetric synthesis are still
in progress in our group.
Table 4
Crystal data
4. Experimental
Compound
1c
4.1. General remarks
Empirical formular
Formular wt
Crystal system
Space group
a (Å)
C
60H54Cu2N2O4
994.13
Tetragonal
P43212
10.4050(15)
10.4050(15)
46.987(9)
90.00
90.00
90.00
5087.0(15)
4
293(2)
The aldehydes were all purified through distillation at low pres-
sure or recrystallization. Solvents were dried according to standard
procedure and distilled prior to use. Most reagents, such as nitro-
methane, phenylalanine, hydroxybenzene groups, and copper ace-
tate monohydrate, were used as received from commercial
sources. Complexes were prepared by a series of reactions. All reac-
tions were carried out under indicated conditions. NMR spectra
were recorded at 300 MHz for 1H and 75 MHz for 13C using CDCl3
as solvent and tetramethylsilane as an internal standard. Infrared
spectra and mass spectra were obtained. The enantiomeric excess
of the Henry products was determined by HPLC on Chiralcel OD-
H or OJ-H column.
b (Å)
c (Å)
a
(°)
b (°)
c
(°)
V (Å3)
Z
T (K)
qcalc (g cmꢀ3
F(000)
)
1.289
2072
0.885
l
(mmꢀ1
)
data/parameters
R1 [I > 2r(I)]
wR2
2673/141
0.0846
0.1963
1.055
5. Preparation for complex 1
Goodness-of-fit
Largest difference in peak and hole (e A3)
1.369, ꢀ1.486
5.1. General experimental procedure for the preparation of
salicylaldehyde derivatives
Crystal size (mm)
X
Y
Z
0.213
0.213
0.502
To a solution of the corresponding phenol (10 mmol) in 10 mL
ethanol was added 3.0 g of NaOH (75 mmol) in 15 mL water. The

1816
G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
resulting solution was heated to 80 °C, and the dropwise addition
of chloroform was started. After the reaction began, further heating
was unnecessary. A total of 2.36 g. (20 mmol) of chloroform were
added so as to maintain gentle refluxing. Stirring was continued
for 1 h after all the chloroform had been added. The ethanol was
removed by reduced pressure, and 1 M HCl was added to neutral-
ize the excess NaOH until pH 2–3. The residue was then extracted
with ethyl acetate three times. The combined organic extracts
were dried using anhydrous Na2SO4 and evaporated under reduced
pressure; the mixture was then purified by column chromatogra-
phy over silica gel to afford salicylaldehyde derivatives 5 with high
purity.
117.8, 118.3, 125.8, 126.1, 126.3, 127.0, 127.2, 128.4, 128.5,
128.6, 129.4, 129.9, 133.6, 139.1, 144.3, 145.7, 159.0, 167.0. HRMS:
calcd for C29H27NO2: 421.2042, found 421.2036.
5.4.2. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-4-methylphenol 6b
½
a 2D5
ꢂ
¼ ꢀ72:0 (c 1.01, CH2Cl2). IR (film cmꢀ1): 3480, 3061, 2924,
2868, 1631, 1492, 1279, 909, 736, 702. 1H NMR (CDCl3, d ppm):
2.18 (s, 3H), 2.85 (dd, J = 10.2, 13.5 Hz, 1H), 2.93 (br, 1H), 3.02 (d,
J = 13.5 Hz, 1H), 4.33 (d, J = 10.2 Hz), 6.65 (s, 1H), 6.78 (d,
J = 8.4 Hz, 1H), 6.96 (d, J = 6.9 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H),
7.14 (m, 3H), 7.25 (m, 4H), 7.38 (m, 2H), 7.48 (d, J = 7.5 Hz, 2H),
7.54 (s, 1H), 7.64 (d, J = 7.5 Hz, 2H), 12.41 (br, 1H). 13C NMR:
20.3, 37.6, 78.9, 79.9, 116.6, 118.2, 126.1, 126.3, 126.4, 127.1,
127.2, 127.8, 128.4, 128.5, 128.6, 129.8, 131.7, 133.4, 139.1,
144.3, 145.5, 158.4, 166.8. HRMS: calcd for C29H27NO2: 421.2042,
found 421.2038.
5.2. Preparation for (S)-ethyl-2-amino-3-phenylpropanoate
The starting material,
L-phenylalanine, is commercially avail-
able. A solution of the -phenylalanine (3 g, 18.3 mmol) in 20 mL
L
ethanol was cooled by ice water. After cooling, 4.6 mL of SOCl2
was added dropwise. The resulting solution was then refluxed for
4 h. Evaporation of the solvent gave a white solid, which was trea-
ted with saturated aqueous Na2CO3 until pH 8–9, after which it
was extracted with ethyl acetate (10 mL ꢁ 3). The combined or-
ganic extracts were dried using anhydrous Na2SO4 and evaporated
under reduced pressure, which gave the (S)-ethyl-2-amino-3-phen-
ylpropanoate (3.395 g, 96% yield).
5.4.3. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-ethylphenol 6c
½
a 2D5
ꢂ
¼ ꢀ50:2 (c 0.96, CH2Cl2). IR (film cmꢀ1): 3438, 3052, 3029,
2967, 2933, 2876, 1622, 1451, 748, 700. 1H NMR (CDCl3, d ppm):
1.22 (m, 3H), 2.65 (m, 2H), 2.88 (dd, J = 2.6, 12.2 Hz, 1H), 3.01 (m,
2H), 4.35 (dd, J = 2.6, 9.9 Hz, 1H), 6.71 (m, 2H), 6.92 (m, 2H), 7.16
(m, 5H), 7.38 (m, 3H), 7.48 (m, 2H), 7.58 (s, 1H), 7.66 (m, 2H),
12.80 (br, 1H). 13C NMR: 13.8, 14.1, 22.5, 23.1, 37.6, 78.8, 79.9,
115.3, 117.8, 118.4, 121.0, 126.1, 126.3, 126.4, 127.0, 127.1,
127.2, 128.4, 128.5, 128.6, 129.4, 129.9, 130.1, 131.8, 131.9,
139.1, 144.3, 145.6, 153.5, 158.7, 167.1. HRMS: calcd for
5.3. Preparation for (S)-2-amino-1,1,3-triphenylpropan-1-ol
In a three-necked round-bottomed flask fitted with a reflux con-
denser, under a nitrogen atmosphere, 1.5 g (62 mmol) furbished
Mg and 20 mL anhydrous diethyl ether, which was treated with so-
dium prior to use, were added. The stir was started and a solution
of bromobenzene (4.34 mL, 42 mmol) in 5 mL diethyl ether was
added dropwise. After the reaction began, the solution maintained
slightly boils through the control of the velocity of addition. After
the addition, the resulting solution was heated under reflux for
0.5 h. The heating equipment was switched off and the addition
of the above (S)-2-ethyl-2-amino-3-phenylpropanoate (2 g,
10.4 mmol) in 10 mL diethyl ether was started. Another reflux of
0.5 h was needed, after which, the resulting solution was cooled
in ice water and saturated NH4Cl aqueous was added until no more
white precipitate was produced. The solution was filtered and the
liquid was extracted by diethyl ether (25 mL ꢁ 3). The combined
organic extracts were dried using anhydrous Na2SO4 and evapo-
rated under reduced pressure to give yellow solid. The solid was
then recrystallized in 30 mL methanol, which gave a white solid
(S)-2-amino-1,1,3-triphenylpropan-1-ol (2.556 g, 81% yield).
C
30H29NO2: 435.2198, found 435.2192.
5.4.4. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-isopropylphenol 6d
½
a 2D5
ꢂ
¼ ꢀ53:2 (c 0.81, CH2Cl2). IR (film cmꢀ1): 3440, 3062, 3029,
2962, 2931, 2872, 1622, 1449, 748, 700. 1H NMR (CDCl3, d ppm):
1.23 (m, 6H), 2.87 (m, 1H), 3.01 (m, 2H), 3.34 (d, J = 12.9 Hz, 1H),
4.36 (dd, J = 1.7, 9.9 Hz, 1H), 6.72 (t, J = 3.0 Hz, 2H), 6.97 (d,
J = 1.3 Hz, 2H), 7.19 (m, 8H), 7.39 (m, 2H), 7.49 (d, J = 7.5 Hz, 2H),
7.59 (s, 1H), 7.66 (d, J = 7.5 Hz, 2H), 12.88 (br, 1H). 13C NMR:
22.5, 22.6, 22.7, 16.3, 27.1, 37.6, 78.7, 79.9, 115.4, 117.9, 118.4,
121.1, 126.1, 126.3, 126.4, 126.5, 126.8, 127.0, 127.2, 128.4,
128.5, 128.6, 129.1, 129.3, 129.9, 136.2, 139.2, 144.3, 145.7,
152.9, 158.1, 167.2. HRMS: calcd for C31H31NO2: 449.2355, found
449.2348.
5.4.5. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-tert-butylphenol 6e
½
a 2D5
ꢂ
¼ ꢀ71:0 (c 0.97, CH2Cl2). IR (film cmꢀ1): 3063, 3029, 2960,
5.4. General procedure for the preparation for chiral Schiff-
base 6
1622, 1436, 909, 734, 702. 1H NMR (CDCl3, d ppm): 1.40 (s, 9H),
2.90 (dd, J = 10.0, 13.7 Hz, 1H), 3.03 (m, 2H), 4.34 (dd, J = 1.8,
10.0 Hz, 1H), 6.68 (d, J = 2.7 Hz, 2H), 6.97 (t, J = 3.8 Hz, 2H), 7.13
(m, 4H), 7.23 (m, 4H), 7.39 (m, 2H), 7.49 (d, J = 7.5 Hz, 2H), 7.60
(s, 1H), 7.67 (d, J = 7.5 Hz, 2H), 13.09 (br, 1H). 13C NMR: 29.5,
34.9, 37.6, 78.7, 80.0, 117.9, 118.5, 126.1, 126.3, 126.4, 127.0,
127.2, 128.4, 128.5, 128.6, 129.7, 129.7, 129.9, 130.0, 137.2,
129.2, 144.3, 145.7, 160.0, 167.5. HRMS: calcd for C32H33NO2:
463.2511, found 463.2503.
To a solution of 0.5 mmol of the above (S)-2-amino-1,1,3-tri-
phenylpropan-1-ol in 5 mL methanol was added 0.55 mmol of
the above 5. The solution was refluxed for 4 h. The methanol was
removed under reduced pressure. The residue was purified by
chromatography (4.76% EtOAc in petroleum) to give, the resulting
chiral Schiff-base as a yellow solid, in high yield (>98%).
5.4.1. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-methylphenol 6a
5.4.6. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-4-tert-butylphenol 6f
½
a 2D5
ꢂ
¼ ꢀ53:2 (c 0.81, CH2Cl2). IR (film cmꢀ1): 3060, 3028, 2926,
½
a 2D5
ꢂ
¼ ꢀ71:3 (c 0.88, CH2Cl2). IR (film cmꢀ1): 3473, 3029, 2959,
1623, 1450, 744, 700. 1H NMR (CDCl3, d ppm): 2.23 (s, 3H), 2.86
(dd, J = 10.2, 13.5 Hz, 1H), 3.01 (br, 1H), 3.01 (d, J = 13.5 Hz, 1H),
4.35 (d, J = 10.2 Hz, 1H), 6.68 (m, 2H), 6.96(d, J = 7.2 Hz, 2H), 7.19
(m, 8H), 7.39 (m, 2H), 7.49 (m, 2H), 7.56 (s, 1H), 7.66 (d,
J = 7.8 Hz, 2H), 12.83 (br, 1H). 13C NMR: 15.5, 37.6, 78.9, 79.9,
1631, 1492, 1262, 742, 700. 1H NMR (CDCl3, d ppm): 1.26 (s, 9H),
2.86 (dd, J = 10.2, 13.5 Hz, 1H), 2.98 (br, 1H), 3.06 (d, J = 13.5 Hz,
1H), 4.36 (d, J = 8.7 Hz, 1H), 6.83 (d, J = 9.1 Hz, 2H), 6.97 (d,
J = 6.4 Hz, 2H), 7.16 (t, J = 7.1 Hz, 3H), 7.26 (m, 5H), 7.39 (t,
J = 7.7 Hz, 2H), 7.49 (d, J = 7.7 Hz, 2H), 7.56 (s, 1H), 7.66 (d,

G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
1817
J = 7.7 Hz, 2H), 12.33 (br, 1H). 13C NMR: 14.3, 31.4, 31.5, 34.0, 37.7,
78.7, 80.0, 116.4, 117.9, 126.2, 126.4, 127.1, 127.2, 128.1, 128.4,
128.5, 128.6, 129.90, 129.94, 139.2, 141.5, 144.3, 145.6, 158.3,
167.2. HRMS: calcd for C32H33NO2: 463.2511, found 463.2506.
the residue was added 10 mL of brine and extracted by benzene
(10 mL ꢁ 3). The combined organic extracts were dried using anhy-
drous Na2SO4, and evaporated under reduced pressure to give a
dark green solid 1.
5.4.7. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-methoxyphenol 6g
5.5.1. Typical experimental procedure for an enantioselective
Henry reaction
½
a 2D5
ꢂ
¼ ꢀ56:1 (c 0.67, CH2Cl2). IR (film cmꢀ1): 3501, 3062, 3028,
To a mixture of complex 1a (0.0125 mmol) and ethanol (2 mL)
at a given temperature was added 2.5 mmol of nitromethane.
The mixture was allowed to stir for 2 h, and 2 (0.5 mmol) was
added. After being stirred for the indicated time, the mixture was
quenched by diluted HCl (0.5 mL, 1 M), and then ethanol was evap-
orated in vacuo. The residue was then extracted with acetic ethyl
ester (2 mL) for three times. Purification by column chromatogra-
phy afforded the desired Henry product 4. The ee value was deter-
mined by HPLC on Chiralcel OD-H or OJ-H column.
2935, 1628, 1467, 1254, 909, 734, 702. 1H NMR (CDCl3, d ppm):
2.86 (dd, J = 10.2, 12.9 Hz, 1H), 2.93 (br, 1H), 3.04 (d, J = 12.9 Hz,
1H), 3.87 (s, 3H), 4.34 (dd, J = 1.7, 10.2 Hz, 1H), 6.47 (dd, J = 0.6,
7.2 Hz, 1H), 6.67 (t, J = 8.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 6.97
(dd, J = 0.8, 7.2 Hz, 2H), 7.13 (m, 4H), 7.24 (m, 3H), 7.38 (t,
J = 7.6 Hz, 2H), 7.48 (d, J = 7.6 Hz, 2H), 7.54 (s, 1H), 7.65 (dd,
J = 0.9, 8.0 Hz, 2H), 13.26 (br, 1H). 13C NMR: 37.6, 56.1, 78.7, 79.9,
114.1, 118.1, 118.3, 123.1, 125.6, 125.9, 126.1, 126.2, 126.4,
127.1, 127.2, 128.37, 128.4, 128.5, 128.6, 128.64, 128.8, 129.2,
129.9, 139.0, 144.2, 145.3, 148.3, 151.2, 166.7. HRMS: calcd for
5.5.2. (S)-1-(4-Nitrophenyl)-2-nitroethanol 4a
C
29H27NO3: 437.1991, found 437.1983.
Compound 4a was prepared according to the general procedure
and purified by column chromatography (16.7% EtOAc in petro-
leum ester) to give an off-white solid (86% yield). Mp: 83–85 °C;
IR (film cmꢀ1): 3401, 2919, 1555, 1416, 1382, 1349, 1086, 856,
754, 727, 697. 1H NMR (CDCl3, d ppm): 3.20 (br, 1H), 4.60 (m,
2H), 5.61 (m, 1H), 7.64 (d, 2H, J = 8.6 Hz), 8.27 (d, 2H, J = 8.6 Hz).
13C NMR: 70.1, 80.7, 124.3, 127.1, 145.1, 148.3. HRMS: calcd for
C8H8N2O5: 212.0433, found 212.0443. Enantiomeric excess was
determined by HPLC5 with a Chiralcel OD-H column (80:20 hex-
anes–isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 22.9 min, major enantiomer tr = 27.8 min; 92% ee;
5.4.8. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-4-methoxyphenol 6h
½
a 2D5
ꢂ
¼ ꢀ54:0 (c 0.68, CH2Cl2). IR (film cmꢀ1): 3389, 3027, 2928,
1633, 1492, 1269, 744, 700. 1H NMR (CDCl3, d ppm): 2.84 (dd,
J = 10.2, 13.2 Hz, 1H), 2.92 (br, 1H), 3.04 (d, J = 13.2 Hz, 1H), 3.68
(s, 3H), 4.34 (dd, J = 1.5, 10.2 Hz, 1H), 6.37 (d, J = 2.7 Hz, 1H), 6.83
(t, J = 3.5 Hz, 1H), 6.96 (dd, J = 1.2, 6.9 Hz, 2H), 7.15 (m, 4H), 7.26
(m, 4H), 7.39 (m, 2H), 7.50 (m, 3H), 7.64 (d, J = 7.2 Hz, 2H), 12.13
(br, 1H). 13C NMR: 37.4, 55.8, 78.8, 79.8, 115.3, 117.4, 118.1,
119.2, 126.0, 126.2, 126.3, 127.0, 127.1, 128.2, 128.26, 128.34,
128.36, 128.4, 128.5, 128.7, 129.7, 138.9, 144.1, 145.3, 151.9,
½
a 2D5
ꢂ
¼ þ35:9 (c 1.01, CH2Cl2).
154.6, 166.3. HRMS: calcd for
437.1985.
C
29H27NO3: 437.1991, found
5.5.3. (S)-1-(2-Nitrophenyl)-2-nitroethanol 4b
Compound 4b was prepared according to the general procedure
and purified by column chromatography (16.7% EtOAc in petro-
leum ester) to give a brown solid (87% yield). Mp: 79–81 °C; IR
(film cmꢀ1): 3537, 1587, 1533, 1422, 1380, 1365, 1091, 1071,
866. 1H NMR (CDCl3, d ppm): 3.24 (br, 1H), 4.56 (dd, 1H, J = 9,
13.8 Hz), 4.88 (dd, 1H, J = 2.1, 13.8 Hz), 6.06 (d, 1H, J = 9 Hz), 7.56
(t, 1H, J = 7.8 Hz), 7.76 (t, 1H, J = 7.8 Hz), 7.96 (d, 1H, J = 8.3 Hz),
8.09 (d, 1H, J = 8.3 Hz). 13C NMR: 66.8, 80.1, 124.9, 128.7, 129.7,
134.3, 134.5, 147.0. HRMS: calcd for C8H8N2O5: 212.0433, found
212.0452. Enantiomeric excess was determined by HPLC5 with a
Chiralcel OD-H column (90:10 hexanes–isopropanol, 0.7 mL/min,
215 nm); minor enantiomer tr = 21.2 min, major enantiomer
5.4.9. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-6-chlorophenol 6i
½
a 2D5
ꢂ
¼ ꢀ58:1 (c 0.90, CH2Cl2). IR (film cmꢀ1): 3385, 3061, 3028,
2932, 1629, 1449, 736, 701. 1H NMR (CDCl3, d ppm): 2.87 (dd,
J = 9.9, 12.9 Hz, 1H), 2.90 (br, 1H), 3.04 (d, J = 12.9 Hz, 1H), 4.37
(dd, J = 1.7, 9.9 Hz, 1H), 6.67 (t, J = 7.7 Hz, 1H), 6.76 (dd, J = 1.4,
7.7 Hz, 1H), 6.96 (dd, J = 1.4, 6.9 Hz, 2H), 7.15 (m, 3H), 7.25 (m,
3H), 7.32 (m, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.48 (t, J = 7.8 Hz, 3H),
7.64 (d, J = 7.5 Hz, 2H), 13.77 (br, 1H). 13C NMR: 37.5, 78.5, 79.8,
118.6, 119.1, 121.7, 126.1, 126.2, 126.6, 127.2, 127.4, 128.5,
128.6, 128.7, 129.8, 130.1, 132.9, 138.8, 144.0, 145.2, 157.5,
166.0. HRMS: calcd for C28H24ClNO2: 441.1496, found 441.1491.
tr = 23.8 min; 92% ee; ½a D25
¼ þ139:7 (c 0.61, CH2Cl2).
ꢂ
5.5.4. (S)-1-(4-Chlorophenyl)-2-nitroethanol 4c
5.4.10. 2-(((S)-1-Hydroxy-1,1,3-triphenylpropan-2-ylimino)-
methyl)-4-chlorophenol 6j
Compound 4c was prepared according to the general procedure
and purified by column chromatography (10% EtOAc in petroleum
ester) to give a colorless oil (81% yield). IR (film cmꢀ1): 3446, 2924,
2255, 1557, 1493, 1379, 1090, 1015, 909, 829, 735, 651, 530; 1H
NMR (CDCl3, d ppm): 3.19 (br, 1H), 4.48 (dd, 1H, J = 3.4, 13.4 Hz),
4.57 (dd, 1H, J = 9.2, 13.4 Hz), 5.44 (dd, 1H, J = 3.4, 9.2 Hz), 7.34
(d, 2H, J = 8.6Hz), 7.38 (d, 2H, J = 8.6 Hz). 13C NMR: 70.4, 81.1,
127.4, 129.3, 134.9, 136.7. HRMS: calcd for C8H8ClNO3: 201.0193,
found 201.0194. Enantiomeric excess was determined by HPLC5
½
a 2D5
ꢂ
¼ ꢀ33:5 (c 0.78, CH2Cl2). IR (film cmꢀ1): 3482, 3060, 3028,
2930, 1632, 1479, 1276, 745, 700. 1H NMR (CDCl3, d ppm): 2.84 (m,
2H), 3.06 (d, J = 13.7 Hz, 1H), 4.35 (t, J = 5.0 Hz, 1H), 6.82 (m, 2H),
6.96 (m, 2H), 7.16 (m, 4H), 7.26 (m, 4H), 7.40 (m, 2H), 7.47 (m,
3H), 7.63 (m, 2H), 12.71 (br, 1H). 13C NMR: 37.5, 78.9, 79.9,
118.5, 119.2, 123.3, 126.2, 126.3, 126.7, 127.2, 127.4, 128.5,
128.6, 128.7, 129.8, 130.6, 130.6, 132.4, 138.8, 144.1, 145.2,
159.4, 165.4. HRMS: calcd for C28H24ClNO2: 441.1496, found
441.1489.
with
a Chiralcel OD–H column (85:15 hexanes–isopropanol,
0.5 mL/min, 215 nm); minor enantiomer tr = 18.4 min, major enan-
tiomer tr = 22.6 min; 90% ee; ½a D25
¼ þ20:5 (c 1.12, CH2Cl2).
ꢂ
5.5. General procedure for complex 1
5.5.5. (S)-1-(3-Chlorophenyl)-2-nitroethanol 4d
To a solution of 0.5 mmol of chiral Schiff-base 6 in 10 mL of
methanol, 0.6 mmol of Cu(OAc)2ꢃH2O were added. The solution
was stirred in the room temperature for 2 h after which 20 mmol
of NaOH were added. Another 6 h of stirring time was needed.
The methanol was evaporated under reduced temperature. To
Compound 4d was prepared according to the general procedure
and purified by column chromatography (10% EtOAc in petroleum
ester) to give a colorless oil (82% yield). IR (film cmꢀ1): 3563, 1597,
1557, 1477, 1422, 1378, 910, 739. 1H NMR (CDCl3, d ppm): 2.92 (br,
1H), 4.51 (dd, 1H, J = 3.4, 13.6 Hz), 4.59 (dd, 1H, J = 8.9, 13.6 Hz),

1818
G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
5.46 (dd, 1H, J = 3.4, 8.9 Hz), 7.35 (m, 4H). 13C NMR: 70.4, 81.1,
124.2, 126.3, 129.2, 130.4, 135.1, 140.2. HRMS: calcd for
C8H8ClNO3: 201.0193, found 201.0195. Enantiomeric excess was
determined by HPLC8q with a Chiralcel OD-H column (85:15 hex-
anes: isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 25.9 min, major enantiomer tr = 31.7 min; 91% ee;
5.5.10. (S)-1-(4-Methoxyphenyl)-2-nitroethanol 4i
Compound 4i was prepared according to the general procedure
and purified by column chromatography (12.5% EtOAc in petro-
leum ester) to give a yellow oil (72% yield). IR (film cmꢀ1): 3464,
2934, 1553, 1514, 1462, 1420, 1379, 1304, 1249, 1178, 1076,
1030, 896, 834, 784, 731, 693. 1H NMR (CDCl3, d ppm): 2.93 (br,
1H), 3.80 (s, 3H), 4.46 (dd, 1H, J = 3.2, 13.1 Hz), 4.58 (dd, 1H,
J = 9.5, 13.1 Hz), 5.38 (dd, 1H, J = 3.2, 9.5 Hz), 6.91 (d, 2H,
J = 8.6 Hz), 7.31 (d, 2H, J = 8.6 Hz). 13C NMR: 55.4, 70.8, 81.3,
114.5, 129.4, 130.4, 160.1. HRMS: calcd for C9H11NO4: 197.0688,
found 197.0693. Enantiomeric excess was determined by HPLC5
½
a 2D5
ꢂ
¼ þ82:1 (c 0.57, CH2Cl2).
5.5.6. (S)-1-(2-Chlorophenyl)-2-nitroethanol 4e
Compound 4e was prepared according to the general procedure
and purified by column chromatography (10% EtOAc in petroleum
ester) to give a colorless oil (85% yield). IR (film cmꢀ1): 3589, 2924,
2256, 1557, 1473, 1442, 1416, 1379, 1344, 1285, 1211, 1131, 1086,
1037, 905, 734, 650, 610. 1H NMR (CDCl3, d ppm): 3.17 (br, 1H),
4.44 (dd, 1H, J = 9.5, 13.5 Hz), 4.65 (dd, 1H, J = 2.5, 13.5 Hz), 5.82
(dd, 1H, J = 2.5, 9.5 Hz), 7.32 (m, 3H), 7.64 (m, 1H). 13C NMR:
68.0, 79.4, 127.6, 127.7, 129.8, 130.0, 131.6, 135.7. HRMS: calcd
for C8H8ClNO3: 201.0193, found 201.0188. Enantiomeric excess
was determined by HPLC5 with a Chiralcel OJ-H column (98:2 hex-
anes–isopropanol, 0.8 mL/min, 215 nm); minor enantiomer
with
a Chiralcel OD-H column (90:10 hexanes–isopropanol,
0.5 mL/min, 215 nm); minor enantiomer tr = 38.7 min, major enan-
tiomer tr = 48.9 min, 84% ee; ½a D25
¼ þ29:0 (c 2.03, CH2Cl2).
ꢂ
5.5.11. (S)-1-(2-Methoxyphenyl)-2-nitroethanol 4j
Compound 4j was prepared according to the general procedure
and purified by column chromatography (14.3% EtOAc in petro-
leum ester) to give a slight yellow oil (83% yield). IR (film cmꢀ1):
3538, 3011, 2944, 1556, 1492, 1347, 1290, 1073, 1026, 910, 859,
735, 616. 1H NMR (CDCl3, d ppm): 3.13 (d, 1H, J = 5.7 Hz), 3.89 (s,
3H), 4.58 (dd, 1H, J = 8.9, 13.0 Hz), 4.66 (dd, 1H, J = 3.3, 13.0 Hz),
5.63–5.66 (m, 1H), 6.92 (m, 1H), 7.03 (m, 1H), 7.34 (m, 1H), 7.45
(m, 1H). 13C NMR: 55.4, 67.8, 79.9, 110.6, 121.1, 126.1, 127.2,
129.8, 156.1. HRMS: calcd for C9H11NO4: 197.0688, found
197.0691. Enantiomeric excess was determined by HPLC5 with a
Chiralcel OD-H column (90:10 hexanes–isopropanol, 0.5 mL/min,
215 nm); minor enantiomer tr = 20.9 min, major enantiomer
tr = 72.8 min, major enantiomer tr = 77.2 min; 96% ee;
þ46:3 ðc 1:07; CH2Cl2Þ.
½
a 2D5
ꢂ
¼
5.5.7. (S)-1-Phenyl-2-nitroethanol 4f
Compound 4f was prepared according to the general procedure
and purified by column chromatography (12.5% EtOAc in petro-
leum ester) to give a colorless oil (76% yield). IR (film cmꢀ1):
3535, 3032, 2920, 1554, 1495, 1453, 1418, 1379, 1290, 1212,
1066, 895, 764, 702, 608. 1H NMR (CDCl3, d ppm): 3.24 (br, 1H),
4.49 (m, 1H), 4.59 (m, 1H), 5.44 (dd, 1H, J = 3.2, 9.5 Hz), 7.40 (m,
5H). 13C NMR: 71.0, 81.2, 126.0, 129.0, 129.0, 138.3. HRMS: calcd
for C8H9NO3: 167.0582, found 167.0579. Enantiomeric excess
was determined by HPLC5 with a Chiralcel OD-H column (85:15
hexanes–isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 19.9 min, major enantiomer tr = 22.4 min; 91% ee;
tr = 23.9 min; 93% ee; ½a D25
¼ þ43:6 (c 1.05, CH2Cl2).
ꢂ
5.5.12. (S)-1-(1-Naphthyl)-2-nitroethanol 4k
Compound 4k was prepared according to the General Procedure
and purified by column chromatography (16.7% EtOAc in petro-
leum ester) to give a yellow solid (80% yield). IR (film cmꢀ1):
3558, 3062, 2922, 1552, 1513, 1418, 1378, 1277, 1204, 1097,
911, 802, 780, 738, 650, 622. 1H NMR (CDCl3, d ppm): 2.92 (br,
1H), 4.66 (m, 2H), 6.26 (m, 1H), 7.55 (m, 3H), 7.76 (m, 1H), 7.87
(m, 2H), 8.02 (m, 1H). 13C NMR: 68.3, 80.8, 121.9, 123.9, 125.5,
126.1, 127.0, 129.3, 129.3, 129.6, 133.68, 133.73. HRMS: calcd for
½
a 2D5
ꢂ
¼ þ38:1 (c 0.98, CH2Cl2).
5.5.8. (S)-2-Nitro-1-p-tolylethanol 4g
Compound 4g was prepared according to the general procedure
and purified by column chromatography (12.5% EtOAc in petro-
leum ester) to give a yellow oil (67% yield). IR (film cmꢀ1): 3548,
3028, 2924, 1555, 1516, 1418, 1378, 1287, 1208, 1077, 910, 819,
734. 1H NMR (CDCl3, d ppm): 2.36 (s, 3H), 2.71 (br, 1H), 4.48 (dd,
1H, J = 2.9, 13.4 Hz), 4.60 (dd, 1H, J = 9.6, 13.4 Hz), 5.42 (dd, 1H,
J = 2.9, 9.6 Hz), 7.20 (d, 2H, J = 7.8 Hz), 7.28 (m, 2H). 13C NMR:
21.2, 71.0, 81.3, 126.0, 129.8, 135.3, 139.0. HRMS: calcd for
C9H11NO3: 181.0739, found 181.0746. Enantiomeric excess was
determined by HPLC8n with a Chiralcel OD-H column (85:15 hex-
anes–isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 18.6 min, major enantiomer tr = 22.8 min; 91% ee;
C
12H11NO3: 217.0739, found 217.0736. Enantiomeric excess was
determined by HPLC5 with a Chiralcel OD-H column (85:15 hex-
anes–isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 24.3 min, major enantiomer tr = 32.7 min; 91% ee;
½
a 2D5
ꢂ
¼ þ24:1 (c 1.06, CH2Cl2).
5.5.13. (S)-1-Nitro-3-phenylpropan-2-ol 4l
Compound 4l was prepared according to the general procedure
and purified by column chromatography (14.3% EtOAc in petro-
leum ester) to give a colorless oil (71% yield). IR (film cmꢀ1):
3431, 2924, 1554, 1453, 1422, 1383, 1089, 756, 702. 1H NMR
(CDCl3, d ppm): 2.60 (br, 1H), 2.81 (dd, 1H, J = 6.4, 14.0 Hz), 2.89
(dd, 1H, J = 7.4, 14.0 Hz), 4.36 (dd, 1H, J = 7.2, 12.3 Hz), 4.43 (dd,
1H, J = 2.7, 12.3 Hz), 4.53 (dd, 1H, J = 4.8, 8.4 Hz), 7.28 (m, 5H).
13C NMR: 40.5, 69.6, 79.8, 127.4, 128.7, 129.0, 136.0. HRMS: calcd
for C9H11NO3: 181.0739, found 181.0741. Enantiomeric excess was
determined by HPLC12 with a Chiralcel OD–H column (90:10 hex-
anes–isopropanol, 0.5 mL/min, 215 nm); minor enantiomer
tr = 30.5 min, major enantiomer tr = 38.6 min; 81% ee;
½
a 2D5
ꢂ
¼ þ23:4 (c 1.12, CH2Cl2).
5.5.9. (S)-2-Nitro-1-o-tolylethanol 4h
Compound 4h was prepared according to the general procedure
and purified by column chromatography (10.0% EtOAc in petro-
leum ester) to give a yellow oil (81% yield). IR (film cmꢀ1): 3551,
3024, 2925, 1557, 1490, 1462, 1418, 1379, 1285, 1218, 1069,
900, 769, 678, 616. 1H NMR (CDCl3, d ppm): 2.40 (s, 3H), 2.69 (br,
1H), 4.44 (dd, 1H, J = 2.5, 13.2 Hz), 4.56 (dd, 1H, J = 9.5, 13.2 Hz),
5.69 (dd, 1H, J = 2.5, 9.5 Hz), 7.24 (m, 3H), 7.51 (m, 1H). 13C NMR:
18.8, 67.9, 80.2, 125.6, 126.7, 128.6, 130.8, 134.6, 136.4. HRMS:
calcd for C9H11NO3: 181.0739, found 181.0751. Enantiomeric ex-
cess was determined by HPLC5 with a Chiralcel OD-H column
(85:15 hexanes–isopropanol, 0.7 mL/min, 215 nm); minor enantio-
mer tr = 11.2 min, major enantiomer tr = 15.8 min; 95% ee;
½
a 2D5
ꢂ
¼ ꢀ43:4 (c 2.17, CH2Cl2).
5.5.14. (S)-4-Methyl-1-nitropentan-2-ol 4m
Compound 4m was prepared according to the General Proce-
dure and purified by column chromatography (14.3% EtOAc in
petroleum ester) to give a colorless oil (76% yield). IR (film
cmꢀ1): 3416, 2960, 1557, 1467, 1384, 1296, 1206, 1144, 1089,
1045, 891, 848, 735, 646. 1H NMR (CDCl3, d ppm): 1.00 (m, 6H),
½
a 2D5
ꢂ
¼ þ51:2 (c 1.01, CH2Cl2).

G. Lai et al. / Tetrahedron: Asymmetry 19 (2008) 1813–1819
1819
1.80 (m, 1H), 2.34 (br, 1H), 4.11 (m, 1H), 4.45 (m, 2H). 13C NMR:
21.8, 23.1, 24.3, 42.5, 67.1, 81.1. HRMS: calcd for C6H13NO3:
147.0895, found 147.0889. Enantiomeric excess was determined
by HPLC5 with a Chiralcel OJ-H column (98:2 hexanes–isopropanol,
0.6 mL/min, 215 nm); minor enantiomer tr = 35.0 min, major enan-
Zhong, Y.-W.; Tian, P.; Lin, G.-Q. Tetrahedron: Asymmetry 2004, 15, 771–776; (g)
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106; (h) Misumi, Y.; Matsumoto, K. Angew. Chem., Int. Ed. 2002, 1031–1033; (i)
Arai, T.; Watanabe, M.; Fujiwara, A.; Yokoyama, N.; Yanagisawa, A. Angew.
Chem., Int. Ed. 2006, 45, 5978–5981; (j) Vongvilai, P.; Angelin, M.; Larsson, R.;
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tiomer tr = 38.4 min; 85% ee; ½a D25
¼ ꢀ1:9 (c 2.31, CH2Cl2).
ꢂ
5.5.15. (S)-1-Nitropentan-2-ol 4n6b
Compound 4n was prepared according to the general procedure
and purified by column chromatography (14.3% EtOAc in petro-
leum ester) to give a colorless oil (70% yield). IR (film cmꢀ1):
3444, 3022, 2964, 2936, 1555, 1464, 1421, 1382, 1285, 1216,
1132, 1085, 1025, 758, 669. 1H NMR (CDCl3, d ppm): 0.97 (t, 3H,
J = 6.9 Hz), 1.51 (m, 4H), 2.52 (br, 1H), 4.35 (m, 1H), 4.42 (m, 2H).
13C NMR: 13.8, 18.5, 35.9, 68.6, 80.8. HRMS: calcd for C5H11NO3:
133.0739, found 133.0735. Enantiomeric excess was determined
by HPLC with a Chiralcel OD-H column (98:2 hexanes–isopropanol,
0.6 mL/min, 215 nm); minor enantiomer tr = 34.4 min, major enan-
tiomer tr = 36.3 min; 85% ee; ½a D25
¼ ꢀ15:8 (c 2.12, CH2Cl2).
ꢂ
Acknowledgment
9. For organocatalysts see: (a) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Adv.
Synth. Catal. 2005, 347, 1643–1648; (b) Sohtome, Y.; Hashimoto, Y.; Nagasawa,
K. Eur. J. Org. Chem. 2006, 2894–2897; (c) Marcelli, T.; van der Haas, R. N. S.; van
Maarseveen, J. H.; Hiemstra, H. Angew. Chem., Int. Ed. 2006, 45, 929–931;
Marcelli, T.; van der Haas, R. N. S.; van Maarseveen, J. H.; Hiemstra, H. Angew.
Chem., Int. Ed. 2006, 45, 7496–7504; (d) Taylor, M. S.; Jacobsen, E. N. Angew.
Chem. Int. Ed. 2006, 45, 1520–1543; (e) Connon, S. J. Chem. Eur. J. 2006, 12,
5418–5427; (f) Pihko, P. M. Angew. Chem., Int. Ed. 2004, 43, 2062–2064; (g)
Schreiner, P. R. Chem. Soc. Rev. 2003, 32, 289–296; (h) Li, H.; Wang, B.; Deng, L. J.
Am. Chem. Soc. 2006, 128, 732–733; (i) Takada, K.; Takemura, N.; Cho, K.;
Sohtome, Y.; Nagasawa, K. Tetrahedron Lett. 2008, 49, 1623–1626.
The authors are grateful to National Natural Science Foundation
of China (Nos. 20472078 and 30572234).
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