Asymmetric Cu-catalyzed Henry reaction using chiral camphor Schiff bases immobilized on a macromolecular chain

Article abstract of DOI:10.1016/j.tetlet.2019.06.006

Immobilized catalysts have attracted chemists’ attention for long time because of convenient recycling, which is very important for some special catalyst even immobilizations accompanying the decrease of catalytic activity and selectivity. Our group focus

Full text of DOI:10.1016/j.tetlet.2019.06.006

Accepted Manuscript
Asymmetric Cu-catalyzed Henry reaction using chiral camphor Schiff bases
Immobilized on a macromolecular chain
Kaihua Zhang, Jialin Sun, Jingwen Xu, Gaoqiang Li, Feng Xu
PII:
S0040-4039(19)30536-2
https://doi.org/10.1016/j.tetlet.2019.06.006
TETL 50847
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
24 April 2019
29 May 2019
5 June 2019
Please cite this article as: Zhang, K., Sun, J., Xu, J., Li, G., Xu, F., Asymmetric Cu-catalyzed Henry reaction using
chiral camphor Schiff bases Immobilized on a macromolecular chain, Tetrahedron Letters (2019), doi: https://
doi.org/10.1016/j.tetlet.2019.06.006
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Tetrahedron Letters
journal homepage: www.elsevier.com
Asymmetric Cu-catalyzed Henry reaction using chiral camphor Schiff bases
Immobilized on a macromolecular chain
Kaihua Zhang, Jialin Sun, Jingwen Xu, Gaoqiang Li, Feng Xu *
Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi’an, Shaanxi
710062, PR China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Immobilized catalysts have attracted chemists’ attention for long time because of convenient
recycling, which is very important for some special catalyst even immobilizations
accompanying the decrease of catalytic activity and selectivity. Our group focused on the
developing chiral catalysts with camphor framework to catalyze various asymmetric reactions
for long time. For easily recycling the unique chiral catalysts, a series of polymer catalysts with
chiral camphor unit were synthesized by RAFT polymerization. Herein, the performance of the
synthesized polymer chiral catalysts was reported by catalyzing asymmetric Henry reaction.
After optimizing the reaction conditions, the synthesized chiral polymer catalyst provides a
good yield and enantioselectivity to the reaction of p-nitrobenzaldehyde and nitromethane. In
the meantime, the recycles and reused properties of synthesized polymer catalysts were
examination by the model asymmetric Henry reaction. The catalyzed activities and
enantioselectivities did not show obviously decrease until recycling five times.
Available online
Keywords:
Recycling
polymer catalysts
RAFT
Henry reaction
2009 Elsevier Ltd. All rights reserved.
reuse and recycles is still a challenge for the development of the
unique chiral catalyst. The immobilization is a very useful
1. Introduction
method for the catalyst recycle and reuse. In this paper, the
sensitive polymer was selected as the supporter to immobilize the
synthesis chiral camphor β-amino alcohols [13], which will take
the advantage of polymer supporter for recycle and chiral catalyst
for high catalytic ability. Even many polymer immobilization
catalysts have been reported [14], the use of camphor-derived
chiral amino alcohol ligands for immobilization into polymer
chains via a chain transfer agent has not been reported [15]. The
new immobilized catalyst easily separate and recycle from the
reaction mixture. The catalyst does not need re-coordinated with
metal salt after recycling and maintaining stable catalytic
efficiency till to five times recycling [16].
The asymmetric Henry reaction is one of the most classical
reactions in organic name reactions. The most prominent feature
of asymmetric Henry reaction is the formation of asymmetric C-
C bonds, which accompanied to form one or two chiral centers.
Generally, Henry reaction occurs between aldehyde or ketone
and nitroalkanes containing active ortho-hydrogen in presence of
an organic base to produce β-nitroalcohol [1], which has wide
range applications in synthesis of natural products and medicines.
β-nitroalcohol is easy to convert other useful intermediate
compounds, such as amino compounds by reduction, conjugated
nitroalkenes by elimination, or aldehydes, ketones, carboxylic
acids by oxidation. In addition, it also can be used as a
nucleophile to participate an addition reaction with an
electrophilic substance [2].
Four different style copolymers with chiral functional group
were designed and synthesized (Scheme 1). The best block
copolymer catalysts was selected by comparing the effects of
copolymerization and the other functional groups, in which we
screened the ligand species, metal salts, solvents, monomer
ratios, ligand amounts, and the ratio of metals.
The key point of the asymmetric Henry reaction lies in the
synthesis of chiral catalyst. Nowadays, there are many mature
catalytic systems applied to the asymmetric Henry reaction. The
main catalyst categories are organic small molecule catalysts [3],
metal complex catalysts [4] and supported catalysts [5]. Among
the metal complex catalyzes the Henry reaction, copper is most
widely used coordination metals, the ligand which reported
mainly include amino alcohol ligands [6], bisoxazoline ligands
[7], bis-imidazoline ligands [8], bisthiazoline ligands [9], Schiff
base ligands [10], Salen ligands [11] and so on. Recently years,
our group focuses on the development new chiral catalyst based
on the natural camphor structure [12]. However, the catalysts
2. Results and discussion
The synthetic process of L1-L4 can be found in the
supporting information. Based on the paper reported the Henry
reaction condition, the catalytic performance of L1-L4 to the
asymmetric Henry reaction was screened by the model reaction
of p-nitrobenzaldehyde and nitromethane using 20mol% ligand
* Corresponding Author. e-mail: fengxu@snnu.edu.cn

S
S
S
S
S
S
10
10
COOH
COOH
4
6
66
4
6
66
O
O
HN
HN
O
O
O
O
OH
OH
OH
OH
CHO
OH
N
HN
OH
OH
Ligand L1
Ligand L2
S
S
S
S
S
S
10
10
COOH
COOH
8
6
42
8
6
42
O
O
HN
HN
O
O
O
O
CHO
OH
N
HN
OH
OH
Ligand L3
Ligand L4
Scheme 1. The structure of L1-L4
and 10mol% CuCl (all the amount of the catalysts are based on
the amount of camphor Schiff base unit) at room temperature in
t-BuOH as the initial reaction condition. The results are listed in
Table 1. L1 show the best results as 82% yield and 79% e.e.
(Table 1, entry 1). Then, the L1 ligand was selected as target to
check the catalytic effect of different molar ratio of copolymer
block to model reaction. The best catalytic property was obtained
as 80% yield and 82% e.e. (Table 2, entry 2) in the ratio of
NIPAM to functional monomer to chain transfer agent to AIBN
as 110 to 10 to 1 to 0.4. Next, different metal salts were used as
the source of coordination metal species to copolymer ligand to
check the catalytic effect. The results are show in Table 3 and
cuprous chloride gave the best result as 80% yield and 82% e.e..
Other metal salts showed inferior performances than cuprous
chloride. Therefore, cuprous chloride was proved to be the best
source of coordination metal species and was used to investigate
the further reaction condition. When the ratio of copolymer
ligand and copper salt was adjusted from 1:1 to 1:2, the model
reaction yield and enantioselectivity were change from 70% and
76% e.e. (Table 3, entry 11) to 74% and 76% e.e. (Table 3, entry
12). In addition, the catalyst loading also affected the reaction
results, when the catalyst loading was reduced to 5mol%, the
yield and enantioselectivity was increased to 85% and 84% e.e.
(Table 3, entry 14). Thus, 5mol% ligand L1 (in definite ratio of
copolymer block) /2.5mol% CuCl complex was selected as the
most efficient catalyst for the model reaction.
Unfortunately, the heterocyclic aldehydes show the lower yield
and inferior enantioselectivity (Table 6, entry 18).
The recycling of new catalytic system was also examined
under the optimal reaction condition by model reaction. After
finished the first cycle, the reaction mixture was added to ether
for separation catalyst after centrifugation. The solution part was
used to separate final product by column chromatography. The
precipitate was used as the second times catalyst. The results of
recycling this new catalytic system were summarized in Table 5.
Those results implied this new catalytic system can maintain
good yields and enantioselectivities until the fifth time recycles
without complement metal salt.
Table 1
Enantioselective Henry reaction of nitromethane with p-
nitrobenzaldehyde using different ligands a
O
OH
*
Ligand (20mol%)
CuCl (10mol%)
t-BuOH, rt, 36h
NO2
H
CH3NO2
+
O2N
O2N
1a
2a
Entry
Ligand
L1
L2
L3
L4
%Yield b
%ee c
Config. d
The solvent effect was examined and summarized in Table
4. Protic solvents (Table 4, entry 1–3) give higher yield and
enantioselectivity than aprotic solvents (Table 4, entries 4–10).
1
2
3
4
82
61
31
56
79
53
15
65
R
R
R
R
Under the optimal reaction condition, the substrate scope of
new catalytic system was investigated between nitromethane and
different aldehydes in the presence of 5mol% L1/2.5mol% CuCl
in t-butanol at room temperature. The results are presented in
table 6. The electronic properties of substitution in aromatic
aldehydes have a great effect on the chemical yield and
enantioselectivity. In generally, an aromatic aldehyde having
electron withdrawing group can produce higher selectivity and
reaction rate than the case with an electron donating group. The
aldehyde, not only with aromatic substitution but also with
heterocyclic substitution, was suitable this new catalytic process.
a All reactions were carried out with 0.5 mmol p-nitrobenzaldehyde and 5
mmol nitromethane in 2 mL t-BuOH.
b Isolated yield after chromatographic purification.
c Determined by chiral HPLC.
d Absolute configuration through other articles comparison.
Table 2
Effect of the Molar ratio of two monomers in the Ligand L1
on the Asymmetric Henry reaction a

OH
*
O
8
9
10
CH3CN
Toluene
CH3NO2
rt
rt
rt
36
36
48
5
52
31
15
44
17
L1
Ligand
(20mol%)
NO2
H
CuCl (10mol%)
CH3NO2
+
t-BuOH, rt, 36h
O2N
O2N
a All reactions were carried out with 0.5 mmol p-nitrobenzaldehyde and 5
mmol nitromethane in 2 mL solvent.
1a
2a
Entry
Molar Ratio b
%Yield c
%ee d
Config. e
b Isolated yield after chromatographic purification.
c Determined by chiral HPLC.
1
2
3
4
220:10:1:0.4
110:10:1:0.4
50:10:1:0.4
10:10:1:0.4
82
80
65
71
79
82
62
64
R
R
R
R
Table 5
Recycling of Catalysts in Asymmetric Henry reactions a
a
All reactions were carried out with 0.5 mmol p-nitrobenzaldehyde and
5 mmol nitromethane in 2 mL t-BuOH.
Molar ratio was the molar ratio of NIPAM, 2-hydroxy-4-[(4-
vinylbenzyl)oxy]benzaldehyde,
O
OH
*
L1
Ligand
(5mol%)
b
NO2
CuCl (2.5mol%)
H
CH3NO2
+
2-Methyl-2-[(dodecy
t-BuOH, rt, 36h
lsulfanylthiocarbonyl)sulfanyl]propanoic acid and AIBN.
c Isolated yield after chromatographic purification.
d Determined by chiral HPLC.
O2N
O2N
1a
2a
e Absolute configuration through literature comparison.
Recycling b
Temp(℃)
Time(h)
%Yield c
%ee d
1
2
3
4
5
rt
rt
rt
rt
rt
36
36
36
36
36
82
80
75
73
60
83
80
82
76
78
Table 3
Effect of metal salt on the asymmetric Henry reaction under
the chiral ligand L1 a
OH
*
O
L1
Ligand
a All reactions were carried out with 0.5 mmol p-nitrobenzaldehyde and 5
mmol nitromethane in 2 mL t-BuOH.
Catalyst recycling times. The catalyst is precipitated by ether and
NO2
H
Metal salt
CH3NO2
+
b
O2N
O2N
t-BuOH, rt, 36h
centrifuged before the next catalytic reaction.
c Isolated yield after chromatographic purification.
d Determined by chiral HPLC.
2a
1a
Entry
Metal salt
Ligand/metal
%Yield b
%ee c
Table 6
1
2
3
4
5
6
7
8
CuCl
CuBr
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
1:1
1:2
2:1
2:1
2:1
2:1
80
75
-
82
70
-
60
35
73
18
21
-
Asymmetric Henry reaction of nitromethane with various
aldehydes a
CuCl2
CuBr2
Cu(OAc)2
Cu(OTf)2
FeCl2
7
L1
Ligand
(5mol%)
82
13
15
8
-
-
70
74
73
85
79
74
OH
*
O
CuCl (2.5mol%)
CH3NO2
+
NO2
R
R
H
t-BuOH, rt
FeCl3
1
2
9
Ni(OTf)2
Zn(OTf)2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
10
11
12
13 d
14 e
15 f
16 g
-
Entry
Aldehyde
Product
Time(h)
%Yield b
%ee c
76
76
64
84
80
61
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-BrC6H4
3-BrC6H4
4-BrC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
3-FC6H4
4-FC6H4
4-CF3C6H4
C6H5
2-MeOC6H4
3-MeC6H4
4-MeC6H4
1-Naphthyl
2-Furyl
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
36
36
36
36
36
36
36
36
36
36
36
36
36
48
48
48
36
36
71
78
85
51
32
43
43
36
48
53
83
35
30
45
32
37
76
37
66
78
84
71
63
49
61
83
69
40
54
78
58
62
48
56
64
63
a All reactions were carried out with 0.5 mmol p-nitrobenzaldehyde and 5
mmol nitromethane in 2 mL t-BuOH.
b Isolated yield after chromatographic purification.
c Determined by chiral HPLC.
d CuCl (1.25mol%) and ligand (2.5mol%) were used.
e CuCl (2.5mol%) and ligand (5mol%) were used.
f CuCl (5mol%) and ligand (10mol%) were used.
g CuCl (12.5mol%) and ligand (25mol%) were used.
Table 4
Effect of Solvents on Asymmetric Henry reaction a
O
OH
*
L1
Ligand
(5mol%)
a All reactions were carried out with 0.5 mmol aldehydes and 5 mmol
nitromethane in 2 mL t-BuOH.
NO2
H
CuCl (2.5mol%)
CH3NO2
+
b Isolated yield after chromatographic purification.
c Determined by chiral HPLC.
O2N
Solvent, rt
O2N
1a
2a
3. Conclusion
Entry
Solvent
i-PrOH
t-BuOH
EtOH
dioxane
THF
Temp(℃)
Time(h)
36
36
36
36
36
36
36
%Yield b
%ee c
71
84
53
2
15
15
11
1
2
3
4
5
6
7
rt
rt
rt
rt
rt
rt
rt
75
85
61
10
31
25
74
Four novel camphor chiral Schiff base block copolymer L1-
L4 were synthesized by RAFT polymerization, which can used as
catalyst for asymmetric Henry reaction giving good results after
coordinated with CuCl. It’s the first time that a polymer with
chiral camphor-derived Schiff base was used as ligand for
copper-catalyzed asymmetric Henry. The catalytic process is
mild, operationally easy, and insensitive to air and water. The
CH2Cl2
DMSO

polymer catalyst can be reused for five times with steady
catalytic ability.
4.2.4. (R)-1-(2-Bromophenyl)-2-nitroethanol 2d
Colorless oil; 51% yield, 71% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 41.677
min, tR(minor) = 46.028 min; 1H NMR (400 MHz, CDCl3) δ 7.60
(dd, J = 8.2, 2.1 Hz, 1H), 7.50 (dd, J = 8.0, 1.2 Hz, 1H), 7.36 –
7.31 (m, 1H), 5.74 (d, J = 9.7 Hz, 1H), 4.65 (d, J = 2.3 Hz, 1H),
4.41 – 4.33 (m, 1H), 3.04 (s, 1H).
4. Experimental section
4.1. General
All chemical reagents were purchased from commercial
suppliers and used as received, if not stated otherwise.
Anhydrous solvents and reagents were absolutized as usual and
distilled prior to use. The1H NMR spectra were recorded on a
JEOL 400 NMR spectrometer (400 MHz for 1H). Chemical shifts
are reported in δ ppm referenced to an internal TMS standard for
1H NMR. IR spectra were recorded on a Bruker Tensor27
spectrometer. The relative molecular weights and polydispersity
index (PDI) were estimated by a gel permeation chromatography
(GPC, Waters Corp., Milford, MA, USA) equipped with Waters
515 pump and Waters 2410 differential refractive index detector.
The apparent particle size and size distribution of polymer
micelles were detected on a dynamic light scattering (DLS)
instrument (BI-90Plus, Brookhaven Instruments Corp.,
Holtsville, NY, USA) equipped with a 15 mM argon ion laser
operating at λ = 660 nm and scattering angle of 90° at room
temperature. The morphology observations were performed on a
transmission electron microscope (TEM, JEM-2100, Hitachi
Corporation, Tokyo, Japan) and operated at an accelerating
voltage of 200 kV. Before measurement, a drop of micellar
solution was dipped onto carbon coated copper grids which were
then dried at ambient temperature. Chemical composition and
chemical state were measured by a X-ray Photoelectron
Spectroscopy (XPS, AXIS ULTRA, Kratos Analytical Ltd). The
reactions were monitored by thin layer chromatography
(TLC)and visualized by UV light (254 nm). Flash column
chromatography was carried out on silica gel (200–400 mesh).
4.2.5. (R)-1-(3-Bromophenyl)-2-nitroethanol 2e
Colorless oil; 32% yield, 63% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 12.824
min, tR(minor) = 16.343 min; 1H NMR (400 MHz, CDCl3) δ 7.59
(s, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.44 – 7.34 (m, 1H), 7.34 – 7.25
(m, 2H), 5.45 (dd, J = 9.3, 3.2 Hz, 1H), 4.62 – 4.49 (m, 2H), 3.08
(s, 1H).
4.2.6. (R)-1-(4-Bromophenyl)-2-nitroethanol 2f
Colorless oil; 43% yield, 49% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 12.777
min, tR(minor) = 16.347 min; 1H NMR (400 MHz, CDCl3) δ 7.47
(d, J = 8.5 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 5.36 (d, J = 9.4 Hz,
1H), 4.54 – 4.38 (m, 2H), 2.88 (d, J = 3.7 Hz, 1H).
4.2.7. (R)-1-(2-Chlorophenyl)-2-nitroethanol 2g
Colorless oil; 43% yield, 61% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 95:5, 1 mL/min, 254 nm): tR(major) = 37.927
1
min, tR(minor) = 40.850 min; H NMR (400 MHz, CDCl3 ) δ
7.59 (d, J = 7.4 Hz, 1H), 7.46 – 7.28 (m, 2H), 7.28 – 7.22 (m,
1H), 6.11 – 5.73 (m, 1H), 4.60 (dd, J = 13.6, 2.4 Hz, 1H), 4.38
(dd, J = 13.6, 9.6 Hz, 1H), 3.02 (s, 1H).
4.2.8. (R)-1-(3-Chlorophenyl)-2-nitroethanol 2h
Colorless oil; 36% yield, 83% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 95:5, 1 mL/min, 254 nm): tR(major) = 34.807
1
min, tR(minor) = 45.022 min; H NMR (400 MHz, CDCl3 ) δ
7.36 (s, 1H), 7.30 – 7.25 (m, 2H), 7.24 – 7.20 (m, 1H), 5.53 –
5.30 (m, 1H), 4.51 (dd, J = 13.5, 9.3 Hz, 1H), 4.44 (dd, J = 13.5,
3.2 Hz, 1H), 2.91 (s, 1H).
4.2 General procedure for the asymmetric Henry reaction
A dried Schlenk tube was charged with L1 (0.025 mmol) in
dry t-BuOH (2 mL), then CuCl (0.0125 mmol) was added. The
reaction mixture was stirred at 25℃ under N2 atmosphere for
overnight. Nitromethane (0.5 mL) was added to the resulting
solution by a syringe. Then the reaction mixture was stirred for
an additional 30 min, and the aldehyde (0.5 mmol) was added.
After that, the reaction mixture was stirred at 25oC (monitoring
by TLC) for assigned time.
4.2.9. (R)-1-(4-Chlorophenyl)-2-nitroethanol 2i
Colorless oil; 48% yield, 69% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 11.445
min, tR(minor) = 14.036 min; 1H NMR (400 MHz, CDCl3 )δ 7.39
(d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 5.46 (d, J = 10.2
Hz, 1H), 4.62 – 4.47 (m, 2H), 2.97 (s, 1H).
4.2.10. (R)-1-(3-Fluorophenyl)-2-nitroethanol 2j
Colorless oil; 53% yield, 40% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 10.561
min, tR(minor) = 12.081 min;1H NMR (400 MHz, CDCl3 ) δ 7.38
(td, J = 8.0, 5.7 Hz, 1H), 7.19 – 7.14 (m, 2H), 5.55 – 5.44 (m,
1H), 4.63 – 4.50 (m, 2H), 3.12 (s, 1H).
After the reaction completed, the catalyst was removed by
using ether precipitation and centrifugation. The solvents were
evaporated under reduced pressure and the residue was purified
by column chromatography (PE/EA = 2:1). The e.e. values were
determined by HPLC analysis with a chiral column.
4.2.11. (R)-1-(4-Fluorophenyl)-2-nitroethanol 2k
Colorless oil; 83% yield, 54% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 10.125
min, tR(minor) = 11.569 min; H NMR (400 MHz, CDCl3 ) δ
7.35 – 7.27 (m, 2H), 7.03 (t, J = 8.7 Hz, 2H), 5.39 (d, J = 9.5 Hz,
1H), 4.56 – 4.40 (m, 2H), 2.87 (s, 1H).
4.2.1. (R)-2-Nitro-1-(2-nitrophenyl)ethanol 2a
Pale Yellow oil; 71% yield, 66% e.e., HPLC (Chiralcel OD-
H, n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) =
13.986 min, tR(minor) = 15.617 min; 1H NMR (400 MHz,
CDCl3) δ 8.01 (d, J = 7.0 Hz, 1H), 7.89 (d, J = 6.9 Hz, 1H), 7.68
(t, J = 7.1 Hz, 1H), 7.53 – 7.46 (m, 1H), 5.98 (d, J = 11.4 Hz,
1H), 4.80 (d, J = 15.8 Hz, 1H), 4.54 – 4.44 (m, 1H), 3.30 (s, 1H).
1
4.2.12. (R)-2-Nitro-1-(4-(trifluoromethyl)phenyl)ethanol 2l
Colorless oil; 35% yield, 78% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 9.493
4.2.2. (R)-2-Nitro-1-(3-nitrophenyl)ethanol 2b
1
min, tR(minor) = 11.604 min; H NMR (400 MHz, CDCl3 ) δ
Yellow solid; 78% yield, 78% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 20.123
min, tR(minor) = 23.550 min; 1H NMR (400 MHz, CDCl3) δ 8.24
(s, 1H), 8.14 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 8.3 Hz, 1H), 7.54 (t,
J = 8.0 Hz, 1H), 5.56 (s, 1H), 4.68 – 4.41 (m, 2H), 3.39 (s, 1H).
7.47 (d, J = 8.2 Hz, 2H), 5.36 (d, J = 9.4 Hz, 1H), 4.50 (dd, J =
13.8, 9.0 Hz, 1H), 4.42 (dd, J = 13.1, 3.5 Hz, 1H), 2.89 (s, 1H).
4.2.13. (R)-2-Nitro-1-phenylethanol 2m
Colorless oil; 30% yield, 58% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 11.890
min, tR(minor) = 14.141 min;1H NMR (400 MHz, CDCl3 ) δ 7.58
(d, J = 7.5 Hz, 1H), 7.30 (d, J = 13.2 Hz, 1H), 7.28 – 7.16 (m,
1H), 5.77 (dd, J = 10.3, 3.3 Hz, 1H), 4.60 (dd, J = 13.6, 2.3 Hz,
2H), 4.38 (dd, J = 13.6, 9.6 Hz, 2H), 2.99 (s, 1H).
4.2.3. (R)-2-Nitro-1-(4-nitrophenyl)ethanol 2c
Yellow solid; 85% yield, 84% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 20.467
min, tR(minor) = 24.025 min; 1H NMR (400 MHz, CDCl3) δ 8.30
– 8.17 (m, 2H), 7.71 – 7.57 (m, 2H), 5.61 (dd, J = 8.0, 4.5 Hz,
1H), 4.68 – 4.54 (m, 2H), 3.71 (d, J = 2.8 Hz, 1H).
4.2.14. (R)-1-(2-methoxyphenyl)-2-nitroethanol 2n

[3] (a) Bandini M, Sinisi R, Umani-Ronchi A. Chem. Commun. 2008; (36):
4360-4362;
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5383-5397;
Colorless oil;45% yield, 62% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 9.897
1
min, tR(minor) = 11.487 min; H NMR (400 MHz, CDCl3 ) δ
7.47 – 7.31 (m, 2H), 6.96 (dd, J = 36.3, 7.9 Hz, 2H), 5.64 (s, 1H),
4.71 – 4.53 (m, 2H), 3.17 (d, J = 6.0 Hz, 1H).
4.2.15. (R)-2-Nitro-1-(m-tolyl)ethanol 2o
Colorless oil; 32% yield, 48% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 9.788
min, tR(minor) = 11.131 min; H NMR (400 MHz, CDCl3 ) δ
7.22 (d, J = 7.5 Hz, 1H), 7.13 (dd, J = 15.8, 7.6 Hz, 3H), 5.40 –
5.34 (m, 1H), 4.54 (dd, J = 13.4, 9.6 Hz, 1H), 4.44 (dd, J = 13.4,
3.0 Hz, 1H), 2.70 (s, 1H), 2.31 (s, 3H).
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1
4.2.16. (R)-2-Nitro-1-(p-tolyl)ethanol 2p
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Colorless oil; 37% yield, 56% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 11.262
1
min, tR(minor) = 14.087 min; H NMR (400 MHz, CDCl3 ) δ
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725-728;
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1813-1819;
7.23 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 5.37 (d, J = 9.7
Hz, 1H), 4.54 (dd, J = 13.3, 9.6 Hz, 1H), 4.48 – 4.40 (m, 1H),
2.66 (s, 1H), 2.30 (s, 3H).
4.2.17. (R)-1-(Naphthalen-1-yl)-2-nitroethanol 2q
Colorless oil; 76% yield, 64% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 15.306
min, tR(minor) = 22.003 min; H NMR (400 MHz, CDCl3 ) δ
7.97 (d, J = 8.3 Hz, 1H), 7.82 (dd, J = 21.8, 8.1 Hz, 2H), 7.69 (d,
J = 7.2 Hz, 1H), 7.56 – 7.41 (m, 3H), 6.19 (d, J = 8.6 Hz, 1H),
4.73 – 4.48 (m, 2H), 2.84 (s, 1H).
(f) Ma K, You J. Chem. Eur. J. 2010; 13(6):1863-1871;
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1
(c) Puglisi A, Benaglia M, Cinquini M, et al. Eur. J. Org. Chem. 2004;
2004(3): 567-573;
4.2.18. (R)-1-(2-furyl)-2-nitroethanol 2r
Colorless oil; 37% yield, 63% e.e., HPLC (Chiralcel OD-H,
n-hexane/i-PrOH, 85:15, 1 mL/min, 254 nm): tR(major) = 11.262
min, tR(minor) = 14.087 min; H NMR (400 MHz, CDCl3 ) δ
7.36 (s, 1H), 6.33 (d, J = 2.8 Hz, 2H), 5.41 (dd, J = 9.1, 3.4 Hz,
1H), 4.72 (dd, J = 13.5, 9.1 Hz, 1H), 4.61 (dd, J = 13.5, 3.4 Hz,
1H), 2.89 (s, 1H).
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1
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Acknowledgments
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We are grateful for financial support from the National
Natural Science Foudation of China (No.21572123, 21172138
and 21302117), the Fundamental Research Funds for the Central
Universities (GK201601003 and GK201603047) and the
Distinguished Doctoral Research Funds from Shaanxi Normal
University (S2011YB04).
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338-343;
Supplementary data
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Supplementary data associated with this article can be found,
in the online version, at
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Highlights
 Chiral camphor unit was immobilized in
polymer chain.
 Chiral polymer was synthesized by RAFT
polymerization.
 The chiral polymer catalyst show high
catalytic ability and recycle four times.

S
10S
S
4
COOH
6
O 66
Ligand L1
(5 mol%)
HN
OH
*
O
CuCl(2.5 mol%)
CH3NO2
+
NO2
O
R
O
R
H
t-BuOH, rt
18 examples




OH
OH
CHO
up to 85% yield
up to 84% e.e.
up to 5 cycles
N
OH
Ligand L1