Design of C2-symmetric salen ligands and their Co(II)- or Yb(III)-complexes, and their role in the reversal of enantioselectivity in the asymmetric Henry reaction

Article abstract of DOI:10.1016/j.tet.2014.05.085

Reversal of enantioselectivity in asymmetric Henry reactions was achieved with novel chiral C₂-symmetric salen ligands bearing morpholine moieties by changing the Lewis acid center from Co(II) to Yb(III). The possible transition state models we

Full text of DOI:10.1016/j.tet.2014.05.085

Accepted Manuscript
Design of C2-symmetric salen ligands and their Co(II)- or Yb(III)- complexes, and
their role in the reversal of enantioselectivity in the asymmetric Henry reaction
Shengying Wu , Jun Tang , Jianwei Han , Dan Mao , Xin Liu , Xing Gao , Jianjun Yu ,
Limin Wang
PII:
S0040-4020(14)00791-1
10.1016/j.tet.2014.05.085
TET 25634
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 March 2014
Revised Date: 12 May 2014
Accepted Date: 22 May 2014
Please cite this article as: Wu S, Tang J, Han J, Mao D, Liu X, Gao X, Yu J, Wang L, Design of
C2-symmetric salen ligands and their Co(II)- or Yb(III)- complexes, and their role in the reversal of
enantioselectivity in the asymmetric Henry reaction, Tetrahedron (2014), doi: 10.1016/j.tet.2014.05.085.
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Design of C2-symmetric salen ligands and
their Co(II)- or Yb(III)- complexes, and their
role in the reversal of enantioselectivity in
the asymmetric Henry reaction
Leave this area blank for abstract info.
a,c
a,c
b
a
a
a
a
a
Shengying Wu, Jun Tang, Jianwei Han,* Dan Mao, Xin Liu, Xing Gao, Jianjun Yu and Limin Wang*
a
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and
Technology, 130 Meilong Road, Shanghai 200237, P. R. China. E-mail: wanglimin@ecust.edu.cn, Tel & Fax:
(
+86)-21-64253881.
b
Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis Shanghai Institute of Organic Chemistry, The
Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai 200032, P. R. China. E-mail:
jianweihan@sioc.ac.cn; Tel & Fax: (+86)-21-54925383.
c
These authors contributed equally to this work.

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Tetrahedron
journal homepage: www.elsevier.com
Design of C2-symmetric salen ligands and their Co(II)- or Yb(III)- complexes,
and their role in the reversal of enantioselectivity in the asymmetric Henry
reaction
a, c
a, c
b,
a
a
a
a
Shengying Wu, Jun Tang, Jianwei Han ∗ , Dan Mao, Xin Liu, Xing Gao, Jianjun Yu and Limin
Wang ∗
a,
a
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai
2
00237, P. R. China.
b
Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis Shanghai Institute of Organic Chemistry, The Chinese Academy of Sciences, 345 Ling Ling Road,
Shanghai 200032, P. R. China.
c
These authors contributed equally to this work.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
2
Reversal of enantioselectivity in asymmetric Henry reactions was achieved with novel chiral C -
symmetric salen ligands bearing morpholine moieties by changing the Lewis acid center from
Co(II) to Yb(III). The possible transition state models were supported by mass spectrometry
experiments.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
Co(II) complex
Yb(III) complex
Enantioselectivity reverse
Lewis acid/base bifunctional catalyst
Henry reaction
—
——
∗
∗
Corresponding author. Tel. & fax: (+86)-21-64253881; e-mail: wanglimin@ecust.edu.cn
Corresponding author. Tel. & fax: (+86)-21-54925383; e-mail: jianweihan@sioc.ac.cn

2
Tetrahedron
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1
. Introduction
It is of great importance to use a single chiral source to obtain
1
both enantioenriched products in asymmetric synthesis. So far,
various types of chiral metal complexes and organocatalysts have
2
been reported in this regard. Reversal of enantioselectivity by
changing metal center of catalytic complexes with the same
chiral ligand has received particular attention since the early
3
work reported by Kreuzfeld and co-workers in 1989. Besides the
catalytic species, unexpected inversion of enantioselectivity by
changing reaction conditions such as solvents, temperature,
additives, were also observed in specific reactions. However,
from a practical point of view, it is also widely accepted that
examination of diverse sets of metal sources is the most potential
avenue for effective stereocontrol. Therefore, design of efficient
and flexible ligands in conjunction with metals of different ionic
radii remained an urgent but challenging research topic.
Henry reaction, a highly versatile carbon–carbon bond
forming reaction, was well known. This reaction can be metal-
4
5
6
7
8
catalyzed such as zinc, copper, cobalt, chromium, magnesium
9
and rare earths . Asymmetric Henry reaction became a good
model for the evaluation of chiral metal (M)-ligand (L*)
complexes since the pioneering work reported by Shibasaki
Scheme 1. Synthesis of the chiral ligands (S)-5 ~ (S)-7.
2. Results and discussion
9a
group in 1992. Du and Xu had also a tridentate bis(oxazoline)
II
II
and bis(thiazoline) ligands for L*-M (M = Cu /Zn ) complexes
in the catalytic asymmetric Henry reaction of α-keto esters with
nitromethane, in this case, both enantiomers were obtained (up to
Inspired by Katsuki’s introduction of binaphthyl unit into the
1
2
10
salen ligand, as shown in Scheme 1, C -symmetric salen ligands
8
5% ee). Recently, Oh group designed a brucine-derived amino
2
13
II
II
bearing morpholine subunit were prepared. Starting with (S)-
alcohol ligand-Cu /Zn catalyst system to induce reversal of
1
1
1
,1’-binaphthyl-2,2’-diol (BINOL), the mono-aldehyde (S)-3 was
enantioselectivity in asymmetric Henry reaction. However,
Most of these work used organic bases as additives, which could
have a great negative effect on the catalytic reactivity and
coordination ability. Thus, we envisioned that a ligand which
incorporated tertiary amine would be functioned as bases without
employing additives.
14
prepared
according
to the
known
literature.
A
morpholinomethyl group was introduced via a Friedel-Crafts
reaction of (S)-3 with morpholinomethanol at high temperature.
After a recrystallization with CH Cl /MeOH (1/2, v/v), the
aldehyde (S)-4 was obtained as a yellow crystal in an enantiopure
form, whose structure was confirmed by X-ray crystallographic
analysis. Condensation of (S)-4 with various 1,2-diamines
furnished Schiff bases as the desired salen ligands (S)-5 ~ (S)-7
efficiently in the yield of 88-96%. Additionally, 3-((E)-(((1R,2R)-
2
2
15
Meanwhile, chiral salen ligands derived from vicinal diamine
and aldehydes were chosen as they could be easily modified and
metallosalen complexes had been proven to be very effective in
12
terms of enantioselectivity. Herein, we report the design and
2
-((E)-(((S)-2,2'-dihydroxy-[1,1'-binaphthalen]-3-
synthesis of novel C -symmetric salen ligands bearing
2
yl)methylene)amino)cyclohexyl)imino)methyl)-[1,1'-
binaphthalene]-2,2'-diol ((S)-8) was also prepared from (S)-3 in
the similar manner (Scheme S1).
morpholine functional group based on BINOL framework for
obtaining both isomers in asymmetric Henry reactions by
changing central metals.
14
Table 1. Screening of metal sources in enantioselective Henry
reaction
a
b
c
Entry
Ligand
Metal
Yield (%)
ee (%)
i
1
2
3
4
(S)-5
(S)-6
(S)-7
(S)-8
(S)-8
(S)-5
(S)-5
(S)-5
(S)-5
(S)-5
(S)-5
(S)-5
Yb( PrO)
3
3
3
3
3
78
70
80
trace
76
trace
72
67
90
59
60 (R)
35 (R)
25 (R)
/
7 (R)
/
37 (R)
15 (R)
85 (S)
racemic
racemic
11 (S)
i
Yb( PrO)
i
Yb( PrO)
i
Yb( PrO)
d
i
5
Yb( PrO)
6
7
8
9
1
1
1
a
/
i
Sc( PrO)
La( PrO)
Co(OAc)
Ni(OAc)
Cu(OAc)
Mn(OAc)
3
i
3
2
(H
2
O)
4
0
1
2
2
2
37
53
2
Reaction conditions: benzaldehyde (0.25 mmol), nitromethane (1.25 mmol),
ligand (6 mol%), metal (5 mol%), methanol (1.5 mL), 24 hours of reaction
time.

3
b
c
d
Isolated yields.
ACCEPTED MANUSC
=
R
2/
MeOH/THF
= 2/1
MeOH/THF
2/1
MeOH/THF
2/1
I
1
PT
8
9
1
5
48
36
36
36
48
48
80
91
95
97
84
93
91 (S)
92 (S)
82 (S)
59 (S)
68 (R)
87 (R)
Determined by chiral HPLC.
15
r.t.
40
15
15
Triethylamine (0.25 mmol) was added.
In connection with our studies concerning rare earth salts as
=
0
=
1
6
Lewis acid catalysts, metallosalen complexes were prepared in
situ by treatment of (S)-3 ~ (S)-7 with ytterbium isopropoxide in
MeOH. Then, we evaluated their performances in the benchmark
Henry reaction of benzaldehyde with nitromethane (Table 1). To
our delight, 5 mol% Yb(O Pr) complexed with 6 mol% (S)-5 at
room temperature was found to give a good yield of (R)-1-(4-
nitrophenyl)-2-nitroethanol in 60% ee, the absolute configuration
was confirmed by comparison of the observed specific rotation
11
MeOH/THF
= 2/1
MeOH/THF
d
d
1
1
a
2
3
=
2/1
MeOH/THF
= 1/4
i
3
Reaction conditions: benzaldehyde (0.25 mmol), nitromethane (1.25 mmol),
2 2 4
ligand (6 mol%), Co(OAc) (H O) (5 mol%), solvent (1.5 mL).
9
b
Isolated yields.
with literature values. Using salen ligands (S)-6 and (S)-7, the
level of asymmetric induction was poor under the same
conditions. With (S)-8 as ligand, the reaction did not occur in
methanol without additives, however, when an equivalent
triethylamine as base additives was employed, the desired
product was obtained in 76% yield and 7% ee. It confirmed the
hypothesis that the morpholinomethyl moiety of salen ligand can
activate the reactants as a bulky base in additive-free conditions.
Hence, the new salen ligand (S)-5 was utilized to screen various
metal sources for the inversion of product selectivity in
asymmmetric Henry reaction. Other rare earth metal such as
La(III) and Sc(III) complexes gave moderate yields and low
enantioselectivities (Table 1, entries 7 and 8). We were pleased to
find that in the presence of 5 mol% Co(OAc) (H O) and (S)-5 in
c
Determined by chiral HPLC.
d
i
Yb(O Pr)
3
was used.
With the optimal reaction condition in hand, we further
studied the generality of asymmetric Henry reaction of various
aldehydes with nitromethane in the presence of catalyst (S)-5
with Co(OAc) (H O) or Yb(O Pr) as shown in Table 3. The
i
2
2
4
3
presence of either electron-withdrawing or electron-donating
substituents at various positions of the aromatic ring of aryl
aldehydes was tolerated with ee value from 80% to 97% when
Co(OAc) (H O) were used for the central metal. As expected,
electron-rich aldehydes resulted in lower reactivity than electron-
deficient aldehydes. Cyclohexanecarbaldehyde gave the product
in only moderate yield but excellent enantioselectivity (Table 3,
entry 12). Cinnamaldehyde gave the corresponding product in 81%
ee, and excellent ee value (>99%) was obtained after
recrystallization (Table 3, entry 13). In contrast, Yb(O Pr) /(S)-5
catalytic system gave (R)-configuration of desired product in the
range of 10 ~ 87% ee (Table 3, entries 1 to 13).
2
2
4
2
2
4
methanol, the enantioselectivity of the reaction was reversed, and
the reaction proceeded smoothly to provide the corresponding
(S)-1-(phenyl)-2-nitroethanol in 90% yield and 85% ee. However,
the metal complexes of (S)-5 with Ni(OAc)2, Cu(OAc) and
i
2
3
Mn(OAc)2 only gave low enantioselectivities and moderate
chemical yields.
Next, an asymmetric Henry reaction of benzaldehyde with
nitromethane was carried out in the presence of cobalt-salen
catalyst to establish the optimum reaction condition (Table 2).
Table 3. The substrate scope of enantioselective Henry
reaction
a
i
Several polar and non-polar solvents (EtOH, PrOH, CH Cl ,
2
2
THF) were screened. The alcohols gave the desired products in
good yields and high enantioselectivities. However, in cases of
CH Cl and THF, only trace amount of products was observed.
2
2
17
Inspired by recent works of enantioselectivity inversion, a co-
solvent pair of MeOH/THF (2/1) at the temperature of 0 C
o
a
i
b
Entry
R
(S)-5/Co(OAc)
Yield
2
(H
2
O)
4
d
(S)-5/Yb(O Pr)
3
resulted in an improvement of product enantioselectivity to the
d
ee (%)
(S)-9
92
88
80
91
84
90
94
93
90
87
91
Yield
ee(%)
higher of 90%. Finally, the reaction temperature was increased to
c
c
(
%)
91
90
95
92
90
89
82
72
82
81
65
88
90
(%)
(R)-9
87
37
16
12
10
58
51
65
66
62
52
33
38
o
1
9
5 C, even higher enantioselectivity was attained (Table 2, entry
1
2
3
4
5
6
7
8
9
Ph
4-ClC H4
93
77
96
98
85
84
91
92
89
81
67
87
84
). Surprisingly, switching cobalt-salen to ytterbium-salen
6
o
complexes by using MeOH/THF (2/1) as solvent at 15 C also led
to the inversion of product enantioselectivity to larger extent
4-NO
4-CNC
4-CF
2
C
6
H
4
6
H
4
3
C
6
H
4
(
(
Table 2, entry 12). Other screenings were also carried out
Tables S1 ~ S2), and MeOH/THF (1/4) gave the best result with
4-FC
2-FC
3-FC
6
6
6
H
H
H
4
4
9
3% yield and 87% ee (Table 2, entry 13).
4
4-MeC
6
H
4
a
Table 2. Optimization of enantioselective Henry reaction
10
4-OMeC H4
6
cyclohexyl
2-furyl
1
1
1
1
2
3
97
e
(E)-
81(>99)
PhCH=CH
a
o
c
Reaction conditions: aldehyde (0.25 mmol), nitromethane (1.25 mmol),
Entry
Solvent
Temp( C)
Time (h) Yield
ee (%)
b
ligand (6 mol%), metal (5 mol%), MeOH/THF (2/1, v/v, 1.5 mL), 36 h of
(%)
1
2
3
4
5
6
MeOH
EtOH
i-PrOH
THF
0
0
0
0
0
0
24
24
24
48
48
48
90
76
74
trace
trace
73
85 (S)
75 (S)
73 (S)
/
reaction time.
b
Identical conditions but otherwise for 48 h in MeOH/THF (1/4, v/v, 1.5 mL).
c
Isolated yields.
CH
MeOH/THF
2/1
MeOH/THF
2
Cl
2
/
90 (S)
d
Determined by chiral HPLC.
=
7
-10
48
23
87 (S)

4
Tetrahedron
ACCEPTED MANUSCRIPT
e
After recrystallization.
Although the structures of catalytic species awaits further
6,18
information, the related structures of Co(II)-salen and Yb(III)-
19
salen complexes were well documented. Based on the
pronounced difference in ionic radii of Co(II) and Yb(III) and the
oxophilic and isotropic nature of ytterbium metals, the
coordination of metal centers with salen ligand (S)-5 in the
formation of metallosalen complexes was proposed in Fig. 1.
Both metallosalen complexes were checked by mass
+
spectrometry experiments. The TOF-HRMS/ES showed a peak
+
at m/z 961.3380, which corresponds to [10] for cobalt complex,
and m/z 1076.3403 which corresponds to [11] for ytterbium
Fig. 1. The TOF-HRMS spectra of (a) Co(II) and (b) Yb(III) complexes.
+
L
complex, respectively. It is worth to note that, in the case o+f
cobalt complex, a peak at m/z 1021.3709 may be the [10+Co]
ion, this results suggested dinuclear structure of cobalt complex
was formed. In the case of ytterbium complex, a peak at m/z
Co
L
N
N
Co
OH
i
+
O
O
1
135.2992 is most likely related to [11+O Pr] , to take account of
O
Hre
O
(S)
the oxophilic and the isotropic nature of ytterbium metals, the
model of 12 has been proposed (Fig. 1). On the basis of the
above experiments, the stereochemical outcome between
different metallosalen complexes can be explained by the
following possible transition state models with both complexes
OH
H
NO2
H
N
CH
N
2
NO2
O
(
Fig. 2). At this stage, although the insight into the mechanism
O
remained unclear since we failed to obtain the crystallographic
information of the catalytic species, from several scenarios we
tried, we hypothesized that the (S) enantiomer is preferred by a
nucleophilic attack of nitromethane on the benzaldehyde from the
re-face under the chiral environment formed by C2-symmetric
chiral ligand and the cobalt atom. In the Yb case, the oxygen
atom of the benzaldehyde was approaching to the ytterbium by
replacing the oxygen of the morpholine group; Meanwhile, the
nitromethane attacks the benzaldehyde from the si-face. It
appears that the tertiary amine moiety participates in the
formation of metallic complexes, and it is essential for the
activation of nitromethane.
H
N
si
N
OH
O
O
O
(R)
Yb
OHi
HO
NO2
H
C
2
PrO
H
NO2
N
N
O
O
Fig. 2. A possible transition state structure.
3
. Conclusion
In summary, we successfully synthesized a class of chiral C -
2
N
N
M
N
N
O
O
O
symmetric salen ligands bearing morpholine functional moiety.
With these ligands in combination with Co(II) or Yb(III),
respectively, a controlled selective methodology in asymmetric
Henry reaction of a range of aldehydes and nitromethane was
developed in obtaining both enantiomeric Henry products.
OH HO
O
O
Yb
OH
HO
N
iPrO
N
N
N
O
O
O
1
0, M= Co; 11, M= Yb
12
4
4
. Experimental section
.1. General procedures
General Methods. Unless otherwise noted, all the reactions
were conducted under argon atmosphere. All reagents and
1
13
solvents were dried and distilled prior to use. H NMR and
C
NMR spectra were recorded at 400 MHz and 100 MHz,
respectively using tetramethylsilane as an internal reference.
Chemical shifts (δ) and coupling constants (J) were expressed in
parts per million and hertz, respectively. Melting points were
uncorrected. High-resolution mass spectrometry (HRMS) was
performed with Electron Ionization (EI) resource or on an ESI-
TOF spectrometer. The ee was determined by HPLC on AD, or
OD column.
4
.2. General Procedure for the Synthesis of (S)-4
Morpholinomethanol (10.0 mL) combining with (S)-3 (1.0 g,
3
.18 mmol) was heated at 110 °C for 72 h. After completion of
the reaction, the mixture was cooled to room temperature and

5
diluted with chloroform (100 mL). The solution
A
w
C
as
C
w
E
as
P
he
T
d
E
w
D
ith MA(m
N
o
U
rp
S
h
C
ol
R
in
I
o
P
m
T
ethyl)-[1,1'-binaphthalene] -2,2'-diol
o
saturated NaHCO (6×20 mL) and water (3×20 mL). The organic
((S)-7). Yellow solid, 208.9 mg, 96% yield, m.p 195-197 C.
-120 (c 0.5, CHCl ). H NMR (400 MHz, CDCl ) δ 12.70
3 3
br s, 2H), 8.89 (s, 2H), 8.12 (s, 2H), 7.92 (d, J = 8.0 Hz, 2H),
.80 (d, J = 8.0 Hz, 2H), 7.69 (s, 2H), 7.32-7.08 (m, 12H), 6.82-
.73 (m, 4H), 4.06 (d, J = 13.6 Hz, 2H), 3.96 (d, J = 13.6 Hz, 2H),
.66 (br s, 8H), 2.65 (br s, 8H). C NMR (100 MHz, CDCl ) δ
61.9 (C=N), 154.2, 153.4, 141.3, 135.7, 135.0, 134.6, 133.8,
129.1, 128.6, 128.5, 128.4, 128.3, 127.8, 126.5, 124.9, 124.8,
123.6, 123.3, 123.3, 121.6, 118.7, 118.3, 117.5, 115.9, 115.8,
3
2
D
0
1
phase was then concentrated under vacuum and the residue was
purified by column chromatograph on silica gel eluted with
petroleum ether / ethyl acetate (10:1) to give (S)-4 in 40% yield,
and the enantiopure form was obtained after a recrystallization
with CH Cl /MeOH.
[α]
(
7
6
3
1
13
3
2
2
4
[
.2.1. (S)-2,2'-dihydroxy-3'-(morpholinomethyl)-
1,1'-binaphthalene] -3-carbaldehyde ((S)-4). Yellow
solid, 526.1 mg, 40% yield, m.p 205-206 C. [α] -152 (c 1.0,
CHCl ). H NMR (400 MHz, CDCl ) δ 11.28 (br s, 1H), 10.46 (s,
o
20
-1
D
66.6, 62.4, 53.0. FT-IR (cm ): 1005, 1032, 1071, 1117, 1150,
1168, 1181, 1252, 1295, 1313, 1343, 1380, 1399, 1431, 1456,
1506, 1601, 2851, 2921, 2959, 3055, 3370. HRMS (ESI) Calcd.
1
3
3
1
8
H), 10.18 (s, 1H), 8.30 (s, 1H), 7.96-7.98 (m, 1H), 7.79 (d, J =
.0 Hz, 1H), 7.69 (s, 1H), 7.38-7.20 (m, 5H), 7.11 (d, J = 8.4 Hz,
H), 4.02 (d, J = 14 Hz, 1H), 3.98 (d, J = 14 Hz, 1H), 3.69 (br s,
+
for [M+H] C H N O 899.3809, found 899.3810.
58
51
4
6
14
1
4
4
.4. General Procedure for the Synthesis of (S)-8
13
H), 2.64 (br s, 4H). C NMR (100 MHz, CDCl ) δ 196.9, 153.1,
3
1
1
1
1
1
3
53.5, 138.0, 137.8, 133.7, 130.4, 130.0, 128.8, 128.3, 127.9,
27.7, 126.5, 125.2, 124.4, 124.3, 123.4, 123.3, 122.2, 118.5,
(S)-3 (0.48 mmol) was dissolved completely in refluxing
ethanol, the yellow solution was then allowed to cool to r.t. and (-
)-(1R, 2R)-cyclohexanediamine (0.24 mmol) was added
dropwise. During this addition, the product precipitated out of
solution. The mixture was then allowed to reflux for 1 h. After
cooling down to r.t., the precipitate was collected by filtration,
and washed with cold ethanol carefully and dried with gentle
heating in vacuo to provide (S)-8 in 85% yield as a pink-orange
powder.
-
1
14.7, 66.6, 62.3, 52.9. FT-IR (cm ): 1003, 1025, 1031, 1072,
102, 1117, 1151, 1171, 1185, 1250, 1269, 1293, 1344, 1383,
423, 1457, 1472, 1503, 1578, 1660, 2845, 2892, 2935, 2959,
058, 3203, 3436. HRMS (EI) Calcd. for C H NO 413.1627,
26
23
4
found 413.1628.
4
.3. General Procedure for the Synthesis of (S)-5 ~ (S)-7
(
S)-4 (0.48 mmol) was dissolved completely in CHCl (2.0
3
4
[
.4.1. 3-((E)-(((1R,2R)-2-((E)-(((S)-2,2'-dihydroxy-
1,1'-binaphthalen] -3-
yl)methylene)amino)cyclohexyl)imino)methyl)-[1,1'-
mL), and diamines NH -X-NH2 (0.24 mmol) was added
dropwise. The yellow solution was then allowed to stir at r.t. for
2
by methanol carefully and dried with gentle heating in vacuo to
provide (S)-5 in 92% yield, (S)-6 in 88% yield, (S)-7 in 96%
yield, respectively.
2
4 h. After removal of the solvent, the crude product was washed
binaphthalene] -2,2'-diol ((S)-8). Pink-orange powder,
o
20
1
45.4 mg, 85% yield, m.p 185-188 C. [α]D -342 (c 0.5,
14 1
CHCl3). H NMR (400 MHz, CDCl ) δ 13.49 (br s, 2H), 8.52 (s,
3
2
H), 7.91-7.85 (m, 8H), 7.33-7.21 (m, 10H), 7.12-7.09 (m, 4H),
5.17 (br s, 2H), 3.33-3.31 (m, 2H), 1.95-1.41 (m, 8H).
.5. General Procedure for the Synthesis of (S), or (R)-9a-m
4
3
.3.1. 3-((E)-(((1R,2R)-2-((E)-(((S)-2,2'-dihydroxy-
'-(morpholinomethyl)-[1,1'-binaphthalen] -3-
4
yl)methylene)amino)cyclohexyl)imino)methyl)-3'-
(
(
[
(
morpholinomethyl)-[1,1'-binaphthalene] -2,2'-diolo
4.5.1. General Procedure for the Synthesis of (S)-
9a~m.
(S)-5). Yellow solid, 201.5 mg, 92% yield, m.p 188-190 C.
20
1
α]D -354 (c 0.5, CHCl ). H NMR (400 MHz, CDCl ) δ 13.10
Ligand (S)-5 (13.8 mg, 6 mol%) was dissolved in THF (0.5
mL), and the solution of cobalt acetate tetrahydrate (3.1 mg, 5
mol%) in MeOH (1.0 mL) was added dropwise. The mixture was
allowed to stir at r.t. for 2 h affording a deep brown slurry, and
nitromethane (125 ꢀL, 1.25 mmol) was added for another 30 min
stirring at r.t. Then aldehyde (0.25 mmol) was added dropwise at
3
3
s, 2H), 10.95 (br s, 2H), 8.51 (s, 2H), 7.81-7.68 (m, 8H), 7.29-
.07 (m, 12H), 4.13 (d, J = 13.6 Hz, 2H), 3.92 (d, J = 13.6 Hz,
7
2
1
1
1
1
1
1
H), 3.71 (br s, 8H), 3.35-3.32 (m, 2H), 2.66 (br s, 8H), 2.00-
13
.62 (m, 8H). C NMR (100 MHz, CDCl ) δ 164.5 (C=N), 153.6,
3
52.4, 134.2, 132.9, 132.6, 127.9, 127.4, 127.3, 127.0, 126.7,
26.5, 125.2, 123.8, 123.6, 122.3, 122.1, 121.9, 119.7, 115.9,
o
o
0
C. The reaction mixture was stirred at 15 C for 36 h. After
-
1
15.2, 70.9, 65.6, 61.4, 52.0, 31.7, 22.9. FT-IR (cm ): 1005,
033, 1071, 1117, 1150, 1169, 1184, 1209, 1252, 1294, 1313,
removal the solvent, the residue was purified by column
chromatograph on silica gel eluted with petroleum ether/ethyl
acetate (20:1 to 10:1) to give (S)-Henry adduct.
343, 1383, 1432, 1506, 1576, 1631, 2855, 2932, 3054, 3447.
+
HRMS (ESI) Calcd. for [M+H] C H N O 905.4278, found
58
57
4
6
9
05.4278.
4.5.2. General Procedure for the Synthesis of (R)-
4
.3.2. 3-((E)-((2-((E)-(((S)-2,2'-dihydroxy-3'-
9a~m.
i
(
morpholinomethyl)-[1,1'-binaphthalen]-3-
Ligand (S)-5 (13.8 mg, 6 mol%) and Yb(O Pr) (4.4 mg, 5
3
yl)methylene)amino)ethyl)imino)methyl)-3'-
mol%) was dissolved in 1/4 MeOH-THF co-solvent. The mixture
was allowed to stir at r.t. for 2 h affording a reddish orange slurry,
and nitromethane (125 ꢀL, 1.25 mmol) was added for another 30
min stirring at r.t. Then aldehyde (0.25 mmol) was added
dropwise at 0 C. The reaction mixture was stirred at 15 C for 48
h. After removal of the solvent, the residue was purified by
column chromatograph on silica gel eluted with petroleum
ether/ethyl acetate (20:1 to 10:1) to give (R)-Henry adduct.
(
(
[
(
morpholinomethyl)-[1,1'-binaphthalene] -2,2'-diolo
(S)-6). Yellow solid, 181.2 mg, 88% yield, m.p 184-185 C.
20
1
α]D -105 (c 1.0, CHCl ). H NMR (400 MHz, CDCl ) δ 13.01
3
3
s, 2H), 11.10 (br s, 2H), 8.59 (s, 2H), 7.87 (s, 2H), 7.82-7.78 (m,
H), 7.67 (s, 2H), 7.29-7.23 (m, 7H), 7.14-7.12 (m, 5H), 4.09 (d,
J = 13.6 Hz, 2H), 4.01-3.88 (m, 6H), 3.68 (br s, 8H), 2.63 (br s,
o
o
4
13
8
1
1
1
1
1
H). C NMR (100 MHz, CDCl ) δ 165.8 (C=N), 153.5, 152.3,
3
34.3, 132.8, 132.5, 127.9, 127.3, 127.3, 127.2, 126.6, 126.5,
25.3, 123.7, 123.7, 122.2, 122.2 (overlapped), 119.6, 116.1,
4
4
.5.3. Experimental datas for (S)- or (R)-9a~m.
.5.3.1. (S)- or (R)- 2-nitro-1-phenylethanol (9a).
-
1
15.0, 65.5, 61.4, 58.7, 51.9. FT-IR (cm ): 1026, 1118, 1150,
184, 1252, 1294, 1314, 1343, 1382, 1431, 1456, 1506, 1576+,
633, 2849, 2920, 3055, 3445. HRMS (ESI) Calcd. for [M+H]
Colorless oil, (S)-product: 38.0 mg, 91% yield, (R)-product: 38.9
mg, 93% yield. H NMR (400 MHz, CDCl ) δ 7.40-7.24 (m, 5H),
1
3
C H N O 851.3809, found 851.3806.
54
51
4
6
5
=
.42-5.38 (m, 1H), 4.56 (dd, J = 9.6 Hz, 13.2 Hz, 1H), 4.46 (dd, J
2.8 Hz, 13.2 Hz, 1H), 3.16 (br s, 1H), The ee was determined
4
(
.3.3. 3-((E)-((2-((E)-(((S)-2,2'-dihydroxy-3'-
morpholinomethyl)-[1,1'-binaphthalen]-3-
yl)methylene)amino)phenyl)imino)methyl)-3'-
by HPLC on Chiralcel OD-H (85:15 n-hexane : isopropanol, 0.8
mL/min, 215 nm), t (minor) = 11.6 min, t (major) = 13.4 min,
R
S

6
Tetrahedron
ACCEPTED MANUSCRIPT
4.5.3.7. (S)-
9
2% ee. t (major) = 13.0 min, t (minor) = 14.9 min, 87% ee.
or
(R)-
1-(2-fluorophenyl)-2-
R
S
Configuration assignment: Absolute configuration of major
isomer was determined by comparison of the retention time with
literature data.
nitroethanol (9g). Colorless oil, (S)-product: 37.9 mg, 82%
yield, (R)-product: 42.1 mg, 91% yield. H NMR (400 MHz,
CDCl ) δ 7.55 (t, J = 7.2 Hz, 1H), 7.38-7.06 (m, 3H), 5.76-5.72
1
11, 20
3
(
m, 1H), 4.65-4.57 (m, 2H), 3.16 (br s, 1H). The ee was
4
.5.3.2. (S)-
or
(R)-
1-(4-chlorophenyl)-2-
determined by HPLC on Chiralcel AD-H (90:10 n-hexane:
isopropanol, 0.9 mL/min, 215 nm), t (major) = 11.3 min, tR
nitroethanol (9b). Pale-yellow oil, (S)-product: 45.2 mg, 90%
yield, (R)-product: 38.7 mg, 77% yield. H NMR (400 MHz,
CDCl ) δ 7.37-7.31 (m, 4H), 5.41 (dd, J = 2.8 Hz, 9.2 Hz, 1H),
4
1
S
1
(minor) = 12.0 min, 94% ee. t (minor) = 11.5 min, t (major) =
S
R
3
12.3 min, 51% ee. Configuration assignment: Absolute
configuration of major isomer was determined by comparison of
the retention time with literature data.
.55 (dd, J = 9.2 Hz, 13.2 Hz, 1H), 4.47 (dd, J = 3.2 Hz, 13.2 Hz,
H), 3.32 (br s, 1H). The ee was determined by HPLC on
7, 21-22
Chiralcel OD-H (90:10 n-hexane : isopropanol, 0.9 mL/min, 215
nm), t (minor) = 14.9 min, t (major) = 18.7 min, 88% ee. t
4.5.3.8. (S)- or (R)-
1-(3-fluorophenyl)-2-
R
S
R
(
major) = 14.6 min, t (minor) = 19.3 min, 37% ee. Configuration
nitroethanol (9h). Colorless oil, (S)-product: 33.3 mg, 72%
yield, (R)-product: 42.6 mg, 92% yield. H NMR (400 MHz,
S
1
assignment: Absolute configuration of major isomer was
determined by comparison of the retention time with literature
data.
CDCl ) δ 7.40-7.34 (m, 1H), 7.27-7.13 (m, 2H), 7.07-7.02 (m,
3
11, 21-22
1H), 5.47-5.43 (m, 1H), 4.60-4.49 (m, 2H), 3.27-3.24 (d, J = 4.0
Hz, 1H). The ee was determined by HPLC on Chiralcel OD-H
4
.5.3.3. (S)-
or
(R)-
2-nitro-1-(4-
(
90:10 n-hexane : isopropanol, 0.9 mL/min, 215 nm), t (minor)
R
nitrophenyl)ethanol (9c). Colorless oil, (S)-product: 50.4
mg, 95% yield, (R)-product: 50.9 mg, 96% yield. H NMR (400
MHz, CDCl ) δ 8.26 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H),
5
1
=
13.3 min, t (major) = 15.7 min, 93% ee. t (major) = 13.0 min,
S R
1
tS (minor) = 15.6 min, 65% ee. Configuration assignment:
Absolute configuration of major isomer was determined by
3
21
.61 (dd, J = 4.4 Hz, 8.4 Hz, 1H), 4.64-4.55 (m, 2H), 3.38 (br s,
H). The ee was determined by HPLC on Chiralcel OD-H (90:10
comparison of the retention time with literature data.
n-hexane : isopropanol, 0.9 mL/min, 215 nm), t (minor) = 29.3
4.5.3.9. (S)- or (R)- 2-nitro-1-p-tolylethanol (9i).
R
min, t (major) = 37.0 min, 80% ee. t (major) = 29.2 min, t
Colorless oil, (S)-product: 37.1 mg, 82% yield, (R)-product: 40.3
S
R
S
1
(minor) = 37.1 min, 8% ee. Configuration assignment: Absolute
mg, 89% yield. H NMR (400 MHz, CDCl ) δ 7.28 (d, J = 8 Hz,
3
configuration of major isomer was determined by comparison of
the retention time with literature data.
2H), 7.21 (d, J = 8 Hz, 2H), 5.43-5.41 (m, 1H), 4.60 (dd, J = 9.6
Hz, 13.2 Hz, 1H), 4.48 (dd, J = 3.2 Hz, 13.2 Hz, 1H), 2.92 (d, J =
21-25
3
.6 Hz, 1H), 2.36 (s, 3H). The ee was determined by HPLC on
4
.5.3.4. (S)- or (R)-
4-(1-hydroxy-2-
Chiralcel OD-H (90:10 n-hexane : isopropanol, 0.9 mL/min, 215
nm), t (minor) = 14.9 min, t (major) = 18.6 min, 90% ee. t
nitroethyl)benzonitrile (9d). Colorless oil, (S)-product:
4
R
S
R
1
4.2 mg, 92% yield, (R)-product: 47.1 mg, 98% yield. H NMR
(major) = 14.6 min, t (minor) = 18.9 min, 66% ee. Configuration
S
(400 MHz, CDCl ) δ 7.71 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.0 Hz,
3
assignment: Absolute configuration of major isomer was
determined by comparison of the retention time with literature
data.
2
H), 5.55 (dd, J = 4.0 Hz, 8.8 Hz, 1H), 4.59 (dd, J = 8.8 Hz, 13.6
11
Hz, 1H), 4.54 (dd, J = 4.0 Hz, 13.6 Hz, 1H), 3.36 (br s, 1H). The
ee was determined by HPLC on Chiralcel OD-H (90:10 n-
hexane : isopropanol, 0.9 mL/min, 215 nm), t (minor) = 30.7
4.5.3.10. (S)-
nitroethanol (9j). Colorless oil, (S)-product: 39.9 mg, 81%
yield, (R)-product: 39.9 mg, 81% yield. H NMR (400 MHz,
or
(R)-
1-(4-methoxyphenyl)-2-
R
min, t (major) = 35.4 min, 91% ee. t (major) = 30.3 min, t
S
R
S
1
(minor) = 35.6 min, 12% ee. Configuration assignment: Absolute
configuration of major isomer was determined by comparison of
the retention time with literature data.
CDCl ) δ 7.32-7.29 (m, 2H), 6.92-6.90 (m, 2H), 5.39 (dd, J = 2.4
Hz, 9.6 Hz, 1H), 4.59 (dd, J = 9.6 Hz, 13.2 Hz, 1H), 4.47 (dd, J =
3
7b,21
3
.2 Hz, 13.2 Hz, 1H), 3.80 (s, 3H), 2.93 (br s, 1H). The ee was
4
.5.3.5. (S)- or (R)-
2-nitro-1-(4-
determined by HPLC on Chiralcel OD-H (90:10 n-hexane :
isopropanol, 0.9 mL/min, 215 nm), tR (minor) = 22.6 min, tS
(
trifluoromethyl)phenyl)ethanol (9e). Colorless oil, (S)-
product: 52.9 mg, 90% yield, (R)-product: 50.0 mg, 85% yield.
(major) = 28.7 min, 87% ee. t (major) = 22.1 min, t (minor) =
R
S
1
H NMR (400 MHz, CDCl ) δ 7.66 (d, J = 8.4 Hz, 2H), 7.54 (d, J
3
28.5 min, 61% ee. Configuration assignment: Absolute
configuration of major isomer was determined by comparison of
the retention time with literature data.
=
4
8.0 Hz, 2H), 5.54-5.52 (m, 1H), 4.59 (dd, J = 9.2, 13.6 Hz, 1H),
.53 (dd, J = 3.6, 13.6 Hz, 1H), 3.33 (d, J = 4.0, 1H). The ee was
11, 23, 26-27
determined by HPLC on Chiralcel OD-H (90:10 n-hexane :
isopropanol, 0.9 mL/min, 215 nm), tR (minor) = 12.1 min, tS
4.5.3.11. (S)- or (R)- 1-cyclohexyl-2-nitroethanol
(
major) = 15.5 min, 84 % ee. t (major) = 12.7 min, t (minor) =
(9k). Colorless oil, (S)-product: 28.1 mg, 65% yield, (R)-
R
S
1
1
6.3 min, 10% ee. Configuration assignment: Absolute
product: 29.0 mg, 67% yield. H NMR (400 MHz, CDCl ) δ 4.49
3
configuration of major isomer was determined by comparison of
the retention time with literature data.
(dd, J = 2.8, 12.8 Hz, 1H), 4.43 (dd, J = 8.8, 12.8 Hz, 1H), 4.13-
4.07 (m, 1H), 2.66 (br s, 1H), 1.85-1.76 (m, 3H), 1.71-1.65 (m,
22
2
H), 1.52-1.43 (m, 1H), 1.33-1.03 (m, 5H). The ee was
4
.5.3.6. (S)- or (R)-
1-(4-fluorophenyl)-2-
determined by HPLC on Chiralcel AD-H (95:5 n-hexane :
isopropanol, 0.9 mL/min, 215 nm), tR (minor) = 21.4 min, tS
nitroethanol (9f). Colorless oil, (S)-product: 41.2 mg, 89%
yield, (R)-product: 38.9 mg, 84% yield. H NMR (400 MHz,
CDCl ) δ 7.38-7.35 (m, 2H), 7.09-7.05 (m, 2H), 5.42 (d, J = 9.2
Hz, 1H), 4.57 (dd, J = 9.6, 13.2 Hz, 1H), 4.48 (dd, J = 3.2, 13.6
Hz, 1H), 3.40 (br s, 1H). The ee was determined by HPLC on
Chiralcel OD-H (90:10 n-hexane : isopropanol, 0.9 mL/min, 215
nm), t (minor) = 13.0 min, t (major) = 15.5 min, 90% ee. t
R
1
(major) = 22.6 min, 91% ee. t (major) = 21.3 min, t (minor) =
R
S
3
22.6 min, 51% ee. Configuration assignment: Absolute
configuration of major isomer was determined by comparison of
the retention time with literature data.
23-25
4.5.3.12. (S)- or (R)- 1-(furan-2-yl)-2-nitroethanol
R
S
(
major) = 13.0 min, t (minor) = 15.4 min, 57% ee. Configuration
(9l). Colorless oil, (S)-product: 34.6 mg, 88% yield, (R)-product:
S
1
assignment: Absolute configuration of major isomer was
determined by comparison of the retention time with literature
data.
34.2 mg, 87% yield. H NMR (400 MHz, CDCl ) δ 7.42-7.41 (m,
3
1H), 6.40-6.38 (m, 2H), 5.47-5.44 (m, 1H), 4.78 (dd, J = 9.2 Hz,
13.2 Hz, 1H), 4.67 (dd, J = 3.2 Hz, 13.2 Hz, 1H), 3.13 (br s, 1H).
The ee was determined by HPLC on Chiralcel AD-H (95:5 n-
18, 21, 26-27

7
hexane : isopropanol, 0.9 mL/min, 215 nm), t (minor) = 27.8
Angew. Chem. Int. Ed. 2012, 51, 1620. (d) Ibrahim, F.; Jaber, N.;
ACCEPTED MANUSCRIPT
R
min, t (major) = 29.2 min, 97% ee. t (major) = 28.3 min, t
Guérineau, V.; Hachem, A.; Ibrahim, G.; Mellah, M.; Schulz, E.
S
R
S
(
minor) = 29.8 min, 32% ee. Configuration assignment: Absolute
Tetrahedron: Asymmetry 2013, 24, 1395.
configuration of major isomer was determined by comparison of
the retention time with literature data.
7b, 11, 21-22
7
(a) Kowalczyk, R.; Sidorowicz, Ł.; Skarzewski, J. Tetrahedron:
Asymmetry 2007, 18, 2581. (b) Kowalczyk, R.; Kwiatkowski, P.;
Skarzewski, J.; Jurczak, J. J. Org. Chem. 2009, 74, 753.
4
2
.5.3.13. (S)- or (R)- (E)-1-nitro-4-phenylbut-3-en-
-ol (9m). Colorless oil, (S)-product: 43.5 mg, 90% yield, (R)-
1
8
9
Corey, E. J.; Ishihara, K. Tetrahedron Lett. 1992, 33, 6807.
product: 40.6 mg, 84% yield. H NMR (400 MHz, CDCl ) δ
3
7
1
.39-7.27 (m, 5H), 6.78 (d, J = 16.0 Hz, 1H), 6.14 (dd, J = 6.4 Hz,
6.0 Hz, 1H), 5.07-5.02 (m, 1H), 4.51 (d, J = 6.4 Hz, 2H), 2.76
(a) Sasai, J.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem.
Soc. 1992, 114, 4418. (b) Sasai, J.; Suzuki, T.; Itoh, N.; Shibasaki, M.
Tetrahedron Lett. 1993, 34, 851. (c) Sasai, H.; Zuzuki, N.; Itoh, K.;
Tanaka, K. T.; Date, K.; Okamura, K.; Shibasaki, M. J. Am. Chem. Soc.
(
br s, 1H). The ee was determined by HPLC on Chiralcel OD-H
(90:10 n-hexane : isopropanol, 0.9 mL/min, 215 nm), t (major) =
S
4
2.9 min, t (minor) = 48.7 min, 81% ee. t (minor) = 42.3 min,
R
S
1
993, 115, 10372.
tR (major) = 48.3 min, 38% ee. Configuration assignment:
Absolute configuration of major isomer was determined by
comparison of the retention time with literature data.
10 Du, D. M.; Lu, S. F.; Fang, T.; Xu, J. X. J. Org. Chem. 2005, 70, 3712.
7b, 21-23
1
1
1
2
Kim, H. Y.; Oh, K. Org. Lett. 2009, 11, 5682.
Acknowledgements
(a) Sasaki, H.; Irie, R.; Hamada, T.; Suzuki, K.; Katsuki, T. Tetrahedron
1994, 50, 11827. (b) Katsuki, T. Synlett 2003, 281. (c) Katsuki, T. Chem.
Soc. Rev. 2004, 33, 437. (d) Matsumoto, K.; Saito, B.; Katsuki, T. Chem.
Commun. 2007, 35, 3691.
This research was supported by the National Nature Science
Foundation of China (NSFC, 21272069, 20672035), the
Fundamental Research Funds for the Central Universities and
Key Laboratory of Organofluorine Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences.
1
3
(a) Raj, S. S. S.; Thirumurugan, R.; Shanmugam, G.; Fun, H-K.;
Manonmani, J.; Kandaswamy, M. Acta Cryst. 1999, C55, 94. (b) Raj, S.
S. S.; Thirumurugan, R.; Shanmugam, G.; Fun, H-K.; Manonmani, J.;
Kandaswamy, M. Acta Cryst. 1999, C55, 894. (c) DiMauro, E. F.;
Kozlowski, M. C. Org. Lett. 2001, 3, 3053.
References and notes
1
(a) Kinting, A.; Kreuzfel H. J.; Abicht, H. P. J. Organometallic Chem.
989, 370, 343. (b) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.
1
Tetrahedron Lett. 1996, 37, 3815. (c) Sibi, M. P.; Shay, J. J.; Liu, M.;
Jasperse, C. P.; J. Am. Chem. Soc. 1998, 120, 6615. (d) Spangler, K. Y.;
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14 Dimauro, E. F.; Kozlowski, M. C. Org. Lett. 2001, 3, 1641.
1
5
CCDC 846007 contains the supplementary crystallographic data. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
2
012, 51, 1187. (f) Alejandro, P.; Ricardo, A.; Leyre, M.; Alberto, M.
C.; Jose, L. G. R.; Jose, A. Chem. Commun. 2012, 48, 9759.
16 (a) Wang, L. M.; Xia, J. J.; Tian, H.; Qin, F.; Qian, C. T.; Sun, J.
Synthesis 2003, 8, 1241. (b) Wang, L. M.; Sheng, J.; Tian, H.; Han, J.
W.; Fan, Z. Y.; Qian, C. T. Synthesis 2004, 18, 3060. (c) Wang, L. M.;
Liu, J. J.; Tian, H.; Qian, C. T.; Sun, J. Adv. Synth. Catal. 2005, 347,
2
3
4
For recent reviews, see: (a) Sibi, M. P.; Liu, M. Curr. Org. Chem. 2001,
5
, 719. (b) Zanoni, G.; Castronovo, F.; Franzini, M.; Vidari, G.;
Giannini, E. Chem. Soc. Rev. 2003, 32, 115. (c) Tanaka, T.; Hayashi, M.
Synthesis 2008, 3361.
6
89. (d) Tang, J.; Wang, L. M.; Mao, D.; Wang, W. B.; Zhang, L.; Wu,
S. Y.; Xie, Y. S. Tetrahedron 2011, 67, 8465. (e) Tang, J.; Wang, L. M.;
Wu, S. Y.; Mao, D. Synlett 2011, 2913. (f) Liu, J. Q.; Shen, Q.; Yu, J. J.;
Zhu, M. Y.; Han, J. W.; Wang, L. M. Eur. J. Org. Chem. 2012, 35,
6933.
(a) Kinting, A.; Kreuzfel, H. J.; Abicht, H. P. J. Organometallic Chem.
1
989, 370, 343. (b) Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima,
Y.; Kanai, W.; Du, M.; Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc.
001, 123, 9908.
2
1
1
7
8
Kostal, J.; Voutchkova, A. M.; Jorgensen, W. L. Org. Lett. 2012, 14,
(a) Trost, B. M.; Yeh, V. S. C.; Ito, H.; Bremeyer, N. Org. Lett. 2002, 4,
621. (b) Bandini, M.; Piccinelli, F.; Tommasi, S.; UmaniRonchi, A.;
260.
2
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8
Tetrahedron
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Ma, K.; You, J. Chem. Eur. J. 2007, 13, 1863.

ACCEPTED MANUSCRIPT
Supporting Information
Design of C -Symmetric Salen Ligands and Their Co(II)- or
2
Yb(III)- Complexes Controlled Reversal of Enantioselectivity in
Asymmetric Henry Reaction
a,c
a,c
b
a
a
a
a
Shengying Wu, Jun Tang, Jianwei Han,* Dan Mao, Xin Liu, Xing Gao, Jianjun Yu and
a
Limin Wang*
a
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University
of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China. E-mail:
wanglimin@ecust.edu.cn, Tel & Fax: (+86)-21-64253881
b
Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic
Chemistry, the Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai 200237, P. R. China.
E-mail: jianweihan@sioc.ac.cn; Tel & Fax: (+86)-21-54925383
c
These authors contributed equally to this work.
1
2
3
4
5
6
. General information……………………………………………....S2
. Synthesis of the chiral ligand (S)-8……………………………....S2
. Tables of solvent and temperature effects of Henry reaction….S2
1
13
. H and C NMR spectra for ligands ………...…………………S4
1
. H NMR spectra for Henry products …….….…………………S11
. HPLC spectra for Henry products ………………………..……S18
S1

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1
) General information
General Methods. Unless otherwise noted, all the reactions were conducted under argon
1
13
atmosphere. All reagents and solvents were dried and distilled prior to use. H NMR and C NMR
spectra were recorded at 400 MHz and 100 MHz, respectively using tetramethylsilane as an
internal reference. Chemical shifts (δ) and coupling constants (J) were expressed in parts per
million and hertz, respectively. Melting points were uncorrected. High-resolution mass
spectrometry (HRMS) was performed with Electron Ionization (EI) resource or on an ESI-TOF
spectrometer. The ee was determined by HPLC on AD, or OD column.
2
) Synthesis of the chiral ligand (S)-8.
Scheme S1 Synthesis of the chiral ligand (S)-8.
3
) Tables of solvent and temperature effects of Henry reaction
i
Table S1. Solvent screening of enantioselective Henry reaction catalyzed by Yb( PrO) /(S)-5
3
a
system.
b
c
Entry
Solvent
MeOH/THF = 2/1
MeOH
Yield(%)
ee(%)
1
2
3
4
5
6
7
8
9
84
68
66
57
52
/
87
EtOH
75
i
PrOH
40
CH CN
n.r
3
CH Cl
n.r
/
2
2
DMF
n.r
/
THF
42
3
MeOH/THF = 4/1
MeOH/THF = 3/2
67
64
77
10
84
S2

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1
1
MeOH/THF = 1/1
MeOH/THF = 2/3
MeOH/THF = 1/4
MeOH/THF = 1/5
MeOH/THF = 1/6
MeOH/THF = 1/7
MeOH/THF = 1/9
90
89
93
78
72
57
46
79
80
87
79
33
50
22
12
13
14
15
16
17
a
Reaction conditions: benzaldehyde (0.25 mmol), nitromethane (1.25 mmol), ligand
i
(
6 mol%), Yb(O Pr) (5 mol%), solvent (1.5 mL), and 48 h for reaction time at 15
3
o
b
c
C. Isolated yields. Determined by chiral HPLC.
i
Table S2. Temperature effect of enantioselective Henry reaction catalyzed by Yb( PrO) /(S)-5
3
a
system.
o
b
c
Entry
Temp ( C)
Time (h)
Yield (%)
ee (%)
1
2
3
4
5
6
-10
0
84
84
72
48
36
24
23
70
82
93
94
98
76
74
5
79
15
r.t.
40
87
65
35
a
Reaction conditions: benzaldehyde (0.25 mmol), nitromethane (1.25 mmol), ligand
i
(
6 mol%), Yb(O Pr) (5 mol%), MeOH/THF (1/4, v/v, 1.5 mL) at different
3
b
c
temperature. Isolated yields. Determined by chiral HPLC.
S3

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1
13
4
) H and C NMR spectra for ligands
1
H NMR spectrum of (S)-1.
1
H NMR spectrum of (S)-2.
S4

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H NMR spectrum of (S)-3.
S5

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1
H NMR spectrum of (S)-4.
1
3
C NMR spectrum of (S)-4.
S6

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H NMR spectrum of (S)-5.
1
3
C NMR spectrum of (S)-5.
S7

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H NMR spectrum of (S)-6.
1
3
C NMR spectrum of (S)-6.
S8

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H NMR spectrum of (S)-7.
1
3
C NMR spectrum of (S)-7.
S9

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H NMR spectrum of (S)-8.
S10

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1
5
) H NMR spectra of Henry products
S11

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S12

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S13

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S14

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S15

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S16

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7
) HPLC spectra of Henry products
9a
HPLC spectrum of racemic-9a.
HPLC spectrum of (S)-9a.
S18

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HPLC spectrum of (R)-9a.
9b
HPLC spectrum of racemic-9b.
S19

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HPLC spectrum of (S)-9b.
HPLC spectrum of (R)-9b.
S20