Enantioselective nitroaldol reaction catalyzed by chiral C 1-tetrahydro-1,1′-bisisoquinoline-copper(I) complexes

Article abstract of DOI:10.1016/j.tetasy.2011.05.013

An efficient catalytic system comprising of chiral C₁- tetrahydro-1,1′-bisisoquinoline and CuCl in the ratio of 2:1 has been developed for the enantioselective Henry reaction. The catalytic efficiencies of the chiral C₁-tetrahydro-1,

Full text of DOI:10.1016/j.tetasy.2011.05.013

Tetrahedron: Asymmetry 22 (2011) 929–935
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective nitroaldol reaction catalyzed by chiral
0
C -tetrahydro-1,1 -bisisoquinoline–copper(I) complexes
1
⇑
Yao Qiong Ji, Gao Qi, Zaher M. A. Judeh
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, N1.2 B1-14, Singapore 637459, Singapore
a r t i c l e i n f o
a b s t r a c t
0
Article history:
Received 22 February 2011
Accepted 19 May 2011
An efficient catalytic system comprising of chiral C -tetrahydro-1,1 -bisisoquinoline and CuCl in the ratio
1
of 2:1 has been developed for the enantioselective Henry reaction. The catalytic efficiencies of the chiral
-tetrahydro-1,1 -bisisoquinolines are governed to a great extent by the structural constraints and the
0
C
1
3
type of substituent on the sp -N. Aromatic and aliphatic aldehydes reacted with nitromethane to give
b-nitroalcohols in very high yields (up to 95%) and enantioselectivities (up to 91% ee). The present cata-
lyst system is simple in operation since no special precautions were taken to exclude moisture or air from
the reaction flask and no additives were required for activation. Nonlinear effects have also been studied
for this reaction.
Ó 2011 Elsevier Ltd. All rights reserved.
1
. Introduction
less basic
2
sp -N
1
1
NH
NH
Na
Nb
The design, synthesis and application of chiral ligands are sig-
0
nificant tasks in asymmetric catalysis. The use of chiral C
bisisoquinolines (Fig. 1) in various asymmetric reactions resulted
in poor to modest enantioselectivities. We have recently disclosed
a straightforward synthesis of the C
2
-1,1 -
H
'
more basic sp3-
H
1
N
0
1
-tetrahydro-1,1 -bisisoquino-
C2-Octahydro-1, 1'-bisisoquinoline
C -Tetrahydro-1, 1'-bisisoquinoline
1
line framework and observed major structural differences between
racemic-1a
0
0
1 2
the C -tetrahydro-1,1 -bisisoquinolines and the C -octahydro-1,1 -
0
Figure 1. General structures of C
1,1 -bisisoquinoline and rac-1a.
2
-octahydro-1,1 -bisisoquinoline, C
1
-tetrahydro-
bisisoquinolines (Fig. 1) with the help of X-ray crystallographic
0
2
0
1
analysis. Potentially, the C -tetrahydro-1,1 -bisisoquinolines pres-
ent structurally robust motifs amenable to stereoelectronic tuning
and optimization and are envisioned to catalyze a wide array of
12
dine–thiourea.
Nevertheless, other complexes such as Co-
0
asymmetric reactions. Indeed, application of C
bisisoquinoline (R)-1a in the enantioselective addition of Et
various aldehydes gave exciting results.2b We decided to further
1
-tetrahydro-1,1 -
13
14a
14b,c
15
salens, Zn-aminoalcohols,
rare-earth-BINOLs
Herein, we report on the application of chiral C
,1 -bisisoquinolines (R)-1a–f (Fig. 2) as ligands for the enantiose-
lective Henry reaction and examine the effects of the substituents
attached to the sp -N on the reactivity and selectivity.
Zn-azacrowns,
have been employed with variable success.
Cr-salens and
2
Zn to
4,16
1
-tetrahydro-
explore and broaden the application of the new chiral C
1
-tetrahy-
0
1
0
dro-1,1 -bisisoquinolines by examining their efficiencies in the
enantioselective Henry reaction. Practically, the enantiopure nitro-
alcohol adducts obtained from this reaction can be transformed
into many valuable chiral building blocks such as nitro alkenes,
aminoalcohols and aminoacids among others.3 Due to its signifi-
cance, the development of catalysts for the enantioselective Henry
3
2
. Results and discussion
0
Racemic C
1
-tetrahydro-1,1 -bisisoquinoline rac-1a was readily
synthesized under the Bischler–Napieralski conditions and re-
solved using (S)-(+)-
-Tetrahydro-1,1 -bisisoquinoline (R)-1a demonstrates
diverse stereoelectronic features: (i) it coordinates to metals
through a strongly basic sp -N atom and a weekly basic sp -N
4
reaction has been escalating since Shibasaki’s first seminal report.
The majority of the successful catalysts reported are copper
a
-methylbenzyl isocyanate to give (R)-1a
5
complexes of chiral nitrogen ligands such as bisoxazolines,
2
a
0
(Fig. 2).
C
1
6
9
7
8
9
bisimidazolines,
(ꢀ)-sparteine,
diamines,
iminopyridines,
10
0
11
aminopyridines, tetrahydrosalens and N,N -dioxides, guani-
3
2
5a
2
atom; (ii) it has a constrained structure whereby the sp -N contain-
1
7
3
⇑
Corresponding author. Fax: +65 67947553.
E-mail address: zaher@ntu.edu.sg (Z.M.A. Judeh).
ing ring is flat due to its aromaticity while the sp -N containing
2
b–d,17
ring assumes a twist-boat conformation
(note: the nitrogens
0
957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.05.013

9
30
Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
Na
Nb
N
O
N
N
O
H
S
N
H
H
O
H
(
R)-1a
(R)-1b
(R)-1c
N
N
N
N
N
O
S
S
N
N
H
N
N
H
H
H
H
H
(
R)-1d
(R)-1e
(R)-1f
0
Figure 2. Chiral C
1
-tetrahydro-1,1 -bisisoquinolines (R)-1a–f.
0
3
0
in C
2
-1,1 -bisisoquinolines (Fig. 1) are both sp hybridized and both
is due to the C1 chiral carbon and not due to the chirality of the
(S)-(ꢀ)-(
2b–d,17
heterocyclic rings assume a twist-boat conformation.
can be easily functionalized at the sp -N (i.e., N
); (iii) it
) to bring further
a)-methylbenzyl substituent, ligand (R)-1f was employed
3
b
(Table 1, entry 6). Again, the product (R)-3a was obtained in 20%
yield and 21% ee (Table 1, entry 6). To confirm that the catalysis ob-
served in entries 5 and 6 (Table 1) is due to the copper complex
with (R)-1e and (R)-1f, we repeated the reaction under exactly
the same conditions with the exception that CuBr was not used.
In these cases, the starting material was recovered unchanged
and no products were formed indicating that (R)-1e and (R)-1f
are unable to catalyze the reaction without CuBr. Further insights
on the reactivity come from the preferential conformations
deduced from X-ray crystallographic analysis of these ligands
although the conformation in the solid and solution states could
be different to some extent. In the case of (R)-1a, copper could
contrasting Lewis acidity effects to the metal center. In the Henry
reaction, the Lewis acidity of the metal center is proven to play
an important role in activating the aldehyde and has tremendous
impact on the enantioinduction.5a Thus, treatment of (R)-1a with
p-toluenesulfonyl chloride, acetyl chloride, 1-naphthyl isocyanate,
a)-methylbenzyl isothiocyanate and cyclohexyl isothiocy-
anate provided ligands (R)-1b–f, respectively, in excellent yields
Fig. 2). The substituents at sp -N of ligands (R)-1b–f were chosen
to provide variable steric bulk and electronic effects at the metal
center.
(S)-(–)-(
2
a
3
(
We started our investigation by employing ligands (R)-1a–1f in
a standard enantioselective addition of nitromethane to benzalde-
hyde 2a to examine their effectiveness as chiral inducers (Table 1).
Therefore, the Henry reaction was performed using a combination
2
b
easily chelate to the syn-oriented nitrogens (N
chiral complexes since there is no impedance resulting from the
low steric hindrance brought by the H group at N . On the contrary,
a b
and N ) to form
b
of 10 mol % ligand, 10 mol % CuBr and 20 equiv MeNO
Ligand (R)-1a gave b-nitroalcohol (R)-3a in excellent 94% yield and
in moderate 68% ee (Table 1, entry 1). Unexpectedly, ligands (R)-
2
in THF at rt.
similar copper complexes could not be obtained in the case of
(R)-1b and (R)-1c due to the extreme crowding brought about by
the bulky p-toluenesulfonyl and acetyl substituents as evidenced
1
b–d gave no products and the starting benzaldehyde 2a was
b
from the X-ray structure. Thus, bulky substituents at N cause se-
recovered back unchanged (Table 1, entries 2–4). This lack of reac-
tivity may be attributed to the ineffective formation of the required
copper complexes. Interestingly, ligand (R)-1e gave (R)-3a in 30%
yield and 24% ee (Table 1, entry 5). To ensure that the induction
vere crowding at the chelating nitrogens and force them to adapt
an anti conformation preventing effective chelation and the forma-
tion of useful metal complexes.
Ligand (R)-1a was used for further optimization of the reaction
conditions. The effects of various protic and aprotic solvents
(
Table 2) were examined under the reaction conditions used in
Table 1
Table 1. Generally, aprotic solvents (Table 2, entries 3–13) were
found to be superior to protic solvents (Table 2, entries 1 and 2)
in terms of yields and enantioselectivities of 3a. Among the aprotic
Asymmetric Henry reaction using ligands (R)-1a–fa
OH
1
1
0 mol% Ligand
0 mol% CuBr
CHO
NO2
(R)
2 2
solvents, ClCH CH Cl gave the best enantioselectivity (77% ee)
+
MeNO2
albeit in a low 45% yield. Generally, ether-type solvents gave high
yields and moderate enantioselectivities (Table 2, entries 8–13).
Based on the above results, further optimizations were explored
(
20 eq.) THF, r.t., 36 h
2a
3a
Yieldb (%)
eec (%)
2 2
using ClCH CH Cl as the solvent of choice.
Entry
Ligand
Next, the effects of various copper sources were examined
Table 3). Copper(I) (Table 3, entries 1–3) showed clear superiority
1
2
3
4
5
6
(R)-1a
(R)-1b
(R)-1c
(R)-1d
(R)-1e
(R)-1f
94
0
0
0
30
20
68
—
—
—
24
21
(
compared to copper(II) sources (Table 3, entries 4–7) which were
either sluggish or ineffective. Among the copper(I) sources exam-
ined, CuCl gave the highest enantioselectivity of 79% ee and was
therefore used for further optimization (Table 3, entry 1).
a
All reactions were performed on a 0.2 mmol scale of benzaldehyde 2a in the
presence of ligand (10 mol %) and CuBr (10 mol %) using MeNO (20 equiv) in THF
(
Subsequently, the effects of ratio of ligand (R)-1a to CuCl, cata-
lyst loading and reaction temperature were examined. When the
amount of CuCl was kept constant at 10 mol %, a gradual increase
in the amount of ligand (R)-1a from 5, 10, 15 to 20 mol % (Table 4
entries 1–4) resulted in a tremendous increase in the reaction rate
and the yield of 3a more than doubled when the amount of ligand
2
1.5 ml) at rt for 36 h.
b
Yields of isolated products.
c
Enantiomeric excesses were determined by HPLC using
a Chiralcel OD-H
column. The absolute configuration (R) was determined by comparison with the
literature values.8
d

Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
931
Table 2
The effect of reaction temperature was examined at 40 °C, 0 °C
and ꢀ20 °C. An increase in the reaction temperature from rt to
40 °C resulted in a faster reaction rate, improved yield of 3a
(78%) but inferior enantioselectivity (70% ee) (Table 4, entry 9 vs
entry 5). However, a decrease in the reaction temperature from
rt to 0 °C gave comparable yield (60%) and higher enantioselectiv-
ity (85% ee) of 3a (Table 4, entry 10 vs entry 5). At ꢀ20 °C, the reac-
tion did not proceed due to poor solubility of the copper complex
a
Screening of solvents in the enantioselective Henry reaction
OH
1
1
0 mol% (R)-1a
CHO
NO2
0 mol% CuBr
(R)
+
MeNO2
20 equ.)
solvent, r.t., 36 h
(
2
a
3a
Entry
Solvent
Yieldb (%)
eec (%)
(Table 4, entry 11).
1
2
3
4
5
6
7
8
9
Methanol
Ethanol
CH
ClCH
CHCl
Toluene
CH CN
THF
Dioxane
84
89
78
45
56
91
89
94
99
38
90
99
35
30
26
57
77
34
29
55
68
42
70
62
64
58
Since the most effective ratio of (R)-1a to CuCl was 2:1 (Table 4,
entry 10), the solvent and copper sources effects were reexamined
in the hope of obtaining better yields and enantioselectivities
(Table 5). Again, the best results obtained in this case are in agree-
ment with the solvent and copper sources effects shown in Table 2
and Table 3, respectively. Dichloroethane (Table 5, entry 1 vs
entries 2–6) using Cu(I) sources (Table 5, entries 1 and 7 vs entry
8) gave the best results.
2
Cl
2
2
2
CH Cl
3
3
10
11
12
13
1,2-Dimethoxyethane
t-BuOMe
Bu
Et
The scope and limitation of the Henry reaction using ligand
2
O
O
(
R)-1a under the optimized conditions (Table 4, entry 10) were
examined. We were delighted to find that a broad range of ali-
phatic and aromatic aldehydes reacted smoothly with MeNO
2
a
All reactions were performed on a 0.2 mmol scale of benzaldehyde 2a in the
2
presence of ligand (10 mol %) and CuBr (10 mol %) using MeNO
given solvent (1.5 ml) at rt for 36 h.
2
(20 equiv) in a
using our catalytic system to give the corresponding b-nitroalco-
hols in high yields and enantioselectivities (Table 6). Aromatic
aldehydes with electron-withdrawing (Table 6, entries 2–6) and
electron-donating substituents (Table 6, entries 7–13) gave simi-
lar yields (up to 95%) and enantioselectivities (up to 91% ee). An
exception to this is 4-nitrobenzaldehyde, which due to its strong
electron-withdrawing nitro group; it exerted a much faster reac-
tion rate that led to higher yield (95%) and lower enantioselectiv-
ity (64% ee). Interestingly, the substitution pattern (Table 6,
entries 3–5, 7–9 and 11–13) at the aromatic rings exhibited no
major effect on the enantioselectivity or yield of the products. In
b
Yield of isolated product.
c
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H col-
umn. The absolute configuration (R) was determined by comparison with the lit-
erature values.8
d
Table 3
a
Screening of copper sources in the enantioselective Henry reaction
OH
1
1
0 mol% (R)-1a
CHO
NO2
0 mol% Cu source
(R)
+
MeNO2
ClCH CH Cl,
general, aliphatic and a,b-conjugated aldehydes give lower
(
20 eq.)
2
2
r.t., 36 h
2
a
3a
enantioselectivities compared to aromatic aldehydes due to the
higher inherent reactivity and poor stereocontrol as a result of
substrate flexibility. We were pleased to discover that the
(R)-1a–Cu(I) complex catalyzed the nitroaldol reaction of aliphatic
Entry
Copper
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
CuCl
CuBr
CuI
55
45
70
0
21
0
79
77
41
—
68
—
and
b-nitroalcohol 3p–3s in up 91% ee (Table 6, entries 16–18).
-Naphthylaldehyde, 2-furaldehyde and cinamaldehyde gave the
a,b-conjugated aldehydes to give the corresponding
CuCl
Cu(OAc)
Cu(NO
Cu(OTf)
2
2
2
3
)
2
corresponding products in very good yields and enantioselectivi-
ties (Table 6, entries 14, 15 and 19).
2
0
—
a
It is essential that new catalysts designed for the Henry reaction
should circumvent side reactions such as the formation of a nitro-
alkene, normal aldol by-products and epimerization of stereogenic
centers remote from the nitro group. Fortunately, with the present
catalytic system, no such products were observed and no special
precautions were taken to exclude moisture or air from the reac-
tion flask.
All reactions were performed on a 0.2 mmol scale of benzaldehyde in the
presence of ligand (10 mol %) and copper sources (10 mol %) using MeNO
20 equiv) in ClCH CH Cl (1.5 ml) at rt for 36 h.
Yields of isolated products.
2
(
2
2
b
c
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H col-
umn. The absolute configuration (R) was determined by comparison with the lit-
erature values.8
d
The nonlineareffects were also examined (Fig. 3). The data shown
in Table 7 for the Henry reaction between benzaldehyde 2a and
(R)-1a was increased from 5 to 10 mol % (Table 4, entries 2 vs 1).
However, the yield of 3a remained unchanged with a further in-
crease in the amount of (R)-1a (Table 4, entry 2 vs entries 3 and
nitromethane seems to fit well with Kagan’s ML
which could mean the involvement of an aggregation of dimers.
4
model system,
18
4
(
). A slight increase in the ee of compound 3a was also observed
Table 4 entries 1–4). However, a gradual increase in the amount
of CuCl from 5, 15 to 20 mol %, while keeping the amount of ligand
R)-1a constant at 10 mol %, led to a significant decrease in the
Assuming the ligands are statistically distributed between the com-
plexes, curve fitting was calculated from the following equation1
8c
with parameters ee
performed with enantiopure ligand), K = [M(L
o
= 85% (enantioselectivity of the reaction
2
(
R
)
3
L
S
] /{[M(L
R
)
4
0
] *
2
yield of 3a from 63% to 19% to 13%, respectively, accompanied by
a slight decrease in enantioselectivity from 83% to 74% to 71%,
respectively, (Table 4, entries 5–7). Based on the above results,
we concluded that the optimal ratio of ligand (R)-1a to CuCl is
[M(L
R
)
(L
2 S
)
2
]} = [M(L
S
)
L
3 R
] /{[M(L
S
)
4
] * [M(L
R
)
2
(L
S
)
2
]} = 1000, ee =
o
64%, g = 0.41 (large predominance of a fairly active and selective
0
2
heterochiral catalyst), and K = [M(L
[M(L
R
)
(L
2 S
)
2
] /{[ M(L
R
)
3
S
L ] *
S
)
L
3 R
]} = 1, f = 2.0 (a more active meso catalyst).
2
:1 (Table 4, entry 5). Attempts to half the catalyst loading while
eeprod ¼ 8ee
o
ꢁ eecat
maintaining the (R)-1a to CuCl ratio at 2:1, resulted in a much low-
er yield of 3a (16%) even at extended reaction time (Table 4, entry
0
2
2
ee
o
o
1
þ ee þ 2gð1 ꢀ ee
Þ
cat
cat ee
8
). Therefore, the optimal ratio between (R)-1a and CuCl is 2:1
ꢂ
4
2
2
ð1 þ eecatÞ þ ð1 ꢀ eecatÞ4 þ 8gð1 ꢀ eecatÞ4 þ 6fð1 ꢀ ee
Þ
cat
using 10 mol % ligand (R)-1a and 5 mol % CuCl loading.

9
32
Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
Table 4
a
Effects of the ratio of (R)-1a to CuCl, catalyst loading and temperature in the asymmetric Henry reaction of benzaldehyde
OH
1
5
0 mol% (R)-1a
mol% copper salt
CHO
NO2
(R)
+
MeNO2
solvent, 0 °C, 48 h
(
20 equ.)
2a
3a
Entry
CuCl (mol%)
(R)-1a (mol%)
Temperature (°C)
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
10
10
10
10
5
15
20
2.5
5
5
10
15
20
10
10
10
5
rt
rt
rt
rt
rt
rt
rt
rt
40
0
84
36
36
36
36
36
36
120
12
72
25
55
56
56
63
19
13
16
78
60
—
73
79
80
82
83
74
71
80
70
85
—
10
10
10
1
1
0
1
5
5
ꢀ20
120
a
b
c
2 2 2
All reactions were performed on a 0.2 mmol scale of benzaldehyde in the presence of ligand (R)-1a and CuCl using MeNO (20 equiv) in ClCH CH Cl (1.5 ml).
Yield of isolated product.
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H column. The absolute configuration (R) was determined by comparison with the literature
values.8d
Table 5
Table 6
a
Screening of solvents and copper sources using a 2:1 ratio of (R)-1a–copper source in
the enantioselective Henry reaction
Scope of (R)-1a in the enantioselective Henry reaction
a
OH
O
10 mol% (R)-1a
OH
5 mol% CuCl
NO2
+
MeNO2
(20 eq.)
(R)
1
5
0 mol% (R)-1a
R
H
R
CHO
NO2
ClCH CH Cl, 0 °C
mol% copper salt
(R)
2
2
3
2
+
MeNO2
solvent, 0 °C, 48 h
(
20 equ.)
Entry
R
Product
Time (h)
Yieldb (%)
eec (%)
2a
3a
1
2
3
4
5
6
7
8
9
Ph
4-NO
4-ClC
3-ClC
2-ClC
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
72
12
48
60
48
72
60
60
48
48
72
48
48
48
48
60
60
48
48
60
95
70
59
72
59
65
57
70
80
60
75
79
85
80
76
73
72
78
85
64
91
87
87
87
88
86
87
82
89
90
91
80
85
88
90
91
81
Entry
Solvent
ClCH CH
Methanol
CH Cl
Toluene
CH CN
THF
Copper
Yieldb (%)
eec (%)
2 6 4
C H
1d
6
H
6
H
6
H
4
2
2
Cl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuBr
60
90
78
70
85
90
55
40
85
36
70
65
70
66
78
62
2
3
4
5
6
4
4
2
2
6 4
4-FC H
4-MeC
3-MeC
2-MeC
6
H
6
H
6
H
4
4
4
3
d
7
ClCH
ClCH
2
CH
CH
2
Cl
Cl
d
10
4-PhC
6
H
8
2
2
Cu(OAc)
2
4
11
4-MeOC
3-MeOC
2-MeOC
2-Naphthyl
2-Fural
n-Bu
6
H
6
H
6
H
4
4
4
a
All reactions were performed on a 0.2 mmol scale of benzaldehyde in the
presence of ligand (R)-1a (10 mol %) and Copper salts (5 mol %) using MeNO
20 equiv) in ClCH CH Cl (1.5 ml).
Yield of isolated product.
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H col-
umn. The absolute configuration (R) was determined by comparison with the lit-
12
13
14
15
16
17
18
19
2
(
2
2
b
c
n-Pr
8d
erature values.
8 17
n-C H
d
Reaction for 72 h.
PhCH@CH–
a
All reactions were performed on a 0.2 mmol scale of benzaldehyde in the
presence of ligand (R)-1a (10 mol %) and CuCl (5 mol %) using MeNO (20 equiv) in
2
ClCH
2
CH
Yield of isolated product.
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H, OJ-H
2
Cl (1.5 ml) at 0 °C.
where g = kRRRS/kRRRR, relative reactivities of hetero (M(L
R
)
3
L
S
) over
b
c
homochiral catalysts, f = kRRSS/kRRRR, relative reactivities of hetero-
meso kind (M(L (L ) over homochiral catalysts, eeprod = ee of
the Henry reaction’s product obtained, ee = ee of the Henry
or AD-H column. The absolute (R) configuration was determined by comparison
R
)
2
S 2
)
with the literature values.5
a,8d
o
reaction’s product obtained using enantiopure homochiral M(L
R
)
4
0
complexes, ee = ee of the obtained Henry reaction’s product using
o
3
0
enantiopure heterochiral M(L
M(L (L as a meso complex and assume no additional stereoiso-
mers involving the metal center),
R
)
3
L
S
complexes (we consider
sp -N. Chiral
1
C -tetrahydro-1,1 -bisisoquinoline (R)-1a proved
R
)
2
S 2
)
to be an effective ligand in the Cu(I)-catalyzed Henry reaction.
The desired products were obtained in excellent yields and
enantioselectivities (up to 91%) with a broad range of aliphatic,
aromatic, heteroaromatic and unsaturated aldehydes. The
18c
eecat = ee of ligand.
3
. Conclusion
4
nonlinear effects fit well with the Kagan’s ML model system.
We have shown that the reactivities and selectivities of chiral
-tetrahydro-1,1 -bisisoquinolines in the Henry reaction are
governed to a great extent by the type of substituent at the
The operational procedure using the present catalyst system is
very simple and does not require exclusion of air or moisture.
The results obtained here pave the way for more applications of
0
C
1

Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
933
4
.2. General procedure for asymmetric Henry reaction
Ligand (0.02 mmol, 10 mol %) and CuCl (0.01 mmol, 5 mol %)
were stirred in ClCH CH Cl (1.5 mL) at rt for 100 min, whereby a
2 2
green solution was obtained. To the above stirred solution, alde-
hyde (0.2 mmol) was added and the mixture was stirred for an-
other 5 min before the dropwise addition of nitromethane
(
4 mmol, 20 equiv). The reaction mixture was further stirred at
the given temperature for a specific time (TLC). The b-nitroalcohol
product was purified on silica gel by flash column chromatography.
4
.2.1. (R)-1-Phenyl-2-nitroethanol (R)-3a
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a colorless oil (60% yield); HPLC analysis: Chiralcel OD-H column
(
90:10 n-hex: IPA, flow rate 0.8 ml/min, 215 nm); major enantio-
mer t = 18.10 min, minor enantiomer t
= 22.20 min; 85% ee; 1
NMR (CDCl , d ppm): 2.76 (1H, br s), 4.39–4.56 (2H, m), 5.37 (1H,
dd, J = 9.3, 9.6 Hz), 7.34–7.40 (5H, m); C NMR: 71.0, 81.3, 126.0,
1
2
H
3
1
3
1
29.0, 129.1 and 138.2.
Figure 3. Nonlinear effect for the Henry reaction of nitromethane and benzalde-
hyde catalyzed by the (R)-1a/CuCl (2/1) system.
4
.2.2. (R)-1-(4-Nitrophenyl)-2-nitroethanol (R)-3b
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 7:3) to give
a yellow oil (95% yield); HPLC analysis: Chiralcel OD-H column
Table 7
(
85:15 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantio-
mer t = 21.10 min, minor enantiomer t
= 25.50 min; 64% ee; 1
NMR (CDCl , d ppm): 3.28 (1H, br s), 4.47–4.66 (2H, m), 5.48–
.5.56 (1H, m), 7.63 (2H, d, J = 8.7 Hz), 8.27 (2H, d, J = 8.7 Hz);
NMR (CDCl , d ppm): 70.0, 80.6, 124.1, 127.0, 145.4 and 148.0.
Nonliear effect under 2:1 ratio of (R)-1a–Copper salt in the enantioselective Henry
reactiona
H
1
2
3
OH
13
5
C
1
0 mol% (R)-1a
CHO
NO2
(
R)
5
mol% CuCl
3
+
MeNO2
(
20 equ.)
ClCH2CH2Cl, 0 °C
4
.2.3. (R)-1-(4-Chlorophenyl)-2-nitroethanol (R)-3c
This compound was prepared according to the Section 4.2 and
3a
2a
% ee Product, 3a b
purified by column chromatography (Hexane–EtOAc 5:1) to give
a colorless oil (70% yield); HPLC analysis: Chiralcel OD-H column
Entry
% ee Catalyst, (R)-1a
1
2
3
4
5
6
7
0
15
40
50
70
90
99
0
10
28
40
61
81
85
(
90:10 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantio-
mer t = 13.90 min, minor enantiomer t
= 17.70 min; 91% ee; 1
NMR (CDCl , d ppm): 2.89 (1H, br s), 4.47–4.62 (2H, m), 5.44–
5.47 (1H, m), 7.34–7.40 (4H, m); C NMR (CDCl
0.1, 127.3, 129.3, 134.9 and 136.5.
1
2
H
3
1
3
3
, d ppm): 70.3,
8
a
All reactions were performed on a 0.2 mmol scale of benzaldehyde in the
presence of ligand (R)-1a (10 mol %) and CuCl (5 mol %) using MeNO (20 equiv) in
ClCH CH Cl (1.5 ml).
4.2.4. (R)-1-(3-Chlorophenyl)-2-nitroethanol (R)-3d
2
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a colorless oil (59% yield); HPLC analysis: Chiralcel OD-H column
(90:10 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantio-
2
2
b
Enantiomeric excesses were determined by HPLC using a Chiralcel OD-H col-
umn. The absolute configuration (R) was determined by comparison with the lit-
erature values.8
d
mer t
NMR (CDCl
m), 7.26–7.73 (4H, m); C NMR (CDCl
r
= 13.6 min, minor enantiomer t
= 16.8 min; 87% ee; 1
H
r
3
, d ppm): 2.96 (1H, br s), 4.49–4.63 (2H, m), 5.40 (1H,
1
3
3
, d ppm): 70.3, 81.0,
0
the C
ric reactions.
1
-tetrahydro-1,1 -bisisoquinoline ligands in various asymmet-
1
24.0, 126.2, 129.1, 130.3, 135.0 and 140.0.
4
.2.5. (R)-1-(2-Chlorophenyl)-2-nitroethanol (R)-3e
This compound was prepared according to the Section 4.2 and
4
4
. Experimental
purified by column chromatography (Hexane–EtOAc 5:1) to give
a colorless oil (72% yield); HPLC analysis: Chiralcel OJ-H column
.1. General
(
90:10 n-hex: IPA, flow rate 0.5 ml/min, 215 nm); major enantio-
1
All commercial chemicals were reagent grade unless other-
1 2
mer t = 82.00 min, minor enantiomer t = 94.37 min; 87% ee; H
wise specified. Analytical thin layer chromatography (TLC) was
performed using Merck 60 254 pre-coated silica gel plates
0.2 mm thickness). Separation of products was achieved using
NMR (CDCl , d ppm): 3.00 (1H, br s), 4.59–4.64 (1H, m), 4.62 (1H,
3
F
dd, J = 13.5, 2.4 Hz), 5.79 (1H, d, J = 9.3 Hz), 7.26–7.34 (3H, m),
1
3
(
7.60 (1H, dd, J = 9.3, 2.1 Hz); C NMR (CDCl , d ppm): 67.8, 79.3,
3
column chromatography on Merck Silica Gel 60 (230–400 mesh).
127.5, 127.6, 129.7, 129.9, 131.5 and 135.5.
1
H (300 MHz) and 13C (75.47 MHz) NMR spectra were recorded
on a Bruker Advanced DPX 300 spectrometer with TMS as an
internal reference. HPLC separations were performed on Agilent
4.2.6. (R)-1-(4-Fluorophenyl)-2-nitroethanol (R)-3f
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 7:3) to give
a colorless oil (59% yield); HPLC analysis: Chiralcel OD-H column
1
100 using Diacel Chiralcel OD-H, OJ-H and AD-H chiral
columns.

9
34
Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
(
90:10 n-hex: IPA, flow rate 0.8 ml/min, 215 nm); major enantio-
m), 5.44 (1H, m), 6.88–6.97 (3H, m), 7.28–7.57 (1H, m); 13C NMR
(CDCl , d ppm): 55.3, 70.9, 81.2, 111.50, 114.4, 118.1, 130.1,
1
mer t
1
= 15.37 min, minor enantiomer t
2
= 18.36 min; 87% ee;
H
3
NMR (CDCl
3
, d ppm): 2.89 (1H, s), 4.46–4.63 (2H, m), 5.47 (1H, d,
139.8 and 160.1.
13
J = 7.5 Hz), 7.07–7.13 (2H, m), 7.37–7.42 (2H, m); C NMR (CDCl
3
,
d ppm): 70.3, 81.2, 115.9, 116.1, 127.7 and 127.8.
4.2.13. (R)-1-(2-Methoxyphenyl)-2-nitroethanol (R)-3m
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 9:1) to give
a yellow oil (79% yield); HPLC analysis: Chiralcel OD-H column
(90:10 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantio-
4
.2.7. (R)-1-(4-Methylphenyl)-2-nitroethanol (R)-3g
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 8:1) to give
a colorless oil (65% yield); HPLC analysis: Chiralcel OD-H column
mer t
NMR (CDCl
1
= 11.14 min, minor enantiomer t
, d ppm): 3.24 (1H, d, J = 6 Hz), 3.90 (3H, s), 4.55–
= 12.91 min; 91% ee; 1
H
2
(
90:10 n-hex: IPA, flow rate 0.5 ml/min, 215 nm); major enantio-
3
1
mer t
NMR (CDCl
1
= 27.8 min, minor enantiomer t
2
= 35.6 min; 88% ee;
H
4.69 (2H, m), 5.62–5.68 (1H, m), 6.93 (1H, d, J = 8 Hz), 7.03 (1H, t,
3
, d ppm): 2.36 (3H, s), 2.48 (1H, s), 4.46–4.64 (2H,
J = 7.5 Hz), 7.35 (1H, t, J = 8 Hz), 7.46 (1H, d, J = 7.5 Hz); 13C NMR
13
m), 5.40–5.46 (1H, m), 7.26–7.30 (4H, m); C NMR (CDCl
ppm): 21.2, 70.9, 81.3, 125.9, 129.7, 135.2 and 139.0.
3
, d
3
(CDCl , d ppm): 55.4, 67.8, 79.9, 110.6, 121.2, 126.0, 127.2, 129.8
and 156.0.
4
.2.8. (R)-1-(3-Methylphenyl)-2-nitroethanol (R)-3h
This compound was prepared according to the Section 4.2 and
4.2.14. (R)-1-(2-Naphthyl)-2-nitroethanol (R)-3n
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 4:1) to give
a yellow solid (85% yield); HPLC analysis: Chiralcel OD-H column
(85:15 n-hex: IPA, flow rate 0.8 ml/min, 215 nm); major enantio-
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (57% yield); HPLC analysis: Chiralcel OD-H column
(
90:10 n-hex: IPA, flow rate 0.5 ml/min, 215 nm); major enantio-
1
= 51.62 min; 80% ee; 1
H
2
mer t
NMR (CDCl
1
= 23.9 min, minor enantiomer t
2
= 27.9 min; 86% ee;
H
mer t
NMR (CDCl
d, J = 6.9 Hz), 7.26–7.54 (3H, m), 7.84–7.88 (4H, m); C NMR
(CDCl , d ppm): 71.2, 81.2, 123.2, 125.3, 126.7, 126.7, 127.8,
28.1, 129.0, 133.2, 133.4 and 135.4.
1
= 36.13 min, minor enantiomer t
3
, d ppm): 2.38 (3H, s), 2.81 (1H, s), 4.50–4.65 (2H, m),
3
, d ppm): 3.04 (1H, br s), 4.54–4.82 (2H, m), 5.61 (1H,
13
13
5
.37–5.45 (1H, m), 7.23–7.32 (4H, m); C NMR (CDCl
3
, d ppm):
2
1.4, 71.1, 81.8, 123.0, 126.6, 128.9, 129.7, 138.0 and 138.9.
3
1
4
.2.9. (R)-1-(2-Methylphenyl)-2-nitroethanol (R)-3i
This compound was prepared according to the Section 4.2 and
4.2.15. (R)-1-(2-Fural)-2-nitroethanol (R)-3o
purified by column chromatography (Hexane–EtOAc 5:1) to give
a colorless oil (70% yield); HPLC analysis: Chiralcel OD-H column
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (80% yield); HPLC analysis: Chiralcel OJ-H column
(90:10 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantio-
(
90:10 n-hex: IPA, flow rate 0.5 ml/min, 215 nm); major enantio-
1
mer t
NMR (CDCl
.60 (2H, m), 5.67–5.72 (1H, m), 7.25–7.31 (3H, m), 7.51–7.56
1
2
= 23.29 min, minor enantiomer t = 36.60 min; 87% ee; H
, d ppm): 2.40 (3H, s), 2.72 (1H, d, J = 3.6 Hz), 4.42–
mer t
NMR (CDCl
5.50 (1H, m), 6.38–6.40 (2H, m), 7.40–7.42 (1H, m); C NMR
(CDCl , d ppm): 64.9, 78.4, 108.2, 100.7, 143.2 and 150.7.
1
= 23.08 min, minor enantiomer t
= 28.49 min; 85% ee; 1
H
2
3
4
3
, d ppm): 2.90 (1H, br s), 4.63–4.84 (2H, m), 5.40–
1
3
13
(
1H, m); C NMR (CDCl
3
, d ppm): 18.9, 68.0, 80.2, 125.6, 126.8,
1
28.8, 130.9, 134.4 and 136.2.
3
4
.2.10. (R)-1-(4-Phenylphenyl)-2-nitroethanol (R)-3j
4.2.16. (R)-1-Nitrohexan-2-ol (R)-3p
This compound was prepared according to the Section 4.2 and
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (76% yield); HPLC analysis: Chiralcel AD-H column
(98:2 n-hex: IPA, flow 0.8 ml/min, 215 nm); major enantiomer
purified by column chromatography (Hexane–EtOAc 5:1) to give
a pale yellow crystalline solid (80% yield); HPLC analysis: Chiralcel
OD-H column (85:15 n-hex: IPA, flow rate 0.8 ml/min, 215 nm);
major enantiomer t
min; 82% ee; H NMR (CDCl , d ppm): 2.88 (1H, d, J = 3.3 Hz),
.36–4.69 (2H, m), 5.52 (1H, d, J = 9.3 Hz), 7.34–7.64 (9H, m);
1
= 19.54 min, minor enantiomer t
2
= 23.80
t
1
= 37.80 min, minor enantiomer t
= 50.51 min; 88% ee; 1H NMR
2
1
3
(CDCl , d ppm): 0.94 (3H, t, J = 6.9 Hz), 1.34–1.61 (6H, m), 2.54
3
1
3
13
4
C
(1H, br s), 4.31–4.49 (3H, m); C NMR (CDCl
3
, d ppm): 13.9,
3
NMR (CDCl , d ppm): 70.8, 81.2, 126.4, 127.1, 127.7, 127.8, 128.9,
22.4, 27.3, 33.4, 68.7 and 80.6.
1
37.0, 140.3 and 142.0.
4
.2.17. (R)-1-Nitropentan-2-ol (R)-3q
This compound was prepared according to the Section 4.2 and
4
.2.11. (R)-1-(4-Methoxyphenyl)-2-nitroethanol (R)-3k
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (60% yield); HPLC analysis: Chiralcel OD-H column
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (73% yield); HPLC analysis: Chiralcel AD-H column
(98:2 n-hex: IPA, flow 1.0 ml/min, 215 nm); major enantiomer
(
85:15 n-hex: IPA, flow rate 0.8 ml/min, 215 nm); major enantio-
t
1
= 33.70 min, minor enantiomer t
= 57.18 min; 90% ee; 1H NMR
2
1
mer t
NMR (CDCl
m), 5.62–5.68 (1H, m), 6.93 (2H, d, J = 8.7 Hz), 7.26–7.34 (2H, m);
1
= 17.01 min, minor enantiomer t
2
= 21.78 min; 89% ee;
H
(CDCl , d ppm): 0.98 (3H, t, J = 6.9 Hz), 1.50–1.59 (4H, m), 2.53
3
1
3
3
, d ppm): 2.73 (1H, br s), 3.81 (3H, s), 4.45–4.66 (2H,
(1H, br s), 4.35–4.46 (3H, m); C NMR (CDCl
3
, d ppm): 13.7,
18.4, 35.8, 68.4 and 80.7.
1
3
3
C NMR (CDCl , d ppm): 55.4, 70.7, 81.3, 114.4, 127.3, 130.2 and
1
60.1.
4.2.18. (R)-1-Nitrodecan-2-ol (R)-3r
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (72% yield); HPLC analysis: Chiralcel AD-H column
(98:2 n-hex: IPA, flow rate 1.0 ml/min, 215 nm); major enantiomer
4
.2.12. (R)-1-(3-Methoxyphenyl)-2-nitroethanol (R)-3l
This compound was prepared according to the Section 4.2 and
purified by column chromatography (Hexane–EtOAc 4:1) to give
a yellow oil (75% yield); HPLC analysis: Chiralcel OD-H column
t
1
= 23.09 min, minor enantiomer t
(CDCl , d ppm): 0.88 (3H, t, J = 6.3), 1.47–1.50 (14H, m), 2.49 (1H,
d, J = 4.5 Hz), 4.34–4.47 (3H, m); C NMR (CDCl
22.6, 25.2, 29.2, 29.3, 29.4, 31.8, 33.7, 68.7 and 80.6.
= 36.73 min; 91% ee; 1H NMR
2
(
90:10 n-hex: IPA, flow rate 0.5 ml/min, 215 nm); major enantio-
3
1
13
mer t
NMR (CDCl
1
= 48.22 min, minor enantiomer t
2
= 63.57 min; 90% ee;
H
3
, d ppm): 14.1,
3
, d ppm): 2.97 (1H, br s), 3.19 (3H, s), 4.72–4.84 (2H,

Y. Qiong Ji et al. / Tetrahedron: Asymmetry 22 (2011) 929–935
935
4
.2.19. (R,E)-1-Nitro-4-phenyl-3-buten-2-ol (R,E)-3s
This compound was prepared according to the Section 4.2 and
234–235; (e) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J. Org. Chem. 2007, 16, 2561–
2574; (f) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C. Tetrahedron: Asymmetry
2006, 17, 3315–3326; (g) Mayani, V. J.; Abdi, S. H. R.; Kureshy, R. I.; Khan, N. H.;
purified by column chromatography (Hexane–EtOAc 5:1) to give
a yellow oil (78% yield); HPLC analysis: Chiralcel OD-H column
Das, A.; Bajaj, H. C. J. Org. Chem. 2010, 75, 6191–6195.
4. Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992, 114,
4418–4420.
(
90:10 n-hex: IPA, flow rate 0.8 ml/min, 215 nm); minor enantio-
5.
(a) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.; Downey, C. W. J.
Am. Chem. Soc. 2003, 125, 12692–12693; (b) Christensen, C.; Juhl, K.; Hazell, R.
G.; Jorgensen, K. A. J. Org. Chem. 2002, 67, 4875–4881; (c) Risgaard, T.; Gothelf,
K. V.; Jorgensen, K. A. Org. Biomol. Chem. 2003, 1, 153–156; (d) Du, D.-M.; Lu,
S.-F.; Fang, T.; Xu, J. J. Org. Chem. 2005, 70, 3712–3715; (e) Lang, K.; Park, J.;
Hong, S. J. Org. Chem. 2010, 75, 6424–6435.
1
mer t
NMR (CDCl
.06 (1H, br s), 6.15 (1H, dd, J = 6.3, 15.9 Hz), 6.79 (1H, d,
r
r
= 38.62 min, major enantiomer t = 42.77 min; 81% ee; H
3
, d ppm): 2.68 (1H, d, J = 3.9 Hz), 4.51–4.61 (2H, m),
5
13
J = 15 Hz), 7.30–7.46 (5H, m); C NMR (CDCl
3
, d ppm): 69.6,
7
9.9, 124.9, 126.7, 128.6, 128.8, 133.7 and 135.5.
6. Ma, K.; You, J. Chem. Eur. J. 2007, 13, 1863–1871.
7.
Maheswaran, H.; Prasanth, K. L.; Krishna, G. G.; Ravikumar, K.; Sridhar, B.;
Kantam, M. L. Chem. Commun. 2006, 4066–4068.
Acknowledgments
8.
(a) Arai, T.; Takashita, R.; Endo, Y.; Watanabe, M.; Yanagisawa, A. J. Org. Chem.
2008, 73, 4903–4906; (b) Arai, T.; Watanabe, M.; Yanagisawa, A. Org. Lett. 2007,
9
, 3595–3597; (c) Bandini, M.; Benaglia, M.; Sinisi, R.; Tommasi, S.; Umani-
We are grateful to the Nanyang Technological University for
financial support (RG27/07), and also appreciate scholarship sup-
port for Y. Qiong Ji from China Scholarship Council.
Ronchi, A. Org. Lett. 2007, 9, 2151–2153; (d) Bandini, M.; Piccinelli, F.; Tommasi,
S.; Umani-Ronchi, A.; Ventrici, C. Chem. Commun. 2007, 616–618.
9. (a) Blay, G.; Climent, E.; Fernández, I.; Hernández-Olmos, V.; Pedro, J. R.
Tetrahedron: Asymmetry 2006, 17, 2046–2049; (b) Blay, G.; Domingo, L. R.;
Hernández-Olmos, V.; Pedro, J. R. Chem. Eur. J. 2008, 14, 4725–4730; (c) Noole,
A.; Lippur, K.; Metsala, A.; Lopp, M.; Kanger, T. J. Org. Chem. 2010, 75, 1313–
References
1
316.
1
.
(a) Cavell, K. J.; Elliott, M. C.; Nielsen, D. J.; Paine, J. S. Dalton Trans. 2006, 4922–
925; (b) Arai, S.; Takita, S.; Nishida, A. Eur. J. Org. Chem. 2005, 24, 5262–5267;
c) Seo, H.; Hirsch-Weil, D. K.; Abboud, A.; Hong, S. J. Org. Chem. 2008, 73, 1983–
986; (d) Baskakov, D.; Herrmann, W. A.; Herdtweck, E.; Hoffmann, S. D.
Organometallics 2007, 26, 626–632; (e) Herrmann, W. A.; Baskakov, D.;
Herdtweck, E.; Hoffmann, S. D.; Bunlaksananusorn, T.; Rampf, F.; Rodefeld, L.
Organometallics 2006, 25, 2449–2456; (f) Hrdina, R.; Dra ccaron ínsk y´ , M.;
Valterová, I.; Hoda ová, J.; Císa rcaron, I.; Kotora, M. Adv. Synth. Catal. 2008, 350,
1
1
0. Xiong, Y.; Wang, F.; Huang, X.; Wen, Y.; Feng, X. Chem. Eur. J. 2007, 13, 829–833.
1. Qin, B.; Xiao, X.; Liu, X.; Huang, J.; Wen, Y.; Feng, X. J. Org. Chem. 2007, 72,
4
(
1
9
323–9328.
2. Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Adv. Synth. Catal. 2005, 347, 1643–
648.
1
1
1
1
3. Kogami, Y.; Nakajima, T.; Ikeno, T.; Yamada, T. Synthesis 2004, 12, 1947–1950.
4. (a) Palomo, C.; Oiarbide, M.; Laso, A. Angew. Chem., Int. Ed. 2005, 44, 3881–
3
884; (b) Trost, B. M.; Yeh, V. S. C. Angew. Chem., Int. Ed. 2002, 41, 861–863; (c)
1
449–1456; Yao, Q.-J.; Judeh, Z. M. A. Tetrahedron 2011, 67, 4086–4092.
Trost, B. M.; Yeh, V. S. C.; Ito, H.; Bremeyer, N. Org. Lett. 2002, 4, 2621–2623.
2
.
.
(a) Qi, G.; Yao, Q.-J.; Judeh, Z. M. A. Tetrahedron 2010, 66, 4195–4205; (b) Qi, G.;
Judeh, Z. M. A. Tetrahedron: Asymmetry 2010, 21, 429–436; (c) Busato, S.; Craig,
D. C.; Judeh, Z. M. A.; Read, R. W. Tetrahedron 2003, 59, 461–472; (d) Craig, D.
C.; Judeh, Z. M. A.; Read, R. W. Aust. J. Chem. 2002, 55, 733–736; (e) Judeh, Z. M.
A.; Ching, C. B.; McCluskey, A.; Bu, J. Tetrahedron Lett. 2002, 43, 5089–5091; (f)
Shen, H.-Y.; Ying, L.-Y.; Jiang, H.-L.; Judeh, Z. M. A. Int. J. Mol. Sci. 2007, 8, 505–
1
1
5. Kowalczyk, R.; Kwiatkowski, P.; Skar z_ ewski, J.; Jurczak, J. J. Org. Chem. 2008, 74,
7
53–756.
6. (a) Arai, T.; Yamada, Y. M. A.; Yamamoto, N.; Sasai, H.; Shibasaki, M. Chem. Eur.
J. 1996, 2, 1368–1372; (b) Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh,
N.; Shibasaki, M. J. Org. Chem. 1995, 60, 7388–7389.
7. Xi, H.-W.; Judeh, Z. M. A.; Lim, K. H. J. Mol. Struct. 2009, 897, 22–31.
8. (a) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998, 37, 2922–2959; (b)
Satyanarayana, T.; Abraham, S.; Kagan, H. B. Angew. Chem., Int. Ed. 2009, 48,
1
1
5
12.
(a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New York, 2001;
b) Rosini, G. In Comprehensive Organic synthesis; Pergamon: New York, 1991;
Vol. 2, (c) Poupart, M.-A.; Fazal, G.; Goulet, S.; Mar, L. T. J. Org. Chem. 1999, 64,
356–1361; (d) Matt, C.; Wagner, A.; Mioskowski, C. J. Org. Chem. 1997, 62,
3
(
4
56–494; (c) Guillaneux, D.; Zhao, S. H.; Samuel, O.; Rainford, D.; Kagan, H. B. J.
Am. Chem. Soc. 1994, 116, 9430–9439.
1