Enantioselective Henry reaction catalyzed by a copper(II) glucoBOX complex

Article abstract of DOI:10.1016/j.tetasy.2011.06.012

A highly enantioselective Henry reaction has been developed using a chiral copper(II)-glucoBOX complex. The catalytic system works well with a wide range of aromatic, aliphatic and heteroaromatic aldehydes to afford the corresponding nitroalkanols with hi

Full text of DOI:10.1016/j.tetasy.2011.06.012

Tetrahedron: Asymmetry 22 (2011) 1169–1175
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective Henry reaction catalyzed by a copper(II) glucoBOX complex
⇑
B. V. Subba Reddy , Jimil George
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly enantioselective Henry reaction has been developed using a chiral copper(II)–glucoBOX complex.
The catalytic system works well with a wide range of aromatic, aliphatic and heteroaromatic aldehydes to
afford the corresponding nitroalkanols with high enantioselectivity (up to 99%) in excellent yields (up to
95%). The catalyst shows good enantioselectivity with 10 mol % of loading at easily attainable tempera-
ture (10 °C) even in the absence of an inert atmosphere.
Received 16 May 2011
Accepted 8 June 2011
Available online 27 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
functionalized b-cyclodextrin19 was used as a chiral host for enan-
tioselective Henry reaction. Apart from the different catalytic sys-
The Henry reaction is a powerful synthetic tool for the stereose-
lective construction of carbon–carbon bonds.1 The enantioselective
version of this reaction is highly important because the resulting
chiral 2-nitro-1-alkanols are versatile intermediates for the syn-
thesis of biologically active molecules2 and can be easily
tems mentioned above, some other metals such as chromium20
and cobalt21 complexes have also afforded good results.
Carbohydrates are well known chiral building blocks for the
synthesis of a wide range of biologically active molecules but the
use of carbohydrates in asymmetric synthesis remains less ex-
plored. A few carbohydrate derived ligands22 have recently been
developed and applied for a few enantioselective reactions such
as alkynylations,23 hydrovinylations24 and hydrogenations.25
Glucosamine derived bis(oxazoline)26 and pyridine bis(oxazoline)
ligands27 are noteworthy for the enantioselective cyclopropanation
and alkynylation of imines, respectively. Inspired by the success of
exploring the sugar based bis(oxazoline) ligands by Boysen et al.,
we became interested in examining the reactivity of glucoBOX in
enantioselective Henry reaction.
Herein, we report for the first time the enantioselective Henry
reaction of a variety aldehydes with nitroalkanes by employing
copper(II) complexes of a glucosamine based bis(oxazoline) ligand.
The chiral copper(II)-bis(oxazoline) complex was prepared in situ
from glucoBOX and Cu(OAc)2ꢀH2O in EtOH at room temperature.
The sugar based bis(oxazoline), that is, glucoBOX was prepared
from glucosamine and dimethyl malonyl chloride using a known
procedure.26a The glucoBOX ligands have almost similar skeleton
in comparison to indaBOX ligands (Fig. 1).
transformed into b-amino alcohols by reduction and
a-hydroxy
ketones or carboxylic acids by a Nef reaction.3 The catalytic enan-
tioselective nitroaldol reaction still has some problems, such as
high catalyst loading4 and the necessity of activation of the nitro-
alkane to a silyl nitronate.5 Therefore, the development of a cata-
lytic asymmetric version of the Henry reaction is of prime
importance.
Several chiral metal complexes have been developed for the
enantioselective Henry reaction,6 especially of aromatic aldehydes.
However, the enantioselective nitroaldol reaction of aliphatic alde-
hydes remains less explored. Most enantioselective Henry reactions
have been reported either with chiral copper catalysts or with chiral
zinc catalysts. Chiral copper complexes show high enantioselectiv-
ities and yields under mild reaction conditions. Chiral zinc cata-
lysts4 were also found to be equally effective for asymmetric
Henry reactions but these reactions of chiral zinc complexes need
to be carried out under strictly dry conditions which limit their
use in large scale synthesis. Chiral ligands such as bisoxazolines,7
sparteine,8 chiral diamines,9 bisoxazolidines,10 N-oxides,11
sulfonamides,12 BoroBox,13 aminopyrineligands,14 bispidine,15
sulfonamides diamine16 and chiral sulfoximines17 have been
utilized with the advantage of excellent coordination of copper
with these nitrogen containing bidentate ligands. A copper-pyri-
dine bis(imidazoline)18 complex was also found to catalyze the
reaction with excellent enantioselectivity. Recently, per-6-amino
O
O
O
O
O
O
AcO
OAc
N
N
N
N
OAc
AcO
AcO
OAc
I
II
indaBOX
glucoBOX
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V. Subba Reddy).
Figure 1. Structures of glucoBOX and indaBOX ligands.
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.06.012

1170
B. V. Subba Reddy, J. George / Tetrahedron: Asymmetry 22 (2011) 1169–1175
Table 1
Screening of various reaction parameters in the enantioselective Henry reaction of 4-bromobenzaldehyde with nitromethane catalyzed by copper(II)-glucoBOX
OH
CH3NO2
CHO
NO2
glucoBOX-metal
Br
Br
EtOH
3
4
Entry
Lewis acid
Catalyst(mol %)
Solventa
T (°C)
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
Cu(OAc)2
Cu(OAc)2
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
EtOH
MeOH
EtOH
EtOH
THF
25
25
25
25
25
25
25
25
25
25
25
0
ꢁ20
10
10
10
10
10
15
15
15
15
15
15
15
15
10
10
10
55
90
40
40
40
40
40
88
86
88
90
60
75
45
45
80
84
71
45
10
83
77
84
84
85
73
68
76
78
55
27
12
12
20
16
27
86
n.d.
89
86
89
88
86
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OTf)2+Et3N
CuCl2+Et3N
Zn(OTf)2+Et3N
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
Cu(OAc)2ꢀH2O
DMF
CH2Cl2
Toluene
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
9
10
11
12
13
14
15
16
17d
18e
20
10
10
EtOH
EtOH
EtOH
a
b
c
All reactions were carried out with 5 equiv, of nitromethane.
Yield refers to pure products after chromatography.
Enantiomeric excess was determined by chiral HPLC.
10 equiv, of nitromethane was used.
d
e
Reaction was carried out with 2 equiv of nitromethane.
2. Results and discussion
Table 2
Enantioselective Henry reaction of aldehydes catalyzed by a Cu(OAc)2.H2O-glucoBOX
complex in EtOH
On the basis of previous studies on the copper catalyzed enan-
tioselective Henry reaction, our first attempt was to carry out the
enantioselective Henry reaction using different copper salts as cat-
alysts. Copper acetate was already known as a very good catalyst
for the enantioselective Henry reaction in the absence of any base
or additive. From this general observation, we began our study
with 4-bromobenzaldehyde and nitromethane as a model reaction
using an in situ generated Cu(II)-chiral complex from anhydrous
Cu(OAc)2 and glucoBOX in ethanol under strictly anhydrous condi-
tions. Although the reaction proceeded smoothly in good yield
(90%), the ee was not so impressive (73%) (Table 1, entry 1). Next,
we attempted the same reaction with a Cu(OAc)2.H2O-glucoBOX
complex at room temperature under a nitrogen atmosphere. There
was no considerable difference in yield, but a slight increase in
enantioselectivity (76%) was observed (Table 1, entry 3). Next,
we performed the reaction with Cu(OAc)2.H2O-glucoBOX in the ab-
sence of a nitrogen atmosphere. Under these conditions, the
enantioselectivity increased again to 78% (Table 1, entry 4). We
also attempted the reaction using a Cu(OAc)2.H2O-glucoBOX com-
plex as a catalyst in different solvents, but none of them gave a
higher ee than EtOH (Table 1).
We next attempted to find the best metal for the enantioselec-
tive Henry reaction (Table 1, entries 9–11). However, no other me-
tal complex was found to give better results than Cu(OAc)2.H2O.
From the above observations, we found that Cu(OAc)2.H2O in EtOH
was the best choice for the present study. Accordingly, we tried to
optimize the reaction by varying the temperature from ꢁ20 °C to
25 °C. A maximum enantiomeric excess was achieved at 10 °C
without affecting the yield (Table 1, entry 14). At low temperature,
for example, below to 0 °C, the reaction was too slow to afford the
product in a reasonable yield (Table 1, entry 12). The enantioselec-
tivity also slightly decreased when decreasing the reaction temper-
glucoBOX (10 mol%)
OH
Cu(OAc)2.H2O (10 mol%)
NO2
R-CHO
R
CH3NO2 ( 5 equiv)
EtOH, 10 0C
4a-y
3a-y
Entry
R
Producta Timeb (h) Yeild (%)c ee (%)d
1
Ph-(3a)
4a
4b
4c
4d
4e
4f
4g
4h
4i
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
85
93
88
79
82
78
84
88
82
88
84
81
84
80
78
95
85
55
46
63
88
93
72
94
92
90
83
91
90
89
91
90
90
89
89
99
90
90
90
77
84
82
82
92
90
85
2
4-CI-C6H4-(3b)
3
4-F-C6H4-(3c)
4
5
6
7
4-NO2-C6H4-(3d)
4-CH3-C6H4-(3e)
4-MeO-C6H4-(3f)
2-Br-C6H4-(3g)
8
9
2-NO2-C6H4-(3h)
2-MeO-C6H4-(3i)
2-CI,4-F-C6H3-(3j)
2,4-Cl2-C6H4-(3k)
3,4-(MeO)2-C6H3-(3l)
2,5-(MeO)2-C6H3-(3m)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
4k
4l
4m
3,4,5-(MeO)3-C6H2 (3n) 4n
1-Naphthyl-(3o)
2-Naphthyl-(3p)
CH3(CH2)2-(3q)
CH3(CH2)4-(3r)
CH3(CH2)7-(3s)
(CH3)2CHCH2-(3t)
2-Thiophenyl-(3u)
2-Furyl-(3v)
4o
4p
4q
4r
4s
4t
4u
4v
4w
trans-Cinnamyl-(3w)
a
All reactions were performed with 0.5 mmol of aldehyde and 5 equiv of nitro-
methane at 10 °C.
b
Catalyst loading was 10 mol % with respect to aldehyde.
Yield was determined after chromatography.
Ee was deteremined by HPLC using chiracel OD-H, AD-H or OJ-H columns using
c
d
a mixture of hexane-isopropyl alcohol as eluent.

B. V. Subba Reddy, J. George / Tetrahedron: Asymmetry 22 (2011) 1169–1175
1171
ature to 0 °C. By decreasing the temperature to below ꢁ20 °C, the
reaction was sluggish and the yield was very low (Table 1, entry
13). To optimize the catalyst loading, the reaction was carried
out with different amounts of the catalyst and we found that
10 mol % of the catalyst was required to give the best results
(Table 1, entry 14). The effect of various equivalents of nitrometh-
ane was studied, (Table 1, entries 16–18) the best results were ob-
tained when 5 equiv of nitromethane were used (Table 1, entry
16).
Next, the scope of the asymmetric Henry reaction was studied
with various aldehydes using this glucoBOX ligand (Table 2). Ini-
tially, we tested the reactivity of benzaldehyde under the
optimized reaction conditions. The corresponding 2-nitro-1-phen-
ylethanol was obtained in 85% yield with 94% ee (Table 2, entry 1).
Then para-substituted benzaldehydes bearing electron donating
and electron withdrawing groups were investigated. All para-
substituted aryl aldehydes gave almost similar enantioselectivities
(Table 2, entries 2–6). Among these, low enantioselectivity was ob-
tained with 4-nitrobenzaldehyde (Table 2, entry 4). The lower
enantioselectivity of 4-nitrobenzaldehyde may be due to the coor-
dinating ability of the nitro group. Similarly, p-anisaldehyde also
gave the product in low yield (78%, Table 2, entry 6). This is due
to the electron donating ability of methoxyl group by which the
electron density increases slightly at carbonyl carbon which dimin-
ishes the reactivity of carbonyl group.
were carried out at room temperature. Although the reactions pro-
ceeded smoothly at room temperature, the corresponding nitroalk-
anols were only obtained in moderate yields with good
diastereoselectivity (Table 3, entries 1 and 2). The enantioselectiv-
ity and diasterimeric ratio were very high when 4-chlorobenzalde-
hyde was treated with nitroethane at 10 °C (Table 3, entry 3).
4-Chlorobenzaldehyde gave excellent diastereoselectivity (13:1,
favoring the anti-isomer). Due to the low conversions and
extended reaction times, the diastereoselective Henry reaction of
higher nitroalkanes was not studied under similar conditions.
Some of the selected examples are shown in Table 3.
From the aforementioned observations, we attempted to pro-
pose a mechanism for the enantioselective nitroaldol reaction.
We assumed that the structure of the copper(II)-glucoBOX complex
possesses two strongly co-ordinating sites almost in a ligand plane.
Due to Jahn-Teller distortion, two weakly co-ordinating sites are
available in a plane perpendicular to the ligand plane. In the tran-
sition state, the aldehyde co-ordinates to the copper complex and
the nitromethane was activated by free acetate ion which is gener-
ated when aldehyde co-ordinates with copper(II)-glucoBOX. The
activated nitromethane may be binding with copper(II)-glucoBOX
as shown in Figure 2. In the transition state, acetate groups of li-
gands are crowding around the aldehyde and nitromethane moi-
ety. The acetate groups orient each other in opposite direction
with respect to its neighboring one. The sterric factors may be a
strong reason why the reaction is very slow at low temperature.
The low reactivity of nitroethane under standard conditions (at
10 °C) may be due to the same steric effect.
To understand the influence of steric factors, several ortho-
substituted benzaldehydes were examined (Table 2, entries 7–9).
In general, ortho-substituted aldehydes gave almost similar yields
and enantioselectivities irrespective of their nature. For example,
o-anisaldehyde gave the same ee as p-anisaldehyde, but the yield
was slightly higher than with p-anisaldehyde (Table 2, entry 9).
However, o-bromobenzaldehyde did not show any significant ef-
fect on the enantioselectivity (Table 2, entry 7).
Table 3
Diastereoselective Henry reaction of nitroethane with aldehydes catalyzed by
Cu(OAc)2.H2O-glucoBOX
A set of disubstituted benzaldehydes bearing electron donating
and electron withdrawing groups were studied (Table 2, entries
10–14). Almost all disubstituted benzaldehydes gave similar
enantioselectivities with slight variations in yields. It is notewor-
thy that 2,5-dimethoxybenzaldehyde gave excellent enantioselec-
tivity (>99%) (Table 2, entry 13). The more sterically crowded
3,4,5-trimethoxybenzaldehyde also gave good enantioselectivity
(90%) and good yield (80%) (Table 2, entry 14).
glucoBox-Cu(OAc)2.H2O
OH
O
(10 mol %)
+
CH3CH2NO2
R
R
H
r.t.
EtOH,
NO2
Entry
R
Producta
Time
(h)b,c
Yield
(%)d
(anti/syn)
eee (%)
(anti/syn)
1
2
3
2-NO2-C6H4–
3,4-CI-C6H3–
4-CI-C6H4–
5a
5b
5c
72
75
60
60
65
75
2.1/1
2.0/1
13/1
68/73
86/71
80/62
Similarly, the sterically hindered - and -naphthaldehydes gave
the nitroaldols with good enantioselectivity without any signifi-
cant difference in yields (Table 2, entries 15 and 16).
a
All reactions were performed with 0.5 mmol of aldehyde in 2 mL EtOH and with
5 equiv of nitroethane.
Inspired by the good results obtained with the aromatic alde-
hydes, we next attempted the Henry reaction with some aliphatic
aldehydes (Table 2, entries 17–20). However, all aliphatic alde-
hydes gave lower yields and enantioselectivities compared to the
aromatic substrates. In the cases of non-branched aliphatic alde-
hydes, the yield decreased with an increase of the chain length
(Table 2, entry 17 and 18). For instance, butyraldehyde gave higher
yield than other aliphatic aldehydes in our study. The highest ee of
84% was obtained with n-hexanal (Table 2, entry 18). However, the
enantioselectivity remains almost the same even when increasing
the chain length of the aldehydes.
In addition to the aromatic and aliphatic substrates, the reactiv-
ity of the heteroaromatic aldehydes was also examined. Both thio-
phene-2-carboxaldehyde and 2-furfuraldehyde gave excellent
yields and enantioselectivities (Table 2, entries 21 and 22).
Thiophene-2-carboxaldehyde gave slightly higher ee (92%), but a
higher yield was obtained with 2-furfuraldehyde. trans-Cinnamal-
dehyde also gave the nitroaldol with high enantioselectivity (85%)
and in good yield (72%) (Table 2, entry 23).
b
All reactions were carried out at 25 °C except entry 3(10 °C).
Catalyst loading was 10 mol % with respect to aldehyde.
Yield was determined after chromatography.
Ee was determined by HPLC using chiracel AD-H column using a mixture of
c
d
e
hexane and isopropanol as eluent.
OAc
O
OAc
OAc
O
OAc
H
H
O
N
N+
Cu
-O
H
z
O
O
OAc
R
O
OAc
OAc
Finally, we attempted the diastereoselective Henry reaction of
aldehydes with nitroethane (Table 3). The diastereoselective nitro-
aldol reactions were too sluggish at 10 °C, hence these reactions
Figure 2. Transition state model for enantioselective Henry reaction catalyzed by
copper(II)-glucoBOX.

1172
B. V. Subba Reddy, J. George / Tetrahedron: Asymmetry 22 (2011) 1169–1175
4.2.2. (R)-2-Nitro-1-phenylethanol7a 4a (Table 2, entry 1)
3. Conclusion
Yield 85%; Enantiomeric excess 94%; 1H NMR (300 MHz, CDCl3):
d 3.50 (s, 1H), 4.34 (dd, J = 3.8, 13.6 Hz, 1H), 4.44 (dd, J = 9.1,
12.8 Hz, 1H), 5.30 (dd, J = 3.8, 9.8 Hz, 1H), 7.22 (m, 5H); 13C NMR
(75 MHz, CDCl3): d 70.6, 80.8, 125.7, 128.5, 128.6, 138.1; HPLC
Analysis: Chiracel OD-H column (85:15, n-hexane–isopropyl alco-
hol, 0.8 mL/min, 215 nm); tR = 11.54 min (major, (R)-isomer);
In conclusion, we have demonstrated a highly enantioselective
nitroaldol (Henry) reaction of aldehydes using a chiral Cu(II)-glu-
coBOX complex under mild reaction conditions. This method is
simple and convenient for the synthesis of a variety of nitroalka-
nols in high yields and enatioselectivity. This method provides
high yields of nitroalkanols (up to 95%) with excellent enantiose-
lectivities (up to >99%) at low catalyst loading (10 mol %). This
chiral complex works well for both aromatic and aliphatic sub-
strates at a practical temperature (10 °C) even in the absence of
an inert atmosphere.
tR = 13.18 min (minor, (S)-isomer); ee 94%; ½a D20
¼ ꢁ42:6 (c 1.0,
ꢂ
CH2Cl2).
4.2.3. (R)-1-(4-Chlorophenyl)-2-nitroethanol7a 4b (Table 2,
entry 2)
Yield 93%; Enantiomeric excess 92%; 1H NMR (300 MHz, CDCl3):
d 3.20 (s, 1H), 4.40 (dd, J = 3.8, 13.6 Hz, 1H), 4.60 (dd, J = 9.1, 13.6 Hz,
1H), 5.36 (dd, J = 3.0, 9.1 Hz, 1H), 7.28 (m, 4H); 13C NMR (75 MHz,
CDCl3): d 70.1, 80.9, 127.2, 128.983, 134.5, 136.6; HPLC Analysis:
Chiracel OD-H column (85:15, n-hexane–isopropyl alcohol,
0.8 mL/min, 215 nm); tR = 11.72 min (major, (R)-isomer);
4. Experimental
4.1. General remarks
tR = 15.62 min (minor, (S)-isomer); ee 92%; ½a D20
ꢁ 38:1 (c 1, CH2Cl2).
ꢂ
All chemicals were purchased commercially and were used
without any further purification. All solvents used were purchased
commercially and purified according to standard procedures. All
nitroalkanols were purified by column chromatography on Silica
gel (60–120 mesh) using hexane–ethyl acetate mixture as eluent.
2-Furaldehyde and cinnamaldehyde were purified by column chro-
matography on alumina prior to use, and all other aldehydes were
used as received. All nitroalkanols were characterized by NMR
spectroscopy. The 1H NMR spectra of all nitroalkanols were re-
corded on either 200 MHz or 300 MHz or 500 MHz instruments
using TMS as an internal standard in CDCl3. The 13C NMR spectra
of all products were recorded on either 75 MHz or 50 MHz instru-
ments using CDCl3 as solvent and reference. The enantiomeric ex-
cesses of all products were determined by HPLC analysis using
Chiracel AD-H, OD-H and OJ-H columns using hexane-isopropyl
alcohol mixtures as eluent. The absolute configurations of all prod-
ucts were determined by comparing specific rotations of the nitro-
alkanols with known compounds or/and by comparison with
analogs or/and by comparison of retention times in HPLC analysis
with literature data (Note: all the HPLC analysis were done based
on previous HPLC conditions reported in the literature included
as reference).
4.2.4. (R)-1-(4-Fluorophenyl)-2-nitroethanol7a 4c (Table 2,
entry 3)
Yield 88%; Enantiomeric excess 90%; 1H NMR (300 MHz, CDCl3):
d 3.10 (s, 1H), 4.40 (dd, J = 3.8, 13.6 Hz, 1H), 4.46 (dd, J = 9.1,
12.8 Hz, 1H), 5.38 (dd, J = 3.0, 9.1 Hz, 1H), 7.02 (m, 2H), 7.34 (m,
2H); 13C NMR (75 MHz, CDCl3): d 70.1, 81.0, 115.6, 11.9, 127.7,
134.0, 161.0, 164.3; HPLC Analysis: Chiracel OD-H column
(90:10, n-hexane–isopropyl alcohol, 1.0 mL/min, 215 nm); tR
=11.30 min (major, (R)-isomer); tR =13.39 min (minor, (S)-isomer);
ee 90%; ½a 2D0
¼ ꢁ42:9 (c 0.99, CH2Cl2).
ꢂ
4.2.5. (R)-2-Nitro-1-(4-nitrophenyl)ethanol7a 4d (Table 2, entry
4)
Yield 79%; enantiomeric excess 83%; 1H NMR (300 MHz, CDCl3):
d 3.24 (s, 1H), 4.52 (m, 2H), 5.55 (m, 1H), 7.58 (d, J = 8.7 Hz, 2H),
8.24 (d, J = 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3): d 69.9, 80.6,
124.0, 126.9, 145.3, 147.9; HPLC Analysis: Chiracel OD-H column
(85:15, n-hexane–isopropyl alcohol, 0.7 mL/min, 254 nm);
tR = 18.43 min (major, (R)-isomer); tR = 23.32 min (minor, (S)-iso-
mer); ee 83%; ½a 2D0
¼ ꢁ33:6 (c 1.1, CH2Cl2).
ꢂ
4.2.6. (R)-2-Nitro-1-p-tolylethanol9e 4e (Table 2, entry 5)
4.2. General procedure for the enantioselective Henry reaction
of aldehyde with nitromethane
Yield 82%, enantiomeric excess 91%. 1H NMR (300 MHz, CDCl3):
d 2.32 (s, 1H), 2.90 (s, 1H), 4.36 (dd, J = 3.2, 13.2 Hz, 1H), 4.48 (dd,
J = 9.4, 13.2 Hz, 1H), 5.30 (d, J = 9.2 Hz, 1H), 7.12 (d, J = 7.9 Hz, 2H),
7.20 (d, J = 8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 20.9, 70.6, 80.9,
125.7, 129.4, 135.1, 138.5; HPLC Analysis: Chiracel OD-H column
(90:10, n-hexane–isopropyl alcohol, 0.7 mL/min, 254 nm);
tR = 18.16 min (major, (R)-isomer); tR = 23.31 min (minor, (S)-iso-
A solution of glucoBOX26a (35 mg, 0.052 mmol) and Cu(OA-
c)2.H2O (10 mg, 0.05 mmol) in ethanol (2 mL) was stirred at
room temperature for 1 h. To this blue colored solution, the
aldehyde (0.5 mmol) was added and the resulting solution was
allowed to stir for 20 min at room temperature. The reaction
mixture was cooled to 10 °C and then nitromethane (5 equiv)
was added. The resulting mixture was stirred at the same
temperature for a specified time (Table 1). The solvent was
removed under reduced pressure and the crude product was
purified by column chromatography on silica gel to afford the
pure nitroalkanol.
mer); ee 91%; ½a 2D0
¼ ꢁ44:3 (c 1.0, CH2Cl2).
ꢂ
4.2.7. 4.3.7(R)-1-(4-Methoxyphenyl)-2-nitroethanol8. 4f
(Table 2, entry 6)
Yield 78%, enantiomeric excess 90%. 1H NMR (500 MHz, CDCl3):
d 3.10 (s, 1H), 3.90 (s, 3H), 4.54 (dd, J = 2.9, 13.7 Hz, 1H), 4.64 (dd,
J = 9.8, 13.7 Hz, 1H), 5.46 (dd, J =2.9, 9.8 Hz, 1H), 7.05 (d, J = 7.8 Hz,
2H), 7.42 (d, J = 8.8 Hz, 2H). 13C NMR (50 MHz, CDCl3): d 55.3, 70.6,
114.3, 127.2, 130.2, 159.9. HPLC Analysis: Chiracel OD-H col-
umn (85:15, n-hexane–isopropyl alcohol, 0.8 mL/min, 215 nm);
tR = 15.713 min (major, (R)-isomer); tR = 19.826 min (minor, (S)-
4.2.1. (R)-1-(4-Bromophenyl)-2-nitroethanol10 4 (Table 1, entry
10)
Yield 83%; Enantiomeric excess: 89%; 1H NMR (300 MHz,
CDCl3): d 3.02 (s, 1H), 4.40 (dd, J = 3.6, 13.6 Hz, 1H), 4.47 (dd,
J = 8.8, 13.4 Hz, 1H), 5.36 (d, J = 8.1 Hz, 1H), 7.24 (d, J = 8.3 Hz,
2H), 7.48 (d, J = 8.3 Hz, 2H); 13C NMR (50 MHz, CDCl3): d 70.1,
807, 122.5, 127.4, 131.8, 136.9; HPLC Analysis: Chiracel OD-H col-
umn (85:15, n-hexane–isopropyl alcohol, 0.8 mL/min, 215 nm);
tR = 12.25 min (major, (R)-isomer); tR = 15.62 min (minor, (S)-iso-
isomer); ee 94%; ½a D20
¼ ꢁ31:9 (c 0.9, CH2Cl2).
ꢂ
4.2.8. (R)-1-(2-Bromophenyl)-2-nitroethanol9e 4g (Table 2,
entry 8)
Yield 84%, enantiomeric excess 89%. 1H NMR (300 MHz, CDCl3):
d 3.06 (s, 1H), 4.30 (dd, J = 9.6, 13.8 Hz, 1H), 4.64 (dd, J = 1.9,
mer); ½a 2D0
¼ ꢁ68:6 (c 1.5, CH2Cl2).
ꢂ

B. V. Subba Reddy, J. George / Tetrahedron: Asymmetry 22 (2011) 1169–1175
1173
13.8 Hz, 1H), 5.70 (d, J = 9.6 Hz, 1H), 7.15 (m, 1H), 7.35 (t, J = 7.4 Hz,
1H), 7.50 (d, J = 7.9 Hz, 1H). 7.64 (d, J = 7.7 Hz, 1H). 13C NMR
(75 MHz, CDCl3): d 69.8, 79.2, 121.2, 127.6, 128.0, 130.0, 132.7,
137.1. HPLC Analysis: Chiracel OD-H column (95:15, n-hexane–
isopropyl alcohol, 0.6 mL/min, 215 nm); tR = 23.497 min (major,
(R)-isomer); tR = 25.691 min (minor, (S)-isomer); ee 89%;
tR = 26.97 min (major, (R)-isomer); tR = 36.20 min (minor, (S)-iso-
mer); ee 89%; ½a 2D5
¼ ꢁ24:6 (c 1, CH2Cl2).
ꢂ
4.2.14. (R)-1-(2,5-Dimethoxyphenyl)-2-nitroethanol30 4m:
(Table 2, entry 14)
Yield 84%, enantiomeric excess 99%; 1H NMR (300 MHz, CDCl3):
d 3.02 (d, J = 5.5 Hz, 1H), 3.76 (s, 3H), 3.82 (s, 3H), 4.38 (dd, J = 9.4,
13.4 Hz, 1H), 4.58 (dd, J = 2.6, 13.2 Hz, 1H), 5.54 (m, H), 6.76 (d,
J = 1.5 Hz, 2H), 7.02(s, 1H). 13C NMR (75 MHz, CDCl3): d 55.8,
67.7, 79.8, 111.4, 113.1, 114.2, 126.9, 149.9, 153.9. HPLC Analysis:
Chiracel OD-H column (85:15, n-hexane–isopropyl alcohol, 0.8 mL/
min, 254 nm); tR = 11.79 min (major, (R)-isomer); tR = 13.97 min
½
a 2D0
ꢂ
¼ ꢁ35:2 (c 1.0, CH2Cl2).
4.2.9. (R)-2-Nitro-1-(2-nitrophenyl)ethanol8 4h (Table 2,
entry 9)
Yield 88%, enantiomeric excess 91%. 1H NMR (300 MHz, CDCl3):
d 3.28 (s, 1H), 4.44 (dd, J = 9.1, 14.4 Hz, 1H), 4.82 (dd, J =3.0,
14.4 Hz, 1H), 5.98 (d, J = 9.6 Hz, 1H), 7.50 (m, 1H), 7.68 (m, 1H),
7.94 (d, J = 6.8 Hz, 1H). 8.4 (d, J = 8.3 Hz, 1H). 13C NMR (75 MHz,
CDCl3): d 66.6, 80.0, 124.8, 128.6, 129.5, 134.2, 134.3, 146.9. HPLC
Analysis: Chiracel OD-H column (90:10, n-hexane–isopropyl alco-
hol, 0.9 mL/min, 215 nm); tR = 16.014 min (major, (R)-isomer);
(minor, (S)-isomer); ee 99%; ½a D20
¼ ꢁ36:6 (c 1.0, CHCl3).
ꢂ
9d
4.2.15. (R)-2-Nitro-1-(3,4,5-trimethoxyphenyl)ethanol
4n
(Table 2, entry 15)
Yield 80%, enantiomeric excess 90%. 1H NMR (300 MHz, CDCl3):
d 3.16 (s, 1H), 3.76 (s, 3H), 3.82 (s, 6H), 4.38 (dd, J = 3.0, 13.0 Hz,
1H), 4.48 (dd, J = 9.4, 13.2 Hz, 1H), 5.28 (d, J = 8.9 Hz, 1H), 6.50 (s,
2H). 13C NMR (75 MHz, CDCl3): d 56.0, 60.8, 71.1, 81.3, 102.7,
134.1, 137.8, 153.4. HPLC Analysis: Chiracel OD-H column (85:15,
n-hexane–isopropyl alcohol, 1.0 mL/min, 254 nm); tR = 29.64 min
(major, (R)-isomer); tR = 38.55 min (minor, (S)-isomer); ee 90%;
tR = 17.838 min (minor, (S)-isomer); ee 91%; ½a D20
¼ ꢁ222:3 (c 1.0,
ꢂ
CH2Cl2).
4.2.10. (R)-1-(2-Methoxyphenyl)-2-nitroethanol7a 4i (Table 2,
entry 10)
Yield 82%, enantiomeric excess 90%. 1H NMR (500 MHz, CDCl3):
d 3.30 (s, 1H), 3.84 (s, 3H), 4.40 (dd, J = 10.0, 13.7 Hz, 1H), 4.54 (dd,
J = 2.7, 12.8 Hz, 1H), 5.53 (d, J = 8.2 Hz, 1H), 6.82 (d, J = 8.2 Hz, 1H),
6.92 (t, J = 7.3 Hz, 1H). 7.22 (m, 1H), 7.38 (d, J = 7.3 Hz, 1 Hz). 13C
NMR (75 MHz, CDCl3): d 67.6, 79.8, 110.4, 121.0, 125.9, 127.1,
129.7, 155.9. HPLC Analysis: Chiracel OD-H column (90:10, n-hex-
ane–isopropyl alcohol, 0.8 mL/min, 215 nm); tR = 13.09 min
(major, (R)-isomer); tR = 15.746 min (minor, (S)-isomer); ee 94%;
½
a 2D0
ꢂ
¼ ꢁ23:6 (c 1.1, CH2Cl2).
4.2.16. (R)-1-(Naphthalen-1-yl)-2-nitroethanol 4o (Table 2,
entry 16)
Yield 78%, enantiomeric excess 90%. 1H NMR (300 MHz, CDCl3):
d 3.12 (s, 1H), 4.48 (dd, J = 9.1, 13.6 Hz, H), 4.56 (dd, J = 3.0, 13.6 Hz,
1H), 6.14 (dd, J = 2.3, 9.1 Hz, 1H), 7.42 (m, 3H), 7.68 (d, J = 6.8 Hz,
1H), 7.76 (m, 2H), 7.94 (d, J = 8.3 Hz, 1H). 13C NMR (75 MHz,
CDCl3): d 67.9, 80.6, 121.7, 123.6, 125.3, 125.8, 126.7, 128.9,
129.3, 133.4, 133.6. HRMS (ESI) calcd for C12H11NO3, 217.0739,
found, 217.0744. HPLC Analysis: Chiracel OD-H column (90:10,
n-hexane–isopropyl alcohol, 1.0 mL/min, 215 nm); tR = 17.11 min
(major, (R)-isomer); tR = 25.57 min (minor, (S)- isomer); ee 90%;
½
a 2D5
ꢂ
¼ ꢁ44:0 (c 1.1, CH2Cl2).
4.2.11. (R)-1-(2-Chloro-4-fluorophenyl)-2-nitroethanol 4j:
(Table 2, entry 11)
Yield 88%; enantiomeric excess 90%; 1H NMR (300 MHz, CDCl3):
d 3.12 (s, 1H), 4.32 (dd, J = 9.8, 13.6 Hz, 1H), 4.58 (dd, J = 2.7,
13.6 Hz, 1H), 5.74 (dd, J = 1.5, 9.8 Hz, 1H), 7.14 (m, 2H), 7.64 (dd,
J = 6.0, 8.3 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 67.3, 79.3, 114.8
(d, J = 20.9 Hz), 117.3 (d, J = 24.7 Hz), 128.8 (d, J = 9.3 Hz), 131.5
(d, J = 2.7 Hz), 132.2 (d, J = 9.8 Hz), 160.8 (d, J = 251.9 Hz). HRMS
(ESI) calcd for C9H9ClFNO3Na, 241.9991, found, 241.9988. HPLC
Analysis: Chiracel AD-H column (90:10, n-hexane–isopropyl alco-
hol, 0.5 mL/min, 215 nm); tR = 17.791 min (major, (R)-isomer);
½
a 2D0
ꢂ
¼ ꢁ24:6 (c 1.0, CH2Cl2).
4.2.17. (R)-1-(Naphthalen-2-yl)-2-nitroethanol28 4p (Table 2,
entry 17)
Yield 95%, enantiomeric excess 90%. 1H NMR (300 MHz, CDCl3):
d 2.92 (s, 1H), 4.48 (dd, J = 3.0, 13.6 Hz, 1H), 4.58 (dd, J = 9.1,
13.6 Hz, 1H), 5.54 (m, 1H), 7.40 (m, 3H), 7.76 (m, 4H). 13C NMR
(75 MHz, CDCl3): d 71.0, 51.1, 123.1, 128.2, 126.6, 127.6, 128.8,
133.0, 133.3, 135.3. HPLC Analysis: Chiracel OD-H column (80:20,
n-hexane–isopropyl alcohol, 1.0 mL/min, 254 nm); tR = 22.98 min
(major, (R)-isomer); tR = 32.50 min (minor, (S)-isomer); ee 90%;
tR = 21.054 min (minor, (S)-isomer); ee 90%; ½a D20
¼ ꢁ82:3 (c 1.46,
ꢂ
CHCl3).
4.2.12. (R)-1-(2,4-Dichlorophenyl)-2-nitroethanol28 4k: (Table 2,
entry 12)
½
a 2D0
ꢂ
¼ ꢁ14:6 (c 1.0, CH2Cl2).
Yield 84%, enantiomeric excess 89%. 1H NMR (200 MHz, CDCl3):
d 3.28 (s, 1H), 4.282 (dd, J = 10.1, 14.3 Hz, 1H), 4.56 (dd, J = 2.5,
13.4 Hz, 1H), 5.68 (d, J = 9.2 Hz, 1H), 7.28 (m, 2H), 7.58 (d,
J = 8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 67.4, 79.1, 127.9,
128.5, 129.5, 132.0, 134.2, 135.2. HPLC Analysis: Chiracel AD-H col-
umn (90:10, n-hexane–isopropyl alcohol, 0.5 mL/min, 215 nm);
tR = 17.683 min (major, (R)-isomer); tR = 21.153 min (minor, (S)-
4.2.18. (R)-1-Nitropentan-2-ol8 4q (Table 2, entry 18)
Yield 85%, enantiomeric excess 77%. 1H NMR (500 MHz, CDCl3):
d 0.94 (t, J = 7.8 Hz, 3H), 1.38 (m, 2H), 1.48 (m, 2H), 2.74 (s, 1H),
4.24 (m, 3H). 13C NMR (50 MHz, CDCl3): d 13.3, 18.1, 35.5, 68.3,
80.6. HPLC Analysis: Chiracel OD-H column (98:02, n-hexane–iso-
propyl alcohol, 0.6 mL/min, 215 nm); tR = 31.58 min (major, (R)-
isomer); tR = 34.93 min (minor, (S)-isomer); ee 77%; ½a D20
¼ ꢁ15:2
ꢂ
isomer)29; ee 89%; ½a 2D0
¼ ꢁ51:1 (c 1, CH2Cl2).
ꢂ
(c 2.1, CH2Cl2).
4.2.19. (R)-1-Nitroheptan-2-ol28 4r (Table 2, entry 19)
4.2.13. (R)-1-(3,4-Dimethoxyphenyl)-2-nitroethanol 4l: (Table 2,
entry 13)
Yield 55%, enantiomeric excess 84%. 1H NMR (300 MHz, CDCl3):
d 0.88 (t, J = 6.8 Hz, 3H), 1.24 (m, 6H), 1.44 (m, 2H), 3.32 (s, 1H),
4.20 (m, 3H). 13C NMR (75 MHz, CDCl3): d 13.6, 22.1, 24.6, 31.1,
33.5, 68.6, 80.5. HPLC Analysis: Chiracel AD-H column (98:02, n-
hexane–isopropyl alcohol, 0.9 mL/min, 215 nm); tR = 33.46 min
(major, (R)-isomer); tR = 48.94 min (minor, (S)-isomer); ee 84%;
Yield 81%, enantiomeric excess 89%. 1H NMR (300 MHz, CDCl3):
d 2.84 (s, 1H), 3.84 (s, 3H), 3.86 (s, 3H), 4.38 (dd, J = 3.0, 13.0 Hz,
1H), 4.48 (dd, J = 9.4, 13.2 Hz, 1H), 5.30 (d, J = 9.3 Hz, 1H), 6.78
(m, 3H). 13C NMR (75 MHz, CDCl3): d 55.9, 70.8, 81.3, 108.7,
111.2, 118.3, 130.7, 149.3. HPLC Analysis: Chiracel OD-H column
(85:15, n-hexane–isopropyl alcohol, 1.0 mL/min, 254 nm);
½
a 2D0
ꢂ
¼ ꢁ8:5 (c 2.5, CH2Cl2).

1174
B. V. Subba Reddy, J. George / Tetrahedron: Asymmetry 22 (2011) 1169–1175
4.2.20. (R)-1-Nitrodecan-2-ol 4s16 (Table 2, entry 20)
(syn-minor); tR = 37.78 (syn-major); ee 73% ½a D20
ꢂ
= +106 (c 1.5,
Yield 46%, enantiomeric excess 82%. 1H NMR (500 MHz, CDCl3):
d 0.84 (t, J = 7.3 Hz, 3H), 1.20 (m, 12H), 1.40 (m, 2H), 2.40 (s, 1H),
4.22 (m, 1H), 4.28 (dd, J = 8.2, 12.8 Hz, 1H), 4.36 (dd, J = 2.7,
12.8 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 14.0, 22.6, 25.1, 29.1,
29.2, 29.3, 31.7, 33.7, 68.7, 80.6. HPLC Analysis: Chiracel AD-H col-
umn (95:05 n-hexane–isopropyl alcohol, 1.0 mL/min, 215 nm);
tR = 11.26 min (major, (R)-isomer); tR = 16.83 min (minor, (S)-iso-
CHCl3).
4.2.26. 1-(3,4-Dichlorophenyl)-2-nitropropan-1-ol 5b (Table 3,
entry 2)
Yield 65%, enantiomeric excess 86% (anti=isomer); enantiomeric
excess 71% (syn=isomer), diasteriomeric ratio 2.0:1 (anti:syn).
Enantiomeric excess and diasteriomeric ratio were determined
by HPLC analysis. 1H NMR (300 MHz, CDCl3): d 1.32 (d, J = 6.8 Hz,
0.8H) (syn), 1.44 (d, J = 6.8 Hz, 1.7H) (anti), 2.80 (s, 1H) (anti/syn),
4.46 (m, 1H) (anti/syn), 4.92 (d, J = 8.7 Hz, 0.3H) (syn), 5.34 (d,
J = 2.5 Hz, 0.8H) (anti) 7.15 (m, 1.1H) (anti/syn), 7.42 (m,
2.1H)(anti/syn). 13C NMR (75 MHz, CDCl3): d 11.9 (anti), 16.3
(syn), 72.3 (anti), 74.9 (syn), 86.9 (anti), 87.9 (syn), 125.5 (anti),
126.1 (syn), 128.1 (anti), 128.9 (syn), 130.7 (anti), 130.9 (syn),
132.7 (anti), 133.1 (anti), 133.3 (syn), 133.4 (syn), 138.4 (syn),
138.5 (anti). Anal. calcd for C9H9Cl2NO2: C, 43.22; H, 3.63; N,
5.60. Found: C, 43.13; H, 3.45; N 5.50. HPLC Analysis: Chiracel
AD-H column (90:10, n-hexane–isopropyl alcohol, 0.5 mL/min,
254 nm); tR = 10.89 min (anti = major); tR = 13.76 min (anti=mi-
nor); ee 86% and tR = 15.67 min (syn = major); tR = 22.79 min
mer); ee 82%; ½a 2D0
= ꢁ4.5 (c 2.5, CH2Cl2).
ꢂ
4.2.21. (R)-4-Methyl-1-nitropentan-2-ol7a 4t (Table 2, entry 21)
Yield 63%, enantiomeric excess 82%. 1H NMR (300 MHz, CDCl3):
d 0.98 (t, J = 6 Hz, 6H), 1.22 (m, 1H), 1.47 (m, 1H), 1.80 (m, 1H), 3.38
(s, 1H), 4.35 (m, 3H); 13C NMR (75 MHz, CDCl3): d 21.4, 22.7, 23.9,
42.2, 66.9, 80.9. HPLC Analysis: Enantiomeric excess was deter-
mined by HPLC with Chiracel OJ-H column (95:05, n-hexane–iso-
propyl alcohol, 0.6 mL/min, 215 nm); tR = 31.58 min (major, (R)-
isomer); tR = 34.93 min (minor, (S)-isomer); ee 82%; ½a D20
ꢂ
= +2.3 (c
2.5, CH2Cl2).
4.2.22. (S)-2-Nitro-1-(thiophen-2-yl)ethanol9c 4u (Table 2,
entry 23)
(syn=minor); ee 71% ½a D20
¼ ꢁ21:8 (c 0.98, CHCl3).
ꢂ
Yield 88%, enantiomeric excess 92%. 1H NMR (300 MHz, CDCl3):
d 2.80 (s, 1H), 4.52 (dd, J =3.4, 13.4 Hz, 1H), 4.60 (dd, J = 9.1,
13.4 Hz, 1H), 5.62 (dd, J = 3.4, 9.0 Hz, 1H), 6.94 (m, 2H), 7.26 (dd,
J = 1.1, 4.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 66.9, 80.7, 15.0,
126.0, 127.1, 141.3. HPLC Analysis: Chiracel OJ-H column (85:15,
n-hexane–isopropyl alcohol, 0.8 mL/min, 215 nm); tR = 26.21 min
4.2.27. 1-(4-Chlorophenyl)-2-nitropropan-1-ol 5c19 (Table 3,
entry 3)
Yield 75%, enantiomeric excess 80% (anti isomer); enantiomeric
excess 62% (syn isomer), diasteriomeric ratio 13:1 (anti:syn). Enan-
tiomeric excess and diasteriomeric ratio were determined by HPLC
analysis. 1H NMR (300 MHz, CDCl3): d 1.30 (d, J = 6.8 Hz, 0.6H)
(syn), 1.44 (d, J = 6.8 Hz, 3.5H)(anti), 2.80 (s, 1.0H)(anti/syn), 4.56
(m, 1.0H)(anti/syn), 4.86 (d, J = 9.1 Hz, 0.3H)(syn), 5.34 (d,
J = 3.0 Hz, 1.3H)(anti) 7.26 (m, 5.6H)(anti/ syn). HPLC Analysis:
Chiracel AD-H column (95:05 n-hexane–isopropyl alcohol,
1.0 mL/min, 225 nm); tR = 14.69 min (anti minor); tR = 15.59 min
(anti major); ee 80% and tR = 20.85 min (syn major); tR = 22.78
(major, (S)-isomer); tR = 31.47 (minor, (R)-isomer); ee 92%; ½a D20
ꢂ
=
+ 20.6 (c 0.25, CH2Cl2).
4.2.23. (S)-1-(Furan-2-yl)-2-nitroethanol9c 4v (Table 2, entry 24)
Yield 93%, enantiomeric excess 90%. 1H NMR (300 MHz, CDCl3):
d 3.0 (s, 1H), 4.58 (dd, J = 3.8, 13.4 Hz, 1H), 4.66 (dd, J = 8.7, 13.4 Hz,
1H), 5.38 (dd, J = 3.8, 8.6 Hz, 1H), 6.34 (m, 2H), 7.36 (m, 1H); 13C
NMR (75 MHz, CDCl3): d 64.7, 78.3, 108.1, 110.6, 143.1, 150.7. HPLC
Analysis: Enantiomeric excess was determined by HPLC with
Chiracel OJ-H column (90:10, n-hexane–isopropyl alcohol,
1.0 mL/min, 215 nm); tR = 20.98 min (major, (S)-isomer);
(syn minor); ee 60%. ½a D20
ꢂ
-11.2 (c 0.6, CHCl3).
References
tR = 25.29 (minor, (R)-isomer); ee 90%; ½a D20
¼ ꢁ355:2 (c 0.25,
ꢂ
1. (a) Henry, L. Compt. Rend. Hebd. Seances Acad. Sci. 1985, 120, 1265; (b) Palomo,
C.; Oiarbide, M.; Mielgo, A. Angew. Chem., Int. Ed. 2004, 43, 5442.
2. (a) Allmendiger, C.; Bauschke, G.; Paintner, F. F. Synlett 2005, 2615; (b) Li, H.;
Wang, B.; Deng, L. J. Am. Chem. Soc. 2006, 128, 732; (c) Paintner, F. F.;
Allmendiger, L.; Bauschke, G.; Klemmann, D. Org. Lett. 2005, 7, 1423.
3. (a) Ono, L. The Nitro Group in Organic Synthesis; Wiley-VCH: New York, 2001; (b)
Rosini, G. In Comprehensive Organic synthesis; Trost, B. M., Fleming, I., Eds.;
Pergmon: Oxford, UK, 1999; vol. 2, p 321;(c) Luzzio, F. A. Tetrahedron 2001, 57, 915.
4. (a) Palomo, C.; Oiarbide, M.; Laso, A. Angew. Chem., Int. Ed. 2005, 44, 3881; (b)
Trost, B. M.; Yeh, V. S. C. Angew. Chem., Int. Ed. 2002, 41, 861.
5. Risgaard, T.; Gothelf, K. V.; Jørgensen, K. A. Org. Biomol. Chem. 2003, 1, 153.
6. For recent reviews see: (a) Palomo, C.; Oirabide, M.; Laso, A. Eur. J. Org. Chem.
2007, 13, 2561; Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C. Tetrahedron:
Asymmetry 2006, 3315, 17; (c) Wang, A. X. In Name Reactions for Homologations;
Li, J. J., Ed.; John Wiley & Sons Inc. Hoboken: NJ, 2009; p 404; (d) Shibasaki, M.;
Sasai, H.; Arai, T. Angew. Chem., Int. Ed. 1997, 36, 1236; (e) Shibasaki, M.;
Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
CH2Cl2).
4.2.24. (R,E)-1-Nitro-4-phenylbut-3-en-2-ol9c 4w (Table 2,
entry 25)
Yield 72%, enantiomeric excess 85%. 1H NMR (300 MHz, CDCl3):
d 2.86 (s, 1H), 4.42 (d, J = 6.0 Hz, 2H), 4.94 (q, J = 6.0, 12.0 Hz, 1H),
6.02 (dd, J = 6.2, 15.8 Hz, 1H), 6.68 (d, J = 15.8 Hz, 1H), 7.22 (m,
5H). 13C NMR (75 MHz, CDCl3): d 69.4, 79.9, 125.4, 126.5, 128.1,
128.7, 32.9; HPLC Analysis: Chiracel OD-H column (85:15, n-hex-
ane–isopropyl alcohol, 0.8 mL/min, 215 nm); tR = 36.4 min (major,
(R)-isomer); tR = 31.9 (minor, (S)- isomer); ee 85%; ½a D20
¼ ꢁ34:2
ꢂ
(c 1, CH2Cl2).
7. (a) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. D.; Downey, C. W. J.
Am. Chem. Soc. 2003, 125, 12692; (b) Ginotra, S. K.; Singh, V. K. Org. Biomol.
Chem. 2007, 5, 3932; (c) Christensen, C.; Juhl, K.; Hazell, R. G.; Jørgensen, K. A. J.
Org. Chem. 2002, 67, 4875; (d) Christensen, C.; Juhl, K.; Jørgensen, K. A. Chem.
Commun. 2001, 2222; (e) Yang, W.; Du, D. M. Eur. J. Org. Chem. 2011, 1552.
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excess 73% (syn-isomer). Diasteriomeric ratio 2.1:1 (anti:syn).
Enantiomeric ratio and diasteriomeric ratio were determined by
HPLC analysis. 1H NMR (300 MHz, CDCl3): d 1.44 (d, J = 7.6 Hz,
3H) (anti), 1.48 (d, J = 6.8 Hz, 1.4H) (syn), 3.40 (s, 1.2H)(anti/syn),
4.86 (dd, J = 6.8, 13.6 Hz, 1.4H) (anti), 5.62 (dd, J = 6.8 Hz, 0.5H)
(syn), 6.02 (s, 1.0H) (anti/syn), 7.44 (m, 1.4H)(anti/ syn), 7.66 (m,
2H)(anti/syn), 7.88 (m, 1.4H) (anti/syn), 8.02 (d, J = 8.3 Hz,
0.9H)(anti/syn). HPLC Analysis: Chiracel AD-H column (90:10, n-
hexane–isopropyl alcohol, 0.5 mL/min, 254 nm); tR = 22.78 min
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