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Cite this: DOI: 10.1039/c6nj01045h
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A new series of bipyridine based chiral
organocatalysts for enantioselective Henry
reaction†
Veeramanoharan Ashokkumar, Kumaraguru Duraimurugan and Ayyanar Siva*
Received (in Montpellier, France)
5th April 2016,
Accepted 21st June 2016
A series of binaphthol based chiral organocatalysts were synthesized and applied as metal-free organocatalysts
in the enantioselective Henry reaction. These organocatalysts enabled the Henry reaction with a lower
concentration of catalysts at room temperature affording the desired S- or undesired R-enantiomers. The
DOI: 10.1039/c6nj01045h
formation of R- and S-enantiomers of b-nitroalcohol products strongly depends on the temperature/
substrate inversion of configuration for the effective catalytic enantioselective Henry reaction in high
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yields (up to 97%) with excellent enantioselectivities (up to 99% ee).
Introduction
The reaction carried out between a carbonyl compound and a
nitroalkane is known as the Henry (or nitroaldol) reaction.1 The
resulting nitroalcohols are often used as valuable synthetic
intermediates in the synthesis of numerous products and
they are biologically important compounds.2–4 Most of the
asymmetric Henry reactions were catalyzed by transition metal
complexes, especially copper complexes and copper salts.5–8
Kitagaki and coworkers9a reported the Henry reaction in the
presence of 5 mol% of bis(thiourea) organocatalyst and 20 mol%
of i-Pr2NEt as a base at 25 1C. They achieved moderate to good
yields (57–89%) and ees (68–97%). Recently, Liu et al.9b have
reported the asymmetric Henry reaction of aldehydes with various
nitroalkanes using 12 mol% of N-monoalkyl-1,2-diamines as a
ligand, 10 mol% of Cu(OAc)2H2O as a catalyst and 7.7 mol% of
triethylamine as a base, and the above-mentioned reaction was
carried out at 40 1C with moderate to good yields (53–97%) and
ees (75–92%). Furthermore, Tanaka et al.9c reported the enantioselective Henry reaction in the presence of the trans-N,N-bisbiphenyl-4-ylmethylcyclohexane-1,2-diamine–CuCl2 complex and
Et3N base at 0 1C with better yields (69–87%) and ees (72–92%)
utilizing 24 h. Furthermore, Lu and co-workers reported the
unexpected inversion of the asymmetric Henry reaction achieved
with the same chiral ligand by changing the Lewis acid center
from the Cu(II) to a Zn(II) metal ion.9d Lovick and Michael
observed an unexpected inversion elicited by monomeric and
dimeric organocatalysts in the course of the Aza–Henry reaction
with very good yield and ees.9e
School of Chemistry, Madurai Kamaraj University, Madurai-625 021, Tamil Nadu,
India. E-mail: drasiva@gmail.com
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nj01045h
Scheme 1 Enantioselective Henry reaction of nitromethane with various
aldehydes.
In this connection, we carried out the enantioselective Henry
reaction under metal free and base free conditions. Our chiral
organocatalysts themselves act as bases as well as catalysts. The
merits of this catalytic system are easy manipulation, mild reaction
conditions, low concentration of catalysts 14–16 (2.5 mol%)
and an easy synthesis of catalysts in high yield. The formation
of R- and S-enantiomers of b-nitroalcohol products strongly
depends on the temperature/substrate inversion of configuration
for the effective catalytic enantioselective Henry reaction in high
yields (up to 97%) with excellent enantioselectivities (up to 99% ee)
at room temperature (Scheme 1).
Hence, to study the catalytic ability of chiral organocatalysts
for the enantioselective Henry reaction of nitroalkanes with
various aldehydes, a series of catalysts 14–16 with various
functional groups (Scheme 2) were synthesized. All the catalysts
were easily prepared from bipyridine derivatives (8, 9, and 10)
and [1,1 0 -binaphthalene]-2,2 0 -diamine 13, which was obtained
from the modified procedure.10–12
Results and discussion
The newly synthesized organocatalysts 14–16 were screened
as enantioselective catalysts for the Henry reaction. From this
survey, an initial attempt was made by treating aldehyde 4a with
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Scheme 2 Synthesis of amide, amine, imine linkaged chiral organocatalysts.
Reagents and conditions: (a) KMnO4/distilled water, (b) i. CH3OH/H2SO4,
ii LiAlH4/THF, (c) PCC/DCM, (d) triflic anhydride, pyridine, DCM/0 1C,
(e) benzophenone imine/K-tOBu/Pd(amphos)Cl2/toluene, (f) DMAP/EDCHCl,
DMF/overnight stirring/rt, (g) DMAP/EDCHCl, DMF/overnight stirring/rt,
(h) ethanol/50 1C/overnight stirring.
Fig. 1
Formerly testified chiral ligands/organocatalysts.
9a–c
nitromethane (5) in the presence of different chiral ligands/
catalysts 1a, 1b, 2, and 3 (Fig. 1) and 14, 15, and 16 (2.5 mol%) in
methanol at room temperature. From the observed results 1a
and 1b are acting poorly as catalysts, even upon increasing the
reaction time from 6 to 48 h (Table 1, entries 1 and 2).
Unfortunately, the presence of the chiral ligand/catalyst 2
and 3 had no significant effect on the reaction, even upon
increasing the reaction time to 72 h (Table 1, entries 2 and 3)
which may be due to the absence of base and metal ion sources
in the reaction medium. However, our newly synthesized chiral
organocatalysts 14, 15 and 16 under the stated conditions
afforded the expected Henry product 6 in good yields (up to
97%) and ees (up to 99%) (Table 1, entries 5–7) in less time
(only 6 h), which indicated that the electronic effects, bipyridine
and hydrogen bonding of the BINOL-moiety were crucial factors
for the catalyst in this reaction. Here, the bipyridine moiety acts
as a base and influences the rate of the reaction.
During the second step in the optimization of the reaction
conditions, the solvent effects were examined and the observed
results are summarized in Table 2 (entries 1–10) and Table S1
(see ESI†). The obtained results clearly shows that the reaction
is highly sensitive to the nature of the solvent employed and
also methanol and ethanol are the best reaction media in terms
of yield and enantioselectivity (Table 2, entries 1 and 2). The
product yield and ee have been found to decrease gradually,
New J. Chem.
Table 1
Catalyst screening for enantioselective Henry reaction
Entry
Ligand/catalyst
Timea (h)
Yieldb (%)
eec (%)
Abs. conf.d
1
2
3
4
5
6
7
1a
1b
2
3
14
15
16
48
48
72
72
06
06
06
65
70
NR
NR
97
96
86
63
67
—
—
98
97
85
S
S
—
—
S
S
S
a
The enantioselective Henry reaction of aldehyde 4a (0.1 mmol),
nitromethane 5 (1.0 mmol), and ligand/catalyst (2.5 mol%) with
1.5 ml of methanol at room temperature and different time intervals.
b
Isolated yield of the purified material. c Enantiopurity was determined by HPLC analysis of the Henry product 6a using a chiral column
(Chiralcel OD-H) with hexane–IPA as an eluent. d Absolute configuration was determined by comparison of the HPLC retention time using
known literature data.8
Table 2
Effect of solvents on enantioselective Henry reaction
Entry
Solvents
Timea (h)
Yieldb (%)
eec (%)
Abs. conf.d
1
2
3
4
5
6
7
8
9
10
CH3OH
C2H5OH
i-PrOH
DCM
THF
EtOAc
CHCl3
o-Xylene
Benzene
CCl4
6
6
6
7
7
8
8
10
10
10
97
97
96
87
85
82
80
75
72
70
98
97
97
86
84
80
82
79
69
59
S
S
S
S
S
S
S
S
S
S
a
The enantioselective Henry reaction of aldehyde 4a (0.1 mmol),
nitromethane 5 (1.0 mmol), and organocatalyst 14 (2.5 mol%) with
1.5 ml of various solvents at room temperature with different time
intervals. b Isolated yield of the purified material. c Enantiopurity was
determined by HPLC analysis of the Henry product 6a using a chiral
column (Chiralcel OD-H) with hexane–IPA as an eluent. d Absolute configuration was determined by comparison of the HPLC retention time using
known literature data.8
using polar to non-polar solvents (Table 2, entries 1–10 and
Table S1 (see ESI†)).
Furthermore, we concluded that the high dielectric constant of
the solvents increases the hydrogen bonding interaction between the
catalyst and the substrate and hence increases the chemical yield
and ee (Table 2, entries 1–10). The order of the dielectric constant of
the solvents is as follows: methanol 4 ethanol 4 i-PrOH 4 DCM 4
THF 4 ethyl acetate 4 chloroform 4 o-xylene 4 benzene 4 CCl4.
This in turn improves the potential effect of the catalyst as well
as effective attraction between the substrate and the catalyst
and hence we observed higher yield and ee in methanol,
ethanol, and i-PrOH media (Table 2, entries 1–3).
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Paper
Furthermore, we plotted the dielectric constant vs. yield/ee
for the Henry reaction; it is understood from Fig. F1 (see ESI†)
that the dielectric constant of the solvent influenced the
chemical yield and ee (Fig. F1a, c and d, see ESI†) of the Henry
products which increased in the presence of both organocatalysts 14 and 16. In order to check the chemical yield conversion
from 0–6 hours, we have taken a counter sample for every
30 minutes. From the obtained results, we plotted time vs yield,
and the product conversion increases gradually at every 30 minutes
for both the catalysts 14 and 16 (Fig. F1b, see ESI†).
Furthermore, the optimization of the Henry reaction of
benzaldehyde 4a with nitromethane 5 was carried out in the
presence of different reaction temperature conditions. From the
observed results, higher chemical yield and ee were obtained at
room temperature (Table 3, entries 1–11 and Table S2 (see ESI†)).
More interestingly, a decrease in the temperature from 30 1C
(RT) to 10 1C, 5 1C, 0 1C, 10 1C and 20 1C in the Henry reaction
leads to an inversion of the product configuration [(R) product]
in the presence of organocatalyst S-BINOL in the form of 14 and
16 as catalysts. This may be due to the restricted interaction
between the catalysts and the substrate on the Re-face upon
lowering the temperature from RT to 20 1C, and hence the
substrate will attack only on the Si-face, so we obtained the
configuration inverted Henry product. In order to investigate
the unusual inversion of configuration 6 due to the change in
the reaction temperature, we carried out the more detailed
investigation of the effect of temperature on the enantioselectivity of the Henry reaction, and the observed results are given
in Table 3 and Table S2 (see ESI†).
Table 3 The optimization of enantioselective Henry reaction under
various temperature conditions
Entry
Condition
Timea (h)
Yieldb (%)
eec (%)
Abs. conf.d
1
2
3
4
5
6
7
8
9
10
11
60 1C
50 1C
30 1C (RT)
25 1C
20 1C
15 1C
10 1C
05 1C
0 1C
10 1C
20 1C
6
6
6
7
7
7
7
7
8
9
10
65
81
97
90
86
82
80
75
90
92
95
67
78
98
90
81
70
63
74
91
93
97
S
S
S
S
S
S
S
R
R
R
R
a
The enantioselective Henry reaction of aldehyde 4a (0.1 mmol),
nitromethane 5 (1.0 mmol), and organocatalyst 14 (2.5 mol%) with
1.5 ml of methanol under various temperature conditions with different
time intervals. b Isolated yield of the purified material. c Enantiopurity
was determined by HPLC analysis of the Henry product 6a using a
chiral column (Chiralcel OD-H) with hexane–IPA as an eluent. d Absolute configuration was determined by comparison of the HPLC retention time using known literature data.8
The inversion of the configuration was investigated by
conducting reactions at several intermediate temperatures
between 30 1C (RT) to 20 1C (Table 3, entries 3–11 and Table S2
(see ESI†)). These experiments show that inversion occurs between
10 1C and 5 1C (Table 3, entries 7–8 and Table S2 (see ESI†)).
Depending on the circumstances, upon increasing the reaction
temperature, the yield and enantioselectivity are decreased
(Table 3, entries 1 and 2 and Table S2 (see ESI†)). This might
be due to the perfect induction between the catalyst and the
substrate at room temperature (30 1C) only, and if we decreased
the reaction temperature below the RT the inversion configuration product was observed. Furthermore the correlation
between the temperature and the enantioselectivity of the Henry
reaction catalyzed by organocatalysts 14 and 16 is depicted in
Fig. 2. The ees from the reactions are expressed as the usual
logarithm of the relative rate constant for the formation of
(S)- and (R)-b-nitroalcohols, ln(kS/kR), which is then plotted as a
function of the inverse temperature (1/T, K1).13 The value of
ln(kS/kR) was calculated according to eqn (1). Hence, we observed
from the Arrhenius plot (Fig. 2, Table 4), the inversion of the
configuration attained at a temperature of B8 1C.
ln(kS/kR) = ln[(100 + %ee)/(100 %ee)]
(1)
Catalyst concentrations also play a crucial role in the Henry
reaction (Table 5). When the amount of catalyst was increased
from 1 to 20 mol%, the yield and ee also increased up to 2.5 mol%
(Table 5, entries 1–4) and when the catalyst concentration was
further increased the product yield and ee’s are reduced (Table 5,
entries 5–10). We plotted the catalyst concentration vs yield/ee’s for
the Henry reaction; from that plot 7.5, 15 and 20 mol% of catalyst
concentration gave moderate yield and poor ee. The low concentration of the catalyst (2.5 mol%) resulted in a higher yield and ee
(Fig. F2, see ESI†). This may be due to catalyst poisoning taking
place in this reaction irrespective of the organocatalysts 14 and 16.
In summary, from these investigations the optimized reaction
conditions are: concentration of organocatalysts (2.5 mol%),
methanol as a solvent and room temperature.
Fig. 2 Correlation between temperature and enantioselectivity of the
Henry reaction with organocatalysts 14 and 16 as represented by a plot
of ln(kS/kR) vs. 1/T.
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Table 4 Temperature dependence of the enantioselectivity in the asymmetric Henry reaction of aldehyde and nitromethane in the presence of
organocatalysts 14 and 16
Conf.a
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ee (%)
ln(kS/kR)
Temp (1/T) 103 Cat. Cat. Cat.
14
16
14
S. no 1C
(K1)
Cat.
16
Cat. 14
Cat. 16
1
2
3
4
5
6
7
8
9
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
R-()
R-()
R-()
R-()
4.5951
2.9444
2.2533
1.7334
1.4816
1.9006
3.0540
3.3167
4.1844
2.3135
2.0906
1.7732
1.4492
1.0577
1.3532
1.5496
1.7732
2.1424
30
25
20
15
10
5
0
10
20
3.30
3.35
3.41
3.47
3.53
3.59
3.66
3.80
3.95
98
90
81
70
63
74
91
93
97
82
78
68
62
56
59
65
71
79
S-(+)
S-(+)
S-(+)
S-(+)
S-(+)
R-()
R-()
R-()
R-()
a
The positive sign of the ee indicates the more predominant formation
of the S-(+) isomer.
Table 5 The enantioselective Henry reaction of aldehyde 4a with nitromethane at different concentrations of organocatalysts 14 and 16
Entry
Catalyst
Mol% of
catalyst
1
2
3
4
5
6
7
8
9
10
14
16
14
16
14
16
14
16
14
16
1.0
1.0
2.5
2.5
7.5
7.5
15.0
15.0
20.0
20.0
Timea
(h)
Yieldb
(%)
eec
(%)
Abs.
conf.d
7.0
7.0
6.0
6.0
5.5
5.5
5.0
5.0
4.5
4.5
85
80
97
86
95
82
90
83
86
80
93
84
98
85
94
81
84
73
80
71
S
S
S
S
S
S
S
S
S
S
a
The enantioselective Henry reaction of aldehyde 4a (0.1 mmol),
nitromethane 5 (1.0 mmol), and various concentrations of organocatalyst 14 and 16 with 1.5 ml of methanol at room temperature with
different time intervals. b Isolated yield of the purified material.
c
Enantiopurity was determined by HPLC analysis of the Henry product
6a using a chiral column (Chiralcel OD-H) with hexane–IPA as an eluent.
d
Absolute configuration was determined by comparison of the HPLC
retention time using known literature data.8
The scope of the organocatalysts was then explored under
the above mentioned optimized conditions. The results are
shown in Table 6. Numerous aldehydes reacted smoothly with
nitromethane to give the desired b-nitroalcohols in good yield
(up to 97%) and enantioselectivity (up to 99%). In comparison
with various substituted aldehydes, the electron-withdrawing
and electron-donating substituents on aromatic aldehydes had
a significant effect on the reaction. The electron-withdrawing
substituents on the aromatic aldehyde exhibited a slightly higher
enantioselectivity when compared to electron-donating substituents (Table 6, entries 4, 5 and 8, 9) and Table S3 (see ESI†). In
addition, para-substituted aromatic aldehydes showed a slightly
higher chemical yield and ee compared to ortho- and metasubstituted benzaldehydes and also requires more reaction
New J. Chem.
Table 6 Enantioselective Henry reaction of nitromethane with various
aromatic/aliphatic aldehydes
Entry
R
Product
Catalyst
Timea
(h)
Yieldb
(%)
eec
(%)
Abs.
conf.d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Ph
4Cl-Ph
4Br-Ph
4CH3-Ph
4OCH3-Ph
2OCH3-Ph
3OCH3-Ph
4NO2-Ph
4CN-Ph
2-Naphthyl
Furfuryl
E-Cinnamyl
–(CH3)2CH
(C2H5)2CH
–CH3(CH2)4
Cyclohexyl
–CH3(CH2)4
Cyclohexyl
Ph
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6o
6p
6a
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
13
13
13
6.0
6.5
6.5
7.0
7.0
10.0
12.0
6.0
6.0
6.5
8.0
8.0
8.0
8.0
8.0
8.0
8.0
8.0
6.0
97
92
93
91
90
86
88
97
97
95
92
82
90
89
90
95
61
67
74
98
93
91
93
96
91
92
99
99
97
94
95
92
93
92
98
48
59
67
S
S
S
S
S
S
S
S
S
S
S
S
R
R
R
R
S
S
S
a
The enantioselective Henry reaction of aldehydes 4a-p (0.1 mmol),
nitromethane 5 (1.0 mmol), organocatalysts 13 & 14, (2.5 mol%) and
1.5 ml of methanol under room temperature conditions with different
time intervals. b Isolated yield of the purified material. c Enantiopurity
was determined by HPLC analysis of the Henry product 6a-p using a chiral
column (Chiralcel OD-H) with hexane–IPA as an eluent. d Absolute
configuration was determined by comparison of the HPLC retention
time using known literature data.8
time when compared to para-substituted aromatic aldehydes
(Table 6, entries 5–7 and Table S3 (see ESI†)).
Among the electron withdrawing substituents, the cyano and
nitro group substituted aromatic aldehydes showed a higher
chemical yield and ee (Table 6, entries 2, 3 and 8, 9 and Table S3
(see ESI†)). This might be due to the fact that electron-withdrawing
groups can enhance the electrophilicity of the carbonyl carbon in the
aldehydes, which facilitates the reaction rate. Furthermore, the
polycyclic aromatic aldehyde (2-naphthaldehyde, Table 6, entry 10)
gave a very good yield and ee. Furthermore, the heteroaromatic
aldehyde, (furfural) also showed a high yield and ee due to the high
chiral inductions between the catalysts and substrates (Table 6,
entry 11). Furthermore, a,b-unsaturated aldehyde (E-cinnamaldehyde)
mediated Henry reaction gave a moderate yield, but higher ee
(Table 6, entry 12). We were delighted to find good to excellent
enantioselectivities and chemical yields for various unbranched,
branched and cyclic aliphatic aldehydes (Table 6, entries 13–16).
Among the aliphatic aldehydes, cyclohexylaldehyde gave a good
yield and ee (Table 6, entry 16). In addition to that, unexpected
inversions of stereochemistry were also found in this study. When
using aromatic aldehydes, (S)-enantiomers were observed. On the
other hand, when using aliphatic aldehydes, (R)-enantiomers
were observed.
This might be explained as follows: generally, the Henry
reaction is reversible14 and the introduction of a bulky cyclic or
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Fig. 3 Plausible transition formation of the ammonium salt mediated
asymmetric direct Henry reaction.
acyclic group at C-2 increases the steric hindrance of the Re face,
thereby making the nucleophilic attack on the carbonyl group
from the Si face approach more favorable, hence we obtain
R-enantiomers. The inversion of the configuration depends on
the steric hindrance of the substrate as well as the chiral induction
between the bipyridine based catalysts. In this regard, we carried
out the Henry reaction in the presence of organocatalysts 13, 14, 15
and 16 (Table 6 and Table S3 (see ESI†)).
From the obtained results, retention of the configuration
was observed when we used an unsubstituted bipyridine organocatalyst viz., 13 (Table 6, entries 17–19). Hence, bipyridine substituted chiral organocatalysts viz., 14, 15 and 16 play a crucial role
in the inversion of configuration of the Henry products 6. Therefore the reaction was carried out under kinetic control at room
temperature giving b-nitroalcohol as the major product. Among
the organocatalysts, amide linked catalyst 14 showed higher yield
and ee due to the presence of intermolecular/intra hydrogen
bonding between catalysts and substrates (Fig. 3 and Tables 1–6
and Tables S1–S3 (see ESI†)).
Conclusions
We have designed and synthesized a series of novel chiral
organocatalysts 14 and 16 for enantioselective Henry reaction.
These catalytic systems gave synthetically valuable b-nitroalcohols
with very good chemical yield and excellent enantioselectivities
for a wide range of aldehydes, including aromatic, aliphatic,
polycyclic aromatic, heteroaromatic and a,b-unsaturated aldehydes. The merits of this catalytic system are its easy manipulation, mild reaction conditions, low concentration of the catalyst,
and an easy synthesis of the catalyst in high yield. Furthermore,
our chiral organocatalysts play a dual role that means they act as a
catalysts as well as bases. The formation of R- and S-enantiomers
of the Henry products strongly depends upon the temperature/
substrate of the Henry reaction. We believe that this study
greatly expands the potential of this approach, through the
addition of aldehydes to nitromethane, toward the preparation
of synthetically valuable, optically active b-nitroalcohols with
very good yield and ee.
Experimental section
Materials and methods
All the chemicals and reagents used in this work were of analytical
grade. (S)-()-1,1 0 -Bi(2-naphthol), triflic anhydride, benzophenone
Paper
imine, 4-(dimethylamino)pyridine, N-(3-dimethylaminopropyl)-N 0 ethylcarbodiimide hydrochloride, LiAlH4, 4-nitrobenzaldehyde,
nitromethane, isobutyraldehyde, hexanal, 2-ethylbutanal, 2-naphthaldehyde, nitroethane, potassium tert-butoxide, cesium carbonate
and potassium carbonate were obtained from Sigma Aldrich.
Benzaldehyde, 4-chlorobenzaldehyde, 4-methylbenzaldehyde,
anisaldehyde, 4-bromobenzaldehyde, 2-methoxybenzaldehyde,
and 3-methoxybenzaldehyde were obtained from Alfa Aesar.
Sodium hydroxide and potassium hydroxide were obtained
from Merck and all the solvents were obtained at the laboratory
reagent grade. The melting points were measured in open
capillary tubes and are uncorrected.
The 1H and 13C NMR spectra were recorded on a Bruker
(Avance) 300 and 400 MHz NMR instrument using TMS as an
internal standard and CDCl3 as a solvent. Standard Bruker
software was used throughout. Chemical shifts are given in
parts per million (d-scale) and the coupling constants are given
in Hertz. Silica gel-G plates (Merck) were used for TLC analysis
with a mixture of n-hexane and ethyl acetate as an eluent. Column
chromatography was carried out in silica gel (60–120 mesh) using
a mixture of n-hexane and ethyl acetate as an eluent. FT-IR
spectroscopy measured in a JASCO FT/IR-410 spectrometer with
KBr as a pellet. HPLC was carried out in a SHIMADZU LC-6AD
with a chiral column (Chiral Cel OD-H), using HPLC grade
n-hexane and isopropanol solvent. Electrospray Ionization
Mass Spectrometry (ESI-MS) analyses were recorded on a LCQ
Fleet, Thermo Fisher Instruments Limited, US. ESI-MS was
performed in the positive ion mode. The collision voltage and
ionization voltage were 70 V and 4.5 kV, respectively, using
nitrogen as the atomization and desolvation gas. The desolvation
temperature was set at 300 1C. Optical rotations were measured on
Rudolph Research Analytical AUTOPOL-II (readability 0.011) and
AUTOPOL-IV (readability 0.0011) automatic polarimeters. Atomic
absorption spectroscopy was carried out using an Elico-SL-173.
Preparation of [2,2 0 -bipyridine]-3,3 0 -dicarboxylic acid (8).
A mixture of 1,10-phenanthroline 7 (2.0 g, 11.9 mmol) and
potassium permanganate (5.26 g, 33.29 mmol) was added to
100 mL of distilled water and refluxed for 6 h with stirring. The
obtained brown precipitate of MnO2 was filtered while hot. The
volume of the filtrate was reduced to B50 mL on a rotary
evaporator. The solution was boiled with 2 g of decolorizing
charcoal and filtered. Then conc. HCl was added dropwise
to the filtrate while needle shaped crystals started forming at
pH B3. The addition of HCl continued until the pH of the
solution reached B2. The white crystalline solid was filtered
off, washed with water, ethanol and dried in vacuo over CaCl2.
The filtrate was collected and the volume was reduced to half
and kept undisturbed overnight while more crystals separated
out. This process was repeated with the filtrates until no more
crystals were formed; the yield is 72% (1.9 g). mp: 250–252 1C.
IR (KBr) cm1: 3415, 3082, 2922, 2854, 2577, 1975, 1716, 1578,
1433, 1384, 1226, 1146, 1121, 1093, 1062, 905, 837. 1H NMR
(300 MHz, CDCl3) dH: 8.66–8.64 (m, 2H), 8.25–8.22 (m, 2H),
7.53–7.49 (m, 2H); 13C NMR (75 MHz, DMSO-d6) dC: 167.2, 158.9,
150.8, 137.8, 127.0, 122.9. ESI-Mass: calculated (m/z) = 244.0484,
found (m/z) = 244.0493.
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Preparation of [2,2 0 -bipyridine]-3,30 -diyldimethanol (9).
[2,2 0 -Bipyridine]-3,3 0 -dicarboxylic acid 8 (0.7 g, 2.86 mmol) was
dissolved in 10 mL of methanol, and after 15 minutes stirring
3 drops of con. H2SO4 were added under cooling conditions.
After completion of the reaction, the reaction mass was
quenched by NaHCO3 solution. After the complete evaporation
of the solvent the resulting ester was formed with 73% yield.
Then the corresponding ester was reduced by LiAlH4 using the
THF solvent. The reaction mixture was stirred for about 18 h and
monitored by TLC; after completion of the reaction, it was
poured into cold water, extracted with dichloromethane, washed
with brine and dried over sodium sulphate. It was concentrated
and purified by column chromatography using petroleum ether
and ethyl acetate as an eluent (6 : 4). The isolated yield of 9 is
70% (0.40 g). mp: 144–145 1C. IR (KBr) cm1: 3610, 3395, 3270,
2950, 2870, 2530, 1965, 1690, 1421, 1375, 1216, 1140, 1117, 1090,
1057, 902, 827. 1H NMR (300 MHz, CDCl3) dH: 8.33 (d, J = 6.6 Hz,
2H), 7.68 (d, J = 5.2 Hz, 2H), 6.91 (t, J = 16.4 Hz, 2H), 5.24 (b, 2H),
4.61 (s, 4H); 13C NMR (75 MHz, CDCl3) dC: 157.1, 147.4, 136.4,
132.1, 118.2, 62.8. ESI-Mass: calculated (m/z) = 216.0899, found
(m/z) = 216.0883.
Preparation of [2,2 0 -bipyridine]-3,3 0 -dicarbaldehyde (10).
[2,2 0 -Bipyridine]-3,3 0 -diyldimethanol 9 (0.4 g, 1.84 mmol) was
dissolved in dichloromethane and then pyridinium chlorochromate (0.76 g, 3.69 mmol) was added; the reaction mass was
stirred for about 7 h. The reaction was monitored by TLC; after
completion of the reaction, it was filtered through Celite, and
then the filtrate was separated by water and ethyl acetate. The
organic layer was dried over sodium sulphate, concentrated
and purified by column chromatography; the isolated yield of
10 is 51% (0.2 g). IR (KBr) cm1: 3390, 3280, 2910, 2840, 2510,
1710, 1590, 1430, 1365, 1210, 1132, 1120, 1080, 1043, 910, 844.
1
H NMR (300 MHz, CDCl3) dH: 9.75(s, 2H), 8.59 (d, J = 6.1 Hz,
2H), 7.90 (d, J = 6.1 Hz, 2H), 7.16 (t, J = 13.8, 2H); 13C NMR
(75 MHz, CDCl3) dC: 191.7, 153.8, 150.6, 137.4, 130.3, 122.3.
ESI-Mass: calculated (m/z) = 212.0586, found (m/z) = 212.0593.
Preparation of [1,10 -binaphthalene]-2,20 -diyl bis(trifluoromethanesulfonate) (12). Commercially available (S)-1,1 0 -bi-2naphthol 11 (1 g, 3.49 mmol) was dissolved in dichloromethane
solvent at 0 1C. Then, pyridine was added (0.56 mL, 6.98 mmol) to
the reaction mixture, and after 15 minutes of stirring triflic
anhydride (1.46 mL, 8.73 mmol) was added. After completion of
the reaction, the reaction mass was quenched by 1.5 N HCl and
ice water, extracted with ethyl acetate, washed with brine and
dried over sodium sulphate. It was concentrated and purified by
column chromatography using petroleum ether and ethyl acetate
as an eluent (8 : 2). The isolated yield of 12 is (1.70 g, 90%). IR
(KBr) cm1: 3070, 2922, 2853, 1625, 1587, 1511, 1405, 1362, 1313,
1248, 1217, 1176, 1138, 1066, 1033, 962, 935, 856, 835, 810.
1
H NMR (300 MHz, CDCl3) dH: 8.07 (d, J = 9.0 Hz, 2H), 7.93
(d, J = 8.2 Hz, 2H), 7.56–7.49 (m, 4H), 7.34 (d, 15.4 Hz, 2H), 7.19
(d, 8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) dC: 145.4, 133.1, 132.3,
131.9, 128.3, 127.9, 127.3, 126.7, 123.4, 120.2, 119.3, 115.9. ESI-Mass:
calculated (m/z) = 549.9979, found (m/z) = 549.9990.
Preparation of [1,1 0 -binaphthalene]-2,2 0 -diamine (13). A
mixture of (1.5 g, 2.72 mmol) [1,1 0 -binaphthalene]-2,2 0 -diyl
New J. Chem.
bis(trifluoromethanesulfonate) 12 and benzophenone imine
(1.05 mL, 6.26 mmol) was dissolved in 15 mL of toluene. After,
10 minutes of nitrogen purging, (0.61 g, 5.45 mmol) potassium
tert-butoxide and a catalytic amount of bis(di-tert-butyl(4dimethylaminophenyl)phosphine)dichloropalladium(II) were added.
After heating the entire reaction mass at 95 1C for about 8 h, the
reaction was monitored by TLC, and the reaction mixture was
poured into 1.5 N HCl solution for neutralization. Then sodium
hydroxide solution was added for the basification of the reaction
mass which was then extracted with ethyl acetate, washed with
brine and dried over sodium sulphate. It was concentrated and
purified by column chromatography using petroleum ether and
ethyl acetate as an eluent (7 : 3). The isolated yield of 13 is 0.54 g
(70%). IR (KBr) cm1: 3486, 3404, 3052, 2922, 2852, 1619, 1594,
1512, 1466, 1436, 1381, 1349, 1321, 1273, 1253, 1216, 1175, 1146,
1023, 867, 823. 1H NMR (300 MHz, CDCl3) dH: 7.96 (d, J = 8.9 Hz,
2H), 7.88 (d, J = 7.9 Hz, 2H), 7.38–7.27 (m, 6H), 7.14 (d, 8.1Hz,
2H), 5.10 (b, 4H); 13C NMR (75 MHz, CDCl3) dC: 152.8, 133.5,
131.5, 129.5, 128.5, 127.6, 124.3, 124.1, 117.9, 111.0. ESI-Mass:
calculated (m/z) = 284.1313, found (m/z) = 283.1327.
Synthesis of amide linkaged organocatalyst 14. A mixture
of [2,2 0 -bipyridine]-3,3 0 -dicarboxylic acid 8 (1 g, 4.09 mmol),
4-dimethylaminopyridine (1.0 g, 8.19 mmol), and EDCHCl
(1.56 g, 8.19 mmol) was taken in anhydrous DMF under a
nitrogen atmosphere at room temperature. After, 15 minutes of
stirring [1,10 -binaphthalene]-2,20 -diamine 13 (1.16 g, 4.09 mmol)
was added. The reaction mass was stirred overnight, after that it
was quenched with ice cold water, extracted with ethyl acetate and
washed with brine solution two times. The reaction mass was
dried over sodium sulphate and purified by column chromatography using petroleum ether and ethyl acetate as an eluent (7 : 3).
The isolated yield of 14 is 82% (1.65 g). IR (KBr) cm1: 3509, 3486,
3434, 3057, 2922, 2852, 1648, 1619, 1596, 1508, 1464, 1435, 1381,
1342, 1273, 1214, 1176, 1146, 1098, 981, 865, 818. 1H NMR
(300 MHz, DMSO-d6) dH: 10.49 (s, 2H), 8.79 (d, J = 4.7 Hz, 2H),
8.64 (d, J = 4.5 Hz, 2H), 8.03–7.86 (m, 8H), 7.29–7.18 (m, 6H); 13C
NMR (75 MHz, CDCl3) dC: 165.7, 152.2, 147.5, 140.2, 138.1, 133.2,
128.5, 127.4, 127.0, 126.2, 125.2, 124.1, 122.1, 121.2, 117.3, 115.6.
ESI-Mass: calculated (m/z) = 492.1586, found (m/z) = 492.1565.
Synthesis of amine linkaged organocatalyst 15. A mixture
of [2,2 0 -bipyridine]-3,3 0 -diyldimethanol 9 (0.8 g, 3.69 mmol),
4-dimethylaminopyridine (0.90 g, 7.39 mmol), and EDCHCl
(0.70 g, 7.39 mmol) was taken in anhydrous DMF under a
nitrogen atmosphere at room temperature. After 15 minutes of
stirring, [1,10 -binaphthalene]-2,2 0 -diamine 13 (1.04 g, 3.69 mmol)
was added into the solution. The reaction mass was stirred
overnight, after that it was quenched with ice cold water,
extracted with ethyl acetate and washed with brine solution
two times. The reaction mass was dried over sodium sulphate
and purified by column chromatography using petroleum ether
and ethyl acetate as an eluent (7 : 3). The isolated yield of 15 is
80% (1.38 g). IR (KBr) cm1: 3467, 3421, 3310, 3076, 2912, 2841,
1640, 1614, 1591, 1504, 1467, 1439, 1385, 1347, 1267, 1217, 1171,
1149, 1092, 982, 860, 812. 1H NMR (300 MHz, CDCl3) dH: 8.80
(d, J = 5.7 Hz, 2H), 8.39 (d, J = 6.7 Hz, 2H), 7.90–7.70 (m, 8H),
7.11–7.01 (m, 4H), 6.68 (t, J = 13.7 Hz, 2H), 5.32 (s, 2H), 4.52
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(s, 4H); 13C NMR (75 MHz, CDCl3) dC: 158.5, 147.6, 146.8, 137.2,
134.1, 131.7, 127.9, 127.6, 126.7, 125.6, 124.4, 121.6, 118.9,
117.5, 115.9, 55.1. ESI-Mass: calculated (m/z) = 464.2001, found
(m/z) = 464.2015.
Synthesis of imine linkaged organocatalyst 16. [2,20 -Bipyridine]0
3,3 -dicarbaldehyde 10 (0.4 g, 1.88 mmol) and [1,10 -binaphthalene]2,2 0 -diamine 13 (0.58 g, 2.07 mmol) were dissolved in 5 mL of
absolute ethanol in a 100 mL RB flask at room temperature. The
reaction mass was completely dissolved in a homogeneous
mixture. The reaction mass was heated up to 50 1C and stirred
overnight; the reaction was monitored by TLC. After completion
of the reaction, the reaction mixture was poured into ice water
and then an off white solid was formed. After that it was filtered,
washed with ice cold water and dried to get pure off white imine
linkaged organocatalyst 16 with 85% (0.73 g) yield. IR (KBr) cm1:
2910, 2834, 1631, 1607, 1587, 1461, 1428, 1381, 1339, 1340, 1260,
1221, 1176, 1154, 1094, 980, 856, 810. 1H NMR (300 MHz, CDCl3)
dH: 8.55–8.33 (m, 8H), 8.15 (d, J = 4.4 Hz, 2H), 7.98 (d, J = 5.3 Hz,
2H), 7.52 (q, J = 16.3 Hz, 4H), 7.36–7.30 (m, 4H); 13C NMR (75 MHz,
CDCl3) dC: 149.8, 135.6, 136.6, 135.6, 133.8, 133.1, 130.4,
128.2, 127.3, 126.7, 125.3, 125.0, 120.7, 112.3. ESI-Mass: calculated
(m/z) = 460.1688, found (m/z) = 460.1663.
General method for the enantioselective Henry reactions of
nitromethane with various aldehydes under organocatalytic
conditions (6(a-p))
A mixture of aldehydes 4 (0.25 mmol), organocatalysts 13, 14,
15, and 16 (2.5 mol%) and nitromethane (10 eq.) were dissolved
in 2 ml of CH3OH. Then, the reaction mixture was stirred for
about 6 h at room temperature. After that the reaction mixture
was extracted with ethyl acetate, washed with water (3 2 ml),
then washed with brine (5 ml), dried over sodium sulphate and
concentrated. The crude material was purified by column chromatography on silica gel (ethyl acetate and petroleum ether as an eluent),
to afford the corresponding Henry products (6(a-p)). The enantiomeric excess of the Henry products was determined by chiral
stationary-phase HPLC analysis.
Characterization of the enantioselective Henry products
(S)-2-Nitro-1-phenylethan-1-ol (6a). Yellow oil, yield: 97%,
[a]25
D = +41.71 (c = 0.95, CH2Cl2, 98% ee, (S)-enantiomer); IR
(KBr) cm1: 3547, 3037, 2927, 1551, 1491, 1453, 1384, 1191,
1096, 1061, 894, 845. 1H NMR (300 MHz, CDCl3) dH 7.33–7.20
(m, 5H), 5.39 (dd, J1 = 5.5 Hz, J2 = 8.3 Hz, 1H), 4.58–4.43 (m, 2H),
3.19 (b, 1H); 13C NMR (75 MHz, CDCl3) dC 138.1, 129.8, 129.7,
127.9, 77.9, 71.5. The enantiomeric excess was determined by
HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10, flow rate:
1 mL min1, retention time: 3.98 min (minor), 9.20 min
(major). The absolute stereochemistry of the Henry product
was denoted as (S) by comparison of the optical data with the
literature reported value.8
(S)-1-(4-Chlorophenyl)-2-nitroethan-1-ol (6b). Colourless oil, yield:
92%, [a]25
D = +20.41 (c = 0.85, CH2Cl2, 93% ee, (S)-enantiomer); IR
(KBr) cm1: 3431, 2911, 1587, 1485, 1419, 1384, 1213, 1195, 1081,
1021, 892, 827. 1H NMR (300 MHz, CDCl3) dH 7.30–7.27 (m, 2H),
7.20–7.17 (m, 2H), 5.40 (dd, J1 = 4.2 Hz, J2 = 8.7 Hz, 1H), 4.57–4.45
Paper
(m, 2H), 3.28 (b, 1H); 13C NMR (75 MHz, CDCl3) dC 138.1, 133.2,
129.7, 127.9, 77.9, 70.5. The enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10,
flow rate: 1 mL min1, retention time: 3.60 min (minor),
6.77 min (major). The absolute stereochemistry of the Henry
product was denoted as (S) by comparison of the optical data
with the literature reported value.8
(S)-1-(4-Bromophenyl)-2-nitroethan-1-ol (6c). Colourless oil, yield:
93%, [a]25
D = +36.21 (c = 1.00, CH2Cl2, 91% ee, (S)-enantiomer); IR
(KBr) cm1: 3425, 1638, 1551, 1496, 1381, 1081, 1006, 823. 1H NMR
(300 MHz, CDCl3) dH 7.51 (d, J = 4.8 Hz, 2H), 7.27 (d, J = 6.4 Hz, 2H),
5.38 (dd, J1 = 3.6 Hz, J2 = 10.4 Hz, 1H), 4.57–4.44 (m, 2H), 3.23 (b, 1H);
13
C NMR (75 MHz, CDCl3) dC 137.3, 132.2, 127.9, 123.1, 81.9, 70.3.
The enantiomeric excess was determined by HPLC, Chiralcel
(OD-H), 254 nm, hexane : IPA 90 : 10, flow rate: 1 mL min1,
retention time: 16.63 min (minor), 39.92 min (major). The
absolute stereochemistry of the Henry product was denoted
as (S) by comparison of the optical data with the literature
reported value.8
(S)-2-Nitro-1-(p-tolyl)ethan-1-ol (6d). Colourless oil, yield:
91%, [a]25
D = +25.71 (c = 0.98, CH2Cl2, 93% ee, (S)-enantiomer);
IR (KBr) cm1: 3529, 3427, 3021, 2928, 1561, 1413, 1381, 1346,
1201, 1072, 1047, 891, 817. 1H NMR (300 MHz, CDCl3) dH 7.48–
7.45 (m, 1H), 7.32–7.28 (m, 1H), 7.28–7.18 (m, 1H), 5.62 (dd,
J1 = 5.2 Hz, J2 = 9.3 Hz, 1H), 4.51–4.36 (m, 2H), 3.04 (b, 1H), 2.36
(s, 3H); 13C NMR (75 MHz, CDCl3) dC 136.4, 134.6, 130.9, 129.9,
128.2, 125.6, 78.1, 68.2, 21.4. The enantiomeric excess was
determined by HPLC, Chiralcel (OD-H), 254 nm, hexane :
IPA 90 : 10, flow rate: 1 mL min1, retention time: 23.06 min
(minor), 34.04 min (major). The absolute stereochemistry of the
Henry product was denoted as (S) by comparison of the optical
data with literature reported value.8
(S)-1-(4-Methoxyphenyl)-2-nitroethan-1-ol (6e). Colourless oil, yield:
90%, [a]25
D = +38.61 (c = 0.92, CH2Cl2, 96% ee, (S)-enantiomer);
IR (KBr) cm1: 3461, 3006, 2931, 2846, 1617, 1581, 1551,
1517, 1469, 1371, 1307, 1256, 1173, 1071, 1036, 894, 832.
1
H NMR (300 MHz, CDCl3) dH 7.34–7.31 (m, 2H), 6.93–6.87
(m, 2H), 5.40 (dd, J1 = 4.1 Hz, J2 = 9.1 Hz, 1H), 4.60 (dd, J1 =
4.3 Hz, J2 = 16.1 Hz, 1H), 4.47 (dd, J1 = 8.1 Hz, J2 = 12.3 Hz, 1H),
3.76 (s, 3H), 2.90 (b, 1H); 13C NMR (75 MHz, CDCl3) dC 159.6,
129.3, 128.3, 114.5, 78.0, 70.7, 55.3. The enantiomeric excess was
determined by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA
90 : 10, flow rate: 1 mL min1, retention time: 12.39 min (minor),
22.24 min (major). The absolute stereochemistry of the Henry
product was denoted as (S) by comparison of the optical data
with the literature reported value.8
(S)-1-(2-Methoxyphenyl)-2-nitroethan-1-ol (6f). Colourless oil, yield:
86%, [a]25
D = +43.41 (c = 1.07, CH2Cl2, 91% ee, (S)-enantiomer);
IR (KBr) cm1: 3531, 3014, 2946, 1607, 1561, 1497, 1383, 1281,
1248, 1209, 1127, 1077, 1029, 894. 1H NMR (300 MHz, CDCl3)
dH 7.42 (dd, J1 = 3.8 Hz, J2 = 7.2 Hz, 1H), 7.32 (td, J1 = 1.2 Hz,
J2 = 10.5 Hz, 1H), 7.0 (dd, J1 = 8.2 Hz, J2 = 17.9 Hz, 1H), 6.90
(d, J = 6.0 Hz, 1H), 5.61 (dd, J1 = 4.8 Hz, J2 = 10.3 Hz, 1H),
4.66–4.54 (m, 2H), 3.87 (s, 3H), 3.24 (b, 1H); 13C NMR
(75 MHz, CDCl3) dC 156.1, 129.9, 127.4, 126.0, 121.3, 110.7,
80.6, 67.9, 55.5. The enantiomeric excess was determined
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NJC
by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10, flow
rate: 1 mL min1, retention time: 11.05 min (minor), 17.05 min
(major). The absolute stereochemistry of the Henry product was
denoted as (S) by comparison of the optical data with the
literature reported value.8
(S)-1-(3-Methoxyphenyl)-2-nitroethan-1-ol (6g). Colourless
oil, yield: 88%, [a]25
D = +34.61 (c = 0.65, CH2Cl2, 92% ee,
(S)-enantiomer); IR (KBr) cm1: 3463, 3004, 2944, 2842, 1605,
1559, 1497, 1375, 1324, 1266, 1153, 1065, 1037, 882. 1H NMR
(300 MHz, CDCl3) dH 7.30 (t, J = 8.6 Hz, 1H), 6.98–6.93 (m, 2H),
6.86 (dd, J1 = 4.6 Hz, J2 = 19.6 Hz, 1H), 5.40 (dd, J1 = 5.2 Hz,
J2 = 10.8 Hz, 1H), 4.60–4.46 (m, 2H), 3.80 (s, 3H), 3.09 (b, 1H);
13
C NMR (75 MHz, CDCl3) dC 160.4, 139.5, 130.4, 118.3, 114.7,
111.4, 81.5, 71.5, 55.0. The enantiomeric excess was determined
by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10, flow
rate: 1 mL min1, retention time: 8.91 min (minor), 30.52 min
(major). The absolute stereochemistry of the Henry product
was denoted as (S) by comparison of the optical data with the
literature reported value.8
(S)-2-Nitro-1-(4-nitrophenyl)ethan-1-ol (6h). Yellow solid,
Mp: 82–84 1C, yield: 97%, [a]25
D = +35.41 (c = 0.94, CH2Cl2,
99% ee, (S)-enantiomer); IR (KBr) cm1: 3520, 3112, 1609, 1552,
1521, 1380, 1347, 1081, 857. 1H NMR (300 MHz, CDCl3) dH 8.29–
8.26 (m, 2H), 7.65–7.62 (m, 2H), 5.62 (dd, J1 = 2.5 Hz, J2 = 8.6 Hz,
1H), 4.64–4.55 (m, 2H), 3.12 (b, 1H); 13C NMR (75 MHz, CDCl3)
dC 147.9, 143.8, 129.4, 124.2, 79.9, 70.7. The enantiomeric
excess was determined by HPLC, Chiralcel (OD-H), 254 nm,
hexane : IPA 90 : 10, flow rate: 1 mL min1, retention time:
19.41 min (minor), 33.97 min (major). The absolute stereochemistry of the Henry product was denoted as (S) by comparison of the optical data with the literature reported value.8
(S)-4-(1-Hydroxy-2-nitroethyl)benzonitrile (6i). Colourless oil, yield:
97%, [a]25
D = +42.41 (c = 0.80, CH2Cl2, 99% ee, (S)-enantiomer); IR
(KBr) cm1: 3413, 2912, 2249, 1605, 1551, 1383, 1213, 1087, 836.
1
H NMR (300 MHz, CDCl3) dH 7.69 (d, J = 4.7 Hz, 2H), 7.55 (d, J =
5.2 Hz, 2H), 5.53 (dd, J1 = 2.9 Hz, J2 = 8.4 Hz, 1H), 4.60–4.50 (m, 2H),
3.26 (b, 1H); 13C NMR (75 MHz, CDCl3) dC 143.2, 132.3, 126.5, 118.3,
112.4, 78.0, 70.3. The enantiomeric excess was determined by
HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10, flow rate:
1 mL min1, retention time: 25.16 min (minor), 51.22 min
(major). The absolute stereochemistry of the Henry product was
denoted as (S) by comparison of the optical data with the
literature reported value.8
(S)-1-(Naphthalen-2-yl)-2-nitroethan-1-ol (6j). Yellow colour
oil, yield: 95%, [a]25
D = +20.61 (c = 0.65, CH2Cl2, 97% ee,
(S)-enantiomer); IR (KBr) cm1: 3435, 3050, 1554, 1412, 1372,
1270, 1129, 1072, 907, 862, 820. 1H NMR (300 MHz, CDCl3) dH
7.89–7.83 (m, 4H), 7.54–7.44 (m, 3H), 5.60 (dd, J1 = 5.3 Hz, J2 =
18.4 Hz, 1H), 4.68 (dd, J1 = 2.6 Hz, J2 = 8.1 Hz, 1H), 4.62 (dd, J1 =
3.7 Hz, J2 = 10.5 Hz, 1H), 2.91 (b, 1H); 13C NMR (75 MHz, CDCl3)
dC 135.8, 133.5, 132.9, 129.0, 128.4, 128.2, 126.2, 125.4, 123.6, 77.8,
71.9. The enantiomeric excess was determined by HPLC, Chiralcel
(OD-H), 254 nm, hexane : IPA 90 : 10, flow rate: 1 mL min1, retention time: 8.76 min (minor), 17.85 min (major). The absolute
stereochemistry of the Henry product was denoted as (S) by comparison of the optical data with the literature reported value.8
New J. Chem.
(S)-1-(Furan-2-yl)-2-nitroethan-1-ol (6k). Colourless oil, yield:
92%, [a]25
D = +37.31 (c = 1.00, CH2Cl2, 94% ee, (S)-enantiomer);
IR (KBr) cm1: 3417, 3291, 1553, 1507, 1386, 1325, 1197, 1156,
1063, 1012, 924, 881. 1H NMR (300 MHz, CDCl3) dH 7.41–7.39
(m, 1H), 6.39–6.35 (m, 2H), 5.45 (d, J = 8.6 Hz, 1H), 4.75–4.67
(m, 2H), 3.16 (b, 1H); 13C NMR (75 MHz, CDCl3) dC 154.5, 143.7,
110.8, 108.3, 78.4, 64.3. The enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10,
flow rate: 1 mL min1, retention time: 7.98 min (minor), 13.59 min
(major). The absolute stereochemistry of the Henry product was
denoted as (S) by comparison of the optical data with the literature
reported value.8
(S,E)-1-Nitro-4-phenylbut-3-en-2-ol (6l). Yellow colour oil, yield:
90%, [a]25
D = +13.61 (c = 0.78, CH2Cl2, 95% ee, (S)-enantiomer); IR
(KBr) cm1: 3432, 3025, 2927, 1657, 1557, 1375, 1197, 1117, 1067,
963, 880. 1H NMR (300 MHz, CDCl3) dH 7.39–7.27 (m, 5H), 6.78 (d,
J = 9.0 Hz, 1H), 6.13 (dd, J1 = 9.4 Hz, J2 = 19.2 Hz, 1H), 5.08–5.05
(m, 1H), 4.51 (d, J = 4.4 Hz, 2H), 2.89 (b, 1H); 13C NMR (75 MHz,
CDCl3) dC 135.2, 133.4, 128.3, 127.9, 126.0, 125.3, 82.2, 69.4. The
enantiomeric excess was determined by HPLC, Chiralcel (OD-H),
254 nm, hexane : IPA 90 : 10, flow rate: 1 mL min1, retention
time: 27.60 min (minor), 40.51 min (major). The absolute stereochemistry of the Henry product was denoted as (S) by comparison
of the optical data with the literature reported value.8
(S)-3-Methyl-1-nitrobutan-2-ol (6m). Yellow oil, yield: 90%,
[a]25
D = 26.71 (c = 0.87, CHCl3, 92% ee, (R)-enantiomer); IR
(KBr) cm1: 3420, 2965, 2871, 1561, 1425, 1389, 1372, 1209,
1150, 1096, 1049, 994, 895, 847. 1H NMR (300 MHz, CDCl3)
dH 4.50 (dd, J1 = 8.8 Hz, J2 = 12.2 Hz, 1H), 4.41 (dd, J1 = 3.4 Hz,
J2 = 15.5 Hz, 1H), 4.10–4.05 (m, 1H), 3.41 (b, 1H), 1.77 (td,
J1 = 7.2 Hz, J2 = 14.9 Hz, 1H), 0.97 (t, J = 9.1 Hz, 6H); 13C NMR
(75 MHz, CDCl3) dC 77.8, 72.3, 31.6, 18.3, 17.3. The enantiomeric
excess was determined by HPLC, Chiralcel (OD-H), 254 nm,
hexane : IPA 90 : 10, flow rate: 1 mL min1, retention time:
3.61 min (major), 17.03 min (minor). The absolute stereochemistry of the Henry product was denoted as (R) by comparison of the optical data with the literature reported value.8
(S)-3-Ethyl-1-nitropentan-2-ol (6n). Colourless oil, yield: 89%,
[a]25
D = 16.41 (c = 1.04, CH2Cl2, 93% ee, (R)-enantiomer); IR
(KBr) cm1: 3429, 2920, 1725, 1551, 1447, 1381, 1341, 1209, 1077,
922. 1H NMR (300 MHz, CDCl3) dH 4.46–4.41 (m, 2H), 4.36–4.31 (m,
1H), 2.52 (b, 1H), 1.58–1.28 (m, 5H), 0.94 (t, J = 11.0 Hz, 6H); 13C
NMR (75 MHz, CDCl3) dC 78.0, 70.3, 44.6, 21.9, 21.4, 11.7, 11.5. The
enantiomeric excess was determined by HPLC, Chiralcel (OD-H),
254 nm, hexane : IPA 90 : 10, flow rate: 1 mL min1, retention time:
3.93 min (major), 12.01 min (minor). The absolute stereochemistry
of the Henry product was denoted as (R) by comparison of the optical
data with the literature reported value.8
(S)-1-Nitroheptan-2-ol (6o). Colourless oil, yield: 90%, [a]25
D =
12.61 (c = 0.92, CHCl3, 92% ee, (R)-enantiomer); IR (KBr) cm1:
3416, 2934, 2865, 1561, 1461, 1427, 1417, 1387, 1203, 1137,
1097, 889. 1H NMR (300 MHz, CDCl3) dH 4.46–4.30 (m, 3H),
2.68 (b, 1H), 1.57–1.46 (m, 3H), 1.39–1.25 (m, 5H), 0.90 (t, J =
10.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) dC 80.7, 68.6,
33.9, 31.7, 25.2, 22.7, 14.2. The enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane : IPA 90 : 10,
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NJC
flow rate: 1 mL min1, retention time: 5.79 min (major), 22.43
min (minor). The absolute stereochemistry of the Henry product
was denoted as (R) by comparison of the optical data with the
literature reported value.8
(S)-1-Cyclohexyl-2-nitroethan-1-ol (6p). Colourless oil, yield:
95%, [a]25
D = 17.31 (c = 0.74, CHCl3, 98% ee, (R)-enantiomer); IR
(KBr) cm1: 3427, 2926, 2859, 1551, 1448, 1387, 1354, 1207,
1114, 1069, 1041, 893, 867. 1H NMR (300 MHz, CDCl3) dH 4.49–
4.37 (m, 2H), 4.06 (d, J = 8.4 Hz, 1H), 2.70 (d, J = 2.3 Hz, 1H),
1.80–1.67 (m, 3H), 1.43–1.03 (m, 8H); 13C NMR (75 MHz, CDCl3)
dC 77.7, 72.3, 41.7, 28.7, 27.2, 26.2, 25.2, 24.5. The enantiomeric
excess was determined by HPLC, Chiralcel (OD-H), 254 nm,
hexane : IPA 90 : 10, flow rate: 1 mL min1, retention time: 13.28
min (major), 33.97 min (minor). The absolute stereochemistry
of the Henry product was denoted as (R) by comparison of the
optical data with the literature reported value.8
Acknowledgements
This work was financially supported by the Department of Science
and Technology, New Delhi, India (Grant No. SR/F/1584/2012-13),
Council of Scientific and Industrial Research, New Delhi, India
(Grant No. 01(2540)/11/EMR-II) and DST-SERB, Extramural Major
Research Project (Grant No. EMR/2015/000969).
Notes and references
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New J. Chem.