S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids: efficient organocatalysts for enantioselective sodium borohydride reductions of prochiral ketones

Article abstract of DOI:10.1016/j.tetasy.2017.02.008

Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of (?)-menthol or (?)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthesized chiral ionic liquids have been characterized by ¹H, ¹³C NMR and Mass spectrometry. Moderate to excellent enantiomeric excess (ee?>?99%) has been obtained in asymmetric sodium borohydride reduction of prochiral ketones using these salts as chiral catalysts.

Full text of DOI:10.1016/j.tetasy.2017.02.008

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids:
efficient organocatalysts for enantioselective sodium borohydride
reductions of prochiral ketones
⇑
Avtar Singh, Harish Kumar Chopra
Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal 148106, Distt. Sangrur (Pb.), India
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of
their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield
optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of
(À)-menthol or (À)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthe-
sized chiral ionic liquids have been characterized by 1H, 13C NMR and Mass spectrometry. Moderate to
excellent enantiomeric excess (ee > 99%) has been obtained in asymmetric sodium borohydride reduction
of prochiral ketones using these salts as chiral catalysts.
Received 17 November 2016
Revised 7 February 2017
Accepted 10 February 2017
Available online xxxx
Ó 2017 Published by Elsevier Ltd.
1. Introduction
special catalysts in synthetic chemistry.13 These salts can be used
to induce asymmetry in synthetically important reactions such as
Ionic liquids comprise a unique class of ionic compounds with
important applications in chemistry and technology.1 These com-
pounds generally have organic moieties as the cationic part and
inorganic anions. The lack of close packing in their motif leads to
low boiling points (generally less than 100 °C), and so they are
often liquid at room temperature and termed as room temperature
ionic liquids. Since their evolution, these compounds have been an
important area of research due to their exciting properties such as
non-volatility, excellent solvent potential, tunable viscosity, con-
ductivity and high thermal stability.2 Due to their solvent and cat-
alytic potential, these compounds are of prime importance in the
field of synthetic organic chemistry.3 Moreover, these compounds
have a wide range of applications in electroanalytical chemistry,4
chromatography,5 extraction,6 polymer chemistry7 and nanotech-
nology.8 Chiral ionic liquids represent a subclass of ionic liquids
with at least one stereogenic unit in their structure. These com-
pounds are well known for their potential in asymmetric synthesis
and catalysis,9 separation science10 and chiral recognition
studies.11 The combination of these species with advanced
chromatographic techniques has started a new era in the field of
chiral separations.12 Many examples can be found in the literature
about the use of these species as organocatalysts in stereoselective
synthesis. The recyclability of these compounds from a reaction
mixture without any loss in catalytic capability makes them very
aldol condensations, hydrogenation reactions, Michael additions,
Diels Alder reactions, and Baylis-Hillman reactions. Some excellent
reviews about the use of chiral ionic liquids in asymmetric
organocatalysts can be found in the literature.14
Enantiopure secondary alcohols are important scaffolds in the
pharmaceutical, fragrance and agrochemical industries.15 A num-
ber of synthetic methods have been developed for the synthesis
of these enantiopure alcohols. In order to enhance the enantiopu-
rity of the products, many metal based catalysts16 and biocata-
lysts16a,17 have been reported. Chiral ionic liquids have also been
employed to catalyze the asymmetric hydrogenation reactions
due to their environmentally friendly nature.18 Recently, we
reported on the use of benzimidazolium based chiral ionic liquids
for the enantioselective reduction of prochiral ketones to chiral
secondary alcohols.19
In continuation of our previous work, we herein report the syn-
thesis of a new family of S-substituted-2-mercaptobenzthiazolium
based chiral ionic liquids, starting from chiral precursors (À)-men-
thol or (À)-borneol. The synthesized compounds were character-
ized using NMR and EI-MS techniques. The synthesized salts
were then tested for their catalytic potential in enantioselective
NaBH4 reductions of prochiral ketones to furnish the correspond-
ing secondary alcohols. These salts were found to be excellent cat-
alysts for these reduction reactions with moderate to excellent
enantiomeric excess being obtained with 10% loading of the
catalyst.
⇑
Corresponding author.
E-mail address: hk67@rediffmail.com (H.K. Chopra).
http://dx.doi.org/10.1016/j.tetasy.2017.02.008
0957-4166/Ó 2017 Published by Elsevier Ltd.
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.02.008

2
A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
O
OH
R1
2. Results and discussion
CIL (10 mol%)
NaBH4, MeOH
R1
In order to enhance our efforts towards the development of new
catalysts/methods for the refinement of organic synthesis,20 we
herein report the synthesis of some new chiral ionic liquids as
organocatalysts for enantioselective reduction of prochiral ketones.
The synthesis of these chiral ionic liquids was carried out under
mild conditions as described in Scheme 1. For the synthesis of
S-substituted-2-mercaptobenzthiazoles; 2-mercaptobenzthiazole
1 was treated with methyl iodide or benzyl chloride under
ultrasound waves (in a probe ultrasonicator) to furnish S-methyl
or S-benzyl derivatives 2a or 2b in good yields. For the synthesis
of optically active esters 3a–b, (À)-menthol [or borneol] was
treated with chloroacetic acid in an ultrasonicator bath employing
iron(III) perchlorate hydrate as the catalyst. In the final step,
2-mercaptobenzthiazole derivatives 2a–b were refluxed with
(À)-menthyl (or bornyl) esters 3a–b to yield the corresponding
chloride salts 4a–d in high yields.
All the synthesized salts were liquid at room temperature and
show negative specific rotation values. Differential scanning
calorimetry results reveals that the glass transition temperature
of these chiral ionic liquids fall in a range of À60 to À70 °C. Impor-
tant physical properties of the synthesized chiral ionic liquids are
enlisted in Table 1.
The catalytic potential of all synthesized chiral ionic liquids in
the sodium borohydride reduction of prochiral ketones to obtain
enantiopure secondary alcohols was also studied. Scheme 2 repre-
sents the reduction reactions in the presence of chiral ionic liquids
in methanol.
X
X
Scheme 2. Enantioselective reduction using chiral ionic liquids 4a–d as
organocatalysts.
excellent enantiomeric excess (4–99%) were achieved in the reduc-
tion reaction. The results of the reduction reactions for various sub-
strates are given in Table 2.
It is evident from Table 2 that in some cases, more than 95% ee
can be achieved while the reaction yield is not much affected by
the variation of the chiral ionic liquid catalyst. Maximum enantiop-
urity (99% ee) was obtained in the case of 4-hydroxyacetophenone
using chiral ionic liquid 4d. Excellent results were obtained in case
of 4-nitroacetophenone and 1-indanone also. The remaining sub-
strates exhibited low to moderate enantiomeric excesses only.
The enantiomeric excesses obtained from this protocol were better
than our previous report.19 A probable mechanism for the reaction
is described in Scheme 3. According to the mechanism, the 1st step
involves the formation of ionic intermediate I. The intermediate I
in the reaction is possible because of formation of contact ion pairs
in the solution. As suggested by Wasserscheid et al., the chirality
transfer is favoured by the presence of the ionic intermediates.21
The existence of an ionic intermediate over the solvated ion pairs
is further approved by the fact that the dilution is not higher.22
The key step in the reaction involves the transfer of the hydride
ion from the intermediate to the substrate molecule which results
in the formation of the product.
Only 10 mol% of these chiral ionic liquids was sufficient to carry
out the enantioselective reduction of various substrates. Low to
R
S
S
N
SH
RX
S
+
N
1
2a: R = methyl
2b: R = benzyl
O
O
Fe(ClO4)3.6H2O
Cl
Cl
or
OH
+
HO
R'O
CH2Cl2
3a-b
ultrasonication
OH
R
S
N
MeCN
reflux
S
O
O
R'
4a
: R = methyl, R' = menthyl
Cl
4b: R = benzyl, R' = menthyl
4c: R = methyl, R' = bornyl
4d: R = benzyl, R' = bornyl
N
S
S
R
4a-d
Scheme 1. Synthesis of chiral ionic liquids.
Table 1
Physical properties of the synthesized salts
25
Entry
Chiral ionic liquid
Physical appearance
Yield (%)
[
a
]
T⁄g (°C)
D
1
2
3
4
4a
4b
4c
4d
Reddish brown liquid
Yellowish liquid
Reddish brown liquid
Pale yellow liquid
81
83
79
78
À39.7
À34.7
À20.2
À19.4
À64.7
À69.6
À69
À60.5
T⁄g (Glass transition temperatures) determined by differential scanning calorimetry analysis.
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.02.008

A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
3
Table 2
Enantioselective reduction of various ketone substrates
Entry
Ketone
Chiral ionic liquid 4a
Chiral Ionic Liquid 4b
Chiral ionic liquid 4c
Chiral ionic liquid 4d
Yield (%)
Time (h)
eea (%)
Yield (%)
Time (h)
eea (%)
Yield (%)
Time (h)
eea (%)
Yield (%)
Time (h)
eea (%)
1
2
3
4
5
6
7
ACP
79
70
76
71
76
69
74
2
2.5
2
2
2
4
12
52
3
5
95
96
78
72
74
70
75
67
72
2
2.5
2
2
2
rac
8
62
7
5
90
72
78
72
76
73
76
72
68
2
2.5
2
2
2
4
12
55
5
12
94
89
76
73
72
73
76
70
72
2
2.5
2
2
2
5
20
99
7
3
86
97
4-Br ACP
4-OH ACP
2-OH ACP
4-OMe ACP
4-NO2 ACP
1-Indanone
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
ACP stands for Acetophenone
a
Determined by GC analysis using Rt-bDEXsm column.
H
OCH3
H
B
H
H
R'
O
R'
Cl-
N
R
N
H
H
O
S
S
NaBH4
+
S
- NaCl
S
R
I
O
O
O
or
R' =
HO
O
R = methyl or benzyl
Scheme 3. Plausible mechanism of the reaction.
temperature was 320 °C. Differential scanning calorimetry analysis
was carried out by using Mettler Toledo 822e differential scanning
calorimetry system. The samples were taken in an aluminum pan
and scanned from À70 °C to 100 °C at a rate of 10 °C/min under
nitrogen atmosphere. 1H NMR, 13C NMR, mass spectra and GC chro-
matograms are given in supplementary information.
3. Conclusion
In conclusion, some new chiral ionic liquids have been synthe-
sized in good yields, starting from easily available natural chiral
precursors and 2-mercaptobenzthiazole derivatives. The synthe-
sized compounds were characterized by 1H, 13C NMR and mass
spectrometry and tested for their catalytic potential in enantiose-
lective sodium borohydride reductions of acetophenone deriva-
tives. Moderate to excellent enantiomeric excesses (ee%) have
been obtained in asymmetric reduction reactions using these chiral
ionic liquids as organocatalysts. Further application of these salts
in chiral recognition studies is still in progress.
4.2. Synthesis of (À)-menthyl chloroacetate 3a or (À)-bornyl
chloroacetate 3b
The synthesis of these optically active esters were carried out
according to the literature.19
4.3. Synthesis of 2-mercaptobenzthiazole derivatives
4. Experimental
4.1. General
2-Mercaptobenzthiazole (30 mmol, 5.02 g) was dissolved in
methanol, and then alkyl (or aryl) halide (30 mmol) was added.
Next, triethylamine (30 mmol) was added and the resulting solu-
tion was treated in a probe ultrasonicator at 25% amplitude for
3–4 h. The reaction progress was monitored by TLC and after com-
pletion of the reaction; the reaction mixture was poured into ice
cold water to give a solid mass. The crude products 2a–b were fil-
tered and recrystallized from ethanol. The melting points and NMR
data of the products were in accordance with the literature.23
All the chemicals used in the synthesis were of research grade, 2-
mercaptobenthiazole (Fluka), (À)-menthol, (À)-borneol and benzyl
chloride (Merck), Iron (III) perchlorate hydrate (Sigma–Aldrich),
choloroacetic acid (HIMEDIA), methyl iodide (LOBA Chemie) were
used without further purification. Pre coated TLC Kieselgel 60
F254 silica gel sheets (Merck) were used to study the reaction pro-
gress. Optical rotations were measured on an Anton Paar digital
polarimeter MCP 500 at 589 nm and having a cell of path length
1 dm. 1H NMR and 13C NMR spectra were recorded on Bruker
Advance II, 400 MHz NMR instrument in CDCl3 using TMS as
standard. NMR data are represented as b = broad, s = singlet,
d = doublet, dd = double doublet, t = triplet, q = quartet and
m = multiplet. The mass spectrometric (EI-MS) analysis was carried
out by using Shimadzu GCMS-QP 2010 Ultra. Enantiomeric excess
(ee) was also determined by Shimadzu GCMS-QP 2010 using
4.3.1. S-Methyl-2-mercaptobenzthiazole 2a
Yellowish solid, mp = 48–50 °C, yield = 84%, 1H NMR (CDCl3,
400 MHz): d 7.88–7.86 (d, 1H, Ar), 7.77–7.74 (d, 1H, Ar), 7.43–
7.39 (t, 1H, Ar), 7.31–7.25 (t, 1H, Ar), 2.79 (s, 3H, SCH3).
4.3.2. S-Benzyl-2-mercaptobenzthiazole 2b
Pale yellow solid, mp = 40–42 °C, yield = 79%, 1H NMR (CDCl3,
400 MHz): d 7.91–7.88 (d, 1H, Ar), 7.76–7.73 (d, 1H, Ar), 7.46–
7.40 (m, 3H, Ar), 7.35–7.25 (m, 4H, Ar), 4.60 (s, 2H, SCH2).
Rt-bDEXsm column (30 m  0.25 mm  0.25
lm) in split mode.
Helium was used as carrier gas at a flow of 0.8 mL/min and injection
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.02.008

4
A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
4.4. Synthesis of chiral ionic liquids 4a–d
was continued for 2–3 h. After the reaction was complete (as indi-
cated by TLC), the contents were added to a separatory funnel and
extracted twice with dichloromethane. The organic layers were
combined and placed over anhydrous sodium sulfate. The solvent
was then evaporated under reduced pressure to afford the
products.
(À)-1-Phenylethanol: Reaction time = 2 h, Yield = 79%, GC
analysis (Rt-bDEXsm column, column oven temperature = 120 °C,
injection temperature 230 °C, carrier gas helium, flow rate
0.80 mL/min, tR1 = 11.98 min; tR2 = 12.16 min).
To a solution of (À)-chloroacetylmenthol (5 mmol, 1164 mg) or
(À)-chloroacetylborneol (5 mmol, 1151 mg) in acetonitrile,
S-methyl/benzyl-mercaptobenzthiazole 2a or 2b (5 mmol) was
added. The reaction mixture was then refluxed and the reaction pro-
gress was checked by TLC. After completion the reaction (50–52 h),
distilled water was added and the product was extracted with
CH2Cl2 and dried over anhydrous Na2SO4. The products 4a–d were
then obtained by evaporating the solvent on a rotary evaporator.
(À)-1-(4-Bromophenyl)-ethanol:
Reaction
time = 2.5 h,
4.4.1. 3-(2-((1R,2S,5R)-2-Isopropyl-5-methylcyclohexyloxy)-2-
oxoethyl)-2-(methylthio)benzo[d]thiazol-3-ium chloride 4a
Yield = 73%, GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 18.70 min; tR2 = 18.75 min).
Reddish brown liquid, yield = 81%, [
a
]
25 = À39.7 (c 0.25, MeOH),
D
1H NMR (CDCl3, 400 MHz): d 7.87–7.85 (d, 1H, Ar), 7.74–7.72 (d,
1H, Ar), 7.41–7.37 (t, 1H, Ar), 7.28–7.24 (t, 1H, Ar), 4.79–4.72 (m,
1H), 4.02 (s, 2H, NCH2), 2.77 (s, 3H, SCH3), 2.03–1.99 (m, 1H),
1.88–1.83 (m, 1H), 1.70–1.64 (d, 2H), 1.49–1.39 (m, 2H), 1.09–
0.96 (m, 2H), 0.92–0.84 (m, 8H), 0.79–0.76 (d, 3H). 13C NMR (CDCl3,
(À)-1-(4-Hydroxyphenyl)-ethanol:
Reaction
time = 2 h,
Yield = 76%. GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 18.33 min; tR2 = 18.44 min).
(À)-1-(2-Hydroxyphenyl)-ethanol:
Reaction
time = 2 h,
100 MHz):
d
168.01, 166.85, 153.37, 135.16, 126.03, 124.93,
Yield = 73%. GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 16.75 min; tR2 = 16.84 min).
124.08, 121.47, 120.94, 71.48, 50.14, 46.92, 45.10, 40.60, 34.10,
31.64, 26.12, 23.24, 21.95, 20.69, 16.29. EI-MS: m/z = 378 [M+cation],
m/z = 363 [M+cation-CH3].
(À)-1-(4-Methoxyphenyl)-ethanol:
Reaction
time = 2 h,
Yield = 76%, GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 16.86 min; tR2 = 16.93 min).
4.4.2. 2-(Benzylthio)3-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclo-
hexyloxy)-2-oxoethyl)benzo[d]thiazol-3-ium chloride 4b
Yellowish liquid, yield = 83%, [
a
]
25 = À34.7° (c 0.25, MeOH), 1H
(À)-1-(4-Nitrophenyl)-ethanol:
Reaction
time = 2 h,
D
NMR (CDCl3, 400 MHz): d 7.90–7.88 (d, 1H, Ar), 7.74–7.72 (d, 1H,
Ar), 7.46–7.39 (m, 3H, Ar), 7.34–7.25 (m, 4H, Ar), 4.80–4.73 (m,
1H), 4.59 (s, 2H, SCH2), 4.03 (d, 2H, NCH2), 2.03–1.98 (m, 1H),
1.88–1.84 (m, 1H), 1.69–1.65 (d, 2H), 1.50–1.38 (m, 2H), 1.10–
0.96 (m, 2H), 0.97–0.85 (m, 8H), 0.81–0.75 (d, 3H). 13C NMR (CDCl3,
Yield = 72%, GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 11.50 min; tR2 = 12.70 min).
(À)-2,3-Dihydro-1H-inden-1-ol:
Reaction
time = 2.5 h,
Yield = 74%, GC analysis (Rt-bDEXsm column, carrier gas helium,
column oven temperature = 120 °C, injection temperature 230 °C,
flow rate 0.80 mL/min, tR1 = 12.49 min; tR2 = 12.70 min).
100 MHz):
d 166.92, 166.45, 153.16, 136.18, 135.33, 129.77,
128.74, 127.79, 126.09, 124.31, 121.56, 121.04, 46.93, 41.23,
40.62, 37.41, 34.11, 31.40, 26.23, 23.37, 22.00, 20.75, 16.30. EI-
MS: m/z = 454 [M+cation].
Acknowledgements
4.4.3. 2-(Methylthio)3-(2-oxo-((1S,2R,4R)-1,7,7-trimethylbicyclo
[2,2,1]heptan-2-yloxy)ethyl)benzo[d]thiazol-3-ium chloride 4c
One of the authors (Avtar Singh) is highly acknowledged to DST
(Department of Science and Technology, Govt. of India) for provid-
ing funds under INSPIRE Fellowship (INSPIRE Fellow No. IF140327).
Authors are grateful to the authorities of Sant Longowal Institute of
Engineering and Technology, Longowal (India) for providing vari-
ous research facilities. Authors are very thankful to the SAIF/CIL,
Panjab University, Chandigarh and DST-SAIF, Kochi (India) for
NMR analysis and differential scanning calorimetry analysis
respectively. Authors are also thankful to Dr. Payal Malik for fruit-
ful discussions.
Reddish brownish liquid, yield = 79%, [
a
]
25 = À20.2 (c 0.25,
D
MeOH), 1H NMR (CDCl3, 400 MHz): d 7.87–7.85 (d, 1H, Ar), 7.76–
7.74 (d, 1H, Ar), 7.43–7.34 (q, 1H, Ar), 7.32–7.26 (q, 1H, Ar),
4.99–4.96 (d, 1H), 4.06 (s, 2H, SCH2), 2.79 (s, 3H, SCH3), 2.41–
2.35 (m, 1H), 1.97–1.90 (m, 1H), 1.78–1.70 (m, 1H), 1.68–1.61
(m, 1H), 1.36–1.22 (m, 2H), 1.04–0.98 (dd, 1H), 0.90 (s, 3H), 0.88
(s, 3H), 0.86 (s, 3H). m/z = 376 [M+cation], m/z = 361 [M+cation-CH3].
4.4.4. 2-(Benzylthio)3-(2-oxo-((1S,2R,4R)-1,7,7-trimethylbicyclo
[2,2,1]heptan-2-yloxy)ethyl)benzo[d]thiazol-3-ium chloride 4d
A. Supplementary material
Pale yellow liquid, yield = 78%, [
a]
25 = À19.4 (c 0.25, MeOH), 1H
D
NMR (CDCl3, 400 MHz): d 7.90–7.88 (d, 1H, Ar), 7.75–7.73 (d, 1H,
Ar), 7.46–7.40 (m, 3H, Ar), 7.35–7.25 (m, 4H, Ar), 4.99–4.95 (d,
1H), 4.60 (s, 2H, SCH2), 4.06 (s, 2H, NCH2), 2.42–2.34 (m, 1H),
1.96–1.90 (m, 1H), 1.80–1.73 (m, 1H), 1.72–1.69(m, 1H), 1.36–
1.21 (m, 2H), 1.04–0.99 (dd, 1H), 0.90 (s, 3H), 0.88 (s, 3H), 0.84
(s, 3H). 13C NMR (CDCl3, 100 MHz): d 167.58, 166.41, 153.17,
136.19, 135.33, 129.13, 128.70, 127.75, 126.06, 124.42, 121.65,
121.05, 48.93, 47.94, 44.84, 41.18, 37.72, 36.54, 27.96, 26.97,
19.66, 18.81, 13.45. m/z = 452 [M+cation].
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2017.02.
008.
References
1. (a) Plechkova, N. V.; Seddon, K. R. Chem. Soc. Rev. 2008, 37, 123–150; (b) Han,
D.; Row, K. H. Molecules 2010, 15, 2405–2426; (c) Silvester, D. S. Analyst 2011,
36, 4871–4882; (d) Osada, I.; de Varies, H.; Scrosati, B.; Passerini, S. Angew.
Chem. Int. Ed. 2016, 55, 500–513.
2. For details about the physicochemical properties of ionic liquids, see (a) Zhang,
S.; Sun, N.; He, X.; Lu, X.; Zhang, X. J. Phys. Chem. Ref. Data 2006, 35, 1475–1517;
(b) Wilkes, J. S. J. Mol. Catal. A: Chem. 2004, 214, 11–17; (c) Deetlefs, M.; Seddon,
K. R.; Shara, M. Phys. Chem. Chem. Phys. 2006, 8, 642–649; (d) Greaves, T. L.;
Drummond, C. J. Chem. Rev. 2008, 108, 206–237; (e) Tshibangu, P. N.;
Ndwandwe, S. N.; Dikio, E. D. Int. J. Electrochem. Sci. 2011, 6, 2201–2213.
3. Reviews on applications of ionic liquids in organic synthesis (a) Welton, T.
Chem. Rev. 1999, 99, 2071–2083; (b) Olivier-Bourbigou, H.; Magna, L.; Morvan,
4.5. Procedure for NaBH4 reduction of ketones in the presence
of chiral ionic liquids18a,19
A mixture of prochiral ketone (2 mmol) and chiral ionic liquid
(10 mol%) was taken in a flask. Sodium borohydride (3 mmol)
was then added to the flask with constant stirring and stirring
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.02.008

A. Singh, H. K. Chopra / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
5
D. Appl. Catal. A 2010, 373, 1–56; (c) Sowmiah, S.; Cheng, C. I.; Chu, Y.-H. Curr.
Org. Synth. 2012, 9, 74–95; (d) Hajipour, A. R.; Rafiee, F. Org. Prep. Proc. Int. 2015,
47, 1–60; (e) Heckel, T.; Konieczna, D. D.; Wilhelm, R. Catalysts 2013, 3, 914–
921.
Tetrahedron: Asymmetry 2015, 26, 1069–1082; (e) Jayachandra, R.; Reddy, S. R.
RSC Adv. 2016, 6, 39758–39761.
12. (a) Yu, J.; Zuo, L.; Liu, H.; Zhang, L.; Guo, X. Biomed. Chromatogr. 2013, 27, 1027–
1033; (b) Zhang, Q.; Du, Y. 2013, 1306, 97–103; (c) Sanchez, F. G.; Diaz, A. N.;
Torreno, E. S.; Aguilar, A.; Lama, I. M.; Algarra, M. Biomed. Chromatogr. 2012, 26,
1241–1246; (d) Zhang, J.; Du, Y.; Zhang, Q.; Lei, Y. Talanta 2014, 119, 193–201.
13. (a) Li, P.; Wang, L.; Zhang, Y.; Wang, G. Tetrahedron 2008, 64, 7633–7638; (b)
Vasiloiu, M.; Leder, S.; Gaertner, P.; Mereiter, K.; Bica, K. Org. Biomol. Chem.
2013, 11, 8092–8102; (c) Xu, D.-Z.; Liu, Y.; Shi, S.; Wang, Y. Tetrahedron:
Asymmetry 2010, 21, 2530–2534; (d) Duan, S.; Jing, X.; Li, D.; Jing, H. J. Mol.
Catal. A: Chem. 2016, 411, 34–39.
14. (a) Prechtl, M. H. G.; Scholten, J. D.; Neto, B. A. D.; Dupont, J. Curr. Org. Chem.
2009, 13, 1259–1277; (b) Bica, K.; Gaertner, P. Eur. J. Org. Chem. 2008, 3235–
3250; (c) Ni, B.; Headly, A. D. Chem. Eur. J. 2010, 16, 4426–4436.
15. (a) Nakamura, K.; Yamanaka, R.; Matsuda, T.; Harada, T. Tetrahedron:
Asymmetry 2003, 14, 2659–2681; (b) Han, M. L.; Hu, X.-P.; Huang, J.-D.;
Chen, L.-G.; Zheng, Z. Tetrahedron: Asymmetry 2011, 22, 222–225.
16. (a) Wu, X.; Li, X.; McConville, M.; Saidi, O.; Xiao, J. J. Mol. Catal. A: Chem. 2006,
247, 153–158; (b) Foubelo, F.; Najera, C.; Yus, M. Tetrahedron: Asymmetry 2015,
26, 769–790; (c) Azizoglu, M.; Erdogan, A.; Arslan, N.; Turgut, Y.; Hosgoren, H.;
Pirinccioglu, N. Tetrahedron: Asymmetry 2016, 27, 769–790.
4. (a) Pandey, S. Anal. Chim. Acta 2006, 556, 38–45; (b) Stockmann, T. J.; Zhang, J.;
Montgomery, A.-M.; Ding, Z. Anal. Chim. Acta 2014, 821, 41–47; (c) Yang, J.;
Wang, Q.; Zhang, M.; Zhang, S.; Zhang, L. Food Chem. 2015, 187, 1–6.
5. (a) Buszewski, B.; Studzinska, S. A. Chromatographia 2008, 68, 1–10; (b) Huang,
Y.; Yao, S.; Song, H. J. Chromatogr. Sci. 2013, 51, 739–752; (c) Berthod, A.; Ruiz-
Angel, M. J.; Carda-Broch, S. J. Chromatogr. A 2008, 1184, 6–18.
6. (a) Zhao, H.; Xia, S.; Ma, P. J. Chem. Technol. Biotecnol. 2005, 80, 1089–1096; (b)
Sukhbaatar, T.; Dourdain, S.; Turgis, R.; Rey, J.; Arrachart, G.; Pellet-Roastaing, S.
Chem. Commun. 2015, 15960–15963; (c) Tang, B.; Bi, W.; Tian, M.; Row, K. H. J.
Chromatogr. B 2012, 904, 1–21; (d) Poole, C. F.; Poole, S. K. J. Chromatogr. A 2010,
1217, 2268–2286.
7. (a) Kubisa, P. J. Polym. Sci. A Polym. Chem. 2013, 43, 4675–4683; (b) Ye, Y.-S.;
Rick, J.; Hwang, B.-J. J. Mater. Chem. A 2013, 1, 2719–2743.
8. (a) Li, N.; Bai, X.; Zhang, S.; Gao, Y.; Zheng, L.; Zhang, J.; Ma, H. J. Dispersion Sci.
Technol. 2008, 29, 1059–1061; (b) Richter, K.; Campbell, P. S.; Baecker, T.;
Schimitzek, A.; Yaprak, D.; Mudring, A.-V. Phys. Status Solidi B 2013, 250, 1152–
1164.
9. (a) Baudequin, C.; Baudoux, J.; Levillain, J.; Cahard, D.; Gaumont, A.-C.;
Plaquevent, J. C. Tetrahedron: Asymmetry 2003, 14, 3081–3093; (b) Li, J.; Hu,
F.; Xie, X.-K.; Liu, F.; Huang, Z.-Z. Catal. Commun. 2009, 11, 276–279; (c)
Larionova, N. A.; Kucherenko, A. S.; Siyutkin, D. E.; Zlotin, S. G. Tetrahedron
2011, 67, 1948–1954; (d) Vasiloiu, M.; Rainer, D.; Gaertner, P.; Reichel, C.;
Schroder, C.; Bica, K. Catal. Today 2013, 200, 80–86; (e) Singh, A.; Chopra, H. K.
17. (a) Matsuda, T.; Yamanaka, R.; Nakamura, K. Tetrahedron: Asymmetry 2009, 20,
513–557; (b) Vitale, P.; D’Introno, C.; Perna, F. M.; Perrone, M. G.; Scilimati, A.
Tetrahedron: Asymmetry 2013, 24, 389–394.
18. (a) Hajipour, A. R.; Karimi, F. Synth. Commun. 2010, 40, 1784–1793; (b) Chen,
D.; Schmitkamp, M.; Francio, G.; Klankermayer, J.; Leitner, W. Angew. Chem.
2008, 120, 7449–7451; (c) Vasiloiu, M.; Gaertner, P.; Zirbas, R.; Bica, K. Eur. J.
Org. Chem. 2015, 2374–2381.
Curr.
Org.
Synth.
2016.
http://dx.doi.org/10.2174/
1570179413666160818145415.
19. Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry 2016, 27, 448–453.
20. (a) Parmar, A.; Kumar, H. Ultrason. Sonochem. 2008, 15, 129–132; (b) Kaur, B.;
Parmar, A.; Kumar, H. Synth. Commun. 2012, 42, 447–453; (c) Parmar, A.;
Kumar, H. Synth. Commun. 2007, 37, 2301–2308; (d) Kaur, B.; Parmar, A.;
Kumar, H. J. Chem. Sci. 2013, 125, 989–992; (e) Puri, S.; Kaur, B.; Parmar, A.;
Kumar, H. Ultrason. Sonochem. 2009, 16, 705–707; (f) Puri, S.; Kaur, B.; Parmar,
A.; Kumar, H. Org. Prep. Proc. Int. 2012, 44, 91–95.
21. (a) Schulz, P. S.; Muller, N.; Bosmann, A.; Wasserscheid, P. Angew. Chem. Int. Ed.
2007, 46, 1293–1295; (b) Wgner, V.; Schulz, P. S.; Wasserscheid, P. J. Mol. Liq.
2014, 192, 177–184.
10. (a) Tran, C. D.; Oliveira, D. Anal. Biochem. 2006, 356, 51–58; (b) Qing, H.; Jiang,
X.; Yu, J. Chirality 2014, 26, 160–165; (c) Mu, X.; Qi, L.; Zhang, H.; Shen, Y.; Qiao,
J.; Ma, H. Talanta 2012, 97, 349–354; (d) Yujiao, W.; Guoyan, W.; Wenyan, Z.;
Hongfen, Z.; Huanwang, J.; Anjia, C. Biomed. Chromatogr. 2014, 28, 610–614; (e)
Sun, X.; Xu, J.; Zhao, X.; Zhai, Y.; Xing, J. Chromatographia 2013, 76, 1013–1019;
(f) Absalan, G.; Alipour, Y.; Rezaei, Z.; Akhond, M. Anal. Methods 2012, 4, 2283–
2287.
11. (a) Yu, S.; Lindeman, S.; Tran, C. D. J. Org. Chem. 2008, 73, 2576–2591; (b)
Bwambok, D. K.; Marwani, H. M.; Fernand, V. E.; Fakayode, S. O.; Lowry, M.;
Negulescu, I.; Strongin, R. M.; Warner, I. M. Chirality 2008, 20, 151–158; (c)
Heckel, T.; Winkel, A.; Wilhelm, R. Tetrahedron: Asymmetry 2013, 24, 1127–
1133; (d) Vasiloiu, M.; Cervenka, I.; Gaertner, P.; Weil, M.; Schroder, C.; Bica, K.
22. Stassen, H. K.; Ludwig, R.; Wulf, A.; Dupont, J. Chem. Eur. J. 2015, 21, 1–13.
23. Deligeorgiev, T.; Kaloyanova, S.; Lesev, N.; Vaquero, J. J. Ultrason. Sonochem.
2010, 17, 783–788.
Please cite this article in press as: Singh, A.; Chopra, H. K. Tetrahedron: Asymmetry (2017), http://dx.doi.org/10.1016/j.tetasy.2017.02.008