Ultrasonic assisted dimeric cinchona based chiral phase transfer catalysts for highly enanatioselective synthesis of epoxidation of α,β-unsaturated ketones

Article abstract of DOI:10.1039/c4ra10952j

New types of bis-quaternary ammonium bromide as chiral multisite phase transfer catalysts derived from cinchona alkaloids have been developed and evaluated for the enantioselective epoxidation of chalcones in the presence of lower concentrations of various oxidants, bases and ultrasonic irradiation conditions. Under optimized conditions, excellent chemical yields of up to 98% along with the highest enantioselectivities of about 98% were obtained by using the reported catalysts.

Full text of DOI:10.1039/c4ra10952j

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Ultrasonic assisted dimeric cinchona based chiral
phase transfer catalysts for highly enanatioselective
synthesis of epoxidation of a,b-unsaturated
ketones†
Cite this: RSC Adv., 2014, 4, 60293
Jayaraman Sivamani, Veeramanoharan Ashokkumar, Velu Sadhasivam,
*
Kumaraguru Duraimurugan and Ayyanar Siva
New types of bis-quaternary ammonium bromide as chiral multisite phase transfer catalysts derived from
cinchona alkaloids have been developed and evaluated for the enantioselective epoxidation of chalcones
in the presence of lower concentrations of various oxidants, bases and ultrasonic irradiation conditions.
Under optimized conditions, excellent chemical yields of up to 98% along with the highest
enantioselectivities of about 98% were obtained by using the reported catalysts.
Received 22nd September 2014
Accepted 27th October 2014
DOI: 10.1039/c4ra10952j
www.rsc.org/advances
1. Introduction
Enantioselective asymmetric epoxidation of electron decient
olens, particularly a,b-unsaturated ketones such as chalcones,
have been investigated and reported under bi functional chiral
phase transfer catalysts.1 The chiral phase transfer catalyst
mediated reactions have unique features due to their simplicity
and many advantages including non-metal containing
compounds as well as environmental friendliness.2 Recently Lygo
et al.,3 and Corey et al.,4 have reported the 9-anthracenylmethyl
group containing cinchona based chiral catalyst 1 with the
commercially available 65% sodium hypochlorite solution as an
oxidant at ꢀ40 ꢁC for the effective epoxidation of chalcones with
moderate yields and ee's. Further, Keiji Maruoka et al.,5 reported
the enantioselective epoxidation of chalcones with good yields
and ee's in the presence of binapthyl based chiral catalysts 2 with
Fig. 1 Previously reported CPTCs.
ꢁ
13% NaOCl at 0 C, but the reaction was carried out longer, i.e.
24–187 h. Even though there are numerous reports6,7 available for
the enantioselective epoxidation of chalcones, their full potential
is yet to be reached or explained in terms of both enantiose-
lectivity and general applicability. Previously reported enantio-
selective epoxidation reactions were carried out at low
temperature (ꢀ40–0 ꢁC). Hence, we focused on the enantiose-
lectivity and the chemical yield of epoxidation reactions (Scheme
1) using new types of bis-quaternary ammonium bromides as
chiral multi-site phase transfer catalysts (CMPTCs 10, Scheme 2)
and ultrasonic irradiation effectively removing the need for
temperature under mild reaction conditions. The chemicals such
Scheme 1 Enantioselective synthesis of chiral epoxidation of chal-
cones under CMPTC conditions.
as catalysts, oxidants and bases are reduced with the substrate for
simplifying the process in keeping with the basic principles of
green chemistry (Fig. 1).
Department of Inorganic Chemistry, School of Chemistry, Madurai Kamaraj
University, Madurai 625 021, Tamilnadu, India. E-mail: drasiva@gmail.com;
ptcsiva@yahoo.co.in; Tel: +91-451-2458471
2. Results and discussion
Asymmetric epoxidation serves as a versatile building block
for the synthesis of metal free organic frameworks. The three-
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra10952j
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Scheme 2 Synthesis of bis quaternary ammonium ion as CMPTC for asymmetric epoxidation reaction.
membered ring system containing epoxide is high ring strain fact that longer reaction times would affect the epoxidation
intermediate, which is more useful for a variety of nucleo- reaction rate which can reduce the yield and enantiomeric
philic ring-opening reactions. Hence, we focused to optimize excess (entries 9–24, Table 1). The formation of higher
the reaction conditions. First, we focused our attention on chemical yields and ee's may be due to the interaction of
nding optimal basic and oxidant conditions for the enan- oxidants (NaOCl) with the b carbon atom of chalcone from
tioselective epoxidation of chalcone in the presence of the upside direction in the 1,4-addition to afford the cong-
different bases under ultrasonic irradiation. It was found that uration of aS and bR isomer 4. The chalcone is located
(entries 1–24, Table 1), the maximum yields and ee's were between the two cinchona units, either in 10a or 10b and the
obtained when KtOBu was used as a base for the epoxidation b-phenyl group of chalcone has a p–p stacking interaction
reaction (entries 3 and 4, Table 1) rather than the other bases with one of the quinoline moieties of the cinchona alkaloid
such as NaOH, KOH, K2CO3 and Cs2CO3. Further, we and also the spacer chain of the stilbene aromatic group has
observed higher chemical yields (99%), and ee's (81%) for the p–p stacking interaction with the chalcone aromatic group
epoxidation of chalcones in the presence of NaOCl as a (Fig. 2). Similarly, the enolate anion of the carbonyl oxygen
oxidant with lesser time; i.e. less than 1 h and other oxidants atom is placed as close to the R4N+ of the catalyst as possible
such as H2O2, PMS, and APS used for this reaction gave good due to van der Waals interactions (Fig. 3). The formation of
yields and moderate ee's. Stereoselectivity was not improved lower yields and ee's, when 10a was used as a CMPTC, R4N+
on changing the oxidants (entries 5–24, Table 1) nor by of the catalyst is ion paired with the oxidant ion and also
changing the base concentrations (entries 5–24, Table 1) for hydrogen bonded with the C9 free –OH containing ammo-
this reaction. Furthermore, we found from Table 1, that the nium salt (10a).
dimeric catalyst 10a showed a moderate yield (up to 98%) and
With these optimized conditions, we then tested the
enantiomeric excess (77–80%) in the presence of PMS, APS epoxide reaction in the presence of different concentrations of
and H2O2 as oxidants (entries 5–8, Table 1), but the reaction catalysts 10 (Table 2). In general, all homogeneous catalysis
times were somewhat higher (3–7 h). This may be due to the reaction rates are directly proportional to the catalyst
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Table 1 Effect of various bases, oxidants and CMPTCs (10) for enan-
tioselective epoxidation reaction
Time Yielda % of eeb
Entry Base
Oxidant Catalyst (h)
(%)
(Abs. conf.)c
1
2
3
4
5
6
7
8
KtOBu
H2O2
H2O2
NaOCl
NaOCl
PMSd
PMSd
APSd
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
3.0
3.0
1.0
1.0
3.5
3.5
3.3
3.3
3.5
3.5
3.5
3.5
5.0
5.0
5.0
5.0
7.0
7.0
7.0
7.0
6.5
6.5
6.5
6.5
95
97
99
96
98
92
91
93
94
95
98
95
96
98
95
97
88
89
91
90
90
93
98
95
73 (2S,3R)
64 (2S,3R)
81 (2S,3R)
79 (2S,3R)
78 (2S,3R)
77 (2S,3R)
80 (2S,3R)
77 (2S,3R)
73 (2S,3R)
65 (2S,3R)
73 (2S,3R)
74 (2S,3R)
77 (2S,3R)
66 (2S,3R)
72 (2S,3R)
76 (2S,3R)
69 (2S,3R)
59 (2S,3R)
67 (2S,3R)
74 (2S,3R)
67 (2S,3R)
59 (2S,3R)
78 (2S,3R)
80 (2S,3R)
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
KtOBu
NaOH
NaOH
NaOH
NaOH
KOH
APSd
9
H2O2
H2O2
NaOCl
NaOCl
H2O2
H2O2
NaOCl
NaOCl
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Fig.
2
Formation of p–p interaction between the spacer chain
KOH
KOH
KOH
(aromatic) of all the CMPTCs with aromatic ring of the chalcones.
Cs2CO3 H2O2
Cs2CO3 H2O2
Cs2CO3 NaOCl
Cs2CO3 NaOCl
K2CO3
K2CO3
K2CO3
K2CO3
H2O2
H2O2
NaOCl
NaOCl
a
b
Isolated yield of puried materials. Enantiomeric excess of 4 was
determined by HPLC analysis using a chiral column (Phenomenex
c
Chiralpack) with hexane–IPA as
a
solvent.
The absolute
conguration of 4 was determined to be (2S,3R) by comparison with
d
the HPLC retention time using known standard.8 PMS – pottassium
peroxy monosulphate, APS – ammonium peroxysulphate.
concentration. Based on the observed results, the catalyst
amount was increased from 1 mol% to 15 mol% for the
epoxidation reaction and the ee's reduced from 81% to 78%
for 10a and 84% to 79% for 10b as catalysts respectively. This
may be due to the catalyst poison taking place in this reaction
irrespective of the catalysts 10a and 10b (entries 1–10, Table 2).
Furthermore, the free C9-OH containing catalyst 10a is more
efficient than the allyl protected catalyst 10b (entries 1–10,
Table 2), because the free –OH containing the catalyst has
more binding with the chalcone and oxidants. Similar reports
were reported by Jew et al., for the enantioselective epoxidation
of chalcone in the presence of various cinchona based alka-
loids as PTCs.9 Generally, the enantioselective epoxidation
reactions were not carried out with both the nucleophile and
electrophile in the same phase. But, in our case, the epoxida-
tion reaction is carried out in the presence of both the nucle-
ophile and electrophile in the organic phase under phase-
transfer reaction conditions, and also the reaction times
Fig. 3 C2 symmetric trans-cinchona bis catalysts strong binding with
the enolate anion of the chalcone and peroxides due to electrostatic
attraction.
were considerably less than the previously reported reaction.7
Such fast enantioselective phase-transfer reactions may
inuence the chemical yields and the enantioselectivities
(Table 3).
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3. Conclusions
In summary, we have successfully synthesized bis-quaternary
ammonium bromides as chiral phase transfer catalysts 10 for
highly enantioselective epoxidation of various a,b-unsaturated
ketones 3 under mild phase-transfer catalysis and ultrasonic
irradiation conditions. In our system, the catalyst provides a
ready to access wide range of useful synthetic transformations
having higher chemical yields and enantiomeric purity. We
believe that the new concept of the present synthetic design
would be valid for the development of other enantioselective
asymmetric phase-transfer reactions using the nucleophiles
being supplied to an aqueous inorganic salt to prochiral
electrophiles.
Table 2 The asymmetric epoxidation of chalcone 3 under various
concentration of CMPTCs 10 (10a/10b)
mol% of
catalyst
Time
(min)
Yielda
(%)
% of eeb
Entry
Catalyst
(Abs. conf.)c
1
2
3
4
5
6
7
8
9
10
10a
10a
10a
10a
10a
10b
10b
10b
10b
10b
1.0
3.0
5.0
10.0
15.0
1.0
3.0
5.0
10.0
15.0
90
75
60
45
25
90
75
60
45
25
93
95
99
96
98
95
96
96
97
98
81 (2S,3R)
81 (2S,3R)
81 (2S,3R)
79 (2S,3R)
78 (2S,3R)
84 (2S,3R)
83 (2S,3R)
79 (2S,3R)
80 (2S,3R)
79 (2S,3R)
4. Experimental section
4.1. Materials and methods
All the chemicals and reagents used in this work were of
analytical grade. Allylbromide, (+)-cinchonine were obtained
from Alfa Aesar, 4-methylbezaldehyde, N-bromosuccinimide,
potassium tert-butoxide, cesium carbonate and potassium
carbonate were obtained from Sigma Aldrich, sodium hyroxide,
pottassium hydroxide, were obtained from Merck and all the
Solvents were obtained from Laboratory Grade.
a
b
Isolated yield of puried materials. Enantiomeric excess of 4 was
determined by HPLC analysis using a chiral column (Phenomenex
c
Chiralpack) with hexane–IPA as
a
solvent.
The absolute
conguration of 4 was determined to be (2S,3R) by comparison of the
HPLC retention time with known data.8
The melting points were measured in open capillary tubes
1
and are uncorrected. The H and 13C NMR spectra were recor-
ded on a Bruker (Avance) 300 and 400 MHz NMR instrument
Table 3 Catalytic asymmetric epoxidation of chalcone derivatives 3 under CMPTCs conditions
Entry
Enone (3)
Ar1
Ar2
Catalyst
Producta
Yieldb (%)
% of eec
Abs. conf.d
1
2
3
4
5
6
7
8
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
3f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
4-Me-C6H4
4-Me-C6H4
4-OMe-C6H4
4-OMe-C6H4
4-Cl-C6H4
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
10a
10b
4a
4a
4b
4b
4c
4c
4d
4d
4e
4e
4f
99
96
94
94
95
96
97
97
95
97
95
95
96
96
98
98
81
79
78
80
83
82
93
92
78
86
82
86
86
89
98
94
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
(2S,3R)
4-Cl-C6H4
4-NO2-C6H4
4-NO2-C6H4
4-Me-C6H4
4-Me-C6H4
4-OMe-C6H4
4-OMe-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-NO2-C6H4
4-NO2-C6H4
9
10
11
12
13
14
15
16
3f
4f
3g
3g
3h
3h
4g
4g
4h
4h
a
The asymmetric epoxidation of chalcones 3 (0.1 mmol), NaOCl (1 mmol), CMPTCs 10 (10a/10b 5 mol%), with 1 mL toluene and 0.5 mL of 10%
KtOBu in ultrasonic conditions. b Isolated yield of puried materials. c Enantiopurity of 4 was determined by HPLC analysis using a chiral column
(Phenomenex Chiralpack) with hexane-IPA as a solvent. d The absolute conguration of 4 was determined to be (2S,3R) by comparison of the HPLC
retention time with known data.8
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using TMS as internal standard and CDCl3 as a solvent. Stan- chromatography (MeOH/CH2Cl2: 1/10) to give a yellow oil (3.205
dard Bruker soware was used throughout. Chemical shis are g, 87% yield). 1H NMR (300 MHz, CDCl3) dH 8.88 (d, J ¼ 4.4 Hz,
given in parts per million (d-scale) and the coupling constants 1H), 8.16–8.08 (m, 2H), 7.71 (dd, J ¼ 8.2, 7.1 Hz, 1H), 7.59–7.53
are given in Hertz. Silica gel-G plates (Merck) were used for TLC (m, 1H), 7.48 (d, J ¼ 4.3 Hz, 1H), 5.98–5.86 (m, 1H), 5.70 (dd, J ¼
analysis with a mixture of n-hexane and ethyl acetate as an 12.0, 5.1 Hz, 1H), 5.22 (dd, J ¼ 12.0, 5.1 Hz, 3H), 4.96 (d, J ¼ 10.0
eluent. Column chromatography was carried out in silica gel Hz, 1H), 4.87 (d, J ¼ 10.4 Hz, 1H), 3.97–3.91 (m, 1H), 3.87–3.80
(60–120 mesh) using n-hexane and ethyl acetate as an eluent. (m, 1H), 3.40 (s, 1H), 3.07 (dd, J ¼ 13.0, 10.3 Hz, 2H), 2.62 (d, J ¼
Electrospray Ionization Mass Spectrometry (ESI-MS) analyses 4.3 Hz, 1H), 2.24 (s, 1H), 1.78 (s, 1H), 1.51 (d, J ¼ 10.0 Hz, 3H),
were recorded in LCQ Fleet, Thermo Fisher Instruments 1.24 (s, 1H), 0.87–0.76 (m, 1H). 13C NMR (75 MHz, CDCl3) dC
Limited, US. ESI-MS was performed in positive ion mode. The 150.05, 148.40, 146.52, 141.80, 134.31, 130.35, 129.09, 126.72,
collision voltage and ionization voltage were ꢀ70 V and ꢀ4.5 kV, 126.41, 123.10, 118.39, 116.89, 114.23, 70.08, 60.53, 57.01,
respectively, using nitrogen as atomization and desolvation gas. 43.17, 39.93, 27.79, 22.03.
The desolvation temperature was set at 300 ꢁC. The relative
amount of each component was determined from the LC-MS
chromatogram, using the area normalization method. The
HPLC were recorded in SHIMADZU LC-6AD with Chiral Column
(Phenomenex Chiralpack), using HPLC grade n-hexane and
isopropanol solvents.
4.5. Synthesis of CMPTCs (10) from (E)-4,4-
bis(bromomethyl)stilbene (7)
4.5.1. Synthesis of cinchonine (contains free C9-OH) based
CMPTC (10a). A mixture of (E)-4,4-bis(bromomethyl)stilbene 7
(0.1 g, 10 mmol), O-allylcinchonine 9 (30 mmol) was dissolved
in 5 mL of THF : ACN (1 : 1 ratio) and was reuxed for over-
night, the white solid was ltered off, washed with diethylether
and dried it, to get pure di-site chiral PTC (10a); (95% yield). 1H
NMR (400 MHz, CDCl3) dH 8.90 (d, J ¼ 4.2 Hz, 2H), 8.07 (d, J ¼
8.3 Hz, 2H), 7.97 (d, J ¼ 4.7 Hz, 4H), 7.92 (s, 2H), 7.85 (d, J ¼ 4.4
Hz, 2H), 7.80 (d, J ¼ 7.9 Hz, 2H), 7.66 (dd, J ¼ 19.1, 5.9 Hz, 4H),
7.61 (d, J ¼ 8.4 Hz, 2H), 7.36 (s, 2H), 6.05 (s, 2H), 5.84 (dd, J ¼
17.5, 7.5 Hz, 2H), 5.58 (d, J ¼ 11.9 Hz, 2H), 5.32–5.19 (m, 2H),
5.14 (s, 4H), 4.20 (s, 2H), 3.67–3.58 (m, 2H), 3.29–3.13 (m, 4H),
3.13–2.96 (m, 4H), 2.91 (d, J ¼ 12.2 Hz, 2H), 1.83 (d, J ¼ 18.1 Hz,
4H), 1.73–1.65 (m, 4H), 1.61–1.56 (m, 2H). 13C NMR (100 MHz,
CDCl3) dC 150.10, 149.41, 148.11, 147.81, 139.12, 134.67, 130.21,
129.83, 129.76, 129.00, 126.75, 125.30, 122.90, 119.58, 118.38,
115.65, 69.97, 59.99, 49.94, 49.10, 39.29, 27.83, 25.32, 21.78,
20.12. ESI-MS (M3+); 954.74.
4.2. Preparation of (E)-4,40-dimethylstilbene (6)10
4-Methylbenzaldehyde 5 (1 mmol), Zn (5 mmol) was dissolved
in THF and the reaction mass was cooled to 0 ꢁC. Further, TiCl4
(5 mmol) was added slowly into the reaction mass under
Nitrogen atmosphere. Finally the reaction mixture was stirred at
room temperature for about 24 h, aer completion of the
starting material; the reaction mixture was poured into the
saturated NH4Cl solution and ltered through celite pad,
extracted with ethyl acetate and washed with brine solution and
concentrated it. The crude material was puried by column
chromatography (n-hexane as an eluent). Yield is 96%. 1H NMR
(300 MHz, CDCl3) dH 7.41 (d, J ¼ 8.1 Hz, 2H), 7.17 (d, J ¼ 8.2 Hz,
2H), 7.05 (s, 1H), 2.36 (s, 3H). 13C NMR (75 MHz, CDCl3) dC
137.18, 134.79, 129.30, 127.68, 126.28, 21.12.
4.5.2. Synthesis of allylated cinchonine based CMPTC
(10b). A mixture of (E)-4,40-bis(bromomethyl)stilbene 7 (0.1 g, 10
mmol), O-allylcinchonine 9 (30 mmol) was dissolved in 5 mL of
EtOH : DMF : ACN (30 : 50 : 20 v/v) and heated to reux for
about overnight, the off white solid was ltered, washed with
diethylether and dried it, to get pure di-site chiral PTC (10b);
4.3. Preparation of (E)-4,40-bis(bromomethyl)stilbene (7)11
The (E)-4,40-dimethylstilbene 6 was brominated by NBS and
CCl4 in the presence of AIBN. Aer reuxing 6 h, completion of
starting material, the reaction mixture was quenched with water
and extracted with ethyl acetate, washed with brine and dried
over sodium sulphate. Concentrated it and puried by column
chromatography (Pet. ether as eluent). Yield is 60%, m.p. 176–
1
(96% yield). H NMR (400 MHz, CDCl3) dH 8.92 (d, J ¼ 3.4 Hz,
2H), 8.23–8.02 (m, 6H), 8.03–7.95 (m, 2H), 7.82 (d, J ¼ 7.7 Hz,
4H), 7.73 (d, J ¼ 6.3 Hz, 4H), 7.57 (d, J ¼ 7.7 Hz, 2H), 7.49 (s, 2H),
6.27–5.99 (m, 4H), 5.96–5.82 (m, 2H), 5.39 (d, J ¼ 17.8 Hz, 4H),
5.30–5.14 (m, 6H), 4.58–4.41 (m, 2H), 4.21 (s, 4H), 4.03–3.94 (m,
2H), 3.53–3.33 (m, 4H), 2.83 (d, J ¼ 9.9 Hz, 2H), 2.42 (d, J ¼ 10.9
Hz, 2H), 2.09 (s, 4H), 1.92–1.68 (m, 8H). 13C NMR (100 MHz,
CDCl3) dC 149.77, 148.43, 142.43, 135.89, 134.97, 133.26, 132.49,
132.40, 130.33, 130.11, 129.91, 128.17, 125.39, 123.49, 119.93,
118.20, 117.87, 70.59, 70.45, 60.11, 49.33, 48.32, 37.01, 27.52,
22.98, 22.16, 18.47. ESI-MS (M3+); 1034.93.
1
ꢁ
178 C. H NMR (300 MHz, CDCl3) dH 7.49 (d, J ¼ 7.8 Hz, 2H),
7.43 (d, J ¼ 8.1 Hz, 2H), 7.29 (s, 1H), 4.54 (s, 2H). 13C NMR (75
MHz, CDCl3) dC 139.11, 138.44, 129.44, 128.33, 127.73, 32.72.
4.4. Preparation of O-allylcinchonine (9)12
To the solution of (+)-cinchonine 8 (3 g, 0.01 mmol) in dried
DMF was added NaH (0.61 g, 60% suspension in mineral oil,
0.025 mmol). The resulting mixture was stirred at room
temperature for 2 h. Then allylbromide (1.35 g, 0.01 mmol) was
added drop wisely in 5 minutes. The resulting mixture was
stirred overnight. When the reaction was completed, brine (35
4.6. General method A for synthesis of chalcones (3a–h)12,13
mL) was added carefully and the resulting mixture was extracted Acetophenone (5 mmol) and aromatic aldehyde (5 mmol) were
with ethyl acetate (3 ꢂ 20 mL), the organic phase was washed dissolved in 2 mL of ethanol and 10% sodium hydroxide was
with brine (3 ꢂ 50 mL), dried over sodium sulphate, and added, the mixture was stirred for 5 min. Aer completion of
concentrated in vacuo. The residue was puried by the reaction, the mixture was poured into ice; the precipitate
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was ltered and recrystallized with ethanol, to get pure
chalcone.
4.6.7. Preparation
of
(E)-1-(4-bromophenyl)-3-(4-
chlorophenyl)prop-2-en-1-one (3g). Synthesized according to
General method A using 4-chlorobenzaldehyde (0.76 g, 5 mmol)
and 4-bromoacetophenone (1 g, 5 mmol); white solid; (98%
yield). m.p. 164–168 ꢁC; 1H NMR (300 MHz, CDCl3) dH 7.88 (d, J
¼ 6.9 Hz, 2H), 7.76 (d, J ¼ 15.7 Hz, 1H), 7.65 (d, J ¼ 8.3 Hz, 2H),
7.57 (d, J ¼ 6.9 Hz, 2H), 7.48 (d, J ¼ 15.7 Hz, 1H), 7.40 (d, J ¼ 8.7
Hz, 2H). 13C NMR (75 MHz, CDCl3) dC 188.89, 143.74, 136.61,
136.57, 133.07, 131.89, 129.92, 129.58, 129.20, 121.69.
4.6.1. Preparation of (E)-1-phenyl-3-p-tolylprop-2-en-1-one
(3a). Synthesized according to General method A using p-tol-
ualdehyde (1.09 g, 5 mmol) and acetophenone (1 g, 5 mmol);
white solid; (98% yield). m.p. 96–97 ꢁC; 1H NMR (300 MHz,
CDCl3) dH 8.05–8.00 (d, J ¼ 8.0 Hz, 2H), 7.80 (d, J ¼ 15.7 Hz, 1H),
7.59–7.48 (m, 6H), 7.24 (d, J ¼ 8.0 Hz, 2H), 2.40 (s, 3H). 13C NMR
(75 MHz, CDCl3) dC 190.32, 144.82, 141.05, 138.37, 132.71,
132.18, 129.75, 128.62, 128.52, 121.09, 121.0, 21.53.
4.6.8. Preparation
of
(E)-1-(4-bromophenyl)-3-(4-
4.6.2. Preparation
of
(E)-3-(4-methoxyphenyl)-1-
nitrophenyl) prop-2-en-1-one (3h). Synthesized according to
General method A using 4-nitrobenzaldehyde (0.76 g, 5 mmol)
and 4-bromoacetophenone (1 g, 5 mmol); orange solid; (98%
yield). m.p. 164–168 ꢁC; 1H NMR (300 MHz, CDCl3) d 8.30 (d, J ¼
8.7 Hz, 2H), 7.90 (t, J ¼ 9.5 Hz, 2H), 7.80 (d, J ¼ 8.5 Hz, 3H), 7.69
(d, J ¼ 8.5 Hz, 2H), 7.60 (d, J ¼ 15.7 Hz, 2H). 13C NMR (75 MHz,
CDCl3) dC 189.66, 148.56, 141.51, 141.05, 137.53, 133.38, 128.94,
128.83, 128.60, 125.72, 124.22.
phenylprop-2-en-1-one (3b). Synthesized according to General
method A using 4-methoxybenzaldehyde (1.11 g, 5 mmol) and
acetophenone (1 g, 5 mmol); pale yellow solid; (98% yield). m.p.
80–82 ꢁC; 1H NMR (300 MHz, CDCl3) d 8.03 (d, J ¼ 7.0 Hz, 2H),
7.81 (d, J ¼ 15.6 Hz, 1H), 7.65–7.57 (m, 3H), 7.51 (d, J ¼ 7.3 Hz,
2H), 7.43 (d, J ¼ 15.6 Hz, 1H), 6.95 (d, J ¼ 8.7 Hz, 2H), 3.87 (s, 3H).
13C NMR (75 MHz, CDCl3) dC 190.17, 161.33, 144.32, 138.14,
132.19, 129.87, 128.20, 128.05, 127.24, 119.40, 114.07, 54.56.
4.6.3. Preparation of (E)-3-(4-chlorophenyl)-1-phenylprop-
2-en-1-one (3c). Synthesized according to General method A
using 4-chlorobenzaldehyde (1.17 g, 5 mmol) and acetophenone
4.7. General procedure for catalytic epoxidation of enones
under CMPTCs conditions (4a–h)
(1 g, 5 mmol); pale yellow solid; (98% yield). m.p. 113–114 ꢁC; 1H To a mixture of enone 4 (10 mg 0.1 mmol), NaOCl (1 mmol) and
NMR (300 MHz, CDCl3) dH 8.03 (d, J ¼ 7.0 Hz, 2H), 7.77 (d, J ¼ CMPTCs 10 (10a/10b, 5 mol%) was dissolved in 1 mL of toluene
15.7 Hz, 1H), 7.64–7.55 (m, 3H), 7.55–7.51 (m, 2H), 7.49 (d, J ¼ and added 0.5 mL of 10% aq. KtOBu. Then the reaction mixture
15.7 Hz, 1H), 7.40 (d, J ¼ 8.5 Hz, 2H). 13C NMR (75 MHz, CDCl3) was ultra sonicated until chalcone disappeared (detected by
dC 190.07, 143.18, 137.93, 133.30, 132.85, 129.51, 129.15, 128.59, TLC), aer that the reaction mixture was extracted with ethyl
128.42, 122.37.
acetate, washed with water (3 ꢂ 2 mL). Further, the reaction
4.6.4. Preparation of (E)-3-(4-nitrophenyl)-1-phenylprop-2- mixture was washed with brine (5 mL), dried over sodium
en-1-one (3d). Synthesized according to General method A sulphate and concentrated it. The crude material was puried by
using 4-nitrobenzaldehyde (1.23 g, 5 mmol) and acetophenone column chromatography with petroleum ether and ethyl acetate
1
ꢁ
(1 g, 5 mmol); orange solid; (98% yield). m.p. 138–140 C; H as eluent gave the epoxidation product. The enantiomeric excess
NMR (300 MHz, CDCl3) d 8.31 (d, J ¼ 8.8 Hz, 2H), 8.06 (d, J ¼ 8.4 was determined by chiral stationary-phase HPLC analysis.
Hz, 2H), 7.82 (dd, J ¼ 17.9, 11.1 Hz, 3H), 7.66 (dd, J ¼ 11.4, 7.6
4.7.1. Characterization of epoxidation compounds (4a–h)
trans-(2S,3R)-Epoxy-3-(4-methylphenyl)-1-phenylproan-1-one (4a).
Hz, 2H), 7.60–7.51 (m, 2H). 13C NMR (75 MHz, CDCl3) dC 189.66,
148.56, 141.51, 141.05, 137.53, 133.38, 128.94, 128.83, 128.60, White solid, m.p. 69–71 ꢁC; 1H NMR (300 MHz, CDCl3) dH 7.82 (d, J
125.72, 124.22.
¼ 7.5 Hz, 2H), 7.44 (t, J ¼ 7.3 Hz, 1H), 7.34 (t, J ¼ 7.6 Hz, 2H), 7.06
4.6.5. Preparation of (E)-1-(4-bromophenyl)-3-p-tolylprop- (d, J ¼ 7.9 Hz, 2H), 6.96 (d, J ¼ 7.9 Hz, 2H), 4.42 (d, J ¼ 6 Hz, 1H),
2-en-1-one (3e). Synthesized according to General method A 4.33 (d, J ¼ 6 Hz, 1H), 2.18 (s, 3H). 13C NMR (75 MHz, CDCl3) dC
using 4-methylbenzaldehyde (0.66 g, 5 mmol) and 4-bromoa- 197.69, 137.37, 136.85, 136.63, 133.00, 129.09, 128.13, 128.06,
cetophenone (1 g, 5 mmol); white solid; (98% yield). m.p. 145– 65.14, 58.22, 21.03. The enantiomeric excess was determined by
147 ꢁC; 1H NMR (300 MHz, CDCl3) d 7.89 (d, J ¼ 8.2 Hz, 2H), 7.81 HPLC, Phenomenex Chiralpack, 254 nm, hexane : IPA ¼ 90 : 10,
(d, J ¼ 15.6 Hz, 1H), 7.69–7.58 (m, 4H), 7.37 (d, J ¼ 15.6 Hz, 1H), ow rate ¼ 1 mL minꢀ1, retention time: 7.81 min (major), 19.29
6.96 (d, J ¼ 8.6 Hz, 2H), 3.88 (s, 3H). 13C NMR (75 MHz, CDCl3) min (minor).
dC 189.32, 161.87, 145.26, 137.23, 131.85, 130.36, 129.96, 127.61,
127.42, 118.98, 114.38, 21.53.
trans-(2S,3R)-Epoxy-3-(4-methoxylphenyl)-1-phenylproan-1-one
(4b). Light yellow solid, m.p. ¼ 81–82 C; H NMR (300 MHz,
1
ꢁ
4.6.6. Preparation
of
(E)-1-(4-bromophenyl)-3-(4- CDCl3) d 8.11 (d, J ¼ 7.0 Hz, 2H), 7.75–7.66 (m, 3H), 7.61 (d, J ¼
methoxyphenyl) prop-2-en-1-one (3f). Synthesized according to 7.5 Hz, 2H), 7.04 (d, J ¼ 8.7 Hz, 2H), 4.42 (d, J ¼ 6 Hz, 1H), 4.33
General method A using 4-methoxybenzaldehyde (0.75 g, 5 (d, J ¼ 6 Hz, 1H), 2.39 (s, 3H). 13C NMR (75 MHz, CDCl3) dC
mmol) and 4-bromoacetophenone (1 g, 5 mmol); white solid; 197.69, 161.52, 144.51, 132.38, 130.06, 128.39, 128.24, 119.59,
(98% yield). m.p. 165–167 ꢁC; 1H NMR (300 MHz, CDCl3) dH 7.88 114.26, 65.14, 58.22, 55.22. The enantiomeric excess was
(d, J ¼ 8.5 Hz, 2H), 7.80 (d, J ¼ 15.7 Hz, 1H), 7.64 (d, J ¼ 8.5 Hz, determined by HPLC, Phenomenex Chiralpack, 254 nm, hex-
2H), 7.54 (d, J ¼ 8.1 Hz, 2H), 7.43 (d, J ¼ 15.7 Hz, 1H), 7.23 (d, J ¼ ane : IPA ¼ 90 : 10, ow rate ¼ 1 mL minꢀ1, retention time: 7.88
7.9 Hz, 2H), 2.39 (s, 3H). 13C NMR (75 MHz, CDCl3) dC 189.34, min (major), 37.12 min (minor).
145.41, 141.26, 137.06, 131.84, 129.95, 129.72, 128.54, 127.66,
120.52, 120.43, 21.10.
trans-(2S,3R)-Epoxy-3-(4-chlorophenyl)-1-phenylproan-1-one (4c).
Yellow solid, m.p. ¼ 68–71 ꢁC; 1H NMR (300 MHz, CDCl3) dH 8.03
(d, J ¼ 7.0 Hz, 2H), 7.62–7.56 (m, 3H), 7.55–7.51 (m, 2H), 7.40 (d, J
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¼ 8.5 Hz, 2H), 4.42 (d, J ¼ 6 Hz, 1H), 4.33 (d, J ¼ 6 Hz, 1H). 13C 2012-13), University Grants Commission, New Delhi, India
NMR (75 MHz, CDCl3) dC 197.69, 137.93, 133.30, 132.85, 129.51, (Grant No. UGC no. 41-215/2012 (SR) and Council of Scientic
129.15, 128.59, 128.42, 65.14, 58.22. The enantiomeric excess was and Industrial Research, New Delhi, India (Grant no. 01(2540)/
determined by HPLC, Phenomenex Chiralpack, 254 nm, hex- 11/EMR-II).
ane : IPA ¼ 90 : 10, ow rate ¼ 1 mL minꢀ1, retention time: 7.87
min (major), 20.11 min (minor).
trans-(2S,3R)-Epoxy-3-(4-nitrophenyl)-1-phenylproan-1-one (4d).
References
1
ꢁ
Yellow solid, m.p. ¼ 140–142 C; H NMR (300 MHz, CDCl3) d
1 For recent reviews, see: (a) M. J. Porter and J. Skidmore,
8.31 (d, J ¼ 8.8 Hz, 2H), 7.82 (dd, J ¼ 17.9, 11.1 Hz, 3H), 7.66 (dd, J
Chem. Commun., 2000, 1215; (b) T. Nemoto, T. Ohshima
¼ 11.4, 7.6 Hz, 2H), 7.60–7.51 (m, 2H), 4.42 (d, J ¼ 6 Hz, 1H), 4.33
(d, J ¼ 6 Hz, 1H). 13C NMR (75 MHz, CDCl3) dC 197.69, 148.56,
and M. Shibasaki, J. Synth. Org. Chem., Jpn., 2002, 60, 94;
´
´
´
(c) D. Dıez, M. G. Nunez, A. B. Anton, P. Garcıa, R. F. Moro,
N. M. Garrido, I. S. Marcos, P. Basabe and J. G. Urones,
Curr. Org. Synth., 2008, 5, 186.
141.05, 137.53, 133.38, 128.94, 128.83, 128.60, 124.22, 65.14,
58.22. The enantiomeric excess was determined by HPLC, Phe-
nomenex Chiralpack, 254 nm, hexane : IPA ¼ 90 : 10, ow rate ¼
1 mL minꢀ1, retention time: 7.90 min (major), 61.97 min (minor).
trans-(2S,3R)-Epoxy-1-(4-bromophenyl)-3-(4-methylphenyl)proan-1-
one (4e). White solid, m.p. 100–101 ꢁC; 1H NMR (300 MHz, CDCl3)
d 7.88 (d, J ¼ 8.2 Hz, 2H), 7.67–7.57 (m, 4H), 6.94 (d, J ¼ 8.6 Hz, 2H),
4.42 (d, J ¼ 6 Hz, 1H), 4.33 (d, J ¼ 6 Hz, 1H), 2.18 (s, 3H). 13C NMR
(75 MHz, CDCl3) dC 197.69, 161.87, 137.23, 131.85, 130.36, 129.96,
127.42, 118.98, 114.38, 65.14, 58.22, 21.03. The enantiomeric
excess was determined by HPLC, Phenomenex Chiralpack, 254
nm, hexane : IPA ¼ 90 : 10, ow rate ¼ 1 mL minꢀ1, retention
time: 7.89 min (major), 46.84 min (minor).
2 For recent representative reviews, see: (a) M. J. O'Donnell, in
Catalytic Asymmetric Synthesis, ed. I. Ojima, Verlag Chemie,
New York, 1993, ch. 8; (b) T. Shioiri and S. Arai, in
Stimulating Concepts in Chemistry, ed. F. Vogtle, J. F. Stoddart
and M. Shibasaki, WILEY-VCH, Weinheim, 2000, p. 123.
3 (a) B. Lygo and P. G. Wainwright, Tetrahedron Lett., 1998, 39,
1599; (b) B. Lygo and P. G. Wainwright, Tetrahedron, 1999,
55, 6289; (c) B. Lygo and D. C. M. To, Tetrahedron Lett.,
2001, 42, 1343.
4 E. J. Corey and F.-Y. Zhang, Org. Lett., 1999, 1, 1287.
5 T. Ooi, D. Ohara, M. Tamura and K. Maruoka, J. Am. Chem.
Soc., 2004, 126, 6844.
6 For other important contributions, see: (a) Y. Harigaya,
H. Yamaguchi and M. Onda, Heterocycles, 1981, 15, 183; (b)
N. Baba, J. Oda and M. Kawaguchi, Agric. Biol. Chem., 1986,
50, 3113; (c) S. Arai, H. Tsuge and T. Shioiri, Tetrahedron
Lett., 1998, 39, 7563; (d) S. Arai, H. Tsuge, M. Oku,
M. Miura and T. Shioiri, Tetrahedron, 2002, 58, 1623; (e)
W. Adam, P. B. Rao, H.-G. Degen, A. Levai, T. Patonay and
trans-(2S,3R)-Epoxy-1-(4-bromophenyl)-3-(4-methoxylphenyl)
proan-1-one (4f). Light yellow solid, m.p. ¼ 81–82 ꢁC; 1H NMR
(300 MHz, CDCl3) dH 7.88 (d, J ¼ 8.5 Hz, 2H), 7.64 (d, J ¼ 8.5
Hz, 2H), 7.54 (d, J ¼ 8.1 Hz, 2H), 7.23 (d, J ¼ 7.9 Hz, 2H), 4.42
(d, J ¼ 6 Hz, 1H), 4.33 (d, J ¼ 6 Hz, 1H), 2.39 (s, 3H). 13C NMR
(75 MHz, CDCl3) dC ¼ 197.69, 145.41, 137.06, 131.84, 129.97,
129.72, 128.51, 127.66, 65.14, 58.22, 21.24. The enantiomeric
excess was determined by HPLC, Phenomenex Chiralpack,
254 nm, hexane : IPA ¼ 90 : 10, ow rate ¼ 1 mL minꢀ1
,
¨
C. R. Saha-Moller, J. Org. Chem., 2002, 67, 259; (f) J. Ye,
retention time: 7.88 min (major), 23.46 min (minor).
Y. Wang, R. Liu, G. Zhang, Q. Zhang, J. Chen and X. Liang,
Chem. Commun., 2003, 2714; (g) M. T. Allingham,
A. Howard-Jones, P. J. Murphy, D. A. Thomas and
P. W. R. Caulkett, Tetrahedron Lett., 2003, 44, 8677.
7 Y. Zhu, Q. Wang, R. G. Cornwall and Y. Shi, Chem. Rev., 2014,
114, 8199.
8 S. Arai, H. Tsuge and T. Shioiri, Tetrahedron Lett., 1998, 39,
7563.
9 (a) S.-s. Jew, J.-H. Lee, B.-S. Jeong, M.-S. Yoo, M.-J. Kim,
Y.-J. Lee, J. Lee, S.-h. Choi, K. Lee, M. S. Lah and
H.-g. Park, Angew. Chem., Int. Ed., 2005, 44, 1383; (b)
S.-s. Jew and H.-g. Park, Chem. Commun., 2009, 7090.
trans-(2S,3R)-Epoxy-1-(4-bromophenyl)-3-(4-chlorophenyl)proan-1-
one (4g). White solid, m.p. 65–66 ꢁC; 1H NMR (300 MHz, CDCl3) dH
7.88 (d, J ¼ 8.3 Hz, 2H), 7.64 (d, J ¼ 6.9 Hz, 2H), 7.57 (d, J ¼ 6.9 Hz,
2H), 7.40 (d, J ¼ 8.7 Hz, 2H), 4.42 (d, J ¼ 6 Hz, 1H), 4.33 (d, J ¼ 6
Hz, 1H). 13C NMR (75 MHz, CDCl3) dC ¼ 197.69, 168.44, 167.81,
136.57, 133.07, 131.89, 129.92, 129.58, 129.20, 128.00, 65.14,
58.22. The enantiomeric excess was determined by HPLC, Phe-
nomenex Chiralpack, 254 nm, hexane : IPA ¼ 90 : 10, ow rate ¼
1 mL minꢀ1, retention time: 7.91 min (major), 22.60 min (minor).
trans-(2S,3R)-Epoxy-1-(4-bromophenyl)-3-(4-nitrophenyl)proan-
1
1-one (4h). White solid, m.p. 130–132 ꢁC; H NMR (300 MHz,
CDCl3) dH 8.30 (d, J ¼ 8.7 Hz, 2H), 7.80 (d, J ¼ 8.5 Hz, 2H), 7.69 (d,
J ¼ 8.5 Hz, 2H), 7.60 (d, J ¼ 8.7 Hz, 2H), 4.42 (d, J ¼ 6 Hz, 1H), 4.33
(d, J ¼ 6 Hz, 1H). 13C NMR (75 MHz, CDCl3) dC 197.69, 148.56,
141.05, 137.53, 133.38, 128.94, 128.83, 128.60, 124.22, 65.14,
58.22. The enantiomeric excess was determined by HPLC, Phe-
nomenex Chiralpack, 254 nm, hexane : IPA ¼ 90 : 10, ow rate ¼
1 mL minꢀ1, retention time: 7.91 min (major), 63.48 min (minor).
¨
10 J. W. Feast, W. P. Lovenich, H. Pushmann and C. Taliani,
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K. Gouthamchandra, R. Jairamc, R. Mahmood and
R. Sankolli, Eur. J. Med. Chem., 2012, 55, 467; (b)
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Acknowledgements
We acknowledge the nancial support of the Department of
Science and Technology, New Delhi, India (Grant no. SR/F/1584/
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 60293–60299 | 60299