Organocatalysis in the stereoselective bromohydrin reaction of alkenes

Article abstract of DOI:10.1139/V10-053

An efficient regio- and stereo-selective (>99:1) trans-bromohydrination (bromohydroxylation and bromomethoxylation) of alkenes including α,β-unsaturated carbonyl compounds with N-bromosuccinimide (NBS) has been achieved by using 1.0 mol% of N,N'-diarylthi

Full text of DOI:10.1139/V10-053

605
Organocatalysis in the stereoselective
bromohydrin reaction of alkenes
Sukanta Bar
Abstract: An efficient regio- and stereo-selective (>99:1) trans-bromohydrination (bromohydroxylation and bromomethoxy-
lation) of alkenes including a,b-unsaturated carbonyl compounds with N-bromosuccinimide (NBS) has been achieved by
using 1.0 mol% of N,N’-diarylthiourea catalyst.
Key words: thiourea, N-halosuccinimide, alkene.
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Resume : On a pu realiser des bromohydrinations trans (bromohydroxylation et bromomethoxylation) d’alcenes regio- et
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stereo-selectives (>99:1) efficaces, y compris des composes carbonyles a,b-insatures, sous l’action du N-bromosuccinimide
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(NBS), en presence de 1,0 mole % de N,N’-diarylthiouree comme catalyseur.
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Mots-cles : thiouree, N-halosuccinimide, alcene.
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[Traduit par la Redaction]
1,2-Halofunctionalization of olefins, for example, halohy-
drin reaction (halohydroxylation and haloalkoxylation) is an
important transformation in organic chemistry.1 The result-
ing 1,2-halohydroxy and alkoxyhalide compounds are versa-
tile precursors in organic, medicinal, as well as industrial
chemistry.2 Owing to the immense importance of vicinal
halohydrins, a number of methods have been developed for
the reaction of aqueous (alcoholic) solutions of alkenes with
molecular halogens, N-halosuccinimides (NXSs),3 TsNBr2,4
N-halosaccharin,5 and metal halides along with an oxidizing
agent.6 Cheap and available NXSs, in particular N-bromo-
succinimide (NBS) and N-chlorosuccinimide (NCS), are the
choice of halogen sources over other hazardous reagents.
However, longer reaction times and low yields, especially
of electron-deficient alkenes, are major hitches. Some at-
tempts are made to improve the reaction by performing in
ionic liquids.7 Herein, we report highly efficient N,N’-
diarylthiourea-catalyzed (1.0 mol% of N,N’-diarylthiourea
(PhNHCSNHPh)) 1,2-bromohydrin reaction of alkenes, in-
cluding a,b-unsaturated carbonyl compounds with high
regio- and diastereo-selectivity (>99:1).
Recently, organocatalysis has become a vast area of re-
search, while interest in catalysis of thiourea has grown.8 In
my continued efforts towards the development of new cata-
lytic methods for the regio- and stereo-selective 1,2-halofunc-
tionalization of alkenes, Lewis acids like metal triflates were
found to activate NXS for the transfer of halogen to alkenes
(Scheme 1).9 This led us to anticipate that unlike Lewis acid,
thiourea derivatives having hydrogen-bonding capability with
carbonyl oxygen might catalyze the electrophilic halogen
transfer from NXS to the olefins (Fig. 1). Recently, thiourea-
catalyzed (H2NCSNH2; 20 mol%) chlorohydrin reaction of al-
kenes was reported by Bentley et al. with poor-to-moderate
stereoselectivity and yields.10
Scheme 1. Lewis acid catalyzed 1,2-halofunctionalization of al-
kenes.
In search for an effective thiourea catalyst for the bromohy-
drin reaction, we first studied the reaction of trans-stilbene 1a
with NBS in aqueous CH3CN with N,N’-diarylthiourea 3 and
simple thiourea, and the results are presented in Table 1. Com-
pared with the non-catalytic reaction (5 h, 56% yield; Table 1,
entry 1), N,N’-diphenylthiourea-catalyzed bromohydrin reaction
of stilbene 1a proceeded very fast at RT, and within 5 min, it
afforded the desired bromohydroxylation product 2a in 86%
yield (Table 1, entry 3) along with 8% of 1,2-dibromostilbene.
Further improvement of the yield as well as product distribu-
tion was observed when the reaction was performed at 0 8C,
1
and no 1,2-dibromostilbene was detected by H NMR spec-
trum analysis of the crude reaction mixture (Table 1, entry 4).
There was no appreciable change in the reactivity and selec-
tivity with thiourea 3b, and 3c containing electron-rich and
electron-deficient arenes, respectively (Table 1, entries 5 and
6), while Thiourea 3d provided the desired product, with 65%
yield along with 16% of the 1,2-dibromostilbene.
In search for an appropriate solvent for the bromohydrin re-
action, we first studied the reaction of trans-stilbene (1a) and
NBS with 1 mol% N,N’-diarylthiourea (PhNHCSNHPh, 3a)
in different solvents. Common organic solvents were used
Received 15 December 2009. Accepted 25 March 2010. Published on the NRC Research Press Web site at canjchem.nrc.ca on 28 May
2010.
S. Bar. Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India. (e-mail: sukantachem@yahoo.com).
Can. J. Chem. 88: 605–612 (2010)
doi:10.1139/V10-053
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Can. J. Chem. Vol. 88, 2010
Fig. 1. Proposed activation of N-bromosuccinimide (NBS) by N,N’-
diarylthiourea.
In summary, we have developed an efficient and general
catalytic method for the bromohydrin reaction (bromohy-
droxylation and bromomethoxylation) of alkenes in the pres-
ence of only 1.0 mol% of N,N’-diarylthiourea using NBS as
halogen source with excellent anti-selectivity and yields.
Experimental section
General methods
Commercial-grade reagents were used without further pu-
rification. Solvents were dried and distilled following usual
protocols. Flash chromatography was carried out using Ran-
kem Silica gel (230–400 mesh) purchased from Rankem, In-
dia. TLC was performed on aluminium-backed plates coated
with Silica gel 60 with F254 indicator (Merck).
for this purpose. Acetone, THF, 1,4-dioxane, and 1,2-dime-
thoxyethane gave 45%–61% yield of the desired product
along with 1,2-dibromostilbene as the byproduct. Other sol-
vents gave very poor results. Acetonitrile was found to be
the best solvent with 95% yield of the desired product. De-
tailed results of the solvent study are summarized in Table 2.
Thus, the best result was obtained when substrate 1a was
treated with 0.01 equiv. of thiourea (PhNHCSNHPh, 3a) and
1.2 equiv. of NBS in 20% aqueous acetonitrile at 0 8C for
1 h. To establish the generality of the thiourea-catalyzed
bromohydrin reaction, it was investigated on other alkenes,
namely, b-propylstyrene, 1,2-dihdronaphthalene, and indene.
All underwent smooth reaction at 0 8C and provided corre-
sponding bromohydrins in excellent yields within an hour
(Table 1, entries 8, 10, and 12).
The 1H NMR spectra were measured on Bruker-200
(200 MHz) and Bruker-400 (400 MHz) spectrometers, and
13C NMR spectra were measured on Bruker-200 (50 MHz)
1
and Bruker-400 (100 MHz) spectrometers using CDCl3. H
NMR chemical shifts are expressed in ppm (d) downfield to
CHCl3 (d = 7.26), and 13C NMR chemical shifts are ex-
pressed in ppm (d) relative to the central CDCl3 resonance
1
(d = 77.0). Coupling constants in H NMR are in Hz. Ele-
mental analyses were carried out on a PerkinElmer 2400-II,
Department of Chemistry, Indian Institute of Technology,
Kharagpur. Melting points were measured in Toshniwal
(India) melting point apparatus. IR spectra were recorded us-
ing PerkinElmer Spectrum R Â I FTIR Spectrometer.
When these alkenes were subjected to bromohydrin reac-
tion at 25 8C, reactions were completed within 5 min but
with 8%–10% less yields, which is due to the formation of
dibromide as the byproduct (Table 1, entries 7, 9, and 11).
In all the above cases, these reactions were anti-selective
General procedure for the N,N’-diarylthiourea-catalyzed
halohydrin reaction of alkenes
Bromohydrination of stilbene 1a
1
and no cis-isomer was formed as revealed by the H NMR
To a well-stirred solution of trans-stilbene (1a) (0.10 g,
0.55 mmol) in 2.75 mL CH3CN:H2O (4:1), PhNHCSNHPh
(1.2 mg, 0.0055 mmol) and NBS (0.118 g, 0.66 mmol)
were added, and the reaction mixture was allowed to stir at
0 8C under argon atmosphere. Progress of the reaction was
monitored by TLC. After 1 h, the solvent was evaporated
under reduced pressure at RT. The crude reaction mass was
subjected to purification by flash column chromatography
using 5% EtOAc in petroleum ether (60–80 8C) to obtain
( )-2a11 (0.146 g, 95%) as a white solid; mp 83–86 8C
spectrum of the crude mixture.
Unfortunately for compounds containing isolated double
bonds like cyclohexene, the reaction was less satisfying, as
a messy reaction mixture was obtained. Similar result was
obtained for ethyl acrylate.
a,b-Unsaturated carbonyls usually undergo slow bromohy-
drin reaction with poor yields of the desired bromohydrins.
So, this catalytic method was studied for a large number of
a,b-unsaturated carbonyls like cinnamates and chalcones
(Table 2). Reaction of methyl cinnamate 4a under the cata-
lytic conditions afforded the desired bromohydrin in 91%
yield at RT after 5 h (Table 3, entry 1) compared with 60%
yield after 18 h for the non-catalytic reaction carried out with
1.6 equiv. of NBS (not shown in Table 3). Electron-rich
cinnamates 4b and 4c provided corresponding bromohydrins
in excellent yields at 0 8C (Table 3, entries 2 and 3).
3,4-Methylenedioxycinnamate (4d) behaved similar to cin-
namate (4a) (Table 3, entry 4). Similar trend was also ob-
served for chalcones. Thus, electron-rich substrates preferred
to show clean reaction at 0 8C, while other substrates reacted
at RT (Table 3, entries 5–10).
1
(lit.11 mp 83–84 8C). H NMR (200 MHz, CDCl3) d: 2.18
(bs, 1H), 5.10 (d, J = 6.8 Hz, 1H), 5.21 (d, J = 6.8 Hz, 1H),
7.36 (m, 10H). Bromohydrin compounds 2b,12 2c,13 2d,14
1
5a,15 5b,15 and 5e16 were characterized by H and 13C NMR
and compared with the reported literature data.
2-Bromo-3-(3,4-dimethoxyphenyl)-3-hydroxy-propionic
acid methyl ester (5c)
Yield: 95%; white solid; mp 133 8C. Rf (25% EtOAc/petro-
leum ether): 0.16. IR (KBr, cm–1) n: 751, 819, 872, 1021, 1037,
1
1142, 1156, 1244, 1274, 1462, 1508, 1747, 3457. H NMR
(200 MHz, CDCl3) d: 3.1 (d, J = 4.8 Hz, 1H), 3.82 (s, 3H),
3.88 (s, 3H), 3.90 (s, 3H), 4.36 (d, J = 8.0 Hz, 1H), 5.04 (dd,
J = 8.0, 4.8 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.93 (m, 2H).
13C NMR (100 MHz, CDCl3) d: 47.6, 53.1, 55.79, 55.83, 74.9,
109.5, 110.7, 119.6, 131.5, 148.9, 149.2, 169.8. Anal. calcd. for
C12H15BrO5: C, 45.16; H, 4.74. Found: C, 45.32; H, 4.51.
To increase the scope of the reaction, we decided to study the
bromomethoxylation reaction of a variety of alkenes. When
methanolic solutions of alkenes, including a,b-unsaturated
carbonyls, were subjected to N,N’-diarylthiourea-catalyzed
bromomethoxylation reaction with NBS, they produced me-
thoxybromides in excellent yields (Table 4).
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Table 1. N,N’-diarylthiourea-catalyzed bromohydrination of alkenes 1.
Table 2. N,N’-Diarylthiourea-catalyzed bromohydrination of alkene 1a with different solvents.
Entry
1
2
3
4
5
6
7
8
Substarte
1a
1a
1a
1a
1a
1a
1a
1a
Solvent
CH3CN
(CH3)2CO
CH2Cl2
CH3Cl
Yield of 2a (%)
Yield of 1,2-dibromo stilbenea(%)
95
56
12
18
10
21
45
8
0
17
15
10
9
12
18
4
CCl4
Cl(CH2)2Cl
OMe(CH2)2OMe
Toluene
THF
9
10
1a
1a
61
48
19
16
1,4-Dioxane
1
aDetermined from the H NMR spectra of the crude reaction mixture with naphthalene as an internal standard.
3-Benzo[1,3]dioxol-5-yl-2-bromo-3-hydroxypropionic acid
methyl ester (5d)
NMR (200 MHz, CDCl3): 3.82 (s, 3H), 4.31 (d, J = 8.6 Hz,
1H), 5.0 (d, J = 8.6 Hz, 1H), 5.98 (s, 2H), 6.82 (m, 3H). 13C
NMR (100 MHz, CDCl3) d: 47.5, 53.2, 74.9, 101.2, 107.0,
108.1, 120.9, 132.8, 147.7, 147.8, 169.8. Anal. calcd. for
C11H11BrO5: C, 43.59; H, 3.66. Found: C, 43.67; H, 3.65.
Yield: 91%; white solid; mp 75 8C. Rf (10% EtOAc/petro-
leum ether): 0.18. IR (KBr, cm–1) n: 814, 929, 1009, 1042,
1
1249, 1297, 1440, 1488, 1504, 1717, 1741, 3418 (br). H
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Can. J. Chem. Vol. 88, 2010
Table 3. N,N’-Diarylthiourea-catalyzed bromohydrination of a,b-unsaturated carbonyls with
NBS in 20% aqueous CH3CN.
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Table 4. N,N’-Diarylthiourea-catalyzed bromomethoxylation of alkenes with NBS in
MeOH.
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Can. J. Chem. Vol. 88, 2010
2-Bromo-3-hydroxy-3-(4-methoxyphenyl)-1-phenylpropan-
1-one (5f)
128.5 (2C), 128.7 (2C), 128.8 (2C), 128.9 (2C), 134.28,
134.31 (2C), 137.8, 194.3. Anal. calcd. for C15H12BrClO2:
C, 53.05; H, 3.56. Found: C, 53.42; H, 3.17.
Yield: 95%; white solid; mp 58 8C. Rf (15% EtOAc/petro-
leum ether): 0.16. IR (KBr, cm–1) n: 625, 684, 811, 834,
1002, 1037, 1176, 1217, 1251, 1282, 1449, 1516, 1594,
Bromomethoxylation of stilbene 1a
1
To a well-stirred solution of trans-stilbene (1a) (0.10 g,
0.55 mmol) in 2.75 mL MeOH, PhNHCSNHPh (1.2 mg,
0.0055 mmol) and NBS (0.118 g, 0.66 mmol) were added,
and the reaction mixture was allowed to stir at 0 8C under
argon atmosphere. Progress of the reaction was monitored
by TLC. After 1 h, the solvent was evaporated at RT under
reduced pressure. The crude reaction mass was subjected to
purification by flash column chromatography using 5%
EtOAc in petroleum ether (60–80 8C) to obtain ( )-6a6d
(0.153 g, 95%) as a white solid; mp 115–118 8C (lit.17 mp
1611, 1679, 2836, 3466 (br). H NMR (200 MHz, CDCl3)
d: 3.45 (d, J = 4.6 Hz, 1H), 3.82 (s, 3H), 5.2 (d, J = 8.4 Hz,
1H), 5.31 (dd, J = 8.6, 4.6 Hz, 1H), 6.92 (m, 2H), 7.37–7.66
(m, 5H), 8.03 (m, 2H). 13C NMR (100 MHz, CDCl3) d: 48.2,
55.2, 74.2, 113.8 (2C), 128.4 (2C), 128.8 (2C), 128.9 (2C),
131.6, 134.1, 134.5, 159.7, 194.6. Anal. calcd. for
C16H15BrO3: C, 57.33; H, 4.51. Found: C, 57.21; H, 4.22.
2-Bromo-3-(3,4-dimethoxyphenyl)-3-hydroxy-1-
phenylpropan-1-one (5g)
1
116–118 8C). H NMR (200 MHz, CDCl3) d: 3.20 (s, 3H),
Yield: 94%; white solid; mp 130 8C. Rf (20% EtOAc/pe-
troleum ether): 0.22. IR (KBr, cm–1) n: 635, 690, 812, 979,
1027, 1135, 1229, 1251, 1463, 1447, 1511, 1595, 1685,
4.65 (d, J = 6.8 Hz, 1H), 5.04 (d, J = 6.8 Hz, 1H), 7.30 (m,
10H). Spectral data of compounds 6c,18 6e, and 6i are con-
sistent with the reported literature data.
1
3498. H NMR (200 MHz, CDCl3) d: 3.45 (d, J = 4.4 Hz,
1H), 3.89 (s, 3H), 3.92 (s, 3H), 5.2 (d, J = 8.2 Hz, 1H), 5.3
(dd, J = 8.8, 4.0 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 7.03 (m,
2H), 7.49 (m, 2H), 7.63 (m, 1H), 8.02 (m, 2H). 13C NMR
(100 MHz, CDCl3) d: 48.2, 55.81, 55.87, 74.5, 109.9, 110.7,
119.8, 128.8 (2C), 128.9 (2C), 131.9, 134.1, 134.5, 148.8,
149.0, 194.6. Anal. calcd. for C17H17BrO4: C, 55.91; H,
4.69. Found: C, 56.06; H, 4.64.
(2-Bromo-methoxypentyl)-benzene (6b)
Yield:: 87%; gummy liquid. Rf (3% EtOAc/petroleum
ether): 0.45. IR (KBr, cm–1) n: 585, 624, 702, 760, 956,
1
1093, 1134, 1168, 1188, 1454, 1494, 2933, 2960. H NMR
(200 MHz, CDCl3) d: 0.92 (t, J = 7.2 Hz, 3H), 1.37–1.94
(m, 4H), 3.34 (s, 3H), 4.19 (m, 1H), 4.40 (d, J = 5.6 Hz,
1H), 7.39 (m, 5H). 13C NMR (100 MHz, CDCl3) d: 13.3,
20.8, 34.9, 57.5, 59.5, 86.7, 127.6 (2C), 128.1, 128.16 (2C),
138.5. Anal. calcd. for C12H17BrO: C, 56.04; H, 6.66.
Found: C, 56.13; H, 6.59.
2-Bromo-3-hydroxy-1-(2-methoxyphenyl)-3 phenylpropan-
1-one (5h)
Yield: 93%; gummy liquid. Rf (10% EtOAc/petroleum
ether): 0.20. IR (KBr, cm–1) n: 567, 756, 930, 979, 1031,
1176, 1250, 1356, 1448, 1514, 1613, 1675, 2054, 2838,
2-Bromo-1-methoxy-1,2,3,4-tetrahydronaphthalene (6d)
Yield: 93%; liquid. Rf (3% EtOAc/petroleum ether): 0.62.
IR (KBr, cm–1) n: 601, 748, 817, 937, 1078, 1117, 1214,
1
3470 (br). H NMR (200 MHz, CDCl3) d: 3.90 (s, 3H), 5.27
(d, J = 7.8 Hz, 1H), 5.62 (d, J = 7.8 Hz, 1H), 7.0 (m, 2H),
7.31–7.55 (m, 6H), 7.78 (dd, J = 7.8, 1.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d: 48.2, 55.2, 74.2, 113.8 (2C), 128.5
(2C), 128.8 (2C), 128.9 (2C), 131.6, 134.1, 134.5, 159.6,
194.4. Anal. calcd. for C16H15BrO3: C, 57.33; H, 4.51.
Found: C, 57.41; H, 4.43.
1
1438, 1455, 1492, 2821, 2928. H NMR (200 MHz, CDCl3)
d: 2.12–2.25 (m, 1H), 2.42–2.56 (m, 1H), 2.77–2.88 (m,
1H), 2.90–3.15 (m, 1H), 3.54 (s, 3H), 4.48 (d, J = 4.0 Hz,
1H), 4.65 (m, 1H), 7.13–7.35 (m, 4H). 13C NMR
(100 MHz, CDCl3) d: 25.8, 26.9, 49.6, 57.4, 81.4, 126.2,
128.3, 128.8, 130.2, 132.9, 135.6. Anal. calcd. for
C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.64; H, 5.34.
2-Bromo-3-(4-fluorophenyl)-3-hydroxy-1-phenylpropan-1-
one (5i)
2-Bromo-3-methoxy-3-(4-methoxyphenyl)-propionic acid
methyl ester (7b)
Yield: 93%; white solid; mp 80 8C. Rf (5% EtOAc/petro-
leum ether): 0.20. IR (KBr, cm–1) n: 548, 686, 814, 836,
1009, 1159, 1231, 1281, 1449, 1594, 1608, 1682, 3298 (br).
1H NMR (200 MHz, CDCl3) d: 3.47 (bs, 1H), 5.15 (d, J =
8.4 Hz, 1H), 5.33 (d, J = 8.4 Hz, 1H), 7.08 (t, J = 8.4 Hz,
2H), 7.48 (m, 3H), 7.63 (t, J = 7.6 Hz, 2H), 8.02 (d, J =
8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) d: 48.0, 73.9,
115.2, 115.4, 128.8 (2C), 129 (3C), 129.1, 134.3, 134.4,
135.2, 162.7 (d, J = 245.5 Hz, 1C), 194.4. Anal. calcd. for
C15H12BrFO2: C, 55.75; H, 3.74. Found: C, 56.29; H, 3.51.
Yield: 95%; white solid; mp 46 8C. Rf (3% EtOAc/petro-
leum ether): 0.25. IR (KBr, cm–1) n: 578, 833, 1031, 1074,
1095, 1150, 1182, 1246, 1281, 1316, 1379, 1438, 1516,
1
1612, 1742, 2940. H NMR (200 MHz, CDCl3) d: 3.19 (s,
3H), 3.82 (s, 3H), 3.84 (s, 3H), 4.21 (d, J = 9.8 Hz, 1H),
4.50 (d, J = 10.0 Hz, 1H), 6.92 (m, 2H), 7.28 (m, 2H). 13C
NMR (100 MHz, CDCl3) d: 47.3, 52.9, 55.1, 57.3, 83.6,
113.7 (2C), 128.7, 129.1 (2C), 159.9, 169.4. Anal. calcd. for
C12H15BrO4: C, 47.54; H, 4.99. Found: C, 47.77; H, 4.98.
2-Bromo-3-(4-chlorophenyl)-3-hydroxy-1-phenylpropan-1-
one (5j)
2-Bromo-3-(3,4-dimethoxyphenyl)-3-methoxypropionic acid
methyl ester (7c)
Yield: 94%; white solid; mp 96 8C. Rf (10% EtOAc/petro-
leum ether): 0.15. IR (KBr, cm–1) n: 544, 646, 682, 779,
808, 834, 1012, 1089, 1219, 1277, 1293, 1376, 1449, 1594,
Yield: 95%; white solid; mp 75 8C. Rf (10% EtOAc/petro-
leum ether): 0.30. IR (KBr, cm–1) n: 646, 817, 855, 1021,
1074, 1104, 1143, 1170, 1236, 1238, 1261, 1294, 1447,
1
1680, 3449 (br). H NMR (200 MHz, CDCl3) d: 3.49 (d, J =
1
4.4 Hz, 1H), 5.10 (d, J = 8.4 Hz, 1H), 5.29 (dd, J = 8.2,
4.0 Hz, 1H), 7.23–7.50 (m, 6H), 7.60 (m, 1H), 7.90 (d, J =
7.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) d: 47.7, 73.9,
1464, 1517, 1593, 1748, 2936, 2964. H NMR (200 MHz,
CDCl3) d: 3.22 (s, 3H), 3.85 (s, 3H), 3.89 (s, 6H), 4.22 (d,
J = 10.0 Hz, 1H), 4.49 (d, J = 9.8 Hz, 1H) 6.88 (m, 3H).
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13C NMR (100 MHz, CDCl3): d 47.3, 52.9, 55.74, 55.81,
57.4, 83.9, 109.8, 110.4, 121.1, 129.0, 149.0, 149.3, 169.4.
Anal. calcd. for C13H17BrO5: C, 46.86; H, 5.14. Found: C,
47.28; H, 5.15.
833, 1071, 1094, 1157, 1225, 1298, 1370, 1446, 1511,
1604, 1684, 2934. H NMR (200 MHz, CDCl3) d: 3.15 (s,
1
3H), 4.81 (d, J = 9.8 Hz, 1H), 5.05 (d, J = 9.8 Hz, 1H),
7.08 (m, 2H), 7.38–7.63 (m, 5H), 8.01 (m, 2H). 13C NMR
(100 MHz, CDCl3) d: 47.2, 57.6, 82.5, 115.2, 115.4, 128.7
(4C), 129.7, 129.8, 133.59, 133.62, 135, 162.9 (d, J =
245.6 Hz, 1C), 192.8. Anal. calcd. for C16H14BrFO2: C,
56.99; H, 4.19. Found: C, 57.39; H, 3.97.
3-Benzo[1,3]dioxol-5-yl-2-bromo-3-methoxypropionic acid
methyl ester (7d)
Yield: 91%; white solid; mp 74 8C. Rf (5% EtOAc/petro-
leum ether): 0.32. IR (KBr, cm–1) n: 559, 631, 655, 818,
924, 961, 1017, 1036, 1066, 1091, 1159, 1251, 1274, 1447,
2-Bromo-3-(4-chlorophenyl)-3-methoxy-1-phenylpropan-1-
one (7j)
1
1489, 1501, 1744. H NMR (200 MHz, CDCl3) d: 3.17 (s,
3H), 3.81 (s, 3H), 4.13 (d, J = 9.8 Hz, 1H), 4.42 (d, J =
9.8 Hz, 1H), 5.95 (s, 2H), 6.81 (m, 3H). 13C NMR
(100 MHz, CDCl3) d: 47.3, 53, 57.4, 83.9, 101.2, 107.5,
107.9, 122.4, 130.7, 147.9, 148.1, 169.4. Anal. calcd. for
C12H13BrO5: C, 45.45; H, 4.13. Found: C, 45.06; H, 4.0.
Yield: 94%; white solid; mp 90 8C. Rf (5% EtOAc/petro-
leum ether): 0.35. IR (KBr, cm–1) n: 686, 807, 991, 1015,
1070, 1094, 1221, 1301, 1370, 1446, 1489, 1596, 1685,
1
2933. H NMR (200 MHz, CDCl3) d: 3.19 (s, 3H), 4.83 (d,
J = 9.8 Hz, 1H), 5.07 (d, J = 10.0 Hz, 1H), 7.41 (s, 4H),
7.43–7.66 (m, 3H), 8.03 (m, 2H), 13C NMR (100 MHz,
CDCl3) d: 46.9, 57.7, 82.6, 128.6 (2C), 128.8 (4C), 129.5
(2C), 133.8, 134.5, 135.0, 136.4, 192.7. Anal. calcd. for
C16H14BrClO2: C, 54.34; H, 3.99. Found: C, 54.73; H, 3.84.
2-Bromo-3-methoxy-3-(4-methoxyphenyl)-1-phenylpropan-
1-one (7f)
Yield: 95%; white solid; mp 90 8C. Rf (5% EtOAc/petro-
leum ether): 0.25. IR (KBr, cm–1) n: 578, 685, 806, 832,
1038, 1074, 1175, 1219, 1254, 1305, 1279, 1373, 1446,
Supplementary data
1
1516, 1611, 1685, 2929. H NMR (200 MHz, CDCl3) d:
Supplementary data for this article (1H and 13C NMR
spectra of compounds 5c–5d, 5f–5j, 6b, 6d, and 7b–7j) are
available on the journal Web site (canjchem.nrc.ca).
3.18 (s, 3H), 3.85 (s, 3H), 4.80 (d, J = 9.8 Hz, 1H), 5.12 (d,
J = 9.8 Hz, 1H), 6.96 (dd, J = 6.6, 2.0 Hz, 2H), 7.39 (dd, J =
6.6, 2.0 Hz, 2H), 7.50–7.62 (m, 3H), 8.06 (d, J = 7.0 Hz,
2H). 13C NMR (100 MHz, CDCl3) d: 47.6, 55.2, 57.4, 82.8,
113.7 (2C), 128.76 (2C), 128.79 (2C), 129.3 (2C), 129.7,
133.7, 135.2, 159.9, 193.2. Anal. calcd. for C17H17BrO3: C,
58.47; H, 4.91. Found: C, 58.40; H, 4.98.
Acknowledgments
I thank the Department of Science and Technology
(DST), New Delhi, for providing financial support for this
work, and I also thank the Council of Science and Industrial
Research (CSIR), New Delhi, for my fellowship.
2-Bromo-3-(3,4-dimethoxyphenyl)-3-methoxy-1-
phenylpropan-1-one (7g)
Yield: 94%; gummy liquid. Rf (10% EtOAc/petroleum
ether): 0.25. IR (KBr, cm–1) n: 577, 686, 806, 832, 1039,
1073, 1095, 1175, 1219, 1254, 1279, 1304, 1373, 1446,
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