A facile one-pot synthesis of α-bromo-α,β-unsaturated esters from alcohols

Article abstract of DOI:10.3390/molecules15053276

Treatment of N-bromosuccinimide (NBS) with (carboethoxymethylene) triphenylphosphorane (1) in CH₂Cl₂ followed by the addition of an alcohol in the presence of manganese dioxide under ultrasonic irradiation constitutes a stereoselective one-pot procedure for the preparation of Z-configured α-bromo-α,β-unsaturated esters in good to excellent yield.

Full text of DOI:10.3390/molecules15053276

Molecules 2010, 15, 3276-3280; doi:10.3390/molecules15053276
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
A Facile One-Pot Synthesis of α-Bromo-α,β-unsaturated Esters
from Alcohols
Usama Karama *, Zeid Al-Othman, Abdullah Al-Majid and Abdulrahman Almansour
Chemistry Department, College of Science, King Saud University, P.O. Box 2455 Riyadh 11451,
Saudi Arabia
*
Author to whom correspondence should be addressed; E-Mail: Karama@ksu.edu.sa.
Received: 9 March 2010; in revised form: 27 April 2010 / Accepted: 29 April 2010 /
Published: 4 May 2010
Abstract: Treatment of N-bromosuccinimide (NBS) with (carboethoxymethylene)
2 2
triphenylphosphorane (1) in CH Cl followed by the addition of an alcohol in the presence
of manganese dioxide under ultrasonic irradiation constitutes a stereoselective one-pot
procedure for the preparation of Z-configured α–bromo-α,β-unsaturated esters in good to
excellent yield.
Keywords: one-pot synthesis; bromoylides; oxidation; α–bromo-α,β-unsaturated esters
1
. Introduction
The Wittig reaction is one of the most powerful and attractive methods for the construction of
various alkenes [1]. Nicolaou and his coworkers [2] have highlighted the utility of the Wittig
olefination and related reactions in natural products synthesis both in the research laboratory and
industrial settings. α–Halo-α,β-unsaturated esters are useful intermediates in organic synthesis [3]. For
example, the synthesis of α–trifluoromethyl-α,β-unsaturated esters was based on trifluoromethylation
of α–iodo-α,β-unsaturated esters [4] as well α-bromo-α,β-unsaturated esters [5]. They are usually
prepared by the Wittig reaction of aldehydes with haloylides [6,7] and condensation of aldehydes with
halo-phosphonates in the presence of a base [8]. Only aldehydes have been used as substrates in this
typical method. Taylor [9] described the development of an in situ alcohol oxidation-Wittig reaction
using (carboethoxymethylene)triphenylphosphorane and manganese dioxide to produce α,β-
unsaturated esters. This method avoids the most common problems associated with the handling of

Molecules 2010, 15
3277
intermediate aldehydes, which are often difficult to isolate due to their volatility, toxicity, penchant to
polymerize or facile hydration [9], and unsuitable for use as substrates.
In this paper we describe a one-pot methodology for the synthesis of (Z)-α–bromo-α,β-unsaturated
esters using the above procedure.
2
. Results and Discussion
Due to our continuing interest in one-pot procedures [10,11], which convert multi-step reactions
into economically and environmentally favored one-pot processes, we decided to combine the
halogenation of an ylide, the oxidation of an alcohol with the cheap reagent MnO as a oxidant and a
2
subsequent Wittig reaction into a one-step procedure. We utilized (carboethoxymethylene)triphenyl-
phosphorane (1) as starting material to react with activated alcohol in the presence of N-bromo-
succinimide and manganese dioxide and found that the tandem reaction of halogenation-oxidation-
Wittig reaction promoted by ultrasound wave took place readily to form the desired product 3 (Scheme 1).
Scheme 1. Tandem halogenation-oxidation-Wittig reaction.
COOEt
NBS, MnO , CH Cl
2
2
2
Ph P CH COOEt + RCH2OH
3
Ultrasound, 10 h
R
Br
(
1)
(2)
(
3)
As shown in Table 1 the one-pot sequential halogenations-oxidation-Wittig reaction of reactive
alcohol such as aromatic, allylic, and propargylic alcohols furnished the corresponding α-bromo-α,β-
unsaturated esters in good yield and very high stereoselectivity. The yield for unreactive alcohols like
alkanols was rather low (entry 7). The E and Z isomers were not separated in any of the reactions, but
1
the Z:E ratios were readily determined by H-NMR spectroscopy as the vinylic protons of the Z
isomers were downfield of those of the E isomers. This assignment was confirmed by NOE analysis of
the allylic alcohol derived from the corresponding esters by DIBAL reduction.
Table 1. One-pot synthesis of (Z)-α-Iodo-α,β-unsaturated esters.
a
b
c
Entry
R
Product
Yield (%)
Z:E
1
3a
85
94:6
95:5
2
3
3b
3c
81
91
89:11
O

Molecules 2010, 15
3278
Table 1. Cont.
Product
a
b
c
Entry
4
R
Yield (%)
Z:E
3d
90
100:0
92:8
C C
5
6
3e
86
CH CH
C C
3
2
3f
87
21
76:24
7
3g
90:10
a
One equiv. of alcohol, 1.3 equiv. of (1), 1.4 equiv. of NBS and 10 equiv. of MnO
2
were used and
b
c
reaction mixture was sonicated for 10 h; Yields were based on alcohols; This ratio was
1
determined by H-NMR spectroscopy.
3. Experimental
3.1. General
-1
IR spectra were recorded on a Perkin-Elmer 883 spectrophotometer and are expressed as ν in cm
NMR spectra were recorded on JEOL ECP 400 (400 MHz) in CDCl
as δ in ppm, and coupling constants (J) were given in Hertz. MS spectra were obtained using EI at
0 eV. The ultrasonic reactions were carried out using a Sonerex 200 operating at 50 W power and a
frequency of 35 kHz.
3
and chemical shifts are expressed
7
3
.2. General procedure for the synthesis of (Z)-α–bromo-α,β-unsaturated esters
Activated manganese dioxide (purchased from Aldrich, 10 mmol) was added to a solution of
(
carboethoxymethylene)triphenylphosphorane (1.3 mmol), N-bromosuccinimide (1.4 mmol) and
alcohol (1 mmol) in CH Cl (12 mL) and the mixture was sonicated for 10 hours. The manganese
dioxide was removed by filtration through Celite, which was washed well with CH Cl , and the
2
2
2
2
combined organic portions were concentrated under vacuum to ca. 1-2 mL, the residue was purified by
column chromatography on silica gel (petroleum ether-ethyl acetate 15:1).
1
(
Z)-Ethyl 2-bromo-3-phenylpropenoate (3a)[12]: Yellow oil, H-NMR: δ = 1.38 (t, J = 7.3 Hz, 3H);
4
.33 (q, J = 7.3 Hz, 2H); 7.41-7.45 (m, 3H, arom-H); 7.83-7.85 (m, 2H, arom-H); 8.21 (s, 1H); IR
+
(
(
ν
max, thin film) 2980, 1724, 1610, 1259, 1037, 765; MS (EI), m/z (%) = 256 (54), 254 [M ] (54), 175
91), 174 (100), 102 (97).
1
(
2Z, 4E)-Ethyl 2-bromo-5-phenylpenta-2,4-dienoate (3b) [12]: Yellow oil, H-NMR: δ = 1.37 (t,
J = 7.3 Hz, 3H); 4.29 (q, J = 7.3 Hz, 2H); 7.04 (d, J = 16.1 Hz), 7.13-7.19 (dd, J = 10.3 Hz,
J = 16.1 Hz), 7.32-7.39 (m, 3H, arom-H); 7.51-7.53 (m, 2H, arom-H); 7.81 (d, J = 10.3 Hz); IR (νmax
thin film) 2980, 1714, 1614, 1583, 1261, 1041, 744; MS (EI), m/z (%) = 282 (26), 282 [M ] (27), 155
,
+
(47), 129 (100), 102 (25).

Molecules 2010, 15
3279
1
(
Z)-Ethyl 3-(furan-2-yl)-2-bromo-3-propenoate (3c) [12]: Yellow oil, H-NMR: δ = 1.33 (t, J = 7.3 Hz,
3
1
1
H); 4.30 (q, J = 7.3 Hz, 2H); 6.54 (m, 1H), 7.42 (d, J = 3 Hz, 1H), 7.57 (d, J = 2 Hz, 1H); 8.13 (s,
+
H); IR (νmax, thin film) 2981, 1716, 1249, 1039, 748; MS (EI), m/z (%) = 246 (39), 244 [M ] (38),
65 (58), 137 (100), 92 (30).
1
(
2Z, 4E)-Ethyl 2-bromohepta-2,4-dienoate (3d): Yellow oil. H-NMR: δ = 1.04 (t, J = 7.3 Hz, 3H);
1
.31(t, J = 6.6 Hz, 3H); 2.22 (quint. J = 7.3 Hz, 2H); 4.25 (q, J = 7.3 Hz, 2H); 6.32-6.44 (m, 2H); 7.63
+
(d, J = 10 Hz, 1H); IR (νmax, thin film) 3055, 1726, 1265, 705; MS (EI), m/z (%) = [M cannot be
detected], 208 (41), 206 (36),106 (39), 104 (39).
1
(
2Z)-Ethyl 2-bromo-5-phenylpent-2-en-4-ynoate (3e): Yellow oil. H-NMR: δ = 1.34 (t, J = 7.3 Hz,
3
H); 4.33 (q, J = 7.3 Hz, 2H); 7.29-7.58 (m, 4H, arom-H); 7.50 (s, 1H); IR (νmax, thin film) 2980,
+
1718, 1265, 738; MS (EI), m/z (%) = 280 (42), 278 [M ] (42), 199 (73), 171 (100), 106 (39), 126 (97).
1
(
Z)-Ethyl 2-bromohept-2-en-4-ynoate (3f): Yellow oil. H-NMR: δ = 1.21 (t, J = 8 Hz, 3H); 1.30
(
t, J = 7.3 Hz, 3H); 2.44 (dq, J = 7.3 Hz, J = 2.2 Hz, 2H), 4.27 (q, J = 7.3 Hz, 2H, 7.26 (t, J = 2.2 Hz,
+
1
1
H); IR (νmax, thin film) 2998, 1718, 1265, 740; MS (EI), m/z (%) = 232 (49), 230 [M ] (51), 186 (40),
51 (96),77 (100).
1
(
Z)-Ethyl 2-bromonon-2-enoate (3g) [13]: Yellow oil, H-NMR: δ = 1.24 (t, J = 7.3 Hz, 3H); 1.27-1.32
m, 11H), 2.33 (q, J = 7.3 Hz, 2H), 4.27 (q, J = 7.3 Hz, 2H); 7.27 (t, J = 7.30 Hz, 1H); IR (νmax, thin
(
film) 2926, 1732, 1259, 1041, 802.
4
. Conclusions
In summary, we have developed an efficient ultrasonic-assisted one-pot general procedure for a
domino primary alcohol oxidation-Wittig reaction for the highly stereoselective synthesis of Z-α-
bromo-α,β-unsaturated esters 3. These results demonstrate the value of ultrasonic- assisted chemistry.
Acknowledgements
Project (Chem/2010/49) was supported by King Saud University, Deanship of Scientific Research,
College of Science Research Center.
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Sample Availability: Samples of the compounds 3a-3g are available from the authors.
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2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open-access article
distributed under the terms and conditions of the Creative Commons Attribution license
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