One-pot combination of the wittig olefination with bromination and oxidation reactions

Article abstract of DOI:10.1080/00397911.2011.614712

A simple one-pot process for in situ bromination of (ethoxycarbonylmethylene)-triphenylphosphorane 1 was carried out. This was followed by oxidation of alcohol using SO₃. Pyridine complex as a mild oxidant and in situ trapping of the aldehyde. This process constitutes a stereoselective one-pot procedure for the preparation of Z-configured-bromo-,- unsaturated esters in good yield.

Full text of DOI:10.1080/00397911.2011.614712

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One-Pot Combination of the Wittig
Olefination with Bromination and
Oxidation Reactions
a
a
a
Usama Karama , Refat Mahfouz , Zeid Al-Othman , Ismail Warad
a
a
&
Abdulrahman Almansour
a
Chemistry Department, College of Science, King Saud University,
Riyadh, Kingdom of Saudi Arabia
Accepted author version posted online: 10 May 2012.Version of
record first published: 21 Dec 2012.
To cite this article: Usama Karama , Refat Mahfouz , Zeid Al-Othman , Ismail Warad & Abdulrahman
Almansour (2013): One-Pot Combination of the Wittig Olefination with Bromination and Oxidation
Reactions, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 43:6, 893-898
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1
Synthetic Communications , 43: 893–898, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.614712
ONE-POT COMBINATION OF THE WITTIG
OLEFINATION WITH BROMINATION AND
OXIDATION REACTIONS
Usama Karama, Refat Mahfouz, Zeid Al-Othman,
Ismail Warad, and Abdulrahman Almansour
Chemistry Department, College of Science, King Saud University, Riyadh,
Kingdom of Saudi Arabia
GRAPHICAL ABSTRACT
Abstract A simple one-pot process for in situ bromination of (ethoxycarbonylmethylene)-
triphenylphosphorane 1 was carried out. This was followed by oxidation of alcohol using
SO
constitutes a stereoselective one-pot procedure for the preparation of Z-configured -bromo-,
unsaturated esters in good yield.
3
. Pyridine complex as a mild oxidant and in situ trapping of the aldehyde. This process
-
Keywords Halogenation; olefination; one-pot synthesis; oxidation
INTRODUCTION
Wittig olefination, which has evolved to include the Horner–Wittig and
Horner–Wadsworth–Emmons reaction, is the most powerful and attractive method
[
for the formation of carbon–carbon double bonds and has been widely used in the
1]
[2]
synthesis of natural products. Recently it was found that alcohols can undergo in
situ oxidation–Wittig reaction with phosphonium ylides to give the corresponding
[
3–7]
olefination products, which have great potential utilities in organic synthesis.
This one-pot methodology removes the need to isolate the intermediate aldehydes
and so is beneficial in terms of time and particularly advantageous if the intermediate
aldehydes are unstable, toxic, or difficult to handle. Therefore, one-pot oxidation–
Wittig reactions of alcohols to a-bromo-a,b-unsaturated esters is attractive.
[
8]
a-bromo-a,b-unsaturated esters are useful intermediate in organic synthesis and
are widely used as precursors for C-C bond formation with conservation of olefin
[
9]
geometry. For example, the synthesis of a-trifluoromethyl-a,b-unsaturated esters,
Received February 28, 2011.
Address correspondence to Usama Karama, Chemistry Department, College of Science, King Saud
University, P. O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia. E-mail: Karama@ksu.edu.sa
8
93

894
U. KARAMA ET AL.
building blocks for the preparation of trifluoromethylated biologically active
[
10,11]
compounds,
is based on trifluoro-methylation of a-iodo-a, b-unsaturated
[
12]
[8]
esters
the Wittig reaction of aldehydes with haloylides
with halo-phosphonates in the presence of a base.
as well a-bromo-a,b-unsaturated esters. They are usually prepared by
[
13,14]
and condensation of aldehydes
[
15]
Recently, we described a
one-pot sequential halogenation–oxidation–Wittig reaction using manganese dioxide
as the oxidant for reactive alcohol such as aromatic, allylic, and propargylic alcohols
[
16,17]
to obtain the corresponding a-halo-a,b-unsaturated esters in good yield,
although this process is limited to activated alcohols. In this article we describe a
one-pot procedure to synthesize (Z)-a-bromo-a,b-unsaturated esters from reactive
as well as unreactive alcohols.
RESULTS AND DISCUSSION
In the framework of our studies on the conversion of multistep reactions into
economically and environmentally favored one-pot processes, we attempted to find
an alternative system for one-pot halogenation=oxidation=Wittig sequences for acti-
vated alcohols as well for alkanols. The in situ halogenations of (ethoxycarbonyl-
[
18]
methylene)triphenylphosphorane 1 was reported by Kayser et al. We carried out
the one-pot halogenation–oxidation–Wittig sequences including Dess–Martin,
pyridinium chlorochromate (PCC), PCC-NaOAc, and pyridinium dichromate
(PDC) oxidants. Unfortunately, all attempts were unsuccessful. We decided to explore
the SO ꢀ pyridine complex, a mild, selective, cheap, safe, and easily handled oxidant,
3
as chemoselective oxidant for primary alcohol in the presence of a free secondary or
[7]
tertiary alcohol. After some experimental work, we were pleased to find that
treatment of (ethoxycarbonylmethylene)triphenylphosphorane 1 (1.5 equiv) with
N-bromosuccinimide (NBS) (1.5 equiv) in dichloromethane followed by addition of
alcohol (1 equiv), SO pyridine complex (3 equiv), dimethylsulfoxide (DMSO), and
3
triethylamine afforded the (Z)-a-bromo-a,b-unsaturated esters 3 in good yield and
very high stereoselectivity as shown in Table 1. In this procedure the stereoselectivity
[
16,17]
was almost greater than our recent procedure using MnO as oxidant.
In all reac-
tions, the E and Z isomers were not separated, but the Z=E ratios were readily deter-
2
1
mined by H NMR spectroscopy. The vinylic protons of Z isomer were downfield of
the E isomer. This assignment was confirmed by nuclear Overhauser effect spec-
troscopy (NOESY) experiments of the allylic alcohol derived from the corresponding
esters by diisobutyialuminumhydride (DIBAL) reduction. NOE effects were observed
between the olefinic proton and the methylic hydrogens of the alcohol.
In conclusion we have developed an efficient one-pot procedure for in situ
halogenation–oxidation–Wittig reaction for the highly stereoselective synthesis of
(Z)-a-bromo-a,b-unsaturated esters from alcohols. This methodology is a safe, econ-
omical, and bench-friendly procedure.
EXPERIMENTAL
Infrared (IR) spectra were recorded on a Perkin-Elmer 883 spectrophotometer
ꢁ
1
and expressed in cm NMR spectra were recorded on a Jeol ECP 400 (400 MHz)
instrument in CDCl . Chemical shifts are expressed as d in parts per million (ppm),
3

WITTIG OLEFINATION
895
Table 1. One-pot synthesis of (Z)-a-bromo-a,b-unsaturated esters
a
b
Entry
R
Product
Yield (%)
87
Z=E
1
3a
95:5
2
3b
55
100:0
3
4
5
3c
3d
3e
77
80
85
100:0
100:0
100:0
6
7
3f
81
86
82:18
89:11
3g
8
3h
76
86:14
a
b
Yields were based on alcohols. This ratio was determined by H NMR spectroscopy.
1
and coupling constants (J) were given in hertz. Mass (MS) spectra were obtained
using electron impact (EI) at 70 eV.
General Procedure for the Synthesis of (Z)-a-Bromo-a,b-unsaturated
Esters
N-Bromosuccinimide (1.5 mmol) was added to a solution of (ethoxycarbonyl-
methylene)-triphenylphosphorane (1.5 mmol) in 6 mL of CH Cl . After 5 min,
2
2

896
U. KARAMA ET AL.
alcohol (1 mmol) in 1 mL of CH Cl was added followed by SO pyridine (3 mmol),
2
2
3
0
.8 mL of DMSO, and 1.4 mL of Et N, and the mixture was stirred for 12 h at room
3
temperature. The reaction mixture was poured on 5% HCl and extracted with
CH Cl The combined organic phases were washed with water and brine, dried over
MgSO , and concentrated in vacuum to ca. 1–2 ml. The residue was purified by
2
2.
4
column chromatography on silica gel (petroleum ether–ethyl acetate 15:1).
(Z)-Ethyl 2-Bromo-3-phenylpropenoate 3a
[
17]
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR (400 MHz, CDCl ): d ¼ 1.38 (t, J ¼ 7.3 Hz, 3H); 4.33 (q, J ¼ 7.3 Hz, 2H),
1
3
1
.41–7.45 (m, 3H, arom-H), 7.83–7.85 (m, 2H, arom-H), 8.21 (s, 1H); C NMR
3
7
(
400 MHz, CDCl ): d ¼ 14.3, 62.8, 113.2, 128.2, 128.4, 130.2, 130.3, 140.8, 163.4;
3
IR (n , thin film) 2980, 1724, 1610, 1259, 1037, 765; MS (EI), m=z (%) ¼ 256
max
þ
(54), 254 [M ] (54), 175 (91), 174 (100), 102 (97).
(
2Z,4E)-Ethyl 2-Bromo-5-phenylpenta-2,4-dienoate 3b
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR: d ¼ 1.37 (t, J ¼ 7.3 Hz, 3H), 4.29 (q, J ¼ 7.3 Hz, 2H), 7.04 (d, J ¼ 16.1 Hz,
[
17]
1
1
1
Hz, H), 7.16 (dd, J ¼ 10.3 Hz, J ¼ 16.1 Hz, H), 7.32–7.39 (m, 3H, arom-H),
1
3
7
.51–7.53 (m, 2H, arom-H), 7.81 (d, J ¼ 10.3 Hz); C NMR (400 MHz, CDCl3):
d ¼ 14.3, 62.5, 114.4, 125.3, 127.5, 127.6, 128.9, 129.7, 141.2, 142.80, 163.1; IR (nmax,
thin film) 2980, 1714, 1614, 1583, 1261, 1041, 744; MS (EI), m=z (%) ¼ 282 (26), 282
þ
[
M ] (27), 155 (47), 129 (100), 102 (25).
(
Z)-Ethyl 3-(Furan-2-yl)-2-Bromo-3-propenoate 3c
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR: d ¼ 1.33 (t, J ¼ 7.3 Hz, 3H), 4.30 (q, J ¼ 7.3 Hz, 2H), 6.54 (m, 1H), 7.42
[
17]
1
1
3
(
d, J ¼ 3 Hz, 1H), 7.57 (d, J ¼ 2 Hz, 1H), 8.13 (s, 1H); C NMR (400 MHz, CDCl ):
3
d ¼ 14.3, 62.7, 112. 3, 112.5, 116.8, 129.1, 145.1, 150.1, 163.1; IR (nmax, thin film)
þ
2
1
981, 1716, 1249, 1039, 748; MS (EI), m=z (%) ¼ 246 (39), 244 [M ] (38), 165 (58),
37 (100), 92 (30).
(
2Z,4E)-Ethyl 2-Bromohepta-2,4-dienoate 3d
Yellow oil. The spectroscopic data matched that reported in the literature,
NMR: d ¼ 1.04 (t, J ¼ 7.3 Hz, 3H), 1.31 (t, J ¼ 6.6 Hz, 3H), 2.22 (quint. J ¼ 7.3 Hz,
[
17] 1
H
1
3
2
H), 4.25 (q, J ¼ 7.3 Hz, 2H), 6.32–6.44 (m, 2H), 7.63 (d, J ¼ 10 Hz); C NMR
(
(
400 MHz, CDCl ): d ¼ 12.8, 14.3, 29.7, 62.4, 112.17, 126.8, 141.6, 149.2, 163.2; IR
3
þ
n
, thin film) 3055, 1726, 1265, 705; MS (EI), m=z (%) ¼ [M cannot be detected],
max
2
08 (41), 206 (36), 106 (39), 104 (39).
(
2Z)-Ethyl 2-Bromo-5-phenylpent-2-en-4-ynoate 3e
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR: d ¼ 1.34 (t, J ¼ 7.3 Hz, 3H), 4.33 (q, J ¼ 7.3 Hz, 2H), 7.29–7.58 (m, 4H,
[
17]
1

WITTIG OLEFINATION
897
1
3
arom-H), 7.50 (s, 1H); C NMR (400 MHz, CDCl ): d ¼ 14.2, 62.9, 86.4, 104.8,
3
1
1
24.2, 128.6, 129.8, 129.0, 131.9, 132.1, 162.16; IR (n , thin film) 2980, 1718,
265, 738; MS (EI), m=z (%) ¼ 280 (42), 278 [M ] (42), 199 (73), 171 (100), 106
max
þ
(39), 126 (97).
(Z)-Ethyl 2-Bromohept-2-en-4-ynoate 3f
[
17]
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR: d ¼ 1.21 (t, J ¼ 8 Hz, 3H), 1.30 (t, J ¼ 7.3 Hz, 3H), 2.44 (dq, J ¼ 7.3 Hz,
1
1
3
J ¼ 2.2 Hz, 2H), 4.27 (q, J ¼ 7.3 Hz, 2H, 7.26 (t, J ¼ 2.2 Hz, 1H); C NMR
(
(
(
400 MHz, CDCl ): d ¼ 13.4, 14.0, 14.2, 62.8, 109.1, 122.6, 124.44, 125.1, 162.3; IR
3
þ
n , thin film) 2998, 1718, 1265, 740; MS (EI), m=z (%) ¼ 232 (49), 230 [M ]
51), 186 (40), 151 (96), 77 (100).
max
(Z)-Ethyl 2-Bromonon-2-enoate 3g
[
17]
Yellow oil. The spectroscopic data matched that reported in the literature,
H NMR: d ¼ 1.24 (t, J ¼ 7.3 Hz, 3H), 1.27–1.32 (m, 11H), 2.33 (q, J ¼ 7.3 Hz,
1
1
3
2
H), 4.27 (q, J ¼ 7.3 Hz, 2H), 7.27 (t, J ¼ 7.30 Hz, 1H); C NMR (400 MHz,
CDCl ): d ¼ 14.1, 14.2, 22.5, 27.6, 29.0, 31.6, 32.2, 62.3, 116.3, 146.3, 162.6; IR (nmax,
3
thin film) 2926, 1732, 1259, 1041, 802.
(Z)-Ethyl 2-Bromonon-5,9-dimethyldeca-2,8-dienoate (3h)
1
Yellow oil, H NMR: d ¼ 0.94 (d, J ¼ 6.6 Hz, 3H), 1.21–1.26 (2H, m), 1.32 (t,
J ¼ 7.3 Hz, 3H), 1.59 (3H, s), 1.69 (3H, s), 1.69–1.74 (1H, m), 2.30–2.35 (1H, m), 4.26
1
3
(
(
1
3
q, J ¼ 7.3 Hz, 2H), 5.08 (t, J ¼ 7.30 Hz, 1H), 7.29 (t, J ¼ 7.30 Hz, 1H); C NMR
400 MHz, CDCl ): d ¼ 14.2, 17.8, 19.8, 25.6, 25.8, 32.1, 36.8, 39.3, 62.4, 117.0,
3
24.3, 131.7, 145.3, 162.6; HRMS (EI) calcd. for C H O Br (Mþ) 302.0881, obsd.
max
1
4
23
2
02.0876; IR (n , thin film) 3003, 2925, 2871, 1715, 1622, 1259, 1217, 1043, 669.
ACKNOWLEDGMENT
The authors extend their appreciation to the Deanship of Scientific Research at
King Saud University for funding the work through Research Group Project No.
RGP-VPP-128.
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