One-pot approach to the conversion of alcohols into α-Iodoα, β-unsaturated Esters

Article abstract of DOI:10.1080/00397910903434570

(Carboethoxymethylene)triphenylphosphorane 1 can undergo the tandem reaction of iodination-oxidation-Wittig reaction with alcohol in the presence of N-iodosuccinimide (NIS) and manganese dioxide. The reaction constitutes a stereoselective one-pot procedure for the preparation of Z-configured α-iodo-α,β-unsaturated esters in good to excellent yield. Copyright Taylor & Francis Group, LLC.

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One-Pot Approach to the Conversion of
Alcohols into α-Iodo-α,β-unsaturated
Esters
Usama Karama a
a Chemistry Department, College of Science, King Saud University,
Riyadh, Saudi Arabia
Published online: 05 Nov 2010.
To cite this article: Usama Karama (2010) One-Pot Approach to the Conversion of Alcohols into
α-Iodo-α,β-unsaturated Esters, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:23, 3447-3451, DOI: 10.1080/00397910903434570
To link to this article: http://dx.doi.org/10.1080/00397910903434570
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Synthetic Communications1, 40: 3447–3451, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903434570
ONE-POT APPROACH TO THE CONVERSION OF
ALCOHOLS INTO a-IODO-a,b-UNSATURATED
ESTERS
Usama Karama
Chemistry Department, College of Science, King Saud University,
Riyadh, Saudi Arabia
(Carboethoxymethylene)triphenylphosphorane 1 can undergo the tandem reaction of
iodination–oxidation–Wittig reaction with alcohol in the presence of N-iodosuccinimide
(NIS) and manganese dioxide. The reaction constitutes a stereoselective one-pot
procedure for the preparation of Z-configured a-iodo-a,b-unsaturated esters in good to
excellent yield.
Keywords: a-Iodo-a,b-unsaturated esters; iodoylides; one-pot synthesis; oxidation
INTRODUCTION
The Wittig olefination is one of the most important methods for the formation
of a carbon–carbon double bond and has been widely used in the synthesis of natural
products.[1] a-Halo-a,b-unsaturated esters are useful intermediates in organic
synthesis.[2] For example, the synthesis of a-trifluoromethyl-a,b-unsaturated esters
was based on trifluoromethylation of a-iodo-a,b-unsaturated esters.[3] They are
usually prepared by the Wittig reaction of aldehydes with haloylides[4–7] and con-
densation of aldehydes with halophosphonates in the presence of a base.[8–11] Only
aldehydes have been used as substrates in this method. However, it has been reported
that aldehydes are difficult to isolate because of their volatility, toxicity, and pench-
ant to polymerize or hydrolyze and are unsuitable for use as substrate. This problem
has been overcome by using in situ–generated aldehydes[12,13] from alcohols.
Alcohols are usually more stable, less volatile, and less toxic than the corresponding
aldehydes. Therefore, a one-pot alcohol oxidation–Wittig reaction to afford a-halo-
a,b-unsaturated esters is much more attractive. Recently, Blackburn et al.[12]
described the development of an in situ alcohol oxidation–Wittig reaction using
(carboethoxymethylene)triphenylphosphorane and manganese dioxide to produce
a,b-unsaturated esters. In this article, we describe a one-pot methodolgy using this
procedure to synthesize (Z)-a-iodo-a,b-unsaturated esters.
Received August 9, 2009.
Address correspondence to Usama Karama, Chemistry Department, College of Science, King Saud
University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. E-mail: Karama@ksu.edu.sa
3447

3448
U. KARAMA
RESULTS AND DISCUSSION
Because of our continuing interest in one-pot methods,[14] we decided to convert
multistep reactions into economically and environmentally favored one-pot processes
for the transformation of alcohols to a-iodo-a,b-unsaturated esters. We considered
combining the halogenations of ylide, oxidation of alcohol, and Wittig reaction into
one tandem reaction. We utilized (carboethoxymethylene)triphenylphosphorane 1 as
starting material to react with activated alcohol in the presence of N-iodosuccinimide
and manganese dioxide and found that the tandem reaction of halogenation–
oxidation–Wittig reaction took place, but the yield of the target product was unsatis-
factory. However, we found that using ultrasonic wave conditions led to enhancement
of the yield. As shown in Table 1, the one-pot sequential halogenation–oxidation–
HWE (Horner–Wadsworth–Emmons) reaction of active alcohols such as aromatic,
allylic, and propargylic alcohols furnished the a-iodo-a,b-unsaturated esters in
Table 1. One-pot synthesis of (Z)-a-iodo-a,b-unsaturated esters
Entry
R
Product
Yield (%)a
Z=Eb
1
3a
86
90:10
2
3b
85
100:0
3
4
3c
3d
81
63
88:12
90:10
5
3e
67
93:7
CH3CH2—CꢀC—
6
7
3f
65
30
91:9
3 g
90:10
8
3 h
23
90:10
aYields were based on alcohols.
bThis ratio was determined by 1H NMR spectroscopy.

a-IODO-a,b-UNSATURATED ESTERS
3449
moderate to good yields and very high stereoselectivity (entries 1–6 in Table 1).
Interestingly, unactivated alcohols such as alkylic alcohols were also successful for this
process (entries 7, 8 in Table 1), but the yields were rather poor. In all reactions, the E
and Z isomers were not separated, but the Z=E ratios were readily determined by 1H
NMR spectroscopy. The vinylic protons of the Z isomer were downfield of the E
isomer. This assignment was confirmed by nuclear Overhauser effect (NOE) analysis
of the allylic alcohol derived from the corresponding esters by diisobutylaluminum-
hydride (DIBAL) reduction.
In conclusion, we have developed an efficient ultrasonic wave–assisted one-pot
halogenation–oxidation–Wittig reaction to directly convert the alcohols to the corre-
sponding (Z)-a-iodo-a,b-unsaturated esters. These results demonstrate the value of
ultrasonic wave–assisted chemistry and provide a good green chemistry procedure.
EXPERIMENTAL
Infrared (IR) spectra were recorded on a Perkin-Elmer 883 spectrophotometer
and expressed as n in cmꢁ1. NMR spectra were recorded on a Jeol ECP 400
(400 MHz) in CDCl3, and chemical shifts are expressed as d in parts per million,
and coupling constants (J) were given in hertz. MS spectra were obtained using
electron impact at 70 eV. The ultrasonic reaction was carried out using Sonerex
50 W power and frequency of 35 kHz.
General Procedure for the Synthesis of (Z)-a-Iodo-a,b-unsaturated
Esters
Activatedmanganesedioxide(10 mmol)wasaddedtoasolutionof(carboethoxy-
methylene) triphenylphosphorane (1.3 mmol), N-iodosuccinimide (1.4 mmol), and
alcohol (1 mmol) in 15 ml CH2Cl2, and the mixture was sonicated for 10 h. The
manganese dioxide was removed by filtration through celite, the celite was washed
well with CH2Cl2, and the combined organic portions were concentrated in vacuo
to ca. 1–2 ml. The residue was purified by column chromatography on silica gel
(petroleum ether–ethyl acetate 20:1).
Selected Data
(Z)-Ethyl 2-iodo-3-phenylpropenoate[3] 3a. Oil. 1H NMR (400MHz,
CDCl3): d ¼ 1.37 (t, J ¼ 7.3 Hz, 3H), 4.33 (q, J ¼ 7.3 Hz, 2H), 7.24–7.76 (5H, aromatic),
8.25 (s, 1H); 13C NMR (CDCl3): d ¼ 14.33, 63.12, 91.20, 128.37, 129.55, 130.09, 135.58,
148.00, 163.85; MS (EI) m=z (%): 302 (85) [Mþ], 175 (50), 147 (100), 102 (90); IR (nmax
,
thin film): 2980 (w), 1712 (s), 1597 (m), 1249 (s), 1033 (s), 765 (m).
(2Z, 4E)-Ethyl 2-iodo-5-phenylpenta-2,4dienoate[3] 3b. Oil. 1H NMR
(400 MHz, CDCl3): d ¼ 1.32 (t, J ¼ 7.3 Hz, 3H), 4.28 (q, J ¼ 7.3 Hz, 2H), 7.01–7.02–
7.14 (m, 2H), 7.34–7.66 (m, 5H, aromatic), 7.75 (d, J ¼ 9.5 Hz, 1H); 13C NMR
(CDCl3): d ¼ 14.34, 62.78, 93.01, 127.68, 128.60, 128.99, 129.77, 135.96, 143.41,
147.57, 163.60; MS (EI) m=z (%): 328 (45) [Mþ], 155 (65), 129 (100), 102 (20); IR
(nmax, thin film): 2978 (m), 1708 (s), 1612 (s), 1257 (s), 1244 (s), 1039 (s), 742 (s).

3450
U. KARAMA
(Z)-Ethyl 3-(furan-2-yl)-2-iodo-3-propenoate[3] 3c. Oil. 1H NMR
(400 MHz, CDCl3): d ¼ 1.31 (t, J ¼ 7.4 Hz, 3H), 4.28 (q, J ¼ 7.4 Hz, 2H), 6.54 (m,
1H), 7.55 (d, J ¼ 3.7 Hz, 1H), 7.59 (d, J ¼ 2.2 Hz, 1H), 8.31 (s, 1H); 13C NMR
(CDCl3): d ¼ 14.32, 63.04, 85.27, 112.01, 116.27, 135.78, 145.17, 150.95, 163.72;
MS (EI) m=z (%): 292 (65) [Mþ], 247 (8), 165 (42), 137 (100), 119 (35); IR (nmax, thin
film): 2980 (m), 1712 (s), 1604 (m), 1234 (s), 1205 (m), 1035 (m), 746 (m).
(2Z, 4E)-Ethyl 2-iodohepta-2,4-dienoate 3d. Oil. 1H NMR (400 MHz,
CDCl3): d ¼ 1.08 (t, J ¼ 7.3 Hz, 3H), 1.32 (t, J ¼ 6.9 Hz, 3H), 2.24 (quan. J ¼ 7.3 Hz,
2H), 4.25 (q, J ¼ 6.9 Hz, 2H), 6.35–6.44 (m, 2H), 7.52 (d, J ¼ 9.5 Hz, 1H); 13C NMR
(CDCl3): d ¼ 14.33, 26.99, 29.78, 62.68, 90.39, 131.25, 148.06, 149.93, 163.74; MS
(EI) m=z (%): 280 (75) [Mþ], 251 (42), 223 (58) 125 (44), 125 (44), 79 (100); HRMS
(EI) calcd. for C9H13O2I (Mþ) 279.9960, obsd. 279.9959; IR (nmax, thin film): 2962
(m), 1712 (s), 1631 (m), 1257 (s), 1220 (m), 1039 (m).
(2Z)-Ethyl 2-iodo-5-phenylpent-2-en-4-ynoate 3e. Oil. 1H NMR
(400 MHz, CDCl3): d ¼ 1.34 (t, J ¼ 7.3 Hz, 3H), 4.31 (q, J ¼ 7.3 Hz, 2H), 7.33–7.38
(m, 3H), 7.55–7.55 (m, 2H), 7.66 (s, 1H);13C NMR (CDCl3): d ¼ 14.26, 63.14,
89.98, 102.54, 104.42, 129.83, 131.81, 131.93,131.96, 132.14, 162.87; MS (EI) m=z
(%): 326 (90) [Mþ], 199 (74), 171 (98), 126 (100); HRMS (EI) calcd. for
C13H11O2I (Mþ) 325.9804, obsd. 325.9804; IR (nmax, thin film): 2962 (m), 1714
(s), 1570 (m), 1259 (s), 1039 (m).
1
(Z)-Ethyl 2-iodohept-2-en-4-ynoate 3f. Oil. H NMR (400 MHz, CDCl3):
d ¼ 1.26 (t, J ¼ 7.3 Hz, 3H), 1.31 (t, J ¼ 7.3 Hz, 2H), 2.46 (qd, J ¼ 7.3 Hz, J ¼ 2.2 Hz,
2H), 7.42 (t, J ¼ 2.2 Hz, 1H); 13C NMR (CDCl3): d ¼ 13.36, 14.22, 29.77, 62.98,
80.91, 101.20, 108.92, 132.75, 163.04; MS (EI) m=z (%): 278 (100) [Mþ], 250 (81),
151 (53), 123 (74), 77 (67); HRMS (EI) calcd. for C9H11O2I (Mþ) 277.9804, obsd.
277.9805; IR (nmax, thin film): 2960 (m), 1724 (s), 1579 (m), 1259 (s), 1217 (m),
1093 (m).
(Z)-Ethyl 2-iodonon-2-enoate 3g. Oil. 1H NMR (400 MHz, CDCl3):
d ¼ 1.27–1.30 (m, 14H), 2.26 (q, J ¼ 7.3 Hz, 2H); 4.21 (q, J ¼ 7.4 Hz, 2H), 7.16 (t,
J ¼ 7.3 Hz, 1H), 13C NMR (CDCl3): d ¼ 14.09, 14.24, 22.57, 27.50, 29.01, 31.63,
37.10, 62.59, 95.19, 153.27, 162.96. MS (EI) m=z (%): 310 (50) [Mþ], 225 (23), 109
(100); HRMS (EI) calcd. for C11H19O2I (Mþ) 310.0429, obsd. 310.0427; IR (nmax
,
thin film): 2927 (m), 1712 (s), 1614 (m), 1242 (s), 1217 (m), 1039 (m), 746 (m).
(Z)-Ethyl 2-iodo-5,9-dimethyldeca-2,8-dienoate 3h. Oil. 1H NMR
(400 MHz, CDCl3): d ¼ 0.95 (d, J ¼ 7.3 Hz, 3H), 1.29–1.32 (m, 2H), 1.30 (t, J ¼ 7.3 Hz,
Hz, 3H), 1.58 (s, 3H), 1.66 (s, 3H), 1.70–1.75 (m, 1H), 1.94–2.02 (m, 2H), 2.13–2.20
(m, 1H), 2.29–2.32 (m, 1H), 4.23 (q, J ¼ 7.3 Hz, 2H), 5.05–5.07 (m, 1H), 7.20 (t,
J ¼ 7.3 Hz, 1H); 13C NMR (CDCl3): d ¼ 14.28, 17.79, 19.84, 25.62, 25.80, 32.24,
36.89, 44.21, 62.68, 96.02, 124.38, 131.66, 152.38, 162.99; MS (EI) m=z (%): 350 (5)
[Mþ], 223 (19), 149 (33), 107 (38), 69 (100); HRMS (EI) calcd. for C14H23O2I
(Mþ) 350.0742, obsd. 350.0745; IR (nmax, thin film): 2962 (m), 1712 (s), 1259 (s),
1095 (s), 1035 (s), 742 (w).

a-IODO-a,b-UNSATURATED ESTERS
3451
ACKNOWLEDGMENT
I thank the Saudi Basic Industries Corporation (SABIC) for financial support
(Project Science-5–2007).
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