An efficient method for the selective iodination of ?±,?2- unsaturated ketones

Article abstract of DOI:10.1055/s-0028-1083200

An efficient approach to ?±,?2-unsaturated ?±'-iodo ketones directly from ?±,?2-unsaturated ketones by selective iodination at the ?±'-position, without effect on the double bond and the activated benzene ring, in the presence of copper (II) oxide/iodine is described. The present method has the advantages of high yields, short reaction times, inexpensive reagents, mild reaction conditions, ease of manipulation, and the formation of cleaner products. ? Georg Thieme Verlag Stuttgart ?· New York.

Full text of DOI:10.1055/s-0028-1083200

PAPER
3675
An Efficient Method for the Selective Iodination of a,b-Unsaturated Ketones
S
elective Iodina
i
tion of
h
a
,
b
-Unsatur
u
ated Ketonesa Wang, Guodong Yin, Jing Qin, Meng Gao, Liping Cao, Anxin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Central China Normal University, Wuhan 430079, P. R. of China
E-mail: chwuax@mail.ccnu.edu.cn
Received 4 July 2008; revised 4 August 2008
Our recent experimental results indicated that a-iodina-
Abstract: An efficient approach to a,b-unsaturated a¢-iodo ketones
tion of carbonyl compounds was excellently achieved by
directly from a,b-unsaturated ketones by selective iodination at the
a copper(II) oxide/iodine system.16 The reaction mecha-
a¢-position, without effect on the double bond and the activated ben-
nism showed that copper(II) oxide promoted the forma-
zene ring, in the presence of copper(II) oxide/iodine is described.
The present method has the advantages of high yields, short reaction tion of a highly reactive enol-form intermediate that could
times, inexpensive reagents, mild reaction conditions, ease of ma-
nipulation, and the formation of cleaner products.
be stabilized by the aromatic ring via p-p conjugated in-
teractions (Scheme 1, n = 0). a,b-Unsaturated a¢-iodo
Key words: iodination, a,b-unsaturated ketones, a,b-unsaturated
a¢-iodo ketones, self-sorting
ketones have potential applications as important interme-
diates in organic synthesis, hence we considered the inser-
tion of a C=C bond (or C≡C bond) between the aromatic
ring and carbonyl group in the aromatic ketone
a,b-Unsaturated a¢-halo ketones have attracted a great (Scheme 1, n = 1, 2) as most probably the a,b-unsaturated
deal of interest due to their applications as important reac- ketone could be selectively iodinated at the a¢-position
tion intermediates in the synthesis of drugs1 and heterocy- without an effect on the double bond and the activated
clic compounds,2 or as important structural fragments benzene ring. The detailed research results are reported in
found in numerous natural products3 (e.g., compounds 1 this paper.
and 2, Figure 1). Probably because N-bromosuccinimide
(NBS), an excellent and efficient brominating reagent,
MeO
Ph
n-Bu
S
R
could react with a,b-unsaturated ketones not only by sub-
stitution at the a¢-position, but also by addition at the dou-
ble bond,4 a,b-unsaturated a¢-bromo ketones are usually
synthesized from the corresponding silyl enol ether1a or by
using pyrrolidone hydrotribromide (PTH)1c as the bromo-
nium source. It is well known that iodo-substituted com-
pounds have higher reactivity than the corresponding
bromo-substituted compounds. To date, although many
excellent methods have been reported for the a-iodination
of carbonyl compounds,5–9 few of them are suitable for
a,b-unsaturated ketone substrates due to harsh reaction
conditions or the use of strong oxidants. In addition, it was
found that the double bond of a,b-unsaturated ketones (a-
position) was easily iodinated by I2/Et3N,10 I2/py/CCl4,11
I
O
OMe
S
R
O
O
R
O
O
Me
I
1
2
Figure 1
O
OH
O
CuO, I2
I
Ar
Ar
Ar
n
n
n
n = 0, 1, 2
enol form
Scheme 1
13
I2/DMAP/K2CO3,12 or I2/Py/PhI(OCOCF3)2 systems.
Only Stavber14 and Kim15 reported one example for the
synthesis of (E)-1-iodo-4-phenylbut-3-en-2-one and (E)-
4-(4-hydroxy-3-methoxyphenyl)-1-iodobut-3-en-2-one
with elemental iodine mediated by 1-(chloromethyl)-4-
fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoro-
borate) (N-F reagent) and bis(tetrabutylammonium) per-
oxydisulfate (iodination at the double bond for a,b-
unsaturated cyclic ketone substrates), respectively. The
use of complex reagents limited substrates scope among
these reported methods.14,15 Accordingly, it is necessary to
establish a simple and efficient method for the selective
iodination of a,b-unsaturated ketones at the a¢-position.
We first synthesized benzalacetone (4a) in 89% yield via
the aldol condensation of benzaldehyde with acetone cat-
alyzed by sodium hydroxide according to a modified
method17 (Table 2, entry 1). In the published papers, it
was found that the solvent played an important role in the
direct a-iodination of carbonyl compounds.8,16b There-
fore, herein benzalacetone (4a) was used as a model sub-
strate to investigate the effect of solvents on the synthesis
of (E)-1-iodo-4-phenylbut-3-en-2-one (10a). The mixture
of benzalacetone (0.5 mmol), copper(II) oxide (0.5
mmol), and iodine (0.5 mmol) in various solvents (6 mL)
was heated at 65 °C for 4–6 hours; the results are summa-
rized in Table 1. The reaction afforded the expected meth-
yl iodinated product 10a instead of iodination at the C=C
bond or on the benzene ring in good yields (68–85%) re-
gardless of the solvent, e.g. methanol, ethanol, propanol,
SYNTHESIS 2008, No. 22, pp 3675–3681
x
x.
x
x
.
2
0
0
8
Advanced online publication: 23.10.2008
DOI: 10.1055/s-0028-1083200; Art ID: F15408SS
© Georg Thieme Verlag Stuttgart · New York

3676
Z. Wang et al.
PAPER
Table 1 Effect of Solvents on the Synthesis of (E)-I-iodo-4-phenyl-
but-3-en-2-one (10a)
Table 2 Synthesis of a,b-Unsaturated Ketones 4 via Aldol Conden-
sation Reactionsa
O
O
O
O
NaOH
R2
R2
I
R1 CHO
+
R1
CuO, I2
40 °C
0.5–28 h
solvent, 65 °C
3
Entry
1
4
4a
10a
R1
Ph
R2
H
H
H
H
H
H
H
H
H
H
H
Me
Productb Yieldc (%)
Entry
Solvent
MeOH
EtOH
Time (h)
Yielda (%)
4a
4b
4c
4d
4e
4f
89
95
90
85
93
84
87
96
80
95d
71
65e
1
2
3
4
5
6
7
8
9
4
4
4
4
4
4
6
6
6
72
80
78
85
68
50
0
2
4-MeC6H4
4-MeOC6H4
4-EtOC6H4
4-ClC6H4
3
PrOH
4
i-PrOH
BuOH
t-BuOH
THF
5
6
2,4-Cl2C6H3
4-BrC6H4
7
4g
4h
4i
8
3-O2NC6H4
9-anthryl
MeCN
benzene
0
9
0
10
11
12
3-MeO-4-HOC6H3
(Z)-CH=CHPh
Ph
4j
a Isolated yield.
4k
propan-2-ol, or butanol (Table 1, entries 1–5). Product
10a was obtained in moderate yield (50%) using tert-butyl
alcohol as a solvent (Table 1, entry 6). However, it was in-
teresting to find that almost no reaction was observed in
aprotic solvents such as tetrahydrofuran, benzene, and
acetonitrile (Table 1, entries 7–9). It was obvious that pro-
pan-2-ol was the optimal solvent in this reaction (Table 1,
entry 4).
4l
a Reagents and conditions: aldehyde (0.1 mol), acetone (20 mL), H2O
(40 mL), 5% NaOH soln (8 mL), 40 °C.
b See ref. 19 for the spectral data of known compounds.
c Isolated yields.
d NaOH (1.2 equiv) was required and diluted HCl was used for treat-
ment of the reaction mixture.
e Benzaldehyde (0.05 mol), butanone (0.06 mol), EtOH (30 mL).
To assess the generality of this iodination method and to
evaluate the electronic influence of the aromatic ring sub-
stituents, a series of other a,b-unsaturated ketones 4b–l
were prepared in 65–96% yields by the above-mentioned
aldol condensation of aldehydes with acetone or butanone
(Table 2, entries 2–12). It should be noted that vanillin
(3j) was condensed with acetone at 40 °C in the presence
of sodium hydroxide (1.2 equiv), followed by acidifica-
tion of the reaction solution using dilute hydrochloric acid
also to afford the desired product (E)-4-(4-hydroxy-3-
methoxyphenyl)but-3-en-2-one (4j) in 95% yield18
(Table 2, entry 10). The structures of all compounds 4 in
Table 2 were confirmed by 1H NMR, which were agree-
ment with data given in the literature.19 Furthermore, the
structure of new compound (E)-4-(9-anthryl)but-3-en-2-
one (4i) was characterized by 13C NMR, MS, and IR. Sub-
sequently, 4j was reacted with benzyl bromide in N,N-
dimethylformamide at 70 °C for eight hours in the pres-
ence of potassium hydroxide to give (E)-4-[4-(benzyl-
oxy)-3-methoxyphenyl]but-3-en-2-one (5) in 90%
yield;20 (E)-4-(4-acetoxy-3-methoxyphenyl)but-3-en-2-
one (6) was obtained in 92% yield by the reaction of 4j
with acetyl chloride for 30 minutes using triethylamine as
an acid-binding agent at room temperature21 (Scheme 2).
Next, other readily synthesized a,b-unsaturated ketones
4b–l in Table 2 were examined for the iodination reaction
using the copper(II) oxide/iodine system under the above-
mentioned optimal reaction conditions, the results are
summarized in Table 3. It could be seen from Table 3 that
as for the derivatives of benzalacetone, the corresponding
a¢-iodinated products 10b–g were obtained in 73–92%
yields while the benzene rings bear electron-donating
groups (e.g., Me, OMe, OEt) or moderate electron-
withdrawing groups (e.g., Cl, Br), and the C=C bonds
were not affected (Table 3, entries 2–7).
O
O
O
b
a
O
HO
BnO
O
OMe
OMe
OMe
6
4j
5
Scheme 2 Reagents and conditions: (a) BnBr, KOH, DMF, 70 °C, 8 h, 90%; (b) AcCl, Et3N, CH2Cl2, r.t., 0.5 h, 92%.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York

PAPER
Selective Iodination of a,b-Unsaturated Ketones
3677
Table 3 Synthesis of a,b-Unsaturated a¢-Iodo Ketones Directly
from a,b-Unsaturated Ketones
Table 3 Synthesis of a,b-Unsaturated a¢-Iodo Ketones Directly
from a,b-Unsaturated Ketones (continued)
O
O
O
O
R1
R2
H
R1
I
R1
R2
H
R1
I
CuO, I2
CuO, I2
R4
R4
R4
i-PrOH, 65 °C
R4
i-PrOH, 65 °C
R3
R2
R3
R3
R2
R3
Time (h) Yielda (%)
Entry Substrate Product
Time (h) Yielda (%)
Entry Substrate Product
O
O
I
I
1
2
3
4
5
4a
4b
4c
4d
4e
4
2
2
2
1
85
92
83
89
89
10
4j
4.5
85
HO
10a
10b
OMe
O
10j
O
I
I
11
12
4k
4l
2
6
79
72
O
10k
10l
O
I
I
MeO
10c
O
O
I
I
13
14
5
6
4
4
87
80
EtO
BnO
10d
OMe
O
10m
I
O
I
Cl
O
10e
O
O
OMe
I
10n
6
7
4f
2.5
4.5
73
82
Cl
Cl
10f
H
O
O
15
(Z)-7
1
65
62
O
O
I
I
4g
Br
10o
10g
O
H
O
I
16
17
(E)-8
10
4
8
9
4h
4i
1.5
70
70
I
O
NO2
10p
10q
10h
10i
O
b
O
9
–
I
I
3
a Isolated yield.
b Trace product was detected by GC-MS.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York

3678
Z. Wang et al.
PAPER
The substrate bearing the strongly electron-withdrawing entry 17). The possible reason for the low yield is that
nitro group on the phenyl ring delivered the iodinated C≡C bond, which can easily react with molecular iodine,
product
(E)-1-iodo-4-(3-nitrophenyl)but-3-en-2-one has higher reactivity than the C=C bond.25
(10h) in slightly lower yield (70%, Table 3, entry 8). In
addition, (E)-4-(9-anthryl)but-3-en-2-one (4i) also pro-
duced (E)-4-(9-anthryl)-1-iodobut-3-en-2-one (10i) in
70% yield (Table 3, entry 9). To our great satisfaction,
compounds 4j, 5, and 6 gave the expected a¢-iodinated
products 10j, 10m, and 10n in 85%, 87%, and 80% yields,
respectively (Table 3, entries 10, 13, and 14). Such an ap-
proach to the synthons 10j, 10m, and 10n could present
new possibilities for the synthesis of analogues of this
type with biomedicinal importance. It should be noted that
sensitive hydroxy group (OH) was not affected under
these mild reaction conditions and the hydrogens of the
acetyl group of compound 6 were not replaced by iodine,
probably due to the difficulty in the formation of the enol
form (see the following reaction mechanism). We also
found that (3E,5E)-6-phenylhexa-3,5-dien-2-one (4k) and
(E)-1-phenylpent-1-en-3-one (4l) delivered the corre-
sponding iodinated products 10k and 10l in 79% and 72%
yields, respectively (Table 3, entries 11 and 12).
It has been reported by Cort26 that copper(II) nitrate could
reoxidize the iodide ion (I–) to molecular iodine (I2) by the
treatment of enol silyl ethers or enol acetates with the cop-
per(II) nitrate/iodine system. In addition, on the basis of
our previous study,16b a hypothetic reaction mechanism is
shown in Scheme 5 using benzalacetone (4a) as an exam-
ple. It is thought that copper(II) oxide plays a multiple role
through random self-sorting. First, it acts as an oxidizing
agent or catalyst to convert molecular iodine into the re-
acting species iodonium ion (I+) analogous to the function
of other metal salts.6b,26b Meanwhile, it can acted as a
weak base to neutralize hydrogen iodide and reoxidize the
iodide ion to molecular iodine together with insoluble
copper(I) iodide and water.
I–
H
O+
OH
I
δ+ δ–
O
enol
I
I
H
O
H
b
a
H
O
OEt
CuO
H
I2
O
O
O
O
8
7 (Z/E = 1:1)
CuI + H2O
4a
I
+
Scheme 3 Reagents and conditions: (a) MeCOCH2CO2Et, piperid-
ine, AcOH, 90%; (b) PhCOCH2COMe, piperidine, AcOH, 78%.
HI
CuO
(i) n-BuLi
(ii) ZnCl2
O
O
(iii) acetyl chloride
I
9
10a
Scheme 4
Scheme 5 Possible reaction mechanism
Encouraged by the success of the above iodination reac-
tions starting from a,b-unsaturated ketones, we turned our
attention to other substrates. As shown in Scheme 3,
Knoevenagel condensation of benzaldehyde with ethyl
acetoacetate catalyzed by piperidine gave compound 7 in
90% yield (Z/E 1:1); the Z-isomer was separated by col-
umn chromatography as a white solid.22 Similarly, the E-
isomer of compound 8 was obtained as the major product
(78%) via condensation of benzaldehyde with benzoylac-
etone.23 We were glad to find that the desired iodinated
products 10o and 10p were also obtained in 65% and 62%
yields from compounds (Z)-7 and (E)-8 respectively
(Table 3, entries 15 and 16). Finally, we synthesized 4-
phenylbut-3-yn-2-one (9) in 89% yield by the reaction of
phenylacetylene with acetyl chloride in the presence of
butyllithium and zinc chloride24 (Scheme 4). The expect-
ed iodinated product 1-iodo-4-phenylbut-3-yn-2-one
(10q) was confirmed by GC-MS using compound 9 as the
starting material, though we did not separate it (Table 3,
In conclusion, a series of a,b-unsaturated ketones have
been synthesized via classical aldol or Knoevenagel con-
densation reactions. An efficient approach to a,b-unsatur-
ated a¢-iodo ketones directly from a,b-unsaturated
ketones by selective iodination at the a¢-position without
effect on the double bond and the activated benzene ring
in the presence of copper(II) oxide/iodine is described.
The possible reaction mechanism shows copper(II) oxide
plays a multiple role in this kind of reaction through ran-
dom self-sorting. The present method has the advantages
of high yields, short reaction times, inexpensive reagents,
mild reaction conditions, ease of manipulation, and the
formation of cleaner products. Moreover, as far as we
know, this is the first systematical investigation of the
synthesis of important a,b-unsaturated a¢-iodo ketones
from a,b-unsaturated ketones.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York

PAPER
Selective Iodination of a,b-Unsaturated Ketones
(E)-1-Iodo-4-(4-methoxyphenyl)but-3-en-2-one (10c)
3679
Finely powdered CuO was purchased from commercial sources
(>98%). 1H spectra were recorded on a Varian Mercury 400 or 600
MHz spectrometer. All 13C NMR spectra were recorded on a Varian
Mercury 400 MHz (13C at 100 MHz) spectrometer. Chemical shifts
are reported relative to TMS (internal standard). IR spectra of sam-
ples as KBr pellets were recorded on a PE-983 spectrophotometer.
MS was carried out on a Finnigan Trace MS spectrometer (EI, 70
eV). Column chromatography was performed on silica gel (200–
300 mesh).
IR (KBr): 3049, 1634, 1599, 1512, 1256, 1177, 1019, 972, 822, 936,
764 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.66 (d, J = 16.2 Hz, 1 H), 7.54 (d,
J = 8.4 Hz, 2 H), 6.93 (d, J = 8.4 Hz, 2 H), 6.77 (d, J = 16.2 Hz, 1
H), 4.00 (s, 2 H), 3.86 (s, 3 H).
13C NMR (CDCl3, 100 MHz): d = 192.2, 161.8, 144.8, 130.3, 126.4,
119.7, 114.3, 55.3, 5.2.
MS (EI, 70 eV): m/z (%) = 302 (22), 175 (16), 161 (100), 147 (19),
103 (22), 77 (14).
(E)-a,b-Unsaturated Ketones 4; General Procedure
To the mixture of aldehyde (0.1 mmol), acetone (20 mL, excess),
and H2O (40 mL) was slowly added 5% aq NaOH soln (8 mL) from
a dropping funnel at 40 °C. After disappearance of the reactant
(TLC), acetone was removed under reduced pressure and the resi-
due was poured into EtOAc (50 mL), the mixture was extracted with
EtOAc (3 × 50 mL), and the combined organic layers were dried
(anhyd Na2SO4). Removal of the solvent and purification of the res-
idue by column chromatography or recrystallization gave the target
products.
(E)-4-(4-Ethoxyphenyl)-1-iodobut-3-en-2-one (10d)
IR (KBr): 3444, 1641, 1620, 1599, 1509, 1252, 1173, 1035, 973,
825, 807 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.65 (d, J = 16.0 Hz, 1 H), 7.52 (d,
J = 8.8 Hz, 2 H), 6.91 (d, J = 8.8 Hz, 2 H), 6.76 (d, J = 16.0 Hz, 1
H), 4.08 (q, J = 7.2 Hz, 2 H), 4.00 (s, 2 H), 1.44 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 192.1, 161.3, 144.9, 130.4, 126.3,
119.6, 114.8, 63.6, 14.6, 5.1.
(E)-4-(9-Anthryl)but-3-en-2-one (4i)
MS (EI, 70 eV): m/z (%) = 316 (100), 189 (30), 176 (78), 175 (96),
147 (61), 133 (65), 91 (32), 77 (19).
IR (KBr): 1665, 1621, 1360, 1252, 737 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.50 (d, J = 16.4 Hz, 1 H), 8.47 (s,
1 H), 8.21 (d, J = 9.2 Hz, 2 H), 8.33 (d, J = 8.8 Hz, 2 H), 7.52–7.26
(m, 4 H), 6.72 (d, J = 16.4 Hz, 1 H), 2.57 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 197.9, 140.4, 135.8, 131.1, 129.2,
129.1, 128.9, 128.4, 126.4, 125.3, 125.0, 28.0.
(E)-4-(4-Chlorophenyl)-1-iodobut-3-en-2-one (10e)
IR (KBr): 3423, 1669, 1641, 1623, 1591, 1490, 1385, 1148, 1088,
980, 835, 881, 791 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.64 (d, J = 16.0 Hz, 1 H), 7.52 (d,
J = 8.4 Hz, 2 H), 7.40 (d, J = 8.4 Hz, 2 H), 6.87 (d, J = 16.0 Hz, 1
H), 4.01 (s, 2 H).
MS (EI, 70 eV): m/z (%) = 246 (35), 204 (73), 202 (100).
13C NMR (100 MHz, CDCl3): d = 191.9, 143.5, 136.9, 132.3, 129.7,
a,b-Unsaturated a¢-Iodo Ketones 10; General Procedure
Finely powdered CuO (0.40 g, 5.0 mmol) and I2 (1.27 g, 5.0 mmol)
were added to a well-stirred soln of a,b-unsaturated ketone (5.0
mmol) in i-PrOH (20 mL). The mixture was stirred for 5 min and
then was heated at 65 °C for 1–10 h. After disappearance of the re-
actant (TLC), the mixture was filtered and the solvent was removed
under reduced pressure (Note: the mixture could not be treated with
Na2S2O3 because it reacted with the iodinated product at r.t.), then
direct purification of the residue by column chromatography (petro-
leum ether–EtOAc) gave the target products in good yield.
129.2, 122.4, 5.0.
MS (EI, 70 eV): m/z (%) = 308 (M + 2), 306 (9), 179 (12), 167 (34),
165 (100), 137 (22), 115 (33), 101 (20), 75 (9).
(E)-4-(2,4-Dichlorophenyl)-1-iodobut-3-en-2-one (10f)
IR (KBr): 3455, 1672, 1649, 1583, 1130, 1101, 984, 866, 829 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.02 (d, J = 16.4 Hz, 1 H), 7.61 (d,
J = 8.8 Hz, 1 H), 7.47 (s, 1 H), 7.30 (d, J = 8.8 Hz, 1 H), 6.84 (d,
J = 16.4 Hz, 1 H), 4.04 (s, 2 H).
(E)-1-Iodo-4-phenylbut-3-en-2-one (10a)15
IR (KBr): 3445, 1640, 1573, 1436, 1270, 1072, 990, 874, 803, 764,
704 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 16.4 Hz, 1 H), 7.59–
7.57 (m, 2 H), 7.43–7.41 (m, 3 H), 6.89 (d, J = 16.4 Hz, 1 H), 4.02
(s, 2 H).
13C NMR (100 MHz, CDCl3): d = 191.6, 139.2, 136.9, 136.0, 130.7,
130.0, 128.4, 127.5, 124.7, 4.7.
MS (EI, 70 eV): m/z (%) = 344 (M + 4, 1), 342 (M+2, 8), 340 (M,
11), 307 (39), 305 (100), 201 (54), 199 (79), 99 (27), 74 (22).
(E)-4-(4-Bromophenyl)-1-iodobut-3-en-2-one (10g)
IR (KBr): 3425, 1670, 1643, 1619, 1583, 1143, 1068, 1007, 981,
879, 832 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.62 (d, J = 16.0 Hz, 1 H), 7.55 (d,
J = 8.4 Hz, 2 H), 7.44 (d, J = 8.4 Hz, 2 H), 6.88 (d, J = 16.0 Hz, 1
H), 4.00 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 192.1, 144.8, 133.8, 130.9, 128.9,
128.4, 122.2, 5.0.
MS (EI, 70 eV): m/z (%) = 272 (13), 146 (33), 144 (39), 131 (100),
104 (17), 91 (8), 78 (7).
13C NMR (100 MHz, CDCl3): d = 191.8, 143.5, 132.8, 132.2, 129.8,
125.3, 122.5, 5.0.
(E)-1-Iodo-4-(4-tolyl)but-3-en-2-one (10b)
IR (KBr): 1669, 1607, 1566, 1382, 1276, 1134, 988, 823 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.67 (d, J = 16.2 Hz, 1 H), 7.48 (d,
J = 7.8 Hz, 2 H), 7.23 (d, J = 7.8 Hz, 2 H), 6.85 (d, J = 16.2 Hz, 1
H), 4.01 (s, 2 H), 2.40 (s, 3 H).
MS (EI, 70 eV): m/z (%) = 352 (M + 2, 8), 352 (M, 8), 212 (57), 211
(60), 209 (100), 208 (63), 115 (52), 102 (31), 101 (22).
(E)-1-Iodo-4-(3-nitrophenyl)but-3-en-2-one (10h)
13C NMR (100 MHz, CDCl3): d = 192.0, 144.8, 141.4, 130.9, 129.5,
IR (KBr): 1695, 1613, 1522, 1348, 1052, 976, 866, 816 cm–1.
128.4, 120.9, 21.4, 5.3.
1H NMR (400 MHz, CDCl3): d = 8.45 (s, 1 H), 8.27 (d, J = 8.4 Hz,
1 H), 7.88 (d, J = 8.4 Hz, 1 H), 7.73 (d, J = 16.0 Hz, 1 H), 7.64 (d,
J = 8.4 Hz, 1 H), 7.02 (d, J = 16.0 Hz, 1 H), 4.03 (s, 2 H).
MS (EI, 70 eV): m/z (%) = 286 (99), 159 (3), 145 (22), 141 (59), 127
(53), 115 (100), 91 (43).
13C NMR (100 MHz, CDCl3): d = 191.4, 148.5, 141.7, 135.6, 134.2,
130.0, 124.9, 124.6, 122.6, 5.1.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York

3680
Z. Wang et al.
PAPER
MS (EI, 70 eV): m/z (%) = 317 (100), 190 (8), 176 (99), 115 (79),
102 (51).
1H NMR (400 MHz, CDCl3): d = 7.65 (d, J = 16.0 Hz, 1 H), 7.19
(dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1 H), 7.65 (d, J = 1.6 Hz, 1 H), 7.09
(d, J = 8.0 Hz, 1 H), 6.82 (d, J = 16.0 Hz, 1 H), 4.02 (s, 2 H), 3.89
(s, 3 H), 2.34 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 192.0, 168.7, 151.3, 144.3, 141.8,
132.8, 123.3, 122.2, 121.7, 111.5, 55.9, 20.6, 4.9.
(E)-4-(9-Anthryl)-1-iodobut-3-en-2-one (10i)
IR (KBr): 1674, 1600, 1405, 1263, 1194, 1040, 994, 889, 841, 782,
737 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.65 (d, J = 16.0 Hz, 1 H), 8.44 (s,
1 H), 8.22 (d, J = 8.4 Hz, 2 H), 8.01 (d, J = 8.4 Hz, 2 H), 7.54–7.47
(m, 4 H), 6.85 (d, J = 16.0 Hz, 1 H), 4.11 (s, 2 H).
MS (EI, 70 eV): m/z (%) = 360 (5), 318 (100), 191 (88), 177 (95),
159 (84), 145 (37), 131 (47), 103 (20), 91 (8).
13C NMR (100 MHz, CDCl3): d = 191.6, 142.1, 131.0, 130.9, 129.4,
128.8, 128.6, 126.5, 125.3, 124.8, 5.2.
Ethyl (E)-2-Benzylidene-4-iodo-3-oxobutanoate (10o)
IR (KBr): 3444, 1717, 1697, 1618, 1257, 1198, 1025, 692 cm–1.
MS (EI, 70 eV): m/z (%) = 372 (14), 245 (41), 202 (100).
1H NMR (400 MHz, CDCl3): d = 7.82 (s, 1 H), 7.42–7.40 (m, 5 H),
4.33 (q, J = 7.2 Hz, 2 H), 4.10 (s, 2 H), 1.36 (t, J = 7.2 Hz, 3 H).
(E)-4-(4-Hydroxy-3-methoxyphenyl)-1-iodobut-3-en-2-one
13C NMR (100 MHz, CDCl3): d = 195.8, 163.9, 144.0, 132.5, 130.9,
(10j)14
130.1, 129.7, 129.0, 128.7, 61.8, 14.1, 8.7.
IR (KBr): 3393, 1674, 1583, 1510, 1426, 1271, 1159, 1044, 1028,
978, 845, 810 cm–1.
MS (EI, 70 eV): m/z (%) = 344 (11), 299 (100), 217 (99), 115 (41),
102 (42), 76 (19).
1H NMR (600 MHz, CDCl3): d = 7.62 (d, J = 15.6 Hz, 1 H), 7.15
(dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1 H), 7.07 (d, J = 1.8 Hz, 1 H), 6.95
(d, J = 8.4 Hz, 1 H), 6.73 (d, J = 15.6 Hz, 1 H), 6.01 (s, 1 H, OH),
4.01 (s, 2 H), 3.95 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 192.4, 148.7, 146.7, 145.4, 126.2,
123.9, 119.6, 114.8, 109.7, 55.9, 4.9.
(Z)-2-Benzylidene-4-iodo-1-phenylbutane-1,3-dione (10p)
IR (KBr): 3444, 1668, 1637, 1617, 1594, 1573, 1233, 1258, 1211,
915, 782, 769 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.99 (s, 1 H), 7.95 (d, J = 8.0 Hz,
2 H), 7.54–7.51 (m, 1 H), 7.41–7.21 (m, 7 H), 4.20 (s, 2 H).
MS (EI, 70 eV): m/z (%) = 318 (100), 191 (2), 141 (23), 103 (33),
91 (16), 77 (11).
13C NMR (100 MHz, CDCl3): d = 196.7, 190.7, 143.5, 135.7, 135.6,
134.1, 132.4, 130.8, 130.4, 129.2, 128.7, 128.6, 2.3.
MS (EI, 70 eV): m/z (%) = 376 (5), 249 (89), 105 (100), 77 (48).
(3E,5E)-1-Iodo-6-phenylhexa-3,5-dien-2-one (10k)
IR (KBr): 3424, 1671, 1583, 1413, 1006, 753, 688, 642 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.50–7.33 (m, 6 H), 7.03–6.88 (m,
2 H), 6.43 (d, J = 15.6 Hz, 1 H), 3.95 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 192.3, 145.0, 142.7, 135.7, 129.5,
128.8, 127.4, 126.1, 125.4, 4.8.
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (Nos. 20672042 and 20872042) and the Graduate’s
Innovation Fund of Central China Normal University (2007).
MS (EI, 70 eV): m/z (%) = 298 (17), 171 (100), 157 (32), 128 (88),
102 (7), 77 (5).
References
(E)-4-Iodo-1-phenylpent-1-en-3-one (10l)
(1) (a) Kusama, H.; Onizawa, Y.; Iwasawa, N. J. Am. Chem.
Soc. 2006, 128, 16500. (b) Babu, K. S.; Li, X.-C.; Jacob, M.
R.; Zhang, Q.; Khan, S. I.; Ferreira, D.; Clark, A. M. J. Med.
Chem. 2006, 49, 7877. (c) Li, X.-C.; Ferreira, D.; Jacob, M.
R.; Zhang, Q.; Khan, S. I.; Elsohly, H. N.; Nagle, D. G.;
Smillie, T. J.; Khan, I. A.; Walker, L. A.; Clark, A. M. J. Am.
Chem. Soc. 2004, 126, 6872.
(2) Bora, U.; Saikia, A.; Boruah, R. C. Org. Lett. 2003, 5, 435.
(3) (a) Parker, D. L. Jr.; Ratcliffe, R. W.; Wilkening, R. R.;
Wildonger, K. J. WO 2001,082,923, 2001. (b) Rohrer, S. P.
WO 2005,099,704, 2005. (c) Tsukano, C.; Siegel, D. R.;
Danishefsky, S. J. Angew. Chem. Int. Ed. 2007, 46, 8840.
(4) (a) Southwick, P. L.; Pursglove, L. A.; Numerof, P. J. Am.
Chem. Soc. 1950, 72, 1600. (b) Southwick, P. L.; Pursglove,
L. A.; Numerof, P. J. Am. Chem. Soc. 1950, 72, 1604.
(c) Cristau, H.-J.; Torreilles, E.; Morand, P.; Christol, H.
Phosphorus, Sulfur Silicon Relat. Elem. 1985, 25, 357.
(5) (a) Okamoto, T.; Kakinami, T.; Nishimura, T.; Hermawan,
I.; Kajigaeshi, S. Bull. Chem. Soc. Jpn. 1992, 65, 1731.
(b) Burluenga, J.; Marco-Arias, M.; González-Bobes, F.;
Ballesteros, A.; González, J. M. Chem. Commun. 2004,
2616.
IR (KBr): 3421 (s), 1680 (s), 1610 (s), 1572 (s), 1444 (s), 1092 (s),
1040 (s), 975 (s), 761 (s), 709 (s), 683 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 16.0 Hz, 1 H), 7.60–
7.56 (m, 2 H), 7.42–7.40 (m, 3 H), 6.93 (d, J = 16.0 Hz, 1 H), 4.87
(q, J = 6.8 Hz, 1 H), 2.00 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 193.7, 144.1, 134.0, 130.7, 128.8,
128.5, 121.8, 24.5, 21.5.
MS (EI, 70 eV): m/z (%) = 286 (12), 159 (10), 131 (76), 127 (39),
103 (47), 91 (30), 77 (89), 51 (100).
(E)-4-[4-(Benzyloxy)-3-methoxyphenyl]-1-iodobut-3-en-2-one
(10m)
IR (KBr): 1667, 1616, 1591, 1512, 1276, 1256, 1138, 993, 917, 867
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.62 (d, J = 16.0 Hz, 1 H), 7.44–
7.32 (m, 5 H), 7.11–7.09 (m, 2 H), 6.89 (d, J = 8.8 Hz, 1 H), 6.73
(d, J = 16.0 Hz, 1 H), 5.22 (s, 2 H), 4.01 (s, 2 H), 3.95 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 192.1, 150.7, 149.5, 145.0, 136.2,
128.5, 128.0, 127.1, 127.0, 123.3, 120.0, 113.0, 110.2, 70.6, 55.9,
5.0.
(6) (a) Higgins, S. D.; Thomas, C. B. J. Chem. Soc., Perkin
Trans. 1 1982, 235. (b) Bekaert, A.; Barberan, O.; Gervais,
M.; Brion, J. D. Tetrahedron Lett. 2000, 41, 2903.
(c) Le Bras, G.; Provot, O.; Bekaert, A.; Peyrat, J.-F.; Alami,
M.; Brion, J.-D. Synthesis 2006, 1537.
MS (EI, 70 eV): m/z (%) = 408 (3), 365 (2), 281 (20), 91 (100).
(E)-4-(4-Acetoxy-3-methoxyphenyl)-1-iodobut-3-en-2-one
(10n)
IR (KBr): 1748, 1668, 1645, 1509, 1226, 1201, 1160, 1121, 1033,
(7) Horiuchi, C. A.; Kiji, S. Bull. Chem. Soc. Jpn. 1997, 70, 421.
985, 914, 864 cm–1.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York

PAPER
(8) (a) Stavber, S.; Jereb, M.; Zupan, M. Chem. Commun. 2002,
488. (b) Pavlinac, J.; Stavber, S.; Zupan, M. J. Org. Chem.
2006, 71, 1027.
(9) (a) Rao, M. L. N.; Jadhav, D. N. Tetrahedron Lett. 2006, 47,
6883. (b) Lee, J. C.; Park, J. Y.; Yoon, S. Y.; Bae, Y. H.; Lee,
S. J. Tetrahedron Lett. 2004, 45, 191. (c) Meshram, H. M.;
Reddy, P. N.; Vishnu, P.; Sadashiv, K.; Yadav, J. S.
Tetrahedron Lett. 2006, 47, 991.
Selective Iodination of a,b-Unsaturated Ketones
3681
(18) (a) Kuo, P. C.; Damu, A. G.; Cherng, C. Y.; Jeng, J. F.; Teng,
C. M.; Cheng, Z. J.; Lee, E. J.; Wu, T. S. Arch. Pharmacal
Res. 2005, 28, 518. (b) Kim, D. S. H. L.; Kim, J. Y. Bioorg.
Med. Chem. Lett. 2004, 14, 1287.
(19) (a) Buszek, K. R.; Brown, N. Org. Lett. 2007, 9, 707.
(b) Lin, Y.-M.; Li, Z.; Casarotto, V.; Ehrmantraut, J.;
Nguyen, A. N. Tetrahedron Lett. 2007, 48, 5531. (c)Peach,
P.; Cross, D. J.; Kenny, J. A.; Mann, I.; Houson, I.;
Campbell, L.; Walsgrove, T.; Wills, M. Tetrahedron 2006,
62, 1864. (d) Peppe, C.; das Chagas, R. P. J. Organomet.
Chem. 2006, 691, 5856. (e) Paul, S.; Gupta, M. Synth.
Commun. 2005, 35, 213. (f) Mitsudo, T.; Takagi, M.;
Zhang, S.-W.; Watanabe, Y. J. Organomet. Chem. 1992,
423, 405.
(10) Kim, J. M.; Na, J. E.; Kim, J. N. Tetrahedron Lett. 2003, 44,
6317.
(11) Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C.
B. W.; Wovkulich, P. M.; Uskoković, M. R. Tetrahedron
Lett. 1992, 33, 917.
(12) Krafft, M. E.; Cran, J. W. Synlett 2005, 1263.
(13) Benhida, R.; Blanchard, P.; Fourrey, J.-L. Tetrahedron Lett.
1998, 39, 6849.
(20) Krishnamurty, H. G.; Ghosh, S. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 1986, 25, 411.
(14) Jereb, M.; Stavber, S.; Zupan, M. Synthesis 2003, 853.
(15) Whang, J. P.; Yang, S. G.; Kim, Y. H. Chem. Commun.
1997, 1355.
(16) (a) Yin, G.; Zhou, B.; Meng, X.; Wu, A.; Pan, Y. Org. Lett.
2006, 8, 2245. (b) Yin, G.; Gao, M.; She, N.; Hu, S.; Wu, A.;
Pan, Y. Synthesis 2007, 3113. (c) Yin, G.; Wang, Z.; Chen,
A.; Wu, A.; Pan, Y. J. Org. Chem. 2008, 73, 3377.
(17) Drake, N. L.; Allen, P. Jr. Org. Synth. Coll. Vol. I; John
Wiley & Sons: London, 1941, 77.
(21) Elias, G.; Roa, M. N. A. Eur. J. Med. Chem. 1988, 23, 379.
(22) Correa, W. H.; Scott, J. L. Green Chem. 2001, 3, 296.
(23) Tanikaga, R.; Konya, N.; Hamamura, K.; Kaji, A. Bull.
Chem. Soc. Jpn. 1988, 61, 3211.
(24) Dos Santos, A. A.; Castelani, P.; Bassora, B. K.; Fogo, J. C.;
Costa, C. E.; Comasseto, J. V. Tetrahedron 2005, 61, 9173.
(25) Dodero, V. I.; Koll, L. C.; Belen Faraoni, M.; Mitchell, T.
N.; Podesta, J. C. J. Org. Chem. 2003, 68, 10087.
(26) (a) Cort, A. D. J. Org. Chem. 1991, 56, 6708. (b) Baird, W.
C. Jr.; Surridge, J. H. J. Org. Chem. 1970, 35, 3436.
Synthesis 2008, No. 22, 3675–3681 © Thieme Stuttgart · New York