AlCl3-NaI(NaBr)-t-BuOH: mild, chemo- and stereoselective reagents for hydrohalogenation of propiolic derivatives

Article abstract of DOI:10.1016/j.tet.2009.08.032

(Z)-β-Iodo-propenamides and -β-iodo-propenoic esters were selectively prepared in high yields, at room temperature, through reaction of 2-propynamides and 2-propynoic esters, respectively, with AlCl₃ and NaI in the presence of t-BuOH in dichlor

Full text of DOI:10.1016/j.tet.2009.08.032

Tetrahedron 65 (2009) 8733–8737
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Tetrahedron
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AlCl3–NaI(NaBr)–t-BuOH: mild, chemo- and stereoselective reagents
for hydrohalogenation of propiolic derivatives
*
*
`
Laurence Feray , Patricia Perfetti, Michele Bertrand
Equipe Chimie Mole´culaire Organique, UMR 6264, Laboratoire Chimie Provence, Aix-Marseille Universite´, Faculte´ des Sciences et Techniques de Saint-Je´roˆme,
service 562, av. Escadrille Normandie Niemen, 13397 Marseille cedex 20, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2009
Received in revised form 12 August 2009
Accepted 12 August 2009
Available online 18 August 2009
(Z)-b-Iodo-propenamides and -b-iodo-propenoic esters were selectively prepared in high yields, at room
temperature, through reaction of 2-propynamides and 2-propynoic esters, respectively, with AlCl3 and
NaI in the presence of t-BuOH in dichloromethane. These experimental conditions are compatible with
the presence of acid sensitive acetal groups. Alternative use of EtOH or H2O in place of t-BuOH was
investigated. (Z)-Bromo-propenamides and corresponding esters were prepared according to a similar
procedure using sodium bromide in refluxing acetonitrile.
Ó 2009 Published by Elsevier Ltd.
1. Introduction
sodium iodide have also been used in the presence of water, to
convert 1,2-allenic sulfoxides into 2-iodoallyl sulfoxides.10
While investigating dialkylzinc-mediated atom transfer radical
addition/cyclization process leading to -alkylidene-
-lactams,1 we
a
g
2. Results and discussion
found out by accident that direct selective hydrohalogenation of
2-propynamides occurred through their reaction with ZnX2 and
t-BuX (X¼Br, I) at room temperature.2 However, this methodology
was not suitable for substrates bearing acid sensitive groups such as
acetals. Direct hydrohalogenation of propynamides had been pre-
viously achieved at room temperature in the presence of Ce(III) salts,
halotrimethylsilanes and NaI in acetonitrile.3 Hydroiodination of
propynoic acid and its derivatives was also known to proceed with
either LiI,4 or NaI,5 in acetic acid at 70 ꢀC.
We have investigated whether the methodology of production
of these functionalized vinyl halides could be further improved. We
report herein a substantial modification of our procedure by using
cheaper reagents, i.e., AlCl3 and NaI in the presence tert-butanol.
The use of water, or ethanol as substitutes for tert-butanol was also
studied. The protocol, initially developed for hydroiodination of
propynamides, was extended to the corresponding esters and
ketones.
Various 2-propynamides (1a–1h) were prepared from propy-
noic acid and amines in the presence of DCC (Scheme 1). In our
previous studies,2 we had speculated that tert-butyl cation acted as
a mild and selective proton donor, according to Scheme 2.11 The
formation of tert-butyl cation from reaction of aluminium tri-
chloride with tert-butyl alcohol is well known in Friedel and Crafts
reactions.12 Therefore, we have first investigated whether hydro-
iodination reactions could be carried out in the presence of
1.5 equiv of aluminium trichloride, 2 equiv of sodium iodide in a 1:9
mixture of t-BuOH and dichloromethane, at room temperature for
18 h.
O
1a-h
O
R2
DCC, HNR1R2
CH2Cl2
N
R1
HO
The association of aluminium trichloride with sodium iodide
has widely been used for selective demethylation of aliphatic
methyl ethers in the presence of aromatic methyl ethers, either in
acetonitrile,6 or under solvent free conditions.7 This reagent is
known to deprotect some specific esters,8,6e and acetals.9,6e In close
connection with the present report, aluminium trichloride and
1a R1 = R2 = allyl
1 = R2 = CH2i-Pr
1 = R2 = Et
1e
1f
R
R1 = H, R2 = CH2CH(OEt)2
1b
1c
R
O
N
Ph
H
N
1g
O
O
O
1h R1 = H, R2 = allyl
R1 = H, R2 = m-PhNO2
1d
* Corresponding authors. Tel.: þ33 491288599.
Scheme 1. Synthesis of propynamides 1a–h.
E-mail address: laurence.feray@univ-cezanne.fr (L. Feray).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.08.032

8734
L. Feray et al. / Tetrahedron 65 (2009) 8733–8737
and t-BuOD in the protonation and deuteration of the intermediate
allenoate.
Sensitive acetal groups, known to be deprotected in the pres-
AlCl3
t-BuOH
Al(OH)Cl3
H donor
t-Bu
ence of AlCl3 and NaI in acetonitrile9 remained unchanged during
the reaction. Propynamides 1b and 1c, bearing acyclic and cyclic
acetal groups, led to vinyl iodides 2b and 2c, in 87% and 89% yields,
respectively, (entries 4–5). This is a significant advantage in using
the bulky tertiary alcohol. All the reactions described in Table 1
were stereoselective and led exclusively to the formation of (Z)-
vinyl iodides. No improvement was observed when replacing
CH2Cl2 with CH3CN.
R2
N
AlCl3
I
AlCl3
O
R1
H
I
O
NR1R2
1
R2
N
O
R1
2
Under specific conditions, ethanol and water could be used in
place of t-BuOH (entries 7–13). It must be noted that, notwith-
standing the fact that AlCl3 is reputedly reacting with protic species
to form HCl,12b no significant hydrochlorination was observed
when the reaction was conducted in the absence of NaI whatever
the used protic species (t-BuOH or EtOH 1:9 (v/v) ratio to CH2Cl2,
i.e., approximately 6 equiv of alcohol), or H2O (1 equiv in CH2Cl2).
As shown in Table 1, reactions carried out in the presence of ethanol
were high yielding and stereoselective. However, acetal depro-
tection occurred with compounds 1b and 1c.
Experiments carried out in the presence of water confirmed the
already mentioned observations concerning hydroiodination of
allenic sulfoxydes.10 High yields could only be observed in the
presence of 1 equiv of H2O (entries 12/13). However, it must be
noticed that acetals were deprotected under these conditions.
As exemplified in Scheme 4, non-terminal alkynes reacted very
slowly at room temperature. Hydroiodination of 1i led to 2i in 69%
yield after refluxing the reaction mixture for 18 h.
I
Scheme 2. Mechanism.
The results are summarized in Table 1. All three components
were necessary for the reaction to proceed. No reaction occurred in
the absence of AlCl3, whereas the reaction in the presence of AlCl3
gave 2a in 90% yield.13 In the presence of only 0.5 equiv of AlCl3,
hydroiodination was slowed down (73% of starting material
remained unchanged after 48 h). In the absence of t-BuOH, the
reaction conducted on diallylpropynamide 1a produced the cor-
responding (Z)-vinyl iodide 2a in only 38% yield while starting
material was recovered in 33% yield (entry 2). A quantitative yield
was reached when tert-butanol was used as solvent (entry 3).
Table 1
Hydroiodination of 1
R2
N
R2
N
1) AlCl3 (1.5 equiv)
NaI (2 equiv)
O
O
R1
R1
Allyl
N
Allyl
N
1) AlCl3 (1.5 equiv)
NaI (2 equiv)
I
ROH: CH2Cl2 (1:9)
room temperature, 18h
2) H2O
O
O
Allyl
Allyl
2
I
1
EtOH:CH3CN (1:9)
reflux, 18h
2i
1i
2) H2O
Entry
1a–e
Alcohol
2a–e
Yield (%)
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1c
1d
1a
1e
1f
1g
1h
1a
1a
t-BuOH
d
2a
2a
2a
2b
2c
2d
2a
2e
2f
2g
2h
2a
2a
90
38a
99b
87
69%
Scheme 4. Hydroiodination of 1i.
t-BuOH
t-BuOH
t-BuOH
t-BuOH
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
89
Stereoselective hydrobromination could be achieved by replac-
ing sodium iodide by sodium bromide (Scheme 5). The reactions
were slower and the highest yields were reached when the AlCl3–
NaBr–t-BuOH system was used in refluxing acetonitrile. Again,
owing to the higher temperature, substrates containing sensitive
acetal moieties (1b, 1c) were degraded in a complex mixture of
unidentified products under these conditions.
84c
82
100
96
88
9
10
11
12
13
80
20c,d
86c,e
H2O
a
1a was recovered in 33% yield.
In 100% t-BuOH.
In CH3CN.
1a was recovered in 79% yield.
Only 1 equiv of H2O was used.
R2
N
R2
N
b
c
1) AlCl3 (1.5 equiv)
NaBr (2 equiv)
O
O
R1
R1
d
e
Br
t-BuOH:CH3CN (1:9)
reflux, 18h
2) H2O
3a, 96%
Since the nature of the proton donor remained hypothetic, the
1
3b, 3c degradation
reaction was performed under the following conditions: t-BuOD/
CH2Cl2 1:9 (v/v), followed by work-up with D2O (Scheme 3). Non-
deuterated- and deuterated-2a were isolated in 70% yield, in
a 54:46 ratio (a similar ratio was obtained upon work-up with H2O).
This result clearly proved the involvement of both tert-butyl cation
3d, 77%
3f, 87%
Scheme 5. Hydrobromination of 1.
Propynoic esters were also transformed into the corresponding
vinyl iodides and bromides in good yields (Scheme 6). No trans-
esterification with ethanol was detected at room temperature. It is
worth noting that, although the AlCl3–NaI system is known to
cleave benzyl esters and esters derived from aromatic acids,8,6e no
trace of the corresponding acid was detected, even when per-
forming the reaction on allylic and benzylic esters 4a and 4b under
refluxing acetonitrile.
1) AlCl3 (1.5 equiv)
NaI (2 equiv)
(Allyl)2N
O
(Allyl)2N
(D)H
O
I
t-BuOD: CH2Cl2 (1:9)
room temperature, 18h
2) D2O
1a
2a:deuterated-2a 54:46
Scheme 3. Deuterium-labelling experiment.

L. Feray et al. / Tetrahedron 65 (2009) 8733–8737
8735
X
(1 equiv) were added and the reaction was allowed to warm up to
room temperature. After one night at room temperature, the so-
lution was filtered through a short pad of silica gel, which was
washed with CH2Cl2. After concentration in vacuo the resulting oil
was purified by FC. Spectral data for 2-propynamides 1a,1 1f,18 1h19
were in accordance with literature.
O
O
(i) or (ii)
R
R
O
O
5a, (i), X = I, EtOH, 75%
5a, (i), X = I, t-BuOH, 71%
5b, (i), X = I, EtOH, 88%
4a, R = Allyl
4b, R = Bn
4c, R = (CH2)3Ph
5c, (i), X = I, t-BuOH, 93%
6a, (ii), X = Br, 57%
6b, (ii), X = Br, 94%
4.2.1. Propynoic acid (2,2-diethoxy-ethyl)-amide (1b). Reacting
propiolic acid (1 mL), DCC (3.34 g) and 2,2-diethoxyethanamine
(2.35 mL), according to the general procedure, led to 1b (2.14 g)
isolated in 71% yield after purification (FC, pentane/ether, 80:20).
(i) 1) AlCl3 (1.5 equiv), NaI (2 equiv),
alcohol : CH2Cl2 (1:9), r.t., 18h, 2) H2O
(ii) 1) AlCl3 (1.5 equiv), NaBr (2 equiv),
1H NMR (CDCl3, 300 MHz):
d
1.21 (t, J¼7.0, 6H), 2.83 (s, 1H), 3.43
(dd, J¼5.1 and 6.1, 2H), 3.54 (dq, J¼9.4 and 7.0, 2H), 3.70 (dq, J¼9.4
t-BuOH : CH3CN (1:9), reflux, 18h, 2) H2O
and 7.0, 2H), 4.52 (t, J¼5.1, 1H), 6.22 (br s, 1H). 13C NMR (CDCl3,
75 MHz):
d
15.6 (CH3ꢂ2), 42.5 (CH2), 63.4 (CH2ꢂ2), 73.9 (C^), 77.6
Scheme 6. Hydrohalogenation of 4.
(^CH), 100.6 (CH), 152.6 (C]O). HRMS for C9H15NO3, [MH]þ calcd:
186.1125; found: 186.1122.
Finally the methodology was shown to apply to phenylpropynone
7 (Scheme 7). Whereas direct hydrohalogenation reactions of similar
compounds were reputed to occur in low yield (<50%),2,4 we were
pleased to notice that, under these new experimental conditions, the
corresponding vinyl iodide 8 and bromide 9 were isolated in 75 and
69% yields, respectively, as single (E)-isomers.14
4.2.2. Propynoic acid (2,2-dimethyl-4-phenyl-1,3-dioxinan-5-yl)-
amide (1c). Reacting propiolic acid (0.5 mL), DCC (1.67 g) and 2,2-
dimethyl-4-phenyl-1,3-dioxan-5-amine (1.68 g), according to the
general procedure, led to 1c (1.83 g) isolated in 87% yield after
purification (FC, pentane/ether, 80:20). 1H NMR (CDCl3, 300 MHz):
d
1.59 (s, 3H), 1.60 (s, 3H), 2.73 (s, 1H), 3.88–3.95 (m, 1H), 4.24–4.32
(m, 2H), 5.22 (d, J¼1.5, 1H), 6.44 (br d, J¼8.5, 1H), 7.26–7.42 (m, 5H).
13C NMR (CDCl3, 75 MHz):
18.9 (CH3), 30.1 (CH3), 47.8 (CH), 64.7
O
O
O
(i) or (ii)
d
Ph
Ph
Br
Ph
I
(CH2), 72.2 (CH), 74.0 (C^), 77.3 (^CH), 100.2 (C), 125.7 (]CH),
128.2 (]CH), 128.8 (]CH), 138.1 (]C), 151.9 (C]O). HRMS for
C15H17NO3, [MH]þ calcd: 260.1281; found: 260.1281.
75%
69%
9
7
8
(i) 1) AlCl3 (1.5 equiv), NaI (2 equiv),
alcohol : CH2Cl2 (1:9), r.t., 18h, 2) H2O
4.2.3. Propynoic acid (3-nitro-phenyl)-amide (1d). Reacting propiolic
acid (0.5 mL), DCC (1.67 g) and 3-nitrobenzenamine (1.11 g),
according to the general procedure, led to 1d (710 mg) isolated in
46% yield after purification (FC, pentane/AcOEt, 80:20). 1H NMR
(ii) 1) AlCl3 (1.5 equiv), NaBr (2 equiv),
t-BuOH : CH3CN (1:9), reflux, 18h, 2) H2O
Scheme 7. Hydrohalogenation of 7.
(DMSO-d6, 300 MHz):
and 8.3,1H), 7.96 (td, J¼2.2 and 8.3,1H), 8.58 (t, J¼2.1,1H),11.3 (s,1H).
13C NMR (DMSO-d6, 75 MHz):
78.2 (^CH), 78.5 (C^), 114.3 (]CH),
119.1 (]CH), 125.9 (]CH), 130.7 (]CH), 139.6 (]C), 148.3 (]C),
150.4 (C]O).
d
4.54 (s, 1H), 7.63 (t, J¼8.3,1H), 7.94 (td, J¼2.4
3. Conclusion
d
In conclusion, this paper describes a new and convenient
method for the preparation of functionalized vinyl iodides, which
are useful building blocks for the synthesis of complex molecules.
Hydroiodination of 2-propynamides was improved by using
AlCl3–NaI–ROH ternary system in CH2Cl2 at room temperature.
The reaction is stereoselective and leads to the formation of (Z)-
iodopropenamides in high yields. It is worth noting that the
methodology tolerates acid sensitive acetal groups when using
tert-butanol, and that ester groups remained unchanged even in
the presence of ethanol. NaBr-mediated hydrobromination
needed refluxing acetonitrile to give product in moderate to good
yield. The methodology was also shown to be suitable to convert
propynoic esters into 3-iodo or 3-bromo-propenoates, without
concomitant transesterification. Interesting yields were reached
with 2-phenylpropynone.
4.2.4. Propynoic acid diisobutylamide (1e). Reacting propiolic
acid (1.8 mL), DCC (6 g) and diisobutylamine (2.7 mL), according
to the general procedure, led to 1e (3.6 g) isolated in 68% yield
after purification (FC, pentane/ether, 90:10). 1H NMR (CDCl3,
300 MHz):
d
0.88 (d, J¼6.6, 6H), 0.92 (d, J¼6.6, 6H), 1.91–2.06 (m,
2H), 3.10 (s, 1H), 3.20 (d, J¼7.7, 2H), 3.38 (d, J¼7.6, 2H). 13C NMR
(CDCl3, 75 MHz):
d
20.3 (2ꢂCH3), 20.5 (2ꢂCH3), 26.7 (CH), 27.7
(CH), 52.1 (CH2), 56.7 (CH2), 76.9 (^CH), 79.2 (C^), 154.3
(C]O). HRMS for C10H17NO, [MH]þ calcd: 182.1539; found:
182.1539.
4.2.5. 1-(2,5-Dihydro-pyrrol-1-yl)-propynone (1g). Reacting pro-
piolic acid (1 mL), DCC (3.34 g) and 2,5-dihydro-1H-pyrrole
(1.23 mL), according to the general procedure, led to 1g (1.43 g)
isolated in 72% yield after purification (FC, pentane/ether, 60:40).
4. Experimental section
4.1. General
1H NMR (CDCl3, 300 MHz):
d
3.08 (s, 1H), 4.22–4.28 (m, 2H), 4.41–
4.47 (m, 2H), 5.80–5.88 (m, 2H). 13C NMR (CDCl3, 75 MHz):
d
52.8
NMR spectra were recorded at 300 MHz (1H) and 75 MHz (13C)
using CDCl3 as the solvent. The J values are given in Hz. Starting
materials 4a,15 4b,16 and 4c17 were prepared according to known
procedures. Spectral data were in accordance with literature.
(CH2), 55.1 (CH2), 76.8 (^CH), 78.0 (C^), 125.3 (]CH), 125.9
(]CH), 151.8 (C]O).
4.2.6. But-2-ynoic acid diallylamide (1i). Reacting butynoic acid
(1.36 g), DCC (3.34 g) and diallylamine (2 mL), according to the
general procedure, led to 1g (1.42 g) isolated in 54% yield after
purification (FC, pentane/ether, 85:15). 1H NMR (CDCl3, 300 MHz):
4.2. General procedure for 2-propynamides synthesis
A solution of propiolic acid (1 equiv) in CH2Cl2 (0.4 M) was
cooled to ꢁ20 ꢀC. Dicyclohexylcarbodiimide (1 equiv) and amine
d
1.95 (s, 3H), 3.92–4.13 (m, 4H), 5.05–5.21 (m, 4H), 5.61–5.81 (m,
2H). 13C NMR (CDCl3, 75 MHz):
d
4.3 (CH3), 46.5 (CH2), 51.0 (CH2),

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L. Feray et al. / Tetrahedron 65 (2009) 8733–8737
73.6 (^C), 89.2 (C^), 118.1 (]CH2), 118.2 (]CH2), 132.6 (]CH),
133.3 (]CH), 154.9 (C]O). HRMS for C10H13NO, [MH]þ calcd:
164.1070; found: 164.1066.
(]CH), 132.1 (]CH), 140.3 (]C), 148.3 (]C), 163.3 (C]O). HRMS
for C9H7IN2O3, [MH]þ calcd: 318.9574; found: 318.9573.
4.3.5. (Z)-3-Iodo-N,N-diisobutyl-acrylamide(2e). Hydroiodination of
1e (50 mg) in the presence of AlCl3 (55 mg) and NaI (83 mg) in
dichloromethane (1.3 mL) and EtOH (0.14 mL) afforded 2e (91 mg)
isolated in 100% yield after flash chromatography (100% pentane
4.3. General procedure for hydroiodination reaction
then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d
1.88 (d, J¼6.6, 6H),
To a solution of substrate (1 equiv) in dichloromethane (or
acetonitrile)/ROH (0.2 M, 9:1, v/v), AlCl3 (1.5 equiv) and sodium
iodide (2 equiv) were added at room temperature under inert at-
mosphere. After 18 h, water was added and the reaction was
extracted twice with dichloromethane. The organic layers were
dried over MgSO4, filtered and concentrated under reduced pres-
sure. Flash chromatography on silica gel afforded the correspond-
ing vinyl iodide.
0.95 (d, J¼6.6, 6H), 1.90 (nonet, J¼6.8, 1H), 2.10 (nonet, J¼6.8, 1H),
3.12 (d, J¼7.6, 2H), 3.24 (d, J¼7.6, 2H), 6.79 (d, J¼8.9, 1H), 7.13 (d,
J¼8.9, 1H). 13C NMR (75 MHz):
d
20.4 (2ꢂCH3), 20.9 (2ꢂCH3), 26.8
(CH), 27.8 (CH), 52.6 (CH2), 56.1 (CH2), 86.1 (]CHI), 135.6 (]CH),
167.7 (C]O). HRMS for C11H20INO, [MH]þ calcd: 310.0662; found:
310.0661.
4.3.6. (Z)-3-Iodo-N,N-diethyl-acrylamide (2f). Hydroiodination of 1f
(50 mg) in the presence of AlCl3 (80 mg) and NaI (120 mg) in
dichloromethane (1.8 mL) and EtOH (0.2 mL) afforded 2f (97 mg)
isolated in 96% yield after flash chromatography (100% pentane then
100% Et2O). Spectral data for 2f were in accordance with literature.3
4.3.1. (Z)-N,N-Diallyl-3-iodo-acrylamide(2a and deuterated-2a). Hydro-
iodination of 1a (50 mg) in the presence of AlCl3 (67 mg) and NaI
(100 mg) in dichloromethane (1.5 mL) and t-BuOH (0.17 mL) afforded
2a (84 mg) isolated in 90% yield after flash chromatography (100%
pentane then 100% Et2O). Spectral data were in accordance with lit-
erature.2 Hydroiodination of 1a (50 mg) in the presence of AlCl3
(67 mg) and NaI (100 mg) in dichloromethane (1.5 mL) and t-BuOD
(0.17 mL) afforded 2a and d-2a (64 mg, 70%, ratio: 54:46) after treat-
ment with D2O and flash chromatography (100% pentane then 100%
4.3.7. (Z)-1-(2,5-Dihydro-pyrrol-1-yl)-3-iodo-propenone (2g). Hydro-
iodination of 1g (50 mg) in the presence of AlCl3 (83 mg) and NaI
(124 mg) in dichloromethane (1.8 mL) and EtOH (0.2 mL) afforded 2g
(91 mg) isolated in 88% yield after flash chromatography (100%
pentane then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d 4.22–4.36 (m,
Et2O). 1H NMR for d-2a (CDCl3, 300 MHz):
(br d, 5.9 Hz, 2H), 5.11–5.28 (m, 4H), 5.68–5.89 (m, 2H), 6.88–6.91 (br
m, 1H). 13C NMR (75 MHz):
47.4 (CH2), 49.9 (CH2), 87.6 (]CHI), 117.9
d
3.85 (br d, 5.1 Hz, 2H), 4.05
4H), 5.78–5.84 (m, 1H), 5.87–5.94 (m, 1H), 7.03 (d, J¼8.9, 1H), 7.11 (d,
J¼8.9, 1H). 13C NMR (75 MHz):
d 53.2 (CH2), 53.7 (CH2), 88.8 (]CHI),
125.1 (]CH), 126.5 (]CH), 133.1 (]CH), 164.6 (C]O). HRMS for
d
(]CH2), 118.4 (]CH2), 132.9 (]CH), 133.1 (]CH), 134.5 (]CD, t
(1:1:1), J¼25), 167.1 (C]O).
C7H8INO, [MH]þ calcd: 249.9723; found: 249.9729.
4.3.8. (Z)-N-Allyl-3-iodo-acrylamide (2h). Hydroiodination of 1h
(50 mg) in the presence of AlCl3 (92 mg) and NaI (138 mg) in
dichloromethane (1.8 mL) and EtOH (0.2 mL) afforded 2h (87 mg)
isolated in 80% yield after flash chromatography (100% pentane
4.3.2. (Z)-N-(2,2-Diethoxy-ethyl)-3-iodo-acrylamide (2b). Hydro-
iodination of 1b (50 mg) in the presence AlCl3 (54 mg) and NaI
(82 mg) in dichloromethane (1.2 mL) and t-BuOH (0.14 mL)
afforded 2b (74 mg) isolated in 87% yield after flash chroma-
tography (100% pentane then 100% Et2O). 1H NMR (CDCl3,
then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d
3.97 (tt, J¼5.9 and 1.5,
2H), 5.16 (dq, J¼10.2 and 1.5, 1H), 5.24 (dq, J¼17.2 and 1.5, 1H), 5.85
300 MHz):
d
1.22 (t, J¼7.0, 6H), 3.49 (t, J¼5.7, 2H), 3.57 (dq, J¼9.4
(ddt, J¼17.2, 10.2 and 5.9, 1H), 6.3 (br s, 1H), 6.91 (d, J¼8.9, 1H), 7.05
and 7.0, 2H), 3.72 (dq, J¼9.4 and 7.0, 2H), 4.57 (t, J¼5.1, 1H), 6.16
(d, J¼8.9, 1H). 13C NMR (75 MHz):
d 42.3 (CH2), 88.6 (]CHI), 117.3
(]CH2), 133.3 (]CH), 134.0 (]CH), 164.8 (C]O). HRMS for
(br s, 1H), 6.87 (d, J¼8.9, 1H), 7.06 (d, J¼8.9, 1H). 13C NMR (CDCl3,
75 MHz):
d
15.7 (CH3ꢂ2), 42.2 (CH2), 63.4 (CH2ꢂ2), 88.5 (]CHI),
C6H8INO, [MH]þ calcd: 237.9723; found: 237.9728.
100.9 (CH), 133.3 (]CH), 164.9 (C]O). HRMS for C9H16INO3,
[MH]þ calcd: 314.0248; found: 314.0248.
4.3.9. (Z)-3-Iodo-but-2-enoic acid diallylamide (2i). Hydroiodination
of 1i (50 mg) in the presence of AlCl3 (65 mg) and NaI (92 mg) in
acetonitrile (1.5 mL) and EtOH (0.15 mL) afforded 2i (62 mg) isolated
in 69% yield after flash chromatography (100% pentane then 100%
4.3.3. (Z)-N-(2,2-Dimethyl-4-phenyl-1,3-dioxinan-5-yl)-3-iodo-
acrylamide (2c). Hydroiodination of 1c (100 mg) in the presence
of AlCl3 (77 mg) and NaI (114 mg) in dichloromethane (1.8 mL)
and t-BuOH (0.2 mL) afforded 2c (133 mg) isolated in 89% yield
after flash chromatography (100% pentane then 100% Et2O). 1H
Et2O). 1H NMR (CDCl3, 300 MHz):
d
2.62 (d, J¼1.5, 3H), 3.87–3.94 (m,
2H), 4.00–4.08 (m, 2H), 5.11–5.30 (m, 4H), 5.68–5.90 (m, 4H), 6.44
(q, J¼1.5, 1H). 13C NMR (75 MHz):
d 33.5 (CH3), 45.9 (CH2), 48.7
NMR (CDCl3, 300 MHz):
d
1.57 (s, 3H), 1.60 (s, 3H), 3.97 (dd,
(CH2), 104.1 (]CI), 116.5 (]CH2), 116.8 (]CH2), 129.0 (]CH), 131.6
(]CH), 131.8 (]CH), 166.3 (C]O). HRMS for C10H14NOI, [MH]þ
calcd: 292.0193; found: 292.0193.
J¼12.1 and 1.7, 1H), 4.28 (dd, J¼12.1 and 1.9, 1H), 4.37 (dq, J¼9.0
and 1.9, 1H), 5.25 (d, J¼1.9, 1H), 6.50 (br d, J¼9.0, 1H), 6.68 (d,
J¼9.1, 1H), 6.92 (d, J¼9.1, 1H). 13C NMR (CDCl3, 75 MHz):
d 18.9
(CH3), 30.0 (CH3), 47.1 (CH), 64.7 (CH2), 72.0 (CH), 88.0 (]CHI),
100.0 (C), 125.6 (]CH), 127.9 (]CH), 128.6 (]CH), 133.2 (]CH),
138.3 (]C), 164.1 (C]O). HRMS for C15H18INO3, [MH]þ calcd:
388.0404; found: 388.0402.
4.3.10. (Z)-3-Iodo-acrylic acid allyl ester (5a). Hydroiodination of 4a
(50 mg) in the presence of AlCl3 (93 mg) and NaI (139 mg) in
dichloromethane (2.1 mL) and EtOH (0.2 mL) afforded 5a (82 mg)
isolated in 75% yield after flash chromatography (100% pentane then
100% Et2O). Spectral data for 5a were in accordance with literature.4b
4.3.4. (Z)-3-Iodo-N-(3-nitro-phenyl)-acrylamide (2d). Hydroiodi-
nation of 1d (50 mg) in the presence of AlCl3 (52 mg) and NaI
(79 mg) in acetonitrile (1.2 mL) and t-BuOH (0.13 mL) afforded 2d
(70 mg) isolated in 84% yield after flash chromatography (100%
4.3.11. (Z)-3-Iodo-acrylic acid benzyl ester (5b). Hydroiodination of
4b (50 mg) in the presence of AlCl3 (62 mg) and NaI (94 mg) in
dichloromethane (1.4 mL) and EtOH (0.15 mL) afforded 5b (79 mg)
isolated in 88% yield after flash chromatography (100% pentane
pentane then 100% Et2O). 1H NMR (DMSO-d6, 300 MHz):
d 7.20 (d,
J¼8.7, 1H), 7.57 (d, J¼8.7, 1H), 7.61 (t, J¼8.3, 1H), 7.92–7.94 (m, 2H),
then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d 5.26 (s, 2H), 6.97 (d,
8.69 (br t, J¼1.5, 1H), 10.7 (s, 1H). 13C NMR (DMSO-d6, 75 MHz):
J¼9.1, 1H), 7.35–7.45 (m, 5H), 7.51 (d, J¼9.1, 1H). 13C NMR (75 MHz):
d
94.2 (]CHI), 113.7 (]CH), 118.5 (]CH), 125.5 (]CH), 130.6
d 67.0 (CH2), 96.0 (]CHI), 128.8 (]CH), 128.9 (]CH), 129.0 (]CH),

L. Feray et al. / Tetrahedron 65 (2009) 8733–8737
8737
130.0 (]CH), 135.9 (]C), 164.8 (C]O). HRMS for C10H9IO2, [MH]þ
calcd: 288.9720; found: 288.9725.
isolated in 87% yield after flash chromatography (100% pentane
then 100% Et2O). Spectral data for 3f were in accordance with
literature.3
4.3.12. (Z)-3-Iodo-acrylic acid 3-phenyl-propyl ester (5c). Hydro-
iodination of 4c (50 mg) in the presence of AlCl3 (53 mg) and NaI
(80 mg) in dichloromethane (1.2 mL) and t-BuOH (0.10 mL) affor-
ded 5c (78 mg) isolated in 93% yield after flash chromatography
4.4.4. (Z)-3-Bromo-acrylic acid allyl ester (6a). Hydrobromination
of 4a (50 mg), in the presence of AlCl3 (93 mg) and NaBr (96 mg) in
acetonitrile (2.1 mL) and t-BuOH (0.2 mL), afforded 6a (50 mg)
isolated in 57% yield after flash chromatography (100% pentane
then 100% Et2O). Spectral data for 6a were in accordance with
literature.4b
(100% pentane then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d 2.05
(tt, J¼7.6 and 6.6, 2H), 2.76 (t, J¼7.6, 2H), 4.25 (t, J¼6.6, 2H), 6.94 (d,
J¼8.9, 1H), 7.13–7.35 (m, 5H), 7.48 (d, J¼8.9, 1H). 13C NMR (75 MHz):
d
30.6 (CH2), 32.6 (CH2), 64.6 (CH2), 95.2 (]CHI), 126.5 (]CH),
128.8 (]CH), 128.9 (]CH), 130.3 (]CH), 141.5 (]C), 165.0 (C]O).
4.4.5. (Z)-3-Bromo-acrylic acid benzyl ester (6b). Hydrobromi-
nation of 4b (50 mg), in the presence of AlCl3 (62 mg) and NaBr
(64 mg) in acetonitrile (1.4 mL) and t-BuOH (0.15 mL), afforded 5b
(71 mg) isolated in 94% yield after flash chromatography (100%
HRMS for C12H13IO2, [MH]þ calcd: 317.0033; found: 317.0034.
4.3.13. (E)-3-Iodo-1-phenyl-propenone (8). Hydroiodination of
phenylpropynone 7 (50 mg) in the presene of AlCl3 (77 mg) and NaI
(115 mg) in dichloromethane (1.8 mL) and EtOH (0.2 mL) afforded 8
(74 mg) isolated in 75% yield after flash chromatography (100%
pentane then 100% Et2O). Spectral data for 7 were in accordance
with literature.4b
pentane then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d 5.25 (s, 2H),
6.69 (d, J¼8.3, 1H), 7.04 (d, J¼8.3, 1H), 7.32–7.47 (m, 5H). 13C NMR
(75 MHz):
d 67.0 (CH2), 122.3 (]CH), 124.6 (]CH), 128.8 (]CH),
128.9 (]CH), 129.0 (]CH), 135.9 (]C), 164.1 (C]O). HRMS for
C10H9BrO2, [MH]þ calcd: 240.9859; found: 240.9859.
4.4. General procedure for hydrobromination reaction
4.4.6. (E)-3-Bromo-1-phenyl-propenone (9). Hydrobromination of
phenylpropynone 7 (50 mg), in the presence of AlCl3 (77 mg) and
NaBr (78 mg) in acetonitrile (1.8 mL) and t-BuOH (0.2 mL), afforded
9 (55 mg) isolated in 69% yield after flash chromatography (100%
pentane then 100% Et2O). Spectral data for 9 were in accordance
with literature.4b
To a solution of substrate (1 equiv) in acetonitrile/t-BuOH (0.2 M,
9:1, v/v) AlCl3 (1.5 equiv) and sodium bromide (2 equiv) were added
at room temperature under inert atmosphere. After 18 h stirring at
reflux, water was added and the reaction was extracted twice with
ether. The organic layers were dried over MgSO4, filtered and con-
centrated under reduced pressure. Flash chromatography on silica
gel afforded the corresponding vinyl bromide.
References and notes
1. Feray, L.; Bertrand, M. P. Eur. J. Org. Chem. 2008, 3164.
2. Feray, L.; Perfetti, P.; Bertrand, M. P. Synlett 2009, 89.
3. Fujisawa, T.; Tanaka, A.; Ukaji, Y. Chem. Lett. 1989, 1255.
4. (a) Ma, S.; Lu, X.; Li, Z. Tetrahedron Lett. 1990, 31, 7653; (b) Ma, S.; Lu, X.; Li, Z.
J. Org. Chem. 1992, 57, 709.
5. Marek, I.; Alexakis, A.; Normant, J.-F. Tetrahedron Lett. 1992, 33, 5329.
6. (a) Node, M.; Ohta, K.; Kajimoto, T.; Nishide, K.; Fujita, E.; Fuji, K. Chem. Pharm.
Bull. 1983, 31, 4178; (b) Akiyama, T.; Takechi, N.; Shima, H.; Ozaki, S. Chem. Lett.
1990, 1881; (c) Akiyama, T.; Takechi, N.; Ozaki, S.; Shiota, K. Bull. Chem. Soc. Jpn.
1992, 65, 366; (d) Blagbrough, I. S.; Hardick, D. J.; Wonnacott, S.; Potter, B. V. L.
Tetrahedron Lett. 1994, 35, 3367; (e) Node, M.; Kajimoto, T.; Nishide, K.; Fujita,
E.; Fuji, K. Bull. Inst. Chem. Res., Kyoto Univ. 1992, 70, 308.
4.4.1. (Z)-N,N-Diallyl-3-bromo-acrylamide (3a). Hydrobromination
of 1a (50 mg), in the presence of AlCl3 (67 mg) and NaBr (69 mg) in
acetonitrile (1.5 mL) and t-BuOH (0.17 mL) afforded 3a (74 mg)
isolated in 96% yield after flash chromatography (100% pentane
then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d
3.86 (br d, J¼5.9, 2H),
4.01 (br d, J¼5.9, 2H), 5.06–5.24 (m, 4H), 5.64–5.83 (m, 2H), 6.58 (d,
J¼8.1, 1H), 6.76 (d, J¼8.1, 1H). 13C NMR (75 MHz):
d 47.1 (CH2), 50.0
(CH2), 113.5 (]CH), 117.9 (]CH2), 118.2 (]CH2), 128.7 (]CH), 132.8
(]CH), 133.1 (]CH), 165.9 (C]O). HRMS for C9H12BrNO, [MH]þ
calcd: 230.0175; found: 230.0180.
7. Ghiaci, M.; Asghari, J. Synth. Commun. 1999, 29, 973.
8. (a) Bhatt, M. V.; Setty, K. S. S. Indian J. Chem., Sect. B 1987, 26, 467; (b) For the
hydrolysis of esters with AlCl3$6H2O/KI/CH3CN/H2O, see: Gogoi, P.; Konwar, D.;
Sharma, S. D.; Gogoi, P. K. Synth. Commun. 2006, 36, 1259.
4.4.2. (Z)-3-Bromo-N-(3-nitro-phenyl)-acrylamide (3d). Hydro-
bromination of 1d (70 mg), in the presence of AlCl3 (73 mg) and
NaBr (76 mg) in acetonitrile (1.7 mL) and t-BuOH (0.18 mL), affor-
ded 3d (77 mg) isolated in 77% yield after flash chromatography
9. (a) Jun, J. G.; Suh, S.; Shin, D. G. J. Chem. Soc., Perkin Trans. 1 1989, 1349.
10. Ma, S.; Wei, Q. Eur. J. Org. Chem. 2000, 1939.
11. The mechanism, involves conjugate addition of halide anion to the activated
substrate. The intermediate allenoate is protonated at the less hindered face of
the double bond, i.e., the opposite side relative to the halogen atom. This
explains the selectivity observed in favour of the (Z)-isomer.
12. (a) Huston, R. C.; Fox, W. B.; Binder, M. N. J. Org. Chem. 1938, 3, 251; (b) Norris,
J. F.; Sturgis, B. M. J. Am. Chem. Soc. 1939, 61, 1413.
13. For sake of comparison all reactions were analyzed after 18 h. However,
monitoring hydroiodination of 1a proved that the reaction was completed
within 4 h. The similarity of isolated yields showed that no further degradation
occurred.
(100% pentane then 100% Et2O). 1H NMR (CDCl3, 300 MHz):
d 6.83
(d, J¼8.5, 1H), 6.95 (d, J¼8.5, 1H), 7.52 (t, J¼8.1, 1H), 7.97–8.07 (m,
2H), 8.48 (br t, J¼2.1, 1H), 8.53 (br s, 1H). 13C NMR (CDCl3, 75 MHz):
d
115.2 (]CH), 117.6 (]CH), 119.7 (]CH), 126.2 (]CH), 128.1
(]CH), 130.3 (]CH), 139.0 (]C), 148.9 (]C), 162.6 (C]O). HRMS
for C9H7BrN2O3, [MH]þ calcd: 270.9713; found: 270.9717.
14. In this case isomerization into the most stable (E)-isomer occurred, see: Ref. 4b.
15. Padwa, A.; Wong, G. S. K. J. Org. Chem. 1986, 51, 3125.
16. Balas, L.; Jousseaume, B.; Langwost, B. Tetrahedron Lett. 1989, 30, 4525.
17. Takai, K.; Kaihara, H.; Higashiura, K.-I.; Ikeda, N. J. Org. Chem. 1997, 62, 8612.
18. Hoberg, H.; Riegel, H. J. J. Organomet. Chem. 1983, 242, 245.
19. Wang, Z.; Lu, X. Tetrahedron 1995, 51, 2639.
4.4.3. (Z)-3-Bromo-N,N-diethyl-acrylamide (3f). Hydrobromination
of 1f (50 mg), in the presence of AlCl3 (80 mg) and NaBr (82 mg) in
acetonitrile (1.8 mL) and t-BuOH (0.2 mL), afforded 3f (72 mg)