Iron catalyzed hydrodebromination of 2-aryl-1,1-dibromo-1-alkenes

Article abstract of DOI:10.1016/S0022-328X(00)00934-7

2-Aryl- or 2-heteroaryl-1,1-dibromo-1-alkenes are reduced by Grignard reagents in a THF + NMP mixture in the presence of a catalytic amount of iron salts, to afford the corresponding E vinyl bromides. Further application to the one pot reduction-cross coupling reaction with Grignard reagents is highlighted.

Full text of DOI:10.1016/S0022-328X(00)00934-7

Journal of Organometallic Chemistry 624 (2001) 131–135
www.elsevier.nl/locate/jorganchem
Iron catalyzed hydrodebromination of 2-aryl-1,1-dibromo-1-alkenes
Mohamed Akram Fakhfakh, Xavier Franck, Reynald Hocquemiller, Bruno Figade`re *
Laboratoire de Pharmacognosie, associe´ au CNRS (BIOCIS), Uni6ersite´ Paris-Sud, Faculte´ de Pharmacie, Rue Jean-Baptiste Cle´ment,
F-92296 Chaˆtenay-Malabry, France
Received 3 October 2000; accepted 6 December 2000
Dedicated with a deep respect and admiration to Professor J. Normant on the occasion of his 65th birthday
Abstract
2-Aryl- or 2-heteroaryl-1,1-dibromo-1-alkenes are reduced by Grignard reagents in a THF+NMP mixture in the presence of
a catalytic amount of iron salts, to afford the corresponding E vinyl bromides. Further application to the one pot reduction-cross
coupling reaction with Grignard reagents is highlighted. © 2001 Elsevier Science B.V. All rights reserved.
Keywords: Hydrodebromination; Grignard reagents; E vinyl bromides
Grignard reagents, in the presence of transition metals
such as Fe, Co, could advantageously perform the
1. Introduction
hydrodebromination of 1,1-dibromo-1-alkenes, and re-
Only three examples of hydrodebromination of 1,1-
port herein our preliminary findings in this area
dibromo-1-alkenes, to our knowledge, were reported in
(Scheme 1).
the literature [1]. These methods suffer from two major
drawbacks; either the corresponding 1-bromo-1-alkene
is obtained as a Z- and E-isomer mixture, and/or toxic
n-Bu3SnH is used in the presence of palladium catalyst.
However, Cahiez and coworkers reported two interest-
ing papers in which they described the reduction of
1-bromo-1-alkenes with Grignard reagents in high
yields when the reaction is performed in the presence of
manganese(II) halide [2], and in some particular cases,
albeit in moderate yields, in the presence of Fe(acac)3
[3a]. We were thus interested to check if the use of
2. Results and discussion
We first used 1,1-dibromo-2-(2-quinolyl)-1-ethene
(1a) as starting material, and studied the reaction con-
ditions (Scheme 1 and Table 1). When 1a was treated
with 1.1 equivalents of i-PrMgCl in the presence of 5%
molar of Fe(acac)3 in a THF+NMP (1:1) mixture
between −10 and 0°C for 3 h, we were relatively
surprised to find out that the desired compound 2a was
obtained in high yield as the sole E-isomer (E\95% by
1H-NMR on the crude mixture). Then we noticed that
after only 30 min of reaction, the 1-bromo-1-alkene (2a)
was obtained with identical high yield (84%). Com-
pound 4a, which could arise from a mono-coupling
reaction of the Grignard reagent with 1a, was not
isolated, neither alkyne 5a resulting from debromohy-
dration. However, in the absence of either Fe(acac)3 or
NMP, no reaction occurred and the starting material
was recovered unchanged. At low temperature no reac-
tion was observed (−78°C, entry 2). Lowering the
catalyst loading to 1 mol% gave lower yields of the
Scheme 1.
* Corresponding author. Tel.: +33-1-4683-5592; fax: +33-1-4683-
5399.
E-mail address: bruno.figadere@cep.u-psud.fr (B. Figade`re).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00934-7

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M.A. Fakhfakh et al. / Journal of Organometallic Chemistry 624 (2001) 131–135
Table 1
Hydrodebromination of 1,1-dibromo-2-(2-quinolyl)-1-ethene (1a) by Grignard reagents in the presence of transition metals in THF, for 30 min
a
Entry
R
Catalyst b
T (°C)
Cosolvent c
Products d (yield)
1
2
3
4
5
6
7
8
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
n-Dodec
i-Pr
Fe (5)
Fe (5)
Fe (5)
None
Fe (1)
Fe (5)
FeCi3 (5)
Co (5)
−10–0
−78
NMP
NMP
None
NMP
NMP
NMP
NMP
NMP
2a (84)
NR
NR
−10–0
−10–0
−10–0
−10–0
−10–0
−10–0
NR
2a (49)
2a (50), 3a (15)
2a (85)
2a (42)
i-Pr
a 1.1 equivalents of RMgX
b Fe(acac)3 or Co(acac)2 (x% molar).
c THF with cosolvent.
d NR: no reaction.
1
desired E-bromoalkene product 2a (49%), together with
some coupled product 1-(2-quinolyl)-3-methyl-1-butene
(5%). However, increasing the amount of catalyst to 20
mol% (result not shown) did not improve the yield of
2a compared to the experiment with 5% of catalyst.
Another experiment (entry 6) showed that n-dodecyl-
magnesium bromide gives the same reaction, since the
desired compound 2a was isolated in 50% yield together
with the cross-coupled product 3a in 15% yield, result-
ing from the Grignard coupling reaction with the so-
formed 1-bromo-1-alkene (2a), as reported by Cahiez
[3a]. This result, with those obtained entry 5, shows
that the reduction step is much more rapid than the
coupling reaction with the so-formed 1-bromo-1-alkene
(2a). When n-dodecylmagnesium bromide was used, we
also isolated dodec-1-ene (3%).
These results indicate that experiments probably pro-
ceeded through a hydrogen b elimination, leading to an
hydridoiron (I) species which in turn is the reactive
species. Felkin, when reducing allylic alcohols with
Grignard reagents in the presence of a Ni(II) catalyst,
proposed an hydridonickel intermediate [4]. Kochi as-
sumed that Fe(III) was also reduced easily by Grignard
reagents to afford an hydridoiron (I) complex [3b].
When FeCl3 was used instead, 2a was obtained in
85% yield, but FeCl3 is not as convenient as Fe(acac)3
because of its hydrophilic properties. We then tried
Co(acac)2 as catalyst for this reaction, since Co(II) is
isoelectronic to Fe(I), and observed that in this case the
desired 1-bromo-1-alkene (2a) was obtained in lower
yield (42%), together with 1-(2-quinolyl)-3-methyl-1-
butene (5%).
the crude H-NMR). However in the case of aliphatic
1,1-dibromo-1-alkenes (1d,e), either the corresponding
alkyne was sometimes obtained, or no reaction oc-
curred. In the case of 1,1-dibromo-1,3-dienes (results
not shown) the expected reduced products are obtained
but in lower yields, and thus further optimizations will
be reported shortly.
The mechanism of this reaction is still unknown, but
two observations should be made regarding the crucial
effect of NMP which was also noted in related reac-
tions [3a,5]. The influence of NMP in our reaction is
highlighted by a comparison with the lack of reduction
reaction in the iron-catalyzed olefin carbometalation
with Grignard reagents in THF, as reported by Naka-
mura [6]. The second remark is the high E stereoselec-
tivity observed, since all intermolecular oxidative
additions of transition metal to 1,1-dihalo-1-alkenes
have occurred onto the trans alkenyl-halide bond in all
cases [7]. Only in intramolecular reactions the (Z)-bro-
mide reacted with an organostannane [8]. A direct
metalation via bromide–magnesium exchange is proba-
bly not involved at such a temperature [9], but a
carbene species (through
Wiechell rearrangement) could interfere in the cases of
a
Fritsch–Buttenberg–
Then several 1,1-dibromo-1-alkenes (1) were treated
under the best reaction conditions (Fe(acac)3 5% molar
in a 1:1 THF+NMP mixture with one equivalent of
i-PrMgCl for 30 min between −10°C and 0°C) and the
results are reported in Scheme 2.
It is worth noting that with aromatic alkenes, yields
of the E-bromoalkenes 2a–c obtained are good and the
stereoselectivity excellent (no Z-isomers observed on
Scheme 2.

M.A. Fakhfakh et al. / Journal of Organometallic Chemistry 624 (2001) 131–135
133
Scheme 3.
transformation. Furthermore, this method is comple-
mentary to the palladium catalyzed n-Bu3SnH-hy-
drogenolysis of these substrates [1c].
non aromatic 1,1-dibromo-1-alkenes. Nevertheless fur-
ther studies are required to elucidate this mechanism.
Then, we decided to study the possibility to perform
the reduction and the cross-coupling reaction in a one-
pot sequence by treating 1,1-dibromo-2-aryl-1-ethenes
(1) either by two equivalents of a Grignard reagent in
the presence of Fe(acac)3 (5%), or by one equivalent of
i-PrMgCl followed by one equivalent of the desired
Grignard reagent (Scheme 3). The study was performed
with 1,1-dibromo-2-quinolyl-1-ethene (1a) and with 1,1-
dibromo-2-(3,4-dimethoxy)phenyl-1-ethene (1b) and
C12H25MgBr. The expected E-1-aryl-tetradec-1-enes
(3a,b) were thus obtained in moderate yields (not
optimized).
When 1a was treated directly by two equivalents of
C12H25MgBr (method A), compound 3a was obtained
in 45% yield, and dodec-1-ene was isolated in 9% yield.
However, when 1a was first treated by one equivalent
of i-PrMgCl and then one equivalent of C12H25MgBr
(method B), 2a was isolated in 63% yield. It is worth
noting that 3b was obtained in 45% yield whatever
method (A or B) was used. We tentatively tried to
increase the yield obtained through method B by using,
in the second addition, either two equivalents of the
Grignard reagent, or by adding 5% of fresh Fe(acac)3,
without success (result not shown). Finally when 1a was
treated through method B but using one equivalent of
phenylmagnesium bromide instead of n-dodecylmagne-
sium bromide, 1-(2-quinolyl)-2-phenylethene (com-
pound 3f [10]) was obtained in 47% yield (not
optimized).
3. Experimental
All reactions were performed under nitrogen. THF
was distilled in the presence of sodium and benzophe-
none. NMP was distilled prior to use. The 1,1-dibro-
moalkenes were synthesized from the corresponding
aldehydes by treatment with carbon tetrabromide and
triphenylphosphine in methylene chloride [11]. i-
PrMgCl was purchased from Aldrich® and n-dodecyl-
magnesium bromide was prepared according to the
usual procedure. Fe(acac)3 and Co(acac)2 (purchased
from Aldrich®) were dried at 100°C for 3 h prior to use,
whereas FeCl3 was dried at 100°C under low pressure
for several hours. 1H- and 13C-NMR spectra were
registered at 200 and 50 MHz, respectively, on a Bruker
1
AC-200 P spectrometer, and the H–1H (COSY-DQF,
1
HOHAHA) and H–13C (HMQC and HMBC) correla-
tion spectra at 400 MHz, on a Bruker ARX-400 spec-
trometer. Chemical shifts are reported as l values (in
parts per million), relative to the residual nondeuterated
solvent signals as internal standard. The splitting pat-
tern abbreviations are as follows: s=singlet, d=dou-
blet, dd=double doublet, t=triplet, q=quadriplet,
m=multiplet.
3.1. Preparation of 1-bromo-1-alkenes (2) by reduction
of l,1-dibromo-1-alkenes (1)
In conclusion, we have shown that alkylmagnesium
halides in the presence of iron(III) catalyst (or
cobalt(II) catalyst) can reduce 1,1-dibromo-2-aryl-1-
alkenes in good yields and excellent stereoselectivity, to
afford the corresponding E-1-bromo-1-alkenes which
can be further used in transition metal catalyzed cross-
coupling reactions with organometallic species. How-
ever, this reaction seems limited, so far, to the
conjugated alkenes. Further studies are in progress to
define the scope and limitation of this new chemical
3.1.1. 1-Bromo-2-(2-quinolyl)ethene (2a)
An orange–red solution of 1,1-dibromoalkene (1a)
(0.200 g, 6.38×10−4 mol) with Fe(acac)3 (11.28 mg,
3.19×10−5 mol, 5 mol%) in 3 ml of THF and 3 ml of
NMP was cooled to −10°C and iso-propylmagnesium
chloride (0.4 ml, 1.8 M, 1.1 equivalents, 7.2×10−4
mol) was added dropwise to immediately afford a dark
brown solution. After 30 min of stirrring, 10 ml of

134
M.A. Fakhfakh et al. / Journal of Organometallic Chemistry 624 (2001) 131–135
water was introduced and the mixture warmed to room
temperature (r.t.). The reaction mixture was extracted
with ethyl ether (3×30 ml) and the organic layers were
combined, washed with an aqueous saturated solution
of NaHCO3, then with brine and dried over MgSO4.
After filtration and evaporation of the solvents, the
crude mixture was purified by flash chromatography
(hexane/EtOAc 92:8) to afford 0.125 g (84%) of 2a:
1H-NMR (200 MHz, CDCl3) l: 7.36 (d, 1H, J=8.4
Hz), 7.37 (d, 1H, J=15.9 Hz), 7.50 (d, 1H, J=13.9
Hz), 7.52 (t, 1H, J=3.6 Hz), 7.70 (t, 1H, J=7.5 Hz),
7.76 (d, 1H, J=8.1 Hz), 8.04 (d, 1H, J=8.5 Hz), 8.10
(d, 1H, J=8.4 Hz); 13C-NMR (50 MHz, CDCl3) l:
154.00, 147.06, 137.53, 136.71, 129.97, 129.35, 127.51,
126.75, 126.51, 119.24, 114.14; MS-ESI m/z: 235 ([M+],
100), 234 (78).
the organic layers were combined, washed with an
aqueous saturated solution of NaHCO3, then with
brine and dried over MgSO4. Alter filtration and evapo-
ration of the solvents, the crude mixture was purified by
flash chromatography (hexane/EtOAc 95:5) to afford
0.047 g (45%) of 3a.
Method B: an orange–red solution of 1,1-dibro-
moalkene (1a) (0.200 g, 6.38×10−4 mol) with Fe(a-
cac)3 (16.4 mg, 4.65×10−5 mol, 5 mol%) in 3 ml of
THF and 3 ml of NMP was cooled to −10°C and
iso-propylmagnesium chloride (0.47 ml, 1.5 M, 1.1
equivalents, 7.1×10−4 mol) was added dropwise to
immediately afford a dark brown solution. After 30
min of stirring C12H25MgBr (2.8 ml, 0.25 M, 1.1 equiv-
alents, 7.02×10−4 mol) was added dropwise. After 3 h
of stirring, 5 ml of water were introduced and the
mixture warmed to r.t. The reaction mixture was ex-
tracted with ethyl ether (3×10 ml) and the organic
layers were combined, washed with an aqueous satu-
rated solution of NaHCO3, then with brine and dried
over MgSO4. After filtration and evaporation of the
solvents, the crude mixture was purified by flash chro-
matography (hexane/EtOAc 95:5) to afford 0.129 g
(63%) of 3a.
3.1.2. 1-Bromo-2-(3,4-dimethoxyphenyl)ethene (2b)
Prepared and purified in the same manner as de-
scribed for 2a from 1b (0.200 g, 6.21×10−4 mol) with
Fe(acac)3 (10 mg, 3.10×10−5 mol, 5 mol%). The crude
mixture was purified by flash chromatography (hexane/
1
EtOAc 85:15) to afford 0.122 g (70%) of 2b: H-NMR
(200 MHz, CDCl3) l: 7.02 (d, 1H, J=14.1 Hz), 6.80
(m, 3H), 6.61 (d, 1H, 1=13.7 Hz), 3.87 (s, 6H); 13C-
NMR (50 MHz, CDCl3) l: 149.28, 149.07, 136.70,
128.94, 119.29, 111.15, 108.58, 55.78; MS-EI m/z: 244
([M+], 92), 242 (100), 229 (38), 227 (40), 120 (82).
1H-NMR (200 MHz, CDCl3) l: 8.06 (d, 1H, J=8.2
Hz), 8.02 (d, 2H, J=6.9 Hz), 7.75 (d, 1H, J=8.4 Hz),
7.67 (ddd, 1H, J=8.4, 7.2, 1.2 Hz), 7.52 (d, 1H, J=8.9
Hz), 7.46 (dd, 1H, J=8.9, 7.1 Hz), 6.84 (dt, 1H,
J=15.8, 6.0 Hz), 6.70 (d, 1H, J=16.1 Hz), 2.32 (q,
2H, J=7.2 Hz), 1.56 (m, 2H), 1.26 (m, 18H), 0.87 (t,
3H, J=6.6 Hz); 13C-NMR (50 MHz, CDCl3) l:
156.40, 148.01, 137.90, 135.97, 130.96, 129.36, 129.04,
127.29, 127.05, 125.67, 118.58, 33.00, 30.87, 29.62,
29.30, 28.86, 22.63, 14.04; MS-ESI m/z: 324 ([MH+]).
3.1.3. 1-Bromo-2-(2-naphthyl)ethene (2c)
Prepared and purified in the same manner as de-
scribed for 2a from 1c (0.150 g, 4.82×10−4 mol) with
Fe(acac)3 (8.5 mg, 2.41×10−5 mol, 5 mol%). The
crude mixture was purified by flash chromatography
1
(hexane) to afford 0.087 g (79%) of 2c: H-NMR (200
3.2.2. 1-(3,4-Dimethoxyphenyl)tetradecene (3b)
MHz, CDCl3) l: 7.82 (m, 4H), 7.49 (m, 3H), 7.27 (d,
1H, J=14.0 Hz), 6.90 (d, 1H, J=14.0 Hz); 13C-NMR
(50 MHz, CDCl3) l: 154.0, 147.06, 137.33, 128.59,
128.34, 128.13, 127.78, 126.63, 126.38, 122.96, 106.88;
MS-EI m/z: 234 ([M+], 71), 232 (77), 198 (55), 172 (77),
155 (61), 127 (100).
Method A: prepared and purified in the same manner
as described for 3a from 1b (0.300 g, 9.31×10−4 mol).
The crude mixture was purified by flash chromatogra-
phy (hexane/EtOAc 92:8) to afford 0.139 g (45%) of 3b.
Method B: an orange–red solution of 1,1-dibro-
moalkene (1b) (0.300 g, 9.31×10−4 mol) with Fe(a-
cac)3 (16.4 mg, 4.65×10−5 mol, 5 mol%) in 4 ml of
THF and 4 ml of NMP was cooled to −10°C and
iso-propylmagnesium chloride (0.5 ml, 2 M, 1.1 equiva-
lents, 1.0×10−4 mol) was added dropwise to immedi-
ately afford a dark brown solution. After 30 min of
stirring, C12H25MgBr (4 ml, 0.25 M, 1.0×10−3 mol,
1.1 equivalents) was added dropwise. After 3 h, 10 ml
of water were introduced and the mixture warmed to
r.t. The reaction mixture was extracted with ethyl ether
(3×30 ml) and the organic layers were combined,
washed with an aqueous saturated solution of
NaHCO3, then with brine and dried over MgSO4. After
filtration and evaporation of the solvents, the crude
mixture was purified by flash chromatography (hexane/
EtOAc 92:8) to afford 0.138 g (44%) of 3b.
3.2. Preparation of alkenes 3 by reduction and
cross-coupling reactions of 1,1-dibromo-1-alkenes (1)
with C12H25MgBr
3.2.1. 1-(2-Quinolyl)tetradecene (3a)
Method A: an orange–red solution of 1,1-dibro-
moalkene (1a) (0.100 g, 3.19×10−4 mol) with Fe(a-
cac)3 (5.6 mg, 1.59×10−5 mol, 5 mol%) in 2 ml of
THF and 2 ml of NMP was cooled to −10°C and
C12H25MgBr (6.4 ml, 0.1 M, 2.1 equivalents, 6.4×10−4
mol) was added dropwise, to immediately afford a dark
brown solution. After 3 h of stirring, 5 ml of water was
introduced and the mixture warmed to r.t. The reaction
mixture was extracted with ethyl ether (3×10 ml) and

M.A. Fakhfakh et al. / Journal of Organometallic Chemistry 624 (2001) 131–135
135
1H-NMR (200 MHz, CDCl3) l: 6.90–6.75 (m, 3H),
6.31 (d, 1H, J=16.2 Hz), 6.12 (dt, 1H, J=16.2, 6.6
Hz), 3.89 (s, 3H), 3.85 (s, 3H), 2.18 (q, 2H, J=6.8 Hz),
1.26 (m, 20H), 0.88 (t, 3H, J=6.2 Hz); 13C-NMR (50
MHz, CDCl3) l: 148.95, 148.15, 131.12, 129.26, 118.71,
111.16, 108.52, 55.83, 55.71, 32.95, 31.88, 29.51, 29.31,
29.28, 22.61, 14.03; MS-EI m/z: 332 ([M+], 26), 177
(100).
[2] G. Cahiez, D. Bernard, J.F. Normant, J. Organomet. Chem. 113
(1976) 107.
[3] (a) G. Cahiez, H. Avedissian, Synthesis (1998) 1199. (b) R.S.
Smith, J.K. Kochi, J. Org. Chem. 41 (1976) 502.
[4] H. Felkin, O. Swierczewski, Tetrahedron 31 (1975) 2735.
[5] G. Cahiez, C. Chaboche, M. Jezequel, Tetrahedon 56 (2000)
2733.
[6] M. Nakamura, A. Hirai, E. Nakamura, J. Am. Chem. Soc. 122
(2000) 978.
[7] For higher reactivity of E halogen atom in (E)- and (Z)-1-halo-
1-alkene in palladium-catalyzed stereoselective coupling reaction,
see: (a) R. Rossi, A. Carpita, Tetrahedron Lett. 27 (1986) 4351.
For higher reactivity of E halogen atom in 1,1-dihalo-1-alkene in
palladium-catalyzed stereoselective monocoupling reactions, see,
RMgX: (b) A. Minato, K. Suzuki, K. Tamao, J. Am. Chem.
Soc. 109 (1987) 1257. RZnX: (c) A. Minato, J. Org. Chem. 56
(1991) 4052. (d) J.S. Panek, T. Hu, J. Org. Chem. 62 (1997) 4912.
RAIR2% : (e) V. Ratovelomanana, A. Hammoud, G. Linstrumelle,
Tetrahedron Lett. 28 (1987) 1649. RB(OR)2: (f) W.R. Roush,
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Acknowledgements
J.C. Jullian is acknowledged for the NMR analyses,
Dr O. Lapre´vote and L. Serani for the MS experiments.
Thanks are due to Dr M. Alami for fruitful discussions.
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