Efficient preparation of terminal conjugated dienes by coupling of dienol phosphates with grignard reagents under iron catalysis

Article abstract of DOI:10.1021/ol800816f

(Chemical Equation Presented) An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)₃ is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.

Full text of DOI:10.1021/ol800816f

ORGANIC
LETTERS
2008
Vol. 10, No. 12
2389-2392
Efficient Preparation of Terminal
Conjugated Dienes by Coupling of
Dienol Phosphates with Grignard
Reagents under Iron Catalysis
Ge´rard Cahiez,* Vanessa Habiak, and Olivier Gager
Laboratoire de Synthe`se Organique Se´lectiVe et de Chimie Organome´tallique
(SOSCO), UMR 8123 CNRS-UCP-ESCOM, 5, Mail Gay-Lussac, NeuVille sur Oise,
F-95031 Cergy-Pontoise cedex, France
gerard.cahiez@chim.u-cergy.fr
Received March 20, 2008
ABSTRACT
An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the
presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone
of Diparopsis castanea according to a very expeditious strategy.
The stereoselective construction of olefins is a very important
step for the preparation of various natural products such as
Scheme 1
.
Straighthforward Strategy for the Synthesis of
Terminal Conjugated Dienes
terpenes1 or insect pheromones.2 Transition-metal-catalyzed
cross-coupling reactions are frequently used because of their
high efficiency in this field. Several compounds mentioned
above have a terminal conjugated dienyl unit like 2 or 4 in
their structure. One of the most straightforward strategies
for introducing such units would be to couple an alkylmetal
derivative with the dienyl halides 1 or 3 (Scheme 1).
Unfortunately, despite its apparent simplicity, this strategy
was very difficult to apply3 because the starting dienyl halides
1 or 3 have a strong tendency to polymerize. A case in point
would be chloroprene, which is the well-known precursor
of a family of synthetic rubbers (e.g., neoprene). It is stored
and transported under inert atmosphere below -10 °C, and
an inhibitor must be added to prevent polymerization.4 As a
rule, butadienyl halides are not easy to store, and their
reactions often lead to large amounts of polymers. As a
consequence, the examples of coupling of 1 or 3 with
(1) (a) Thomas, A. F.; Heathcock, C. H.; ApSimon, J. W.; Hooper, J. W.
The Total Synthesis of Natural Products; ApSimon, J. W., Ed.; Wiley &
Sons: New York, 1973; Vol. 2, pp 1-640. (b) Thomas, A. F.; Bessie`re, Y.
The Total Synthesis of Natural Products; ApSimon, J. W., Ed.; Wiley &
Sons: New York, 1981; Vol. 4, p 451.
(2) Mori, K. The Total Synthesis of Natural Products; ApSimon, J. W.,
Ed.; Wiley & Sons: New York, 1992; Vol. 9, p. 1.
10.1021/ol800816f CCC: $40.75
Published on Web 05/14/2008
2008 American Chemical Society

Grignard reagents, which are one of the most interesting
organometallics for preparative large-scale procedure, are
very rare.3c,d
reaction compares very favorably to the similar palladium
or nickel procedures since it is highly stereo- and chemose-
lective and leads to excellent yields of olefins. Under iron
catalysis, the oxidative addition step is clearly easier than
with palladium or nickel. Thus, even the less reactive alkenyl
chlorides or enol phosphates easily react. In light of these
results, we thought that it would probably be possible to
couple dienol phosphates, which are much more stable than
the corresponding dienyl halides. Thus, they can be stored
at room temperature without any special precaution and are
easily purified by distillation or by chromatography on a
silica gel column. According to our experience with enol
phosphates, the first experiment was performed in THF, at
-20 °C, in the presence of 1% Fe(acac)3 and 9 equivalents
of NMP (Table 1, entry 1). Under these conditions, butadi-
To overcome this difficulty, we would now like to report
a general and very efficient method for preparing terminal
dienes: the iron-catalyzed cross-coupling reaction between
Grignard reagents and terminal dienol phosphates.5
In the past years, iron-catalyzed cross-coupling reactions
have been extensively studied by us6 and others.7 In 1998,
we showed that Grignard reagents readily couple with alkenyl
halides in the presence of both iron salts and NMP.6d The
(3) Only very few examples of cross-coupling reactions with halo-1,3-
butadienes have been reported. (a) The coupling of 1-octyne with the (Z)-
and (E)-1-chloro-1,3-butadienes under the Sonogashira conditions: Huynh,
C.; Alami, M.; Linstrumelle, G. Synth. Commun. 1994, 24, 2273. (b) The
Ni-catalyzed coupling reaction of (Z)-1-heptenylcyanocuprate with 1-bromo-
1,3-butadiene, which leads to 65% yield of (E,Z)-1,3,5-undecatriene:
Alexakis, A.; Barthel, A. M.; Normant, J. F.; Fugier, C.; Leroux, M. Synth.
Commun. 1992, 22, 1839. (c) The Ni-catalyzed coupling of chloroprene
with PhMgBr (yield 65%): Tamao, K.; Sumitani, K.; Zembayashi, M.;
Fujioka, A.; Kodama, S.-i.; Nakajima, I.; Minato, A.; Kumada, M. Bull.
Chem. Soc. Jpn. 1976, 49, 1958. (d) Me3SiCH2MgCl: Sakurai, H.; Hosomi,
A.; Saito, M.; Sasaki, K.; Iguchi, H.; Sasaki, J.-i.; Araki, Y. Tetrahedron
1983, 39, 883.
Table 1. Iron-Catalyzed Cross-Coupling Reaction of OctMgCl
with 1-Butadienyl Phosphate 5a
(4) Ullmann’s Encyclopedia of Industrial Chemistry, 6th ed.; Wiley-
VCH: Weinheim, 2003; Vol. 8, p 89.
entry
solvent
Fe(acac)3 (%)
temp (°C)
yield (%)
(5) To the best of our knowledge, no example of cross-coupling reaction
from terminal dienyl phosphates has been reported. For a nickel-catalyzed
coupling of nonterminal dienyl phosphate with Grignard reagents, see: Sofia,
A.; Karlstro¨m, E.; Itami, K.; Ba¨ckvall, J.-E. J. Org. Chem. 1999, 64, 1745.
(6) (a) Cahiez, G.; Chavant, P. Y.; Metais, E. Tetrahedron Lett. 1992,
33, 5245. (b) Cahiez, G.; Marquais, S. Tetrahedron Lett. 1996, 37, 1773.
(c) Cahiez, G.; Marquais, S. Pure Appl. Chem. 1996, 68, 53. (d) Cahiez,
G.; Avedissian, H. Synthesis 1998, 1199. (e) Dohle, W.; Kopp, F.; Cahiez,
G.; Knochel, P. Synlett 2001, 1901. (f) Duplais, C.; Bures, F.; Korn, T.;
Sapountzis, I.; Cahiez, G.; Knochel, P. Angew. Chem., Int. Ed. 2004, 43,
2968. (g) Cahiez, G.; Chaboche, C.; Mahuteau-Betzer, F.; Ahr, M. Org.
Lett. 2005, 7, 1943. (h) Cahiez, G.; Habiak, V.; Duplais, C.; Moyeux, A.
Angew. Chem., Int. Ed. 2007, 46, 4364. (i) Cahiez, G.; Duplais, C.; Moyeux,
A. Org. Lett. 2007, 9, 3253. (j) Cahiez, G.; Moyeux, A.; Buendia, J.; Duplais,
C. J. Am. Chem. Soc. 2007, 129, 13788.
1
2
3
4
5
6
7
8
9
THF/NMPb
THF
ether
DME
THF
THF
THF
THF
THF
1
1
1
1
5
0.5
1
1
1
-20
-20
-20
-20
-20
-20
0
54
82
75
79
78
40
86
92
91
20
40
a OctMgCl (13 mmol) was added dropwise for 10 min to a solution of
dienol phosphate 5 (10 mmol) and iron acetylacetonate (0.5-5 mol %, see
table) in the solvent mentioned above (30 mL) under stirring. b Nine
equivalents of NMP based on dienol phosphate.
(7) (a) Fu¨rstner, A.; Leitner, A.; Me´ndez, M.; Krause, H. J. Am. Chem.
Soc. 2002, 124, 13856. (b) Fu¨rstner, A.; Leitner, A. Angew. Chem., Int.
Ed. 2002, 41, 609. (c) Quintin, J.; Frank, X.; Hocquemiller, R.; Figade`re,
B. Tettrahedron Lett. 2002, 43, 3547. (d) Martin, R.; Fu¨rstner, A. Angew.
Chem., Int. Ed. 2004, 43, 3955. (e) Scheiper, B.; Bonnekessel, M.; Krause,
H.; Fu¨rstner, A. J. Org. Chem. 2004, 69, 3943. (f) Nakamura, M.; Matsuo,
K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc. 2004, 126, 3686. (g) Dos Santos,
M.; Franck, X.; Hocquemiller, R.; Figade`re, B.; Peyrat, J.-F.; Provot, O.;
Brion, J.-D.; Alami, M. Synlett 2004, 2697. (h) Nagano, T.; Hayashi, T.
Org. Lett. 2004, 6, 1297. (i) Bedford, R. B.; Bruce, D. W.; Frost, R. M.;
Goodby, J. W.; Hird, M. Chem. Commun. 2004, 2822. (j) Martin, R.;
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D. W.; Frost, R. M.; Hird, M. Chem. Commun. 2005, 4161. (n) Bedford,
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M. J. Org. Chem. 2006, 71, 1104. (o) Zhang, D.; Ready, J. J. Am. Chem.
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71, 6637. (q) Durandetti, M.; Perichon, J. Tetrahedron Lett. 2006, 47, 6255.
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F.; Olsson, R. Org. Lett. 2006, 8, 1771. (s) Plietker, B. Angew. Chem., Int.
Ed. 2006, 45, 1469. (t) Dunet, G.; Knochel, P. Synlett 2006, 407. (u)
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Correa, A.; Bolm, C. Angew. Chem., Int. Ed. 2007, 46, 8862. (w) Lu, Z.;
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Guerinot, A.; Reymond, S.; Cossy, J. Angew. Chem., Int. Ed. 2007, 46,
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934. (aa) Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2007, 129,
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enyl-diethylphosphate 5 coupled with octylmagnesium chlo-
ride to give 1,3-dodecadiene 6 in only 54% yield.
In fact, we found that in the case of dienol phosphates,
the presence of NMP is detrimental. Thus, in THF alone the
yield is clearly better (82%, Table 1, entry 2). The reaction
can also be performed in ether or in DME, but the yields
are slightly lower (Table 1, entries 3 and 4). There is no
advantage to using more than 1% Fe(acac)3 (Table 1, entry
5). On the other hand, the yield significantly decreases when
using only 0.5% (Table 1, entry 6). Finally, we found that,
contrary to enol phosphates, dienol phosphates react more
efficiently at room temperature since the coupling product
is then obtained in excellent yields (Table 1, entry 8).
(8) Fe-Catalyzed Coupling Reaction of Dienol Phosphates with
Grignard Reagents. General Procedure. An oven-dried and nitrogen-
flushed 250 mL four-necked flask, equipped with a mechanical stirrer and
a thermometer, was charged with a solution of Fe(acac)3 (1 mol%, 0.25
mmol) in THF (50 mL). The dienol phosphate (25 mmol) was added at
once under stirring, and then the Grignard reagent (30 mmol) was added
dropwise for 20 min. After 15 min, the reaction mixture was quenched
with a 1 M aqueous HCl solution (50 mL). The aqueous phase was extracted
with cyclohexane (3 × 30 mL), dried with MgSO4, and concentrated under
reduced pressure. The product was purified by distillation or by column
chromatography (see Supporting Information).
2390
Org. Lett., Vol. 10, No. 12, 2008

Several terminal dienol phosphates were coupled in
excellent yields with octylmagnesium chloride (Table 2,
efficient strategy. This is well-illustrated by the synthesis of
the pheromone of Diparopsis castanea9 described in Scheme
3. It is, to the best of our knowledge, the most expeditious
and efficient preparative route reported until now.10
Table 2. Iron-Catalyzed Cross-Coupling Reaction of Dienol and
Trienol Phosphates with Grignard Reagentsa
Scheme 3
.
Synthesis of the Insect Pheromone of Diparopsis
castanea (Red Bollworm Moth) 16
In conclusion, we have shown that the coupling of
Grignard reagents with terminal dienol and trienol phosphates
is efficiently catalyzed by 1 mol % Fe(acac)3. The reaction
is stereoselective and gives excellent yields of terminal
conjugated dienes or trienes. It is the first general transition-
metal-catalyzed reaction to achieve such a coupling. The
synthetic interest of this new method of preparation of
terminal dienes and trienes is well-illustrated by the expedi-
tious preparation of an insect pheromone depicted in Scheme
3. The extension of the scope of iron catalysis in preparative
a All reactions were performed on a 25 mmol scale. For a general
procedure see ref . b Yield of isolated product.
entries 1, 2, and 7). A terminal conjugated trienol phosphate
was also used successfully (entry 3). The reaction can be
extended to cyclic or acyclic nonterminal dienol phosphates
(entries 4-6 and 8). Secondary aliphatic Grignard reagents
(entry 6) led to the expected coupling product in satisfactory
yields.
(9) Nesbitt, B. F.; Beevor, P. S.; Cole, R. A.; Lester, R.; Poppi, R. G.
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H. Chem. Lett. 1983, 1003. (r) Balezina, G. G.; Ishmuratov, G. Yu.;
Odinokov, V. N.; Selimov, F. A.; Dzhemilev, U. M.; Tolstitov, G. A. Chem.
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Lett. 1985, 26, 5791. (v) Yamada, S.; Ohsawa, H.; Suzuki, T.; Takayama,
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1235.
Scheme 2
.
Iron-Catalyzed Cross-Coupling Reaction of Dienol
Phosphate 5 with Aryl Grignard Reagents
Aryl Grignard reagents can also be used; however, a partial
isomerization occurs during the coupling (Scheme 2).
This procedure makes it possible to prepare various
compounds of biological interest having a terminal dienic
system, such as insect pheromones, according to a very
(11) Cahiez, G.; Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1978,
18, 3013.
Org. Lett., Vol. 10, No. 12, 2008
2391

organic chemistry is a very important target for sustainable
development.
Supporting Information Available: Detailed experimen-
tal procedures and complete compounds characterization
data. This material is available free or charge via the Internet
at http://pubs.acs.org.
Acknowledgment. The authors thank the CNRS and the
Ecole Supe´rieure de Chimie Organique et Mine´rale (ES-
COM) for their financial support as well as a grant to O.G.
and V.H.
OL800816F
2392
Org. Lett., Vol. 10, No. 12, 2008