Application of (2E,4E)-5-bromo-2,4-pentadienal in palladium catalyzed cross-coupling: Easy access to (2E,4E)-2,4-dienals

Article abstract of DOI:10.1055/s-1998-1672

Palladium catalyzed cross-coupling reactions of (2E,4E)-5-bromo-2,4-pentadienal 1 with organozinc reagents gives an easy access to the corresponding (2E,4E)-2,4-dienals. The improved preparation of all trans 1 by isomerization of its (2E,4Z) isomer is reported.

Full text of DOI:10.1055/s-1998-1672

April 1998
SYNLETT
411
Application of (2E,4E)-5-Bromo-2,4-Pentadienal in Palladium Catalyzed Cross-Coupling:
Easy Access to (2E,4E)-2,4-Dienals
Nicolas Vicart, Dominique Castet-Caillabet, Yvan Ramondenc, Gérard Plé and Lucette Duhamel*
Université de Rouen, UPRES A 6014 et IRCOF, F-76821 Mont Saint Aignan Cédex, France
Fax 33 + 02.35.52.24.11; E-mail: Lucette.Duhamel@univ-rouen.fr
Dedicated to the memory of Pr. J-M. Poirier
Received 9 December 1997
Abstract: Palladium catalyzed cross-coupling reactions of (2E,4E)-5-
bromo-2,4-pentadienal 1 with organozinc reagents gives an easy access
to the corresponding (2E,4E)-2,4-dienals. The improved preparation of
all trans 1 by isomerization of its (2E,4Z) isomer is reported.
Acetylenic aldehydes 3g and 3h are new.10,11 They are potential
precursors of 2,4,6-trienals by simple selective reduction of the triple
bond. Moreover, the synthesis of alkyne 3h, bearing the labile
trimethylsilyl group,12 shows that functionalized dienic aldehydes are in
the reach of this methodology.
In the course of our studies about convergent synthesis of polyenic
1
2
compounds, we recently reported the preparation of (2E,4E)-5-bromo-
2
It is noteworthy that our strategy allows preparation of various (2E,4E)
dienals in only one step from all trans aldehyde 1. Access to large
amounts of this starting material remained a drawback to this method.
Actually, its preparation by bromination of glutaconaldehyde potassium
salt 4 (Scheme 2) afforded a mixture of 1 and its (2E,4Z) isomer 5
which were separated by flash chromatography or crystallization.2
Therefore, a stereoselective route to all trans 1 as a single isomer
constituted a synthetic challenge. Advantage has been taken of the two
following points: i) each pure isomeric form 1 or 5 could be converted
into the thermodynamic 50/50 mixture of isomers, by standing at room
,5-pentadienal 1. We2 and others have taken advantage of the
carbonyl group's potential through Wittig, Grignard or oxidation
reactions. In this paper, we report the use of 1 as a brominated vinylic
entity in palladium catalyzed cross-coupling without any protection of
the aldehydic function (Scheme 1). Their high efficiency in such
processes, their easy access and low reactivity with aldehydes, led us to
select the mild organozinc reagents for this purpose.
3
4
5
6
temperature in hydrated chloroform; ii) the (2E,4E) isomer
preferentially crystallizes in diethyl ether.2
1
Scheme 1
7
Aldehyde 1 was treated in standard conditions with various organozinc
species 2a-h, easily prepared in situ from corresponding
bromomagnesium-(2a,c and f) or lithium-reagents (2b,d,e,g and h) and
zinc bromide, in the presence of catalytic amounts of
tetrakis(triphenylphoshine)palladium in THF. Results are reported in the
table.
Scheme 2
So, to the oily mixture of isomers 1 and 5 (ca. 70/30) dissolved in
diethyl ether was added a catalytic amount of p-toluenesulfonic acid.
Slow vacuum removing of the solvent at room temperature afforded a
solid product. 200 MHz 1H NMR analysis demonstrated its high
isomeric purity (1/5 = 98/2).13
We assume that the acid catalyzed thermodynamic equilibration
between isomers 1 and 5 occurs rapidly in solution and that the
preferential crystallization of all trans 1 transforms the whole initial
mixture into this stereoisomer.
In conclusion, we report a significant improvement to the preparation of
(2E,4E)-5-bromo-2,4-pentadienal 1. We have also established that this
bromo-aldehyde could be converted into (2E,4E) dienals by simple
palladium catalyzed cross-coupling with organozinc reagents, without
any protection of the carbonyl group, providing a new synthetic
application of this versatile reagent.2 Extension to other nucleophiles,
especially functionalized ones, and application of this last methodology
to natural product synthesis is currently under way and will be reported
elsewhere.
In all cases, rapid reactions occurred (TLC analysis) at room
temperature with alkyl, aryl, vinyl or alkynyl zinc reagents and
corresponding (2E,4E) dienals 3a-h were isolated as single isomers. We
never observed any addition of the organometallic species on the
carbonyl group. Yields were generally good after flash chromatography
purification.
,3
Dienals 2a-f were already described.8,9 However, recent literature in
this area shows that there is still a need for pratical synthetic
1
,8,9
methods.

4
12
LETTERS
SYNLETT
Aknowledgment: The authors thank Pr. J. Goré (Université Claude
Bernard Lyon 1, France) who has made possible this fruitful
collaboration.
addition (10 min), all the starting aldehyde 1 was consumed as
demonstrated by TLC analysis (light petroleum ether / Et O = 80 /
2
20). The final red mixture was diluted with Et O (20 ml) and
2
washed with water (20 ml). The aqueous phase was extracted with
Et O (3 x 20 ml). The organic layers were combined, washed with
2
References and Notes
brine (20 ml), dried on MgSO , and evaporated. Purification by
4
(
1) a) Duhamel, L.; Plé, G.; Ramondenc, Y. Tetrahedron Lett. 1989,
0, 7372-7380. b) Contreras, B.; Duhamel, L.; Plé, G. Synth.
flash chromatography on silica gel (light petroleum ether / Et O =
2
3
95 / 5) afforded pure dienal 3h (0.155g). Yield: 87 %.
Commun. 1990, 20, 2983-2990. c) Duhamel, L.; Guillemont, J.;
Le Gallic, Y.; PLé, G.; Poirier, J.M.; Ramondenc, Y.; Chabardes,
P. Tetrahedron Lett. 1990, 31, 3129-3133. d) Ramondenc, Y.; Plé,
G. Tetrahedron 1993, 49, 10855-10876.
(
8) For examples in polyenic natural product synthesis see: a) Nozoe,
S.; Kikuchi, K.; Ishii, N.; Ohta, T. Tetrahedron Lett. 1992, 33,
7551-7552. b) Ripoche, I.; Bennis, K.; Canet, J-L.; Gelas, J.;
Troin, Y. Tetrahedron Lett. 1996, 37, 3991-3992. c) Peng, Z-H.;
Li, Y-L.; Wu, W-L.; Liu, C-X.; Wu, Y-L. J. Chem. Soc., Perkin
Trans. 1 1996, 1057-1066. d) Gonzàlez, A.; Aiguadé, J.; Urpi, F.;
Vilarrasa, J. Tetrahedron Lett. 1996, 37, 8949-8952.
(
2) a) Soullez, D. Ph. D. Thesis, Rouen, 1994. b) Soullez, D.; Plé, G.;
Duhamel, L.; Duhamel, P. J. Chem. Soc., Chem. Commun. 1995,
563-564. c) Soullez, D.; Plé, G.; Duhamel, L. J. Chem. Soc.,
Perkin Trans. 1 1997, 1639-1645.
(
9) For other preparations of dienals and spectral data examples see:
(3) Macdonald, G.; Lewis, N.J.; Taylor, R.J.K. J. Chem. Soc., Chem.
Commun. 1996, 2647-2648.
a) Bellassoued, M.; Salemkour, M. Tetrahedron, 1996, 52, 4607-
4
624. b) Friedli, A.C.; Yang, E.; Marder, S.R. Tetrahedron 1997,
(
4) a) Heck, R.F. Palladium Reagents in Organic Syntheses;
Academic Press: London, 1985. b) Tsuji, J. Palladium Reagents
and Catalysts. Innovation in Organic Synthesis; John Wiley and
Sons: Chichester, 1995.
5
3, 2717-2730 and references cited therein. See also Ref. 8c.
1
(
10) New compounds gave satisfactory H and 13C NMR, IR and MS
analysis.
(
11) For cross-coupling reactions of acetylenic and selective reduction
(
5) Only a few examples of palladium catalyzed cross-coupling of
halogenated vinylic or aromatic aldehydes have been reported so
far in the literature: a) Watanabe, T.; Miyaura, N.; Suzuki, A.
J. Organomet. Chem. 1993, 444, C1-C3. b) Gilchrist, T.L.; Healy,
M.A.M. Tetrahedron 1993, 49, 2543-2556. c) Gao, Y.; Harada,
K.; Hata, T.; Urabe, H.; Sato, F. J. Org. Chem. 1995, 60, 290-291.
d) Shi, G-Q.; Huang, X-H.; Hong, F. J. Org. Chem. 1996, 61,
see: Crousse, B.; Alami, M.; Linstrumelle, G. Synlett 1997, 992-
994 and references cited therein.
(12) For an example of the use of trimethylsilylated alkyne as vinylic
anion equivalent in polyene synthesis, see: Lipshutz, B.H.;
Lindsley, C. J. Am. Chem. Soc. 1997, 119, 4555-4559.
(13) Typical procedure: Bromine (3.15g, 19.7 mmol) in CH Cl (20
2
2
3
200-3204.
ml) was added dropwise to triphenylphosphine (5.37g, 20.4
mmol) in CH2Cl2 (80 ml) under argon at 0 °C. Glutaconaldehyde
potassium salt 414 (2.27 g, 14.2 mmol) was immediately added in
one portion and this suspension was stirred at room temperature
for four hours. The final black solution was filtered through a
small pad (c.a. 50g) of Merck silica gel 60 (40-63 µm), to
eliminate the resulting triphenylphosphine oxide and potassium
bromide, and evaporated. The residue was chromatographed on
(
6) a) Erdik, E. Tetrahedron 1992, 48, 9577-9648. b) Knochel, P.;
Singer, D. Chem. Rev. 1993, 93, 2117-2188. c) Rieke, R.D.;
Hanson, M.V. Tetrahedron 1997, 53, 1925-1956.
(
7) Typical procedure for palladium catalyzed cross-coupling
experiments: preparation of dienal 3i:
a) Preparation of the alkynyl zinc bromide 2i:
n-Butyllithium (0.520 ml, 2.5 M in hexanes, 1.30 mmol) was
added to a solution of trimethylsilylacetylene (0.185 ml, 1.30
mmol) in THF (2mL) at 0° C under argon. The mixture was stirred
at room temperature for 1 hour, then cooled to -50 °C and ZnBr2
silica gel (light petroleum ether / Et O : 90/10) affording a
2
mixture of bromopentadienals (1/5 = 70/30) with an overall yield
of 84%. To 1.28 g (8.00 mmol) of this mixture in anhydrous Et O
2
(20 ml) para-toluenesulfonic acid (0.10 g, 0.52 mmol) was added.
(
0.337 g, 1.50 mmol) dissolved in THF (3 ml) was added via a
After stirring for 5 min under argon, the solvent was slowly
removed in vacuo at room temperature and a grey solid was
canula. The resulting solution was then allowed to warm up to
room temperature.
b) Palladium catalyzed cross-coupling: Solid 1 (0.160 g, 1.00
recovered. It was then dissolved in Et O (10 mL) and the solution
2
was forced through silica gel, affording pure (2E,4E)-5-bromo-
mmol) and Pd(PPh ) (0.058 g, 0.05 mmol) were flushed under
3
4
2,4-pentadienal 1 80 % yield from glutaconaldehyde potassium
argon for 5 min. THF (2 ml) was added and the resulting yellow
solution was stirred at room temperature. The preceding solution
of zinc reagent 2h was then added dropwise. At the end of the
salt 4.
(14) Becher, J. Org. Synth. 1980, 59, 79-84.