Palladium catalyzed cross-coupling reaction of functional organozinc reagents with (2E,4E)- and (2E,4Z)-5-bromopenta-2,4-dienals: Easy access to functional conjugated dienic aldehydes

Article abstract of DOI:10.1081/SCC-120018769

Functional zinc reagents can be applied to palladium catalyzed cross-coupling reaction with (2E,4E)- and (2E,4Z)-5-bromopenta-2,4-dienal. The corresponding functional dienic aldehydes were obtained in goods yields. From the (2E,4E) isomer, the (2E,4E) dienals were isolated as single isomer according to a total stereoselective reaction. But, from the (2E,4Z) isomer the coupling reaction has lead to a mixture of (2E,4E) and (2E,4Z) isomers. A mechanism for the loss of stereoselectivity in the last case is proposed.

Full text of DOI:10.1081/SCC-120018769

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Palladium Catalyzed Cross-Coupling Reaction of
Functional Organozinc Reagents with (2E,4E)- and
(2E,4Z)-5-Bromopenta-2,4-dienals: Easy Access to
Functional Conjugated Dienic Aldehydes
Nicolas Vicart a , Gérard-Simplice Saboukoulou a , Yvan Ramondenc a & Gérard Plé a
a Université de Rouen , IRCOF , F-Mont Saint Aignan, Cedex, France
Published online: 16 Aug 2006.
To cite this article: Nicolas Vicart , Gérard-Simplice Saboukoulou , Yvan Ramondenc & Gérard Plé (2003) Palladium Catalyzed
Cross-Coupling Reaction of Functional Organozinc Reagents with (2E,4E)- and (2E,4Z)-5-Bromopenta-2,4-dienals: Easy Access
to Functional Conjugated Dienic Aldehydes, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 33:9, 1509-1521, DOI: 10.1081/SCC-120018769
To link to this article: http://dx.doi.org/10.1081/SCC-120018769
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 9, pp. 1509–1521, 2003
Palladium Catalyzed Cross-Coupling Reaction of
Functional Organozinc Reagents with
(2E,4E )- and (2E,4Z )-5-Bromopenta-2,4-dienals:
Easy Access to Functional Conjugated
Dienic Aldehydes
Nicolas Vicart, Gerard-Simplice Saboukoulou,
*
Yvan Ramondenc, and Gerard Ple
Universite de Rouen, IRCOF,
F-Mont Saint Aignan, Cedex, France
ABSTRACT
Functional zinc reagents can be applied to palladium catalyzed cross-
coupling reaction with (2E,4E )- and (2E,4Z )-5-bromopenta-2,4-
dienal. The corresponding functional dienic aldehydes were obtained
in goodsyields. From the (2 E,4E ) isomer, the (2E,4E ) dienalswere
isolated as single isomer according to a total stereoselective reaction.
But, from the (2E,4Z ) isomer the coupling reaction has lead to a
*Correspondence: Gerard Ple, Universite de Rouen, IRCOF, UMR 6014 CNRS,
F-Mont Saint Aignan, Cedex, France; E-mail: gerard.ple@univ-rouen.fr.
1509
DOI: 10.1081/SCC-120018769
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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1510
Vicart et al.
mixture of (2E,4E ) and (2E,4Z ) isomers. A mechanism for the loss
of stereoselectivity in the last case is proposed.
In the course of our studies about polyenes synthesis,[1] we reported[2]
a stereoselective synthetic method of (2E,4E ) dienalsbased on palladium
catalyzed cross-coupling reaction of organozinc reagents with (2E,4E )-
5-bromopenta-2,4-dienal 1. In the preliminary note,[2] reactionswere
conducted with simple organozinc reagents. In this article, we report
an extension of this palladium catalyzed cross-coupling reaction
using various functional organozinc reagents 3 with (2E,4E ) dienal
1 and its(2 E,4Z ) isomer 2,[3] without any protection of the aldehydic
function.
Palladium Catalyzed Cross-coupling Reaction of (2E,4E )-5-
Bromopenta-2,4-dienal 1
The functional organozinc reagentswere prepared by transmetalla-
tion reactions( 3a and 3g–i), from organolithium reagentsand zinc dibro-
mide (ZnBr2), or by direct insertion of zinc metal into a carbon–halogen
bond (3b–f ), using zinc dust activated successively by 1,2-dibromoethane
and chlorotrimethylsilane.[4] When the organometallic reagents 3a–e in
tetrahydrofuran (THF) solution, having an acetylenic, an ester, a nitrile
group or a chloride atom, were added dropwise, at room temperature, to
a THF solution of catalytic amounts of tetrakis(triphenylphosphine)pal-
ladium (Pd(PPh3)4) and of aldehyde 1, fast and complete consumption of
the starting material 1 occurred, asobesrved by thin layer chromatog-
raphy (TLC). After hydrolysis and purification by silica gel column
chromatography (light petroleum ether/Et2O: 95/5), dienals 4a–e were
isolated pure in good yields (Sch. 1; Table 1). The structure and
the stereochemistry of these compounds 4a–e have been determined
1
using H NMR spectroscopy. For all the nucleophiles 3a–e employed,
the reaction carried out with 1 hasoccurred with total retention of
configuration.
Additionally, we never observed any addition of the organometallic
reagents 3a–e on the carbonyl group.
In the other hand, when Reformatsky reagent 3f wasuesd in an
attempt of reaction in similar conditions, no expected coupling product
wasformed but b-hydroxyester 6 (Sch. 2) hasbeen isolated in 49% yield
(Table 1, Entry 6). It seems clear and noteworthy for this last example

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Palladium Catalyzed Cross-Coupling Reaction
1511
Scheme 1.
Table 1. Cross-coupling reaction of 1 with functional organozinc reagents 3.
Entry
1
R—ZnX
3
Product
Yield (%)a
87
3ab
4a
2
3
4
3bc
3cc
3dc
4b
4c
4d
73
92
85
5
6
3ec
3f c
4e
6
72
49
aYields of isolated pure products after silica gel column chromatography.
bPrepared by metal exchange.
cPrepared by direct insertion of zinc metal.
Scheme 2.

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1512
Vicart et al.
that the zinc–palladium exchange step was too slow to compete with the
normal Reformatsky reaction.[5]
Palladium Catalyzed Cross-coupling Reaction of
(2E,4Z )-5-Bromopenta-2,4-dienal 2
Aswell asreactionsdone with iosmer
1, the palladium catalyzed
cross-coupling reaction of (2E,4Z )-5-bromopenta-2,4-dienal 2 with func-
tional zinc reagents 3a,b and 3g–i, hasoccurred instantaneously at room
temperature (Sch. 3; Table 2).
1
By H NMR spectroscopy analysis of the obtained crude products,
we have detected a mixture of two isomers (2E,4E ) 4 and (2E,4Z ) 5
(Sch. 3; Table 2); percentagesdetermined by thisway. The ratio,s
reported in Table 2, have been easily determined by integration of the
1H aldehydic signals of isomers 4 and 5. In all the cases, the aldehydic
Scheme 3.
Table 2. Cross-coupling reaction of 2 with functional organozinc reagents 3.
Entry
1
R—ZnX
3
Products
4/5d
Yield (%)a
64
3ab
4a þ 5a
83/17
2
3
3bc
3gb
4b þ 5b
4g þ 5g
85/15
84/16
77
80
4
5
3hb
3ib
4h þ 5h
75/25
31
78
4i þ 5i
33/67
aGlobal yieldsof products4 þ 5 after silica gel column chromatography.
bPrepared by metal exchange.
cPrepared by direct insertion of zinc metal.
1
dDetermined by H NMR (200 MHz) on the crude product.

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Palladium Catalyzed Cross-Coupling Reaction
1513
proton of (2E,4E ) isomer 4 exhibitsa doublet at a higher field than the
(2E,4Z ) isomer 5. After purification by silica gel column chromatography
(light petroleum ether/Et2O: 95/5), we have determined the structure and
the stereochemistry of these compounds 4a,b, 4g–i, 5a,b, and 5g–i using
1H NMR spectroscopy.
Contrary to the coupling reaction performed with 1, thislast reaction
carried out with 2 doesn’t occur with total retention of configuration.
Such loss of stereochemistry in palladium catalyzed cross-coupling
[6]
reaction israther unusual.
In order to explain the mechanism of this surprising process, we have
studied the isomeric stability of the starting material 2 in the reaction
conditions. By stirring a solution of this compound 2 with lithium bro-
mide (LiBr) (1 molar equiv.), ZnBr2 (1 molar equiv.), and Pd(PPh3)4
(5%) in THF at room temperature for 24 h, after hydrolysis, the
isomer 2 wasrecovered without any isomerization (in 90% yield).
To explain the loss of stereoselectivity observed during our cross-
coupling experimentswith (2 E,4Z )-5-bromopenta-2,4-dienal 2, we pro-
pose the following mechanism for this process (Sch. 4). In a first instance,
oxidative addition of 2 to the Pd0 complex allowsthe formation of a Pd II
complex 7. Subsequent metal exchange with organozinc reagent 3 leads
to a new PdII 8 complex and formation of ZnBr2. A reductive elimination
step take place, generating a new Pd0 complex 9 where the palladium
Scheme 4.

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1514
Vicart et al.
Scheme 5.
metal atom isliganded by the terminal p-bond of the cross-coupling
product 5. If the normal dissociation of the diene 5 from the Pd0 complex
9 occurs at this stage, the product shows a (E,Z ) stereochemistry,
identical to the starting material 2 one (Path a). On the other hand, if
an association of the aldehydic group and Lewis acid zinc bromide takes
place, Pd0L2 complex can play a nucleophile role (Path b). A syn p-allyl
complex 10 can be formed. A p–s–p equilibrium isthen involved (via 11)
in favor of the anti p-allyl complex 12 because of lower steric hindrance
between the R group and one of the phosphines.[7] After dissociation of
ZnBr2 and Pd0L2 from 13, the resulting isomerized (2E,4E ) 4 derivative is
formed.
In application of thismethodology, we have performed thisreaction
to the stereoselective synthesis of (9E,11E )-1-acetoxy tetradeca-9,11,13-
triene 14, an isomer of a female sex pheromone isolated from two
species of Lepidoptera, Ectomyelois ceratoniae (Pyralidae) and Stenoma
cecropia (Stenomidae).[8] Compound 4b isthe key intermediate in our
synthetic procedure of 14 (Sch. 5), it hasbeen converted into 14 by a
simple Wittig reaction in 74% yield. From commercial 8-bromooctanol,
compound 14 hasbeen obtained in four tsepswith an overall yield of
49% (Sch. 5).
In conclusion, we report a short and general synthetic method for the
access to functional dienals. They have been obtained with good yields by
palladium catalyzed cross-coupling reaction of various functional
organozinc reagentswith (2 E,4E ) and (2E,4Z )-5-bromopenta-2,4-dienal
1 and 2, without any protection of the carbonyl group. From the isomer
(2E,4E ) 1, the reaction isdone with a total retention of configuration.
Surprisingly, in the same conditions the isomer (2E,4Z ) 2 leadsto a
mixture of isomers; a mechanism is proposed. This methodology can
allowed a rapid access to natural or not natural polyenic products.
EXPERIMENTAL
Infrared spectra were recorded on a Perkin–Elmer 16 PC FT–IR
spectrometer as thin films. NMR spectra were recorded on a Bruker

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Palladium Catalyzed Cross-Coupling Reaction
1515
AC 200 MHz; CDCl3 was used as solvent. No SiMe4 wasadded; rather,
shifts were referenced to the solvent line (chemical shifts ꢀ in ppm and
coupling constants J in Hz). Mass spectra were performed on an ATI-
Unicam Automass apparatus, fitted (or not) with a GC–mass coupling
(high-resolution J&W column, 30 m, 0.25 mm ID, 0.25 rate: 1.2 mL/min).
Analytical TLC wasperformed on Kieselgel 60F-254-0.25 mm platesand
developed with UV 250 nm or phosphomolybdic acid. Products were
purified by silica gel column chromatography (SDS Company, over
230–400 mesh). All reactions were carried out under dry Ar. Solvents
were purified according to standard procedures.
GENERAL PROCEDURE I
Thisrepresentative procedure hasbeen applied for Entry 1, Table 1,
and Entries1, 3–5, Table 2.
Preparation of (2E,4E )-7-Trimethylsilylhepta-2,4-dien-6-ynal
4a[2,9] (Entry 1, Table 1)
(a) Preparation of Trimethylsilylacetynyl Zinc Bromide 3a
n-Butyllithium (0.520 mL, 2.5 M in hexane, 1.3 mmol) wasadded to a
solution of trimethylsilylacetylene (0.185 mL, 1.3 mmol) in THF (2 mL) at
0ꢀC under argon. The mixture wasstirred at room temperature for 1 h,
then cooled to À50ꢀC. ZnBr2 (0.337 g, 1.5 mmol), dissolved in THF
(3 mL), was added via a canula. The resulting solution was then allowed
to warm up to room temperature.
(b) Palladium Catalyzed Cross-coupling Reaction of 3a with 1
(2E,4E)-7-Trimethylsilylhepta-2,4-dien-6-ynal 4a (Entry 1, Table 1).
Aldehyde 1 (0.160 g, 1.00 mmol) and Pd(PPh3)4 (0.058 g, 0.05 mmol)
were flushed under 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 3a (0.26 M in THF, 5 mL, 1.30 mmol, 1.3 equiv.)
wasthen added dropwies. At the end of the addition (10 min), all the
starting aldehyde 1 was consumed as demonstrated by TLC analysis
(light petroleum ether/Et2O ¼ 80/20). The final red mixture wasdiluted

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with Et2O (20 mL) and washed with water (20 mL). The aqueous phase
wasextracted with Et O (3 ꢁ 20 mL). The organic layerswere combined,
2
washed with brine (20 mL), dried on MgSO4, and evaporated.
Purification by silica gel column chromatography (light petroleum
ether/Et2O ¼ 95/5) afforded pure dienal 4a asa yellow oil (0.155 g).
1
Yield 87%. H NMR (CDCl3, 200 MHz): 9.49 (d, J ¼ 7.9, 1H, CHO);
7.02 (dd, J ¼ 15.2 and 11.1, 1H, H-3); 6.72 (dd, J ¼ 15.4 and 11.1, 1H,
H-4); 6.11 (dd, J ¼ 15.2 and 7.9, 1H, H-2); 6.00 (d, J ¼ 15.4, 1H, H-5);
0.13 (s, 9H, CH3). 13C NMR (CDCl3, 50 MHz): 192.9 (CHO); 149.6
(C-3); 139.3 (C-5); 132.9 (C-4); 120.9 (C-2); 103.6 (C-6); 102.9 (C-7);
À0.4 (CH3). IR (ꢁmax/cmÀ1): 2960; 2900; 2814; 2732; 2148; 2112; 1682;
1610; 1408; 1290; 1250; 1200; 1158; 1140; 1066; 986; 846. MS: 178 (Mþꢂ,
16); 163 (M–CH3, 74); 137 (26); 135 (37); 105 (19); 99 (11); 91 (11); 89
(100); 83 (30); 77 (32); 75 (38); 73 (39); 69 (13); 67 (18); 59 (21). Anal.
calcd. for C10H14OSi: C, 67.36; H, 7.91; Found: C, 67.43; H, 7.69.
GENERAL PROCEDURE II
Thisrepreesntative procedure hasbeen applied for Entries2–6,
Table 1 and Entry 2, Table 2.
Preparation of (2E,4E )-13-Acetoxytrideca-2,4-dienal 4b
(Entry 2, Table 1)
(a) Preparation of 8-Bromooctyl Acetate
To a stirred solution of 8-bromooctanol (0.89 g, 4.28 mmol) in
CH2Cl2 at 0ꢀC were successively added dropwise acetic anhydride
(0.52 mL, 5.51 mmol), triethylamine (2.50 mL, 18.00 mmol), and dimethy-
laminopyridine (0.06 g, 0.49 mmol). After 1 h, the reaction mixture was
treated with diluted aqueousHCl (20 mL of a 1 M solution). The product
wasextracted by CH 2Cl2 (2 ꢁ 10 mL). The organic layer waswashed with
saturated aqueous solution of NaHCO3 (10 mL), dried over MgSO4, and
evaporated. The product wasdiluted with CH Cl2 and filtrated through
2
silica gel. Evaporation gave 1.07 g of colorless oil (yield 100%). 1H NMR
(CDCl3, 200 MHz): 3.91 (t, J ¼ 6.6, 2H, H-1); 3.27 (t, J ¼ 6.6, 2H, H-8);
1.90 (s, 3H, CH3); 1.72 (m, 2H, H-2); 1.48 (m, 2H, H-7); 1.38–1.12 (m,
8H, H-3, 4, 5, and 6). 13C NMR (CDCl3, 50 MHz): 170.8 (C¼O); 64.3
(C-1); 33.6 (C-2); 32.6 (C-8); 28.8; 28.4 (2C); 27.9; 25.6; 20.8 (CH3).

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Palladium Catalyzed Cross-Coupling Reaction
1517
IR (ꢁmax/cmÀ1): 2932; 2856; 1740; 1464; 1420; 1385; 1364; 1238; 1036;
724; 644.
(b) Preparation of 8-Iodooctyl Acetate
A solution of 8-bromooctyl acetate (1.07 g, 4.28 mmol) and of
sodium iodide (2.24 g, 14.98 mmol) in acetone (40 mL) was stirred
under reflux for 14 h. After evaporation, the crude product wasdiluted
in CH2Cl2 and filtrated over silica gel. Evaporation followed by bulb to
bulb distillation (125ꢀC/0.2 mbar) gave 1.20 g of the expected iodide
(yield 94%). 1H NMR (CDCl3, 200 MHz): 3.95 (t, J ¼ 6.6, 2H, H-1);
3.09 (t, J ¼ 6.9, 2H, H-8); 1.94 (s, 3H, CH3); 1.77 (m, 2H, H-2); 1.52
(m, 2H, H-7); 1.42–1.11 (m, 8H, H-3, 4, 5, and 6). 13C NMR (CDCl3,
50 MHz): 170.9 (C¼O); 64.3 (C-1); 33.3 (C-2); 30.3; 28.9; 28.4; 28.3; 25.7;
20.9 (CH3); 7.0 (C-8). IR (ꢁmax/cmÀ1): 2930; 2854; 1738; 1458; 1386; 1364;
1238; 1168; 1042; 722; 634.
(c) Preparation of 8-Acetoxyoctyl Zinc Iodide 3b
Zinc dust (0.53 g, 8.11 mmol) was poured in a three-necked flask and
flushed with argon under stirring for 15 min, then covered by THF
(2 mL). Dibromoethane (0.02 mL, 0.23 mmol) wasadded and the mixture
heated to reflux with a heat gun. After 10 min, the last two steps were
repeated twice. After return to room temperature, TMSCl (0.15 mL,
1.20 mmol) wasadded and the mixture tsirred for 10 min. 8-Iodooctyl
acetate (1.20 g, 4.03 mmol) wasadded dropwise and the reaction mixture
wastsirred at 45 ꢀC for 4 h. After return to room temperature, THF
(2 mL) was added and the stirring was stopped. The remaining zinc
powder was allowed to settle and the clear green solution of 3b was
separated with a syringe.
(d) Palladium Catalyzed Cross-coupling Reaction of 3b with 1
(2E,4E )-13-Acetoxytrideca-2,4-dienal 4b (Entry 2, Table 1).
According to the procedure described for the preparation of the com-
pound 4a, from aldehyde 1 (0.160 g, 1.00 mmol), Pd(PPh3)4 (0.058 g,
0.05 mmol) and the preceding solution of 3b (1 M in THF, 2 mL,
2 mmol, 2 equiv.), we have isolated and identified, after purification by
silica gel column chromatography (light petroleum ether/Et2O: 95/5),

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Vicart et al.
0.185 g of compound 4b asa colorlesoil. Yield 73%. 1H NMR (CDCl3,
200 MHz): 9.45 (d, J ¼ 8.0, 1H, CHO); 7.02 (m, 1H, H-3); 6.22 (m, 2H, H-
4 and 5); 5.99 (dd, J ¼ 15.4 and 8.0, 1H, H-2); 3.96 (t, J ¼ 6.6, 2H, H-13);
2.15 (m, 2H, H-6); 1.96 (s, 3H, CH3); 1.52 (m, 2H, H-12); 1.36 (m, 2H, H-
7); 1.42–1.13 (m, 8H, H-8, 9, 10, and 11). 13C NMR (CDCl3, 50 MHz):
193.8 (CHO); 171.1 (COO); 152.8 (C-3); 147.2 (C-5); 129.9 and 128.6 (C-2
and C-4); 64.4 (C-13); 33.1 (C-6); 29.2 (2C); 29.0 (2C); 28.4 (2C); 20.9
(CH3). IR (ꢁmax/cmÀ1): 2940; 2745; 1730; 1678; 1643; 1365; 1240. MS: 252
(Mþꢂ, 3); 157 (18); 139 (12); 123 (23); 112 (13); 111 (12); 110 (12); 102
(21); 97 (93); 95 (27); 94 (14); 93 (16); 86 (53); 85 (19); 84 (79); 83 (65); 82
(49); 80 (14); 79 (23); 73 (33); 71 (35); 70 (49); 68 (60); 67 (10); 61 (100).
Anal. calcd. for C15H24O3: C, 71.39; H, 9.59; Found: C, 71.23; H, 9.83.
(2E,4E )-9-Acetoxynona-2,4-dienal 4c (Entry 3, Table 1). (0.180 g,
1
yellow oil). Yield 92%. H NMR (CDCl3, 200 MHz): 9.48 (d, J ¼ 7.8,
1H, CHO); 7.03 (dd, J ¼ 15.1 and 9.9, 1H, H-3); 6.35–6.12 (m, 2H, H-4
and 5); 6.02 (dd, J ¼ 15.1 and 7.8, 1H, H-2); 4.01 (t, J ¼ 6.4, 2H, H-9);
2.20 (m, 2H, H-6); 1.99 (s, 3H, CH3); 1.65–1.42 (m, 4H, H-7 and 8).
13C NMR (CDCl3, 50 MHz): 193.8 (CHO); 171.0 (COO); 152.4 (C-3);
146.0 (C-5); 130.2 (C-4); 129.0 (C-2); 64.0 (C-9); 32.6 (C-6); 28.0 (C-8);
24.8 (C-7); 20.9 (CH3). IR (ꢁmax/cmÀ1): 2944; 2744; 1732; 1682; 1640;
1366; 1242. MS: 196 (Mþꢂ, 1); 136 (28); 134 (13); 121 (12); 118 (31);
117 (16); 108 (34); 107 (55); 100 (14); 95 (26); 91 (25); 81 (87); 80 (100);
77 (33); 71 (32); 70 (23); 68 (79); 67 (68); 66 (48). Anal. calcd. for
C11H16O3: C, 67.32; H, 8.22; Found: C, 67.49; H, 8.07.
(2E,4E )-8-Cyanoocta-2,4-dienal 4d (Entry 4, Table 1). (0.126 g,
1
yellow oil). Yield 85%. H NMR (CDCl3, 200 MHz): 9.52 (d, J ¼ 7.8,
1H, CHO); 7.06 (dd, J ¼ 15.4 and 10.2, 1H, H-3); 6.36 (dd, J ¼ 15.0
and 10.2, 1H, H-4); 6.25–6.00 (m, 2H, H-2 and 5); 2.50–2.30 (m, 4H,
H-6 and 8); 1.81 (m, 2H, H-7). 13C NMR (CDCl3, 50 MHz): 193.8
(CHO); 151.7 (C-3); 143.2 (C-5); 130.8 (C-4); 130.2 (C-2); 115.1 (CN);
31.6 (C-6); 24.1 (C-7); 16.5 (C-8). IR (ꢁmax/cmÀ1): 2960; 2246; 1770; 1616;
1426; 1348; 1298; 1266; 1176; 1160; 954; 858. MS: 150 (M þ 1., 57); 149
(Mþꢂ, 9); 133 (7); 132 (14); 122 (51); 120 (28); 109 (10); 107 (20); 105 (33);
96 (13); 95 (19); 91 (40); 83 (20); 81 (100); 79 (96); 77 (37); 69 (34); 68 (24);
67 (52); 65 (27); 57 (48); 56 (16); 55 (87). Anal. calcd. for C15H24O3: C,
72.46; H, 7.43; Found: C, 72.31; H, 7.33.
(2E,4E )-9-Chloronona-2,4-dienal 4e (Entry 5, Table 1). (0.124 g,
1
yellow oil). Yield 72%. H NMR (CDCl3, 200 MHz): 9.47 (d, J ¼ 8.0,
1H, CHO); 7.02 (dd, J ¼ 15.4 and 9.3, 1H, H-3); 6.27–6.18 (m, 2H, H-4
and 5); 6.00 (dd, J ¼ 15.4 and 8.0, 1H, H-2); 3.48 (t, J ¼ 6.2, 2H, H-9);
2.20 (m, 2H, H-6); 1.81–1.52 (m, 4H, H-7 and 8). 13C NMR (CDCl3,
50 MHz): 193.7 (CHO); 152.3 (C-3); 145.9 (C-5); 130.2 (C-4); 129.0

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Palladium Catalyzed Cross-Coupling Reaction
1519
(C-2); 44.6 (C-9); 32.2 (C-6); 31.8 (C-8); 25.6 (C-7). IR (ꢁmax/cmÀ1): 2938;
1682; 1640; 1260; 1168; 1118; 1014; 988; 798. Anal. calcd. for C9H13ClO:
C, 62.61; H, 7.59; Found: C, 62.42; H, 7.37.
(2E,4Z )-7-Trimethylsilylhepta-2,4-dien-6-ynal 5a (Entry 1, Table 2).
According to the general procedure I, we have obtained a yellow oil
(0.114 g, yield 64%) asa mixture of 4a (83%) and of 5a (17%). Anal.
calcd. for C10H14OSi: C, 67.36; H, 7.91; Found: C, 67.58; H, 7.78.
Compound 5a: 1H NMR (CDCl3, 200 MHz): 9.64 (d, J ¼ 7.9, 1H,
CHO); 7.57 (dd, J ¼ 15.5 and 11.3, 1H, H-3); 6.61 (t, J ¼ 11.0, 1H, H-4);
6.22 (dd, J ¼ 15.5 and 7.9, 1H, H-2); 5.89 (d, J ¼ 10.6, 1H, H-5); 0.22 (s,
9H, CH3). 13C NMR (CDCl3, 50 MHz): 193.7 (CHO); 146.8 (C-3); 137.3
(C-5); 133.3 (C-4); 118.8 (C-2); 106.8 (C-7); 100.4 (C-6); À0.5 (CH3).
(2E,4Z )-13-Acetoxytrideca-2,4-dienal 5b (Entry 2, Table 2). Accord-
ing to the general procedure II, we have obtained a yellow oil (0.194 g,
yield 77%) asa mixture of 4b (85%) and of 5b (15%). Anal. calcd. for
C15H24O3: C, 71.39; H, 9.59; Found: C, 71.52; H, 9.72. Compound 5b:
1H NMR (CDCl3, 200 MHz): 9.57 (d, J ¼ 8.0, 1H, CHO); 7.41 (dd,
J ¼ 15.7 and 11.1, 1H, H-3); 6.30–5.85 (m, 3H, H-2, 4 and 5); 4.00
(t, J ¼ 6.7, 2H, H-13); 2.30 (dt, J ¼ 10.4 and 7.3, 2H, H-6); 2.00 (s, 3H,
CH3); 1.57 (m, 2H, H-12); 1.43–1.18 (m, 10H, H-7, 8, 9, 10, and 11).
(2E,4E )-Dodeca-2,4-dien-6-ynal 4g (Entry 3, Table 2). According
to the general procedure I, we have obtained a yellow oil (0.141 g,
yield 80%) asa mixture of 4g (84%) and of 5g (16%). Anal. calcd. for
C12H16O: C, 81.77; H, 9.15; Found: C, 81.59; H, 9.32. Compound 4g:
1H NMR (CDCl3, 200 MHz): 9.51 (d, J ¼ 7.9, 1H, CHO); 7.05 (dd,
J ¼ 15.2 and 11.1, 1H, H-3); 6.65 (dd, J ¼ 15.1 and 11.1, 1H, H-4);
6.15–6.00 (m, 2H, H-2 and 5); 2.35 (m, 2H, H-8); 1.44 (m, 2H, H-9);
1.40–1.15 (m, 4H, H-10 and 11); 0.86 (t, J ¼ 7.0, 3H, CH3). 13C NMR
(CDCl3, 50 MHz): 193.1 (CHO); 150.4 (C-3); 137.4 (C-5); 131.9 (C-4);
122.4 (C-2); 102.8 (C-6); 99.9 (C-7); 31.0 (C-8); 28.0 (C-9); 22.1 (C-10);
19.7 (C-11); 13.9 (CH3). IR (ꢁmax/cmÀ1): 2956; 2932; 2860; 2734; 2206;
1682; 1610; 1466; 1428; 1378; 1290; 1250; 1156; 1106; 1074; 984. MS: 176
(Mþꢂ, 2); 175 (1); 167 (12); 161 (M-CH3, 2); 149 (39); 133 (12); 120 (13);
119 (62); 118 (11); 105 (68); 91 (58); 79 (21); 77 (20); 71 (52); 70 (18); 69
(23); 57 (100). Compound 5g: (2E,4Z)-Dodeca-2,4-dien-6-ynal: 1H NMR
(CDCl3, 200 MHz): 9.62 (d, J ¼ 7.9, 1H, CHO); 7.57 (dd, J ¼ 15.4 and
11.3, 1H, H-3); 6.52 (t, J ¼ 10.8, 1H, H-4); 6.18 (dd, J ¼ 15.4 and 7.9, 1H,
H-2); 5.88 (d, J ¼ 10.4, 1H, H-5); 2.40 (m, 2H, H-8); 1.59 (m, 2H, H-9);
1.25–0.95 (m, 4H, H-10 and 11); 0.88 (t, J ¼ 6.6, 3H, CH3). 13C NMR
(CDCl3, 50 MHz): 193.6 (CHO); 147.3 (C-3); 135.2 (C-5); 132.4 (C-4);
120.0 (C-2); 102.6 (C-6); 100.5 (C-7); 30.9 (C-8); 28.0 (C-9); 21.9 (C-10);
19.6 (C-11); 13.7 (CH3).

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1520
Vicart et al.
(2E,4E)-Deca-2,4-dienal 4h[2,10] (Entry 4, Table 2). According to the
general procedure I, we have obtained a yellow oil (0.047 g, yield 31%) as
a mixture of 4h (75%) and of 5h (25%). Anal. calcd. for C10H16O: C,
1
78.90; H, 10.59; Found: C, 78.67; H, 10.83. Compound 4h: H NMR
(CDCl3, 200 MHz): 9.50 (d, J ¼ 8.0, 1H, CHO); 7.06 (m, 1H, H-3); 6.27
(m, 2H, H-4 and 5); 6.05 (dd, J ¼ 15.4 and 8.0, 1H, H-2); 2.19 (m, 2H,
H-6); 1.43 (m, 2H, H-7); 1.32–1.18 (m, 4H, H-8 and 9); 0.87 (t, J ¼ 6.9,
3H, CH3). 13C NMR (CDCl3, 50 MHz): 194.0 (CHO); 152.9 (C-3); 147.4
(C-5); 129.9 (C-4); 128.6 (C-2); 33.1 (C-6); 31.3, 28.2, and 22.4 (C-7, 8,
and 9); 13.9 (CH3). Compound 5h: (2E,4Z )-deca-2,4-dienal[11]: 1H NMR
(CDCl3, 200 MHz): 9.58 (d, J ¼ 8.0, 1H, CHO); 7.42 (dd, J ¼ 15.2 and
11.3, 1H, H-3); 6.30–5.85 (m, 3H, H-2, 4, and 5); 2.30 (q, J ¼ 7.1, 2H,
H-6); 1.50–1.18 (m, 6H, H-7, 8 and 9); 0.86 (t, J ¼ 6.6, 3H, CH3).
13C NMR (CDCl3, 50 MHz): 193.9 (CHO); 146.8 (C-3); 147.4 (C-5);
131.6 (C-4); 126.6 (C-2); 31.3 (C-6); 28.8, 28.3 and 22.4 (C-7, 8, and 9);
13.9 (CH3).
(2E,4E )-5-Phenylpenta-2,4-dienal 4i (Entry 5, Table 2). According to
the general procedure I, we have obtained a yellow oil (0.123 g, yield
78%) asa mixture of 4i (33%) and of 5i (67%). Compound 4i:
1H NMR (CDCl3, 200 MHz) (in agreement with our previously reported
data.[12,13]): 9.58 (d, J ¼ 8.0, 1H, CHO); 7.50–7.45 (m, 2H, H-phenyl);
7.42–7.32 (m, 3H, H-phenyl); 7.23 (m, 1H, H-3); 7.02–6.95 (m, 2H, H-4
and 5); 6.29 (dd, J ¼ 14.9 and 8.0, 1H, H-2). 13C NMR (CDCl3, 50 MHz):
193.4 (CHO); 151.9 (C-3); 142.2 (C-5); 135.3 (C-phenyl, quat.); 131.2
(C-phenyl, para); 129.4 (C-4); 128.6 (2C, C-phenyl, meta); 127.3 (2C,
C-phenyl, ortho); 125.9 (C-2). MS: 158 (Mþꢂ, 70); 129 (100); 115 (40);
105 (58); 91 (22); 77 (75). Compound 5i: (2E,4Z -5-phenylpenta-2,4-
dienal: 1H NMR (CDCl3, 200 MHz): 9.61 (d, J ¼ 8.0, 1H, CHO); all
other signals are partially or totally overlapped by isomer 4i ones.
13C NMR (CDCl3, 50 MHz): 193.7 (CHO); 147.6 (C-3); 139.8 (C-5);
135.8 (C-phenyl, quat.); 133.4 (C-phenyl, para); 129.5 (C-4); 128.6 (2C,
C-phenyl, meta); 127.3 (2C, C-phenyl, ortho); 125.9 (C-2).
(4E,6E )-Methyl-3-hydroxy-7-bromohepta-4,6-dienoate 6 (Entry 6,
Table 1). According to the general procedure II, we have obtained a
1
yellow oil (0.115 g, yield 49%). H NMR (CDCl3, 200 MHz): 6.60 (m,
1H, H-5); 6.20 (m, 2H, H-4 and H-7); 5.69 (dd, J ¼ 14.6 and 10.9, 1H,
H-6); 4.57 (m, 1H, H-3); 3.67 (s, 3H, CH3); 3.05 (s, 1H, OH); 2.52 (m, 2H,
H-2). 13C NMR (CDCl3, 200 MHz): 172.3 (C¼O); 136.4 (C-5); 134.5
(C-6); 127.9 (C-4); 109.6 (C-7); 67.9 (C-3); 51.8 (CH3); 40.9 (C-2). IR
(ꢁmax/cmÀ1): 3448; 2952; 1734; 1584; 1438; 900. MS: 236 and 234
(Mþꢂ, 1); 218 and 216 (10); 137 (17); 134 (20); 132 (21); 123 (16); 106
(17); 105 (30); 95 (19); 94 (25); 91 (24); 82 (32); 81 (89); 79 (20); 78 (66); 77

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Palladium Catalyzed Cross-Coupling Reaction
1521
(78); 74 (15); 67 (32); 66 (22); 65 (28); 59 (100). Anal. calcd. for
C8H11BrO3: C, 40.87; H, 4.72; Found: C, 40.80; H, 4.69.
(2E,4E )-14-Acetoxytetradeca-1,3,5-triene 14. To a stirred suspension
of methyltriphenylphosphomium bromide (0.186 g, 0.52 mmol) in THF
(4 mL) at À50ꢀC wasadded 0.062 g (0.55 mmol) of t-BuOK. After 1 h,
0.101 g (0.40 mmol) of 4b in THF (1 mL) wasadded. The mixture was
allowed to warm to 0ꢀC for 30 min then diluted with Et2O (20 mL) and
water (20 mL). The aqueouslayer wasextracted by Et 2O (2 ꢁ 20 mL).
The organic layerswere combined, wahsed with brine (20 mL), dried
over MgSO4, and evaporated. Purification of the crude product by
silica gel column chromatography (light petroleum ether/Et2O: 95/5)
afforded 14 asa yellow oil (0.074 g, yield 74%). The analytical data of
14 were consistent with those published.[8]
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3. Soullez, D.; Ple, G.; Duhamel, L.; Duhamel, P. J. Chem. Soc. Chem.
Commun. 1995, 563–564.
4. Knochel, P.; Singer, D. Chem. Rev. 1993, 93, 2117–2188.
5. Furstner, A. Synthesis 1989, 571–590.
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Synthesis; John Wiley and Sons: Chichester, 1995.
8. Tellier, F. Synth. Commun. 1991, 2287–2294.
9. Lipshutz, B.H.; Pfeiffer, S.S.; Chrisman, W. Tetrahedron Lett. 1999,
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10. Binns, F.; Hayes, R.; Hodgetts, K.J.; Saengchantara, S.T.; Wallace,
Wallis, C.J. Tetrahedron 1996, 52, 3631–3658.
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569–577.
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Received in the UK February 11, 2002

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