Oxidative addition of N-halosuccinimides to palladium(0): The discovery of neutral palladium(II) imidate complexes, which enhance Stille coupling of allylic and benzylic halides

Article abstract of DOI:10.1016/j.tet.2005.06.080

The Stille coupling of organostannanes and organohalides, mediated by air and moisture stable palladium(II) phosphine complexes containing succinimide or phthalimide (imidate) ligands, has been investigated. An efficient synthetic route to several palladium(II) complexes containing succinimide and phthalimide ligands, has been developed. cis-Bromobis(triphenylphosphine)(N-succinimide) palladium(II) [(Ph₃P)₂Pd(N-Succ)Br] is shown to mediate the Stille coupling of allylic and benzylic halides with alkenyl, aryl and allyl stannanes. In competition experiments between 4-nitrobromobenzene and benzyl bromide with a cis-stannylvinyl ester, (Ph₃P)₂Pd(N-Succ)Br preferentially cross-couples benzyl bromide, whereas with other commonly employed precatalysts 4-nitrobromobenzene undergoes preferential cross-coupling. Furthermore, preferential reaction of deactivated benzyl bromides over activated benzyl bromides is observed for the first time. The type of halide and presence of a succinimide ligand are essential for effective Stille coupling. The type of phosphine ligand is also shown to alter the catalytic activity of palladium(II) succinimide complexes.

Full text of DOI:10.1016/j.tet.2005.06.080

Tetrahedron 61 (2005) 9736–9751
Oxidative addition of N-halosuccinimides to palladium(0):
the discovery of neutral palladium(II) imidate complexes,
which enhance Stille coupling of allylic and benzylic halides
*
Catherine M. Crawforth, Suzanne Burling, Ian J. S. Fairlamb, Anant R. Kapdi,
*
Richard J. K. Taylor and Adrian C. Whitwood
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Received 21 March 2005; revised 10 June 2005; accepted 24 June 2005
Available online 26 July 2005
Abstract—The Stille coupling of organostannanes and organohalides, mediated by air and moisture stable palladium(II) phosphine
complexes containing succinimide or phthalimide (imidate) ligands, has been investigated. An efficient synthetic route to several
palladium(II) complexes containing succinimide and phthalimide ligands, has been developed. cis-Bromobis(triphenylphosphine)
(N-succinimide)palladium(II) [(Ph3P)2Pd(N-Succ)Br] is shown to mediate the Stille coupling of allylic and benzylic halides with alkenyl,
aryl and allyl stannanes. In competition experiments between 4-nitrobromobenzene and benzyl bromide with a cis-stannylvinyl ester,
(Ph3P)2Pd(N-Succ)Br preferentially cross-couples benzyl bromide, whereas with other commonly employed precatalysts 4-nitrobromo-
benzene undergoes preferential cross-coupling. Furthermore, preferential reaction of deactivated benzyl bromides over activated benzyl
bromides is observed for the first time. The type of halide and presence of a succinimide ligand are essential for effective Stille coupling. The
type of phosphine ligand is also shown to alter the catalytic activity of palladium(II) succinimide complexes.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
including hindered derivatives, are now available. Coupling
of deactivated substrates such as aryl chlorides, not possible
prior to 1998, is facilitated by electron rich bulky two-
electron donor ligands such as t-Bu3P6 and N-heterocyclic
carbenes.7 The importance attached to the use of an
activating donor ligand (strong s-donor) derives from pro-
motion of the oxidative addition process. Steric and elec-
tronic properties of ligands also produce pronounced effects,
usually by influencing the intrinsic stability/reactivity of the
palladium intermediates throughout the catalytic cycle.8
The use of co-catalysts/additives and variation of the solvent
can also be employed to optimize the efficiency of Stille
coupling processes.9
Great progress has been made in the development of
transition metal-catalysed processes for the formation of
carbon–carbon bonds.1 Palladium-catalyzed processes, to
date, represent the most frequently applied of these
reactions and are increasingly being employed in synthetic
routes to complex biological targets and therapeutic agents.2
The Stille coupling reaction between organohalides and
organostannanes, mediated by palladium, has attracted con-
siderable attention and has been used as a ‘test-bed’ for
the development of highly active palladium catalysts.3,4 The
broad utility of the Stille reaction is primarily due to the
accessibility of a diverse range of organostannanes, their air
and moisture stability and their excellent functional group
compatibility, although the toxicity of organotin compounds
can present problems. The scope of the Stille reaction has
been substantially expanded recently, through state-of-the-
art developments in the creation of highly active catalysts
that operate under mild conditions.5 Room temperature
protocols for reactions employing organobromides,
Halide counterions are also known to play an important role
in palladium-mediated cross-coupling processes, as well as
in other transition metal-mediated reactions.10 Pseudo-
halides (OAc, OTf) can also be influential: for example, in
studies by Bedford and co-workers using palladacycles as
pre-catalysts, the catalyst activity and lifetime, were
dependent on the nature of the pseudohalide.11 Compre-
hensive support for the involvement of halide/pseudohalide
anions in palladium-catalysed cross-coupling reactions has
been elegantly demonstrated by Amatore and Jutand.12
Thus, in the presence of halides, the existence of an
Keywords: Pseudohalide effect; Stille coupling reaction; Cross-coupling
reaction; Coupling reaction.
Corresponding authors. Tel.: C44 1904 43 4091; fax: C44 1904 43
2516; e-mail addresses: ijsf1@york.ac.uk; rjkt1@york.ac.uk
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.080

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9737
alternative catalytic cycle involving tricoordinated anionic
complexes such as L2Pd(0)ClK and L2Pd(0)OAcK has been
demonstrated. Dimeric anionic palladium–halide complexes
such as [Pd2I6][Y2], where YZDMFHC or Et3NHC, have
also been detected.13 In addition, when palladium(II) pre-
cursors, for example, Pd(Ph3P)2Cl2 or Pd(OAc)2, are
employed in coupling reactions, it has been proposed that
anionic complexes are active catalysts as well as low-
ligated, palladium ‘LnPd(0)’ (L is usually R3P and nZ1 or 2).
Importantly, the nature of the halide or pseudohalide
influences the reactivity of these palladium intermediates.
In the absence of halide, the reduced species undergoes
rapid reaction to form metallic palladium, which is clearly a
therefore semi-purified by passage through a very short
silica column. In this form, 2 underwent efficient Stille
coupling with organostannane 3 and catalytic (PPh3)4Pd to
give 4 in 78% yield. As large quantities of 4 were required,
the use of CBr4/Ph3P17 was investigated in order to improve
the yield of bromide 2. However, when 2 prepared via this
route, was subjected to the Stille reaction as before, no
coupling was observed. The reaction was repeated many
times without success (purification of solvents/reagents and
the use of freshly prepared (Ph3P)4Pd did not alter the
outcome).
This surprising result led us to compare the two procedures.
It seemed likely that traces of an ‘impurity’ were being
carried through undetected with 2; that is, something
remaining from the NBS method could be acting to promote
the coupling process or something from the CBr4 method
could be inhibiting coupling. The CBr4/Ph3P method
produces Ph3PO and CHBr3, but excess starting reagents
could also be present. However, CHBr3 might be expected
to enhance the Stille reaction as CHBr3 is known to react
with Pd2dba3/t-Bu3P to give a palladium(I) dimer [Pd2(m-
Br)2(t-Bu3P)2],18 which is a highly active catalyst for cross-
coupling (amination)19 and an excellent source of mono-
ligated palladium(0) ‘t-Bu3P-Pd(0)’.
limitation. Halide binding serves to stabilize the L Pd(0)
n
complex. The halide could also stabilize palladium clusters
or colloids, which act as a reservoir14 of active catalytic
Pd(0) species (neutral or anionic).
We have been interested in harnessing halide and pseudo-
halide effects in the design of improved catalysts for Stille
coupling, as this is a potentially tunable property that could
be exploited in increasing reactivity and substrate scope, but
might also produce selective processes. This interest has
been driven by our recent finding that succinimide, a
pseudohalide, shows intriguing effects in the Stille
reaction.15 At the present time, it has not been established
how this ligand exerts its effect, but it is clearly more than
just a simple halide mimetic. Mechanistic studies are ongoing
but in this paper, the preparation and application of Pd(II)
succinimide and phthalimide complexes are discussed.
Given that Ph3P and Ph3PO are present in both methods,
attention was turned to the importance of the NBS. It
seemed possible that trace amounts of NBS could be carried
through the silica column with 2, then activating the
subsequent Stille coupling in a manner yet to be revealed.
Indeed, on closer examination of the 1H NMR spectrum of 2
used in the successful coupling process, a small singlet was
observed at d 2.7 (CDCl3, 400 MHz), which corresponds to
NBS. We therefore repeated the Stille coupling reaction of
2, formed using the CBr4 method, with stannane 3 but on
this occasion added an equimolar amount of NBS with
respect to the (Ph3P)4Pd. We were delighted to observe that
this formerly unsuccessful process, now proceeded to give 4
in 76% yield.
2. Results
2.1. The initial observation
During the course of synthetic studies towards inthomycin
C, a Stille coupling of oxazole bromide 2 with E,E,E-triene
3 was investigated (2C3/4, Scheme 1).
Bromide 2 was initially obtained from alcohol 1 using
N-bromosuccinimide (NBS)/triphenylphosphine.16 How-
ever, it proved to be sensitive to light, temperature, moisture
and prolonged chromatography (although at K20 8C in the
dark it was largely unchanged after one month); it was
In order to establish that the above observation had some
generality, we studied its value in another problematic
process investigated during the inthomycin programme
(Scheme 2).
Scheme 1. i, Ph3P, NBS, THF, 25 8C, 1 h; ii, 3 (1.05 equiv), Pd(Ph3P)4 (0.05 equiv), toluene, reflux, 20 h; iii, Ph3P, CBr4, CH2Cl2, 0 8C; iv, as for ii with added
NBS (0.05 equiv).

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C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
21.93). Changing to (Ph3P)4Pd as the palladium(0) source,
resulted in a rapid initial reaction but low conversion, as the
additional phosphine removes NBS from the system as the
phosphonium salt: addition of excess NBS (w3 equiv) pushes
the reaction to completion, but the yield of 9, although
improved, was modest (31%).
We discovered that improved yields of 9 could be obtained
from Pd2dba3 dba simply by reversing the order of addition
of reagents given in the published procedure.20 Reaction
of Pd2dba3 dba (1 equiv) with Ph3P (4 equiv) in CH2Cl2
produced an intense orange colour, which can be attributed
to the formation of ‘(Ph3P)2Pd(0)-h2-dba’ (Scheme 3).21
Addition of a solution of NBS in CH2Cl2 at 21 8C after
0.15 h caused the reaction mixture to change to a bright
yellow colour. The small amount of precipitate, which is
trans-(Ph3P)2PdBr2 is then removed by filtration. Addition
of petroleum ether to the resultant filtrate produced a creamy
yellow precipitate of 9 in yields, which varied between 20
and 52%. However, switching to Pd2dba3$CHCl3 as the
palladium source resulted in an improvement to 74% yield.
Complex 9 was crystallised from CH2Cl2/diethyl ether (1:5,
24 h, K20 8C) to give fine yellow crystals, which were
characterised by X-ray diffraction and NMR spectroscopic
studies.15a
Scheme 2. i, Toluene, reflux, 3 h.
Reaction of E-bis-1,2-(tributylstannyl)ethene 5, with ethyl
2-iodo-2Z-propenoate 6 using (Ph3P)4Pd had been shown to
give 11% of the mono-coupled product Z,E-7 and 10% of
the corresponding E,E-isomer. Repeating the reaction but
with addition of an equimolar amount of NBS with respect
to the (Ph3P)4Pd, resulted in the formation of 49% of Z,E-7
and 31% of Z,E,Z-8. The stereoselectivity observed in the
NBS-modified process was noteworthy, as was the
improvement of the overall yield from 21 to 80%.
The results shown in Schemes 1 and 2 indicated that the
combination of NBS and (Ph3P)4Pd had generated a highly
active palladium catalyst. A search of the literature revealed
that the oxidative addition of NBS to palladium(0) and
platinum(0) precursors to give air and moisture stable
complexes cis-(Ph3P)2M(N-Succ)Br (MZPd or Pt), had
been reported by Serrano and co-workers, although the
catalytic properties of these complexes were not studied.20
We therefore, decided to prepare such complexes and
investigate their value in Stille coupling reactions.
Scheme 3. i, Pd2dba3$CHCl3 (0.5 equiv), Ph3P (2 equiv), CH2Cl2, 25 8C, 0.
2 h; ii, NBS (1 equiv), 0.2 h.
2.2. Preparation of Pd(imidate)(Ph3P)2X complexes (XZ
halide or imidate; imidateZsuccinimide or phthalimide)
Related palladium complexes such as Pd2dba3$solvent;
solventZbenzene, toluene or CH2Cl2, can also be used to
prepare 9, as can Pd2[3,5,30,50-(MeO)4-dba]3$CH2Cl2.22 In
this complex, the electron-rich dba dissociates more rapidly
from palladium(0) than unsubstituted dba, increasing the
relative rate of the oxidative addition process.23 Using this
precursor, a yield of 82% of 9 was attained. It should be
noted that small quantities of trans-(Ph3P)2PdBr2 were
obtained if the reaction concentration exceeded 11 mM.
Increasing the reaction temperature also leads to increasing
amounts of trans-(Ph3P)2PdBr2 but keeping the reaction
temperature in the range 15–21 8C avoids the problem. It is
believed that trans-(Ph3P)2PdBr2 is formed via a bridged
halide intermediate species, produced by dimerisation/
disproportionation of two molecules of 9.
The published procedure for the preparation of cis-(Ph3P)2-
Pd(N-Succ)Br 9 utilised Pd2dba3 dba (dbaZE,E-dibenzyli-
dene acetone) and NBS in dry CH2Cl2 at ambient temperature,
followed by addition of 2 equiv of Ph3P. In our hands 9 was
obtained in low yields (w10%) with another palladium
complex being isolated as a yellow precipitate in 30–40%
yields, whose formation was dependent on a number of
variables (vide infra). Recrystallisation of this major product
followed by X-ray crystallography (Fig. 1), allowed identifi-
cation as trans-(Ph3P)2PdBr2 (31P NMR, 202 MHz, CD2Cl2, d
We next examined whether other N-halo-succinimides,
phthalimides and acetamides could used to prepare similar
complexes to 9. Using the optimum procedure for 9, but
employing N-chlorosuccinimide (NCS) and N-iodosuccin-
imide (NIS), gave the chloro- 10 and iodo- 11 analogues in
ca. 22, and 50% yields, respectively, (Scheme 4). The lower
yields are again due to the formation of complexes of the
type (Ph3P)2PdX2 (XZCl, I). In fact, it was not possible to
isolate 10 in pure form due to this impurity. Complexes 10
and 11 exhibit a trans-geometry around the palladium(II)
Figure 1. X-ray crystal structure of (Ph3P)2PdBr2. Thermal ellipsoids are
shown at 50% probability level.

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9739
(2JPPZ8.39 Hz) is similar to that seen in 9 (2JPPZ
8.49 Hz). Interestingly, the formation of (Ph3P)2PdBr2 is
not observed in this reaction. On the other hand, the
oxidative addition of N-bromoacetamide (NBA) to Pd2-
dba3$CHCl3 to yield 13 was unsuccessful, affording
(Ph3P)2PdBr2 in 49% yield.
2.3. Preparation of succinimide complexes containing
bidentate ligands
Reaction of Pd2dba3$CHCl3 with bidentate ligands,
followed by oxidative addition with NBS was achieved
using 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(di-
cyclohexylphosphino)ethane (dcpe) and 1,10-bis(diphenyl-
phosphino)ferrocene (dppf) (Scheme 5). For dppe, 14 was
isolated in 59% yield (d 23.95, br s; and 61.87, br s; 31P
NMR, 161.2 MHz, CDCl3), whereas the more electron
rich and bulky dcpe ligand gave 15 in a poor 13% yield (d
Scheme 4. Synthesis of other imidato palladium(II) complexes. i,
Pd2dba3$CHCl3 (0.5 equiv), Ph3P (2.0 equiv), CH2Cl2, 25 8C, 0.2 h, then
NBS, NCS or NIS (1 equiv), 0.2 h; ii, as for i, but using NBP (1 equiv); iii,
as for i, but using NBA (1 equiv).
88.68, d, 2JPPZ8.39 Hz; and d 91.30, d, 2JPPZ8.39 Hz; 31
P
NMR, 202 MHz, CD2Cl2). The ferrocenyl ligand, dppf, also
underwent reaction giving 16 in 43% yield (d 24.52, br s;
2
and d 35.10, d, JPPZ5.95 Hz; 31P NMR, 202 MHz,
centre (based on a singlet signals observed by 31P NMR
spectroscopy). On steric grounds, one might predict such a
geometry for iodide 11, but the fact that the NBS reaction
gave cis-9, led us to predict that 10 might be cis as well. We
presume that for 10 the trans-geometry is best rationalised
by the relatively strong p-donor nature of chlorine—and
with succinimide being a good p-acceptor, the trans-effect
dominates.
CDCl3). In all three cases the products were formed as
the cis-isomers. The reaction of (G)-BINAP was also
attempted, but the expected complex 17 was not formed
(several species were shown to be present by 31P NMR
spectroscopy).
It was not possible to obtain an X-ray crystal structure of
chloride 10 but the X-ray structure of 11 was solved,
confirming the trans-geometry and indicating extensive
p-stacking interactions between the phosphorus aryl
substituents and the succinimide methylene groups
(Fig. 2). This interaction appears to shield both faces of
the succinimide ring, but as two signals are observed for the
succinimide methylene protons in CDCl3, it would appear
that the faces are differentially shielded.
Scheme 5. i, Pd2dba3$CHCl3 (0.5 equiv), ligand (1.0 equiv), CH2Cl2,
25 8C, 0.2 h, then add NBS (1 equiv), 0.2 h. dppeZ1,2-bis(diphenyl
phosphino)ethane, dcpeZ1,2-bis(dicyclohexylphosphino)ethane and
dppfZ1,10-bis(diphenylphosphino)ferrocene.
2.4. Stille coupling of allylic and benzylic substrates
Figure 2. X-ray structure of 11. Thermal ellipsoids are shown at 50%
probability level.
With several palladium(II) imidate complexes in hand, we
moved on to study their catalytic properties. The Stille
coupling of benzyl bromide 19 with Z-organostannane 20
at 60 8C to give Z-2 was used as the benchmark reaction
(the reactions proceed significantly slower at temperatures
!50 8C). The reactions mediated by our novel palladium
imidate catalyst systems and a range of related catalysts/
The oxidative addition of N-bromophthalimide (NBP) to
Pd2dba3$CHCl3 proceeded in a similar manner to the
reaction with NBS, providing 12 in 70% yield (Scheme 4).
The cis-geometry was confirmed by two inequivalent
phosphorus signals as doublets at d 24.89 and 33.80. The
two-bond phosphorus–phosphorus coupling constant

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C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
Table 1. Comparison of various palladium complexes in the benchmark Stille coupling reactiona
Entry
Complex
Time/h
Isolated yields/%b
Z-21
E-21
22
1
2
3
4
5
6
7
8
(Ph3P)4Pdc
18
18
18
18
18
18
18
18
18
18
1.5
18
1.5 (18)
18
18
18
48
17
16
13
23
19
66
83
61
33
76
99
56
72 (98)
87
43
64
10
—
25
28
—
30
—
—
—
—
—
—
—
—
3
—
5
—
—
5f
Pd(OAc)2, Ph3Pd
Pd2(dba)3.dba, Ph3Pe
(Ph3P)2PdBr2
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)4Pd, NBSg
—
—
—
—
—
—
—
—
—
—
—
—
—
—
(Ph3P)4Pd, NCSg
9
(Ph3P)4Pd, NISg
10
11
12
13
14
15
16
17
18
19
Pd2(dba)3.dba, Ph3P, NBSg
(Ph3P)2Pd(N-succ)Br, 9
(Ph3P)2Pd(N-succ)I, 11
(Ph3P)2Pd(N-phthal)Br,h 12
(dppe)Pd(N-succ)Br, 14
(dcpe)Pd(N-succ)Br, 15
(dppf)Pd(N-succ)Br, 16
(Ph3P)2Pd(N-succ)2, 23
(Ph3P)2Pd(N-phthal)2, 24
NBS with no added palladiumi
—
—
—
—
—
48
3
11
2
a Reaction conditions: benzyl bromide 19 (1 equiv), organostannane Z-20 (1.2 equiv), [Pd] (0.05 equiv), toluene, 60 8C.
b Isolated yield after KF work-up and chromatography. Note: A DBU/I2/Et2O work-up for this specific reaction results in rapid regio- and stereo-isomerisation
(!2 min).
c Freshly prepared from (Ph3P)2PdCl2, NH2NH2 in EtOH at 120 8C.
d 3 equiv of Ph3P were used w.r.t. to Pd.
e 2 equiv of Ph3P were used w.r.t. to Pd.
f
A mixture of stereoisomers were observed (E:Z, 1:0.9).
g 1 equiv of the N-halosuccinimide was added w.r.t. to Pd.
h Numbers in brackets are the time after 18 h reaction and the corresponding yield, respectively.
i
NBS (5 mol%) was added under the reaction conditions described in a—but in the absence of palladium (new glassware was employed for this reaction).
precatalysts are summarised in Table 1. The known catalysts/
precatalysts (Ph3P)2PdBr2, (Ph3P)2Pd(Bn)Br, (Ph3P)2PdCl2
and (Ph3P)4Pd are commercially available and (Ph3P)2Pd
(Bn)Br 18, was prepared by a reported procedure.24
33%, respectively, entries 8 and 9). The use of the catalyst
formed by the addition of NBS to Pd2dba3 dba/Ph3P
provided Z-21 exclusively in 76% yield (entry 10).
We then moved on to investigate pre-prepared complexes
(entries 11–18). (Ph3P)2Pd(N-succ)Br 9 exhibited the best
result by some margin (entry 11). The reaction was
complete after 1.5 h and gave a 99% isolated yield of 21
(confirmed by several runs: Lowest yield 92%). The iodo
relative, (Ph3P)2Pd(N-succ)I 11 gave a 56% yield, high-
lighting the importance of the halide (entry 12). It was
anticipated that (Ph3P)2Pd(N-phthal)Br 12 would show
similar catalytic activity to (Ph3P)2Pd(N-succ)Br 9, and so
it was compared (entry 13). Although the yield was good
(72%) after 1.5 h, a reaction time of 18 h was needed for the
reaction to reach completion indicating a clear difference
between the two imidate ligands.
With (Ph3P)4Pd alone, a 17% yield of Z-21 was obtained
after 24 h (entry 1). Use of a Pd(OAc)2/Ph3P combination
gave a mixture of the stereoisomers, Z-21 and E-21, and the
regioisomer E-22, in overall 46% yield (entry 2). Another
classic combination is Pd2dba3 dba/Ph3P (entry 3). A
mixture of Z-21 and E-21 was obtained in this reaction,
which favoured the latter compound, but the overall yield
was again modest (41%). The reaction mediated by
(Ph3P)2PdBr2 gave only a 23% yield of Z-21, albeit exclu-
sively (entry 4). The neutral oxidative addition intermediate,
in Stille couplings mediated by Pd/Ph3P catalyst systems
with benzyl bromide, is (Ph3P)2Pd(Bn)Br. The use of this
complex or (Ph3P)2Pd(Bn)Cl in the benchmark reaction
gave reasonable yields (entries 5 and 6). However, the
former showed poor selectivity, whereas the latter gave
Z-21, exclusively in 66% yield (entry 6).
The bidentate ligand complexes (dppe)Pd(N-succ)Br 14,
(dcpe)Pd(N-succ)Br 15 and (dppf)Pd(N-succ)Br 16 were
studied next (entries 14–16); all promoted the reaction but
all required longer reaction times than (Ph3P)2Pd(N-succ)Br
15c
Having obtained results for comparison, we then examined
succinimide-based catalysts. Catalysts formed in situ were
examined first (entries 7–10). The addition of NBS to
(Ph3P)4Pd gave Z-21 as the sole product in an excellent 83%
yield (entry 7). Other N-halosuccinimides, NCS and NIS,
also promoted the reaction, but to a lesser extent (61 and
9. For completeness, the (Ph3P)2Pd(N-succ)2
23 and
(Ph3P)2Pd(N-phthal)225 24 relatives were screened to assess
the importance of the halide in the palladium complex
(entries 17 and 18). In stark contrast to the other catalysts
containing imidate ligands, very poor yields were observed
after 48 h (10 and 11% yield, respectively). It is clear that

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9741
the presence and nature of the halide are important for the
efficacy of this reaction. In the absence of Pd, catalytic NBS
(5 mol%), under the same reaction conditions, shows
negligible conversion (2% yield, entry 19), confirming the
importance of Pd.
stereo-selectivity observed throughout the series. The
exception was the reaction of geranyl bromide E-25 with
phenylstannane 29, which give E-37 in only 34% yield after
18 h (entry 4).
Thus, with a range of benzylic (entry 1) and allylic
bromides, vinylstannanes 31 and 33, and phenylstannane
29, undergo efficient coupling (entries 2,3, 5–7). The
reaction of an allylstannane 41 with E-cinnamyl bromide
E-27, which is formally an sp3–sp3 type of coupling process,
also proceeds efficiently (entry 8). Benzyl chloride also
underwent efficient coupling reactions (entries 9–10), the
reaction with Z-20 at 60 8C giving Z-21 in 81% yield (entry
9). However, 48 h at 60 8C was required for complete
consumption of benzyl chloride 43: Increasing the reaction
temperature to 110 8C reduced the reaction time to 18 h
(isomerisation is observed if longer reflux times are
employed at this temperature). The reaction of E-20,
under the same reactions conditions with elevated tempera-
ture, gave E-21 in 68% yield after 18 h (entry 10). A
literature survey reveals that few Stille couplings of benzyl
chloride have been reported,4b,15b and the majority of
reactions require harsh conditions or toxic additives, for
example, HMPA.
It should be noted that when using many of the standard
palladium complexes (Table 1, entries 1–6), a precipitate of
palladium black is observed whereas with (Ph3P)2Pd(N-
succ)Br 9, the reaction remains yellow (in the absence of air
and moisture) at the completion of the coupling process and
no precipitate is observed. Also noteworthy is the fact that
elevated temperatures can lead to additional isomerisation.
For example, coupling using (Ph3P)2Pd(N-succ)Br 9, which
was stereoselective at 60 8C (entry 11), gave isomeric
mixtures (E:ZZ80:20) when the reaction was carried out at
reflux. We established that this process was mediated by
palladium by carrying out control experiments. Thus, pure
Z-21 was refluxed in toluene, in the presence and absence of
(Ph3P)2Pd(N-succ)Br 9. In the presence of (Ph3P)2Pd(N-
succ)Br after 0.5 h at reflux, cis–trans isomerisation was
observed by 1H NMR analysis (E:ZZ35:65) whereas in the
absence of palladium, no stereoisomerisation was detected
(even after 24 h).
We next carried out experiments to compare coupling
reactions of a range of allylic and benzylic substrates using
(Ph3P)2Pd(N-succ)Br 9 and other typical catalysts (Table 2).
Thus, geranyl bromide 25 underwent coupling with Z-
stannyl ester Z-20 to give adduct 26 (entry 1). As can be
seen, with (Ph3P)2Pd(N-succ)Br 9- product E,Z-26 was
obtained in 67% yield, with complete preservation of alkene
stereochemistry, whereas the other catalysts gave much
lower yields with evidence of product isomerisation.
2.5. Stille coupling of aryl substrates
Having established that (Ph3P)2Pd(N-succ)Br 9 is an
efficient catalyst for the Stille coupling of allyl and benzylic
substrates, coupling reactions with aryl substrates were
investigated. 4-Nitrobromobenzene 44 was selected as the
model substrate, as it is known to be one of the most active
electrophilic substrates for Stille coupling.5 Tributylvinyltin
33 was chosen as the coupling partner (Scheme 6 and
Table 4).
For the related E-stannyl ester E-20 coupling with geranyl
bromide 25, all catalysts gave similar yields, although
(Ph3P)2Pd(N-succ)Br 9 was again the catalyst of choice
(entry 2). For the coupling between Z-20 and cinnamyl
bromide to give E,Z-28 (entry 3), the best yield (86%) was
again obtained using (Ph3P)2Pd(N-succ)Br 9. Comparable
results were seen in the coupling of E-20 with cinnamyl
bromide E-27 (entry 4). Again, complete stereoselectivity
was observed in these processes.
After 5 h at reflux, (Ph3P)4Pd gave the coupled product in
65% yield (entry 1). Higher yields were obtained using
(Ph3P)2Pd(Bn)Cl and (Ph3P)2Pd(Bn)Br (entries 2 and 3,
respectively). However, when the reaction was carried out
in the presence of the (Ph3P)4Pd/NBS combination (entry
4), the yield dropped to 35% (after 24 h), showing for the
first time that this system could be less active than
(Ph3P)4Pd alone! (Ph3P)2Pd(N-succ)Br 9 gave an improved
yield (66%), but a substantially longer reaction time was
required (24 h, entry 5). Thus, for a typical aryl halide Stille
coupling, standard catalyst systems are more efficient than
both the (Ph3P)4Pd/NBS combination and (Ph3P)2Pd(N-
succ)Br 9. Similar results were obtained using bromoben-
zene as the substrate.
The corresponding coupling of benzyl bromide 19 and E-20
was investigated next and predicted to give similar results to
the corresponding benchmark study involving benzyl
bromide and Z-20 (Table 1), but this turned out not to be
the case (entry 5). With all catalysts, the yields were good to
excellent (O90% using (Ph3P)2Pd(Bn)Cl and (Ph3P)2Pd(N-
succ)Br 9). Interestingly, it was noted that the reaction time
for the coupling of benzyl bromide 19 and E-20 with
(Ph3P)2Pd(N-succ)Br 9 as catalyst was much longer (5 h vs
1.5 h) than that corresponding with Z-20 (Table 2, entry 5 vs
Table 1, entry 11). The reaction of phenylstannane 29 with
19 to give 30, proceeded well with all four catalysts
(entry 6).
2.6. Competition Stille coupling reactions
The efficiency of (Ph3P)2Pd(N-succ)Br 9 as a catalyst for
allylic/benzylic halide coupling reactions, compared to its
low reactivity for the coupling of aryl halides was of some
interest. Several competition experiments were therefore
devised to evaluate the substrate scope against different
palladium catalyst systems. In the first example, bromo-
benzene 46, benzyl bromide 19 and Z-vinylstannane 20 (in a
1:1:1 ratio) were subjected to the reaction conditions
outlined in Scheme 7 and Table 5. Two major products
To assess the substrate scope in benzylic/allylic Stille
reactions mediated by (Ph3P)2Pd(N-Succ)Br 9, several
other reactions were studied (Table 3). All but one of
the examples gave good yields, with high regio- and

Table 2. Stille coupling reactions mediated by a range of palladium sourcesa
Entry
1
Organostannane
Organohalide
Catalyst
Time/h
Cross-coupled product
Yield/%b
(Ph3P)4Pd
24
24
24
24
11
30c
32c
67
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
Z-20
E-25
E-25
E,Z-26
E,E-26
2
3
(Ph3P)4Pd
24
24
24
24
51
55
49
56
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
E-20
(Ph3P)4Pd
24
20
20
13
56
78
71
86
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
Z-20
E-27
E,Z-28
4
5
6
(Ph3P)4Pd
23
18
24
13
56
77
58
81
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
E-20
E-27
E,E-28
(Ph3P)4Pd
24
5
24
5
73
97
71
95
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
E-20
19
E-21
(Ph3P)4Pd
24
24
24
24
90
97
90
93
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(N-succ)Br, 9
29
19
30
a Reaction conditions: allylic/benzylic bromide (0.25 mmol), organostannane (0.3 mmol), C6H5CH3 (2.5 mL) at 60 8C, under an inert atmosphere of N2.
b Isolated yields after KF work-up and chromatography.
1
c w1% of the E-isomer was detected by H NMR spectroscopy.

Table 3. Products from the Stille coupling of allylic or benzylic substrates with organostannanes, mediated by (Ph3P)2Pd(N-Succ)Br, 9a
Entry
1
Organostannane
Organohalide
19
Coupled product
Yield/%b
84
Reaction time/h
20
32
31
33
2
67
6
34
35
3
4
78
34
18
18
33
E-36
E-25
E-25
29
E-37
5
6
7
8
9
92
79
18
20
18
24
48
33
31
E-27
E-38
E-39
E-27
E-27
E-27
79
29
41
E-40
70
E-42
81c
Z-20
43
Z-21
10
68d
18
E-20
43
E-21
a Reaction conditions: allylic/benzylic bromide (0.25 mmol), organostannane (0.3 mmol), C6H5CH3 (2.5 mL) at 60 8C, under an inert atmosphere of N2.
b Isolated yields after KF workup and column chromatography.
c 79% after 18 h when reaction conducted at 110 8C.
d Reaction conducted at 110 8C.

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C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
Scheme 6. Stille coupling of 4-nitrobromobenzene 44 with tributylvinyltin
33. i, [Pd] (0.05 equiv.), toluene, reflux, 6 h (for details, see Table 4).
Table 4. Stille coupling of a vinylstannane with 4-nitrobromobenzene
Entry
Complex
Time/h
Isolated yield/
%
1
2
3
4
5
(Ph3P)4Pd
5
5
5
24
24
65
80
86
35
66
(Ph3P)2Pd(Bn)Cl
(Ph3P)2Pd(Bn)Br
(Ph3P)4PdCNBS
(Ph3P)2Pd(N-succ)Br 9
Scheme 7. Competition experiment between aryl and benzylic bromides. i,
[Pd] (0.05 equiv), toluene, reflux, 18 h (for details, see Table 5).
Table 5. Competition study between benzyl bromide and bromobenzene
were expected from this reaction, namely Z-21 from benzyl
bromide 19, and Z-47 from bromobenzene 46.
Entry
Complex
Isolated yield/%
Z-21 Z-47 (E-47)
1
2
3
4
5
(Ph3P)4Pd
(Ph3P)2PdBr2
(Ph3P)2Pd(Bn)Br
(Ph3P)2Pd(N-succ)Br
(Ph3P)2Pd(N-succ)BrCLiBr
0
0
16
86
45
39 (9)
21 (15)
36
0
22
In the reactions mediated by (Ph3P)4Pd and (Ph3P)2PdBr2,
Z-21 was not detected, the only product isolated being the
bromobenzene adduct Z-47, along with the corresponding
E-isomer (entries 1 and 2). The use of (Ph3P)2Pd(Bn)Br
promoted some coupling with benzyl bromide, but again the
coupling with bromobenzene 46 predominated (entry 3). A
major switch in selectivity was observed when (Ph3P)2
Pd(N-succ)Br was employed as catalyst (entry 4). In this
reaction, no aryl coupling was observed, only coupling with
benzyl bromide giving Z-21 (86%). The major difference
between this catalyst system and (Ph3P)2Pd(Bn)Br or
(Ph3P)2PdBr2 is the presence of the succinimide ligand, as
opposed to the benzyl or bromide ligands, respectively. It
seemed possible that a bromide salt could influence
selectivity. Addition of lithium bromide to the (Ph3P)2Pd
(N-succ)Br coupling competition reaction had a profound
effect, causing a large reduction in the selectivity, although
Z-21 still predominated (entry 5). The results in Table 5
clearly demonstrate the importance of the succinimide
ligand for selectivity (which we will now refer to as the
succinimide effect).
indicating that there is essentially no difference in the
reactivity of either substrate in coupling reactions mediated
by (Ph3P)2Pd(N-Succ)Br 9. The complete consumption of
Z-20 demonstrates the efficiency of these reactions.
3. Discussion and conclusions
The results above indicate that (Ph3P)2Pd(N-Succ)Br 9 is an
effective mediator of Stille coupling reactions involving
allylic and benzylic halides. At the present time, we cannot
state unambiguously whether (Ph3P)2Pd(N-Succ)Br 9 is a
catalyst or precatalyst. A more thorough investigation into
the mechanism of Stille coupling reactions mediated by
(Ph3P)2Pd(N-Succ)Br is required before a detailed proposal
can be made. Important observations have, however, been
made in the present study: (1) that in allylic/benzylic Stille
processes, increased yields and higher catalytic activity are
observed for succinimide-containing palladium complexes,
when compared to related palladium(II) complexes contain-
ing only Ph3P as the donor ligand; (2) the increased
reactivity of stannnane Z-20 compared to its E-isomer in
Stille couplings mediated by (Ph3P)2Pd(N-Succ)Br 9; (3)
the preferential Stille coupling of electron-rich benzyl
bromides versus electron poor benzyl bromides with
stannane Z-20; (4) the benzylic versus aryl selectivity
observed for (Ph3P)2Pd(N-Succ)Br 9 compared to common
palladium catalysts/precatalysts.
The effect of electron-releasing and withdrawing groups in
the benzylic coupling partner, relative to benzyl bromide
itself, was evaluated in a second competition study with
stannane Z-20 (Scheme 8). The outcome from these
experiments was once again surprising. 4-Nitrobenzyl
bromide 48 was expected to react faster than benzyl
bromide 19 but actually the benzyl bromide adduct
Z-21 was produced in 36% yield, compared to only 14% of
Z-49 (Eq. 1, Scheme 8). In a reaction containing
4-methoxybenzyl bromide 50 and benzyl bromide 19 itself,
the product that predominated (Z-51) was derived from the
methoxylated substrate (Eq. 2, Scheme 8). These results
exhibit a reversal of the expected reactivity.
To elaborate on the second point. In reactions mediated by
(Ph3P)2Pd(N-Succ)Br 9 the increased reactivity demon-
strated by stannane Z-20 over E-20 with respect to benzyl
bromide 19 and geranyl bromide E-25 is an intriguing
observation. In related studies, Takeda and co-workers
showed that b-tributylstannyl-a,b-unsaturated ketones were
relatively poor nucleophiles in Stille coupling—coordin-
ation of the oxygen lone pair electrons to the Bu3Sn group
In the third competition experiment, the coupling reaction of
stannane Z-20 with 4-nitrobromobenzene 40 and
4-nitrobenzyl bromide 36 was compared (Scheme 9).
No selectivity was observed in this reaction, where 51 and
48 reacted equally well to give the cross-coupled products
Z-49 and Z-52 in 48% and 49% yield, respectively,

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9745
Scheme 8. Competition reactions employing electron-rich and electron-poor benzyl bromides. i, (Ph3P)2Pd(N-succ)Br (0.05 equiv), toluene, 60 8C, 18 h.
(Ph3P)2Pd(Bn)Br and (Ph3P)2Pd(Bn)Cl, whereas a good
yield was obtained for (Ph3P)2Pd(N-Succ)Br 9. In contrast
to this observation, negligible differences were seen for
E-20 with these palladium complexes (entry 2, Table 2; also
entries 4 and 5). For Z-20, there is a possibility that the
succinimide ligand is activating tin intramolecularly, as
shown in Scheme 11 (intermolecular activation is also
possible but seems less likely). It is known that there is
significant electron repulsion between the nitrogen lone pair
electrons and the dp electrons of palladium(II).27 This
promotes electron delocalisation onto the carbonyl sub-
stituent. h2-Alkene coordination of Z-20 to the palladium
centre facilitates O-coordination, and hence activation, from
Scheme 9. Competition between nitro-substituted aryl and benzylic
bromide substrates.
a neighbouring succinimide ligand (a chelation-controlled
activation process). We presume that the trans-stannane
E-20, does not experience the same activation, possibly due
to the incorrect orientation of the Bu3Sn group (and ester
group).
Scheme 10. Activation at tin by Et3N and deactivation by O/Sn
coordination.
Scheme 11. Activation at tin by the succinimide ligand.
deactivating the cis-vinyl stannane towards transmetallation
(Scheme 10).26
To summarise, the preparation of (Ph3P)2Pd(N-Succ)Br 9
and several other novel succinimide and phthalimide-
containing palladium complexes, has been described. The
complex (Ph3P)2Pd(N-Succ)Br 9 has been shown to be an
efficient catalyst for the Stille coupling reactions of a range
In Takeda’s study, copper(I) and triethylamine (Et3N)
were required to activate stannane 53 to Stille coupling
reactions with benzylic and aryl halides. The former was
used to promote the transmetallation step, either by
of allylic and benzylic halides with different vinylstannanes.
scavenging excess phosphine ligands or by becoming
In a number of these reactions, a comparison of the catalytic
involved in a Sn/Cu pre-transmetallative process (the
activities of several different palladium complexes has been
carried out. Competition reactions and preliminary mechan-
istic observations have been reported herein, which indicate
the novel selectivity of (Ph3P)2Pd(N-Succ)Br 9 and lead
to the proposal of a succinimide effect in Stille coupling
reactions. Further synthetic studies, as well as mechanistic
investigations concerning the oxidation states and geo-
metries of key palladium intermediates (neutral or anionic),
possibly involving radicals, in the catalytic cycle, are
continuing in our laboratories.
vinylcuprate is more reactive). It was proposed that the
amine donor ligand disrupted O/Sn coordination to give
an activated stannane (through Et3N/Sn coordination).
The higher reactivity of stannane Z-20 over E-20
observed in Stille reactions mediated by (Ph3P)2Pd(N-
Succ)Br 9 is therefore surprising.
Further, analysis of the coupling of E-25 with both Z-20 and
E-20 shows a unique trend (entries 1 and 2, Table 2).
For Z-20, deactivation is clearly seen using (Ph3P)4Pd,

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C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
4. Experimental
propenoate (0.43 mL, 2.0 mmol) in THF (25 mL) at
K78 8C. After 15 min, the aldehyde (prepared above) in
THF (25 mL) was added. The reaction was stirred at
K78 8C for 1 h before addition of saturated aq NH4Cl
(10 mL), whereupon it was warmed to ambient temperature.
The resulting mixture was extracted with Et2O (3!10 mL),
the combined organic extracts dried over Na2SO4 and
the solvent removed in vacuo. Purification by column
chromatography using PE–EtOAc–TEA, (97:2:1) afforded
the title compound (0.35 g, 58%) as a pale yellow oil.
RfZ0.74 (CH2Cl2); dH (270 MHz, CDCl3) 0.87–0.96 (18H,
m, BuCCHh3), 1.25–1.38 (6H, m, Bu), 1.43–1.56 (6H, m,
4.1. General details
See reference for general experimental information.15c
The following routine compounds show comparable
characterisation data according to literature precedent: 1,
3-oxazol-5-ylmethanol (1),28 E-bis-1,2-tributylstanny-
lethene (E-5),29 ethyl 3-iodo-2Z-propenoate (Z-6),30 ethyl
3-(tributylstannyl)-2Z-propenoate (Z-20), ethyl 3-(tributyl-
stannyl)-2E-propenoate (E-20),45 ethyl (2Z)-4-phenyl-2-
butenoate (Z-21),31 ethyl (2E)-4-phenyl-2-butenoate (E-21),32
ethyl (3E)-4-phenyl-3-butenoate (E-22),33 diphenylmethane
(30),34 2-ethoxy-3-phenylpropene (31),35 1-allyl-4-nitro-
benzene (35),36 (2E)-3,7-dimethyl-1-phenyl-2,6-octadiene
(E-37),37 (1E)-1,4-pentadienylbenzene (E-38),38 1,3-diphe-
nylpropene (E-40),39 1E-phenyl-1,5-hexadiene (E-42),40
1-nitro-4-vinylbenzene (45),41 ethyl (2Z)-3-phenyl-2-
propenoate (Z-47)42 and ethyl (2E)-3-phenyl-2-propenoate
(E-47).42
4
Bu), 1.97 (3H, d, JZ1.0 CHf3), 4.20 (2H, q, JZ7.0 Hz,
CHg2), 6.37–6.55 (2H, m, CHcCd), superimposed by 6.49
(1H, d, 3JZ11.5 Hz, CHa), 6.64 (1H, dd, 3JZ11.5, 9.0 Hz,
CHb), 7.21 (1H, d, 3JZ8.5 Hz, CHe); dC (67.9 MHz,
CDCl3) 9.7 (CH2), 12.8 (CH3), 13.8 (CH3), 14.4 (CH3),
27.4 (CH2), 29.2 (CH2), 60.6 (CH2), 126.6 (CH), 127.6 (C),
138.3 (CH), 140.7 (CH), 141.8 (CH), 146.5 (CH), 168.5 (C);
nmax (neat, cmK1) 2925, 2854, 1705, 1618, 1454, 1367,
1277, 1232, 1113, 1095, and 1000 cmK1; m/z (CI), 457
(MHC, 84%), 399 (58), 308 (100), 167 (35); [HRMS (CI):
calcd for C22H41O1216Sn, 453.2124. Found: MHC, 453.2119
(1.0 ppm error)]. Stereochemistry of new double bond
confirmed by quantitative NOE measurements (500 MHz):
3.8% NOE observed between CHf3 and CHd.
4.1.1. 5-(Bromomethyl)-1,3-oxazole (2). Method A.36 NBS
(recrystallised from H2O) (0.237 g, 1.33 mmol) was added
to a solution of 1 (0.12 g, 1.21 mmol) and Ph3P (0.35 g,
1.33 mmol) in CH2Cl2 (4 mL). The reaction was stirred at
ambient temperature for 1 h then concentrated in vacuo
and passed directly through a short plug of silica using
PE–EtOAc (1:1, v:v) as the eluent. This afforded the title
compound 2 as a colourless oil (0.058 g, 30%). The
compound was extremely unstable, but it may be stored in
the freezer at K20 8C. RfZ0.37 (PE–EtOAc, 1:1); RfZ0.26
(CH2Cl2); dH (270 MHz; CDCl3) 2.85 (1H, br s, OHd), 4.68
(2H, s, CHc2), 7.00 (1H, s, CHb), 7.85 (1H, s, CHa)
(consistent with data previously reported).36
4.1.3. Ethyl (2E,4E,6E)-2-methyl-8-(1,3-oxazole-5-yl)-2,
4,6-octatrienoate (E,E,E-4).
(Ph3P)4Pd (5.0 mg, 0.05 equiv, 5 mol%) was added to a
solution of 3 (0.40 g, 0.79 mmol) and 2 (0.122 g, 0.75 mmol)
(synthesised by method A) in dry degassed toluene (5 mL)
and heated to reflux in the dark for 20 h. After this time, the
reaction was cooled to ambient temperature, then the
solvent removed in vacuo. The resulting syrup was purified
by column chromatography using PE–EtOAc (1:1) as the
eluent. This afforded the title compound as a bright yellow
oil (0.152 g, 82%). RfZ0.31 (PE–EtOAc, 1:1, v:v); dH
(270 MHz, CDCl3) 1.27 (3H, t,3JZ7.5 Hz, CH3k), 1.92 (3H,
Method B.43 Carbon tetrabromide (0.68 g, 2.0 mmol) was
added to a solution of 1 (0.169 g, 1.7 mmol) and Ph3P
(0.58 g, 2.2 mmol) in CH2Cl2 (10 mL) cooled to 0 8C. The
reaction was stirred at 0 8C for 1 h, concentrated in vacuo
and passed directly through a short plug of silica using
PE–EtOAc (1:1, v:v) as the eluent, giving the title
compound 2 as a colourless oil (0.148 g, 54%).
s, CHi3), 3.50 (2H, d, JZ7.0 Hz CHc2), 4.18 (2H, q, 3JZ7.
3
4.1.2. Ethyl (2E,4E,6E)-2-methyl-7-(tributylstannyl)-2,4,
6-heptatrienoate (E,E,E-3).
5 Hz, CHj2), 5.89 (1H, dt, 3JZ15.0, 7.0 Hz, CHd), 6.24 (1H,
3
dd, JZ15.0, 11.5 Hz, CHe), 6.49 (2H, m, CHfCg), 6.79
3
(1H, s, CHb), 7.19 (1H, d, JZ12.0 Hz, CHh), 7.78 (1H, s,
CHa); dC (67.9 MHz, CDCl3) 12.6 (CH3), 14.2 (CH3), 28.8
(CH2), 60.5 (CH2), 122.7 (CH), 127.5 (CH), 127.6 (CH),
130.8 (CH), 132.9 (CH), 137.6 (CH), 138.0 (CH), 150.2 (C),
150.4 (C), 168.2 (C); nmax (film) 2956, 2929, 1701, 1614,
TPAP (0.024 g, 0.007 mmol) was added to a cooled mixture
(0 8C) of (2E,4E)-5 (tributylstannyl)-2,4-pentadien-1-ol
˚
(0.50 g, 1.34 mmol), powdered 4 A molecular sieves (0.50 g)
1510, 1464, 1367, 1257, 1225, 1103, 991 and 964 cmK1
;
m/z (CI), 248 (MHC, 100%), 234 (10), 174 (7), 82 (6);
[HRMS (CI): calcd for C14H18O3N, 248.1287. Found:
MHC, 248.1287 (0.2 ppm error)]. Stereochemistry of new
double bond confirmed by a quantitative an NOE
experiment 4.5% NOE observed between CHf3 and CHe.
and NMO (0.24 g, 2.0 mmol) in CH2Cl2 (10 mL). The
green solution was stirred for 90 min, then the solvent was
removed in vacuo. Subsequent purification by column
chromatography using CH2Cl2 as the eluent afforded (2E,
4E)-5-(tributylstannyl)-2,4- pentadienal as a pale yellow oil,
which was used directly in the following reaction: KHMDS
(0.5 M in toluene, 4.0 mL, 2.0 mmol) was added dropwise
to a stirred solution of ethyl 2-(diethoxyphosphoryl)
4.1.4. Ethyl (2Z,4E)-5-(tributylstannyl)penta-2,4-dieno-
ate (Z,E-7) and diethyl octa-2Z,4E,6Z-triendioate (Z,E,Z-
8). The palladium catalyst (0.05 equiv, 5 mol%) was added

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9747
to a solution of E-5 (1.0 g, 1.65 mmol) and Z-6 (0.36 g,
1.6 mmol) in dry degassed toluene (10 mL). The reaction
was heated to reflux for 3 h. The reaction was allowed to
cool to ambient temperature, whereupon a saturated aq KF
(10 mL) was added. The mixture was stirred vigorously for
1 h, then filtered through Celitew, and the residue rinsed
with Et2O (2!10 mL). The filtrate was washed with
saturated aq NaCl and then dried (Na2SO4). Subsequent
purification by column chromatography, using PE–EtOAc–
TEA (97:2:1) as the eluent, afforded the title compounds as
pale yellow oils, in yields specified in the text. Data for ethyl
(2Z,4E)-5-(tributylstannyl)penta-2,4-dienoate (Z,E-7):
obtained as a yellow oil. RfZ0.60 (PE–EtOAc, 9:1, v:v);
dH (270 MHz, CDCl3) 0.86–0.98 (15H, m, Bu), 1.24–1.38
(9H, m, CH2 of Bu and CHf3), 1.24–1.38 (6H, m, Bu), 4.20
4.1.6. trans-Chlorobis(triphenylphosphine)(succinimide)
palladium(II) (trans-10). Following a similar procedure to
cis-9. To a Schlenk tube containing vacuum dried Pd2dba3$
CHCl3 (104 mg, 0.1 mmol) and Ph3P (105 mg, 0.4 mmol)
in dry CH2Cl2 (8 mL) at 21 8C under N2, was stirred for
0.2 h, after, which time an orange colour persisted. Then
N-chlorosuccinimide (NCS) (0.018 g, 0.25 mmol) (recrystal-
lised from H2O and dried under high vacuum) in CH2Cl2
(2 mL), was added in one portion. The solution went pale
orange. The mixture was stirred for 0.5 h. The solution was
reduced to a third of its original volume in vacuo and then
petroleum ether (2 mL) added to precipitate the complex.
This gave the title compound as a cream solid (0.033 g,
22%). nmax (CHCl3, cmK1) 1633 (C]O); dH (270 MHz,
CDCl3, selected data) 1.32 (2H, br s, CH2A), 1.69 (2H, br s,
CH2B), 7.26–7.62 (18H, m, Ph–H), 7.70–7.91 (12H, m, Ph–H);
dP (109.1 MHz, CDCl3) 23.45 (2P, s, P1–P2); m/z (FAB),
764 (MHC, 2), 728 (12), 629 (5), 339 (100).
3
3
4
(2H, q, JZ7.0 Hz, CHe2), 5.58 (1H, dd, JZ11.5 Hz, JZ
1.0 Hz CHd), 6.50 (1H, ddd, 3JZ11.5, 10.5 Hz, 4JZ1.0 Hz,
CHc) 6.75 (1H, dd, JZ19.0 Hz, JZ1.0 Hz, CHa) 7.81
(1H, ddd, 3JZ19.0, 10.5 Hz, 4JZ1.0 Hz, CHb); dC
(67.9 MHz, CDCl3), 9.6 (CH2), 13.6 (CH3), 14.3 (CH3),
27.2 (CH2), 20.0 (CH2), 59.9 (CH2), 115.9 (CH), 142.5
3
4
4.1.7. trans-Iodobis(triphenylphosphine)(succinimide)
palladium(II) (trans-11). Following a similar procedure
to cis-9. To a Schlenk tube containing vacuum dried
Pd2dba3$CHCl3 (104 mg, 0.1 mmol) and Ph3P (105 mg,
0.4 mmol) in dry CH2Cl2 (8 mL) at 21 8C under N2, was
stirred for 0.2 h, after, which time an orange colour
persisted. Then, N-iodosuccinimide (NIS) (0.056 g,
0.25 mmol) in CH2Cl2 (2 mL) was added in one portion.
The solution went yellow immediately. A small amount of a
precipitate (0.028 g) was formed ((Ph3P)2PdI2), which was
filtered. The solution was reduced to a third of its original
volume in vacuo and then petroleum ether (2 mL) added to
precipitate the complex. This gave the title compound as a
cream solid, which was crystallised from a layered solvent
system (CH2Cl2/hexane, 1/4, c 0.1 M) by slow evaporation
in air (0.086 g, 50%). Mp 197–199 8C (decomp.); dH
(400 MHz, CDCl3) 1.32 (2H, s, CH2A), 1.62 (2H, s,
CH2B), 5.30 (1H, s, 1⁄2CH2Cl2 of recrystallization), 7.37–
7.47 (18H, m, Ph–H), 7.78–7.82 (12H, m, Ph–H); dP
(CH), 146.5 (CH), 147.8 (CH), 166.2 (C); nmax (neat, cmK1
)
2958, 1718, 1616, 1550 and 1162; m/z (CI), 417 (MHC,
17%), 308 (100); [HRMS (CI): calcd for C19H37O1216Sn,
413.1807. Found: MHC, 413.1811 (1.1 ppm error)]. Data
for diethyl octa-2Z,4E,6Z-triendioate (Z,E,Z-8): obtained as
a white solid; RfZ0.34 (PE–EtOAc, 9:1, v:v); mp 53.0–
3
53.5 8C; dH (270 MHz, CDCl3) 1.30 (3H, t, JZ7.5 Hz,
3
3
CHa3), 4.20 (2H, q, JZ7.5 Hz, CHb2), 5.81 (1H, d, JZ
11.0 Hz, CHc), 6.71 (1H, ddd, JZ11.0, 10.5,4JZ3.0 Hz,
3
CHd), 7.76 (1H, dd, 3JZ10.5, 3.0 Hz, CHe); dC (67.9 MHz,
CDCl3), 14.2 (CH3), 60.2 (CH2), 120.7 (CH), 135.9 (CH),
143.38 (CH), 166.1 (C); nmax (nujol, cmK1) 1718, 1616 and
1165; m/z (EI) 224 (MC, 53%), 195 (91), 167 (70), 149
(100); [HRMS (EI): calcd for C12H16O4, 224.1049. Found:
MC, 224.1043 (2.5 ppm error)].
(161 MHz, CDCl3) 21.65 (2P, s, P1–P2); nmax (CHCl3, cmK1
)
4.1.5. cis-Bromobis(triphenylphosphine)(succinimide)
palladium(II) (cis-9). To a Schlenk tube containing vacuum
dried Pd2dba3$CHCl3 (100 mg, 0.097 mmol) and Ph3P
(101.4 mg, 0.387 mmol) in dry CH2Cl2 (7 mL) at 21 8C
under N2, was stirred for 0.2 h, after, which time an orange
colour persisted. A solution of recrystallised N-bromo-
succinimide (34.5 mg, 0.194 mmol) in dry CH2Cl2 (2 mL)
was added in one portion and the mixture stirred for 0.2 h. If
a precipitate is observed, filter off—this is (Ph3P)2PdBr2).
The resulting yellow solution was concentrated in vacuo to a
third of its original volume and petroleum ether added to
precipitate the complex. The creamy yellow solid was
filtered and washed with small quantities of hexane, which
is the title compound (104 mg, 74% yield). A small quantity
of cis-9 was recrystallised by slow vapour diffusion of Et2O
in a CH2Cl2 solution of the complex (5:1) at 0 8C for 2 days.
nmax (CH2Cl2, cmK1) 1631 (C]O); dH (500 MHz, CD2Cl2)
1631 (C]O); m/z (FAB), 764 (MHC, 1), 728 (M–Cl. 16),
665 (8), 629 (58), 495 (50); [HRMS (FAB): 100% rel.
abundance, MHCC40H35NO2P1205PdIZ856.024].
4.1.8. cis-Bromobis(triphenylphosphine)(N-phthalimide)
palladium(II) (trans-12). Following a similar procedure to
cis-9. To a Schlenk tube containing vacuum dried Pd2dba3$
CHCl3 (104 mg, 0.1 mmol) and Ph3P (105 mg, 0.4 mmol)
in dry CH2Cl2 (8 mL) at 21 8C under N2, was stirred for
0.2 h, after, which time an orange colour persisted. Then,
N-bromophthalimide (57 mg, 0.25 mmol) in CH2Cl2 (2 mL)
was added in one portion. The solution went yellow
immediately. The solution was reduced to a third of its
original volume in vacuo and then diethyl ether (2 mL)
added to precipitate the complex. This gave the title
complex as a pale yellow solid (0.120 g, 70%). Mp 199–
203 8C (decomp.); (270 MHz, CDCl3) 5.30 (2H, s, CH2Cl2
of recrystallization), 7.12–7.42 (27H, m, Ph–H), 7.62–7.86
2
3
0
0
1.59 (2H, dd, JHaHa Z16.5 Hz, JHaHb Z4.1 Hz, CHA and
2
3
0
0
0
CHA ), 2.20 (2H, dd, JHbHb Z16.5 Hz, JHbHa Z4.5 Hz,
CHB and CHB ), 7.1–7.6 (30H, m, Ph–H); dP (202 MHz,
(7H, m, Ph–H); dP (109.1 MHz, CDCl3) 33.80 (1P, d, 2JPPZ
0
CD2Cl2) 23.96 (1P, d, 2JPPZ8.49 Hz, P1(cis)) and 32.91 (1P,
d, 2JPPZ8.49 Hz, P2(trans)); m/z (FAB), 810 (MHC, 4), 710
(29), 629 (17), 339 (100), 263 (Ph3PHC, 28), 183 (43), 154
(79). Anal. Calcd for C40H34BrNO2P2Pd$1⁄2 CH2Cl2, C,
57.36; H, 4.23; N, 1.63. Found C, 57.49; H, 3.99; N, 1.66.
2
8.39 Hz), 24.89 (1P, JPPZ8.39 Hz); nmax (CHCl3, cmK1
)
1651 (C]O), 1628 (C]C); m/z (FAB), 858 (MHC, 4%),
776 (21), 711 (25), 629 (15), 332 (100); [HRMS (FAB):
100% rel. abundance, MHCC44H35NO2P281BrPdZ
858.036].

9748
C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
4.1.9. cis-Bromobis(1,2-bis(diphenylphosphino)ethane)
(succinimide)palladium(II) (cis-14). Following a similar
procedure to cis-9. To a Schlenk tube containing vacuum
dried Pd2dba3$CHCl3 (104 mg, 0.1 mmol) and 1,2-bis(di-
phenylphosphino)ethane (104 mg, 0.26 mmol) in dry
CH2Cl2 (8 mL) at 21 8C under N2, was stirred for 0.2 h,
after, which time an orange colour persisted (0.25 h). A
solution of recrystallised N-bromosuccinimide (46 mg,
0.26 mmol) in dry CH2Cl2 (2 mL) was added in one portion.
The solution rapidly turned to a yellow colour. The solution
was reduced to half of its original volume in vacuo and then
petroleum ether (2 mL) added to precipitate the complex.
This gave the title compound as a cream solid (209 mg,
59%). dH (270 MHz, CDCl3) 2.09–2.16 (4H, br, 2!CH2
dppe backbone), 2.24–2.29 (4H, m, 2!CH2 of succini-
mide), 5.30 (1H, s, 1⁄2CH2Cl2 of recrystallization), 7.15–7.68
(30H, m, phenyl groups); dP (161.2 MHz, CDCl3) 23.95 (1P,
br s), 61.87 (1P, br s) (consistent with data previously
reported).44
(M–Br, 15), 741 (M–N-Succ, 2), 555 (32) (the correct
isotopic distribution was observed for the molecular ion of
this complex).
4.1.12. trans-Bis(triphenylphosphine)palladium(II)
(benzyl) bromide (trans-18). Prepared by an alternative
procedure to that reported.45 To a Schlenk tube containing
vacuum dried Pd2dba3$CHCl3 (100 mg, 0.097 mmol) in dry
CH2Cl2 (3 mL), under N2, was added a solution of PPh3
(101.4 mg, 0.387 mmol) in dry CH2Cl2 (2.5 mL). The
mixture was stirred for 0.2 h, after, which time an orange
colour persisted. A solution of benzyl bromide in CH2Cl2
(2 mL) was added in one portion. The mixture turned a
yellow colour after a few minutes, although stirring was
continued for 0.5 h. The solution was concentrated in vacuo
to a third of its original volume and petroleum ether added
to precipitate the complex, trans-Pd(Bn)(PPh3)2Br. The
yellow solid was filtered and washed with diethyl ether
(117 mg, 76%); mp 124–125 8C (decomp.), lit.124–
130 8C;45 dH (CDCl3, 300 MHz) 2.73 (2H, br s, CH2),
7.37–7.70 (35H, m, Ph–H). dP (CDCl3, 121 MHz) 23.26
(2P, s, P1–P2). A broad signal at d 30.43 (s) is also observed.
4.1.10. cis-Bromobis(1,2-bis(dicyclohexylphosphino)
ethane) (succinimide)palladium(II) (cis-15). Following a
similar procedure to cis-9. To a Schlenk tube containing
vacuum dried Pd2dba3$CHCl3 (41 mg, 39.6 mmol) and 1,2-
bis(dicyclohexylphosphino)ethane (34 mg, 793 mmol) in
dry CH2Cl2 (4 mL) at 21 8C under N2, was stirred for
0.5 h, after, which time an orange colour persisted. A solu-
tion of recrystallised N-bromosuccinimide (14 mg, 79.3 mmol)
in dry CH2Cl2 (1 mL) was added in one portion. The
solution rapidly turned a red colour. The solution was
reduced to half of its original volume in vacuo and then
petroleum ether (2 mL) added to precipitate the complex.
This gave the title compound as a pale red solid (7.3 mg,
13%). dH (500 MHz, CDCl3) 1.24–1.55 (24H, br, Cy–H),
4.2. General Stille coupling procedure
To a solution of the organohalide (0.25 mmol, 1 equiv) and
the organostannane (0.3 mmol, 1.2 equiv) in dry degassed
(freeze–pump–thaw cycles) toluene (2.5 mL), was added
the palladium catalyst (0.0125 mmol, 0.05 equiv). The
mixture was placed under a dry N2 atmosphere and heated
to 60 8C in the dark (flask was covered with domestic foil)
for the specified time. All reactions were followed by TLC,
GC or GC/MS analysis. On completion, the reaction was
cooled to ambient temperature, then saturated aqueous KF
(2.5 mL) was added and the mixture stirred vigorously for
1 h. The mixture was filtered through Celitew, and the
residue rinsed with Et2O (2!5 mL), washed with saturated
aqueous NaCl (2!2.5 mL) and dried (MgSO4). Concen-
tration in vacuo and subsequent purification by column
chromatography (using EtOAc–hexane or PE mixtures)
gave the products as oils.
0
1.65–1.96 (20H, br, Cy–H), 1.41 (2H, br s, CHA and CHA ),
0
2.15 (2H, br s, CHB and CHB ), 2.47 (2H, br s, CH2 dcpe
backbone), 2.69 (2H, br s, CH2 dcpe backbone), 7.41–7.43
(12H, m, Ph–H), 7.64 (8H, m, Ph–H). dP (202 MHz, CDCl3)
2
88.68 (1P, br s), 91.30 (1P, d, JPPZ8.39 Hz) (pure to the
limits of detection). m/z (FAB) 708 (MHC, 9), 626 (M–Br,
21), 528 (32), 423 (100), 341 (21) (the correct isotopic
distribution was observed for the molecular ion of this
complex).
4.2.1. Ethyl (2Z,5E)-6,10-dimethyl-2,5,9-undecatrienno-
ate (Z,Z-26).
4.1.11. cis-Bromobis(1,10-bis(diphenylphosphino)ferro-
cene) (succinimide)palladium(II) (cis-16). Following a
similar procedure to cis-9. To a Schlenk tube containing
vacuum dried Pd2dba3$CHCl3 (60 mg, 58 mmol) and
1,10-bis(diphenylphosphino)ferrocene (67.5 mg, 0.12 mmol)
in dry CH2Cl2 (8 mL) at 21 8C under N2, was stirred for
0.2 h, after, which time an orange colour persisted. A
solution of recrystallised N-bromosuccinimide (21.6 mg,
0.12 mmol) in dry CH2Cl2 (1 mL) was added in one portion.
No obvious colour change was observed. The solution was
reduced to half of its original volume in vacuo and then
petroleum ether (2 mL) added to precipitate an orange
complex. This gave the title compound as an orange solid
(48 mg, 49%). dH (500 MHz, CDCl3) 1.56 (2H, m, CHA and
The title compound was obtained as a pale yellow oil. RfZ
0.50 (PE–EtOAc, 9:1); dH (400 MHz, CDCl3) 1.29 (3H, t,
3JZ7.5 Hz CH3k), 1.59 (6H, s, CH3a), 1.67 (3H, s CHe3), 1.98–
2.10 (4H, m, CHc2Cd), 3.36 (2H, dd, 3JZ7.5, 7.5 Hz, CHg2),
3
3
4.17 (2H, q, JZ7.5 Hz, CHj2), 5.09 (1H, tt, JZ6.5 Hz,
3
4
4JZ1.0 Hz, CHb), 5.16 (1H, td, JZ7.5 Hz, JZ1.0 Hz,
3
3
CHf), 5.74 (1H, dm, JZ11.5 Hz, CHi), 6.13 (1H, dt, JZ
11.5, 7.5 Hz, CHf); dC (100.6 MHz, CDCl3), 14.4 (CH3), 16.
3 (CH3), 17.8 (CH3), 25.8 (CH3), 26.6 (CH2), 28.2 (CH2),
39.7 (CH2), 60.0 (CH2), 119.0 (CH), 120.6 (CH), 124.2
(CH), 128.7 (CH), 131.6 (C), 137.6 (C), 166.6 (C). nmax
(neat, cmK1) 2981, 2938, 1717, 1644, 1450, 1373, 1268,
0
0
CHA ), 2.22 (2H, m, CHB and CHB ), 3.37 (1H, m, Cp–H),
4.16(1H, m, Cp–H), 4.60(1H, m, Cp–H), 5.20(1H, m, Cp–H),
7.20–8.21 (20H, br. m, Ph–H). dP (202 MHz, CDCl3) 24.57
2
2
(1P, d, JPPZ6.36 Hz), 35.13 (1P, d, JPPZ6.36 Hz) (pure
to the limits of detection). m/z (FAB) 840 (MHC, 3), 760

C. M. Crawforth et al. / Tetrahedron 61 (2005) 9736–9751
9749
1182, 1095 and 1032; m/z (CI), 254 (MNHC4 , 26%), 237
(MHC, 100), 191 (28), 163 (53), 123 (86), 69 (58) 41 (34);
[HRMS (CI): calcd for C15H25O2, 237.1855. Found: MHC,
237.1855 (0.8 ppm error)].
(MHC, 100); 171 (6), 143 (16), 128 (11), 115 (6); [HRMS
(CI): calcd for C14H20NO2, 234.1494. Found: MNHC4 ,
234.1496 (0.7 ppm error)].
4.2.5. (4E)-5,9-Dimethyl-1,4,9-decatriene (E-36). The title
compound was obtained as a colourless oil. RfZ0.73 (PE–
EtOAc, 9:1) on alumina; dH (270 MHz, CDCl3) 1.61 (6H, s,
CH3a), 1.69 (3H, s, CH3e), 1.99–2.10 (4H, m, CHc2Cd), 2.75
(2H, app. br. t, dd, 3JZ7.0, 6.5 Hz, CHg2), 4.96 (1H, dd, 3JZ
4.2.2. Ethyl (2Z,5E)-6,10-dimethyl-2,5,9-undecatrienno-
ate (E,E-26).
2
3
15.5 Hz, JZ1.0 Hz, CHi2 cis), 5.01 (1H, dd, JZ19.5 Hz,
4JZ1.0 Hz, CH2i trans), 5.08– 5.19 (2H, m, CH’sf and b), 5.80
(1H, m, CHh); dC (100.6 MHz, CDCl3), 23.4, 25.7, 267 31.9,
32.2, 39.7, 114.0, 114.2, 121.3, 122.3, 124.3, 137.5; m/z
(EI), 164 [MC] (2%), 149 (5), 123 (10), 94 (14), 69 (100),
41 (57); [HRMS (EI): calcd for C12H20, 164.1565. Found:
MC, 164.1561 (2.2 ppm error)].
The title compound was obtained as a colourless oil.
RfZ0.44 (PE–EtOAc, 9:1); dH (400 MHz, CDCl3) 1.27
(3H, t, 3JZ7.0 Hz CH3k), 1.59 (6H, s, 2!CHa3), 1.68
(3H, s, CHe3, NB. Isomerisation to cis observed as a
singlet at 1.72), 2.00– 2.11 (4H, m, 2!CHc2Cd), 2.88
3
(2H, app. br. t, dd, JZ7.5, 6.0 Hz, CHg2), 4.18 (2H, q,
3JZ7.0 Hz, CHj2), 5.06 (1H, m, CHb), 5.13 (1H, br. t,
3JZ7.5 Hz, CHf), 5.79 (1H, dt, 3JZ15.5 Hz, 4JZ2.
0 Hz, CHi), 6.92 (1H, dt, 3JZ15.5, 6.0 Hz, CHh); dC
(100.6 MHz, CDCl3), 14.2 (CH3), 16.0 (CH3), 17.6
(CH3), 25.6 (CH3), 26.4 (CH2), 30.6 (CH2), 39.6 (CH2),
60.1 (CH2), 118.9 (CH), 120.9 (CH), 124.0 (CH), 131.6
4.2.6. Ethoxy-5-phenyl-(1,4E)-pentadiene (E-39). The
title compound was obtained as a colourless oil. RfZ
0.73 (PE–EtOAc, 9:1) on alumina; dH (400 MHz, CDCl3)
3
3
1.23 (3H, t, JZ7.0 Hz CHf3), 2.91 (2H, dd, JZ7.0 Hz,
CHc2), 3.67 (2H, q, JZ7.0 Hz, CHe2), 3.83 (1H, d, JZ
3
3
2.0 Hz, CH2d,trans), 3.84 (1H, d, JZ2.0 Hz, CHd2,cis), 6.19
3
(1H, dt, 3JZ16.0, 7.0 Hz CHb), 6.36 (1H, d, 3JZ
16.0 Hz, CHa), 7.10–7.15 (1H, m, CH3), 7.16– 7.23 (2H,
m, CH1), 7.23–7.30 (2H, m, CH2); dC (100.6 MHz,
CDCl3), 14.5 (CH3), 38.7 (CH2), 62.9 (CH2), 81.4 (CH2),
126.1 (CH), 126.6 (CH), 127.1 (CH), 128.4 (CH), 131.6
(CH), 137.5 (C), 161.7 (C); nmax (film, cmK1) 3028,
2978, 2927, 1653, 1599, 1496, 1448, 1425, 1385, 1294,
1277, 1227, 1192, 1117, 1070, 966, 800, 744 and 692;
m/z (CI), 189 (MHC, 100%), 143 (11); [HRMS (CI): calcd
for C13H17O1, 189.1279. Found: MHC, 189.1278 (0.8 ppm
error)].
(C), 138.3 (C), 147.7 (CH), 166.7 (C); nmax (neat, cmK1
)
2967, 2926, 1722, 1651, 1448, 1370, 1321, 1266, 1172,
1094 and 1043; m/z (CI), 254 (MNHC4 , 10%), 237 (MHC,
77), 191 (46), 163 (100), 123 (45); [HRMS (CI): calcd for
C15H25O2, 237.1854. Found: MHC, 237.1849 (2.2 ppm
error)].
4.2.3. Ethyl (2Z,5E)-6-phenyl-2,5-hexadienoate (E,Z-28).
The title compound was obtained as a colourless yellow oil.
RfZ0.36 (PE–EtOAc, 9:1, v:v); dH (270 MHz, CDCl3) 1.28
3
3
(3H, t, JZ7.0 Hz CHg3), 3.55 (2H, dd, JZ6.5, 7.5 Hz,
CHc2), 4.17 (2H, q, JZ7.0 Hz, CHf2), 5.82 (1H, dt, JZ
3
3
11.5 Hz, JZ1.5 Hz, CHe), 6.19 (1H, dt, JZ16.0, 6.5 Hz
CHf), 6.25 (1H, dt, 3JZ11.5, 7.5 Hz CHd), 6.43 (1H, d, 3JZ
16.0 Hz, CHg), 7.14–7.33 (5 H, m, Aryl); dC (67.9 MHz,
CDCl3), 14.2 (CH3), 32.3 (CH2), 59.9 (CH2), 120.2 (CH),
126.0 (CH), 126.8 (CH), 127.1 (CH), 128.5 (CH), 131.4
4
3
4.2.7. Ethyl (2Z)-4-(4-nitrophenyl)-2-butenoate (Z-49).
The title compound was obtained as a pale yellow oil. RfZ
0.30 (PE–EtOAc, 9:1); dH (400 MHz, CDCl3) 1.30 (3H, t,
3JZ7.0 Hz CH3), 4.14 (2H, d, 3JZ7.5 Hz, CH2), 4.21 (2H,
q, 3JZ7.0 Hz, CH2), 5.95 (1H, dd, 3JZ11.5 Hz, 4JZ
1.0 Hz, CH), 6.31 (1H, dt, 3JZ11.5, 7.5 Hz, CH), 7.40 (2H,
d, 3JZ8.5 Hz CH), 8.17 (2H, d, 3JZ8.5 Hz, CH); dC
(100.6 MHz, CDCl3), 14.2 (CH3), 38.4 (CH2), 60.2 (CH2),
122.3 (CH), 126.3 (CH), 128.7 (CH), 137.8 (C), 147.2 (CH),
166.5 (C), 171.6 (C); nmax (neat, cmK1) 2957, 2925, 2854,
1716, 1682, 1645, 1600, 1521, 1346, 1206, 1167 and 1037;
m/z (CI), 253 (MNHC4 , 53%), 223, (16), 216 (25), 206 (100),
199 (21); [HRMS (CI): calcd for C12H17O4N2, 253.1188.
Found: MNHC4 , 253.1188 (0.2 ppm error)].
(CH), 137.3 (C), 146.8 (CH), 166.3 (C); nmax (film, cmK1
)
3028, 2982, 1717, 1642, 1448, 1413, 1199, 1168, 034, 966,
823, 744 and 694; m/z (CI), 243 (MNHC4 , 25%), 217 (MHC,
100); 188 (12), 169 (16), 143 (22), 125 (12), 112 (7), 106
(12); [HRMS (CI): calcd for C14H17O2, 217.1229. Found:
MHC, 217.1230 (0.5 ppm error)].
4.2.4. Ethyl (2E,5E)-6-phenyl-2,5-hexadienoate (E,E-28).
The title compound was obtained as a pale yellow oil. RfZ
0.20 (PE–EtOAc, 9:1); dH (400 MHz, CDCl3) 1.18 (3H, t,
3JZ7.0 Hz CH3), 3.00 (2H, ddd, 3JZ6.5, 6.5 Hz, 4JZ
3
1.5 Hz, CH2), 4.09 (2H, q, JZ7.0 Hz, CH2), 5.80 (1H, dt,
3JZ15.5 Hz, 4JZ1.5 Hz, CH), 6.08 (1H, dt, 3JZ16.0,
3
Acknowledgements
6.5 Hz CH), 6.34 (1H, d, JZ16.0 Hz CH), 6.94 (1H, dt,
3JZ15.5, 6.5 Hz, CH), 7.14 (1H, m, aromatic CH), 7.19–
7.26 (4H, m, Ph–H); dC (100.6 MHz, CDCl3), 14.2 (CH3),
35.2 (CH2), 60.2 (CH2), 122.4 (CH), 125.5 (CH), 126.2
(CH), 127.5 (CH), 128.7 (CH), 132.6 (CH), 137.2 (C), 146.6
(CH), 166.6 (C); nmax (film, cmK1) 3058, 3027, 2982, 2934,
2903, 1719, 1652, 1448, 1367, 1322, 1267, 1201, 1159,
1092, 1042 and 967; m/z (CI), 234 (MNHC4 , 22%), 217
I. J. S. F. thanks Johnson Matthey PLC (UK) for a generous
loan of palladium salts. We thank the EPSRC for a PhD
studentship for C.M.C (GR/N06977). We are grateful to
Drs. J. L. Serrano (Cartagena, Spain), J. M. Lynam and A. F.
Lee (York) for informative discussions, and Nicholas M.
Chaignon (ERASMUS scheme) for preliminary experiments.

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´ ´ ´
Lee, A. F.; Sanchez, G.; Lopez, G.; Serrano, J. L.; Garcıa, L.;
´ ´
Perez, J.; Perez, E. Dalton Trans. 2004, 3970.
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