Bis(triphenylphosphine)palladium(II)phthalimide - An easily prepared precatalyst for efficient Suzuki-Miyaura coupling of aryl bromides

Article abstract of DOI:10.1016/j.molcata.2004.05.008

In this paper we report the synthesis and application of a novel palladium(II) complex, bis(triphenylphosphine)palladium(II)phthalimide 1. Its utility in the Suzuki-Miyaura coupling of aryl bromides with a variety of aryl- and heteroarylboronic acids, under relatively mild conditions, is described. Complex 1 is easily prepared from tetrakis(triphenylphosphine)palladium(0) and phthalimide in 78% yield and is air, light and moisture stable. On following the kinetics of the cross-coupling reaction of 4-nitro-1-bromobenzene with phenylboronic acid, mediated by 1 (1 mol%) in THF/aqueous 1 M Na ₂CO₃ (1/1, v/v) at 60°C, an initial induction period is observed, indicating that 1 is a precatalyst. The described work extends on our recent finding that 'imidate' type ligands have an influence in palladium-catalysed cross-coupling processes.

Full text of DOI:10.1016/j.molcata.2004.05.008

Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
Bis(triphenylphosphine)palladium(II)phthalimide – an easily prepared
precatalyst for efficient Suzuki–Miyaura coupling of aryl bromides
Nicholas M. Chaignon, Ian J.S. Fairlamb∗, Anant R. Kapdi,
Richard J.K. Taylor, Adrian C. Whitwood
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Received 27 April 2004; received in revised form 5 May 2004; accepted 6 May 2004
Available online 7 July 2004
Abstract
In this paper we report the synthesis and application of a novel palladium(II) complex, bis(triphenylphosphine)palladium(II)phthalimide 1.
Its utility in the Suzuki-Miyaura coupling of aryl bromides with a variety of aryl- and heteroarylboronic acids, under relatively mild conditions,
is described. Complex 1 is easily prepared from tetrakis(triphenylphosphine)palladium(0) and phthalimide in 78% yield and is air, light and
moisture stable. On following the kinetics of the cross-coupling reaction of 4-nitro-1-bromobenzene with phenylboronic acid, mediated by
1 (1 mol%) in THF/aqueous 1 M Na2CO3 (1/1, v/v) at 60 ◦C, an initial induction period is observed, indicating that 1 is a precatalyst. The
described work extends on our recent finding that ‘imidate’ type ligands have an influence in palladium-catalysed cross-coupling processes.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Palladium; Cross-coupling; Biaryls; Heteroaryls; Catalysis
1. Introduction
or side-products, which might contaminate final products
(Eq. (1)).
Palladium-catalysed carbon-carbon and carbon-hetero-
atom bond-forming technologies represent some of the most
applied and important transformations in organic synthesis
[1,2]. Examples include Hartwig–Buchwald amination [3],
Heck [4], Negishi [5], Sonogashira [6,7], Stille [8,9] and
Suzuki–Miyaura [10–13] coupling processes. The last two
reactions are arguably the most important in natural product
and materials synthesis, and although Stille coupling at the
present time is the most powerful, Suzuki–Miyaura coupling
is of increasing importance in industry. This is particularly
in the pharmaceutical sector where tin toxicity, as well as
the problems associated with the removal of tin byproducts,
limits the use of the Stille methodology. Suzuki–Miyaura
coupling, in which organohalides react with organoboronic
acids in the presence of base and a Pd(0) catalyst, or a
Pd(II) precatalyst, is particularly useful, as it occurs gener-
ally under mild conditions and does not produce toxic waste
[Pd]
R − X + Rꢀ − B(OH)2 −−→ R − Rꢀ
(1)
Base
This process has recently become a benchmark reaction by
which new catalysts/precatalysts are screened and tested.
Indeed, highly active Pd-catalysts have been developed by
a number of research groups over the last 5 or so years
[14–32]. The catalyst activity is usually tuned or attenuated
through changes in the coordinating ligand for palladium.
Here, use of electron-rich alkyl phosphines, such as (t-Bu)3P
or biphenyl(t-Bu)2P as well as others, N-heterocyclic car-
benes or phosphinites represent the most important, recently
developed ligand systems [14]. Various electronic (␴-donor
and/or ␲-acceptor) and steric (changes in bite and cone an-
gles) properties of these ligands are important in tuning
the reactivity of the nucleophilic low-coordinated d10 Pd(0)
centre—the species that is often considered the active cat-
alyst species, whether anionic or neutral (vide infra). The
number of available Pd(0) catalysts has been expanded upon
recently, most notably by Beller and co-workers [33,34], al-
though the air and moisture sensitivity of these catalysts,
which require some special handling and storage, could
∗
Corresponding author. Tel.: +44 1904 434091;
fax: +44 1904 432516.
E-mail address: ijsf1@york.ac.uk (I.J.S. Fairlamb).
1381-1169/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2004.05.008

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N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
limit their utility. Pd(II) complexes, usually d8/16-electron
species, are more stable and may be stored for prolonged
periods without any deleterious loss of activity observed.
Classically, it has been assumed that Pd(II) precatalysts
are reduced to give an active Pd(0) species, although re-
cent studies by Amatore and Jutand have demonstrated that
halide ligands from Pd(II) precatalysts, or the halide sub-
strate, could play a decisive role in the catalytic cycle –
anionic Pd(0) species containing one halide ligand, of the
type [L2Pd(0)X]− (L = R3P), have been implicated [35,36].
Somewhat surprisingly, the role of the halide ligand [37]
in palladium(II) precatalysts has received little attention,
particularly with respect to activity and substrate selectiv-
ity. Recent observations by our group suggest that alter-
ation of this ligand could influence the catalytic properties
of the active palladium species, whether that be an anionic
or neutral Pd(II) or Pd(0) species. The availability of only
four halides (F, Cl, Br and I) is quite restrictive in tuning
the catalytic properties of the palladium centre, albeit still
quite revealing. However, access to a plethora of pseudo-
halide ligands, such as alkoxides, acetate and imides, al-
lows us to probe their effect, if any, in classical Pd-catalysed
cross-coupling processes. Imidate ligands, such as depro-
tonated succinimide, maleimide and derivatives, and ph-
thalimide have been described as pseudohalides, exerting
potentially exploitable effects for metal centres [38]. Imi-
dates may also act as hemilabile ligands, deriving from their
ability to act as either monodentate or bidentate ligands
we detail the synthesis of a novel palladium complex, namely
bis(triphenylphosphine)palladium(II)phthalimide 1, and its
application as an efficient precatalyst for Suzuki–Miyaura
coupling of aryl bromides with aryl and heteroarylboronic
acids.
2. Results and discussion
The oxidative addition of succinimide to (Ph3P)4Pt and
(Ph3P)4Pd, to give (Ph3P)2Pt(N-Succ)H and (Ph3P)2Pd(N-
Succ)2, respectively, has been investigated by Roundhill [41]
and ourselves [42]. In analogous fashion, we have found that
the readily available complex, (Ph3P)4Pd, reacted with two
equivalents of phthalimide in benzene at 25 ◦C for 15 h to
give the novel trans-complex 1 in 78% yield (Fig. 1).
The mechanism by which complex 1 is formed appears
unusual. It was proposed by Roundhill that a Pd(IV) species
could be a transient intermediate to 1– rapid reductive elim-
ination of H2 is expected [43]. Such a species was also
proposed by Colquhoun and co-workers for the oxidative
addition of succinimide to low-valent metal centres [38].
It is also possible that 1 is formed by ␴-bond metathesis,
which would also result in H2 production. The 31P NMR
spectrum of 1 in CDCl3 exhibits one singlet at δ 20.13,
although the geometry around the palladium centre cannot
be confirmed by this, as the phosphorus signal for both the
cis- and trans-isomers would be expected to appear as a
singlet, due to symmetry. Single crystals of 1 suitable for
=
(N–bonded, C O→Pd coordination) [39,40]. In this paper,
via
O
O
H
O
N
H
N
(IV)
O
O
Ph3P
(Ph3P)4Pd (1 eqv.)
N
H
Pd(IV)
Pd
(II)
Pd
O
Ph3P
O
H
O
Benzene,
25oC,
12 h
Ph3P
N
PPh3
+ Ph3P
- Phthalimide
- Ph3P
+ Phthalimide
σ-bond metathesis
Rapid
H2
O
O
N
H
N
PPh3
(II)
(II)
Pd
O
Ph3P
H
+ Ph3P
Pd
O
O
O
N
O
Ph3P
N
O
H2
1, 78%
Fig. 1. Synthesis of 1 from (Ph3P)4Pd and two equivalents of phthalimide in benzene at 25 ◦C.

N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
193
Fig. 2. ORTEP representation of complex 1. Thermal ellipsoids are drawn at 50% probability.
X-ray analysis were grown from dichloromethane (0.83 M
solution) by slow evaporation over 72 h at 20 ◦C [44].
The X-ray crystallographic data confirms the trans-
geometry around the Pd-centre. The unit cell contains two
molecules (Fig. 2)1.
It is interesting to note that the carbonyl groups exhibit
moderate ␲–␲-stacking interactions with alternatively posi-
tioned aromatic groups (from Ph3P) and that the phthalimide
ligands deviate slightly from the plane, minimizing interac-
tions with the nitrogen lone pair electrons (dihedral angle:
C5−N2−N1−C1, θ = 6◦). This deviation is less than that
seen in bis(triphenylphosphine)palladium(II)succinimide
(dihedral angle: C5−N2−N1−C1, θ = 13◦). It is also noted
that there is negligible ␲–␲-stacking between molecules –
moderate face-to-edge and edge-to-edge stacking interac-
tions are observed.
reacted with phenylboronic acid 3a in 3 h to give biphenyl
4a in 85% yield (entry 1). The more activated arylboronic
acid 3b coupled to 2a to give 4b in 89% yield, again after
3 h (entry 2). Similarly, the less reactive arylboronic acids 3c
and 3d reacted with 2a to give 4c and 4d in 79% and 91%,
respectively (entries 3 and 4). The activated aryl bromide
substrates 2b and 2c reacted with 3a-d to give 4e-f and 4h-l
in yields >81%, with the exception of the cross-coupling of
2b with 3c to give 4g which proceeded in 69% yield – all
these reactions were complete in essentially 4 h or less (en-
tries 5–12). The deactivated substrate 2e reacted with 3a to
give 2-methoxybiphenyl 4m in 76% yield in 6 h (entry 13).
Indeed, substrate 2e further reacted with 3e and 3f to give the
cross-coupled products 4n and 4o in 77% and 68% yields,
respectively, again after 6 h (entries 14 and 15), demonstrat-
ing that vinylboronic acids and heteroarylboronic acids can
be employed successfully. The activated substrate 2f reacted
with 3a to give 4p in 81% yield after 5 h (entry 16). In a
similar manner to 2e, substrate 2f reacted with 3e and 3f to
give 4q and 4r in 71% and 80% yields, respectively (en-
tries 17 and 18). These results demonstrate that activated and
deactivated substrates with ortho-substituents are tolerated,
which are often problematic in coupling reactions mediated
by more bulky ligand systems [44]. In the last set of exam-
ples, the sterically hindered and deactivated substrate 2g was
shown to cross-couple with 3a-d to give the coupled prod-
ucts 4s-v in yields >68% in reaction times (12–15 h) that
were slightly longer than that seen above (entries 19–22).
2.1. Suzuki–Miyaura coupling mediated by 1
The reactions of selected benchmark activated and de-
activated aryl bromides (2a-g) with four arylboronic acids
(3a-d), an alkenylboronic acid (3e) and a heteroarylboronic
acid (3f) were carried out, in the presence of 1 mol% of 1
(lowering the catalyst loading to 0.1 mol% generally results
in lower product conversions) at 60 ◦C in a THF/1 M aque-
ous Na2CO3 solvent mixture, to give the cross-coupled prod-
ucts (4a-v, Table 1). In the first example, bromobenzene 2a
1
The X-ray structure of
1 has been deposited to the Cam-
2.2. Suzuki–Miyaura coupling of a brominated 2-pyrones
bridge crystallographic database (UK): CCDC 237081. Crystal data
for PdP2O4N2C52H38 a
:
M
= 923.18, triclinic, space group P-1,
= 10.6513(14) Å; b = 11.7510(15) Å; c = 18.594(2) Å, β = 103.620(3)◦,
V = 2058.6(4) Å3, Z = 2, T = 115(2) K, Dc = 1.489 Mg/m3, µ(Mo-K␣)
0.580 mm−1, R1 = 0.0387, wR2 = 0.0727, GOF = 1.033 for 553 pa-
rameters and 11774 reflections. Data collection on a Bruker Smart CCD.
Structure solution and refinement was performed using the program
SHELXL-97.
Interest in coupling heteroaromatic ring systems, clearly,
stems from the use of heteroaromatic moieties in medici-
nal and biologically relevant targets. However, it is often the
case that classic coupling reactions fail to produce yields
of products comparable to reactions giving simple biaryls.

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N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
Table 1
Suzuki cross-coupling of aryl halides and organoboronic acids mediated by (Ph3P)2Pd(N-Phthal)2
1
Entry
Aryl bromide
Aryl boronic acid
Product
Time (h)
3
Yield (%)
85
1
2
3
4
2a
2a
2a
3
3
3
89
79
91
R = CHO, 4c
R = Cl, 4d
5
6
7
8
3a
3b
3c
3d
3
3
3
4
88
81
69
86
2b
2b
2b
Rꢀ = 4-COCH3, R = Me, 4f
Rꢀ = 4-COCH3, R = CHO, 4g
Rꢀ = 4-COCH3, R = Cl, 4h
9
3a
3b
3c
3d
Rꢀ = 4-NO2, R = H, 4I
Rꢀ = 4-NO2, R = Me, 4j
Rꢀ = 4-NO2, R = CHO, 4k
Rꢀ = 4-NO2, R = Cl, 4l
4
4
4
4
91
90
82
85
10
11
12
2c
2c
2c
13
14
3a
Rꢀ = 2-OMe, R = H, 4m
6
6
76
77
2e
2e
15
16
6
5
68
81
3a
Rꢀ = 2-CO2Me, R = H, 4p
17
18
2f
2f
5
5
71
80
19
20
21
22
3a
3b
3c
3d
R = H, 4s
12
12
15
15
77
80
68
83
2g
2g
2g
R = Me, 4t
R = CHO, 4u
R = Cl, 4v
Reaction conditions: aryl bromide (1.05 eqv.), organoboronic acid (1.0 eqv.), 1 (1 mol%), 1 M Na2CO3, THF, 60 ◦C (unless otherwise stated). Isolated
yields after chromatography.

N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
195
Table 2
Suzuki cross-coupling of 2h and organoboronic acids mediated by (Ph3P)2Pd(N-Phthal)21
Entry
Aryl boronic acid
Product
Time (h)
Yield (%)
1
2
3
4
5
6
3a
4w
6
86 (56)
85 (52)
74 (20)
88 (53)
90 (–)
3b
4x
6
3c
4y
8
3d
4z
10
6
3e
4aa
3f
4ab
2
88 (27)
Reaction conditions: 2h (1.05 eqv.), organoboronic acid (1.0 eqv.), 1 (1 mol%), 1 M Na2CO3, THF, 60 ◦C (unless otherwise stated).
Isolated yields after chromatography. Numbers in brackets are yields from reactions employing Pd(OAc)2 (6 mol%), Ph3P (18 mol%), Na2CO3 (2 M),
EtOH/benzene (1/1, v/v) at reflux (∼90 ◦C) taken from reference [45].
Alternative processes, such as hydrodehalogenation and ho-
mocoupling, may become involved to the extent that they
can be major competing reaction pathways. Thus, in the
search for more active and selective catalysts/precatalysts, it
is important to screen more unusual, but challenging, sub-
strates that contain heteroaromatic ring-systems. For medic-
inal targets it is desirable to employ reactions that avoid
toxic side-products, which is one of the distinct advan-
tages of Suzuki–Miyaura coupling (vide supra). Lowering
catalyst loadings also reduces the amount of trace quan-
tities of palladium present in the final products. In recent
work, we have applied Suzuki–Miyaura methodology to
the synthesis of novel chemotherapeutic agents based on
the 2-pyrone-ring system [45–48]. The electrophilic part-
ner is 4-bromo-6-methyl-2-pyrone 2h, which we have estab-
lished is a relatively activated substrate. Optimised condi-
tions were developed, so as to avoid 2-pyrone ring-opening
and/or rearrangement, that are essential for high yields (stan-
dard conditions: Pd(OAc)2 (6 mol%), Ph3P (18 mol%), 2 M
Na2CO3, EtOH/benzene (1/1, v/v), reflux (∼90 ◦C). In an
effort to obtain higher yields, under less forcing conditions,
Suzuki–Miyaura coupling of 2h with 3a-f, mediated by 1
were investigated (Table 2).
On initial inspection of Table 2, it is clear that 1 is
able to efficiently mediate the cross-coupling of 2h with
organoboronic acids 3a-f. In all cases, with the exception of
3e, higher yields and more purer products (>90%; in selected
examples >95%, pure by inspection of the 1H NMR spectra
of the crude products) are obtained compared to those pre-
viously reported, using Pd(OAc)2 as the catalyst [45]. For
example, 3a reacted with 2h to give 4w in 86% yield after
6 h, which compares to 56% under our previous best con-
ditions (entry 1, Table 2). 4-Methylphenylboronic acid 3b
reacts equally well with 2h to give 4x in 85% after 6 h, again
comparing favourably to our previous best (entry 2). The
yield from the less activated 4-formylphenylboronic acid 3c
improves tremendously on our previous best (entry 3). A
further improvement is also seen for 4-chlorophenylboronic

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N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
O
acid 3d (entry 4). 3-Thiopheneboronic acid 3e reacts equally
well with 2h to give compound 4aa in 90% yield (entry 5).
In the last example, E-phenylethenylboronic acid 3f reacts
in less than 2 h to give 4ab in 88% yield, which improves
significantly on the 27% yield previously reported (entry 6).
The synthetic results clearly demonstrate the versatility of
1 under relatively low catalyst loading conditions, not only
for simple aryl systems but also for the more demanding
heterocyclic 2-pyrones.
N
O
O
Na
N
O
R' B(OH)2
R' B(OH)2
THF / H2O
Na
Scheme 1. Possible activation of the organoboronic acid by sodium ph-
thalimide.
In an effort to determine whether 1 is a precatalyst or
the actual catalyst, the evolution of product 4i from the
cross-coupling of 4-nitro-bromobenzene 2c with 3a was fol-
lowed by the withdrawal of small aliquots of the reaction
mixture by gas-tight syringe under an atmosphere of N2 at
appropriate time intervals – samples were quenched by pas-
sage through a short silica-plug eluted with CH2Cl2 and
then a solution of dppe added to ensure that the sample had
been completely quenched for accurate gas chromatographic
analysis of the reaction kinetics (at room temperature) [49].
The formation of 4i and disappearance of 2c are shown in
Fig. 3.
The kinetic profile indicates an induction period in the
initial stages of the reaction (∼0.25 h). The formation of a
trace quantity of biphenyl (∼0.01 eqv.) is noted at this point
– the amount of which does not increase throughout the
course of the reaction, indicating it was formed during the
induction period. After 0.5 h, the reaction enters into a linear
regime until it reaches ∼80% conversion at 3 h. A retardation
in rate is seen at this point, and after 5 h a 97% conversion
to 4i is observed. The induction period and the formation of
biphenyl, presumably formed through reaction of Pd(II) with
two equivalents of 3a (per Pd) to generate “(Ph3P)2Pd(0)”,
imply that 1 is a precatalyst. At this point, the question as to
whether phthalimidate is involved throughout the remaining
course of the reaction needed to be addressed. Clearly, it is
possible that its effect is to activate the organoboronic acid
to undergo transmetallation (Scheme 1).
To address this issue, a profile of the reaction of 2c with 3a
(illustrating the disappearance of 2c) mediated by (Ph3P)4Pd
(1 mol%) with one equivalent of sodium phthalimide (NaPh-
thal) was generated (by GC analysis). The stoichiometric re-
action was carried out in the presence and absence of aque-
ous 1 M Na2CO3. A reaction profile is shown for (Ph3P)4Pd
with 2 mol% NaPhthal, under the standard reaction condi-
tions. For comparison, the profile from the reaction mediated
by 1 is included (Fig. 4).
The profiles under the different reaction conditions are
quite revealing. Firstly, the reaction mediated by (Ph3P)4Pd
in the presence of NaPhthal (1 eqv.) in THF/1 M Na2CO3 at
60 ◦C showed a lengthy induction period. After 3 h the re-
action began to turn over at a relatively modest rate (∼40%
conversion to 4i after 6 h). In the absence of 1 M Na2CO3,
the same reaction results in negligible conversion after 6 h
(<3%). Both reaction profiles indicate that NaPhthal does
not activate 3a. The reaction in the presence of only 0.02
equivalents of NaPhthal exhibited a profile similar to the
profile observed for the reaction mediated by 1 under the
same conditions, albeit with a slightly longer induction pe-
100
90
80
70
60
50
40
30
20
10
0
100
90
80
70
60
50
40
30
20
10
0
0
60
120
180
240
300
360
Time / h
Fig. 4. Kinetic profiles for the reaction of 2c and 3a to give 4i: open
square, mediated by (Ph3P)4Pd (1 mol%) in THF/1 M Na2CO3 (1/1, v/v)
in the presence of sodium phthalimide (1 eqv.) at 60 ◦C; closed square,
mediated by (Ph3P)4Pd (1 mol%) in THF/H2O (1/1, v/v) in the presence
of sodium phthalimide (1 eqv.) at 60 ◦C; open circle (Ph3P)4Pd (1 mol%)
in THF/1 M Na2CO3 (1/1, v/v) in the presence of sodium phthalimide
(0.02 eqv.) at 60 ◦C; closed circle, mediated by 1 (1 mol%) in THF/1 M
Na2CO3 (1/1, v/v).
0
100
200
Time / min
300
Fig. 3. Kinetic profile for the reaction of 2c and 3a mediated by 1 to
give 4i (1 mol%).

N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
197
riod. After 1 h, the reaction profile enters a linear regime,
reaching 97% conversion after 5 h.
0.45 mmol), Na2CO3 (1 M (aqueous), 1 mL), THF (1.5 mL)
and catalyst 1 (3.3 mg, 4.1 ␮mol, 0.01 eqv.) were degassed
via three ‘freeze-pump-thaw’ cycles. The resulting mixture
was heated at 60 ◦C for the specified time. The reaction
mixture was allowed to cool to room temperature and water
(10 mL) added. The mixture was extracted with CH2Cl2 (3
× 10 mL), and the organic extracts were dried (MgSO4),
filtered and concentrated in vacuo. Purification by flash
chromatography gave biphenyl as a white solid.
3. Conclusions
In conclusion, we have synthesised the novel pal-
ladium(II) complex 1 and applied it to the successful
Suzuki–Miyaura coupling of a range of aryl and heteroaryl
bromides with aryl, vinyl and heteroarylboronic acids un-
der relatively low catalyst loadings. Complex 1 is easy to
synthesise, may be stored for prolonged periods and is air,
light and moisture stable. Furthermore, a marked improve-
ment in the yields of the cross-coupling products from the
brominated 2-pyrone 2h was seen over our previous best
conditions. We have determined that sodium phthalimide
does not activate the organoboronic acid. The true involve-
ment of this imidate ligand, amongst others, as well as its
effect in promoting Pd-catalysed cross-coupling processes,
is part of on-going studies in our group.
The following compounds characterized by 1H, 13C
NMR spectroscopy and mass spectrometry are known
within the literature: biphenyl 4a [52], 4-methylbiphenyl
4b [45], 4ꢀ-formylbiphenyl 4c [53], 4-chlorobiphenyl 4d
[46] 4-acetylbiphenyl 4e [54], 4-acetyl-4ꢀ-methylbiphenyl
4f [55], 4-acetyl-4ꢀ-formylbiphenyl 4g [56], 4-acetyl-
4ꢀ-chlorobiphenyl 4h [57], 4-nitrobiphenyl 4i [58], 4-
nitro-4ꢀ-methylbiphenyl 4j [59], 4ꢀ-nitro-biphenyl-4-
carbaldehyde 4k [60], 4-nitro-4ꢀ-chlorobiphenyl 4l [61], 2-
methoxybiphenyl 4m [62], 3-(2-methoxyphenyl)thiophene
4n [63], 2-methoxy-trans-stilbene 4o [64], 2-methoxycarbo-
nylbiphenyl 4p [65], 3-(2-methoxycarbonylphenyl)thiophene
4q [66], 2-methoxycarbonyl-trans-stilbene 4r [67], 2,6-
dimethylbiphenyl 4s [68], 2,6-dimethyl-4ꢀ-methylbiphenyl
4t [42], 2,6-dimethyl-4ꢀ-formylbiphenyl 4u [42], 2,6-
dimethyl-4ꢀ-chlorobiphenyl 4v [69], 4-bromo-6-methyl-2-
pyrone 2h [48], 4-phenyl-6-methyl-2-pyrone 4w, 4-(4ꢀ-
methylphenyl)-6-methyl-2-pyrone 4x [48], 4-(4ꢀ-formyl-
phenyl)-6-methyl-2-pyrone 4y [48], 4-(4ꢀ-chlorophenyl)-
6-methyl-2-pyrone 4z [48], 4-(2ꢀ-phenyl-trans-ethenyl)-6-
methyl-2-pyrone 4ab [48].
4. Experimental
THF was dried over sodium–benzophenone ketyl (dis-
tilled prior to use). Benzene was distill over calcium hy-
dride (distilled prior to use). All reactions were conducted
under an inert atmosphere of Ar or N2 on a Schlenk line.
Pd(PPh3)4 was prepared by reduction of (Ph3P)2PdCl2 with
hydrazine [50]. (PPh3)2PdCl2 was prepared from PdCl2 in
refluxing DMSO and PPh3 (2 eqv.) using a known proce-
dure [51]. Melting points were recorded on an electrother-
mal IA9000 Digital Melting Point Apparatus and are un-
corrected. TLC analysis was performed on Merck 5554
aluminum-backed silica gel plates and compounds visu-
alised by ultraviolet light (254 nm), phosphomolybdic acid
solution (5% in EtOH), or 1% ninhydrin in EtOH. 1H NMR
spectra were recorded at 270 MHz using a JEOL EX270
spectrometer or at 400 MHz using a JEOL ECX400 spec-
trometer; 13C NMR spectra at 67.9 or 100.5 MHz. Chemical
shifts are reported ins parts per million (δ) downfield from
an internal tetramethylsilane reference. Coupling constants
(J values) are reported in hertz (Hz).
4.2. 3-(2-Methoxycarbonylphenyl)thiophene (4q)
Mp 151–152 ◦C; vmax (CH2Cl2, cm−1) 1643, 1558, 1459,
1430, 1317, 1249, 1054, 948, 875; 1H NMR (400 MHz,
CDCl3) 2.24 (s, 3H), 6.22 (s, 1H), 6.27 (s, 1H), 7.29 (m,
1H), 7.37 (m, 1H), 7.61 (d, 1H); 13C NMR (100 MHz,
CDCl3) 20.14, 102.91, 106.61, 125.38, 125.77, 127.54,
137.33, 149.10, 162.076, 163.68. MS (EI) m/z 192 (M+,
45), 177 (10), 164 (100), 135 (34), 121 (56), 91 (6), 77 (8),
69 (12), 43 (25).
4.3. [Bis(triphenylphosphine)(bis(N-phthalimide))
GC conditions: Analysis was performed using a Var-
ian CP-3800 GC equipped with a CP-8400 Autosampler.
Separation was achieved using a DB-1 column (30 m ×
0.32 mm, 0.25 ␮m film thickness) with carrier gas flow rate
of 3 mL min−1 and a temperature ramp from 50 to 250 ◦C
at 20 ◦C min−1. The injection volume was 1 ␮L with a split
ratio of 50.
palladium(II)] (1)
Freshly prepared (Ph3P)4Pd (170 mg, 0.147 mmol) was
dissolved in dry benzene (10 mL) and N-phthalimide
(43.3 mg, 0.294 mmol) was added. The solution goes from
an intense yellow colour to a pale yellow after only a
few minutes, and a white crystalline salt begins to slowly
appear. After ∼12 h the solid was filtered (no special pre-
cautions), washed with benzene and dried in vacuo to give
the complex as a white powder. A small quantity (∼30 mg)
of the complex was crystallised from CH2Cl2/ether (1/5,
v/v) to give colourless crystals. Yield: 106.4 mg, 78.5%; Mp
= 247–248 ◦C; vmax (CH2Cl2, cm−1) 2986, 3054, 1664,
4.1. Typical Suzuki reaction
All reactions were performed in a Radleys carousel
adapted for rigorous inert atmosphere reactions. Phenyl-
boronic acid (50 mg, 0.41 mmol), bromobenzene (70.7 mg,

198
N.M. Chaignon et al. / Journal of Molecular Catalysis A: Chemical 219 (2004) 191–199
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Acknowledgements
The University of York is thanked for funding through an
innovation and research priming fund grant (to I.J.S.F.). Dr’s
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´
Jason M. Lynam and Jose Luis Serrano Martınez are thanked
for general discussions regarding this work. Dr. Adam F.
Lee is thanked for providing analytical equipment and space
within his laboratory.
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