A new precatalyst for the Suzuki reaction - A pyridyl-bridged dinuclear palladium complex as a source of mono-ligated palladiuin(0)

Article abstract of DOI:10.1039/b401077a

A dinuclear pyridyl-bridged palladium complex, trans-(P,N)-[PdBr(μ- C₅H₄N-C²,N)(PPh₃)]₂ 1, was obtained from material isolated from the Suzuki cross-coupling reaction of 2-bromopyridine with 2,4-difluorophenylboronic acid in the presence of catalytic (PPh₃)₄Pd. Complex 1 is an effective precatalyst for the Suzuki cross-coupling reactions of a variety organoboronic acids and aryl bromides, and represents a useful source of mono-ligated palladium(0), "(Ph₃P)Pd(0)".

Full text of DOI:10.1039/b401077a

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P A P E R
A new precatalyst for the Suzuki reaction—a pyridyl-bridged
dinuclear palladium complex as a source of mono-ligated
palladium(0)
a
a
b
a
b
Andrew Beeby,* Sylvia Bettington, Ian J. S. Fairlamb,* Andr e´ s E. Goeta, Anant R. Kapdi,
b
a
Elina H. Niemel a¨ and Amber L. Thompson
a
Department of Chemistry, University of Durham, South Road, Durham,
UK DH1 3LE. E-mail: andrew.beeby@durham.ac.uk; Fax: þ44 (0)191 384 4737;
Tel: þ44 (0)191 334 2023
b
Department of Chemistry, University of York, Heslington, York, UK YO10 5DD.
E-mail: ijsf1@york.ac.uk; Fax: þ44 (0)1904 432516; Tel: þ44 (0)1904 434091
Received (in Durham, UK) 22nd January 2004, Accepted 3rd March 2004
First published as an Advance Article on the web 31st March 2004
2
5 4 3 2
A dinuclear pyridyl-bridged palladium complex, trans-(P,N)-[PdBr(m-C H N-C ,N)(PPh )] 1, was
obtained from material isolated from the Suzuki cross-coupling reaction of 2-bromopyridine with
,4-difluorophenylboronic acid in the presence of catalytic (PPh Pd. Complex 1 is an effective
precatalyst for the Suzuki cross-coupling reactions of a variety organoboronic acids and aryl
2
3 4
)
3
bromides, and represents a useful source of mono-ligated palladium(0), ‘‘(Ph P)Pd(0)’’.
Introduction
Palladium-catalyzed C–C and C–X bond forming processes
are amongst the most important reactions in organic synth-
esis. The Pd-catalyzed cross-coupling reaction of organo-
1
halides with organoboronic acids, the Suzuki reaction,
represents a key transformation in both academic and indus-
trial sectors. The catalyst of choice, particularly in natural
2
3 4
product synthesis, is still (Ph P) Pd(0), even though a signifi-
cant step change in the field has been recently observed in
the development of highly active, electron rich Pd-catalysts,
possessing increased catalytic lifetimes. The nature of the
3
Scheme 1 Eqn. [1], first isolation of 1 Suzuki reaction of 2 and 3.
Eqn. [2], direct reaction of 2 with (Ph P) Pd to give 1.
3
4
‘
catalytically active’ species, in particular, the number of
phosphine ligands necessary to aid transmetallation, reductive
elimination and to stabilize the Pd-centre, has often been ques-
tioned. Classically it has been assumed that two phosphine
revealed the component to be a co-crystal of 1 and 4
(
4
Fig. 1).y
ligands are required for catalyst activity, but studies with
electron rich, bulky ligands, such as (t-Bu) P and (t-Bu) -
Each palladium atom exhibits a square-planar geometry
with the bromide and carbon bonds in a trans configuration.
3
2
(
biphenyl)P, have demonstrated that it is very likely that
˚
The Pd–Pd interatomic distance is 3.2338(4) A and is consis-
5
only one ligand remains on Pd. It would be interesting to study
Pd-precursors that allow for the generation of mono-ligated
Pd-species in the absence of dibenzylideneacetone (dba).
8
tent with the structure reported (3.194(2) A) and the chlorine
˚
9
analogue (3.165(3) A), previously published. This suggests
˚
6
that the interaction may be weak; although a search of the
Cambridge Structural Database (Version 1.5, November
Herein we describe the use of trans-(P,N)-[PdBr(m-C
5
4
H N-
10
2
C ,N)(PPh )] 1 in the Suzuki reaction, which is expected to
7
3
2
11
002, 272 066 entries) using ConQuest shows that similar
2
species occupy a range of 2.543–3.315 A with a mean average
3
give ‘‘(Ph P)Pd(0)’’. Our findings, suggesting 1 as a suitable
precursor catalyst, are discussed.
˚
˚
of 2.795 A. The central ring of our structure possesses two pyr-
idine rings bridging the palladium atoms with the nitrogen
trans to triphenylphosphine and carbon trans to bromine in
ꢀ
both cases. These planes are inclined at an angle of 81.2 form-
ing a six-membered ring in a boat conformation. The oxidative
Results and discussion
Our initial studies were concerned with a side-product
obtained from the Suzuki reaction of 2-bromopyridine 2
with 2,4-difluorophenylboronic acid 3 catalyzed by (Ph
(
3
P)
4
Pd
y Chemical
formula:
C
46
H
38Br
2
N
2
¯
P
2
Pd
2
,
7 2
0.5(C11H NF ),
˚
M
1
r
¼ 1148.93, T ¼ 120 K, triclinic (P1), a ¼ 10.4525(4) A, b ¼
Scheme 1, eqn. [1]). The expected cross-coupled product 4
˚
˚
ꢀ
ꢀ
3.0911(5) A, c ¼ 17.7535(6) A, a ¼ 81.5170(10) , b ¼ 78.849(2) ,
was isolated in 82% yield; however, we were somewhat
curious about the presence of a yellow component obtained
from chromatography, which crystallized on evaporation to
give pale brown diamond crystals in 0.11% yield. Suitable
crystals for X-ray diffraction studies were chosen, which
ꢀ
˚
3
ꢁ1
g ¼ 70.8180(10) , V ¼ 2241.84(14) A , Z ¼ 2, m ¼ 2.699 mm , Data/
restraints/parameters ¼ 11754/1/561, int ¼ 0.0418, Final
.0431 wR
R
R
1
¼
0
2
¼ 0.0898 [I > 2s(I)]. CCDC reference number 207524.
See http://www.rsc.org/suppdata/nj/b4/b401077a/ for crystallo-
graphic data in .cif or other electronic format.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
6
00
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5

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Bromobenzene 5a reacts with 6a, 4-methylbenzeneboronic
acid 6b, 4-formylbenzeneboronic acid 6c and 4-chlorobenzene-
boronic acid 6d in yields between 62–75% (entries 1–4). The
turnover numbers per hour for these reactions were good
ꢁ1
(
206–250 TON h ). 4-Bromoacetophenone 5b couples effec-
tively with 6a–d in yields of 64–76% (entries 5–8). The turnover
numbers per hour were lower than seen in reactions with 5a
ꢁ
1
107–127 TON h ). A similar observation is apparent with
(
the activated substrate, 4-nitro-1-bromobenzene 5c (108–122
ꢁ
1
TON h , entries 9–12). Methyl benzoate 5d couples satisfac-
torily with 6a–d (52–72% yields, entries 13–16). The less acti-
vated substrate, 2-methyl-1-bromobenzene 5e couples well
with 6a–d (62–75% yields, entries 17–20), with surprisingly
higher values observed for the turnover numbers per hour
ꢁ
1
(
207–250 TON h ). Indeed, 2-methoxy-1-bromobenzene 5f
couples equally well (74–81% yields, entries 21–24) in good
ꢁ
1
turnover numbers (123–135 TON h ). The sterically hin-
dered, deactivated substrate 2,6-dimethyl-1-bromobenzene 5g
(
50–71% yields, entries 25–28) gave the lowest turnover num-
ꢁ
1
bers per hour seen in this series (21–30 TON h ). However,
the fact that the unactivated substrates 5e and 5f couple more
effectively than the more activated substrates 5b and 5c is an
interesting observation.
The effect of additional Ph
probed systematically (Table 2). We chose 2-bromopyridine
as the substrate for reaction with phenylboronic acid 6a
3
P on the reaction rate was
2
Fig. 1 Crystal structure of 1 with thermal ellipsoids at 50%. The
structure of 2-(2,4-difluorophenyl)pyridine, 4, with which 1 is co-
crystallised, is also shown. The disorder is omitted for clarity.
under identical conditions to those given in Table 1. All reac-
tions were stopped after 3 h (quenched by passing the mixture
through a plug of silica gel). The Ph P ligand (1, 2 and 4
1
3
3
3
equivalents of Ph P were added per equivalent of 1; from a
stock solution in dry THF) was added via microsyringe prior
to addition of 1 to the reaction mixture. An obvious trend
was seen in these reactions, where additional Ph P clearly
addition of 2-, 3- and 4-bromopyridines to (Ph P) Pd results in
3
4
the formation of dimeric metallated pyridine species, such as
8
1.
Complex 1 was thus synthesised by direct reaction of
P) Pd with 2 to give 1 in 81% yield, possessing identical
H, P NMR spectroscopic and ESI spectrometric data to
3
reduces the turnover numbers per hour (entries 1–4, Table
2). In the absence of the additional Ph P, the cross-coupled
product 4a was produced in 74% after 3 h (entry 1, 123
(
Ph
3
4
1
31
3
the material isolated in the reaction of 2 and 3 (Scheme 1,
eqn. [2]).
ꢁ
1
TON h ). In the presence of 1 equivalent of Ph
lent per Pd), 4a was produced in 69% (entry 2, 115 TON h ).
On increasing to 2 equivalents of Ph P (1 equivalent per Pd),
a was produced in 62% (entry 3, 103 TON h ). Finally,
increasing the amount of Ph P to 4 equivalents (2 equivalents
3
P (0.5 equiva-
ꢁ1
We questioned whether 1 represented an intermediate cata-
lyst resting state in the reaction of 2 and 3, which led us to
study 1 as a general precatalyst for the Suzuki cross-coupling
3
ꢁ1
4
1
2
reaction. In the first reaction, 1 (0.2 mol%) was added to a
mixture of 2 and phenylboronic acid 6a in THF–1 M Na CO
3
ꢁ
1
per Pd), 4a was produced in 51% (entry 4, 85 TON h ). A
comparison of entries 1, 3 and 4 formally allows us to co-
2
3
ꢀ
at 80 C (Scheme 2, eqn. [1]). After 15 h the reaction was judged
complete (TLC), with workup and purification by flash
chromatography, affording the cross-coupled product 4a in
rrelate the effect of mono-ligated palladium(0) (Ph
bis-ligated palladium(0) ((Ph P) Pd(0)) and tris-ligated palla-
dium(0) ((Ph P) Pd(0)). Thus in these reactions, excess Ph
slows down catalysis.
3
P-Pd(0)),
3
2
3
P
68% yield.
3
3
Reaction of 6-methoxy-2-bromopyridine 2a with 6a under
the same conditions gave the cross-coupled product 4b in
Complex 1 has previously been employed as a precatalyst
for the cross-coupling reaction of chloropyridine with methyl-
7
7% yield ( Scheme 2, eqn. [1]). We subsequently found that
1
4
ꢀ
magnesium bromide. The occurrence of the reaction was
rationalised generally by displacement of the bromide ligand
from a monomeric species by an incoming nucleophile (Nu),
the reaction of 2 with 6a could be conducted at 60 C, proceed-
ing in slightly higher yield (74%). Room temperature reactions
with these substrates in the presence of 1 were sluggish, but
encouraged by our results, we investigated the cross-coupling
reactions of several aryl bromides and aryl boronic acids in
1
n
to generate [Pd(Nu)(Z -C
4
5
H
4
N-C )(PPh
). Reductive elimination provides Nu-C H N as the cross-
3
)
2
] (where n ¼ 3 or
1
5
5 4
ꢀ
3 2
coupled product and regenerates (Ph P) Pd as the active cata-
the presence of 1 at 60 C (Table 1).
lytic species. However, such a proposal would have to occur
through disproportionation of Ph P from the mono-phosphine
3
palladium species to give the bis-phosphine palladium and a
naked palladium species, which presumably would aggregate
and precipitate out of solution. In our reactions we do not
1
6
observe the formation of palladium black.
Given our results, we propose that a mono-ligated phos-
phine species (Ph P-Pd(0)) is essential for higher turnover num-
bers. A precatalytic cycle based on the classical mechanism is
3
1
7
proposed from precatalyst 1 (Fig. 2). The dimeric precatalyst
is expected to be in equilibrium with a 14-electron mono-
1
0
18
meric species 1 . Transmetallation with an activated aryl-
boronic acid will then occur through formal displacement of
bromide to give Pd(II) intermediate I. Reductive elimination
will then generate the cross-coupled product 4a and give the
Scheme 2 Eqn. [1], use of 1 as a precatalyst for reaction of 2 and 6a.
Eqn. [2], use of 1 as a precatalyst for reaction of 2a and 6a.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5
601

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Table 1 Suzuki cross-coupling of aryl bromides and aryl boronic acids catalysed by pyridyl complex 1
b
ꢁ1 c
Entry
1
Aryl bromide
Arylboronic acid
Product
Time/h
1.5
Yield (%)
62
TON h
206
2
3
5a
5a
1.5
1.5
63
75
210
250
R ¼ CHO, 7c
R ¼ Cl, 7d
4
5
5a
1.5
3
74
64
247
107
6a
0
0
0
6
7
8
5b
5b
5b
6b
6c
6d
R ¼ 4-COCH
3
3
3
, R ¼ Me, 7f
, R ¼ CHO, 7g
, R ¼ Cl, 7h
3
3
3
69
71
76
115
118
127
R ¼ 4-COCH
R ¼ 4-COCH
0
9
6a
R ¼ 4-NO
2
, R ¼ H, 7i
3
65
108
0
0
0
10
11
12
5c
5c
5c
6b
6c
6d
R ¼ 4-NO
2
2
2
, R ¼ Me, 7j
, R ¼ CHO, 7k
, R ¼ Cl, 7l
3
3
3
66
68
73
110
113
122
R ¼ 4-NO
R ¼ 4-NO
0
13
6a
R ¼ 2-CO
2
Me, R ¼ H, 7m
4
62
78
0
0
0
14
15
16
5d
5d
5d
6b
6c
6d
R ¼ 2-CO
2
2
2
Me, R ¼ Me, 7n
Me, R ¼ CHO, 7o
Me, R ¼ Cl, 7p
4
4
4
52
71
72
65
89
90
R ¼ 2-CO
R ¼ 2-CO
0
17
6a
R ¼ 2-Me, R ¼ H, 7q
1.5
63
210
0
0
0
18
19
20
5e
5e
5e
6b
6c
6d
R ¼ 2-Me, R ¼ Me, 7r
1.5
1.5
1.5
62
74
75
207
247
250
R ¼ 2-Me, R ¼ CHO, 7s
R ¼ 2-Me, R ¼ Cl, 7t
0
21
6a
R ¼ 2-OMe, R ¼ H, 7u
3
76
127
0
0
2
2
2
3
5f
5f
6b
6c
R ¼ 2-OMe, R ¼ Me, 7v
3
3
81
74
135
123
R ¼ 2-OMe, R ¼ CHO, 7w
0
2
4
5
5f
6d
6a
R ¼ 2-OMe, R ¼ Cl, 7x
3
77
63
128
26
2
12
2
2
2
6
7
8
5g
5g
5g
6b
6c
6d
R ¼ Me, 7z
R ¼ CHO, 7a’
R ¼ Cl, 7b’
12
12
12
50
61
71
21
25
30
a
b
ꢀ
Reaction conditions: aryl bromide (1.05 eq.), aryl boronic acid (1.0 eq.), 1 (0.2 mol%), 1 M Na –THF (1 : 2 v/v), 60 C with magnetic stirring.
c
Isolated yields after chromatography. TON h : calculated by considering the number of moles of desired product produced per mole of
2
CO
3
ꢁ1
catalyst used per hour.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
6
02
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5

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Table 2 Effect of excess triphenylphosphine on Suzuki coupling
of 2 with 6a using precatalyst
of this complex is its stability under ambient conditions (air
and moisture stable), unlike other commonly employed Pd(0)
3 4
catalysts, e.g. (Ph P) Pd, which are readily oxidised to Pd(II)
species in air. Complex 1 is easily synthesised in high yield
and may be used at low catalyst loadings (0.2 mol%), under
relatively mild conditions (60 C). Investigations into the effect
of additional phosphine on the rate of reaction demonstrated
an interesting trend. Here it was shown that excess phosphine
1
ꢀ
b
c
ꢁ1 d
TON h
Entry Additional Ph
3
P (%)
Time/h Yield (%)
(
3
> 1 Ph P per Pd) slows downs catalysis, which is presumably
associated with transmetallation and reductive elimination
steps, key events that are ultimately dependant on ligand dis-
sociation. Finally, this study demonstrates how important it
is to isolate every component from a reaction mixture—by
doing this we have ultimately been led to the identification
of a new precatalyst for the Suzuki reaction.
1
2
3
4
0
3
3
3
3
74
69
62
51
123
115
103
85
0.1
0.2
0.4
a
Reactions performed with 0.2 mol% catalyst using the conditions
b
and reagents described in Table 1. Ph
3
P stock solutions were pre-
pared using dry THF and the appropriate aliquot added to the reac-
c
1
tion mixture at t ¼ 0. Yields calculated from the H NMR spectra
d
ꢁ1
Experimental
of the isolated material (crude). TON h : calculated by considering
the number of moles of desired product produced per mole of catalyst
used per hour.
THF was dried over sodium–benzophenone ketyl (distilled
prior to use). All reactions were conducted under an inert
atmosphere of Ar or N2 on a Schlenk line. Pd(PPh3)4 was
1
9
prepared by reduction of (Ph
3 2 2
P) PdCl with hydrazine.
mono-ligated species II. This species can now proceed into the
standard catalytic cycle. Standard oxidative addition with the
appropriate organohalide gives III. Transmetallation of III
with the activated arylboronic acid affords IV, which then
undergoes reductive elimination to reveal the cross-coupled
product, regenerating the monomeric palladium(0) species II
as a consequence.
(PPh ) PdCl was prepared from PdCl (provided by Johnson
3
2
2
2
Matthey as a loan) in refluxing DMSO and PPh (2 eq.) using
3
2
0
a known procedure. Melting points were recorded on an elec-
trothermal IA9000 Digital Melting Point Apparatus and are
uncorrected. TLC analysis was performed on Merck 5554 alu-
minium backed silica gel plates and compounds visualized by
ultraviolet light (254 nm), phosphomolybdic acid solution
1
Support for the precatalytic cycle comes by following the
reaction of 4-nitrobromobenzene 5c with phenylboronic acid
(5% in EtOH), or 1% ninhydrin in EtOH. H NMR spectra
were recorded at 270 MHz using a JEOL EX270 spectrometer
ꢀ
13
or at 400 MHz using a JEOL ECX400 spectrometer; C NMR
6
a, in the presence of precatalyst 1 (5 mol%) at 60 C, by
GC-MS analysis. The first turnover should produce 2-phenyl-
pyridine 4a. After ca. 1 min of the reaction, 4a is produced, via
the precatalyst cycle. The formation of 7i and disappearance of
spectra at 67.9 or 100.5 MHz. Chemical shifts are reported in
parts per million (d) downfield from an internal tetramethyl-
silane reference. Coupling constants (J values) are reported in
hertz (Hz), and spin multiplicities are indicated by the follow-
ing symbols: s (singlet), d (doublet), t (triplet), q (quartet), qn
(quintet), sx (sextet), m (multiplet), br (broad).
5c is then observed (over 3 h), which is expected if mono-
ligated palladium(0) species II then enters the standard cataly-
tic cycle.
To summarise, we have conducted the first Suzuki cross-
coupling reactions employing precatalyst 1. A great advantage
1
13
The following compounds were characterized by H,
NMR and mass spectrometry and compared to the known
C
Fig. 2 The catalytic cycle employing precatalyst 1 in Suzuki cross-coupling reactions.
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5
603

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2
literature data: 4-acetylbiphenyl 7c, biphenyl 7a, 4-nitrobi-
phenyl 7i, 2,6-dimethylbiphenyl 7y, 2-methoxycarbonylbi-
1
22
ꢁ3
crystals (20 mg, 1.1 ꢂ 10 %). d
H 3
(400 MHz, CDCl ) 8.58 (1H,
2
3
24
m), 7.85 (6H, m), 7.36 (3H, m), 7.28 (6H, m), 6.61 (1H, m),
6.49 (2H, m); d (121 MHz, CDCl ) 30.79. Electrospray mass
P 3
spectrometry in acetonitrile gives similar results to those
reported previously.
2
5
26
phenyl 7m, 2-methylbiphenyl 7q, 2-methoxybiphenyl 7u,
27
28
0
2
2
0
4
2
-methylbiphenyl 7b,
0
4-acetyl-4 -methylbiphenyl 7f,
21
15
,6-dimethyl-4 -methylbiphenyl 7z,
0
2-methoxycarbonyl-4 -
2
9
28
methylbiphenyl
7n,
-methoxy-4 -methylbiphenyl 7v,
2,4 -dimethylbiphenyl
0
7r,
4 -formylbiphenyl 7c,
0
21
26
2
4
7
4
7
4
2
0
30
0
2
-acetyl-4 -formylbiphenyl 7g,
2-methyl-4 -formylbiphenyl
Direct preparation of trans-(P,N)-[PdBr-(m-C H N-C ,N)
5
4
2
s, 4 -chlorobiphenyl 7d, 4-acetyl-4 -chlorobiphenyl 7h,
6
0
26
0
31
(
3 2
PPh )] (1)
0
32
-nitro-4 -chlorobiphenyl 7l, 2,6-dimethyl-4 -chlorobiphenyl
0
0
33
b , 2-methoxycarbonyl-4 -chlorobiphenyl 7p, 2-methyl-
0
32
Tetrakistriphenylphosphine palladium(0) (600 mg, 0.48 mmol)
was dissolved in toluene (40 mL) to produce a bright clear yel-
low solution. 2-Bromopyridine (137 mg, 0.87 mmol, 1.8 eq.)
0
33
0
26
-chlorobiphenyl 7t, 2-methoxy-4 -chlorobiphenyl 7x and
0
34
-methoxycarbonyl-4 -formylbiphenyl 7p.
ꢀ
was then added. The resulting mixture was heated to 90 C
for 4 h, during which time the solution became cloudy and a
pale green-yellow colour. The reaction mixture was cooled to
room temperature and filtered. The green-yellow precipitate
was collected and washed thoroughly with diethyl ether
2
-Phenylpyridine 4a
d
H
(300 MHz, CDCl
3
) 8.66 (1H, dt, J ¼ 4.2 Hz, CH), 7.91
(
2H, m, 2 ꢂ CH), 7.70 (2H, m, 2 ꢂ CH), 7.42 (3H, m,
þ
(
5 ꢂ 10 mL) and subsequently dissolved in chloroform. The fil-
3
ꢂ CH), 7.21 (1H, m, CH); MS (ESþ): 156.1 (M þ H) .
trate was evaporated to dryness and the solid recrystallized
from chloroform and n-hexane to give the pure product as a
green-yellow crystalline solid (205 mg, 81%). dH and dP data
were identical to that given above.
2
-Methoxy-6-phenylpyridine 4b
d
H
(300 MHz, CDCl
3
) 8.09 (2H, d, J ¼ 7.2 Hz, 2 ꢂ CH), 7.65
(
1H, t, J ¼ 7.5 Hz, CH), 7.45 (4H, m, 4 ꢂ CH), 6.73 (1H, d,
J ¼ 8.1 Hz, CH), 4.08 (3H, s, CH
3
); MS (ESþ): 186.1
þ
(
M þ H) .
Typical Suzuki reaction
Phenylboronic acid (50 mg, 0.41 mmol), 2-bromopyridine
(
0
4
-Nitro-4 -methylbiphenyl 7j
71.3 mg, 0.45 mmol, 1.1 eq.), Na
2 3
CO (1 M (aq.), 1 ml),
THF (1.5 mL) and Pd-dimer crystals (1 mg, 0.95 mmoles,
d
H
(400 MHz, CDCl
3
) 8.22 (2H, d, J ¼ 7.9 Hz, CH), 7.66 (2H,
0
.21 mol%) were degassed via three ‘freeze–pump–thaw’
d, J ¼ 7.9 Hz, 2 ꢂ CH), 7.64 (2H, d, J ¼ 8.1 Hz, CH), 7.24
2H, d, J ¼ 8.1 Hz, 2 ꢂ CH), 2.35 (3H, s, CH ); d (100
MHz, CDCl ) 149.05, 139.05, 135.91, 132.60, 129.88, 127.45,
ꢀ
cycles. The resulting mixture was heated at 60 C overnight
during which the clear solution became bright yellow in colour.
The reaction mixture was allowed to cool to room temperature
after which water (10 mL) was added. The mixture was then
extracted with dichloromethane (3 ꢂ 10 mL) and the organic
(
3
C
3
þ
127.19, 124.07, 21.19; MS (EI) m/z 213 (M , 100), 75, 152,
115, 165, 183.
4
extracts dried (MgSO ), filtered and concentrated in vacuo.
0
4
-Nitro-4 -formylbiphenyl 7k
Purification by flash chromatography gave the pure cross-
coupled product, 2-phenylpyridine, as a pale yellow liquid
dH (400 MHz, CDCl ) 10.08 (1H, s, CHO), 8.10 (2H, d,
3
1
(43 mg, 68%). H NMR 300 MHz (CDCl
J ¼ 8.8 Hz, 2 ꢂ CH), 8.01 (2H, d, J ¼ 8.8 Hz, 2 ꢂ CH), 7.98
3
) d: 8.66 (1H, dt,
(
2
2H, d, J ¼ 8.5 Hz, 2 ꢂ CH), 7.66 (2H, d, J ¼ 8.5 Hz,
J ¼ 4.2 Hz), 7.91 (2H, m), 7.70 (2H, m), 7.42 (3H, m), 7.21
þ
þ
ꢂ CH); MS (EI) m/z 227 (M , 78), 152, 210, 76.
(1H, m); MS (ESþ): 156.1 (M þ H) .
0
0
2
,6-Dimethyl-4 -formylbiphenyl 7a
(400 MHz, CDCl
) 9.98 (1H, s, CHO), 7.36 (2H, d, J ¼ 6.7
Crystal structure determination of trans-(P,N)-
2
N-C ,N)(PPh
d
H
3
[
PdBr(m-C
5
H
4
3
)]
2
y
Hz, 2 ꢂ CH), 7.34 (1H, d, J ¼ 7.1Hz, CH), 7.33 (2H, m,
Single crystal X-ray diffraction experiments were carried out at
1
2
ꢂ CH), 7.29 (2H, m, 2 ꢂ CH), 1.93 (6H, s, 2 ꢂ CH
3
).
20 K using graphite monochromated Mo Ka radiation
˚
(
diffractometer. The temperature was controlled using a Cryo-
l ¼ 0.71073 A) on a Bruker SMART-CCD 1K area detector
0
2
-Methoxy-4 -formylbiphenyl 7w
3
stream N open-flow cooling device. Five series of narrow
5
d
H
(400 MHz, CDCl
3
) d 10.00 (1H, s, CHO), 7.85 (2H, d,
2
ꢀ
J ¼ 8.2 Hz, 2 ꢂ CH), 7.42 (2H, d, J ¼ 8.2 Hz, 2 ꢂ CH),
.23–7.13 (4H, m, 4 ꢂ CH), 2.208 (3H, s, OCH ); d (100
MHz, CDCl ) 192.31, 148.70, 140.88, 135.19, 130.20, 129.27,
28.34, 128.22, 127.57, 127.50, 56.38.
o-scans (0.3 ) were performed at several j-settings to cover
a sphere of data to a maximum resolution of between 0.70
7
3
C
˚
and 0.77 A. Cell parameters were initially determined using
3
3
6
the SMART software, and raw frame data were integrated
and cell parameters refined using the SAINT program. The
structure was solved by direct methods and refined by
1
2
Original isolation of trans-(P,N)-[PdBr-(m-C H N-C ,N)
5
4
2
full-matrix least squares on F using the SHELXTL soft-
ware. The reflection intensities were corrected by numerical
(
PPh
3
)]
2
(1)
37
2,4-Difluorophenylboronic acid 3 (5g, 32 mmol), 2-bromopyr-
idine 2 (5.5 g, 3.3 mL, 35 mmol. 1.1 eq.), Na CO (1M aq., 50
integration based on measurements and indexing of the crystal
faces (using SHELXTL software). The structure is of a co-
crystal of 1 and 4. Both 1 and 4 have disorder which is
modeled. For 1, one of the phenyl rings from the each PPh3
ligand is disordered such that there are two positions, each
with 50% occupancy. All non-hydrogen atoms were refined with
anisotrpic displacement parameters. 4 occupies a possition on
an inversion centre, which relates the two components. Aniso-
tropic refinement of 4 is unstable, so all atoms were refined
with isotropically. Hydrogen atoms for both 1 and 4 were
refined using a riding model.
2
3
mL), THF (100 mL) and Pd(PPh
%
3
)
4
(0.75 g, 0.6 mmol, 2 mol
ꢀ
) were heated overnight in a nitrogen atmosphere at 80 C
with continuous stirring. The reaction was cooled to room
temperature and water (200 mL) was added. The resulting mix-
ture was extracted with ethyl acetate (5 ꢂ 100 mL), dried
(
4
MgSO ), filtered and evaporated in vacuo. Flash chromato-
graphy afforded 2-(2,4-difluorophenyl)pyridine 4, as a pale yel-
low liquid (5.0 g, 82%). Complex 1 was isolated from a fraction
containing the impure product as pale brown diamond shaped
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
6
04
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5

View Article Online
reaction which irreversibly inhibits catalysis: E. H. Niemela,
A. F. Lee and I. J. S. Fairlamb, Tetrahedron Lett., 2004, in press.
K. Isobe and S. Kawaguchi, Heterocycles, 1981, 16, 1603–1612.
C. H. C. Clavius, J. S. L. Yeo, Z. H. Loh, J. J. Vittal, W.
Henderson and T. S. A. Hor, J. Chem. Soc. Dalton. Trans.,
Acknowledgements
1
1
4
5
We would like to thank EPSRC (SLB and ALT) for their
financial support and Professor T. B. Marder for his helpful
discussions and suggestions. IJSF thanks for the University
of York for financial assistance and Johnson Matthey for a
generous loan of palladium salts.
1
998, 3777–3784.
1
6
7
If the reactions are opened up to air, palladium black is produced
in <0.5 h.
It is appreciated that an anionic cycle could be operative from 1
by which the mono-ligated palladium(0) species is generated (such
1
3
as (Ph P-Pd(0)-Br(–)). For detailed information related to this
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3
3
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P have been isolated and characterized, see: J. P. Stambuli,
9
6
7
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2
3
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1
larger samples are required it is possible to add two equivalents
0
37 SHELXL, version 5.1, Bruker Analytical Instruments Inc,
Madison, Wisconsin, USA, 1999.
(
per Pd) of 1,1 -diphenylphosphinoethane (dppe) to the crude
T h i s j o u r n a l i s Q T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 4
N e w . J . C h e m . , 2 0 0 4 , 2 8 , 6 0 0 – 6 0 5
605