Pd complexes of iminophosphine ligands: A homogeneous molecular catalyst for Suzuki-Miyaura cross-coupling reactions under mild conditions

Article abstract of DOI:10.1016/j.molcata.2009.08.003

The complexes formed by combining Pd(OAc)₂ and iminophosphine ligands (P^N) are active catalysts in Suzuki-Miyaura cross-coupling reactions under mild conditions. Aryl bromides and iodides, as well as benzyl chlorides give the corresponding cou

Full text of DOI:10.1016/j.molcata.2009.08.003

Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Pd complexes of iminophosphine ligands: A homogeneous molecular catalyst
for Suzuki–Miyaura cross-coupling reactions under mild conditions
Sabrina M. Nobre, Adriano L. Monteiro∗
Laboratory of Molecular Catalysis, Instituto de Química – UFRGS, Av. Bento Gonc¸ alves, 9500 Porto Alegre 91501-970, CP 15003, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
ˆ
Article history:
Received 11 May 2009
Received in revised form 24 July 2009
Accepted 3 August 2009
Available online 8 August 2009
The complexes formed by combining Pd(OAc)2 and iminophosphine ligands (PN) are active catalysts in
Suzuki–Miyaura cross-coupling reactions under mild conditions. Aryl bromides and iodides, as well as
benzyl chlorides give the corresponding coupled products in high yields at low temperatures (25–50 ◦C)
using these catalysts. Iminophosphines containing the most sterically demanding groups attached to
the N-imino moiety were the most effective ligands. New divalent Pd complexes of known iminophos-
phines were synthesised and their activity was compared with the in situ generated catalyst system. The
Keywords:
Suzuki–Miyaura coupling
Palladium
Iminophosphine ligands
Palladacycles
Poisoning tests
ˆ
complex resulting from the oxidative addition of 4-bromo anisole [Pd(4-CH3OC6H4)Br(PN)] was more
active than the in situ generated system. However, palladacycles containing the iminophosphine ligand
(e.g., {[C6H4CH(Me)2St-Bu]Pd(PN)} PF6−) were less active than the in situ generated catalyst due to the
+
ˆ
greater stability of the complexes that involve two bidentate ligands. Poisoning tests demonstrated that
homogeneous mononuclear palladium species containing the iminophsophine ligand were responsible
for the catalytic activity.
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
are active catalysts for cross-coupling reactions (Suzuki–Miyaura
[25,26], Heck [27–29], and Stille [30,31]), ethylene oligomerizations
The palladium-catalyzed Suzuki–Miyaura cross-coupling reac-
tions are one of the most efficient methods for the construction of
[32,33], hydroaminations [34], terminal alkyne arylations [35],
and allylic alkylation reactions [36]. Scrivanti et al. have reported
that ␩2-(olefin)palladium(0) complexes containing iminophos-
phine ligands are highly efficient catalysts for the coupling of
aryl bromides with boronic acids [25,26]. Their catalytic activity
is strongly dependent on the reaction conditions and on the nature
of the ligands, while the olefin plays an important role in stabi-
lizing the catalyst [26]. In this paper, we wish to report (1) the
synthesis and characterization of new divalent Pd iminophosphine
complexes, (2) the optimization of an in situ generated catalyst
system composed of Pd(OAc)2 and an iminophosphine ligand for
Suzuki–Miyaura reactions under mild conditions, and (3) a com-
parison of the catalytic activities of the in situ generated system
with that of the new preformed complexes (Scheme 1). In addition
we employed poisoning tests to evaluate the nature of the actual
catalytic species.
Caryl–Caryl bonds and have found widespread use in organic synthe-
sis [1–4]. Indeed, various efficient Pd catalyst precursors have been
developed in recent years that allow aryl halides to be effectively
coupled with aryl boronic acids under mild reaction conditions [5].
As part of our ongoing research addressing C–C bond formation by
cross-coupling reactions, we studied palladacycles [6–8], ligandless
Pd [9], and PPh3–Pd mixtures [10–12] in order to obtain simple
and efficient catalytic systems for Pd-catalyzed Suzuki–Miyaura
reactions [13–21]. Among the several classes of phosphine lig-
and described in the literature for Pd-catalyzed Suzuki–Miyaura
reactions, we became interested in iminophosphophine ligands.
These are bidentate ligands with both hard and soft donor atoms
and are expected to exhibit hemi-labile behavior when coordi-
nated to palladium [22,23]. These ligands can easily be obtained
from the reaction of o-(diphenylphosphine)benzaldeyde with an
amine [24]. Additionally, we can modulate the steric and elec-
tronic properties of the N atom by choosing an appropriate amine.
Thus, iminophosphine ligands in the context of Pd complexes
2. Experimental
2.1. General methods
All catalytic reactions were carried out under an argon atmo-
sphere in oven-dried resealable Schlenk tubes. Chemicals were
purchased from commercial sources, and were used without
∗
Corresponding author. Tel.: +55 51 33086303; fax: +55 51 33087304.
E-mail address: adriano.monteiro@ufrgs.br (A.L. Monteiro).
1381-1169/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2009.08.003

66
S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
Scheme 1. Pd iminophosphine complexes as catalyst precursors for Suzuki–Miyaura cross-coupling reactions.
further purification. Palladacycle
4
[37] and iminophosphine
diisopropylphenylamine 1a (45 mg, 0.1 mmol) dissolved in acetone
(5 mL) and KPF6 (18.4 mg, 0.1 mmol) were added to the suspension,
and the mixture was refluxed for 1 h. The solution was filtered
though CeliteTM and concentrated under reduced pressure. The
resulting residue was washed with ether (3× 15 mL). After recrys-
tallization from acetone–hexane (1:1) complex 3 was obtained as
a yellow solid (63.4 mg, 70%). 1H NMR (300 MHz, CDCl3): ı (ppm)
8.24 (s, 1H), 7.94–6.69 (m), 6.59 (t, J 7.5 Hz, 1H), 3.32 (t, J 7.5 Hz,
1H), 4.14–4.08 (m, 1H), 3.0 (sept, J 6.9 Hz, 1H), 2.84 (sept, J 6.9 Hz,
1H), 2.10 (d, J 6.9 Hz, 3H), 1.36 (d, J 6.9 Hz, 3H), 1.28 (d, J 6.9 Hz,
3H), 1.21 (d, J 6.9 Hz, 3H), 0.73 (s, 9H), 0.23 (d, J 6.9 Hz, 3H). 13C
NMR (75 MHz, CDCl3): ı (ppm) 170.9, 170.9, 158.8, 150.5, 150.1,
141.5, 141.3,140.3, 139.4, 139.2; 136.7, 135.7, 135.6, 135.7, 135.0,
134.5, 133.8, 132.5, 131.1, 130.9, 129.5, 129.1, 127.9, 127.5, 127.3,
127.2, 127.1, 126.9, 125.9, 125.4, 124.8, 124.7, 123.4, 53.0, 52.3, 31.5,
29.7, 29.6, 27.1, 26.8, 24.5, 23.9, 22.3. 31P NMR (121 MHz, H3PO4):
ı (ppm) 30.39 (s), −143 (sept, JP–F 712 Hz). IR ꢀ (cm−1): 2956, 2924,
2854, 1615 (C N), 1571, 1459, 1439, 1377, 1160, 1097. ESI(+) MS:
ligands (see supporting information) were prepared as reported
in the literature. NMR spectra were recorded on a Varian XL300
spectrometer. Infrared spectra were performed on a Bomem B-102
spectrometer. Mass spectra were obtained on a Shimadzu QP-5050
gas chromatograph/mass spectrometer (GC/MS) using EI methods
(70 eV). Gas chromatography (GC) analyses were performed on a
Hewlett-Packard 5890 Gas Chromatograph equipped with a flame
ionization detector (FID) and a 30-m capillary column containing
a dimethylpolysiloxane stationary phase. ESI mass spectra were
obtained in positive ion mode on a Micromass QTof instrument in
an ESI–QTOF configuration with a 7000 mass resolving power in
the TOF mass analyzer. The following typical operating conditions
were used with methanol solutions of the analyte: a 3 kV capillary
voltage and a 10 V cone voltage. X-ray structure analyses were
performed by the IQ-UFSM. Data from crystals were collected on
a Bruker Kappa APEX-II CCD 3 kW sealed tube system. Diamond
visual crystal structure information system, version 2.1 was used
to generate the molecular representations.
+
ˆ
{[C6H4CH(Me) StBu]Pd(PN)} (m/z): 748.2382 (calc’d = 748.2374).
ˆ
2.2. Synthesis of complex [Pd(4-CH3OC6H4)Br(PN)] (2)
2.4. Catalytic Suzuki–Miyaura cross-coupling reactions
A
purple solution of Pd2(dba)3 (81.35 mg, 0.089 mmol)
In a typical experiment, an oven-dried resealable Schlenk flask
was evacuated and back filled with argon then charged with
Pd(OAc)2 (0.01 mmol), iminophosphine 1a (0.01 mmol), aryl halide
(1 mmol), arylboronic acid (1.5 mmol), and dioxane (6 mL). The
reaction was stirred at room temperature for 10 min, and then
KOH (2 mmol) was added. The reaction mixture was stirred at the
desired temperature for the chosen amount of time. After which the
solution was then taken up in ether (30 mL), washed with aqueous
NaOH (1 M, 2× 5 mL) and brine (2× 5 mL), and dried over MgSO4.
After purification by flash chromatography, the biphenyl product
was characterized by 1H and 13C NMR, and GC–MS.
(dba = trans,trans-dibenzylideneacetone), P(o-tolyl)3 (108.22 mg,
0.356 mmol), and 4-bromoanisole (84.15 mg, 0.45 mmol) in
benzene (15 mL) was stirred at room temperature for 6 h. N-(2-
(Diphenylphosphino)benzylidene)-2,6-diisopropylphenylamine
(1a) was added and the solution was stirred at room temperature
for an additional 16 h. After filtration through CeliteTM, the solvent
was removed under reduced pressure. The residue was washed
with ether (4× 20 mL) and dried under vacuum giving complex 2
as a yellow solid (87%). 1H NMR (300 MHz, CDCl3): ı (ppm) 8.06
(s, 1H), 7.73–7.11 (m, 17H), 6.86 (d, J 8.4 Hz, 2H), 6.29 (d, J 8.4 Hz,
2H), 3.6 (s, 3H), 3.2 (sept, J 6.9 Hz, 2H), 1.45 (d, J 6.9 Hz, 6H), 0.98
(d, J 6.9 Hz, 6H), (Me)2. 13C NMR (75 MHz, CDCl3): ı (ppm) 167.5,
156.3, 150.6, 140.6; 137.9, 137.8, 137.36, 134.8, 134.6, 134.3, 134.1,
133.7, 132.6, 131.4, 130.6, 129.9, 129.6, 129.5, 129.3, 129.2, 127.9,
127.4, 124.1, 123.9, 113.9, 68.6, 55.8, 29.5, 26.3, 25.3, 23.8. 31P
NMR (121 MHz, H3PO4): ı (ppm) 21.9. IR ꢀ (cm−1): 2955, 2925,
2854, 2360, 2341, 1615 (C N), 1463, 1378, 1262, 1235.
2.5. CS2 poisoning studies
An oven-dried resealable Schlenk flask was charged with
Pd(OAc)2 (1.12 mg, 0.005 mmol), N-(2ꢀ-diphenylphosphino-
benzylidene)-2,6-diisopropylphenylamine (0.005 mmol), KOH
(56 mg, 1 mmol), phenylboronic acid (91.5 mg, 0.75 mmol), 4-
bromoacetophenone (99.5 mg, 0.5 mmol), and dioxane (6 mL). The
reaction mixture was stirred at 50 ◦C for 30 min (40% conversion).
A solution of CS2 in dioxane was then added (corresponding to 0,
0.5, 1.0, or 1.5 equiv. of CS2). The mixture was stirred at 50 ◦C and
further conversion was followed by GC over 3 days.
+
−
ˆ
2.3. Synthesis of complex {[C6H4CH(Me)2St-Bu]Pd(PN)} PF6 (3)
A Schlenk flask was charged with palladacycle (4) (39.5 mg,
0.1 mmol) and acetone (5 mL) and stirred at room tem-
perature for 5 min. N-(2ꢀ-Diphenylphosphinobenzylidene)-2,6-

S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
67
2.6. Hg(0) poisoning studies
at 50 ◦C for 16 h without any significative reaction (<1% coupling
product formation).
An oven-dried resealable Schlenk flask was charged with
Pd(OAc)2 (1.12 mg, 0.005 mmol), N-(2ꢀ-diphenylphosphinobenzyl-
idene)-2,6-diisopropylphenyl-amine (0.005 mmol) and dioxane
(4 mL). The mixture was stirred at rt for 15 min. Then aryl bro-
mide (0.5 mmol), phenylboronic acid (91.5 mg, 0.75 mmol), KOH
(56 mg, 1 mmol), and dioxane (2 mL) were added. The reaction
mixture was stirred at 50 ◦C for 30 min. Then Hg(0) (500 equiv. rel-
ative to Pd(OAc)2) was added and the reaction mixture was stirred
(900 rpm) at 50 ◦C for 41 h.
3. Results and discussion
3.1. Synthesis and characterization of oxidative addition
palladium complex 2 and palladacycle 3 containing an
iminophosphine ligand
Complex 2 was obtained using the procedure described for the
synthesis of[Pd(Ar)Br{(S)-BINAP}]complexes [38,39]. The complex
resulting from a 1:4 mixture of [Pd2(dba)3] and P(o-tolyl)3 in ben-
zene was reacted with an arylbromide to generate the correspond-
ing bromide dimer [Pd(␮-Br)(C6H4OCH3-4){P(o-tolyl)3}]2 in situ.
The addition of 2 equiv of N-(2-(diphenylphosphino)benzylidene)-
2,6-diisopropylphenylamine (1a) gave complex 2 in 87% yield
(Scheme 2). Cationic palladacycle 3 containing an iminophosphine
ligand was prepared using the procedure described in the liter-
ature for the synthesis of similar complexes containing N-based
palladacycles [40]. Therefore, treating the chloro-bridged sulfur-
containing palladacycle 4 with the iminophosphine ligand 1a in
the presence of a stoichiometric amount of KPF6 gave complex 3 in
70% yield.
Aryl halide
Conversion at 30 min
Conversion at 41 h
4-Bromoacetophenone
4-Bromotoluene
40%
22%
91%
44%
2.7. Typical procedure for Maitlis’s test
An oven-dried resealable Schlenk flask was charged with
Pd(OAc)2 (1.12 mg, 0.005 mmol), N-(2ꢀ-diphenylphosphinobenzyl-
idene)-2,6-diisopropylphenyl-amine (0.005 mmol) and diox-
ane (4 mL). The mixture was stirred at rt for 15 min. Then
4-bromotoluene (0.5 mmol), phenylboronic acid (91.5 mg,
0.75 mmol), KOH (56 mg, 1 mmol), and dioxane (2 mL) were
added. The reaction mixture was stirred at 50 ◦C for 30 min (25%
conversion). Then, the reaction mixture was filtered through a
sintered glass filter under argon and both the filtrate and the
remaining cellulose were evaluated for the coupling reaction.
KOH (56 mg, 1 mmol) was added to the filtrate and the reaction
mixture was stirred at 50 ◦C for 16 h giving a 45% conversion. The
cellulose was washed with dioxane (3× 5 mL) and transferred to
an oven-dried resealable Schlenk flask along with aryl bromide
(0.5 mmol), phenylboronic acid (91.5 mg, 0.75 mmol), KOH (56 mg,
1 mmol), and dioxane (6 mL). The reaction mixture was stirred
Complexes 2 and 3 were characterized by standard spectro-
scopic techniques and the complexes’ structures were determined
in the solid state by X-ray diffraction analysis. The 31P NMR spec-
tra of complexes 2 and 3 displayed singlets at ı 22.4 ppm and
ı 30.4 ppm, respectively, which confirmed the coordination of
the phosphine ligand to the palladium center (free ligand 1a ı
−15.1 ppm) [40,41]. Cationic complex 3 also displayed the typi-
cal septuplet resonance in the 31P NMR spectra due to the PF6
−
anion. IR analysis showed the ꢀ (C N) band of the free ligand 1a
at 1625 cm−1, whereas this absorption was shifted to 1615 cm−1 in
both complexes due to the coordination of the imino group’s nitro-
gen to the palladium center [26,41]. ESI MS analysis of a methanol
Scheme 2. Synthesis of complexes 2 and 3.

68
S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
Fig. 1. (a) ESI mass spectrum (positive mode) showing the experimental isotopic distribution pattern of 2 in methanol. (b) Simulated isotopic distribution pattern of
[Pd(C6H4OCH3-4)(2-(PPh2)C6H4-1-CH=NC6H3-iPr2-2,6)]+. (c) ESI mass spectrum (positive mode) showing the experimental isotopic distribution pattern of 3 in methanol.
(d) Simulated isotopic distribution pattern of 3.
solution of complex 2 showed a main peak at m/z = 662.2, which
presented the isotopic patterns corresponding to loss of a bromine
atom to form for the cationic complex [M−Br]+ (Fig. 1a and b). Com-
plex 3 is cationic and therefore the ESI MS analysis on positive mode
showed the cationic complex’s molecular ion at m/z = 748.2 with
the expected isotopic pattern (Fig. 1c and d).
Single crystals of complexes 2 and 3 suitable for X-ray anal-
ysis were obtained by slow evaporation of chloroform solutions.
In both complexes the planar arrangement around the palladium
atom is slightly distorted (Figs. 2 and 3; Table 1). These palladium
complexes may exist as two geometrical isomers, but 31P NMR
analysis indicates the presence of only one isomer in solution. X-
ray structural analysis showed the ligand arrangement with the
aryl ligand trans to the imino group in both complexes, as already
observed for related complexes in the solid state and in solution
[22,27,40,42–44]. All the bonds and the bond angles involving the
Pd atom lie within the normal range, except the larger deviation
of the P1-Pd-S angle (167.38(3)◦) in complex 3 [22,27,40,42,43].
This angular deviation is attributed to the steric effect of the 2,6-
diisopropylphenyl group and the StBu moiety.
.
3.2. Suzuki–Miyaura cross-coupling reaction: optimization of an
in situ generated catalyst system formed from Pd(OAc)2 and
iminophosphine ligands
Scrivanti et al. reported that the success of Suzuki–Miyaura
reactions involving ␩2-(olefin)palladium(0)iminophosphine com-
plexes as catalysts is strongly dependent on the reaction conditions
and on the nature of the ligands. Under optimized conditions, the
reactions were carried out in aromatic solvents in the presence of
K2CO3 at 90–110 ◦C [26]. We decided to investigate the perfor-
mance of the catalyst system formed in situ from Pd(OAc)2 and
an iminophosphine ligand in the absence of an olefin ligand and
Fig. 2. Image of complex 2. All hydrogen atoms are omitted for clarity.

S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
69
(50 ◦C) the iminophosphine ligand 1b gave complete conversion
whereas PPh3 gave only 44% conversion under the same conditions
(Table 2, entries 3 and 4). Using either ligand 1b or PPh3 no activ-
ity was observed at room temperature (Table 2, entries 5 and 6). It
is interesting to note that when we replaced the tert-butyl group
on the imino moiety with a 2,6-diisopropylphenyl group (ligand
1a), we did observe some activity at room temperature (18% con-
version, Table 2, entry 7). As already observed for Suzuki–Miyaura
couplings using Pd(OAc)2/PPh3 as a catalyst precursor, KOH was
the base of choice (Table 2, entries 8–14). Dioxane gave the best
results among the solvents examined (Table 2, entries 14–19). It
has been proposed that the transmetalation step in these reactions
proceeds through the intermediacy of a complex containing an O-
bonded boron anion when K2CO3 is used as the base in toluene [26].
Although we cannot exclude the possibility of a similar intermedi-
ate under our conditions (KOH and dioxane), a transmetalation step
involving an organoborate ArB(OH)3− is more likely to be operative
in the presence of KOH [45–47].
After determining the optimal base and solvent, we used these
conditions to evaluate the effect of the ligand (Table 3, entries
1–4). All of the iminophosphine ligands tested gave superior results
as compared with PPh3. As evident from Table 2 (entries 6 and
7) and Table 3 (entries 1–5), iminophosphine 1a, which contains
the most hindered group attached to the N-imino group, was
the most effective ligand. The opposite effect was noted with
␩2-(olefin)palladium(0)iminophosphine complexes. Higher reac-
tion rates were observed when the substituent on the N-imino
group was an aromatic group of low steric hindrance [26]. The
apparent contradiction can be rationalized by considering the
stability of the actual catalytic species proposed by Scrivanti et
al. In both cases, coordinatively unsaturated and highly active
(iminophosphine)Pd(0) complexes would be formed in the reduc-
tive elimination step, and this complex’s oxidative addition of
an aryl bromide would represent the start of a new catalytic
cycle (Scheme 3). The presence of this coordinatively unsaturated
species leads to the formation of metallic palladium particles. How-
ever, the coordination of an olefin to the (iminophosphine)Pd(0)
complex prevents this decomposition pathway, and the coordi-
nation of the olefin to the palladium center is favored by less
bulky substituents on the N-imino group [26,48]. In our case, no
olefin ligand is present and the only way to prevent (or min-
imize) the decomposition pathway is to protect the palladium
Fig. 3. Image of complex 3. All hydrogen atoms are omitted for clarity.
Table 1
Selected bond lengths (Å) and angles (◦) for complexes 2 and 3.
Lengths
Angles
2
Pd-C32
Pd-N
Pd-P
2.028(6)
2.188(5)
2.238(16)
2.485(8)
C32-Pd-P
N-Pd-P
N-Pd-Br
C32-Pd-N
88.08(17)
90.83(13)
92.87(13)
178.5(2)
Pd-Br
C
32-Pd-Br
88.18(16)
175.28(5)
P-Pd-Br
Pd-C32
Pd-N
Pd-P1
Pd-S
2.023(3)
2.154(2)
2.274(8)
2.365(8)
C32-Pd-P
N-Pd-P
92.61(8)
89.48(6)
82.66 (8)
94.21 (6)
174.32(10)
167.38(3)
3
C
32-Pd-S
N-Pd-S
C32-Pd-N
P1-Pd-S
at milder reaction temperatures (Table 2). For the initial screening,
we compared iminophosphine 1b with the most common and inex-
pensive phosphine ligand, PPh3, using dioxane as the solvent and
CS2CO3 as a base (Table 2). Both ligands gave complete conversion
after 2 h at 130 ◦C (Table 2, entries 1 and 2). At milder temperatures
Table 2
Effect of the different parameters on the Pd-catalyzed Suzuki–Miyaura cross-coupling reaction between 4-bromotoluene and phenylboronic acida.
Entry
Ligand
Solvent
Base
Temp (◦C)
Time (h)
Conv (%)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
18
19
PPh3
1b
PPh3
1b
PPh3
1b
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
DMA
CS2CO3
CS2CO3
CS2CO3
CS2CO3
CS2CO3
CS2CO3
CS2CO3
CS2CO3
CSF
K3PO4
K3PO4
K2CO3
NaOAc
KOH
KOH
KOH
KOH
KOH
KOH
KOH
130
130
50
50
25
25
25
50
50
50
50
50
50
50
50
50
50
50
50
50
2
2
2
2
3
3
3
1
1
1
1
1
1
1
1
1
1
1
1
1
100
100
44
96
–
100
100
38
95
–
–
–
18
46
30
22
22
36
13
99
74
72
69
65
23
72
16
30
29
20
20
21
10
99
50
44
42
36
7
DMF
EtOH
MeOH/THF
MeCN
PhMe
1b
14
a
Reaction conditions: 4-bromotoluene (0.5 mmol), phenylboronic acid (0.75 mmol), base (1 mmol), Pd(OAc)2 (1 mol%), 1a or 1b (1 mol%), PPh3 (2 mol%), solvent (4 mL).
Yields determined by GC.
b

70
S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
Table 3
Effect of the ligand on Pd-catalyzed Suzuki–Miyaura cross-coupling reactions between 4-bromotoluene and phenylboronic acida.
Entry
ArBr
Ligand
Pd (mol%)
Temp (◦C)
Time (h)
Conv (%)
Yield (%)b
1
2
3
4
5
6
7
8
9
4-MeOC6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-AcC6H4Br
4-AcC6H4Br
4-AcC6H4Br
4-AcC6H4Br
4-AcC6H4Br
1a
1b
1c
PPh3
1a
1a
1a
1a
1a
1
1
1
1
50
50
50
50
25
25
50
50
50
1
1
1
100
99
91
66
100
10
100
82
19
100
99
87
53
100
10
100
80
17
1
1
16
16
16
16
16
0.1
0.2
0.1
0.02
a
Reaction conditions: aryl halide (0.5 mmol), phenylboronic acid (0.75 mmol), KOH(1 mmol), Pd(OAc)2:ligand = 1:1, dioxane (4 mL).
Yields determined by GC.
b
coordination sites by using iminophosphines with hindered sub-
stituents.
After establishing the best solvent, base, and ligand for the
substituted biaryl was obtained in 89% yield (Table 4, entry 6). The
reaction is more sensitive to steric hinderance from ortho sub-
stituents on the aryl boronic acid (Table 4, compare entries 5 and
7). Thus, the coupling reaction of 4-bromoacetophenone with 2,4,6-
trimethylphenylboronic acid gave only 13% of the desired coupling
product along with a 67% yield of the reduced product acetophe-
none (Table 4, entry 7). These results clearly indicate that in the
classical Suzuki–Miyaura coupling mechanism the transmetalation
step is much more sensitive to steric effects than the oxidative addi-
tion step. The catalytic system is also efficient for the coupling of
benzyl chlorides and diarylmethanes were obtained in high yields
(Table 4, entries 8–9). Even without a specific optimization for
the benzyl chlorides coupling reaction, the results obtained using
1 mol% of Pd loading are similar to those described in the literature
[15,49–53].
reaction, we investigated the palladium loading required for
low temperature reactions (Table 3, entries 6–10). Activated
aryl bromides, such as 4-bromoacetophenone, can be coupled at
room temperature by using 1 mol% Pd (Table 3, entry 5). When
the temperature was increased to 50 ◦C a loading of 0.2 mol%
Pd was sufficient to achieve complete conversion of the acti-
vated substrate 4-bromoacetophenone (Table 3, entry 5). Under
the same conditions a loading of 1 mol% Pd was necessary to
achieve complete conversion of the deactivated substrate 4-
bromoanisole (Table 3, entry 1). It is important to note that TONs
of up to 80,000 were obtained at higher temperatures (110 ◦C)
using ␩2-(olefin)palladium(0)iminophosphine complexes as cata-
lyst precursors [26].
Coupling reactions involving several aryl halides and a variety of
arylboronic acids were examined under the optimized conditions
(Table 4). Aryl bromides and iodides containing para electron-
withdrawing and electron-donating groups reacted to furnish the
corresponding biaryl products in high yields (81–98% yield, Table 4,
entries 1–4). A challenging issue in Suzuki–Miyaura coupling reac-
tions is the difficulty of coupling sterically hindered substrates
[5]. By increasing the temperature to 80 ◦C, a good yield of the
biphenyl product could be obtained even with two ortho sub-
stituents on the aryl halide (Table 4, entries 5 and 6). Moderate yield
and reactivity were observed with the aryl bromide containing
two ortho substituents (Table 4, entries 5 and 6), but a tri-ortho-
3.3. Suzuki–Miyaura cross-coupling reaction: comparison of the
preformed complexes 2 and 3 with the in situ generated catalyst,
and poisoning tests
We have performed a comparison between the catalytic activity
of the in situ generated system and the new preformed complexes
2 and 3. At room temperature the activity of the catalyst generated
in situ by combining Pd(OAc)2 and 1 equiv. of iminophosphine 1a is
less than that of complex 2 (Table 5, entries 1 and 2). This result was
expected since complex 2 is an intermediate in the catalytic cycle
(Scheme 3), while coordination of the ligand and reduction of the
Pd(II) species to a Pd(0) species are required to form the catalytically
active species from the mixture of Pd(OAc)2 + 1a. Complete conver-
sion was obtained after 2 h both for the mixture of Pd(OAc)2 + 1a
and for complex 2 at 50 ◦C (Table 5, entries 4 and 5). Surprisingly,
complex 3 was almost inactive at room temperature (Table 5, entry
3), and even at 50 ◦C the conversion was not complete after 2 h
(Table 5, entries 6 and 7). These results indicate that the coordi-
nation of two bidentate ligands to the Pd center gives a very stable
complex, which is therefore a less active catalyst. On the other hand,
no significative differences were observed in the product coupling
yield by premixing Pd(OAc)2 and 1a in dioxane prior to adding base,
boronic acid and aryl halide (Table 5, entries 4 and 5).
Discerning between homogenous and heterogeneous Pd cat-
alyst systems is not a trivial task [54,55]. For Suzuki–Miyaura
reactions in the presence of the sulfur-containing palladacycle 4,
the addition of Hg immediately suppressed the catalytic activ-
ity. Quantitative poisoning experiments with CS2 indicated that
0.375 equiv. of CS2 were necessary to completely terminate the
reaction, indicating that only part of the palladium added to
the reaction is active as a catalyst [56]. Although we were not
able to determine the nature of the ligand-free palladium cata-
lyst (homogenous or heterogeneous), TEM analysis indicated the
presence of palladium nanoparticles. While the addition of Hg to
Heck reactions catalyzed by iminosphosphine–Pd(0) complexes at
Scheme 3. Simplified catalytic cycle for Suzuki–Miyaura cross-coupling reactions.

S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
71
Table 4
Pd-catalyzed Suzuki–Miyaura cross-coupling reaction between substituted haloarenes and phenylboronic acids using 1a as liganda.
Entry
ArX
ArꢀB(OH)2
Temp (◦C)
Coupling product (%)
1
50
98
2
50
93
3
4
30
30
98
81
5
80
93
6
80
89b
7
80
13c
8
9
80
80
85
92
10
80
87
a
Reaction conditions: aryl or benzyl halide (1 mmol), arylboronic acid (1.5 mmol), KOH (2 mmol), Pd(Oac)2 (1 mol%), 1a (1 mol%), dioxane (4 mL), 16 h (reaction times are
unoptimized).
b
Yield determined by GC (89% conversion).
A 67% yield of hydrodebrominated product (acetophenone) was isolated.
c

72
S.M. Nobre, A.L. Monteiro / Journal of Molecular Catalysis A: Chemical 313 (2009) 65–73
Table 5
Comparison of the reactivity of the catalyst formed from Pd(OAc)2 + 1a to complexes 2 and 3 in the Pd-catalyzed Suzuki–Miyaura cross-coupling reaction between 4-
bromotoluene and phenylboronic acida.
Entry
Catalyst
Temp (◦C)
Time (h)
Conv (%)
Yield (%)b
1
2
3
4
Pd(Oac)2 + 1a
2
3
25
25
25
2
2
2
0.5
2
0.5
2
2
37
85
2
38
100
40
100
100
96
36
83
2
37
100
38
100
100
96
Pd(OAc)2 + 1a
50
Pd(OAc)2 + 1ab
5
50
6
7
2
3
50
50
2
a
Reaction conditions: 4-bromotoluene (0.5 mmol), phenylboronic acid (0.75 mmol), KOH (1 mmol), Pd(OAc)2 and 1a, 2, or 3 (1 mol%), dioxane (4 mL), 2 h.
Yields determined by GC. Pd(OAc)2 and 1a were premixed in dioxane and stirred at room temperature for 15 min prior to adding the substrates.
b
140 ◦C completely stopped the reactions, the addition of PPh3 (0.05
using the Pd rettained in the cellulose. These results also support
the presence of a soluble catalyst (homogeneous catalysis).
or 0.1 equiv.) or of thiophenol (0.05 or 0.1 equiv.) had no effect
[28]. For the Pd(OAc)2 + 1a mixture and complexes 2 and 3 we
used Hg and CS2 poisoning tests in order to determine if the actual
catalyst was the molecular iminophosphine Pd complex or ligand-
free colloidal palladium nanoparticles or clusters. We performed
the Hg poisoning experiment in a coupling reaction between 4-
bromoacetophenone and phenylboronic acid (1 mol% Pd, 2 equiv.
KOH, dioxane, 50 ◦C). Under these conditions 40% conversion was
achieved after 30 min, and then Hg (200 equiv.) was added. In all
cases the reaction did not stop (∼ 90% conversion), indicating that
monometallic species (PdL) are the true active species rather than
Pd nanoparticles or clusters particles [54,55,57]. It is important to
mention that the ligand identity had a significant effect on catalyst
efficiency (Table 2). We also used the Hg poisoning test in a cou-
pling reaction between a deactivated aryl halide (4-bromotoluene)
and phenylboronic acid. The reaction mixture was stirred at 50 ◦C
for 30 min (22% conversion). Then Hg (0) (500 equiv. relative to
Pd(OAc)2) was added and the reaction mixture was stirred at 50 ◦C
for 41 h affording 44% conversion. These results can be rational-
ized assuming that molecular palladium species containing the
iminophosphine ligand are responsible for the catalytic activity.
Hg(0) does not quench the reaction because these Pd(0) species are
protected by the ligand. The fact that Hg(0) did not stop the reaction
immediately but causes incomplete conversion can be explained by
the ligand dissociation. The “naked’ molecular palladium species
formed will react with Hg(0) [55] decreasing the catalytic species
concentration until complete deactivation. Therefore, we cannot
exclude the possibility that phosphine-free complex or colloid are
also active species for the catalytic reaction.
Quantitative poisoning experiments with CS2 have been
employed to determine the number of catalytically active metal
atoms and provide evidence as to the nature of the catalyst (homo-
geneous or heterogeneous) [58,59]. We performed CS2 poisoning
experiments in coupling reactions between 4-bromoacetophenone
and phenylboronic acid using the same conditions that were used
in the Hg test. Under these conditions 40% conversion was achieved
after 30 min. At which point, different amounts of CS2 in dioxane
were added (0, 0.5, 1, or 1.5 equiv. of CS2) to different trials, and
the reactions were analyzed by GC over 3 days. It was found that
1.5 equiv. of CS2 were necessary to completely terminate the reac-
tion, which also indicates that the catalyst is of a molecular nature
[55].
4. Conclusions
In conclusion, the catalyst formed in situ by mixing Pd(OAc)2
and an iminophosphine ligand is active in the Suzuki–Miyaura
cross-coupling reaction. Aryl bromides, iodides, and benzyl chlo-
rides give the corresponding coupling products in high yields at
low temperatures (25–50 ◦C). Only hindered substrates required
higher temperatures (80 ◦C). The iminophosphines that contain
the most hindered groups attached to the N-imino group were
the most effective ligands, probably due to the steric effect of
the iminophosphine that prevents the catalyst’s decomposition
to inactive palladium black. New divalent Pd complexes contain-
ing iminophosphine ligands were obtained and compared with
the in situ generated system. The relative activity of the catalysts
ˆ
ˆ
was [Pd(4-CH3OC6H4)Br(PN)] > Pd(OAc)2 + PN > {[C6H4CH(Me)2St-
+
−
.
ˆ
Bu]Pd(PN)} PF6
The decreased activity of the palladacycle
containing the iminophosphine ligand can be correlated to the sta-
bilization of the complex caused by having two bidentate ligands.
Poisoning tests indicate that homogeneous molecular palladium
species containing the iminophosphine ligand are responsible for
the catalytic activity, or, to be more cautious, that it is at least a
strongly contributing reaction pathway.
Acknowledgments
We thank CNPq, FAPERGS, and INCT-Catalise for partial financial
support, and CNPq for a scholarship to S.M.N. We also thank Prof.
Ernesto S. Lang and Dr. Davi Back (UFSM) for collecting the X-ray
diffraction data.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2009.08.003.
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