A nonsymmetric pincer-type palladium catalyst in Suzuki, Sonogashira, and Hiyama couplings in neat water

Article abstract of DOI:10.1021/om800175a

A new PCN palladium pincer complex containing a phosphinoamino group has been synthesized, fully characterized, and applied to Hiyama, copper-free Sonogashira, and Suzuki cross-coupling reactions performed in water. The use of the latter catalyst provides competitive yields, catalyst loadings, and reaction media.

Full text of DOI:10.1021/om800175a

Organometallics 2008, 27, 2833–2839
2833
A Nonsymmetric Pincer-Type Palladium Catalyst In Suzuki,
Sonogashira, and Hiyama Couplings in Neat Water
Blanca Ine´s,† Raul SanMartin,*,† Fa´tima Churruca,† Esther Dom´ınguez,*,†
Miren Karmele Urtiaga,‡ and Mar´ıa Isabel Arriortua‡
Kimika Organikoa II Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea, 644 P.K.
48080 Bilbao, Spain and Departmento de Mineralog´ıa y Petrolog´ıa, UniVersidad del Pa´ıs Vasco, Apdo
644, 48080 Bilbao, Spain
ReceiVed February 25, 2008
A new PCN palladium pincer complex containing a phosphinoamino group has been synthesized,
fully characterized, and applied to Hiyama, copper-free Sonogashira, and Suzuki cross-coupling reactions
performed in water. The use of the latter catalyst provides competitive yields, catalyst loadings, and
reaction media.
Introduction
Among the plethora of palladium catalysts employed for a
good number of modern organic transformations, pincer-type
palladium complexes constitute an appealing niche due to their
suitable balance between stability and reactivity.1 In the context
of cross-coupling reactions, the latter complexes allow for the
use of minimal amounts of such homogeneous catalysts.2 In
addition to an improved catalytic efficiency, much effort has
been devoted to the development of more sustainable conditions,
such as the recovery of the catalyst or the use of environmentally
more friendly reaction media.3,4 Water is a nonflammable, safe,
and cheap solvent with a great potential, since organic products
can be readily separated from the aqueous layer and many
reactions proceed with better selectivity in aqueous environ-
Figure 1. Existing PCN palladium complexes.
ments. Moreover, in some cases, mostly depending on the
stability of the catalyst, reuse of the aqueous layer containing
Scheme 1. Retrosynthetic Analysis of 1
the catalyst has been reported.5
Following our research on the development of new catalytic
systems to perform cross-coupling reactions,6 we envisaged the
construction of the new nonsymmetric PCN pincer-type pal-
ladium complex 1 according to the retrosynthetic Scheme 1.
Unlike the vast majority of the existing pincers, the nonsym-
metry of 1 could provide a better tuning of its catalytic
properties, but at the cost of a more challenging synthetic route,
as the scarcity of the existing palladium PCN pincers strongly
suggests (Figure 1).7–10 Dupont and Monteiro described the
synthesis of complex 3,7 which was subsequently applied to
Suzuki coupling,8 and the group of Motoyama prepared palla-
dacycle 4 in order to use it as a catalyst in stereoselective
transformations.9 Recently, Song et al. prepared and character-
ized complexes 5 and 6.10
* To whom correspondence should be addressed. E-mail:
raul.sanmartin@ehu.es (R.S.). Tel: 0034 946015435. Fax: 0034 946012748.
† Euskal Herriko Unibertsitatea.
‡ Universidad del Pa´ıs Vasco.
(1) (a) Albrecht, M.; van Koten, G. Angew. Chem., Int. Ed. 2001, 40,
3750. (b) Singleton, J. T. Tetrahedron 2003, 59, 1837. (c) Peris, E.; Crabtree,
R. H. Coord. Chem. ReV. 2004, 248, 2239.
(2) (a) DeVasher, R. B.; Moore, L. R.; Shaughnessy, K. H. J. Org. Chem.
2004, 69, 7919. (b) Braunstein, P. J. Organomet. Chem. 2004, 689, 3953.
(c) Van de Weghe, P. Lett. Org. Chem. 2005, 2, 113. (d) Hahn, F. E.; Jahnke,
M. C.; Pape, T. Organometallics 2006, 25, 5927.
(3) (a) Botella, L.; Na´jera, C. J. Organomet. Chem. 2002, 663, 46. (b)
Liang, L.-C.; Chien, P.-S.; Huang, M.-H. Organometallics 2005, 24, 353.
(4) (a) Ogo, S.; Takebe, Y.; Uehara, K.; Yamazaki, T.; Nakai, H.;
Watanabe, Y.; Fukuzumi, S. Organometallics 2006, 25, 331. (b) Nakai,
H.; Ogo, S.; Watanabe, Y. Organometallics 2002, 21, 1647.
(5) (a) Shaughnessy, K. H.; DeVasher, R. B. Curr. Org. Chem. 2005,
9, 585. (b) Dallinger, D.; Kappe, C. O. Chem. ReV. 2007, 107, 2563. (c)
Li, C.-J.; Liang, C. Chem. Soc. ReV. 2006, 35, 68–82. (d) Carril, M.;
SanMartin, R.; Dom´ınguez, E. Chem. Soc. ReV. 2008, 37, 0000.
(6) (a) Churruca, F.; SanMartin, R.; Tellitu, I.; Dom´ınguez, E. Synlett
2005, 3116. (b) Churruca, F.; SanMartin, R.; Tellitu, I.; Dom´ınguez, E.
Tetrahedron Lett. 2006, 47, 3233. (c) Churruca, F.; SanMartin, R.; Ine´s,
B.; Tellitu, I.; Dom´ınguez, E. AdV. Synth. Catal. 2006, 348, 1836.
(7) Rosa, G. R.; Ebeling, G.; Dupont, J.; Monteiro, A. L. Synthesis 2003,
2894.
(8) (a) DaSilveira Neto, B. A.; Lopes, A. S.; Ebeling, G.; Gonc¸alves,
R. S.; Costa, V. E. U.; Quina, F. H.; Dupont, J. Tetrahedron 2005, 61,
10975. (b) Mancilha, F. S.; DaSilveira Neto, B. A.; Lopes, A. S.; Moreira,
P. F.; Quina, F. H.; Gonc¸alves, R. S.; Dupont, J. Eur. J. Org. Chem. 2006,
4924. (c) Rosa, G. R.; Rosa, C. H.; Rominger, F.; Dupont, J.; Monteiro,
A. L. Inorg. Chim. Acta 2006, 359, 1947. (d) Consorti, C. S.; Ebeling, G.;
Flores, F. R.; Rominger, F.; Dupont, J. AdV. Synth. Catal. 2004, 346, 617.
(9) Motoyama, Y.; Shimozono, K.; Nishiyama, H. Inorg. Chim. Acta
2006, 359, 1725.
(10) Gong, J.-F.; Zhang, Y.-H.; Song, M.-P.; Xu, C. Organometallics
2007, 26, 6487.
10.1021/om800175a CCC: $40.75
2008 American Chemical Society
Publication on Web 05/21/2008

2834 Organometallics, Vol. 27, No. 12, 2008
Ine´s et al.
Scheme 2. Synthesis of Palladium Complex 1
Herein we report the synthesis and the most relevant catalytic
properties of new complex 1 in Suzuki, Sonogashira, and
Hiyama cross-coupling reactions, mainly performed in aqueous
media.
Results and Discussion
After reduction of the readily available11 1-(3-nitrophe-
nyl)pyrazole 7 to amine 2, treatment with ClPPh2 provided the
air-sensitive, unstable ligand 8, which was reacted without
further purification with Pd(COD)Cl2 in toluene to provide the
target pincer 1 (Scheme 2). In this key step, a 31P NMR
monitoring of the transformation to phosphinamine 8 (δP 28
ppm), the suitable proportion of hexane and toluene solvents
(1:9) and a quick filtering of the crude product onto a suspension
of Pd(COD)Cl2 in degassed toluene under argon became
especially crucial. The so-obtained complex 1 was found to be
air and thermally stable.
Figure 2. Molecular structure of the PCN pincer complex 1.
Ellipsoids are given at the 50% probability level.
Table 1. Selected Bond Lengths (Å) and Angles (deg) of PCN
Complex 1
Bond Lengths (Å)
Pd-C(9)
Pd-N(1)
Pd-P
1.957(8)
2.080(7)
2.208(2)
Pd-Cl
P-N(3)
N(3)-C(8)
2.386(2)
1.654(7)
1.396(10)
Several techniques were employed in order to confirm the
structure of palladacycle 1. The shift from 28 ppm (intermediate
8) to a singlet at 91 ppm in the 31P NMR spectrum of 1
suggested coordination to palladium. In addition, loss of
hydrogen at the central aromatic proton due to palladation was
confirmed by 1H NMR, DEPT, and HSQC experiments. Finally,
a simple recrystallization of palladacycle 1 in acetone provided
monocrystals suitable for X-ray diffractometry analysis. Figure
2 and Table 1 show the main structural features of 1. In addition
to other spectroscopic evidence, the short C9-Pd distance
(1.957(8) Å), comparable to that of other PCP and PCN
pincers,8c,10,12 ensures an effective palladation of this aromatic
carbon, an a priori difficult task if the already reported failures
at the formation of pincer complexes by C-H activation of
nonhalogenated aromatic positions are considered.13 It can
therefore be suggested, in comparison with other reported
pincers,13 that this difficult reaction is driven by the additional
stability gained by this PCN system, in a fashion similar to that
for the reported complexes 5 and 6.10 The strongly distorted
square planar geometry around the palladium atom is also
remarkable, as shown by the Cl-Pd-C9 and P-Pd-N1 bond
angles. The small (160.6°) P-Pd-N1 bond angle is in ac-
cordance with a pincer consisting of two five-membered-ring
Bond Angles (deg)
N(3)-P-C(16)
N(3)-P-C(10)
C(16)-P-C(10)
108.0(4)
106.3(4)
103.1(4)
N(3)-P-Pd
Cl-Pd-C(9)
N(1)-Pd--P
104.4(2)
175.6(2)
160.6(2)
Dihedral Angles (deg)
P-N(3)-C(8)-C(7)
N(1)-N(2)-C(4)-C(5)
Pd-N(1)-N(2)-C(4)
Pd-P-N(3)-C(8)
-179.8(7)
-179.9(8)
-0.4(9)
-0.6(7)
palladacycles14 and reflects a relative steric strain of the almost
planar (see torsion angles of Table 1) tetracyclic core, which
probably influences its catalytic activity. Figure 3 shows the
unit cell featuring a central inversion center (i) in the intermo-
lecular packing, which is further stabilized by a weak intermo-
lecular π-π type interaction between the bicyclic R1-R2
pyrazolopalladacycle moieties15 (see Figure 4) and a linear
N3-H22 · · · Cl hydrogen bonding defined by N3-H22 ) 0.73
Å, H22 · · · Cl ) 2.56 Å, and N3-Cl ) 3.25 Å (Figure 5).
Having fully characterized palladacycle 1, its catalytic activity
was preliminarily evaluated with Hiyama cross-coupling. Al-
(14) (a) Loch, J. A.; Albrecht, M.; Peris, E.; Mata, J.; Faller, J. W.;
Crabtree, R. H. Organometallics 2002, 21, 700. (b) Morales-Morales, D.;
Grause, C.; Kasaoka, K.; Redo´n, R.; Cramer, R. E.; Jensen, C. M. Inorg.
Chim. Acta 2000, 300-302, 958. (c) Bedford, R. B.; Draper, S. M.; Scully,
P. N.; Welch, S. L. New J. Chem. 2000, 24, 745.
(11) de la Hoz, A.; D´ıaz-Ortiz, A.; Elguero, J.; Mart´ınez, L. J.; Moreno,
A.; Sa´nchez-Migallo´n, A. Tetrahedron 2001, 57, 4397.
(12) Kimura, T.; Uozumi, Y. Organometallics 2006, 25, 4883.
(13) (a) Steenwinkel, P.; Gossage, R. A.; van Koten, G. Chem. Eur. J.
1998, 4, 759. (b) Jung, I. G.; Son, S. U.; Park, K. H.; Chung, K.-C.; Lee,
J. W.; Chung, Y. K. Organometallics 2003, 22, 4715.
(15) The nature and extent of the π-π interactions were evaluated by
the program CONTACTOS. See: Albert, A.; Cano, F. H. In Cristalograf´ıa;
Herna´ndez-Cano, F., Foces-Foces, C., Mart´ınez-Ripoll, M., Eds.; Publica-
ciones CSIC: Madrid, 1995; p 183

A Nonsymmetric Pincer-Type Palladium Catalyst
Organometallics, Vol. 27, No. 12, 2008 2835
Figure 3. Perspective view of the unit cell of 1.
Figure 5. One-dimensional chain structure of complex 1 formed
by C-H · · · Cl hydrogen bonds.
Table 2. Preliminary Hiyama Coupling Assays Performed with
Catalyst 1
entry
Ar
method A (%)a
method B (%)a
1
2
3
4-AcC6H4
4-MeOC6H4
4-NO2C6H4
82 (80)b
28
61 (57)b
40
51
Figure 4. Intermolecular π-π interactions.
13c
though the pioneering work by Hiyama et al. claimed the need
of fluoride ions in order to facilitate the transmetalation step,16
it has been shown that the latter process can be similarly
promoted by sodium hydroxide.17 Accordingly, the two proce-
dures displayed in Table 2 were assayed in order to arylate
(trimethoxysilyl)benzene, one of them in aqueous media, as
imposed by one of our main aims in this research. Moderate
yields were obtained by both protocols, and relatively high
loadings were required. Nevertheless, it should be pointed out
that, as far as we know, this is the first example of a Hiyama
coupling or arylation with an arylsilane derivative performed
by a palladium complex of a tridentate ligand.
a Determined by 1H NMR spectroscopy on the basis of the amount of
starting aryl halide. Diethylene glycol dimethyl ether was used as
internal standard. b Isolated yields (flash column chromatography). c 4
mol % of 1 was required.
sources and ligands of bibliographic procedures,18 were applied
to arylation of phenylacetylene with a series of aryl iodides,
providing moderate to good yields in most cases. Although
thermal activation provides generally better results (method C),
there is no clear trend on whether the electronic properties of
the iodides influence the reaction outcome. Again, aqueous
conditions employing complex 1 resulted in comparative
efficiency (Table 3). Our previous work on NCN pincer
complexes had provided an exceedingly effective catalyst (TON
values up to 8 × 105),6a but the versatility of the presented PCN
complex 1 for working under different reaction conditions,
including aqueous mixtures, cannot be overlooked.
Copper-free Sonogashira coupling was the next process in
which the activity of catalyst 1 was examined. Three different
reaction conditions, in which complex 1 replaced palladium
Finally, the catalytic activity of palladacycle 1 was thoroughly
tested in Suzuki cross-coupling, a more adequate reaction for
(16) (a) Hatanaka, Y.; Hiyama, T J. Org. Chem. 1988, 53, 918. See
also: (b) Hatanaka, Y.; Fukushima, S.; Hiyama, T. Chem. Lett. 1989, 1711.
(c) Hiyama, T. J. Organomet. Chem. 2002, 653, 58.
(18) (a) Li, J.-H.; Liang, Y.; Xie, Y.-X. J. Org. Chem. 2005, 70, 4393.
(b) Liang, B.; Dai, M.; Chen, J.; Yang, Z. J. Org. Chem. 2005, 70, 391. (c)
Heidenreich, R. G.; Kohler, K.; Krauter, J. G. E.; Pietsch, J. Synlett 2002,
1118.
(17) (a) Handy, C. J.; Manoso, A. S.; McEroy, W. T.; Seganish, W. M.;
DeShong, P. Tetrahedron 2005, 61, 12201. (b) Gordillo, A.; de Jesu´s, E.;
Lo´pez-Mardomingo, C. Org. Lett. 2006, 8, 3517.

2836 Organometallics, Vol. 27, No. 12, 2008
Ine´s et al.
Table 3. Copper-Free Sonogashira Alkynylation Assays Performed
with Catalyst 1
Table 4. Selected Suzuki Coupling Assays Catalyzed by 1
entry
Ar
A (%)a
B (%)a
C (%)a
1
2
3
4
5
6
7
8
Ph
84 (80)b
77
52
33
71
83 (78)b
44
50
62
73
>99 (96)b
1-Naphc
93
11
4-MeOC6H4
2-MeC6H4
3-MeC6H4
4-NH2C6H4
4-NO2C6H4
4-ClC6H4
89
84
entry
reacn conditionsa
(amt (%))b
<5
1
2
3
4
5
6
7
8
9a, 1 (2 mol %), K2CO3, MeOH, 25 °C
9a, 1 (2 mol %), K2CO3, EtOH, 25 °C
11a (>99)
11a (>99)
11a (<5)
11a (72)
36
16
75
97 (92)b
<5
60 (57)b
<5
60 (55)b
>99
9a, 1 (10-2 mol %), K2CO3, MeOH, 25 °C
9a, 1 (10-2 mol %), K2CO3, EtOH, 25 °C
9b, 1 (10-2 mol %), K2CO3, EtOH, 25 °C
9a, 1 (10-2 mol %), K2CO3, MeOH:H2O (3:1), 25 °C
a Determined by 1H NMR spectroscopy on the basis of the amount of
starting aryl halide. Diethylene glycol dimethyl ether was used as
internal standard. b Isolated yields (flash column chromatography).
c 1-Naph ) 1-naphthyl.
11b (41)
9a, 1 (10-2 mol %), K2CO3, EtOH:H2O (3:1), 25 °C 11a (10)
9a, 1 (10-2 mol %), K2CO3, MeOH:H2O (3:1), 60 °C 11a (80)
9a, 1 (10-2 mol %), K2CO3, EtOH:H2O (3:1), 60 °C 11a (51)
9
10
11
12
13
14
15
16
17
18
19
20
21
9a, 1 (10-2 mol %), K2CO3, EtOH, 60 °C
9a, 1 (2 mol %), K2CO3, H2O, 25 °C
11a (34)
use of an aqueous environment.19 Taking into account our
experience in this process,6a,c a brief optimization of experi-
mental conditions was performed using phenylboronic and
4-methoxyphenylboronic acids (9a,b) and 4-bromoacetophenone
(10a) as model substrates (Table 4). Although coupling in
MeOH or EtOH was effected with excellent results at room
temperature (Table 4, entries 1 and 2), a reduction in catalyst
loading or change in the boronic acid employed provoked a
decrease in reaction yields (entries 3-5), a problem that was
not sorted out by the use of aqueous mixtures of these alcohols
or higher temperatures (entries 6-10). Next, a set of different
assays were performed employing water as the only solvent
(entries 11-23), providing the conditions displayed in entry 21
(0.01 mol % of 1, 2.0 equiv of K2CO3, 1 mL of H2O per mmol
of aryl halide, 100 °C, 2 h) as the most convenient for the
synthesis of both biaryls 11a,b. It should be pointed out that,
in contrast with other catalytic systems that require specific
bases/additives or relative amounts of starting materials,20 the
use of pincer 1 in water proved to be quite insensible to such
variables/variations, a clear advantage from a practical point of
view. The latter optimized conditions were applied to an array
of arylboronic acids and aryl halides, providing the results
displayed in Table 5. Good to excellent yields were obtained
in all cases, regardless of the electronic or steric nature of the
coupling partners.
Due to the excellent results achieved, most of the biaryls 11
were prepared from aryl bromides, although iodides proved to
be useful coupling partners (Table 5, entries 15 and 16) and
even 4-chloroacetophenone coupled with phenylboronic acid
with an acceptable yield (entry 5), but higher temperature and
catalyst loading and longer reaction times were required. Taking
the generation of biaryl 11a as a model reaction, the amount of
catalyst was gradually decreased to 10-4 mol %, still resulting
in quantitative yield (>99%). When 10-5 mol % of catalyst 1
was employed, an 82% yield was observed, thus achieving a
TON value of 8 200 000, the highest reported so far for a Suzuki
coupling catalyzed by a PCN pincer complex.21 The same
protocol was applied to the coupling between 1-naphthyl
11a (>99)
11a (>99)
11a (62)
11a (>99)
11b (80)
11a (>99)
11a (>99)
11a (74)
11a (>99)
11a (>99)
11b (>99)
11a (95)
9a, 1 (2 mol %), K2CO3, H2O, 50 °C
9a, 1 (10-2 mol %), K2CO3, H2O, 25 °C
9a, 1 (10-2 mol %), K2CO3, H2O, 50 °C
9b, 1 (10-2 mol %), K2CO3, H2O, 50 °C
9a, 1 (10-2 mol %), K3PO4, H2O, 100 °C
9a, 1 (10-2 mol %), Na2CO3, H2O, 100 °C
9a, 1 (10-2 mol %), NaOH, H2O, 100 °C
9a, 1 (10-2 mol %), KOH, H2O, 100 °C
9a, 1 (10-2 mol %), K2CO3, H2O, 100 °C
9b, 1 (10-2 mol %), K2CO3, H2O, 100 °C
22c 9a, 1 (10-2 mol %), K2CO3, H2O, 100 °C
23d 9a, 1 (10-2 mol %), K2CO3, H2O, 100 °C
11a (96)
a 1.5 equiv of 9, 1.0 equiv of 10a, and 2.0 equiv of base were
employed for a reaction time of 2 h. b Determined by 1H NMR on the
basis of the amount of starting aryl halide. Diethylene glycol dimethyl
ether was used as internal standard. c 1.0 equiv of 9 was used. d 1.2
equiv of 9 was used.
bromide and 1-naphthylboronic acid leading to 1,1′-binaphthyl
(11p), reaching in this case a TON value of 3 700 000.
At this point, a comparison in terms of catalytic efficiency
and scope of application can be established between our complex
1 and other structurally related phosphinite-type PCN pincer
catalysts. Dupont et al. employed palladium complex 3 to
catalyze Mizoroki-Heck reactions in DMA, obtaining excellent
yields and TONs (up to 1 000 000).8d The same group also
assayed Suzuki coupling in 1,4-dioxane of 4,7-dibromo-2,1,3-
benzothiadiazoles,8a 5,8-dibromoquinoxalines,8b and a range of
aryl bromides and chlorides8c with good yields but using high
catalyst loadings.21 The group of Motoyama prepared the
asymmetric “Phemox-OP” derived complex 4, but its application
to catalysis is still under investigation.9 Recently, Song et al.
prepared phosphinite complexes 5 and 6 and studied their
catalytic properties in the Suzuki cross-coupling of phenylbo-
ronic acid in DMF. They concluded that the best results
(moderate to good yields employing two aryl chlorides and
several aryl bromides) were obtained by means of complexes 5
having the dicyclohexylphosphinoxy group (R ) Cy; R1 ) H,
Me), again with relatively high catalyst loading.10,21 Our
complex 1, bearing the key (diphenylphosphino)amino moiety,
has proven to be an excellent, much more efficient, and general
catalyst in Suzuki coupling and shows a satisfactory activity in
Sonogashira and pioneering Hiyama coupling reactions, with
(19) See for example: (a) Genet, J. P.; Savignac, M. J. Organomet. Chem.
1999, 576, 305. (b) Zhao, Y.; Zhou, Y.; Ma, D.; Liu, J.; Li, L.; Zhang,
T. Y.; Zhang, H Org. Biomol. Chem. 2003, 1, 1643. (c) Andrade, C. K. Z.;
Alves, L. M. Curr. Org. Chem. 2005, 9, 195.
(20) See for example: Hahn, F. E.; Jahnke, M. C.; Pape, T. Organo-
metallics 2007, 26, 150. (b) Vicente, J.; Abad, J.-A.; Lo´pez-Serrano, J.;
Jones, P. G.; Na´jera, C.; Botella-Segura, L. Organometallics 2005, 24, 5044.
(21) Dupont, Monteiro et al. and Song et al. reported TONs up to 480
and 1400 with their PCN pincers in Suzuki coupling, respectively.8c,10

A Nonsymmetric Pincer-Type Palladium Catalyst
Organometallics, Vol. 27, No. 12, 2008 2837
Table 5. Biaryls Prepared by Suzuki Coupling Employing Catalyst
1
between aqueous and nonaqueous protocols have been per-
formed, providing promising results in Hiyama and Sonogashira
couplings, reactions which have been catalyzed for the first time
by a PCN catalyst. The reported examples in arylation of
organosilicon compounds (Hiyama) are pioneering in the field
of pincer palladium catalysts. Finally, a general, highly efficient
aqueous protocol for the Suzuki coupling of aryl halides
catalyzed by our PCN pincer complex is presented. This
procedure can be accomplished with notably high TON num-
bers, and in addition to the simplicity of the catalyst separation/
product isolation method, effective reuse of the aqueous layer
containing the catalyst is also featured.
entry
X
Ar1
Ar2
11 (%)a
1
2
Br
Br
Br
Br
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
4-AcC6H4
4-AcC6H4
4-AcC6H4
4-AcC6H4
4-AcC6H4
3-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-NO2C6H4
4-NO2C6H4
4-CNC6H4
4-CNC6H4
4-CNC6H4
1-Naph
4-MeOC6H4
Ph
4-FC6H4
1-Naph
Ph
4-MeOC6H4
Ph
4-MeOC6H4
Ph
11a (>99) (97)b
11b (>99)
11c (92)
11d (>99)
11b (72)
3
4c
5d
6
11e (>99)
11f (87)
7
8
9
11g (87) (83)b
11h (>99) (96)b
11i (>99)
The catalytic activity of the presented PCN pincer complex
in other palladium-catalyzed reactions is currently being inves-
tigated in our laboratories.
10
11
12
13c
14c
15
16
17c
18c
4-MeOC6H4
Ph
11j (>99)
11k (>99)
11l (>99)
4-MeOC6H4
1-Naph
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
1-Naph
Ph
Experimental Section
11m (78) (75)b
11n (96)
Ph
General Procedures. All reagents were purchased and used as
1
received except when indicated. H and 13C NMR spectra were
I
Br
Br
3,5-Me2C6H3
1-Naph
2-PhC6H4
11o (80)
11p (>99)
11q (>99)
1
recorded on a Bruker AC-300 instrument (300 MHz for H and
75.4 MHz for 13C) at 20 °C. Chemical shifts (δ) are given in ppm
downfield from Me4Si and are referenced as internal standard to
the residual solvent (unless indicated) CDCl3 (δ 7.26 for 1H and δ
77.00 for 13C). 31P NMR spectra were recorded on a Bruker AV-
a Determined by NMR on the basis of the amount of starting aryl
halide. Diethylene glycol dimethyl ether was used as internal standard.
b Yields in italics are isolated yields (flash column chromatography).
c 1-Naph: 1-Naphthyl; 2-PhPh: 2-Biphenyl. d 1.0 equiv. of
4-chloroacetophenone, 1.5 equiv. of phenylboronic acid, 1.0 equiv. of
n-Bu4NI and 2 mol% of 1 were used at 150 °C for a reaction time of 4
h
1
500 (500 MHz for H and 202.4 MHz for 31P). Chemical shifts
(δ) were measured in ppm relative to H3PO4 (δ 0.00 for 31P) as
external standard. Coupling constants, J, are reported in hertz (Hz).
Melting points were determined in a capillary tube and are
uncorrected. TLC was carried out on SiO2 (silica gel 60 F254,
Merck), and the spots were located with UV light. Flash chroma-
tography was carried out on SiO2 (silica gel 60, Merck, 230-400
mesh ASTM). IR spectra were recorded on a Perkin-Elmer 1600
FT infrared spectrophotometer as KBr plates or as thin films, and
only noteworthy absorptions are reported in cm-1. Drying of
organic extracts during workup of reactions was performed over
anhydrous Na2SO4. Evaporation of solvents was accomplished with
a Bu¨chi rotatory evaporator. LRMS and HRMS were measured
using a Waters GCT mass spectrometer. A prismatic single crystal
was selected under a polarizing microscope and mounted on a glass
fiber. Single-crystal X-ray diffraction data were collected at room
temperature on an Oxford Diffraction XCALIBUR2 automatic
diffractometer (Mo KR radiation) equipped with a CCD detector.
Lattice constants were obtained by using a standard program
belonging to the software of the diffractometer, confirming at the
sametimethegoodqualityofthesinglecrystal.TheLorentz-polarization
and absorption corrections were made with the diffractometer
software, taking into account the size and shape of the crystal. The
structures were solved by direct methods (SHELXS9723) and
subsequent difference Fourier calculations. Details of the crystal
structure determination of 1 are given in Table 6.
the crucial advantage of the use of aqueous environments. It
can be tentatively proposed that both the relatively distorted
square planar geometry due to a higher ring strain (a pincer
consisting of two different five-membered-ring palladacycles)
and the phosphinoamino function have a beneficial effect not
only in the activity of pincer 1 but also in its solubility in
aqueous media and stability under the reaction conditions.
Recycling of catalyst 1 in the Suzuki coupling reaction leading
to 11a (1.5 equiv of 9a, 1.0 equiv of 10a, 0.01 mol % of 1, 2.0
equiv of K2CO3, H2O, 100 °C, 2 h) was finally assayed. Taking
into account the simple workup required to obtain the formed
biaryl 11a (extraction of the aqueous reaction mixture with
diethyl ether or dichloromethane), further runs with the same
aqueous layer containing the catalyst were performed after
adding starting materials 9a and 10a and K2CO3. Although the
first and second runs provided the same results (>99% yield),
a dramatic decrease was observed in the third run (9% yield),
probably due to a gradual decomposition of catalyst 1 under
the reaction conditions.22
To summarize, a new PCN-type palladium pincer complex
containing a phosphinoamino group has been readily prepared
by a one-pot phosphorylation/palladation of 3-(pyrazol-1-
yl)benzenamine. This hydrophilic complex not only surpasses
all the existing PCN pincer complexes in catalytic activity but
also allows the reaction to be conducted in aqueous media, with
all the advantages that it implies. Moreover, comparisons
Synthesis of Amine 2. A solution of the nitro derivate 7 (100
mg, 0.5 mmol) in EtOH (0.63 mL) was added to a solution of AcOH
in H2O (20%, 0.26 mL). Iron dust (236.4 mg, 4.2 mmol) was added,
and the mixture was refluxed for 3.5 h under vigorous agitation.
After it was cooled, the mixture was diluted with EtOAc (4 mL)
and filtered through a plug of Celite, the filter cake being further
washed with EtOAc (6 mL). The resulting solution was washed
with a 5% aqueous NaHCO3 solution (1 × 4 mL) and H2O (2 × 3
mL) and dried over anhydrous sodium sulfate. The solvent was
removed in vacuo, and the residue was purified by flash chroma-
tography (40% hexane/EtOAc) to provide 60.7 mg (72% yield) of
3-pyrazol-1-ylphenylamine (2) as greenish prisms. Mp: 37-39 °C
(22) For a review on the role of active species in Suzuki couplings,
see: (a) Phan, N. T. S.; van der Sluys, M.; Jones, C. W. AdV. Synth. Catal.
2006, 348, 609. The decomposition of several palladacycles to form active
Pd(0) clusters or colloids has been reported. See, for example: (b) Gaikwad,
A. V.; Gadi Rothenberg, G. Phys. Chem. Chem. Phys. 2006, 8, 3669. (c)
Bergbreiter, D. A.; Osburn, P. L.; Frels, J. D. AdV. Synth. Catal. 2005,
347, 172. Interestingly, although 31P NMR of the aqueous layer after the
first run (concentrated in vacuo and redissolved in acetone-d6) showed as
the main signal that at 91.3 ppm corresponding to complex 1, after the
second run the intensity of the latter signal had significantly diminished in
favor of other unidentified ones.
1
(40% hexane/EtOAc). H NMR (300 MHz, CDCl3): δ 3.82 (2H,
(23) Sheldrick, G. M. SHELXS97: Program for the Refinement of
Crystal Structures; University of Go¨ttingen, Go¨ttingen, Germany, 1997.

2838 Organometallics, Vol. 27, No. 12, 2008
Ine´s et al.
Table 6. Summary of Crystal Structure Determination for PCN
Complex 1
Method B. Pincer complex 1 (4 mol %) was added to a
mixture of trimethoxyphenylsilane (1.2 mmol), Bu4NF (2 mmol),
and o-xylene (1 mL) in a 5 mL round-bottom flask under an argon
atmosphere. The mixture was stirred for 10 min at room temper-
ature, and the aryl bromide was added (1 mmol). After it was stirred
at 80 °C for 4 h, the reaction mixture was cooled and H2O (5 mL)
was added. The aqueous layer was extracted with Et2O (3 × 6 mL).
The combined organic extracts were dried over sodium sulfate and
concentrated in vacuo. The residue was dissolved in CDCl3 and
analyzed by 1H NMR using diethylene glycol dimethyl ether as an
internal standard.
formula
mol wt
C21H17ClN3PPd
484.20
cryst syst, space group
unit cell dimens a, b, c (Å)
R, ꢀ, γ (deg)
orthorhombic, Pbca
15.4670(7), 15.8451(7), 15.8451(7)
90, 90, 90
3883.3(3), 8
1.656
V (Å3), Z
Fcalcd (g cm-3
F(000)
)
1936
θ range (deg)
2.87-23.82
µ (mm-1
)
1.186
no. of collected/unique rflns
22 903/2974 (R(int) ) 0.0856)
1.532
General Procedure for Sonogashira Cross-Coupling
Reactions. Method A. Pincer complex 1 (2 mol %) was added to
a mixture of aryl iodide (1 mmol), phenylacetylene (1.5 mmol),
NEt3 (3 mmol), and CH3CN (5 mL) in a 10 mL round-bottom flask
open to the atmosphere. After it was stirred for 12 h at room
temperature, the reaction mixture was cooled and H2O (5 mL) was
added. The aqueous layer was extracted with EtOAc (3 × 6 mL).
The combined organic extracts were dried over sodium sulfate and
concentrated in vacuo. The residue was dissolved in CDCl3 and
analyzed by 1H NMR using diethylene glycol dimethyl ether as an
internal standard.
Method B. Pincer complex 1 (2 mol %) was added to a
mixture of aryl iodide (1 mmol), phenylacetylene (1.5 mmol),
pyrrolidine (1 mmol), and H2O (1.5 mL) in a 5 mL round-bottom
flask open to the atmosphere. After it was stirred for 12 h at 50
°C, the reaction mixture was cooled and H2O (5 mL) was added.
The aqueous layer was extracted with EtAcO (3 × 6 mL). The
combined organic extracts were dried over sodium sulfate and
concentrated in vacuo. The residue was dissolved in CDCl3 and
analyzed by 1H NMR using diethylene glycol dimethyl ether as
an internal standard.
Method C. Pincer complex 1 (2 mol %) was added to a
mixture of aryl iodide (1 mmol), phenylacetylene (1.5 mmol),
and pyrrolidine (2 mL) in a 5 mL round-bottom flask open to
the atmosphere. After it was stirred at 100 °C for 6 h, the reaction
mixture was cooled and the solvent was removed under reduced
pressure. The residue was dissolved in CDCl3 and analyzed by
1H NMR using diethylene glycol dimethyl ether as an internal
standard.
Suzuki Cross-Coupling Reactions. General Procedure. Pincer
complex 1 (0.01 mol %) was added to a mixture of aryl halide (1
mmol), arylboronic acid (1.5 mmol), K2CO3 (2 mmol), and water
(1 mL) in a 5 mL round-bottom flask open to the atmosphere. After
it was stirred at 100 °C for 2 h, the reaction mixture was cooled
and Na2CO3 (5 mL of a 10% solution in water) was added. The
aqueous layer was extracted with CH2Cl2 (3 × 6 mL). The
combined organic extracts were dried over sodium sulfate and
concentrated in vacuo. The residue was dissolved in CDCl3 and
analyzed by 1H NMR using diethylene glycol dimethyl ether as an
internal standard.
goodness of fit on F2
final R indices (I > 2σ(I))
R indices (all data)
R1 ) 0.0951, wR2 ) 0.1241
R1 ) 0.0988, wR2 ) 0.1254
+0.443 and -0.483
largest diff peak and hole (e Å-3
)
NH2), 6.43 (s, 1H, Hpyr-4), 6.58 (d, J ) 7.92 Hz, 1H, Harom-6),
6.99 (d, J ) 7.96 Hz, 1H, Harom-4), 7.08 (s, 1H, Harom-2), 7.19 (t,
J ) 7.98 Hz, 1H, Harom-5), 7.69 (s, 1H, Hpyr-3), 7.87 (d, J ) 2.28
Hz, 1H, Hpyr-5). 13C NMR (75.5 MHz, CDCl3): δ 105.3 (Carom-2),
106.9 (Cpyr-4), 108.1 (Carom-4), 112.6 (Carom-6), 126.5 (Cpyr-5), 129.7
(Carom-5), 140.3 (Cpyr-3), 140.5 (Carom-3), 147.5 (Carom-1). Anal.
Calcd for C9H9N3: C, 67.90; H, 5.70; N, 26.40. Found: C, 67.87;
H, 5.71; N, 26.42. HRMS (EI): m/z calcd for C9H9N3 159.0796,
found 159.0799.
Synthesis of [2-(1H-Pyrazolyl-KN2)-6-((diphenylphosphino)
amine-KP)phenyl-KC1]palladium(II) Chloride (1). A solution of
ClPPh2 (0.56 mL, 3.1 mmol) in dry, degassed toluene (9.6 mL)
was added dropwise to a solution of amine 2 (500 mg, 3.1 mmol)
and NEt3 (0.43 mL, 3.14 mmol) in a degassed mixture of anhydrous
toluene and hexane (9:1; 37.3 mL) under argon at room temperature
in a Schlenk tube. The mixture was stirred at the same temperature
for 10 h. After verification by 31P NMR that the main signal
appeared at 28.5 ppm, the crude mixture was filtered under argon
and, without further purification, added to a suspension of Pd-
(COD)Cl2 (897.9 mg, 3.14 mmol) in dry, degassed toluene (39 mL)
at room temperature. The mixture was heated to reflux with stirring
for 4 h. After it was cooled, the crude reaction mixture was filtered,
the filtrand was washed with acetone (400 mL), and the filtrate
was concentrated in vacuo. The residue was redissolved in acetone
(2 mL) and cooled to -20 °C to provide a suspension, which was
filtered to yield 979.9 mg (64%) of complex 1 as a green powder.
Mp: 210-212 °C dec. 31P NMR (202.4 MHz, acetone-d6): δ 91.3.
1H NMR (300 MHz, acetone-d6): δ 6.67-6.69 (m, 1H, H-2),
6.70-6.72 (m, 1H, H-6), 7.03-7.08 (m, 2H, H-5, H-7), 7.51-7.57
(m, 6H, H-12, H-13, H-14, H-18, H-19, H-20), 7.95 (s, 1H, H-1),
8.05-8.09 (m, 4H, H-11, H-15, H-17, H-21), 8.53 (d, J ) 2.25
1
Hz, 1H, H-3). 13C NMR H (75.5 MHz, acetone-d6): δ 103.5 (C-
5), 106.8 (d, J ) 4.13 Hz, C-2), 108.2 (d, J ) 19.09 Hz, C-7),
126.9 (C-6), 127.4 (C-3), 128.6 (d, J ) 11.64 Hz, C-12, C-14, C-18,
C-20), 131.3 (d, J ) 2.73 Hz, C-13, C-19), 131.8 (d, J ) 13.73
Hz, C-11, C-15, C-17, C-21), 133.32 (C-4), 133.7 (C-8), 134.6 (d,
J ) 13.38 Hz, C-10, C-16), 139.5 (d, J ) 2.93 Hz, C-1), 143.4
(C-9). Anal. Calcd for C21H17ClN3PPd: C, 52.09; H, 3.54; N, 8.68;
Found: C, 52.12; H, 3.53; N, 8.65; HRMS (EI): m/z calcd for
C21H17ClN3PPd 482.9883, found 482.9889.
General Procedure for Hiyama Cross-Coupling Reactions.
Method A. Pincer complex 1 (2 mol %) was added to a mixture of
trimethoxyphenylsilane (1.2 mmol), NaOH (2.5 mmol), and water (5
mL) in a 10 mL round-bottom flask open to the atmosphere. The
mixture was stirred for 10 min at room temperature, and the aryl
bromide was added (1 mmol). After it was stirred at 140 °C for 1.5 h,
the reaction mixture was cooled and H2O (5 mL) was added. The
aqueous layer was extracted with Et2O (3 × 6 mL). The combined
organic extracts were dried over sodium sulfate and concentrated in
vacuo. The residue was dissolved in CDCl3 and analyzed by 1H NMR
using diethylene glycol dimethyl ether as internal standard.
Reuse of Catalyst 1 in Suzuki Couplings. A 5 mL round-bottom
flask was charged with ArBr (1 mmol), ArB(OH)2 (1.5 mmol),
catalyst 1 (0.01 mol %), K2CO3 (2 mmol), and water (1 mL). The
mixture was stirred at 100 °C for 2 h in air. After the mixture was
cooled, the aqueous layer was extracted with dichloromethane (3
× 3 mL), and the flask was charged again with aryl bromide (1
mmol), arylboronic acid (1.5 mmol) and K2CO3 (2 mmol). Every
time, after cooling and extraction with CH2Cl2 (3 × 3 mL), the
reagents and base were added and the reaction was repeated. As
previously explained in the General Procedure, the combined
organic extracts were dried over sodium sulfate and evacuated in
vacuo and the residue was analyzed by 1H NMR using diethylene
glycol dimethyl ether as an internal standard.
Acknowledgment. This research was supported by the
Regional Government of Biscay/Basque Government/

A Nonsymmetric Pincer-Type Palladium Catalyst
Organometallics, Vol. 27, No. 12, 2008 2839
Supporting Information Available: A CIF file giving full
University of the Basque Country (Projects DIPE 06/10,
UNESCO07/08, and GIU06IT-349-07) and the Spanish
Ministry of Education and Science (MEC CTQ2007-64501).
B.I. thanks the University of the Basque Country (UPV/
EHU) for a predoctoral scholarship. We also thank Petronor,
SA for a generous donation of hexane.
1
crystallographic data for complex 1 and text giving H and 13C
NMR data of all coupling products. This material is available free
of charge via the Internet at http://pubs.acs.org.
OM800175A