(IPr)Pd(pydc) (pydc = pyridine-2,6-dicarboxylate) - A highly active precatalyst for the sterically hindered C-N coupling reactions

Article abstract of DOI:10.1016/j.jorganchem.2013.03.021

A new class of well-defined NHC-Pd complexes incorporating a pyridine-2-carboxylate or pyridine-2,6-dicarboxylate ligand has been synthesized. These novel complexes exhibited prominent catalytic activity in the sterically hindered C-N coupling reactions at elevated temperature, but relatively inferior reactivity at low temperature. The distinctly different reactivity of these NHC-Pd complexes was presumed to be associated with their unique structures of ancillary ligands.

Full text of DOI:10.1016/j.jorganchem.2013.03.021

Journal of Organometallic Chemistry 737 (2013) 12e20
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Journal of Organometallic Chemistry
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(IPr)Pd(pydc) (pydc ¼ pyridine-2,6-dicarboxylate) e A highly active precatalyst
for the sterically hindered CeN coupling reactions
*
*
Yan-Jing Li, Jin-Ling Zhang, Xiao-Jian Li, Yu Geng, Xiao-Hua Xu , Zhong Jin
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new class of well-defined NHCePd complexes incorporating a pyridine-2-carboxylate or pyridine-2,6-
dicarboxylate ligand has been synthesized. These novel complexes exhibited prominent catalytic activity
in the sterically hindered CeN coupling reactions at elevated temperature, but relatively inferior reac-
tivity at low temperature. The distinctly different reactivity of these NHCePd complexes was presumed
to be associated with their unique structures of ancillary ligands.
Received 17 December 2012
Received in revised form
26 February 2013
Accepted 12 March 2013
Ó 2013 Elsevier B.V. All rights reserved.
Keywords:
N-Heterocyclic carbene
Palladium
BuchwaldeHartwig reaction
Cross-coupling
Ancillary ligand
1. Introduction
NHC backbone [7e10]. Meanwhile, except for the dominant NHC
ligand, other ancillary ligands around the palladium center also
The use of N-heterocyclic carbenes (NHCs) as supporting ligands
in the palladium-mediated homogeneous catalysis has witnessed
an impressive progress over the past decade [1,2]. To date, a great
number of the structurally diverse NHC-containing palladium
complexes have been prepared and characterized. These prevailing
NHCePd complexes have proven to be exceedingly versatile and
robust precatalysts in the widespread CeC, Ceheteroatom bond-
play a very crucial role to their catalytic performance. By replace-
ment of the allyl group with the cinnamyl group in (NHC)Pd(allyl)Cl
complexes, in 2006 Nolan developed a new class of precatalysts
with enhanced catalytic activity which probably resulted from an
accelerated activation step from the corresponding NHCePd(II)
complex to the active [(NHC)Pd0] species [11]. Conversely, a dra-
matic reduction of catalytic activity was discovered by Organ when
using more electrophilic 2,6-lutidine instead of 3-chloropyridine in
the precatalysts of PEPPSI family [10]. A balance of the pyridine
ligand detaching from and reattaching to the [NHCePd0] complex
in solution was thus implied. Moreover, Nolan discovered in the
type of (NHC)Pd(acac)Cl (acac ¼ acetylacetonato) complexes that
various substituted patterns in the acac group would give rise to the
distinctly different reactivity [12]. Recently, we also observed that
the steric and electronic nature of the sal (sal ¼ salicylaldimine)
ligand in the (NHC)Pd(sal)Cl complexes showed a significant effect
on their catalytic performance [13]. Incorporating the electron-
withdrawing group(s) into N-substituted aryl group in the sal
unit would led to the extremely increased reactivity in the ami-
nation reactions of aryl chlorides. More recently, Navarro reported a
formation reactions [3]. Due to stronger
s-donor property of
NHCs [4], air- and moisture-stability, easy handling, and ready
structure modification, well-defined monoligated NHCePd(II)
complexes [2f,2g,2l] have shown superior catalytic reactivity rela-
tive to the bulky tertiary phosphine/Pd systems [5], especially in
the field of Pd-catalyzed cross-coupling reactions. Generally, they
consist of an accurate 1:1 ratio of Pd/NHC (Scheme 1) that avoid the
use of excess costly ligand and, more important, usually exhibit
enhanced reactivity associated with easy activation to a highly
active low-coordinate [LPd0] species [6].
The catalytic activity of these NHCePd complexes significantly
related to the NHC and other ancillary ligands around Pd center. In a
series of investigation, Nolan, Glorius, and Organ have demon-
strated that the reactivity profile of NHCePd complexes related
substantially to the steric nature of N-substituent groups R in the
new family of complexes (NHC)PdCl2(tea) using intermediate
s-
donor capability triethylamine (tea) as a “throw-away” neutral
ligand [14]. These complexes exhibited higher catalytic activity at
lower temperature than the corresponding 3-chloropyridine
counterparts.
* Corresponding authors. Tel.: þ86 22 2350 1785; fax: þ86 22 2350 3691.
E-mail address: zjin@nankai.edu.cn (Z. Jin).
0022-328X/$ e see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jorganchem.2013.03.021

Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
13
a base (method B), the desired NHCePd complexes 1e4 could also
be obtained in satisfied yields [17]. The requisite [NHCePdCl2] di-
mers could be conveniently prepared from Pd(OAc)2 [8],
(PhCN)2PdCl2 [18], or [Pd(h
3-allyl)Cl]2 [19]. The structures of all four
complexes were fully characterized by means of elemental analysis,
1H and 13C NMR spectroscopy, and ESI-MS. These complexes
commonly exhibit high air- and moisture-stability, allowing for
indefinite storage and easy handling on the benchtop.
2.2. X-ray crystal structures of (NHC)Pd(pyc)Cl and (NHC)Pd(pydc)
complexes
Scheme 1. Well-defined monoligated NHCePd(II) complexes.
Suitable crystals for single-crystal diffraction analyses of (NHC)
Pd(pyc)Cl and (NHC)Pd(pydc) complexes 1e4 were obtained by
slow diffusion of n-pentane into dichloromethane solution (Figs. 1
and 2). Selected bond lengths and angles for compounds 1 and 3
were listed in the captions for figure, respectively. The crystal
structures revealed unambiguously a [O,N] bidentate chelate co-
ordination in complexes 1 and 2, and a slightly distorted square-
plane geometry around the palladium center. Like the pre-
As part of our ongoing project aimed to explore new types of
well-defined NHCePd complexes with improved catalytic profiles,
we envision incorporation of a pyridine-2-carboxylate (pyc) or
pyridine-2,6-dicarboxylate (pydc) [15] anion ligand into the NHCe
Pd(II) complex to form a new class of [O,N] or [O,N,O] chelate NHCe
Pd complexes. Organ and co-workers have discovered in the PEPPSI
catalyst family that, as an ancillary ligand, substituted pyridine
played an extremely important role in the activation of precatalyst
[10]. 2,6-Lutidine instead of 3-chloropyridine retarded greatly the
disassociation rate of ancillary ligand. We also observed in the
(NHC)Pd(sal)Cl complexes that the decreased strength of the PdeN
bond led to easier activation of the complex [13]. As a result, the
presence of electron-withdrawing carboxylate group(s), decreasing
greatly the charge density of pyridine ring, may cause a weakened
NePd coordination which facilitates disassociation of ancillary
ligand from the Pd center and accelerated formation of the active
[(NHC)Pd0] species.
catalysts of the PEPPSI family [9,10,16], the neutral
s-donating
pyridine nitrogen atom is located trans to the NHC ligand, while the
carboxylate oxygen anion is situated in the cis to the NHC ligand in a
direction opposite the chloride anion. While in complexes 3 and 4,
a unique [O,N,O] tridentate trans-chelating planar configuration
was observed. From the crystal X-ray diffraction data, due to in-
duction by [O,N,O] tridentate chelating coordination of pyridine-
2,6-dicarboxylate, the distances of the PdeCcarbene bonds in com-
ꢀ
ꢀ
plexes 3 and 4 are 2.005 A and 1.996 A in solid crystals, respectively,
ꢀ
which are obviously larger than those of complexes 1 and 2 (1.963 A
for 1 and 1.970 A for 2, respectively). In addition, the PdeCcarbene
ꢀ
bonds of complexes 3 and 4 are also comparatively longer than
those of NHCePd complexes [(IPr)PdCl2]2 dimer [18b] and (IPr)
Pd(3-chloropyridine)Cl2 [10] (1.9553 A and 1.962 A, respectively).
Generally, the longer PdeCcarbene bond facilitated oxidative addi-
tion of [(NHC)Pd0] species to the sterically encumbered electrophile
2. Results and discussion
ꢀ
ꢀ
2.1. Synthesis of (NHC)Pd(pyc)Cl and (NHC)Pd(pydc) complexes
We therefore commenced synthesizing well-defined NHCePd
complexes 1e4 (Scheme 2). Initially, using the protocol analogous
to Organ’s procedure [16], these NHCePd complexes were prepared
from salts NHC$HX and PdCl2 in a straightforward one-pot proce-
dure (method A). For picolinate-containing complexes 1 and 2,
modest to good yields were obtained under the standard reaction
conditions. However, with the sterically encumbered pyridine-2,6-
dicarboxylic acid, reaction only gave the desired precatalysts 3 and
4 in poor yields along with remarkable degraded Pd black. As a
result, an alternative, more efficient synthetic method was pursued
for improving yields. To our delight, through straightforward
cleavage of the [NHCePdCl2] dimers with two equivalents of 2-
picolinic acid or pyridine-2,6-dicarboxylic acid in the presence of
Fig. 1. Crystal structure of complex
1 with thermal ellipsoids drawn at the 50%
probability level and most H atoms (except those in the backbone of NHC) and co-
crystallizing solvent molecules have been omitted for clarity. Selected bond lengths
ꢀ
ꢀ
(A) and angles ( ): Pd(1)eC(7) 1.963(2), Pd(1)eO(1) 2.0219(17), Pd(1)eN(1) 2.067(2),
Pd(1) eCl(1) 2.2773(7); O(1)ePd(1)eN(1) 81.59(8), O(1)ePd(1)eCl(1) 178.39(5), C(7)e
Pd(1)eO(1) 89.84(8), N(1)ePd(1)eCl(1) 96.80(6), N(2)eC(7)eN(2A) 105.39(19), O(1) e
Pd(1)eN(1) 81.59 (8).
Scheme 2. Synthesis of NHCePd complexes 1e4.

14
Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
PEPPSI family derivative (IPr)PdCl2(3-chloropyridine) (IPr-PEPPSI),
all four complexes exhibited the inferior reactivity under the re-
action conditions (Fig. 3). To our surprise, when the coupling re-
actions were carried out at elevated temperature (100 ꢀC), an
obviously different reactivity between complexes 1e4 and the
control catalysts was observed (Fig. 4).
Under the optimized conditions, a significant difference in cat-
alytic performance between complexes 1e4 was also observed
(Table 1). Compared to complexes 1 and 2, complexes 3 and 4
showed obviously superior reactivity. In all cases, unsaturated NHC
palladium complexes were more effective catalysts than their
saturated counterparts [21]. Amongst them, (IPr)Pd(pydc) 3 was
found to be the most active catalyst for the coupling reactions. For
example, coupling reaction employing complex 3 as a catalyst
afforded the corresponding N-mesityl morpholine in an isolated
yield of 93% within mere 20 min (entry 3, Table 1).
Furthermore, complex 3 was also found to show the predomi-
nant reactivity in the coupling of a variety of aliphatic amines with
the sterically encumbered aryl chlorides (Table 2). Generally, using
complex 3 at 1.0 mol % catalyst loading, the sterically congested aryl
chlorides were capable of coupling with various cyclic and acyclic
aliphatic amines in high yields within no more than 1 h. Unfortu-
nately, piperidine proved less reactive relative to morpholine under
the present system (entry 3, Table 2). In addition, coupling with
mono-protected N-tosyl piperizine also afforded the desired
product in a decreased yield even at a longer reaction time, which
probably resulted from the low solubility of protected amine sub-
strate in 1,4-dioxane (entries 5 and 10, Table 2).
The sterically congested N,N-diarylamines have recently proven
mild and extremely active dehydrative agents for ester condensa-
tion process [22]. (IPr)Pd(pydc) 3 was also found to be the highly
active catalyst for coupling of the sterically demanding aryl chlo-
rides with aromatic amines (Table 3). As illustrated, most of the
sterically crowded diarylamines could be obtained in excellent
yields within no more than 30 min. In general, coupling reactions
were more sensitive to the bulkiness of aryl chloride substrates
than that of aromatic amines. With more bulky aryl chlorides, such
as 2,6-diisopropylphenyl chloride, a longer reaction time was
required for complete conversion (entries 11 and 12, Table 3).
Notably, using complex 3 as a catalyst, 1,10-biphenyl-2,20-diamine is
also capable of coupling with the sterically congested aryl chlorides
Fig. 2. Crystal structure of complex 3 with thermal ellipsoids drawn at the 50%
probability level and most H atoms (except those in the backbone of NHC) and co-
crystallizing solvent molecules have been omitted for clarity. Selected bond lengths
(A) and angles (ꢀ): Pd(1)eC(22) 2.005(2), Pd(1)eO(1) 2.0398(16), Pd(1)eO(3)
ꢀ
2.0407(15), Pd(1)eN(1) 1.9430(18); O(1)ePd(1)eN(1) 80.71(7), O(3)ePd(1)eN(1)
80.48(7), O(1)ePd(1)eO(3) 161.16(6), C(22)ePd(1)eN(1) 177.19(8), N(2)eC(22)eN(3)
104.98(19).
substrates because of the decreased steric propelment from the
bulky NHC ligand.
2.3. Catalytic studies of (NHC)Pd(pyc)Cl and (NHC)Pd(pydc)
complexes in BuchwaldeHartwig cross-coupling reactions
With these complexes in hand, their catalytic activities in
BuchwaldeHartwig coupling reactions were subsequently investi-
gated. In initial experiments using mesityl chloride and morpholine
as the coupling partners, NaOtBu and 1,4-dioxane were identified
to be the optimal base and solvent for the coupling reactions. At the
beginning, coupling reactions were performed at 50 ꢀC using the
conditions for PEPPSI catalysts reported by Organ and co-workers
[20]. However, relative to the control dimer [(IPr)PdCl2]2 and
Fig. 3. Coupling reactions between mesityl chloride and morpholine at 50 ꢀC with
[(IPr)PdCl2]2 dimer, IPr-PEPPSI, complexes 1 and 3 at 1.0 mol % catalyst loading (for
[(IPr)PdCl2]2 dimer, 0.5 mol % catalyst was used).
Fig. 4. Coupling reactions between mesityl chloride and morpholine at 100 ꢀC with
[(IPr)PdCl2]2 dimer, IPr-PEPPSI, complexes 1 and 3 at 1.0 mol % catalyst loading (for
[(IPr)PdCl2]2 dimer, 0.5 mol % catalyst was used).

Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
15
Table 1
BuchwaldeHartwig coupling catalyzed by complexes 1e4.a
Table 2
Cross-coupling of the sterically hindered aryl chlorides with aliphatic amines.a
Entry
NHCePd complex
Time (min)
Yield (%)b
Entry
1
ArCl
Amine
Product
Time (min) Yield (%)b
1
2
3
1
2
3
4
20
20
20
20
20
20
86
79
93
88
62
75
20
15
20
30
30
15
93
4
5c
6
[(IPr)PdCl2]2
IPr-PEPPSI
a
Reaction conditions: mesityl chloride (1 mmol), morpholine (1.1 mmol), NHCe
Pd complex (1 mol %), NaOtBu (1.5 mmol), 1,4-dioxane (3 mL), T 100 ꢀC.
2
3
4
5
6
92
b
Isolated yield on average of two runs.
0.5 mol % of [(IPr)PdCl2]2 dimer.
c
65
to provide the corresponding N,N0-diaryl substituted derivatives
(entries 13 and 14, Table 3), which have proven the essential
building blocks of a new class of secondary phosphine oxides
(SPOs) preligands developed recently by us [23].
95
Nolan and co-workers have demonstrated elegantly that
enhanced catalytic activity in the NHCePd complexes could be
achieved by accelerating the corresponding activation step from
NHCePdII complex to active [(NHC)Pd0] species [11]. From the
crystal X-ray diffraction data of complexes 3 and 4, there are two
adjacent acute angles (N(1)ePd(1)eO(1) and N(1)ePd(1)eO(3)
angles) in the molecular structures of complexes 3 and 4 (80.71ꢀ
and 80.79ꢀ, respectively) (Scheme 3), which caused an increased
ring strain in each cycle around the Pd center. As a result, high
reactivity of complexes 3 and 4 probably attributed to the increased
ring strain, which caused an accelerated activation step from the
corresponding NHCePdII complex to the [NHCePd0] species at
elevated temperature, whereas at low temperature complexes 3
and 4 were relatively inert toward activation by base due to the
58 (86)c
91
7
60
25
90d,e
firmly [O,N,O] chelating d-coordination. In addition, considering
that all of these NHCePd(II) complexes were transformed into the
same [(NHC)Pd0] species in solution, their dramatically different
reactivity were probably associated with effect of other ancillary
ligand. As a result, a balance of the pyridine-2,6-dicarboxylate
ligand detaching from and reattaching to the [NHCePd0] complex
in solution was not completely excluded yet [10,14]. When pyri-
dine-2,6-dicarboxylate ligand reattached to the Pd0 center, except
for stabilizing the [NHCePd0] species and lengthening the lifetime
of catalyst, it also probably induced a longer CcarbeneePd bond.
Using an in situ trapping experiment carried out in the presence
of PPh3, the activation of Pd(II) to Pd(0) for the complex 3 was
investigated with various bases used at 50 ꢀC and 100 ꢀC, respec-
tively (Fig. 5). Regardless of the activation route, a complex was
formed when NaOtBu was used as a base (Fig. 5(b) and (c)). The
existence of such a complex was confirmed by observation of the
formation of known (IPr)Pd(PPh3) (31P NMR 33.4 ppm) [24]. As
illustrated in Fig. 5, the activation rate of the precatalyst 3 at 100 ꢀC
(Fig. 5(c)) was obviously faster than that at 50 ꢀC (Fig. 5(b)).
Although the exact activation pathway was not known at this stage,
a mechanism proposed originally by Hartwig is probably involved,
in which the alkoxide base acts as an initiator and leads to the
formation of an alkoxidepalladium species [25]. Relatively, the use
of Cs2CO3 instead of NaOtBu did not give rise to the desired NHCe
Pd0 species at the same condition (Fig. 5(d)). Furthermore, the
catalytic effect of ancillary ligand was studied by ligand exchanging
experiments (Scheme 4). When additional 1 mol % PPh3 was pre-
sent in the coupling reaction between mesityl chloride and
8
91
9
40
90
10
11
12
120
37 (75)c
30
90
45
96
(continued on next page)

16
Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
Table 2 (continued )
The tube was then caped with a rubber septum and evacuated and
backfilled with argon. This sequence was repeated three times. 1,4-
Dioxane (10 mL) was injected through the septum. The mixture was
then stirred at a pre-heated oil bath (80 ꢀC) for 20 h. The reaction
mixture was cooled to room temperature and CH2Cl2 (25 mL)
added. After filtration via a short pad of celite, the filtrate was
condensed under vacuum and the residue was purified by flash
chromatography on silica gel to provide the desired 1and 2.
Complex 1: Yellow solid, yield 65%. M.p. > 280 ꢀC. 1H NMR
Entry
13
ArCl
Amine
Product
Time (min) Yield (%)b
60
86
14
15
20
95
87
(400 MHz, CDCl3):
5H), 7.18 (s, 2H), 2.95 (m, 4H), 1.41 (d, 12H), 1.13 (d, 12H). 13C NMR
(75 MHz, CDCl3): 172.8, 157.2, 151.2, 146.8, 146.5, 139.2, 134.5,
d 8.55 (d, 1H), 7.80 (t, 2H), 7.49 (t, 2H), 7.34 (m,
d
15
130.4, 126.7, 126.2, 125.2, 124.1, 28.6, 26.2, 22.9. Anal. Calcd for
C33H40ClN3O2Pd: C, 60.74; H, 6.18; N, 6.44. Found: C, 60.67; H, 6.10;
N, 6.38. MS (ESI): m/z 652 (Mþ þ H).
Complex 2: Yellow solid, yield 56%. M.p. > 280 ꢀC. 1H NMR
a
Reaction conditions: aryl chloride (1 mmol), amine (1.1 mmol), 3 (1 mol %),
NaOtBu (1.5 mmol), 1,4-dioxane (3 mL), T 100 ꢀC.
(400 MHz, CDCl3):
5H), 4.11 (s, 4H), 3.44 (m, 4H), 1.40 (d, 12H), 1.12 (d, 12H). 13C NMR
(75 MHz, CDCl3): 187.6,172.7,151.2,147.7,146.4,139.2,134.6,129.6,
d 8.51 (d, 1H), 7.78 (t, 2H), 7.40 (t, 2H), 7.28 (m,
b
Isolated yield on average of two runs.
Yield was reported in the parentheses using 1,4-dioxane (10 mL) for 120 min.
2 mol % of complex 3 were used.
2 mmol morpholine were used.
c
d
d
e
126.6, 126.2, 124.5, 53.7, 28.7, 26.6, 23.8. Anal. Calcd for
C33H42ClN3O2Pd: C, 60.55; H, 6.47; N, 6.42. Found: C, 60.66; H, 6.49;
N, 6.46. MS (ESI): m/z 654 (Mþ þ H).
morpholine, only trace amount coupling product was obtained
under the aforementioned standard conditions (Scheme 4). In
contrast, by adding
increased yield (91%) was achieved in the coupling reaction cata-
lyzed by [(IPr)PdCl2]2 dimer.
4.3. General procedure for preparation of complexes 3 and 4
(method B)
1 mol % pyridine-2,6-dicarboxylic acid,
In air, to a Schlenk tube that closed with a screw cap fitted with a
septum and was equipped with a magnetic stir bar were added in
turn [(NHC)PdCl2]2 dimer (0.5 mmol, 568 mg), Cs2CO3 (2.6 mmol,
848 mg), and pyridine-2,6-dicarboxylate (2.5 mmol, 418 mg). The
tube was then caped with a rubber septum and evacuated and
backfilled with argon. This sequence was repeated three times. 1,4-
Dioxane (10 mL) was injected through the septum. The mixture was
then stirred at a pre-heated oil bath (80 ꢀC) for 20 h. The reaction
mixture was cooled to room temperature and CH2Cl2 (25 mL)
added. After filtration via a short pad of celite, the filtrate was
condensed under vacuum and the residue was purified by flash
chromatography on silica gel to provide the desired 3 and 4.
Complex 3: Yellow solid, yield 85%. M.p. > 280 ꢀC. 1H NMR
3. Conclusion
In conclusion, we have developed a new class of well-defined
NHCePd complexes incorporating pyridine-2-carboxylate or pyri-
dine-2,6-dicarboxylate as an ancillary ligand. Among them, com-
plex (IPr)Pd(pydc) 3 showed an obviously enhanced catalytic
potential in the BuchwaldeHartwig reactions of the sterically
hindered coupling substrates at elevated temperature. Further ap-
plications of this type of air-stable NHCePd complexes for other
cross-coupling reactions are currently underway.
4. Experimental section
(400 MHz, CDCl3):
4H), 7.22 (s, 2H), 2.70 (m, 4H), 1.39 (d, 12H), 1.16 (d, 12H). 13C NMR
(75 MHz, CDCl3): 171.9, 164.0, 147.9, 146.6, 140.4, 134.1, 130.5,
d 7.95 (t, 1H), 7.70 (d, 2H), 7.51 (t, 2H), 7.36 (m,
4.1. General comments
d
127.0, 125.2, 124.2, 28.7, 25.6, 23.1. Anal. Calcd for C34H39N3O4Pd: C,
61.86; H, 5.96; N, 6.37. Found: C, 61.67; H, 5.90; N, 6.38. MS (ESI): m/
z 660 (Mþ þ H).
All cross-coupling reactions were carried out in dry Ar2 using
the standard Schlenk technique unless indicated. All solvents were
dried according to the common methods prior to use. Aryl chlorides
were used as received from commercial availability or prepared via
the classical Sandmeyer reactions from the corresponding aryl
amines. Aliphatic and aryl amines were used as received from
commercial availability. 1H and 13C Nuclear Magnetic Resonance
(NMR) spectra were recorded on a Bruker AV400 spectrometer at
ambient temperature in CDCl3 (Cambridge Isotope Laboratories,
Inc). ESI mass spectra were recorded on Thermo Finnigan LCQ
Advantage spectrometers. Elemental analyses were performed on a
PerkineElmer 240C analyzer. Melt points of compounds were
recorded with uncorrected thermometers. Flash column chroma-
tography was performed on silica gel 60 (230e400 mesh).
Complex 4: Yellow solid, yield 83%. M.p. > 280 ꢀC. 1H NMR
(400 MHz, CDCl3):
4H), 4.13 (s, 4H), 3.23 (m, 4H), 1.44 (d, 12H), 1.30 (d, 12H). 13C NMR
(75 MHz, CDCl3): 192.9, 171.9, 147.7, 140.4, 134.0, 130.0, 127.0,
d 7.93 (t, 1H), 7.70 (d, 2H), 7.43 (t, 2H), 7.30 (m,
d
124.7, 53.9, 28.8, 26.0, 23.9. Anal. Calcd for C34H41N3O4Pd: C, 61.67;
H, 6.24; N, 6.35. Found: C, 61.67; H, 6.20; N, 6.41. MS (ESI): m/z 662
(Mþ þ H).
4.4. General procedure for the BuchwaldeHartwig amination
reactions
In air, to a Schlenk tube that closed with a screw cap fitted with a
septum and was equipped with a magnetic stir bar were added in
turn complex 3 (0.01 mmol, 7 mg), and NaOBut (1.5 mmol, 144 mg).
The tube was then caped with a rubber septum and evacuated and
backfilled with argon. This sequence was repeated three times. Aryl
chloride (1.0 mmol) and amine (1.1 mmol) was injected through the
septum by syringe, followed by addition of dry 1,4-dioxane (10 mL).
The mixture was then stirred at a pre-heated oil bath (100 ꢀC) for
the indicated time. The reaction mixture was cooled to room
4.2. General procedure for preparation of complexes 1 and 2
(method A)
In air, to a Schlenk tube that closed with a screw cap fitted with a
septum and was equipped with a magnetic stir bar were added in
turn NHC$HCl (1.1 mmol, 468 mg), PdCl2 (1.0 mmol, 177 mg),
Cs2CO3 (5 mmol, 1.63 g), and 2-nicotinic acid (1.1 mmol, 136 mg).

Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
17
Table 3
Cross-coupling of the sterically hindered aryl chlorides with anilines.a
Entry
1
ArCl
Aniline
Product
Time (min)
10
Yield (%)b
98
2
3
10
10
99
99
4
5
10
15
98
97
6
15
15
20
25
20
60
97
96
97
98
94
7
8
9
10
11
95c,d
(continued on next page)

18
Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
Table 3 (continued )
Entry
ArCl
Aniline
Product
Time (min)
60
Yield (%)b
12
13
54c,d
60
60
79e
14
74e
a
Reaction conditions: ArCl (1 mmol), amine (1.1 mmol), complex 3 (1 mol %), NaOtBu (1.5 mmol), 1,4-dioxane (3 mL), T 100 ꢀC.
Isolated yield on average of two runs.
2 mol % of 3 were used.
2 mmol ArNH2 were used.
2.0 equiv ArCl per equivalent ArNH2 were used.
b
c
d
e
Scheme 3. Precatalyst activation and possible balance between (NHC)Pd0 and ancillary ligand.
Fig. 5. Generation of Pd(0) species monitored by 31P NMR spectra. (a) 31P NMR spectra of free PPh3; (b) Base: NaOtBu, reaction temperature: 50 ꢀC; (c) Base: NaOtBu, reaction
temperature: 100 ꢀC; (d) Base: Cs2CO3, reaction temperature: 100 ꢀC.

Y.-J. Li et al. / Journal of Organometallic Chemistry 737 (2013) 12e20
19
Scheme 4. Effect of ancillary ligands on the coupling reaction.
Table 4
Crystallographic data for complexes 1e4.
1
2
3
4
Chemical formula
Space group
Cryst syst
C
33H40ClN3O2Pd
C33H42ClN3O2Pd
Pnma
Orthorhombic
15.965(4)
21.221(5)
11.055(3)
90.00
90.00
90.00
4
1.462
0.89
1696
1.92e27.87
39,520
4586/0.0487
230/0
C34H39N3O4Pd
Pe1
Triclinic
10.268(2)
16.765(3)
17.991(4)
91.540(5)
90.425(5)
90.179(6)
4
1.416
0.64
1368
1.68e27.86
35,544
C34H41N3O4Pd
P2(1)2(1)2(1)
Orthorhombic
13.181(4)
14.373(4)
20.024(6)
90.00
90.00
90.00
4
1.457
0.81
1712
1.74e27.91
40,028
Pnma
Orthorhombic
16.029(2)
21.122(3)
10.9821(16)
90.00
90.00
90.00
ꢀ
a, A
ꢀ
b, A
ꢀ
c, A
ꢀ
ꢀ
ꢀ
a
,
b
,
g
,
Z
4
Dcalc., g cmꢁ3
1.469
0.89
1688
1.9e27.9
34,483
4565/0.035
230/0
m
(Mo), mmꢁ1
F(000)
q
range, ꢀ
No. of reflns. collected
No. of unique reflns/Rint
No. of params/restraints
14,564/0.0466
773/0
9074/0.0723
442/0
Final R indices [I > 2
s(I)]
R1 ¼ 0.0293, wR2 ¼ 0.0708
R1 ¼ 0.0329, wR2 ¼ 0.0728
1.064
1.00 and ꢁ0.77
R1 ¼ 0.0363, wR2 ¼ 0.0808
R1 ¼ 0.0396, wR2 ¼ 0.0828
1.111
1.07 and ꢁ0.83
R1 ¼ 0.0363, wR2 ¼ 0.0713
R1 ¼ 0.0466, wR2 ¼ 0.0749
1.060
0.69 and ꢁ0.98
R1 ¼ 0.0443, wR2 ¼ 0.0954
R1 ¼ 0.0477, wR2 ¼ 0.0974
1.037
0.61 and ꢁ0.76
R indices (all indices)
Goodness-of-fit on F2
ꢀꢁ3
Peak/hole, e A
temperature and CH2Cl2 (25 mL) added. After filtration via a short
pad of celite, the filtrate was condensed under vacuum and the
residue was purified by flash chromatography on silica gel to pro-
vide the desired coupling products. Yields of isolated products were
reported in Tables 1e3.
Appendix A. Supplementary material
CCDC 873328e873331 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
4.5. X-ray diffraction analysis
Appendix B. Supplementary data
Suitable crystals of 1e4 for X-ray diffraction were obtained by
slow diffusion of n-pentane into dichloride methane solution.
Crystallographic data was collected on a Bruker SMART CCD area
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.jorganchem.2013.03.021.
detector diffractometer with graphite-monochromated Mo K
a
ra-
ꢀ
diation (l 0.71073 A). Diffraction measurements were made at
References
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