A heteroleptic palladium(II) complex containing a bidentate carbene/amido ligand and 3-(trifluoromethyl)-5-(2-pyridyl)pyrazolate: Fast catalyst activation in the heck coupling reaction

Article abstract of DOI:10.1021/om100819q

A multicomponent reaction between PdCl₂, fppzH, and [LH ¹H²]Cl in the presence of K₂CO₃ (L = bidentate amido/carbene; fppzH = 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole) allows the preparation of PdL(fppz) in good yield. The analogous platinum complex, however, needs to be prepared by a two-step procedure. The new palladium(II) and platinum(II) complexes were characterized by 1D and 2D NMR spectroscopy, X-ray crystallography, electrospray ionization mass spectrometry, and elemental analyses. X-ray photoelectron spectroscopy indicates the high electron richness of the palladium atoms in PdL(fppz). These palladium complexes are efficient in catalyzing Heck coupling reactions with challenging aryl halide substrates. The catalyst activation in PdL(fppz) is significantly faster than that in cis-PdL₂. A mere 0.5 mol % of palladium loading is enough to afford a 82% yield of coupled product from 4-chloroanisole and styrene in 24 h.

Full text of DOI:10.1021/om100819q

Organometallics 2010, 29, 6473–6481 6473
DOI: 10.1021/om100819q
A Heteroleptic Palladium(II) Complex Containing a Bidentate Carbene/
Amido Ligand and 3-(Trifluoromethyl)-5-(2-pyridyl)pyrazolate:
Fast Catalyst Activation in the Heck Coupling Reaction
Ming-Han Sie, Yuan-Hsin Hsieh, Yi-Hua Tsai, Jia-Rong Wu, Shih-Jung Chen,
P. Vijaya Kumar, Jenn-Huei Lii, and Hon Man Lee*
Department of Chemistry, National Changhua University of Education, Changhua 50058,
Taiwan, Republic of China
Received August 22, 2010
A multicomponent reaction between PdCl2, fppzH, and [LH1H2]Cl in the presence of K2CO3 (L=
bidentate amido/carbene; fppzH = 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole) allows the preparation
of PdL(fppz) in good yield. The analogous platinum complex, however, needs to be prepared by a two-
step procedure. The new palladium(II) and platinum(II) complexes were characterized by 1D and 2D
NMR spectroscopy, X-ray crystallography, electrospray ionization mass spectrometry, and elemental
analyses. X-ray photoelectron spectroscopy indicates the high electron richness of the palladium atoms
in PdL(fppz). These palladium complexes are efficient in catalyzing Heck coupling reactions with
challenging aryl halide substrates. The catalyst activation in PdL(fppz) is significantly faster than that
in cis-PdL2. A mere 0.5 mol % of palladium loading is enough to afford a 82% yield of coupled product
from 4-chloroanisole and styrene in 24 h.
Chart 1. Bidentate Palladium and Platinum Complexes
Introduction
The palladium-catalyzed Heck reaction is a powerful tool
for the preparation of arylated alkenes in fine chemical
synthesis.1-5 In comparison to aryl bromides and iodides,
aryl chlorides are attractive substrates for Heck reactions in
industrial applications because of their low cost and wide
availability. However, these substrates, especially those de-
activated aryl chlorides, are generally unreactive and typi-
cally harsh reaction conditions are required for their feasible
utilization.6 Palladium complexes with bulky electron-rich
phosphine ligands and P-containing palladacycles have de-
monstrated excellent Heck coupling activities with deactivated
aryl chloride substrates.7-9 The air sensitivity and high cost of
these ligands are, however, their major drawbacks. N-hetero-
cyclic carbene (NHC) ligands have been proven to be highly
versatile in a wide range of coupling reactions.8,10-17 However,
the activity of catalysts based on NHC ligands has been mostly
limited to activated and nonactivated substrates.8,18-34 In a
recent work, we demonstrated that the palladium(II) NHC
complexes cis-1 are highly promising precatalysts for Heck
*To whom correspondence should be addressed. Tel: þ886 4 7232105,
ext. 3523. Fax: þ886 4 7211190. E-mail: leehm@cc.ncue.edu.tw.
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2010 American Chemical Society
Published on Web 11/02/2010
pubs.acs.org/Organometallics

6474 Organometallics, Vol. 29, No. 23, 2010
Scheme 1. Multicomponent Synthesis of Pd(L)(fppz) Complexes
Sie et al.
Scheme 2. Sequential Synthesis of the Pt(L)(fppz) Complex
reactions (Chart 1), capable of utilizing deactivated aryl chlo-
rides as substrates.35 In addition to the robust NHC donor,
the anionic amide group of the chelate ligand can impart a
high electron density on the metal center,36-41 thus favoring
the oxidative addition of a strong C-Cl bond.42,43 The
palladium(II) complex cis-1 is indeed a good precursor for
active palladium(0) species. For deactivating aryl chlorides
and bulky aryl bromides substrates, cis-1 is even more
efficient than its palladium(0) precatalyst.35 However, cis-1
needs a long catalyst activation time; in the reaction between
styrene and 4-chloroacetophenone, it takes about 1 h. The
formation of active species from cis-1 should involve ligand
dissociation, allowing subsequent substrate coordination, and
this process is slow due to the two strongly binding bidentate
NHC/amide ligands. We envisioned that replacement of one
of the bidentate carbene/amide ligands with a similar anionic
but weaker binding ligand may result in a more efficient
catalyst with a faster activation period. Hence, the known
bidentate fppz ligand (fppz=3-(trifluoromethyl)-5-(2-pyridyl)-
pyrazolate) consisting of pyrazolate and pyridine functional-
ities was selected. Herein, we report on our successful attempt
in carrying out a straightforward multicomponent reaction
(MCR) to obtain pure palladium complex 3. Such a fine-tuned
heteroleptic complex shows promising catalytic activity in
Heck coupling reactions with a range of aryl bromides and
chloride substrates.
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Results and Discussion
Preparation of Palladium(II) Carbene Complexes. The new
palladium complexes PdL(fppz) (3a-c) were successfully
synthesized by a one-pot reaction between PdCl2, [LH1H2]-
Cl (2a-c) (H1=NH proton; H2=NCHN proton), fppzH,
and K2CO3 as base in DMF at 50 °C (Scheme 1). Such MCR
protocol is desirable due to simplicity in operation, time
savings, and reduced waste. The reaction is highly chemose-
lective, as the known homoleptic complex 1 or Pd(fppz)2 was
not observed in a noticeable amount. After thorough wash-
ing with methanol, pure solids of 3a-c were obtained with
good yields ranging from 64 to 77%. These compounds are
air-stable in the solid form and readily soluble in halogenated
solvents. The three new compounds are neutral Pd(L)(fppz)
complexes which have been characterized by 1H and 13C{1H}
NMR spectroscopy, elemental analyses, electrospray ioniza-
tion mass spectrometry (ESI-MS), and X-ray crystallo-
graphic studies. The successful chelation of the bidentate
carbene and fppz ligands are inferred by the disappearance of
the original H1, H2, and NH protons on the [LH1H2]Cl and
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Article
Organometallics, Vol. 29, No. 23, 2010 6475
Table 1. Crystallographic Data of 3a-c and 5
3a
3b
3c
5
empirical formula
formula wt
cryst syst
C
21H17F3N6OPd
C27H21F3N6OPd
608.90
triclinic
P1
12.7589(2)
14.0925(2)
14.1825(3)
92.1710(10)
95.8850(10)
103.8680(10)
2457.54(7)
150(2)
C31H23F3N6OPd 0.25CH2Cl2
C21H17F3N6OPt
621.50
triclinic
P1
7.837(4)
11.700(6)
12.451(6)
74.083(15)
88.881(15)
71.196(14)
1036.3(9)
150(2)
3
532.81
triclinic
P1
680.19
triclinic
P1
space group
˚
a, A
7.7528(4)
11.5739(5)
12.4410(6)
74.197(2)
89.651(2)
72.023(2)
1017.99(8)
150(2)
12.526(2)
12.809(2)
19.525(4)
99.602(4)
95.938(4)
111.943(4)
2817.6(9)
150(2)
˚
b, A
˚
c, A
R, deg
β, deg
γ, deg
3
˚
V, A
T, K
Z
2
5222
290
0.0375
0.0995
4
12 492
685
0.0301
0.0822
P
4
10 762
781
0.0544
0.1568
2
5224
290
0.0450
0.1044
no. of unique data
no. of params refined
R1a (I > 2σ(I ))
wR2b (all data)
P
P
P
a R1 = (||Fo| - |Fc||)/ |Fo|. b wR2 = [ (|Fo|2 - |Fc|2)2/ (Fo2)]1/2
.
˚
Table 2. Selected Bond Distances (A) and Angles (deg) of 3a-c
fppzH ligand precursors. The diastereotopic nature of the
methylene protons further confirms the bidentate chelation
of the carbene ligand. The assignments of these diastereo-
topic signals are assisted by acquiring their HMBC spectra
(see Figure 1S in the Supporting Information for the HMBC
spectrum of 3c). For example, the cross-peak analyses in 3c
established that the doublets at 4.40 and 5.45 ppm are
attached to the same carbon adjacent to the CdO group,
whereas those at 6.00 and 6.71 ppm belong to the methylene
protons adjacent to the naphthyl group. The carbene signals
for 3a-c are located easily at ca. 156 ppm, since in each case
the quaternary carbon uniquely correlates with all the methy-
lene protons in its HMBC spectrum. These carbene signals are
shifted upfield compared with those of cis (∼164 ppm) and
trans (∼170 ppm) isomers of the bis-bidentate complex 1.36 In
fact, theseupfieldcarbene resonances indicate the stereochem-
istry of these complexes as depicted in Scheme 1, since carbene
resonances at ca. 150 ppm are characteristic for a palladium-
(II) complex with carbene trans to a pyridine moiety.36,44-46
Such stereochemistry was eventually confirmed by an X-ray
diffraction study. Thus, the MCR is highly stereoselective,
producing only the isomer with the carbene moiety trans to
the pyridine (A). The absence of the other isomer with the two
ligands in cis positions (B) can be revealed from the computa-
tional studies with the B3LYP functional. In the gas phase,
complexes 3a-c in formA arethermodynamically muchmore
stable than the other isomeric forms by 13.9, 9.9, and 9.9 kcal/
mol, respectively. It is worth mentioning that the stereochem-
istry in A with a trans disposition of the two neutral atoms and
the two anionic donors is relevant to that in the PEPSSI
complexes reported by Organ et al.17,45,46
and 5a
3a
3bb
3cb
5
M1-C1
1.969(3)
2.046(3)
2.122(3)
1.998(3)
1.957(2)
1.977(5)
2.058(5)
2.132(4)
2.009(4)
85.2(2)
1.968(7)
2.049(6)
2.108(5)
1.996(6)
85.9(3)
98.6(3)
97.1(2)
78.5(2)
176.8(3)
175.4(2)
M1-N3
2.0404(18)
2.1303(18)
2.0098(18)
84.82(8)
98.41(5)
97.05(7)
79.54(7)
175.93(8)
175.60(7)
M1-N4
M1-N5
C1-M1-N3
C1-M1-N5
N3-M1-N4
N4- M1-N5
C1-M1-N4
N3-M1-N5
85.77(13)
97.55(12)
97.89(11)
78.84(11)
175.76(13)
176.52(11)
98.2(2)
97.64(18)
78.97(18)
177.1(2)
176.38(18)
a M = Pd for 3a-c and M = Pt for 5. b Only data from one of the two
independent molecules are given.
target analogous Pt complex was successfully prepared
in sequential steps. The fppzH ligand is introduced to
the platinum metal first by preparing the known complex
Pt(fppzH)Cl2 (Scheme 2). A subsequent carbene transfer
reaction between Ag(LH1)Cl (4) and Pt(fppzH)Cl2 in the
presence of K2CO3 affords Pt(L)(fppz) complex 5 in 44%
yield (Scheme 2). The silver complex 4 was straightforwardly
prepared by the reaction of Ag2O and 2a in DMF. Similar
silver carbene complexes bearing the carbene/amide ligands
have been reported previously.47,48 Complex 5 is air-stable
with average solubility in halogenated solvents. The spectro-
scopic data of 5 are essentially similar to those of its palladium
analogue 3a. The carbene signal is observed at 156.3 ppm,
comparing favorably with that of 155.5 ppm in 3a.
Crystallographic Studies. The structures of Pd complexes
3a-c and the Pt complex 5 have been successfully determined
by X-ray diffraction studies. Crystallographic data and their
selected bond distances and angles are given in Table 1 and 2,
respectively. Figures 1 and 2 give their thermal ellipsoid plots,
confirming the trans disposition of the carbene and pyridine
moieties. The geometric parameters of the Pd complex 3a and
its analogous Pt complex 5 are highly comparable to each
other. All these complexes adopt a distorted-square-planar
coordination geometry. The bite angle of the carbene is greater
than that of fppz ligand (ca. 85° vs 79°). In each complex, the
three M-N distances are significantly different in length. In
Preparation of an Analogous Platinum(II) Complex. To
investigate whether the MCR protocol is also suitable for the
preparation of analogous platinum complexes, the reaction
between K2PtCl4, ligand precursor 2a, fppzH, and base was
carried out. However, this failed to yield a desirable product.
The 1H NMR spectrum of the reaction mixture shows
the formation of Pt(fppzH)Cl2 and unreacted 2a. Instead, the
(44) Grundemann, S.; Albrecht, M.; Kovacevic, A.; Faller, J. W.;
Crabtree, R. H. Dalton Trans. 2002, 2163.
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E. A. B.; O0Brien, C. J.; Valente, C. Chem. Eur. J. 2006, 12, 4749.
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G. A.; Lough, A.; Hopkinson, A. C.; Organ, M. G. Chem. Eur. J. 2006,
12, 4743.
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Inorg. Chim. Acta 2008, 361, 2973.
(48) John, A.; Ghosh, P. Dalton Trans. 2010, 39, 7183.

6476 Organometallics, Vol. 29, No. 23, 2010
Sie et al.
Figure 1. Molecular structures of 3a (left) and 5 (right) with 50% probability ellipsoids. Hydrogen atoms have been omitted for clarity.
Figure 2. Molecular structures of 3b (left) and 3c (right) with 50% probability ellipsoids. Only one of their independent molecules in an
asymmetric unit is shown. Hydrogen atoms have been omitted for clarity.
Table 3. Mizoroki-Heck Reactiona
entry
cat.
3b
time
2 h
2 h
2 h
2 h
2 h
2 h
2 h
temp, °C
heating
yield, %
6:60
1
2
3
4
5
6
7
8
9
120
130
140
140
140
140
160
140
140
conventional
conventional
conventional
conventional
conventional
conventional
conventional
MW
0
90
96
98
96
89
97
98
15
3b
92:8
93:7
94:6
93:7
94:6
94:6
91:9
100:0
cis-1b
3a
3b
3c
3b
3b
cis-1b
15 min
15 min
MW
a Conditions: 1 mmol of aryl halide, 1.4 mmol of alkene, 1.1 mmol of NaOAc, 2 g of TBAB, 0.5 mol % of [Pd] cat., 15 min-2 h, 120-160 °C. Yields
and selectivity were determined by NMR using 1,3,5-trimethoxybenzene as internal standard.
general, the metal-pyridine bond trans to the carbene moiety
341.7 and 336.6 eV in cis-1b, in support of our prediction that
the fppz ligand is less basic than the carbene ligand. Intrigu-
ingly, these binding energies in 3a-c and cis-1b are compar-
able to those in elemental Pd(0) (340.5 and 335.1 eV)49 and
Pd0(LH1)2(MA) (LH1 derived from 2 with R = Ph) (MA =
maleic anhydride) (340.7 and 335.4 eV) and thus are very
low for the Pd(II) atoms,50 reflecting the strong electron-
donating effect of the bidentate ligands. For comparison, the
corresponding binding energies in a Pd(II) complex with a
˚
is the longest (M1-N4 distance ∼2.12 A), followed by the
˚
metal-amido bond (M1-N3 distance ∼2.05 A). The metal-
˚
pyrazole bond is the shortest (M1-N5 distance ∼2.00 A).
˚
The Pd-C distances in 3a-c are ca. 1.97 A: that is, shorter
than that in trans-1b (2.020(4) A) but comparable to that in
˚
cis-1b (1.966(2) A).36 The Pd1-N3 distances, in contrast, are
˚
˚
shorter than that of 2.081(1) A in cis-1b but similar to that of
36
˚
2.051(4) A in trans-1b.
X-ray Photoelectron Spectroscopy (XPS). The electronic
properties of 3a-c were investigated by XPS. The binding
energies of Pd electrons in the core 3d3/2 and the 3d5/2 orbitals
in 3a-c are essentially identical at about 342.6 and 337.4 eV,
respectively. These values are somewhat higher than those of
(49) Moulder, J. F.; Stickle, W. F.; Sobol, P. E.; Bomben, K. D.,
Handbook of X-ray Photoelectron Spectroscopy; Perkin-Elmer: Waltham,
MA, 1992.
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Article
Organometallics, Vol. 29, No. 23, 2010 6477
In particular, the highly deactivating substrate 5-bromo-
1,2,3-trimethoxybenzene can be utilized to generate the
coupled product in 72% yield (entry 5). Changing styrene
to n-butyl acrylate as a coupling partner results in, however,
a lower yield of coupled products (entries 13-15). (E)-
3,4,5,40-Tetramethoxystilbene (12), designated as DMU-
212, is a strong candidate for antitumor applications.54
Entry 12 shows that it can be prepared in 59% yield with
only a 0.5 mol % Pd precatalyst loading. Our protocol is
much more cost-effective than the reported procedure
requiring 40 mol % of Pd loading.54 Hindered aryl bro-
mides with two ortho substituents can also be coupled
effectively (entries 7, 10 and 16, 17). For example, decent
53 and 55% yields of 11 and 17, respectively, can be
achieved from the very bulky 1-bromo-2,4,6-triisopropyl-
benzene (entries 10 and 17). Complex 3b delivers somewhat
better yields of coupled products than cis-1b, as indicated
by entry 5 vs 6 and 10 vs 11. Lowering the precatalyst
loading below 0.5 mol % led to inferior yields of products,
as indicated in entries 1-3 and 7-9.
Figure 3. The time-yield curves of 3b vs cis-1b in the Heck
coupling reaction of 4-chloroacetophone and styrene.
bidentate carbene ligand with abnormal binding are much
higher at ca. 348.0 and 342.6 eV.51
The catalyst system of 3b is also effective for a range of aryl
chlorides (Table 5). Excellent yields of coupled products can
be achieved within 2 h with activated aryl chlorides (entries 1,
2, 5, 6, 19, 20, and 22-25). A longer reaction time of 12 h is
needed for the nonactivated substrate chlorobenzene, gen-
erating coupled products with styrene and n-butyl acrylate in
87 and 68% yields, respectively (entries 12 and 26). Different
isomers of chlorotoluene can also be coupled with styrene
(entries 13, 15, and 16). A 60% yield of coupled product can
be achieved from 4-chlorotoluene, whereas in contrast the
yield drops to 37% with 2-chlorotoluene, indicating the
significance of steric hindrance for aryl chloride substrates.
The catalyst system is also capable of employing deactivated
aryl chlorides as coupling partners (entries 17, 18 and 29, 30).
A reasonable 66% of coupled product can be obtained from
4-chloroanisole and styrene (entry 17). Further prolonging
the reaction time to 24 h affords a good yield of 82% (entry
18). Entry 9 vs entry 11 again illustrates the faster activation
of 3b such that a 94% yield of coupled product can already be
obtained already from 4-chlorobenzonitrile in 1 h, whereas
catalyst activation of cis-1b was not yet completed. Never-
theless, a similar level of yields was achieved from cis-1b and
3b in the long run (entries 13 vs 14 and 20 vs 21). The catalytic
data suggest that 3b and cis-1b share a similar catalytic path-
way via the plausible 14-electron active species [Pd0L]-.
However, replacement with the weaker binding fppz ligand in
3b leads to a faster catalyst activation because of the more
facile ligand dissociation. The optimal precatalyst loading
is again 0.5 mol %, as reduction of the palladium amount
to 0.1 or 0.2 mol % led to greatly inferior yields (entries 2-4
and 6-8).
Catalytic Studies. The catalytic performance of complexes
3a-c in Heck coupling reactions of aryl halides with alkenes
was studied. The reaction between 4-chloroacetophenone and
styrene was chosen as the benchmark reaction for initial
investigation. We employed our previous conditions of light
palladium loading of 0.5 mol % and the cheap ionic liquid tetra-
n-butylammonium bromide (TBAB) as solvent (Table 3).35
Entry 1 shows that no coupling activity was observed at 120 °C.
An increment of just 10 °C results in a surge of coupled product.
The phenomenon, also demonstrated in cis-1b previously, can
be explained by the feasible formation of an active Pd0 species,
suchas[Pd0L]-, only above a critical temperature. As shown by
entries 2, 5, and 7, the best temperature for the catalytic reaction
is at 140 °C, producing an excellent yield of 96% coupled
product in 2 h. Complexes 3a,b and cis-1b essentially produced
the same overall yields, reflected by entries 3-5. Complex 3c
with N-naphthylmethyl substitutions, in contrast, gave poorer
yields (entry 6).
The time-yield relationship of cis-1b vs 3b in the initial 2 h
was studied. Figure 3 clearly illustrates the success of our
design principle by using a weaker binding ligand of the fppz
ligand in 3b, as cis-1b needs about 1 h of catalyst activation,
whereas the process takes just ca. 30 min for 3b.
Microwave-assisted synthesis is a valuable technique
for organic chemists because the radiation can enhance the
reaction rate and in many cases improve product yields as
well.52,53 Entry 8 in Table 3 shows that 3b affords an excellent
yield of 98% coupled product in just 15 min with microwave
heating. In sharp contrast, cis-1b affords a much lower yield
of 15% under identical conditions (entry 9), confirming once
again that catalyst activation of 3b is much faster.
Conclusions. The multicomponent reaction between the
imidazolium ligand precursor fppzH and PdCl2 is highly
chemo- and regioselective, affording pure Pd(L)(fppz) in
good yield. The geometrical isomer with carbene and pyr-
idine groups trans to each other was thermodynamically
much more stable. For the preparation of the analogous
platinum(II) complex, however, a two-step reaction con-
sisting of a carbene transfer step has to be employed. We
demonstrated that fine tuning of palladium precatalyst with
a slightly weaker binding fppz ligand replacing one of the two
Next, we tested the activity of 3b in utilizing hindered
aryl bromide substrates (Table 4). A general condition
was established involving 0.5 mol % of 3b at 140 °C in 12
h. Indeed, the catalyst system is capable of delivering good
trans product yields with a range of challenging aryl bromide
substrates. Generally, good yields of coupled products can be
obtained from the reactions between deactivated aryl bromides
bearing methoxyl groups and styrene (entries 1, 4, and 5).
(51) Heckenroth, M.; Kluser, E.; Neels, A.; Albrecht, M. Angew.
Chem., Int. Ed. 2007, 46, 6293.
(52) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250.
(53) Leadbeater, N. E. Chem. Commun. 2005, 2881.
(54) Cross, G. G.; Eisnor, C. R.; Gossage, R. A.; Jenkins, H. A.
Tetrahedron Lett. 2006, 47, 2245.

6478 Organometallics, Vol. 29, No. 23, 2010
Table 4. Heck Reactions of Bulky Aryl Bromidesa
Sie et al.
a Conditions: 1 mmol of aryl halide, 1.4 mmol of alkene, 1.1 mmol of NaOAc, 2 g of TBAB, 0.50 mol % of [Pd] cat. unless stated otherwise, 140 °C,
12 h, isolated yields. b 0.20 mol % of [Pd] cat. c 0.10 mol % of [Pd] cat.
bidentate carbene/amido ligands in cis-1 is feasible, leading
to faster catalyst activation. The new catalyst is a highly
effective precatalyst for Heck coupling reactions with a wide
range of aryl halides, including deactivated aryl chloride
substrates.
Experimental Section
General Procedure. All manipulations were performed under
a dry nitrogen atmosphere using standard Schlenk techniques.
Solvents were dried with standard procedures. Starting chemicals
were purchased from commercial source and used as received.

Article
Organometallics, Vol. 29, No. 23, 2010 6479
Table 5. Heck Reactions of Aryl Chloridesa
a Conditions: 1 mmol of aryl halide, 1.4 mmol of alkene, 1.1 mmol of NaOAc, 2 g of TBAB, 0.50 mol % of [Pd] cat. unless stated otherwise, 1-24 h,
140 °C, isolated yields. b 0.20 mol % [Pd] cat. c 0.10 mol % [Pd] cat.

6480 Organometallics, Vol. 29, No. 23, 2010
Sie et al.
cis-1b,36 2,36 fppzH,55 and Pt(fppzH)Cl256 were prepared accord-
diffusion of diethyl ether into a dichloromethane solution of
the solid.
1
ing to the literature procedure. H, and 13C{1H} NMR spectra
wererecorded at 300.13 and 75.48 MHz, respectively, on a Bruker
AV-300 spectrometer. The chemical shifts for 1H and 13C spectra
were referenced by the residual solvent signals relative to tetra-
methylsilane at 0 ppm. Elemental analysis was performed on a
Thermo Flash 2000 CHN-O elemental analyzer. Microwave
irradiation experiments were conducted in a Milestone Start S
microwave system. Reaction times refer to hold times at the
temperature indicated in Table 5. The temperature was measured
with an IR sensor on the outside of the reaction vessel. ESI-MS
was carried out on a Finnigan/Thermo Quest MAT 95XL mass
spectrometer at National Chung Hsing University (Taiwan).
X-ray photoelectron spectroscopy was performed on a ESCA
PHI 1600 system using Mg KR radiation (hν = 1253.6 eV) at
National Tsing Hua University (Taiwan).
Synthesis of 3a. To a 50 mL Schlenk flask containing a mix-
ture of PdCl2 (0.20 g, 1.13 mmol), 2a (0.28 g, 1.13 mmol),
2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridine (0.24 g, 1.13
mmol), and K2CO3 (0.47 g, 3.39 mmol) in DMF (20 mL) was
added dry DMF (20 mL). The mixture was heated at 50 °C with
stirring for 10 h. The solvent was completely removed under
vacuum. The residue was dissolved in dichloromethane. The
organic layer was then washed twice with water. After drying
with anhydrous magnesium sulfate, the solvent was completely
removed under vacuum. The residue was washed twice with a
small amount of methanol. The air-stable white solid was then
filtered on a frit and dried under vacuum. Yield: 0.46 g, 77%. Mp:
301.7-307.5 °C dec. Anal. Calcd for C21H17F3N6OPd: C, 47.34;
H, 3.22; N, 15.77. Found: C, 47.05; H, 3.30; N, 15.71. 1H NMR
(CDCl3): δ 4.18 (s, 3H, CH3), 4.37 (d, 2J(H,H) = 14.3 Hz, 1H,
CHAHBCO), 5.37 (d, 2J(H,H) = 14.6 Hz, 1H, CHAHBCO), 6.77
(s, 1H, pyrazole H), 6.78-6.85 (m, 1H, Ph H), 6.94 (d, 3J(H,H) =
1.8 Hz, 1H, imi H), 6.96-7.01 (m, 1H, Py H), 7.06 (d, 3J(H,H) =
1.8 Hz, 1H, imi H), 7.20 (t, 3J(H,H) = 7.7 Hz, 2H, Ph H), 7.38 (d,
3J(H,H) = 5.6 Hz, 1H, Py H), 7.49 (d, 3J(H,H) = 7.9 Hz, 1H, Py
H), 7.68 (td, 3J(H,H) = 7.7 Hz, 4J(H,H) = 1.3 Hz, 1H, Py H),
8.02 (d, 3J(H,H) = 7.6 Hz, 2H, Ph H). 13C{1H} NMR (CDCl3):
δ 38.2 (CH3), 58.5 (CH2), 101.2 (pyrazole CH), 118.9, 122.0 (q,
1JCF = 268.4 Hz, CF3), 121.7, 121.8, 122.4, 123.4, 126.2, 128.0,
139.3, 143.5 (q, 2JCF = 36.3 Hz, pyrazole C), 147.0, 148.6, 151.1,
153.2, 155.5 (PdC), 169.2 (CO). ESI-MS: m/z 533.0 [M þ H]þ.
Crystals suitable for X-ray crystallography were obtained by
vapor diffusion of hexane into a chloroform solution containing
the compound.
Synthesis of 3c. The procedure was similar to that of 3a.
Complex 2c (0.06 g, 0.17 mmol), 2-(3-(trifluoromethyl)-1H-
pyrazol-5-yl)pyridine (0.04 g, 0.17 mmol), and K2CO3 (0.07 g,
0.51 mmol) were used. An off-white solid was obtained.
Yield: 0.07 g, 64%. Mp: 270.7-275.0 °C dec. Anal. Calcd for
C31H23F3N6OPd: C, 56.50; H, 3.52; N, 12.75. Found: C, 56.19;
H,3.69; N, 12.63. 1H NMR (CDCl3): δ 4.40 (d, 2J(H,H) = 14.4
2
Hz, 1H, CHAHBCO), 5.45 (d, J(H,H) = 14.4 Hz, 1H, CHA-
HBCO), 6.00 (d, 2J(H,H) = 15.9 Hz, 1H, CHCHDNp), 6.71
(d, 2J(H,H) = 15.9 Hz, 1H, CHCHDNp), 6.76 (d, 3J(H,H) = 1.8
Hz, 1H, imi H), 6.79-6.81 (m, 2H, pyrazole H and Py H), 6.95 (t,
3J(H,H) = 7.2 Hz, 1H, Ph H), 7.00 (d, 3J(H,H) = 1.8 Hz, imi H),
7.13 (t, 3J(H,H) = 8.1 Hz, 2H, Ph H), 7.24 (d, 3J(H,H) = 7.8 Hz,
1H, Np H), 7.37-7.48 (m, 5H, Py H and Np H), 7.65 (td, 3J(H,
H) = 7.8 Hz, 4J(H,H) = 1.2 Hz, 1H, Py H), 7.85 (t, 3J(H,H) =
7.2 Hz, 2H, Np H), 7.91 (d, 3J(H,H) = 7.8 Hz, 2H, Ph H), 8.09
3
(d, J(H,H) = 7.8 Hz, 1H, Np H). 13C{1H} NMR (CDCl3):
δ 50.1 (CH2Np), 58.7 (CH2CO), 101.4 (pyrazole CH), 119.0,
121.6, 121.7, 122.1 (q, 1J(C,F) = 268.3 Hz, CF3), 123.0, 123.3,
125.5, 126.1, 126.2, 126.8, 127.1, 128.0, 128.7, 129.1, 131.1,
2
131.7, 133.7, 139.3, 143.6 (q, J(C,F) = 36.4 Hz, pyrazole C),
146.9, 148.6, 151.2, 153.2, 155.9 (PdC), 169.2 (CO). ESI-MS:
m/z 659.0 [M þ H]þ. Crystals suitable for X-ray crystallography
were obtained by vapor diffusion of diethyl ether into a dichlor-
omethane solution of the solid.
Synthesis of 4. A mixture of 2a (0.15 g, 0.60 mmol) and Ag2O
(0.069 g, 0.30 mmol) in DMF (30 mL) was stirred at room
temperature for 8 h. Light was excluded by covering the flask
with aluminum foil. The mixture was filtered through a plug of
Celite. The solvent was removed completely under vacuum. The
residual white solid was washed with diethyl ether (2 ꢀ 15 mL),
filtered on a frit under N2, and dried under vacuum. Yield: 0.11
g, 49%. Mp: 135.8-149.5 °C. Anal. Calcd for C12H13N3OAgCl:
C, 40.20; H, 3.65; N, 11.72. Found: C, 40.11; H, 3.71; N, 11.39.
1H NMR (CDCl3): δ 3.78 (s, 3H, CH3), 5.03 (s, 2H, CH2), 7.20
(t, 3J(H,H) = 7.7 Hz, 1H, Ph H), 7.31 (t, 3J(H,H) = 7.7 Hz, 2H,
Ph H), 7.43 (s, 1H, imi H), 7.46 (s, 1H, imi H), 7.57 (d, 3J(H,H) =
7.9 Hz, 1H, Ph H). 10.40 (s, 1H, NH). 13C{1H} NMR (CDCl3): δ
38.5 (CH3), 53.9 (CH2), 119.7, 122.9, 123.9, 124.1, 129.3, 138.9,
165.8 (CO), 180.5 (AgC).
Synthesis of 5. A mixture of Pt(fppzH)Cl2 (0.21 g, 0.44 mmol),
4 (0.16 g, 0.44 mmol), and K2CO3 (0.18 g, 0.88 mmol) in DMF
(15mL) wasstirredat80°C for8 h. The solventwas thenremoved
completely under vacuum. The solvent was completely removed
under vacuum. The residue was dissolved in dichloromethane.
The organic layer was then washed twice with water. After it was
dried with anhydrous magnesium sulfate, the solvent was com-
pletely removed under vacuum. The residue was thoroughly
washed with methanol. The pale yellow solid was then filtered
on a frit and dried under vacuum. Yield: 0.10 g, 44%. Mp:
338.8-340.6 °C. Anal. Calcd for C21H17F3N6OPt: C, 40.59; H,
Synthesis of 3b. The procedure was identical with that of 3a
except that 2b (0.37 g, 1.13 mmol) was used instead. A pale
yellow solid was obtained. Yield: 0.49 g, 72%. Mp: 278.4-
282.6 °C dec. Anal. Calcd for C27H21F3N6OPd: C, 53.26; H,
1
3.48; N, 13.80. Found: C, 52.90; H, 3.71; N, 13.81. H NMR
(CDCl3): δ 4.39 (d, 2J(H,H) = 14.4 Hz, 1H, CHAHBCO), 5.40
2
2
(d, J(H,H) = 14.4 Hz, 1H, CHAHBCO), 5.43 (d, J(H,H) =
15.0 Hz, 1H, CHCHDPh), 6.22 (d, 2J(H,H) = 15.0 Hz, 1H,
CHCHDPh), 6.76-6.81 (m, 2H, pyrazole H and Py H), 6.90 (d,
3J(H,H) = 1.8 Hz, 1H, imi H), 6.93-6.95 (m, 1H, Py H), 7.05 (d,
3J(H,H) = 1.5 Hz, 1H, imi H), 7.10 (t, 3J(H,H) = 7.7 Hz, 2H, Ph
H), 7.24-7.37 (m, 6H, Ph H and Py H), 7.47 (d, 3J(H,H) = 7.8
Hz, 1H, Py H), 7.66 (td, 3J(H,H) = 7.8 Hz, 4J(H,H) = 1.5 Hz,
1
2.76; N, 13.52. Found: C, 40.90; H, 2.57; N, 13.03. H NMR
2
(CDCl3): δ 4.14 (s, 3H, NCH3), 4.29 (d, J(H,H) = 14.3 Hz,
1H, COCHAHB), 5.22 (d, 2J(H,H) = 14.0 Hz, 1H, COCHAHB),
6.76 (s, 1H, pyrazole H), 6.85 (td, 3J(H,H) = 6.6 Hz, 4J(H,H) =
1.2 Hz, 1H, Py H), 6.94 (d, 3J(H,H) = 2.1 Hz, 1H, imi H), 6.97
(t, 3J(H,H) = 7.2 Hz, 1H, Ph H), 7.04 (d, 3J(H,H) = 2.1 Hz, 1H,
imi H), 7.19 (t, 3J(H,H) = 7.8 Hz, 2H, Ph H), 7.53 (d, 3J(H,H) =
7.8 Hz, 1H, Py H), 7.69-7.76 (m, 2H, Py H), 7.99 (d, 3J(H,H) =
7.6 Hz, 2H, Ph H). 13C{1H} NMR (CDCl3): δ 37.8 (CH3), 57.7
(CH2), 101.8 (pyrazole CH), 118.9, 121.1 (q, 1J(C,F) = 179.9 Hz,
CF3), 121.7, 122.4, 123.4, 126.2, 128.0, 139.4, 143.4 (q, 2J(C,F) =
68.6 Hz, pyrazole C), 147.2, 148.6, 151.1, 154.3, 156.3 (PdC),
169.2 (CO). ESI-MS: m/z 622.1 [M þ H]þ. Crystals suitable
for X-ray crystallography were obtained by vapor diffusion of
diethyl ether into a dichloromethane solution of the solid.
Catalytic Heck Reaction. In a typical run, a Schlenk tube
was charged with aryl halide (1.0 mmol), alkene (1.4 mmol),
3
1H, Py H), 7.73 (d, J(H,H) = 7.9 Hz, 2H, Ph H). 13C{1H}
NMR (CDCl3): δ 54.0 (CH2Ph), 58.7 (CH2CO), 101.3 (pyrazole
CH), 118.9, 121.7 (imi-C), 122.3 (q, 1J(C,F) = 267.8 Hz, CF3),
123.2, 126.1, 127.9, 128.2, 128.3, 128.9, 136.5, 139.3, 143.5 (q,
2J(C,F) = 36.2 Hz, pyrazole C), 146.8, 148.5, 151.1, 153.0, 155.7
(PdC), 169.1 (CO). ESI-MS: m/z 609.1 [M þ H]þ. Crystals
suitable for X-ray crystallography were obtained by vapor
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Article
Organometallics, Vol. 29, No. 23, 2010 6481
˚
anhydrous sodium acetate (1.1 mmol), palladium precatalyst
(0.5 mol %), and 2 g of TBAB. The flask was thoroughly
degassed and then placed in a preheated oil bath or under
microwave irradiation at the appropriate temperature listed
in Table 5. After the mixture was cooled, the mixture was
diluted with water (10 mL) and extracted with diethyl ether
(3ꢀ10 mL). The combined organic portions were then dried
over anhydrous sodium sulfate. After filtration, the solvent
was removed completely under vacuum. Products 6,57 7-9,58
10,59 11,60 12,54 13,61 14,62 15,35 16,61 17,63 18-21,57 22,64 23
and 24,57 25 and 26,65 and 27-3066 were identified by compar-
ison of their NMR data with those in the literature; NMR
yields and regioselectivity were determined by integration ratio
using 1,3,5-trimethoxylbenzene as internal standard. Isolated
yields were obtained after purification with column chroma-
tography on silica gel.
KR radiation (λ = 0.710 73 A) at 150(2) K. The data were
corrected for Lorentz and polarization effects using the Bruker
SAINT software, and an absorption correction was performed
using the SADABS program.67
Computational Details. We used the three-parameter hybrid
of exact exchange and Becke’s exchange energy functional,68
plus Lee, Yang, and Parr’s gradient-corrected correlation en-
ergy functional (B3LYP).69 For the optimization of molecular
geometries, we used the LANL2DZ effective core potential plus
basis functions.70
Solution and Structure Refinements. All the structures were
solved by direct methods and refined by full-matrix least-squares
methods against F2 with the SHELXTL software package.71 All
non-H atoms were refined anisotropically. H atoms were fixed at
calculated positions and refined with the use of a riding model.
Crystallographic data are given in Table 1. CCDC-787474 (3a),
X-ray Data Collection. Typically, the crystals were removed
from the vial with a small amount of mother liquor and imme-
diately coated with Paratone-N oil on a glass slide. A suitable
crystal was mounted on a glass fiber with silicone grease and
placed in the cold stream of a Bruker APEX II equipped with a
CCD area detector and a graphite monochromator utilizing Mo
-787475 (3b), -787476 (3c 0.25CH2Cl2), and -787477 (5) con-
3
tain supplementary crystallographic data for this paper. These
data can obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgment. We are grateful to the National
Science Council of Taiwan for financial support of this
work. We also thank the National Center for High-
performance Computing of Taiwan for computing time
and financial support of the Conquest software.
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Supporting Information Available: CIF files giving full crys-
tallographic data for 3a-c and 5 and a figure giving the HMBC
spectrum of 3c. This material is available free of charge via the
Internet at http://pubs.acs.org.
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