Development of Structurally Diverse N-Heterocyclic Carbene Ligands via Palladium-Copper-Catalyzed Decarboxylative Arylation of Pyrazolo[1,5-a]pyridine-3-carboxylic Acid

Article abstract of DOI:10.1002/adsc.201600480

A series of fused non-classical normal N-heterocyclic carbenes, Pyrpy-NHC precursors derived from pyrazolo[1,5-a]pyridines, has been prepared using palladium-copper-catalyzed decarboxylative arylation of pyrazolo[1,5-a]pyridine-3-carboxylic acid. Air-stable palladium and rhodium complexes of these ligands have been synthesized via mild transmetallation of Ag-Pyrpy-NHC. The structural properties of Rh(Pyrpy-NHC)(COD)Cl complexes were determined via X-ray analysis. The measurement of the CO stretching frequencies of dicarbonyl Rh-Pyrpy-NHC complexes revealed that the electron donating strength of Pyrpy-NHC could be tuned by varying the substituents of the aryl group. A catalytic study of the Pd-Pyrpy-NHC complexes revealed promising activity in the Suzuki–Miyaura reaction under ambient atmospheric conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.201600480

FULL PAPERS
DOI: 10.1002/adsc.201600480
Development of Structurally Diverse N-Heterocyclic Carbene Li-
gands via Palladium-Copper-Catalyzed Decarboxylative Arylation
of Pyrazolo[1,5-a]pyridine-3-carboxylic Acid
Khyarul Alam,+a Seong Min Kim,+a Do Joong Kim,a and Jin Kyoon Parka,*
a
Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 609-735, Korea
Fax : (+82)-51-510-7421; Phone: (+82)-51-510-2242
address:; e-mail: pjkyoon@pusan.ac.kr
+
These authors contributed equally.
Received: May 5, 2016; Revised: June 4, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600480.
Abstract: A series of fused non-classical normal N- the CO stretching frequencies of dicarbonyl Rh-
heterocyclic carbenes, Pyrpy-NHC precursors de- Pyrpy-NHC complexes revealed that the electron do-
rived from pyrazolo[1,5-a]pyridines, has been pre- nating strength of Pyrpy-NHC could be tuned by
pared using palladium-copper-catalyzed decarboxyla- varying the substituents of the aryl group. A catalytic
tive arylation of pyrazolo[1,5-a]pyridine-3-carboxylic study of the Pd-Pyrpy-NHC complexes revealed
acid. Air-stable palladium and rhodium complexes of promising activity in the Suzuki–Miyaura reaction
these ligands have been synthesized via mild trans- under ambient atmospheric conditions.
metallation of Ag-Pyrpy-NHC. The structural prop-
erties of Rh(Pyrpy-NHC)(COD)Cl complexes were Keywords: carbenes; decarboxylative coupling;
determined via X-ray analysis. The measurement of ligand design; palladium; rhodium
Introduction
than classical nNHCs, which have two adjacent nitro-
gens.[7] The distinguishable features of aNHCs are
N-Heterocyclic carbenes (NHCs) have been studied also observed in the properties of coordinated metal
extensively in organometallic chemistry and there has centers, such as the coordination geometry and elec-
been explosive development in the field of transition- tron density.[8] Selected examples of aNHCs/MICs de-
metal-catalyzed reactions over the last decades.[1] Al- rived from imidazole (A),[9a] triazole (B),[9b] and imi-
though phosphine-metal complexes have shown paral- dazopyridine (C and D)[9c–d] are shown in Figure 1.
lel unique reactivities and selectivities in many reac-
Recently, the Huynh group developed non-classical
tions, the preference for NHCs over phosphine li- nNHC E, where the carbene carbon environment re-
gands is due to the excellent stability of NHC-metal sembles that of aNHCs, derived from pyrazole and in-
complexes towards air and moisture owing to the dazole.[10a–d] Interestingly, they found that Indy-NHC
strong metal-carbene bond[2] as well as high reactivi- E has even more sigma-donating capability than some
ties.[3] Among the currently accepted NHC ligands, aNHCs. The Zhao group prepared a series of Indy-
the two major classes are the normal NHCs (nNHCs), NHCs, such as F, by introducing various N-substitu-
which have a resonance form with all-zero formal ents for steric and electronic tuning and reported
charges, and abnormal NHCs (aNHCs) or mesoionic their catalytic activity in a Au-catalyzed reaction.[10e]
carbenes (MICs), which should have a formal charge Knowing these unique properties of non-classical
on the canonical structure.[4]
nNHCs, we envisioned using pyrazolo[1,5-a]pyridine
Since the introduction of the first example by the (Pyrpy) as a new backbone for a non-classical nNHC,
Crabtree group,[5] great progress has been made in Pyrpy-NHC (G) and surmised that varying C-substitu-
the development of aNHCs/MICs[4a,6] because ents may lead to a wide range of novel properties,
aNHCs/MICs, which have a carbon and a nitrogen ad- since most synthetic tools for NHCs focus only on in-
jacent to carbene carbon, are known to be stronger troducing N-substituents for tunable electronic and
sigma donors and sometimes have better reactivity steric properties. However, we found that having ster-
Adv. Synth. Catal. 0000, 000, 0 – 0
1
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
lative coupling reactions and N-alkylations along with
the characterizations of their metal complexes (Rh-
Pyrpy-NHC and Pd-Pyrpy-NHC) and the catalytic ac-
tivities of Pd-Pyrpy-NHC complexes.
Results and Discussion
Decarboxylative arylation of pyrazolo[1,5-a]pyridine-
3-carboxylic acid
Since the Nilsson group introduced the decarboxyla-
tive Ullmann reaction,[16] many practical methods
have been developed.[17] We began by testing the typi-
cal conditions developed by the Forgione and Bilo-
deau group (Table 1).[18] In the presence of Bu4NCl,
we obtained arylated product 2a in 52% yield and
protodecarboxylated product 2aꢀ in 47% yield
Figure 1. Selected examples of aNHCs/MICs (A–D) and
non-classical nNHC (E–G) precursors.
ically demanding C-substituents on NHCs is rare
owing to the lack of synthetic approaches.
Table 1. Screening of decarboxylative coupling using Pd cat-
alysts.[a]
Since pyrazolo[1,5-a]pyridines are an important
class of biologically active compounds[11] and are also
used to develop luminescent compounds,[12] there are
a number of reports that describe the facile synthesis
of 2-substituted or 2,3-disubstituted pyrazolo[1,5-a]-
pyridines,[13] but few synthetic methods for 3-substitut-
ed pyrazolo[1,5-a]pyridine derivatives have been re-
ported (Scheme 1).[14] Conventional multistep cou-
pling methods for the synthesis of 3-substituted deriv-
atives suffer from limited scope, low yield, and use of
expensive starting materials.[14a–b] Furthermore, recent
direct C-3 arylations of pyrazolo[1,5-a]pyridines de-
veloped by the Wu group required four equivalents of
aryl iodide with 30 h of reaction time.[14c] Regarding
the development of pyrazolo[1,5-a]pyridine-based
NHC ligands, a better synthetic method for sterically
demanding 3-substituted pyrazolo[1,5-a]pyridines was
needed. We surmised that decarboxylative arylations
would be more flexible synthetic alternatives, because
pyrazolo[1,5-a]pyridine-3-carboxylic acids are easy to
access,[15] and utilizing aryl bromides as substrates in
a short reaction time could be beneficial. Herein, we
report the synthesis of 3-substituted pyrazolo[1,5-
a]pyridines and Pyrpy-NHC precursors via decarboxy-
Entry
Catalyst
Additive
Yield [%]
of 2a/2a’[b]
1
2
Pd[P(tBu)3]2
Pd[P(tBu)3]2
Pd(OAc)2 + P(tBu)3
Pd(OAc)2 + P(tBu)3
Pd[P(tBu)3]2
Bu4NCl
–
Bu4NCl
–
–
–
52/47
56/26
3[c]
4[c]
5[e]
6[f]
29/28(43)[d]
31/0
<5/95
0/100
Pd[P(tBu)3]2
[a]
Conditions: pyrazolo[1,5-a]pyridine-3-carboxylic acid, 1a
(1.0 equiv), bromobenzene (2.0 equiv), Pd catalyst
(5 mol%), Cs2CO3 (1.5 equiv), additive (1.0 equiv), DMF
(0.1M), 1608C.
[b]
1
Yield based on H NMR using dibromomethane as an in-
ternal standard.
[c]
[d]
[e]
[f]
P(tBu)3·HBF4 (5 mol%) was used.
Isolated yield of butyl ester is shown in parentheses.
In toluene.
In dioxane.
Scheme 1. Synthesis of 3-substituted pyrazolo[1,5-a]pyridines.
Adv. Synth. Catal. 0000, 000, 0 – 0
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
(entry 1).[19] Although protodecarboxylation de- The yield of 2a increased to 92% with lesser amount
creased in the absence of Bu4NCl, the amount of the of 2aꢀ using Pd(PPh3)4 (entry 4). After screening the
arylated product did not increase (entry 2). Interest- bases by using K2CO3 and Ag2CO3, Cs2CO3 turned
.
ingly, when we added Pd(OAc)2 and P(tBu)3 HBF4 in out to be the best (entry 4 vs. 5 and 6). Bipyridine
the presence of Bu4NCl, butyl ester was isolated in had a detrimental effect, affording 2aꢀ in 62% yield
43% yield from the reaction of 1a with Bu4NCl (entry 7). To our delight, CuCl gave the highest yield
before the decarboxylative coupling (entry 3). We ob- (97%) with almost no formation of 2aꢀ among the
tained the arylated product in 31% yield with no for- copper sources (entry 9 vs. 4 and 8). The amount of
mation of the protodecarboxylated product in the ab- bromobenzene could be further reduced without de-
sence of Bu4NCl (entry 4). Non-polar solvents, tolu- creasing the yield (entry 10). In the absence of CuCl
ene and 1,4-dioxane, gave little or no desired product and 1,10-phenanthroline, the yield of 2a decreased to
but mostly protodecarboxylated product (entries 5 62% with 26% of 2aꢀ (entry 11).
and 6).
With the optimized conditions in hand, we investi-
After we found that the Pd-only conditions did not gated the substrate scope with a variety of aryl bro-
work well, we decided to test the Pd/Cu bimetallic mides, and the results are summarized in Table 3. The
system developed by the Goossen group (Table 2).[20] aryl bromides with a methyl group at the ortho, para,
Under these conditions (5 mol% of Pd[P(tBu)3]2, and meta positions reacted smoothly and afforded
10 mol% of Cu2O, and 10 mol% of 1,10-phenanthro- coupling products 2b–d in 87–88% yields. A bulky
line), we obtained the arylated product in 87% yield substituent at the para position did not affect the
with 9% of 2aꢀ (entry 1). Bidentate dppf (1,1’-bis(di- yield of product 2e (86% yield). However, di- and tri-
phenylphosphino)ferrocene) ligand did not increase methyl-substituted derivatives gave slightly lower
the yield of 2a, but the yield of 2aꢀ increased yields, especially with substituents at the ortho posi-
(entry 2). Adding Pd2(dba)3 (dba=dibenzylideneace- tion (2f–h). Although aryl bromides with both elec-
tone) without using a phosphine ligand gave 2a and tron-donating and withdrawing groups were well tol-
2aꢀ in 84% and 10% yields, respectively (entry 3). erated to give 2i–m in 70–90% yields, the CF3 group
resulted in moderate yields for 2n–o (68% and 67%,
respectively). Despite low yields, highly sterically de-
manding aryl bromides, such as those with a diisoprop-
Table 2. Decarboxylative coupling under Goossenꢂs condi-
yl group at the 2 and 4 positions, gave desired prod-
tions.[a]
ucts 2p–q in 42% and 40% yields, respectively. 2-Bro-
monaphthalene also readily reacted to give 2r in 84%
yield. 3-Bromopyridine was also tolerated, giving
71% yield of 2s. 2-Substituted pyrazolo[1,5-a]pyri-
dine-3-carboxylic acid was also tolerated with
15 mol% of Pd(PPh3)4. 2,3-Diphenylpyrazolo[1,5-
a]pyridine 3a was obtained in 63% yield and the aryl
bromide with electron donating and withdrawing
group gave moderate yields of 3b (60%) and 3c
(65%). 3-Bromopyridine gave 47% yield of 3d.
Entry
Pd
Cu/Ligand[b]
Yield [%]
of 2a/2a’[c]
1
2
3
4
Pd[P(tBu)3]2
Pd(dppf)Cl2
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Cu2O/phen
Cu2O/phen
Cu2O/phen
Cu2O/phen
Cu2O/phen
Cu2O/phen
Cu2O/bipy
CuI/phen
CuCl/phen
CuCl/phen
–
87/9
81/16
84/10
92/6
58/36
15/74
30/62
79/11
97/-
5[d]
6[e]
7
Synthesis of Pyrpy-NHC ligand precursors
The synthetic pathway for Pyrpy-NHC ligand precur-
sors 4a–g is outlined in Scheme 2. Treatment of pyra-
zolo[1,5-a]pyridine derivatives with 2-iodopropane at
1208C led to the formation of pyrazolo[1,5-a]pyridini-
um iodides in good yields. Anion exchange of iodide
with chloride was performed simply by passing the so-
lution through a column of ion exchange resin Dowex
1ꢁ8 chloride form, and compounds 4a–g were ob-
8
9
10[f]
11
97/–
62/26
[a]
Conditions: pyrazolo[1,5-a]pyridine-3-carboxylic acid, 1a
(1.0 equiv), bromobenzene (2.0 equiv), Pd catalyst
(5 mol%), Cu catalyst (10 mol%), ligand (10 mol%),
Cs2CO3 (1.5 equiv), DMF (0.1M), 1608C.
Phen=1,10-phenanthroline, bipy=2,2’-bipyridine.
Yield based on H NMR using dibromomethane as an in-
1
tained in quantitative yields. The H NMR spectra of
[b]
[c]
compounds 4a–g showed the characteristic singlet
peak at d ꢀ 7.98–9.14 ppm arising from the C-2
proton of pyrazolo[1,5-a]pyridinium chloride salt.[22]
1
ternal standard.
K2CO3 was used
Ag2CO3 was used
Bromobenzene (1.5 equiv) was used.
[d]
[e]
[f]
Adv. Synth. Catal. 0000, 000, 0 – 0
3
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Table 3. Decarboxylative arylations with various aryl bromides.[a,b]
[a]
Conditions: pyrazolo[1,5-a]pyridine-3-carboxylic acid, 1 (1.0 equiv), aryl bromide (1.5 equiv), Pd cata-
lyst (5 mol%), Cu catalyst (10 mol%), ligand (10 mol%), Cs2CO3 (1.5 equiv), DMF (0.1M), 1608C,
7 h.
Isolated yield.
Reaction time was 8 h.
Reaction time was 12 h.
[b]
[c]
[d]
[e]
Aryl bromide (2.0 equiv) was used.
Pd[P(tBu)3]2 was used instead because triphenylphosphine oxide was inseparable in the case of
[f]
Pd(PPh3)4.
Pd catalyst (15 mol%) was used.
[g]
Synthesis and structures of Rh-Pyrpy-NHC
complexes
were well characterized on the basis of their spectro-
scopic data. The H NMR spectra of the complexes
featured the absence of the characteristic singlet peak
1
Since silver transmetallation is a well-established arising from the C-2 proton of pyrazolo[1,5-a]pyridini-
method for the synthesis of NHC-metal complexes,[23] um salt at around 7.98–9.14 ppm, and the 13C NMR
we treated 4a–g with Ag2O (0.5 equiv) in CH2Cl2 to spectra revealed a doublet peak at d ꢀ 188 ppm aris-
obtain the corresponding Ag-Pyrpy-NHC complexes. ing from the C-2 carbon bound to the Rh center. The
In situ addition of [Rh(COD)Cl]2 (0.5 equiv) (COD= 1H NMR spectrum of complex 5b showed two similar
1,5-cyclooctadiene) to the silver reaction mixture af- sets of doublet peak at ꢀ 8.40 ppm, which indicated
forded corresponding Rh-Pyrpy-NHC complexes 5a–g two structural isomers arising owing to the position of
in good yields (Scheme 2). All of the Rh complexes the methyl group (R1) above or below the ring
Adv. Synth. Catal. 0000, 000, 0 – 0
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Scheme 2. Synthesis of Pyrpy-NHC precursors and their metal (Rh and Pd) complexes.
system. 13C NMR also support this observation show-
ing two characteristic doublet of Ccarbene bonded to
Rh.
Table 4. Selected bond lengths [ꢃ] and angles [8] for com-
plexes 5a and 5e.
Bond Param[a]
5a
5e
Suitable single crystals of complexes 5a and 5e for
X-ray analysis were obtained via careful layering of
pentane with a CH2Cl2 solution. Their molecular
structures are shown in Figure 2. Some selected geo-
metrical parameters are given in Table 4. The coordi-
nation sphere is square planar for both complexes.
The Rh-Ccarbene bond length is 2.024(3) ꢃ for 5a and
À
Rh1-C1
Rh1-Cl1
C1-N1
C1-C2
N1-N2
2.024(3)
2.391(8)
1.366(3)
1.408(4)
1.370(3)
105.8(2)
88.62(9)
123.6(2)
130.2(2)
99.8(3)
2.043(2)
2.392(6)
1.372(3)
1.404(3)
1.374(2)
105.8(2)
90.83(6)
120.1(1)
134.1(1)
–112.4(2)
70.1(3)
C2-C1-N1
2.043(2) ꢃ for 5e, consistent with a Rh C single C1-Rh1-Cl1
Rh1-C1-N1
Rh1-C1-C2
Cl1-Rh1-C1-C2
C1-C2-C8(C11)-C9(C12)
bond. The torsional angle of the pyrazolo[1,5-a]pyri-
dine ring system to the coordination plane is 99.88 for
5a and À112.48 for 5e, indicating significant deviation
in orientation. Also, the torsional angle of the pyrazo-
lo[1,5-a]pyridine ring system to the C3-substituted
aryl ring is À34.98 for 5a and 70.18 for 5e, indicating
that the orientation of the aryl group changed with
–34.9(4)
[a]
Atom label for complex 5e shown in bracket.
the introduction of steric bulk. To measure the steric Synthesis of dicarbonyl Rh-Pyrpy-NHC complexes
bulk provided by the ligands, the%Vbur of complexes
5a and 5e was calculated using crystallographic data To determine the electronic effects of these new
with the help of the SambVca program developed by Pyrpy-NHC ligands, the corresponding rhodium dicar-
Cavallo and co-workers,[24] and%Vbur values of 28.7 bonyl complexes 6a–g, were synthesized by bubbling
for 5a and 31.9 for 5e were obtained.
CO through solutions of complexes 5a–g in CH2Cl2 at
Figure 2. Molecular structures of complexes 5a and 5e (H atoms are not shown for clarity).[21]
Adv. Synth. Catal. 0000, 000, 0 – 0
5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Table 5. Stretching frequencies for complexes 6a–g.
could be attributed to easier rotation of the C3-substi-
av
Entry
Complex
nCO
(cmÀ1)
nCO
(cmÀ1)
TEP[a]
(cmÀ1)
tuted phenyl group, which pushes the ortho phenyl
À
C H bonds closer to the palladium center. Fortunate-
ly, ligand precursors 4b–e with R1 and/or R2 alkyl
groups, containing a chloride counter anion, gave de-
sired products 7b–e in good yields, while an iodide
counter anion was unsuccessful. Also, the NMR spec-
trum of complex 7b showed two similar sets of peak
patterns indicating two structural isomers arising
owing to the position of the methyl group (R1) above
or below the ring system.
1
2
3
4
5
6
7
6a
6b
6c
6d
6e
6f
6g
2064.7, 1988.0
2063.6, 1986.6
2064.4, 1986.2
2064.1, 1985.9
2064.8, 1986.4
2067.2, 1990.1
2069.1, 1992.4
2026.3
2025.1
2025.3
2025.0
2025.6
2028.6
2030.7
2041.2
2040.2
2040.4
2040.2
2040.7
2043.0
2044.7
[a]
TEP calculated by using the following equation: TEP=
0.8001 nCOav/Rh + 420.0 cmÀ1.
Catalytic studies of palladium complexes
room temperature for 15 min, which caused the quick
substitution of COD ligands with CO ligands The catalytic activities of the Pd-Pyrpy-NHC com-
(Scheme 2). The average CO stretching frequencies plexes in the Suzuki–Miyaura coupling reaction were
(nCOav) of these CO ligands in the complexes ranged tested under ambient atmosphere using 4-bromoto-
from 2025 to 2031 cmÀ1, as shown in Table 5. To com- luene and phenylboronic acid as model substrates.
pare the donor strengths of these ligands with those Using complex 7c, we optimized the reaction condi-
of other carbenes, the TEP (Tolman electronic param- tions by determining the GC conversion and yield
av
eter) was calculated by using nCO according to the using dodecane as an internal standard, and the re-
reference studies by Crabtree and co-workers[25a] and sults are summarized in Table 6. The reaction was per-
by Nolan and co-workers.[25b] Regarding the TEP of formed using 4-bromotoluene (1.0 equiv) and phenyl-
electron-withdrawing substituents, F at the para posi- boronic acid (1.5 equiv) in the presence of 2.0 equiv
tion has a value of 2043 cmÀ1, while CF3 has a value of base and 1.0 mol% of 7c at 808C. Toluene was the
of 2045 cmÀ1, indicating weaker electron-donating optimum solvent among the tested solvents (1,4-diox-
properties compared to other Pyrpy-NHCs. More- ane, N,N-dimethylformamide (DMF), dimethylaceta-
over, we found that our Pyrpy-NHC ranked highest mide (DMA), CH3CN, and tetrahydrofuran (THF))
among other NHCs, indicating strong sigma electron- using K2CO3 (entries 1–5). The other bases (Cs2CO3,
donor property (Scheme 3).[26]
Na2CO3, KOtBu, K3PO4, and KF) were also tested in
toluene, but K2CO3 turned out to be the best (en-
tries 6–11). When we doubled the amount of phenyl-
boronic acid, yield increased to 99% (entry 12). De-
creasing the amount of catalyst to 0.5 mol% resulted
Synthesis of Pd-Pyrpy-NHC complexes
A similar silver transmetallation approach using in nearly the same yield (entry 13).
[Pd(allyl)Cl]2 was used for the synthesis of Pd-Pyrpy-
To compare the reactivities of Pd-Pyrpy-NHC com-
NHC complexes 7b–e (Scheme 2). Initial attempts plexes 7b–e, we investigated reaction conversion
with
1-isopropyl-3-phenylpyrazolo[1,5-a]pyridinium under the optimized condition (Table 7 and Figure 3).
salt, 4a, which has no substituent on the ortho posi- We found that complex 7c revealed the best catalytic
tion of the ancillary phenyl group, failed to give activity among others.[27] For the comparison with
a stable palladium complex. This lack of stability classical nNHC, we tested (SIMes)Pd(allyl)Cl and
Scheme 3. Comparison of TEPs of different NHC ligands.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Table 6. Optimization of Suzuki–Miyaura reaction using
7c.[a]
Entry
Solvent
Base
Yield (%)[b]
1
2
3
4
5
6
7
8
dioxane
DMF
DMA
CH3CN
THF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Na2CO3
KOtBu
K3PO4
KF
<5
NR
NR
<5
<5
84
18
<5
28
79
26
99
98
9
10
11
12[c]
13[c,d]
Figure 3. Reaction profiles catalyzed by 7b–e, (SIMes)Pd(al-
lyl)Cl, and (IMes)Pd(allyl)Cl.
K2CO3
K2CO3
[a]
Reaction conditions: 4-bromotoluene (1.0 equiv), phenyl-
boronic acid (1.5 equiv), base (2.0 equiv), Pd catalyst 7c
(1 mol%), solvent (0.2M), 808C.
GC yield using dodecane as an internal standard.
Phenylboronic acid (2.0 equiv).
ed under the optimized conditions, and the results are
summarized in Table 8. Activated, unactivated, and
deactivated aryl bromides coupled smoothly with phe-
nylboronic acid to give good to excellent yields (77–
[b]
[c]
[d]
0.5 mol% of 7c was used
Table 8. Substrate scope.[a]
Table 7. Comparison of Pd-Pyrpy-NHC catalysts.[a]
Entry
X
R
Yield (%)[b]
1
2
3
4
5
6
7
8
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
CH2Br
Br
Cl
H
2-Me
3-Me
4-Me
98
79
96
94
87
82
79
51
62
77
98
96
98
92
98
75
93
24
66
2-CF3
2,3-Me,Me
3,4-Me,Me
2,6-Me,Me
2,4,6-Me,Me,Me
4-tBu
4-COMe
4-CN
4-NO2
4-NH2
4-OMe
H
2-pyridine
4-COMe
4-COMe
Entry
Catalyst
Conversion/yield (%)
1
2
3
4
5
6
7b
7c
7d
7e
83/80
97/96
77/77
78/76
38/35
21/11
9
10
11
12
13
14
15
16
17
18[c]
19[d]
(SIMes)Pd(allyl)Cl
(IMes)Pd(allyl)Cl
[a]
Reaction conditions: 4-bromotoluene (1.0 equiv), phenyl-
boronic acid (2.0 equiv), K2CO3 (2.0 equiv), Pd catalyst
(0.5 mol%), toluene (0.2M), 808C.
GC conversion/yield using dodecane as an internal stan-
dard.
[b]
Cl
[a]
Reaction conditions: aryl halide (1.0 equiv), phenylbor-
onic acid (2.0 equiv), K2CO3 (2.0 equiv), catalyst 7c
(0.5 mol%), toluene (0.2m), 808C.
Isolated yield.
K3PO4 (2.0 equiv), 1208C.
K3PO4 (2.0 equiv), phenylboronic acid (3.0 equiv), cata-
lyst 7e (1 mol%), 1208C.
(IMes)Pd(allyl)Cl[28] in the same condition and found
21% and 38% conversion in 2 h, respectively. The
conversion was stalled after 20 min presumably due to
the catalyst degradation.
The couplings of phenylboronic acid with a number
of aryl halides using complex 7c were then investigat-
[b]
[c]
[d]
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
zation mode: ESI). Flash column chromatography was per-
formed with Merck silica gel 60 (230–400 mesh).
99%), and a wide range of functional groups was tol-
erated. However, reduced yields were observed with
sterically hindered aryl bromides (entries 8 and 9).
Coupling between sp3-carbons and sp2-carbons was
achieved by using benzyl bromide and phenylboronic
acid in 75% yield (entry 16). 2-Bromopyridine also
gave the coupling product in excellent yield
(entry 17). Aryl chloride derivatives failed to couple
with phenylboronic acid under the optimized condi-
tions. However, the desired product was obtained in
24% yield along with the product of homocoupling of
phenylboronic acid when the base was changed to
K3PO4 and temperature was increased to 1208C
(entry 18). A longer reaction time did not affect the
yield, which may be attributed to catalyst decomposi-
tion. The use of catalyst 7e, which could have better
stability owing to the sterically bulky wing tip, with
3.0 equiv of phenylboronic acid under an inert atmos-
phere increased the yield to 66%, minimizing the for-
mation of the homocoupled product (entry 19).
General procedure for synthesis of 3-substituted
pyrazolo[1,5-a]pyridines 2a–s
Pyrazolo[1,5-a]pyridine-3-carboxylic acid (0.24 mmol), aryl-
bromide derivatives (0.36 mmol), Pd(PPh3)4 (0.012 mmol),
copper(I) chloride (0.024 mmol), 1,10-phenanthroline
(0.024 mmol), cesium carbonate (0.36 mmol) and DMF
(2.4 mL) were added to screw-capped vial. The reaction
mixture was heated to 1608C in an aluminum heating block
for 7–12 h. After cooling to room temperature, the reaction
mixture was filtered through Celite and washed with
CH2Cl2. The solvent was concentrated and the residue was
purified by silica gel flash chromatography to afford the de-
sired products 2a–s.
General method for the synthesis of ligand precursors
4a–g
A septum-capped vial (7 mL) was charged with 3-substitut-
ed pyrazolo[1,5-a]pyridine derivatives (1.0 mmol) and 2-io-
dopropane (16.0 mmol). The reaction mixture was then
stirred at 1208C for 24–48 h. Subsequently, Et2O (2 mL) was
added. The resulting precipitate was filtered off and recrys-
tallized from CH2Cl2/Et2O. A solution of the above iodoni-
um salt in MeOH was passed through a column of Dowex
1ꢁ8 chloride anion exchange beads. MeOH was removed
under reduced pressure and the resulting precipitate was re-
crystallized from CH2Cl2/Et2O to give analytically pure
Conclusions
We have developed an efficient method for direct
synthesis of 3-substituted pyrazolo[1,5-a]pyridine de-
rivatives via decarboxylative arylation using a Pd/Cu
bimetallic system. This method can also be applied to
the synthesis of multi-substituted pyrazolo[1,5-a]pyri- products 4a–g.
dine derivatives. We have also designed and synthe-
sized a series of Pyrpy-NHC ligand precursors derived
from the pyrazolo[1,5-a]pyridine backbone. Air-stable
Pd and Rh complexes of these ligands were synthe-
sized via mild transmetallation of Ag-Pyrpy-NHC to
the corresponding metal complexes and characterized
using X-ray and NMR analysis. The Pd-Pyrpy-NHC
complexes showed promising catalytic activity in the
Suzuki–Miyaura reaction.
General method for the synthesis of rhodium
complexes 5a–g
To a solution of pyrazolo[1,5-a]pyridinium chloride salt
(0.1 mmol) in dry CH2Cl2, Ag2O (0.05 mmol) was added,
and the mixture was stirred at room temperature in the dark
for 3–16 h. The reaction mixture was filtered through Celite
to give a clear solution. [Rh(COD)Cl]2 (0.05 mmol) was
added to the solution, and the mixture was stirred for 4 h.
The suspension was filtered through Celite and the solvent
was removed under reduced pressure. Analytically pure
compounds 5a–g were obtained after elution through a short
path column of alumina using CH2Cl2.
Experimental Section
General method for the synthesis of dicarbonyl
rhodium complexes 6a–g
General information
All reagents were prepared using chemicals obtained from
commercial sources and used without purification unless
otherwise noted. Decarboxylative arylation reactions were
performed in 7 mL vials in an aluminum heating block. All
reactions were monitored using GC and 1H NMR and by
analytical thin layer chromatography (TLC) using Merck
pre-coated silica gel glass plates (0.25 mm) with F254 indica-
Through a solution of complexes 5a–g in CH2Cl2, CO was
bubbled for 15 min at room temperature. The solvent was
removed under reduced pressure and washed with hexanes
to give rhodium dicarbonyl complexes 6a–g.
General method for the synthesis of palladium
complexes 7b–e
1
tor. H NMR and 13C NMR spectra were recorded in CDCl3
(Cambridge Isotope Laboratories, Inc.) with a 300 MHz
Fourier transform spectrometer. Chemical shifts (d) are
given in ppm and coupling constants (J) are given in Hz. In-
frared (IR) spectra are reported in frequency of the absorp-
tion (cmÀ1). High-resolution mass spectra (HRMS) were ac-
quired on a high-resolution Q-TOF mass spectrometer (ioni-
To
a
solution of pyrazolo[1,5-a]pyridinium chloride
(0.1 mmol) in dry CH2Cl2, Ag2O (0.05 mmol) was added and
the mixture was stirred at room temperature in the dark for
3–16 h. The reaction mixture was filtered through Celite to
give a clear solution. [Pd(allyl)Cl]2 (0.05 mmol) was added
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
to the solution, and the mixture was stirred for 4 h. The sus-
pension was filtered through Celite, and the solvent was re-
moved under reduced pressure. Analytically pure com-
pounds 7b–e were obtained after elution through a short
path column of alumina using CH2Cl2.
[6] O. Schuster, L. Yang, H. G. Raubenheimer, M. Al-
brecht, Chem. Rev. 2009, 109, 3445–3478.
[7] a) A. R. Chianese, A. Kovacevic, B. M. Zeglis, J. W.
Faller, R. H. Crabtree, Organometallics 2004, 23, 2461–
2468; b) R. Tonner, G. Heydenrych, G. Frenking,
Chem. Asian J. 2007, 2, 1555–1567; c) X. Xu, B. Xu, Y.
Li, S. H. Hong, Organometallics 2010, 29, 6343–6349;
d) T. Nakamura, T. Terashima, K. Ogata, S.-I. Fukuza-
wa, Org. Lett. 2011, 13, 620–623; e) X. Gong, H.
Zhang, X. Li, Tetrahedron Lett. 2011, 52, 5596–5600;
f) S. Saha, T. Ghatak, B. Saha, H. Doucet, J. K. Bera,
Organometallics 2012, 31, 5500–5505; g) M. Hecken-
roth, E. Kluser, A. Neels, M. Albrecht, Angew. Chem.
2007, 119, 6409–6412; Angew. Chem. Int. Ed. 2007, 46,
6293–6296.
General procedure for the Suzuki–Miyaura reaction
To a 7 mL vial equipped with a magnetic stir bar, catalyst 7c
(0.5 mol%, 0.001 mmol), K2CO3 (0.4 mmol), ArB(OH)2
(0.4 mmol), toluene (1.0 mL), and aryl halide (0.2 mmol)
were added under ambient atmosphere. The reaction mix-
ture stirred at 808C, and the progress of the reaction was
monitored by GC. Upon complete consumption of aryl
halide, the mixture was allowed to cool to room tempera-
ture, quenched with water, and extracted with CH2Cl2. The
organic layer was dried over MgSO4, filtered, and concen-
trated. The residue obtained was purified by column chro-
matography with Et2O/EtOAc as the eluent.
[8] a) M. Albrecht, Chem. Commun. 2008, 3601–3610;
b) S.-J. Chen, Y.-D. Lin, Y.-H. Chiang, H. M. Lee, Eur.
J. Inorg. Chem. 2014, 1492–1501; c) M. Heckenroth, A.
Neels, M. G. Garnier, P. Aebi, A. W. Ehlers, M. Al-
brecht, Chem. Eur. J. 2009, 15, 9375–9386.
[9] a) E. Aldeco-Perez, A. J. Rosenthal, B. Donnadieu, P.
Parameswaran, G. Frenking, G. Bertrand, Science 2009,
326, 556–559; b) P. Mathew, A. Neels, M. Albrecht, J.
Am. Chem. Soc. 2008, 130, 13534–13535; c) M. Alcara-
zo, S. J. Roseblade, A. R. Cowley, R. Fernꢅndez, J. M.
Brown, J. M. Lassaletta, J. Am. Chem. Soc. 2005, 127,
3290–3291; d) G. Song, Y. Zhang, X. Li, Organometal-
lics 2008, 27, 1936–1943.
Acknowledgements
This work was supported by a 2-Year Research Grant of
Pusan National University.
[10] a) H. V. Huynh, Y. Han, R. Jothibasu, J. A. Yang, Orga-
nometallics 2009, 28, 5395–5404; b) R. Jothibasu, H. V.
Huynh, Chem. Commun. 2010, 46, 2986–2988; c) H. Si-
varam, R. Jothibasu, H. V. Huynh, Organometallics
2012, 31, 1195–1203; d) J. C. Bernhammer, N. X.
Chong, R. Jothibasu, B. Zhou, H. V. Huynh, Organo-
metallics 2014, 33, 3607–3617; e) Y. Zhou, Q. Liu, W.
Lv, Q. Pang, R. Ben, Y. Qian, J. Zhao, Organometallics
2013, 32, 3753–3759.
[11] a) J. D. Kendall, A. J. Marshall, A. C. Giddens, K. Y.
Tsang, M. Boyd, R. Frederick, C. L. Lill, W.-J. Lee, S.
Kolekar, M. Chao, A. Malik, S. Yu, C. Chaussade,
C. M. Buchanan, G. W. Rewcastle, B. C. Baguley, J. U.
Flanagan, W. A. Denny, P. R. Shepherd, Med. Chem.
Commun. 2014, 5, 41–46; b) B. A. Johns, K. S. Gud-
mundsson, S. H. Allen, Bioorg. Med. Chem. Lett. 2007,
17, 2858–2862; c) J. Tang, B. Wang, T. Wu, J. Wan, Z.
Tu, M. Njire, B. Wan, S. G. Franzblauc, T. Zhang, X.
Lu, K. Ding, ACS Med. Chem. Lett. 2015, 6, 814–818.
[12] K. H. Park, Blue luminescent compounds, WO
2013163019 A1, 2013.
[13] a) J. J. Mousseau, A. Fortier, A. B. Charette, Org. Lett.
2010, 12, 516–519; b) J. J. Mousseau, J. A. Bull, C. L.
Ladd, A. Fortier, D. S. Roman, A. B. Charette, J. Org.
Chem. 2011, 76, 8243–8261; c) Y. Hoashi, T. Takai, E.
Kotani, T. Koike, Tetrahedron Lett. 2013, 54, 2199–
2202; d) D. C. Mohan, C. Ravi, S. N. Rao, S. Adimur-
thy, Org. Biomol. Chem. 2015, 13, 3556–3560; e) J. D.
Kendall, Current Organic Chemistry 2011, 15, 2481–
2518.
[14] a) P. A. Bethel, A. D. Campbell, F. W. Goldberg, P. D.
Kemmitt, G. M. Lamont, A. Suleman, Tetrahedron
2012, 68, 5434–5444; b) S. Lçber, T. Aboul-Fadl, H.
Hꢄbner, P. Gmeiner, Bioorg. Med. Chem. Lett. 2002,
References
[1] a) W. A. Herrmann, Angew. Chem. 2002, 114, 1342–
1363; Angew. Chem. Int. Ed. 2002, 41, 1290–1309;
b) E. A. B. Kantchev, C. J. OꢂBrien, M. G. Organ,
Angew. Chem. 2007, 119, 2824–2870; Angew. Chem.
Int. Ed. 2007, 46, 2768–2813; c) J. D. Egbert, C. S. J.
Cazin, S. P. Nolan, Catal. Sci. Technol. 2013, 3, 912–926;
d) K. Riener, S. Haslinger, A. Raba, M. P. Hçgerl, M.
Cokoja, W. A. Herrmann, F. E. Kꢄhn, Chem. Rev. 2014,
114, 5215–5272; e) S. Dıez-Gonzalez, N. Marion, S. P.
Nolan, Chem. Rev. 2009, 109, 3612–3676; f) L.-A.
Schaper, S. J. Hock, W. A. Herrmann, F. E. Kꢄhn,
Angew. Chem. 2013, 125, 284–304; Angew. Chem. Int.
Ed. 2013, 52, 270–289; g) J. C. Garrison, W. J. Youngs,
Chem. Rev. 2005, 105, 3978–4008.
[2] a) H. Jacobsen, A. Correa, A. Poater, C. Costabile, L.
Cavallo, Coord. Chem. Rev. 2009, 253, 687–703; b) S.
Diez-Gonzalez, S. P. Nolan, Coord. Chem. Rev. 2007,
251, 874–883; c) L. Cavallo, A. Correa, C. Costabile, H.
Jacobsen, J. Organomet. Chem. 2005, 690, 5407–5413.
[3] C. M. Crudden, D. P. Allen, Coord. Chem. Rev. 2004,
248, 2247–2273.
[4] a) R. H. Crabtree, Coord. Chem. Rev. 2013, 257, 755–
766; b) A. Krꢄger, M. Albrecht, Aust. J. Chem. 2011,
64, 1113–1117.
[5] a) S. Grꢄndemann, A. Kovacevic, M. Albrecht, J. W.
Faller, R. H. Crabtree, Chem. Commun. 2001, 2274–
2275; b) S. Grꢄndemann, A. Kovacevic, M. Albrecht,
J. W. Faller, R. H. Crabtree, J. Am. Chem. Soc. 2002,
124, 10473–10481; c) L. N. Appelhans, D. Zuccaccia, A.
Kovacevic, A. R. Chianese, J. R. Miecznikowski, A.
Macchioni, E. Clot, O. Eisenstein, R. H. Crabtree, J.
Am. Chem. Soc. 2005, 127, 16299–16311.
Adv. Synth. Catal. 0000, 000, 0 – 0
9
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
12, 633–636; c) H.-C. Wu, J.-H. Chu, C.-W. Li, L.-C.
Hwang, M.-J. Wu, Organometallics 2016, 35, 288–300;
we reported one example of decarboxylative coupling
using phenyl bromide: d) K. H. Oh, S. M. Kim, M. J.
Lee, J. K. Park, Adv. Synth. Catal. 2015, 357, 3927–
3935.
Kim, K. H. Oh, J. K. Park, Green Chem. 2014, 16,
4098–4101.
[23] J. C. Garrison, W. J. Youngs, Chem. Rev. 2005, 105,
3978–4008.
[24] A. Poater, B. Cosenza, A. Correa, S. Giudice, F.
Ragone, V. Scarano, L. Cavallo, Eur. J. Inorg. Chem.
2009, 1759–1766.
[25] a) A. R. Chianese, X. Li, M. C. Janzen, J. W. Faller,
R. H. Crabtree, Organometallics 2003, 22, 1663–1667;
b) R. A. Kelly, H. Clavier, S. Giudice, N. M. Scott,
E. D. Stevens, J. Bordner, I. Samardjiev, C. D. Hoff, L.
Cavallo, S. P. Nolan, Organometallics 2008, 27, 202–210;
c) T. Drçge, F. Glorius, Angew. Chem. 2010, 122, 7094–
7107; Angew. Chem. Int. Ed. 2010, 49, 6940–6952.
[15] a) Y. Xiong, B. Ullman, J.-S. K. Choi, M. Cherrier, S.
Strah-Pleynet, M. Decaire, K. Feichtinger, J. M. Frazer,
W. H. Yoon, K. Whelan, E. K. Sanabria, A. J. Grottick,
H. Al-Shamma, G. Semple, Bioorg. Med. Chem. Lett.
2012, 22, 1870–1873; b) S. Lçber, H. Hꢄbner, P. Gmein-
er, Bioorg. Med. Chem. Lett. 1999, 9, 97–102.
[16] M. Nilsson, Acta Chem. Scand. 1966, 20, 423–426.
[17] For review papers, see: a) N. Rodrꢆguez, L. J. Goossen,
Chem. Soc. Rev. 2011, 40, 5030–5048; b) S. Rui, L. Lei,
Sci. China Chem. 2011, 54, 1670–1687; c) L. J. Goossen,
N. Rodrꢆguez, K. Goossen, Angew. Chem. 2008, 120,
3144–3164; Angew. Chem. Int. Ed. 2008, 47, 3100–3120;
d) K. Park, S. Lee, RSC Adv. 2013, 3, 14165–14182; for
recent Pd/Ag-catalyzed arylation, see: e) J.-B. E. Y.
Rouchet, C. Schneider, C. Fruit, C. Hoarau, J. Org.
Chem. 2015, 80, 5919–5927; for recent Ag-catalyzed ar-
ylation, see: f) J. Kan, S. Huang, J. Lin, M. Zhang, W.
Su, Angew. Chem. 2015, 127, 2227–2231; Angew. Chem.
Int. Ed. 2015, 54, 2199–2203; for recent Ni-catalyzed ar-
ylation, see: g) J. M. Crawford, K. E. Shelton, E. K.
Reeves, B. K. Sadarananda, D. Kalyani, Org. Chem.
Front. 2015, 2, 726–729. For recent Cu-catalyzed aryla-
tion, see; h) L. Chen, L. Ju, K. A. Bustin, J. M. Hoover,
Chem. Commun. 2015, 51, 15059–15062.
[18] P. Forgione, M.-C. Brochu, M. St-Onge, K. H. Thesen,
M. D. Bailey, F. Bilodeau, J. Am. Chem. Soc. 2006, 128,
11350–11351.
[19] K. Fagnou, M. Lautens, Angew. Chem. 2002, 114, 26–
49; Angew. Chem. Int. Ed. 2002, 41, 26–47.
[20] L. J. Goossen, G. Deng, L. M. Levy, Science 2006, 313,
662–664.
[21] CCDC 1477499 (5a) and CCDC 1477496 (5e) contain
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
[26] The TEPs of NHCs were calculated according to the
av/Rh
following equation. TEP=0.8001nCO
and TEP=0.8475nCO
+ 420.0 cmÀ1
+ 336.2 cmÀ1; a) R. Jothibasu,
av/Ir
H. V. Huynh, Chem. Commun. 2010, 46, 2986–2988; for
(NHC)Rh(CO)2Cl complex 8, nCOsym =2069, nCO
1991; b) P. Mathew, A. Neels, M. Albrecht, J. Am.
Chem. Soc. 2008, 130, 13534–13535; for
(NHC)Rh(CO)2Cl complex 9, nCOsym =2075, nCO
1996; c) K. Denk, P. Sirsch, W. A. Herrmann, J. Orga-
nomet. Chem. 2002, 649, 219–224; for
(NHC)Rh(CO)2Cl complex 10, nCOsym =2081, nCO
=
asym
asym
=
asym
=
1996; d) V. Cꢇsar, N. Lugan, G. Lavigne, Eur. J. Inorg.
Chem. 2010, 361–365; for (NHC)Rh(CO)2Cl complex
11 (in cmÀ1), nCOsym =2086, nCOasym =2005; e) Y. Zhou,
Q. Liu, W. Lv, Q. Pang, R. Ben, Y. Qian, J. Zhao, Orga-
nometallics 2013, 32, 3753–3759; for (NHC)Rh(CO)2Cl
complex 12, nCOsym =2068, nCOasym =1987; f) M. Alcara-
zo, S. J. Roseblade, A. R. Cowley, R. Fernꢅndez, J. M.
Brown, J. M. Lassaletta, J. Am. Chem. Soc. 2005, 127,
sym
3290–3291; for (NHC)Rh(CO)2Cl complex 13, nCO
=
2072, nCOasym =1992; g) C. A. Urbina-Blanco, X. Ban-
treil, H. Clavier, A. M. Z. Slawin, S. P. Nolan, Beilstein
J.
Org.
Chem.
2010,
6,
1120–1126;
for
=
asym
(NHC)Rh(CO)2Cl complex 14, nCOsym =2077, nCO
1996; h) R. A. Kelly, H. Clavier, S. Giudice, N. M.
Scott, E. D. Stevens, J. Bordner, I. Samardjiev, C. D.
Cambridge
www.ccdc.cam.ac.uk/data_request/cif.
Crystallographic Data
Centre via
Hoff, L. Cavallo, S. P. Nolan, Organometallics 2008, 27,
sym
202–210; for (NHC)Ir(CO)2Cl complex 15, nCO
=
[22] The distinguishable difference in NMR for both chlo-
ride and iodide salt is that the doublet of the C-7
proton of the iodide salt is somewhat downfield shifted
compared to that of chloride salt. For an alternative
synthetic method for the salt preparation, see: D. J.
2072, nCOasym =1989.
[27] Base upon the similar TEP values of 7c and 7d, sigma
donation should not be the only factor for reactivity.
[28] L. Canovese, F. Visentin, C. Levi, A. Dolmella, Dalton
Trans. 2011, 40, 966–981.
Adv. Synth. Catal. 0000, 000, 0 – 0
10
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
Development of Structurally Diverse N-Heterocyclic
Carbene Ligands via Palladium-Copper-Catalyzed
Decarboxylative Arylation of Pyrazolo[1,5-a]pyridine-3-
carboxylic Acid
11
Adv. Synth. Catal. 2016, 358, 1 – 11
Khyarul Alam, Seong Min Kim, Do Joong Kim,
Jin Kyoon Park*
Adv. Synth. Catal. 0000, 000, 0 – 0
11
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!