Steric Effect of Carboxylate Ligands on Pd-Catalyzed Intramolecular C(sp2)–H and C(sp3)–H Arylation Reactions

Article abstract of DOI:10.1002/anie.201804566

A bulky carboxylic acid bearing three cyclohexylmethyl substituents at the α-position, namely, tri(cyclohexylmethyl)acetic acid, is demonstrated to act as an efficient ligand source in Pd-catalyzed intramolecular C(sp²)?H and C(sp³)?H arylation reactions. The reactions proceed smoothly under mild reaction conditions, even at room temperature due to the steric bulk of the carboxylate ligands, which accelerates the rate-determining C?H bond activation step in the catalytic cycle.

Full text of DOI:10.1002/anie.201804566

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Steric Effect of Carboxylate Ligands on Pd-Catalyzed
Intramolecular C(sp2)-H and C(sp3)-H Bond Arylation Reactions
Authors: Yutaka Tanji, Naoya Mitsutake, Tetsuaki Fujihara, and
Yasushi Tsuji
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201804566
Angew. Chem. 10.1002/ange.201804566
Link to VoR: http://dx.doi.org/10.1002/anie.201804566
http://dx.doi.org/10.1002/ange.201804566

10.1002/anie.201804566
Angewandte Chemie International Edition
COMMUNICATION
Steric Effect of Carboxylate Ligands on Pd-Catalyzed
Intramolecular C(sp2)–H and C(sp3)–H Bond Arylation Reactions
Yutaka Tanji, Naoya Mitsutake, Tetsuaki Fujihara,* and Yasushi Tsuji*
[a]
Y. Tanji, N. Mitsutake, Prof. Dr. T. Fujihara, Prof. Dr. Y. Tsuji
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering
Kyoto University, Kyoto 615-8510 (Japan)
E-mail: tfuji@scl.kyoto-u.ac.jp, ytsuji@scl.kyoto-u.ac.jp
Supporting information for this article is given via a link at the end of the document.
Abstract: A bulky carboxylic acid bearing three cyclohexylmethyl
substituents at the -position, i.e., tri(cyclohexylmethyl)acetic acid, is
demonstrated to act as an efficient ligand source in the Pd-catalyzed
intramolecular C(sp2)–H and C(sp3)–H bond arylation reactions. The
reactions proceed smoothly under mild reaction conditions, even at
room temperature, taking advantage of the steric bulk of the
carboxylate ligands, which accelerates the rate-determining C–H
bond activation step in the catalytic cycle.
evaluate them as carboxylate ligands in the Pd-catalyzed
intramolecular C(sp2)–H and C(sp3)–H bond arylation reactions.
The steric effect of added carboxylic acids was found to be crucial.
Thus, the addition of carboxylic acid of suitable steric bulk
remarkably enhanced the catalytic activity and the C–H arylation
reactions were shown to occur under milder reaction conditions,
even at room temperature.
First, various carboxylic acids were screened as ligand
sources for the Pd-catalyzed intramolecular C(sp2)–H bond
arylation reaction using (2-bromobenzyloxy)benzene (2a)[3e,11] as
a substrate. The intramolecular C–H arylation reactions are
usually performed at a high reaction temperature (over 100 °C);[3]
however, herein, the reactions in Table 1 were performed at a low
temperature (70 °C) for short reaction time (3 h) to evaluate the
efficiency of the added carboxylic acid (1) evidently, employing 30
mol% of 1 in the presence of a catalytic amount (3.0 mol%) of
PdCl2, and K2CO3 (1.5 equiv) in N,N-dimethylacetamide (DMA)
(conditions A). In the study reported by Fagnou, phosphine ligand
was added to the Pd catalytic system.[2a-b,3,4,5a–d] However, Hartwig
observed that the reactions proceeded in a similar manner without
the need for adding phosphines.[12] Therefore, for an
unambiguous observation of the effect of the carboxylic acid, we
performed the reactions without adding any phosphine ligand. As
catalyst precursors, PdCl2 and Pd(OAc)2 were examined and
comparable results were found under the present reaction
conditions. Thus, PdCl2 was selected as a catalyst precursor to
eliminate contamination by acetate ligand. Pivalic acid (1a)
proved ineffective at 70 °C and product (3a) was obtained in only
14% yield (entry 1, Table 1), whereas the yield increased to 78%
at 110 °C and 85% at 125 °C. In the absence of the added
carboxylic acid, only a trace amount of 3a was detected in the
reactions performed at 70–125 °C. In addition, -mono- (1b and
1c) and -di- (1d and 1e) substituted carboxylic acids were not
effective as ligands (entries 2–5). As for -tri-substituted
carboxylic acids, 1-adamantanecarboxylic acid (1f) was also
inefficient (entry 6). However, other -tri-substituted carboxylic
acids such as 1g, 1h, 1i, 1j, and 1k afforded 3a in higher or
comparable yields compared with 1a (entries 7–11). Eventually,
1l bearing three cyclohexylmethyl substituents at the -position
afforded 3a in 93% yield (entry 12). Carboxylic acids containing
aromatic rings such as 1m, 1n, 1o, and 1p were ineffective
(entries 13-16). Furthermore, at even 25 °C with 1l using 1,3-
dimethyl-2-imidazolidinone (DMI) as a solvent and Rb2CO3 as a
base (conditions B), 3a was obtained in 97% GC yield and 95%
Carboxylate ligands have proved to be invaluable
components in transition metal-catalyzed carbon–hydrogen (C–
H) bond activation reactions.[1] A pioneering study reported by
Fagnou showed that in Pd-catalyzed C–H bond arylation
reactions, the pivalate ligand is particularly efficient compared to
the conventional acetate ligand.[2] The addition of pivalic acid
allows realizing milder reaction conditions in various
intramolecular C–H arylation reactions[3] as well as in the
intermolecular C–H arylation of electron-deficient arenes[4] and
electron-rich heteroarenes.[5] Pivalate is a slightly stronger base
than acetate (the pKa values[6] of pivalic acid and acetic acid are
5.03 and 4.76, respectively), which facilitates the intramolecular
deprotonation step.[7] In contrast, the steric effect of the
carboxylate ligand could be crucial. However, only a few studies
have elucidated the specific effect of the steric bulk of carboxylate
ligands on the catalytic C–H bond activation reactions.[3e,5g,8] In
fact, only known bulky carboxylic acids such as pivalic and 1-
adamantanecarboxylic acids are currently employed as efficient
carboxylate ligand sources.[2-5] Recently, Thompson et al.
extensively studied the steric effect of carboxylate ligands using
24 different carboxylic acids as additives in the Pd-catalyzed
direct arylation polymerization (DArP) at 160 °C.[9] The results
indicated that the yields of the polymers were not affected by the
steric bulk of added carboxylic acids, whereas the smallest one,
i.e., cyclopropanecarboxylic acid, provided a polymer with very
high molecular weight.
We previously developed various bulky ligands such as
pyridines,[10a] amines,[10b] phosphines,[10c-e] and N-heterocyclic
carbenes[10f] bearing substantial steric bulk, which enabled high
catalytic activities by suppressing aggregation of catalyst species.
We envisioned that carboxylate ligands of appropriate steric bulk,
not basicity, would realize highly active catalysts for C–H bond
activation reactions. Herein, we describe the design and
preparation of carboxylic acids of different steric congestion, and
1
This article is protected by copyright. All rights reserved.

10.1002/anie.201804566
Angewandte Chemie International Edition
COMMUNICATION
isolated yield (entry 12). As a Pd catalyst precursor, Pd(OAc)2 and
Pd(NO3)2 in place of PdCl2 in entry 12 under conditions B also
afforded 3a in 87% and 96% yields, respectively. In contrast, 1a
only provided 3a in 20% yield under conditions B (entry 1).[13]
Other -mono- (1b and 1c), -di- (1d and 1e), and -tri-
substituted carboxylic acids (1f–k and 1m) or aromatic carboxylic
acids (1n–p) proved less effective than 1l under conditions B
(entries 2–11 and 13-16). From these results, it can be concluded
that 1l was the most effective carboxylate ligand source under
conditions A and B (entry 12).[13]
It is well known that the pKa values of carboxylic acids are
closely related to the maximum values of their molecular
electrostatic potential (max MEP).[14] Thus, pKa values of 1f–l
were assessed with the max MEP values calculated via DFT
method (B3LYP/6-311G++(2d,p)).[15] Even with almost similar
pKa values of 1f–l (5.27–5.63),[16] efficiency of the added 1f–l
differed largely among each other (Table 1). This suggests that
steric effects rather than electronic effects (basicity) of 1 are
responsible for the efficiency in the C–H arylation reactions.
Next, with the selected carboxylic acid 1l in hand, various
substrates (2b–r) were examined (Table 2). A wide variety of
fanctionalities were torelated, and products having methoxy (3b),
chloro (3c), formyl (3d), methoxycarbonyl (3e), acetyl (3f), cyano
(3g), trifluoromethyl (3h) and nitro (3i) substituents were
successfully obtained at 25°C in high isolated yields (entries 1–8).
Substrates with amine (2j: Ms = SO2CH3) and amide (2k) tethers
also afforded the products (3j and 3k) at 25°C in high isolated
yields (entries 9–10), whereas 3l with an ester tether was
obtained in 83% yield at 50°C (entry 11). When the reaction of 2l
using 1a at higher temperature (100 °C), most of 2l was
decomposed and 3l was not obtained at all. The C(sp2)–H bond
arylation of naphthalene and thiophene rings provided six-
membered rings (3m and 3n) in high yields at 25 °C (entries 12–
13). Furthermore, five-membered rings were easily afforded at
25 °C via the C(sp2)–H bond arylation of indole ring (3o), whereas
9-fluorenone (3p) and carbazole (3q) skeltons were similarly
constructed at 50 °C and at 60 °C, respectively (entries 14–16).
In addition, a seven-membered ring product (3r) was smoothly
afforded at 70 °C (entry 17).
Table 1. Effect of Carboxylic Acid Additives on the Pd-catalyzed C-H Arylation
Reaction of 2a
Table 2. Intramolecular C(sp2)–H Arylation of Various Substrates[a]
PdCl2 (5.0 mol%)
Conditions A (at 70 ºC)[a] or
Conditions B (at 25 ºC)[b]
O
1l
(30 mol%)
O
Ar
Rb2CO3 (1.5 eq.)
H
Ar
Br
in DMI
25 °C, 24 h
H
Br
2b-r
3a
2a
entry
3b-r
isolated yield
entry
Carboxylic Acid
GC yield[c] Conditions A, Conditions B
O
1[b]R = OMe ( ) 91%
3b
5[b]R = COMe ( ) 99%
3f
NMs
COOH
1
2
3
4
5
2
3
R = Cl (3c) 99%
6
7
R = CN (3g) 91%
COOH
1d
3d
3h
(
R = CHO ( ) 99%
R = CF3
) 91%
COOH
COOH
CH3COOH
9
4[b]R = COOMe ( ) 99% 8 R = NO2
(
3e
3i
) 85%
3j
R
N
1a
14%, 20%
1b
8%, 2%
1c
11%, 3%
1e
10%, 8%
91%
12%, 6%
O
O
O
N
O
S
O
6
7
8
11[c,d]
[c]
10 3k
3l
123m
13 3n
COOH
COOH
COOH
89%
83%
94%
92%
1f
8%, 9%
1g
21%, 20%
1h
13%, 30%
O
N
SO2
H
N
N
9
10
11
12
[e]
15[c,d]
16
17[c,f,g]
14 3o
83%
3p
3q
74%
3r
COOH
COOH
COOH
COOH
91%
78%
[a] Conditions: 2 (0.20 mmol), PdCl2 (0.010 mmol, 5.0 mol %), 1l (0.060 mmol,
30 mol %), Rb2CO3 (0.30 mmol, 1.5 equiv) in DMI (0.50 mL) at 25 °C for 24 h.
[b] For 40 h. [c] K2CO3 instead of Rb2CO3. [d] At 50 °C. [e] At 60 °C. [f] At
70 °C. [g] DMA instead of DMI.
1i
1j
1k
64%, 25%
1l
93%, 97% (95%)[d]
29%, 77%
13%, 49%
13
14
15
16
COOH
COOH
COOH
In general, intramolecular C(sp3)–H arylation reactions are
known to require high reaction temperatures (~150 °C).[2b,3c,d] In
contrast, when the reaction of 2s was performed with 1l at 90 °C
in the presence of a catalytic amount (5.0 mol%) of PdCl2 and
K2CO3 (1.5 equiv) in DMA without added phosphine ligands, the
corresponding product 3s was obtained in 84% isolated yield
(Scheme 1a). Once again, 3s was not obtained in the absence of
carboxylic acids. In Scheme 1a, 1a in place of 1l under otherwise
identical conditions afforded 3s in only 3% yield at 90 °C,[17]
whereas the yields increased to 48% at 150 °C. When 1b, 1c, 1d,
1e, 1f, 1i, or 1k was used instead of 1l in Scheme 1a, 3s was
obtained in only 0%, 2%, 3%, 16%, 12%, 9%, or 32% yields,
COOH
1m
20%, 1%
1n
3%, 0%
1o
11%, 2%
1p
5%, 1%
[a] Conditions A: 2a (0.20 mmol), PdCl2 (0.0060 mmol, 3.0 mol %), carboxylic
acid (1, 0.060 mmol, 30 mol %), K2CO3 (0.30 mmol, 1.5 equiv) in DMA (1.50 mL)
at 70 °C for 3 h. [b] Conditions B: PdCl2 (0.010 mmol, 5.0 mol %), carboxylic acid
(1, 0.060 mmol, 30 mol %), Rb2CO3 (0.30 mmol, 1.5 equiv) in DMI (0.50 mL), 2a
(0.20 mmol) at 25 °C for 40 h. [c] Determined by GC analysis using an internal
standard method. [d] Yield of isolated product
2
This article is protected by copyright. All rights reserved.

10.1002/anie.201804566
Angewandte Chemie International Edition
COMMUNICATION
respectively. Thus, again, 1l was demonstrated to be particularly
effective in the C(sp3)-H arylation.[17] Moreover, upon addition of
1l, substrates 2t and 2u afforded the corresponding products 3t
and 3u in 84% and 76% isolated yields at 90 °C and 60 °C,
respectively (Scheme 1b, c).
PdCl2 (5.0 mol%)
1l
(30 mol%)
K2CO3 (1.5 eq.)
R
R
H
in DMA
Br
at 90 ºC or 60 ºC
3s-u
isolated yield
2s-u
(a)
(b)
O
(c)[b]
O
N
O
N
O2N
Figure 1. X-ray Structure of 1l
3s
84%
3t
84%
3u
76%
[a] Conditions: 2s-u (0.20 mmol), PdCl2 (0.010 mmol, 5.0 mol%), 1l (0.060
mmol, 30 mol %), K2CO3 (0.30 mmol, 1.5 equiv) in DMA (2.0 mL) at 90 °C for
16 h. [b] At 60 °C.
Cotton et al. examined the X-ray crystal structures of three
Pd carboxylates of formula [Pd(O2CR1)2]3 (R1 = Et, tBu, 2,4,6-
MeC6H2),[18a] finding that all these complexes had analogous
trimer structures containing Pd3 triangles with each pair of Pd
atoms bridged by two carboxylate ligands. Notably, these
structures are very similar to the trimer structure of the
corresponding acetate complex.[18b,c] Ozawa et al. reported the
structures of [PdPh(-O2CR2)(PPh3)]n (R2 = CH3 and tBu)
complexes[18d] relevant to active catalyst species in DArP.[9,18e] In
this case, they found that acetate and pivalate complexes had
almost similar dimer structures: [PdPh(-O2CR2)(PPh3)]2 (R2 =
CH3 and tBu). Thus, the structures and nuclearity of these
carboxylate complexes did not seem to be affected by the
carboxylate ligands. In contrast, 1l introduces a considerable
steric bulk around the Pd center as suggested by Figure 1 and
Scheme 2 (R = Cy). Therefore, in the present study, the unique
steric effect of 1l as a ligand source most likely generates an
extremely active mononuclear Pd catalyst species, which could
accelerate the rate-determining C–H bond cleavage step even
under mild reaction conditions. Further studies on the reaction
mechanism are currently in progress.
Scheme 1. Intramolecular C(sp3)–H Arylation Reactions[a]
Kinetic isotope effect (KIE) was measured by comparing initial
rates of the reactions using 2a and 2a-d3 (2-BrC6H4CH2-O-(2,4,6-
d3C6H2) under conditions A, affording kH/kD = 4.68.[15] Thus, the
C–H bond cleavage step must be involved in the rate-determining
step.
From the results obtained, the steric effect of the carboxylate
ligands can be considered crucial in the present reaction (vide
supra). The steric effect of -tri-substituted carboxylic acids could
be evaluated by analyzing the C1(carbonyl carbon)–C2(-C)–
C3(-C)–C4(-C) dihedral angle,  (Scheme 2). To this end, single
crystals of 1l suitable for X-ray crystallographic analysis were
successfully obtained and the corresponding X-ray structure is
shown in Figure 1. The dihedral angles  obtained from the X-ray
structure are 28.2°, 68.8°, and 178.9° (R = Cy: cyclo-C6H11 in
Scheme 2). Further DFT optimization (with B3LYP/6-
311G++(2d,p)) with the X-ray structure in Figure 1 as an initial
structure afforded the dihedral angles  of 54.5°, 65.9°, and
175.2°. Accordingly, two of the three Cy- substituents would be
located in close proximity to the carboxy group causing
considerable steric congestion around the coordination site of Pd.
In contrast, such steric effect cannot be expected for pivalic acid
(R = H in Scheme 2).
In summary, we found that a bulky carboxylic acid bearing
three cyclohexylmethyl substituents at the -position worked as
an efficient ligand in the Pd-catalyzed intramolecular C(sp2)–H
and C(sp3)–H bond arylation reactions. The reactions proceed
smoothly under very mild conditions, even at room temperature.
Studies to extend the scope of 1l to a variety of C–H activation
reactions are currently underway.[19]
1
COOH

4
4
3
2
1
R
H
2
(RCH2)3–C–COOH



3
R
R
H
Scheme 2. Dihedral Angle for -tri-Substituted Carboxylic Acid
3
This article is protected by copyright. All rights reserved.

10.1002/anie.201804566
Angewandte Chemie International Edition
COMMUNICATION
[13] Fagnou at al. reported that the use of (4-FC6H4)3P or PPh3 with 1a
enhanced the catalytic reactivity in the C(sp2)–H arylation reaction.[3e]
However, the addition of 5 mol% of (4-FC6H4)3P or PPh3 to entry 1 in
Table 1 under conditions B resulted in the formation of 3a in only 7%
yield in both cases. Furthermore, upon addition of 5 mol% of (4-FC6H4)3P
or PPh3 to entry 12 in Table 1 (with 1l) under conditions B, the yield of 3a
decreased considerably from 97% to 14% or 16%, respectively. When
the loading of 1l was reduced to 10 mol% under conditions B, the reaction
perfectly proceeded after 72 h.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Number
17H03096 in Grant-in-Aid for Scientific Research (B) from MEXT,
Japan (YT). TF acknowledged JSPS KAKENHI Grant Number
JP16H01020 in Precisely Designed Catalysts with Customized
Scaffolding from MEXT, Japan.
[14] a) S. Liu, L. G. Pedersen, J. Phys. Chem. A 2009, 113, 3648; b) M. Virant,
S. D. T. Talian, Č. Podlipnik, B. Hribar-Lee, Acta. Chim. Slov. 2017, 64,
560.
Keywords: Arylation • Carboxylic Acid • C-H Activation •
Palladium
[15] See Supporting Information for details.
[16] pKa values of 1a-p: 1a (5.03),[6] 1b (4.76),[6] 1c (4.85),[6] 1d (4.84),[6] 1e
(4.91),[6] 1f (5.50), 1g (5.35), 1h (5.63), 1i (5.39), 1j (5.63), 1k (5.27),1l
References:
(5.37), 1m (4.88), 1n (4.20),[6] 1o (5.37), 1p (3.69). [6]
.
[17] The use of PCy3ꞏHBF4[2b,3c,d] (10 mol%) with 1a under otherwise identical
reaction conditions only increased slightly the yield of 3s from 3% to 5%.
Furthermore, the use of PCy3·HBF4 (10 mol%) with 1l in Scheme 1a
afforded a dramatic decrease of the yield of 3s from 84% to 6%.
[18] a) D. P. Bancroft, F. A. Cotton, L. R. Falvello, W. Schwotzer, Polyhedron,
1988, 7, 615; b) T. A. Stephenson, S. M. Morehouse, A. R. Powell, J. P.
Heffer, G. Wilkinson, J. Chem. Soc. 1965, 3632; c) A. C. Skapski, M. L.
Smart, J. Chem. Soc. D, Chem. Commun. 1970, 658; d) M. Wakioka, Y.
Nakamura, Q. Wang, F. Ozawa, Organometallics 2012, 31, 4810; e) Q.
Wang, R. Takita, Y. Kikuzaki, F. Ozawa, J. Am. Chem. Soc. 2010, 132,
11420.
[1]
[2]
[3]
For reviews, see: a) D. Lapointe, K. Fagnou, Chem. Lett. 2010, 39, 1118;
b) L. Ackermann, Acc. Chem. Res. 2014, 47, 281; c) L. Ackermann,
Chem. Rev. 2011, 111, 1315.
a) M. Lafrance, K. Fagnou, J. Am. Chem. Soc. 2006, 128, 16496; b) S.
Rousseaux, S. I. Gorelsky, B. K. W. Chung, K. Fagnou, J. Am. Chem.
Soc. 2010, 132, 10692.
a) Y. Minami, Y. Noguchi, T. Hiyama, J. Am. Chem. Soc. 2017, 139,
14013; b) S. Rousseaux, M. Davi, J. Sofack-Kreutzer, C. Pierre, C. E.
Kefalidis, E. Clot, K. Fagnou, O. Baudoin, J. Am. Chem. Soc. 2010, 132,
10706; c) D. Garcia-Cuadrado, P. de Mendoza, A. A. C. Braga, F.
Maseras, A. M. Echavarren, J. Am. Chem. Soc. 2007, 129, 6880; d) S.
Pascual, P. de Mendoza, A. A. C. Braga, Tetrahedron 2008, 64, 6021; e)
M. Lafrance, D. Lapointe, K. Fagnou, Tetrahedron 2008, 64, 6015.
a) L.-C. Campeau, D. R. Stuart, J.-P. Leclerc, M. Bertrand-Laperle, E.
Villemure, H.-Y. Sun, S. Lasserre, N. Guimond, M. Lecavallier, K.
Fagnou, J. Am. Chem. Soc. 2009, 131, 3291; b) L.-C. Campeau, M.
Bertrand-Laperle, J.-P. Leclerc, E. Villemure, S. Gorelsky, K. Fagnou, J.
Am. Chem. Soc. 2008, 130, 3276; c) M. P. Huestis, K. Fagnou, Org. Lett.
2009, 11, 1357; d) L. Caron, L.-C. Campeau, K. Fagnou, Org. Lett. 2008,
10, 4533; e) D. J. Schipper, M. El-Salfiti, C. J. Whipp, K. Fagnou,
Tetrahedron 2009, 65, 4977.
[19] When the intermolecular C-H arylation reaction of 4-bromotoluene with
benzene was carried out, 1l was not effective (See Supporting
Information for details).
[4]
[5]
a) S. I. Gorelsky, D. Lapointe, K. Fagnou, J. Am. Chem. Soc. 2008, 130,
10848; b) B. Liégault, I. Petrov, S. I. Gorelsky, K. Fagnou, J. Org. Chem.
2010, 75, 1047; c) B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K.
Fagnou, J. Org. Chem. 2009, 74, 1826; d) O. René, D. Lapointr, K.
Fagnou, Org. Lett. 2009, 11, 4560; e) L. Ackermann, R. Vicente, R. Born,
Adv. Synth. Catal. 2008, 350, 741; f) L. Ackermann, A. Althammer, S.
Fenner, Angew. Chem. 2009, 121, 207; Angew. Chem. Int. Ed. 2009, 48,
201; g) D. Zhao, W. Wang, S. Lian, F. Yang, J. Lan, J. You, Chem. Eur.
J. 2009, 15, 1337.
[6]
[7]
Handbook of Chemistry and Physics, 87th ed.; D. R. Lide, Ed.; CRC
Press: Boca Raton, 2006; 8.
a) D. L. Davies, S. M. A. Donald, S. A. Macgregor, J. Am. Chem. Soc.
2005, 127, 13754; b) Vicente, J.; Saura-Llamas, I. Comments Inorg.
Chem. 2007, 28, 39.
[8]
[9]
a) M. Lafrance, S. I. Gorelsky, K. Fagnou, J. Am. Chem. Soc. 2007, 129,
14570. b) L.; Ackermann, A. V. Lygin, Org. Lett. 2011, 13, 3332.
A. E. Rudenko, B. C. Thompson, Macromolecules, 2015, 48, 569.
[10] a) T. Iwasawa, M. Tokunaga, Y. Obora, Y Tsuji, J. Am. Chem. Soc. 2004,
126, 6554; b) H. Aoyama, M. Tokunaga, J. Kiyosu, T. Iwasawa, Y. Obora,
Y. Tsuji, J. Am. Chem. Soc. 2005, 127, 10474; c) O. Niyomura, M.
Tokunaga, Y. Obora, T. Iwasawa, Y. Tsuji, Angew. Chem. 2003, 115,
1325; Angew. Chem. Int. Ed. 2003, 42, 1287; d) T. Fujihara, S. Yoshida,
H. Ohta, Y. Tsuji, Angew. Chem. 2008, 120, 8434; Angew. Chem. Int. Ed.
2008, 47, 8310; e) T. Fujihara, K. Semba, J. Terao, Y. Tsuji, Angew.
Chem. 2010, 122, 1514; Angew. Chem. Int. Ed. 2010, 49, 1472; f) T.
Fujihara, Y. Tomike, T. Ohtake, J. Terao, Y. Tsuji, Chem. Commun. 2011,
47, 9699; g) T. Fujihara, A. Yoshida, M. Satou, Y. Tanji, J. Terao, Y. Tsuji,
Catal. Commun. 2016, 84, 71.
[11] L.-C. Campeau, M. Parisien, M. Leblanc, K. Fagnou, J. Am. Chem. Soc.
2004, 126, 9186.
[12] Y. Tan, J. F. Hartwig, J. Am. Chem. Soc. 2011, 133, 3308.
4
This article is protected by copyright. All rights reserved.

10.1002/anie.201804566
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
The design and preparation of carboxylic acids of different steric congestion, and evaluation of them as carboxylate ligands in the Pd-
catalyzed intramolecular C(sp2)–H and C(sp3)–H bond arylation reactions. It can be concluded that a bulky carboxylic acid bearing
three cyclohexylmethyl substituents at the -position, i.e., tri(cyclohexylmethyl)acetic acid was the most effective carboxylate ligand
source.
5
This article is protected by copyright. All rights reserved.