Ligand-Promoted Palladium-Catalyzed C?H Acetoxylation of Simple Arenes

Article abstract of DOI:10.1002/cctc.201600757

The palladium-catalyzed C?H oxidation of simple arenes is an attractive strategy to obtain phenols, which have many applications in the fine chemicals industry. Although some advances have been made in this research area, low reactivity and selectivity are, in general, observed. This report describes a new catalytic system for the efficient C?H acetoxylation of simple arenes based on Pd(OAc)₂ and a pyridinecarboxylic acid ligand.

Full text of DOI:10.1002/cctc.201600757

DOI: 10.1002/cctc.201600757
Communications
Ligand-Promoted Palladium-Catalyzed CÀH Acetoxylation
of Simple Arenes
Carolina Valderas, Kananat Naksomboon, and M. ꢀngeles Fernꢁndez-IbꢁÇez*[a]
The palladium-catalyzed CÀH oxidation of simple arenes is an
attractive strategy to obtain phenols, which have many appli-
cations in the fine chemicals industry. Although some advances
have been made in this research area, low reactivity and selec-
tivity are, in general, observed. This report describes a new cat-
alytic system for the efficient CÀH acetoxylation of simple
arenes based on Pd(OAc)2 and a pyridinecarboxylic acid ligand.
simple arenes by using PhI(OAc)2 as the oxidant and partially
controls the site selectivity of the reaction.[10] Less-active cata-
lytic systems for the CÀH acetoxylation of arenes by using dif-
ferent types of ligands and oxidants have been described.[11]
Herein, we report a new catalytic system based on a bidentate
picolinic acid ligand for the Pd(OAc)2-catalyzed CÀH acetoxyla-
tion of simple arenes by using PhI(OAc)2 as the oxidant. The
presence of the picolinic acid ligand enhanced the reactivity
and provided the highest turnover number (TON=7800) re-
ported for the Pd(OAc)2-catalyzed CÀH acetoxylation of ben-
zene and, furthermore, increased the site selectivity of the
reaction with substituted arenes.
Metal-catalyzed CÀH functionalization has emerged as a power-
ful tool to construct complex molecules with the potential to
revolutionize chemical synthesis.[1] However, this approach is
still in its infancy and many challenges need to be overcome
before this strategy can become a routine synthetic tool for or-
ganic chemists. The main limitations of this approach are the
low reactivity of the CÀH bond and the low selectivity ob-
tained in substrates that contain diverse CÀH bonds. In gener-
al, these limitations can be circumvented by using directing
groups that are able to increase the reactivity and selectivity of
the CÀH functionalization process.[2–4] Nevertheless, the use of
directing groups generally implies the addition of two extra
steps in the synthetic sequence, the introduction and removal
of the directing group, which frustrates the real goal of this
strategy. An ideal approach to increase the reactivity and selec-
tivity of these processes is the use of suitable ligands. Howev-
er, to date only a limited number of ligands are able to pro-
mote the direct functionalization of CÀH bonds,[5] and in the
majority of these examples, the presence of a directing group
is still required. Therefore, to unlock the full potential of metal-
catalyzed CÀH functionalization, the discovery of new ligands
capable of increasing the reactivity and selectivity of these
processes is of central importance.
Our ligand design was inspired by the recent success of pyri-
dine ligands in Pd-catalyzed CÀH functionalization reac-
tions[5b,10,12] as well as by the fact that carboxylic acids are ca-
pable to assist CÀH bond cleavage[13] in a wide number of
metal-catalyzed CÀH functionalization reactions, including CÀH
acetoxylation.[14] We envisioned that the combination of both
functionalities would enhance the reactivity and site selectivity
of the Pd-catalyzed CÀH acetoxylation of simple arenes as well
as the stability of the catalyst.
In our model reaction involving the use of benzene,
Pd(OAc)2 (2 mol%), and PhI(OAc)2 (1 equiv.) in AcOH/Ac2O, we
tested different pyridinecarboxylic acid derivatives (Scheme 1).
The reactions were performed by using Pd(OAc)2 (2 mol%) and
a 1:1 ratio of Pd/ligand, and the mixtures were stirred at 1008C
for 3 h, the moment at which the formation of Pd black was
detected in the majority of the reactions.
We clearly observed that the addition of the picolinic acid
ligand enhanced the reactivity of the CÀH acetoxylation of
benzene (50% yield, see kinetic profile in the Supporting Infor-
mation). The reaction proceeded without the formation of by-
products; neither overoxidation of phenyl acetate nor biphenyl
were observed in the reaction. The screening of other commer-
cially available pyridinecarboxylic acid derivatives as ligands
did not provide a significant difference in the outcome of the
reaction; nevertheless, some trends were identified. If electron-
donating groups were attached to the C6 position of the pico-
linic acid ligand (e.g., 6-methylpicolinic acid and 6-methoxypi-
colinic acid), phenyl acetate (1) was obtained in lower yields
(38–43%). If electron-withdrawing groups were attached to
the C6 position of the picolinic acid ligand [e.g., 6-fluoropico-
linic acid and 6-(trifluoromethyl)picolinic acid], phenyl acetate
(1) was delivered in comparable yields (52–55%) with the ex-
ception of 6-nitropicolinic acid, which provided phenyl acetate
(1) in only 17% yield. Moreover, similar results were obtained if
the reaction was performed in the presence of 5-fluoropicolinic
acid, 2-quinolinecarboxylic acid, 8-quinolinecarboxylic acid, or
2-pyridinesulfonic acid ligands.
The direct oxidation of simple arenes is an attractive process
to obtain phenols, which have many applications in organic
synthesis.[6,7] The palladium-catalyzed CÀH acetoxylation of
benzene has been described in the presence of strong oxi-
dants (e.g., K2Cr2O7, K2S2O8),[8] albeit with low catalytic turnover
and significant formation of the biphenyl byproduct. In 1996,
Crabtree reported the use of PhI(OAc)2 as an oxidant, and it
showed higher activity and precluded the formation of biphen-
yl.[9] More recently, Sanford described that the addition of pyri-
dine accelerates the Pd(OAc)2-catalyzed CÀH acetoxylation of
[a] Dr. C. Valderas, K. Naksomboon, Dr. M. ꢀ. Fernꢁndez-IbꢁÇez
Van’t Hoff Institute for Molecular Sciences
University of Amsterdam
Science Park 904, 1098 XH Amsterdam (The Netherlands)
E-mail: m.a.fernandezibanez@uva.nl
Supporting Information for this article can be found under http://
dx.doi.org/10.1002/cctc.201600757.
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the reaction was performed with 3 mol% of ligand, the prod-
uct was obtained in only 27% yield (Table 1, entry 5), and no
product formation was observed upon using 4 mol% of ligand
(Table 1, entry 6). In all these reactions using 2 mol% of
Pd(OAc)2 and different amounts of 6-fluoropicolinic acid, an in-
soluble palladium complex precipitated, which was isolated by
filtration from the mixture and identified by IR spectroscopy
and mass spectrometry as complex 2 (Scheme 2).
Scheme 2. Synthesis of palladium complexes 2 and 3.
Palladium complex 2 possess two molecules of the ligand
and was independently prepared by the reaction of Pd(OAc)2
with 2 equivalents of 6-fluoropicolinic acid in CH2Cl2 at room
temperature to confirm its identity. In addition, similar results
were observed if the CÀH acetoxylation of benzene was per-
formed by using picolinic acid as the ligand. In this case, the
solid that precipitated from the reaction was identified as pal-
ladium complex 3.[15] Both palladium complexes were found to
be insoluble at room temperature in all solvents tested and
nearly inactive in the CÀH acetoxylation of benzene. Indeed,
the CÀH acetoxylation of benzene in the presence of com-
plex 2 (2 mol%) at 1008C after 14 h provided phenyl acetate
(1) in only 15% yield. Under the same reaction conditions
upon using complex 3 (2 mol%), no conversion into phenyl
acetate (1) was observed. These results explain why low con-
versions were observed upon increasing the amount of ligand
(Table 1, entries 5 and 6). Notably, during the reaction and in-
dependent of the amount of ligand added, these inactive com-
plexes were formed, which lowered the real catalyst loading.
The high catalytic activity observed for this system can be at-
tributed to the formation of the active catalyst, which we spec-
ulate is a monomeric complex with one ligand (see Scheme 3).
We next explored the catalyst loading for the CÀH acetoxyla-
tion of benzene by using a Pd(OAc)2/6-fluoropicolinic acid ratio
of 1:0.75. As shown in Table 2, the addition of 4 mol%
Pd(OAc)2 led to the formation of phenyl acetate (1) in 69%
yield (Table 2, entry 1). Upon performing the reactions with Pd
loadings between 3 and 1.5 mol%, the yields of the product
were approximately 54–56% (Table 2, entries 2–4). Slightly
lower yields were observed upon employing a catalyst loading
of 1 or 0.5 mol% (Table 2, entries 5 and 6). In a previous report
for the CÀH acetoxylation of benzene it was observed that the
reaction stopped after the formation of Pd black.[10a] In all
these reactions, the formation of Pd black was observed after
3 h with the exception of the reaction performed in the pres-
ence of 0.5 mol% Pd(OAc)2. Therefore, we repeated the CÀH
acetoxylation of benzene with 0.5 mol% Pd(OAc)2, and the
mixture was stirred until the formation of Pd black was ob-
Scheme 1. Screening of bidentate ligands in the Pd-catalyzed CÀH acetoxy-
lation of benzene.[a]
Different palladium salts and solvents were evaluated in the
model reaction by using picolinic acid as the ligand without
any significant improvement in the yield of phenyl acetate (1)
(see Supporting Information). We next optimized the ligand/Pd
ratio in the CÀH acetoxylation of benzene at 1008C by using
2 mol% of Pd(OAc)2 and 6-fluoropicolinic acid as the ligand
(Table 1).
The reaction proceeded with similar yields by using 2 or
1.5 mol% of the ligand (Table 1, entries 3 and 4) and with
a minimal deleterious effect in the yield by using 0.5 mol% of
the ligand (Table 1, entry 1; 50% yield). On the other hand, if
Table 1. Optimization of the ligand ratio in the Pd-catalyzed CÀH
acetoxylation of benzene.
Entry
6-Fluoropicolinic acid [mol%]
Yield[a] [%]
1
2
3
4
5
6
0.5
1
1.5
2
3
4
50
52
56
55
27
0
[a] Yields were determined by GC analysis by using PhCl as an internal
standard.
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Scheme 3. Proposed mechanism with Pd(OAc)2/6-fluoropicolinic acid.
Table 2. Catalyst loading study for the CÀH acetoxylation of benzene.
After proving the high activity of the new catalytic system in
the CÀH acetoxylation of benzene, we evaluated different sub-
stituted arenes (Table 3).[16] PhI(OAc)2 was used as the oxidant
for all substrates and we compared the conditions without
(conditions A) or with 6-fluoropicolinic acid (conditions B) for
each substrate.
The reaction of 1,2-dichlorobenzene under conditions A pro-
vided almost an equimolecular mixture of acetoxylated prod-
ucts in 9% yield. In contrast, the reaction in the presence of 6-
fluoropicolinic acid provided the regioisomeric products in
74% yield with a clear preference to activate the least sterically
hindered CÀH bond (4a/4b=11:89). In a similar manner, the
reaction with 1,3-dibromobenzene as the starting material fur-
nished the corresponding products in low yield (36%) under
conditions A and in 86% yield under conditions B. Regarding
the site selectivity, regioisomer 5b, derived from acetoxylation
at the electronically more activated and least hindered posi-
tion, was obtained in higher ratio than that observed under
conditions A (Table 3, entry 2). The reaction of naphthalene
provided the acetoxylated product in good yield under both
conditions, and the site selectivity was enhanced towards the
functionalization of the least sterically hindered CÀH bond
under conditions B (6a/6b=29:71; Table 3, entry 3). Similar be-
havior was observed in the reaction with o-xylene, which
showed an increase in site selectivity in the presence of the
ligand (7a/7b=23:77; Table 3, entry 4).
The reaction employing monosubstituted arenes, different
behaviors were observed depending of the nature of the sub-
stituent. Under both conditions, the reaction of toluene gave
good yields and low site selectivity (Table 3, entry 5). In a similar
manner, under both conditions, the reaction of anisole provid-
ed moderate to low yields and site selectivity (Table 3, entry 6).
On the other hand, the reaction of bromobenzene furnished
the acetoxylated product in a slightly higher yield and site se-
lectivity under conditions B than under conditions A (Table 3,
entry 7). The reaction of trifluoromethylbenzene (Table 3,
entry 8) or ethyl benzoate (Table 3, entry 9) under conditions A
provided a mixture of acetoxylated products in low yields (18–
Entry
Pd(OAc)2 [mol%]
Reaction time [h]
Yield[a] [%]
TON
1
2
3
4
5
6
7
8
4
3
2
1.5
1
0.5
0.5
0.1
0.01
2
3
3
3
3
3
69
56
55
54
47
35
59
75
78
76
67
17
19
–
36
47
3
–
7.5
24
309
14
3
118
750
7800
38
9
10
11[b]
2
–
[a] Yields were determined by GC analysis by using PhCl as an internal
standard. [b] 0.37m concentration.
served (7.5 h), and in this case, phenyl acetate (1) was deliv-
ered in 59% yield (Table 2, entry 7). Importantly, the reaction
provided 78% yield of phenyl acetate (1) in the presence of
0.01 mol% catalyst, which led to the highest TON (7800) re-
ported for the Pd(OAc)2-catalyzed CÀH acetoxylation of ben-
zene (Table 2, entry 9). Although this result was extremely posi-
tive, we were concerned about the high yield obtained relative
to previous experiments. We hypothesized that lower concen-
trations as well as longer reaction times led to higher yields,
even if Pd black was formed. Indeed, the reaction performed
with the use of 2 mol% Pd furnished phenyl acetate (1) in
55% yield after 3 h (Table 2, entry 3) and in 76% yield after
14 h (Table 2, entry 10) even if the formation of Pd black was
observed after 2 h. In addition, a higher yield (67%) was ob-
served if the reaction was performed at higher dilution (0.37m
vs. 1.12m; Table 2, entry 11).
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Finally, we performed some experiments to gain
more insight into the mechanism of this transforma-
Table 3. Pd-catalyzed CÀH acetoxylation of mono- and disubstituted arenes.[a]
1
tion. We first followed the reaction by H NMR spec-
troscopy, which showed the formation of some palla-
dium complexes. Unfortunately, we were not able to
identified these complexes that were different from
the ones formed in the stoichiometric reaction of
Pd(OAc)2 and the picolinic acid derivatives. After-
wards, we compared the CÀH acetoxylation of ben-
zene to that of [D6]benzene (see the Supporting In-
formation), which gave a large kinetic isotope effect
(4). In addition, a zero-order dependence in PhI(OAc)2
was observed in the reaction by using the initial rate
method (see the Supporting Information). These re-
sults indicate that the CÀH activation is the rate-limit-
ing step.[17] We determined the order of the reaction
in Pd. The plot of the logarithms of the reaction rate
against the concentration provided a straight line
with a slope of 0.3, which suggested a trimeric preca-
talyst. With these data we proposed the mechanism
outlined in Scheme 3 in which a trimeric precatalyst
enters the catalytic cycle by dissociation to a mono-
mer and the CÀH activation is the rate-limiting step.
Entry
1
Product
Yield [%] (Selectivity)[b]
Conditions A
Conditions B
9 (a/b=44:56)
74 (a/b=11:89)
2
3
4
5
6
36 (a/b/c=14:17:69)
81 (a/b=57:43)
86 (a/b/c=5:50:45)
69 (a/b=29:71)
40 (a/b=38:62)
54 (a/b=23:77)
70 (o/m/p=37:32:31)
46 (o/m/p=39:4:56)
62 (o/m/p=29:35:36)
37 (o/m/p=21:11:68)
In conclusion, we developed
a new catalytic
system for the direct CÀH acetoxylation of simple
arenes based on Pd(OAc)2 and a 6-fluoropicolinic acid
ligand that shows high reactivity and site selectivity.
This system proved to be active at low catalyst load-
ings, which led to the highest turnover number re-
ported to date for the palladium-catalyzed CÀH ace-
toxylation of benzene. The precipitation during the
CÀH acetoxylation of an inactive palladium complex
bearing two molecules of the ligand suggests that
this system may be more reactive than it shows. The
site selectivity of the acetoxylation of the arenes is
dictated by both electronic and steric factors. Overall,
this catalytic system shows promising perspectives in
terms of reactivity and selectivity in the CÀH oxida-
tion field. Current efforts are focused on expanding
the application of this catalytic system and on gain-
ing detailed mechanistic insight into this transforma-
tion.
7
8
9
71 (o/m/p=35:39:25)
18 (o/m/p=33:55:17)
19 (o/m/p=24:47:29)
93 (o/m/p=16:49:35)
94 (o/m/p=5:85:10)
64 (o/m/p=9:63:28)
[a] Conditions A: Pd(OAc)2 (2 mol%); conditions B: Pd(OAc)2 (2 mol%) and 6-fluoropi-
colinic acid (2 mol%). [b] Yields and selectivities were determined by GC analysis by
using PhCl as an internal standard.
19%). When the reactions were performed in the presence of
the ligand, an increase on reactivity and site selectivity was ob-
served. In both cases, the meta isomer was the major product,
which was obtained from functionalization at the electronically
more activated position. In general, reactions with arenes bear-
Experimental Section
ing electron-withdrawing groups led to higher yields of the
products in the presence of the 6-fluoropicolinic acid ligand,
whereas the reaction with electron-rich arenes under condi-
tions A or B afforded similar yields. The site selectivity in the
presence of the 6-fluoropicolinic acid ligand is controlled by
both steric and electronic factors, with preferential functionali-
zation at the most electronic-rich and least sterically hindered
position in the arene. The effect on the reactivity and site se-
lectivity of the reaction upon using MesI(OAc)2 (Mes=2,4,6-tri-
methylphenyl) was evaluated with and without 6-fluoropicolin-
ic acid, but no improvement was observed (see the Supporting
Information).
General procedure for the CÀH acetoxylation of benzene
PhI(OAc)2 (180 mg, 0.56 mmol, 1.00 equiv.), Pd(OAc)2 (2.5 mg,
11.2 mmol, 0.02 equiv.), and 6-fluoropyridine-2-carboxylic acid
(1.6 mg, 11.2 mmol, 0.02 equiv.) were weighed into a pressure vial.
Glacial acetic acid and acetic anhydride (1.12m, in a ratio of 9:1)
were added. The resulting suspension was stirred at RT for 15 s
and then benzene (0.5 mL, 437 mg, 5.6 mmol, 10.0 equiv.) was
added. The vial was sealed with a Teflon-lined cap, and the mixture
was heated to 1008C by using a preheated bath oil. At the end of
the reaction, the vial was cooled to RT, and PhCl (20 mL) was added
as an internal standard for quantitative GC analysis. The mixture
was diluted with EtOAc (1 mL) and filtered through a plug of
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Communications
b) L. Eberson, L. Jonsson, Acta Chem. Scand. Ser. B 1974, 28, 771; c) L.
Eberson, L. Jonsson, Acta Chem. Scand. Ser. B 1976, 30, 361; d) L. Eber-
son, L. Jonsson, Justus Liebigs Ann. Chem. 1977, 233; e) For Pd-catalyzed
CÀH acetoxylation of arenes using chromates as oxidant, see: f) L. M.
Stock, K. Tse, L. J. Vorvick, S. A. Walstrum, J. Org. Chem. 1981, 46, 1757;
g) P. M. Henry, J. Org. Chem. 1971, 36, 1886.
Celite. The filtrate was extracted with a saturated aqueous solution
of K2CO3 (3m in deionized H2O, 2ꢃ2 mL) to quench and separate
the acid. The organic layer was then carefully separated and dilut-
ed with additional EtOAc to a total volume of 10 mL. The resulting
solution was analyzed by GC.
[9] T. Yoneyama, R. H. Crabtree, J. Mol. Catal. A 1996, 108, 35.
[10] a) M. H. Emmert, A. K. Cook, Y. J. Xie, M. S. Sanford, Angew. Chem. Int. Ed.
2011, 50, 9409; Angew. Chem. 2011, 123, 9581; b) A. K. Cook, M. S. San-
ford, J. Am. Chem. Soc. 2015, 137, 3109.
Acknowledgements
[11] a) J. B. Gary, A. K. Cook, M. S. Sanford, ACS Catal. 2013, 3, 700; b) F. Tato,
A. Garcꢄa-Domꢄnguez, D. J. Cardenas, Organometallics 2013, 32, 7487;
c) A. K. Cook, M. H. Emmert, M. S. Sanford, Org. Lett. 2013, 15, 5428.
[12] For some representative examples on the use of pyridine derivatives as
ligands to promote the CÀH functionalization, see: a) J. He, R. Takise, H.
Fu, Y. Q. Yu, J. Am. Chem. Soc. 2015, 137, 4618; b) R. Y. Zhu, K. Tanaka,
G. C. Li, J. He, H. Y. Fu, S. H. Li, J. Q. Yu, J. Am. Chem. Soc. 2015, 137,
7067; c) G. Chen, T. Shigenari, P. Jain, Z. Zhang, Z. Jin, J. He, S. Li, C. Ma-
pelli, M. M. Miller, M. A. Poss, P. M. Scola, K. S. Yeung, J. Q. Yu, J. Am.
Chem. Soc. 2015, 137, 3338; d) H. Xu, M. Shang, H. X. Dai, J. Q. Yu, Org.
Lett. 2015, 17, 3830; e) H. Jiang, J. He, T. Liu, J. Q. Yu, J. Am. Chem. Soc.
2016, 138, 2055.
[13] For pioneer works on proton abstraction mechanism, see: a) M. La-
france, K. Fagnou, J. Am. Chem. Soc. 2006, 128, 16496; b) D. Garcꢄa-Cua-
drado, A. A. C. Braga, F. Maseras, A. M. Echavarren, J. Am. Chem. Soc.
2006, 128, 1066; c) For general reviews on carboxylate-assisted transi-
tion metal-catalyzed CÀH functionalization, see: d) L. Ackermann, Chem.
Rev. 2011, 111, 1315; e) J. Granell, M. Martꢄnez, Dalton Trans. 2012, 41,
11243.
We acknowledge financial support from the Netherlands Organi-
zation for Scientific Research (NWO) though a VIDI grant
(723.013.006). We thank Prof. Joost Reek for allowing access to
his GC facilities.
Keywords: arenes · CÀH activation · N,O ligands · oxidation ·
palladium
[1] For general reviews on CÀH functionalization, see: a) K. Godula, D.
Sames, Science 2006, 312, 67; b) X. Chen, K. M. Engle, D. H. Wang, J. Q.
Yu, Angew. Chem. Int. Ed. 2009, 48, 5094; Angew. Chem. 2009, 121,
5196; c) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; d) L.
McMurray, F. O’Hara, M. J. Gaunt, Chem. Soc. Rev. 2011, 40, 1885; e) J.
Wencel-Delord, T. Drçge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40,
4740; f) For a special issue dedicated to this topic, see: Acc. Chem. Res.
2012, Issue 6, 777–958; g) J. Wencel-Delord, F. Glorius, Nat. Chem.
2013, 5, 369; h) A. F. M. Noisier, M. A. Brimble, Chem. Rev. 2014, 114,
8775.
[2] For a review on CÀH functionalization summarizing diverse type of di-
recting groups, see: Z. Chen, B. Wang, J. Zhang, W. Yu, Z. Liu, Y. Zhang,
Org. Chem. Front. 2015, 2, 1107.
[3] For reviews on CÀH functionalization with substrates bearing remova-
ble or traceless directing groups, see: a) G. Rousseau, B. Breit, Angew.
Chem. Int. Ed. 2011, 50, 2450; Angew. Chem. 2011, 123, 2498; b) F.
Zhang, D. R. Spring, Chem. Soc. Rev. 2014, 43, 6906.
[14] D. Wang, P. Y. Zavalij, A. N. Vedernikov, Organometallics 2013, 32, 4882.
[15] S. Taubmann, H. G. Alt, J. Mol. Catal. A 2008, 289, 44.
[16] We have tested different heteroarenes under standard reaction condi-
tions. The reaction of furan, pyrrole and pyridine did not provide the
acetoxylated products. The reaction of 1-Boc-indol furnished the diace-
toxylated product with and without ligand, which is formed by the re-
action of only PhI(OAc)2.(Q. Liu, Q. Y. Zhao, J. Liu, P. Wu, H. Yia, A. Lei,
Chem. Commun. 2012, 48, 3239).
[17] For selected examples where cyclopalladation is the rate limiting step,
see: a) M. D. K. Boele, G. P. F. van Strijdonck, A. H. M. de Vries, P. C. J.
Kamer, J. G. de Vries, P. W. N. M. van Leeuwen, J. Am. Chem. Soc. 2002,
124, 1586; b) V. G. Zaitsev, O. Daugulis, J. Am. Chem. Soc. 2005, 127,
4156; c) X. Chen, C. E. Goodhue, J.-Q. Yu, J. Am. Chem. Soc. 2006, 128,
12634; d) L. V. Desai, K. J. Stowers, M. S. Sanford, J. Am. Chem. Soc.
2008, 130, 13285; e) J.-X. Yan, H. Li, X.-W. Liu, J.-L. Shi, X. Wang, Z.-J. Shi,
Angew. Chem. Int. Ed. 2014, 53, 4945; Angew. Chem. 2014, 126, 5045.
[4] For a review on CÀH functionalization of substrates that do not bear di-
recting groups, see: N. Kuhl, M. N. Hopkinson, J. Wencel-Delord, F. Glo-
rius, Angew. Chem. Int. Ed. 2012, 51, 10236; Angew. Chem. 2012, 124,
10382.
[5] a) L.-C. Campeau, D. R. Stuart, K. Fagnou, Aldrichimica Acta 2007, 40, 35;
b) K. M. Engle, J. Q. Yu, J. Org. Chem. 2013, 78, 8927.
[6] J. H. P. Tyman, Synthetic and Natural Phenols, Elsevier, New York, 1996.
[7] For some representative examples of Pd-catalyzed CÀH acetoxylation of
arenes using directing groups, see: a) A. R. Dick, K. L. Hull, M. S. Sanford,
J. Am. Chem. Soc. 2004, 126, 2300; b) X. Chen, X. S. Hao, C. E. Goodhue,
J. Q. Yu, J. Am. Chem. Soc. 2006, 128, 6790; c) B. V. S. Reddy, L. R. Reddy,
E. J. Corey, Org. Lett. 2006, 8, 3391; d) F. J. Chen, S. Zhao, F. Hu, Q.
Zhang, S. Q. Zhang, B. F. Shi, Chem. Sci. 2013, 4, 4187.
Received: June 22, 2016
Revised: July 18, 2016
[8] For Pd-catalyzed CÀH acetoxylation of arenes using K2S2O8 as oxidant,
see: a) L. Eberson, L. Jonsson, J. Chem. Soc. Chem. Commun. 1974, 885;
Published online on && &&, 0000
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
5
ꢂ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

COMMUNICATIONS
C. Valderas, K. Naksomboon,
M. ꢀ. Fernꢁndez-IbꢁÇez*
&& – &&
Ligand-Promoted Palladium-Catalyzed
CÀH Acetoxylation of Simple Arenes
Fast and selective: A catalytic system
based on a bidentate picolinic acid
ligand and Pd(OAc)2, capable of increas-
ing the reactivity and site selectivity of
the CÀH acetoxylation of simple arenes,
is reported.
&
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
6
ꢂ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!