Palladium catalysts containing pyridinium-substituted pyridine ligands for the C-H oxygenation of benzene with K2S2O8

Article abstract of DOI:10.1021/cs300786j

This manuscript describes the development of Pd catalysts with pyridinium-substituted pyridine ligands for the C-H oxygenation of benzene with potassium persulfate. These new catalysts provide dramatically improved activity compared to simple Pd(OAc)₂ in this transformation. Furthermore, the reaction proceeds with high selectivity for phenyl acetate over biphenyl. Preliminary investigations suggest that a key role for the cationic pyridinium ligand is to serve as a phase transfer catalyst for the K₂S ₂O₈ oxidant.

Full text of DOI:10.1021/cs300786j

Research Article
pubs.acs.org/acscatalysis
Palladium Catalysts Containing Pyridinium-Substituted Pyridine
Ligands for the C−H Oxygenation of Benzene with K S O
2
2 8
J. Brannon Gary, Amanda K. Cook, and Melanie S. Sanford*
Department of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, Michigan 48109, United States
S Supporting Information
*
ABSTRACT: This manuscript describes the development of
Pd catalysts with pyridinium-substituted pyridine ligands for the
C−H oxygenation of benzene with potassium persulfate. These
new catalysts provide dramatically improved activity compared
to simple Pd(OAc) in this transformation. Furthermore, the
2
reaction proceeds with high selectivity for phenyl acetate over
biphenyl. Preliminary investigations suggest that a key role for
the cationic pyridinium ligand is to serve as a phase transfer catalyst for the K S O oxidant.
2
2
8
KEYWORDS: oxidation, palladium, catalysis, benzene, ligand, cationic, phase-transfer
1
8
INTRODUCTION
reagent is expensive (approximately $425/mol); furthermore,
iodobenzene and AcOH are formed as stoichiometric by-
products. In addition, PhI(OAc)2 and PhI both contain
aromatic C−H bonds that undergo competing C−H oxygen-
ation under the reaction conditions. This side reaction
■
The development of catalysts for the efficient and selective
C−H oxygenation of benzene and other arenes remains an
important challenge in catalysis.
1
−5
Such transformations
provide a potentially attractive direct route from simple arene
1
6
3
significantly reduces the yield of phenyl acetate.
derivatives to phenols. In addition, these methods could also
Persulfate-based oxidants are potentially attractive alterna-
tives for these transformations. K S O is more than an order of
magnitude less expensive than PhI(OAc)2, and the byproducts
of this oxidant are easily separable, water-soluble salts. Our group
has previously shown that K S O serves as an effective oxidant for
Pd(OAc) -catalyzed ligand-directed C−H oxidation reactions of
pyridine and oxime ether derivatives. This confirms that K S O
is sufficiently reactive to promote C−O bond formation at Pd.
However, despite this promising precedent, the use of K S O in
nondirected Pd-catalyzed arene oxidations has historically proven
challenging. The most successful example was reported more than
find application in the direct C−H functionalization of more
complex aromatic substrates including pharmaceuticals, agro-
chemicals, and natural products.
A number of reports have shown that Pd(OAc) catalyzes the
C−H oxygenation of benzene.
the reaction suffers from (i) slow rates (generally <2 turnovers h ),
ii) low turnover numbers (often <10), and (iii) modest selectivity
for PhOAc, with competitive formation of biphenyl.
has sought to identify alternative Pd-based catalysts that address
many of these limitations. Most recently, we showed that the use of
2
2
8
18
4
,6,7
2
1
,2,8−14
2
2
8
However, with this catalyst,
−1
2
19
2
2
8
(
9−15
Our group
2
2
8
pyridine as a supporting ligand for Pd(OAc) results in dramatically
improved catalyst performance in the Pd-catalyzed C−H
acetoxylation of benzene with PhI(OAc) (eq 1).
2
3
0 years ago, and involved the Pd(OAc) -catalyzed conversion of
2
16,17
benzene to phenyl acetate with K S O with extremely low
2 2 8
13
The
2
turnover numbers (<10) and reaction yields (<30%).
The current manuscript describes our development of Pd-
pyridine catalysts for the oxidation of benzene with K S O . We
2
2
8
demonstrate that the combination of Pd(OAc)2 and a
monodentate pyridinium-substituted pyridine ligand provides
a particularly active catalyst for this transformation. The
mechanistic origins of this high activity are discussed.
RESULTS AND DISCUSSION
■
pyridine-ligated Pd catalyst provides turnover numbers of >4500
and increases the reaction rate by more than an order of magnitude
The C−H oxygenation of benzene (10 equiv) with K S O
(1 equiv) as the terminal oxidant and limiting reagent was evaluated
2
2
8
16
compared to Pd(OAc) , alone. Additionally, the Pd-pyridine
2
at 80 °C in AcOH/Ac O (9:1). As shown in Table 1, entry 1,
2
catalyst affords high (>30:1) selectivity for PhOAc over biphenyl.
Notably, this catalyst system is generated in situ, and optimal
activity is observed using an approximately 1:1 molar ratio of
pyridine:Pd(OAc)2.
Pd(OAc) is a poor catalyst for this reaction under these
2
Received: December 4, 2012
Revised: February 5, 2013
While this method represents a significant advance, the use of
PhI(OAc) as the terminal oxidant is a major limitation. This
2
©
XXXX American Chemical Society
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dx.doi.org/10.1021/cs300786j | ACS Catal. 2013, 3, 700−703

ACS Catalysis
Research Article
1
13
conditions. The use of 2 mol % of Pd(OAc) resulted in only 0.8%
ligands were fully characterized by H and C NMR spectroscopy
as well as elemental analysis.
2
yield of phenyl acetate (approximately 0.5 turnovers) after 24 h.
Pyridine-ligated catalysts were next examined for this
transformation. As discussed above, we have previously
Ligands L2 and L3 provided significant improvements in the
rate and chemoselectivity of Pd-catalyzed benzene acetoxylation
with K S O . The use of L2 or L3 (2 mol %) in conjunction
2
2
8
with Pd(OAc) (2 mol %) afforded PhOAc in 71 and 65% yield,
respectively, after 24 h (Table 1, entries 3 and 4). Additionally, the
selectivity for PhOAc versus PhPh was high in both cases
2
Table 1. Initial Evaluation of Pd Catalyst Activity for
Benzene C−H Acetoxylation as a Function of Pyridine
Ligand
(approximately 36:1 for L2 and 65:1 for L3).
A more detailed comparison of the reactivity of Pd(OAc)2,
Pd(OAc) /pyridine, and Pd(OAc) /L2 is shown in Figure 2.
2
2
a
a
entry
ligand
yield PhOAc (%)
yield PhPh (%)
1
2
3
4
none
pyridine
L2
0.8
37
0.6
2.0
1.9
1.1
71
L3
65
a
Reaction conditions: benzene (1.00 mL, 874 mg, 11.2 mmol, 10.0 equiv),
K S O (303 mg, 1.12 mmol, 1.00 equiv), AcOH (0.90 mL), Ac O
2
2
8
2
(
0.10 mL), Pd(OAc)2 (5.0 mg, 22.4 μmol, 0.020 equiv), and
pyridine (1.81 μL, 1.77 mg, 22.4 μmol, 0.020 equiv), L2 (14.3 mg,
2.4 μmol, 0.020 equiv) or L3 (14.3 mg, 22.4 μmol, 0.020 equiv)
were combined and sealed in a 1-dram vial and reacted at 80 °C for
4 h. Yields determined by GC.
2
2
shown that the combination of Pd(OAc) and pyridine (in
2
an approximately 1:1 ratio) generates a highly active catalyst for
1
6
benzene C−H acetoxylation with PhI(OAc) as the oxidant.
2
Similarly, the addition of 2 mol % of pyridine to the K S O
2
2
8
reaction under otherwise identical conditions led to an
enhancement in both yield and catalyst turnovers (Table 1,
entry 2). However, the rate of this reaction remained slow, and
only 37% yield of phenyl acetate was obtained after 24 h.
Furthermore, a significant quantity of biphenyl (2% yield,
PhOAc:PhPh ratio = 14:1) was formed in this transformation.
In an effort to identify more reactive catalysts, we next examined
cationic pyridinium-substituted pyridine ligands L2 and L3
Figure 2. Time study of benzene C−H acetoxylation with K S O
2
2
8
catalyzed by Pd(OAc) , Pd(OAc) /pyridine, and Pd(OAc) /L2.
2
2
2
Reaction conditions: benzene (1.00 mL, 874 mg, 11.2 mmol, 10.0
equiv), K (303 mg, 1.12 mmol, 1.00 equiv), AcOH (0.90 mL),
Ac O (0.10 mL), Pd(OAc) (5.0 mg, 22.4 μmol, 0.020 equiv), and
S O
2 2 8
2
2
pyridine (1.81 μL, 1.77 mg, 22.4 μmol, 0.020 equiv), or L2 (14.3 mg,
2.4 μmol, 0.020 equiv) were combined and sealed in a 1-dram vial
2
and reacted at 80 °C. Yields determined by GC.
(Figure 1). We hypothesized that these ligands might enhance
The initial rate with Pd(OAc) /L2 is approximately 5 times
2
faster than that with Pd(OAc) /pyridine and at least 2 orders of
2
magnitude faster than that with Pd(OAc) alone. Furthermore,
2
the Pd(OAc) /L2-catalyzed reaction proceeds to higher overall
2
yield at completion than the analogous Pd(OAc) /pyridine
2
system (71% versus 64%, respectively).
As noted in Figure 2, this C−H acetoxylation reaction proceeded
to less than 75% yield in all cases. (Note that the yields are based on
K S O as the limiting reagent.) This is not due to overoxidation of
2
2
8
the benzene substrate. Under the standard conditions, <4% yield of
diacetoxybenzene was observed. Instead, the observed yields are
believed to be due to competing thermal decomposition of K S O
Figure 1. Cationic pyridine derivatives.
2
2
8
22−24
catalyst reactivity based on our prior studies of the bidentate
in acetic acid, a well precedented process.
Increasing the
20
analogue L1. Our previous work showed that Pd and Pt
complexes of L1 catalyze benzene C−H activation (as measured
by H/D exchange) with 10−100-fold faster rates than those
reaction temperature to 120 °C appears to accelerate competing
oxidant decomposition. While the initial rate of C−H acetoxylation
was significantly faster at 120 °C than at 80 °C (yield after 2 h was
24% versus 7%), the reaction proceeded to a maximum of only 44%
yield at 120 °C. We attribute this to increased background
decomposition of K S O .
20
containing neutral bipyridine derivatives. By analogy, we
anticipated that L2 and L3 might outperform pyridine as ligands
in Pd-catalyzed benzene C−H activation/acetoxylation. Pyridines
L2 and L3 were synthesized by condensation of 2,4,6-tris(4-(t-
butyl)phenyl)pyrylium tetrafluoroborate with the corresponding
2
2
8
The combination of 1 equiv of pyridine or L2 with 1 equiv of
Pd(OAc) is expected to generate a number of equilibrating
2
21
aminopyridine (see Supporting Information for details). The
species in solution, including monopyridine complex A and
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Research Article
bis-pyridine adduct B (eq 2). We have previously hypothesized
that A (or a related acetate bridged dimer) is the most active
1
6,25
catalyst generated under these conditions.
On the basis of this mechanistic framework, there are several
possible factors that could contribute to the observed rate
enhancement with cationic ligand L2. These include: (1)
electronic effects (i.e., the electron withdrawing pyridinium
substituent leads to a more electrophilic Pd catalyst (A) that is
then more reactive toward benzene C−H activation); (2)
equilibrium effects (i.e., the large size and cationic charge of
ligand L2 result in an increased equilibrium population of the
most active monopyridine catalyst A); or (3) phase transfer
effects (i.e., the cationic pyridine ligand serves as a phase
2−
transfer catalyst to bring poorly soluble S O
into solution
2
8
and into contact with the Pd catalyst). Experiments designed to
preliminarily test each of these possibilities are described in
detail below.
Electronic Effects. To test the role of electronic effects, we
compared catalyst activity in the presence of L2 to that with
Figure 3. Time study of benzene C−H acetoxylation with K S O
2
2
8
catalyzed by Pd(OAc) /pyridine, Pd(OAc) /3-fluoropyridine, and
2
2
Pd(OAc) /L2. Reaction conditions: benzene (1.00 mL, 874 mg,
2
1
1.2 mmol, 10.0 equiv), K S O (303 mg, 1.12 mmol, 1.00 equiv),
2 2 8
AcOH (0.90 mL), Ac O (0.10 mL), Pd(OAc) (5.0 mg, 22.4 μmol,
2
2
3
-fluoropyridine (3-F-pyr). The Hammett σ-value for a meta-
0
.020 equiv), and pyridine (1.81 μL, 1.77 mg, 22.4 μmol, 0.020 equiv),
26
fluoro group is the same as that for a meta-pyridinium
substituent (σ = 0.34 in both cases), indicating that these
L2 (14.3 mg, 22.4 μmol, 0.020 equiv), or 3-fluoropyridine (1.92 μL,
2.17 mg, 22.4 μmol, 0.020 equiv) were combined and sealed in a 1-
dram vial and reacted at 80 °C. Yields determined by GC.
2
6
ligands should have comparable electronic properties. As shown
in Figure 3, the Pd(OAc) /3-fluoropyridine catalyst system
2
showed essentially identical reactivity to Pd(OAc) /pyridine. In
2
addition, the chemoselectivity with pyr and 3-F-pyr were both
lower than with L2 (PhOAc:PhPh ratio = 14:1, 20:1, and 36:1
respectively). Collectively, this data suggests against a purely
electronic effect.
Equilibrium Effects. If equilibrium effects were the main
factor responsible for the enhanced reactivity of Pd(OAc) /L2,
2
this catalyst would be expected to outperform Pd(OAc)2/
pyridine in other C−H oxidation reactions as well. To test this
possibility, we compared the two catalysts using PhI(OAc) as
2
the oxidant under otherwise identical conditions. As shown in
Figure 4, with PhI(OAc) , the pyridine and pyridinium-derived
2
catalysts afforded nearly identical reaction rates. This suggests
that the favorable effect of ligand L2 does not transfer to other
C−H oxidation reactions.
Figure 4. Time study of benzene C−H acetoxylation with PhI(OAc)
2
Phase Transfer Effects. To test the effect of phase transfer
catalysts on this system, we added 2 mol % of NEt BF (a
catalyzed by Pd(OAc) /pyridine and Pd(OAc) /L2. Yields deter-
2
2
4
4
mined by GC based on PhCl as a standard. Reaction conditions:
benzene (1.00 mL, 874 mg, 11.2 mmol, 10.0 equiv), PhI(OAc)2
known phase transfer catalyst) to the Pd(OAc) /pyridine-
2
catalyzed reaction. As shown in Figure 5, the NEt BF led to a
4
4
(361 mg, 1.12 mmol, 1.00 equiv), AcOH (0.90 mL), Ac O (0.10 mL),
2
significant acceleration of the initial reaction rate, very similar to
that observed with L2. However, the overall yield was lower with
Pd(OAc) /pyridine/NEt BF versus Pd(OAc) /L2 (52%
Pd(OAc) (5.0 mg, 22.4 μmol, 0.020 equiv), and pyridine (1.81 μL,
2
1.77 mg, 22.4 μmol, 0.020 equiv) or L2 (14.3 mg, 22.4 μmol, 0.020
equiv) were combined and sealed in a 1-dram vial and reacted at 80 °C.
Yields determined by GC.
2
4
4
2
versus 71%). A variety of other phase transfer catalysts had
similar effects on the Pd(OAc) /pyridine-catalyzed reaction
2
27
(
see Supporting Information for full details). The lower yields
conventional phase transfer catalysts like NEt BF may be due
4
4
observed in the presence of tetraalkyammonium salts are likely
due to their reported ability to catalyze the conversion of
to differences in the rate of undesired K S O to AcOOH
2 2 8
conversion between these systems and/or anion pairing
between the persulfate anion and the cationic Pd-ligated
complex. Notably, Neumann has proposed similar accelerative
effects of interactions between cationic ligands and anionic
oxidants in Pd/polyoxometallate-catalyzed Wacker oxidation
24
K S O to peracetic acid in AcOH. Importantly, peracetic acid
2
2
8
is not a viable oxidant for this C−H acetoxylation reaction (see
Supporting Information).
Overall, these results lead us to conclude that phase transfer
catalysis is a key factor in the enhanced reaction rate with ligand
L2. The differences in yield observed between L2 and more
28
reactions and in Pt/polyoxometalate-catalyzed CH oxida-
tion.
4
2
9,30
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Research Article
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Figure 5. Time study of benzene C−H acetoxylation with K S O
2
2
8
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4
4
1
1.2 mmol, 10.0 equiv), K S O (303 mg, 1.12 mmol, 1.00 equiv),
2 2 8
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2
2
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4
4
2
μmol, 2.0 mol %) (or no NEt BF ) were combined and sealed in a 1-
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4
4
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2
CONCLUSIONS
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■
(
1
(
In conclusion, this manuscript describes the development of Pd
catalysts containing pyridinium-substituted pyridine ligands for the
C−H oxygenation of benzene with potassium persulfate. These
new catalysts provide dramatically improved activity compared to
Pd(OAc)2 in this transformation. Furthermore, the reaction
proceeds with high selectivity for phenyl acetate over biphenyl.
Preliminary mechanistic investigations suggest that a key role for
the cationic ligand is to serve as a phase transfer catalyst to bring
(
̈
S O : Kholdeeva, O. A.; Kozhevnikov, I.
2 2 8
1
2−
poorly soluble S O into solution and into contact with the Pd
2
8
(
2
2
8
catalyst. This represents one of an expanding number of reports
suggesting that ionic association between ligands and oxidants can
serve as a valuable design principle in oxidation catalysis.
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24) Phase transfer catalyzed conversion of K S O to peracetic acid
1
28,29,31
(
2
2
8
(
which is not a viable oxidant for C−H acetoxylation under these
ASSOCIATED CONTENT
Supporting Information
Synthesis and characterization of new ligands and experimental
procedures for all catalytic reactions. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
conditions): Pande, X.; Jain, Y. Synth. Commun. 1988, 17, 2123−2127.
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5072−5074.
*
S
(
(
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27) Notably, the addition of 2 mol % of NEt BF to the Pd(OAc) /
4
4
2
L2-catalyzed C−H acetoxylation reactions resulted in a faster initial
rate (14% versus 8% at 2 h) but a slightly lower overall yield (yield =
6
AUTHOR INFORMATION
Corresponding Author
E-mail: mssanfor@umich.edu.
■
*
9%).
(
28) Ettedgui, J.; Neumann, R. J. Am. Chem. Soc. 2009, 131, 4−5.
(29) Bar-Nahum, I.; Khenkin, A. M.; Neumann, R. J. Am. Chem. Soc.
Notes
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(
2
(
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
2
■
Posner, Y.; Weiner, L.; Neumann, R. J. Am. Chem. Soc. 2011, 133,
88−190.
This work was supported by NSF under the CCI Center for
Enabling New Technologies through Catalysis (CENTC)
Phase II Renewal, CHE-1205189. We thank Professors Karen
Goldberg, Bill Jones, Mike Heinekey, Elon Ison, and Jim Mayer
for valuable discussions. A.K.C. thanks the Rackham Graduate
School for a predoctoral fellowship.
1
7
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dx.doi.org/10.1021/cs300786j | ACS Catal. 2013, 3, 700−703