Palladium-catalyzed aerobic acetoxylation of benzene using NOx-based redox mediators

Article abstract of DOI:10.1016/j.jorganchem.2015.03.003

Palladium-catalyzed methods for C-H oxygenation with O₂ as the stoichiometric oxidant are limited. Here, we describe the use of nitrite and nitrate sources as NO_x-based redox mediators in the acetoxylation of benzene. The conditions completely avoid formation of biphenyl as a side product, and strongly favor formation of phenyl acetate over nitrobenzene (PhOAc:PhNO₂ ratios up to 40:1). Under the optimized reaction conditions, with 0.1 mol% Pd(OAc)₂, 136 turnovers of Pd are achieved with only 1 atm of O₂ pressure.

Full text of DOI:10.1016/j.jorganchem.2015.03.003

Journal of Organometallic Chemistry xxx (2015) 1e6
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Palladium-catalyzed aerobic acetoxylation of benzene using
NO -based redox mediators
x
*
Susan L. Zultanski, Shannon S. Stahl
Department of Chemistry, University of WisconsineMadison, 1101 University Ave., Madison, Wisconsin 53706, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 January 2015
Received in revised form
Palladium-catalyzed methods for CeH oxygenation with O2 as the stoichiometric oxidant are limited.
Here, we describe the use of nitrite and nitrate sources as NO
ylation of benzene. The conditions completely avoid formation of biphenyl as a side product, and strongly
favor formation of phenyl acetate over nitrobenzene (PhOAc:PhNO ratios up to 40:1). Under the opti-
x
-based redox mediators in the acetox-
3
March 2015
2
Accepted 4 March 2015
Available online xxx
mized reaction conditions, with 0.1 mol% Pd(OAc)
pressure.
2
, 136 turnovers of Pd are achieved with only 1 atm of
O
2
Dedicated to the memory of Alexander E.
Shilov, an inspirational scientist who had a
profound impact on the field of catalysis.
© 2015 Elsevier B.V. All rights reserved.
Keywords:
Aerobic oxidation
Palladium
Benzene
Phenyl acetate
CeH activation
Nitric acid
Introduction
synthesis of phenol with O
reductant [15 atm of each, turnover numbers (TON) ¼ 12] [8]. Yin
recently reported a Pd(OAc) /2,2’-bipyrimidine-catalyzed process
using 20 atm of O , where selectivity was diverted from biphenyl to
2
in combination with CO as a sacrificial
Direct, selective oxidation of benzene to phenol and other ox-
ygenates has been a major focus of attention in catalysis research
2
2
[
1], and palladium-catalyzed routes have shown significant prom-
phenol when redox-inactive metals such as aluminum triflate were
included in the reaction mixture (TON ¼ 10.6) [9]. The most
2
ise [2]. Pd-catalyzed activation of an sp CeH bond in benzene
generates a phenyl-Pd species that can be trapped by various
II
effective methods to date, however, employ Pd(OAc)
2
in combina-
stoichiometric oxidants, such as PhI(OAc)
2
and persulfate, to afford
tion with a heteropolyacid (HPA), H3þx[PMo12exV O40], cocatalyst.
x
III
IV
phenyl-Pd or -Pd species. These high-valent intermediates un-
dergo facile CeO reductive elimination to afford phenyl acetate and
related oxygenation products (Fig. 1) [3,4,5]. The development of an
Schuchardt used a heteropolyacid with a vanadium content of
x ¼ 3.3 to achieve up to 600 Pd turnovers for phenol formation,
2
although a very high O pressure (60 atm) was required [10].
effective method for benzene oxygenation capable of using O
the oxidant remains a prominent challenge and goal of contem-
porary research [6].
2
as
Kozhevnikov showed that a different HPA (x ¼ 2) could shift the
reaction from preferential biphenyl formation to phenol formation
by increasing the water content in a H
[11]. In this case, only modest turnovers (TON ꢀ 23) for phenol
formation were observed, at 5 atm O . Finally, Ashland Oil patented
the oxygenation of benzene with longer chain carboxylic acids. The
reaction was performed in the presence of catalytic Pd(OAc)
Sb(OAc) and Cr(OAc) at a low pressure of O (1 atm), achieving up
to 90 turnovers with octanoic acid [12].
2
O:AcOH solvent mixture
Precedents for Pd-catalyzed oxygenation of benzene with O
the oxidant are relatively limited [7], and the best examples typi-
cally require very high (unsafe) O pressures. For example, Fujiwara
disclosed Pd(OAc) /1,10-phenanthroline-catalyzed selective
2
as
2
2
2
2
,
3
3
2
Pd-catalyzed oxidation of benzene under aerobic conditions
typically affords biphenyl as the major reaction product [13]. A
*
Corresponding author.
E-mail address: stahl@chem.wisc.edu (S.S. Stahl).
http://dx.doi.org/10.1016/j.jorganchem.2015.03.003
022-328X/© 2015 Elsevier B.V. All rights reserved.
0
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S.L. Zultanski, S.S. Stahl / Journal of Organometallic Chemistry xxx (2015) 1e6
2 x
Fig. 2. Potential products from the reaction of benzene with Pd/O /NO . Top (unde-
sired) pathway: dimerization. Middle (undesired) pathway: nitration. Lower (desired)
pathway: acetoxylation.
Fig. 1. General proposed reaction mechanism for palladium-catalyzed benzene CeH
acetoxylation.
x
In the present study, we explore the use of NO -based co-
catalysts in the palladium-catalyzed aerobic oxidation of benzene
to phenyl acetate. Of particular interest is the identification of re-
2
action conditions that use low pressures of O and achieve high
selectivity for phenyl acetate relative to the potential by-products
biphenyl and nitrobenzene (Fig. 2).
particular challenge in realizing a high-turnover process for ben-
zene oxygenation is the typical inability of O to react directly with
2
phenyl-palladium(II) species to afford a high-valent species that
can undergo facile CeO bond formation. Recently, well-defined
organopalladium(II) complexes with multidentate ligands have
Results and discussion
2
been shown to react with O to afford organopalladium(III) and/or
organopalladium(IV) complexes [14,15]; however, the specialized
ligands used to achieve these transformations exhibit limited or no
catalytic reactivity [16].
A number of historical and recent studies suggest that nitrogen
x
oxide (NO ) species [17] could serve as effective cocatalysts or
stoichiometric mediators in aerobic palladium-catalyzed CeH
oxidation reactions. For example, Bao recently used sodium nitrite
as a cocatalyst to achieve aerobic trifluoroacetoxylation of methane
Our initial studies of palladium-catalyzed oxidation of benzene
were carried out in the absence of NO
x
sources in order to establish
benchmarks for benzene reactivity with Pd(OAc)
dissolved in acetic acid (1:29 M ratio) and heated to 100 C in the
2
. Benzene was
ꢁ
2 2
presence of 1 mol% Pd(OAc) and 1 atm of O . These conditions
exhibited low conversion of benzene to oxidation products,
resulting in 0.4 turnovers to biphenyl and phenol/phenyl acetate in
a 1:1 ratio of CeO:CeC coupling products (Table 1, entry 1). A minor
[
18] and Sanford used sodium nitrate as an additive in ligand-
improvement was observed when Pd(OAc)
.1 mol% loading. The CeO coupling products were slightly favored
over biphenyl (1.7:1); however, the overall reactivity still remained
2
was decreased to
3
directed aerobic acetoxylation of sp CeH bonds [19]. Older pre-
0
cedents exist for application of similar concepts in the oxidation of
benzene. In 1969, Tisue reported Pd(OAc) -catalyzed oxidation of
2
benzene in the presence of sodium nitrite, leading to formation of
nitrobenzene in preference to phenyl acetate (Eq. (1);
low (TON ¼ 1.2). Negligible changes were observed when the O
2
partial pressure was increased to 10 atm (entry 3).
The latter results suggests that CeO coupling does not result
from direct reaction of O with a phenyl-palladium(II) intermediate
and is consistent with previous observations that O is kinetically
PhNO
2
:PhOAc ¼ 1.3:1; TON ¼ 6, with respect to PhOAc) [20]. Asahi
2
later published a patent in which they described preferential for-
mation of phenyl acetate over nitrobenzene (Eq. (2);
2
inert toward direct reaction with organopalladium(II) species [24].
The origin of the small quantities of benzene oxygenation products
in these reactions is not currently understood.
PhOAc:PhNO
modified conditions, most notably using a very high pressure of O
19 atm) [21,22]. More recently, NO -based reaction partners have
been used in palladium-catalyzed, ligand-directed CeH nitration
reactions [23]. Collectively, these results highlight the ability of NO
2
¼ 7:1; TON ¼ 41, with respect to PhOAc) under
2
(
x
We then turned our attention to reactions incorporating NO
based cocatalysts (Table 2). When Pd(OAc) (1 mol%) was used with
0 mol% of tert-butyl nitrite as a NO source under 1 atm of O
x
-
2
x
1
x
2
,
species to promote carbon-heteroatom bond formation in Pd-
catalyzed CeH oxidation; however, they also draw attention to
potential challenges in controlling product selectivity.
benzene oxidation exhibited a strong preference for phenyl acetate
formation over nitrobenzene and biphenyl side products,
PhOAc:PhNO
was detected). None of these oxidation products are observed if the
same reaction is performed in the absence of Pd(OAc) . This
2
:PhꢂPh 10:1:0.8 (Table 2, entry 1; only trace phenol
2
observation shows that nitrobenzene formation is a palladium-
catalyzed process and does not arise from electrophilic nitration
under the reaction conditions. Recent mechanistic studies of
palladium-catalyzed aerobic oxidative coupling of arenes revealed
(1)
that biaryl formation proceeds via a bimetallic process involving
II
transmetalation between two L
n
Pd ArX species [25]. Therefore, we
conjectured that biphenyl formation could be minimized by
reducing the catalyst loading. When the Pd(OAc) and tert-butyl
2
nitrite loadings were reduced to 0.1 and 1mol%, respectively, no
biphenyl was observed, and the TON with respect to PhOAc for-
mation increased from 4 to 21. A similar PhOAc:PhNO
was observed (PhOAc:PhNO
¼ 8.4:1, entry 2). Increasing the O
partial pressure from 1 to 10 atm led to a slight increase in the
palladium TON (26), but the PhOAc:PhNO ratio improved to 27:1
entry 3). Other changes to the reaction conditions, especially
2
selectivity
2
2
(2)
2
(
x
focused on the catalyst loading and identity of the NO source, did
not lead to significant improvements (entries 4ꢂ9).
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S.L. Zultanski, S.S. Stahl / Journal of Organometallic Chemistry xxx (2015) 1e6
3
Table 1
Varying the mol% of fuming HNO
led to modest reductions in
3
Pd-catalyzed aerobic oxidative coupling of benzene in acetic acid: Product ratios in
the absence of a redox mediator.
turnover number (entries 5ꢂ7). When the optimized conditions,
with 30 mol% fuming nitric acid, were conducted under N instead
of O , nitrobenzene is the major product (PhOAc:PhNO
¼ 1:1.2;
entry 7). This result shows that the NO species can serve as
competent oxidants, but they favor CeN bond formation, rather
than CeO bond formation in the absence of O . The optimized
2
2
2
x
2
conditions in Table 3, entry 4 afford a 13.6% yield of phenyl acetate,
which compares favorably to previous methods for palladium-
Entry
%Pda
O
2
(atm)b
A:B (mmol)
TONc
1
2
3
1.0
0.1
0.1
1
1
10
1.0:1.0
1.7:1.0
1.6:1.0
0.4
1.1
0.8
catalyzed oxidation of benzene to phenyl acetate using PhI(OAc)
and potassium persulfate as stoichiometric oxidants (7.5% [5a] and
.1% [5f] yields, respectively). Additionally, the optimized condi-
2
7
a
7
mmol scale; see SI for additional information.
tions from entry 4 can be conducted under 1 atm of air instead of
b
c
“
1 atm O in N . “10 atm O
2
” ¼ 11 atm of 9% O
2
2
2
” ¼ 111 atm of 9% O
2 2
in N .
ꢁ
O
2
, adjusting the temperature to 85 C, to afford a still high turn-
Based on combined GC yields of PhOAc, PhOH, and PhꢂPh.
over number of 120, while the PhOAc:PhNO
entry 9).
A likely catalytic cycle for Pd(OAc)
benzene to phenyl acetate is illustrated in Fig. 3. Benzene CeH
activation by palladium(II) [L Pd(OAc) affords phenyl-
palladium(II) intermediate. Two-electron oxidation of 1 by NO
2
ratio improved to 40:1
(
2
x
/NO -catalyzed oxidation of
Table 2
2 x x
Pd(OAc) /NO -catalyzed aerobic acetoxylation of benzene with low NO loading.
n
2
]
a
2
could then generate a phenyl-palladium(IV) species 2, which can
undergo facile CeO reductive elimination to afford phenyl acetate
and the original L
mirrors other proposed Pd
ene and alkane oxygenation, in which various oxidants (e.g.
PhI(OAc) ) are used to generate species similar to 2 [3a]. The
proposed catalytically relevant oxidant NO can be generated via
thermal decomposition of HNO (Eq. (3)) [29], and the reduced
NO species NO is well known to undergo facile aerobic oxidation
to NO
n 2
Pd(OAc) catalyst. This proposed catalytic cycle
II/IV
II
III
(and Pd /Pd dimer) cycles for ar-
%Pda
(atm)b
TON (Pd)c
PhOAc: PhNO d
Entry
% NO
x
O
2
2
2
1
2
3
4
5
6
7
8
9
1.0
0.1
0.1
0.1
0.1
0.1
0.05
0.2
0.1
10% t-BuONO
1% t-BuONO
1% t-BuONO
1% n-pentylONO
1
1
4.0
21
26
25
23
15
22
21
12
10:1e
8.4:1
27:1
25:1
26:1
22:1
25:1
11:1
33:1
2
10
10
10
10
10
10
10
3
x
1% NaNO
3
[17].
2
1% fuming HNO
0.5% t-BuONO
2% t-BuONO
3
4
HNO
3
/4NO
2
þO
2
þ2H
2
O
(3)
2 x
(or other NO species) in
0.5% t-BuONO
The direct involvement of NO
a
Entries 1 & 2 were conducted in sealed pressure tubes with teflon caps
1.75 mmol scale; 0.55 M). Entries 3ꢂ9 were conducted in Parr reactor vessels
oxidizing the phenyl-palladium(II) intermediate is supported by
(
(
7 mmol scale; 0.55 M). No PhOAc or PhNO
2
is observed in the absence of Pd(OAc)
2
.
the observation of significant catalytic turnover (TON ¼ 19),
b
For entries 3ꢂ9, “10 atm O
2
” ¼ 111 atm of 9% O
2
in N
2
.
2
when the reaction is carried out in the absence of O . Further-
c
d
e
TONs were calculated based on calibrated GC yields of PhOAc.
Based on the ratio of calibrated GC yields.
more, increased formation of nitrobenzene under these condi-
tions (together with the lack of background nitration in the
Ratio of PhOAc:PhꢂPh (mmol) is 10:0.8. For all other entries, biphenyl is not
absence of palladium) implicates N-coordination of
species to palladium, which then participates in CeN reductive
elimination. The change in PhOAc:PhNO product selectivity
under N suggests that O plays a role beyond oxidation of NO to
NO
In Table 2, increasing the O
ment of the PhOAc:PhNO ratio from 8.4:1 to 27:1 (entries 2 vs 3).
Similarly, in Table 3, altering the reaction conditions from an O to a
atmosphere (1 atm in each case), significantly decreased the
PhOAc:PhNO product ratio from 26:1 to 1:1.2 (entries 4 vs 8) [30].
The reaction of NO species with organopalladium complexes has
a NO
x
observed.
2
2
2
The active NO
conditions, and addition of another dose of NO
x
species appears to decompose under the reaction
(in this case, tert-
2
.
x
2
pressure resulted in an improve-
butyl nitrite) reinitiates the reaction [26]. This observation,
together with the modest turnover numbers observed in Table 1
prompted us to investigate the use of larger quantities of NO
sources for the reaction. In addition, we elected to focus on low-
pressure reaction conditions (pO
¼ 1 atm).
Use of 30 mol% tert-butyl nitrite under 1 atm O
resulted in low catalyst turnover (Table 3, entry 1). We speculated
that this poor result could reflect the deleterious consequence of
generating larger quantities of tert-butoxyl radicals in the forma-
tion of NO from tert-butyl nitrite [27]. Therefore, other NO
were tested. When 30 mol% NaNO was employed, the turnover
number increased to 59 and led to a PhOAc:PhNO ratio of 9:1
entry 2) [28]. Further improvements were observed upon using
0 mol% HNO (70% in H O), which led to a turnover number of 115
entry 3). The best results were obtained with 30 mol% fuming
HNO , which led to a turnover number of 136 (entry 4). The
selectivity for PhOAc over PhNO remained very good under these
2
2
x
N
2
2
2
x
2
, however,
received relatively little attention, but fundamental studies of
Campora and coworkers potentially provide insights into the
selectivity trends just noted [31]. A nitrosyl-organopalladium(IV)
complex bearing a tris(pyrazolyl)borate ancillary ligand (3) was
x
sources
2
synthesized and shown to react with O to afford the corresponding
3
O-bound nitrate complex 4 (Fig. 4). Anaerobic conditions could
result in accumulation of NO, which could then coordinate to
organopalladium species and lead to CeN bond formation (the
2
(
3
(
3
2
details of which are not yet understood). In the presence of O
2
,
nitric oxide could convert to NO via direct oxidation by molecular
2
3
oxygen, as shown in Fig. 3, or a bound nitrosyl ligand could undergo
oxidation to a nitrate ligand within the palladium coordination
sphere, as shown in Fig. 4. Either pathway could result in prefer-
ential CeO reductive elimination with a more-basic acetate ligand
2
conditions (PhOAc:PhNO
of a large quantity of NO
were detected, even when the yield of PhOAc surpasses 10%.
2
¼ 26:1, entry 4), in spite of the presence
x
. Only traces of diacetoxylated products
(cf. Fig. 3).
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S.L. Zultanski, S.S. Stahl / Journal of Organometallic Chemistry xxx (2015) 1e6
Table 3
x
Pd-catalyzed and NO -mediated aerobic acetoxylation of benzene: Optimization of turnover numbers.
Entrya
% NO
TON (Pd)b
PhOAc:PhNO c
2
x
1
2
3
30% t-BuONO
4
59
4:1
9:1
30% NaNO
30% aq. HNO
30% fuming HNO
3
3
(70%)
115
136
100
127
116
19
25:1
26:1
29:1
22:1
18:1
1:1.2
40:1
d
4
3
5
6
7
8
10% fuming HNO
50% fuming HNO
70% fuming HNO
30% fuming HNO
3
3
3
3
; N
2
(1 atm) instead of O
2
e
ꢁ
9
30% fuming HNO
3
, 85 C, air (1 atm) instead of O
2
120
a
1
.2 mmol scale; 0.55 M. Reactions were conducted in sealed pressure tubes with teflon caps. Biphenyl is not observed.
b
c
TONs were calculated based on calibrated GC yields of PhOAc.
Based on the ratio of calibrated GC yields.
Average of four experiments. Standard deviation for TON: 9.9. Standard deviation for ratio of PhOAc:PhNO : 3.3.
2
d
e
13.56 mmol scale; 0.55 M. Reaction was conducted in a flask equipped with a reflux condenser. Biphenyl is not observed.
Conclusions
Company) using 45-mL Hastelloy C-276 vessels. GC analyses were
carried out on a Shimadzu Gas Chromatograph GC-1010 Plus, with a
Phenomenex Zebron ZB-Wax column (30 m L x 0.25 mm
ID x 0.25 mm df).
Note: 1) It is important that the ratio of solution:headspace for
these reactions be between 1:1.8 and 1:3.5 in order to achieve
optimal results. 2) Because NO species will react with rubber, it is
x
important that teflon caps, and not septa, be used for these
reactions.
In conclusion, we have demonstrated that NO
effective redox mediators for palladium-catalyzed aerobic acetox-
ylation of benzene under only 1 atm of O . Promising turnover
numbers of >100 and high selectivities for phenyl acetate have
been achieved. Biphenyl formation is negligible under these reac-
tion conditions, and phenyl acetate to nitrobenzene ratios of up to
x
sources serve as
2
4
0:1 are accessible.
Reactions were optimized with respect to temperature, con-
centration, and ratio of solution:headspace (not shown).
Experimental
General considerations
Table 1: General procedure
A 45-mL Hastelloy C-276 vessel was charged with a teflon stir-
The following reagents were purchased and used as received:
benzene (Aldrich, anhydrous, 100-mL sure-seal bottles), acetic acid
bar, the specified mol% of Pd(OAc) , as indicated in Table 2 (it is
2
easiest to use a stock solution of Pd(OAc) /AcOH), a total of 12.1 mL
2
(
Aldrich, >99.99%, trace metals basis), nitric acid (Aldrich, red
of AcOH, and benzene (626
ml, 7 mmol). The reactor was sealed,
fuming), palladium(II) acetate (Strem). The use of these high-purity
reagents is extremely important in order to achieve optimal re-
pressurized to either 11 atm or 111 atm of 9% O /N (effectively
2
2
ꢁ
1 atm of O or 10 atm of O ), and then heated to 100 C and stirred
2 2
sults. All reactions using 1 atm of pure O
dried Ace pressure tubes (9 mL, bushing type, front seal,
0.3 cm L x 13 mm O.D.). All reactions using 9% O /N were carried
out in a Series 5000 Multiple Reactor System (Parr Instrument
2
were carried out in oven-
vigorously for 10 h. The vessel was then allowed to cool to room
temperature and the reaction mixture was analyzed by GC analysis
using chlorobenzene as an internal standard. TONs are reported
based on mmol PhOAc þ mmol PhOH þ mmol PhꢂPh. Ratios of
2
2
2
(
PhOAc þ PhOH):PhꢂPh are based on mmol of products.
Table 2, entries 1 & 2: General procedure
An oven-dried Ace pressure tube (9 mL, bushing type, front seal,
20.3 cm L x 13 mm O.D.) was charged with a teflon stirbar, the
Fig. 3. A possible catalytic cycle for palladium-catalyzed, NO
acetoxylation.
x
-mediated benzene CeH
Fig. 4. NO
presence of O
x
-bound organopalladium(IV) complexes synthesized by Campora. In the
, 3 converts to 4.
2
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S.L. Zultanski, S.S. Stahl / Journal of Organometallic Chemistry xxx (2015) 1e6
5
specified mol% of Pd(OAc)
use a stock solution of Pd(OAc)
AcOH. The tube was capped with a septum and purged for 2 min
with an oxygen balloon, while stirring. Benzene (158 l, 1.75 mmol)
was added via syringe, followed by the specified quantity of the
2
as indicated in Table 2 (it is easiest to
Note: In a more rigorous approach for reactions run in Ace
pressure tubes, Ace pressure tubes with plunger valves (e.g. Ace
glass manufacturer #8648-164) were used. In this case, a pressure
2
/AcOH), and a total of 3.0 mL of
m
tube was charged with a Teflon stirbar, Pd(OAc)
2
, AcOH, PhH and
the NO source. The tube was sealed with a Teflon cap containing a
x
NO
x
source. The rubber septum was removed, quickly capped with
plunger valve. The top of the plunger valve was connected to a
three-way valve; one valve connected to a vacuum pump, and one
ꢁ
a Teflon cap, and stirred vigorously in a 100 C oil bath for 10 h (the
oil bath level is the same height as the solution level of the reac-
tion). The pressure tube was then allowed to cool to room tem-
perature and the reaction mixture was analyzed by GC analysis
using chlorobenzene as an internal standard. TONs are reported
valve connected to an O
using a dry ice bath, evacuated under reduced pressure with the
plunger valve open, and then backfilled with 1 atm of pure O The
plunger valve was closed and the reaction mixture was allowed to
warm to room temperature. This evacuation/backfilling with O
2
balloon. The reaction mixture was frozen
2
solely based on mmol PhOAc. Ratios of PhOAc:PhNO
mmol of products.
2
are based on
2
procedure was conducted two more times, and then the sealed
ꢁ
reaction mixture was stirred vigorously in a 100 C oil bath for the
Table 2, entries 3ꢂ9: General procedure
indicated time. The pressure tube was then allowed to cool to room
temperature and the reaction mixture was analyzed by GC analysis
using chlorobenzene as an internal standard. Results using this
approach were comparable to the less rigorous approach using Ace
pressure tubes with simple Teflon caps.
A 45-mL Hastelloy C-276 vessel was charged with a teflon stir-
bar, the specified mol% of Pd(OAc)
easiest to use a stock solution of Pd(OAc)
of AcOH, benzene (626 l, 7 mmol), and the specified quantity of
2
as indicated in Table 2 (it is
2
/AcOH), a total of 12.1 mL
m
the NO
/N
x
source. The reactor was sealed, pressurized to 111 atm of 9%
, and then heated to 100 C and stirred vigorously for 10 h.
ꢁ
O
2
2
Acknowledgments
The vessel was then allowed to cool to room temperature and the
reaction mixture was analyzed by GC analysis using chlorobenzene
as an internal standard. TONs are reported solely based on mmol
This work was supported by the National Institute of General
Medical Sciences of the National Institutes of Health (R01-
GM067173 to S.S.S. and a Ruth L. Kirchstein National Service
Award (F32-GM109569) to S.L.Z.).
2
PhOAc. Ratios of PhOAc:PhNO are based on mmol of products.
Table 3: General procedure
An oven-dried Ace pressure tube (9 mL, bushing type, front seal,
0.3 cm L x 13 mm O.D.) was charged with a teflon stirbar, 100 l of
a 0.00012 M Pd(OAc) /AcOH stock solution (stock solution: 26.9 mg
in 10 mL of AcOH; 0.0012 mmol Pd(OAc) per reaction), and 1.9 mL
of AcOH. The tube was capped with a septum and purged for 2 min
with an oxygen balloon, while stirring (exception: for entry 8, N
was used in place of O ). Benzene (108 l, 1.2 mmol) was added via
syringe, followed by the specified quantity of the NO source, via
References
2
m
[1] (a) K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, fourth ed., Wiley-
VCH, New York, 2003;
2
2
(b) M. Weber, M. Weber, M. Kleine-Boymann, Phenol Ullmann’s Encycl. Ind.
Chem. 26 (2004) 503e519;
(c) R.J. Schmidt, App. Catal. A 280 (2005) 89e103.
2
[
2] For a review on transition metal catalyzed synthesis of hydroxylated arenes,
2
m
see: D.A. Alonso, C. N ꢀa jera, I.M. Pastor, M. Yus Chem. Eur. J. 16 (2010)
x
5274e5284.
II/IV
and PdII/III CꢂH activation chemistry in catalysis, see: (a)
syringe. The rubber septum was removed, quickly capped with a
[3] For reviews on Pd
ꢁ
K. Mu n~ iz, Angew. Chem. Int. Ed. 48 (2009) 9412e9423;
Teflon cap, and stirred vigorously in a 100 C oil bath for 24 h (the
(
(
b) T.W. Lyons, M.S. Sanford, Chem. Rev. 110 (2010) 1147e1169;
c) K.M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res. 45 (2012)
oil bath level is the same height as the solution level of the reac-
tion). The pressure tube was then allowed to cool to room tem-
perature and the reaction mixture was analyzed by GC analysis
using chlorobenzene as an internal standard. TONs are reported
788e802;
d) D.C. Powers, T. Ritter, Acc. Chem. Res. 45 (2012) 840e850.
(
[
4] For a general review on CꢂH activation of simple arenes, including Pd-
catalyzed processes, see: N. Kuhl, M.H. Hopkinson, J. Wencel-Delord,
F. Glorius Angew. Chem. Int. Ed. 51 (2012) 10236e10254.
solely based on mmol PhOAc. Ratios of PhOAc:PhNO
mmol of products.
2
are based on
[5] For examples of palladium-catalyzed CꢂH oxygenation of simple arenes, see:
(a) T. Yoneyama, R.H. Crabtree, J. Mol. Catal. A 108 (1996) 35e40;
(b) F. Shibahara, S. Kinoshita, K. Nozaki, Org. Lett. 6 (2004) 2437e2439;
(c) M.H. Emmert, A.K. Cook, Y.J. Xie, M.S. Sanford, Angew. Chem. Int. Ed. 50
*Entry 4 is the average of 4 runs:
Run 1: TON ¼ 137; 28:1 PhOAc:PhNO
2
(2011) 9409e9412;
d) F. Tato, A. García-Domínguez, D.J. C aꢀ rdenas, Organometallics 32 (2013)
487e7494;
e) A.K. Cook, M.H. Emmert, M.S. Sanford, Org. Lett. 15 (2013) 5428e5431;
(
7
(
Run 2: TON ¼ 136; 26:1 PhOAc:PhNO
2
Run 3: TON ¼ 121; 30:1 PhOAc:PhNO
Run 4: TON ¼ 149; 21:1 PhOAc:PhNO
Standard deviation for TON: 9.9
2
2
(f) J.B. Gary, A.K. Cook, M.S. Sanford, ACS Catal. 3 (2013) 700e703.
6] (a) B. Cornils, W.A. Herrmann, J. Catal. 216 (2003) 23e31;
[
(
b) B. Lücke, K.V. Narayana, A. Martin, K. J a€ hnisch, Adv. Synth. Catal. 346
(2004) 1407e1484.
Standard deviation for PhOAc:PhNO
2
ratio: 3.3
[
7] For examples in which low (ꢀ 5) turnover numbers were observed, see: (a)
L.N. Pachkovskaya, K.I. Matveev, G.N. Il’inich, N.K. Eremenko, Kinet. Catal. 18
(
(
1977) 1040e1043;
b) P. Liang, H. Xiong, H. Guo, G. Yin, Catal. Commun. 11 (2010) 560e562.
Table 3, entry 9: Procedure
An oven-dried 100-mL round-bottom flask was charged with a
teflon stirbar, 500 l of a 0.027 M Pd(OAc) /AcOH stock solution
stock solution: 30.4 mg in 5 mL of AcOH; 0.0136 mmol Pd(OAc)
per reaction), AcOH (22.7 mL), benzene (1.21 mL, 13.56 mmol), and
[8] (a) T. Jintoku, H. Taniguchi, Y. Fujiwara, Chem. Lett. (1987) 1865e1868;
m
2
(b) T. Jintoku, K. Takaki, Y. Fujiwara, Y. Fuchita, K. Hiraki, Bull. Chem. Soc. Jpn.
6
9] H. Guo, Z. Chen, F. Mei, D. Zhu, H. Xiong, G. Yin, Chem. Asian J. 8 (2013)
3 (1990) 438e441.
(
2
[
888e891.
fuming HNO
3
(173
m
L, 4.07 mmol). The flask was equipped with a
[10] L.C. Passoni, A.T. Cruz, R. Buffon, U. Schuchardt, J. Mol, Catal. A 120 (1997)
ꢁ
117e123.
reflux condenser (open top) and stirred vigorously in a 85 C oil
bath for 24 h. The mixture was then allowed to cool to room
temperature and the reaction mixture was analyzed by GC analysis
using chlorobenzene as an internal standard. TONs are reported
solely based on mmol PhOAc. Ratios of PhOAc:PhNO
mmol of products.
[
[
11] H.A. Burton, I.V. Kozhevnikov, J. Mol. Catal. A 185 (2002) 285e290.
12] Ashland Oil, Inc., Ashland, KY. Manufacture of Aryl Esters. US Patent
4,465,633, August 14, 1984.
[13] For leading references, see: (a) S. Mukhopadhyay, G. Rothenberg, G. Lando,
K. Agbaria, M. Kazanci, Y. Sasson, Adv. Synth. Catal. 343 (2001) 455e459;
2
are based on
(b) T. Yokota, S. Sakaguchi, Y. Ishii, Adv. Synth. Catal. 344 (2002) 849e854;
(c) Y. Izawa, S.S. Stahl, Adv. Synth. Catal. 352 (2010) 3223e3229.
Please cite this article in press as: S.L. Zultanski, S.S. Stahl, Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.03.003

6
S.L. Zultanski, S.S. Stahl / Journal of Organometallic Chemistry xxx (2015) 1e6
[
14] For fundamental studies of L
n
PdMe
2
complexes that react directly with O
2
,
Pittsburgh, PA. . U. S. Pat. 3,542,852, November 24, 1970.
(b) (PhOAc TON ¼ 9 or less) Asahi Kasei Co., Tokyo, Japan. Process for Pre-
paring Phenyl Acetate and Related Products. US Patent 3,887,608, June 3,
1975.
III
IV
including the formation of well defined Pd or Pd products, see: (a)
L. Boisvert, M.C. Denney, S.K. Hanson, K.I. Goldberg, J. Am. Chem. Soc. 131
(
2009) 15802e15814;
(
b) J.R. Khusnutdinova, N.P. Rath, L.M. Mirica, J. Am. Chem. Soc. 134 (2012)
[23] (a) W. Zhang, S. Lou, Y. Liu, Z. Xu, J. Org. Chem. 78 (2013) 5932e5948;
(b) W. Zhang, D. Wu, J. Zhang, Y. Liu, Eur. J. Org. Chem. (2014) 5827e5835;
(c) B. Majhi, D. Kundu, S. Ahammed, B.C. Ranu, Chem. Eur. J. 20 (2014)
9862e9866.
2
414e2422;
c) J.R. Khusnutdinova, F. Qu, Y. Zhang, N.P. Rath, L.M. Mirica, Organometallics
1 (2012) 4627e4630;
d) F. Tang, Y. Zhang, N.P. Rath, L.M. Mirica, Organometallics 31 (2012)
690e6696.
15] For a stoichiometric reaction of a L
J.R. Khusnutdinova, N.P. Rath, L.M. Mirica Chem. Commun. 50 (2014)
036e3039.
(
3
(
6
[24] T. Diao, S.S. Stahl, Polyhedron 84 (2014) 96e102.
[25] D. Wang, Y. Izawa, S.S. Stahl, J. Am. Chem. Soc. 136 (2014) 9914e9917.
[26] A reaction using the same conditions as those described in Table 2, entry 2,
was run to approximately 70% completion (3h), at which point an additional
1 mol% tert-butyl nitrite was added. This resulted in an improvement in the Pd
TON to 32, as compared to 21 in Table 2, entry 2. In contrast, addition of
another aliquot of palladium does not results in improved turnover numbers,
II
[
[
n 2
Pd (aryl)(alkyl) species with O , see: F. Qu,
3
16] For examples of ligand-directed, catalytic CꢂH oxygenation reactions using
O2 as the oxidant, see: (a) J. Zhang, E. Khaskin, N.P. Anderson, P.Y. Zavalij,
A.N. Vedernikov, Chem. Commun. (2008) 3625e3627;
indicating that the limitation in these reactions is associated with the NO
source, not the palladium source.
x
(
(
b) Y.-H. Zhang, Y.-Q. Yu, J. Am. Chem. Soc. 131 (2009) 14654e14655;
c) D. Wang, P.Y. Zavalij, A.N. Vedernikov, Organometallics 32 (2013)
[27] S.-i. Uchiumi, K. Ataka, T. Matsuzaki, J. Organomet. Chem. 576 (1999)
4882e4891.
279e289.
[
[
17] D.S. Bohle, in: R.G. Hicks (Ed.), The Nitrogen Oxides: Persistant Radicals and
van der Waals Complex Dimers. In Stable Radicals: Fundamental and Applied
Aspects of Odd-Electron Compounds, John Wiley & Sons, Ltd., UK, 2010, pp.
[28] Metal nitrites such as NaNO
neous room temperature reaction with acetic acid to generate NO, NO
O, lending to a difficult reaction setup.
[29] (a) M. Theimann, E. Scheibler, K.W. Weigland, Nitric Acid, Nitrous Acid, and
Nitrogen Oxides, Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH,
Weinheim, 2005;
2
afforded variable results due to their sponta-
2
and
H
2
1
47e171.
18] Z. An, X. Pan, X. Liu, X. Han, X. Bao, J. Am. Chem. Soc. 128 (2006)
6028e16029.
1
[
[
[
19] K.J. Stowers, A. Kubota, M.S. Sanford, Chem. Sci. 3 (2012) 3192e3195.
20] T. Tisue, W.J. Downs, Chem. Commun. (1969) 410.
21] Asahi Kasei Co, Osaka, Japan. Process for Preparing Phenyl Esters of Aliphatic
Carboxylic Acids. US Patent 3,772,383, November 13, 1973.
22] For additional examples, see:
(b) W. Laue, M. Theimann, E. Schiebler, K.W. Wiegland, Nitrates and Nitrites,
Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.
[30] Note: the reaction conducted under N
2
is not completely devoid of O
/ 2 H
2
, as O
þ O
2
is
).
generated via HNO thermal decomposition: 4 HNO
[31] J. Campora, P. Palma, D. del Rio, E. Carmona, C. Graiff, A. Tiripicchio, Organ-
3
3
2
O þ 4 NO
2
2
[
(
a) ( yields for PhOAc are <1%) Gulf Research & Development Company,
ometallics 22 (2003) 3345e3347.
Please cite this article in press as: S.L. Zultanski, S.S. Stahl, Journal of Organometallic Chemistry (2015), http://dx.doi.org/10.1016/
j.jorganchem.2015.03.003