Nitrosonium-Mediated Phenol-Arene Cross-Coupling Involving Direct C-H Activation

Article abstract of DOI:10.1071/CH16622

The nitrosonium ion (NO⁺) is a highly versatile nitration and nitrosation reagent, as well as a strong one-electron oxidant. Herein, we describe an environmentally benign and mild method for the in situ formation of NO⁺ from readily

Full text of DOI:10.1071/CH16622

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
http://dx.doi.org/10.1071/CH16622
Nitrosonium-Mediated Phenol–Arene Cross-Coupling
Involving Direct C–H Activation
A
B C
,
A C
,
Anna Eisenhofer, Uta Wille,
and Burkhard Konig
¨
A
Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy,
University of Regensburg, D-93040 Regensburg, Germany.
Schoolof Chemistry, Bio21Institute, The University of Melbourne, 30 Flemington Road,
Parkville, Vic. 3010, Australia.
B
C
Corresponding authors. Email: uwille@unimelb.edu.au; burkhard.koenig@ur.de
The nitrosonium ion (NOþ) is a highly versatile nitration and nitrosation reagent, as well as a strong one-electron oxidant.
Herein, we describe an environmentally benign and mild method for the in situ formation of NOþ from readily available
inorganic nitrate salts, i.e. lithium nitrate, through a finely tuned interplay between formic acid and MeOH, which are used
as the solvent system. This methodology was applied to the NOþ-induced oxidative C–H activation of methoxy-
substituted phenols, which are versatile lignin-derived aromatic feedstocks, to achieve C–C cross-coupling reactions with
arenes. The regeneration of NOþ by atmospheric molecular oxygen enables substoichiometric use of the nitrate.
Manuscript received: 3 November 2016.
Manuscript accepted: 15 December 2016.
Published online:
6 February 2017.
by NO3ꢀ should proceed with significantly higher rates than with
non-hydroxylated arenes (rate constant for 2-methoxy-4-
methylphenol (1a): k ¼ 8.41 ꢂ 10ꢁ11 cm3 moleculeꢁ1 sꢁ1 and
for1,2-dimethoxybenzene:k ¼ 9.80 ꢂ 10ꢁ15 cm3 moleculeꢁ1 sꢁ1
at 218C in the gas phase).[8] The reaction with phenols is
assumed to involve formation of a phenoxyl radical, either
through direct hydrogen abstraction or through oxidative elec-
tron transfer, followed by deprotonation (the mechanism is
shown in Scheme S1 in the Supplementary Material).[8,9]
Phenoxyl radicals are important intermediates in the electro-
chemical,[10] and iron-catalyzed[11] C–C cross-coupling with
electron-rich arenes byꢀdirect C–H activation. Thus, the differ-
ent reactivity of NO3 towards phenols and arenes would
provide a unique possibility for selective activation and cross-
coupling, avoiding side reactions like homocoupling of the
electron-rich arene coupling partner.[12] In particular, applica-
tion of photocatalytically generated NO3ꢀ for the selective C–H
Introduction
Lignin is a complex amorphous biopolymer and a major com-
ponent of natural woods. Its unique structure that comprises
different methoxylated phenylpropane units makes lignin a
viable, abundant natural resource for the sustainable production
of aromatic compounds. For example, the catalytic depo-
lymerization of lignin typically provides a mixture of substituted
phenols, for example guaiacol and syringol derivatives.[1] In
light of the continuing decline of fossil fuel resources the
development of synthetic methods that enable transformation and
functionalization of lignin-derived phenolic and oxygenated
aromatics is becoming an increasingly important area of research.
The research group of one of us has a long-standing interest
in exploring ꢀthe application of the highly reactive nitrate
radicals, NO3 , as both oxygen atom donor and as one-electron
oxidant (E (NO3 /NO3ꢁ) ¼ 2.0 V versus standard calomel elec-
ꢀ
trode (SCE) in acetonitrile (MeCN)) in synthetic organic chem-
istry.[2,3] However, a major limitation has been the somewhat
laborious methods for their generation, such as electrochemical
anodic oxidation of inorganic nitrate salts,[4] reaction of nitrogen
dioxide with ozone,[5] or photolysis of ceric ammonium nitrate
(CAN) with UV light (l ¼ 350 nm).[2,6] We therefore recently
initiated a research program to explore NO3ꢀ generation through
oxidation of inorganic nitrates using visible light photoredox
catalysis. In the presence of the organic dye 9-mesityl-10-
methylacridinium perchlorate (Acrþ-Mes, 1)[7] and oxygen in
air as terminal oxidant, NO3ꢀ could be produced (Scheme 1) and
successfully applied to the oxidation of alkynes and aliphatic
alcohols.[7a]
hν
ꢀ
NO3
NO3
ꢁ
N
ClO4ꢀ
1
ꢀ
O2
O2
ꢀ
We wanted to extend this methodology to the NO3 -induced
oxidation of aromatic compounds. In fact, comparative mecha-
nistic studies in the gas phase revealed that oxidation of phenols
ꢀ
2
Scheme 1. Formation of NO3 by photooxidative activation of NO3
using Acrþ-Mes 1 as organic photocatalyst and air as terminal oxidant.[7a]
Journal compilation ꢀ CSIRO 2017
www.publish.csiro.au/journals/ajc

B
A. Eisenhofer, U. Wille, and B. Ko¨nig
activation of phenols and subsequent C–C cross-coupling with
arenes,[13] would represent a mild, metal-free, and operationally
simple alternative approach to conventional cross-coupling
strategies for aromatic compounds.
In this paper we report on the findings of this study, which has
led to the serendipitous discovery of a novel methodology to
generate nitrosonium ions (NOþ) from lithium nitrate (LiNO3)
that can be used to achieve unsymmetrical aromatic cross-
coupling reactions.
noting that arene homocoupling products 1bb or 2bb were not
detected under these conditions.
A possible explanation for the low product formation is the
high reactivity and limited lifetime of the putative intermedia-
tely formed phenoxyl radical. In order to increase its lifetime we
explored the reaction using the fluorinated alcohol 1,1,1,3,3,3-
hexafluoro-2-propanol (HFIP) as solvent, which is known to
stabilise electrophilic radical intermediates and to enable selec-
tive reaction with the most nucleophilic species present in the
reaction mixture.[15] Unfortunately, performing the reaction in a
mixture of HFIP/MeOH (8 : 2) did not improve either the yield
or selectivity of the reaction (entries 5, 6).
Results and Discussion
For the initial investigations the optimized conditions for the
ꢀ
We next explored a 9 : 1 mixture of formic acid and methanol
as a solvent system, which has been shown in electrochemical
studies on phenol–arene C–C cross-coupling reactions to pro-
vide similar solvent properties and stabilising effects as fluori-
nated alcohols, albeit with slightly reduced yields.[16] To our
delight, under these conditions formation of the desired cross-
coupling products 1ab and 2ab clearly occurred, which was
confirmed by the [Mþ] signal in the GC-MS at m/z 304.1 for
both products. Thus, the reaction between the methoxyphenol
1a and arene 1b provided the cross-coupling product 1ab as a
1 : 10 mixture of isomers (entry 7). In addition a minor signal at
m/z 334.1 was observed, which could be assigned to the homo-
coupling product 1bb. The reaction involving trimethoxybenzene
2b gave also two cross-coupling products 2ab, with a remarkable
selectivity (1: 50) for one isomer (entry 8). The corresponding
homocoupling product 2bb could not be detected, which is most
likely due to a higher steric hindrance of the arene 2b compared
with 1b and its less favourable oxidation potential, i.e. Eox
(1b) ¼ 1.01 V versus SCE and Eox (2b) ¼ 1.34V versus SCE in
MeCN.[14] Interestingly, both reaction time and equivalents of the
NO3 -mediated oxidation of aliphatic alcohols were applied
(5 mol-% Acrþ-Mes 1 and 0.5–2.0 equiv. LiNO3 in MeCN open
to air at room temperature).[7a] 2-Methoxy-4-methylphenol (1a)
was usedas a model phenolic compound(Eox (1a) ¼ 1.10 V versus
SCE in MeCN),[14] which was treated with 3 equivalents of 1,2,
4-trimethoxybenzene (1b) or 1,3,5-trimethoxybenzene (2b).
The product distribution was qualitatively analyzed by gas
chromatography–mass spectrometry (GC-MS). The results are
compiled in Table 1.
Interestingly, although MeCN hasꢀb[e3,e5nb,6f,r7eaq] uently used as a
solvent for reactions involving NO3 ,
almost no con-
version of the starting materials and only trace amounts of the
homocoupling product (1aa) could be detected, which was
identified by the [Mþ] signal at m/z 274.1 (entries 1, 2). Using
silver nitrate (AgNO3) as a source of nitrate ions did not improve
the outcome (entry 3). Prolonged reaction times led to formation
of traces of the desired cross-coupling products ab as a mixture
of isomers, which was confirmed by the [Mþ] signal in the
GC-MS at m/z 304.1 for 1ab and 2ab (entries 3, 4). It is worth
Table 1. Phenol–arene cross-coupling: Screening of experimental conditions
Possible by-products
OMe
OH
OMe
OMe
OH
0.5–2.0 equiv. LiNO3
OMe
OH
5 mol-% Acrꢁ-Mes 1
OMe
ꢁ
1aa
HO
air, rt, blue LEDs
MeO
OMe
OMe
OMe
MeO
OMe
3 equiv.
MeO
1a
1b: 1,2,4-trimethoxybenzene
2b: 1,3,5-trimethoxybenzene
1ab
2ab
OMe
MeO
1bb
2bb
MeO
OMe
Entry
Arene
Solvent
Equiv. LiNO3
Time [h]
Products
1
2
1b
1b
1b
2b
1b
2b
1b
2b
1b
1b
MeCN
MeCN
MeCN
MeCN
0.5
2
4
4
1aa (traces)
1aa (traces)
3
2A
18
22
17
20
17
20
4
1aa (traces, 1 isomer) E 1ab (traces, 2 isomers)
1aa (traces, 2 isomers, 1 : 1) E 2ab (traces, 2 isomers, 1 : 10)
1aa (traces, 1 isomer) , 1ab (traces, 2 isomers, 1 : 10)
1aa (traces, 1 isomer) , 2ab (traces, 2 isomers, 1 : 1)
1ab (2 isomers, 1 : 10) . 1bb (1 isomer)
4
2
5
HFIP/MeOH (8 : 2)
2
2
2
2
1
6
HFIP/MeOH (8 : 2)
7
formic acid/MeOH (9 : 1)
formic acid/MeOH (9 : 1)
formic acid/MeOH (9 : 1)
formic acid/MeOH (9 : 1)
8
2ab (2 isomers, 1 : 50)
9
1ab (2 isomers, 1 : 10) . 1bb (1 isomer)
1ab (traces, 2 isomers, 1 : 5) . 1bb (traces)
10
–
4
AAgNO3 was used instead of LiNO3.

Nitrosonium-Mediated Phenol-Arene Cross-Coupling
C
nitrate salt could be reduced without dramatically decreasing the
conversion of the reactants (entry 9). On the other hand, in the
absence of LiNO3 the coupling products 1ab and 1bb were only
detected in trace amounts (entry 10) confirming that nitrate is
essential for the reaction.
yields of cross-coupling products were observed when MeOH
ꢀ
was added at the starting point of NO2 evolution (reaction
conditions B). When MeOH was added before the gas evolu-
tion occurred (reaction conditions A) or delayed after 10–15 s
of brown gas evolution (reaction conditions C) the yields
decreased. This can be rationalised by the low solubility of
After this initial qualitative screening, we performed a series
of quantitative control experiments for the reaction of 1a with 1b
to validate the photocatalytic nature of the reaction.[13] Yields
were determined by GC using 2-methylnaphthalene as an
internal standard, which was calibrated against authentic sam-
ples of 1ab and 1bb (see Supplementary Material). The results
are compiled in Table 2. To our surprise, the cross-coupling
product 1ab could be obtained in comparable yields without
either Acrþ-Mes 1 or blue light irradiation (entries 2, 5, 8). This
clearly indicates that the reaction was not photocatalytic and that
the role of the nitrate salt required reconsideration, since
ꢀ
ꢀ
NO2 in pure formic acid, which led to NO2 loss through
degassing. Addition of MeOH to the reaction mixture pre-
vented degassing and enabled cross-coupling. (iv) Changing
the order of solvent addition, i.e. first MeOH, second formic
acid, yielded almost no conversion. Obviously, highly acidic
conditions are required in the initial stage of the reaction,
which is provided by formic acid. Overall these findings are a
clear indication for in situ formation of a catalytically active
species.
Based on these findings and literature data on the reactions
between nitric and formic acid,[17,18] we propose that the nitro-
sonium cation (NOþ) is the key-species formed in our reaction
system, which acts as a substoichiometric oxidant and initiates
oxidation of aromaticcompounds(E (NOþ/NOꢀ) ¼ 1.27 V versus
SCE in MeCN).[19] In Scheme 2 is shown the proposed
mechanistic rationale for the in situ formation of NOþ. Under
the acidic conditions of the reaction system, partial protonation of
nitrate leads to nitric acid (Eqn 1). The latter is known to be
reduced to nitrous acid (HNO2) by formic acid, with release
of carbon dioxide (CO2) as by-product (Eqn 2). Nitrous acid
is in equilibrium with its anhydride (N2O3) (Eqn 3), which
ꢀ
formation of NO3 without the photocatalyst system should
not be possible.[7a] In addition, we also found a strong depen-
dence between the reaction outcome and the order of addition of
the reactants, in particular with regards to the timing of the
MeOH addition to the mixture of LiNO3 and formic acid (the
phenol 1a and arene 1b were always added last; entries 1–3, 4–6,
or 7–9). We noticed that: (i) treatment of LiNO3 with formic acid
led, after an induction period of ,10 s, to a colour change to faint
blue that is characteristic for N2O3,[17] and which disappeared
after 1 s with evolution of a colourless gas (CO2); (ii) after
ꢀ
additional 5–10 s a brown gas (NO2 ) evolved; (iii) the highest
Table 2. Influence of the time delay between the addition of formic acid and MeOH
Standard conditions:
OMe
OMe
1 equiv. LiNO3
5 mol-% Acrꢁ-Mes 1
OMe
OMe
OH
OH
MeO
MeO
OMe
ꢁ
ꢁ
Formic acid/MeOH (9:1)
air, rt, 4 h, blue LEDs
OMe
OMe
OMe
OMe
MeO
3 equiv.
MeO
MeO
1a
1b
1ab
1bb
Entry
Variation from standard conditionsA
MeOH additionB
Conv. 1aC [%]
Yield 1abC, D [%]
Selectivity abD : bb
1
2
3
–
–
–
A
B
C
2
91
12
0
–
86E
7 : 1
4 : 1
14
4
5
6
without light
without light
without light
A
B
C
1
90
50
0
–
63E
7 : 1
17 : 1
47
7
without Acrþ-Mes
A
B
C
B
B
–
1
74
6
–
8
without Acrþ-Mes
77
3
7 : 1
6 : 1
7 : 1
6 : 1
9
without Acrþ-Mes
without light/without Acrþ-Mes 0.5 equiv. LiNO3
without light/without Acrþ-Mes 0.25 equiv. LiNO3
10
11
93
27
78E
28
12
13
without light/without Acrþ-Mes formic
acid/MeOH (1 : 9) 0.5 equiv. LiNO3
without light/without Acrþ-Mes formic
acid/MeOH (1 : 1) 0.5 equiv. LiNO3
B
B
12F
traces
21E
–
91
38 : 1
AOrder of addition: 1) LiNO3, and if mentioned photocatalyst Acrþ-Mes 1, 2) formic acid, 3) MeOH, 4) 1,2,4-trimethoxybenzene 1b, 5) 2-methoxy-4-
methylphenol 1a.
BA: before bubbling occurs; B: at the starting point of brown gas evolution; C: after 10–15 s of brown gas evolution.
CConversion and yields were determined by GC using 2-methylnaphthalene as the internal standard.
DMain isomer.
EOveroxidation to yield a teraryl product was observed ([Mþ] at m/z 470.2).
FFormation of the homocoupling product 1aa was observed, the mass peak of 1bb was not detected.

D
A. Eisenhofer, U. Wille, and B. Ko¨nig
dissociates at room temperature into nitric oxide (NOꢀ) and
of light (entry 10) indicated a thermal and not a photochemical
process.
ꢀ
ꢀ
nitrogen dioxide (NO2 ) (Eqn 4). NO2 is in equilibrium with
its dimer dinitrogen tetroxide (N2O4), which dissociates ionically
to NOþNO3ꢁ in the polar and acidic solvent system (Eqn 5).[18]
NO3ꢁ re-enters the reaction system through Eqn 1. An alternative
formation mechanism, which considers the direct formation of
NOþ from HNO2 is given in the Supplementary Material.[18]
The NOþ-mediated oxidation of arenes involves intermediate
formation of a charge transfer (CT) complex between NOþ and
the arene.[19c,20] The actual electron transfer could principally
occur either through a thermal equilibrium reaction, or photo-
chemically (Eqn 6, for a detailed mechanism see the Supple-
mentary Material). A comparison of the reaction outcome
(using method B) under photocatalytic (entry 2), photochemi-
cal (entry 8), and photocatalyst-free conditions in the absence
Interestingly, only few examples are known for NOþ-mediated
dehydrogenativearenecouplingreactions, whicharelimitedtothe
homocoupling of activated arenes[19b,21] and to intramolecular
coupling reactions.[22] As NOþ sources, NOþBF4ꢁ or other NOþ
precursors in combination with strong acids (NaNO2/CF3SO3H or
ꢀ
NO2 /CF3COOH) were applied. The access to NOþ from readily
available non-toxic nitrate salts through a finely tuned interplay
between formic acid and MeOH discovered in this study could
provide a mild and attractive alternative approach to this syntheti-
cally versatile intermediate avoiding the use of carcinogenic
ꢀ
NaNO2 and toxic NO2 gas in combination with harsh acid
conditions.[23]
In fact, reduction of the amount of LiNO3 from 1.0 to 0.5
equiv. provides the product in comparable yields (Table 2, entry
10). This shows that NOþ is regenerated under the applied
conditions and can be used substoichiometrically. A further
decrease to 0.25 equiv. of LiNO3 led to reduced conversion and
yield (entry 11). Variations of the ratio of formic acid to MeOH
had a significant impact on the conversion and product distribu-
tion (entries 12, 13). By applying formic acid/MeOH (1: 9), low
conversion of the starting material 1a was observed. In contrast, a
1 : 1 formic acid/MeOH mixture resulted in an increased over-
oxidation to produce a teraryl adduct consisting of one phenol and
two arene moieties (not shown), which was identified by its
molecular ion at m/z 470.2. Best results were obtained for 0.5
equiv. of LiNO3 in a formic acid/MeOH mixture of 9 : 1 and an
excess of the arene coupling partner 1b of 3 equiv. (entry 10).
Although various radical and ionic nitrogen oxides are
formed as intermediates in this reaction, which could principally
also lead to aromatic nitration[19c,20b,21b,24] and nitrosa-
tion[19c,20c] products, the mass balance for the phenolic com-
pound 1a under most conditions showed a relatively clean
conversion into the aforementioned products (Table 2).[25] In
contrast to this, the mass balance for 1,2,4-trimethoxybenzene
1b suggests the occurrence of side reactions. In fact, we
observed colour changes upon addition of the aromatic compo-
nents to the formic acid/MeOH/LiNO3 mixture (method B).
(a)
ꢀ
Hꢁ
HNO3
HNO2
(1)
(2)
(3)
ꢁ
NO3
ꢁ
ꢁ
ꢁ
H2O
HCOOH
2 HNO2
HNO3
CO2
ꢁ
N2O3(aq)
H2O
Faint blue color
N2O3
NO
ꢁ
NO2
(4)
(5)
Brown gas
ꢀ
NOꢁ NO3
2 NO2
N2O4
Active species
(b)
CT complex
[ArH, NOꢁ]
ArH
NOꢁ
hν
(6)
Thermal
[ArHꢁ, NO]
Scheme 2. Proposed in situ generation of the active NOþ species (a)
and mechanism of the NOþ-mediated oxidation of aromatic compounds
(b).[18,19c,20]
3 equiv.
R2
b
OH
OH
0.5 equiv. LiNO3
R1
R1
R2
Formic acid/MeOH (9 : 1)
air, rt
a
ab
Hꢁ, eꢀ
NOꢁ
ꢁ NOꢁ
LiNO3
ꢀNO
ꢀHꢁ
ꢀNO
ꢀHꢁ
b
R2
OH
O
O
O
O
R1
R1
R1
R1
R1
R2
R2
H
H
Electrophilic phenoxyl radical
Regeneration of NOꢁ by oxygen
2 NO O2 2 NO2
ꢀ
ꢁ
N2O4
NOꢁNO3
Scheme 3. Proposed mechanism for the NOþ-mediated phenol–arene cross-dehydrogenative coupling.[27]

Nitrosonium-Mediated Phenol-Arene Cross-Coupling
E
This could be due to nitrosation as a minor pathway,[26] but no
products could be isolated or detected. The observed colour
changes could also result from the formation of CT complexes
between NOþ and the aromatic components.[20b] The nitration
of the starting materials 1a ([Mþ] signal in the GC-MS at m/z
183.1) and 1b ([Mþ] signal in the GC-MS at m/z 213.1) could be
detected in traces for the MeOH addition method B, method A
showed no nitration, and for method C trace amounts of nitration
could be observed in some cases. The amount of nitration
products correlates with the product formation 1ab.
a rate of 108C minꢁ1 over a period of 18 min until the final
temperature (2508C) was reached and maintained for 17 min. A
calibration was performed using the internal standard method
(multi-level calibration, internal standard: 2-methylnaphthalene).
Authentic samples of each compound were used for calibration.
General Procedure
In a snap vial equipped with a magnetic stirring bar the
respective amount of LiNO3 and 5 mol-% Acrþ-Mes 1 (if
mentioned) were dissolved in 1 mL of the formic acid/MeOH
mixture (method of MeOH addition and ratio as indicated). The
arene 1b (3.0 equiv., 0.70 mmol) and phenol component 1a (1.0
equiv., 0.23 mmol) were added successively and the resulting
mixture was stirred at room temperature open to air for the
indicated time. If mentioned the sample was irradiated through
the vial’s plane bottom side with blue LEDs. After the addition
of the internal standard, the sample was filtered over a small plug
of silica gel. The plug was rinsed with MeOH (1 : 1), diluted, and
submitted to GC-MS.
Based on these results, we propose the following mechanism
for the NOþ-induced phenol–arene C–C cross-coupling
(Scheme 3): NOþ is formed in situ from the nitrate salt by
treatment withformicacid and MeOH according to Scheme 2.[18]
NOþ oxidizes the phenol component a, which undergoes depro-
tonation to give an electrophilic phenoxyl radical that is trapped
by the electron-rich arene nucleophile b.[27] The final C–C cross-
coupling product ab is formed after a second oxidation/
deprotonation step. The two equivalents of NOꢀ formed in this
ꢀ [18a,21]
sequence are re-oxidized by oxygen in air to NO2 ,
which
.
ꢁ [18a,e]
is in equilibrium with the dimer N2O4 or NOþNO3
Supplementary Material
However, further experiments are required to provide more
detailed insight into the mechanism, for example by using
NOþ scavengers (e.g. azides) and variation of the NOþ source.
Experimental details, cꢀyclic voltammetry data, and a detailed
mechanism of the NO3 -induced oxidation of phenols and the
NOþ-mediated arene oxidation as well as an alternative pathway
for the in situ NOþ formation and regeneration are available on
the Journal’s website.
Conclusion
In conclusion, an environmentally friendly and mild protocol for
the in situ formation of highly oxidizing NOþ could be devel-
oped. The nitrosonium cation NOþ can be conveniently gener-
ated from readily available nitrate salts by a combination of
formic acid and MeOH as solvent system. Apart from its role as
acid, the reducing properties of formic acid are decisive for the
generation of NOþ. Methanol as co-solvent is essential to pre-
Acknowledgements
This work was financially supported by the German Science Foundation
(DFG) (GRK 1626, Chemical Photocatalysis) and the German Academic
Exchange Service (DAAD). A. E. thanks the Deutsche Bundesstiftung
Umwelt (DBU) for a graduate scholarship.
ꢀ
vent degassing of NO2 , which is formed as an intermediate and
constitutes a precursor for NOþ. The method was applied to the
NOþ-induced oxidative phenol–arene C–C cross-coupling of
typical lignin-derived platform chemicals. Regeneration of the
oxidant by air enables the substoichiometric use of NOþ or the
corresponding nitrate source, respectively.
References
[1] J. Zakzeski, P. C. A. Bruijnincx, A. L. Jongerius, B. M. Weckhuysen,
Chem. Rev. 2010, 110, 3552. doi:10.1021/CR900354U
[2] U. Wille, Chem. – Eur. J. 2002, 8, 340. doi:10.1002/1521-3765
(20020118)8:2,340::AID-CHEM340.3.0.CO;2-4
[3] E. Baciocchi, T. D. Giacco, S. M. Murgia, G. V. Sebastiani, J. Chem.
Soc., Chem. Commun. 1987, 1246. doi:10.1039/C39870001246
[4] T. Shono, M. Chuankamnerdkarn, H. Maekawa, M. Ishifune,
S. Kashimura, Synthesis 1994, 895. doi:10.1055/S-1994-25594
[5] (a) R. P. Wayne, I. Barnes, P. Biggs, J. P. Burrows, C. E. Canosa-Mas,
J. Hjorth, G. Le Bras, G. K. Moortgat, D. Perner, G. Poulet, G. Restelli,
H. Sidebottom, Atmos. Environ. Part A 1991, 25, 1. doi:10.1016/0960-
1686(91)90192-A
Experimental
General Information and Materials
Commercial reagents and starting materials were purchased and
used without further purification. NMR spectra were recorded
on a Varian INOVA 400 (1H at 400 MHz and 13C at 100 MHz).
Cyclic voltammetry (CV) measurements were conducted with a
three-electrode potentiostat galvanostat PGSTAT302N from
Metrohm Autolab. A glassy carbon working electrode, a plati-
num counter electrode, and a silver wire as reference electrode
were used. Potentials were converted into SCE reference values
according to Pavlishchuk and Addison.[28] Photocatalytic
reactions were performed with blue light emitting diodes
(LEDs) (Osram Oslon SSL 80, lPeak ¼ 440 nm, royal blue,
operated at 700 mA).
(b) L. F. Gamon, J. M. White, U. Wille, Org. Biomol. Chem. 2014, 12,
8280. doi:10.1039/C4OB01577K
[6] D. C. E. Sigmund, U. Wille, Chem. Commun. 2008, 2121. doi:10.1039/
B803456G
[7] (a) T. Hering, T. Slanina, A. Hancock, U. Wille, B. Ko¨nig, Chem.
Commun. 2015, 51, 6568. doi:10.1039/C5CC01580D
(b) N. A. Romero, D. A. Nicewicz, J. Am. Chem. Soc. 2014, 136,
17024. doi:10.1021/JA506228U
[8] A. Lauraguais, A. El Zein, C. Coeur, E. Obeid, A. Cassez, M.-T.
Rayez, J.-C. Rayez, J. Phys. Chem. A 2016, 120, 2691. doi:10.1021/
ACS.JPCA.6B02729
Quantitative GC-MS Investigations (Table 2)
[9] (a) W. P. L. Carter, A. M. Winer, J. N. Pitts, Environ. Sci. Technol.
GC-MS measurements were performed on a 7890A GC system
from Agilent Technologies with an Agilent 5975 MSD Detector.
Data acquisition and evaluation was done with an MSD
ChemStation E.02.02.1431. The GC-MS oven temperature
program was adjusted as follows: an initial temperature of 708C
was maintained for 5 min, the temperature was then increased at
1981, 15, 829. doi:10.1021/ES00089A009
(b) R. Atkinson, S. M. Aschmann, J. Arey, Environ. Sci. Technol.
1992, 26, 1397. doi:10.1021/ES00031A018
(c) R. I. Olariu, I. Barnes, I. Bejan, C. Arsene, D. Vione, B. Klotz,
K. H. Becker, Environ. Sci. Technol. 2013, 47, 7729. doi:10.1021/
ES401096W

F
A. Eisenhofer, U. Wille, and B. Ko¨nig
[10] (a) A. Kirste, G. Schnakenburg, F. Stecker, A. Fischer, S. R.
Waldvogel, Angew. Chem. Int. Ed. 2010, 49, 971. doi:10.1002/
ANIE.200904763
(c) C. J. G. Raw, J. Frierdich, F. Perrino, G. Jex, J. Phys. Chem. 1978,
82, 1952. doi:10.1021/J100506A020
(d) J. C. Fanning, Coord. Chem. Rev. 2000, 199, 159 and references
therein. doi:10.1016/S0010-8545(99)00143-5
(e) M. Shiri, M. A. Zolfigol, H. G. Kruger, Z. Tanbakouchian, Tetra-
(b) A. Kirste, B. Elsler, G. Schnakenburg, S. R. Waldvogel, J. Am.
Chem. Soc. 2012, 134, 3571. doi:10.1021/JA211005G
(c) B. Elsler, A. Wiebe, D. Schollmeyer, K. M. Dyballa, R. Franke,
S. R. Waldvogel, Chem. – Eur. J. 2015, 21, 12321. doi:10.1002/
CHEM.201501604
hedron 2010, 66, 9077. doi:10.1016/J.TET.2010.09.057
(f) The role of MeOH is assumed either to increase solubility of NO2
ꢀ
and the dimer N2O4 or as mediator by the reaction with NO2ꢀ/N2O4 to
methyl nitrite, which can act as a source of NOþ under acidic
conditions: A. D. Yoffe, P. Gray, J. Chem. Soc. 1951, 1412.
[19] (a) L. Eberson, F. Radner, Acc. Chem. Res. 1987, 20, 53. doi:10.1021/
AR00134A002
[11] (a) E. Gaster, Y. Vainer, A. Regev, S. Narute, K. Sudheendran,
A. Werbeloff, H. Shalit, D. Pappo, Angew. Chem. Int. Ed. 2015, 54,
4198. doi:10.1002/ANIE.201409694
(b) A. Dyadyuk, K. Sudheendran, Y. Vainer, V. Vershinin, A. I.
Shames, D. Pappo, Org. Lett. 2016, 18, 4324. doi:10.1021/ACS.
ORGLETT.6B02064
(b) E. K. Kim, J. K. Kochi, J. Am. Chem. Soc. 1991, 113, 4962.
doi:10.1021/JA00013A036
(c) J. H. Ridd, D. Pletcher, X. Qiao, J. R. A. Pascal, A. J. Bard, G. W.
[12] Selected reviews on oxidative aromatic (cross-)coupling reactions:
(a) H. Musso, Angew. Chem. Int. Ed. Engl. 1963, 2, 723. doi:10.1002/
ANIE.196307231
˚
Francis, J. Szu´nyog, B. Langstro¨m, Acta Chem. Scand. 1998, 52, 11.
doi:10.3891/ACTA.CHEM.SCAND.52-0011
[20] (a) G. I. Borodkin, V. G. Shubin, Russ. Chem. Rev. 2001, 70, 211.
doi:10.1070/RC2001V070N03ABEH000634
(b) M. Grzybowski, K. Skonieczny, H. Butenscho¨n, D. T. Gryko,
Angew. Chem. Int. Ed. 2013, 52, 9900. doi:10.1002/ANIE.201210238
(c) Y. Kita, T. Dohi, K. Morimoto, J. Synth. Org. Chem. Jpn. 2011, 69,
1241. doi:10.5059/YUKIGOSEIKYOKAISHI.69.1241
(d) J. A. Ashenhurst, Chem. Soc. Rev. 2010, 39, 540. doi:10.1039/
B907809F
(b) E. Bosch, J. K. Kochi, J. Org. Chem. 1994, 59, 3314. doi:10.1021/
JO00091A018
(c) E. Bosch, J. K. Kochi, J. Org. Chem. 1994, 59, 5573. doi:10.1021/
JO00098A015
(e) G. P. McGlacken, L. M. Bateman, Chem. Soc. Rev. 2009, 38, 2447.
doi:10.1039/B805701J
[21] (a) F. Radner, J. Org. Chem. 1988, 53, 702. doi:10.1021/JO00238A045
(b) M. Tanaka, H. Nakashima, M. Fujiwara, H. Ando, Y. Souma,
J. Org. Chem. 1996, 61, 788. doi:10.1021/JO950814B
[22] (a) B. Su, L. Li, Y. Hu, Y. Liu, Q. Wang, Adv. Synth. Catal. 2012, 354,
383. doi:10.1002/ADSC.201100578
[13] From thermodynamic considerations the excited state of acridinium
catalyst 1 can be reductively quenched by activated arenes and phenols
and thus an alternative mechanism without the involvement of NO3ꢀ is
possible. However, Table 1 excludes the reductive quenching by
activated arenes as an efficient pathway: (a) N. A. Romero, K. A.
Margrey, N. E. Tay, D. A. Nicewicz, Science 2015, 349, 1326. doi:10.
1126/SCIENCE.AAC9895
(b) B. Su, M. Deng, Q. Wang, Org. Lett. 2013, 15, 1606. doi:10.1021/
OL400388J
[23] It cannot be excluded that the initial oxidation is initiated by NO2
ꢀ
.
However, NO2ꢀ is a considerably weaker oxidant (Ered (NO2ꢀ/NO2ꢁ) ¼
(b) K. Ohkubo, K. Mizushima, R. Iwata, S. Fukuzumi, Chem. Sci.
0.45–0.78 V versus SCE)[5b,19c] compared to NOþ.
2011, 2, 715. doi:10.1039/C0SC00535E
[14] The potentials were determined by cyclic voltammetry (CV); see
Supplementary Material for details.
[24] E. K. Kim, J. K. Kochi, J. Org. Chem. 1989, 54, 1692. doi:10.1021/
JO00268A036
[25] Tanaka et al.[21b] explained the high preference for C–C bond forma-
tion for the NOBF4-catalyzed homocoupling of naphthalene deriva-
tives due to the addition of superacids, which are reported to inhibit
nitration. We hypothesized that formic acid prevents nitrosation and
nitration through a similar mechanism.
[15] (a) L. Eberson, M. P. Hartshorn, O. Persson, J. Chem. Soc., Perkin
Trans. 2 1995, 1735. doi:10.1039/P29950001735
(b) L. Eberson, O. Persson, M. P. Hartshorn, Angew. Chem. Int. Ed.
Engl. 1995, 34, 2268. doi:10.1002/ANIE.199522681
(c) L. Eberson, M. P. Hartshorn, O. Persson, F. Radner, Chem. Com-
mun. 1996, 2105. doi:10.1039/CC9960002105
(d) A. Berkessel, J. A. Adrio, D. Hu¨ttenhain, J. M. Neudo¨rfl, J. Am.
Chem. Soc. 2006, 128, 8421. doi:10.1021/JA0545463
(e) T. Dohi, N. Yamaoka, Y. Kita, Tetrahedron 2010, 66, 5775.
doi:10.1016/J.TET.2010.04.116
[26] Gowenlock et al. observed an intense green colour upon treatment of
1,3-dimethoxybenzene 3b with the equilibrium mixture NO2ꢀ/N2O4 in
dichloromethane. The colour was assigned to a nitrosation reaction and
subsequent oxidation: B. G. Gowenlock, B. King, J. Pfab, J. Chem.
Res. 2000, 2000, 276. Treatment of 3b with formic acid/MeOH (9 : 1),
LiNO3 (0.5 equiv.) (method B) results in an intense emerald green
colour, which implies the formation of traces of nitrosation products
and gives indirꢁect evidence to the formation of NO2ꢀ/N2O4 and the
[16] (a) T. Kashiwagi, B. Elsler, S. R. Waldvogel, T. Fuchigami, M. Atobe,
J. Electrochem. Soc. 2013, 160, G3058. doi:10.1149/2.011307JES
(b) B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R.
Waldvogel, Angew. Chem. Int. Ed. 2014, 53, 5210.
[17] J. S. Morgan, J. Chem. Soc. Trans. 1916, 109, 274. doi:10.1039/
CT9160900274
ionic NOþNO3
.
[27] The cross-coupling can also be initiated by the oxidation of arene b and
subsequent trapping with the phenol component a as indicated by the
formation of the cross-coupling product bb.
[18] (a) P. Gray, A. D. Yoffe, Chem. Rev. 1955, 55, 1069. doi:10.1021/
CR50006A001
[28] V. V. Pavlishchuk, A. W. Addison, Inorg. Chim. Acta 2000, 298, 97.
doi:10.1016/S0020-1693(99)00407-7
(b) M. Qureshi, W. Husain, J. P. Rawat, Anal. Chem. 1963, 35, 1592.
doi:10.1021/AC60204A014