Nitrosation of aryl and heteroaryltrifluoroborates with nitrosonium tetrafluoroborate

Article abstract of DOI:10.1021/jo300551m

Organotrifluoroborates have emerged as an alternative to toxic and air- and moisture-sensitive organometallic species for the synthesis of functionalized aryl and heteroaryl compounds. It has been shown that the trifluoroborate moiety can be easily converted into a variety of different substituents in a late synthetic stage. In this paper, we disclose a mild, selective, and convenient method for the ipso-nitrosation of organotrifluoroborates using nitrosonium tetrafluoroborate (NOBF₄). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.

Full text of DOI:10.1021/jo300551m

Article
pubs.acs.org/joc
Nitrosation of Aryl and Heteroaryltrifluoroborates with Nitrosonium
Tetrafluoroborate
Gary A. Molander* and Livia N. Cavalcanti
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
Pennsylvania 19104-6323, United States
S
* Supporting Information
ABSTRACT: Organotrifluoroborates have emerged as an alternative to toxic and
air- and moisture-sensitive organometallic species for the synthesis of
functionalized aryl and heteroaryl compounds. It has been shown that the
trifluoroborate moiety can be easily converted into a variety of different
substituents in a late synthetic stage. In this paper, we disclose a mild, selective,
and convenient method for the ipso-nitrosation of organotrifluoroborates using
nitrosonium tetrafluoroborate (NOBF4). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso
products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.
examples using organometallic species and the drawbacks
associated with oxidation reactions of aryl and heteroarylnitroso
synthesis (e.g., functional group tolerance and side product
formation), we were interested in finding a novel, rapid, and
mild method to synthesize nitrosoarene derivatives.
The ipso-substitution of arylboron species, as previously
demonstrated for halogenation21 and nitration22 of arylboronic
acids, provides a potential means to accomplish this goal.
Recently, our group published the chlorodeboronation of aryl
and heteroaryltrifluoroborates, which most likely occurs by an
ipso-substitution (Scheme 2).23
Trifluoroborates have emerged as an alternative to toxic
organometallic species, such as organostannanes, and to
boronic acids, which, although nontoxic, are compounds
susceptible to undesired side reactions with common reagents,
such as acids and bases.24 The tetracoordinate nature of the
trifluoroborates makes them resistant to a variety of reaction
conditions and, therefore, allows one to build complexity into a
molecule while leaving the carbon−boron bond intact. This
valuable bond can then be further converted in a later synthetic
step into a variety of groups such as boronic acids,25 alcohols,26
and halogens.21a−c,23 Moreover, trifluoroborates can be
synthesized by a variety of complementary methods, including
transmetalation (via metal−halogen exchange or directed
metalation), Miyaura borylation, and C−H activation, all of
which combine to afford an enormous diversity of available
substructures (Scheme 3). Furthermore, in contrast to the
corresponding aryl and heteroarylboronic acids, trifluoroborates
are air and moisture stable and can be stored on the bench for
months without appreciable decomposition.27
INTRODUCTION
■
Nitroso compounds are versatile synthetic intermediates and
have been utilized in a variety of transformations1 such as
nitroso aldol reactions,2 [4 + 2],3 [3 + 3],4 and [2 + 2]5
cycloadditions, ene reactions,6 addition of Grignard reagents,7
reactions with alkynes to yield indoles,8 coupling with amines
to afford azo compounds,9 oxidation to nitro compounds,10 and
reduction to amines11 (Scheme 1). Additionally, aromatic
nitroso species have shown some activity against HIV-1
infectivity.12 Despite their potentially wide applications, many
of these reported methods utilize a single or limited subset of
nitroso aromatics, presumably because of the lack of synthetic
methods available to synthesize a diverse set of functionalized
nitrosoarenes.
The first synthesis of nitrosobenzene was published by
Baeyer over a century ago.13 Since then, various methods have
been published to afford nitrosoarenes.14 Among them, the
oxidation of anilines to the corresponding nitrosoarene is the
most widely utilized.15 Although many protocols for this
conversion are reported in the literature, their reliance on the
availability of anilines makes them somewhat limited in scope.
Furthermore, the use of oxidants restricts the range of
functional groups allowed in this transformation. As an
example, aldehyde-containing nitrosoarenes cannot be made
by this method. Another problem generally associated with this
method is the formation of undesired side products such as azo
and azoxy compounds.14 Moreover, few heteroarylnitroso
compounds have been obtained by this method, and those
that have been accessed have been confined to nitrogen-
containing heterocycles.16 Nitrosation of simple arenes17 and
arylmetallics (e.g., organotin,18 thallium,19 and silicon20
compounds) have also been reported in the literature using
electrophilic nitrosonium reagents. For both of these types of
transformations the reaction only works for aryl species
containing electron-donating groups, which limits the breadth
of nitroso products that can be accessed. Because of the limited
In this paper, we disclose the ipso-nitrosation of a broad
range of aryl and heteroaryltrifluoroborates containing both
electron-donating and electron-withdrawing groups. To the
Received: March 17, 2012
Published: April 24, 2012
© 2012 American Chemical Society
4402
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
Scheme 1
Scheme 2
Table 1. Optimization with Sodium Nitrite
reaction time
entry
solvent
EtOAc
temperature
(h)
11B NMR/GC−MS
1
2
3
4
rt
rt
rt
rt
48
48
18
4
S.M.
best of our knowledge, this is the first nitrosation of an
organoboron species, and the transformation presented is
arguably the most broadly applicable approach to this
underrepresented class of molecules.
CH3CN
heptane
H2O
S.M.
S.M.
1a: protodeboronation
(1:1)
5
6
7
8
EtOAc/
H2O
rt
4
4
4
2
1a: protodeboronation
(3:1)
RESULTS AND DISCUSSION
■
CH3CN/
H2O
rt
1a: protodeboronation
(2:1)
On the basis of the ipso-nitration of boronic acids with nitrate
salts developed by Olah and co-workers,23 we began the
screening for nitrosation of organotrifluoroborates with sodium
nitrite in different solvents (Table 1). The choice of this nitrite
salt was made by the ready availability and low cost of this
reagent. After optimization, we determined that the reaction of
potassium trifluoro(4-methoxyphenyl)borate with NaNO2 (1.5
equiv) in heptane/H2O at 50 °C afforded the desired nitrosated
product in 89% isolated yield.
heptane/
H2O
rt
1a
heptane/
H2O
50 °C
1a (89% isolated yield)
With these conditions in hand, we began to examine the
nitrosation of a variety of aryltrifluoroborates (Scheme 4).
Phenyltrifluoroborates bearing electron-donating groups were
Scheme 3
4403
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
Scheme 4
Table 2. Optimization of the Nitrosation of Potassium [1,1′-
Biphenyl]-4-yltrifluoroborate
reaction
entry
1
NO agent
NaNO2
solvent
time
GC−MS
heptane/H2O
(1:1)
4 h
protodeboronation
2
3
4
5
6
7
8
KNO2
heptane/H2O
(1:1)
4 h
2 h
1 h
1 h
1 h
1 h
30 s
protodeboronation
protodeboronation
protodeboronation
protodeboronation
protodeboronation
protodeboronation
AgNO2
heptane/H2O
(1:1)
NaNO2/HCl heptane/H2O
(1:1)
KNO2/HCl
heptane/H2O
(1:1)
AgNO2/HCl heptane/H2O
(1:1)
NaNO2/
TMSCI
CH2CI2/H2O
(1:1)
successfully converted into the corresponding nitrosobenzene
in good yields. Unfortunately, electron-neutral aryltrifluorobo-
rates (e.g., biphenyl) and electron-withdrawing (ester) groups
inhibited this transformation, and only the protodeboronated
products were obtained.
NOBF4
CH3CN
product (90% isolated
yield)
Instead, a mixture of nitroso, nitro, and protodeboronation
products is observed.
The results obtained further demonstrated that the reaction
does not occur in the absence of water and that only electron-
rich aryltrifluoroborates afforded the desired product. Thus, we
hypothesized that aqueous conditions are necessary to form the
tricoordinate boron species in situ,28 and this species, now
possessing a Lewis acidic boron moiety with an empty p-orbital,
could then undergo attack of sodium nitrite to form an ate-
complex and a more electrophilic NO+, with subsequent ipso-
substitution affording the nitroso product (Scheme 5).
To improve the scope of this reaction, the nitrosation of
potassium [1,1′-biphenyl]-4-yltrifluoroborate was further opti-
mized. A variety of solvents, additives, nitrosating agents, and
temperatures were investigated. As illustrated in Table 2, the
use of other nitrite salts, such as KNO2 and AgNO2 (Table 2,
entries 1−3), were inefficient for this transformation. The use
With the optimal conditions in hand, the scope of the
reaction for electron-donating and electron-neutral aryltrifluor-
oborates was investigated (Table 3). In all cases, the reaction
was complete in only 30 s and afforded the desired product in
good to excellent yields. The method proved to be selective,
and aryltrifluoroborates containing ortho, meta, and para
substituents were readily converted to the corresponding
nitrosobenzene (Table 3, entries 1−3). This regioselectivity
cannot be attained by the direct nitrosation of arenes. The
reaction was scaled up to 1 g, and the product was obtained in
excellent yield (Table 3, entry 1). Sterically hindered substrates
also afforded the desired product in good yield. Importantly,
potassium (3,5-diisopropylphenyl)trifluoroborate, made by
direct C−H activation of arenes30 was converted into 1,3-
diisopropyl-5-nitrosobenzene in 88% yield (Table 3, entry 9).
This illustrates a unique substitution pattern, because the
corresponding aryl chloride (necessary for preparation of the
amine utilized for the oxidation method previously mentioned)
has very limited availability. Surprisingly, the reaction of
potassium trifluoro(4-hydroxyphenyl)borate yielded the corre-
sponding nitrophenol as a mixture of regioisomers (eq 1).
of acid additives for in situ formation of NO+18 29 also did not
c,
afford the desired nitroso product, and only protodeboronation
was observed (Table 2, entries 4−7). Fortunately, the use of
nitrosonium tetrafluoroborate (1.03 equiv) in CH3CN (0.2 M)
at room temperature in an open flask proved to be efficient for
this transformation, affording the nitroso product in 90%
isolated yield. Importantly, the reaction can be followed
visually. The slurry formed by the trifluoroborate in CH3CN
becomes a bright green, homogeneous solution almost
immediately. The crude reaction is then worked up by addition
of water followed by dichloromethane extraction, with
subsequent filtration through a plug of silica providing the
product in high purity. A prolonged reaction time leads to
oxidation of the formed nitroso product and affords a mixture
of this compound along with the corresponding nitroaromatic.
The use of more than 1.03 equiv of nitrosonium tetrafluor-
oborate does not fully convert the nitroso into the nitro group.
Subsequently, the reaction of aryltrifluoroborates bearing
electron-withdrawing groups was investigated (Table 4).
Scheme 5
4404
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
oxidation of the aldehyde group (Table 4, entries 4−6). These
aldehyde-containing nitroso products were previously obtained
only by a four step procedure from the corresponding
nitroarene.31 As illustrated previously with potassium (3,5-
diisopropylphenyl)trifluoroborate (Table 3, entry 9), we were
able to synthesize methyl 3-methyl-5-nitrosobenzoate and 1-
methoxy-3-nitroso-5-(trifluoromethyl)benzene (Table 4, en-
tries 10 and 11) from trifluoroborates made by C−H activation.
Furthermore, the conversion of aryltrifluoroborates containing
halogens into the corresponding nitroso product was
accomplished in good yields (Table 4, entries 12−15).
Table 3. Nitrosation of Electron-Rich and Electron-Neutral
Potassium Aryltrifluoroborates
a
To expand the scope of this reaction further, we turned our
attention to the reaction of heteroaryltrifluoroborates. Once
more, this transformation was accomplished for a variety of
substrates, including dibenzofuranyl, dibenzothienyl, benzo-
thienyl, indolyl, pyrimidinyl, and pyridinyl derivatives, affording
the nitrosoheteroaryl products in good yields (Table 5).
Furthermore, products 3e, 3f, and 3g (Table 5, entries 5−6)
were obtained with no observed nitrosation of the heterocyclic
nitrogen.32 To the best of our knowledge, all compounds
illustrated in Table 5 were never before synthesized by any
other method. However, for 5-membered heteroaryltrifluor-
oborates (e.g., thienyl, furanyl, pyrrolyl, isoxazolyl, and
pyrazolyl) and fused system with the trifluoroborate substituent
within the 5-membered heterocycle (e.g., 2- or 3-substituted
dibenzofuranyl, dibenzothienyl, and indolyl), the reaction was
inefficient, and only protodeboronated product was recovered.
Moreover, the reaction with 3-trifluoroboratopyridines con-
taining a substituent at the 6 position afforded a mixture of
nitro and dinitro products, and no nitroso derivatives were
observed (eq 2). The use of more than 1 equiv of NOBF4 did
not give the dinitro product; instead, a mixture of products
along with protodeboronation was observed. The same pattern
was observed for quinolines bearing trifluoroborates at the 2, 3,
and 4 positions, where a mixture of nitro and dinitro derivatives
was obtained.
Interestingly, 5-nitrosoisoquinoline 3h (Table 5, entry 8) was
obtained as a yellow solid that upon exposure to air would turn
black and could not be further purified. The crude material
appeared to be very pure by 1H NMR (see spectra in
Supporting Information), which led to the conclusion that the
nitroso product obtained is not stable. To circumvent this
problem, a one-pot nitrosation of potassium trifluoro-
(isoquinolin-5-yl)borate, 4a, followed by Diels−Alder reaction
with cyclohexa-1,3-diene 4b, was investigated (eq 3).13 The
reaction afforded the Diels−Alder adduct in 65% yield over two
steps.
With the success of the nitroso one-pot Diels−Alder
reaction, we were interested in illustrating other reactions
that potentially unstable arylnitroso compounds can undergo
(Scheme 6). Nitrogen-containing compounds are found in a
variety of pharmaceuticals and are also the building blocks for
important synthetic transformations.33 Therefore, potassium
methyl 3-trifluoroboratobenzoate was subjected to the nitro-
a
Reaction conditions: 1 mmol of aryltrifluoroborate and NOBF4 (1.03
equiv) in 3 mL of CH3CN for 30 s at room temperature in an open
flask. 5 mmol scale.
b
Methods such as direct nitrosation of arenes and other
organometallic species have proven inefficient in the
production of nitrosobenzenes with electron-poor groups.18−21
In our hands, aryltrifluoroborates containing ester, ketone,
aldehyde, nitrile, amide, nitro, and carboxylic acid groups
(Table 4, entries 1−9) were converted into the corresponding
nitroso compounds in good yields without affecting the
aforementioned, embedded functional groups. The reaction
was regiospecific, and ortho, meta, and para substituted
nitrosobenzenes were obtained. Importantly, aldehyde-contain-
ing aryltrifluoroborates afforded the corresponding nitro-
sobenzaldehyde in good yields and high regioselectivity without
4405
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
a
Table 4. Nitrosation of Electron-Poor Potassium Aryltrifluoroborates
a
Reaction conditions: 1 mmol of aryltrifluoroborate and NOBF4 (1.03 equiv) in 3 mL of CH3CN for 30 s at room temperature in an open flask.
yield over the two steps. The one-pot nitrosation-reduction of
the in situ formed methyl 3-nitrosobenzoate was performed,
and the methyl 3-aminobenzoate, 5c, was obtained in 72%
overall yield. The one-pot nitrosation/Diels−Alder reaction
was also accomplished, with the oxazabicyclo benzoate 5d
being isolated in 82% yield.
Finally, as illustrated in Scheme 7, different boron derivatives
were tested under the same reaction conditions. 4-Methox-
yphenylboronic acid afforded the product in nearly the same
yield as the trifluoroborates, while the boronate esters were not
successful in this transformation, instead providing the nitroso
product in moderate yields after 1 h with starting material being
recovered.
In summary, it has been demonstrated that the nitrosation of
a broad range of aryl and heteroaryltrifluoroborates can be
carried out under extraordinarily mild reaction conditions.
Aryltrifluoroborates containing different functional groups, such
as esters, ketones, aldehydes, nitriles, and amides were
sation protocol followed by different transformations, and
diverse nitrogen-containing products were obtained. The one-
pot reaction of the aforementioned trifluoroborate with NOBF4
followed by addition of NaBH4 afforded the corresponding
azoxy product, 5a, in 87% overall yield. Methyl 3-nitrobenzoate
5b was also obtained by a two-step procedure from the
corresponding trifluoroborate. In this case, a minimal workup
of the nitrosation reaction was necessary before addition of the
oxidant. Nevertheless, the desired product was obtained in 86%
4406
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
Table 5. Nitrosation of Potassium
Heteroaryltrifluoroborates
EXPERIMENTAL SECTION
■
a
General Procedure for the Preparation of Potassium Aryl
and Heteroaryltrifluoroborates from Boronic Acids. Following a
published literature procedure,34 to a solution of the corresponding
boronic acid in MeOH (3.5 M or enough MeOH to give a free-flowing
suspension) under N2 was added KHF2 (3 equiv of a 4.5 M solution in
H2O) dropwise at 0 °C. The ice-water bath was removed, and the
reaction was stirred at rt until 11B NMR indicated completion of the
reaction (∼2 min). The crude mixture was concentrated and dried
overnight in vacuo. The crude solid was purified using continuous
Soxhlet extraction (4 h) with acetone (60 mL). The collected solvent
was concentrated and then redissolved in a minimal amount of acetone
(5 mL). The addition of Et2O (30 mL) led to the precipitation of the
product. The product was filtered, concentrated, and dried in vacuo to
afford the pure organotrifluoroborates.
General Procedure for Aryl C−H Borylation. Following the
procedure published by Hartwig and co-workers,35 in a glovebox, to an
oven-dried glass vessel capable of being sealed with a Teflon cap (for
microwave vials) were added B2pin2, (1 equiv), [Ir(COD)(OMe)]2
(0.1 mol %), and dtbpy (0.2 mol %). The vessel was sealed and
removed from the glovebox. THF (1 M degassed) was added via
syringe followed by the addition of the 1,3-substituted arene (1.5
equiv). The reaction mixture was heated in a sealed vessel at 80 °C for
16 h. The reaction was allowed to cool to rt, and then KHF2 (3 equiv
of a 4.5 M solution in H2O) was added dropwise at 0 °C. The ice-
water bath was removed, and the reaction was stirred at rt until 11B
NMR indicated completion of the reaction (∼2 min). The crude
mixture was concentrated and dried overnight in vacuo. The crude
solid was purified using continuous Soxhlet extraction (4 h) with
acetone (60 mL). The collected solvent was concentrated and then
redissolved in a minimal amount of acetone (5 mL). The addition of
Et2O (30 mL) led to the precipitation of the product. The product was
filtered, concentrated, and dried in vacuo to afford the pure
organotrifluoroborates.
General Procedure A: Nitrosation of Aryltrifluoroborates
with NaNO2. To a 20 mL glass microwave vial containing a solution
of potassium organotrifluoroborate (1 mmol) in heptane/H2O (1:1, 5
mL, 0.2 M) was added NaNO2 (104 mg, 1.5 mmol, 1.5 equiv) in one
portion. The reaction was stirred open to air at 50 °C until the
trifluoroborate was consumed (as indicated by 11B NMR). To the
crude mixture were added H2O (20 mL) and CH2Cl2 (10 mL). The
layers were separated, and the aqueous layer was extracted with
CH2Cl2 (3 × 10 mL). The combined organic layers were dried
(Na2SO4), filtered, and concentrated under reduced pressure. The
products were obtained in high purity after filtration through a small
plug of silica topped with Celite, eluting with CH2Cl2.
General Procedure B: Nitrosation of Aryl and Heteroaryltri-
fluoroborates with NOBF4. To a 20 mL glass microwave vial
containing a solution of potassium organotrifluoroborate (1 mmol) in
CH3CN (3 mL, 0.33 M) was added NOBF4 (120 mg, 1.03 mmol, 1.03
equiv) in one portion. The reaction was stirred open to air at rt until
the reaction became homogeneous. The reaction changed from a
white slurry to a green or black solution. To the crude mixture were
added H2O (20 mL) and CH2Cl2 (10 mL). The layers were separated,
and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated under reduced pressure. In general, the product was
obtained in high purity after filtration through a small plug of silica
topped with Celite, eluting with CH2Cl2/hexanes. In specific cases,
trace impurities were removed by column chromatography using
CH2Cl2/hexanes or EtOAc/hexanes to afford the desired pure
product.
a
Reaction conditions: 1 mmol of aryltrifluoroborate and NOBF4 (1.03
equiv) in 3 mL of CH3CN for 30 s at room temperature in an open
flask. NMR yield using EtOAc as internal standard.
b
successfully converted into the nitroso product, while leaving
the aforementioned groups intact. Furthermore, nitrogen-
containing heteroaryltrifluoroborates underwent nitrosation
selectively, and no nitrosation of the nitrogen atom was
observed. Despite their simplicity, most of the nitroso
compounds prepared were previously unknown, highlighting
the lack of synthetic methods available for this important class
of molecules. The versatility of the nitroso products obtained
has been illustrated by converting these intermediates in a
variety of one-pot transformations, demonstrating that even
those nitrosoarenes that may have limited stability can be
employed as useful substrates for further synthetic applications.
1-Methoxy-4-nitrosobenzene (1a).8a General procedure B was
employed using potassium 4-methoxyphenyltrifluoroborate (214 mg, 1
mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was complete
in 30 s. The desired pure product was obtained in 95% yield (130 mg,
0.95 mmol) as a green oil after filtration through a short plug of silica
topped with Celite using hexanes/CH2Cl2 (3:1): 1H NMR (500 MHz,
CDCl3) δ 7.91 (d, J = 6.5 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 3.94 (s,
3H); 13C NMR (125.8 MHz, CDCl3) δ 165.6, 163.9, 124.3, 113.8,
4407
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
Scheme 6
through a short plug of silica topped with Celite using hexanes/
CH2Cl2 (3:1): H NMR (500 MHz, CDCl3) δ 6.65 (d, J = 2.5 Hz,
Scheme 7
1
1H), 6.50 (d, J = 9 Hz, 1H) 6.34 (m, 1H), 4.22 (s, 3H), 3.92 (s, 3H);
13C NMR (125.8 MHz, CDCl3) δ 168.5, 164.4, 157.1, 112.1, 105.8,
98.5, 56.9, 56.2; IR (neat) 1600, 1397, 1246, 1014, 837 cm−1; HRMS
(ESI) m/z calcd. for C8H10NO3 (M + H)+ 168.0661, found 168.0664.
1-(Benzyloxy)-4-nitrosobenzene (1d). General procedure B was
employed using potassium (4-(benzyloxy)phenyl)trifluoroborate (290
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 30 s. The desired pure product was obtained in 92% yield
(196 mg, 0.92 mmol) as a blue solid, mp 81−83 °C, after filtration
through a short plug of silica topped with Celite using hexanes/
1
CH2Cl2 (3:1): H NMR (500 MHz, CDCl3) δ 7.93 (brs, 2H), 7.45−
7.37 (m, 5H), 7.10 (t, J = 8 Hz, 2H), 5.21 (s, 2H); 13C NMR (125.8
MHz, CDCl3) δ 164.9, 164.1, 135.6, 129.0, 128.7, 127.7, 114.9, 70.8;
IR (neat) 1598, 1502, 1262, 1117, 844, 730 cm−1; HRMS (ESI) m/z
calcd. for C13H11NO2 (M)+ 213.0790, found 213.0797.
55.9; IR (neat) 1598, 1504, 1411, 1263, 1020, 837 cm−1; HRMS (ESI)
m/z calcd. for C7H8NO2 (M + H)+ 138.0555, found 138.0558.
1-Methoxy-3-nitrosobenzene (1b). General procedure B was
employed using potassium 3-methoxyphenyltrifluoroborate (214 mg,
1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 30 s. The desired pure product was obtained in 89% yield
(122 mg, 0.89 mmol) as a green oil after column chromatography with
hexanes/CH2Cl2 (3:1) as eluent: 1H NMR (500 MHz, CDCl3) δ 8.02
(m, 1H), 7.60 (t, J = 8 Hz, 1H), 7.28 (m, 1H), 6.89 (t, J = 2 Hz, 1H),
3.86 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 166.9, 160.5, 130.5,
122.9, 119.8, 99.8, 55.8; IR (neat) 1604, 1483, 1384, 1041, 789 cm−1;
HRMS (ESI) m/z calcd. for C7H8NO2 (M + H)+ 138.0555, found
138.0558.
6-Nitroso-2,3-dihydrobenzo[b][1,4]dioxine (1e). General proce-
dure B was employed using potassium (2,3-dihydrobenzo[b][1,4]-
dioxin-6-yl)trifluoroborate (242 mg, 1 mmol) and NOBF4 (120 mg,
1.03 mmol). The reaction was complete in 30 s. The desired pure
product was obtained in 91% yield (150 mg, 0.91 mmol) as a green
solid, mp 88−90 °C, after column chromatography with hexanes/
1
CH2Cl2 (3:1) as eluent: H NMR (500 MHz, CDCl3) δ 7.84 (d, J =
7.5 Hz, 1H), 7.13 (s, 1H), 7.08 (d, J = 8.5 Hz, 1H), 4.38−4.36 (m,
2H), 4.33−4.31 (m, 2H); 13C NMR (125.8 MHz, CDCl3) δ 163.6,
150.9, 143.9, 120.8, 117.6, 107.7, 65.1, 64.2; IR (neat) 1591, 1495,
1280, 1054, 913 cm−1; HRMS (ESI) m/z calcd. for C8H8NO3 (M +
H)+ 166.0504, found 166.0504.
4-Nitrosobiphenyl (1f).36 General procedure B was employed using
potassium biphenyl-4-yltrifluoroborate (260 mg, 1 mmol) and NOBF4
(120 mg, 1.03 mmol). The reaction was complete in 30 s. The desired
pure product was obtained in 90% yield (165 mg, 0.90 mmol) as an
orange solid, mp 72−74 °C (lit.34 73−74 °C), after filtration through a
short plug of silica topped with Celite using hexanes/CH2Cl2 (3:1):
2,4-Dimethoxy-1-nitrosobenzene (1c). General procedure B was
employed using potassium (2,4-dimethoxyphenyl)trifluoroborate (244
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 30 s. The desired pure product was obtained in 91% yield
(152 mg, 0.91 mmol) as a green solid, mp 93−95 °C, after filtration
4408
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
754, 685 cm−1; HRMS (ESI) m/z calcd. for C8H8NO3 (M + H)+
166.0504, found 166.0510.
1H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.5 Hz, 2H), 7.83 (d, J = 8
Hz, 2H), 7.68−7.66 (m, 2H), 7.52−7.49 (m, 2H), 7.45 (m, 1H); 13C
NMR (125.8 MHz, CDCl3) δ 165.12, 148.2, 139.3, 129.3, 129.1,
128.0, 127.6, 121.8; IR (neat) 1483, 1249, 760, 695 cm−1; HRMS
(ESI) m/z calcd. for C12H10NO (M + H)+ 184.0762, found 184.0758.
1-tert-Butyl-4-nitrosobenzene (1g). General procedure B was
employed using potassium (4-tert-butylphenyl)trifluoroborate (240
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 30 s. The desired pure product was obtained in 93% yield
(152 mg, 0.93 mmol) as a green oil after filtration through a short plug
1-(3-Nitrosophenyl)ethanone (2c). General procedure B was
employed using potassium (3-acetylphenyl)trifluoroborate (226 mg,
1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 1 min. The desired pure product was obtained in 94%
yield (140 mg, 0.94 mmol) as a light yellow solid, mp 78−80 °C (lit.38
81.5 °C), after filtration through a short plug of silica topped with
1
Celite using CH2Cl2: H NMR (500 MHz, CDCl3) δ 8.47 (t, J = 1.5
Hz, 1H), 8.33 (m, 1H), 8.05 (m, 1H), 7.75 (t, J = 8 Hz, 1H), 2.73 (s,
3H); 13C NMR (125.8 MHz, CDCl3) δ 196.8, 165.0, 138.2, 134.3,
130.0, 124.3, 121.0, 26.9; IR (neat) 1691, 1248, 800, 676 cm−1; HRMS
(CI) m/z calcd. for C8H8NO2 (M + H)+ 150.0555, found 150.0557.
3-Nitrosobenzaldehyde (2d). General procedure B was employed
using potassium trifluoro(3-formylphenyl)borate (212 mg, 1 mmol)
and NOBF4 (120 mg, 1.03 mmol). The reaction was complete in 1
min. The desired pure product was obtained in 88% yield (119 mg,
0.88 mmol) as a light yellow solid, mp 106−108 °C (lit.42 106.5−107
°C), after filtration through a short plug of silica topped with Celite
using CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 10.20 (s, 1H), 8.38 (s,
1H), 8.26 (m, 1H), 8.15 (m, 1H), 7.83 (t, J = 8 Hz, 1H); 13C NMR
(125.8 MHz, CDCl3) δ 190.9, 164.7, 137.4, 135.0, 130.5, 125.7, 121.7;
IR (neat) 1689, 1257, 1121, 678 cm−1; HRMS (ESI) m/z calcd. for
C7H6NO2 (M + H)+ 136.0399, found 136.0402.
1
of silica topped with Celite using hexanes/CH2Cl2 (3:1): H NMR
(500 MHz, CDCl3) δ 7.83 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 9 Hz, 2H),
1.37 (s, 9H); 13C NMR (125.8 MHz, CDCl3) δ 165.3, 159.9, 126.2,
121.1, 35.7, 31.1; IR (neat) 1601, 1509, 1453, 1124, 1099, 840, 710
cm−1; HRMS (ESI) m/z calcd. for C10H14NO (M + H)+ 164.1075,
found 164.1082.
1,3,5-Trimethyl-2-nitrosobenzene (1h).17a General procedure B
was employed using potassium trifluoro(mesityl)borate (260 mg, 1
mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was complete
in 30 s. The desired pure product was obtained in 92% yield (137 mg,
0.90 mmol) as a white solid, mp 120−122 °C (lit.17a 121−122 °C),
after filtration column chromatography with hexanes/CH2Cl2 (3:1) as
eluent: 1H NMR (500 MHz, CDCl3) δ 6.99 (s, 2H), 2.62 (s, 2H), 2.41
(s, 4H), 2.34 (s, 1H), 2.33 (s, 2H); 13C NMR (125.8 MHz, CDCl3) δ
140.7, 139.3, 132.7, 129.9, 21.2, 18.7; IR (neat) 1603, 1475, 1245, 807
cm−1; HRMS (ESI) m/z calcd. for C9H12NO (M + H)+ 150.0919,
found 150.0919.
4-Nitrosobenzaldehyde (2e).31a General procedure B was
employed using potassium trifluoro(4-formylphenyl)borate (212 mg,
1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 1 min. The desired pure product was obtained in 94%
yield (127 mg, 0.94 mmol) as a light yellow solid, mp 135−137 °C
(lit.41 135−136 °C), after filtration through a short plug of silica
1,3-Diisopropyl-5-nitrosobenzene (1i). General procedure B was
employed using potassium (3,5-diisopropylphenyl)trifluoroborate
(268 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction
was complete in 30 s. The desired pure product was obtained in 88%
yield (168 mg, 0.88 mmol) as a green oil after filtration through a short
plug of silica topped with Celite using hexanes/CH2Cl2 (3:1): 1H
NMR (500 MHz, CDCl3) δ 7.61 (s, 2H), 7.46 (s, 1H), 3.07−3.01 (m,
2H), 1.32 (d, J = 7 Hz, 12 H); 13C NMR (125.8 MHz, CDCl3) δ
167.4, 150.5, 132.7, 117.0, 34.1, 24.0; IR (neat) 1608, 1493, 1096, 886,
694 cm−1; HRMS (ESI) m/z calcd. for C12H18NO (M + H)+
192.1388, found 192.1384.
1
topped with Celite using CH2Cl2: H NMR (500 MHz, CDCl3) δ
10.20 (s, 1H), 8.17 (d, J = 8.5 Hz, 2H), 8.04 (d, J = 8 Hz, 2H); 13C
NMR (125.8 MHz, CDCl3) δ 191.4, 163.9, 139.6, 131.2, 121.2; IR
(neat) 1691, 1259, 789 cm−1; HRMS (CI) m/z calcd. for C7H5NO2
(M)+ 135.0320, found 135.0322.
2-Nitrosobenzaldehyde (2f).43 General procedure B was employed
using potassium trifluoro(2-formylphenyl)borate (212 mg, 1 mmol)
and NOBF4 (120 mg, 1.03 mmol). The reaction was complete in 1
min. The desired pure product was obtained in 78% yield (105 mg,
0.78 mmol) as a light yellow solid, mp 110−112 °C (lit.12 110 °C),
after filtration through a short plug of silica topped with Celite using
4-Nitrophenol (1j).37 General procedure B was employed using
potassium trifluoro(4-hydroxyphenyl)borate (200 mg, 1 mmol) and
NOBF4 (120 mg, 1.03 mmol). The reaction was complete in 30 s. In
this case no nitroso product was observed and a mixture of 4-
nitrophenol and 2-nitrophenol (10% NMR yield) was obtained. The
pure 4-nitrophenol product was obtained in 71% yield (99 mg, 0.71
mmol) as a yellow solid, mp 108−110 °C (lit.38 109−110 °C), after
1
CH2Cl2: H NMR (500 MHz, CDCl3) δ 12.1 (s, 1H), 8.22 (m, 1H),
7.91 (t, J = 7.5 Hz, 1H), 7.69 (m, 1H), 6.44 (m, 1H); 13C NMR (125.8
MHz, CDCl3) δ 193.5, 162.2, 136.6, 134.2, 132.8, 127.8, 106.7; IR
(neat) 1702, 1248, 1196, 768 cm−1; HRMS (ESI) m/z calcd. for
C7H6NO2 (M + H)+ 136.0399, found 136.0404.
1
column chromatography with hexanes/CH2Cl2 (2:1) as eluent: H
4-Nitrosobenzonitrile (2g).44 General procedure B was employed
using potassium (4-cyanophenyl)trifluoroborate (209 mg, 1 mmol)
and NOBF4 (120 mg, 1.03 mmol). The reaction was complete in 1
min. The desired pure product was obtained in 89% yield (117 mg,
0.94 mmol) as a light yellow solid, mp 128−130 °C (lit.42 128−129
°C), after filtration through a short plug of silica topped with Celite
NMR (500 MHz, CDCl3) δ 8.18 (d, J = 9.5 Hz, 2H), 6.92 (d, J = 9 Hz,
2H), 5.72 (s, 1H); 13C NMR (125.8 MHz, CDCl3) δ 161.6, 141.7,
126.5, 115.9; IR (neat) 3359, 1592, 1488, 1331, 1113, 844 cm−1.
Methyl 4-Nitrosobenzoate (2a).39 General procedure B was
employed using potassium trifluoro(4-(methoxycarbonyl)phenyl)-
borate (242 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The
reaction was complete in 1 min. The desired pure product was
obtained in 95% yield (157 mg, 0.95 mmol) as a light yellow solid, mp
123−125 °C (lit.40 129.5 °C), after filtration through a short plug of
silica topped with Celite using CH2Cl2: 1H NMR (500 MHz, CDCl3)
δ 8.28 (d, J = 8 Hz, 2H), 7.92 (d, J = 8 Hz, 2H), 3.97 (s, 3H); 13C
NMR (125.8 MHz, CDCl3) δ 165.9, 164.5, 135.3, 131.2, 120.5, 52.9;
IR (neat) 1727, 1441, 1266, 766, 694 cm−1; HRMS (ESI) m/z calcd.
for C8H8NO3 (M + H)+ 166.0504, found 166.0510.
1
using CH2Cl2: H NMR (500 MHz, CDCl3) δ 7.97 (s, 4 H); 13C
NMR (125.8 MHz, CDCl3) δ 162.3, 134.1, 120.9, 118.5, 117.6; IR
(neat) 2239, 1499, 1252, 868 cm−1; HRMS (ESI) m/z calcd. for
C7H4N2O (M)+ 132.0324, found 132.032.
N-(3-Nitrosophenyl)acetamide (2h). General procedure B was
employed using potassium (3-acetamidophenyl)trifluoroborate (241
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 1 min. The desired pure product was obtained in 91%
yield (149 mg, 0.91 mmol) as a light yellow solid, mp 118−120 °C,
after filtration through a short plug of silica topped with Celite using
CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J = 8 Hz, 1H), 7.84
(d, J = 8 Hz, 1H), 7.79 (s, 1H), 7.61 (t, J = 8 Hz, 1H), 7.55 (s, 1H),
2.24 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 168.9, 165.9, 139.2,
130.2, 126.5, 118.8, 110.3, 24.8; IR (neat) 1672, 1598, 1492, 1076, 800
cm−1; HRMS (ESI) m/z calcd. for C8H9N2O2 (M + H)+ 165.0664,
found 165.0659.
Methyl 3-Nitrosobenzoate (2b).15b General procedure B was
employed using potassium trifluoro(3-(methoxycarbonyl)phenyl)-
borate (242 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The
reaction was complete in 1 min. The desired pure product was
obtained in 96% yield (158 mg, 0.96 mmol) as a light yellow solid, mp
91−93 °C (lit.41 93 °C), after filtration through a short plug of silica
topped with Celite using CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 8.60
(t, J = 1.5 Hz, 1H), 8.39 (m, 1H), 8.01 (m, 1H), 7.71 (t, J = 7.5 Hz,
1H), 4.01 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 165.8, 164.9,
135.8, 131.9, 129.7, 123.9, 122.6, 52.8; IR (neat) 1727, 1433, 1259,
3-Nitro-5-nitrosobenzoic Acid (2i). General procedure B was
employed using potassium (3-carboxy-5-nitrophenyl)trifluoroborate
4409
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
(273 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction
was complete in 1 min. The desired pure product was obtained in 92%
yield (180 mg, 0.92 mmol) as a green solid, mp 148−150 °C, after
filtration through a short plug of silica topped with Celite using
166.9 (m), 164.8 (d, J = 13 Hz), 153.3 (d, J = 4 Hz), 112.0 (m), 106.4
(m). 19F NMR (470.8 MHz, CDCl3) δ −94.4, −123.7; IR (neat) 1613,
1501, 1241, 845 cm−1; HRMS (ESI) m/z calcd. for C6H4NOF2 (M +
H)+ 144.0261, found 144.0260.
1
CH2Cl2: H NMR (500 MHz, CDCl3) δ 9.30 (t, J = 2 Hz, 1H), 9.10
4-Nitrosodibenzo[b,d]furan (3a). General procedure B was
employed using potassium dibenzo[b,d]furan-4-yltrifluoroborate (274
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 30 s. The desired pure product was obtained in 85% yield
(168 mg, 0.85 mmol) as a green solid, mp 84−86 °C, after filtration
(s, 1H), 8.78 (t, J = 1.5 Hz, 1H); 13C NMR (125.8 MHz, CDCl3) δ
168.6, 162.5, 149.5, 132.8, 129.6, 128.0, 118.2; IR (neat) 3095, 1700,
1545, 1294, 1177, 918, 736 cm−1; HRMS (ESI) m/z calcd. for
C7H3N2O5 (M − H)− 195.0042, found 195.0045.
1
Methyl 3-Methyl-5-nitrosobenzoate (2j). General procedure B was
employed using potassium trifluoro(3-(methoxycarbonyl)-5-
methylphenyl)borate (256 mg, 1 mmol) and NOBF4 (120 mg, 1.03
mmol). The reaction was complete in 1 min. The desired pure product
was obtained in 91% yield (163 mg, 0.91 mmol) as a yellow solid, mp
68−70 °C, after filtration through a short plug of silica topped with
through a short plug of silica topped with Celite using CH2Cl2: H
NMR (500 MHz, CDCl3) δ 8.26 (m, 1H), 8.01 (m, 1H), 7.78 (d, J = 8
Hz, 1H), 7.59−7.56 (m, 2H), 7.49−7.44 (m, 2H); 13C NMR (125.8
MHz, CDCl3) δ 157.4, 153.3, 148.8, 128.7, 128.5, 128.4, 124.1, 122.6,
122.5, 121.0, 116.3, 112.7; IR (neat) 1456, 1417, 1174, 1107, 830, 744
cm−1; HRMS (CI) m/z calcd. for C12H8NO2 (M + H)+ 198.0555,
found 198.0553.
1
Celite using CH2Cl2: H NMR (500 MHz, CDCl3) δ 8.44 (s, 1H),
8.20 (s, 1H), 7.73 (s, 1H), 3.99 (s, 3H), 2.55 (s, 3H); 13C NMR
(125.8 MHz, CDCl3) δ 165.9, 165.3, 140.1, 136.3, 131.6, 123.9, 120.6,
52.7, 21.2; IR (neat) 1726, 1445, 1253, 1134, 760 cm−1; HRMS (ESI)
m/z calcd. for C9H10NO3 (M + H)+ 180.0661, found 180.0667.
1-Methoxy-3-nitroso-5-(trifluoromethyl)benzene (2k). General
procedure B was employed using potassium trifluoro(3-methoxy-5-
(trifluoromethyl)phenyl)borate (282 mg, 1 mmol) and NOBF4 (120
mg, 1.03 mmol). The reaction was complete in 10 min. The desired
pure product was obtained in 81% yield (166 mg, 0.81 mmol) as a
green oil after filtration through a short plug of silica topped with
4-Nitrosodibenzo[b,d]thiophene (3b). General procedure B was
employed using potassium dibenzo[b,d]thiophen-4-yltrifluoroborate
(290 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction
was complete in 30 s. The desired pure product was obtained in 80%
yield (171 mg, 0.80 mmol) as a green solid, mp 115−117 °C, after
filtration through a short plug of silica topped with Celite using
CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 9.56 (m, 1H), 8.46 (m, 1H),
8.15 (m, 1H), 7.93−7.89 (m, 2H), 7.53−7.50 (m, 2H); 13C NMR
(125.8 MHz, CDCl3) δ 162.9, 142.1, 138.1, 137.9, 132.4, 128.2, 127.8,
125.9, 125.5, 123.7, 121.7, 120.1; IR (neat) 1421, 1190, 1086, 920, 750
cm−1; HRMS (ESI) m/z calcd. for C12H8NOS (M + H)+ 214.0327,
found 214.0336.
4-Nitrosobenzo[b]thiophene (3c). General procedure B was
employed using potassium benzo[b]thiophen-4-yltrifluoroborate
(240 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction
was complete in 30 s. The desired pure product was obtained in 81%
yield (132 mg, 0.81 mmol) as a yellow solid, mp 76−78 °C, after
filtration through a short plug of silica topped with Celite using
CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 8.48 (d, J = 8 Hz, 1H), 8.31
(m, 1H), 8.22 (d, J = 8 Hz, 1H), 7.86 (d, J = 5.5 Hz, 1H), 7.72 (t, J =
7.5 Hz, 1H); 13C NMR (125.8 MHz, CDCl3) δ 160.6, 142.8, 134.1,
130.2, 127.0, 126.8, 124.2, 121.7; IR (neat) 1450, 1265, 861, 746 cm−1;
HRMS (ESI) m/z calcd. for C8H6NOS (M + H)+ 164.0170, found
164.0168.
tert-Butyl 5-Nitroso-1H-indole-1-carboxylate (3d). General proce-
dure B was employed using potassium (1-(tert-butoxycarbonyl)-1H-
indol-5-yl)trifluoroborate (323 mg, 1 mmol) and NOBF4 (120 mg,
1.03 mmol). The reaction was complete in 30 s. The desired pure
product was obtained in 73% yield (180 mg, 0.73 mmol) as a green
solid, mp 101−103 °C, after filtration through a short plug of silica
topped with Celite using CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 8.43
(s, 1H), 8.26 (d, J = 8.5 Hz, 1H), 7.72 (d, J = 4 Hz, 1H), 7.61 (d, J =
8.5 Hz, 1H), 6.83 (d, J = 3.5 Hz, 1H), 1.70 (s, 9H); 13C NMR (125.8
MHz, CDCl3) δ 164.8, 149.2, 139.0, 130.6, 128.8, 119.7, 115.3, 115.1,
109.3, 85.2, 28.2; IR (neat) 1743, 1467, 1325, 1155, 1071, 721 cm−1;
HRMS (ESI) m/z calcd. for C13H13N2O3 (M − H)− 245.0926, found
245.0932.
1
Celite using CH2Cl2: H NMR (500 MHz, CDCl3) δ 8.11 (s, 1H),
7.50 (s, 1H), 7.21 (m, 1H), 3.93 (s, 3H); 13C NMR (125.8 MHz,
CDCl3) δ 165.2, 161.0, 133.4 (d, J = 34 Hz), 123.3 (m), 118.4 (d, J =
3.5 Hz), 114.0 (d, J = 3.5 Hz), 104.8, 56.3. 19F NMR (470.8 MHz,
CDCl3) δ −62.9; IR (neat) 1507, 1325, 1131, 1046, 873, 688 cm−1;
HRMS (ESI) m/z calcd. for C8H7NO2F3 (M + H)+ 206.0429, found
206.0431.
1-Iodo-4-nitrosobenzene (2l).45 General procedure B was
employed using potassium trifluoro(4-iodophenyl)borate (310 mg, 1
mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was complete
in 1 min. The desired pure product was obtained in 92% yield (214
mg, 0.92 mmol) as a green solid, mp 100−102 °C (lit.46 104−106 °C),
after filtration through a short plug of silica topped with Celite using
CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J = 8.5 Hz, 2H), 7.60
(d, J = 8.5 Hz, 2H); 13C NMR (125.8 MHz, CDCl3) δ 164.3, 138.9,
122.0, 105.6; IR (neat) 1579, 1481, 1113, 822 cm−1.
1-Bromo-4-nitrosobenzene (2m).8a General procedure B was
employed using potassium (4-bromophenyl)trifluoroborate (263 mg,
1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 1 min. The desired pure product was obtained in 94%
yield (175 mg, 0.94 mmol) as a light yellow solid, mp 92−94 °C (lit.8a
99−101 °C), after filtration through a short plug of silica topped with
Celite using CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 7.78 (s, 4H); 13
C
NMR (125.8 MHz, CDCl3) δ 164.0, 132.9, 131.8, 122.3; IR (neat)
1478, 1257, 1011, 856 cm−1; HRMS (ESI) m/z calcd. for C6H5NOBr
(M + H)+ 185.9554, found 185.9555.
1-Chloro-4-nitrosobenzene (2n).15d General procedure B was
employed using potassium (4-chlorophenyl)trifluoroborate (219 mg, 1
mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was complete
in 1 min. The desired pure product was obtained in 92% yield (130
mg, 0.92 mmol) as a light yellow solid, mp 87−89 °C (lit.47 88−89
°C), after filtration through a short plug of silica topped with Celite
using CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 9 Hz, 2H),
7.60 (d, J = 9 Hz, 2H); 13C NMR (125.8 MHz, CDCl3) δ 164.0, 142.6,
129.8, 122.3; IR (neat) 1481, 1256, 1089, 857 cm−1; HRMS (CI) m/z
calcd. for C6H5NOCl (M + H)+ 142.0060, found 142.0056.
2,4-Dimethoxy-5-nitrosopyrimidine (3e). General procedure B was
employed using potassium (2,4-dimethoxypyrimidin-5-yl)-
trifluoroborate (246 mg, 1 mmol) and NOBF4 (120 mg, 1.03
mmol). The reaction was complete in 30 s. The desired pure product
was obtained in 82% yield (139 mg, 0.82 mmol) as a green solid, mp
78−80 °C, after filtration through a short plug of silica topped with
1
Celite using CH2Cl2: H NMR (500 MHz, CDCl3) δ 8.18 (s, 1H),
4.33 (s, 3H), 4.16 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 166.6,
166.3, 149.6, 149.2, 56.5, 55.4; IR (neat) 1594, 1547, 1474, 1314,
1054, 796 cm−1; HRMS (ESI) m/z calcd. for C6H8N3O3 (M + H)+
170.0566, found 170.0570.
1,4-Difluoro-2-nitrosobenzene (2o). General procedure B was
employed using potassium (2,5-difluorophenyl)trifluoroborate (220
mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction was
complete in 10 min. The desired pure product was obtained in 81%
yield (116 mg, 0.81 mmol) as a white solid, mp 35−37 °C, after
filtration through a short plug of silica topped with Celite using
CH2Cl2: 1H NMR (500 MHz, CDCl3) δ 7.22 (m, 1H), 6.87 (m, 1H),
6.61 (m, 1H); 13C NMR (125.8 MHz, CDCl3) δ 168.9 (d, J = 12 Hz),
4-(5-Nitrosopyrimidin-2-yl)morpholine (3f). General procedure B
was employed using potassium trifluoro(2-morpholinopyrimidin-5-
yl)borate (271 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The
reaction was complete in 30 s. The desired pure product was obtained
in 76% yield (148 mg, 0.76 mmol) as a green solid, mp 151−153 °C,
1
after column chromatography with CH2Cl2 as eluent: H NMR (500
4410
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
MHz, CDCl3) δ 9.07 (s, 2H), 4.00 (t, J = 5 Hz, 4H), 3.79 (t, J = 5 Hz,
4H); 13C NMR (125.8 MHz, CDCl3) δ 161.5, 154.8, 133.6, 66.6, 44.8;
IR (neat) 2359, 1601, 1548, 1329, 1109, 790 cm−1; HRMS (ESI) m/z
calcd. for C8H11N4O2 (M + H)+ 195.0882, found 195.0884.
2,6-Dimethoxy-3-nitrosopyridine (3g). General procedure B was
employed using potassium (2,6-dimethoxypyridin-3-yl)trifluoroborate
(245 mg, 1 mmol) and NOBF4 (120 mg, 1.03 mmol). The reaction
was complete in 30 s. The desired pure product was obtained in 72%
yield (121 mg, 0.72 mmol) as a green solid, mp 95−97 °C, after
column chromatography with CH2Cl2 as eluent: 1H NMR (500 MHz,
CDCl3) δ 6.87 (d, J = 8.5 Hz, 1H), 6.23 (d, J = 8.5 Hz, 1H), 4.37 (s,
3H), 4.11 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 168.3, 165.6,
151.2, 122.1, 103.3, 54.8; IR (neat) 1588, 1384, 1286, 1001, 825 cm−1;
HRMS (ESI) m/z calcd. for C7H9N2O3 (M + H)+ 169.0613, found
169.0618.
(methoxycarbonyl)phenyl)borate (242 mg, 1 mmol) in CH3CN (3
mL, 0.33 M) was added NOBF4 (120 mg, 1.03 mmol, 1.03 equiv) in
one portion. After 30 s, the solvent was removed and EtOH was added
(3.5 mL, 0.3 M), followed by (NH4)2SO4 (1 g, 5 mmol, 5 equiv) and
NaBH4 (661 mg, 3 mmol, 3 equiv). The flask was then capped
(exothermic reaction) and stirred at rt for 30 min. The reaction
mixture changed from green to yellow. To the crude mixture were
added H2O (20 mL) and EtOAc (10 mL). The layers were separated,
and the aqueous layer was extracted with EtOAc (3 × 10 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated under reduced pressure. Purification by filtration through
a short plug of silica topped with Celite using EtOAc afforded the pure
product in 87% yield (137 mg, 0.44 mmol) as a yellow solid, mp 135−
137 °C (lit.46 135 °C): 1H NMR (500 MHz, CDCl3) δ 8.96 (d, J = 2
Hz, 1H), 8.77 (t, J = 2 Hz, 1H), 8.51 (m, 1H), 8.42 (m, 1H), 8.25 (d, J
= 7.5 Hz, 1H), 8.07 (d, J = 7.5 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.57
(t, J = 7.5 Hz, 1H), 3.99 (s, 3H), 3.96 (s, 3H); 13C NMR (125.8 MHz,
CDCl3) δ 166.5, 165.8, 148.4, 143.9, 132.9, 131.4, 131.1, 130.8, 129.6,
129.3, 129.0, 127.2, 126.7, 123.7, 52.7, 52.5; IR (neat) 1726, 1466,
1301, 1267, 1083, 753 cm−1; HRMS (ESI) m/z calcd. for C16H15N2O5
(M + H)+ 315.0981, found 315.0981.
5-Nitrosoisoquinoline (3h). General procedure B was employed
using potassium trifluoro(isoquinolin-5-yl)borate (235 mg, 1 mmol)
and NOBF4 (120 mg, 1.03 mmol). The reaction was complete in 30 s.
The desired pure product was obtained in 62% yield (NMR yield) as a
yellow solid that upon exposure to air becomes black after column
1
chromatography with EtOAc/CH2Cl2 (1:1) as eluent: H NMR (500
MHz, CDCl3) δ 9.49 (s, 1H), 9.41 (d, J = 6 Hz, 1H), 8.97 (d, J = 6 Hz,
1H), 8.40 (d, J = 8 Hz, 1H), 7.73 (t, J = 8 Hz, 1H), 7.14 (q, J = 1 and 8
Hz, 1H); 13C NMR (125.8 MHz, CDCl3) δ 157.7, 152.6, 147.2, 136.4,
131.5, 129.6, 126.2, 116.2, 114.0.
Procedure for Formation of Nitro Compounds: Synthesis of
Methyl 3-Nitrobenzoate (5b).50 Adapted from a previously
reported method.15b To a 20 mL glass microwave vial containing
potassium trifluoro(3-(methoxycarbonyl)phenyl)borate (242 mg, 1
mmol) in CH3CN (3 mL, 0.33 M) was added NOBF4 (120 mg, 1.03
mmol, 1.03 equiv) in one portion. After 30 s, the crude mixture was
filtered through a plug of silica topped with Celite using CH2Cl2, the
solvent was removed, and acetone/H2O (1:1, 5 mL) was added. To
the solution was then added Oxone (461 mg, 1.5 mmol, 1.5 equiv).
The flask was then capped and stirred at 60 °C for 2 h. The reaction
solution changed from green to yellow. To the crude mixture were
added H2O (20 mL) and EtOAc (10 mL). The layers were separated,
and the aqueous layer was extracted with EtOAc (3 × 10 mL). The
combined organic layers were dried (Na2SO4), filtered, and
concentrated under reduced pressure. Purification by filtration through
a short plug of silica topped with Celite using EtOAc afforded the pure
product in 86% yield (156 mg, 0.86 mmol) as a yellow solid, mp 75−
General Procedure C: One-Pot Nitrosation/Diels−Alder.
Adapted from a previously reported method.15a To a 20 mL glass
microwave vial containing a solution of potassium organotrifluor-
oborate (1 mmol) in CH3CN (3 mL, 0.33 M) was added 1,3-
cyclohexadiene (114 μL, 1.2 mmol, 1.2 equiv). To the mixture was
added NOBF4 (120 mg, 1.03 mmol, 1.03 equiv) in one portion. The
flask was then capped (exothermic reaction) and stirred for 2 h. To the
crude mixture were added H2O (20 mL) and EtOAc (10 mL). The
layers were separated, and the aqueous layer was extracted with EtOAc
(3 × 10 mL). The combined organic layers were dried (Na2SO4),
filtered, and concentrated under reduced pressure. The product was
purified by column chromatography using EtOAc/hexanes.
3-(Isoquinolin-5-yl)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (4c). Gen-
eral procedure C was employed using potassium trifluoro(isoquinolin-
5-yl)borate (235 mg, 1 mmol), 1,3-cyclohexadiene (114 μL, 1.2 mmol,
1.2 equiv), and NOBF4 (120 mg, 1.03 mmol). The desired pure
product was obtained in 65% yield (155 mg, 0.65 mmol) as a yellow
solid, mp 68−70 °C, after column chromatography with EtOAc/
hexanes (1:1) as eluent: 1H NMR (500 MHz, CDCl3) δ 9.19 (s, 1H),
8.51 (d, J = 6 Hz, 1H), 7.91 (d, J = 6 Hz, 1H), 7.64 (d, J = 8 Hz, 1H),
7.45 (t, J = 8 Hz, 1H), 7.37 (m, 1H), 6.75 (d, J = 2 and 6.5 Hz, 1H),
5.96 (t, J = 6.5 Hz, 1H), 4.82 (m, 1H), 4.34 (m, 1H), 2.51 (m, 1H),
2.36 (m, 1H), 1.60 (m, 1H), 1.50 (m, 1H); 13C NMR (125.8 MHz,
CDCl3) δ 152.6, 146.1, 142.5, 132.1, 129.1, 129.1, 128.9, 126.8, 123.1,
120.5, 116.0, 69.5, 56.9, 23.7, 22.0; IR (neat) 1579, 1371, 1271, 932,
838, 768 cm−1; HRMS (ESI) m/z calcd. for C15H15N2O (M + H)+
239.1184, found 239.1183.
77 °C (lit.48 77−79 °C): H NMR (500 MHz, CDCl3) δ 8.87 (t, J =
1
1.5 Hz, 1H), 8.42 (m, 1H), 8.37 (m, 1H), 7.67 (t, J = 8.5 Hz, 1H),
3.99 (s, 3H); 13C NMR (125.8 MHz, CDCl3) δ 164.9, 148.3, 135.2,
131.9, 129.6, 127.4, 124.6, 52.8; IR (neat) 3098, 1718, 1527, 1350,
1290, 1269, 1134, 720 cm−1.
One-Pot Procedure for Formation of Aniline Compounds:
Synthesis of Methyl 3-Aminobenzoate (5c).51 Adapted from a
previously reported method.52 To a 20 mL glass microwave vial
containing potassium trifluoro(3-(methoxycarbonyl)phenyl)borate
(242 mg, 1 mmol) in CH3CN (3 mL, 0.33 M) was added nitrosonium
tetrafluoroborate (120 mg, 1.03 mmol, 1.03 equiv) in one portion.
EtOH (2 mL) and SnCl2·2H2O (1.13 g, 5 mmol, 5 equiv) were added
after 30 s. The flask was then capped, and the reaction was stirred at 80
°C for 2 h. To the crude mixture was added 5% NaHCO3 (3 mL, or
enough to make the pH slightly basic, 7−9). The resulting emulsion
was filtered, and the solid was washed with H2O (10 mL) and EtOAc
(10 mL). The layers of the filtrate were separated, and the aqueous
layer was extracted with EtOAc (3 × 10 mL). The combined organic
layers were dried (Na2SO4), filtered, and concentrated under reduced
pressure. Purification by filtration through a short plug of silica topped
with Celite using EtOAc afforded the pure product as a yellow oil in
72% yield (109 mg, 0.72 mmol): 1H NMR (500 MHz, CDCl3) δ 7.42
(m, 1H), 7.35 (t, J = 2 Hz, 1H), 7.21 (t, J = 8 Hz, 1H), 6.85 (m, 1H),
3.89 (s, 3H), 3.79 (brs, 2H); 13C NMR (125.8 MHz, CDCl3) δ 167.4,
146.6, 131.3, 129.4, 119.8, 119.5, 115.9, 52.2; IR (neat) 3372, 2951,
1710, 1603, 1239, 753 cm−1; HRMS (ESI) m/z calcd. for C8H10NO2
(M + H)+ 152.0712, found 152.0713.
Methyl 3-(2-Oxa-3-azabicyclo[2.2.2]oct-5-en-3-yl)benzoate (5d).
General procedure C was employed using potassium trifluoro(3-
(methoxycarbonyl)phenyl)borate (242 mg, 1 mmol), 1,3-cyclo-
hexadiene (114 μL, 1.2 mmol, 1.2 equiv), and NOBF4 (120 mg,
1.03 mmol). The desired pure product was obtained in 82% yield (201
mg, 0.82 mmol) as a yellow solid, mp 87−89 °C, after column
1
chromatography with EtOAc/hexanes (5:1) as eluent: H NMR (500
MHz, CDCl3) δ 7.66 (s, 1H), 7.58 (m, 1H), 7.26 (t, J = 8 Hz, 1H),
7.19 (m, 1H), 6.57 (m, 1H), 6.12 (m, 1H), 4.73 (m, 1H), 4.48 (m,
1H), 3.88 (s, 3H), 2.29−2.22 (m, 2H), 1.57 (m, 1H), 1.38 (m, 1H);
13C NMR (125.8 MHz, CDCl3) δ 167.3, 152.7, 131.9, 130.5, 129.9,
128.6, 123.3, 122.1, 118.4, 69.5, 56.6, 52.2, 24.0, 21.4; IR (neat) 1719,
1439, 1270, 944, 759 cm−1; HRMS (ESI) m/z calcd. for C14H16NO3
(M + H)+ 246.1130, found 246.1130.
One-Pot Procedure for Formation of Azoxy Compound:
Synthesis of 1,2-Bis(3-(methoxycarbonyl)phenyl)diazene
Oxide (5a).48 Adapted from a previously reported method.49 To a
20 mL glass microwave vial containing potassium trifluoro(3-
4411
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
Soc. 1963, 85, 1165. (d) Johnson, N. A.; Guld, E. S. J. Am. Chem. Soc.
1973, 95, 5198.
(11) For selected examples, see: (a) Feuer, H.; Braunstein, D. M. J.
Org. Chem. 1969, 34, 2024. (b) Fischer, B.; Sheihet, L. J. Org. Chem.
1998, 63, 393. (c) Baik, W.; Rhee, J. U.; Lee, S. H.; Lee, N. H.; Kim, B.
H.; Kim., K. S. Tetrahedron Lett. 1995, 36, 2793.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H, 13C, and 19F spectra for all compounds prepared
by the method described. This material is available free of
charge via the Internet at http://pubs.acs.org
(12) Rice, W. G.; Schaeffer, C. A.; Graham, L.; Bu, M.; McDougal, J.
S.; Orloff, S. L.; Villinger, F.; Young, M.; Oroszlan, S.; Fesen, M. R.;
Pommier, Y.; Mendeleyev, J.; Kun, E. Nature 1993, 361, 473.
(13) Baeyer, A. Chem. Ber. 1874, 7, 1638.
(14) For a review on the synthesis of nitroso compounds, see:
Gowenlock, B. G.; Richter-Addo, G. B. Chem. Rev. 2004, 104, 3315.
(15) For selected examples, see: (a) Zhao, D.; Johansson, M.;
Backvall, J.-E. Eur. J. Org. Chem. 2007, 4431. (b) Priewisch, B.; Ruck-
Braun, K. J. Org. Chem. 2005, 70, 2350. (c) Bordoloi, A.; Halligudi, S.
B. Adv. Synth. Catal. 2007, 2085. (d) Defoin, A. Synthesis 2004, 706.
(e) Gowenlock, B. G.; Maidment, M. J.; Orrell, K. G.; Prokes, I.;
Roberts, J. R. J. Chem. Soc. 2001, 1904.
(16) For selected examples, see: (a) Lin, W.; Gupta, A.; Kim, K. H.;
Mendel, D.; Miller, M. J. Org. Lett. 2009, 11, 449. (b) Rogers, M. A. T.
J. Chem. Soc. 1943, 590. (c) Tedder, J. M.; Webster, B. J. Chem. Soc.
1960, 3270. (d) Alkorta, I.; Garcia-Gomez, C.; Paz, J. L. G.; Jimeno,
M. L.; Aran, V. J. J. Chem. Soc. 1996, 293.
(17) For selected examples, see: (a) Bosch, E.; Kochi, J. K. J. Org.
Chem. 1994, 59, 5573. (b) Zyk, N. V.; Nesterov, E. E.; Khiobystov, A.
N.; Zefirov, N. S. Russ. Chem. Bull. 1999, 48, 506. (c) Atherton, J. H.;
Moodie, R. B.; Noble, D. R. J. Chem. Soc., Perkin Trans. 2 1999, 699.
(d) D’Amicoc, J. J.; Tung, C. C.; Walker, L. A. J. Am. Chem. Soc. 1959,
81, 5957.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gmolandr@sas.upenn.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was generously supported by the NIGMS (R01
GM086209, GM035249). We acknowledge Conselho Nacional
de Desenvolvimento Cientifico e Tecnologico (CNPq) for
Graduate Research Fellowship to L.N.C. We also acknowledge
Aldrich, BoroChem, and Frontier Scientific for their donation
of the boronic acids used to prepare the organotrifluoroborates.
Dr. Rakesh Kohli (University of Pennsylvania) is acknowledged
for obtaining the HRMS data.
REFERENCES
■
(1) (a) Patai, S. The Chemistry of Amino, Nitroso, Nitro and Related
Groups; Wiley-VCH: Weinheim, 1996. (b) Momiyama, N.;
Yamammoto, H. Chem. Commun. 2005, 3514.
(2) For selected examples see: (a) Momiyama, N.; Yamamoto, H. J.
Am. Chem. Soc. 2005, 127, 1080. (b) Momiyama, N.; Yamamoto, H. J.
Am. Chem. Soc. 2003, 125, 6038. (c) Momiyama, N.; Yamamoto, H. J.
Am. Chem. Soc. 2004, 126, 5360.
(3) For selected examples, see: (a) Yamamoto, Y.; Yamamoto, H. J.
Am. Chem. Soc. 2004, 126, 4128. (b) Stephenson, G. R.; Balfe, A. M.;
Hughes, D. L.; Kelsey, R. D. Tetrahedron Lett. 2010, 51, 6806.
(c) Sakai, H.; Ding, X.; Yoshida, T.; Fujinami, S.; Ukaji, Y.; Inomata, K.
Heterocycles 2008, 76, 1285. (d) Jana, C. K.; Studer, A. Chem.Eur. J.
2008, 14, 6326. (e) Jana, C. K.; Grimme, S.; Studer, A. Chem.Eur. J.
2009, 15, 9078. (f) Calvet, G.; Coote, S. C.; Blanchard, N.;
Kouklovsky, C. Tetrahedron 2010, 66, 2969. (g) Jana, C. K.; Studer,
A. Angew. Chem., Int. Ed. 2007, 46, 6542. (h) Yamamoto, Y.;
Yamamoto, H. Angew. Chem., Int. Ed. 2005, 44, 7082.
(18) Bartlett, E. H.; Eaborn, C.; Walton, D. R. M. J. Chem. Soc. C
1970, 1717.
(19) Taylor, E. C.; Danforth, R. H.; McKillop, A. J. Org. Chem. 1973,
38, 2088.
(20) Birkofer, L.; Franz, M. Chem. Ber. 1971, 104, 3062.
(21) For selected examples, see: (a) Yao, M.- L.; Reddy, M. S.; Yong,
L.; Walsh, I.; Blevins, D. W.; Kabalka, G. W. Org. Lett. 2010, 12, 700.
(b) Kabalka, G. W.; Mereddy, A. R. Organometallics 2004, 23, 4519.
(c) Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2004, 45, 343.
(d) Thiebes, C.; Prakash, G. K.; Petasis, N. A.; Olah, G. A. Synlett
1998, 141. (e) Szumigala, R. H.; Devine, P. N.; Gauthier, D. R., Jr.;
Volante, R. P. J. Org. Chem. 2004, 69, 566.
(22) (a) Salzbrunn, S.; Simon, J.; Prakash, G. K. S.; Petasis, N. A.;
Olah, G. A. Synlett 2000, 1485. (b) Prakash, G. K. S.; Panja, C.;
Mathew, T.; Surampudi, V.; Petasis, N. A.; Olah, G. A. Org. Lett. 2004,
6, 2205.
(4) Pagar, V. V.; Jadhav, A. M.; Liu, R.-S. J. Am. Chem. Soc. 2011, 133,
(23) Molander, G. A.; Cavalcanti, L. N. J. Org. Chem. 2011, 76, 7195.
(24) For reviews, see: (a) Darses, S.; Genet, J.-P. Chem. Rev. 2008,
108, 288. (b) Doucet, H. Eur. J. Org. Chem. 2008, 2013. (c) Molander,
G. A.; Ellis, N. M. Acc. Chem. Res. 2007, 40, 275. (d) Stefani, H. A.;
Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623. (e) Molander, G.
A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49. (f) Darses, S.; Genet,
J.-P. Eur. J. Org. Chem. 2003, 4313.
(25) (a) Kabalka, G. W.; Coltuclu, V. Tetrahedron Lett. 2009, 50,
6271. (b) Molander, G. A.; Cavalcanti, L. N.; Canturk, B.; Pan, P.-S.;
Kennedy, L. E. J. Org. Chem. 2009, 74, 7364.
(26) Xu, J.; Wang, X.; Shao, C.; Su, D.; Cheng, G.; Hu, Y. Org. Lett.
2010, 12, 1964. (b) Molander, G. A.; Cavalcanti, L. N. J. Org. Chem.
2011, 76, 623.
(27) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
(28) Ting, R.; Harwig, C. W.; Lo, J.; Li, Y.; Adam, M. J.; Ruth, T. J.;
Perrin, D. M. J. Org. Chem. 2008, 73, 4662.
(29) For selected examples, see: (a) Baeyer, A.; Caro, H. Chem. Ber.
1874, 7, 963. (b) Radner, F.; Wall, A.; Loncar, M. Acta Chem. Scand.
1990, 44, 152.
(30) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. Angew.
Chem., Int. Ed. 2002, 41, 3056.
(31) (a) Creary, X.; Engel, P. S.; Kavaluskas, N.; Pan, L.; Wolf, A. J.
Org. Chem. 1999, 64, 5634. (b) Morrison, J.; Wan, P.; Corrie, J. E. T.;
Munasinghe, V. R. N. Can. J. Chem. 2003, 81, 586.
20728.
(5) For selected examples see: (a) Ginsburg, V. A. Russ. J. Org. Chem.
1974, 10, 1427. (b) Barr, A.; Hazeldine, R. N. J. Chem. Soc. 1955,
1881. (c) Dochnahl, M.; Fu, G. C. Angew. Chem., Int. Ed. 2009, 48,
2391. (d) Wang, T.; Huang, X.-L.; Ye. Org. Biomol. Chem. 2010, 8,
5007.
(6) Adam, W.; Krebs, O. Chem. Rev. 2003, 103, 4131 and references
therein.
(7) (a) Aston, A.; Menard, M. J. Am. Chem. Soc. 1935, 57, 1922.
(b) Forrester, A. R.; Hepburn, S. P. J. Chem. Soc. C 1971, 3322.
(c) Goldman, J. Tetrahedron 1973, 29, 3833.
(8) For selected examples, see: (a) Tibiletti, F.; Simonetti, M.;
Nicholas, K. M.; Palmisano, G.; Parravicini, M.; Imbesi, F.; Tollari, S.;
Penoni, A. Tetrahedron 2010, 66, 1280. (b) Penoni, A.; Volkman, J.;
Nicholas, K. M. Org. Lett. 2002, 4, 699. (c) Penoni, A.; Palmisano, G.;
Broggini, G.; Kadowaki, A.; Nicholas, K. M. J. Org. Chem. 2006, 71,
823. (d) Penoni, A.; Palmisano, G.; Zhao, Y.-L.; Houk, K. N.;
Volkman, J.; Nicholas, K. M. J. Am. Chem. Soc. 2009, 131, 653.
(e) Lamar, A. A.; Nicholas, K. M. Tetrahedron 2009, 65, 3829.
(9) Goelitz, P.; Meijere, A. Angew. Chem. 1977, 89, 892.
(10) For selected examples see: (a) McKillop, A.; Tarbin, J. A.
Tetrahedron 1987, 43, 1753. (b) Astolfi, P.; Carloni, P.; Damiani, E.;
Greci, L.; Marini, M.; Rizzoli, C.; Stipa, P. Eur. J. Org. Chem. 2008,
3279. (c) Ibne-Rasa, K. M.; Lauro, C. G.; Edwards, J. O. J. Am. Chem.
4412
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413

The Journal of Organic Chemistry
Article
(32) Olah, G. A.; Olah, J. A.; Overchuck, N. A. J. Org. Chem. 1965,
30, 3373.
(33) For selected examples, see: (a) Hamon, F.; Djedaini-Pilard, F.;
Barbot, F.; Len, C. Tetrahedron 2009, 65, 10105. (b) Burkhardt, E. R.;
Matos, K. Chem. Rev. 2006, 106, 2617. (c) Adams, J. P. J. Chem. Soc.,
Perkin Trans. 1 2002, 2586. (d) Tafesh, A. M.; Weiguny, J. Chem. Rev.
1996, 96, 2035. (e) Kumar, G. S.; Neckers, D. C. Chem. Rev. 1989, 89,
1915. (f) Ikeda, T.; Tsutumi, O. Science 1995, 268, 1873. (g) Campbell,
D.; Dix, L. R.; Rostron, P. Dyes Pigm. 1995, 29, 77. (h) Waghmode, S.
B.; Sabne, S. M.; Sivasanker, S. Green Chem. 2001, 3, 285. (i) Sakaue,
S.; Tsubakino, T.; Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1993, 58, 3633.
(j) Muller, W. E. The Benzodiazepine Receptor; Cambridge University
Press: New York, 1988. (k) Belciug, M.; Ananthanarayanan, V. S. J.
Med. Chem. 1994, 37, 4392. (l) Zollinger, H. Color Chemistry; Wiley-
VCH: New York, 1987; p 161. (m) Fan, F.-R. F.; Yao, Y.; Cai, L.;
Cheng, L.; Tour, J. M.; Bard, A. J. J. Am. Chem. Soc. 2004, 126, 4035.
(34) Molander, G. A.; Canturk, B.; Kennedy, L. E. J. Org. Chem.
2009, 74, 973.
(35) Murphy, J. M.; Tzschucke, C. C.; Hartwig, J. F. Org. Lett. 2007,
9, 757.
(36) Pace, G.; Ferri, V.; Grave, C.; Elbing, M.; von Hanisch, C.;
Zharnikov, M.; Mayor, M.; Rampi, M. A.; Samori, P. Proc. Natl. Acad.
Sci. U. S. A. 2007, 104, 9937.
(37) Zarchi, M. A. K.; Rahmani, F. J. Appl. Polym. Sci. 2011, 120,
2830.
(38) Marshall, L. J.; Cable, K. M.; Botting, N. P. Tetrahedron 2009,
65, 8165.
(39) Krakert, S.; Terfort, A. Aust. J. Chem. 2010, 63, 303.
(40) Gowenlock, B. G.; Pfab, J.; Young, V. M. J. Chem. Soc., Perkin
Trans. 2 1997, 1793.
(41) Alway, W. Chem. Ber. 1903, 36, 2312.
(42) Bamberger, E. Chem. Ber. 1895, 28, 248.
(43) Il’ichev, Y. V.; Schwoerer, M. A.; Wirz, J. J. Am. Chem. Soc. 2004,
126, 4581.
(44) Zarwell, S.; Rueck-Braun, K. Tetrahedron Lett. 2008, 49, 4020.
(45) Biljan, I.; Cvjetojevic, G.; Novak, P.; Mihalic, Z.; Vancik, H.;
Smrecki, V.; Babic, D.; Mali, G.; Plavec, J. J. Mol. Struct. 2010, 979, 22.
(46) Tsuzuki, U.; Hirasawa. Chem. Ber. 1941, 74, 616.
(47) Knight, G. T.; Loadman, M. J. R. J. Chem. Soc., Perkin Trans. 2
1973, 1550.
(48) Gebhardt, C.; Priewisch, B.; Irran, E.; Ruck-Braun, K. Synthesis
̈
2008, 1889.
(49) Gohain, S.; Prajapati, D.; Sandhu, J. S. Chem. Lett. 1995, 725.
(50) Aridoss, G.; Laali, K. K. J. Org. Chem. 2011, 76, 8088.
(51) Monguchi, Y.; Maejima, T.; Mori, S.; Maegawa, T.; Sajiki, H.
Chem.Eur. J. 2010, 16, 7372.
(52) Bellamy, F. D.; Ou, K. Tetrahedron Lett. 1984, 25, 839.
4413
dx.doi.org/10.1021/jo300551m | J. Org. Chem. 2012, 77, 4402−4413