Ipso-Nitrosation of arylboronic acids with chlorotrimethylsilane and sodium nitrite

Article abstract of DOI:10.1016/j.tetlet.2014.01.138

Nitroso compounds are versatile reagents in synthetic organic chemistry. Herein, we disclose a feasible protocol for the ipso-nitrosation of aryl boronic acids using chlorotrimethylsilane-sodium nitrite unison as nitrosation reagent system.

Full text of DOI:10.1016/j.tetlet.2014.01.138

Accepted Manuscript
ipso-Nitrosation of Arylboronic Acids with Chlorotrimethylsilane and Sodium
Nitrite
G.K. Surya Prakash, Laxman Gurung, Philipp Christoph Schmid, Fang Wang,
Tisa Elizabeth Thomas, Chiradeep Panja, Thomas Mathew, George A. Olah
PII:
S0040-4039(14)00194-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.01.138
TETL 44171
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 January 2014
24 January 2014
28 January 2014
Please cite this article as: Surya Prakash, G.K., Gurung, L., Schmid, P.C., Wang, F., Thomas, T.E., Panja, C.,
Mathew, T., Olah, G.A., ipso-Nitrosation of Arylboronic Acids with Chlorotrimethylsilane and Sodium Nitrite,
Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.01.138
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Graphical Abstract
ipso-Nitrosation of Arylboronic Acids with
Chlorotrimethylsilane and Sodium Nitrite
Leave this area blank for abstract info.
G. K. Surya Prakash,* Laxman Gurung, Philipp Christoph Schmid, Fang Wang, Tisa Elizabeth Thomas,
Chiradeep Panja, Thomas Mathew,* and George A. Olah
B(OH)2
NO
conditions
r.t.
+
NaNO2
TMSCl +
R
R

1
Tetrahedron Letters
journal homepage: www.els evier.com
ipso-Nitrosation of Arylboronic Acids with Chlorotrimethylsilane and Sodium Nitrite
G. K. Surya Prakash,* Laxman Gurung, Philipp Christoph Schmid, Fang Wang, Tisa Elizabeth Thomas,
Chiradeep Panja, Thomas Mathew,* and George A. Olah
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, California 90089-1661
Fax: +1-213-740-6679
ARTICLE INFO
ABSTRACT
Article history:
Received
Nitroso compounds are versatile reagents in synthetic organic chemistry. Herein, we disclose a
feasible protocol for the ipso-nitrosation of aryl boronic acids using chlorotrimethylsilane-
sodium nitrite unison as nitrosation reagent system.
Received in revised form
Accepted
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
ipso-nitrosation
boronic acids
chlorotrimethylsilane
nitrosoarenes
regioselectivity
synthesis, including oxidation of aniline derivatives (Scheme 1,
Eq. 1), reduction of nitroarenes (Scheme 1, Eq. 2), and
electrophilic nitrosation of aryl metallic compounds (Scheme 1,
Eq. 3).14,15 Direct nitrosation of arenes can also be achieved using
nitrosonium salts (NO+X-)16 through a Wheland intermediate
(Ar(H)NO+) (Scheme 1, Eq. 4).17 In addition to nitrosonium salts,
other nitrosating agents, such as alkyl nitrites,18 have also been
utilized. Despite the fact that many nitrosoarenes have been
obtained via the above mentioned methods, these methods
remain disadvantaged in some aspects, such as substrate scope,
regioselectivity, or the availability of relevant reagents. Recently,
Molander and co-worker disclosed the facile ipso-nitrosation of
aryl and heteroaryltrifluoroborates as well as arylboronic acid and
esters using nitrosonium tetrafluoroborate (NO+BF4-), which
demonstrates remarkable selectivity and substrate scope (Scheme
1, Eq. 5).19 To seek for an alternative synthetic protocol
exploiting readily available nitrosating reagents, we describe the
ipso-nitrosation reaction of arylboronic acids with sodium nitrite
and chlorotrimethylsilane.
Bearing a lone pair of electrons on nitrogen and a highly
polarized N-O double bond, nitroso compounds can act both as
nucleophiles and electrophiles. Such dually reactive nature
allows nitroso compounds to participate in many chemical
transformations,1 such as ene reactions,2 nitroso aldol reactions,3
coupling reactions with alkynes4 and amines,5 and Grignard
reactions.6 Moreover, nitroso compounds have been exploited in
Scheme 1. Synthetic routes towards nitrosoarenes
various cycloaddition reactions7 and redox reactions.8,9 Apart
from these synthetic utilities, nitrosobenzenes have also been
utilized as radical scavengers,10 antioxidants in lubricating oil,11
metal coordinating agents,12 and antiviral compounds.13 Although
nitroso compounds have been widely utilized, facile synthetic
approach towards these compounds are still limited. Up to date,
—sev—era—l methods have been developed for aromatic nitrosoarene
* E-mail address: gprakash@usc.edu, (G. K. Surya Prakash),
Scheme 2. Proposed mechanism of ipso-nitrosation of
phenylboronic acid with NaNO2 and TMSCl.
tmathew@usc.edu (Thomas Mathew).

2
Tetrahedron letters
We previously reported the ipso-nitration of arylboronic
substituted phenylboronic acids are also considered to be
“electron-rich”, relatively lower yields and poor
acids using TMSCl and nitrate salts,20 which allowed the in situ
generation of the nitrating species TMSONO2. Parallel to this
work, Yamamoto et al. recently showed that in situ generated
R3SiONO could serve as an effective nitrosating reagent to react
with silyl enol ethers.21 On the basis of these reports, we
envisioned that ipso-nitrosation of arylboronic acids could be
achieved using NaNO2-TMSCl system. We began our
chemoselectivities were obtained with these substrates (Table 2,
Entries 13 and 14), implying that the inductive effect of oxygen
may also play a pivotal role in reaction yield. Experimental
procedure and the spectral data of the isolated nitroso products
are given in the reference section.25
investigation
with
4-methoxyphenylboronic
acid
(4-
Table 2. ipso-Nitrosation of arylboronic acidsa
MeOPhB(OH)2), which was expected to possess enhanced
reactivity due to the electron-donating MeO- group. The reaction
was performed by adding 4-MeOPhB(OH)2 (1.0 equiv, 93%
boroxine content, determined by 1H NMR)22 to a stirred mixture
of NaNO2 (2.2 equiv) and TMSCl (2.2 equiv) in anhydrous
dichloromethane under argon at room temperature. GC-MS
analysis of the reaction mixture did not show any detectable
progress even after stirring for 72 h (Table 1, Entry 1). This
unsuccessful result was probably due to the low ionic
dissociation constant of sodium nitrite in dichloromethane.
Further investigation was thus carried out under similar reaction
conditions with the addition of 0.5 eq. of water (Table 1, Entry
2). GC-MS and TLC analysis of the reaction mixture indicated
the formation of 4-methoxynitrosobenzene and the complete
consumption of 4-MeOPhB(OH)2 after 3 h, confirming the
crucial role of water. Additional optimization revealed that the
reaction could also be promoted with moisture in air, thereby
considerably streamlining the operation (Table 1, Entry 3). With
these reaction conditions in hand, further exploration was
focused on solvent effects. Similar to the nitration reactions using
TMSCl and NaNO3,20 chlorinated solvents were generally
suitable for the present reaction (Table 1, Entries 4 and 5),
whereas highly polar/coordinating solvents generally led to
inferior results (Table 1, Entries 6-8).
Table 1. Optimization of reaction conditionsa
aReaction conditions: arylboronic acid (0.5 mmol), TMSCl
(1.1 mmol) and sodium nitrite (1.1 mmol) in CH2Cl2, stirred under air
at room temperature; the conversion was determined by GC-MS;
bconversions and yields were determined by GC and were not
calibrated; cthe numbers in parentheses are isolated yields.
aIsolated yield; bdetermined by GC-MS analysis without calibration.
To elucidate the mechanistic aspects of the reaction, a series
of control experiments were carried out. As it is known that
arylboronic acids can trimerize to form the corresponding
boroxines, we determined the composition of two samples of
phenylboronic acid (A and B). According to 1H NMR
spectroscopy,22 Samples A and B contained respectively 95
mol% and 68 mol% triphenylboroxine (PhBO)3. While the ipso-
substitution reaction with (PhBO)3 (Sample A) proceeded
smoothly under open air conditions, the reaction was found to be
retarded under argon-protected anhydrous conditions (Scheme 3,
eq. 2). By adding 0.5 equiv. of water to the reaction with Sample
A (containing 95 mol% (PhBO)3), nitrobenzene was obtained as
the major product, thereby suggesting the essential role of water
(Scheme 3, Eq. 3). In contrast, using Sample B as the starting
material, nitrosobenzene and nitrobenzene were afforded in a
ratio of 15:85% in the absence of water and oxygen (Scheme 3,
With the optimized reaction conditions in hand, we examined
the scope of the protocol. As shown in Table 2, although 2,4,6-
trifluorophenylboronic acid and 4-phenylphenylboronic acid
were inert under the reaction conditions, most arylboronic acids
could participate in the reaction. It was found that 4-alkoxy- and
4-phenoxyboronic acids underwent the reaction smoothly to
afford the corresponding nitrosoarenes in both high yields and
good chemoselectivities (Table 2, Entries 9-12). Noticeably,
although arylboronic acids bearing electron-withdrawing
substituents also participated in the reaction, nitroarenes were
obtained as the major products (Table 2, Entries 1, 4-6, 8, 14). In
general, the amount of nitro products was found to decrease with
the increase of the electron donating ability of the substituents
(through resonance effects). Despite the fact that 2-alkoxy

3
Eq. 4). The delineated observation could be ascribed to the in situ
trimerization of PhB(OH)2, which could release a small amount
of water to facilitate the reaction. It is worth mentioning that the
necessity of water was also noticed by Molander and co-worker
in the reaction between aryltrifluoroborates and sodium nitrite.19
However, water in Molander’s reaction was proposed to allow
the formation of tricoordinate boron species from
aryltrifluoroborates, which in turn facilitates the nitrosation.
Financial support by the Loker Hydrocarbon Research
Institute is gratefully acknowledged.
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(Scheme 3, Eq. 2-4). This hypothesis was made further evident
by the fact that nitrosobenzene was not oxidized in the presence
of TMSCl or NaNO2 under open-air conditions (Scheme 3, Eq. 5-
7). On the other hand, although nitrosobenzene was found to
convert to nitrobenzene with a mixture of TMSCl and NaNO2 in
the presence of air, such a conversion was not observed under
inert atmosphere (Scheme 3, Eq. 8 and 9). This result showed
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that the oxidation of nitrosobenzene originated from
a
combination of TMSCl, NaNO2 and water which could
presumably lead to the formation of HNO2. As HNO2 can readily
undergo disproportionation to render HNO3 and NO,23 the in situ
oxidation of nitrosobenzene can be ascribed to the presence of
these two species.24 Noticeably, the in situ oxidation of
nitrosoarenes was also observed in the reaction between
aryltrifluoroborates and NO+BF4-, indicating the intrinsic lability
of nitrosoarenes under direct nitrosation reaction conditions.
14.
15.
In conclusion, we have demonstrated that the combination of
chlorotrimethylsilane-nitrite salt could be used as a viable system
for the ipso-nitrosation of electron-rich arylboronic acids.
Arylboronic acids bearing electron-withdrawing groups, although
undergo ipso-functionalization, generally lead to nitration
products instead of desired nitroso compounds. This observation
is similar to many other direct nitrosation reactions, in which
nitrosoarenes are in situ oxidized. Attempts to tackle this problem
are currently under investigation in our laboratory.
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Acknowledgment

4
Tetrahedron letters
22.
It has been shown that the composition of aryl boronic acids and
1H NMR (400 MHz, CDCl3, 25 °C): δ 7.92 (d, br, 3J = 7.9 Hz, 2H),
7.03 (d, 3J = 9.1 Hz, 2H), 3.95 (s, 3H). 13C NMR (100 MHz, CDCl3,
25 °C): δ 165.0, 164.0, 124.5 (br), 113.9, 56.0.
triarylboroxines can be determined via 1H NMR spectroscopy.
Tokunaga, Y.; Ueno, H.; Shimomura, Y.; Seo, T. Heterocycles 2002,
57, 787- 790.
1-Ethoxy-4-nitrosobenzene: Green-blue oil, 48% yield. The product
was contaminated with 3 mol% 1-ethoxy-4-nitrobenzene as indicated
by 1H NMR.
1H NMR (400 MHz, CDCl3, 25 °C): δ 7.89 (d, br, 3J = 6.8 Hz, 2H),
6.99 (d, 3J = 9.2 Hz, 2H), 4.17 (q, 3J = 7.0 Hz, 2H), 1.46 (t, 3J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3, 25 °C): δ 165.1, 164.0,
124.5 (br), 114.2, 64.5, 14.6.
23.
24.
Decomposition of HNO2, Bonner, F. T.; Donald, C. E.; Martin, M. N.,
J. Chem. Soc., Dalton Trans. Inorg. Chem. 1989, 527-532; (b)
Hodgson, H. H.; Nicholson, D. E., J. Chem. Soc. 1941, 470-475.
Oxidation of nitrosobenzene with NO2 or NO, Astolfi, P.; Carloni, P.;
Damiani, E.; Creci, L.; Marini, M.; Rizzoli, C.; Stipa, P., Eur. J. Org.
Chem. 2008, 3279-3285. Oxidation of nitrosobenzene with nitric acid,
see references 324-327 in reference 1a.
Experimental: Unless otherwise mentioned, all the chemicals were
purchased from commercial sources and used without further
purification. Silica gel chromatography was performed to isolate the
products using Biotage SNAP Cartridges KP-Sil 10 g or 25 g with
hexane-dichloromethane, dichloromethane or dichloromethane-ethyl
1-Isopropoxy-4-nitrosobenzene: Green-blue oil, 58% yield. The
product was contaminated with 9 mol% 1-isopropoxy-4-nitrobenzene
as indicated by 1H NMR.
25.
1H NMR (400 MHz, CDCl3, 25 °C): δ 7.89 (br, 2H), 6.98 (d, 3J =
7.9 Hz, 2H), 4.73 (hept, 3J = 6.4 Hz, 6H), 1.41 (d, 3J = 6.4 Hz, 1H).
13C NMR (100 MHz, CDCl3, 25 °C): δ 164.4, 163.9, 124.5 (br), 115.0,
71.0, 21.9.
acetate solvent systems as eluent. H and 13C spectra were recorded on
1
400 MHz Varian NMR spectrometer. 1H NMR chemical shifts were
determined relative to residual solvent peak of CDCl3 (at 7.26 ppm).
13C NMR shifts were determined relative to the solvent peak of CDCl3
(at 77.16 ppm). Mass spectra were recorded on spectrometer in the
ESI mode. The yields determined by GC-MS analysis were not
calibrated with internal standard.
1-Phenoxy-4-nitrosobenzene: Green-blue oil, 52% yield. The product
was found to be contaminated with 15 mol% 1-phenoxy-4-
nitrobenzene as indicated by 1H NMR (400 MHz, CDCl3, 25 °C): δ
7.90 (d, br, 3J = 7.9 Hz, 2H), 7.45 (d, 3J = 7.6 Hz, 2H), 7.27 (d, 3J =
7.4 Hz, 1H), 7.12 (d, 3J = 8.7 Hz, 2H), 7.08 (d, 3J = 7.8 Hz, 2H). 13C
NMR (100 MHz, CDCl3, 25 °C): δ 164.3, 163.8, 154.5, 130.3, 125.5,
125.0 (br), 120.8, 116.7.
General procedure for the ipso-nitrosation of arylboronic acids with
NaNO2 and TMSCl: To CH2Cl2 (5 mL) in a 15 mL pressure tube were
added NaNO2 (76 mg, 1.1 mmol) and TMSCl (120 mg, 1.1 mmol)
with stirring. Arylboronic acid (0.5 mmol) was added after 5 min. The
tube was purged with argon after the color change (15-60 min) and
continued to stir. The reaction was monitored by TLC (CH2Cl2/ethyl
acetate = 6:4) and GC. After TLC showed the complete consumption
of the arylboronic acid, the mixture was filtered. The filtrate was dried
over Na2SO4 and the volatile materials were evaporated under reduced
pressure. The crude product was purified by column chromatography
using CH2Cl2 as eluent.
1-Methoxy-4-nitrosobenzene: Green-blue oil, 72% yield. The product
was contaminated with
indicated by 1H NMR.
5 mol% 1-methoxy-4-nitrobenzene as