Synthesis of 2-nitro- and 2,2′-dinitrobiphenyls by means of the suzuki cross-coupling reaction

Article abstract of DOI:10.1021/jo051589t

Mechanistic investigations and protocols for the synthesis of 2-nitrobiphenyls and 2,2′-dinitrobiphenyls are disclosed. It is revealed that obstacles appear during the transmetalation step when the phenylboronic acid is substituted with a nitro group in the 2-position, whereas when substituted in the 3- or 4-positions, the reaction follows similar patterns as found in the electrophilic substitution of nitrobenzenes, an observation that may be attributed to the elimination step of the catalytic cycle.

Full text of DOI:10.1021/jo051589t

means of various previously reported methods4 utilizing
2-nitrobiphenyls 4 as substrates.
Synthesis of 2-Nitro- and
2,2′-Dinitrobiphenyls by Means of the
Suzuki Cross-Coupling Reaction
Initially we believed that the unsymmetrical substi-
tuted 2,2′-dinitrobiphenyls 3 (R′ * R′′) would be easily
accessible by means of the palladium-catalyzed Suzuki
cross-coupling reaction,5 since that protocol is one of the
most efficient methods for the construction of C(sp2)-
C(sp2) bonds: reaction of 2-nitrohalobenzenes 1 with
2-nitrophenylboronic acids 2 in the presence of a pal-
ladium catalyst. A literature screening revealed a vast
amount of material concerning the Suzuki cross-coupling
reaction,6 but surprisingly, very few reports touched on
the preparation of nitro-substituted biphenyls, and to the
best of our knowledge, any prior reports concern the
preparation of unsymmetrically substituted 2,2′-dinitro-
biphenyls 3. Some recent reports, however, disclosed
findings concerning the Suzuki cross-coupling of 2-nitro-
halobenzenes with 2-substituted phenylboronic acid7-13
that possibly could be utilized for our synthetic pathway
to the carbazole 8 framework.
Raquel Rodr´ıguez Gonza´lez, Lucia Liguori,
Alberto Martinez Carrillo, and Hans-Rene´ Bjørsvik*
Department of Chemistry, University of Bergen,
Alle´gaten 41, N-5007 Bergen, Norway
hans.bjorsvik@kj.uib.no
Received July 29, 2005
Pd Catalysts. Suzuki cross-coupling reactions using
a series of various ligands for the palladium catalyst has
been reported,14,15 a feature that was included in our
initial screening for suitable reaction conditions to our
targets. Some of the most frequently used catalysts in
this context are Pd(PPh3)4, Pd(OAc)2, and PdCl2 when the
halobenzene is bromide or iodide. Preparation of 4-meth-
yl-2,2′-dinitrobiphenyl 3b was attempted according to the
protocols by Buchwald and co-workers14 and by Tao and
Boykin.15 However, under these conditions, the trials
provided only low yields.
Phase Transfer Catalysts. Tetrabutylammonium
bromide (TBAB) is known to stabilize colloidal palladium
nanoparticles that act as catalysts in the Suzuki coupling
of aryl bromides.16 Bedford and co-workers17 have shown
that palladium acetate with TBAB in water could be used
as an effective catalyst for the Suzuki cross-coupling
Mechanistic investigations and protocols for the synthesis
of 2-nitrobiphenyls and 2,2′-dinitrobiphenyls are disclosed.
It is revealed that obstacles appear during the transmeta-
lation step when the phenylboronic acid is substituted with
a nitro group in the 2-position, whereas when substituted
in the 3- or 4-positions, the reaction follows similar patterns
as found in the electrophilic substitution of nitrobenzenes,
an observation that may be attributed to the elimination step
of the catalytic cycle.
Projects in progress in our laboratory envisaged access
to unsymmetrical substituted 2,2′-dinitrobiphenyls 3
(R′ * R′′) and 2-nitrobiphenyls 4 (R′ * R′′). The first
mentioned class of compounds was required for the
synthesis of various substituted benzo[c]cinnolines 7 and
other compounds containing similar frameworks. 2-Ni-
trobiphenyls 4 were required for the synthesis of various
substituted 9H-carbazoles 8 in general and carbazomy-
cines (A-H)1 in particular. Symmetrically substituted 2,2′-
dinitrobiphenyls could easily be prepared according to an
Ullmann-type protocol,2 after which the biphenyl could
be submitted to our recently disclosed process for the
preparation of the benzo[c]cinnoline framework.3 The
desired 9H-carbazole skeleton 8 might be arrived at by
(4) (a) Cadogan, J. I. G. Synthesis 1969, 11. (b) Tsui, F.-P.; Vogel,
T. M.; Zon, G. J. Org. Chem. 1975, 40, 761. (c) Freeman, A. W.; Urvoy,
M.; Criswell, M. E. J. Org. Chem. 2005, 70, 5014.
(5) See, for example: (a) Suzuki, A. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998; pp 49-97. (b) Stanforth, S. P. Tetrahedron 1998, 54,
263.
(6) A search in the SciFinder Scholar (mid January 2005) utilizing
the option explore by research topic using the phrase “Suzuki cross
coupling” revealed as results: (a) 733 references containing “Suzuki
cross coupling” as entered, and (b) 1214 references containing the
concept “Suzuki cross coupling”.
(7) Anderson, J. C.; Namli, H.; Roberts, C. A. Tetrahedron. 1997,
53 (44), 15123.
(8) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(9) Iihama, T.; Fu, J. M.; Bourguignon, M.; Snieckus, V. Synthesis
1989, 3, 184.
* To whom correspondence should be addressed. Ph +47 55 58 34
52. Fax +47 55 58 34 52.
(10) Manka, J. T.; Guo, F.; Huang, J.; Yin, H.; Farrar, J. M.;
Sienkowska, M.; Benin, V.; Kaszynski, P. J. Org. Chem. 2003, 68, 9574.
(11) Arcadi, A.; Cerichelli, G.; Chiarini, M.; Correa, M.; Zorzan, D.
Euro. J. Org. Chem. 2003, 4080.
(1) (a) Sakano, K.; Ishimaru, K.; Nakamura, S. J. Antibiot. 1980,
33, 683. (b) Sakano, K.; Nakamura, S. J. Antibiot. 1980, 33, 961. (c)
Kaneda, M.; Sakano, K.; Nakamura, S.; Kushi, Y.; Iitaka, Y. Hetero-
cycles 1981, 15, 993. (d) Kondo, S.; Katayama, M.; Marumo, S. J.
Antibiot. 1986, 39, 727. (e) Naid, T.; Kitahara, T.; Kaneda, M.;
Nakamura, S. J. Antibiot. 1987, 40, 157. (f) Kaneda, M.; Naid, T.;
Kitahara, T.; Nakamura, S.; Hirata, T.; Suga, T. J. Antibiot. 1988, 41,
602.
(12) Liu, J.; Diwu, Z.; Leung, W.-Y.; Lu, Y.; Patch, B.; Hugland, R.
P. Tetrahedron Lett. 2003, 44, 4355.
(13) Li, J.-H.; Liu, W.-J. Org Lett. 2004, 6, 2809.
(14) Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am.
Chem. Soc. 1999, 121, 9550.
(15) Tao, B.; Boykin, D. W. Tetrahedron Lett. 2002, 43, 4955.
(16) Reetz, M. T.; Westermann, E. Angew. Chem., Int. Ed.; 2000,
39, 165.
(2) Hassan, J.; Se´vignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. Rev. 2002, 102, 1359.
(3) Bjørsvik, H.-R.; Gonza´lez, R. R.; Liguori, L. J. Org. Chem. 2004,
69, 7720.
(17) Bedford, R. B.; Blake, M. E.; Butts, C. P.; Holder, D. Chem.
Commun. 2003, 466.
10.1021/jo051589t CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/14/2005
J. Org. Chem. 2005, 70, 9591-9594
9591

SCHEME 1
reaction. Arcadi and co-workers11 used Pd/C in a mixture
of cetyl trimethylammonium bromide (CTAB) and water
for the preparation of 2-nitrobiphenyl 4a in high yields.
Our attempts to synthesize 4-methyl-2,2′-dinitrobiphenyl
3b by reacting 1-iodo-4-methyl-2-nitrobenzene with 2-ni-
trophenylboronic acid with either (Ph3P)4Pd or Pd/C as
catalysts provided, however, only the Ullmann product
4,4′-dimethyl-2,2′-dinitrobiphenyl via homocoupling of
the halo-aryl compound.18
Solvents. The use of a wide selection of solvents has
been reported for the Suzuki cross-coupling reac-
tion.8,10-13,19-25 During our introductory screening for
suitable reaction conditions, a series of solvents was
therefore included in our assessment. Our list of solvent
investigated included acetone,13 dimethyl formamide
(DMF)19-21 water,11,12,22,23 toluene,8,10,24,25 1,4-dioxane,15
and dimethyl sulfoxide (DMSO).26 The results of those
experiments, however, failed to provide high yields
comparable to those reported for other substituted bi-
phenyls. Biphasic solvent systems, such as DMF and
water in the presence of a phase transfer catalyst, for
example, TBAB, has been used for Pd(OAc)2-catalyzed
Suzuki coupling reactions.20,22,23 Our attempt to utilize
such conditions for the synthesis of 2,2′-dinitrobiphenyl
3a revealed nevertheless a dramatic decrease in the yield
(10-20%) compared to the reported examples lacking the
nitro group in the 2,2′-positions.
although the generality of these protocols is not clear.
In the present project, we have thus investigated the
effect of the base, pathway (b), Scheme 1. Throughout
our base screening, the following compounds were inves-
tigated: KH2PO4, K2HPO4, K3PO4,20,24,25 Na2CO3,8,10,22
K2CO3,11-13 Ba(OH)2,19 and Et3N.21 Trial reaction of
2-nitrophenylboronic acid and 2-nitro-halobenzene with
KH2PO4 as base in combination with the biphasic solvent
system DMF-H2O provided a yield of 30%27 of 2,2′-
dinitrobiphenyl 3a. These promising results prompted us
to perform a thorough investigation of that protocol by
means of statistical experimental design28 and multi-
variate regression,29 although further improvements with
respect to the yields were not accomplished. Neverthe-
less, the protocol found to provide the highest yield of
2,2′-dinitrobiphenyl 3a27 was subjected to further explor-
ative investigation. An increased quantity of the catalyst
Pd(OAc)2, augmenting from 2 to 10 mol %, did not provide
an improved yield of the desired product 3a, but a
significant quantity of 6 (pathway (g), Scheme 1) was
found. A yield of 29% of 6 was achieved when 10 mol %
of Pd(OAc)2 was used compared to a yield of 13% when 2
mol % Pd(OAc)2 was used. However, several attempts to
use the most common catalyst, Pd(PPh3)4, for the Suzuki
cross-coupling reaction for our target 3 provided only low
yields. Changing the halogen atom (Br, I) of the 2-nitro-
halobenzene did not appear to play any significant role
for the course of the reaction. It is known that phenyl-
boronic acid 2 may undergo homocoupling to provide the
Bases. Various base-solvent combinations have been
reported to give improved Suzuki cross-coupling reaction,
(18) Reaction Conditions. K2CO3 (3.2 mmol), Pd(PPh3)4 or Pd/C
(3%), CTAB (1 mmol), 1-iodo-4-methyl-2-nitrobenzene (1.6 mmol) and
2-nitrophenylboronic acid (1 mmol) were placed under N2 in a sealed
tube with H2O (8 mL). The mixture was stirred and heated at 150 °C
for 4 h, samples were analyzed by GC-MS, and % yields were
calculated by means of a correction factor with 1-chloro-2,4-dinitroben-
zene as internal standard. The homocoupling product 4,4′-dimethyl-
2,2′-dinitrobiphenyl was obtained in 7% yield with (Ph3P)4Pd as
catalyst and 36% yield with Pd/C as catalyst.
(27) Reaction Conditions. KH2PO4 (2.0 mmol), Pd(OAc)2 (0.02
mmol), TBAB (0.2 mmol), 1-bromo-2-nitrobenzene (1.0 mmol) 1, and
2-nitrophenylboronic acid (1.5 mmol) 2 were placed under N2 atmo-
sphere into a sealed tube that contained DMF/H2O (5 mL:0.25 mL).
The resulting mixture was stirred and heated at 150 °C for 20 h,
samples were analyzed by GC-MS, and % yields were calculated by
means of a correction factor with 1-chloro-2,4-dinitrobenzene as
internal standard. Title compound 2,2′-dinitrobiphenyl was determined
in a yield of 30%.
(28) See, for example: (a) Box, G. E. P.; Hunter, W. G.; Hunter, J.
S. Statistics for Experimenters. An Introduction to Design, Data
Analysis, and Model Building; Wiley: New York, 1978. (b) Box, G. E.
P.; Draper, N. R. Empirical Model-Building and Response Surfaces;
Wiley: New York, 1987.
(19) Ghosez, L.; Franc, C.; Denonne, F.; Cuisinier, C.; Touillaux, R.
Can. J. Chem. 2001, 79, 1827.
(20) Zim, D.; Monteiro, A. L.; Dupont, J. Tetrahedron Lett. 2000,
41, 8199.
(21) Thompson, W. J.; Gaudino, J. J. Org. Chem. 1984, 49, 5237.
(22) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4 (17), 2973.
(23) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi, U.
J. Org. Chem. 1997, 62, 7170.
(29) See, for example: (a) Draper, N. R.; Smith, H. Applied Regres-
sion Analysis, 3rd ed.; Wiley: New York, 1998. (b) Montgomery, D.
C.; Peck, E. A. Introduction to Linear Regression Analysis; Wiley: New
York, 1982. (c) Malinowski, E. R. Factor Analysis in Chemistry, 3 ed.;
Wiley: New York, 2002.
(24) Fu, G. C.; Littke, A. F. Angew. Chem., Int. Ed. 2002, 41, 4176.
(25) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 12051.
(26) Heiden, M.; Plenio, H. Chem.-Eur. J. 2004, 10, 1789.
9592 J. Org. Chem., Vol. 70, No. 23, 2005

SCHEME 2. Suzuki Cross-Coupling Trials with
KH2PO4 as Base in DMF and H2O
FIGURE 1. Synthesis of 2-nitrobiphenyl in various solvents.
Conditions: K2CO3 (2 mmol, 0.276 g), Pd(OAc)2 (0.02 mmol,
4.5 mg), 1-iodo-2-nitrobenzene (1 mmol, 0.249 g), and phenyl-
boronic acid (1 mmol, 0.122 g) were placed under N2 atmo-
sphere in a round-bottom flask containing solvent/water (5
mL:1 mL) or solvent (5 mL). The reaction mixture was stirred
at 20 °C for 1.5-6 h.
SCHEME 3. Suzuki Cross-Coupling Trials with
K2CO3 as Base in CH3OH and H2O
c
a Reaction time ) 48h. bReaction time ) 72 h. Heated at 125
°C for 20 h. dReaction conditions provided in ref 27. nd ) not
detected.
symmetrical substituted biphenyl 6.30 Dyker and Kell-
ner31 have reported that the Ullmann products are
produced under Suzuki conditions in high yield as a
result of the electron-withdrawing group (NO2). Pd(OAc)2
in DMF (or DMA) contributed also to induction of the
Pd-catalyzed Ullmann coupling reaction of aryl iodides
or bromides. Crossover experiments that were performed
revealed that our protocol27 also provided the Ullmann-
type coupling products 5 and 6. Homocoupling of 1-halo-
2-nitrobenzene 1 following pathway (f), Scheme 1, pro-
vides the symmetrically substituted product 5 (R′ )
4-CH3), whereas homocoupling of phenylboronic acid 2,
pathway (g), Scheme 1, will provide the symmetrical
substituted compound 6.
Various 2′-Substituted 2-Nitrobiphenyls. The pro-
tocol developed above27 was also tried for the synthesis
of a series of various 2′-substituted 2-nitrobiphenyls, see
Scheme 2. Even though high conversions (60-100%) were
achieved, the yield varied in the range 3-58%, which
immediately suggests a subtle balance of steric and
electronic influence in the various substitutents. The
obstacles with the NO2 group in the 2-position may be
related to findings disclosed in a recent report32 that
states not only that the 2-nitro group of the reacting
species operates as an electron-withdrawing group but
also that the nitro group intervenes in the coordination
of the incoming palladium atom.
a Reaction was carried out in methanol (5 mL). bThe halo-aryl
reagent for this experiment was 1-chloro-2,4-dinitrobenzene, a
reaction that provided 2,4-dinitrobiphenyl as the only product. nd
) not detected.
acetone as reaction medium. The reaction temperatures
were in the range 60-110 °C with a reaction time of 1-24
h. During the present study, further investigations of
analogous protocols with potassium carbonate as the base
have been carried out. Figure 1 shows the course of the
reaction of four discrete Suzuki cross-coupling experi-
ments, namely, with DMF-water (5:1), acetone-water
(5:1), methanol-water (5:1) or pure methanol as reaction
medium, respectively.
As the reaction profiles illustrate, the two reactions
conducted with DMF-water and methanol-water as
reaction media both provided 2-nitrobiphenyl in quanti-
tative yields after only 1.5 h of reaction time. The other
two experiments approached quantitative yields as well,
although after an additional 4.5 h of reaction time. In
contrast to prior work, our protocol requires a lower
reaction temperature, namely, within a temperature
range of only 20-50 °C. Moreover, our protocol did not
require the presence of any phase transfer catalyst or any
supporting ligand for the palladium catalyst. Attempt to
synthesis 2,2′-dinitrobiphenyl 3 with this protocol failed.
This spurred us on to undertake investigations that could
reveal information about which step in the catalytic cycle
(Scheme 1) was being obstructed. Since the reaction
between the 2-nitro-haloarene 1 (R1 ) NO2, R′ ) H) and
phenylboronic acid 2 (R2 ) R′′ ) H) proceeds smoothly
in high yield (Scheme 3), a comparative experiment was
to react a haloarene 1 (R1 ) R′ ) H) with 2-nitrophenyl
boronic acid 2 (R2 ) NO2, R′′ ) H), a reaction that failed.
Some recent reports on the synthesis of 2-nitrobi-
phenyl11-13 disclose the utilization of potassium carbonate
as base in combination with various polar solvents,
namely, water with TBAB, water with CTAB, or pure
(30) (a) Scrivanti, A.; Beghetto, V.; Matteoli, U.; Antonaroli, S.;
Marini, A.; Mandoj, F.; Paolesse, R. O; Crociani, B. Tetrahedron Lett.
2004, 45(30), 5861. (b) Parrish, J. P.; Jung, Y. C.; Floyd, R. J.; Jung,
K. W. Tetrahedron Lett. 2002, 43(44), 7899. (c) Smith, K. A.; Campi,
E. M.; Jackson, W. R.; Marcuccio, S.; Naeslund, C. G. M.; Deacon, G.
B. Synlett, 1997, 1, 131. (d) Wong, M. S.; Zhang, X. L. Tetrahedron
Lett. 2001, 42(24), 4087.
(31) Dyker, G.; Kellner, A. J. Organomet. Chem. 1998, 555, 141.
(32) (a) Widdowson, D. A.; Wilhelm, R. Chem. Commun. 2003, 578.
(b) Jakt, M.; Johannissen, L.; Rzepa, H. S.; Widdowson, D. A.; Wilhelm,
R. J. Chem. Soc., Perkin Trans. 2 2002, 576.
J. Org. Chem, Vol. 70, No. 23, 2005 9593

SCHEME 4. Suzuki Cross-Coupling Experiments
with K2CO3 as Base in Methanol and Water
SCHEME 6. 2-Nitro-phenylboronic Acid Degraded
to Nitrobenzene under the Influence of Palladium
In conclusion, we have disclosed new protocols for the
synthesis of unsymmetrical substituted 2-nitrobiphenyls
4 and unsymmetrical substituted 2,2′-dinitrobiphenyls 3,
although in only low yields in the case of the latter class
of compounds. It is found that the nitro group of 2-ni-
trosubstituted phenylboronic acids intervenes during the
reaction and represents an obstacle for the course of the
Suzuki-type reaction. Moreover, when 2-nitrophenylbo-
ronic acid is reacted with a non-nitro-substituted ha-
loarene, a significant homocoupling of the haloarene
proceeds concomitant with the Suzuki cross-coupling
reaction.
SCHEME 5. Attempt To Synthesize 3,3′-, 4,4′-, and
2,3′-Dinitrobiphenyl by Means of Suzuki Cross-
Coupling with KH2PO4 as Base in DMF and H2O
Experimental Section
These experiments show that the reaction step (a), the
oxidative addition, proceeds without any obstacle with
the nitro group present, which was confirmed by the
reaction between 2,4-dinitrochlorobenzene and phenyl-
boronic acid, a reaction that provided nearly quantitative
yield of the expected product 2,4-dinitrobiphenyl 4g.
Widdowson and Wilhelm32a have proposed that a nitro
group in the 2-position may coordinate an incoming Pd
atom. In view of that we initially assumed that this also
was the major reason for the obstacles related to the
formation of 2,2′-dinitrobenzene 3. It was therefore
surprising to observe that the corresponding reaction
with 3-nitrophenylboronic acid proceeded much faster
than with 4-nitrophenylboronic acid, Scheme 4.
These observations could not be attributed to the
transmetalation step and to NO2-Pd coordination only
but rather to the elimination step, pathway (e) of Scheme
1. If the elimination step of the catalytic cycle is consid-
ered to be analogous with the behavior of SEAr reactions
in the presence of strongly deactivating substituents,
Scheme 4 reveals somewhat expected proportions be-
tween the outcome of the experiments. With the NO2
group in the 2- and 4-position, unstable resonance forms
of the intermediate appear, while this is not the case with
the NO2 group in the 3-position. Moreover, similar results
were achieved in trials to synthesize 3,3′-dinitrobiphenyl
10, 4,4′-dinitrobiphenyl 11, and 2,3′-dinitrobiphenyl 12,
Scheme 5.
Representative Procedure with KH2PO4 as Base in
DMF and H2O. A sealed tube or a round-bottom flask equipped
with reflux condenser with N2 atmosphere was charged with
KH2PO4 (1.3 mmol, 0.177 g), 2-nitrophenylboronic acid (1.5
mmol, 0.228 g), TBAB (0.2 mmol, 0.065 g), 1-iodo-2-nitrobenzene
(1 mmol, 0.249 g), and Pd(OAc)2 (0.02 mmol, 4.48 mg), using a
mixture of DMF (5 mL) in H2O (0.75 mL). The reaction mixture
was heated at 100 °C (oil bath) with stirring for 24 h. The
resulting mixture was diluted with H2O (30 mL) and extracted
with ether (3 × 30 mL). The organic phase was analyzed by GC-
MS with internal standard. Target product 2,2′-dinitrobiphenyl
was obtained in a yield of 27-30%. Only small quantities of
unconverted 1-iodo-2-nitrobenzene and small quantities of ni-
trobenzene formed via degradation of 2-nitrophenylboronic acid
were determined in the final reaction mixture.
Representative Procedure with K2CO3 as Base in CH3OH
and H2O. To a round-bottom flask under N2 atmosphere was
transferred a solution of methanol (5 mL) and water (1 mL).
K2CO3 (2.0 mmol, 0.276 g), Pd(OAc)2 (0.02 mmol, 4.5 mg), the
nitrohalobenzene (1.0 mmol), and the phenylboronic acid (1.0-
1.2 mmol) were then added. The resulting reaction mixture was
heated at 20-75 °C under stirring. Samples were withdrawn
(1.5-28 h) and analyzed by GC-MS. A correction factor with
1-chloro-2,4-dinitrobenzene as the standard was used for the
purpose of quantification.
Workup and Purification. The crude product obtained after
evaporation under reduced pressure was added to n-hexane and
heated with a heating gun until reflux. The resulting yellow
solution was filtered and allowed to cool, and white crystals (22
mg, ∼100% purity measured by GC) of triphenyl boroxin were
formed, which were removed by filtration. The hexane solution
was evaporated under reduced pressure to afford yellow crystals
(73 mg, ∼100% purity measured with GC, 93% recovery from
the total yield) of target product 2-nitrobiphenyl.
2-Nitrophenylboronic acid degrades very rapidly under
the influence of palladium, Scheme 6. When the corre-
sponding experiment is conducted in the absence of
palladium, even at elevated temperatures, only a small
fraction of the 2-nitrophenylboronic acid is degraded into
nitrobenzene. The iodobenzene is found untouched in
both cases and suggests that Pd catalyses the degrada-
tion of 2-nitrophenylboronic acid into nitrobenzene. This
degradation reaction of the boronic acid group appears
to be much faster than the oxidative addition step,
pathway (a) of Scheme 1.
Acknowledgment. Economic support from the Re-
search Council of Norway (R.R.G.) is gratefully acknowl-
edged. Professor George Francis is acknowledged for
linguistic assistance.
Supporting Information Available: General experimen-
tal information and copies of 1H NMR spectra for compounds
3a, 4a-d, 4f-g, 10, and 12-14. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO051589T
9594 J. Org. Chem., Vol. 70, No. 23, 2005