A Highly Efficient Pd(PPh3)4-Catalyzed Suzuki Cross-Coupling Method for the Preparation of 2-Nitrobiphenyls from 1-Chloro-2-nitrobenzenes and Phenylboronic Acids

Article abstract of DOI:10.1002/ejoc.201501487

A simple and efficient method for Suzuki cross-coupling of highly substituted and congested 1-chloro-2-nitrobenzene with phenylboronic acid was developed, investigated, and optimized. The reaction conditions comprises a mixture of MeOH and water (4:1) as the reaction medium, readily available and cheap Pd(PPh₃)₄ as catalyst, sodium carbonate as base, and microwave heating, which affords a fast reaction rate with good outcomes. The procedure was proven to have high functional group tolerance with phenylboronic acid and for 1-chloro-2-nitrobenzene and thus is a general method for the synthesis of 2-nitrobiphenyl. The target scaffold, 2-nitrobiphenyls, was produced in excellent yields with excellent selectivities in all cases. An efficient microwave-assisted and Pd(PPh₃)₄-catalyzed Suzuki cross-coupling method for the synthesis of 2-nitrobiphenyls from 1-chloro-2-nitrobenzenes and phenylboronic acids is disclosed. The method exhibits excellent selectivity and fast reaction rates, provides high to excellent yields, and tolerates both electron-withdrawing and -donating groups.

Full text of DOI:10.1002/ejoc.201501487

DOI: 10.1002/ejoc.201501487
Full Paper
Suzuki Cross-Coupling
A Highly Efficient Pd(PPh3)4-Catalyzed Suzuki Cross-Coupling
Method for the Preparation of 2-Nitrobiphenyls from 1-Chloro-
2-nitrobenzenes and Phenylboronic Acids
Vijayaragavan Elumalai,[a] Alexander H. Sandtorv,[a] and Hans-René Bjørsvik*[a]
Abstract: A simple and efficient method for Suzuki cross-cou- microwave heating, which affords a fast reaction rate with good
pling of highly substituted and congested 1-chloro-2-nitrobenz- outcomes. The procedure was proven to have high functional
ene with phenylboronic acid was developed, investigated, and group tolerance with phenylboronic acid and for 1-chloro-2-
optimized. The reaction conditions comprises a mixture of nitrobenzene and thus is a general method for the synthesis of
MeOH and water (4:1) as the reaction medium, readily available 2-nitrobiphenyl. The target scaffold, 2-nitrobiphenyls, was pro-
and cheap Pd(PPh3)4 as catalyst, sodium carbonate as base, and duced in excellent yields with excellent selectivities in all cases.
Introduction
in the presence of a base and Pd(PPh3)4 as catalyst.[12] However,
because the C–Cl bond is less activated towards oxidative addi-
tion, a general application of chlorobenzenes as one of the re-
action partners in the Suzuki cross-coupling reaction has been
a long-standing and challenging task for the Suzuki cross-cou-
pling method. Although some of the first examples to involve
chloro-arenes[13] as reaction partners in this cross-coupling re-
action were disclosed about forty years ago, further significant
advances were not revealed until various palladium complexes
were introduced as catalysts to facilitate the Suzuki cross-cou-
pling reaction.[14] Even if simple catalysts, such as Pd(OAc)2 have
been shown to operate to some extent with chlorobenzenes in
the Suzuki cross-coupling reaction,[15] the greatest successes
were obtained when ingenious and dedicated ligands[16] were
installed on Pd to form the catalyst. In this context, particularly
complex elaborated phosphorus ligand have been devised, syn-
thesized, and used for the purpose.[17] These ligands have,
among other features, increased electron density around the
Pd center, which helps to facilitate the C–Cl oxidative cleavage
and assist cross-coupling,[3a,18–23] but due to their high degree
of elaboration, such ligands are expensive and not achievable
for larger scale reactions.
The biphenyl scaffold constitutes a fundamental structural moi-
ety for several application areas, which includes herbicides,[1]
fungicides[2] catalyst ligands,[3] liquid crystals,[4] active pharma-
ceutical ingredients, and drug candidates.[5] Moreover, 2-N-sub-
stituted biphenyls are of notable interest because such frame-
works can act as precursors for the essential 1H-carbazole
framework.[6]
Methods, such as the Ullmann,[7] Gomberg–Bachmann,[8]
and Suzuki cross-coupling reactions[9] are used for the prepara-
tion of biphenyls, of which the latter is the most efficient
method for the construction of C(sp2)–C(sp2) bonds in organic
synthesis and in the fine chemical industry.[10]
Freeman and collaborators[6d] disclosed in 2005 a method
for the synthesis of 2-nitrobiphenyls by using Pd(PPh3)4 as a
catalyst. In contrast to the method we disclose herein, their
method required long reaction times (up to 42 h) and a large
surplus of base to synthesize the target 2-nitrobiphenyls. Re-
cently, Gooßen and collaborators[11] disclosed a method for the
synthesis of 2-nitrobiphenyls by means of a decarboxylative Hi-
yama coupling reaction, which uses a trimetallic Pd/Cu/Ag cata-
lytic system at high temperatures. However, the Suzuki cross-
coupling reaction has emerged as the method with the most
attractive features for the purpose of preparation of biphenyls,
which includes mild reaction conditions, tolerance of water,
generally high functional group tolerance, and high selectivity
and yields.
Results and Discussion
For our project, we needed access to unusually congested bi-
phenyl 5 (Scheme 1), which we devised as a key intermediate
Originally, the Suzuki cross-coupling reaction was performed in a new total synthesis for the carbazole alkaloids carbazomy-
by reacting organic boronic acids with bromo- and iodoarenes cin G and H.[24]
One of the key steps in this synthesis was devised and devel-
[a] Department of Chemistry, University of Bergen,
oped in our group several years ago, namely a Suzuki cross-
coupling reaction[25] that was needed to join congested 1-iodo-
Allégaten 41, 5007 Bergen, Norway
E-mail: hans.bjorsvik@kj.uib.no
http://folk.uib.no/nkjhn/
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501487.
2-nitrobenzene (3I) and phenylboronic acid. An accompanying
scope and limitation study revealed that the method operated
to provide 2-nitrobiphenyls in high yields by reacting 1-iodo-2-
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z1–z4 a statistical experimental design 2k + c = 24 + 2 = 18 was
created, which is listed in standard order in Table 1, but it was
performed in random order in the laboratory.
Table 1. Statistical experimental design used for the investigation and optimi-
zation of the Suzuki cross-coupling with Pd(PPh3)4 as catalyst.
Experimental variables and selected levels
Experimental variables
Reaction temperature [°C] 90
Reaction time [min]
Quantity Na2CO3 [g]
Loading Pd(PPh3)4 [mmol] 0.022
–1 (L)
0
100
60
0.19
0.0435
+1 (H)
110
75
0.23
0.065
z1
z2
z3
z4
45
0.15
Experimental design: 2k + c, k = 4, c = 2 ⇒ 24 + 2 = 18
[a]
#
Experimental variables[b]
Response[c]
z1 [°C]
z2 [min]
z3 [g] z4 [mmol]
y [%]
1
2
3
4
5
6
7
8
90
110
90
110
90
110
90
110
90
110
90
110
90
110
90
110
100
100
120
45
45
75
75
45
45
75
75
45
45
75
75
45
45
75
75
60
60
30
0.15
0.15
0.15
0.15
0.23
0.23
0.23
0.23
0.15
0.15
0.15
0.15
0.23
0.23
0.23
0.23
0.19
0.19
0.10
0.022
0.022
0.022
0.022
0.022
0.022
0.022
0.022
0.065
0.065
0.065
0.065
0.065
0.065
0.065
0.065
0.0435
0.0435
0.025
8
44
15
35
25
39
29
43
22
30
27
32
16
29
20
39
19
21
53
Scheme 1. Chlorination or iodination followed by Suzuki coupling reaction
steps that lead to 3,5-dimethoxy-4-methyl-6-nitro-1,1′-biphenyl-2-ol.
nitrobenzenes with phenylboronic acids by using Pd(PPh3)4 as
catalyst, with any of the solvent pairs, dimethylformamide/wa-
ter, acetone/water, methanol/water, or methanol, as reaction
medium. To implement the cross-coupling step for congested
1-iodo-2-nitrobenzene (3I), which we attempted by means of
an iodination method disclosed by Crich and collaborators.[26]
This method afforded 3I but only in a low yield (≈ 30 %). Never-
theless, a much larger problem arose, because we were not able
to reproduce the iodination step 1 → 3I in accordance with this
method (Scheme 1, Method A). We assumed the obstacle in
this process to be due to the iodine purity. We were about to
abandon the outlined strategy to lead to 1H-carbazole scaffold
through the 2-nitro-1,1′-biphenyl, at which point we discovered
a halogenating method suitable for various N-heterocycles.[27]
These results made us wonder whether this method could op-
erate for the iodination 1 → 3I with N,N′-diiodo-5,5-dimethyl-
hydantoin as iodination reagent (similar to Scheme 1,
Method B), however, iodination trials failed. Subsequently, we
attempted to perform bromination with the corresponding
N,N′-dibromo-5,5-dimethylhydantoin, however, this also did not
work. Attempts with N,N′-dichloro-5,5-dimethylhydantoin (DCH)
2Cl reacted smoothly to provide chlorinated benzene 3Cl
(Scheme 1, Method B) in quantitative yield. With chlorinated
product 3Cl in hand, we wanted to establish a Suzuki cross-
9
10
11
12
13
14
15
16
17
18
Opt.[d]
[a] The experiments were carried out in a random order. [b] 2-Chloro-4,6-
dimethoxy-5-methyl-3-nitrophenol (3Cl; 0.21 g, 0.85 mmol) was used as a
substrate in all of the experiments. [c] Measured response from each experi-
ment y = GC–MS measured yield of target product 3,5-dimethoxy-4-methyl-
6-nitro-1,1′-biphenyl-2-ol (5). [d] Optimized conditions expressed in coded
format: reaction temperature (x1) = +2, reaction time (x2) = –2, quantity of
base (x3) ≈ –2, and Pd-catalyst loading (x4) ≈ –1.
The results of the experiments were evaluated by analyzing
the post-reaction mixture by means of GC–MS, the results of
which are given in the right hand column of Table 1.
Modeling
coupling reaction 3Cl + 4 → 5. We attempted our previously To facilitate the estimation of the model terms, the experimen-
disclosed Suzuki cross-coupling method developed for iodo- tal variables z1–z4 were scaled in accordance with Equation (1)
benzenes,[25] which successfully afforded target molecule 3,5- that produced design matrix D in the scaled variables x1–x4,
dimethoxy-4-methyl-6-nitro-1,1′-biphenyl-2-ol (5), but only in which were then used to produce model matrix M by using
low yield (≈ 30 %). This encouraging result prompted us to per- Equation (2). In these equations, zk is the experimental variable
form a systematic optimization by means of statistical experi- k expressed in real units and variable xk is the identical variable
mental design,[28] multivariate regression analysis,[29,30] and re- provided in scaled units. zk,L and zk,H are the selected low (L)
sponse surface methodology.[31] In this context, we assumed and high (H) experimental values expressed in the real units of
that the reaction temperature (z1), the reaction time (z2), the the experimental variable zk. The selected levels (L, 0, H) are
quantity of base (z3), and the amount of catalyst (z4) were the provided in the upper part of Table 1. The scaling by means of
variables that affected the performance of the reaction in terms Equation (1) gives all the experimental variables low values
of yield and selectivity. By using the experimental variables xk,L = –1 and correspondingly the high values xk,H = +1.
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that the regression coefficients ꢀ1, ꢀ2, ꢀ3 (positive signs) and ꢀ4
(negative sign) should be included in the model. Moreover, the
interaction terms ꢀ14 and ꢀ34 (negative signs) and ꢀ134 (positive
sign) might also be included. The final multivariate model, see
Equation (5), was subsequently used to produce the iso-contour
response surface projections of the Suzuki cross-coupling reac-
tion (Figure 2).
(1)
(2)
Multiple linear regression,[29] Equation (3), was used to esti-
mate the model shown in Equation (4) by means of MATLAB[32]
computer software and in-house coded routines that previously
have been benchmarked against commercial software, such as
SAS.[33]
(3)
(4)
The estimated regression coefficients were analyzed with a
cumulative normal distribution plot (Figure 1), which suggest
Figure 1. Cumulative normal distribution plot and regression coefficient spec-
trum estimated for the Suzuki cross-coupling reaction: 3Cl + 4 → 5.
Figure 2. iso-Contour projection of the response surface prepared for predictive purposes. The iso-contour lines created by the model Equation (4) display
the predicted yield (y) of target molecule 2-nitrobiphenyl 7. How to read the graphic: the outer horizontal frame line shows the variation in the quantity of
the sodium carbonate (x3), and the vertical frame line displays the effect of the reaction time (x2). Each variable has five discrete levels [–2 –1 0 +1 +2]. The
25 subplots within the outer frame lines show the iso-contour lines projections of the response surfaces when the two experimental variables — reaction
temperature (x1) and quantity of Pd catalyst (x4) — are continuously varied within a range that corresponds to [–2 +2].
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from the sub plot found in the lower left-hand corner of the
Figure 2.
The model predicts that a low quantity of base (z3; 0.10 g),
short reaction time (z2; 30 min), high reaction temperature (z1;
120 °C), and low Pd-catalyst loading (z4; 0.022 mmol) are opti-
mal.
(5)
The plots within Figure 2 were subsequently used to predict
the conditions of a higher yielding procedure for the Suzuki
These selections were made to simultaneously obtain opti-
cross-coupling reaction. The optimized conditions were taken mized yields and to minimize inputs (that is amounts of rea-
Table 2. Library for the investigation of the scope and limitation of the Pd(PPh3)4-catalysed Suzuki cross-coupling reaction that involves 1-chloro-2-nitroben-
zenes (3) and phenylboronic acids (4) as reaction partners.
[a] Conversion yield based on GC/isolated yield after column chromatography; n.d.: not detected. [b] The isolated product in this reaction was the 2-
nitrobiphenyl that resulted from a dehydrodebromination reaction.
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gents and Pd catalyst, and shorten reaction times). This was variety of electron-donating and electron-withdrawing func-
possible to achieve by means of the sub-plot in the lower left tional groups was outlined and tested by means of the
corner of Figure 2. This sub-plot predicts a yield of ≥ 50 %.
The predicted reaction conditions were used in following-
up experiments to achieve a maximum yield of 53 % of target
molecule 5. This result corresponds to an increased yield of (53
– 32) 21 %-point and is a relative improvement of > 65 % by
using only a simple Pd(PPh3)4 as catalyst in the Suzuki cross-
coupling reaction.
Owing to the good result we attained with congested
chloroarene 3Cl, we were eager to explore whether the devel-
oped and optimized reaction conditions could operate as a
general method for the coupling of 1-chloro-2-nitrobenzenes
and phenylboronic acids with Pd(PPh3)4 as the only catalyst.
established procedure for the 3Cl + 4 → 5 cross-coupling reac-
tion.
The only change to the method made was to reduce quan-
tity of phenylboronic acid used (2.3 equiv. → 1.5 equiv.). As
Table 2 reveals, the developed method proceeds with excellent
yields in most cases and demonstrates high functional group
tolerance. In addition to these advantages, the method takes
place at a significantly faster rate than previously published
methods that involve chlorobenzenes. Furthermore, the
method was also investigated by using a similar library that
contained bromobenzenes in place of chlorobenzenes as the
coupling partner to phenylboronic acid. A library composed of
13 entries (Table 3) of 1-bromo-2-nitrobenzenes and phenyl-
boronic acids was explored to evaluate the scope and limita-
Investigation of the Scope and Limitation of the Method
A test library (Table 2) composed of 18 various combinations tions of the method by using 1-bromo-2-nitrobenzenes as the
of phenylboronic acids and 1-chloro-2-nitrobenzenes with a haloarene.
Table 3. Library for the investigation of the scope and limitation of the Pd(PPh3)4-catalysed Suzuki cross-coupling reaction that involves 1-bromo-2-nitro-
benzenes (6) and phenylboronic acids (4) as reaction partners.
[a] Conversion yield based on GC/Isolated yield after column chromatography; n.d.: not detected.
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phenylboronic acid (1.5 mmol), Na2CO3 (1.1 mmol), tetrabutylam-
monium bromide (TBAB; 0.08 mmol), and Pd(PPh3)4 (0.026 mmol,
2.6 mol-%) were added. The vial was sealed and argon was carefully
flushed through the septa before a mixture of MeOH (4 mL) and
water (1 mL) was added. The vial was submerged in the microwave
cavity for 30 min at 120 °C. The post-reaction mixture was cooled
to room temperature, and methanol was removed under reduced
pressure. The reaction mixture was diluted with diethyl ether
(30 mL) and washed with water (40 mL). The aqueous phase was
extracted with diethyl ether (2 × 50 mL) and the organic phases
were combined and dried with Na2SO4. The drying agent was fil-
tered off and the crude product purified by flash chromatography
[ethyl acetate/hexane (mixture of isomers)] to afford 2-nitrobiphen-
yls.
Conclusions
In summary, we have designed, developed, and optimized a
fast and efficient Suzuki cross-coupling reaction for the synthe-
sis of 2-nitro-1,1′-biphenyls in high to excellent yield by using
1-chloro-2-nitrobenzenes and phenylboronic acids as reaction
partners. The method demonstrates high functional group tol-
erance with both 1-chloro-2-nitrobenzenes and the phenyl-
boronic acids. The method was originally developed to couple
a highly congested halo-arene with phenylboronic acid. In con-
trast to previously disclosed studies that relate to chloro-
benzenes as a reactant in the Suzuki cross-coupling reaction,
we utilized cheap, simple, and commonly exploited catalyst tet-
rakis(triphenylphosphine)-palladium(0). This was made possible
by fine-tuning the experimental conditions assisted by multi-
variate design and modeling to inform a fast, selective, and
high-yielding cross-coupling method. This study demonstrates
how multivariate design and modeling might be used in explor-
ative synthesis to develop new catalyzed synthetic methods
and, as in this case, replace the need for dedicated and sophisti-
cated catalyst ligands.
Suzuki Cross-Coupling Reaction with Chlorobenzenes
2,4-Dimethoxy-3-methyl-5-nitrophenol (1) [136763-93-3]: A so-
lution of conc. HCl (13 mL) in MeOH (25 mL) was added to 2,4-
dimethoxy-3-methyl-5-nitrophenyl acetate (1.9 g, 7.45 mmol) at
0 °C. The reaction mixture was stirred for 1 h at 70 °C at reflux
temperatures. After cooling to r.t. the solvent was removed under
reduced pressure. The crude product was diluted with water
(50 mL) and extracted with EtOAc (2 × 50 mL). The organic layers
were combined and dried with Na2SO4 to afford the title compound
as an orange solid (1.40 g, 88 %), m.p. 53–55 °C. Rf = 0.65 (EtOAc/
Experimental Section
1
hexane, 40:60). H NMR (400 MHz, CDCl3): δ = 7.29 (s, 1 H), 5.56 (s,
1 H), 3.79 (s, 6 H), 2.23 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
149.9, 146.4, 145, 140.2, 127.4, 109.3, 62.1, 61.1, 10 ppm. MS (EI):
m/z (%) = 213 (100) [M+], 183 (7), 166 (53), 152 (21), 137 (40), 125
Experimental Details: All reagents and solvents were purchased
from commercial sources and used as received. Melting points were
determined in open capillaries. Reagent grade chemicals were pur-
chased from commercial sources and used without further purifica-
tion. All reaction mixtures and column eluents were monitored by
TLC (TLC plates Merck Kieselgel 60 F254). The TLC plates were ob-
served under UV light at λ = 254 nm and λ = 365 nm. IR spectra
were recorded as KBr discs with a Shimadzu FTIR-8300 spectropho-
tometer, and 1H and 13C NMR spectra were recorded with Bruker
AV 400 MHz and 500 MHz instruments. High-resolution mass spec-
tra (HRMS) were performed with a Q-TOF Micro YA263 instrument.
(40), 122 (26), 77 (30), 53 (45). IR: ν = 3404, 3083, 2929, 2846,
˜
1500 cm–1
.
2-Chloro 4,6-dimethoxy-5-methyl-3-nitrophenol (3Cl): To a solu-
tion of 2,4-dimethoxy-3-methyl-5-nitrophenol (0.311 g, 0.145 mmol)
in EtOH (15 mL), DCH (146 mg, 0.0741 mmol) was added followed
by conc. H2SO4 dropwise (≈ 24 drops) with good stirring. After the
addition was completed, the reaction mixture was quenched with
NaOH (4.1 M, 5 mL). A heavy red precipitation was observed during
the addition of NaOH, which was neutralized with acetic acid (pH
≈ 4), and the resulting mixture was diluted with water (25 mL) and
extracted with diethyl ether (3 × 40 mL). The organic layers were
combined and dried with Na2SO4. The crude product was isolated
by flash chromatography (CH2Cl2/hexane, 40:60) to afford the title
compound as pale yellow crystals (0.34 g, 95 %), m.p. 118.5 °C. Rf =
General Methods: GC analyses were performed with a capillary gas
chromatograph equipped with a fused silica column (l25 m,
0.20 mm i.d.,0.33 mm film thickness) at a helium pressure of
200 kPa, split less/split injector and flame ionization detector. Mass
spectra were obtained with a GC–MS instrument, with a gas chro-
matograph equipped with a fused silica column (l30 m, 0.25 mm
i.d., 0.25 mm film thickness) and helium as the carrier gas. DART-
mass spectra were obtained by using PEG as an internal standard
in positive ionization mode with a TOF mass analyzer. 1H and 13C
NMR spectra were recorded at ambient temperature at a frequency
of 400 and 100 MHz, respectively.
1
0.29 (CH2Cl2/hexane, 60:40). H NMR (400 MHz, CDCl3): δ = 5.91 (s,
1 H), 3.87 (s, 3 H), 3.80 (s, 3 H), 2.26 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 147.5, 144.0, 142.7, 125.6, 109.3, 62.9, 61.0, 9.9 ppm. MS
(EI): m/z (%) = 247 (100) [M+], 217 (5), 213 (16), 186 (25), 171 (27),
138 (26), 108 (20), 83 (22), 77 (48), 67 (32). HRMS (EI): calcd. for
C9H10ClNO5 247.0248; found 247.0248. IR: ν = 3406, 3083, 2970,
˜
The chemical shifts are reported in ppm relative to residual CHCl3
for proton (δ = 7.26 ppm) and CDCl3 for carbon (δ = 77.0 ppm)
with tetramethylsilane as an external reference. Flash chromatogra-
phy was performed by using the indicated solvent system and silica
gel (230–400 mesh). All reagents used were commercially available
from Aldrich Chemical Co. For new compounds HRMS data were
also recorded.
2929, 2846, 1500, 1108 cm–1
.
2-Iodo 4,6-dimethoxy-5-methyl-3-nitrophenol (3I): A solution of
KI (0.332 g, 2 mmol) and iodine (0.295 g, 1.16 mmol) in H2O (1 mL)
was added dropwise to an aqueous solution of BuNH2 (20 %;
1.5 mL) and acetic acid 2,4-dimethoxy-3-methyl-5-nitrophenyl (4;
0.170 g, 0.67 mmol), for 1–2 min at room temperature. The resulting
dark mixture was stirred for 30 min at room temperature, and then
poured into CH2Cl2 (50 mL). The organic layer was washed with
aqueous sodium thiosulfate (10 %; 30 mL), dried with anhydrous
Na2SO4, and filtered. After removal of the solvent in vacuo, the final
crude (0.100 g) contained 5 as major product in 32 % yield (81 %
The microwave-assisted experiments were performed by means of
a Biotage Initiator Sixty EXP Microwave System, that operates at 0–
400 W at 2.45 GHz, in the temperature range of 40–250 °C, a pres-
sure range of 0–20 bar (2 MPa, 290 psi), and with reactor vial vol-
umes of 0.2–20 mL.
purity), and 2,4-dimethoxy-3-methyl-5-nitrophenol as a major impu-
1
General Procedure for the Suzuki Cross-Coupling Reaction: Into rity. C9H10NO5I MW 339.09. H NMR (200 MHz, CDCl3): δ = 3.85 [s,
a microwave vial, 1-chloro (or bromo)-2-nitrobenzene (1 mmol), 3 H, -OMe], 3.79 [s, 3 H, -OMe], 2.26 [s, 3 H, -Me] ppm. 13C NMR
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(200 MHz, CDCl3): δ = 146.7, 146.0, 144.3, 127.0, 71.1, 62.9, 61.1,
10.1 ppm. MS: m/z (%) = 339 (100), 324 (3), 278 (14), 263 (19), 248
H), 7.01–7.11 (td, J = 1.2, 7.6 Hz, 1 H), 6.90–6.93 (dd, J = 0.8, 8.4 Hz,
1 H), 3.71 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 155.8, 149.7,
(6), 235 (6), 207 (8), 179 (14), 167 (19), 151 (13), 136 (22), 123 (15), 133.1, 132.8, 132.5, 129.8, 129.7, 128, 127, 123.9, 121.2, 110.6,
108 (39), 93 (13), 79 (38), 67 (47), 53 (40), 43 (16).
55.2 ppm. MS (EI): m/z (%) = 231.2 (3), 230.2 (25), 229 (98) [M+],
197.9 (47), 184 (33), 170 (82), 168 (99), 152 (50), 139 (100), 115 (86),
3,5-Dimethoxy-4-methyl-6-nitrobiphenyl-2-ol (5): In a micro-
wave tube, 2-chloro-4,6-dimethoxy-5-methyl-3-nitrophenol (6;
0.21 g, 0.85 mmol), phenyl boronic acid (0.24 g, 1.97 mmol), Na2CO3
(0.10 g, 0.94 mmol), TBAB (0.021 g, 0.065 mmol) and Pd(PPh3)4
(0.025 g, 0.022 mmol) were added. The reaction mixture was care-
fully flushed with argon before adding a mixture of MeOH (4 mL)
and water (1 mL), The tube was sealed and placed into the micro-
wave cavity for 30 min at 120 °C. Then the reaction mixture was
washed with water (40 mL) and extracted with diethyl ether (2 ×
25 mL). The organic extracts were combined and dried with Na2SO4.
The crude product was isolated by flash chromatography (CH2Cl2/
hexane, 15:85) to afford the title compound as a white powder
89 (26), 77 (35), 63 (45). IR: ν = 2950, 1500, 1355 cm–1. The recorded
˜
spectroscopic data were in accordance with the literature.[35]
2-Methyl-2′-nitro-1,1′-biphenyl (5d) [67992-12-5]: 1-Chloro-2-
nitrobenzene (0.25 g, 1.59 mmol), 2-methylphenylboronic acid
(0.324 g, 2.38 mmol), Na2CO3 (0.185 g, 1.75 mmol), TBAB (0.041 g,
0.127 mmol), and Pd(PPh3)4 (0.048 g, 0.042 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 5:95) as a
yellow liquid (0.3112 g, 92 %). Rf = 0.53 (EtOAc/hexane, 20:80). 1H
NMR (400 MHz, CDCl3): δ = 7.90–7.93 (dd, J = 1.2, 8.4 Hz, 1 H), 7.53–
7.58 (td, J = 1.2, 7.6 Hz, 1 H), 7.42–7.46 (td, J = 1.6, 8 Hz, 1 H), 7.24–
7.27 (dd, J = 1.6, 8 Hz, 1 H), 7.13–7.23 (m, 3 H), 7.01–7.03 (dd, J =
0.8, 7.6 Hz, 1 H), 2.03 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
149.1, 137.5, 136.5, 135.6, 132.6, 132.2, 130, 128.3, 128.2, 125.8,
124.1, 19.9 ppm. MS (EI): m/z (%) = 214.2 (2), 213 (15) [M+], 195.9
(48), 166.1 (64), 164.9 (100), 151.6 (39), 139 (19), 115 (28), 88.9 (12),
1
(0.125 g, 51 %), m.p. 102.5 °C. Rf = 0.49 (CH2Cl2/hexane, 60:40). H
NMR (400 MHz, CDCl3): δ = 7.34–7.45 (m, 5 H), 5.57 (s, 1 H), 3.88 (s,
3 H), 3.83 (s, 3 H), 2.33 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
147.2, 143.2, 142.9, 130.8, 129.4, 128.9, 128.8, 125.6, 119.4, 62.8, 61.0,
10.0 ppm. MS (EI): m/z (%) = 289 (100) [M+], 272 (7), 246 (20), 207
(24), 199 (13), 169 (13), 141 (20), 129 (40), 115 (33), 102 (12), 83 (23),
77 (20). HRMS (ESI): calcd. for C15H15NO5 [M + Na+] 312.0848; found
82.2 (43), 63 (18). IR: ν = 3062, 2360, 2342, 1521, 1346 cm–1. The
˜
recorded spectroscopic data were in accordance with the litera-
ture.[25]
312.0846. IR: ν = 3481, 2927, 2850, 1530, 1370 cm–1
.
˜
4-Methyl-2-nitro-1,1′-biphenyl (5e) [39554-87-5]: 4-Chloro-3-
nitrotoluene (0.25 g, 1.46 mmol), phenylboronic acid (0.267 g,
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.12 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 10:90) as a
pale orange liquid (0.239 g, 77 %). Rf = 0.63(EtOAc/hexane, 20:80).
1H NMR (400 MHz, CDCl3): δ = 7.67 (s, 1 H), 7.39–7.44 (m, 4 H), 7.30–
7.34 (m, 3 H), 2.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
149.1, 138.7, 137.4, 133.5, 133.1, 131.8, 128.7, 128, 127.9, 124.4,
20.9 ppm. MS (EI): m/z (%) = 214.2 (7), 212.8 (52) [M+], 184.5 (81),
164 (98), 151.4 (100), 127.1 (99), 1149 (52), 90.7 (31), 88.8 (41), 82
4′-Chloro-2-nitro-1,1′-biphenyl (5a) [6271-80-3]: 1-Chloro-2-
nitrobenzene (0.25 g, 1.59 mmol), 4-chlorophenylboronic acid
(0.373 g, 2.39 mmol), Na2CO3 (0.185 g, 1.75 mmol), TBAB (0.041 g,
0.13 mmol), and Pd(PPh3)4 (0.048 g, 0.042 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 5:95) as a
yellow crystalline solid (0.315 g, 85 %), m.p. 59 °C. Rf = 0.58 (EtOAc/
hexane, 20:80). 1H NMR (400 MHz, CDCl3): δ = 7.79–7.82 (dd, J =
1.2, 8 Hz, 1 H), 7.53–7.57 (td, J = 1.2, 7.6 Hz, 1 H), 7.41–7.45 (td, J =
1.2, 8 Hz, 1 H), 7.31–7.34 (m, 3 H), 7.16–7.19 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 149.1, 135.9, 135.2, 134.5, 132.5, 131.9, 129.3,
128.9, 128.6, 124.3 ppm. MS (EI): m/z (%) = 237.2 (1), 236.1 (8), 233.3
(99) [M+], 215.9 (42), 198 (48), 168.3 (98), 149.9 (100), 139.2 (98),
(68), 76.5 (71). IR: ν = 3028, 1523, 1351 cm–1. The recorded spectro-
˜
scopic data were in accordance with the literature.[36]
115.1 (94), 97.7 (35), 74.23 (99), 62.3 (87). IR: ν = 1521, 1347,
˜
827 cm–1. The recorded spectroscopic data were in accordance with
the literature.[34]
4′-Chloro-4-methyl-2-nitro-1,1′-biphenyl (5f): 4-Chloro-3-nitro-
toluene (0.25 g, 1.46 mmol), 4-chlorophenylboronic acid (0.342 g,
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.12 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 10:90) as a
yellow liquid (0.291 g, 80 %). Rf = 0.63 (EtOAc/hexane, 20:80). 1H
NMR (400 MHz, CDCl3): δ = 7.69 (s, 1 H), 7.41–7.44 (dd, J = 1.2, 8 Hz,
1 H), 7.37–7.40 (m, 2 H), 7.28 (d, J = 7.6 Hz, 1 H), 7.21–7.24 (m, 2 H),
2.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.9, 139.2, 136,
134.2, 133.3, 132.4, 131.6, 129.3, 128.9, 124.6, 20.9 ppm. HRMS (EI):
4′-Ethyl-2-nitro-1,1′-biphenyl (5b) [166589-62-4]: 1-Chloro-2-
nitrobenzene (0.25 g, 1.59 mmol), 4-ethylphenylboronic acid
(0.358 g, 2.39 mmol), Na2CO3 (0.185 g, 1.75 mmol), TBAB (0.041 g,
0.127 mmol), and Pd(PPh3)4 (0.048 g, 0.042 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 5:95) as a
yellow liquid (0.301 g, 84 %). Rf = 0.66 (EtOAc/hexane, 20:80). 1H
NMR (400 MHz, CDCl3): δ = 7.72–7.75 (dd, J = 1.2, 7.2 Hz, 1 H), 7.49–
7.53 (td, J = 1.2, 7.6 Hz, 1 H), 7.35–7.39 (m, 2 H), 7.15–7.19 (m, 4 H),
2.62 (q, J = 7.6 Hz, 2 H), 1.19 (t, J = 7.6 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 147.8, 134.7, 133, 130.6, 130.4, 126.7, 126.3,
126.2, 122.7, 122.4, 27, 13.7 ppm. MS (EI): m/z (%) = 228.2 (4), 227
(35) [M+], 210 (19), 198 (27), 181.9 (54), 164.9 (100), 151.6 (61), 129.1
calcd. for C13H10ClNO2 247.0400; found 247.0400. IR: ν = 2924, 1525,
˜
1347, 817 cm–1
.
4′-Ethyl-4-methyl-2-nitro-1,1′-biphenyl (5g): 4-Chloro-3-nitrotol-
uene (0.25 g, 1.46 mmol), 4-ethylphenylboronic acid (0.328 g,
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.12 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
(21), 115 (27), 88.8 (16), 82 (33), 76 (20). IR: ν = 2964, 1521,
˜
1351 cm–1
.
2-Methoxy-2′-nitro-1,1′-biphenyl (5c) [6460-92-0]: 1-Chloro-2- pound was isolated by chromatography (EtOAc/hexane, 10:90) as a
nitrobenzene (0.25 g, 1.59 mmol), 2-methoxyphenylboronic acid yellow solid (0.327 g, 93 %), m.p. 53.6 °C. Rf = 0.73(EtOAc/hexane,
(0.362 g, 2.38 mmol), Na2CO3 (0.185 g, 1.75 mmol), TBAB (0.041 g, 20:80). 1H NMR (400 MHz, CDCl3): δ = 7.68 (s, 1 H), 7.44–746 (dd,
0.13 mmol), and Pd(PPh3)4 (0.048 g, 0.042 mmol). The title com- J = 1.2, 8 Hz, 1 H), 7.36–7.38 (d, J = 8 Hz, 1 H), 7.26–7.31 (m, 4 H),
pound was isolated by chromatography (EtOAc/hexane, 10:90) as a 2.74 (q, J = 7.6 Hz, 2 H), 2.51 (s, 3 H), 1.32 (t, J = 7.6 Hz, 3 H) ppm.
pale green solid (0.264 g, 73 %), m.p. 78.9 °C. Rf = 0.53 (EtOAc/
13C NMR (100 MHz, CDCl3): δ = 149.2, 144.2, 138.4, 134.6, 133.4,
hexane, 20:80). 1H NMR (400 MHz, CDCl3): δ = 7.92–7.94 (dd, J = 133, 131.7, 128.2, 127.9, 124.3, 28.6, 20.9, 15.4 ppm. HRMS (ESI):
1.2, 8 Hz, 1 H), 7.63–7.66 (td, J = 1.2, 7.6 Hz, 1 H), 7.45–7.49 (td, J = calcd. for C15H15NO2Na [M + Na+] 264.1000; found 260.1001. IR: ν =
1.6, 8 Hz, 1 H), 7.37–7.43 (m, 4 H), 7.31–7.33 (dd, J = 1.6, 7.2 Hz, 1
˜
2969, 2932, 1525, 1354 cm–1
.
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2′,4-Dimethyl-2-nitro-1,1′-biphenyl (5h): 4-Chloro-3-nitrotoluene 242.0453; found 242.0455. IR: ν = 2515, 1693, 1537, 1350 cm–1. The
˜
(0.25 g, 1.46 mmol), 2-methylphenylboronic acid (0.298 g, recorded spectroscopic data were in accordance with the litera-
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.12 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 10:90) as a
yellow liquid (0.280 g, 85 %). Rf = 0.71 (EtOAc/hexane, 20:80). 1H
NMR (400 MHz, CDCl3): δ = 7.73 (s, 1 H), 7.35–7.37 (dd, J = 1.2,
7.2 Hz, 1 H), 7.12–7.22 (m, 4 H), 7.00–7.01 (dd, J = 1.2, 8.4 Hz, 1 H),
2.41 (s, 3 H), 2.02 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.9,
138.7, 137.5, 135.8, 133.6, 133.4, 132, 129.9, 128.4, 128, 125.7, 124.4,
21, 19.9 ppm. HRMS (ESI): calcd. for C14H13NO2Na [M + Na+]
ture.[6d]
2′-Nitro-1,1′-biphenyl-4-carbaldehyde (5l) [169188-17-4]: 1-
Chloro-2-nitrobenzene (0.25 g, 1.59 mmol), 4-formylphenylboronic
acid (0.358 g, 2.39 mmol), Na2CO3 (0.185 g, 1.75 mmol), TBAB
(0.041 g, 0.127 mmol), and Pd(PPh3)4 (0.048 g, 0.042 mmol). The
title compound was isolated by chromatography (CH2Cl2/hexane,
50:50) as yellow crystals (0.287 g, 80 %), m.p. 102.3 °C. Rf = 0.33
(CH2Cl2/hexane, 50:50). 1H NMR (400 MHz, CDCl3): δ = 10.01 (s, 1
H), 7.93–7.96 (m, 3 H), 7.66–7.70 (td, J = 1.2, 7.2 Hz, 1 H), 7.54–7.58
(td, J = 1.2, 8 Hz, 1 H), 7.48–7.50 (dd, J = 1.6, 6.4 Hz, 2 H), 7.44–7.46
250.0844; found 250.0845. IR: ν = 2923, 1524, 1349 cm–1
.
˜
2′-Methoxy-4-methyl-2-nitro-1,1′-biphenyl (5i): 4-Chloro-3-nitro- (dd, J = 1.6, 8 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 191.8,
toluene (0.25 g, 1.46 mmol), 2-methoxyphenylboronic acid (0.333 g, 148.8, 143.8, 135.8, 135.4, 132.9, 131.7, 130, 129.1, 128.7, 124.5 ppm.
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g, 0.12 mmol)
MS (EI): m/z (%) = 226.7 (95) [M+], 210 (62), 198.6 (100), 168.5 (99),
and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title compound was iso- 150.1 (100), 113.8 (99), 101.2 (92), 74.3 (99). IR: ν = 2859, 1693, 1505,
˜
lated by chromatography (EtOAc/hexane, 10:90) as a pale-yellow 1351 cm–1
.
solid (0.265 g, 75 %), m.p. 101 °C. Rf = 0.61 (EtOAc/hexane, 20:80).
4′-Methyl-2′-nitro-1,1′-biphenyl-4-carbaldehyde (5m): 4-Chloro-
3-nitrotoluene (0.25 g, 1.46 mmol), 4-formylphenylboronic acid
(0.328 g, 2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.117 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (CH2Cl2/hexane, 40:60) as
yellow crystals (0.309 g, 88 %), m.p. 106 °C. Rf = 0.29 (CH2Cl2/hexane,
1H NMR (400 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.43–7.45 (dd, J = 0.8,
7.6 Hz, 1 H), 7.35–7.39 (td, J = 1.6, 8 Hz, 1 H), 7.28–7.31 (m, 2 H),
7.05–7.09 (td, J = 1.2, 7.6 Hz, 1 H), 6.90 (d, J = 8 Hz, 1 H), 3.70 (s, 3
H), 2.46 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 155.9, 149.5,
138.5, 133.5, 132.3, 130.1, 129.7, 129.6, 127, 124.3, 121.2, 110.6, 55.2,
20.9 ppm. HRMS (ESI): calcd. for C14H13NO3Na [M + Na+] 266.0793;
1
50:50). H NMR (400 MHz, CDCl3): δ = 10.05 (s, 1 H), 7.91–7.93 (m,
found 266.0795. IR: ν = 2963, 2835, 1501, 1356 cm–1
.
˜
2 H), 7.76 (s, 1 H), 7.45–7.48 (m, 3 H), 7.32 (d, J = 8 Hz, 1 H), 2.49 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 191.8, 148.6, 143.9, 139.8,
135.7, 133.5, 132.5, 131.5, 129.8, 128.7, 124.9, 21 ppm. HRMS (ESI):
(2-Nitro-1,1′-biphenyl-4-yl)(phenyl)methanone (5j) [857493-17-
5]: 4-Chloro-3-nitrobenzophenone (0.25 g, 0.96 mmol), phenyl-
boronic acid (0.176 g, 1.44 mmol), Na2CO3 (0.112 g, 1.06 mmol),
TBAB (0.025 g, 0.08 mmol), and Pd(PPh3)4 (0.029 g, 0.025 mmol).
The title compound was isolated by chromatography (EtOAc/hex-
ane, 10:90) as a pale yellow crystalline solid (0.260 g, 89 %), m.p.
115.8 °C. Rf = 0.61 (EtOAc/hexane, 20:80). 1H NMR (400 MHz, CDCl3):
δ = 8.26 (d, J = 1.6 Hz, 1 H), 8.05–8.07 (dd, J = 2, 8 Hz, 1 H), 7.84–
7.86 (dd, J = 0.8, 8 Hz, 2 H), 7.64–7.68 (m, 1 H), 7.53–7.61 (m, 3 H),
7.45–7.48 (m, 3 H), 7.36–7.39 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 193.9, 149.1, 139.8, 137.5, 136.4, 136.4, 133.3, 133.2,
132.2, 130, 128.9, 128.8, 127.8, 125.6 ppm. MS (EI): m/z (%) = 304.3
(1), 302.9 (9) [M+], 274.8 (28), 258 (6), 225.9 (7), 207 (9), 197.9 (6),
170 (16), 150.6 (22), 138.9 (8), 105 (98), 78.3 (5), 76.9 (100), 62.7 (5),
calcd. for C14H11NO3Na (MeOH) [M
+
Na+] 296.0899; found
296.0899. IR: ν = 2854, 2750, 1696, 1521, 1351 cm–1
.
˜
4′-Methyl-2′-nitro-1,1′-biphenyl-4-ol (5n) [1620094-10-1]: 4-
Chloro-3-nitrotoluene (0.25 g, 1.46 mmol), 4-hydroxyphenylboronic
acid (0.302 g, 2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB
(0.038 g, 0.117 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The
title compound was isolated by chromatography (CH2Cl2/hexane,
80:20) as a dark yellow liquid (0.208 g, 62 %). Rf = 0.26 (CH2Cl2/
hexane, 90:10). 1H NMR (400 MHz, CDCl3): δ = 7.61 (s, 1 H), 7.38–
7.40 (dd, J = 0.8, 8 Hz, 1 H), 7.30 (d, J = 7.6 Hz, 1 H), 7.15–7.19 (m,
2 H), 6.84–6.88 (m, 2 H), 5.52 (s, 1 H), 2.45 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 155.7, 149.2, 138.3, 133, 131.7, 129.6, 129.3,
124.3, 115.7, 20.8 ppm. MS (EI): 231.2 (1), 230.2 (10), 228.9 (100)
[M+], 212 (26), 196 (8), 183.9 (57), 167.9 (35), 151.7 (49), 127.4 (56),
50.9 (17). IR: ν = 1661, 1515, 1360 cm–1. The recorded spectroscopic
˜
data were in accordance with the literature.[6d]
114.9 (32), 77 (22), 75.6 (30). IR: ν = 3284, 1701, 1520, 1355 cm–1
.
2-Nitro-1,1′-biphenyl-4-carboxylic Acid (5k) [99847-12-8]: 4-
Chloro-3-nitrobenzoic acid (0.25 g, 1.24 mmol), phenylboronic acid
(0.226 g, 1.85 mmol), Na2CO3 (0.145 g, 1.37 mmol), TBAB (0.032 g,
0.10 mmol), and Pd(PPh3)4 (0.037 g, 0.032 mmol) were added. The
reaction mixture was carefully flushed with argon before adding a
mixture of MeOH (4 mL) and water (1 mL). The tube was sealed
and placed into the microwave cavity for 30 min at 120 °C. After
this time, the reaction mixture was cooled to room temp. and the
solvent was removed under reduced pressure. Then the reaction
˜
4-Methyl-2-nitro-4′-vinyl-1,1′-biphenyl (5o): 4-Chloro-3-nitrotolu-
ene (0.25 g, 1.46 mmol), 4-vinylphenylboronic acid (0.324 g,
2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
0.117 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (CH2Cl2/hexane, 40:60) as
yellow crystals (0.265 g, 76 %), m.p. 73.6 °C. Rf = 0.69 (CH2Cl2/hex-
ane, 50:50). 1H NMR (400 MHz, CDCl3): δ = 7.58 (s, 1 H), 7.32–7.38
(m, 3 H), 7.24 (d, J = 8 Hz, 1 H), 7.17–7.20 (m, 2 H), 6.63–6.70 (m, 1
H), 5.69–5.74 (dd, J = 0.4, 17.6 Hz, 1 H), 5.20–5.23 (m, 1 H), 2.38 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.1, 138.7, 137.3, 136.8,
136.2, 133.1, 133.1, 131.6, 128.1, 126.5, 124.5, 114.6, 20.9 ppm.
HRMS (ESI): calcd. for C15H13NO2Na [M + Na+] 262.0844; found
mixture was washed with water (40 mL) and acidified with HCl (1 N,
pH = 1–2) and filtered. The obtained solid contains both acid com-
pound and biphenyl (impurity). Water (5 mL) was added to the
flask, which contained the obtained solid. The solid was basified
with NaOH (4
M; pH = 10–12) and extracted with CH2Cl2 (2 × 40 mL).
262.0845. IR: ν = 3064, 1514, 1359 cm–1
.
˜
The aqueous layer was then acidified with HCl (1
N; pH = 1–2) and
filtered to afford compound 5k as a pale yellow solid (0.215 g,
72 %), m.p. 189.9 °C. 1H NMR (400 MHz, CDCl3): δ = 8.58 (d, J =
4′-Methyl-2′-nitro-1,1′-biphenyl-2-carbonitrile (5p): 4-Chloro-3-
nitrotoluene (0.25 g, 1.46 mmol), 2-cyanophenylboronic acid
1.6 Hz, 1 H), 8.33–8.36 (dd, J = 1.6, 8.0 Hz, 1 H), 7.61 (d, J = 8.0 Hz, (0.322 g, 2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB (0.038 g,
1 H), 7.45–7.49 (m, 3 H), 7.35–7.37 (m, 2 H) ppm. 13C NMR (100 MHz,
0.117 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The title com-
pound was isolated by chromatography (CH2Cl2/hexane, 50:50) as
CDCl3): δ = 169.5, 149.4, 141.3, 136.2, 133.4, 132.5, 129.5, 129.1, 129,
127.7, 125.9 ppm. HRMS (ESI–): calcd for C13H8NO4 [M+ – H] pale-yellow crystals (0.110 g, 32 %), m.p. 97.6 °C. Rf = 0.39 (CH2Cl2/
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hexane, 50:50). 1H NMR (400 MHz, CDCl3): δ = 7.96 (s, 1 H), 7.74– phenyl)boronic acid (0.264 g, 1.74 mmol), Na2CO3 (0.135 g,
7.77 (dd, J = 1.2, 8 Hz, 1 H), 7.61–7.65 (td, J = 1.6, 8 Hz, 1 H), 7.48–
1.27 mmol), TBAB (0.030 g, 0.09 mmol), and Pd(PPh3)4 (0.035 g,
7.54 (m, 2 H), 7.31–7.34 (m, 2 H), 2.52 (s, 3 H) ppm. 13C NMR 0.030 mmol). The title compound was isolated by chromatography
(100 MHz, CDCl3): δ = 148, 142.2, 140.7, 134.1, 132.9, 132.7, 132, (EtOAc/hexane, 5:95) as a yellow liquid (0.255 g, 90 %). Rf = 0.48
1
130.5, 129, 128.3, 125.4, 117.6, 112.3, 21.1 ppm. HRMS (ESI): calcd.
(EtOAc/hexane, 10:90). H NMR (500 MHz, CDCl3): δ = 7.64 (s, 1 H),
for C14H10N2O2Na [M + Na+] 261.0640; found 261.0641. IR: ν = 2919, 7.40–7.41 (dd, J = 1, 8 Hz, 1 H), 7.30–7.33 (m, 2 H), 6.91–6.93 (m, 1
˜
2360, 2340, 2233, 1519, 1351 cm–1
.
H), 6.86–6.88 (dd, J = 1, 7.5 Hz, 1 H), 6.83–6.84 (m, 1 H), 3.81 (s, 3
H), 2.46 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 159.7, 149.2,
138.8, 138.7, 133.3, 133.0, 131.6, 129.7, 124.3, 120.3, 113.7, 113.5,
55.3, 20.9 ppm. MS (EI): m/z (%) = 243 (73) [M+], 215 (65), 184 (41),
172 (54), 152 (100), 144 (55), 115 (52), 76 (28), 63 (33), 55 (66). IR:
N,N-4′-Trimethyl-2′-nitro-1,1′-biphenyl-4-amine (5q): 4-Chloro-3-
nitrotoluene (0.25 g, 1.46 mmol), 4-(dimethylamino)phenylboronic
acid (0.361 g, 2.19 mmol), Na2CO3 (0.170 g, 1.60 mmol), TBAB
(0.038 g, 0.117 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol). The
title compound was isolated by chromatography (CH2Cl2/hexane,
30:70) as dark orange crystals (0.201 g, 53 %), m.p. 136 °C. Rf = 0.24
ν = 2938, 2836, 1525, 1355 cm–1
.
˜
4,4′-Dichloro-2-nitro-1,1′-biphenyl (5v) [192942-45-3]: 1-Bromo-
4-chloro-2-nitrobenzene (0.25 g, 1.06 mmol), (4-chlorophenyl)-
boronic acid (0.249 g, 1.59 mmol), Na2CO3 (0.124 g, 1.17 mmol),
TBAB (0.027 g, 0.084 mmol), and Pd(PPh3)4 (0.032 g, 0.028 mmol).
The title compound was isolated by chromatography (EtOAc/hex-
ane, 5:95) as a yellow solid (0.232 g, 82 %), m.p. 87.1 °C. Rf = 0.56
(EtOAc/hexane, 10:90). 1H NMR (500 MHz, CDCl3): δ = 7.88 (d, J =
2.5 Hz, 1 H), 7.59–7.61 (dd, J = 2, 8.5 Hz, 1 H), 7.39–7.41 (dd, J = 2,
6.5 Hz, 2 H), 7.36 (d, J = 8 Hz, 1 H), 7.21–7.22 (dd, J = 2, 6.5 Hz, 2
H) ppm. 13C NMR (125 MHz, CDCl3): δ = 149.3, 134.9, 134.8, 134.4,
133.7, 132.9, 132.6, 129.2, 129.1, 124.4 ppm. MS (EI): m/z (%) = 269
(28), 267 (43) [M+], 232 (31), 204 (54), 186 (100), 176 (43), 150 (89),
1
(CH2Cl2/hexane, 30:70). H NMR (400 MHz, CDCl3): δ = 7.57 (s, 1 H),
7.31–7.38 (m, 2 H), 7.17–7.21 (m, 2 H), 6.76 (d, J = 8.8 Hz, 2 H), 2.99
(s, 6 H), 2.43 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 150.1,
149.2, 137.4, 133.4, 132.8, 131.6, 128.7, 124.8, 124.3, 112.5, 40.5,
20.8 ppm. HRMS (ESI): calcd. for C15H17N2O2H [M + H+] 257.1290;
found 257.1291. IR: ν = 2880, 2811, 1610, 1521, 1361 cm–1
.
˜
Suzuki Cross-Coupling Reaction with Bromobenzenes
4′-Chloro-4-methoxy-2-nitro-1,1′-biphenyl (5r) [41734-95-6]: 1-
Bromo-4-methoxy-2-nitrobenzene (0.25 g, 1.08 mmol), (4-chloro-
phenyl)boronic acid (0.253 g, 1.62 mmol), Na2CO3 (0.126 g,
1.19 mmol), TBAB (0.028 g, 0.087 mmol), and Pd(PPh3)4 (0.032 g,
0.028 mmol). The title compound was isolated by chromatography
(EtOAc/hexane, 10:90) as a yellow solid (0.275 g, 95 %), m.p. 77.8 °C.
139 (51), 93 (45), 75 (94). IR: ν = 3091, 1518, 13548, 815 cm–1
.
˜
4-Chloro-2-nitro-1,1′-biphenyl (5w) [29608-78-4]: 1-Bromo-4-
Rf = 0.40 (EtOAc/hexane, 10:90). 1H NMR (500 MHz, CDCl3): δ = 7.38– chloro-2-nitrobenzene (0.25 g, 1.06 mmol), phenylboronic acid
7.39 (m, 2 H), 7.36 (s, 1 H), 7.30 (d, J = 8.5 Hz, 1 H), 7.20–7.21 (m, 2
(0.194 g, 1.59 mmol), Na2CO3 (0.124 g, 1.17 mmol), TBAB (0.027 g,
H), 7.14–7.16 (dd, J = 2.5, 8.5 Hz,1 H), 3.90 (s, 3 H) ppm. 13C NMR 0.084 mmol), and Pd(PPh3)4 (0.032 g, 0.028 mmol). The title com-
(125 MHz, CDCl3): δ = 159.4, 149.5, 135.9, 134.0, 132.7, 129.4, 128.8,
pound was isolated by chromatography (EtOAc/hexane, 5:95) as a
127.5, 118.8, 109.2, 56.0 ppm. MS (EI): m/z (%) = 265 (38), 263 (87) yellow liquid (0.220 g, 89 %). Rf = 0.69(EtOAc/hexane, 10:90). 1H
[M+], 246 (15), 228 (28), 200 (36), 182 (45), 170 (37), 139 (100), 113
NMR (500 MHz, CDCl3): δ = 7.85 (d, J = 2 Hz, 1 H), 7.58–7.60 (dd,
J = 2.5, 8.5 Hz, 1 H), 7.38–7.43 (m, 4 H), 7.28–7.29 (m, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 149.5, 136.3, 134.8, 133.0, 132.4, 129.2,
128.8, 128.6, 127.8, 124.2 ppm. MS (EI): m/z (%) = 235 (10), 233 (30)
[M+], 216 (40), 205 (48), 188 (26), 168 (52), 152 (100), 115 (60), 75
(14), 75 (13), 69 (31). IR: ν = 3084, 3017, 2983, 2942, 2841, 1529,
˜
1358, 817 cm–1
.
4-Methoxy-2-nitro-1,1′-biphenyl (5s) [16098-16-1]: 1-Bromo-4-
methoxy-2-nitrobenzene (0.25 g, 1.08 mmol), phenylboronic acid
(0.198 g, 1.62 mmol), Na2CO3 (0.126 g, 1.19 mmol), TBAB (0.028 g,
0.087 mmol), and Pd(PPh3)4 (0.032 g, 0.028 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 5:95) as
dark yellow crystals (0.223 g, 90 %), m.p. 72.1 °C. Rf = 0.45 (EtOAc/
hexane, 10:90). 1H NMR (500 MHz, CDCl3): δ = 7.37–7.42 (m, 4 H),
7.34 (d, J = 8.5, 7.6 Hz, 1 H), 7.27–7.29 (m, 2 H), 7.14–7.16 (dd, J =
2.5, 8.5 Hz,1 H), 3.90 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
159.1, 149.7, 137.3, 132.8, 128.7, 128.6, 128.0, 127.9, 118.7, 109.0,
55.9 ppm. MS (EI): m/z (%) = 229 (85) [M+], 212 (58), 201 (34), 184
(56), 63 (40). IR: ν = 3063, 3028, 1529, 1349, 773 cm–1
.
˜
1-(2-Nitro-1,1′-biphenyl-4-yl)ethan-1-one (5x) [42771-77-7]: 1-
(4-bromo-3-nitrophenyl)ethan-1-one (0.25 g, 1.02 mmol), phenyl-
boronic acid (0.187 g, 1.59 mmol), Na2CO3 (0.119 g, 1.12 mmol),
TBAB (0.026 g, 0.080 mmol), and Pd(PPh3)4 (0.031 g, 0.027 mmol).
The title compound was isolated by chromatography (EtOAc/hex-
ane, 10:90) as a yellow solid (0.246 g, 83 %), m.p. 106.7 °C. Rf =
0.17(EtOAc/hexane, 10:90). 1H NMR (500 MHz, CDCl3): δ = 8.39 (d,
J = 1.5 Hz, 1 H), 8.17–8.19 (dd, J = 2, 8 Hz, 1 H), 7.57 (d, J = 8 Hz, 1
H), 7.44–7.46 (m, 3 H), 7.32–7.34 (m, 2 H), 2.68 (s, 3 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 195.4, 149.5, 140.4, 136.8, 136.3, 132.5,
131.4, 129.0, 128.9, 127.7, 124.0, 26.7 ppm. MS (EI): m/z (%) = 241
(31) [M+], 224 (35), 213 (54), 198 (39), 170 (46), 151 (100), 142 (47),
(53), 168 (74), 139 (100), 128 (78), 102 (23), 63 (36). IR: ν = 2917,
˜
2849, 1526, 1346 cm–1
.
2′-Chloro-4-methyl-2-nitro-1,1′-biphenyl (5t): 1-Bromo-4-methyl-
2-nitrobenzene (0.25 g, 1.16 mmol), (2-chlorophenyl)boronic acid
(0.272 g, 1.74 mmol), Na2CO3 (0.135 g, 1.27 mmol), TBAB (0.030 g,
0.09 mmol), and Pd(PPh3)4 (0.035 g, 0.030 mmol). The title com-
pound was isolated by chromatography (EtOAc/hexane, 5:95) as
light brown crystals (0.256 g, 90 %), m.p. 72.6 °C. Rf = 0.55 (EtOAc/
hexane, 10:90). 1H NMR (500 MHz, CDCl3): δ = 7.91 (s, 1 H), 7.47–
7.49 (dd, J = 0.5, 7.5 Hz, 1 H), 7.44–7.45 (m, 1 H), 7.32–7.34 (m, 2 H),
7.24–7.26 (m, 2 H), 2.50 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 148.4, 139.6, 137.2, 133.7, 132.9, 132.2, 131.5, 130.0, 129.4, 129.3,
126.9, 124.8, 21.0 ppm. HRMS (DART): calcd. for C13H1135ClNO2 [M
+ H+] 248.0478; found 248.0478, calcd. for C13H1137ClNO2 250.0478;
139 (35), 115 (33), 76 (25), 63 (31). IR: ν = 3095, 1683, 1519,
˜
1352 cm–1. The recorded spectroscopic data were in accordance
with the previously disclosed H NMR spectroscopic data.[6d]
1
1-(4′-Chloro-2-nitro-1,1′-biphenyl-4-yl)ethan-1-one (5y) [52806-
84-5]: 1-(4-Bromo-3-nitrophenyl)ethan-1-one (0.25 g, 1.02 mmol),
(4-chlorophenyl)boronic acid (0.239 g, 1.59 mmol), Na2CO3 (0.119 g,
1.12 mmol), TBAB (0.026 g, 0.080 mmol) and Pd(PPh3)4 (0.031 g,
0.027 mmol). The title compound was isolated by chromatography
(EtOAc/hexane, 10:90) as a yellow solid (0.220 g, 80 %), m.p.
101.3 °C. Rf = 0.14(EtOAc/hexane, 10:90). 1H NMR (500 MHz, CDCl3):
δ = 8.42 (d, J = 2 Hz, 1 H), 8.18–8.20 (dd, J = 1.5, 8 Hz, 1 H), 7.54
found 248.0449 IR: ν = 3057, 2922, 1522, 1352, 754 cm–1
.
˜
3′-Methoxy-4-methyl-2-nitro-1,1′-biphenyl (5u) [943620-21-1]: (d, J = 8 Hz, 1 H), 7.43–7.44 (dd, J = 1.5, 6.5 Hz, 2 H), 7.26–7.28 (dd,
1-Bromo-4-methyl-2-nitrobenzene (0.25 g, 1.16 mmol), (3-methoxy-
J = 1.5, 6.5 Hz, 2 H), 2.69 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
Eur. J. Org. Chem. 2016, 1344–1354
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1352
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[3]
a) D. W. Old, J. P. Wolfe, S. L. Buchwald, J. Am. Chem. Soc. 1998, 120,
9722–9723; b) M. Kettunen, C. Vedder, F. Schaper, M. Leskela, I. Muti-
kainen, H.-H. Brintzinger, Organometallics 2004, 23, 3800–3807; c) R.
Pratap, D. Parrish, P. Gunda, D. Venkataraman, M. K. Lakshman, J. Am.
Chem. Soc. 2009, 131, 12240–12249.
δ = 195.2, 149.3, 139.2, 137.1, 135.3, 134.8, 132.4, 131.5, 129.2, 129.1,
124.1, 26.7 ppm. MS (EI): m/z (%) = 277 (36), 275 (94) [M+], 260 (47),
240 (69), 214 (48), 186 (72), 179 (91), 170 (58), 151 (100), 139 (55),
75 (98). IR: ν = 3073, 1698, 1521, 1350, 817 cm–1
.
˜
1-(2′-Methyl-2-nitro-1,1′-biphenyl-4-yl)ethan-1-one (5z): 1-(4-
Bromo-3-nitrophenyl)ethan-1-one (0.25 g, 1.02 mmol), 2-methyl-
phenylboronic acid (0.208 g, 1.53 mmol), Na2CO3 (0.119 g,
1.12 mmol), TBAB (0.026 g, 0.080 mmol), and Pd(PPh3)4 (0.031 g,
0.027 mmol). The title compound was isolated by chromatography
(EtOAc/hexane, 15:85) as a yellow solid (0.216 g, 83 %), m.p. 59.5 °C.
[4]
[5]
R. P. Lemieux, Acc. Chem. Res. 2001, 11, 845–853.
a) R. Kannan, D. H. Williams, J. Org. Chem. 1987, 52, 5435–5437; b) K.
Hsieh, T. R. LaHann, R. C. Speth, J. Med. Chem. 1989, 32, 898–903.
[6]
a) W. C. P. Tsang, N. Zheng, S. L. Buchwald, J. Am. Chem. Soc. 2005, 127,
14560–14561; b) W. C. P. Tsang, R. H. Mundey, G. Brasche, N. Zheng, S. L.
Buchwald, J. Org. Chem. 2008, 73, 7603–7610; c) A. P. Antonchick, R.
Samanta, K. Kulikov, J. Lategahn, Angew. Chem. Int. Ed. 2011, 50, 8605–
8608; Angew. Chem. 2011, 123, 8764–8767; d) A. W. Freeman, M. Urvoy,
M. E. Criswell, J. Org. Chem. 2005, 70, 5014–5019; e) H. Peng, X. Chen, Y.
Chen, Q. He, Y. Xie, C. Yang, Tetrahedron 2011, 67, 5725–5731.
1
Rf = 0.22(EtOAc/hexane, 10:90). H NMR (400 MHz, CDCl3): δ = 8.46
(d, J = 2 Hz, 1 H), 8.12–8.15 (dd, J = 2, 10 Hz, 1 H), 7.40 (d, J =
9.5 Hz, 1 H), 7.16–7.28 (m, 3 H), 7.00–7.02 (dd, J = 1, 9.5 Hz, 1 H),
2.64 (s, 3 H), 2.03 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.5,
149.3, 140.9, 137.0, 136.5, 135.3, 132.9, 131.6, 130.2 128.7, 127.9,
125.9, 124.0, 26.7, 19.9 ppm. HRMS (DART): calcd. for C15H14NO3
[7]
a) F. Ullmann, J. Bielecki, Ber. Dtsch. Chem. Ges. 1901, 34, 2174–2185; b)
F. Ullmann, Justus Liebigs Ann. Chem. 1904, 332, 38–81; c) P. E. Fanta,
Synthesis 1974, 9–21.
[M + H+] 256.0974; found 256.0974. IR: ν = 2923, 1689, 1529,
˜
[8]
[9]
M. Gomberg, W. E. Bachmann, J. Am. Chem. Soc. 1924, 42, 2339–2343.
1351 cm–1
.
a) N. Miyaura, Y. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 20, 3437–
3440; b) A. Suzuki, Pure Appl. Chem. 1994, 66, 213–222; c) N. Miyaura, A.
Suzuki, Chem. Rev. 1995, 95, 2457–2483; d) A. Suzuki, in: Metal-catalyzed
Cross-coupling Reactions (Eds.: F. Diederich, P. J. Stang), VCH: Weinheim,
Germany, 1998, p. 49–97; e) A. Suzuki, J. Organomet. Chem. 1999, 576,
147–168; f) A. Suzuki, in: Handbook of Organopalladium Chemistry for
Organic Synthesis (Ed.: E. Negishi), Wiley, New York, 2002, p. 249–262; g)
A. Suzuki, Nobel Lecture: Cross-coupling Reactions of Organoboranes: An
Easy Way for C–C Bonding; Nobelprize.org. Nobel Media AB 2013. Web.
2 Oct 2013.
1-(2′-Methoxy-2-nitro-1,1′-biphenyl-4-yl)ethan-1-one (5æ): 1-(4-
Bromo-3-nitrophenyl)ethan-1-one (0.25 g, 1.02 mmol), (2-methoxy-
phenyl)boronic acid (0.232 g, 1.53 mmol), Na2CO3 (0.119 g,
1.12 mmol), TBAB (0.026 g, 0.080 mmol), and Pd(PPh3)4 (0.031 g,
0.027 mmol). The title compound was isolated by chromatography
(EtOAc/hexane, 15:85) as a yellow solid (0.216 g, 83 %), m.p.
113.1 °C. Rf = 0.14(EtOAc/hexane, 10:90). 1H NMR (400 MHz, CDCl3):
δ = 8.40 (d, J = 2 Hz, 1 H), 8.12–8.14 (dd, J = 2, 10 Hz, 1 H), 7.46 (d,
J = 10 Hz, 1 H), 7.33–7.37 (m, 1 H), 7.25–7.27 (dd, J = 2, 9 Hz, 1 H),
7.02–7.06 (td, J = 1, 9.5 Hz, 1 H), 6.85 (d, J = 10 Hz, 1 H), 3.63 (s, 3
H), 2.61 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.7, 155.7,
149.8, 137.5, 136.6, 133.0, 131.8, 130.6, 129.6, 126.0, 123.8, 121.4,
110.7, 55.2, 26.7 ppm. HRMS (DART): calcd. for C15H14NO4 [M + H+]
[10]
Organometallics as catalysts, in: the fine chemical industry M. Beller, H.-U.
Blaser, Top. Organomet. Chem. 2012, 42, 1–154.
[11]
[12]
D. Katayev, B. Exner, L. J. Gooßen, ChemCatChem 2015, 7, 2028–2032.
a) N. Miyaura, K. Yamada, A. Suzuki, Tetrahedron Lett. 1979, 20, 3437–
3440; b) N. Miyaura, A. Suzuki, J. Chem. Soc., Chem. Commun. 1979, 866–
867; c) A. Suzuki, H. C. Brown, Organic synthesis via boranes, vol. 3, Suzuki
coupling, Aldrich Chemical Company Inc. 2003.
272.0923; found 272.0923. IR: ν = 2910, 1689, 1537, 1363 cm–1
.
˜
1-(4′-Ethyl-2-nitro-1,1′-biphenyl-4-yl)ethan-1-one (5ø): 1-(4-
Bromo-3-nitrophenyl)ethan-1-one (0.25 g, 1.02 mmol), (4-ethyl-
phenyl)boronic acid (0.229 g, 1.53 mmol), Na2CO3 (0.119 g,
1.12 mmol), TBAB (0.026 g, 0.080 mmol), and Pd(PPh3)4 (0.031 g,
0.027 mmol). The title compound was isolated by chromatography
(EtOAc/hexane, 10:90) as yellow crystals (0.205 g, 75 %), m.p.
[13]
For some examples, see: a) W. J. Thompson, J. H. Jones, P. A. Lyle, J. E.
Thies, J. Org. Chem. 1988, 53, 2052–2055; b) M. B. Mitchell, P. J. Wallbank,
Tetrahedron Lett. 1991, 32, 2273–2276; c) N. W. Alcock, J. M. Brown, D. I.
Hulmes, Tetrahedron: Asymmetry 1993, 4, 743–756; d) M. Uemura, H.
Nishimura, K. Kamikawa, K. Nakayama, Y. Hayashi, Tetrahedron Lett. 1994,
35, 1909–1912; e) H. Zhang, K. S. Chan, Tetrahedron Lett. 1996, 37, 1043–
1044; f) W. Shen, Tetrahedron Lett. 1997, 38, 5575–5578.
1
79.3 °C. Rf = 0.19(EtOAc/hexane, 10:90). H NMR (500 MHz, CDCl3):
δ = 8.36 (d, J = 1.5 Hz, 1 H), 8.15–8.17 (dd, J = 1.5, 8 Hz, 1 H), 7.57
(d, J = 8 Hz, 1 H), 7.25–7.29 (m, 4 H), 2.71 (q, J = 7.5 Hz, 2 H), 2.67
(s, 3 H), 1.28 (t, J = 8 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
195.4, 149.5, 145.3, 140.4, 136.5, 133.5, 132.4, 131.3, 128.5, 127.7,
123.9, 28.6, 26.7, 15.3 ppm. HRMS (DART): calcd. for C16H16NO3 [M
[14]
M. Beller, H. Fischer, W. A. Herrmann, K. Ofele, C. Brossmer, Angew. Chem.
Int. Ed. Engl. 1995, 34, 1848–1849; Angew. Chem. Int. Ed. 1995, 34, 000–
000; Angew. Chem. 1995, 107, 1992–1993.
[15]
[16]
L. Liu, W. Wang, C. Xiao, J. Organomet. Chem. 2014, 749, 83–87.
For some examples, see: a) M. T. Reetz, R. Breinbauer, K. Wanninger,
Tetrahedron Lett. 1996, 37, 4499–4502; b) G. Y. Li, Angew. Chem. Int. Ed.
2001, 40, 1513–1516; Angew. Chem. 2001, 113, 1561–1564; c) W. A. Herr-
mann, B. V. P. Wohm, C. W. K. Gstottmayr, M. Grosche, C.-P. Reisinger, T.
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Andrews, Y. Sun, J. R. Sowa Jr., Org. Lett. 2001, 3, 1555–1557.
+ H+] 270.1130; found 270.1130. IR: ν = 2965, 2929, 2870, 1689,
˜
1532, 1356 cm–1
.
Acknowledgments
[17]
a) N. Kataoka, Q. Shelby, J. P. Stambuli, J. F. Hartwig, J. Org. Chem. 2002,
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Molecules 2015, 20, 7528–7557.
V. E. and A. H. S. gratefully acknowledge the Department of
Chemistry at the University of Bergen for funding their research
fellowships. Dr. Bjarte Holmelid is acknowledged for excellent
technical support with the HRMS analyses.
Keywords: Synthetic methods · Homogeneous catalysis ·
Cross-coupling · Palladium · Multivariate regression analysis
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Received: November 25, 2015
Published Online: February 8, 2016
Eur. J. Org. Chem. 2016, 1344–1354
www.eurjoc.org
1354
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim