Palladium-Catalyzed Direct Monoarylation of Aryl C?H Bonds with Iodoarenes

Article abstract of DOI:10.1002/cctc.201700138

The transition-metal-catalyzed direct arylation of nonactivated aryl C?H bonds with iodoarenes has emerged as an important method for the construction of biaryls. Generally, the direct arylation reaction proceeds in the presence of stoichiometric Ag additives; moreover, the diarylation product is often unavoidable if there are two identical aromatic C?H bonds in the substrate. Herein we disclose an efficient Pd(OAc)₂/trifluoroacetic acid/O₂ catalytic system that promotes direct arylation reactions of a variety of aromatic C?H bonds with diverse iodoarenes under Ag-free conditions. The coupling reaction possesses a complete monoarylation selectivity. This approach provides a straightforward, facile, and economical route to biaryls.

Full text of DOI:10.1002/cctc.201700138

Accepted Article
Title: Palladium-Catalyzed Direct Monoarylation of Aryl C-H Bond with
Iodoarenes
Authors: Li Su, Dong-Dong Guo, Bin Li, Shi-Huan Guo, Gao-Fei Pan,
Ya-Ru Gao, and Yong-Qiang Wang
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To be cited as: ChemCatChem 10.1002/cctc.201700138
Link to VoR: http://dx.doi.org/10.1002/cctc.201700138
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10.1002/cctc.201700138
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Palladium-Catalyzed Direct Monoarylation of Aryl C-H Bond with
Iodoarenes
Li Su, Dong-Dong Guo, Bin Li, Shi-Huan Guo, Gao-Fei Pan, Ya-Ru Gao, Yong-Qiang Wang[a]*
Abstract: Transition-metal-catalyzed direct arylation of nonactivated
aryl C-H bond with iodoarenes has now emerged as an important
method for the construction of biaryls. Generally, the direct arylation
reaction proceeds in the presence of stoichiometric silver additives;
moreover, diarylation product is often unavoidable when there are
two identical aromatic C–H bonds in the substrate. We herein
disclose an efficient Pd(OAc)2/TFA/O2 catalysis system that could
promote direct arylation reactions of a variety of aromatic C−H
bonds with diverse iodoarenes under silver-free conditions. The
coupling reaction possesses complete monoarylation selectivity. The
approach provides a straightforward, facile, and economical route to
biaryls.
one ortho substituent is present, or there is a substituent at an
arene meta position to protect one of ortho C-H bond by steric
hindrance. In spite of its products being interesting structures in
organic materials, the diarylation still is a limitation in the
synthesis of diverse polyaryl molecules.
Recently, Larrosa et al. demonstrated that the role of silver
salt in several Pd-catalyzed C-H arylation processes of
iodoarenes is only iodide scavenger through the formation and
precipitation of the insoluble AgI salts, thereby keeping catalytic
active PdII from forming inactive PdI2.[11] Meanwhile, they
developed an elegant KOAc/NMe4Cl combination to replace
silver salt and successfully applied it in a range of C-H arylations
of iodoarenes.[11,12] Inspired by the research, we envisioned that
trifluoroacetic acid (TFA) might also take place of silver salt in
the process. The idea was based on following considerations
that i) TFA and Pd(OAc)2 can facilitate the generation of more
electropositive [PdO2CCF3]+ species, which, compared with
[PdOAc]+, is easier to form phenyl-Pd complexes through
electrophilic substitution of C-H bonds at ortho position[13] and ii)
although the induction of TFA could not completely prevent the
formation of PdI2, the high concentration of TFA could push the
equilibrium between PdI2 and Pd(TFA)2 to favor the latter, thus
keeping enough active PdII to catalyze the coupling reaction.
Furthermore, because of no induction of other metal ion in the
reaction system, the approach is favourable, compared to
previous methods, to the recovery of noble metal palladium in
amplified preparation.
Introduction
The biaryl motif is a key structural component of diverse
natural products, functional materials, and pharmaceuticals
active compounds.[1] As a result, the development of efficient
method for aryl-aryl bond construction has been attracting
significant attentions from the synthesis community.[2] Over the
past decade, transition-metal-catalyzed direct arylations of
nonactivated aryl C-H bonds have been greatly studied due to
their synthesis efficiency and minimization of atomic waste
compared to traditionally cross-couplings of organometallic aryls
with aryl halides.[3-5] In 2005, Daugulis and Zaitsev reported a
pioneering palladium-catalyzed direct coupling of aromatic C-H
bond of anilides with iodoarenes in the presence of AgOAc (1
equiv).[6] Since then, the powerful PdII/AgI/ArI reaction system
and its modifications have been successfully used in various aryl
C-H bond direct arylation.[7,8] Despite these considerable
advances, the method suffers from two major drawbacks: i) the
requirement for stoichiometric silver additives in order to
scavenge iodide. Nevertheless, due to their good oxidizability
and catalytic activity, the silver(I) species sometimes cause
undesired side reactions.[9] Moreover, silver salts are expensive,
thereby increasing the overall cost of the process; ii) the
challenge of the monoarylations. Currently, the diarylation
products can be obtained unavoidably when there are two
identical aromatic C–H bonds in the substrate. For example, in
the directing-group-assisted arylation of ortho aromatic C-H
bonds,[6,10] high selective monoarylation is achieved only when
Results and Discussion
Given the good directing capacity of pyridine and the
importance of pyridine-containing biaryls in medicinal
chemistry,[14] we initially evaluated the PdII/TFA-promoted
arylation strategy with 2-phenylpyridine (1a) and iodobenzene
(2a) as the model substrate (Table 1). First, the solvent
screening was performed with Pd(OAc)2 (10 mol%) as catalyst
and TFA (5 equiv.) as additive (entries 1-6). Gratifyingly, acetic
acid and anisole[15] were competent to the transformation, and
mixed solvent, acetic acid / anisole (1:1) gave the best yield
(55%)(entry 6). It should be noteworthy that the reaction
possessed complete monoarylation selectivity without diarylation
product observed in spite of 1a having two identical aromatic C–
H bonds at ortho position of pyridine group. To our surprise, the
atmosphere of the reaction clearly affected the transformation,
and O2 atmosphere provided much better result than air or Ar
(entries 6-8). At present the detail of the O2 function in the
reaction is unclear, and studies on related mechanism are
ongoing. Increasing the amount of TFA gave improved yields
(entries 9-13), with 8.0 equiv. of TFA affording the best yield
(95%) (entry 11). Using other palladium sources, Pd(TFA)2
provided the moderate yield (entry 13); the lower yield indicated
[a]
Li Su, Dong-Dong Guo, Bin Li, Shi-Huan Guo, Gao-Fei Pan, Ya-Ru
Gao, Yong-Qiang Wang*
Key Laboratory of Synthetic and Natural Functional Molecule
Chemistry of Ministry of Education, Department of Chemistry &
Materials Science
Northwest University
Xi’an 710069 (PR. China)
E-mail: wangyq@nwu.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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Table 1. Optimization of Reaction Conditions[a]
entry
catalyst
additive
(equiv)
TFA (5)
solvent
yield
(%)[b]
0
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
PdCl2
DMSO
2
TFA (5)
TFA (5)
TFA (5)
TFA (5)
TFA (5)
TFA (5)
TFA (5)
TFA (1)
TFA (3)
TFA (8)
TFA(10)
TFA (8)
TFA (8)
TFA (8)
TFA (8)
1,4-diioxane
32
0
3
DMF
4
anisole
43
45
55
80
48
18
45
95
93
50
<10
<10
<10
5
acetic acid
6
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
7[c]
8]d]
9[c]
10[c]
11[c]
12[c]
13[c]
14[c]
15[c]
16[c]
Pd(OH)2
Pd(PPh3)2Cl2
17[c,e]
PdI2
PdI2
-
acetic acid / anisole (1:1)
acetic acid / anisole (1:1)
0
18[c,e]
TFA (8)
15
[a] Reaction conditions: 1 (0.323 mmol), Pd(OAc)2 (0.032 mmol), 2 (0.485
mmol), TFA (2.584 mmol), AcOH / anisole (1:1) (1 mL), under O2 (1 atm),
100 ℃, 20-40 h. [b] Isolated yield. [c] 1a (8 mmol) was used.
[a] Reaction conditions: 1a (0.323 mmol, 50 mg), Pd(OAc)2 (0.032 mmol, 7
mg), 2a (0.485 mmol, 99 mg), TFA, solvent (1 mL), under air, 100 °C, 30 h. [b]
Isolated yield. [c] Under O2 (1 atm). [d] Under Ar (1 atm). [e] 72 h.
Scheme 1. Substrate Scope of 2-Arylpyridines and Iodoarenes[a,b]
that the fresh [PdO2CCF3]+ generated in situ had better catalytic
activity. Pd(OH)2, PdCl2 and Pd(PPh3)2Cl2 could not promote the
reaction effectively (entries 14-16). As our assumption above,
PdI2 did not work for the reaction (entry 17). Nevertheless, when
TFA (8 equiv.) was introduced into the PdI2 reaction system, the
desired 3a was produced albeit only in 15% yield (entry 18).
These results demonstrated our assumption that TFA are able to
regenerate catalytically active PdII in situ.
Cl and Br) were tolerated under our reaction conditions (3e-3g).
These were synthetically interesting results, because such
substituents could be versatile handles for further
transformations. Interestingly, other aromatic substrates, such
as 2-iodothiophene and 2- iodonaphthalene also were suitable
substrates for the reaction to give the corresponding products (3l,
3m) with three different aromatic rings in good yields. Then,
different substituted 2-arylpyridines at para-position, which also
possess two identical aromatic C–H bonds at ortho position of
pyridine group, were examined with iodobenzene as its partner.
Delightedly, all reactions afforded the desired products in good
yields. And the complete monoarylation selectivity was
highlighted again. The molecular structures of compounds 3h
and 3q were confirmed by X-ray crystallographic analysis.
With the optimal reaction conditions in hand, we moved on to
explore the substrate scope of the 2-arylpyridines and
iodoarenes. The results were summarized in Scheme 1. We first
examined the substituent effect of iodobenzene with 1a as a
partner. A broad range of substituent groups with diverse steric
and electronic properties (ether, alkyl, halide, acetyl and nitro
groups) at the ortho-, meta- or para-positions of the benzene
ring were compatible with this procedure, affording the
corresponding products in 56–95% yields, with complete
monoarylation selectivity (3b-3k). It is noteworthy that halides (F,
Next, we estimated the combination of Pd(OAc)2/TFA/O2 might
be a general catalysis system for the direct arylations of aryl C-H
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10.1002/cctc.201700138
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bond with iodoarenes. Therefore, a wide variety of direct C-H
arylation reactions with iodoarenes were investigated (Scheme
2). Changing pyridine directing group to phenyl substituted
pyridine (1w), quinoline (1x), isoquinoline (1y) and imidazole (1z)
did not affect the efficiency of the direct C-H arylation reaction.
They all underwent smooth reactions furnishing the desired
products in good yields (3w-3z). Finally, we were pleased to find
that the catalysis system could be readily extended to the direct
arylation of acetylaniline. Iodoarenes having various substitutes
(Me, OMe, Cl and Br) successfully coupled with acetylaniline,
providing the corresponding diaryls (3a’-3i’) in 47-82% yields. It
is worthwhile to note that all these direct C-H arylation reactions
were complete monoarylation selectivity without diarylation
product detected. The molecular structures of compounds 3x
and 3b’ were confirmed by X-ray crystallographic analysis.
Scheme 3. The reaction of the second arylation
I
Pd(OAc)2 (10 mol%)
AcOH/Anisole (1:1)
+
TFA, O , 100
℃
2
6
2a
yield 0%
5
Scheme 4. The reaction of biphenyl with iodobenzene
all, demonstrating that nitrogen atom of the pyridyl very likely
participated in the reaction. We next wondered if there were
radicals involving in the reaction. When the radical scavenging
reagent TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) was
introduced into the standard reaction system of 1a with 2a, the
reaction proceeded normally, showing low possibility of radical
process.
Based on above results and literature reports,[4a,16] a plausible
mechanism was proposed as scheme 5. Pd(OAc)2 is treated
with TFA to obtain active Pd(O2CCF3)+,[13] which affords the five-
membered palladacycle species
I through coordination of
nitrogen of pyridyl and subsequent ortho-position C-H bond
activation. Then, oxidative addition of aryl iodide to PdII species I
affords PdIV species, following reductive elimination to generate
the desired product; however,
a transmetalation process
between two palladium centers is also possible. Currently, we
think the excellent monoarylation selectivity lies in the mild
reaction condition and steric hindrance of aryl restricting the
formation of favorable five-membered palladacycle intermediate
on the other side.
[a] Reaction conditions: 1 (0.323 mmol), Pd(OAc)2 (0.032 mmol), 2 (0.485
mmol), TFA (2.584 mmol), AcOH / anisole (1:1) (1 mL), under O2 (1 atm),
100 ℃, 20-40 h. [b] Isolated yield. [c] Acetylaniline (1b’,10 mmol) was used.
Scheme 2. Scope of Various Arenes and Iodoarenes[a,b]
We further demonstrated the scalability of this protocol to
prepare 1.66 g of 3a (Scheme 1, 90% yield) and 1.12 g of 3b’
(Scheme 2, 53% yield) under the standard conditions,
respectively. The synthetic potential of the monoarylation
products can be exploited through the second otho-C-H arylation.
The monoarylation product 3b’ reacted with 4-iodotoluene using
Pd(OAc)2 (5 mol %) as the catalyst, AgOAc as the oxidant and
TFA as solvent to produce compound 4 in 56% yield[6] ( Scheme
3).
Scheme 5. Proposed Reaction Mechanism
To gain insight into the reaction mechanism, biphenyl (5) was
used as the substrate to react with iodobenzene (2a) under the
standard conditions (Scheme 4). The reaction didn’t happen at
Conclusions
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1
1149, 1022, 756 cm-1. H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 4.0 Hz,
1H), 7.71 (dd, J = 8.0 Hz, 4.0 Hz, 1H), 7.45-7.48 (m, 3H), 7.39-7.32 (m,
1H), 7.16-7.01 (m, 5H), 6.91 (d, J = 8.0 Hz, 1H), 2.32 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 159.4, 149.5, 140.6, 139.4, 138.4, 136.4, 135.3,
130.6, 130.5, 129.6, 128.9, 128.6, 127.5, 125.5, 121.3, 21.2. HRMS (ESI)
m/z calcd for C18H16N [M + H]+ 246.1277, found 246.1275.
In summary, we have developed an efficient Pd(OAc)2/TFA/O2
catalysis system that could promote direct arylations of a variety
of
arenes
including
arylpyridine,
benzoquinoline,
benzoisoquinoline, 2-phenylimidazole and acetylaniline with
diverse substituted iodoarenes under silver-free conditions. The
coupling reactions possess complete monoarylation selectivity.
The approach provides a straightforward, facile, and economical
route to biaryls under mild reaction conditions. Detailed
mechanistic investigations and the applications of the reaction
are currently underway.
2-[2-(4-Nitrobenzene)]phenylpyridine (3c)[5b] Prepared according to
general procedure to afford as light green solid (56 mg, 63% yield), Rf =
0.30 (EtOAc/hexanes = 1:10); m. p. = 107-108 ℃. IR (KBr): 3049, 1925,
1595, 1516, 1344, 1103, 1014, 852, 748 cm-1. 1H NMR (400 MHz, CDCl3)
δ 8.66-8.58 (m, 1H), 8.17-8.09 (m, 2H), 7.77-7.69 (m, 1H), 7.62-7.46 (m,
4H), 7.38-7.32 (m, 2H), 7.27-7.14 (m, 1H), 7.10-6.96 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ 158.5, 149.6, 148.4, 146.6, 139.7, 138.4, 135.9,
130.8, 130.4, 130.3, 128.9, 128.9, 125.0, 123.3, 121.9. HRMS (ESI) m/z
calcd for C17H13N2O2 [M + H]+ 277.0972, found 277.0967.
Experimental Section
General Information
1-(2'-(Pyridin-2-yl)-[1,1'-biphenyl]-4-yl)ethanone
(3d)[11]
Prepared
according to general procedure to afford as light yellow solid (53 mg,
61% yield), Rf = 0.30 (EtOAc/hexanes = 1:10); m. p. = 101-103 ℃. IR
(KBr): 3041, 2920, 1938, 1672, 1581, 1743, 1354, 1269, 1113, 957, 841,
All commercial reagents and solvents were used as received without
further purification. Reactions were followed with TLC (0.254 mm silica
gel 60-F plates). Visualization was accomplished with UV light. Flash
chromatographies were carried out on silica gel 200-300 mesh. Melting
points (m. p.) were measured on electrothermal digital melting point
apparatus and were uncorrected. 1HNMR and 13CNMR spectra were
recorded at 400 MHz using CDCl3 as solvent. Spectra were referenced
internally to the residual proton resonance in CDCl3 (δ 7.26 ppm) or
tetramethylsilane (TMS, δ 0.00 ppm) as the internal standard. Chemical
shifts (δ) were reported as part per million (ppm) in δ scale downfield
from TMS. Multiplicities are reported as follows: s = singlet, d = doublet, t
= triplet, m = multiplet, Infrared (IR) data were recorded as films on
potassium bromide plates on a Bruker Tensor 27 FT-IR spectrometer.
Absorbance frequencies are reported in reciprocal centimeters (cm-
1).High resolution mass spectra were acquired on a Bruker Daltonics
MicroTof-QII mass spectrometer. X-ray crystal structure analyses were
measured on Bruker Smart APEXIICCD instrument using Mo-Kα
radiation. The structures were solved and refined using the SHELXTL
software package.
1
756 cm-1. H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 4.0 Hz, 1H), 7.75 (d,
J = 8.0 Hz, 2H), 7.65-7.58 (m, 1H), 7.45-7.39 (m, 2H), 7.36-7.32 (m, 2H),
7.20-7.15 (m, 2H), 7.05 (m, 1H), 6.85 (d, J = 8.0 Hz, 1H), 2.50 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 198.0, 158.8, 149.6, 146.5, 139.6, 139.5,
135.6, 135.3, 130.7, 130.4, 129.9, 128.7, 128.4, 128.2, 125.3, 121.7,
26.7. HRMS (ESI) m/z calcd for C19H16NO [M + H]+ 274.1226, found
274.1217.
2-[2-(4-Fluorobenzene)]phenylpyridine (3e)[5e] Prepared according to
general procedure to afford as white solid (57 mg, 72% yield), Rf = 0.30
(EtOAc/hexanes= 1:8); m. p. = 102-105 ℃. IR (KBr): 3006, 2924, 1900,
1728, 1583, 1456, 1423, 1217, 1092, 839, 750, 557 cm-1. 1H NMR (400
MHz, CDCl3) δ 8.62 (s, 1H), 7.73-7.60 (m, 1H), 7.50-7.35 (m, 4H), 7.16-
7.05 (m, 3H), 6.97-6.81 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 161.9 (JC-
= 224.0 Hz), 159.1, 149.5, 139.5, 137.3, 135.4, 131.2 (JC-F = 8.0 Hz),
F
130.5, 130.4, 128.6, 127.8, 125.3, 121.5, 115.1, 114.9. HRMS (ESI) m/z
calcd for C17H13FN [M + H]+ 250.1027, found 250.1026.
2-[2-(4-Chlorophenyl)]phenylpyridine (3f)[5h] Prepared according to
general procedure to afford as light yellow solid (63 mg, 74% yield), Rf =
0.30 (EtOAc/hexanes = 1:10); m. p. = 98-100 ℃. IR (KBr): 3053, 1913,
1583, 1454, 1279, 1090, 997, 754, 557, 517 cm-1. 1H NMR (400 MHz,
CDCl3) δ 8.74-8.59 (m, 1H), 7.79-7.67 (m, 1H), 7.56-7.42 (m, 4H), 7.28-
7.21 (m, 2H), 7.19-7.08 (m, 3H), 6.99-6.89 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ 159.0, 149.6, 139.8, 139.5, 139.3, 135.5, 132.8, 131.0, 130.6,
130.4, 128.7, 128.3, 128.0, 125.3, 121.5. HRMS (ESI) m/z calcd for
C17H13ClN [M + H]+ 266.0731, found 266.0724.
General procedure for the preparation of 3
A sealed tube containing the 2-phenyl pyridine 1 (0.32 mmol), Pd(OAc)2
(10%, 0.032 mmol, 7 mg), was evacuation and filled with dioxygen gas
using an oxygen containing balloon. Then acetic acid / anisole (1:1, 1
mL), Iodobenzene (0.48 mmol, 98 mg) and trifluoroacetate (TFA) (2.58
mmol, 0.2 mL) were sequentially added to the system via syringe under
an oxygen atmosphere. The mixture was heated to 100 ℃ for 20-40 h.
Then the reaction mixture was cooled to room temperature, diluted with
EtOAc (10 mL) and washed with saturated aqueous NaHCO3 (3 × 2 mL).
The combined organic phase was dried (Na2SO4) and concentrated
under reduced pressure. Purification by flash chromatography afforded
the product 3.
2-[2-(4-Bromobenzene)]phenylpyridine (3g)[5e] Prepared according to
general procedure to afford as white solid (67 mg, 68% yield), Rf = 0.30
(EtOAc/hexanes = 1:3); m. p. = 97-99 ℃. IR (KBr): 3053, 1915, 1581,
1454, 1279, 1153, 997, 754, 557 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.62
(d, J = 4.0 Hz, 1H), 7.73-7.63 (m, 1H), 7.49-7.33 (m, 6H), 7.17-7.08 (m,
1H), 7.02 (d, J = 8.1 Hz, 2H), 6.92 (d, J = 7.8 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ 159.0, 149.6, 140.3, 139.5, 139.3, 135.5, 131.3, 131.2,
130.6, 130.3, 128.7, 128.01, 125.3, 121.6, 121.1. HRMS (ESI) m/z calcd
for C17H13BrN [M + H]+ 310.0226, found 310.0217.
Chemical Characterisation
2-(Biphenyl-2-yl)pyridine (3a)[5h] Prepared according to general
procedure to afford as white solid (70 mg, 95% yield), Rf = 0.32
(EtOAc/hexanes = 1:4); m. p. = 87-90 ℃. IR (KBr): 3057, 1732, 1583,
1425, 1288, 989, 748, 696 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.64-8.62
(m, 1H), 7.71-7.69 (m, 1H), 7.48-7.23 (m, 3H), 7.39-7.34 (m, 1H), 7.25-
7.21 (m, 3H), 7.18-7.19 (m, 2H), 7.10-7.07 (m, 1H), 6.88 (d, J = 8.0 Hz,
1H). 13C NMR (100 MHz, CDCl3) δ 159.3, 149.5, 141.4, 140.6 139.5,
135.2, 130.5 (2C), 129.7, 128.6, 128.1, 127.7, 126.7, 125.4, 121.4.
HRMS (ESI) m/z calcd for C17H14N [M + H]+ 232.1121, found 232.1129.
2-[2-(4-Methoxyphenyl)]phenylpyridine (3h)[5h] Prepared according to
general procedure to afford as light yellow solid (59 mg, 70% yield), Rf =
0.30 (EtOAc/hexanes = 1:5); m. p. = 63-64 ℃. IR (KBr): 3008, 2927,
1606, 1512, 1427, 1240, 1028, 758, 561 cm-1. 1H NMR (400 MHz, CDCl3)
δ 8.64 (d, J = 4.0 Hz, 1H), 7.68-7.63 (m, 1H), 7.47-7.37 (m, 4H), 7.13-
7.04 (m, 3H), 6.90 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 2H), 3.78 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 159.5, 158.5, 149.5, 140.2, 139.4,
135.3, 133.7, 130.8, 130.5, 130.5, 128.5, 127.3, 125.4, 121.3, 113.5, 55.2.
HRMS (ESI) m/z calcd for C18H16NO [M + H]+ 262.1226, found 262.1221.
2-[2-(4-Methylphenyl)]phenylpyridine (3b)[5h] Prepared according to
general procedure to afford as colourless oil (56 mg, 71% yield), Rf =
0.30 (EtOAc/hexanes = 1:8). IR (KBr): 3018, 2924, 1911, 1585, 1460,
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CCDC 1526791 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre.
2-(4'-Fluoro-4-methylbiphenyl-2-yl)pyridine (3o) Prepared according
to general procedure to afford as white solid (65 mg, 77% yield), Rf =
0.30 (EtOAc/hexanes = 1:8); m. p. = 103-104 ℃. IR (KBr): 3055, 2922,
1587, 1506, 1417, 1217, 1092, 987, 833, 744, 550 cm-1. 1HNMR (400
MHz, CDCl3) δ 8.66 (s, 1H), 7.69-7.57 (m, 1H), 7.48-7.39 (m, 1H), 7.35-
7.30 (m, 1H), 7.20-7.12 (m, 3H), 7.12-6.74 (m, 4H), 2.49 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 161.9 (JC-F = 250.0 Hz), 159.2 (JC-F = 8.3
Hz),149.5, 139.4, 138.5, 137.5, 135.3, 131.2, 131.1, 130.5, 128.5, 125.3,
121.3, 115.1, 114.9, 21.2. HRMS (ESI) m/z calcd for C18H15FN [M + H]+
264.1183, found 264.1171.
2-[2-(3-Methylphenyl)]phenylpyridine (3i)[5h] Prepared according to
general procedure to afford as white solid (53 mg, 67% yield), Rf = 0.30
(EtOAc/hexanes = 1:15); m. p. = 103-105 ℃. IR (KBr): 3057, 2920, 1583,
1425, 1271, 1086, 984, 758, 700, 767 cm-1. 1H NMR (400 MHz, CDCl3) δ
8.68-8.56 (m, 1H), 7.75-7.66 (m, 1H), 7.51-7.42 (m, 3H), 7.42-7.35 (m,
1H), 7.14-7.08 (m, 2H), 7.07-7.01 (m, 2H), 6.96-6.88 (m, 2H), 2.27 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 159.3, 149.4, 141.2, 140.7, 139.42,
137.7, 135.2, 130.5, 130.5, 130.4, 128.5, 127.9, 127.6, 127.5, 126.9,
125.4, 121.3, 21.4. HRMS (ESI) m/z calcd for C18H16N [M + H]+ 246.1277,
found 246.1270.
2-(4'-Chloro-4-methylbiphenyl-2-yl)pyridine (3p) Prepared according
to general procedure to afford as yellow solid (59 mg, 66% yield), Rf =
0.30 (EtOAc/hexanes = 1:8) ; m. p. = 103-104 ℃. IR (KBr): 2924, 1907,
1587, 1462, 1257, 1092, 829, 752, 582, 474 cm-1. 1H NMR (400 MHz,
CDCl3) δ 8.70-8.62 (m, 1H), 7.72-7.55 (m, 1H), 7.51-7.39 (m, 1H), 7.36-
7.30 (m, 1H), 7.28-7.20 (m, 3H), 7.18-7.09 (m, 3H), 6.97-6.89 (m, 1H),
2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.0, 149.5, 140.0, 139.2,
138.5, 136.7, 135.5, 132.7, 131.1, 131.0, 130.6, 128.7, 128.3, 125.3,
121.4, 21.3. HRMS (ESI) m/z calcd for C18H15ClN [M + H]+ 280.0888,
found 280.0877.
2-[2-(3-Methoxyphenyl)]phenylpyridine (3j)[5h] Prepared according to
general procedure to afford as light yellow solid (65 mg, 78% yield), Rf =
0.30 (EtOAc/hexanes = 1:10); m. p. = 78-79 ℃. IR (KBr): 3059, 2925,
1515, 1462, 1292, 1213, 1047, 864, 756 cm-1. 1H NMR (400 MHz, CDCl3)
δ 8.78-8.59 (m, 1H), 7.80-7.71 (m, 1H), 7.51 (s, 3H), 7.47-7.39 (m, 1H),
7.24-7.10 (m, 2H), 7.02-6.94 (m, 1H), 6.87-6.78 (m, 2H), 6.74 (s, 1H),
3.67 (s, 3H).13C NMR (100 MHz, CDCl3) δ 159.3, 159.2, 149.4, 142.7,
140.5, 139.5, 135.3, 130.5, 130.4, 129.1, 128.6, 127.8, 125.4, 122.2,
121.4, 114.9, 112.9, 55.1. HRMS (ESI) m/z calcd for C18H16N [M + H]+
262.1226, found 262.1217.
2-(4'-Methoxy-4-methylbiphenyl-2-yl)pyridine
(3q)[5h]
Prepared
according to general procedure to afford as white solid (71 mg, 81%
yield), Rf = 0.30 (EtOAc/hexanes = 1:5); m. p. = 92-94 ℃. IR (KBr): 2999,
2914, 2035, 1915, 1610, 1460, 1429, 1246, 1142, 1026, 837, 737 cm-1.
1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.66-7.53 (m, 1H), 7.41-7.31
(m, 1H), 7.26-7.19 (m, 2H), 7.11-6.99 (m, 3H), 6.91-6.82 (m, 1H), 6.81-
6.71 (m, 2H), 3.76 (s, 3H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
154.7, 153.7, 144.7, 135.3, 133.6, 131.9, 130.5, 129.1, 126.5, 126.0,
125.8, 123.4, 120.7, 116.4, 108.8, 50.5, 16.5. HRMS (ESI) m/z calcd for
C19H18NO [M + H]+ 276.1383, found 276.1370. CCDC 1526790 contains
the supplementary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic Data
Centre.
1-(2'-(Pyridin-2-yl)-[1,1'-biphenyl]-2-yl)ethan-1-one
(3k) Prepared
according to general procedure to afford as brown solid (49 mg, 56%
yield), Rf = 0.30 (EtOAc/hexanes = 1:4); m. p. = 99-100 ℃. IR (KBr):
3051, 2924, 1936, 1680, 1577, 1429, 1352, 1250, 1012, 953, 756, 594,
511 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.62-8.56 (m, 1H), 7.80-7.73
(m1H), 7.58-7.48 (m, 3H), 7.45-7.33 (m, 4H), 7.23-7.18 (m, 1H), 7.15-
7.10 (m, 1H), 7.01-6.96 (m, 1H), 2.11 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 202.4, 158.3, 149.4, 140.6, 140.3, 139.7, 139.5, 135.5, 131.6, 130.8,
130.4(2C), 128.6, 128.3, 128.1, 127.1, 124.9, 121.5, 29.4. HRMS (ESI)
m/z calcd for C19H16NO [M + H]+ 274.1226, found 274.1215.
2-(3'-Methyl-5-methylbiphenyl-2-yl)pyridine (3r) Prepared according to
general procedure to afford as colourless oil (47 mg, 78% yield), Rf =
0.30 (EtOAc/hexanes = 1:10), IR (KBr): 2924, 1716, 1585, 1462, 1290,
1142, 787, 596, 519 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.72-8.63 (m, 1H),
7.72-7.62 (m, 1H), 7.45-7.37 (m, 1H), 7.34-7.28 (m, 2H,) 7.17-7.07 (m,
4H), 7.00-6.89 (m, 2H), 2.49 (s, 3H), 2.32 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 159.3, 149.3, 141.4, 140.56, 138.3, 137.7, 136.7, 135.1, 131.2,
130.5, 130.4, 128.3, 127.9, 127.4, 126.9, 125.4, 121.1, 21.4, 21.3. HRMS
(ESI) m/ zcalcd for C19H18N [M + H]+ 260.1434, found 260.1422.
2-(2-(Thiophene-2-yl)phenyl)pyridine (3l)[17] Prepared according to
general procedure to afford as light yellow oil (49 mg, 64% yield), Rf =
0.30 (EtOAc/hexanes = 1:30), IR (KBr): 3060, 2924, 1923, 1585, 1462,
1259, 1151, 1022, 795, 754, 492 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.65
(d, J = 4.0 Hz, 1H), 7.65-7.47 (m, 3H), 7.46-7.37 (m, 2H), 7.25-7.04 (m,
3H), 6.99-6.79 (m, 1H), 6.69 (d, J = 3.2 Hz, 1H).13C NMR (100 MHz,
CDCl3) δ 159.3, 149.5, 142.9, 139.9, 135.5, 133.1, 130.7, 130.5, 128.5,
128.1, 127.1, 127.0, 125.7, 125.0, 121.8. HRMS (ESI) m/z calcd for
C15H12NS [M + H]+ 238.0685, found 238.0673.
2-(3'-Methoxy-5-methylbiphenyl-2-yl)pyridine
(3s)[5h]
Prepared
2-(2-(Naphthalen-2-yl)phenyl)pyridine (3m)[5n] Prepared according to
general procedure to afford as colourless oil (46 mg, 51% yield), Rf =
0.30 (EtOAc/hexanes = 1:15), IR (KBr): 3055, 2924, 1921, 1585, 1462,
1219, 1022, 822, 754, 621, 478 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.67-
8.58 (m, 1H), 7.74-7.68 (m, 4H), 7.61 (d, J = 8.0 Hz, 1H), 7.54-7.46 (m,
3H), 7.45-7.37 (m, 2H), 7.28-7.21 (m, 1H), 7.15 (m, 1H), 7.03 (dd, J = 8.0
Hz, 4.0Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ
159.2, 149.6, 140.5, 139.7, 139.1, 135.4, 133.4, 132.2, 130.9, 130.7,
128.7, 128.3(2C), 128.1, 127.9, 127.7, 127.4, 126.1, 125.9, 125.5, 121.4.
HRMS (ESI) m/z calcd for C21H16N [M + H]+ 282.1277, found 282.1261.
according to general procedure to afford as light yellow oil (71 mg, 81%
yield), Rf = 0.30 (EtOAc/hexanes = 1:5), IR (KBr): 2925, 1921, 1732,
1581, 1462, 1225, 1041, 785, 536 cm-1. 1H NMR (400 MHz, CDCl3) δ
8.62 (s, 1H), 7.59 (s, 1H), 7.36 (s, 1H), 7.26 (s, 2H), 7.20-7.01 (m, 2H),
6.93-6.83 (m, 1H), 6.82-6.72 (m, 2H), 6.68 (s, 1H), 3.62 (s, 3H), 2.43 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 154.6, 154.5, 144.6, 138.1, 135.6,
133.6, 132.0, 130.5, 126.3, 125.7, 124.3, 123.8, 120.7, 117.4, 116.5,
110.1, 108.1, 50.4, 16.5. HRMS(ESI) m/z calcd for C19H18ON [M + H]+
276.1383, found 276.1370.
2-(5-Methoxybiphenyl-2-yl)pyridine (3t)[5h] Prepared according to
general procedure to afford as light yellow solid (70 mg, 83% yield), Rf =
0.30 (EtOAc/hexanes = 1:10); m. p. = 68-69 ℃. IR (KBr): 3057, 2933,
1720, 1597, 1464, 1319, 1215, 1038, 987, 860, 791, 698 cm-1. 1H NMR
(400 MHz, CDCl3) δ 8.70-8.60 (m, 1H), 7.76-7.68 (m, 1H), 7.42-7.35 (m,
1H), 7.31-7.27 (m, 3H), 7.25-7.20 (m, 2H), 7.13-7.05 (m, 2H), 7.01 (s,
1H), 6.89-6.81 (m, 1H), 3.93 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ
159.6, 158.9, 149.4, 142.0, 141.4, 135.1, 132.3, 131.9, 129.6, 128.1,
126.9, 125.4, 120.9, 115.7, 113.3, 55.4. HRMS (ESI) m/z calcd for
C18H16ON [M + H]+ 262.1226, found 262.1213.
2-(4'-Methyl-4-methylbiphenyl-2-yl)pyridine (3n) Prepared according
to general procedure to afford as light yellow solid (70 mg 82% yield), Rf
= 0.30 (EtOAc/hexanes = 1:10); m. p. = 69-75 ℃. IR (KBr): 2918, 1726,
1587, 1458, 1219, 1045, 785, 742 cm-1. 1H NMR (400 MHz, CDCl3) δ
8.66-8.57 (m, 1H), 7.64-7.55 (m, 1H), 7.38-7.33 (m, 1H), 7.26-7.17 (m,
2H), 7.09-7.00 (m, 5H), 6.90-6.82 (m, 1H), 2.42 (s, 3H), 2.30 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 159.3, 149.2, 140.4, 138.5, 138.4, 136.5,
136.3, 135.3, 131.3, 130.5, 129.6, 128.8, 128.2, 125.5, 121.2, 21.3, 21.2.
HRMS (ESI) m/z calcd for C19H18N [M + H]+ 260.1434, found 260.1424.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201700138
ChemCatChem
FULL PAPER
1
6-(Pyridin-2-yl)-[1,1'-biphenyl]-3-carbaldehyde
(3u)[5b]
Prepared
.
1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.1 Hz, 1H), 7.39-7.32 (m,
according to general procedure to afford as yellow solid (46 mg, 56%
yield), Rf = 0.30 (EtOAc/hexanes = 1:25); m. p. = 84-85 ℃. IR (KBr):
3055, 2924, 2723, 1697, 1585, 1462, 1261, 1178, 1026, 839, 756 cm-1.
1H NMR (400 MHz, CDCl3) δ 10.17 (s, 1H), 8.72 (s, 1H), 8.19-7.98 (m,
2H), 7.97-7.87 (m, 1H), 7.54-7.42 (m, 1H), 7.31 (s, 3H), 7.23 (s, 3H),
7.01-6.92 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 192.4, 157.9, 149.7,
145.0, 141.5, 140.0, 136.2, 135.5, 132.0, 131.5, 129.6, 128.6, 128.3,
127.4, 125.4, 122.2. HRMS (ESI) m/z calcd for C18H14ON [M + H]+
260.1070, found 260.1062.
2H), 7.26-7.11 (m, 6H), 2.41 (s, 3H), 2.01 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 168.3, 138.7, 138.0, 134.7, 132.2, 130.0 (2C), 128.9, 128.7,
128.3, 126.2, 124.3, 121.5, 24.7, 21.5. HRMS (ESI) m/z calcd for
C15H16ON [M + H]+ 226.1226, found 226.1223.
N-(Biphenyl-2-yl)acetamide (3b')[23] Prepared according to general
procedure to afford as green solid (35 mg, 52% yield), Rf = 0.30
(EtOAc/hexanes = 1:4); m. p. = 83-85 ℃. IR (KBr): 3282, 3028, 2920,
1955, 1655, 1527, 1431, 1298, 1007, 742, 519 cm-1. 1H NMR (400 MHz,
CDCl3) δ 8.25 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 8.0 Hz, 2H), 7.42-7.33 (m,
4H), 7.26-7.14 (m, 3H), 2.01 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.3,
138.2, 134.7, 132.3, 130.1, 129.2, 129.1, 128.4, 128.0, 124.4, 121.8,
24.6. HRMS (ESI) m/z calcd for C14H14ON [M + H]+ 212.1070, found
212.1076. CCDC 1526796 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre.
2-(5-Bromobiphenyl-2-yl)pyridine (3v) Prepared according to general
procedure to afford as yellow solid (75 mg, 76% yield), Rf = 0.30
(EtOAc/hexanes = 1:25); m. p. = 132-135 ℃. IR (KBr): 3035, 2924, 1647,
1581, 1460, 1288, 1086, 1011, 829, 777 cm-1. 1H NMR (400 MHz, CDCl3)
δ 8.70 -8.64 (m, 1H), 7.63 (s, 3H), 7.46-7.37 (m, 1H), 7.31-7.26 (m, 3H),
7.21-7.13 (m, 3H), 6.92-6.84 (m, 1H). 13C NMR (100 MHz, CDCl3) δ
158.1, 149.6, 142.5, 131.0, 138.3, 135.4, 133.2, 132.1, 130.6, 129.5,
128.3, 127.3, 125.3, 122.6, 121.7. HRMS (ESI) m/z calcd for C17H13BrN
[M + H]+ 310.0226, found 310.0221.
N-(4'-Methyl-[1,1'-biphenyl]-2-yl)acetamide (3c')[18] Prepared according
to general procedure to afford as brown solid (43 mg, 60% yield), Rf =
0.30 (EtOAc/hexanes = 1:4), m. p. = 99-102 ℃. IR (KBr): 3340, 2922,
1909, 1520, 1441, 1009, 754, 519 cm-1. 1H NMR (400 MHz, CDCl3) δ
2-([1,1'-Biphenyl]-2-yl)-6-phenylpyridine (3w)[24] Prepared according to
general procedure to afford as white solid (75 mg, 76% yield), Rf = 0.30
(EtOAc/hexanes = 1:100); m. p. = 84-85 ℃. IR (KBr): 3051, 2922, 1930,
8.25 (d, J = 8.2 Hz, 1H), 7.37-7.14 (m, 8H), 2.42 (s, 3H), 2.02 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 168.3, 137.8, 135.1, 134.8, 132.1, 130.1,
129.8, 129.1, 128.3, 124.4, 121.6, 24.7, 21.3. HRMS (ESI) m/z calcd for
C15H16ON [M + H]+ 226.1226, found 226.1217.
1
1564, 1439, 1254, 1169, 987, 754, 694 cm-1. H NMR (100 MHz, CDCl3)
δ 7.92-7.84 (m, 3H), 7.63-7.54 (m, 5H), 7.52-7.43 (m, 3H), 7.36-7.30 (m,
5H), 7.12-7.05 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 158.9, 156.8,
141.9, 1410, 139.7, 139.6, 136.3, 130.8, 130.7, 129.8, 128.8, 128.6 (2C),
128.1, 127.7, 127.1, 126.6, 123.3, 118.1. HRMS (ESI) m/z calcd for
C23H18N [M + H]+ 308.1434, found 308.1426.
N-(4'-Chloro-[1,1'-biphenyl]-2-yl)acetamide
(3d')[20]
Prepared
according to general procedure to afford as brown white solid (41 mg,
52% yield), Rf = 0.3 (CH2Cl2), m. p. = 121-122 ℃. IR (KBr): 3276, 2924,
1651, 1284, 1007, 760, 602 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J
= 8.1 Hz, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.33-7.28 (m, 1H), 7.24 (d, J = 8.4
Hz, 2H), 7.12-7.10 (m, 2H), 6.95 (s, 1H), 1.96 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 168.4, 136.6, 134.6, 134.1, 131.4, 130.6, 130.0, 129.3, 128.8,
124.7, 122.3, 24.6. HRMS (ESI) m/z calcd for C14H13ClON [M + H]+
246.0680, found 246.0689.
2-([1,1'-Biphenyl]-2-yl)quinoline (3x)[21] Prepared according to general
procedure to afford as white solid (57.6 mg, 64% yield), Rf = 0.30
(EtOAc/hexanes = 1:50); m. p. = 100-101 ℃. IR (KBr): 3059, 2925, 2480,
1954, 1676, 1599, 1500, 1311, 1217, 1072, 1034, 947, 768, 519 cm-1. 1H
NMR (400 MHz, CDCl3) δ 8.24-8.19 (m, 1H), 7.91-7.85 (m, 1H), 7.82-
7.77 (m, 1H), 7.76-7.70 (m, 2H), 7.55-7.49 (m, 4H), 7.23 (s, 5H), 6.99-
6.90 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 159.9, 148.3, 141.2, 140.8,
139.8, 134.8, 130.9, 130.6, 129.9, 129.6, 129.4, 129.0 128.2, 127.9,
127.5, 126.9, 126.6, 126.4, 123.6. HRMS (ESI) m/z calcd for C21H16N [M
N-(4'-Bromo-[1,1'-biphenyl]-2-yl)acetamide
(3e')[19]
Prepared
according to general procedure to afford as brown solid (51 mg, 55%
yield), Rf = 0.3 (CH2Cl2), m. p. = 135-136 ℃. IR (KBr): 3265, 2922, 1651,
1286, 1003, 760 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.1 1H),
7.61 (d, J = 8.2 Hz, 2H), 7.41-7.34 (m 1H), 7.30-7.15 (m 4H), 7.05 (s 1H),
2.04 (s 3H). 13C NMR (100 MHz, CDCl3) δ 168.4, 137.1, 134.5, 132.3,
130.4, 130.0, 128.8, 124.8, 122.4, 122.3, 100.0, 24.6. HRMS (ESI) m/z
calcd for C14H13BrON [M + H]+ 290.0175, found 290.0166.
+
H]+ 282.1277, found 282.1262. CCDC 1526795 contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic Data
Centre.
1-([1,1'-Biphenyl]-2-yl)isoquinoline (3y) Prepared according to general
procedure to afford as white solid (67 mg, 74% yield), Rf = 0.30
(EtOAc/hexanes = 1:15); m. p. = 86-89 ℃. IR (KBr): 3049, 2924, 1552,
N-(4'-Methoxy-[1,1'-biphenyl]-2-yl)acetamide
(3f')[20]
Prepared
according to general procedure to afford as brown solid (63 mg, 82%
yield), Rf = 0.3 (CH2Cl2/CH3OH = 100:1), m. p. = 128-129 ℃. IR (KBr):
3350, 2920, 1516, 1240, 769 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.24 (d,
J = 8.2 Hz, 1H), 7.37-7.27 (m, 3H), 7.25-7.11 (m, 3H), 7.01 (d, J = 8.6 Hz,
2H), 3.87 (s, 3H), 2.03 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.3,
159.3, 134.9, 131.9, 130.4, 130.2, 130.2, 128.1, 124.3, 121.6, 114.5,
55.4, 24.7. HRMS (ESI) m/z calcd for C15H16ClO2N [M + H]+ 242.1176,
Found 242.1174.
1
1379, 1263, 1071, 1024, 746, 698, 521 cm-1. H NMR (400 MHz, CDCl3)
δ 8.62-8.53 (m, 1H), 7.80-7.73 (m, 1H), 7.67-7.53 (m, 7H), 7.39-7.33 (m,
1H), 7.16-7.10 (m, 2H), 7.09-6.99 (m, 3H). 13C NMR (100 MHz, CDCl3) δ
161.3, 142.0, 141.6, 141.1, 138.2, 136.0 130.7, 130.0, 129.8, 129.1,
128.8, 127.7, 127.5, 127.3(2C), 126.8, 126.6, 126.5, 119.9. HRMS (ESI)
m/z calcd for C21H16N [M + H]+ 282.1277, found 282.1265.
2-(Biphenyl-2-yl)-imidazole (3z)[22] Prepared according to general
procedure to afford as brown solid (42 mg, 57% yield), Rf = 0.30
(EtOAc/CH2Cl2 = 1:20); m. p. = 217-219 ℃. IR (KBr): 3026, 2908, 1572,
N-(3-Methoxy-[1,1'-biphenyl]-2-yl)acetamide
(3g')[20]
Prepared
according to general procedure to afford as colourless oil (36.2 mg, 47%
yield), Rf = 0.3 (EtOAc/hexanes = 1:2), IR (KBr): 3249, 2924, 1660, 1468,
1261, 1018, 760, 521 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.33-7.30 (m,
1
1427, 1298 cm-1. H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.0, 1.6 Hz,
1H), 7.46-7.39 (m, 5H), 7.30-7.33 (m, 3H), 6.91 (s, 2H). 13C NMR (100
MHz, CDCl3) δ 146.1, 141.1, 139.2, 130.6, 129.5, 129.2(2C), 128.9 (2C),
128.8, 128.6, 128.0, 127.9. HRMS (ESI) m/z calcd for C15H13N2 [M + H]+
221.1073, found 221.1072.
6H), 6.94 (d, J = 7.9 Hz, 2H), 6.69 (s, 1H), 3.86 (s, 3H), 1.98 (s, 3H). 13
C
NMR (100 MHz, CDCl3) δ 169.6, 155.1, 141.1, 139.5, 128.63, 128.2,
128.1, 127.3, 122.9, 122.4, 110.5, 55.8, 23.2. HRMS (ESI) m/z calcd for
C15H16NO2 [M + H]+ 242.1176, Found 242.1174.
N-(3'-Methyl-[1,1'-biphenyl]-2-yl)acetamide (3a')[20] Prepared according
to general procedure to afford as brown oil (47 mg, 65% yield), Rf = 0.3
(EtOAc/hexanes = 1:5). IR (KBr): 3267, 2924, 1522, 1444, 1038, 758 cm-
N-(4-Methyl-[1,1'-biphenyl]-2-yl)acetamide (3h')[25] Prepared according
to general procedure to afford as brown solid (41.0 mg, 57% yield), Rf =
0.3 (CH2Cl2/CH3OH = 100:1), m. p. = 135-137 ℃. IR (KBr): 3230, 2922,
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1655, 1296, 1028, 698, 609 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.08 (s,
1H), 7.47 (t, J = 7.3 Hz, 2H), 7.42-7.32 (m, 3H), 7.13 (d, J = 7.7 Hz, 2H),
7.00 (d, J = 7.6 Hz, 1H), 2.40 (s, 3H), 2.01 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 168.3, 138.5, 138.2, 134.4, 129.9, 129.6, 129.3, 129.1, 127.8,
125.3, 122.3, 24.6, 21.5. HRMS (ESI) m/z calcd for C15H16NO [M + H]+
226.1226, Found 226.1229.
Eur. J. 2012, 18, 9452; (h) G. Rouquet, N. Chatani, Angew. Chem.
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2016, 20, 867.
N-(4-Bromo-[1,1'-biphenyl]-2-yl)acetamide (3i')[26] Prepared according
to general procedure to afford as brown solid (55.4 mg, 60% yield), Rf =
0.3 (EtOAc/hexanes = 1:4), m. p. = 105-108 ℃. IR (KBr): 3261, 2922,
1657, 1284, 1007, 698, 598 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
1H), 7.52-7.41 (m, 3H), 7.37-7.27 (m, 3H), 7.15 (s, 1H), 7.09 (d, J = 8.2
Hz, 1H), 2.01 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.2, 137.1, 135.9,
131.2, 130.7, 129.3, 129.1, 128.4, 127.3, 124.1, 122.1, 24.7. HRMS (ESI)
m/z calcd for C14H12BrNO [M + H]+ 290.0175, Found 290.0163.
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N-(4-methyl-[1,1':3',1''-terphenyl]-2'-yl)acetamide (4). The solution of
4-Iodotoluene (1.0 mmol), N-([1,1'-biphenyl]-2-yl)acetamide (0.5 mmol),
palladium acetate (0.025 mmol), silver acetate (1.0 mmol) in TFA (2 mL)
in a dram screw-cap vial was heated at 120 ℃ for 12 h. The reaction was
generally stopped when no more precipitate was formed. The reaction
mixture was diluted with touene (5 mL), and the solution was decanted
and the precipitate was washed with toluene (2 × 5 mL). Combined
organic solutions were evaporated under reduced pressure. Product was
isolated by flash chromatography on silica gel. to afford 4 as white solid
(80.0 mg, 56% yield), Rf = 0.3 (CH2Cl2/CH3OH = 100:1), m. p. = 171-
175℃. IR (KBr): 3242, 2922, 1653, 1365, 1018, 804, 507 cm-1. H NMR
1
(400 MHz, CDCl3) δ 7.34-7.31 (m, 5 H), 7.28-7.26 (m, 2H), 7.24-7.12 (m,
5H), 6.54 (s, 1H), 2.31 (s, 3H), 1.63 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 169.5, 140.9, 140.8, 139.9, 137.0, 136.8, 131.2, 130.1, 129.8, 129.0,
128.8, 128.6, 128.2, 127.8, 127.3, 22.9, 21.3. HRMS (ESI) m/z calcd for
C21H20NO+ [M + H]+ 302.1539, Found 302.1547.
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This research was supported by the National Natural Science
Foundation of China (NSFC-21572178, 21272185).
Keywords: Palladium-catalysis • Arylation • Iodoarenes • C–H
Activation • Biaryls
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Text for Table of Contents
Li Su, Dong-Dong Guo, Bin Li, Shi-Huan
Guo, Gao-Fei Pan, Ya-Ru Gao, Yong-
Qiang Wang*
Page No. – Page No.
Palladium-Catalyzed Direct
Monoarylation of Aryl C-H Bond with
Iodoarenes
Biaryls synthesis: An efficient Pd(OAc)2/TFA/O2 catalysis system that could promote direct arylation reactions of a variety of
aromatic C−H bonds with diverse iodoarenes under silver-free conditions has been developed. The approach possesses complete
monoarylation selectivity, and provides a straightforward, facile, and economical route to biaryls.
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