Nickel-Catalyzed Cross-Coupling of Aryl 2-Pyridyl Ethers with Organozinc Reagents: Removal of the Directing Group via Cleavage of the Carbon-Oxygen Bonds

Article abstract of DOI:10.1021/acs.joc.0c02389

Reaction of aryl 2-pyridyl ethers with arylzinc reagents under catalysis of NiCl2(PCy3)2 affords aryl-aryl cross-coupling products via selective cleavage of CAr-OPy bonds. The reaction features a wide substrate range and good compatibility of functional groups. β-H-free alkylzinc reagents are also applicable as the nucleophiles in the transformation, whereas β-H-containing alkylzinc reagents lead to a mixture of cross-coupling and hydrogenation products.

Full text of DOI:10.1021/acs.joc.0c02389

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Article
Nickel-Catalyzed Cross-Coupling of Aryl 2‑Pyridyl Ethers with
Organozinc Reagents: Removal of the Directing Group via Cleavage
of the Carbon−Oxygen Bonds
Wei-Can Dai, Bo Yang, Shi-He Xu, and Zhong-Xia Wang*
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ABSTRACT: Reaction of aryl 2-pyridyl ethers with arylzinc reagents
under catalysis of NiCl2(PCy3)2 affords aryl−aryl cross-coupling
products via selective cleavage of CAr−OPy bonds. The reaction
features a wide substrate range and good compatibility of functional
groups. β-H-free alkylzinc reagents are also applicable as the
nucleophiles in the transformation, whereas β-H-containing alkylzinc reagents lead to a mixture of cross-coupling and hydrogenation
products.
organozinc reagents with aryl 2-pyridyl ethers. Herein, we
report the results.
INTRODUCTION
■
The 2-pyridyloxy (OPy) group as a directing group is widely
used in transition-metal-catalyzed activation and transforma-
tion of C−H bonds of aromatic systems.1 Removing or
transforming the OPy unit after directing C−H functionaliza-
tion will expand the synthetic utility and hence is an important
research topic. In recent years, methodologies have been
developed to perform the transformations.2,3 For example,
Chatani and Feng, respectively, carried out borylation of aryl 2-
pyridyl ethers via rhodium-, nickel-, or iron-catalyzed C−OPy
bond activation.4 Zeng et al. reported chromium-catalyzed
Kumada arylation of aryl 2-pyridyl ethers via C−OPy bond
cleavage.5 Li et al. reported nickel-catalyzed silylmethylation of
naphthyl 2-pyridyl ether via reaction with Sc-
(CH2SiMe3)3(THF)2.6 We performed amination, alkylation,
silylation, and hydrogenation of aryl 2-pyridyl ethers via
activation of the C−OPy bonds under nickel catalysis.7−10
Although sighificant progresses have been achieved, the
methods are still limited. It is desirable to further develop
methodologies to expand the synthetic utility of the
compounds containing a 2-pyridyloxy directing group.
On the other hand, biaryls and alkyl-substituted arenes are
important classes of compounds in natural product chemistry,
agrochemicals, liquid crystals, pharmaceuticals, and advanced
materials.11 They can be synthesized via transition-metal-
catalyzed cross coupling of aryl electrophiles with appropriate
organometallic reagents.11,12 A series of phenol derivatives
including aryl triflates, aryl mesylates, aryl carbamates, aryl
carbonates, and aryl ethers have been demonstrated to be
applicable as the electrophiles.2,13 Reaction of aryl 2-pyridyl
ethers with aryl Grignard reagents under catalysis of chromium
was also reported.5 Compared with Grignard reagents,
organozinc reagents normally have better functional group
compatibility. Hence, we initiated a study of reaction of
RESULTS AND DISCUSSION
■
Reaction of 2-(4-tert-butylphenoxy)pyridine (1a) with p-
Me2NC6H4ZnCl (2a) was employed as model reaction to
screen catalysts and optimize reaction conditions. It was
reported that nickel catalysts can activate most C−O bonds of
aryl ethers and esters.13 We also demonstrated that
NiCl2(PCy3)2 can catalyze coupling of aryl 2-pyridyl ethers
with silylzinc reagents.9 Hence, we chose various nickel
complexes to test. NiCl2(DME) showed very low catalytic
activity in THF at 100 °C. NiCl2(PPh3)2 exhibited slightly
higher activity than NiCl2(DME) (Table 1, entries 1 and 2).
NiCl2(PCy3)2 displayed much higher activity than
NiCl2(PPh3)2 and NiCl2(DME) under the same conditions.
In the presence of 10 mol % NiCl2(PCy3)2 the reaction gave
72% product yield (Table 1, entry 3). This is attributed to
electron-rich and bulky properties of PCy3 which make for
oxidative addition of the C−O bond to the PCy3-coordinated
nickel center and next reductive elimination after trans-
matalation. The nickel complexes with bidentate phosphine
ligands such as Ni(COD)2/dcype, NiCl2(dppe), and
NiCl2(dppf) were also less active. They catalyzed the model
reaction to result in the desired product in 13−36% yields,
respectively (Table 1, entries 4−6). Next, we tested the solvent
effect employing NiCl2(PCy3)2 as the catalyst (Table 1, entries
Received: October 9, 2020
Published: January 14, 2021
https://dx.doi.org/10.1021/acs.joc.0c02389
© 2021 American Chemical Society
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a
a
Table 1. Optimization of Reaction Conditions
Table 2. Effect of the Li+ and Mg2+ Ions
yield
b
entry
preparation method of p-Me2NC6H4ZnCl
(%)
b
entry
[Ni] (mol %)
solvent
yield (%)
1
2
reaction of p-Me2NC6H4MgBr with an equiv of ZnCl2.
43
64
1
2
3
4
5
6
7
8
9
NiCl2(DME) (10)
NiCl2(PPh3)2 (10)
NiCl2(PCy3)2 (10)
Ni(COD)2 (10) dcype (10)
NiCl2(dppe) (10)
NiCl2(dppf) (10)
THF
THF
THF
THF
THF
THF
dioxane
toluene
7
reaction of p-Me2NC6H4Li
(prepared from nBuLi and p-Me2NC6H4Br) with an equiv
of ZnCl2.
reaction of p-Me2NC6H4Li
(prepared from nBuLi and p-Me2NC6H4Br) with an equiv
of ZnCl2 in the presence of 1 equiv of MgCl2.
13
72
36
22
13
13
6
85
76
90
79
98
3
89
a
The reactions were performed employing 0.2 mmol 2-(4-(tert-
butyl)phenoxy)pyridine and 0.24 mmol of 4-N,N-dimethylphenylzinc
chloride in 1.5 mL of solvent. The yield was obtained according to
the integral ratio of the H NMR spectrum of the reaction mixture,
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (10)
NiCl2(PCy3)2 (7.5)
NiCl2(PCy3)2 (5)
b
THF/NMP (1:1)
THF/NMP (1:2)
THF/NMP (2:1)
THF/DMF (1:1)
THF/DMAc (1:1)
THF/DMAc (1:1)
THF/DMAc (1:1)
THF/DMAc (1:1)
THF/DMAc (1:1)
THF/DMAc (1:1)
1
10
11
12
13
14
15
using (oxybis(methylene))dibenzene as an internal standard.
ether.14 The presence of the Li+ ion may also lead to formation
of trimetallic adducts and zincates. The formation of trimetallic
adducts breaks the aggregation of ArZnCl with MgCl2, and the
formation of zincates enhances the reactivity of the zinc
reagents.15
c
98(98 )
94
93
98
87
d
16
NiCl2(PCy3)2 (7.5)
NiCl2(PCy3)2 (7.5)
NiCl2(PCy3)2 (7.5)
e
17
18
f
Next, we examined substrate scope under the optimized
conditions (Table 3). Reaction of p-Me2NC6H4ZnCl with
several aryl 2-pyridyl ethers was first examined. Phenyl 2-
pyridyl ether exhibited high reactivity. Surprisingly, 2-([1,1′-
biphenyl]-4-yloxy)pyridine showed markedly lower reactivity
than 2-(4-tert-butylphenoxy)pyridine or phenyl 2-pyridyl ether
for unclear reasons (entry 14, Table 1 and entries 1 and 2,
Table 3). The reaction of 2-([1,1′-biphenyl]-4-yloxy)pyridine
with p-Me2NC6H4ZnCl gave only 70% product yield. The
existence of ortho-substituents on the phenyl rings of aryl 2-
pyridyl ethers did not lead to decrease of product yields
(entries 3 and 4). Conversely, reaction of 2-([1,1′-biphenyl]-2-
yloxy)pyridine gave higher yield than that of 2-([1,1′-
biphenyl]-4-yloxy)pyridine. Reaction of 2-(2,6-
dimethylphenoxy)pyridine gave very good product yield
(entry 4). Reaction of aryl 2-pyridyl ethers with electron-
withdrawing groups on the phenyl rings including 2-(4-
fluorophenoxy)pyridine, 2-(4-(trifluoromethyl)phenoxy)-
pyridine, and N,N-diethyl-4-(pyridin-2-yloxy)benzamide gave
38−72% yields (entries 5−7). Low yield of the reaction of 2-
(4-fluorophenoxy)pyridine might be because of the existence
of side reaction of the C−F bond cleavage (entry 5).16 Both 2-
(naphthalen-1-yloxy)pyridine and 2-(naphthalen-2-yloxy)-
pyridine also exhibited good reactivity. Their reactions with
p-Me2NC6H4ZnCl afforded the corresponding products in 80
and 77% yields, respectively (entries 8 and 9). Reaction of p-
MeOC6H4ZnCl as an electron-rich nucleophile with 2-(4-(tert-
butyl)phenoxy)pyridine afforded the coupling product in 81%
yield. However, reaction of electron-rich benzo[d][1,3]dioxol-
5-ylzinc chloride with 2-(4-(tert-butyl)phenoxy)pyridine led to
only 55% product yield for unclear reason (entries 10 and 11).
p-MeC6 H4 ZnCl reacted smoothly with 2-(4-
methoxyphenoxy)pyridine, 2-(2-methoxyphenoxy)pyridine, 4-
(pyridin-2-yloxy)benzonitrile, isopropyl 4-(pyridin-2-yloxy)-
benzoate, and ethyl 2-(pyridin-2-yloxy)benzoate, respectively,
affording the corresponding coupling products in 54−74%
yields (entries 12−16). Among the ether reactants, 4-(pyridin-
2-yloxy)benzonitrile resulted in lower product yield. This is
a
The reactions were performed employing 0.2 mmol of 2-(4-(tert-
butyl)phenoxy)pyridine and 0.24 mmol of 4-N,N-dimethylphenylzinc
chloride in 1.5 mL of solvent; 4-N,N-dimethylphenylzinc chloride was
prepared by reaction of 4-N,N-dimethylphenylmagnesium bromide
with an equimolar amount of ZnCl2 in the presence of 1.0 equiv of
LiCl. The yield was calculated based on the integral ratio of H
NMR spectrum of the reaction mixture, using (oxybis(methylene))-
dibenzene as internal standard. Isolated yield. The reaction
temperature was 85 °C. The reaction was run for 12 h. The
reaction was run for 8 h.
b
1
c
d
e
f
7−13). Both 1,4-dioxane and toluene were not apposite
solvents for this conversion. Mixed solvents of THF and NMP
(1-methylpyrrolidin-2-one), DMF (N,N-dimethylformamide),
or DMAc (N,N-dimethylacetamide) were also tested. A 1:1
mixture of THF and DMAc was demonstrated to be the most
suitable solvent for this transformation. We also tried to
decrease amount of NiCl2(PCy3)2. 7.5 mol % of NiCl2(PCy3)2
exhibited the same catalytic result as that of 10 mol % loading.
5 mol % loading of NiCl2(PCy3)2 resulted in some lower yield
(Table 1, entries 14 and 15). Screening of reaction
temperature and time showed that 100 °C and 12 h were
optimal. Lower temperature and shorter time led to yield
decrease (Table 1, entries 16−18).
It has been reported that the presence of Li+ and Mg2+ ions
in the zinc reagents was very important in the Negishi cross-
coupling. In the current reaction, we also examined the effect
of Li+ and Mg2+ ions (Table 2). Without the Li+ ion, the
reaction led to low product yield under the optimized
conditions. Without Mg2+ ion, the reaction gave 64% product
yield which was still lower than that shown in Table 1 (entry
13). Hence, it seems that the presence of an equiv of Mg2+ ion
and an equiv of Li+ ion in the reaction system was optimal for
this transformation. Role of Li+ and Mg2+ ions might be
multifold. Li+ and Mg2+ ions as a Lewis acid might activate aryl
2-pyridine ether via complexation with N and O atoms as well
as π-complexation with the aromatic ring of aryl 2-pyridine
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ascribed to the existence of side reactions possibly via cleavage
of the C−CN bond.17 After the reaction ran for 12 h, thin-layer
chromatography (TLC) analysis showed that 4-(pyridin-2-
yloxy)benzonitrile was completely consumed and some
byproducts were formed. We did not isolate and analyze the
byproducts because of too small amounts. Reaction of 2-(4-
methoxyphenoxy)pyridine and 2-(2-methoxyphenoxy)pyridine
also exhibited formation of byproducts from the TLC analyses.
This probably results from cleavage of the C−OMe bonds
under the current reaction conditions.13e,f o-MeC6H4ZnCl also
exhibited good reactivity. Its reaction with N,N-dimethyl-3-
(pyridin-2-yloxy)aniline and isopropyl 4-(pyridin-2-yloxy)-
benzoate afforded the corresponding products in 85 and 65%
yields, respectively (entries 17 and 18). The zinc reagents with
conjugated or extended aromatic systems showed excellent
reactivity. Respective reaction of (1,1′-biphenyl)-3-ylzinc
chloride and (6-methoxynaphthalen-2-yl)zinc chloride with
aryl 2-pyridyl ethers formed the products in excellent yields
(entries 19 and 20). Electron-poor arylzinc reagents can also
react with aryl 2-pyridyl ethers. Reaction of p-CF3C6H4ZnCl
with N,N-dimethyl-3-(pyridin-2-yloxy)aniline afforded the
desired product in 53% yield and with isopropyl 4-(pyridin-
2-yloxy)benzoate formed the product in 85% yield (entries 21
and 22). In addition, benzyl 2-pyridyl ether also reacted with p-
Me2NC6H4ZnCl smoothly, affording 4-benzyl-N,N-dimethyla-
niline in 86% yield (entry 23).
Table 3. Reactions of Arylzinc Chloride with Aryl 2-Pyridyl
Ethers
a
Alkylation of aryl 2-pyridyl ethers through cross-coupling
reaction has not been reported. We examined reaction of aryl
2-pyridyl ethers with alkylzinc reagents under the same
conditions as above (Table 4). Both MeZnCl and PhCH2ZnCl
reacted smoothly with various aryl 2-pyridyl ethers, including
2-([1,1′-biphenyl]-4-yloxy)pyridine, 2-([1,1′-biphenyl]-2-
yloxy)pyridine, isopropyl 4-(pyridin-2-yloxy)benzoate, N,N-
dimethyl-3-(pyridin-2-yloxy)aniline, and ethyl 2-(pyridin-2-
yloxy)benzoate, affording the corresponding products in 63−
87% yields (entries 1−6). The reaction results were
comparable with those of reaction of arylzinc reagents
(Table 3). Reaction of β-H-containing alkylzinc reagents
such as EtZnCl and iPrZnCl resulted in a mixture of cross-
coupling and hydrogenation products. For example, reaction of
EtZnCl with 2-([1,1′-biphenyl]-4-yloxy)pyridine afforded a
mixture of 4-ethyl-1,1′-biphenyl (27%) and 1,1′-biphenyl
(44%) (entry 7). Ni(COD)2/dcype-catalyzed reaction of
EtZnCl with 2-([1,1′-biphenyl]-4-yloxy)pyridine also pro-
duced a mixture of 4-ethyl-1,1′-biphenyl (39%) and 1,1′-
biphenyl (5%) (entry 8). In this reaction, the ethylation
product is dominant. Use of a bidentate ligand significantly
retards β-H elimination in the catalytic process.18
The reaction conditions also suited for a larger scale of
synthesis. For example, reaction of 5 mmol of 2-(4-(tert-
butyl)phenoxy)pyridine with 1.2 equiv of p-Me2NC6H4ZnCl
under the standard conditions gave 4′-(tert-butyl)-N,N-
dimethyl-[1,1′-biphenyl]-4-amine in 87% yield (Scheme 1).
Preliminary mechanistic studies were performed. First, the
combination of Ni(COD)2 (7.5 mol %) and PCy3 (15 mol %)
can effectively catalyze the reaction of 2-(4-(tert-butyl)
phenoxy)pyridine with p-Me2NC6H4ZnCl to form the desired
product in 98% yield. This shows the catalytically active species
might be a Ni(0) compound. In the presence of an equimolar
amount of 1,1-diphenylethlyene additive, the reaction of 2-(4-
(tert-butyl)phenoxy)pyridine with p-Me2NC6H4ZnCl under
the optimized conditions led to the product in 94% yield
(Scheme 2b). It seems that the reaction may not be a free
a
The reactions were performed according to the conditions shown by
the above equation; 0.3 mmol of aryl 2-pyridyl ethers, 0.36 mmol of
arylzinc reagents, and 2 mL of solvent were used. Arylzinc reagents
were prepared by reaction of the Grignard reagent with ZnCl2 in the
b
presence of 1.0 equiv of LiCl. Isolated yield.
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mode. Hence, we speculate that a N,O-chelate zinc
intermediate might be formed, which weakens the CAr−O
bond. Coordination of zinc with the N and O atoms and
following transmetalation might be the rate-determining step
because the steric hindrance effect of the pyridyl group on the
reaction is much larger than that of the aryl group. On the basis
Table 4. Reaction of Aryl 2-Pyridyl Ethers with Alkylzinc
Reagents
a
of the experimental facts and literature reports,4a,c,5,19
a
plausible mechanism is proposed in Scheme 3. Thus,
Ni(PCy3)2Cl2 is first reduced to L2Ni(0) (A) by the zinc
reagent. Then, oxidative addition reaction of the Ni(0) species
with aryl 2-pyridyl ether-coordinated zinc forms intermediate
B. Transmetalation of B (via C) affords L2Ni(R)Ar (D) which
undergoes reductive elimination to give the cross-coupling
species and the Ni(0) complex A. This is a simplified catalytic
cycle. As mentioned above, the nucleophilic reagents may be a
complex adduct of RZnCl with Mg2+ and Li+ ions rather than
simple RZnCl. Meanwhile, Mg2+ and Li+ ions may also act as
Lewis acids to weaken the C−O bond of aryl 2-pyridyl ethers
via coordination with the O or N atoms. In addition, it is
believed that ligand dissociation is involved in the process of
catalytic reaction. A bidentate ligand is more difficult to
dissociate from the nickel center than a monodentate ligand.
This may be the reason why the Ni−PCy3 complex exbibits
higher catalytic activity than the Ni−bidentate phosphine
complexes such as Ni(COD)2/dcype.19
CONCLUSIONS
■
We demonstrated that NiCl2(PCy3)2 can effectively catalyze
the reaction of aryl 2-pyridyl ethers with arylzinc reagents via
selective cleavage of CAr−OPy bonds. The protocol suited for a
wide substrate range, including sterically hindered substrates
and electron-rich and electron-poor aromatic substrates. A
range of functional groups such as F, CF3, COOEt, COOiPr,
C(O)NEt2, OMe, and NMe2 can be tolerated. β-H-free
alkylzinc reagents also reacted smoothly with various aryl 2-
pyridyl ethers to afford Csp −Csp cross-coupling products.
a
The reactions were performed according to the conditions shown by
the above equation; 0.3 mmol of aryl 2-pyridyl ethers, 0.36 mmol of
organozinc reagents, and 2 mL of solvent were used. The organozinc
reagents were prepared by reaction of Grignard reagent with ZnCl2 in
2
3
However, the reaction of β-H-containing alkylzinc reagents
resulted in a mixture of cross-coupling and hydrogenation
products.
b
c
the presence of 1.0 equiv of LiCl. Isolated yield. The yield was
obtained based on weight of the isolated mixture and integral ratio of
d
the 1H NMR of the two components. A combination of 7.5 mol % of
Ni(COD)2 and 7.5 mol % of dcype was used as the catalyst.
EXPERIMENTAL SECTION
■
All reactions were run under N2 using standard Schlenk and vacuum
line techniques. Tetrahydrofuran and toluene were purified using JC
Meyer Phoenix Solvent Systems. NMP, DMF, and DMAc were dried
using 4 Å molecular sieves, fractionally distilled under reduced
pressure and stored under N2 atmosphere. 1,4-Dioxane was distilled
under nitrogen over sodium and degassed prior to use. Aryl 2-pyridyl
ethers,3a,20 NiCl2(DME),21 NiCl2(dppe),22 and NiCl2(dppf)22 were
synthesized according to the literature procedures. CDCl3 was
obtained from Cambridge Isotope Laboratories. NiCl2(PCy3)2 and
NiCl2(PPh3)2 were purchased from Energy Chemical and used as
received. Ni(COD)2 was purchased from Alfa Aesar and used as
received. Anhydrous ZnCl2 and LiCl were obtained from reagent
suppliers and dried in vacuo at 140 °C for 12 h prior to use. Other
chemicals were purchased from reagent suppliers and used as
received. NMR spectra were measured with a Bruker AV400
Scheme 1. Gram-Scale of Reaction
radical process. In addition, reaction of 3-([1,1′-biphenyl]-4-
yloxy)pyridine (1r) with p-Me2NC6H4ZnCl under the same
conditions gave only trace amount of the cross-coupling
product (Scheme 2c), and reaction of 4-([1,1′-biphenyl]-4-
yloxy)pyridine (1s) with p-Me2NC6H4ZnCl resulted in the
desired product in 18% yield (Scheme 2d). These results seem
to support the CAr−O bond activation via a N,O-chelate nickel
mode. However, reaction of 2-(4-(tert-butyl)phenoxy)-6-
methylpyridine (1t) with p-Me2NC6H4ZnCl afforded the
desired product in only 8% yield (Scheme 2e), whereas
reaction of 2-(2,6-dimethylphenoxy)pyridine (1e) with p-
Me2NC6H4ZnCl at the same conditions gave the desired
product in 83% yield (entry 4, Table 3). These experimental
facts are inconsistent with the N,O-chelate nickel reaction
1
spectrometer or a Bruker AV500 spectrometer at 25 °C. The H
NMR chemical shifts were referenced to TMS; the 13C NMR
chemical shifts were recorded relative to the solvent resonance. High-
resolution mass spectra (HRMS) were recorded with a Thermo
Fisher LTQ Orbitrap XL mass spectrometer.
General Procedure for the Catalytic Coupling of Aryl 2-
Pyridyl Ethers with Organozinc Reagents. NiCl2(PCy3)2 (16 mg,
0.023 mmol, 0.075 equiv), aryl 2-pyridyl ethers (0.30 mmol, 1 equiv),
and DMAc (1.0 mL) were successively put into a Schlenk tube. Then,
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Scheme 2. Mechanistic Studies
Gram-Scale Reaction. NiCl2(PCy3)2 (0.259 g, 0.375 mmol), 2-
(4-(tert-butyl)phenoxy) pyridine (1.14 g, 5.0 mmol), and DMAc (17
mL) were put into a Schlenk tube. To the stirred mixture was added
p-Me2NC6H4ZnCl (17 mL, 0.36 M solution in THF, 6.1 mmol). The
resulting mixture was continually stirred at 100 °C (oil bath) for 12 h,
cooled to room temperature, and H2O (30 mL) and HOAc (1 mL)
were added. The mixture was extracted with diethyl ether (3 × 30
mL). The combined ether phases were dried with anhydrous Na2SO4
and concentrated by rotary evaporation. The residue was purified by
column chromatography (silica gel, eluting with a mixture of
petroleum ether and EtOAc 60:1 v/v) to give a white solid (1.11 g,
87%).
Scheme 3. Proposed Catalytic Cycle
Ni(COD)2/dcype-Catalyzed Reaction of 2-([1,1′-Biphenyl]-4-
yloxy)pyridine with EtZnCl. Ni(COD)2 (6.2 mg, 0.023 mmol),
dcype (9.5 mg, 0.023 mmol), 2-([1,1′-biphenyl]-4-yloxy) pyridine
(74 mg, 0.30 mmol), and DMAc (1.0 mL) were put into a Schlenk
tube. To the stirred solution was added EtZnCl (1.0 mL, 0.36 M
solution in THF, 0.36 mmol) at room temperature. The resulting
mixture was continually stirred at 100 °C (oil bath) for 12 h and then
cooled to room temperature. H2O (10 mL) and several drops of
HOAc were added. The mixture was extracted with diethyl ether (3 ×
10 mL). The combined ether phases were dried with anhydrous
Na2SO4 and concentrated by rotary evaporation. The residue was
purified by column chromatography (silica gel, eluting with petroleum
ether) to give a white solid (24 mg) as a mixture of 4-ethylbiphenyl
(39%)23 and biphenyl (5%).24
organozinc reagents (1.0 mL, 0.36 M solution in THF, 0.36 mmol, 1.2
equiv) were added to the stirred mixture. The resulting mixture was
continually stirred at 100 °C (oil bath) for 12 h and then cooled to
room temperature. H2O (10 mL) and several drops of HOAc were
added. The mixture was extracted with diethyl ether (3 × 10 mL).
The combined ether phases were dried with anhydrous Na2SO4 and
concentrated by rotary evaporation. The residue was purified by
column chromatography (silica gel).
4′-(tert-Butyl)-N,N-dimethyl-[1,1′-biphenyl]-4-amine (3a).25 Elu-
tion with petroleum ether/EtOAc 50/1 (v/v), white solid, yield 74
mg (98%). 1H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 4H),
7.42 (d, J = 8.5 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 2.98 (s, 6H), 1.35
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(s, 9H). 13C{1H} NMR (101 MHz, CDCl3): δ 149.9, 149.0, 138.5,
129.4, 127.7, 126.1, 125.7, 112.9, 40.8, 34.6, 31.6.
1.35 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3): δ 159.1, 149.7,
138.1, 133.8, 128.1, 126.5, 125.8, 114.3, 55.5, 34.6, 31.5.
5-(4-(tert-Butyl)phenyl)benzo[d][1,3]dioxole (3l). Elution with
N,N-Dimethyl-[1,1′-biphenyl]-4-amine (3b).26 Elution with petro-
1
petroleum ether/EtOAc 40/1 (v/v), brown solid, yield 42 mg
leum ether/EtOAc 50/1 (v/v), white solid, yield 54 mg (91%). H
1
(55%). H NMR (400 MHz, CDCl3): δ 7.49−7.40 (m, 4H), 7.09−
NMR (400 MHz, CDCl3): δ 7.56 (d, J = 7.8 Hz, 2H), 7.53−7.48 (m,
2H), 7.40 (t, J = 7.6 Hz, 2H), 7.26 t, (J = 7.3 Hz, 1H), 6.81 (d, J = 8.7
Hz, 2H), 2.99 (d, J = 1.2 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 150.1, 141.6, 129.4, 128.8, 127.8, 126.4, 126.1, 112.9, 40.7.
N,N-Dimethyl-[1,1′:4′,1″-terphenyl]-4-amine (3c).27 Elution with
petroleum ether/EtOAc 50/1 (v/v), brown solid, yield 57 mg (70%).
1H NMR (400 MHz, CDCl3): δ 7.67−7.60 (m, 6H), 7.56 (d, J = 8.7
Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 6.82 (d, J =
8.7 Hz, 2H), 3.00 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
150.2, 141.1, 140.3, 138.9, 128.9, 128.8, 127.8, 127.5, 127.2, 127.1,
126.7, 112.9, 40.7.
7.02 (m, 2H), 6.67 (d, J = 8.0 Hz, 1H), 5.99 (s, 2H), 1.35 (s, 9H).
13C{1H} NMR (101 MHz, CDCl3): δ 150.1, 148.2, 147.0, 138.2,
135.6, 126.7, 125.8, 120.6, 108.7, 107.7, 101.2, 34.6, 31.5. HRMS
(ESI) m/z: [M + H]+ calcd for C17H19O2, 255.1380; found, 255.1377.
4-Methoxy-4′-methyl-1,1′-biphenyl (3m).28 Elution with petro-
1
leum ether/EtOAc 40/1 (v/v), white solid, yield 37 mg (62%). H
NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.1
Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.84 (s,
3H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 159.1,
138.1, 136.5, 133.9, 129.6, 128.1, 126.7, 114.3, 55.5, 21.2.
2-Methoxy-4′-methyl-1,1′-biphenyl (3n).32 Elution with petro-
N,N-Dimethyl-[1,1′:2′,1″-terphenyl]-4-amine (3d).28 Elution with
petroleum ether/EtOAc 50/1 (v/v), brown solid, yield 77 mg (85%).
1H NMR (400 MHz, CDCl3): δ 7.37−7.20 (m, 4H), 7.18−7.05 (m,
5H), 6.92 (d, J = 8.8 Hz, 2H), 6.49 (d, J = 8.8 Hz, 2H), 2.81 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 149.2, 142.3, 140.7, 140.4,
130.8, 130.7, 130.6, 130.0, 129.6, 128.0, 127.6, 126.7, 126.3, 112.1,
40.6.
1
leum ether/EtOAc 40/1 (v/v), white solid, yield 41 mg (69%) H
NMR (400 MHz, CDCl3): δ 7.42 (d, J = 8.2 Hz, 2H), 7.32−7.26 (m,
2H), 7.24−7.18 (m, 2H), 7.00 (dt, J = 7.5, 1.1 Hz, 1H), 6.96 (d, J =
7.8 Hz, 1H), 3.79 (s, 3H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3): δ 156.6, 136.7, 135.7, 130.9, 130.8, 129.5, 128.9, 128.5,
120.9, 111.3, 55.6, 21.3.
4′-Methyl-[1,1′-biphenyl]-4-carbonitrile (3o).32 Elution with
petroleum ether/EtOAc 50/1 (v/v), white solid, yield 31 mg
N,N,2′,6′-Tetramethyl-[1,1′-biphenyl]-4-amine (3e).29 Elution
with petroleum ether/EtOAc 50/1 (v/v), white solid, yield 56 mg
(83%). 1H NMR (400 MHz, CDCl3): δ 7.16−7.06 (m, 3H), 7.01 (d,
J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 2.99 (s, 6H), 2.07 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 149.3, 142.2, 137.0, 129.9,
1
(54%). H NMR (400 MHz, CDCl3): δ 7.70 (d, J = 8.6 Hz, 2H),
7.66 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 7.9 Hz,
2H), 2.41 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 145.7,
138.9, 136.4, 132.7, 130.0, 127.6, 127.2, 119.2, 110.6, 21.3.
129.3, 127.3, 126.7, 112.5, 40.8, 21.1.
Isopropyl 4′-Methyl-[1,1′-biphenyl]-4-carboxylate (3p). Elution
with petroleum ether/EtOAc 60/1 (v/v), white solid, yield 53 mg
(70%). 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 8.6 Hz, 2H), 7.55
(d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H),
5.19 (hept, J = 6.2 Hz, 1H), 2.32 (s, 3H), 1.30 (d, J = 6.3 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 166.2, 145.5, 138.1, 137.3,
130.1, 129.8, 129.5, 127.2, 126.8, 68.4, 22.1, 21.3. HRMS (ESI) m/z:
[M + H]+ calcd for, 255.1380; found, 255.1378.
4′-Fluoro-N,N-dimethyl-[1,1′-biphenyl]-4-amine (3f).30 Elution
with petroleum ether/EtOAc 50/1 (v/v), brown solid, yield 24 mg
(38%). 1H NMR (400 MHz, CDCl3): δ 7.52−7.46 (m, 2H), 7.44 (d,
J = 9.0 Hz, 2H), 7.07 (t, J = 8.8 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H),
2.99 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ 161.9 (d, J =
245.4 Hz), 150.1, 137.5 (d, J = 3.0 Hz), 128.5, 127.8 (d, J = 8.1 Hz),
127.7, 115.5 (d, J = 21.2 Hz), 112.9, 40.7.
Ethyl 4′-Methyl-[1,1′-biphenyl]-2-carboxylate (3q).33 Elution
with petroleum ether/EtOAc 60/1 (v/v), white solid, yield 53 mg
N,N-Dimethyl-4′-(trifluoromethyl)-[1,1′-biphenyl]-4-amine
(3g).26 Elution with petroleum ether/EtOAc 50/1 (v/v), white solid,
1
yield 58 mg (72%). H NMR (400 MHz, CDCl3): δ 7.68−7.60 (m,
1
(74%). H NMR (400 MHz, CDCl3): δ 7.79 (dd, J = 7.7, 1.4 Hz,
4H), 7.52 (d, J = 8.9 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.01 (s, 6H).
1H), 7.49 (dt, J = 7.5, 1.4 Hz, 1H), 7.40−7.32 (m, 2H), 7.25−7.15
(m, 4H), 4.11 (q, J = 7.1 Hz, 2H), 2.39 (s, 3H), 1.03 (t, J = 7.1 Hz,
3H). 13C{1H} NMR (101 MHz, CDCl3): δ 169.0, 142.5, 138.6, 136.9,
131.4, 131.1, 130.7, 129.7, 128.8, 128.4, 127.0, 61.0, 21.3, 13.8.
N,N,2′-Trimethyl-[1,1′-biphenyl]-3-amine (3r). Elution with pe-
troleum ether/EtOAc 50/1 (v/v), white solid, yield 54 mg (85%). 1H
NMR (400 MHz, CDCl3): δ 7.30−7.18 (m, 5H), 6.75−6.65 (m, 3H),
2.96 (s, 6H), 2.29 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ
150.5, 143.0, 135.6, 130.3, 129.8, 128.8, 127.2, 125.7, 117.8, 113.7,
111.1, 40.8, 20.6. HRMS (ESI) m/z: [M + H]+ calcd for C15H18N,
212.1434; found, 212.1430.
Isopropyl 2′-Methyl-[1,1′-biphenyl]-4-carboxylate (3s). Elution
with petroleum ether/EtOAc 60/1 (v/v), white solid, yield 50 mg
(65%). 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.1 Hz, 2H), 7.39
(d, J = 8.2 Hz, 2H), 7.31−7.19 (m, 4H), 5.29 (hept, J = 6.3 Hz, 1H),
2.26 (s, 3H), 1.39 (d, J = 6.3 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 166.2, 146.7, 141.1, 135.3, 130.6, 129.7, 129.5, 129.3,
127.9, 126.0, 68.5, 22.1, 20.5. HRMS (ESI) m/z: [M + H]+ calcd for
C17H19O2, 255.1380; found, 255.1375.
13C{1H} NMR (101 MHz, CDCl3): δ 150.7, 144.8, 128.0, 127.99 (q,
J = 32.1 Hz), 127.4, 126.4, 125.7 (q, J = 3.8 Hz), 124.7 (q, J = 272.7
Hz), 112.8, 40.6.
4′-(Dimethylamino)-N,N-diethyl-[1,1′-biphenyl]-4-carboxamide
(3h).26 Elution with petroleum ether/EtOAc 40/1 (v/v), white solid,
1
yield 53 mg (60%). H NMR (400 MHz, CDCl3): δ 7.56 (d, J = 8.3
Hz, 2H), 7.50 (d, J = 8.9 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 6.79 (d, J
= 8.8 Hz, 2H), 3.53 (b, 2H), 3.32 (b, 2H), 2.98 (s, 6H), 1.22 (b, 3H),
1.16 (b, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 171.5, 150.3,
142.1, 134.7, 128.1, 127.7, 126.9, 126.0, 112.7, 43.5, 40.5, 39.3, 14.3,
13.0.
N,N-Dimethyl-4-(naphthalen-1-yl)aniline (3i).30 Elution with
petroleum ether/EtOAc 60/1 (v/v), brown solid, yield 59 mg
1
(80%). H NMR (400 MHz, CDCl3): δ 8.01 (dd, J = 0.7, 8.4 Hz,
1H), 7.90−7.84 (m, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.54−7.35 (m,
6H), 6.85 (d, J = 8.8 Hz, 2H), 3.01 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3): δ 149.9, 140.6, 134.0, 132.1, 130.9, 128.9, 128.3,
127.0, 126.9, 126.5, 125.8, 125.7, 125.6, 112.4, 40.8.
N,N-Dimethyl-4-(naphthalen-2-yl)aniline (3j).30 Elution with
petroleum ether/EtOAc 60/1 (v/v), yellow solid, yield 57 mg
(77%). 1H NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.88−7.77 (m,
3H), 7.75−7.68 (m, 1H), 7.62 (d, J = 8.9 Hz, 2H), 7.49−7.36 (m,
2H), 6.80 (d, J = 8.8 Hz, 2H), 2.96 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3): δ 150.1, 138.7, 134.0, 132.2, 129.1, 128.3, 128.1,
127.7, 126.2, 125.4, 125.3, 124.3, 113.0, 40.7.
Isopropyl [1,1′:3′,1″-Terphenyl]-4-carboxylate (3t). Elution with
petroleum ether/EtOAc 60/1 (v/v), white solid, yield 86 mg (90%).
1H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.3 Hz, 2H), 7.82 (t, J =
1.7 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.67−7.57 (m, 4H), 7.56−7.51
(m, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.41−7.35 (m, 1H), 5.32 (hept, J =
6.2 Hz, 1H), 1.43 (d, J = 6.3 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 166.1, 145.5, 142.1, 141.1, 140.8, 130.2, 129.9, 129.5,
129.0, 127.7, 127.4, 127.2, 127.1, 126.4, 126.35, 68.5, 22.1. HRMS
(ESI) m/z: [M + H]+ calcd for C22H21O2 ([M + H]+), 317.1536;
found, 317.1534.
4-(tert-Butyl)-4′-methoxy-1,1′-biphenyl (3k).31 Elution with
petroleum ether/EtOAc 40/1 (v/v), white solid, yield 58 mg
1
(81%). H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 8.8 Hz, 1H),
2-(4-(tert-Butyl)phenyl)-6-methoxynaphthalene (3u).34 Elution
with petroleum ether/EtOAc 50/1 (v/v), white solid, yield 82 mg
7.49 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 2.2 Hz, 1H), 7.47 (d, J = 2.2 Hz,
1H), 7.44 (d, J = 8.6 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H),
2240
https://dx.doi.org/10.1021/acs.joc.0c02389
J. Org. Chem. 2021, 86, 2235−2243

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(95%). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 1.6 Hz, 1H), 7.77
(dd, J = 8.8, 2.0 Hz, 2H), 7.70 (dd, J = 8.5, 1.9 Hz, 1H), 7.63 (d, J =
8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.18−7.11 (m, 2H), 3.91 (s,
3H), 1.37 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3): δ 157.8,
150.2, 138.4, 136.4, 133.8, 129.8, 129.4, 127.3, 127.0, 126.2, 125.9,
125.5, 119.2, 105.7, 55.4, 34.7, 31.5.
biphenyl (yield of 4-ethyl-1,1′-biphenyl is 39%). NMR spectra of 4-
1
ethyl-1,1′-biphenyl: H NMR (500 MHz, CDCl3): δ 7.62−7.55 (m,
2H), 7.52 (d, J = 8.2 Hz, 2H), 7.46−7.39 (m, 2H), 7.37−7.30 (m,
1H), 7.27 (d, J = 8.1 Hz, 2H), 2.69 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6
Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 143.5, 141.3, 138.7,
128.8, 128.4, 127.21, 127.15, 127.1, 28.7, 15.7.
N,N-Dimethyl-4′-(trifluoromethyl)-[1,1′-biphenyl]-3-amine (3v).
Mechanistic Studies. Reaction of 2-(4-(tert-Butyl)phenoxy)-
pyridine with p-Me2NC6H4ZnCl under Catalysis of Ni(COD)2−PCy3.
Ni(COD)2 (4 mg, 0.0145 mmol), PCy3 (0.047 mL, 20 wt % in
toluene, 0.029 mmol), and DMAc (0.75 mL) were put into a Schlenk
tube. The mixture was stirred for 5 min at room temperature. To the
solution were successively added 2-(4-(tert-butyl)phenoxy)pyridine
(45 mg, 0.2 mmol) and p-Me2NC6H4ZnCl (0.75 mL, 0.32 M solution
in THF, 0.24 mmol) with stirring. The resulting mixture was
continually stirred at 100 °C for 12 h and then cooled to room
temperature. H2O (10 mL), and several drops of HOAc were added.
The mixture was extracted with diethyl ether (3 × 10 mL). The
combined ether phases were added Bn2O (0.019 mL, 0.1 mmol).
Solvent was removed by rotary evaporation. The residue was
Elution with petroleum ether/EtOAc 50/1 (v/v), brown solid, yield
1
42 mg (53%). H NMR (400 MHz, CDCl3): δ 7.72−7.63 (m, 4H),
7.33 (t, J = 7.9 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 6.89 (t, J = 2.0 Hz,
1H), 6.78 (dd, J = 8.2, 2.4 Hz, 1H), 3.01 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3): δ 151.1, 145.9, 141.0, 129.8, 129.3 (q, J = 32.5 Hz),
127.7, 125.7 (q, J = 3.8 Hz), 124.5 (q, J = 272.7 Hz), 115.8, 112.5,
111.5, 40.8. HRMS (ESI) m/z: [M + H]+ calcd for C15H15F3N,
266.1151; found, 266.1148.
Isopropyl 4′-(Trifluoromethyl)-[1,1′-biphenyl]-4-carboxylate
(3w).35 Elution with petroleum ether/EtOAc 60/1 (v/v), white
solid, yield 78 mg (84%). 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J =
8.6 Hz, 2H), 7.71 (s, 4H), 7.65 (d, J = 8.6 Hz, 2H), 5.29 (hept, J = 6.3
Hz, 1H), 1.40 (d, J = 6.3 Hz, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 165.9, 144.0, 143.7, 130.7, 130.3, 130.2 (q, J = 32.7 Hz),
127.7, 127.3, 126.0 (q, J = 3.7 Hz), 124.3 (q, J = 272.7 Hz), 68.7,
22.1.
1
determined by the H NMR spectrum to calculate yield based on
the integral ratio. 98% yield of 1a was obtained.
NiCl2(PCy3)2-Catalyzed Reaction of 2-(4-(tert-Butyl)phenoxy)-
pyridine with p-Me2NC6H4ZnCl in the Presence of 1,1-Dipheny-
lethlyene. NiCl2(PCy3)2 (10 mg, 0.015 mmol) and DMAc (0.75 mL)
were put into a Schlenk tube. To the solution were successively added
2-(4-(tert-butyl)phenoxy)pyridine (45 mg, 0.2 mmol), 1,1-dipheny-
lethlyene (36 mg, 0.2 mmol), and p-Me2NC6H4ZnCl (0.75 mL, 0.32
M solution in THF, 0.24 mmol) with stirring. The resulting mixture
was continually stirred at 100 °C (oil bath) for 12 h and then cooled
to room temperature. H2O (10 mL), and several drops of HOAc were
added. The mixture was extracted with diethyl ether (3 × 10 mL).
The combined ether phases were added to Bn2O (0.019 mL, 0.1
mmol). Solvent was removed by rotary evaporation. The residue was
determined by the 1H NMR spectrum to calculate yield based on the
integral ratio. 94% yield of 3a was obtained.
NiCl2(PCy3)2-Catalyzed Reaction of 4-([1,1′-Biphenyl]-4-yloxy)-
pyridine with p-Me2NC6H4ZnCl. NiCl2(PCy3)2 (8.6 mg, 0.0124
mmol), 4-([1,1′-biphenyl]-4-yloxy) pyridine (41 mg, 0.166 mmol),
and DMAc (0.62 mL) were put into a Schlenk tube. To the solution
was added p-Me2NC6H4ZnCl (0.62 mL, 0.32 M solution in THF, 0.2
mmol) with stirring. The resulting mixture was continually stirred at
100 °C (oil bath) for 12 h and then cooled to room temperature. H2O
(10 mL) and several drops of HOAc were added. The mixture was
extracted with diethyl ether (3 × 10 mL). The combined ether phases
were dried with anhydrous Na2SO4 and concentrated by rotary
evaporation. The residue was purified by column chromatography
(silica gel) to give 3c (8 mg, 18%).
NiCl2(PCy3)2-Catalyzed Reaction of 2-(4-(tert-Butyl)phenoxy)-3-
methylpyridine with p-Me2NC6H4ZnCl. NiCl2(PCy3)2 (16 mg, 0.023
mmol), 2-(4-(tert-butyl)phenoxy)-3-methyl pyridine (73 mg, 0.30
mmol), and DMAc (1.0 mL) were put into a Schlenk tube. p-
NMe2C6H4ZnCl (1.0 mL, 0.36 M solution in THF, 0.36 mmol) was
added into the mixture with stirring. The resulting mixture was
continually stirred at 100 °C (oil bath) for 12 h and then cooled to
room temperature. H2O (10 mL) and several drops of HOAc were
added. The mixture was extracted with diethyl ether (3 × 10 mL).
The combined ether phases were dried with anhydrous Na2SO4 and
concentrated by rotary evaporation. The residue was purified by
column chromatography (silica gel) to give 3a as a white solid (6.1
mg, 8%).
4-([1,1′-Biphenyl]-4-ylmethyl)-N,N-dimethylaniline (3x). Elution
with petroleum ether/EtOAc 50/1 (v/v), white solid, yield 74 mg
1
(86%). H NMR (400 MHz, CDCl3): δ 7.58−7.53 (m, 2H), 7.51−
7.46 (m, 2H), 7.48 (t, J = 7.6 Hz, 2H), 7.33−7.27 (m, 1H), 7.24 (d, J
= 8.1 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 6.69 (d, J = 8.6 Hz, 2H), 3.92
(s, 2H), 2.89 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ 149.3,
141.4, 141.2, 138.9, 129.7, 129.3, 129.2, 128.8, 127.2, 127.1, 127.09,
113.1, 40.9, 40.7. HRMS (ESI) m/z: [M + H]+ calcd for C21H22N,
288.1747; found, 288.1744.
4-Methyl-1,1′-biphenyl (4a).36 Elution with petroleum ether,
1
white solid, yield 37 mg (73%). H NMR (400 MHz, CDCl3): δ
7.57 (d, J = 7.4 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.41 (t, J = 7.7 Hz,
2H), 7.31 (t, J = 7.3 Hz, 1H), 7.23 (d, J = 8.1 Hz, 2H), 2.38 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3): δ 141.3, 138.5, 137.1, 129.6,
128.8, 127.1, 21.2.
2-Methyl-1,1′-biphenyl (4b).36 Elution with petroleum ether,
1
white solid, yield 41 mg (81%). H NMR (400 MHz, CDCl3): δ
7.40 (t, J = 7.4 Hz, 2H), 7.36−7.29 (m, 3H), 7.28−7.21 (m, 4H),
2.27 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 142.1, 135.5,
130.4, 129.9, 129.3, 128.2, 127.4, 126.9, 125.9, 20.6.
Isopropyl 4-Methylbenzoate (4c).37 Elution with petroleum ether/
1
EtOAc 100/1 (v/v), white solid, yield 38 mg (71%). H NMR (400
MHz, CDCl3): δ 7.93 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H),
5.24 (hept, J = 6.3 Hz, 1H), 2.40 (s, 3H), 1.36 (d, J = 6.3 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 166.3, 143.4, 129.7, 129.1,
128.3, 68.2, 22.1, 21.7.
3-Benzyl-N,N-dimethylaniline (4d).38 Elution with petroleum
ether/EtOAc 100/1 (v/v), yellow solid, yield 54 mg (85%). 1H
NMR (400 MHz, CDCl3): δ 7.31−7.10 (m, 6H), 6.62−6.52 (m, 3H),
3.93 (s, 2H), 2.89 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3): δ
150.9, 142.0, 141.6, 129.2, 129.0, 128.5, 126.0, 117.6, 113.5, 110.6,
42.5, 40.7.
4-Benzyl-1,1′-biphenyl (4e).39 Elution with petroleum ether, white
solid, yield 64 mg (87%). 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J =
7.2 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.34−
7.16 (m, 8H), 4.00 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
141.1, 140.4, 139.2, 129.5, 129.1, 128.9, 128.6, 127.3, 127.2, 127.1,
126.3, 41.7.
Isopropyl 4-Benzylbenzoate (4f). Elution with petroleum ether/
EtOAc 100/1 (v/v), yellow oil, yield 54 mg (71%). H NMR (400
1
ASSOCIATED CONTENT
■
MHz, CDCl3): δ 7.96 (d, J = 8.2 Hz, 2H), 7.34−7.11 (m, 7H), 5.23
(hept, J = 6.2 Hz, 1H), 4.02 (s, 2H), 1.35 (d, J = 6.2 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 166.2, 146.4, 140.3, 129.9,
129.0, 128.98, 128.95, 128.7, 126.5, 68.3, 42.0, 22.1. HRMS (ESI) m/
z: [M + H]+ calcd for C17H19O2, 255.1380; found, 255.1375.
4-Ethyl-1,1′-biphenyl (4g).23 Elution with petroleum ether, white
solid, yield 20 mg as a 9:1 mixture of 4-ethyl-1,1′-biphenyl and
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02389.
1
Copies of H and 13C NMR spectra of the reaction
products (PDF)
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Article
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AUTHOR INFORMATION
Corresponding Author
■
Zhong-Xia Wang − CAS Key Laboratory of Soft Matter
Chemistry and Department of Chemistry, University of
Science and Technology of China, Hefei, Anhui 230026, P. R.
China; Collaborative Innovation Center of Chemical Science
and Engineering (Tianjin), Tianjin 300072, P. R. China;
orcid.org/0000-0001-8126-8778; Phone: +86 551
63603043; Email: zxwang@ustc.edu.cn
Authors
Wei-Can Dai − CAS Key Laboratory of Soft Matter Chemistry
and Department of Chemistry, University of Science and
Technology of China, Hefei, Anhui 230026, P. R. China
Bo Yang − CAS Key Laboratory of Soft Matter Chemistry and
Department of Chemistry, University of Science and
Technology of China, Hefei, Anhui 230026, P. R. China;
orcid.org/0000-0003-0612-5712
Shi-He Xu − CAS Key Laboratory of Soft Matter Chemistry
and Department of Chemistry, University of Science and
Technology of China, Hefei, Anhui 230026, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02389
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Aromatic Compounds; Mortier, J., Ed.; John Wiley & Sons: Hoboken,
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Basic Research Program of China
(grant no. 2015CB856600) for financial support. We also
thank Wei-Ze Li for performing the additional experiments.
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