Synthesis of Biaryls via Decarbonylative Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Aryl Anhydrides

Article abstract of DOI:10.1021/acs.joc.0c02266

Transition metal-catalyzed cross-couplings have been widely employed in the synthesis of many important molecules in synthetic chemistry for the construction of diverse C-C bonds. Conventional cross-coupling reactions require active electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly enough. Herein, we disclose the first nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl anhydrides and arylboronic acids for the synthesis of biaryls in a decarbonylation manner. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process.

Full text of DOI:10.1021/acs.joc.0c02266

pubs.acs.org/joc
Article
Synthesis of Biaryls via Decarbonylative Nickel-Catalyzed Suzuki−
Miyaura Cross-Coupling of Aryl Anhydrides
Jing-Ya Zhou, Rui-Qing Liu, Cheng-Yi Wang, and Yong-Ming Zhu*
Cite This: https://dx.doi.org/10.1021/acs.joc.0c02266
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Transition metal-catalyzed cross-couplings have been widely employed in the synthesis of many important molecules
in synthetic chemistry for the construction of diverse C−C bonds. Conventional cross-coupling reactions require active electrophilic
coupling partners, such as organohalides or sulfonates, which are not environmentally friendly enough. Herein, we disclose the first
nickel-catalyzed Suzuki−Miyaura cross-coupling of aryl anhydrides and arylboronic acids for the synthesis of biaryls in a
decarbonylation manner. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating
substituents in this process.
acids react with arylboronic acids in a decarbonylative manner
(Scheme 1a). Michal Szostak’s group9 have successfully
reported that nickel and palladium catalyze the amide
decarbonylation Suzuki−Miyaura cross-coupling reaction for
the synthesis of biaryl groups through the selective activation
of the N−C(O) bond of the amide. At the same time, their
research team also reported that palladium catalyzed the cross-
coupling reaction between carboxylic acid and phenylboronic
acid10 (Scheme 1b). Sanford’ group developed a nickel-
catalyzed coupling of arylboronic acids with acid fluorides,
which are formed in situ from readily available carboxylic
acids11 (Scheme 1c). Gooßen first obtained an asymmetric
biaryl group under the rhodium-catalyzed decarbonylation
cross-coupling reaction of aryl anhydrides with triaryl
boroxines12 (Scheme 1d). In 2019, Rueping’s research group
reported an unconventional Suzuki-type method for synthesiz-
ing biaryls. This method through nickel-catalyzed aldehydes
and organoboron reagents cross-couple under base-free
conditions.13 For economic and environmental considerations,
we chose to use nickel as a catalyst. Furthermore, the use of the
earth-abundant first-row metal nickel as a catalyst in the target
coupling makes this reaction commercially more appealing.
INTRODUCTION
■
Substituted biphenyls are key structural motifs in bioactive
medicinal agents, natural products, and polymers.1 Cross-
coupling reactions catalyzed by transition metals have become
indispensable tools for the construction of C−C bonds.2 The
Suzuki−Miyaura cross-coupling is one of the most important
and prevalent methods for the construction of C−C bonds in
organic and medicinal chemistry.3 Arylboronic acids appeared
to be the preferred carbon nucleophile because they are readily
available,4 nontoxic, and air- and-moisture stable compounds
that are resistant to the presence of a variety of sensitive
functions. Although the traditional cross-coupling reaction
between the organoboron nucleophile and haloaryl electro-
phile5 has been widely used in synthetic transformation, the
generation of corrosive halogens is detrimental from synthetic
and environmental perspectives. In recent years, with the rapid
development of organometallic chemistry, there is a growing
interest in the use of aroyl compounds in metal-catalyzed
decarboxylative or decarbonylative coupling reactions.6 How-
ever, in catalytic cross-coupling reactions, the decarbonylation
step was found to be less favorable and aryl ketones were easily
formed.7 Therefore, in recent years, organic scientists have
devoted to the development of cross-coupling methods that
are beneficial to the decarbonylation process. At present, there
have been reports of palladium, rhodium, and nickel transition
metal-catalyzed decarbonylation cross-coupling reactions
(Scheme 1). For example, Itami et al.8 reported using a user-
friendly and inexpensive nickel catalyst; a range of phenyl
esters of aromatic, heteroaromatic, and aliphatic carboxylic
Received: September 21, 2020
https://dx.doi.org/10.1021/acs.joc.0c02266
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Scheme 1. Different Catalytic Conditions for the Synthesis of Biphenyls
Our laboratory has previously reported that anhydrides and
thiophenols build C−S bonds through decarbonylation or
decarbonylation accompanied by decarboxylation under the
catalysis of nickel.14 Because most carboxylic acids can be
easily (and possibly in situ) converted to anhydrides,15 our
primary goal is to develop a catalytic system capable of
coupling anhydrides with arylboronic acids.
°C was found to be optimal (Table 1, entry 9). With other air-
stable nickel sources such as NiCl2 and Ni(OAC)2·4H2O, the
yield was reduced compared to the Ni(PCy3)2Cl2 (Table 1,
entry 10−11). Compared with other ligands, PCy3 was the
most optimal for this reaction (Table 1, entry 12−13). When
no additional ligand is added, the yield of the target product
decreased (Table 1, entry 14). No product was observed in the
absence of a nickel catalyst (Table 1, entry 15).
After establishing optimal catalytic conditions [Ni-
(PCy3)2Cl2, PCy3, Cs2CO3 and toluene, 150 °C, and 24 h],
the scope of this novel Suzuki−Miyaura biaryl cross-coupling
of anhydrides was next investigated (Table 2). As shown in
Table 2, we found that in this catalytic system, the reaction
range is very wide and can tolerate the coupling of electron-
rich (Table 2, 3a−h, 3j−r), electron-neutral (Table 2, 3i), and
electron-withdrawing (Table 2, 3t−x) substrates. Phenyl-
boronic acids of electron-rich groups such as methoxy, ethoxy,
hydrocarbyl, and silane reacted smoothly to provide the
corresponding substituted biphenyls. In addition to the low
yield of some target products, such as 3j, 3l, 3m, and 3q, most
electron-rich groups were transferred into the cross-coupling
products in moderate to excellent yields. The hindered
substrate showed good reactivity, and the target product was
obtained in a moderate yield (Table 2, 3n−o). Furthermore, in
addition to the product 3t, moderate yields were obtained with
phenylboronic acids bearing electron-withdrawing substitu-
RESULTS AND DISCUSSION
■
We initiated this study by finding suitable catalytic conditions
for the decarbonylative cross-coupling of aryl anhydrides and
arylboronic acids, using 2-naphthoic anhydride (1a) and (4-
methoxyphenyl) boronic acid (2a) as model substrates. We
focused on the use of nickel(II) as a catalyst because of its low
cost and stability under air and moisture conditions.16,17 Key
optimization results are shown in Table 1. We found that in
the presence of 5 mol % Ni(PCy3)2Cl2, 10 mol % PCy3, and
3.0 equiv of K3PO4, a small amount of decarbonylated cross-
coupling target products was formed. Among various bases
(Table 1, entry 1−6), a dramatic effect of Cs2CO3 was
observed with 88% yield of 3a (Table 1, entry 3). Under these
reaction conditions, a decrease in the yield was observed by
employing 1,4-dioxane as the solvent (Table 1, entry 7). It is
worth noting that when the loading of Cs2CO3 was increased
to 4.5 equiv, the yield of the target product decreased (Table 1,
entry 8). The temperature effect was also examined and 150
B
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a
Table 1. Optimization of Ni-Catalyzed Suzuki Biaryl Synthesis Through Coupling of Anhydrides with Arylboronic Acids
entry
Ni cat.
ligand
base
solvent
toluene
yield (%)
1
2
3
4
5
6
7
8
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
Ni(PCy3)2Cl2
NiCl2
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PCy3
PPh3
dppp
K3PO4
trace
38
88
30
26
K2CO3
Cs2CO3
CsF
toluene
toluene
toluene
toluene
toluene
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
ButONa
ButOK
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
none
72
b
40
c
9
37
d
10
11
12
13
14
15
none
Ni(OAc)2·4H2O
Ni(PPh3)2Cl2
Ni(dppp)Cl2
Ni(PCy3)2Cl2
none
trace
21
45
none
PCy3
a
General conditions: the reactions were run on 0.2 mmol 2-naphthoic anhydride in solvent (1.5 mL), (4-methoxyphenyl)boronic acid (1.5 equiv),
catalyst (5 mol %), ligand (10 mol %), and base (3.0 equiv) under nitrogen in a sealed tube at 150 °C for 24 h. Isolated yield after purification of
b
c
d
column chromatography. Cs2CO3 (4.5 equiv). 130 °C. NiCl2 (5 mol %), PCy3 (20 mol %).
ents; it may be due to the strong electron-withdrawing effect,
leading to a decrease in the yield of the product 3t. Fluorinated
biaryl compounds (Table 2, 3u−v) are obtained in good
yields. It has been reported in the literature that fluorinated
biaryls have an important value in pharmaceutical and
materials chemistry.18
The range of anhydride composition was investigated using
4-methoxyphenylboronic acid as a standard substrate (Table 3,
4a−4j). In addition to the lower yield of sterically hindered
anhydrides (Table 3, 4a), coupling products of anhydrides
with electron-neutral (Table 3, 4b), electron-withdrawing
(Table 3, 4f−g), or electron-rich (Table 3, 4c−4e, 4j) groups
all have moderate yields. To our surprise, proper addition of
boric acid, cinnamic anhydride, and biphenyl anhydride can
also be applicable to this reaction (Table 3, 4h−i). At the same
time, we also used different anhydrides to cross-react with
different phenylboronic acids (Table 3, 4k−4m) and also
obtained moderate yields.
with Ni0 to form an intermediate C. The resulting acylnickel-
(II) intermediate C undergoes a transmetalation step with
phenylboronic acid D, generating the acylnickel(II) species E.
Decarbonylation of the intermediate E gives the compound F.
Finally, the compound F undergoes reductive elimination to
obtain cross-coupling products and the active Ni0 catalytic
species.
CONCLUSIONS
■
In summary, we have developed a nickel-catalyzed decarbon-
ylative Suzuki−Miyaura coupling of anhydrides with arylbor-
onic acids. The reaction has a wide substrate range and
operational simplicity and employs a cost-effective, air-stable
Ni(II) precatalyst. This process is a supplement to the
traditional cross-coupling methods, which also indicates that
decarbonyl cross-coupling may have a significant impact on the
modern era of organic synthesis.
EXPERIMENTAL SECTION
We conducted research using asymmetric anhydride as the
raw material to clarify the mechanism (Scheme 2). It was
found that two decarbonylation products can be separated.
Therefore, we believe that anhydrides may react in two ways. It
can be seen from Scheme 2 that the napthyl moiety has higher
reactivity than phenyl. The reactivity of electron-donating
groups or electron-withdrawing groups attached to the
benzene ring is almost the same. The steric hindrance has a
little influence on the reactivity.
In order to prove the practicability of this method as a
synthetic tool, we carried out a scale-up experiment on the
product 3b and the yield was 71% (Scheme 3).
Based on the abovementioned experimental results and
previous literature reports,9a a plausible mechanism of the
Ni(II)-catalyzed decarbonylation cross-coupling reaction of
anhydrides and phenylboronic acids is shown in Scheme 4.
First, the substrate anhydride B undergoes oxidative addition
■
General Information. In addition to benzoic anhydride, other
monoanhydrides were prepared according to previously reported
methods.15a Reactants and reagents were purchased from commercial
suppliers and used without further purification. All anhydrous solvents
used in the reactions were dried and freshly distilled. Thin-layer
chromatography (TLC) was performed on silica HSGF254 plates.
Melting points were determined with a digital melting-point
1
apparatus. H (400 MHz) and 13C(101 MHz) NMR spectra were
obtained from solutions in CDCl3 or with tetramethylsilane as an
internal standard using 400 MHz spectrometers. High-resolution mass
spectrum (HRMS) analyses were carried out on an electrospray
ionization or atmospheric pressure chemical ionization (ESI or APCI)
apparatus using time-of-flight (TOF) mass spectrometry.
General Procedure for Decarbonylative Suzuki−Miyaura
Coupling of Anhydrides. Anhydride (0.2 mmol), the arylboronic
acid substrate (0.3 mmol), Ni(PCy3)2Cl2 (6 mg, 0.01 mmol), PCy3 (7
mg, 0.02 mmol), and Cs2CO3 (195 mg, 0.6 mmol) were successively
added into a 15 mL sealed tube, using anhydrous toluene (1.5 mL) as
C
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Table 2. Nickel-Catalyzed Suzuki Biaryl Synthesis Through Cross-Coupling of 2-Naphthoic Anhydride with Arylboronic
a b
,
Acids
a
General conditions: the reactions were run on 0.2 mmol acid anhydride under nitrogen in a sealed tube, using R−B(OH)2 (1.5 equiv),
b
c
Ni(PCy3)2Cl2 (5 mol %), PCy3 (10 mol %), and Cs2CO3 (3.0 equiv) in toluene (1.5 mL) at 150 °C for 24 h. Isolated yields. R−B(OH)2 (3.0
equiv).
the solvent. The mixture was stirred in a 150 °C oil bath under
nitrogen for 24 h. Upon completion of the reaction as indicated by
TLC, the mixture was diluted with EtOAc and then filtered through a
pad of Celite. The solvent was removed under vacuum. The residue
was purified on a silica gel column (petroleum ether) to give the pure
target product.
3-Chlorobenzoic Anhydride (1c).15a White solid (529 mg, 90%).
1H NMR (400 MHz, CDCl3): δ 8.11 (s, 2H), 8.04 (d, J = 7.8 Hz,
2H), 7.67 (d, J = 7.8 Hz, 2H), 7.50 (t, J = 7.9 Hz, 2H).
4-Chlorobenzoic Anhydride (1d).15a White solid (513 mg, 87%).
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.3 Hz, 4H), 7.52 (d, J =
8.3 Hz, 4H).
2-Methylbenzoic Anhydride (1e).15a White solid (482 mg, 95%).
1H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 7.8 Hz, 2H), 7.51 (t, J =
7.4 Hz, 2H), 7.35−7.30 (m, 4H).
2-Naphthoic Anhydride (1a).15a White solid (568 mg, 85%). H
1
NMR (400 MHz, CDCl3): δ 8.79 (s, 2H), 8.20 (d, J = 8.4 Hz, 2H),
8.03 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 8.4 Hz, 3H), 7.95 (d, J = 8.4 Hz,
2H), 7.68 (t, J = 7.2 Hz, 2H), 7.61 (t, J = 7.2 Hz, 2H).
3-Methylbenzoic Anhydride (1f).15a Yellow solid (442 mg, 85%).
1H NMR (400 MHz, CDCl3): δ 7.96 (s, 2H), 7.95 (d, J = 7.2 Hz,
2H), 7.48 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H), 2.45 (s, 6H).
4-Methylbenzoic Anhydride (1g).15a White solid (458 mg, 88%).
1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 7.6 Hz, 4H), 7.32 (d, J =
7.6 Hz, 4H), 2.46 (s, 6H).
1-Naphthoic Anhydride (1b).15a White solid (567 mg, 87%). H
1
NMR (400 MHz, CDCl3): δ 9.15 (d, J = 8.6 Hz, 2H), 8.44 (d, J = 7.2
Hz, 2H), 8.15 (d, J = 8.1 Hz, 2H), 7.95 (d, J = 8.1 Hz, 2H), 7.71 (t, J
= 7.6 Hz, 2H), 7.66−7.50 (m, 4H).
D
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a b
,
Table 3. Nickel-Catalyzed Suzuki Biaryl Synthesis Through Cross-Coupling of Anhydrides with Arylboronic Acid
a
General conditions: the reactions were run on 0.2 mmol acid anhydride under nitrogen in a sealed tube, using R−B(OH)2 (1.5 equiv),
b
Ni(PCy3)2Cl2 (5 mol %), PCy3 (10 mol %), Cs2CO3 (3.0 equiv), and H3BO3 (1.5 equiv) in toluene (1.5 mL) at 150 °C for 24 h. Isolated yields.
c
H3BO3 (2 equiv).
Scheme 2. Asymmetric Anhydride Selectivity Experiment
E
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Scheme 3. Scale-Up Experiment
Scheme 4. Plausible Reaction Mechanism
3-Methoxybenzoic Anhydride (1h).15a White solid (526 mg,
92%). 1H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 7.6 Hz, 2H), 7.63
(s, 2H), 7.41 (t, J = 8.0 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 3.86 (s,
6H).
5-(Naphthalen-2-yl)benzo[d][1,3]dioxole (3c).20 White solid (37
mg, 75%); mp 88.7−89.7 °C. EtOAc/petroleum ether = 1:80. H
1
NMR (400 MHz, CDCl3): δ 7.94 (s, 1H), 7.85 (m, J = 8.6, 3.4 Hz,
3H), 7.66 (dd, J = 8.5, 1.8 Hz, 1H), 7.52−7.41 (m, 2H), 7.21−7.15
(m, 2H), 6.91 (d, J = 7.9 Hz, 1H), 6.00 (s, 2H). 13C{1H} (101 MHz,
CDCl3): δ 148.2 (s), 147.2 (s), 138.2 (s), 135.5 (s), 133.7 (s), 132.4
(s), 128.4 (s), 128.1 (s), 127.6 (s), 126.3 (s), 125.8 (s), 125.5 (s),
125.3 (s), 121.0 (s), 108.7 (s), 107.9 (s), 101.2 (s).
4-Methoxybenzoic Anhydride (1i).15a White solid (549 mg, 96%).
1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.5 Hz, 4H), 6.98 (d, J =
8.5 Hz, 4H), 3.90 (s, 6H).
3,5-Difluorobenzoic Anhydride (1j).15a White solid (483 mg,
82%). 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J = 4.5 Hz, 4H), 7.17
(t, J = 7.8 Hz, 2H).
2-(4-(tert-Butyl)phenyl)naphthalene (3d).19 White solid (41 mg,
1
79%); mp 115.3−116.7 °C. Petroleum ether. H NMR (400 MHz,
Cinnamic Anhydride (1k).15a White solid (500 mg, 90%). 1H
NMR (400 MHz, CDCl3): δ 7.87 (d, J = 15.9 Hz, 2H), 7.63−7.56
(m, 4H), 7.44 (d, J = 6.1 Hz, 6H), 6.54 (d, J = 15.9 Hz, 2H).
[1,1′-Biphenyl]-4-carboxylic Anhydride (1l).15a White solid (642
mg, 85%). 1H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 8.0 Hz, 1H),
7.76 (d, J = 8.1 Hz, 1H), 7.66 (d, J = 7.4 Hz, 1H), 7.47 (dt, J = 26.5,
7.1 Hz, 2H), 7.26 (s, 1H).
CDCl3): δ 8.03 (s, 1H), 7.93−7.82 (m, 3H), 7.75 (d, J = 8.4 Hz, 1H),
7.67 (d, J = 8.2 Hz, 2H), 7.55−7.43 (m, 4H), 1.38 (s, 9H). 13C{1H}
(101 MHz, CDCl3): δ 150.4 (s), 138.4 (s), 138.2 (s), 133.7 (s), 132.5
(s), 128.2 (d, J = 17.2 Hz), 127.6 (s), 127.0 (s), 126.2 (s), 125.81 (s),
125.75 (s), 125.6 (s), 125.5 (s), 34.6 (s), 31.4 (s).
Trimethyl(4-(naphthalen-2-yl)phenyl)silane (3e).21 White solid
(39 mg, 71%); mp 108.6−109.7 °C. EtOAc/petroleum ether = 1:60.
1H NMR (400 MHz, CDCl3): δ 8.07 (s, 1H), 7.96−7.85 (m, 3H),
7.80−7.71 (m, 3H), 7.67 (d, J = 7.5 Hz, 2H), 7.56−7.46 (m, 2H),
0.34 (s, 9H). 13C{1H} (101 MHz, CDCl3): δ 141.5 (s), 139.4 (s),
138.5 (s), 133.9 (s), 133.7 (s), 132.7 (s), 128.4 (s), 128.2 (s), 127.6
(s), 126.7 (s), 126.3 (s), 125.9 (s), 125.8 (s), 125.5 (s), −1.1 (s).
2-(4-Ethoxyphenyl)naphthalene (3f).22 White solid (37 mg,
75%); mp 116.5−117.4 °C. EtOAc/petroleum ether = 1:80. 1H
NMR (400 MHz, CDCl3): δ 7.99 (s, 1H), 7.92−7.82 (m, 3H), 7.72
(d, J = 8.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.53−7.41 (m, 2H),
7.01 (d, J = 8.4 Hz, 2H), 4.10 (q, J = 6.9 Hz, 2H), 1.46 (t, J = 6.9 Hz,
3H). 13C{1H} (101 MHz, CDCl3): δ 158.6 (s), 138.2 (s), 133.7 (s),
133.4 (s), 132.3 (s), 128.4 (s), 128.3 (s), 128.0 (s), 127.6 (s), 126.2
(s), 125.6 (s), 125.4 (s), 125.0 (s), 114.9 (s), 63.5 (s), 14.9 (s).
2-(3,5-Dimethylphenyl)naphthalene (3g).19 White solid (38 mg,
82%); mp 62.5−63.3 °C. Petroleum ether. 1H NMR (400 MHz,
CDCl3): δ 8.02 (s, 1H), 7.93−7.82 (m, 8.4 Hz, 3H), 7.74 (d, J = 8.3
2-(4-Methoxyphenyl)naphthalene (3a).19 White solid (41 mg,
88%); mp 116.8−117.3 °C. EtOAc/petroleum ether = 1:80. 1H NMR
(400 MHz, CDCl3): δ 8.02 (s, 1H), 7.97−7.83 (m, 3H), 7.74 (d, J =
8.3 Hz, 1H), 7.69 (d, J = 8.2 Hz, 2H), 7.57−7.44 (m, 2H), 7.05 (d, J
= 8.2 Hz, 2H), 3.89 (s, 3H). 13C{1H} (101 MHz, CDCl3): δ 159.2
(s), 138.1 (s), 133.7 (s), 133.6 (s), 132.3 (s), 128.4 (s), 128.3 (s),
128.0 (s), 127.6 (s), 126.2 (s), 125.6 (s), 125.4 (s), 125.0 (s), 114.3
(s), 55.3 (s).
2-(3,5-Dimethoxyphenyl)naphthalene (3b).19 Yellow oil (43 mg,
81%). EtOAc/petroleum ether = 1:40. 1H NMR (400 MHz, CDCl3):
δ 8.03 (s, 1H), 7.93−7.82 (m, 3H), 7.72 (d, J = 8.4 Hz, 1H), 7.57−
7.44 (m, 2H), 6.86 (d, J = 1.6 Hz, 2H), 6.50 (s, 1H), 3.88 (s, 6H).
13C{1H} (101 MHz, CDCl3): δ 161.1 (s), 143.4 (s), 138.5 (s), 133.6
(s), 132.8 (s), 128.3 (s), 128.2 (s), 127.6 (s), 126.3 (s), 126.0 (s),
125.9 (s), 125.6 (s), 105.7 (s), 99.4 (s), 55.5 (s).
F
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
Hz, 1H), 7.54−7.43 (m, 2H), 7.34 (s, 2H), 7.03 (s, 1H), 2.42 (s, 6H).
13C{1H} (101 MHz, CDCl3): δ 141.1 (s), 138.8 (s), 138.4 (s), 132.6
(s), 129.0 (s), 128.2 (s), 128.1 (s), 127.6 (s), 126.2 (s), 125.8 (s),
125.7 (s), 125.7 (s), 125.3 (s), 21.4 (s).
NMR (400 MHz, CDCl3): δ 8.00 (s, 1H), 7.93−7.82 (m, 3H), 7.77−
7.63 (m, 3H), 7.54−7.43 (m, 2H), 7.36 (t, J = 7.7 Hz, 2H), 7.19−
7.01 (m, 5H). 13C{1H} (101 MHz, CDCl3): δ 157.1 (s), 156.9 (s),
137.8 (s), 136.1 (s), 133.7 (s), 132.4 (s), 129.8 (s), 128.7 (s), 128.4
(s), 128.1 (s), 127.6 (s), 126.3 (s), 125.8 (s), 125.4 (s), 123.4 (s),
119.1 (s), 119.0 (s). HRMS (APCI-TOF) m/z: [M]+ calcd for
C22H16O, 296.1201; found, 296.1197.
2-(4-Isopropylphenyl)naphthalene (3h).21 White solid (33 mg,
69%); mp 72.6−73.4 °C. Petroleum ether. 1H NMR (400 MHz,
CDCl3): δ 8.03 (s, 1H), 7.94−7.82 (m, 3H), 7.75 (d, J = 8.4 Hz, 1H),
7.66 (d, J = 8.0 Hz, 2H), 7.54−7.43 (m, 2H), 7.35 (d, J = 7.9 Hz,
2H), 3.03−2.93 (m, 1H), 1.32 (s, 3H), 1.30 (s, 3H). 13C{1H} (101
MHz, CDCl3): δ 148.1 (s), 138.6 (s), 138.5 (s), 133.7 (s), 132.5 (s),
128.3 (s), 128.1 (s), 127.6 (s), 127.3 (s), 127.0 (s), 126.2 (s), 125.7
(s), 125.6 (s), 125.5 (s), 33.8 (s), 24.0 (s).
2-(4-Methoxy-3,5-dimethylphenyl)naphthalene (3q). Yellow oil
1
(24 mg, 45%). EtOAc/petroleum ether = 1:80. H NMR (400 MHz,
CDCl3): δ 7.98 (s, 1H), 7.91−7.82 (m, 3H), 7.70 (d, J = 8.4 Hz, 1H),
7.53−7.42 (m, 2H), 7.37 (s, 2H), 3.78 (s, 3H), 2.38 (s, 6H). 13C{1H}
(101 MHz, CDCl3): δ 156.7 (s), 138.3 (s), 136.6 (s), 133.7 (s), 132.4
(s), 131.2 (s), 128.2 (s), 128.1 (s), 127.8 (s), 127.6 (s), 126.2 (s),
125.7 (s), 125.6 (s), 125.4 (s), 59.8 (s), 16.3 (s). 13C{1H} (101 MHz,
CDCl3): δ 163.6 (s), 145.2 (s), 137.7 (s), 135.2 (s), 133.7 (s), 132.5
(s), 130.0 (s), 128.7 (s), 128.1 (s), 127.7 (s), 126.5 (s), 126.0 (s),
125.2 (s), 125.0 (s), 110.9 (s), 53.6 (s). HRMS (APCI-TOF) m/z:
[M + H]+ calcd for C19H19O, 263.1436; found, 263.1433.
2-Methoxy-5-(naphthalen-2-yl)pyridine (3r). White solid (25 mg,
53%); mp 106.2−107.1 °C. EtOAc/petroleum ether = 1:40. 1H NMR
(400 MHz, CDCl3): δ 8.52 (s, 1H), 7.99−7.83 (m, 5H), 7.67 (d, J =
8.4 Hz, 1H), 7.55−7.45 (m, 2H), 6.88 (d, J = 8.5 Hz, 1H), 4.02 (s,
3H). 13C{1H} (101 MHz, CDCl3): δ 163.6 (s), 145.2 (s), 137.7 (s),
128.7 (s), 128.1 (s), 127.7 (s), 126.5 (s), 126.0 (s), 125.2 (s), 125.0
(s), 110.9 (s), 53.6 (s). HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C16H14NO, 236.1075; found, 236.1073.
2-Phenylnaphthalene (3i).19 White solid (31 mg, 76%); mp
1
105.6−106.7 °C. Petroleum ether. H NMR (400 MHz, CDCl3): δ
8.04 (s, 1H), 7.94−7.82 (m, 3H), 7.73 (t, J = 8.8 Hz, 3H), 7.55−7.43
(m, 4H), 7.37 (t, J = 7.2 Hz, 1H). 13C{1H} (101 MHz, CDCl3): δ
141.1 (s), 138.5 (s), 133.7 (s), 132.6 (s), 128.8 (s), 128.4 (s), 128.2
(s), 127.6 (s), 127.4 (s), 127.3 (s), 126.3 (s), 125.9 (d, J = 12.6 Hz),
125.6 (s).
2-(3-(Benzyloxy)phenyl)naphthalene (3j).23 White solid (26 mg,
42%); mp 157.3−159.5 °C. EtOAc/petroleum ether = 1:70. 1H NMR
(400 MHz, CDCl3): δ 8.02 (s, 1H), 7.93−7.83 (m, 3H), 7.75−7.69
(m, 1H), 7.53−7.45 (m, 4H), 7.44−7.37 (m, 3H), 7.37−7.30 (m,
3H), 7.03−6.96 (m, 1H), 5.15 (s, 2H). 13C{1H} (101 MHz, CDCl3):
δ 159.2 (s), 142.7 (s), 138.3 (s), 137.0 (s), 133.6 (s), 132.7 (s), 129.9
(s), 128.6 (s), 128.4 (s), 128.2 (s), 128.0 (s), 127.6 (s), 127.6 (s),
126.3 (s), 126.0 (s), 125.9 (s), 125.5 (s), 120.2 (s), 114.2 (s), 113.6
(s), 70.1 (s).
2-(3-Chloro-4-methoxyphenyl)naphthalene (3s). (34 mg, 63%);
1
mp 139.1−140.3 °C. EtOAc/petroleum ether = 1:80. H NMR (400
2-(4-Propoxyphenyl)naphthalene (3k). White solid (39 mg,
74%); mp 132.7−133.5 °C. EtOAc/petroleum ether = 1:80. 1H
NMR (400 MHz, CDCl3): δ 7.97 (s, 1H), 7.91−7.79 (m, 3H), 7.70
(d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.52−7.39 (m, 2H),
7.00 (d, J = 8.4 Hz, 2H), 3.97 (t, J = 6.5 Hz, 2H), 1.89−1.78 (m, 2H),
1.06 (t, J = 7.4 Hz, 3H). 13C{1H} (101 MHz, CDCl3): δ 158.8 (s),
138.2 (s), 133.7 (s), 133.4 (s), 132.3 (s), 128.4 (s), 128.3 (s), 128.0
(s), 127.6 (s), 126.2 (s), 125.6 (s), 125.4 (s), 125.0 (s), 114.9 (s),
69.6 (s), 22.6 (s), 10.5 (s). HRMS (APCI-TOF) m/z: [M + H]+
calcd for C19H19O, 263.1436; found, 263.1437.
MHz, CDCl3): δ 7.97 (d, J = 1.5 Hz, 1H), 7.93−7.84 (m, 3H), 7.75
(d, J = 2.3 Hz, 1H), 7.68 (dd, J = 8.5, 1.8 Hz, 1H), 7.58 (dd, J = 8.5,
2.3 Hz, 1H), 7.54−7.44 (m, 2H), 7.04 (d, J = 8.5 Hz, 1H), 3.97 (s,
3H). 13C{1H} (101 MHz, CDCl3): δ 154.5 (s), 136.8 (s), 134.6 (s),
133.6 (s), 132.5 (s), 129.1 (s), 128.5 (s), 128.1 (s), 127.6 (s), 126.5
(s), 126.4 (s), 126.0 (s), 125.3 (s), 125.1 (s), 122.9 (s), 112.3 (s),
56.3 (s). HRMS (APCI-TOF) m/z: [M]+ calcd for C17H13ClO,
268.0655; found, 268.0653.
2-(4-Chlorophenyl)naphthalene (3t).22 White solid (21 mg,
1
44%); mp 130.3−131.4 °C. Petroleum ether. H NMR (400 MHz,
2-(p-Tolyl)naphthalene (3l).19 White solid (19 mg, 44%); mp
88.3−89.1 °C. Petroleum ether. 1H NMR (400 MHz, CDCl3): δ 8.02
(s, 1H), 7.94−7.82 (m, 3H), 7.74 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.8
Hz, 2H), 7.53−7.42 (m, 2H), 7.30 (d, J = 7.7 Hz, 2H), 2.42 (s, 3H).
13C{1H} (101 MHz, CDCl3): δ 138.5 (s), 138.2 (s), 137.2 (s), 133.7
(s), 132.5 (s), 129.6 (s), 128.3 (s), 128.1 (s), 127.6 (s), 127.2 (s),
126.2 (s), 125.8 (s), 125.5 (s), 125.4 (s), 21.1 (s).
CDCl3): δ 8.00 (s, 1H), 7.95−7.83 (m, 3H), 7.69 (d, J = 8.5 Hz, 1H),
7.64 (d, J = 8.3 Hz, 2H), 7.55−7.48 (m, 2H), 7.45 (d, J = 8.3 Hz,
2H). 13C{1H} (101 MHz, CDCl3): δ 139.6 (s), 137.3 (s), 133.6 (s),
133.5 (s), 132.7 (s), 129.0 (s), 128.6 (s), 128.6 (s), 128.2 (s), 127.7
(s), 126.5 (s), 126.1 (s), 125.7 (s), 125.2 (s).
2-(3,5-Difluorophenyl)naphthalene (3u).25 White solid (36 mg,
1
75%); mp 118.5−119.6 °C. Petroleum ether. H NMR (400 MHz,
2-(m-Tolyl)naphthalene (3m).19 Colorless oil (19 mg, 44%).
Petroleum ether. 1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H), 7.94−
7.82 (m, 3H), 7.74 (d, J = 8.4 Hz, 1H), 7.57−7.43 (m, 4H), 7.37 (t, J
= 7.5 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 2.46 (s, 3H). 13C{1H} (101
MHz, CDCl3): δ 141.1 (s), 138.7 (s), 138.4 (s), 133.7 (s), 132.6 (s),
128.8 (s), 128.3 (s), 128.2 (s), 128.2 (s), 128.1 (s), 127.6 (s), 126.2
(s), 125.8 (s), 125.7 (s), 125.7 (s), 124.5 (s), 21.6 (s).
CDCl3): δ 8.01 (s, 1H), 7.97−7.82 (m, 3H), 7.66 (d, J = 8.4 Hz, 1H),
7.59−7.46 (m, 2H), 7.25−7.19 (m, 2H), 6.82 (t, J = 8.7 Hz, 1H).
13C{1H} (101 MHz, CDCl3): δ 163.4 (dd, JC−F = 13.2, 248.9 Hz),
144.5 (t, JC−F = 9.5 Hz), 136.2 (t, JC−F = 2.6 Hz), 133.5 (s), 133.1 (s),
128.8 (s), 128.3 (s), 127.7 (s), 126.7 (s), 126.6 (s), 126.1 (s), 124.8
(s), 110.2 (dd, JC−F = 7.1, 18.8 Hz), 102.6 (t, JC−F = 25.6 Hz).
2-(3-Fluorophenyl)naphthalene (3v).26 White solid (28 mg,
63%); mp 79.4−81.0 °C. Petroleum ether. 1H NMR (400 MHz,
CDCl3): δ 8.03 (s, 1H), 7.97−7.82 (m, 3H), 7.71 (d, J = 8.4 Hz, 1H),
7.56−7.47 (m, 3H), 7.47−7.39 (m, 2H), 7.07 (t, J = 8.1 Hz, 1H).
13C{1H} (101 MHz, CDCl3): δ 163.3 (d, JC−F = 246.5 Hz), 143.4 (d,
JC−F = 7.8 Hz), 137.2 (d, JC−F = 2.2 Hz), 133.6 (s), 132.8 (s), 130.3
(d, JC−F = 8.4 Hz), 128.6 (s), 128.2 (s), 127.7 (s), 126.5 (s), 126.2
2-(2-Methoxyphenyl)naphthalene (3n).20 Yellow oil (29 mg,
62%). EtOAc/petroleum ether = 1:80. 1H NMR (400 MHz, CDCl3):
δ 7.96 (s, 1H), 7.86 (d, J = 7.6 Hz, 3H), 7.69 (d, J = 8.4 Hz, 1H),
7.51−7.40 (m, 3H), 7.36 (t, J = 7.7 Hz, 1H), 7.13−6.98 (m, 2H),
3.82 (s, 3H). 13C{1H} (101 MHz, CDCl3): δ 156.7 (s), 136.2 (s),
133.4 (s), 132.4 (s), 131.1 (s), 130.7 (s), 128.8 (s), 128.1 (s), 128.1
(s), 127.6 (s), 127.2 (s), 125.9 (s), 125.8 (s), 120.9 (s), 111.3 (s),
55.6 (s).
(s), 126.0 (s), 125.2 (s), 123.0 (d, JC−F = 2.7 Hz), 114.2 (dd, JC−F
=
2-(2,4-Dimethoxyphenyl)naphthalene (3o).24 Yellow oil (34 mg,
64%). EtOAc/petroleum ether = 1:40. 1H NMR (400 MHz, CDCl3):
δ 7.92 (s, 1H), 7.84 (d, J = 8.4 Hz, 3H), 7.66 (d, J = 8.4 Hz, 1H),
7.50−7.41 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 7.2 Hz,
2H), 3.88 (s, 3H), 3.82 (s, 3H). 13C{1H} (101 MHz, CDCl3): δ 160.4
(s), 157.7 (s), 136.0 (s), 133.5 (s), 132.2 (s), 131.5 (s), 128.2 (s),
128.0 (s), 127.8 (s), 127.5 (s), 127.1 (s), 125.8 (s), 125.6 (s), 123.6
(s), 104.7 (s), 99.1 (s), 55.5 (s).
13.6, 22.1 Hz).
2-(3-(Trifluoromethyl)phenyl)naphthalene (3w). White solid (40
1
mg, 74%); mp 59.2−60.1 °C. Petroleum ether. H NMR (400 MHz,
CDCl3): δ 8.05 (s, 1H), 8.01−7.84 (m, 5H), 7.73 (d, J = 8.3 Hz, 1H),
7.67−7.56 (m, 2H), 7.57−7.45 (m, 2H). 13C{1H} (101 MHz,
CDCl3): δ 141.9 (s), 137.0 (s), 133.6 (s), 132.9 (s), 130.7 (s), 129.3
(s), 128.8 (s), 128.3 (s), 127.7 (s), 126.6 (s), 126.4 (s), 126.2 (s),
125.2 (s), 124.2 (q, JC−F = 3.8 Hz), 124.0 (q, JC−F = 3.8 Hz), 122.9 (q,
JC−F = 273.4 Hz). HRMS (APCI-TOF) m/z: [M]+ calcd for
C17H11F3, 272.0813; found, 272.0813.
2-(4-Phenoxyphenyl)naphthalene (3p). White solid (31 mg,
53%); mp 128.1−128.9 °C. EtOAc/petroleum ether = 1:80. 1H
G
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2-(3-Chlorophenyl)naphthalene (3x).27 White solid (41 mg,
86%); mp 67.8−69.1 °C. Petroleum ether. 1H NMR (400 MHz,
CDCl3): δ 8.01 (s, 1H), 7.89 (m, 3H), 7.69 (d, J = 7.7 Hz, 2H),
7.63−7.56 (m, 1H), 7.50 (d, J = 3.8 Hz, 2H), 7.40 (t, J = 7.6 Hz, 1H),
7.35 (d, J = 7.6 Hz, 1H). 13C{1H} (101 MHz, CDCl3): δ 143.0 (s),
137.1 (s), 134.7 (s), 133.6 (s), 132.8 (s), 130.1 (s), 128.6 (s), 128.2
(s), 127.7 (s), 127.5 (s), 127.3 (s), 126.5 (s), 126.3 (s), 126.0 (s),
125.5 (s), 125.2 (s).
4,4′-Dimethoxy-1,1′-biphenyl (4j).32 White solid (23 mg, 54%);
1
mp 171−172 °C. EtOAc/petroleum ether = 1:40. H NMR (400
MHz, CDCl3): δ 7.50−7.47 (m, 2H), 7.47−7.44 (m, 2H), 6.98−6.96
(m, 2H), 6.95−6.93 (m, 2H), 3.84 (s, 6H). 13C{1H} (101 MHz,
CDCl3): δ 158.7 (s), 133.5 (s), 127.7 (s), 114.1 (s), 55.3 (s).
4′-(tert-Butyl)-3-methoxy-1,1′-biphenyl (4k).34 Yellow oil (24 mg,
50%). EtOAc/petroleum ether = 1:100. 1H NMR (400 MHz,
CDCl3): δ 7.56−7.51 (m, 2H), 7.49−7.43 (m, 2H), 7.37−7.31 (m,
1H), 7.21−7.15 (m, 1H), 7.14−7.10 (m, 1H), 6.90−6.85 (m, 1H),
3.86 (s, 3H), 1.36 (s, 9H). 13C{1H} (101 MHz, CDCl3): δ 159.9 (s),
150.4 (s), 142.6 (s), 138.2 (s), 129.7 (s), 126.8 (s), 125.7 (s), 119.6
(s), 112.7 (s), 112.4 (s), 55.3 (s), 34.5 (s), 31.4 (s).
1-(4-Methoxyphenyl)naphthalene (4a).28 White solid (21 mg,
45%); mp 113.7−114.6 °C. EtOAc/petroleum ether = 1:80. 1H NMR
(400 MHz, CDCl3): δ 7.91 (t, J = 9.1 Hz, 2H), 7.84 (d, J = 8.2 Hz,
1H), 7.54−7.46 (m, 2H), 7.42 (t, J = 8.2 Hz, 4H), 7.03 (d, J = 8.4 Hz,
2H), 3.90 (s, 3H). 13C{1H} (101 MHz, CDCl3): δ 158.9 (s), 139.9
(s), 133.8 (s), 133.1 (s), 131.8 (s), 131.1 (s), 128.2 (s), 127.3 (s),
126.9 (s), 126.1 (s), 125.9 (s), 125.7 (s), 125.4 (s), 113.7 (s), 55.4
(s).
4-Isopropyl-1,1′-biphenyl (4l).35 Colorless Oil (20 mg, 48%)
petroleum ether. 1H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 7.5 Hz,
2H), 7.52 (d, J = 7.4 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.33−7.28 (m,
3H), 3.02−2.89 (m, 1H), 1.29 (d, J = 6.8 Hz, 8H). 13C{1H} (101
MHz, CDCl3): δ 148.0 (s), 141.2 (s), 138.7 (s), 128.7 (s), 127.1 (s),
127.0 (s), 126.9 (s), 126.8 (s), 33.8 (s), 24.0 (s).
4-Methoxy-1,1′-biphenyl (4b).29 White solid (24 mg, 65%); mp
95.5−96.7 °C. EtOAc/petroleum ether = 1:100. 1H NMR (400 MHz,
CDCl3): δ 7.54 (t, J = 8.2 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.30 (t, J
= 7.2 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 3.85 (s, 1H). 13C{1H} (101
MHz, CDCl3): δ 159.1 (s), 140.8 (s), 133.8 (s), 128.7 (s), 128.1 (s),
126.7 (s), 126.6 (s), 114.2 (s), 55.3 (s).
2-(3-Chlorophenyl)-6-methoxynaphthalene (4m). (36 mg, 67%);
1
mp 99.6−100.6 °C. EtOAc/petroleum ether = 1:100. H NMR (400
MHz, CDCl3): δ 7.93 (s, 1H), 7.78 (t, J = 7.6 Hz, 2H), 7.65 (d, J =
9.8 Hz, 2H), 7.55 (d, J = 7.5 Hz, 1H), 7.37 (t, J = 7.7 Hz, 1H), 7.30
(d, J = 7.8 Hz, 1H), 7.16 (d, J = 12.4 Hz, 2H), 3.93 (s, 3H). 13C{1H}
(101 MHz, CDCl3): δ 158.0 (s), 143.1 (s), 134.9 (s), 134.7 (s), 134.1
(s), 130.0 (s), 129.8 (s), 129.1 (s), 127.4 (s), 127.3 (s), 127.0 (s),
125.8 (s), 125.7 (s), 125.3 (s), 119.4 (s), 105.6 (s), 55.4 (s). HRMS
(APCI-TOF) m/z: [M]+ calcd for C17H13ClO, 268.0655; found,
268.0654..
4′-Methoxy-2-methyl-1,1′-biphenyl (4c).30 Colorless oil (22 mg,
55%). EtOAc/petroleum ether = 1:100. 1H NMR (400 MHz,
CDCl3): δ 7.28−7.24 (m, 4H), 7.23−7.20 (m, 2H), 6.97−6.95 (m,
1H), 6.95−6.93 (m, 1H), 3.85 (s, 3H), 2.28 (s, 3H). 13C{1H} (101
MHz, CDCl3): δ 158.5 (s), 141.5 (s), 135.5 (s), 134.3 (s), 130.3 (s),
130.2 (s), 129.9 (s), 127.0 (s), 125.7 (s), 113.5 (s), 55.3 (s).
4′-Methoxy-3-methyl-1,1′-biphenyl (4d).29 White solid (22 mg,
1
ASSOCIATED CONTENT
* Supporting Information
55%); mp 51.5−52.8 °C. EtOAc/petroleum ether = 1:100. H NMR
■
(400 MHz, CDCl3): δ 7.52 (d, J = 8.2 Hz, 2H), 7.39−7.28 (m, 3H),
7.12 (d, J = 6.9 Hz, 1H), 6.97 (d, J = 8.1 Hz, 2H), 3.85 (s, 3H), 2.41
(s, 3H). 13C{1H} (101 MHz, CDCl3): δ 159.1 (s), 140.8 (s), 138.3
(s), 133.9 (s), 128.6 (s), 128.1 (s), 127.6 (s), 127.4 (s), 123.8 (s),
114.1 (s), 55.3 (s), 21.5 (s).
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02266.
1H NMR and 13C NMR spectra and HRMS spectra
(PDF)
4-Methoxy-4′-methyl-1,1′-biphenyl (4e).29 White solid (27 mg,
1
68%); mp 88.4−89.5 °C. EtOAc/petroleum ether = 1:100. H NMR
(400 MHz, CDCl3): δ 7.51 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 7.6 Hz,
2H), 7.26−7.21 (m, 2H), 6.96 (d, J = 8.2 Hz, 2H), 3.84 (s, 3H), 2.38
(s, 3H). 13C{1H} (101 MHz, CDCl3): δ 158.9 (s), 138.0 (s), 136.3
(s), 133.7 (s), 129.4 (s), 127.9 (s), 126.6 (s), 114.1 (s), 55.3 (s), 21.0
(s).
AUTHOR INFORMATION
Corresponding Author
■
Yong-Ming Zhu − College of Pharmaceutical Sciences, Soochow
University, Suzhou 215123, China; orcid.org/0000-0002-
7078-7908; Email: zhuyongming@suda.edu.cn
4-Chloro-4′-methoxy-1,1′-biphenyl (4f).31 White solid (25 mg,
57%); mp 110.1−112.4 °C. EtOAc/petroleum ether = 1:100. 1H
NMR (400 MHz, CDCl3): δ 7.57−7.42 (m, 4H), 7.37 (d, J = 7.8 Hz,
2H), 6.97 (d, J = 8.0 Hz, 2H), 3.85 (s, 3H). 13C{1H} (101 MHz,
CDCl3): δ 159.3 (s), 139.3 (s), 132.6 (s), 132.5 (s), 128.8 (s), 128.0
(s), 127.9 (s), 114.3 (s), 55.4 (s).
Authors
Jing-Ya Zhou − College of Pharmaceutical Sciences, Soochow
University, Suzhou 215123, China
Rui-Qing Liu − College of Pharmaceutical Sciences, Soochow
University, Suzhou 215123, China
Cheng-Yi Wang − College of Pharmaceutical Sciences, Soochow
University, Suzhou 215123, China
3,5-Difluoro-4′-methoxy-1,1′-biphenyl (4g).32 White solid (23
mg, 52%); 73.2−75.9 °C. EtOAc/petroleum ether = 1:100. 1H NMR
(400 MHz, CDCl3): δ 7.51−7.46 (m, 2H), 7.09−7.02 (m, 2H),
7.01−6.95 (m, 2H), 6.77−6.69 (m, 1H), 3.86 (s, 3H). 13C{1H} (101
MHz, CDCl3): δ 164.5 (d, J = 13.2 Hz), 162.1 (d, J = 13.3 Hz), 160.0
(s), 144.1 (t), 131.3 (t), 128.1 (s), 114.4 (s), 109.4 (d, J = 7.0 Hz),
109.3 (d, J = 7.0 Hz), 101.8 (t), 55.4 (s).
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02266
(E)-1-Methoxy-4-styrylbenzene (4h).31 White solid (18 mg, 43%);
mp 134.5−135.8 °C. EtOAc/petroleum ether = 1:100. 1H NMR (400
MHz, CDCl3): δ 7.52−7.43 (m, 4H), 7.37−7.31 (m, 2H), 7.22 (d, J =
7.4 Hz, 1H), 7.10−6.94 (m, 2H), 6.92−6.87 (m, 2H), 3.83 (s, 3H).
13C{1H} (101 MHz, CDCl3): δ 159.3 (s), 137.6 (s), 130.1 (s), 128.6
(s), 128.2 (s), 127.7 (s), 127.2 (s), 126.6 (s), 126.2 (s), 114.1 (s),
55.3 (s).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the financial support by PAPD (A
Project Funded by the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions).
4-Methoxy-1,1′:4′,1″-Terphenyl (4i).33 White solid (26 mg, 50%);
mp 225.3−225.8 °C. EtOAc/petroleum ether = 1:100. 1H NMR (400
MHz, CDCl3): δ 7.70−7.60 (m, 6H), 7.58 (d, J = 8.0 Hz, 2H), 7.45
(t, J = 7.1 Hz, 2H), 7.35 (t, J = 7.0 Hz, 1H), 7.00 (d, J = 7.9 Hz, 2H),
3.86 (s, 3H). 13C{1H} (101 MHz, CDCl3): δ 159.2 (s), 140.8 (s),
139.7 (s), 139.5 (s), 133.2 (s), 128.8 (s), 128.0 (s), 127.4 (s), 127.2
(s), 127.03 (s), 126.98 (s), 114.3 (s), 55.4 (s).
REFERENCES
■
́
(1) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Aryl−aryl bond formation one century after the discovery of the
Ullmann reaction. Chem. Rev. 2002, 102, 1359−1470.
H
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
̈
(2) (a) De Meijere, A.; Brase, S.; Oestreich, M. Metal Catalyzed
(17) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Recent advances in
homogeneous nickel catalysis. Nature 2014, 509, 299−309.
(18) Partyka, D. V. Transmetalation of unsaturated carbon
nucleophiles from boron-containing species to the mid to late d-
block metals of relevance to catalytic C−X coupling reactions (X= C,
F, N, O, Pb, S, Se, Te). Chem. Rev. 2011, 111, 1529−1595.
(19) Cao, Z.-C.; Luo, Q.-Y.; Shi, Z.-J. Practical cross-coupling
between O-based electrophiles and aryl bromides via Ni catalysis. Org.
Lett. 2016, 18, 5978−5981.
(20) Chung, K. H.; So, C. M.; Wong, S. M.; Luk, C. H.; Zhou, Z.;
Lau, C. P.; Kwong, F. Y. An efficient palladium−benzimidazolyl
phosphine complex for the Suzuki−Miyaura coupling of aryl
mesylates: facile ligand synthesis and metal complex characterization.
Chem. Commun. 2012, 48, 1967−1969.
(21) Cao, Z.-C.; Xie, S.-J.; Fang, H.; Shi, Z.-J. Ni-catalyzed cross-
coupling of dimethyl aryl amines with arylboronic esters under
reductive conditions. J. Am. Chem. Soc. 2018, 140, 13575−13579.
(22) Minami, H.; Saito, T.; Wang, C.; Uchiyama, M. Organo-
aluminum-Mediated Direct Cross-Coupling Reactions. Angew. Chem.,
Int. Ed. 2015, 54, 4665−4668.
Cross-Coupling Reactions and More; John Wiley & Sons, 2013.
(b) Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling
reactions of organoboron compounds. Chem. Rev. 1995, 95, 2457−
2483.
(3) (a) Suzuki, A. Cross-coupling reactions of organoboranes: an
easy way to construct C-C bonds (Nobel Lecture). Angew. Chem., Int.
Ed. 2011, 50, 6722−6737. (b) Blakemore, D. C.; Castro, L.;
Churcher, I.; Rees, D. C.; Thomas, A. W.; Wilson, D. M.; Wood,
A. Organic synthesis provides opportunities to transform drug
discovery. Nat. Chem. 2018, 10, 383−394.
(4) (a) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. Palladium-
catalyzed borylation of aryl halides or triflates with dialkoxyborane: A
novel and facile synthetic route to arylboronates. J. Org. Chem. 2000,
65, 164−168. (b) Ishiyama, T.; Murata, M.; Miyaura, N. Palladium
(0)-catalyzed cross-coupling reaction of alkoxydiboron with haloar-
enes: a direct procedure for arylboronic esters. J. Org. Chem. 1995, 60,
7508−7510.
̈
(5) De Meijere, A.; Brase, S.; Oestreich, M. Metal Catalyzed Cross-
Coupling Reactions and More; John Wiley & Sons, 2013.
(23) Zhang, Z.-B.; Ji, C.-L.; Yang, C.; Chen, J.; Hong, X.; Xia, J.-B.
Nickel-Catalyzed Kumada Coupling of Boc-Activated Aromatic
Amines via Nondirected Selective Aryl C−N Bond Cleavage. Org.
Lett. 2019, 21, 1226−1231.
(24) Petronzi, C.; Filosa, R.; Peduto, A.; Monti, M. C.; Margarucci,
L.; Massa, A.; Ercolino, S. F.; Bizzarro, V.; Parente, L.; Riccio, R.; de
Caprariis, P. Structure-based design, synthesis and preliminary anti-
inflammatory activity of bolinaquinone analogues. Eur. J. Med. Chem.
2011, 46, 488−496.
(25) Wu, G.-J.; Han, F.-S.; Zhao, Y.-L. Palladacycles derived from
arylphosphinamides for mild Suzuki-Miyaura cross-couplings. RSC
Adv. 2015, 5, 69776−69781.
(26) Li, B.-J.; Li, Y.-Z.; Lu, X.-Y.; Liu, J.; Guan, B.-T.; Shi, Z.-J.
Cross-Coupling of Aryl/Alkenyl Pivalates with Organozinc Reagents
through Nickel-Catalyzed C-O Bond Activation under Mild Reaction
Conditions. Angew. Chem., Int. Ed. 2008, 47, 10124−10127.
(27) Zhou, H.; Li, J.; Yang, H.; Xia, C.; Jiang, G. Triarylphosphines
as Aryl Donors for Pd(II)-Catalyzed Aromatic Coupling of
Oxabenzonorbornadienes. Org. Lett. 2015, 17, 4628−4631.
(28) Wei, J.; Liu, K.-M.; Duan, X.-F. Cobalt-Catalyzed Biaryl
Couplings via C-F Bond Activation in the Absence of Phosphine or
NHC Ligands. J. Org. Chem. 2017, 82, 1291−1300.
(29) Ghosh, R.; Sarkar, A. Bidentate P, N−P Ligand for Nickel-
Catalyzed Cross-Coupling of Aryl or Benzyl Chlorides with ArMgX. J.
Org. Chem. 2010, 75, 8283−8286.
(30) Chen, K.; Chen, W.; Yi, X.; Chen, W.; Liu, M.; Wu, H.
Sterically hindered N-heterocyclic carbene/palladium (ii) catalyzed
Suzuki−Miyaura coupling of nitrobenzenes. Chem. Commun. 2019,
55, 9287−9290.
(6) (a) Goossen, L. J.; Rodríguez, N.; Goossen, K. Carboxylic acids
as substrates in homogeneous catalysis. Angew. Chem., Int. Ed. 2008,
47, 3100−3120. (b) Dzik, W. I.; Lange, P. P.; Goossen, L. J.
Carboxylates as sources of carbon nucleophiles and electrophiles:
comparison of decarboxylative and decarbonylative pathways. Chem.
Sci. 2012, 3, 2671−2678.
(7) (a) Frost, C. G.; Wadsworth, K. J. Rhodium catalysed addition of
boronic acids to anhydrides: a new method for the synthesis of
ketones. Chem. Commun. 2001, 2316−2317. (b) Oguma, K.; Miura,
M.; Satoh, T.; Nomura, M. Rhodium-catalyzed coupling of sodium
tetraphenylborate with acid anhydrides in the presence or absence of
norbornene. J. Organomet. Chem. 2002, 648, 297−301.
(8) Muto, K.; Yamaguchi, J.; Musaev, D. G.; Itami, K. Decarbon-
ylative organoboron cross-coupling of esters by nickel catalysis. Nat.
Commun. 2015, 6, 7508.
(9) (a) Shi, S.; Meng, G.; Szostak, M. Synthesis of Biaryls through
Nickel-Catalyzed Suzuki−Miyaura coupling of amides by carbon−
nitrogen bond cleavage. Angew. Chem., Int. Ed. 2016, 55, 6959−6963.
(b) Zhou, T.; Ji, C.-L.; Hong, X.; Szostak, M. Palladium-catalyzed
decarbonylative Suzuki−Miyaura cross-coupling of amides by
carbon−nitrogen bond activation. Chem. Sci. 2019, 10, 9865−9871.
(10) Liu, C.; Ji, C.-L.; Qin, Z.-X.; Hong, X.; Szostak, M. Synthesis of
Biaryls via Decarbonylative Palladium-Catalyzed Suzuki-Miyaura
Cross-Coupling of Carboxylic Acids. iScience 2019, 19, 749−759.
(11) Malapit, C. A.; Bour, J. R.; Brigham, C. E.; Sanford, M. S. Base-
free nickel-catalysed decarbonylative Suzuki−Miyaura coupling of
acid fluorides. Nature 2018, 563, 100−104.
(12) Gooßen, L. J.; Paetzold, J. New Synthesis of Biaryls via Rh-
Catalyzed Decarbonylative Suzuki-Coupling of Carboxylic Anhydrides
with Arylboroxines. Adv. Synth. Catal. 2004, 346, 1665−1668.
(13) Guo, L.; Srimontree, W.; Zhu, C.; Maity, B.; Liu, X. Q.;
Cavallo, L.; Rueping, M. Nickel-catalyzed Suzuki−Miyaura cross-
couplings of aldehydes. Nat. Commun. 2019, 10, 1957.
(31) Quibell, J. M.; Duan, G.; Perry, G. J. P.; Larrosa, I.
Decarboxylative Suzuki−Miyaura coupling of (hetero)aromatic
carboxylic acids using iodine as the terminal oxidant. Chem. Commun.
2019, 55, 6445−6448.
(32) Salemi, H.; Kaboudin, B.; Kazemi, F.; Yokomatsu, T. Highly
water-dispersible magnetite nanoparticle supported-palladium−β-
cyclodextrin as an efficient catalyst for Suzuki−Miyaura and
Sonogashira coupling reactions. RSC Adv. 2016, 6, 52656−52664.
(33) Seo, T.; Ishiyama, T.; Kubota, K.; Ito, H. Solid-state Suzuki−
Miyaura cross-coupling reactions: olefin-accelerated C−C coupling
using mechanochemistry. Chem. Sci. 2019, 10, 8202−8210.
(34) Lee, H. W.; So, C. M.; Yuen, O. Y.; Wong, W.; Kwong, F. Y.
Palladium-catalyzed cross-coupling of (hetero)aryl or alkenyl
sulfonates with aryl titanium as the multi-functional reagent. Org.
Chem. Front. 2020, 7, 926.
(14) Zhou, J.-Y.; Tao, S.-W.; Liu, R.-Q.; Zhu, Y.-M. Forging C−S
Bonds through Nickel-Catalyzed Aryl Anhydrides with Thiophenols:
Decarbonylation or Decarbonylation Accompanied by Decarboxyla-
tion. J. Org. Chem. 2019, 84, 11891−11901.
́
̋
́
(15) (a) Spranitz, P.; Soregi, P.; Botlik, B.; Berta, M.; Soos, T.
Organocatalytic Desymmetrisation of Fittig’s Lactones: Deuterium as
a Reporter Tag for Hidden Racemisation. Synthesis 2019, 51, 1263−
1272. (b) Phakhodee, W.; Duangkamol, C.; Wangngae, S.;
Pattarawarapan, M. Acid anhydrides and the unexpected N, N-
diethylamides derived from the reaction of carboxylic acids with
Ph3P/I2/Et3N. Tetrahedron Lett. 2016, 57, 325−328. (c) Burton, S.
G.; Kaye, P. T. A convenient preparation of carboxylic acid
anhydrides using a “supported” phosphorus pentoxide reagent.
Synth. Commun. 1989, 19, 3331−3335.
(35) Schmidt, A.; Rahimi, A. A versatile catalyst system for Suzuki−
Miyaura syntheses of sterically hindered biaryls employing a
cyclobutene-1, 2-bis (imidazolium) salt. Chem. Commun. 2010, 46,
2995−2997.
(16) Yamaguchi, J.; Muto, K.; Itami, K. Recent Progress in Nickel-
Catalyzed Biaryl Coupling. Eur. J. Org. Chem. 2013, 2013, 19−30.
I
https://dx.doi.org/10.1021/acs.joc.0c02266
J. Org. Chem. XXXX, XXX, XXX−XXX