Palladium-catalyzed decarbonylative suzuki-miyaura coupling of amides to achieve biaryls via C-N bond cleavage

Article abstract of DOI:10.1021/acs.joc.9b01103

The palladium-catalyzed decarbonylative Suzuki-Miyaura coupling of amides via selective amide C-N bond cleavage was reported, which afforded mild access to substitute biaryl products in the presence of low catalyst loading with NaHCO₃ as the base in good yields within 4 h (29 examples).

Full text of DOI:10.1021/acs.joc.9b01103

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Featured Article
Palladium-Catalyzed Decarbonylative Suzuki-Miyaura
Coupling of Amides to Achieve Biaryls via C-N Bond Cleavage
Zhongfeng Luo, Li Xiong, Tingting Liu, Yuqi Zhang, Siqi
Lu, Yuwen Chen, Weijie Guo, Yulin Zhu, and Zhuo Zeng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01103 • Publication Date (Web): 25 Jul 2019
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Palladium-Catalyzed Decarbonylative Suzuki-Miyaura Coupling of
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Amides to Achieve Biaryls via C-N Bond Cleavage
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Zhongfeng Luo,a Li Xiong,a Tingting Liu,a Yuqi Zhang,a Siqi Lu,a Yuwen Chen,a Weijie Guo,a Yulin
Zhu,a,* Zhuo Zengab,*
aCollege of Chemistry and Environment, South China Normal University, Guangzhou 510006, People’s
Republic of China
bKey Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai, 200032, China
O
3 mol% Pd(PPh3)Cl2
3 equiv NaHCO3
R1
Ar
N
Ar'
B(OH)2
O
Ar Ar'
R2
toluene/dioxane(5/1)
150 ºC, 4 h
O
O
O
up to 88%
29 examples
R1
S
N
N
N
N
R2
=
short reaction time
,
,
O
O
O
ABSTRACT: The palladium-catalyzed decarbonylative Suzuki-Miyaura coupling of
amides via selective amides C-N bond cleavage was reported, which afforded a mild
access to substitute biaryl products in the presence of low catalyst loading with
NaHCO3 as base in good yields within 4 hours (29 examples).
KEYWORDS: Palladium-catalyzed; Amides; Decarbonylative; Suzuki-Miyaura
coupling; Biaryls
INTRODUCTION
Suzuki-Miyaura coupling is a powerful approach to carbon–carbon bond-formation,1
which is widely incorporated into the development of new pharmaceuticals,
agrochemicals and advanced materials.2 Moreover, it was one of the subjects of the
Nobel Prize for Chemistry in 2010.3
In recent decades, Suzuki-Miyaura coupling of electrophiles, including aryl
halides,1b, 3a aryl ethers,4a-4b carbamates,4c-4d sulfamates,4c carboxylic acids,4e-4f aryl
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amines,4g and other compounds,4h-4k with organoboron nucleophiles was successfully
developed. In recent years, notable progress in the field of activated amides as
unconventional electrophiles for Suzuki-Miyaura coupling reaction has also been
achieved.5 Of note, Suzuki-Miyaura coupling of aryl amides with arylborons mainly
gives ketones (Scheme 1a).6-11 In this process of coupling, activated amides undergo
metal insertion into the amide C-N bond to obtain acyl-metal intermediate. Immediately,
acyl-metal intermediate can undergo direct transmetalation, following reductive
elimination to afford acyl cross-coupling product. Alternatively, the acyl-intermediate,
which was produced by selective oxidative addition of transition-metal to activated
amide C-N bond, can be also subjected to a decarbonylative procedure, prior to or after
the transmetalation step. This process ultimately depends on the ability of acyl-metal to
undergo carbon monoxide de-insertion.5f, 12
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Up to now the Suzuki–Miyaura decarbonylative coupling of amides still remains a
challenge, for it is hard to choose suitable transition-metal catalyst to furnish the process
of carbon monoxide de-insertion. Preliminary studies have shown palladium-catalyzed
decarbonylative cross-coupling reactions of amides, such as retro-
8b
hydroamidocarbonylation,8a Heck reaction,5b,
cyanation,13a phosphorylation,13b
alkynylation,13c and borylation13d were well described.
To the best of our knowledge, two examples of nickel catalyzed decarbonylative
Suzuki–Miyaura coupling of amides were reported by Szostak et al. (Scheme 1b).14, 10f
There is much interest in the development of palladium-catalyzed decarbonylative
Suzuki–Miyaura coupling of amides, which can be as a simple method to form carbon-
carbon bond. Hence, we report the first case of palladium-catalyzed decarbonylative
Suzuki−Miyaura coupling of amides to offer a new arylation routine in the synthesis of
various biaryls (Scheme 1c).
Scheme 1. Previously reported Suzuki cross-coupling of amides
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(a) Transition-metal (Pd, Ni) catalyzed acylation Suzuki-Miyaura coupling6-11
5
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8
O
O
R1
Transition-metal (Pd, Ni) cat.
R
N
R2
Ar
B(OH)2
R
Ar
9
(b) Nickel-catalyzed decabonyative arylation Suzuki-Miyaura coupling
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O
5 mol% Ni(PCy3)2Cl2
4.5 equiv Na2CO3
R1
Ar
B(OH)2
R Ar
R
N
dioxane, 150 ºC, 12 h
R2
O
R1
Ac
N
N
N
R2
=
Ph
,
O
201614
201810f
(c) This work
Palladium-catalyzed decabonyative arylation Suzuki-Miyaura coupling
O
O
3 mol% Pd(PPh3)Cl2
3 equiv NaHCO3
O
S
R
N
R Ar
Ar
B(OH)2
toluene/dioxane (5/1)
150 ºC, 4 h
O
Saccharin available and inexpensive short reaction time
The amide air-moisture-stabilized, and high stability
RESULTS AND DISCUSSION
In 2016, our group and professor Szostak simultaneously reported Pd-catalyzed
Suzuki coupling acylation of N-acylsaccharin.9a,
As an acyl-source, N-
11b
acylsaccharins have several advantages: (a) N-acylsaccharins can be easily prepared
from saccharin that is virtually nontoxic, ecofriendly industrial raw materials; (b) N-
acylsaccharins are crystalline, benign and shelf-stable reagents, which could be
selectively activated at the exo-cyclic C-N bond by a transition metal catalyst; (c) N-
acylsaccharins are efficient functional group transfer reagents in acylation reactions. It
is significative and worthwhile to develop N-acylsaccharins which have other
advantageous applications. Therefore, in 2017, our group presented Rh-catalyzed
decarbonylative C-H functionalization of N-acylsaccharins.15
Inspired by the superior reactivity of N-acylsaccharin, N-benzoylsaccharin 1a and
para-methoxylphenylboronic acid 2e were employed as substrates to synthesize
decarbonylative arylation product biaryls at 150 °C (Table 1). The catalysts, ligands,
bases, and solvents were optimized to determine the best reaction conditions. Initially,
we attempted to achieve this transformation by adding 3 mol% of Pd(PPh3)2Cl2 catalyst
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and K2CO3, resulting the corresponding biaryl in 25% yield. By contrast, the compound
3a was delivered at trace yield and afforded by-product of ketones in the presence of
Pd(OAc)2, Pd(dba)2, (IPr)Pd(allyl)Cl, and Ni(PPh3)2Cl2 catalyst (Table 1, Entries 1-5).
The ligand is also a key factor and substantially influences the yield. PPh3 was found
to be the most efficient ligand, whereas P(t-Bu)3, PCy3, dppp, dppb and dcype delivered
the product (3a) in lower yields and obtained by-product of ketones (Table 1, Entries
6–11). In almost every case, NaHCO3 provided a higher yield of the desired product
than other kinds of bases (Table 1, Entries 12-16). The choice of solvent also influences
the reaction rate and selectivity, as well as equilibria. We changed the solvent polarity
to afford great chemoselective and solubility.16 As shown in the table 1, toluene /1,4-
dioxane (5/1) is the best choice (Table 1, Entries 17−22).
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Besides, the effect of the catalyst loading was also evaluated, and the yield decreased
dramatically when the loading of Pd(PPh3)2Cl2 decreased from 3 to 1 and 0.5 mol%
(Table 1, Entries 23-24). While 1 equiv. water was added to the reaction mixture under
standard condition, no decarbonylative coupling reaction occurred. It is possible that
the amide substrate was decomposed or hydrolyzed (Table 1, Entry 25). Hence, we
deduced that the saccharin was released in the reaction process as a poison. Based on
these screening experiments, the optimized conditions for Suzuki−Miyaura coupling of
amide were set as 3 mol% Pd(PPh3)2Cl2, and 3 equiv of NaHCO3 in super dry
toluene/1,4-dioxane (5/1) at 150 °C for 4 hours.
Table 1. Optimization of Reaction Conditionsa
O
OMe
O
O
B(OH)2
catalyst, ligand, solvent
base, 150 ºC
S
N
MeO
O
3a
1a
2e
entry
catalyst
ligand
none
PPh3
base
solvent
toluene
toluene
yieldb (%)
25
1
2
Pd(PPh3)2Cl2
Pd(OAc)2
K2CO3
K2CO3
trace
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Pd(dba)2
PPh3
K2CO3
K2CO3
K2CO3
toluene
trace
trace
trace
60
(IPr)Pd(allyl)Cl none
toluene
toluene
5
Ni(PPh3)2Cl2
Pd(PPh3)2Cl2
PdCl2
none
none
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6
K2CO3 toluene/1,4-dioxane (5:1)
7
P(t-Bu)3 K2CO3 toluene/1,4-dioxane (5:1)
trace
25
8
PdCl2
PCy3
dppp
dppb
dcype
none
none
none
none
none
none
none
none
none
none
none
none
K2CO3 toluene/1,4-dioxane (5:1)
K2CO3 toluene/1,4-dioxane (5:1)
K2CO3 toluene/1,4-dioxane (5:1)
K2CO3 toluene/1,4-dioxane (5:1)
K3PO4 toluene/1,4-dioxane (5:1)
Na2CO3 toluene/1,4-dioxane (5:1)
CsCO3 toluene/1,4-dioxane (5:1)
9c
10c
11c
PdCl2
<5
PdCl2
<5
PdCl2
trace
43
12 Pd(PPh3)2Cl2
13 Pd(PPh3)2Cl2
14 Pd(PPh3)2Cl2
15 Pd(PPh3)2Cl2
16 Pd(PPh3)2Cl2
17 Pd(PPh3)2Cl2
18 Pd(PPh3)2Cl2
19 Pd(PPh3)2Cl2
20 Pd(PPh3)2Cl2
21 Pd(PPh3)2Cl2
22 Pd(PPh3)2Cl2
23d Pd(PPh3)2Cl2
70
trace
trace
88
KOH
toluene/1,4-dioxane (5:1)
NaHCO3 toluene/1,4-dioxane (5:1)
NaHCO3 toluene/1,4-dioxane (4:1)
NaHCO3 toluene/1,4-dioxane (3:1)
NaHCO3 toluene/1,4-dioxane (2:1)
81
73
67
NaHCO3
NaHCO3
NaHCO3
DMF
DMSO
<5
<5
1,4-dioxane
45
NaHCO3 toluene/1,4-dioxane (5:1)
63
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24e Pd(PPh3)2Cl2
25f Pd(PPh3)2Cl2
none
none
NaHCO3 toluene/1,4-dioxane (5:1)
NaHCO3 toluene/1,4-dioxane (5:1)
48
trace
7
8
9
a Conditions: 1a (0.2 mmol, 1.0 equiv), 2e (0.4 mmol, 2.0 equiv), catalyst (3 mol%),
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ligand (6 mol%), base (3.0 equiv), and solvent (1.8 M). The mixture was stirred
b
c
and heated at 150 °C for 4 h (under a nitrogen atmosphere). Isolated yield.
d
e
Ligand (3 mol%). Catalyst (1 mol%). Catalyst (0.5 mol%). f Added 1.0 equiv.
water.
Under optimizing reaction conditions, we turned to examine the functional-group
tolerance of N-acylsaccharins in this approach (Scheme 2). N-benzoylsaccharin 1a was
employed as substrate and resulted in highest yield (3a, 88%). To investigate the
influence of electronic effects, mara-methoxylphenylboronic acid (2a) was used as a
standard. Several N-acylsaccharins bearing electron-donating substituents at the para-
positions were coupled with 2a to provide corresponding biaryls in good yields (3b, 3c,
3d). N-Acylsaccharins with electron-withdrawing substrates (1d), and (1e) gave desired
products in 56% and 70% yields (3e, 3f). Besides, steric hindrance on the N-
acylsaccharins (1g, 1h) were well-tolerated. Also, 2-naphthoyl (1i) and heteroaromatic
(1l) amides proved good reactivity and afforded the corresponding products in 61% and
53% yields (3i, 3l).To our delight, the utilization of the halide substituents F (1j) and
Cl (1k) afforded the corresponding products in 57% and 74% yields (3j, 3k).
Scheme 2. Scope of amide coupling partnersa
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O
O
B(OH)2
3 mol% Pd(PPh3)Cl2
R
O
S
N
3 equiv NaHCO3
R
R
R
toluene/dioxane (5/1)
O
150 ºC, 4 h
1
2
3
9
OMe
Me
OMe
OMe
10
11
12
13
14
15
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OMe
OMe
MeO
3b
3d
: 58%
OMe
: 63%
: 70%
: 57%
3a
3e
3c
: 62%
Me
: 88%
OMe
OMe
OMe
F3C
NC
3g
: 75%
3h
: 66%
3f
: 56%
OMe
OMe
OMe
Cl
F
S
3i
: 61%
3j
3k
: 74%
3l
: 53%
a Conditions: 1 (0.2 mmol, 1.0 equiv), 2 (0.4 mmol, 2.0 equiv), Pd(PPh3)2Cl2 (3 mol%),
NaHCO3 (3.0 equiv), and toluene/1,4-dioxane (5:1) (1.8 M). The mixture stirred and
heated at 150 °C for 4 h (under a nitrogen atmosphere).
Subsequently, the scope of arylboronic acid coupling partners was examined
(Scheme 3). Obviously, a variety of arylboronic acids, including electron-neutral, ‐poor,
and ‐rich compounds, afforded the desired products (3b, 3c, 3d, 3e, 3f, 3m, 3n) in 57-
72% yields. Meanwhile, steric-hindered arylboronic acids (2i, 2j) and halogen-
substituted substrates (2k, 2l, 2m) are well tolerated. The heterocyclic group such as 3-
thienyl also manifested good reactivity and delivered the desired product in 52% yields
(3p). 4-Methylthio-substituted and bis-ortho-substituted substrates resulted in low yield
(3r, 44%; 3t, 41%). Notably, naphthyl (2p), biaryl (2q), and disubstrate (2r) substituted
arylboronic acids were also applied in this transformation, resulting in good yields (3i,
3q, 3s). The yield of above-mentioned products, which range from 41% to 88%, were
isolated by column chromatography. Ketone byproducts were not noted under standard
conditions due to higher temperature (150 °C), but can be seen at lower temperatures6-
11 (110 °C).
Scheme 3. Scope of boronic acids coupling partnersa
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O
O
B(OH)2
3 mol% Pd(PPh3)Cl2
3 equiv NaHCO3
R
O
S
N
R
R
R
toluene/dioxane (5/1)
O
150 ºC, 4 h
1
2
3
9
MeO
Me
MeO
MeO
MeO
MeO
MeO
10
11
12
13
14
15
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OMe
Me
3c
: 68%
3b
: 65%
3m
3d
3g
: 72%
: 67%
Me
MeO
MeO
CN
CF3
CO2Me
3e
: 62%
3f
3n
: 64%
: 57%
: 66%
MeO
MeO
MeO
MeO
MeO
MeO
Cl
F
F
3j
3i
: 60%
3h
3o
3r
: 65%
: 52%
: 59%
3k
: 62%
MeO
MeO
MeO
S
S
3p
3q
: 7
: 71%
0%
: 44%
MeO
Me
Me
3t
: 41%
Me
3s
: 75%
a Conditions: 1 (0.2 mmol, 1.0 equiv), 2 (0.4 mmol, 2.0 equiv), Pd(PPh3)2Cl2 (3 mol%),
NaHCO3 (3.0 equiv), and toluene/1,4-dioxane (5:1) (1.8 M). The mixture stirred and
heated at 150 °C for 4 h (under a nitrogen atmosphere).
Four amides (1m, 1n, 1o and 1p) were employed in this catalytic system, and used
to compare with N-benzoylsaccharin (1a) under the standard conditions. There was no
ideal product of 3a when 1p was mixed with 2e under the standard conditions. What’s
more, the yield of other amides (1m, 1n, 1o) was lower than N-benzoylsaccharin
(Scheme 4). As previous report, N-acylsaccharins contained electron-withdrawing
sulfonyl moiety9a and distortion of the amide bond to explain ground-state
destabilization11b which could demonstrate its high reactivity.
Scheme 4. Control condition
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OMe
O
3 mol% Pd(PPh3)Cl2
B(OH)2
R1
3 equiv NaHCO3
N
R2
toluene/dioxane (5/1)
150 ºC, 4 h
MeO
O
1
2e
3a
O
O
10
11
12
13
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R1
O
Ph
Boc
S
N
N
N
N
N
=
N
R2
Ts
Boc
,
,
,
O
O
O
,
1a
1m
1n
1o
28%
1p
yield:
88%
78%
62%
tace
A scaled-up experiment was performed using a N-benzoylsaccharin 1a and 2e as
substrates, and 61% yield was achieved, implying its possible applications of this
method in synthetic chemistry (Scheme 5).
Scheme 5. A scaled-up experiment of the reaction
O
OMe
O
3 mol% Pd(PPh3)Cl2
3 equiv NaHCO3
O
B(OH)2
S
N
toluene/dioxane (5/1)
150 ºC, 4 h
MeO
O
3a
1a
4 mmol
2e
yield: 61%
Theoretical value: 1.15 g
Theoretical value: 0.74 g
Experimental value: 0.45 g
Based on typical Suzuki cross-coupling3a and amides Suzuki decarbonylative
coupling,5c, 5f, 14 a plausible mechanism was proposed (Scheme 6): (i) oxidative
addition of the N-acylsaccharins gave acylpalladium(II) complex II; (ii) following
transmetalation to produce complex III, and then rapidly transform to afford complex
IV; (iii) then, decarbonylation process of complex IV gave complex V, which
undergoes reductive elimination to produce 3 and regenerate Pd(0) species I.
Scheme 6. Proposed mechanism
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NaHCO3
Pd(PPh3)2Cl
ArB(OH)2
6
7
8
9
O
O
O
S
Ar1 Ar
Ar1
N
Ar
L2Pd(0)
Ar
3
O
oxidation
addition
1
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I
Ar1
Ar1
Ar
O O
S
O
II
(II)Pd
L
V
L2(II)Pd
N
L
transmetallation
O
decarbonylation
L = phosphine, CO
150 C
NaHCO3
ArB(OH)2
O
2
Ar
O
O
Ar1
Pd(II)
L
S
O
Na N
Ar
Ar1
IV
HO
Pd
(II)
O
O
B
L
OH
O
O
H
III
Na
CONCLUSIONS
In conclusion, we have developed a simple and efficient method for the palladium-
catalyzed decarbonylative Suzuki–Miyaura coupling of amides with arylboronic acids
via selective cleavage C-N bond. The easily prepared, commercially available and
highly stable regents promoted us to employ N-acylsaccharins and arylboronic acids as
effective decarbonylative coupling partners. The study of the substrate scope showed
that the reaction tolerated a broad range of substituents containing electron-donating,
electron-neutral and electron-withdrawing groups on both coupling partners.
Furthermore, this work provides the first example of the use of N-acylsaccharins as aryl
precursors for the synthesis of biaryls by palladium-catalyzed decarbonylative
coupling.
EXPERIMENT SECTION
Caution: No problems were encountered while handling these compounds. The
pressure sensitivities of pressure tube with glass thickness have not been determined.
However, they must be synthesized only in millimole amounts and handled with
extreme care.
General Method. The sealed tube (the pressure tube with glass thickness could
withstand six atmospheres) purchased from BEIJING SYNTHWARE GLASS. All
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reactants were commercially available and prepared. All solvents were used as
purchased from China suppliers. Super dry solvent 1,4-dioxane, toluene, DMF, and
DMSO were used without any pretreatment. HRMS (ion trap) were obtained from mass
spectrometer (ESI). Flash column chromatography was performed using 200-300 mesh
silica gel. 1H NMR, 13C NMR, and 19F NMR data were recorded with Varian AS (400
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o
MHz) and AVANCE NEO Bruker (600 MHz, 500 MHz) spectrometers at 25 C in
CDCl3 with tetramethylsiliane as an internal standard. Melting points were uncorrected
General Procedure for Synthesis of N-acylsaccharins.15
NEt3 (5 mmol, 1.0 equiv), DMAc (typically, 6 mL), and saccharin (5 mmol, 1.0 equiv,
slowly added into the mixture) were added to a 25 mL round-bottomed flask. Acyl
chloride (typically, 1.0 equiv) was dropwise added to the reaction mixture with
vigorous stirring at 0 oC in ice-water bath, and maintained the temperature at 0 oC for
1h. After the indicated time, the reaction mixture was poured into 80 ml water and
extracted with ethyl acetate three times (10 mL every time). The organic layer was
combined and washed with brine three times (15 mL every time), dried, and
concentrated. The obtained residue was purified by column chromatography (petroleum
ether/EtOAc = 3/1) to afford N-acylsaccharins.
General Procedure for Synthesis of Biaryls.
Arylboronic acid 2a-2s (0.4 mmol, 2.0 equiv), N-acylsaccharins 1a-1l (0.2 mmol, 1.0
equiv), NaHCO3 (3.0 equiv), Pd (PPh3)2Cl2 (typically, 3 mol%), and toluene/dioxane
[Super dry solvent, 1.8 mL (5/1)] were added to an oven-dried sealed tube (10 mL)
equipped with a stir bar. The reaction mixture was stirred at 150 °C in an oil bath for 4
h under the protection of a nitrogen atmosphere. After the mixture cooling to room
temperature, the solvent was removed. The residue was purified by silica gel column
chromatography using petroleum ether/EtOAc (50/1) as eluent to afford biaryls.
General Procedure for the Scaled-up Experiment.
Arylboronic acid 2e (8 mmol, 2.0 equiv), N-acylsaccharins 1a (4 mmol, 1.0 equiv),
NaHCO3 (3.0 equiv), Pd (PPh3)2Cl2 (typically, 3 mol%), and toluene/dioxane [Super
dry solvent, 12 mL (5/1)] were added to an oven-dried sealed tube (48 mL) equipped
with a stir bar. The reaction mixture was stirred at 150 °C in an oil bath for 4 h under
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the protection of a nitrogen atmosphere. After the mixture cooling to room temperature,
the solvent was removed. The residue was purified by silica gel column
chromatography using petroleum ether/EtOAc (50/1) as eluent to afford biaryls. This
approach could be given 61% 4-methoxy-1,1'-biphenyl (3a).
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General Procedure for the Control Condition.
Arylboronic acid 2e (0.4 mmol, 2.0 equiv), N-acylsaccharins 1m-1p (0.2 mmol, 1.0
equiv), NaHCO3 (3.0 equiv), Pd (PPh3)2Cl2 (typically, 3 mol%), and toluene/dioxane
[Super dry solvent, 1.8 mL (5/1)] were added to an oven-dried sealed tube (10 mL)
equipped with a stir bar. The reaction mixture was stirred at 150 °C in an oil bath for 4
h under the protection of a nitrogen atmosphere. After the mixture cooling to room
temperature, the solvent was removed. The residue was purified by silica gel column
chromatography using petroleum ether/EtOAc (50/1) as eluent to afford 3a in 78%,
62%, 28%, and trace yield.
The less reactive amides of the 1o and 1p easily decomposed at 150 °C under
standard conditions, so the desired product was obtained in low yields. In addition, the
1m and 1n produced less acylation by-products monitored by TLC.
N-Benzoylsaccharin (1a). Following general procedure for synthesis of N-
acylsaccharins, 1a was purified by column chromatography (petroleum ether/EtOAc =
3/1).White solid (1.12 g, 78%). mp 151-152 oC. 1H NMR (400 MHz, CDCl3) δ 8.13 (d,
J = 7.6 Hz, 1H), 8.03 – 7.99 (m, 2H), 7.95 – 7.89 (m, J = 8.4, 5.9, 2.8 Hz, 1H), 7.76 (d,
J = 7.5 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H). Spectral data match
those previously reported.15
N-(4-Methylbenzoyl)saccharin (1b). Following general procedure for synthesis of
N-acylsaccharins, 1b was purified by column chromatography (petroleum ether/EtOAc
= 3/1). White solid (1.14 g, 76%). mp 157-158 oC. 1H NMR (400 MHz, CDCl3) δ 8.12
(d, J = 7.5 Hz, 1H), 7.99 (d, J = 4.0 Hz, 2H), 7.92 – 7.88 (m, 1H), 7.68 (d, J = 8.1 Hz,
2H), 7.29 (d, J = 8.2 Hz, 2H), 2.44 (s, 3H). Spectral data match those previously
reported.9a
N-(3-Methoxybenzoyl)saccharin (1c). Following general procedure for synthesis
of N-acylsaccharins, 1c was purified by column chromatography (petroleum
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ether/EtOAc = 3/1). White solid (1.28 g, 82%). mp 145-146 C. 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 8.02 – 7.97 (m, 2H), 7.93 – 7.90 (m, 1H), 7.40 (t, J
= 7.8 Hz, 1H), 7.35 – 7.28 (t, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 1H), 3.86 (s, 3H).
Spectral data match those previously reported.15
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N-(4-Methoxybenzoyl)saccharin (1d). Following general procedure for synthesis
of N-acylsaccharins, 1d was purified by column chromatography (petroleum
ether/EtOAc = 3/1). White solid (1.32 g, 83%). mp 143-144 oC. 1H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 7.6 Hz, 1H), 7.98 (d, J = 3.8 Hz, 2H), 7.95 – 7.87 (m, 1H), 7.81
(d, J = 8.9 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 3.89 (s, 3H). Spectral data match those
previously reported.15
N-(4-(Trifluoromethyl)benzoyl)saccharin (1e). Following general procedure for
synthesis of N-acylsaccharins, 1e was purified by column chromatography (petroleum
o
1
ether/EtOAc = 3/1).White solid (1.01 g, 57%). mp 162-163 C. H NMR (400 MHz,
CDCl3) δ 8.13 (d, J = 7.6 Hz, 1H), 8.09 – 7.99 (m, 2H), 7.99 – 7.91 (m, 1H), 7.84 (d, J
= 8.1 Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -63.23 (s).
Spectral data match those previously reported.15
N-(4-Cyanobenzoyl)saccharin (1f). Following general procedure for synthesis of
N-acylsaccharins, 1f was purified by column chromatography (petroleum ether/EtOAc
= 3/1). White solid (748.80 mg, 48%). mp 166-167 oC. 1H NMR (400 MHz, CDCl3) δ
8.13 (d, J = 7.5 Hz, 1H), 8.07 – 8.01 (m, 2H), 7.99 – 7.93 (m, 1H), 7.80 (s, 4H). Spectral
data match those previously reported.15
N-(2-Methylbenzoyl)saccharin (1g). Following general procedure for synthesis of
N-acylsaccharins, 1g was purified by column chromatography (petroleum ether/EtOAc
= 3/1). White solid (933.10 mg, 63%). mp 158-159 oC. 1H NMR (400 MHz, CDCl3) δ
8.06 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 3.9 Hz, 2H), 7.91 (dd, J = 7.9, 3.9 Hz, 1H), 7.46
(t, J = 7.6 Hz, 1H), 7.40 (d, J = 7.5 Hz, 1H), 7.30 (dd, J = 7.6, 3.9 Hz, 2H), 2.44 (s, 3H).
Spectral data match those previously reported.9a
N-(2-Methoxybenzoyl)saccharin (1h). Following general procedure for synthesis
of N-acylsaccharins, 1h was purified by column chromatography (petroleum
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ether/EtOAc = 3/1).White solid (808.35 mg g, 51%). mp 148-149 C. H NMR (400
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MHz, CDCl3) δ 8.08 (d, J = 7.6 Hz, 1H), 8.03 – 7.97 (m, 2H), 7.90 (td, J = 8.0, 2.0 Hz,
1H), 7.58 – 7.51 (m, 2H), 7.09 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 9.2 Hz, 1H), 3.72 (s,
3H). Spectral data match those previously reported.15
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N-(2-Naphthoyl)saccharin (1i). Following general procedure for synthesis of N-
acylsaccharins, 1i was purified by column chromatography (petroleum ether/EtOAc =
3/1). White solid (1.15 g, 68%). mp 153-154 oC. 1H NMR (400 MHz, CDCl3) δ 8.35 (s,
1H), 8.14 (d, J = 7.9 Hz, 1H), 8.08 – 7.98 (m, 2H), 7.97 – 7.88 (m, 4H), 7.77 (dd, J =
8.6, 1.4 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H). Spectral data match
those previously reported.15
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N-(4-Fluorobenzoyl)saccharin (1j). Following general procedure for synthesis of
N-acylsaccharins, 1j was purified by column chromatography (petroleum ether/EtOAc
= 3/1). White solid (1.16 g, 76%). mp 170-171 oC. 1H NMR (400 MHz, CDCl3) δ 8.12
(d, J = 7.6 Hz, 1H), 8.04 – 7.95 (m, 2H), 7.95 – 7.88 (m, 1H), 7.85 – 7.71 (m, 2H), 7.16
(t, J = 8.4 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -102.65 (s). Spectral data match
those previously reported.9a
N-(4-Chlorobenzoyl)saccharin (1k). Following general procedure for synthesis of
N-acylsaccharins, 1k was purified by column chromatography (petroleum ether/EtOAc
= 3/1). White solid (1.14 g, 71%). mp 202-203 oC. 1H NMR (400 MHz, CDCl3) δ 8.14
(d, J = 7.7 Hz, 1H), 8.02 (d, J = 3.9 Hz, 2H), 7.97 – 7.91 (m, 1H), 7.71 (d, J = 8.5 Hz,
2H), 7.48 (d, J = 8.5 Hz, 2H). Spectral data match those previously reported.15
N-(Thiophene-2-carbonyl)saccharin (1l). Following general procedure for
synthesis of N-acylsaccharins, 1l was purified by column chromatography (petroleum
o
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ether/EtOAc = 3/1). White solid (919.80 mg, 63%). mp 136-138 C. H NMR (400
MHz, CDCl3) δ 8.18 (d, J = 7.5 Hz, 1H), 8.04 – 7.89 (m, 4H), 7.84 (dd, J = 4.9, 0.9 Hz,
1H), 7.19 (t, J = 4.5 Hz, 1H). Spectral data match those previously reported.15
1-Benzoylpiperidine-2,6-dione (1m). Following general procedure of literature, 1m
was purified by column chromatography (petroleum ether/EtOAc = 3/1). White solid
(0.92 g, 85%). mp 111-113 oC. 1H NMR (600 MHz, CDCl3) δ 7.85 (d, J = 7.4 Hz, 2H),
7.61 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 2.70 (t, J = 6.6 Hz, 4H), 2.10 – 2.01
(m, 2H). Spectral data match those previously reported.15
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1-Benzoylpyrrolidine-2,5-dione (1n). Following general procedure of literature, 1n
was purified by column chromatography (petroleum ether/EtOAc = 3/1). White solid
(0.84 g, 83%). mp 129-130 oC. 1H NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H),
7.65 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 2.90 (s, 4H). Spectral data match those
previously reported.15
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N-phenyl-N-tosylbenzamide (1o). Following general procedure of literature, 1o
was purified by column chromatography (petroleum ether/EtOAc = 3/1). White solid
(1.51 g, 86%). mp 135-136 oC.1H NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H),
7.44 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.30 – 7.26 (m, 4H), 7.16 (dd, J =
10.0, 5.2 Hz, 4H), 2.45 (s, 3H). Spectral data match those previously reported.15
N, N-Boc2-benzamide (1p). Following general procedure of literature, 1p was
purified by column chromatography (petroleum ether/EtOAc = 3/1). White solid (1.35
g, 84%). mp 61-62 oC.1H NMR (400 MHz, CDCl3) δ 7.82 (t, J = 6.5 Hz, 2H), 7.59 (t,
J = 7.2 Hz, 1H), 7.47 (t, J = 6.6 Hz, 2H), 1.36 (s, 18H). Spectral data match those
previously reported.15
4-Methoxy-1,1'-biphenyl (3a). Following general procedure for synthesis of biaryls,
3a purified by column chromatography (Petroleum ether/EtOAc = 50/1). White solid
o
1
(32.38 mg, 88%). mp 87-88 C. H NMR (400 MHz, CDCl3) δ 7.62 – 7.49 (m, 4H),
7.42 (t, J = 7.7 Hz, 2H), 7.31 (t, J = 7.3 Hz, 1H), 7.01 – 6.96 (m, 2H), 3.86 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 159.2, 140.9, 133.8, 128.8, 128.2, 114.2, 55.4.
Spectral data match those previously reported.17
3-Methoxy-1,1'-biphenyl (3b). Following general procedure for synthesis of biaryls,
3b purified by column chromatography (Petroleum ether/EtOAc = 50/1). White solid
(23.18 mg, 63%). mp 89-90 oC. 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 2H),
7.44 (t, J = 7.5 Hz, 2H), 7.36 (tt, J = 7.3, 3.8 Hz, 2H), 7.19 (d, J = 7.1 Hz, 1H), 7.14 (s,
1H), 6.91 (dd, J = 8.2, 1.9 Hz, 1H), 3.87 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3) δ
159.9, 142.8, 141.1, 129.8, 128.8, 127.4, 127.2, 119.7, 112.9, 112.7, 55.3. Spectral data
match those previously reported.17
3-Methoxy-4'-methyl-1,1'-biphenyl (3c). Following general procedure for
synthesis of biaryls, 3c purified by column chromatography (Petroleum ether/EtOAc =
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50/1). White solid (24.55 mg, 62%). mp 75-76 oC. 1H NMR (400 MHz, CDCl3) δ 7.49
(d, J = 8.0 Hz, 2H), 7.35 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 7.8 Hz, 2H), 7.17 (d, J = 7.7
Hz, 1H), 7.12 (s, 1H), 6.88 (dd, J = 8.2, 2.4 Hz, 1H), 3.87 (s, 3H), 2.40 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 159.9, 142.7, 138.2, 137.2, 129.7, 129.5, 127.0, 119.5, 112.7,
112.4, 55.3, 21.1. Spectral data match those previously reported.18
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3,4'-Dimethoxy-1,1'-biphenyl (3d). Following general procedure for synthesis of
biaryls, 3d purified by column chromatography (petroleum ether/EtOAc = 40/1). White
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1
solid (24.82 mg, 58%). mp 57-58 C. H NMR (600 MHz, CDCl3) δ 7.53 (d, J = 8.8
Hz, 2H), 7.34 (t, J = 7.9 Hz, 1H), 7.15 (dd, J = 7.7, 0.5 Hz, 1H), 7.11 – 7.07 (m, 1H),
6.98 (d, J = 8.8 Hz, 2H), 6.90 – 6.83 (m, 1H), 3.87 (s, 3H), 3.86 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 159.9, 142.4, 133.6, 129.7, 128.2, 119.3, 114.2, 112.6, 112.1, 55.4,
55.3. Spectral data match those previously reported.19
3-Methoxy-4'-(trifluoromethyl)-1,1'-biphenyl (3e). Following general procedure
for synthesis of biaryls, 3e purified by column chromatography (petroleum
ether/EtOAc = 40/1). A pale yellow solid (28.22 mg, 56%). mp 148-149 oC. 1H NMR
(400 MHz, CDCl3) δ 7.69 (s, 4H), 7.39 (t, J = 8.0 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H),
7.12 (s, 1H), 6.95 (dd, J = 8.2, 1.8 Hz, 1H), 3.88 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 160.1, 144.6, 141.3, 130.0, 129.5 (q, J1 = 32.0 Hz), 127.5, 125.7 (q, J2 = 3.0
Hz), 119.8, 113.5, 113.2, 55.4. 19F NMR (376 MHz, CDCl3) δ -62.44 (s). Spectral data
match those previously reported.19
3'-Methoxy-[1,1'-biphenyl]-4-carbonitrile (3f). Following general procedure for
synthesis of biaryls, 3f purified by column chromatography (petroleum ether/EtOAc =
o
1
50/1). A pale yellow solid (29.26 mg, 88%). mp 108-109 C. H NMR (400 MHz,
CDCl3) δ 7.68 (q, J = 8.3 Hz, 4H), 7.39 (t, J = 7.9 Hz, 1H), 7.16 (d, J = 7.7 Hz, 1H),
7.10 (s, 1H), 6.96 (d, J = 8.2 Hz, 1H), 3.86 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3)
δ 160.2, 145.6, 140.7, 132.6, 130.2, 127.8, 119.7, 118.9, 113.9, 113.1, 111.1, 55.4.
Spectral data match those previously reported.20
3'-Methoxy-2-methyl-1,1'-biphenyl (3g). Following general procedure for
synthesis of biaryls, 3g purified by column chromatography (petroleum ether/EtOAc =
1
50/1). Colorless oil (29.70 mg, 75%). H NMR (600 MHz, CDCl3) δ 7.33 (t, J = 7.9
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Hz, 1H), 7.28 – 7.26 (m, 2H), 7.26 – 7.23 (m, 2H), 6.96 – 6.84 (m, 3H), 3.84 (s, 3H),
2.29 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 159.3, 143.4, 141.8, 135.4, 130.3,
129.7, 129.0, 127.3, 125.7, 121.7, 114.9, 112.3, 55.3, 20.4. Spectral data match those
previously reported.18
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2-Methoxy-1,1'-biphenyl (3h). Following general procedure for synthesis of biaryls,
3h purified by column chromatography (petroleum ether/EtOAc = 50/1). Colorless oil
(24.29 mg, 66%). 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.1 Hz, 2H), 7.41 (t, J =
7.5 Hz, 2H), 7.37 – 7.29 (m, 3H), 7.04 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 8.6 Hz, 1H), 3.82
(s, 3H). 13C NMR{1H} (125 MHz, CDCl3) δ 156.5, 138.6, 130.9, 130.7, 129.6, 128.7,
128.0, 127.0, 120.9, 111.21, 55.6. Spectral data match those previously reported.17
2-(3-Methoxyphenyl)naphthalene (3i). Following general procedure for synthesis
of biaryls, 3i purified by column chromatography (petroleum ether/EtOAc = 50/1).
White solid (28.55 mg, 61%). mp 68-69 oC. 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H),
7.96 – 7.83 (m, 3H), 7.75 (d, J = 8.5 Hz, 1H), 7.56 – 7.46 (m, 2H), 7.41 (t, J = 7.9 Hz,
1H), 7.32 (d, J = 7.8 Hz, 1H), 7.26 (s, 1H), 6.94 (d, J = 9.8 Hz, 1H), 3.91 (s, 3H). 13C
NMR{1H} (100 MHz, CDCl3) δ 160.1, 142.7, 138.5, 133.7, 132.7, 129.9, 128.4, 128.2,
127.7, 126.3, 126.0, 125.9, 125.6, 120.0, 113.2, 112.8, 55.4. Spectral data match those
previously reported.21
4'-Fluoro-3-methoxy-1,1'-biphenyl (3j). Following general procedure for synthesis
of biaryls, 3j purified by column chromatography (petroleum ether/EtOAc = 50/1).
White solid (23.03 mg, 57%). mp 69-70 oC.1H NMR (600 MHz, CDCl3) δ 7.58 – 7.50
(m, 2H), 7.35 (t, J = 7.9 Hz, 1H), 7.12 (t, J = 8.6 Hz, 3H), 7.07 (s, 1H), 6.90 (d, J = 5.9
Hz, 1H), 3.87 (s, 3H). 13C NMR{1H} (100 MHz, CDCl3) δ 163.8, 161.3, 160.0, 141.8,
137.2, 129.8, 128.7 (d, J3 = 8.0 Hz), 119.5, 115.6 (d, J2 = 22.0 Hz), 112.7 (d, J1 = 29.0
Hz), 55.3. 19F NMR (565 MHz, CDCl3) δ -115.58 (t, J = 6.9 Hz). Spectral data match
those previously reported.19
4'-Chloro-3-methoxy-1,1'-biphenyl (3k). Following general procedure for
synthesis of biaryls, 3k purified by column chromatography (petroleum ether/EtOAc =
o
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50/1). White solid (32.26 mg, 74%). mp 114-115 C. H NMR (600 MHz, CDCl3) δ
7.51 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 7.36 (t, J = 7.9 Hz, 1H), 7.14 (d, J =
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7.7 Hz, 1H), 7.08 (d, J = 1.8 Hz, 1H), 6.91 (dd, J = 8.1, 2.3 Hz, 1H), 3.87 (s, 3H). 13C
NMR{1H} (100 MHz, CDCl3) δ 160.0, 141.5, 139.5, 133.5, 129.9, 128.9, 128.4, 119.5,
112.9, 112.8, 55.3. Spectral data match those previously reported.22
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2-(3-Methoxyphenyl)thiophene (3l). Following general procedure for synthesis of
biaryls, 3l purified by column chromatography (petroleum ether/EtOAc = 50/1). A pale
yellow solid (20.14 mg, 53%). mp 117-118 oC. 1H NMR (600 MHz, CDCl3) δ 7.36 (ddd,
J = 8.2, 7.6, 1.8 Hz, 1H), 7.27 (d, J = 0.9 Hz, 1H), 7.26 – 7.23 (m, 1H), 7.20 (d, J = 7.3
Hz, 1H), 7.16 (dd, J = 7.4, 1.8 Hz, 1H), 7.03 (td, J = 7.4, 1.0 Hz, 1H), 6.98 (d, J = 8.3
Hz, 1H), 3.78 (s, 3H). 13C NMR{1H} (100 MHz, CDCl3) δ 156.6, 138.7, 131.0, 130.0,
129.6, 128.6, 127.3, 125.4, 120.5, 110.7, 55.4. Spectral data match those previously
reported.23
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3-Methoxy-3'-methyl-1,1'-biphenyl (3m). Following general procedure for
synthesis of biaryls, 3m purified by column chromatography (petroleum ether/EtOAc
= 50/1). Colorless oil (28.51 mg, 72%). 1H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 11.4
Hz, 2H), 7.38 – 7.33 (m, 2H), 7.21 – 7.17 (m, 2H), 7.15 – 7.12 (m, 1H), 6.91 (dd, J =
8.2, 2.5 Hz, 1H), 3.88 (s, 3H), 2.44 (s, 3H).13C NMR{1H} (100 MHz, CDCl3) δ 159.9,
142.9, 141.1, 138.3, 129.7, 128.6, 128.2, 128.0, 124.3, 119.7, 112.9, 112.7, 55.3, 21.5.
Spectral data match those previously reported.22
Methyl 3'-methoxy-[1,1'-biphenyl]-4-carboxylate (3n). Following general
procedure for synthesis of biaryls, 3n purified by column chromatography (petroleum
ether/EtOAc = 40/1).White solid (30.98 mg, 64%). mp 53-54 oC. 1H NMR (600 MHz,
CDCl3) δ 8.10 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 7.9 Hz, 1H),
7.21 (d, J = 7.7 Hz, 1H), 7.17 – 7.13 (m, 1H), 6.94 (dd, J = 8.2, 2.4 Hz, 1H), 3.94 (s,
3H), 3.88 (s, 3H).13C NMR{1H} (100 MHz, CDCl3) δ 167.0, 160.1, 145.5, 141.5, 130.1,
130.0, 129.1, 127.1, 119.8, 113.5, 113.1, 55.4, 52.1. Spectral data match those
previously reported.24
2-Fluoro-3'-methoxy-1,1'-biphenyl (3o). Following general procedure for
synthesis of biaryls, 3o purified by column chromatography (petroleum ether/EtOAc =
50/1). White solid (23.84 mg, 59%). mp 74-75 oC. 1H NMR (600 MHz, CDCl3) δ 7.47
– 7.43 (m, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.34 – 7.30 (m, 1H), 7.21 (td, J = 7.5, 1.1 Hz,
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(s, 3H). C{1H} NMR (100 MHz, CDCl3) δ 159.7 (d, J1 = 247.0 Hz), 159.5, 137.1,
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130.7 (d, J2 = 3.4 Hz), 129.4, 129.1, 128.9, 124.2, 124.2, 121.4 (d, J4= 2.8 Hz), 116.1,
115.9, 114.6 (d, J3 = 3.0 Hz), 113.2, 55.2. 19F NMR (565 MHz, CDCl3) δ -117.64 (t, J
= 11.6 Hz). HRMS (ESI-ion trap) m/z: [M+H]+ calcd for C13H12OF: 203.0867; Found
203.0859.
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3-(3-Methoxyphenyl)thiophene (3p). Following general procedure for synthesis of
biaryls, 3p purified by column chromatography (petroleum ether/EtOAc). Light brown
oil (19.76 mg, 52%). 1H NMR (600 MHz, CDCl3) δ 7.46 (t, J = 2.1 Hz, 1H), 7.38 (d, J
= 2.2 Hz, 2H), 7.32 (t, J = 7.9 Hz, 1H), 7.20 (d, J = 7.7 Hz, 1H), 7.16 – 7.13 (m, 1H),
6.85 (dd, J = 8.2, 2.5 Hz, 1H), 3.86 (s, 3H).13C{1H} NMR (100 MHz, CDCl3) δ 160.0,
142.3, 137.3, 129.8, 126.4, 126.2, 120.5, 119.1, 112.5, 112.3, 55.3. Spectral data match
those previously reported.25
3-Methoxy-1,1':4',1''-terphenyl (3q). Following general procedure for synthesis of
biaryls, 3q purified by column chromatography (petroleum ether/EtOAc = 40/1). White
solid (36.4 mg, 70%). mp 105-106 oC. 1H NMR (600 MHz, CDCl3) δ 7.69 (s, 4H), 7.66
(d, J = 7.1 Hz, 2H), 7.47 (t, J = 7.7 Hz, 2H), 7.38 (q, J = 7.7 Hz, 2H), 7.25 (d, J = 8.1
Hz, 1H), 7.21 – 7.17 (m, 1H), 6.93 (dd, J = 8.0, 2.2 Hz, 1H), 3.89 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 160.0, 142.3, 140.7, 140.3, 140.0, 129.8, 128.8, 127.6, 127.5,
127.4, 127.1, 119.6, 112.8, 112.8, 55.3. Spectral data match those previously reported.21
(3'-Methoxy-[1,1'-biphenyl]-4-yl)(methyl)sulfane (3r). Following general
procedure for synthesis of biaryls, 3r purified by column chromatography (petroleum
ether/EtOAc = 50/1). Light brown oil (20.24 mg, 44%). 1H NMR (600 MHz, CDCl3) δ
7.52 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.16 (d, J =
7.7 Hz, 1H), 7.11 – 7.08 (m, 1H), 6.89 (dd, J = 8.2, 2.5 Hz, 1H), 3.87 (s, 3H), 2.52 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 160.0, 142.1, 137.9, 137.8, 129.8, 127.5,
126.9, 119.4, 112.7, 112.6, 55.3, 15.9. Spectral data match those previously reported.26
3'-Methoxy-3,5-dimethyl-1,1'-biphenyl (3s). Following general procedure for
synthesis of biaryls, 3s purified by column chromatography (petroleum ether/EtOAc =
50/1). White solid (31.80 mg, 75%). mp 50-51 oC. 1H NMR (600 MHz, CDCl3) δ 7.34
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(t, J = 7.9 Hz, 1H), 7.21 (s, 2H), 7.19 – 7.15 (m, 1H), 7.13 – 7.10 (m, 1H), 7.01 (s, 1H),
6.92 – 6.85 (m, 1H), 3.87 (s, 3H), 2.39 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ
159.9, 143.0, 141.1, 138.2, 129.6, 129.1, 125.1, 119.7, 112.9, 112.6, 55.3, 21.4. Spectral
data match those previously reported.27
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2'-Methoxy-2-methyl-1,1'-biphenyl (3t). Following general procedure for
synthesis of biaryls, 3t purified by column chromatography (petroleum ether/EtOAc =
50/1). White solid (14.66 mg, 37%). mp 43-44 oC. 1H NMR (600 MHz, CDCl3) δ 7.36
(ddd, J = 8.3, 7.5, 1.8 Hz, 1H), 7.27 (dd, J = 3.9, 1.6 Hz, 2H), 7.26 – 7.23 (m, 1H), 7.20
(d, J = 7.2 Hz, 1H), 7.16 (dd, J = 7.4, 1.8 Hz, 1H), 7.02 (td, J = 7.4, 1.0 Hz, 1H), 6.98
13
(d, J = 8.3 Hz, 1H), 3.77 (s, 3H), 2.15 (s, 3H). C NMR{1H} (125 MHz, CDCl3) δ
156.6, 138.6, 136.8, 131.0, 130.0, 129.6, 128.6, 127.3, 126.9, 125.4, 120.4, 110.6, 55.42,
19.9. Spectral data match those previously reported.28
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website
at http://pubs.acs.org. Copies of 1H, 13C{1H}, and 19F NMR of 3a-3t.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: zhuoz@scnu.edu.cn
*E-mail: labzhu@aliyun.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully thank the Science and Technology Planning Project of Guangdong
Province (2017A010103017), Special Innovation Projects of Common Universities in
Guangdong Province (20178S0182), and National Natural Science Foundation of
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REFERENCES
(1) (a) Molander, G. A.; Biolatto, B. Palladium-Catalyzed Suzuki−Miyaura Cross-
Coupling Reactions of Potassium Aryl- and Heteroaryltrifluoroborates. J. Org. Chem.
2003, 68, 4302-4314. (b) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S.
L. Catalysts for Suzuki−Miyaura Coupling Processes:ꢀScope and Studies of the Effect
of Ligand Structure. J. Am. Chem. Soc. 2005, 127, 4685-4696. (c) Quasdorf, K. W.;
Riener, M.; Petrova, K. V.; Garg, N. K. Suzuki−Miyaura Coupling of Aryl Carbamates,
Carbonates, and Sulfamates. J. Am. Chem. Soc. 2009, 131, 17748-17749. (d) Han, F.-
S. Transition-metal-catalyzed Suzuki–Miyaura cross-coupling reactions: a remarkable
advance from palladium to nickel catalysts. Chem. Soc. Rev. 2013, 42, 5270-5298. (e)
Lennox, A. J. J.; Lloyd-Jones, G. C. Selection of boron reagents for Suzuki–Miyaura
coupling. Chem. Soc. Rev. 2014, 43, 412-443. (f) W.B. Fyfe, J.; Watson, A. Recent
Developments in Organoboron Chemistry: Old Dogs, New Tricks. Chem, 2017, 3, 31-
55; (g) 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.
(2) (a) Hassan, J.; Sévignon, 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. (b) Horton, D. A.; Bourne, G. T.; Smythe, M. L. The Combinatorial
Synthesis of Bicyclic Privileged Structures or Privileged Substructures. Chem. Rev.
2003, 103, 893-930. (c) Hussain, I.; Singh, T. Synthesis of Biaryls through Aromatic
C-H Bond Activation: A Review of Recent Developments. Adv. Synth. Catal. 2014,
356, 1661-1696.
(3) (a) Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of
Organoboron Compounds. Chem. Rev. 1995, 95, 2457-2483. (b) Suzuki, A. Cross-
Coupling Reactions of Organoboranes: An Easy Way to Construct C-C Bonds (Nobel
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Page 22 of 29
1
2
3
4
5
6
7
8
Lecture). Angew. Chem. Int. Ed. 2011, 50, 6722-6737. (c) Lennox, A. J. J.; Lloyd-Jones,
G. C. Transmetalation in the Suzuki–Miyaura Coupling: The Fork in the Trail. Angew.
Chem. Int. Ed. 2013, 52, 7362-7370.
9
(4) (a) Cornella, J.; Zarate, C.; Martin, R. Metal-catalyzed activation of ethers via C–O
bond cleavage: a new strategy for molecular diversity. Chem. Soc. Rev. 2014, 43, 8081-
8097. (b) Muto, K.; Yamaguchi, J.; Musaev, D. G.; Itami, K. Decarbonylative
organoboron cross-coupling of esters by nickel catalysis. Nat. Commun. 2015, 6, 7508.
(c) Antoft-Finch, A.; Blackburn, T.; Snieckus, V. N, N-Diethyl O-Carbamate: Directed
Metalation Group and Orthogonal Suzuki−Miyaura Cross-Coupling Partner. J. Am.
Chem. Soc. 2009, 131, 17750-17752. (d) Quasdorf, K. W.; Antoft-Finch, A.; Liu, P.;
Silberstein, A. L.; Komaromi, A.; Blackburn, T.; Ramgren, S. D.; Houk, K. N.;
Snieckus, V.; Garg, N. K. Suzuki−Miyaura Cross-Coupling of Aryl Carbamates and
Sulfamates: Experimental and Computational Studies. J. Am. Chem. Soc. 2011, 133,
6352-6363. (e) Dai, J. J.; Liu, J. H.; Luo, D.-F.; Liu, L. Pd-catalysed decarboxylative
Suzuki reactions and orthogonal Cu-based O-arylation of aromatic carboxylic acids.
Chem. Commun. 2011, 47, 677-679. (f) Gooßen, L. J.; Ghosh, K. A new practical
ketone synthesis directly from carboxylic acids: first application of coupling reagents
in palladium catalysis. Chem. Commun. 2001, 2084-2085. (g) 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. (h) 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. (i) Tobisu, M.; Chatani, N. Cross-Couplings Using
Aryl Ethers via C–O Bond Activation Enabled by Nickel Catalysts. Accounts Chem.
Res. 2015, 48, 1717-1726. (j) Rygus, J. P. G.; Crudden, C. M. Enantiospecific and
Iterative Suzuki–Miyaura Cross-Couplings. J. Am. Chem. Soc. 2017, 139, 18124-18137.
(k) Ben Halima, T.; Zhang, W.; Yalaoui, I.; Hong, X.; Yang, Y. F.; Houk, K. N.;
Newman, S. G. Palladium-Catalyzed Suzuki–Miyaura Coupling of Aryl Esters. J. Am.
Chem. Soc. 2017, 139, 1311-1318.
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11
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13
14
15
16
17
18
19
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21
22
23
24
25
26
27
28
29
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35
36
37
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41
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43
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45
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49
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59
60
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7
8
9
(5) (a) Meng, G.; Shi, S.; Szostak, M. Cross-Coupling of Amides by N–C Bond
Activation. Synlett 2016, 27, 2530–2540; (b) Liu, C.; Meng, G.; Szostak, M. N-
Acylsaccharins as Amide-Based Arylating Reagents via Chemoselective N–C
Cleavage: Pd-Catalyzed Decarbonylative Heck Reaction. J. Org. Chem. 2016, 81,
12023-12030. (c) Liu, C.; Szostak, M. Twisted Amides: From Obscurity to Broadly
Useful Transition-Metal Catalyzed Reactions by N-C Amide Bond Activation. Chem.
Eur. J., 2016, 23, 7157 – 7173 (d) Takise, R.; Muto, K.; Yamaguchi, J. Cross-coupling
of aromatic esters and amides. Chem. Soc. Rev. 2017, 46, 5864-5888. (e)
Chatupheeraphat, A.; Liao, H.-H.; Srimontree, W.; Guo, L.; Minenkov, Y.; Poater, A.;
Cavallo, L.; Rueping, M. Ligand-Controlled Chemoselective C(acyl)–O Bond vs
C(aryl)–C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)–C(sp3)
Cross-Couplings. J. Am. Chem. Soc. 2018, 140, 3724-3735. (f) Liu, C.; Szostak, M.
Decarbonylative cross-coupling of amides. Org. Biomol. Chem. 2018, 16, 7998-8010.
(g) Liu, X.; Hsiao, C.-C.; Guo, L.; Rueping, M. Cross-Coupling of Amides with
Alkylboranes via Nickel-Catalyzed C–N Bond Cleavage. Org. Lett. 2018, 20, 2976-
2979. (h) Buchspies, J.; Szostak, M. Recent Advances in Acyl Suzuki Cross-Coupling.
Catalysts 2019, 9. 53.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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34
35
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41
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43
44
45
46
47
48
49
50
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52
53
54
55
56
57
58
59
60
(6) (a) Li, X.; Zou, G. Acylative Suzuki coupling of amides: acyl-nitrogen activation
via synergy of independently modifiable activating groups. Chem. Commun. 2015, 51,
5089-5092. (b) Li, X.; Zou, G. Palladium-catalyzed acylative cross-coupling of amides
with diarylborinic acids and sodium tetraarylborates. J. Organomet. Chem. 2015, 794,
136-145. (c) Shi, W.; Zou, G. Palladium-Catalyzed Room Temperature Acylative
Cross-Coupling of Activated Amides with Trialkylboranes. Molecules 2018, 23. (d)
Wang, C.; Huang, L.; Wang, F.; Zou, G. Highly efficient synthesis of aryl ketones by
PEPPSI-palladium catalyzed acylative Suzuki coupling of amides with diarylborinic
acids. Tetrahedron Lett. 2018, 59, 2299-2301.
(7) (a) Hie, L.; Fine Nathel, N. F.; Shah, T. K.; Baker, E. L.; Hong, X.; Yang, Y.-F.;
Liu, P.; Houk, K. N.; Garg, N. K. Conversion of amides to esters by the nickel-catalysed
activation of amide C–N bonds. Nature 2015, 524, 79-83. (b) Weires, N. A.; Baker, E.
L.; Garg, N. K. Nickel-catalysed Suzuki–Miyaura coupling of amides. Nat. Chem. 2015,
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2
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5
6
7
8
9
8, 75-79. (c) Dander, J. E.; Weires, N. A.; Garg, N. K. Benchtop Delivery of Ni(cod)2
using Paraffin Capsules. Org. Lett. 2016, 18, 3934-3936. (d) Hie, L.; Baker Emma, L.;
Anthony Sarah, M.; Desrosiers, J. N.; Senanayake, C.; Garg Neil, K. Nickel‐Catalyzed
Esterification of Aliphatic Amides. Angew. Chem. Int. Ed. 2016, 55, 15129-15132. (e)
Baker, E. L.; Yamano, M. M.; Zhou, Y.; Anthony, S. M.; Garg, N. K. A two-step
approach to achieve secondary amide transamidation enabled by nickel catalysis. Nat.
Commun. 2016, 7, 11554. (f) Dander, J. E.; Baker, E.; Garg, N. K. Nickel-catalyzed
transamidation of aliphatic amide derivatives. Chem. Sci. 2017, 8, 6433-6438. (g)
Weires, N. A.; Caspi, D. D.; Garg, N. K. Kinetic Modeling of the Nickel-Catalyzed
Esterification of Amides. ACS Catal. 2017, 7, 4381-4385. (h) Boit, T. B.; Weires, N.
A.; Kim, J.; Garg, N. K. Nickel-Catalyzed Suzuki–Miyaura Coupling of Aliphatic
Amides. ACS Catal. 2018, 8, 1003-1008.
10
11
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19
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45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) (a) Meng, G.; Szostak, M. Sterically Controlled Pd-Catalyzed Chemoselective
Ketone Synthesis via N–C Cleavage in Twisted Amides. Org. Lett. 2015, 17, 4364-
4367. (b) Meng, G.; Szostak, M. General Olefin Synthesis by the Palladium‐Catalyzed
Heck Reaction of Amides: Sterically Controlled Chemoselective N-C Activation.
Angew. Chem. Int. Ed. 2015, 54, 14518-14522. (c) Liu, C.; Achtenhagen, M.; Szostak,
M. Chemoselective Ketone Synthesis by the Addition of Organometallics to N-
Acylazetidines. Org. Lett. 2016, 18, 2375-2378. (d) Meng, G.; Shi, S.; Szostak, M.
Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Amides via Site-Selective
N–C Bond Cleavage by Cooperative Catalysis. ACS Catal. 2016, 6, 7335-7339. (e)
Meng, G.; Szostak, M. Palladium-catalyzed Suzuki-Miyaura coupling of amides by
carbon-nitrogen cleavage: general strategy for amide N-C bond activation. Org. Biomol.
Chem. 2016, 14, 5690-5707. (f) 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. (g) Shi, S.; Szostak, M.
Nickel-Catalyzed Diaryl Ketone Synthesis by N–C Cleavage: Direct Negishi Cross-
Coupling of Primary Amides by Site-Selective N, N-Di-Boc Activation. Org. Lett. 2016,
18, 5872-5875. (h) Szostak, R.; Shi, S.; Meng, G.; Lalancette, R.; Szostak, M. Ground-
State Distortion in N-Acyl-tert-butyl-carbamates (Boc) and N-Acyl-tosylamides (Ts):
ACS Paragon Plus Environment

Page 25 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
Twisted Amides of Relevance to Amide N–C Cross-Coupling. J. Org. Chem. 2016, 81,
8091-8094.
7
8
9
(9) (a) Liu, C.; Meng, G.; Liu, Y.; Liu, R.; Lalancette, R.; Szostak, R.; Szostak, M. N-
Acylsaccharins: Stable Electrophilic Amide-Based Acyl Transfer Reagents in Pd-
Catalyzed Suzuki–Miyaura Coupling via N–C Cleavage. Org. Lett. 2016, 18, 4194-
4197. (b) Lei, P.; Meng, G.; Ling, Y.; An, J.; Szostak, M. Pd-PEPPSI: Pd-NHC
Precatalyst for Suzuki–Miyaura Cross-Coupling Reactions of Amides. J. Org. Chem.
2017, 82, 6638-6646. (c) Lei, P.; Meng, G.; Shi, S.; Ling, Y.; An, J.; Szostak, R.;
Szostak, M. Suzuki-Miyaura cross-coupling of amides and esters at room temperature:
Correlation with barriers to rotation around C-N and C-O bonds. Chem. Sci. 2017, 8,
6525-6530. (d) Lei, P.; Meng, G.; Szostak, M. General Method for the Suzuki–Miyaura
Cross-Coupling of Amides Using Commercially Available, Air- and Moisture-Stable
Palladium/NHC (NHC = N-Heterocyclic Carbene) Complexes. ACS Catal. 2017, 7,
1960-1965. (e) Liu, C.; Liu, Y.; Liu, R.; Lalancette, R.; Szostak, R.; Szostak, M.
Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of N-Mesylamides by N–C
Cleavage: Electronic Effect of the Mesyl Group. Org. Lett. 2017, 19, 1434-1437. (f)
Osumi, Y.; Liu, C.; Szostak, M. N-Acylsuccinimides: twist-controlled, acyl-transfer
reagents in Suzuki-Miyaura cross-coupling by N-C amide bond activation. Org. Biomol.
Chem. 2017, 15, 8867-8871.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
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38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) (a) Lei, P.; Meng, G.; Ling, Y.; An, J.; Nolan, S. P.; Szostak, M. General Method
for the Suzuki–Miyaura Cross-Coupling of Primary Amide-Derived Electrophiles
Enabled by [Pd(NHC)(cin)Cl] at Room Temperature. Org. Lett. 2017, 19, 6510-6513.
(b) Meng, G.; Lalancette, R.; Szostak, R.; Szostak, M. N-Methylamino Pyrimidyl
Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N–
C(O) Cleavage. Org. Lett. 2017, 19, 4656-4659. (c) Meng, G.; Szostak, R.; Szostak, M.
Suzuki–Miyaura Cross-Coupling of N-Acylpyrroles and Pyrazoles: Planar,
Electronically Activated Amides in Catalytic N–C Cleavage. Org. Lett. 2017, 19, 3596-
3599. (d) Shi, S.; Nolan, S. P.; Szostak, M. Well-Defined Palladium(II)–NHC
Precatalysts for Cross-Coupling Reactions of Amides and Esters by Selective N–C/O–
C Cleavage. Accounts Chem. Res. 2018, 51, 2589-2599. (e) Li, G.; Lei, P.; Szostak, M.;
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The Journal of Organic Chemistry
Page 26 of 29
1
2
3
4
5
6
7
8
9
Casals-Cruañas, E.; Poater, A.; Cavallo, L.; Nolan, S. P. Mechanistic Study of Suzuki–
Miyaura Cross-Coupling Reactions of Amides Mediated by [Pd(NHC)(allyl)Cl]
Precatalysts. ChemCatChem 2018, 10, 3096-3106. (f) Liu, C.; Li, G.; Shi, S.; Meng,
G.; Lalancette, R.; Szostak, R.; Szostak, M. Acyl and Decarbonylative Suzuki Coupling
of N-Acetyl Amides: Electronic Tuning of Twisted, Acyclic Amides in Catalytic
Carbon–Nitrogen Bond Cleavage. ACS Catal. 2018, 8, 9131-9139. (g) Meng, G.;
Szostak, M. Palladium/NHC (NHC = N-Heterocyclic Carbene)-Catalyzed B-Alkyl
Suzuki Cross-Coupling of Amides by Selective N–C Bond Cleavage. Org. Lett. 2018,
20, 6789-6793.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(11) (a) Wang, T.; Xie, H.; Liu, L.; Zhao, W.-X. N-Heterocyclic carbene-palladium(II)
complexes with benzoxazole or benzothiazole ligands: Synthesis, characterization, and
application to Suzuki–Miyaura cross-coupling reaction. J. Organomet. Chem. 2016,
804, 73-79. (b) Wu, H.; Li, Y.; Cui, M.; Jian, J.; Zeng, Z. Suzuki Coupling of Amides
via Palladium‐Catalyzed C–N Cleavage of N‐Acylsaccharins. Adv. Synth. Catal. 2016,
358, 3876-3880. (c) Amani, J.; Alam, R.; Badir, S.; Molander, G. A. Synergistic
Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones via N–C
Cleavage of Imides. Org. Lett. 2017, 19, 2426-2429. (d) Cui, M.; Chen, Z.; Liu, T.;
Wang, H.; Zeng, Z. N-Acylsuccinimides: Efficient acylative coupling reagents in
palladium-catalyzed Suzuki coupling via CN cleavage. Tetrahedron Lett. 2017, 58,
3819-3822. (e) Lim, M.; Kim, H.; Ban, J.; Son, J.; Lee, J. K.; Min, S.-J.; Lee, S. U.;
Rhee, H. Palladium-Catalyzed Carbonylative Coupling Reactions of N,N-
Bis(methanesulfonyl)amides through C–N Bond Cleavage. Eur. J. Org. Chem. 2018,
2018, 5717-5724. (f) Luo, Z.; Liu, T.; Guo, W.; Wang, Z.; Huang, J.; Zhu, Y.; Zeng, Z.
N-Acyl-5,5-dimethylhydantoin, a New Mild Acyl-Transfer Reagent in Pd Catalysis:
Highly Efficient Synthesis of Functionalized Ketones. Org. Process Res. Dev. 2018,
22, 1188-1199. (g) Wang, T.; Guo, J.; Wang, H.; Guo, H.; Jia, D.; Zhang, W.; Liu, L.
N-heterocyclic carbene palladium(II)-catalyzed Suzuki-Miyaura cross coupling of N-
acylsuccinimides by C-N cleavage. J. Organomet. Chem. 2018, 877, 80-84.
(12) (a) Cavell, K. J. Recent fundamental studies on migratory insertion into metal-
carbon bonds. Coordin. Chem. Rev. 1996, 155, 209-243. (b) Brennführer, A.; Neumann,
ACS Paragon Plus Environment

Page 27 of 29
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
H.; Beller, M. Palladium-Catalyzed Carbonylation Reactions of Aryl Halides and
Related Compounds. Angew. Chem. Int. Ed. 2009, 48, 4114-4133. (c) Friis, S. D.;
Lindhardt, A. T.; Skrydstrup, T. The Development and Application of Two-Chamber
Reactors and Carbon Monoxide Precursors for Safe Carbonylation Reactions. Accounts
Chem. Res. 2016, 49, 594-605.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) (a) Shi, S.; Szostak, M. Decarbonylative Cyanation of Amides by Palladium
Catalysis. Org. Lett. 2017, 19, 3095-3098. (b) Liu, C.; Szostak, M. Decarbonylative
Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross-
Coupling of Amide Derivatives. Angew. Chem. Int. Ed. 2017, 56, 12718-12722. (c) Liu,
L.; Zhou, D.; Liu, M.; Zhou, Y.; Chen, T. Palladium-Catalyzed Decarbonylative
Alkynylation of Amides. Org. Lett. 2018, 20, 2741-2744. (d) Shi, S.; Szostak, M.,
Decarbonylative Borylation of Amides by Palladium Catalysis. ACS Omega 2019, 4,
4901-4907.
(14) 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.
(15) Wu, H.; Liu, T.; Cui, M.; Li, Y.; Jian, J.; Wang, H.; Zeng, Z. Rhodium-catalyzed
C–H functionalization with N-acylsaccharins. Org. Biomol. Chem. 2017, 15, 536-540.
(16) Sherwood, J.; Clark, J. H.; Fairlamb, I. J. S.; Slattery, J. M. Solvent effects in
palladium catalysed cross-coupling reactions. Green Chem. 2019, 21, 2164-2213.
(17) Mäsing, F.; Nüsse, H.; Klingauf, J.; Studer, A. Visible-Light-Enabled Preparation
of Palladium Nanoparticles and Application as Catalysts for Suzuki–Miyaura Coupling.
Org. Lett. 2018, 20, 752-755.
(18) Wang, F.; Li, C.; Chen, H.; Jiang, R.; Sun, L.-D.; Li, Q.; Wang, J.; Yu, J. C.; Yan,
C.-H. Plasmonic Harvesting of Light Energy for Suzuki Coupling Reactions. J. Am.
Chem. Soc. 2013, 135, 5588-5601.
(19) Zinser, C. M.; Warren, K. G.; Meadows, R. E.; Nahra, F.; Al-Majid, A. M.; Barakat,
A.; Islam, M. S.; Nolan, S. P.; Cazin, C. S. J. Towards environmentally friendlier
Suzuki–Miyaura reactions with precursors of Pd-NHC (NHC = N-heterocyclic carbene)
complexes. Green Chem. 2018, 20, 3246-3252.
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The Journal of Organic Chemistry
Page 28 of 29
1
2
3
4
5
6
7
8
(20) Gan, Y.; Wang, G.; Xie, X.; Liu, Y. Nickel-Catalyzed Cyanation of Phenol
Derivatives with Zn(CN)2 Involving C–O Bond Cleavage. J. Org. Chem. 2018, 83,
14036-14048.
9
(21) Fan, F.; Tang, J.; Luo, M.; Zeng, X. Chromium-Catalyzed Regioselective Kumada
Arylative Cross-Coupling of C(aryl)–O Bonds with a Traceless Activation Strategy. J.
Org. Chem. 2018, 83, 13549-13559.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(22) Thapa, S.; Basnet, P.; Gurung, S. K.; Giri, R. Copper-catalysed cross-coupling of
arylzirconium reagents with aryl and heteroaryl iodides. Chem. Commun. 2015, 51,
4009-4012.
(23) Oster, A.; Hinsberger, S.; Werth, R.; Marchais-Oberwinkler, S.; Frotscher, M.;
Hartmann, R. W. Bicyclic Substituted Hydroxyphenylmethanones as Novel Inhibitors
of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of
Estrogen-Dependent Diseases. J. Med. Chem. 2010, 53, 8176-8186.
(24) Dansereau, J.; Gautreau, S.; Gagnon, A. Synthesis of Highly Functionalized Diaryl
Ketones by Palladium-Catalyzed Carbonylative Cross-Coupling Reaction Between
Triarylbismuthines and Aryl (Heteroaryl) Iodides. ChemistrySelect 2017, 2, 2593-2599.
(25) Chen, X.; Zhou, L.; Li, Y.; Xie, T.; Zhou, S. Synthesis of Heteroaryl Compounds
through Cross-Coupling Reaction of Aryl Bromides or Benzyl Halides with Thienyl
and Pyridyl Aluminum Reagents. J. Org. Chem. 2014, 79, 230-239.
(26) Ito, T.; Iwai, T.; Mizuno, T.; Ishino, Y. Palladium-Catalyzed Cross-Coupling
Reaction of Potassium Diaryldifluoroborates with Aryl Halides. Synlett 2003, 2003,
1435-1438.
(27) Cornella, J.; Righi, M.; Larrosa, I. Carboxylic Acids as Traceless Directing Groups
for Formal meta-Selective Direct Arylation. Angew. Chem. Int. Ed. 2011, 50, 9429-
9432.
(28) Ackermann, L.; Potukuchi, H. K.; Althammer, A.; Born, R.; Mayer, P. Tetra-ortho-
Substituted Biaryls through Palladium-Catalyzed Suzuki−Miyaura Couplings with a
Diaminochlorophosphine Ligand. Org. Lett. 2010, 12, 1004-1007.
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Graphic for the Table of Content
O
3 mol% Pd(PPh3)Cl2
3 equiv NaHCO3
R1
R
N
Ar
B(OH)2
R
Ar
R2
toluene/dioxane(5/1)
150 ºC, 4 h
R = aryl, heterocyclic
R1
broad function group tolerance & wide scope
N
R2
sterically-distorted amides
short reaction time up to 88% yield
=
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