Water Phase, Room Temperature, Ligand-Free Suzuki–Miyaura Cross-Coupling: A Green Gateway to Aryl Ketones by C–N Bond Cleavage

Article abstract of DOI:10.1002/ejoc.201901730

We report herein a green strategy for synthesis of aryl ketones from twisted amides by using Pd(OAc)₂ as catalysts. This method shows high functional group tolerance to offer a variety of ketones in good yields under mild conditions (up to 94 %). Notably, this methodology demonstrates the first water phase, room temperature, ligand-free Suzuki–Miyaura coupling through C–N bond cleavage, which is environmentally friendly and might facilitate the development of amide based green chemistry.

Full text of DOI:10.1002/ejoc.201901730

A Journal of
Accepted Article
Title: Water Phase/Room Temperature/Ligand-Free Suzuki–Miyaura
Cross-Coupling: A Green Gateway to Aryl Ketones by C-N Bond
Cleavage
Authors: Yuqi Zhang, Zijia Wang, Zhao Tang, Zhongfeng Luo,
Hongxiang Wu, Tingting Liu, Yulin Zhu, and Zhuo Zeng
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901730
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901730
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10.1002/ejoc.201901730
European Journal of Organic Chemistry
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Water Phase/Room Temperature/Ligand-Free Suzuki–Miyaura
Cross-Coupling: A Green Gateway to Aryl Ketones by C-N Bond
Cleavage
Yuqi Zhang,[a] Zijia Wang,[a] Zhao Tang,[b] Zhongfeng Luo,[a] Hongxiang Wu,[a] Tingting Liu, * [a]
Yulin Zhu, * [a] Zhuo Zeng* [a, c]
Abstract: We report herein a green strategy for synthesis of aryl
ketones from twist amides by using Pd(OAc)2 as catalysts. This
method shows high functional group tolerance to offer a variety of
ketones in good yields under the mild conditions (up to 94%). Notably,
this methodology demonstrates the first water phase/room
temperature/ligand-free Suzuki-Miyaura coupling via C-N bond
cleavage, which is environmentally friendly and might facilitate the
development of amides green chemistry.
for amides. Green procedure of coupling reaction is booming, and
a lot of ligand-free or green solvent coupling reactions are rapidly
developing. Recently, some chemists such as Basu,[11] Liu,[12]
Bora,[13] Liu,[14] Schatz,[15] Sarma,[16] Handa[17] (Scheme 1-B)
reported a series of ligand-free Suzuki-Miyaura coupling reaction
to yield the biaryl products. Since the first research reported by
Genêt group in 1997, potassium aryltrifluoroborates were widely
used as an alternative to organoboronic acid in Suzuki–Miyaura
coupling
reaction
recently.[18]
Furthermore,
potassium
aryltrifluoroborates are also stable in air, easy to synthesize and
mass storage, which is still highly desirable to develop the
potential applications in green synthesis. More notably, potassium
aryltrifluoroborates is more effective in cross-coupling reactions
than aryl borate in the presence of water. [19] As the most abundant
resource on the Earth, water is a desirable solvent for chemical
reactions due to its low cost, safety, non-toxic, non-inflammable
and environment-friendly.[20] Furthermore, it was confirmed that
water can promotes the Suzuki–Miyaura coupling in previous
works.[6g,6x,22] However, in consideration of limited reactant
solubility or lessen stability of catalysts in water, an efficient
Suzuki–Miyaura coupling for synthesis of aryl ketones in aqueous
media without any ligands or additive is rarely reported. With
continued interest in the development of activated amide
chemical conversion,[5] it is valuable for us to develop a simple
and environmentally friendly method for synthesis of aryl ketones
from amides. Herein, we firstly utilize the high reactivity N-
acylsuccinimides and potassium aryltrifluoroborates to develop
water phase/room temperature/ligand-free Suzuki–Miyaura
coupling by C-N bonds cleavage (Scheme 1 C).
Introduction
Aryl ketones are commonly utilized in the synthesis of
pharmaceuticals and functional materials.[1,2] Over the past
decades, palladium-catalyzed Suzuki–Miyaura coupling reaction
of electrophiles, including aryl halides,[3] esters[4] and amides[5-10]
with organoboron nucleophiles for synthesizing a series of aryl
ketones has been developed. It has become one of the most
powerful and important synthetic methods to construct aryl
ketones via selective C-N bond transformations of activated
amides. Recently, transition metal-catalyzed amides Suzuki–
Miyaura coupling for synthesis of aryl ketones has been
developed by Szostak,[6] Zou,[7] Huang,[8] Garg[9] and
Yamaguchi[10] (Scheme 1-A1). However, most of these reactions
need bulky or electron-rich phosphine or N-heterocyclic carbenes
as ligands, which are air, moisture-sensitive and environmentally
unfriendly (Scheme 1-A2). Furthermore, these ligands are
usually synthesized by multistep reaction that may result in high
cost. Some toxic organic solvents such as toluene, 1,4-dioxane
and DMF are employed in these transformations, but how to
dispose and recycle them will be an obstacle to the
industrialization process. Considering the above-mentioned, it’s
critical to exploit an economical and high-efficiency transformation
[a]
Y. Zhang, Dr. Z. Wang, Z. Luo, H. Wu, Dr. T. Liu, Prof. Dr. Y. Zhu,
Prof. Dr. Z. Zeng
College of Chemistry, South China Normal University,
Guangzhou 510006, Guangdong (P. R. China)
E-mail: liutt5@163.com; Iabzhu@aliyun.com; zhuoz@scnu.edu.cn
Z. Tang
Class Zheng, International Department, The Affiliated High School
of SCNU
[b]
[c]
Guangzhou, China, 516006
Prof. Dr. Z. Zeng
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Science, 345 LingLing
Road, Shanghai 200032, China
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Catalysts, ligands, bases, solvents and temperature were
optimized, and the corresponding details are summarized in
Table 1. Initially, we attempt to achieve this transformation in the
presence of 5 mol% Pd(OAc)2 catalyst with Na2CO3 as the base
resulted in the corresponding ketone in 83% yield (Table 1, entry
1). Optimization of palladium catalysts indicated that Pd(OAc)2
gave the best results. Collectively, palladium was the most active
catalyst in this transformation (Table 1, entries 2-3). Encouraged
by the Ni catalyst acyl transfer coupling reaction,[21] several nickel
catalysts, such as Ni(COD)2, NiCl2, were investigated. After
several experiments, we found these nickel catalysts did not show
compatibility with this reaction (Table 1, entries 4-5). Copper
catalysts were then screened, and exhibit low catalytic activity
(Table 1, entries 6-7). Generally, it is important to select an
appropriate ligand for Suzuki-Miyaura coupling reaction. Notably,
several phosphine ligands were not found to be effective in
increasing the yield (Table1, entries 8-10). Furtherly, the reaction
was conducted under the ligand-free condition, and the product
ketone was obtained in high yield. The identity of the base is not
negligible, and only 21% yield occurred under base-free condition
(Table1, entries 11). Among a series of bases (Table 1, entries
12-17), including Na2CO3, K2CO3, Li2CO3, Et3N, NaHCO3, K3PO4,
Pyridine, the K2CO3 exhibits highly efficient and markedly
increased the yield of the desired product at 85% (Table1, entries
13). The solvent plays a critical impact on the efficiency of this
reaction[22a] (Table 1, entries 18-21). Other solvents, such as THF,
CH3CN and toluene resulted in the decreasing of yield. It was
observed that some water was added to the toluene solvent, it led
to an increase in yield from 38% to 47%, which indicated that
water can promote the solubility of these reactants (Table1,
entries 20-21). After the examination for reaction temperature
(Table1, entries 22-24), room temperature is preferred in terms of
the yield. Besides, the effect of the catalyst loading was also
evaluated, and the yield decreased dramatically when the loading
of Pd(OAc)2 was reduced from 5 mol% to 3 mol% (Table 1,
entries 25). The yield with the catalyst loading 8 mol% have the
same result with 5% catalyst loading (Table 1, entries 26).
Finally, the best condition for this Suzuki-Miyaura coupling
reaction via C–N cleavage of N-acylsuccinimides was set as 5
mol% Pd(OAc)2 in the presence of K2CO3 in water at room
temperature. Notably, this reaction can proceed smoothly under
the air atmosphere with a simplified operation procedure. The
high yield obtained with the optimized conditions encouraged us
to use N-acylsuccinimides and potassium aryltrifluoroborates to
synthesize a variety of aryl ketones.
Scheme 1. Suzuki-Miyaura coupling of amides.
Results and Discussion
In 2017, Szostak and our groups both reported Pd-catalyzed
Suzuki-Miyaura coupling acylation of N-acylsuccinimides,[5b,
6h]
respectively. As an acyl-source, N-acylsuccinimides have several
advantages: (a) N-acylsuccinimides can be efficiently synthesized
from succinimides that are virtually nontoxic and widely available
commodity chemical; (b) N-acylsuccinimides are crystalline,
benign and shelf-stable reagents, which demonstrate high atom
utilization and efficient functional group transfer reagents in
acylation reactions. Due to the above characteristics, N-
acylsuccinimides might be suitable electrophiles in water phase
Suzuki-Miyaura coupling. N-acylsuccinimide 1a was selected to
couple with potassium aryltrifluoroborate 2a as the model.
Table 1. Optimization of reaction conditions.[a]
Temperature
(oC)
Yield b
(%)
Entry
Catalyst
Base
Solvent
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1
2
Pd(OAc)2
PdCl2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
None
H2O
H2O
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
83
80
3
Pd/C
H2O
42
4
Ni(COD)2
NiCl2
H2O
0
5
H2O
0
6
Cu(OAc)2
CuI
H2O
trace
trace
52
7
H2O
8c
9d
10e
11
12
13
14
15
16
17
18
19
20
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
H2O
H2O
28
H2O
76
H2O
21
Li2CO3
K2CO3
H2O
75
H2O
85
Et3N
H2O
72
NaHCO3
K3PO4
H2O
50
H2O
53
Scheme 2. Scope of amides in the cross-coupling with potassium
Pyridine
K2CO3
H2O
trace
47
aryltrifluoroborates
THF
K2CO3
CH3CN
Toluene
Toluene/
H2O(10:1)
H2O
32
Furthermore, the scope of the potassium aryltrifluoroborates
coupling partner was focused in Scheme 3. A series of the
potassium aryltrifluoroborates with electron-donating substituents
(2c-2e, 2m-2n) in the ortho, meta, para-positions were reacted
with N-acylsuccinimides to provide corresponding aryl ketones in
high yields. Halogen groups (2g, 2h) exhibit good substrates
suitability reached 82% and 78%. Moreover, the heterocyclic ring
(2i), disubstituted (2q) and electrophilic carbonyl groups, such as
esters (2o) and ketones (2p) are also compatible underwent
acylation.
K2CO3
38
21
Pd(OAc)2
K2CO3
rt
47
22
23
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
60
80
100
rt
74
80
80
77
85
H2O
24
H2O
25f
26g
H2O
H2O
rt
[a]Conditions (unless otherwise noted): 1a (0.3 mmol, 1.0 equiv.), 2b (1.5 equiv.),
catalyst (5 mol%), base (2.0 equiv.), solvent (2.0 mL), rt, 6 h, trace < 5%. [b]
Isolated yield. [c] ligand: PPh3. [d] ligand: PCy3. [e] ligand: dppf. [f] catalyst (3
mol%). [g] Catalyst (8 mol%).
With the optimized conditions in hand, we intended to examine
the scope of amides using 2a as a standard reactant (Scheme 2).
Neutral (1a), steric-hindrance in ortho, meta, para-positions (1b,
1c, 1d) were tested with excellent reaction efficiency. It is worth
noting that electron-withdrawing substituents (1f, 1l) are better-
tolerated than the electron-donating substituents (1e). The
utilization of the halide substituents 4-fluoro (1g) and 4-chloro (1h)
afforded the desired products in 85% and 53% yields. When the
substituent is a heterocyclic ring (1i-k), the functional group is
generally applicable.
Scheme 3. Scope of potassium aryltrifluoroborates in the cross-coupling with
amides.
Several studies were conducted to acquire further insight into
the reaction mechanism (Scheme 4). (A) Electron-deficient
aromatic amides coupled with electron-rich nucleophiles showing
the highest reactivity (93%); (B) Electron-rich aromatic amides
indicated no preference, whether electron-deficient or electron-
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rich nucleophile; (C) Intermolecular competition experiments of
different substituted amides established that electron-deficient
aromatic amides are inherently more preferentially (4-CF3/4-MeO
= 78:22). (D) Further competition experiments revealed electron-
deficient potassium aryltrifluoroborates are more reactive (4-
CF3:4-MeO = 69:31).
Scheme 5. Reactivity of cross-coupling.
The solvent is very important in Suzuki cross-coupling reaction,
as it is in most solution-based chemical transformations. It is
definitely not a free choice of solvent when the reaction is
operated at industrial scales. The selection of solvents,
considering its purchasing to disposal or recovery, becomes very
crucial. Some polar aprotic solvents (DMF, DMAc, NMP)
favoured for many cross-couplings will be possibly subject to
tighter regulation in the future.[22a,23] Recently, chemists focus on
the application of water as a sole solvent for cross-coupling.
There are two advantages for water: 1) it is easy to separate and
recycle from the reaction mixture; 2) the product is obtained in an
environmentally friendly way. But at the same time, the
disadvantages of water as a solvent in organic reactions cannot
be ignored.[24] By-products such as inorganic salts remain in
water and cannot be directly discharged. To make up for these
shortcomings, the reusability of the aqueous phase was next
investigated (Figure 1). The experimental details were provided
in experimental section. Four cycles were observed to provide
the conversion of the reactant to the required aryl ketone 3a, with
a slight loss of yield from 85% to 78%.
[a] General condition: amide (0.3 mmol), potassium organotrifluoroborates (1.5
equiv.), Pd(OAc)2 (5 mol%), K2CO3 (2.0 equiv.), H2O (2.0 mL), rt, 6 h.
Scheme 4. Electron effect experiments.
As shown in Scheme 5a, some activated amides displayed
different reactivity under the optimized conditions. The coupling
yields of N-acylsuccinimides (1a), N-acyl-glutarimides (1r), N-
acyl-5,5-dimethylhydantoins (1s), N-acylsaccharins (1t) and N, N-
di-Boc-amides (1u) reached 85%, 78%, 65%, 32% and 18%,
respectively. However, activated amide substrates N-Ph-N-Ts-
benzamides (1v) and N-Bn-N-Boc-benzamides (1w), were found
to be not suitable for this methodology. Professor Szostak[6i-l]
demonstrated the cross-coupling of N-C bonds of twisted amides,
who suggested that the twist value as low as about 40-50° may
be sufficient to promote N-protonation of amide bonds. Hence, the
high conversion of N-acylsuccinimides (1a) is due to "half-twist"
(τ = 45°) which leads to a compromise between reactivity and
stability.
Similarly, potassium phenyl trifluoroborate is not the only
suitable nucleophile, and phenylboronic acid and its pinacol ester
are also compatible with this reaction (Scheme 5b). Nevertheless,
potassium phenyl trifluoroborate demonstrated higher reactivity
than others, 2a, 2x and 2y, with yield at 85%, 41% and 30%,
respectively.
Figure 1. Isolation and recycling of the aqueous phase.
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As previous report, aryl ketones were prepared by the Friedel-
Crafts acylation process, but serval drawbacks such as limited
scope substrates, harsh conditions, and unfriendly environmental
for this process restricted its industrial application.[25] Therefore,
seeking for simple and green synthetic routine is particularly
important. Bis(4-fluorophenyl)-methanone is an important
pharmaceutical intermediate for the synthesis of cerebrovascular
dilatation flunarizine.[26] A gram-scale experiment was performed
using 1g (1.768 g, 8 mmol), 2g (2.424 g, 12 mmol) and Pd(OAc)2
(89.8 mg, 0.4 mmol) were stirred in the presence of K2CO3 in
water at room temperature to afford 1.465
g of bis(4-
fluorophenyl)-methanone 3gg (84%) (Scheme 6). Compared with
several reported synthetic routines, this methodology is simple,
efficient, and green. Notably, the solvent can be recycled at least
4 times, which is suitable for scale-up production. The details
were provided in the experimental section (Figure 2).
Scheme 7. Proposed mechanism for palladium-catalyzed acylative Suzuki–
Miyaura coupling of N-acylsuccinimides.
Conclusions
In conclusion, a green process for C–N bond cleavage by
utilizing
N-acylsuccinimides
couple
with
potassium
aryltrifluoroborates has been firstly reported. This approach
presents pure water phase and ligand-free Suzuki-Miyaura
coupling at room temperature, which demonstrates as an efficient
green procedure. This methodology highlights that water can be
used as a recyclable and sustainable medium to reduce the
pollution of organic solvent/chemical waste, indicating a green
and practical innovation for the traditional procedure of aryl
ketones synthesis.
Experimental Section
Scheme 6. Comparison of gram-level reaction synthesis methods.
List of known compounds/general methods: All reactants reported in
the manuscript are commercially available and have been prepared by the
method reported previously. N-acylsuccinimides were prepared by the
general methods. All solvents were purchased at the China supplier and
used without any purification. All commercially available reagents and
catalysts were purchased from China supplier Energy Chemical with purity
98%. Flash chromatography was performed using 200-300 mesh silica gel.
1H and 19F NMR data were recorded with AVANCE NEO Bruker (600 MHz)
and Varian AS (400 MHz) spectrometers in CDCl3 with tetramethylsiliane
as an internal standard. 1H NMR data are given for all compounds in the
ESI.
i
ii
(a)
(b)
(c)
Figure 2. (a) Start scale-up reaction; (b) Finished scale-up reaction; (c) Purified
procedure.
General procedure for amides synthesis: An oven-dried round-
bottomed flask (100 mL) equipped with a stir bar was charged with Et3N
(10 mmol, 2.0 equiv.), DMAP (typically, 0.25 equiv.), dichloromethane (40
mL) and amine (5 mmol, 1.0 equiv., slowly added into the mixture). Acyl
chloride (typically, 1.0 equiv.) was added dropwise to the reaction mixture
with vigorous stirring at 0 oC, and the reaction mixture was stirred overnight
at room temperature. After the indicated time, the reaction mixture was
washed with HCl (1.0 N, 30 mL), water (30 mL), brine (30 mL), dried, and
concentrated. The crude product was purified by recrystallization to afford
analytically pure product.
General procedure for potassium aryltrifluoroborates synthesis:
Most of the potassium alkyltrifluoroborates were purchased commercially.
In cases where the desired potassium organotrifluoroborate was not
available, the corresponding boronic acid derivative was converted to the
trifluoroborate by the following procedure: Saturated KHF2 (4.5 M) solution
was added dropwise into the solution of boronic acid derivative in MeOH
Reaction flow-process: i) Reaction procedure，ii) Isolation products.
Based on the palladium hydroxide catalytic intermediate was
elegantly proven by Molloy et al,[22] our conjecture on the
mechanism of this reaction is as follows (Scheme 7): (i) oxidative
addition took place at the C–N bond of the N-acylsuccinimides to
form an acylpalladium (II) complex; (ii) in the presence of water
and base generate the hydroxide anion which exchanges with the
succinimide ligand on the palladium complex created after
oxidative addition; (iii) the transmetalation of potassium
aryltrifluoroborates proceeds through a Pd–O–B complex amide
palladium(II) hydroxides; (iv) reductive elimination occurred to
form the new C–C bond and regenerate the Pd(0) species.
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(0.1 M) and stirred over 2h at 0 °C. After completion of the reaction,
collecting sediment by vacuum filtration. After remaining solid was
dissolved in hot acetonitrile and filtered, the filtrate was separation by
vacuum filtration, concentrated to obtain a white powder.
General Procedure for Suzuki-Miyaura Coupling of Amides: An oven-
dried test tube (10 mL) equipped with a stir bar was charged with amides
(0.3 mmol, 1.0 equiv.), potassium organotrifluoroborate (0.45 mmol, 1.5
equiv.), K2CO3 (2.0 equiv.) and Pd(OAc)2 (typically, 5 mol%). Water
(typically, 2 mL) was added with vigorous stirring, the reaction mixture was
stirred for 6 h at room temperature. After the indicated time, the reaction
mixture was extracted by EtOAc (5×3 mL). The organic extracts were dried
over anhydrous MgSO4 and concentrated. The obtained residue was
purified by column chromatography to afford target product.
Recycling Experiments: An oven-dried test tube (10 mL) equipped with
a stir bar was charged with 1a (0.30 mmol), 1e (1.5 equiv.), Pd(OAc)2 (5
mol%) and K2CO3 (2.0 equiv.) in water (2 mL) for 6 h at room temperature.
After the indicated time, the mixture was extracted by EtOAc (5×2 mL). In
one aspect, the organic layer is separated and purified by column
chromatography to obtain the target product. On the other hand, the water
is heated until the EtOAc is completely evaporated, and the raw material
is added again for the next cycle operation. Repeated four operations, with
a slight loss of yield, which prove water can be used as a recyclable and
sustainable medium.
General procedure for the scaled-up experiment: An oven-dried beaker
(100 mL) equipped with a stir bar was charged with 1g (8.0 mmol, 1.0
equiv.), 2g (1.5 equiv.), K2CO3 (2.0 equiv.) and Pd(OAc)2 (typically, 5
mol %). Water (typically, 20 mL) was added with vigorous stirring, the
reaction mixture was stirred for 9 h at room temperature. After the indicated
time, the reaction mixture was extracted by EtOAc (5×30 mL). The organic
extracts were dried over anhydrous MgSO4 and concentrated. The residue
was dissolved in petroleum ether/EtOAc (50/1) and filtered with suction
through a short pad of silica gel packed with petroleum ether/EtOAc (50/1)
in a 50 mL fritted funnel. Then the silica gel pad was washed with 350 mL
petroleum ether/EtOAc (50/1). The organic phases were combined and
concentrated by rotary evaporation to provide the crude product. The
crude product was purified by recrystallization from petroleum ether/EtOAc
(1/30) to obtain 3gg. Concentrated the mother liquor by rotary evaporation
to recrystallization again, which will provide a second crop of products.
This approach could be given in 84% yield.
1-(4-(Trifluoromethyl)benzoyl)pyrrolidine-2,5-dione (1f).5b Following
general procedure. 1f was purified by recrystallization to afford a white
solid (0.94 g, 69.3%). H NMR (600 MHz, CDCl3) δ 7.94 (d, J = 8.2 Hz,
2H), 7.76 (d, J = 8.4 Hz, 2H), 2.96 (s, 4H); 19F NMR (565 MHz, CDCl3) δ
= -63.35
1
1-(4-Fluorobenzoyl)pyrrolidine-2,5-dione (1g).5b Following general
procedure, 1g was purified by recrystallization to afford a white solid (0.87g,
78.8%). 1H NMR (400 MHz, CDCl3) δ 7.90 – 7.83 (m, 2H), 7.19 – 7.11 (m,
2H), 2.91 (s, 4H); 19F NMR (376 MHz, CDCl3) δ -100.76
1-(4-Chlorobenzoyl)pyrrolidine-2,5-dione (1h).5b Following general
procedure, 1h was purified by recrystallization to afford a white solid (0.76
g, 63.7%). 1H NMR (600 MHz, CDCl3) δ 7.84 – 7.77 (m, 2H), 7.53 – 7.47
(m, 2H), 2.96 (s, 4H).
1-(2-Naphthoyl)pyrrolidine-2,5-dione
(1i).5b
Following
general
procedure, 1i was purified by recrystallization to afford a white solid (0.71
g, 61.2%). 1H NMR (600 MHz, CDCl3) δ 8.38 (s, 1H), 8.01 – 7.88 (m, 4H),
7.71 – 7.65 (m, 1H), 7.64 – 7.56 (m, 1H), 7.28 (s, 4H).
1-(Thiophene-2-carbonyl)pyrrolidine-2,5-dione
(1j).27
Following
general procedure, 1j was purified by recrystallization to afford a white
solid (0.82g,78.5%). 1H NMR (600 MHz, CDCl3) δ 7.84 (dd, J = 4.9, 1.1 Hz,
1H), 7.72 (dd, J = 3.9, 1.1 Hz, 1H), 7.18 (dd, J = 4.9, 4.0 Hz, 1H), 2.93 (s,
4H).
1-(Furan-2-carbonyl)pyrrolidine-2,5-dione (1k).6h Following general
procedure, 1k was purified by recrystallization to afford a white solid (0.65
g,67.5%). 1H NMR (600 MHz, CDCl3) δ 7.69 – 7.67 (m, 1H), 7.46 – 7.38
(m, 1H), 6.64 (dd, J = 3.7, 1.7 Hz, 1H), 2.92 (s, 4H).
1-(4-acetylbenzoyl)pyrrolidine-2,5-dione (1l).6h Following general
procedure, 1l was purified by recrystallization to afford a white solid (0.65
g, 53%); 1H NMR (600 MHz, CDCl3) δ 8.22 – 8.01 (m, 2H), 7.94 – 7.84 (m,
2H), 3.95 (s, 3H), 2.93 (s, 4H).
N-Benzoylpiperidine-2,6-dione (1r).5b Following general procedure of
the literature, 1r was purified by recrystallization to afford a white solid. 1H
NMR (600 MHz, CDCl3) δ 7.89 (dd, J = 8.4, 1.2 Hz, 2H), 7.69 – 7.65 (m,
1H), 7.54 – 7.49 (m, 2H), 3.06 – 2.67 (m, 4H), 2.50 – 1.96 (m, 2H).
3-Benzoyl-5,5-dimethylimidazolidine-2,4-dione
(1s).5a
Following
general procedure of the literature, 1s was purified by recrystallization to
afford a white solid. 1H NMR (600 MHz, CDCl3) δ 7.85 (dd, J = 8.4, 1.2 Hz,
2H), 7.72 – 7.64 (m, 1H), 7.52 (dd, J = 8.2, 7.5 Hz, 2H), 6.55 (s, 1H), 1.57
(s, 6H).
N-Benzoylsaccharin (1t).5d Following general procedure of the literature,
1t was purified by recrystallization to afford a white solid. 1H NMR (600
MHz, CDCl3) δ 8.15 (d, J = 7.7 Hz, 1H), 8.03 (dd, J = 7.5, 6.5 Hz, 2H), 7.97
– 7.93 (m, 1H), 7.79 (dd, J = 8.3, 1.2 Hz, 2H), 7.68 (dd, J = 10.7, 4.4 Hz,
1H), 7.56 – 7.50 (m, 2H).
N, N-di-Boc-amides (1u).6w Following general procedure of the literature,
1u was purified by recrystallization to afford a white solid. 1H NMR (400
MHz, CDCl3) δ 7.82 (m, J = 6.5 Hz, 2H), 7.59 (m, J = 6.7 Hz, 1H), 7.47 (m,
J = 6.6 Hz, 2H), 1.36 (d, J = 5.4 Hz, 18H).
N-Ph-N-Ts-benzamides (1v).5d Following general procedure of the
literature, 1v was purified by recrystallization to afford a white solid. 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 – 7.25 (m, 4H), 7.16 (dd, J = 10.0, 5.2 Hz,
4H), 2.45 (s, 3H).
N-Bn-N-Boc-benzamides (1w).6p Following general procedure of the
literature, 1w was purified by recrystallization to afford a white solid. 1H
NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.5 Hz, 2H), 7.48 – 7.41 (m, 3H),
7.40 – 7.30 (m, 4H), 7.26 (dd, J = 8.6, 5.8 Hz, 1H), 4.99 (s, 2H), 1.12 (s,
9H).
Characterization data of amides:
N-Benzoylpyrrolidine-2,5-dione (1a). 5b Following general procedure, 1a
was purified by recrystallization to afford a white solid (0.86 g, 84.7%). 1H
NMR (600 MHz, CDCl3) δ 7.89 – 7.85 (m, 2H), 7.72 – 7.66 (m, 1H), 7.55 –
7.50 (m, 2H), 2.95 (s, 4H).
1-(2-Methylbenzoyl)pyrrolidine-2,5-dione (1b).6h Following general
procedure, 1b was purified by recrystallization to afford a white solid (0.47
g, 43.6%). 1H NMR (600 MHz, CDCl3) δ 7.54 – 7.47 (m, 2H), 7.35 (d, J =
7.6 Hz, 1H), 7.32 – 7.25 (m, 1H), 2.91 (s, 4H), 2.61 (s, 3H).
1-(3-Methylbenzoyl)pyrrolidine-2,5-dione (1c).27 Following general
procedure, 1c was purified by recrystallization to afford a white solid (0.69
g, 63.5%). 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.60 (d, J = 7.7 Hz,
1H), 7.45 (d, J = 7.6 Hz, 1H), 7.36 (t, J = 7.7 Hz, 1H), 2.91 (s, 4H), 2.39 (s,
3H). 13C NMR (151 MHz, CDCl3) δ = 197.05, 138.19, 137.75, 137.62,
133.26, 132.40, 130.50, 130.09, 128.28, 128.13, 127.42, 21.40.
1-(4-Methylbenzoyl)pyrrolidine-2,5-dione (1d).5b Following general
procedure, 1d was purified by recrystallization to afford a white solid (0.86
g, 79%). 1H NMR (600 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H), 7.31 (d, J
= 8.0 Hz, 2H), 2.95 (s, 4H), 2.46 (s, 3H).
1-(4-Methoxybenzoyl)pyrrolidine-2,5-dione (1e).5b Following general
procedure, 1e was purified by recrystallization to afford a yellow solid (1.01
g, 86.7%). 1H NMR (600 MHz, CDCl3) δ 8.02 – 7.75 (m, 2H), 7.05 – 6.85
(m, 2H), 3.99 – 3.69 (m, 3H), 3.10 – 2.75 (m, 4H). 13C NMR (151 MHz,
CDCl3) δ = 195.60, 163.24, 138.30, 132.58, 131.91, 130.17, 129.74,
128.20, 113.57, 55.51.
variation of amides:
Benzophenone (3a).5d Following general procedure for Suzuki-Miyaura
coupling of amides, 3a was purified by column chromatography
(Petroleum ether/EtOAc = 50/1) to afford a white solid (46.4 mg,85%).1H
NMR (600 MHz, CDCl3) δ 7.82 (dd, J = 8.3, 1.3 Hz, 4H), 7.62 – 7.57 (m,
2H), 7.49 (dd, J = 11.0, 4.5 Hz, 4H).
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Phenyl(o-tolyl)methanone (3b).6h Following general procedure for
Suzuki-Miyaura coupling of amides, 3b was purified by column
chromatography (Petroleum ether/EtOAc = 50/1) to afford a colorless oily
liquid (51.74 mg, 88%). 1H NMR (400 MHz, CDCl3) δ 7.81 (dd, J = 8.0, 0.8
Hz, 2H), 7.58 (m, J = 7.4 Hz, 1H), 7.46 (m, J = 7.6 Hz, 2H), 7.39 (dd, J =
10.6, 4.3 Hz, 1H), 7.31 (t, J = 8.4 Hz, 2H), 7.25 (dd, J = 9.7, 5.1 Hz, 1H),
2.32 (s, 3H).
1-(4-Benzoylphenyl)ethanone (3l).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3l was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
(55.7 mg, 79%); H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.2 Hz, 2H),
7.86 – 7.84 (m, 2H), 7.81 (dd, J = 8.2, 1.3 Hz, 2H), 7.64 – 7.61 (m, 1H),
7.51 (t, J = 7.8 Hz, 2H), 3.97 (s, 3H).
1
Phenyl(m-tolyl)methanone (3c).27 Following general procedure for
Suzuki-Miyaura coupling of amides, 3c was purified by column
chromatography (Petroleum ether/EtOAc = 50/1) to afford a colorless oily
liquid (54.1 mg, 92%). 1H NMR (600 MHz, CDCl3) δ 7.71 (dd, J = 8.3, 1.2
Hz, 2H), 7.54 (s, 1H), 7.51 – 7.47 (m, 2H), 7.40 – 7.36 (m, 2H), 7.30 (d, J
= 7.5 Hz, 1H), 7.26 (t, J = 7.5 Hz, 1H), 2.32 (s, 3H).
Phenyl(p-tolyl)methanone (3d).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3d was purified by column
chromatography (Petroleum ether/EtOAc = 50/1) to afford a white solid
(54.7 mg, 93%) 1H NMR (600 MHz, ) δ 7.78 (dd, J = 8.2, 1.3 Hz, 2H), 7.73
(d, J = 8.1 Hz, 2H), 7.58 (m, J = 8.1 Hz, 1H), 7.48 (m, J = 7.7 Hz, 2H), 7.28
(d, J = 7.9 Hz, 2H), 2.44 (s, 3H).
(4-Methoxyphenyl)(phenyl)methanone (3e).5d Following general
procedure for Suzuki-Miyaura coupling of amides, 3e was purified by
column chromatography (Petroleum ether/EtOAc = 30/1) to afford a white
solid (42.6 mg, 67%). 1H NMR (600 MHz, CDCl3) δ 7.85 (d, J = 8.9 Hz, 2H),
7.77 (d, J = 7.0 Hz, 2H), 7.59 (m, J = 7.4 Hz, 1H), 7.49 (m, J = 7.7 Hz, 2H),
6.98 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H).
variation of potassium organotrifluoroborate:
Phenyl(m-tolyl)methanone (3c).27 Following general procedure for
Suzuki-Miyaura coupling of amides, 3c was purified by column
chromatography (Petroleum ether/EtOAc = 50/1) to afford a colorless oily
liquid (44.7 mg, 76%). 1H NMR (600 MHz, CDCl3) δ 7.71 (dd, J = 8.3, 1.2
Hz, 2H), 7.54 (s, 1H), 7.51 – 7.47 (m, 2H), 7.40 – 7.36 (m, 2H), 7.30 (d, J
= 7.5 Hz, 1H), 7.26 (t, J = 7.5 Hz, 1H), 2.32 (s, 3H).
Phenyl(p-tolyl)methanone (3d).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3d was purified by column
chromatography (Petroleum ether/EtOAc = 50/1) to afford a colorless oily
liquid (47.0 mg, 80%) 1H NMR (600 MHz, CDCl3 ) δ 7.78 (dd, J = 8.2, 1.3
Hz, 2H), 7.73 (d, J = 8.1 Hz, 2H), 7.58 (m, J = 8.1 Hz, 1H), 7.48 (m, J = 7.7
Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 2.44 (s, 3H).
(4-Methoxyphenyl)(phenyl)methanone (3e).5d Following general
procedure for Suzuki-Miyaura coupling of amides, 3e was purified by
column chromatography (Petroleum ether/EtOAc = 30/1) to afford a white
solid (56.0mg, 88%). 1H NMR (600 MHz, CDCl3) δ 7.85 (d, J = 8.9 Hz, 2H),
7.77 (d, J = 7.0 Hz, 2H), 7.59 (m, J = 7.4 Hz, 1H), 7.49 (m, J = 7.7 Hz, 2H),
6.98 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H).
(3-Methoxyphenyl)(phenyl)methanone (3m).5b Following general
procedure for Suzuki-Miyaura coupling of amides, 3m was purified by
column chromatography (Petroleum ether/EtOAc = 20/1) to afford a
colorless oily liquid (52.2mg, 82%). 1H NMR (400 MHz, CDCl3) δ 7.81 (dd,
J = 8.1, 1.0 Hz, 2H), 7.58 (dd, J = 10.9, 4.0 Hz, 1H), 7.48 (m, J = 7.6 Hz,
2H), 7.36 (m, J = 7.6, 3.1 Hz, 3H), 7.13 (m, J = 7.7, 2.6, 1.4 Hz, 1H), 3.86
(s, 3H).
(2-Methoxyphenyl)(phenyl)methanone (3n).5d Following general
procedure for Suzuki-Miyaura coupling of amides, 3n was purified by
column chromatography (Petroleum ether/EtOAc = 20/1) to afford a
colorless oily liquid (41.4 mg, 65%). 1H NMR (600 MHz, CDCl3) δ 7.87 –
7.77 (m, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.47 (td, J = 8.4, 1.7 Hz, 1H), 7.43
(t, J = 7.8 Hz, 2H), 7.36 (dd, J = 7.5, 1.7 Hz, 1H), 7.04 (td, J = 7.4, 0.6 Hz,
1H), 7.01 – 6.98 (m, 1H), 3.71 (s, 3H). 13C NMR (151 MHz, CDCl3) δ =
196.39, 157.26, 137.73, 132.84, 131.81, 131.36, 129.72, 129.48, 128.76,
128.13, 120.41, 111.39, 55.50.
Phenyl(4-(trifluoromethyl)phenyl)methanone (3f).5d Following general
procedure for Suzuki-Miyaura coupling of amides, 3f was purified by
column chromatography (Petroleum ether/EtOAc = 30/1) to afford a white
solid (70.5 mg, 94%). 1H NMR (600 MHz, CDCl3) δ = 7.92 (d, J = 8.0 Hz,
2H), 7.83 (d, J = 7.1 Hz, 2H), 7.78 (d, J = 8.1 Hz, 2H), 7.66 (m, J = 6.9 Hz,
1H), 7.54 (m, J = 7.8 Hz, 2H). 13C NMR (151 MHz, ) δ = 195.48, 140.70,
136.70, 133.79, 133.57, 133.06, 130.07, 128.50, 125.31, 124.55, 122.75.
19F NMR (565 MHz, CDCl3) δ = -62.92
(4-Fluorophenyl)(phenyl)methanone
(3g).5d
Following
general
procedure for Suzuki-Miyaura coupling of amides, 3g was purified by
column chromatography (Petroleum ether/EtOAc = 50/1) to afford a white
solid (51.0 mg, 85%). 1H NMR (600 MHz, ) δ 7.78 (dd, J = 8.2, 1.3 Hz, 1H),
7.73 (d, J = 8.1 Hz, 1H), 7.58 (m, J = 8.1 Hz, 1H), 7.48 (m, J = 7.7 Hz, 1H),
7.28 (d, J = 7.9 Hz, 1H). 13C NMR (151 MHz, ) δ = 195.26, 169.84, 166.22,
164.54, 137.49, 133.79, 132.65, 132.45, 129.86, 128.34, 115.44. 19F NMR
(565 MHz, CDCl3) δ = -105.91.
(4-Chlorophenyl)(phenyl)methanone (3h).5d
Following general
procedure for Suzuki-Miyaura coupling of amides, 3h was purified by
column chromatography (Petroleum ether/EtOAc = 50/1) to afford a white
solid (34.3 mg, 53%). 1H NMR (400 MHz, cdcl3) δ 7.88 – 7.80 (m, 2H), 7.79
– 7.69 (m, 2H), 7.58 (m, J = 7.4 Hz, 1H), 7.47 (m, J = 7.9 Hz, 2H), 7.14 (m,
J = 8.7 Hz, 2H).
Naphthalen-2-yl(phenyl)methanone (3i).5d Following general procedure
for Suzuki-Miyaura coupling of amides, 3i was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
(48.7 mg, 70%). 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.97 (d, J = 9.8
Hz, 2H), 7.91 (dd, J = 4.9, 4.4 Hz, 2H), 7.87 (dd, J = 8.0, 1.0 Hz, 2H), 7.62
(m, J = 6.3, 3.6, 1.2 Hz, 2H), 7.55 (m, J = 15.0, 4.2 Hz, 3H).
Phenyl(thiophen-2-yl)methanone (3j).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3j was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a yellowish oily
liquid (25.9 mg, 46%). 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.4 Hz,
2H), 7.73 (dd, J = 4.9, 0.7 Hz, 1H), 7.68 – 7.61 (m, 1H), 7.60 (m, J = 7.4
Hz, 1H), 7.50 (m, J = 7.5 Hz, 2H), 7.17 (dd, J = 4.7, 4.0 Hz, 1H).
Furan-2-yl(phenyl)methanone (3k).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3k was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a yellowish oily
liquid (26.8 mg, 52%). 1H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 8.1, 1.0
Hz, 2H), 7.71 (d, J = 1.0 Hz, 1H), 7.60 (m, J = 7.4 Hz, 1H), 7.50 (m, J = 7.6
Hz, 2H), 7.24 (d, J = 3.6 Hz, 1H), 6.60 (dd, J = 3.6, 1.7 Hz, 1H).
Phenyl(4-(trifluoromethyl)phenyl)methanone (3f).5d Following general
procedure for Suzuki-Miyaura coupling of amides, 3f was purified by
column chromatography (Petroleum ether/EtOAc = 30/1) to afford a white
solid (38.3 mg, 51%). 1H NMR (600 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 2H),
7.83 (d, J = 7.1 Hz, 2H), 7.78 (d, J = 8.1 Hz, 2H), 7.66 (m, J = 6.9 Hz, 1H),
7.54 (m, J = 7.8 Hz, 2H). 19F NMR (565 MHz, CDCl3) δ = -62.92
(4-Fluorophenyl)(phenyl)methanone
(3g).5d
Following
general
procedure for Suzuki-Miyaura coupling of amides, 3g was purified by
column chromatography (Petroleum ether/EtOAc = 50/1) to afford a white
solid (49.2 mg, 82%). 1H NMR (600 MHz, CDCl3) δ 7.78 (dd, J = 8.2, 1.3
Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.58 (m, J = 8.1 Hz, 1H), 7.48 (m, J = 7.7
Hz, 1H), 7.28 (d, J = 7.9 Hz, 1H). 19F NMR (565 MHz, CDCl3) δ = -105.91
(4-Chlorophenyl)(phenyl)methanone
(3h).5d
Following
general
procedure for Suzuki-Miyaura coupling of amides, 3h was purified by
column chromatography (Petroleum ether/EtOAc = 50/1) to afford a white
solid (50.5 mg, 78%). 1H NMR (400 MHz, CDCl3) δ 7.88 – 7.80 (m, 2H),
7.79 – 7.69 (m, 2H), 7.58 (m, J = 7.4 Hz, 1H), 7.47 (m, J = 7.9 Hz, 2H),
7.14 (m, J = 8.7 Hz, 2H).
Naphthalen-2-yl(phenyl)methanone (3i).5d Following general procedure
for Suzuki-Miyaura coupling of amides, 3i was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
49.4 mg, 71%). 1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.97 (d, J = 9.8
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10.1002/ejoc.201901730
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FULL PAPER
Hz, 2H), 7.91 (dd, J = 4.9, 4.4 Hz, 2H), 7.87 (dd, J = 8.0, 1.0 Hz, 2H), 7.62
(m, J = 6.3, 3.6, 1.2 Hz, 2H), 7.55 (m, J = 15.0, 4.2 Hz, 3H).
Keywords: Water phase • Room temperature • Ligand-free •
Suzuki-Miyaura coupling • Ketones
Methyl-4-benzoylbenzoate (3o).5d Following general procedure for
Suzuki-Miyaura coupling of amides, 3o was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
[1] (a) G. Bringmann, C. M. Gampe, Y. Reichert, T. Bruhn, J. H. Faber, M.
Mikyna, M. Reichert, M. Leippe, R. Brun and C. Gelhaus, J. Mater. Chem.,
2007, 50, 6104-6115; (b) S. Gobbi, A. Cavalli, M. Negri, K. E. Schewe, F.
Belluti, L. Piazzi, R. W. Hartmann, M. Recanatini and A. Bisi, J. Mater. Chem.,
2007, 50, 3420-3422; (c) A. Taladriz, A. Healy, E. J. Flores Pérez, V. Herrero
García, C. Ríos Martínez, A. A. M. Alkhaldi, A. A. Eze, M. Kaiser, H. P. de
Koning, A. Chana and C. Dardonville, J. Mater Chem., 2012, 55, 2606-2622.
[2] (a) R. Hu, J. L. Maldonado, M. Rodriguez, C. Deng, C. K. W. Jim, J. W. Y.
Lam, M. M. F. Yuen, G. Ramos-Ortiz and B. Z. Tang, J. Mater. Chem., 2012,
22, 232-240; (b) Y. Yu, J. Li, S. Chen, Y. Hong, K. M. Ng, K. Q. Luo and B.
Z. Tang, ACS Appl. Mater. Interfaces., 2013, 5, 4613-4616; (c) H.-Q. Peng,
J.-F. Xu, Y.-Z. Chen, L.-Z. Wu, C.-H. Tung and Q.-Z. Yang, Chem. Commun.,
2014, 50, 1334-1337.
1
(40.32 mg, 56%). H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.3 Hz, 2H),
7.83 (d, J = 8.3 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 7.61 (t, J = 6.4 Hz, 1H),
7.49 (t, J = 7.6 Hz, 2H), 3.96 (s, 3H).
1-(3-Benzoylphenyl)ethanone (3p).6g Following general procedure for
Suzuki-Miyaura coupling of amides, 3p was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
(34.3 mg, 51%); 1H NMR (600 MHz, CDCl3) δ 8.38 (s, 1H), 8.20 (d, J = 7.8
Hz, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.85 – 7.79 (m, 2H), 7.63 (dt, J = 12.2,
7.6 Hz, 2H), 7.52 (t, J = 7.7 Hz, 2H), 2.66 (s, 3H).
(3,4-Dimethoxyphenyl)(phenyl)methanone (3q).6g Following general
procedure for Suzuki-Miyaura coupling of amides, 3q was purified by
column chromatography (Petroleum ether/EtOAc = 20/1) to afford a white
1
solid (34.1 mg, 47%). H NMR (400 MHz, CDCl3) δ 7.75 (dd, J = 8.1, 1.1
Hz, 2H), 7.62 – 7.53 (m, 1H), 7.47 (dd, J = 12.6, 4.6 Hz, 3H), 7.37 (dd, J =
8.4, 2.0 Hz, 1H), 6.91 (dd, J = 17.6, 5.5 Hz, 1H), 3.95 (s, 3H), 3.94 (s, 3H).
[3] (a) A. F. Littke and G. C. Fu, Angew. Chem., Int. Ed., 2002, 41, 4176-4211;
(b) A. Suzuki, Angew. Chem., Int. Ed., 2011, 50, 6722-6737.
Characterization data of disubstituted ketones:
Bis (4-(trifluoromethyl) phenyl) methanone (3ff).6q Following general
procedure for Suzuki-Miyaura coupling of amides, 3ff was purified by
column chromatography (Petroleum ether/EtOAc = 30/1) to afford a white
[4] (a) H. Tatamidani, F. Kakiuchi and N. Chatani, Org. Lett., 2004, 6, 3597-
3599; (b) H. Tatamidani, K. Yokota, F. Kakiuchi and N. Chatani, J. Org.
Chem., 2004, 69, 5615-5621.
1
solid (53.4 mg, 56%). H NMR (600 MHz, CDCl3) δ 7.91 (d, J = 8.1 Hz,
[5] (a) Z. Luo, T. Liu, W. Guo, Z. Wang, J. Huang, Y. Zhu and Z. Zeng, Org.
Process Res. Dev., 2018, 22, 1188-1199; (b) M. Cui, Z. Chen, T. Liu, H.
Wang and Z. Zeng, Tetrahedron Lett., 2017, 58, 3819-3822; (c) H. Wu, B.
Xu, Y. Li, F. Hong, D. Zhu, J. Jian, X. Pu and Z. Zeng, J. Org. Chem., 2016,
81, 2987-92; (d) H. Wu, Y. Li, M. Cui, J. Jian and Z. Zeng, Adv. Synth. Catal.,
2016, 358, 3876-3880; (e) M. Cui, H. Wu, J. Jian, H. Wang, C. Liu, S. Daniel
and Z. Zeng, Chem. Commun., 2016, 52, 12076-12079; (f) Y. Li, H. Wu and
Z. Zeng, Eur. J. Org. Chem., 2019, 2019, 4357-4361; (g) Z. Luo, L. Xiong, T.
Liu, Y. Zhang, S. Lu, Y. Chen, W. Guo, Y. Zhu and Z. Zeng, J. Org. Chem.,
2019, 84, 10559-10568; (h) Z. Luo, H. Wu, Y. Li, Y. Chen, J. Nie, S. Lu, Y.
Zhu and Z. Zeng, Adv. Synth. Catal., 2019, 361, 4117-4125; (i) W. Guo, J.
Huang, H. Wu, T. Liu, Z. Luo, J. Jian and Z. Zeng, Org. Chem. Front., 2018,
5, 2950-2954; (j) J. Jian, Z. Wang, L. Chen, Y. Gu, L. Miao, Y. Liu and Z.
Zeng, Synth., 2019, 51, 4078-4084.
4H), 7.79 (d, J = 8.2 Hz, 4H). 13C NMR (151 MHz, CDCl3) δ = 194.38,
139.77, 134.38, 130.23, 125.62, 124.44, 122.63, 120.83. 19F NMR (565
MHz, CDCl3) δ = -63.18.
(4-Methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone
(3fe).6q
Following general procedure for Suzuki-Miyaura coupling of amides, 3fe
was purified by column chromatography (Petroleum ether/EtOAc = 30/1)
to afford a white solid (78.1 mg, 93%). 1H NMR (600 MHz, CDCl3) δ 7.90
– 7.83 (m, 4H), 7.77 (d, J = 8.1 Hz, 2H), 7.05 – 6.96 (m, 2H), 3.92 (s, 3H).
19F NMR (565 MHz, CDCl3) δ = -62.91.
(4-Methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone
(3ef).6q
Following general procedure for Suzuki-Miyaura coupling of amides, 3ef
was purified by column chromatography (Petroleum ether/EtOAc = 30/1)
to afford a white solid (57.1 mg, 68%). 1H NMR (600 MHz, CDCl3) δ 7.90
– 7.83 (m, 4H), 7.77 (d, J = 8.1 Hz, 2H), 7.05 – 6.96 (m, 2H), 3.92 (s, 3H).
19F NMR (565 MHz, CDCl3) δ = -62.91.
Bis(4-methoxyphenyl)methanone (3ee).6q Following general procedure
for Suzuki-Miyaura coupling of amides, 3ee was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
(51.5 mg, 71%). 1H NMR (600 MHz, CDCl3) δ 7.87 – 7.74 (m, 4H), 6.98 (d,
J = 8.8 Hz, 4H), 3.91 (s, 6H). 13C NMR (151 MHz, CDCl3) δ = 194.49,
162.85, 132.24, 130.77, 113.47, 55.48.
Bis(4-fluorophenyl)-methanone (3gg).28 Following general procedure
for Suzuki-Miyaura coupling of amides, 3gg was purified by column
chromatography (Petroleum ether/EtOAc = 20/1) to afford a white solid
(51.5 mg, 84%); 1H NMR (600 MHz, CDCl3) δ 7.86 – 7.81 (m, 1H), 7.19 (t,
J = 8.6 Hz, 1H). 13C NMR (151 MHz, CDCl3) δ = 193.81, 166.25, 164.56,
133.71, 132.51, 115.57. 19F NMR (565 MHz, CDCl3) δ -105.72 – -105.80
(m, 1H).
[6] (a) G. Meng, M. Szostak, Org. Lett. 2015, 17, 4364-4367; (b) C. Liu, G.
Meng, M. Szostak, J. Org. Chem., 2016, 81, 12023-12030; (c) G. Meng,
S. Shi, M. Szostak, ACS Catalysis 2016, 6, 7335-7339; (d) G. Meng, R.
Lalancette, R. Szostak, M. Szostak, Org. Lett. 2017, 19, 4656-4659; (e) G.
Meng, R. Szostak, M. Szostak, Org. Lett. 2017, 19, 3596-3599; (f) S. Shi, R.
Lalancette, R. Szostak and M. Szostak, Org. Lett., 2019, 21, 1253-1257; (g)
P. Lei, G. Meng, Y. Ling, J. An, S. P. Nolan, M. Szostak, Org. Lett. 2017, 19,
6510-6513; (h) Y. Osumi, C. Liu and M. Szostak, Org. Biomol. Chem., 2017,
15, 8867-8871; (i) G. Meng, S. Shi, R. Lalancette, R. Szostak and M.
Szostak, J. Am. Chem. Soc., 2018, 140, 727-734; (j) R. Szostak, J. Aubé, M.
Szostak, Chem. Commun. 2015, 51, 6395-6398; (k) V. Pace, W. Holzer, G.
Meng, S. Shi, R. Lalancette, R. Szostak, M. Szostak, Chem. – A Eur. J. 2016,
22, 14494-14498; (l) R. Szostak, S. Shi, G. Meng, R. Lalancette, M. Szostak,
J. Org. Chem., 2016, 81, 8091-8094; (m) C. Liu, S. Shi, Y. Liu, R. Liu, R.
Lalancette, R. Szostak, M. Szostak, Org. Lett. 2018, 20, 7771-7774; (n) C.
Liu, G. Meng, Y. Liu, R. Liu, R. Lalancette, R. Szostak and M. Szostak, Org.
Lett., 2016, 18, 4194-4197; (o) G. Meng and M. Szostak, Eur. J. Org. Chem.,
2018, 2018, 2352-2365; (p) G. Meng, P. Lei and M. Szostak, Org. Lett., 2017,
19, 2158-2161; (q) P. Lei, G. Meng, Y. Ling, J. An and M. Szostak, J. Org.
Acknowledgements
The authors gratefully acknowledge the support of Science and
Technology Planning Project of Guangdong Province
(2017A010103017), National Natural Science Foundation of
China (51703069, 21272080), Special Innovation Projects of
Common Universities in Guangdong Province (20178S0182).
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Chem., 2017, 82, 6638-6646; (r) P. Lei, Y. Ling, J. An, S. P. Nolan, M.
Szostak, Adv. Synth. Catal. 2019, 361, 5654-5660; (s) M. Szostak, S. Shi,
Synth. 2017, 49, 3602-3608; (t) M. Rahman, J. Buchspies,
M.Szostak, Catalysts, 2019, 9, 129; (u) J. Buchspies,, M.Szostak, Catalysts,
2019, 9, 53; (v) S. Shi, S. P. Nolan, M. Szostak, Acc. Chem. Res., 2018, 51,
2589-2599; (w) S. Shi and M. Szostak, Org. Lett., 2016, 18, 5872-5875; (x)
G. Li, P. Lei, M. Szostak, E. Casals‐Cruañas, A. Poater, L. Cavallo and S.
P. Nolan, ChemCatChem, 2018, 10, 3096-3106.
[16] P. R. Boruah, A. A. Ali, B. Saikia and D. Sarma, Green Chem., 2015, 17,
1442-1445.
[17] S. Handa, F. Ibrahim, T. N. Ansari and F. Gallou, ChemCatChem, 2018, 10,
4229-4233.
[18] (a) E. Vedejs, R. W. Chapman, S. C. Fields, S. Lin and M. R. Schrimpf, J.
Org. Chem., 1995, 60, 3020-3027; (b) S. Darses, G. Michaud and J.-P.
Genêt, Eur. J. Org. Chem., 1999, 1999, 1875-1883; (c) E. Vedejs, S. C.
Fields, R. Hayashi, S. R. Hitchcock, D. R. Powell and M. R. Schrimpf, J. Am.
Chem. Soc., 1999, 121, 2460-2470.
[7] (a) X. Li and G. Zou, Chem. Commun., 2015, 51, 5089-5092; (b) X. Li and
G. Zou, J. Organomet. Chem., 2015, 794, 136-145.
[19] N. Zhang, D. J. Hoffman, N. Gutsche, J. Gupta and V. Percec, J. Org. Chem.,
2012, 77, 5956-5964.
[8] (a) P.-Q. Huang, Y.-H. Huang and K.-J. Xiao, J. Org. Chem., 2016, 81, 9020-
9027; (b) P.-Q. Huang and H. Chen, Chem. Commun., 2017, 53, 12584-
12587; (c) P.-Q. Huang and H. Geng, Green Chem., 2018, 20, 593-599; (d)
J.-F. Zheng, X.-N. Hu, Z. Xu, D.-C. Cai, T.-L. Shen and P.-Q. Huang, J. Org.
Chem., 2017, 82, 9693-9703; (e) P.-Q. Huang, Q.-W. Lang, A.-E. Wang and
J.-F. Zheng, Chem. Commun., 2015, 51, 1096-1099; (f) P.-Q. Huang, W. Ou
and F. Han, Chem. Commun., 2016, 52, 11967-11970; (g) H. Chen, J.-L. Ye
and P.-Q. Huang, Org. Chem. Front., 2018, 5, 943-947; (h) P.-Q. Huang, W.
Ou, K.-J. Xiao and A.-E. Wang, Chem. Commun., 2014, 50, 8761-8763.
[9] (a) L. Hie, N. F. Fine Nathel, T. K. Shah, E. L. Baker, X. Hong, Y.-F. Yang, P.
Liu, K. N. Houk and N. K. Garg, Nature, 2015, 524, 79; (b) N. A. Weires, E.
L. Baker and N. K. Garg, Nat. Chem., 2015, 8, 75; (c) E. L. Baker, M. M.
Yamano, Y. Zhou, S. M. Anthony and N. K. Garg, Nat. Commun., 2016, 7,
11554.
[20] (a) S. Bonollo, D. Lanari and L. Vaccaro, Eur. J. Org. Chem., 2011, 2011,
2587-2598; (b) C. M. Kleiner and P. R. Schreiner, Chem. Commun., 2006,
41, 4315-4317; (c) C.-J. Li, Chem. Rev., 2005, 105, 3095-3166; (d) J. E. Klijn
and J. B. F. N. Engberts, Nature, 2005, 435, 746-747; (e) W. Chen, W. Yang,
R. Wu and D. Yang, Green Chem., 2018, 20, 2512-2518.
[21] J. Amani, R. Alam, S. Badir and G. A. Molander, Org. Lett., 2017, 19, 2426-
2429.
[22] (a) J. Sherwood, J. H. Clark, I. J. S. Fairlamb and J. M. Slattery, Green
Chem., 2019, 21, 2164-2213; (b) B. P. Carrow, J. F. Hartwig, J. Am. Chem.
Soc. 2011, 133, 2116-2119; (c) J. J. Molloy, C. P. Seath, M. J. West, C.
McLaughlin, N. J. Fazakerley, A. R. Kennedy, D. J. Nelson, A. J. B. Watson,
J. Am. Chem. Soc. 2018, 140, 126-130.
[23] J. Sherwood, T. J. Farmer, J. H. Clark, Chem 2018, 4, 2010-2012.
[24] D.G. Blackmond, A. Armstrong, V. Coombe, A. Wells, Angew. Chem. Int.
Ed. 2007, 46, 3798-3800.
[10] (a) R. Takise, K. Muto and J. Yamaguchi, Chem. Soc. Rev., 2017, 46, 5864-
5888; (b) J. Yamaguchi, K. Muto and K. Itami, Eur. J. Org. Chem., 2013,
2013, 19-30; (c) K. Amaike, K. Muto, J. Yamaguchi and K. Itami, J. Am.
Chem. Soc., 2012, 134, 13573-13576.
[25] G. Sartori and R. Maggi, Advances in Friedel-Crafts acylation reactions:
Catalytic and green processes, CRC Press, 2009.
[11] B. Basu, K. Biswas, S. Kundu and S. Ghosh, Green Chem., 2010, 12, 1734-
1738.
[26] (a) B. Holmes, R. Brogden, R. Heel, T. Speight and G. Avery, Drugs, 1984,
27, 6-44; (b) M. De Ryck, J. Van Reempts, M. Borgers, A. Wauquier and P.
Janssen, Stroke, 1989, 20, 1383-1390.
[12] C. Liu, Q. Ni, F. Bao and J. Qiu, Green Chem., 2011, 13, 1260-1266.
[13] M. Mondal and U. Bora, Green Chem., 2012, 14, 1873-1876.
[14] L. Liu, Y. Dong and N. Tang, Green Chem., 2014, 16, 2185-2189.
[15] I. Hoffmann, B. Blumenröder, S. Onodi neé Thumann, S. Dommer and J.
Schatz, Green Chem., 2015, 17, 3844-3857.
[27] J. Amani, R. Alam, S.Badir, G. A. Molander, Org. Lett. 2017, 19, 2426-2429.
[28] J. Zhong, W. P. To, Y. Liu, W. Lu, C. M. Che, Chem. Sci., 2019, 10, 4883-
4889.
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Text for Table of Contents
Key Topic: Green Suzuki-Miyaura
coupling; C-N bond cleavage
An
environmentally
friendly
Author(s), Corresponding Author(s)*
palladium-catalyzed Suzuki-Miyaura
coupling reaction of twist amides with
potassium aryl trifluoroborates has
been developed, generating ketones
under pure water phase, room
temperature and ligand-free condition.
Yuqi Zhang, Zijia Wang, Zhao Tang,
Zhongfeng Luo, Hongxiang Wu, Tingting
Liu * Yulin Zhu* Zhuo Zeng *
Page No. – Page No.
Water Phase/Room Temperature/
Ligand-Free Suzuki–Miyaura
Coupling: A green Gateway to Aryl
Ketones by C-N Bond Cleavage
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