Palladium-catalyzed C-H bond acylation of acetanilides with benzylic alcohols under aqueous conditions

Article abstract of DOI:10.1002/ejoc.201500016

Palladium-catalyzed dehydrogenative coupling reactions between acetanilides and benzylic alcohols under aqueous conditions are reported. A wide range of benzophenone derivatives could be obtained in good to excellent yields up to 98 %. Mechanism studies showed that a bimetallic palladium cyclopalladated complex might be involved in the catalysis.

Full text of DOI:10.1002/ejoc.201500016

Job/Unit: O50016
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Date: 24-02-15 16:30:54
Pages: 8
FULL PAPER
DOI: 10.1002/ejoc.201500016
Palladium-Catalyzed C–H Bond Acylation of Acetanilides with Benzylic
Alcohols under Aqueous Conditions
Feihua Luo,[a,b] Jun Yang,[a] Zhengkai Li,[a] Haifeng Xiang,[a] and Xiangge Zhou*[a]
Keywords: Synthetic methods / Acylation / Radical reactions / C–H activation / Palladium / Reaction mechanisms
Palladium-catalyzed dehydrogenative coupling reactions be- tives could be obtained in good to excellent yields up to 98%.
tween acetanilides and benzylic alcohols under aqueous con-
Mechanism studies showed that a bimetallic palladium
ditions are reported. A wide range of benzophenone deriva- cyclopalladated complex might be involved in the catalysis.
acid, followed by oxidation of the corresponding secondary
Introduction
alcohols by using various oxidants.[2]
Aryl ketones are a class of important compounds found
On the other hand, transition-metal-catalyzed direct C–
in the pharmaceutical, fragrance, dye, and agrochemical in- H bond functionalization is one of the most important
dustries.[1] Traditional methods for the synthesis of aryl transformations in recent organic synthetic strategies.[3] The
ketones rely mainly on the Friedel–Crafts acylation of aro- combination of transition-metal catalysts and directing
matic compounds in the presence of Lewis or Brønsted groups is a useful strategy that can be used to facilitate se
Scheme 1. Recent strategies for the acylation of acetanilides under mild conditions.
[a] Institute of Homogeneous Catalysis, College of Chemistry,
lective C–H bond cleavage, which would afford valuable
transformations of C–H bonds into C–C or C–heteroatom
bonds.[4,5] Although tremendous progress has been made in
this field, the reaction usually requires harsh reaction condi-
tions such as high temperature, long reaction time, and an
inert atmosphere. Therefore, the development of efficient
transition-metal-catalyzed oxidative couplings based on
Sichuan University,
Chengdu 610064, P. R. China
E-mail: zhouxiangge@scu.edu.cn
http://chem.scu.edu.cn/test/jiaoshi/zhouxiangge
[b] Department of Chemistry and Chemical Engineering, Sichuan
University of Arts and Science,
Dazhou 635000, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500016.
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F. Luo, J. Yang, Z. Li, H. Xiang, X. Zhou
FULL PAPER
highly active catalyst systems under mild reaction condi- Table 1. Optimization of reaction conditions.[a]
tions is still in high demand.
Recently, the synthesis of aromatic ketones from phenyl
pyridines or acetanilides has been achieved by palladium-
catalyzed oxidative coupling of aldehydes,[6] ketocarboxylic
acids,[7] toluene,[8] and alcohols.[9] Among them, several ex-
amples of palladium-catalyzed oxidative C–H bond acyl-
ation through functional group-directed ortho-substitution
under mild conditions were reported, as shown in
Scheme 1.[6c,6d,7a]
From the perspective of green chemistry, water is usually
regarded as an ideal reaction medium because of its natural,
inexpensive, nontoxic, and environmentally friendly charac-
teristics.[10] Therefore, we were inspired to use water-soluble
alcohols as potential coupling partners in the acylation re-
action. As part of our ongoing interest in aqueous cataly-
sis,[11] herein is described a new direct acylation method that
can be used to form aryl ketones from acetanilides and
benzylic alcohols in water (Scheme 1).
Entry Solvent Detergent
Additive
Time [h] Yield [%][b]
1
H2O
–
–
24
24
24
24
24
24
24
24
24
24
12
8
70
93
trace
n.r.
21
30
27
20
71
2
H2O
–
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
3
4
5
6
7
8
9
MeCN
DMSO
MeOH
dioxane
DCE
toluene
H2O
–
–
–
–
–
–
SDS (5%)
10
11
12
13
14[c]
H2O
H2O
H2O
H2O
TBAB (5%) TFA (30%)
73
94
92
–
–
–
–
TFA (30%)
TFA (30%)
TFA (30%)
TFA (30%)
4
65
H2O
8
75
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), Pd(OAc)2
(10%mmol), TBHP (0.8 mmol), solvent (0.4 mL), 40 °C. [b] Iso-
lated yield. [c] Reducing the Pd(OAc)2 to 5% under the standard
conditions.
Results and Discussion
Initially, acetanilide (1a) and benzylic alcohol (2a) were
treated with 10 mol-% Pd(OAc)2 and tert-butyl hydroperox-
ide (TBHP, 70 wt.-% in water) as oxidant at 40 °C, which
are conditions that were formerly reported for the cleavage
of ortho-C–H bonds by PdII catalysts in some cases.[6d,12]
To our delight, 70% yield of the corresponding ketone 3a
was obtained (Table 1, entry 1). Moreover, when a catalytic
amount of trifluoroacetic acid (TFA) (30%) was used as
additive, the yield improved significantly to 93% (entry 2).
For comparison with reported procedures, other organic
solvents were tested, but the use of methanol, dioxane,
dichloromethane and toluene resulted in lower yields rang-
ing from 20 to 30% (entries 5–8), whereas dimethyl sulfox-
ide (DMSO) and MeCN gave negligible yields (entries 3
and 4). These phenomena indicated that the use of water as
“green” solvent would be crucial for the reaction. Interest-
ingly, detergent, which was reported[6d,13] to promote reac-
tions under aqueous conditions, was not beneficial to the
catalysis in this experiment, with lower yields of 71 and
73% being obtained in the presence of sodium dodecyl sulf-
onate (SDS) and tetra-butyl ammonium bromide (TBAB),
respectively (entry 9). Further optimization of reaction con-
ditions showed that 8 h reaction time was sufficient for ca-
talysis (entries 11–13). It was noted that a lower yield (75%)
was obtained when the dosage of Pd catalyst was reduced
from 10 to 5% (entry 14).
Table 2. Scope of N-acetanilides for the Pd-catalyzed C–H acyla-
tion.[a], [b]
.
With the optimized reaction conditions in hand, we then
carried out a substrate scope study of a range of acet-
anilides with benzylic alcohol. As shown in Table 2, this
transformation was compatible with substituted acet-
anilides 3a–g, and substrates containing electron-donating
groups provided much higher yields than their electron-
withdrawing counterparts, which seemed to be consistent
with an electrophilic palladation mechanism.[14] On the
[a] Reaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), Pd(OAc)2
(10mmol-%), TBHP (0.8 mmol), TFA (30%), H2O (0.4 mL), 40 °C,
other hand, steric hindrance had a significant effect on the 24 h. [b] Isolated yield.
2
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Pd-Catalyzed C–H Bond Acylation
results. For example, electron-donating groups such as a anilide (1b) with Pd(OAc)2 in the presence of trifluoroacetic
methoxy, methyl, or ethyl group at the meta- or para-posi- acid in CH2Cl2 at 40 °C, gave a cyclopalladated intermedi-
tions provided good yields up to 95% (3a–e, 3i, an 3j), ate complex I, the structure of which was confirmed by X-
whereas the use of ortho-methoxyacetanilide resulted in a ray crystallography (Figure 1).
moderate yield of 65% (3h).[7a]
A substrate scope study of different benzylic alcohols
was then performed. As shown in Table 3, electronic effects
of substituents had some influence on the results, and either
electron-donating (OMe, Me and iPr) or electron-with-
drawing groups (F, Cl, and Br) were compatible with the
current reaction conditions (3k–x). As observed in previous
studies,[7,15] steric hindrance also had little influence on the
Scheme 2. Preparation of cyclopalladated Pd complex I.
reaction. For example, para- and ortho-methoxy substituted
benzylic alcohol gave similar results of 92 and 97% yields,
respectively (3o and 3p). The best result (98% yield) was
obtained in the case of meta-methylbenzylic alcohol.
Table 3. Acylation reaction of acetanilides with benzylic
alcohols.[a], [b]
.
Figure 1. X-ray structure of cyclopalladated Pd complex I.
Moreover, when complex I (5 mol-%) was added as cata-
lyst instead of Pd(OAc)2 under the standard reaction condi-
tions, the desired product 3k could be obtained in 78%
yield (Scheme 3, a). The desired product 3k could also be
isolated in 86% yield by using an equivalent amount of
complex I instead of Pd(OAc)2 and acetanilide under the
standard conditions (Scheme 3, b), which further confirmed
that complex I might be the actual intermediate during the
catalysis. When one equivalent of 2,2,6,6-tetramethylpiper-
idine-1-oxyl (TEMPO; a radical trapping regent) was added
to the reaction, the transformation was suppressed remark-
ably (Scheme 3, c), suggesting that a free radical mechanism
might be involved.
[a] Reaction conditions: 1b (0.2 mmol), 2 (0.4 mmol), Pd(OAc)2
(10%), TBHP (0.8 mmol), TFA (30%), H2O (0.4 mL), 40 °C, 24 h.
[b] Isolated yield.
Based on these preliminary results and on previous re-
ports,[6d,7b,16] a plausible mechanism for this reaction is pro-
posed as shown in Scheme 4. Firstly, through ligand-di-
To gain a better understanding of the reaction mecha- rected C–H activation of acetanilide, a bimetallic palladium
nism, we isolated and characterized the intermediate from cyclopalladated intermediate A (complex I) is formed,
the reaction between Pd(OAc)2 and acetanilide. As shown which is similar to metallocycles reported by other
in Scheme 2, treatment of an equivalent amount of acet- groups.[17] At the same time, the alcohol is oxidized to alde-
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F. Luo, J. Yang, Z. Li, H. Xiang, X. Zhou
FULL PAPER
employed in this reaction mean that this approach has the
potential to be used in the synthesis of other organic com-
pounds. Further studies and applications of this environ-
mentally friendly direct acylation strategy are underway in
our laboratory.
Experimental Section
General Information: Analytical thin-layer chromatography (TLC)
was performed with silica gel GF254 plates. Column chromatog-
raphy was performed with silica gel (300–400 mesh) eluting with
ethyl acetate and petroleum. All products were characterized by
1
NMR spectroscopy and HRMS. H NMR spectra were recorded
at 400 MHz and 13C NMR spectra were recorded at 100 MHz
(Bruker DPX) with CDCl3 or [D6]DMSO as solvent. Chemical
shifts are reported in ppm using TMS as internal standard. IR
spectra were recorded with a Bruker TENSOR 27 FTIR spectro-
photometer as KBr pellets. HRMS was recorded with a commercial
apparatus (ESI Source, TOF).
Scheme 3. Mechanistic studies on the C–H bond acylation.
Preparation of Acetanilide. General Procedure:[7a] To a solution of
aniline (10.0 mmol) in CH2Cl2 (20 mL) at room temperature in a
single-neck, round-bottomed flask, was slowly added acetic
anhydride (1.22 g, 12.0 mmol, 1.2 equiv.) by using a syringe. The
solution was stirred at room temperature and the progress of the
reaction was monitored by TLC. Upon completion, the reaction
mixture was washed with a saturated solution of sodium carbonate,
the organic layers were dried with Na2SO4, and the solvent was
removed under reduced pressure. The residue was subsequently
purified by recrystallization.
hyde by TBHP and then transferred to an acyl radical ac-
cording to a previous report.[9b] The PdII intermediate A
would then react with the acyl radical to afford the PdIII or
PdIV intermediate B by oxidative addition.[18] Finally, inter-
mediate B undergoes reductive elimination to generate the
acylation product and PdII is regenerated for the next cata-
lytic cycle.
Synthesis of Aryl Ketone 3a. Typical Procedure: A screw-capped
vial with stir bar was charged with Pd(OAc)2 (10 mol-%), acet-
anilide (0.2 mmol, 1 equiv.), and H2O (0.4 mL). TFA (4.5 μL,
0.06 mmol, 30 mol-%) was added, followed by benzylic alcohol
(0.4 mmol, 2 equiv.) and TBHP (100 μL, 0.8 mmol, 4 equiv., 70%
in H2O). The reaction vessel was closed, and the reaction mixture
was stirred at 40 °C. After 8 h, the reaction mixture was washed
with EtOAc and the organic layer was washed with water, dried
with magnesium sulfate, and concentrated. The crude product was
purified by column chromatography (petroleum/EtOAc) and the
relevant fractions were collected and concentrated to provide 3a
(44.5 mg, 93%) as a pale-yellow solid.
Synthesis of Bimetallic Palladium Complex I: In a one-dram vial
was added acetanilide (1b; 27.0 mg, 0.2 mmol), Pd(OAc)2 (44.8 mg,
0.2 mmol), and dichloromethane (10 mL). Trifluoroacetic acid
(22.8 mg, 0.2 mmol) was subsequently added into the vial and the
resulting solution was heated to 40 °C for 3 h. After cooling to
ambient temperature, the reaction mixture was concentrated in
vacuo and the resulting residue was redissolved in hexanes (2 mL).
After 2 h, precipitation of the desired complex occurred. The sus-
pension was filtered through Celite and washed with hexanes
(2ϫ0.3 mL). The residue was washed with dichloromethane and
the wash solution was subsequently collected and concentrated in
vacuo to afford the bimetallic palladacycle I (58.2 mg, 82%) as a
yellow solid. Recrystallization of the yellow solid from dichloro-
methane gave single crystals that were suitable for X-ray analysis.
Scheme 4. Proposed reaction pathway.
Conclusions
A new and efficient method has been developed for direct
ortho-acylation of anilides with benzylic alcohols through
sp2 C–H bond activation. This palladium-catalyzed oxidat-
ive coupling reaction was accomplished at temperatures un-
der 40 °C in water in the presence of a catalytic amount of
TFA, with TBHP as oxidant. The reaction exhibited good
Compound Characterization Data
N-(2-Benzoyl-5-methoxyphenyl)acetamide (3a):[6g] Yield 51 mg
1
(95%); pale-yellow solid. H NMR (400 MHz, CDCl3): δ = 11.59
(s, 1 H), 8.41 (d, J = 2.6 Hz, 1 H), 7.66–7.46 (m, 6 H), 6.58 (dd, J
functional group tolerance. The mild reaction conditions = 8.9, 2.6 Hz, 1 H), 3.92 (s, 3 H), 2.27 (s, 3 H) ppm. 13C NMR
4
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Pd-Catalyzed C–H Bond Acylation
(101 MHz, CDCl3): δ = 199.00, 169.60, 164.64, 143.88, 139.51,
136.23, 131.69, 129.30, 128.22, 115.49, 108.93, 104.80, 55.64,
25.52 ppm. ESI-MS: m/z calcd. for [C16H15NO3]+ 269.1052; found
269.1076.
55.96, 23.54 ppm. ESI-MS: m/z calcd. for [C16H15NO3]+ 269.1052;
found 269.1065.
N-[2-(3,4-Dimethoxybenzoyl)-5-methoxyphenyl]acetamide
(3i):
Yield 63 mg (96%); light-yellow liquid. 1H NMR (400 MHz,
N-(2-Benzoyl-4-methylphenyl)acetamide (3b):[6g] Yield 45.5 mg CDCl3): δ = 11.26 (s, 1 H), 8.34 (d, J = 2.5 Hz, 1 H), 7.56 (d, J =
(90%); white solid. 1H NMR (400 MHz, CDCl3): δ = 10.65 (s, 1
H), 8.51 (d, J = 8.5 Hz, 1 H), 7.75–7.33 (m, 7 H), 2.31 (s, 3 H),
2.22 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 199.65,
168.97, 138.72, 137.99, 134.86, 133.48, 132.43, 131.65, 129.86,
128.31, 123.50, 121.61, 25.17, 20.73 ppm. ESI-MS: m/z calcd. for
[C16H15NO2]+ 253.1103; found 253.1121.
8.8 Hz, 1 H), 7.36–7.12 (m, 2 H), 6.92 (d, J = 8.3 Hz, 1 H), 6.59
(dd, J = 8.8, 2.6 Hz, 1 H), 4.00–3.89 (m, 9 H), 2.24 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 197.46, 169.45, 164.13, 152.59,
148.87, 143.15, 135.49, 131.79, 124.56, 116.27, 112.16, 109.86,
108.77, 105.15, 56.10, 56.02, 55.63, 25.45 ppm. IR (KBr): ν = 3410
˜
(νN–H), 1690 (νC=O), 1620 (νC=O) cm–1. ESI-MS: m/z calcd. for
[C18H19NO5]+ 329.1263; found 329.1291.
N-(2-Benzoyl-4-ethylphenyl)acetamide (3c): Yield 44.5 mg (83%);
light-yellow solid. 1H NMR (400 MHz, CDCl3): δ = 10.65 (s, 1 H), N-[2-(3,5-Dimethoxybenzoyl)-5-methoxyphenyl]acetamide
(3j):
1
8.52 (d, J = 8.5 Hz, 1 H), 7.77–7.34 (m, 8 H), 2.61 (q, J = 7.6 Hz, Yield 59.2 mg (90%); white solid. H NMR (400 MHz, CDCl3): δ
2 H), 2.23 (s, 4 H), 1.20 (t, J = 7.6 Hz, 4 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 199.68, 169.00, 138.73, 138.13, 138.08,
133.73, 132.47, 129.92, 128.30, 126.94, 123.57, 121.73, 28.11, 25.17,
= 11.54 (s, 1 H), 8.39 (d, J = 2.6 Hz, 1 H), 7.58 (d, J = 8.9 Hz, 1
H), 6.86–6.41 (m, 4 H), 3.91 (s, 3 H), 3.83 (s, 6 H), 2.26 (s, 3
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 198.65, 169.60, 164.74,
15.52 ppm. IR (KBr): ν
= 3210 (νN–H), 1670 (νC=O), 1658 160.49, 143.86, 141.35, 136.26, 115.34, 108.93, 107.09, 104.76,
˜
(νC=O) cm–1. ESI-MS: m/z calcd. for [C17H17NO2]+ 267.1259; found
103.91, 55.65, 55.57, 25.53 ppm. IR (KBr): ν = 3420 (νN–H), 1690
˜
267.1287.
(νC=O), 1615 (νC=O) cm–1. ESI-MS: m/z calcd. for [C18H19NO5]+
329.1263; found 329.1276.
N-(2-Benzoyl-5-methylphenyl)acetamide (3d):[6g] Yield 46.7 mg
(92%); white solid. 1H NMR (400 MHz, CDCl3): δ = 11.01 (s, 1
H), 8.50 (s, 1 H), 7.80–7.37 (m, 6 H), 6.88 (d, J = 8.1 Hz, 1 H),
N-(2-Benzoylphenyl)acetamide (3k):[6g] Yield 44.5 mg (93%); color-
1
less liquid. H NMR (400 MHz, CDCl3): δ = 10.83 (s, 1 H), 8.65
2.43 (s, 3 H), 2.22 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ (d, J = 8.3 Hz, 1 H), 7.84–7.39 (m, 7 H), 7.16–7.00 (m, 1 H), 2.24
= 199.60, 169.23, 145.81, 140.81, 138.99, 133.89, 132.19, 129.70,
128.26, 122.92, 121.67, 120.52, 25.37, 22.17 ppm. ESI-MS: m/z
calcd. for [C16H15NO2]+ 253.1103; found 253.1128.
(s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 199.72, 169.16,
140.50, 138.64, 134.26, 133.51, 132.49, 129.88, 128.33, 123.25,
122.04, 121.52, 25.27 ppm. ESI-MS: m/z calcd. for [C15H13NO2]+
239.0946; found 239.0971.
N-(2-Benzoyl-5-ethylphenyl)acetamide (3e): Yield 50.4 mg (94%);
1
colorless liquid. H NMR (400 MHz, CDCl3): δ = 11.02 (s, 1 H),
N-[2-(4-Methylbenzoyl)phenyl]acetamide (3l):[7a] Yield 47 mg (93%);
1
8.53 (s, 1 H), 7.83–7.32 (m, 6 H), 6.90 (d, J = 8.1 Hz, 1 H), 2.72 white solid. H NMR (400 MHz, CDCl3): δ = 10.74 (s, 1 H), 8.62
(q, J = 7.6 Hz, 2 H), 2.22 (s, 3 H), 1.28 (t, J = 7.6 Hz, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 199.61, 169.25, 151.94, 140.96,
139.00, 134.03, 132.18, 129.71, 128.26, 121.67, 120.71, 120.65,
(d, J = 8.4 Hz, 1 H), 7.67–7.54 (m, 4 H), 7.31 (d, J = 8.0 Hz, 2 H),
7.10 (td, J = 7.7, 1.1 Hz, 1 H), 2.47 (s, 3 H), 2.24 (s, 3 H) ppm. 13
C
NMR (101 MHz, CDCl3): δ = 199.31, 169.11, 143.48, 140.24,
29.39, 25.38, 15.05 ppm. IR (KBr): ν = 3210 (νN–H), 1670 (νC=O),
135.85, 133.94, 133.26, 130.20, 129.02, 123.68, 122.00, 121.55,
˜
1645 (νC=O) cm–1. ESI-MS: m/z calcd. for [C17H17NO2]+ 267.1259; 25.25, 21.65 ppm. ESI-MS: m/z calcd. for [C16H15NO2]+ 253.1103;
found 267.1287.
found 253.1112.
N-(2-Benzoyl-4-fluorophenyl)acetamide (3f):[7a] Yield 35 mg (68%); N-[2-(3-Methylbenzoyl)phenyl]acetamide (3m):[6d] Yield 49.2 mg
1
white solid. H NMR (400 MHz, CDCl3): δ = 10.50 (s, 1 H), 8.59
(dd, J = 9.2, 5.1 Hz, 1 H), 7.71 (dd, J = 5.2, 3.3 Hz, 2 H), 7.67–
7.59 (m, 1 H), 7.56–7.47 (m, 2 H), 7.33–7.20 (m, 2 H), 2.21 (s, 3
(98%); white solid. 1H NMR (400 MHz, CDCl3): δ = 10.83 (s, 1
H), 8.64 (d, J = 8.2 Hz, 1 H), 7.63–7.46 (m, 4 H), 7.40 (dt, J =
15.0, 7.5 Hz, 2 H), 7.15–7.03 (m, 1 H), 2.44 (s, 3 H), 2.24 (s, 3
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 198.31 (s), 169.05 (s), H) ppm. 13C NMR (101 MHz, CDCl3): δ = 199.97, 169.18, 140.42,
156.92 (d, J = 244.4 Hz), 137.81 (s), 136.48 (s), 133.01 (s), 129.90 138.67, 138.27, 134.17, 133.51, 133.29, 130.29, 128.16, 127.19,
(s), 128.54 (s), 124.81 (s), 123.72 (d, J = 7.1 Hz), 120.99 (d, JC,F
=
123.42, 122.04, 121.49, 25.27, 21.35 ppm. ESI-MS: m/z calcd. for
21.8 Hz), 119.17 (d, JC,F = 23.7 Hz), 25.10 (s) ppm. ESI-MS: m/z
[C16H15NO2]+ 253.1103; found 253.1126.
calcd. for [C15H12FNO2]+ 257.0852; found 257.0881.
N-[2-(2-Methylbenzoyl)phenyl]acetamide (3n):[6d] Yield 48.6 mg
N-(2-Benzoyl-5-fluorophenyl)acetamide (3g):[7a] Yield 42.4 mg (96%); white solid. 1H NMR (400 MHz, CDCl3): δ = 11.55 (s, 1
(82%); white solid. 1H NMR (400 MHz, CDCl3): δ = 11.14 (s, 1
H), 8.44 (dd, J = 11.8, 2.6 Hz, 1 H), 7.67–7.31 (m, 6 H), 6.83–6.50
(m, 1 H), 2.17 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
H), 8.76 (dd, J = 8.5, 0.8 Hz, 1 H), 7.61–7.52 (m, 1 H), 7.43–7.20
(m, 5 H), 7.00 (td, J = 8.0, 1.1 Hz, 1 H), 2.29 (d, J = 5.3 Hz, 6
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 202.87, 169.52, 141.55,
139.30, 135.89, 135.30, 134.50, 130.93, 130.24, 127.88, 125.37,
198.96, 169.43, 166.03 (d, JC,F = 254.7 Hz), 143.37 (d, JC,F
=
13.2 Hz), 138.75, 136.32, 136.21, 132.42, 129.57, 128.42, 118.98 (d, 122.46, 122.15, 120.73, 25.55, 19.74 ppm. ESI-MS: m/z calcd. for
JC,F = 2.8 Hz), 109.19 (d, JC,F = 22.4 Hz), 108.38 (d, JC,F
=
[C16H15NO2]+ 253.1103; found 253.1109.
28.0 Hz), 25.38 ppm. ESI-MS: m/z calcd. for [C15H12FNO2]+
N-[2-(4-Methoxybenzoyl)phenyl]acetamide (3o):[6d] Yield 49.8 mg
(92%); colorless liquid. 1H NMR (400 MHz, CDCl3): δ = 10.54 (s,
257.0852; found 257.0876.
N-(2-Benzoyl-6-methoxyphenyl)acetamide (3h):[6g] Yield 35 mg 1 H), 8.58 (d, J = 8.4 Hz, 1 H), 7.79–7.73 (m, 2 H), 7.60–7.52 (m,
(65%); yellow solid. 1H NMR (400 MHz, CDCl3): δ = 8.05–7.76
(m, 3 H), 7.56 (t, J = 7.4 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.25–
7.13 (m, 1 H), 7.09–6.89 (m, 1 H), 3.86 (s, 1 H), 2.03 (s, 1 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 195.34, 168.33, 151.87, 137.07,
134.03, 132.63, 130.35, 128.07, 124.99, 124.05, 121.39, 112.95,
2 H), 7.11 (td, J = 7.7, 1.0 Hz, 1 H), 7.03–6.94 (m, 2 H), 3.91 (s, 3
H), 2.22 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 197.92,
169.02, 163.45, 139.83, 133.53, 132.74, 132.61, 130.91, 124.25,
122.05, 121.72, 113.65, 55.55, 25.19 ppm. ESI-MS: m/z calcd. for
[C16H15NO3]+ 269.1052; found 269.1076.
Eur. J. Org. Chem. 0000, 0–0
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F. Luo, J. Yang, Z. Li, H. Xiang, X. Zhou
140.28 (s), 134.73 (d, JC,F = 3.1 Hz), 134.28 (s), 133.05 (s), 132.60
FULL PAPER
N-[2-(2-Methoxybenzoyl)phenyl]acetamide (3p):[6d] Yield 52 mg
(97%); colorless liquid. 1H NMR (400 MHz, CDCl3): δ = 11.62 (s, (d, JC,F = 9.2 Hz), 123.35 (s), 122.16 (s), 121.77 (s), 115.57 (d, JC,F
1 H), 8.76 (dd, J = 8.5, 0.7 Hz, 1 H), 7.51 (dddd, J = 17.4, 16.5, = 22.0 Hz), 25.24 (s) ppm. ESI-MS: m/z calcd. for [C15H12FNO2]+
7.8, 1.5 Hz, 3 H), 7.29 (dd, J = 7.6, 1.6 Hz, 1 H), 7.21–6.88 (m, 3
H), 3.77 (s, 3 H), 2.29 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 200.58, 169.53, 156.81, 141.33, 135.06, 134.52, 131.95, 129.10,
129.07, 122.57, 122.00, 120.49, 120.45, 111.45, 55.65, 25.56 ppm.
ESI-MS: m/z calcd. for [C16H15NO3]+ 269.1052; found 269.1068.
257.0852; found 257.0869.
N-{2-[4-(Trifluoromethyl)benzoyl]phenyl}acetamide (3x):[9a] Yield
52.3 mg (85%); white solid. 1H NMR (400 MHz, CDCl3): δ = 10.88
(s, 1 H), 8.69 (d, J = 8.5 Hz, 1 H), 7.79 (q, J = 8.5 Hz, 4 H), 7.70–
7.58 (m, 1 H), 7.51 (dd, J = 7.9, 1.4 Hz, 1 H), 7.20–7.00 (m, 1 H),
2.27 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 198.61,
169.24, 141.85, 140.91, 135.04, 133.90, 133.54, 129.90, 125.39 (q, J
= 3.7 Hz), 122.37, 122.20, 121.64, 25.31 ppm. ESI-MS: m/z calcd.
for [C16H12F3NO2]+ 307.0820; found 307.0847.
N-[2-(4-Isopropyl)phenyl]acetamide (3q): Yield 49.2 mg (87%); col-
orless liquid. 1H NMR (400 MHz, CDCl3): δ = 10.75 (s, 1 H), 8.62
(d, J = 8.2 Hz, 1 H), 7.71–7.65 (m, 2 H), 7.62–7.55 (m, 2 H), 7.36
(d, J = 8.2 Hz, 2 H), 7.10 (td, J = 7.7, 1.1 Hz, 1 H), 3.02 (dt, J =
13.8, 6.9 Hz, 1 H), 2.23 (s, 3 H), 1.32 (d, J = 6.9 Hz, 6 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 199.30, 169.11, 154.23, 140.23,
136.21, 133.92, 133.29, 130.34, 126.45, 123.72, 122.01, 121.56,
CCDC-1045081 (for complex I) contains the supplementary crys-
tallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
34.28, 25.22, 23.70 ppm. IR (KBr): ν = 3290 (νN–H), 1695 (νC=O),
˜
1630 (νC=O) cm–1. ESI-MS: m/z calcd. for [C18H19NO2]+ 281.1416;
Supporting Information (see footnote on the first page of this arti-
cle): Copies of 1H NMR and 13C NMR spectra for all compounds
with crystal data for complex I.
found 231.1442.
N-[2-(2-Chlorobenzoyl)phenyl]acetamide (3r):[7a] Yield 48.8 mg
(89%); white solid. 1H NMR (400 MHz, CDCl3): δ = 11.56 (s, 1
H), 8.82 (dd, J = 8.5, 0.8 Hz, 1 H), 7.60 (ddd, J = 8.6, 7.5, 1.5 Hz,
1 H), 7.53–7.31 (m, 5 H), 7.06–7.00 (m, 1 H), 2.31 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 199.22, 169.58, 141.93, 138.80,
135.91, 134.57, 131.18, 130.93, 130.13, 128.65, 126.74, 122.25,
121.28, 120.64, 25.62 ppm. ESI-MS: m/z calcd. for [C15H12ClNO2]+
273.0557; found 273.0586.
Acknowledgments
The authors are grateful to the National Natural Science Founda-
tion of China (NSFC) (grant numbers 21272161, 21372163,
21472128, J1103315, J1310008) and the Ministry of Education
(grant number 20120181110050) for financial support.
N-[2-(3-Chlorobenzoyl)phenyl]acetamide (3s):[7a] Yield 48.2 mg
(88%); light-yellow solid. H NMR (400 MHz, CDCl3): δ = 10.77
1
(s, 1 H), 8.65 (d, J = 8.4 Hz, 1 H), 7.73–7.41 (m, 6 H), 7.15–7.09
(m, 1 H), 2.25 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
198.16, 169.18, 140.65, 140.28, 134.73, 133.36, 132.38, 129.66,
129.63, 127.92, 127.59, 122.66, 122.21, 121.64, 25.28 ppm. ESI-MS:
m/z calcd. for [C15H12ClNO2]+ 273.0557; found 273.0579.
[1] a) J. A. Horsely, Chemtech 1997, 10, 45–49; b) H. Surburg, J.
Panten, Common Fragrance and Flavor Materials, 5th ed.,
Wiley-VCH, Weinheim, Germany, 2006; c) J. J. Eisch, P. O. Fre-
gene, Eur. J. Org. Chem. 2008, 26, 4482–4492.
[2] a) R. Liu, X. Liang, C. Dong, X. Hu, J. Am. Chem. Soc. 2004,
126, 4112–4113; b) G. Sartori, R. Maggi, Chem. Rev. 2006, 106,
1077–1104; c) X. He, Z. Shen, W. Mo, N. Sun, B. Hu, X. Hu,
Adv. Synth. Catal. 2009, 351, 89–92; d) G. Sartori, R. Maggi,
Advances in Friedel Crafts Acylation Reactions, CRC Press,
Boca Raton, FL, 2010; e) Y. Yuan, X. Shi, W. Liu, Synlett
2011, 559–564.
[3] a) J. Wencel-Delord, T. Drçge, F. Liu, F. Glorius, Chem. Soc.
Rev. 2011, 40, 4740–4761; b) T.-S. Mei, L. Kou, S. Ma, K. M.
Engle, J.-Q. Yu, Synthesis 2012, 44, 1778–1791; c) C. Liu, H.
Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780–1824; d)
T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147–1169;
e) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem. Res. 2009,
42, 1074–1086; f) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu,
Angew. Chem. Int. Ed. 2009, 48, 5094–5115; Angew. Chem.
2009, 121, 5196–5217; g) T.-S. Mei, L. Kou, S. MA, K. M.
Engle, J.-Q. Yu, Synthesis 2012, 44, 1778–1791; h) S. R. Neu-
feldt, M. S. Sanford, Acc. Chem. Res. 2012, 45, 936–946.
[4] a) G. Dyker, Handbook of C–H Transformations: Applications
in Organic Synthesis Wiley-VCH, Weinheim, Germany, 2005;
b) J. Q. Yu, Z. J. Shi, C–H Activation, Springer, Berlin, 2010;
c) Activation and Functionalization of C–H Bond (Eds.: K. I.
Goldberg, A. S. Goldman), ACS Symposium Series 885,
American Chemical Society, Washington, DC, 2004.
[5] For recent selected examples of C–H activations and C–C bond
formations, see: a) C. S. Feung, V. M. Dong, Chem. Rev. 2011,
111, 1215–1292; b) J. A. Ashenhurst, Chem. Soc. Rev. 2010, 39,
540–548; c) I. Hussain, T. Singh, Adv. Synth. Catal. 2014, 356,
1661–1696; d) Z. Shi, B. Li, X. Wan, J. Cheng, Z. Fang, B.
Cao, C. Qin, Y. Wang, Angew. Chem. Int. Ed. 2007, 46, 5554–
5658; Angew. Chem. 2007, 119, 5650–5654; e) G. Deng, L.
Zhao, C.-J. Li, Angew. Chem. Int. Ed. 2008, 47, 6278–6282;
Angew. Chem. 2008, 120, 6374–6378; f) D. Pan, A. Chen, Y.
Su, W. Zhou, S. Li, W. Jia, J. Xiao, Q. Liu, L. Zhang, N. Jiao,
N-[2-(4-Chlorobenzoyl)phenyl]acetamide (3t):[7a] Yield 51 mg (93%);
1
white solid. H NMR (400 MHz, CDCl3): δ = 10.71 (s, 1 H), 8.63
(d, J = 8.4 Hz, 1 H), 7.69–7.46 (m, 6 H), 7.11 (td, J = 7.9, 1.1 Hz,
1 H), 2.24 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 198.28,
169.14, 140.45, 139.03, 136.87, 134.48, 133.14, 131.31, 128.68,
123.02, 122.15, 121.71, 25.26 ppm. ESI-MS: m/z calcd. for
[C15H12ClNO2]+ 273.0557; found 273.0573.
N-[2-(4-Bromobenzoyl)phenyl]acetamide (3u):[7a] Yield 42.1 mg
(97%); white solid. 1H NMR (400 MHz, CDCl3): δ = 10.71 (s, 1
H), 8.62 (d, J = 8.3 Hz, 1 H), 7.67–7.48 (m, 6 H), 7.09 (td, J = 7.9,
1.1 Hz, 1 H), 2.22 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 198.44, 169.15, 140.47, 137.31, 134.52, 133.17, 131.66, 131.40,
127.60, 122.95, 122.16, 121.70, 25.27 ppm. ESI-MS: m/z calcd. for
[C15H12BrNO2]– 317.0551; found 317.0578.
N-[2-(2-Fluorobenzoyl)phenyl]acetamide (3v):[7a] Yield 61.6 mg
(82%); white solid. 1H NMR (400 MHz, CDCl3): δ = 11.34 (s, 1
H), 8.75 (d, J = 8.5 Hz, 1 H), 7.63–7.40 (m, 4 H), 7.32–7.14 (m, 2
H), 7.09–7.01 (m, 1 H), 2.27 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 197.05, 169.45, 159.47 (d, J = 252.1 Hz), 141.31,
135.54, 134.14, 133.04 (d, JC,F = 8.3 Hz), 130.18 (d, JC,F = 2.2 Hz),
127.59 (d, JC,F = 14.8 Hz), 124.28 (d, JC,F = 3.6 Hz), 122.27,
120.77, 116.36 (d, JC,F = 21.5 Hz), 25.50 ppm. ESI-MS: m/z calcd.
for [C15H12FNO2]+ 257.0852; found 257.0881.
N-[2-(4-Fluorobenzoyl)phenyl]acetamide (3w):[7a] Yield 46.3 mg
(90%); white solid. 1H NMR (400 MHz, CDCl3): δ = 10.63 (s, 1
H), 8.60 (d, J = 8.4 Hz, 1 H), 7.79–7.72 (m, 2 H), 7.62–7.49 (m, 2
H), 7.21–7.06 (m, 3 H), 2.22 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 198.00 (s), 169.13 (s), 165.40 (d, JC,F = 254.8 Hz),
6
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Pd-Catalyzed C–H Bond Acylation
Angew. Chem. Int. Ed. 2008, 47, 4729–4732; 11, 1171–1174;
Angew. Chem. 2008, 120, 4807–4810; g) G. Deng, K. Ueda, S.
Yanagisawa, K. Itami, C.-J. Li, Chem. Eur. J. 2009, 15, 333–
337; h) K. M. Engle, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc.
2010, 132, 14137–14151; i) Z. Ye, G. Lv, W. Wang, M. Zhang,
J. Cheng, Angew. Chem. Int. Ed. 2010, 49, 3671–3674; Angew.
Chem. 2010, 122, 3753–3756; j) Y. Li, B.-J. Li, W.-H. Wang,
W.-P. Huang, X.-S. Zhang, K. Chen, Z. J. Shi, Angew. Chem.
Int. Ed. 2011, 50, 2115–2119; Angew. Chem. 2011, 123, 2163–
2167.
mun. 2008, 1241–1243; d) S. A. Ohnmacht, A. J. Culshaw,
M. F. Greaney, Org. Lett. 2010, 12, 224–226; e) P. B. Arockiam,
C. Fischmeister, C. Bruneau, P. H. Dixneuf, Angew. Chem. Int.
Ed. 2010, 49, 6629–6632; Angew. Chem. 2010, 122, 6779–6782;
f) L. Ackermann, J. Pospech, H. K. Potukuchi, Org. Lett. 2012,
14, 2146–2149; g) S. Islam, I. Larrosa, Chem. Eur. J. 2013, 19,
15093–15096.
[11]
For selected recent examples, see: a) L. Liang, Z. Li, X. Zhou,
Org. Lett. 2009, 11, 3294–3297; b) Y. Wang, Z. Wu, L. Wang,
Z. Li, X. Zhou, Chem. Eur. J. 2009, 15, 8971–8974; c) L. Jing,
J. Wei, L. Zhou, Z. Huang, Z. Li, X. Zhou, Chem. Commun.
2010, 46, 4767–4769; d) F. Ke, Y. Qu, Z. Jiang, Z. Li, D. Wu,
X. Zhou, Org. Lett. 2011, 13, 454–457; e) Y. Qu, F. Ke, L.
Zhou, H. Xiang, D. Wu, X. Zhou, Chem. Commun. 2011, 47,
3912–3914; f) Z. Li, L. Wang, X. Zhou, Adv. Synth. Catal.
2012, 354, 584–588; g) H. Deng, Z. Li, F. Ke, X. Zhou, Chem.
Eur. J. 2012, 18, 4840–4843; h) Z. Wu, F. Luo, S. Chen, Z. Li,
H. Xiang, X. Zhou, Chem. Commun. 2013, 49, 7653–7655.
a) J.-R. Wang, C.-T. Yang, L. Liu, Q.-X. Guo, Tetrahedron
Lett. 2007, 48, 5449–5453; b) C. E. Houlden, C. D. Bailey, J. G.
Ford, M. R. Gagné, G. C. Lloyd-Jones, K. I. Booker-Milburn,
J. Am. Chem. Soc. 2008, 130, 10066–10067; c) C. E. Houlden,
M. Hutchby, C. D. Bailey, J. G. Ford, S. N. G. Tyler, M. R.
Gagné, G. C. Lloyd-Jones, K. I. Booker-Milburn, Angew.
Chem. Int. Ed. 2009, 48, 1830–1833; Angew. Chem. 2009, 121,
1862–1865; d) R. Giri, J. K. Lam, J.-Q. Yu, J. Am. Chem. Soc.
2010, 132, 686–693.
[6] a) O. Baslé, J. Bidange, Q. Shuai, C. J. Li, Adv. Synth. Catal.
2010, 352, 1145–1149; b) S. Ko, B. Kang, S. Chang, Angew.
Chem. Int. Ed. 2005, 44, 455–457; Angew. Chem. 2005, 117,
459–461; c) B.-X. Tang, R.-J. Song, C.-Y. Wu, Y. Liu, M.-B.
Zhou, W.-T. Wei, G.-B. Deng, D.-L. Yin, J.-H. Li, J. Am. Chem.
Soc. 2010, 132, 8900–8902; d) C. Li, L. Wang, P. Li, W. Zhou,
Chem. Eur. J. 2011, 17, 10208–10212; e) Y. Wu, B. Li, F. Mao,
X. Li, F. Y. Kwong, Org. Lett. 2011, 13, 3258–3261; f) C. W.
Chan, Z. Zhou, W.-Y. Yu, Adv. Synth. Catal. 2011, 353, 2999–
3006; g) F. Szabó, J. Daru, D. Simkó, T. Z. Nagy, A. Stirling,
Z. Nováka, Adv. Synth. Catal. 2013, 355, 685–691.
[7] a) P. Fang, M. Z. Li, H. B. Ge, J. Am. Chem. Soc. 2010, 132,
11898–11899; b) J. M. Miao, H. B. Ge, Org. Lett. 2013, 15,
2930–2933.
[8] a) S. Guin, S. K. Rout, A. Banerjee, S. Nandi, B. K. Patel, Org.
Lett. 2012, 14, 5294–5297; b) F. Xiong, C. Qian, D. G. Lin, W.
Zeng, X. X. Lu, Org. Lett. 2013, 15, 5444–5447.
[12]
[9] a) Y. Yuan, D. T. Chen, X. W. Wang, Adv. Synth. Catal. 2011,
353, 3373–3379; b) F. H. Xiao, Q. Shuai, F. Zhao, O. Baslé,
G. J. Deng, C. J. Li, Org. Lett. 2011, 13, 1614–1617; c) S.
Sharma, M. Kim, J. Park, M. Kim, J. H. Kwak, I. S. Kim, Eur.
J. Org. Chem. 2013, 6656–6665; d) J. Park, A. Kim, S. Sharma,
M. Kim, E. Park, Y. Jeon, Y. Lee, J. H. Kwak, Y. H. Jung, I. S.
Kim, Org. Biomol. Chem. 2013, 11, 2766–2771; e) M. Kim, S.
Sharma, J. Park, M. Kim, Y. Choi, Y. Jeon, J. H. Kwak, I. S.
Kim, Tetrahedron 2013, 69, 6552–6559; f) H. Tang, C. Qian,
D. G. Lin, H. F. Jiang, W. Zeng, Adv. Synth. Catal. 2014, 356,
519–527.
[10] For selected examples of transition-metal-catalyzed C–H acti-
vation in or on water, see: a) G. L. Turner, J. A. Morris, M. F.
Greaney, Angew. Chem. Int. Ed. 2007, 46, 7996–8000; Angew.
Chem. 2007, 119, 8142–8146; b) E. F. Flegeau, M. E. Popkin,
M. F. Greaney, Org. Lett. 2008, 10, 2717–2720; c) S. A. Ohn-
macht, P. Mamone, A. J. Culshaw, M. F. Greaney, Chem. Com-
[13]
[14]
T. Nishikata, A. R. Abela, B. H. Lipshutz, Angew. Chem. Int.
Ed. 2010, 49, 781–784; Angew. Chem. 2010, 122, 793–796.
B. Martín-Matute, C. Mateo, D. J. Cárdenas, A. M. Echav-
arren, Chem. Eur. J. 2001, 7, 2341–2348.
[15] M. Z. Li, H. B. Ge, Org. Lett. 2010, 12, 3464–3467.
[16] Z. C. Wang, Q. S. Tian, X. Yu, C. X. Kuang, Adv. Synth. Catal.
2014, 356, 961–966.
[17] a) R. Giri, J. Q. Yu, J. Am. Chem. Soc. 2008, 130, 14082–14083;
b) R. Giri, J. K. Lam, J. Q. Yu, J. Am. Chem. Soc. 2010, 132,
686–693; c) J. X. Yan, H. Li, X. W. Liu, J. L. Shi, X. Wang,
Z. J. Shi, Angew. Chem. Int. Ed. 2014, 53, 4945–4949; Angew.
Chem. 2014, 126, 5045–5049.
[18] P. P. Duan, Y. F. Yang, R. Ben, Y. Y. Yan, J. Zhao, Chem. Sci.
2014, 5, 1574–1578.
Received: January 6, 2015
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
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Date: 24-02-15 16:30:54
Pages: 8
F. Luo, J. Yang, Z. Li, H. Xiang, X. Zhou
FULL PAPER
C–H Activation
F. Luo, J. Yang, Z. Li, H. Xiang,
X. Zhou* ........................................... 1–8
Palladium-Catalyzed C–H Bond Acylation
of Acetanilides with Benzylic Alcohols un-
der Aqueous Conditions
Palladium-catalyzed dehydrogenative cou-
pling reactions between acetanilides and
benzylic alcohols under aqueous con-
ditions are reported. A wide range of
benzophenone derivatives could be ob-
tained in good to excellent yields up to
98%. Mechanism studies showed that a bi-
metallic palladium cyclopalladated com-
plex might be involved in the catalysis.
Keywords: Synthetic methods / Acylation /
Radical reactions / C–H activation / Pal-
ladium / Reaction mechanisms
8
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