Aldehydes and ketones formation: Copper-catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids

Article abstract of DOI:10.1021/jo402778p

Aromatic aldehydes or ketones from copper catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids have been synthesized. This reaction combined decarboxylation, dioxygen activation, and C-H bond oxidation steps in a one-pot protocol with molecular oxygen as the sole terminal oxidant. This reaction represents a novel decarboxylation of an sp³-hybridized carbon and the use of a benzylic carboxylic acid as a source of carbonyl compounds.

Full text of DOI:10.1021/jo402778p

Note
pubs.acs.org/joc
Aldehydes and Ketones Formation: Copper-Catalyzed Aerobic
Oxidative Decarboxylation of Phenylacetic Acids and
α‑Hydroxyphenylacetic Acids
Qiang Feng and Qiuling Song*
Institute of Next Generation Matter Transformation, College of Chemical Engineering at Huaqiao University, Xiamen, Fujian,
361021, China
S
* Supporting Information
ABSTRACT: Aromatic aldehydes or ketones from copper
catalyzed aerobic oxidative decarboxylation of phenylacetic
acids and α-hydroxyphenylacetic acids have been synthesized.
This reaction combined decarboxylation, dioxygen activation,
and C−H bond oxidation steps in a one-pot protocol with
molecular oxygen as the sole terminal oxidant. This reaction
represents a novel decarboxylation of an sp3-hybridized carbon
and the use of a benzylic carboxylic acid as a source of carbonyl
compounds.
he transition-metal-catalyzed C−C bond cleavage has
application of phenylacetic acids (and α-hydroxyphenylacetic
acids).
T
attracted much attention in recent years and has emerged
as one of the major themes in organic synthetic chemistry.1
This protocol leads to direct transformation of some inert
starting materials and makes the reactions much simpler, easier,
and cleaner. However, due to the inert nature of carbon−
carbon σ-bonds, the selective cleavage of the C−C bond is a
tremendous challenge for synthetic chemists and biologists as
well. As one C−C cleavage strategy, transition-metal-catalyzed
decarboxylation has attracted significant attention since the
pioneering work of Myers,2 Goossen,3 and Forgione4 due to
the “neutral” conditions, the readily available starting materials,
and the nontoxic byproduct (CO2). Among all types of
decarboxylation5 reactions, decarboxylation at an sp3-hybridized
carbon for functional group introduction is relative rare6 and
remains a significant challenge. Liu and his co-workers
developed several elegant palladium-catalyzed decarboxylations
using a variety of aliphatic carboxylate salts6b,c,7 in the past few
years, yet the direct transition-metal-catalyzed decarboxylation
of sp3-hybridized carboxylic acids with formation of a new C
O bond in the adjacent carbon with O2 as the oxidant is rare.8
Aldehydes and ketones are important organic compounds and
have been widely used in synthetic organic chemistry. Very
recently Bi et al. reported a novel aldehyde formation by
chemoselective oxidative C(CO)−C(methyl) bond cleavage
catalyzed by CuI and O2.9 In continuation of our interest in C−
C cleavage via transition-metal-catalyzed organic reactions, we
herein report a novel Cu(II)-catalyzed aerobic oxidative
decarboxylation of phenylacetic acids and α-hydroxyphenyl-
acetic acids to aldehydes, without overoxidation into carboxylic
acids. This reaction proceeds smoothly via decarboxylation,
dioxygen activation, and oxidation of phenylacetic acid (and α-
hydroxyphenylacetic acids) to afford aldehydes (or ketones).
This transformation represents a novel protocol for the
We began our evaluation with 4-methoxyphenylacetic acid
(1) under Cu(OAc)2/O2 as a model reaction (Table 1). DMF
was investigated first, and to our delight, the desired product
was formed in 83% yield (Table 1, entry 1) with 10 mol %
Cu(OAc)2 at 120 °C under 1 atm of O2. When the solvent was
switched to DMSO, 4-methoxybenzaldehyde was obtained in
92% yield (Table 1, entry 2). However, when the temperature
was reduced to 60 °C, no product was formed at all, and at 100
°C only a 12% yield of product was obtained (Table 1, entries 3
and 4). Interestingly, upon increasing the catalyst loading from
10 to 20 mol % at 120 °C, the yield dropped from 92% to 65%
(Table 1, entry 5). Yet continuously reducing the catalyst
loading to 5 mol % gave only 38% of the desired product.
Several other copper catalysts were investigated at 120 °C; all
showed inferior efficiencies for this transformation (Table 1,
entries 7−10). When O2 was replaced by air or N2, only 42%
and 10%, respectively, of the desired product was formed
(Table 1, entries 11−12); these results suggested that O2 is
essential for the success of this transformation and that
Cu(OAc)2 and DMSO also play crucial roles in this
transformation. After screening, the optimal reaction conditions
eventually emerged as 4-methoxyphenylacetic acid (1) (0.5
mmol) and Cu(OAc)2 (10 mol %) at 120 °C in DMSO (0.75
mL) under an O2 atmosphere.
After establishing the optimized reaction conditions, we
explored the substrate scope of phenylacetic acids (Table 2).
Phenylacetic acids bearing electron-donating groups on the
aromatic rings gave the desired products in good to excellent
yields (2−4, 16−17 and 20 in Table 2). Phenylacetic acids
Received: December 18, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo402778p | J. Org. Chem. XXXX, XXX, XXX−XXX

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Note
a
Table 1. Condition Screening
Table 2. Copper-Catalyzed Aerobic Oxidative
a b
,
Decarboxylation of Phenylacetic Acid to Aldehydes
temp
time
(h)
yield
(%)
entry
1
catalyst
oxidant solvent
(°C)
Cu(OAc)2
(10mol %)
O2
O2
O2
O2
O2
O2
O2
O2
DMF
120
120
60
18
18
18
18
18
18
18
18
83
92
0
2
3
4
5
6
7
8
Cu(OAc)2
(10 mol %)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Cu(OAc)2
(10 mol %)
Cu(OAc)2
(10 mol %)
100
120
120
120
120
12
b
Cu(OAc)2
(20 mol %)
65
Cu(OAc)2
(5 mol %)
38
89
45
Cu(OTf)2
(10 mol %)
Cu(TFA)2
(10 mol %)
9
CuBr2 (10 mol %)
O2
O2
DMSO
DMSO
120
120
18
18
trace
49
10
CuSO4
(10 mol %)
11
12
Cu(OAc)2
air
N2
DMSO
DMSO
120
120
18
18
42
10
(10 mol %)
Cu(OAc)2
(10 mol %)
a
Reaction conditions: phenyl acetic acid (0.5 mmol), catalyst in
solvent (0.75 mL) in a sealed tube under corresponding atmosphere.
b
Possible that the excess catalyst decomposes some reactive
intermediate.
a
Reaction conditions: 1 (0.5 mmol), Cu(OAc)2 (10 mol %), DMSO
b
possessing electron-withdrawing groups on the aromatic ring
also reacted smoothly under standard conditions, and the
desired aldehydes were obtained in good to excellent yields
(Table 2, 5−15, 23−24). The position of the substituents on
the aromatic rings had an effect on yields (Table 2, 2−3, 5−6,
7−9, 10−12, 13−15, and 23−24), with o-substitution usually
giving lower yields of the aldehydes when compared to m- and
p-substitution, probably as a result of steric hindrance. Both 1-
naphthylacetic acid and 2-naphthylacetic acid reacted well and
gave the corresponding aldehydes in 83% and 93% yields
(Table 2, 18 and 19). Heteroaromatic acetic acids also worked
well under standard conditions; for instance, 3-pyridinecarbox-
aldehyde and 2-thiophenecarboxaldehyde were obtained from
3-pyridylacetic acid and 2-thienylacetic acid in 70% and 72%
yields, respectively (Table 2, 21 and 22).
Generally speaking, there is little difference in yields among
most functional groups. However, a nitro group on the
aromatic ring did give surprising results. When o-nitrophenyl-
acetic acid and p-nitrophenylacetic acid in order to correspond
to the following o-methylnitrobenzene and 4-methylnitroben-
zene were used under standard conditions, o-methylnitro-
benzene and 4-methylnitrobenzene were formed in 52% and
44% yields in addition to the desired aldehydes (only 46% and
55% yields, respectively) (Table 2, 23-b and 24-b). These
results provided some hints with regard to the reaction
mechanisms. It showed that the decarboxylation to generate an
aliphatic radical is likely the first step, and this radical may be
further oxidized into a carbonyl group or instead trapped at this
stage. When substituents on methyl group were used as starting
materials, corresponding ketones were obtained (Table 2, 25,
26, and 27). As the bulkiness of the substituents increased
(0.75 mL), O2; the reaction was monitored by TLC plate. Isolated
yield. Detected by GC and GCMS. Detected by TLC plate and GC.
c
d
(from methyl to isopropyl to cyclopentyl), the yields of
corresponding ketones decreased, and with cyclopentyl on the
methylene group, no desired product was obtained. Fluoro,
chloro, bromo, methoxy, methyl, tert-butyl, nitro, and
trifluoromethyl groups were all well tolerated under the
standard reaction conditions, and heteroaromatics were also
well tolerated. This is the first example of a synthesis of
aromatic aldehydes or ketones via decarboxylation of phenyl-
acetic acid under a Cu-catalyzed oxidation reaction with O2 as
the terminal oxidant, and the process utilizes phenylacetic acid
as an aromatic acyl surrogate.
Intrigued by the above results, we applied the same
conditions to α-hydroxyphenylacetic acids. To our delight, 4-
methoxybenzaldehyde (2) was obtained in 75% yield (Table 3,
entry 9). Without further optimization, we found that α-
hydroxyphenylacetic acids worked well under standard
conditions to give corresponding aldehydes in moderate to
good yields (Table 3). And both electron-donating and
-withdrawing groups worked well and halo-substituted α-
hydroxyphenylacetic acid survived well, leading to halo-
substituted benzaldehyes, which could be used for further
transformation. Notably, when 2-cyclopentyl-2-hydroxy-2-
phenylacetic acid (Table 3, 38) was subjected to the standard
conditions, cyclopentyl phenyl ketone (27) was obtained in
93% yield (Table 3, entry 11). And two other aromatic ketones
(42 and 43) were also obtained in excellent yields under the
standard conditions (Table 3, entries 12−13).
B
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The Journal of Organic Chemistry
Note
2): phenylacetic acid is decarboxylated to give an active copper
species, which was further oxidized into aldehydes.
Table 3. Copper-Catalyzed Aerobic Oxidative
Decarboxylation of α-Hydroxyphenylacetic Acid to
Aldehydes and Ketones
Scheme 2. Plausible Reaction Mechanism
In summary, Cu(II)/O2 systems that catalyze the oxidative
decarboxylation of phenylacetic acids and α-hydroxyphenyl-
acetic acids have been developed. Aldehydes (or ketones) were
obtained from phenylacetic acids and α-hydroxyphenylacetic
acids in good to excellent yields. The excellent functional group
tolerance observed recommends that these methods be applied
for the synthesis of medically important compounds. These
reactions will expand the utility of decarboxylation in organic
synthesis.
EXPERIMENTAL SECTION
■
General Information. All experiments were conducted with a
sealed pressure vessel. Flash column chromatography was performed
over silica gel (200−300 mesh). 1H NMR spectra were recorded on a
400 M spectrometers. Chemical shifts (in ppm) were referenced to
CDCl3 (δ = 7.26 ppm) as an internal standard. 13C NMR spectra were
obtained by using the same NMR spectrometers and were calibrated
with CDCl3 (δ = 77.0 ppm). Unless otherwise noted, all starting
materials obtained from commercial suppliers were used without
further purification.
Procedure and Characterization Data for Products. 4-
Methoxybenzaldehyde (2, CAS: 123-11-5).10 A sealed pressure vessel
was charged with 2-(4-methoxyphenyl) acetic acid (83.0 mg, 0.5
mmol), Cu(OAc)2 (9 mg, 10 mol %, 0.05 mmol), and DMSO (0.75
mL). The resulting solution was purged by O2 and then sealed, with
subsequent stirring at 120 °C under O2 (monitored by TLC and GC).
Upon completion of the reaction, ethyl acetate (20 mL) was added,
the organic layer was washed with H2O (20 mL) solution twice and
brine (20 mL) once, and the combined aqueous layers was extracted
with ethyl acetate (20 mL) twice. The combine organic layers were
dried over anhydrous Na2SO4. The solvents were removed via rotary
evaporator, and the residue was purified with flash chromatography
(silica gel, ethyl acetate/petroleum ether = 50:1) to give 4-
methoxybenzaldehyde 2 in 92% yield (62.6 mg) as a faint yellow oil
In order to elucidate the reaction mechanism, several control
experiments were carried out. Since the reaction involves
oxygen, radical trapping experiments were conducted by
employing 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
with phenylacetic acid under standard conditions; the results
showed that the reactions were inhibited by TEMPO (Scheme
1, eq 1). The reaction of 2-oxo-2-phenylacetic acid under
standard conditions suggested that it could not be an
intermediate of the reaction because the majority of it was
converted into benzoic acids (Scheme 1, eq 2). Based on the
above results, we give a plausible reaction mechanism (Scheme
1
liquid. H NMR: (400 MHz, CDCl3, ppm) δ 9.81 (1H, s), 7.77−7.75
(2H, m), 6.94−6.92 (2H, m), 3.81 (3H, m). 13C{1H} NMR (100
MHz, CDCl3, ppm) δ 190.6, 164.4, 131.7, 129.7, 114.1, 55.3.
The same procedure was used for 2-hydroxy-2-(4-methoxyphenyl)-
acetic acid 36 and gave 51.0 mg of 4-methoxybenzaldehyde 2 in 75%
yield.
Scheme 1. Control Experiments under Standard Conditions
with Phenylacetic Acids
2-Methoxybenzaldehyde (3, CAS: 135-02-4).10 42% yield (28.6
mg) as a colorless crystal. 1H NMR: (400 MHz, CDCl3, ppm) δ 10.39
(1H, s), 7.74 (1H, dd, J = 7.6, 0.8 Hz), 7.73−7.44 (1H, m), 6.92 (q, J =
7.0 Hz). 3.83 (3H, s). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ
189.6, 161.8, 135.9, 128.3, 124.7, 120.5, 111.7, 55.5. Mp 35−39 °C.
4-(tert-Butyl)benzaldehyde (4, CAS: 939-97-9).11 87% yield (70.5
mg) as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ
9.96 (1H, s), 7.80 (2H, d, J = 8.0 Hz), 7.54 (2H, d, J = 8.0 Hz), 1.34
(9H, s). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 191.9, 158.3,
134.0, 129.6, 125.9, 35.2, 31.0.
C
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The Journal of Organic Chemistry
Note
4-(Trifluoromethyl)benzaldehyde (5, CAS: 455-19-6).12 94% yield
(81.8 mg) as a faint yellow oil liquid. H NMR: (400 MHz, CDCl3,
The same procedure was used for 2-(2-bromophenyl)-2-hydroxy-
acetic acid 35 and gave 48.1 mg of 2-bromobenzaldehyde 13 in 52%
yield.
1
ppm) δ 10.07 (1H, s), 7.98 (2H, d, J = 8.4 Hz), 7.77 (2H, d, J = 8.4
4-Bromobenzaldehyde (14, CAS: 1122-91-4).10 90% yield (83.2
mg) as a faint yellow solid liquid. 1H NMR: (400 MHz, CDCl3, ppm)
δ 9.92 (1H, s), 7.69 (2H, d, J = 8.4 Hz), 7.62 (2H, d, J = 8.4 Hz).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 190.8, 134.9, 132.2, 130.8,
129.5.
Hz). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 191.0, 138.7, 135.5
(q, J = 65.0 Hz), 129.8, 126.0 (d, J = 3.7 Hz), 123.4 (q, JCF = 271.3
3
Hz, CF).
2-(Trifluoromethyl)benzaldehyde (6, CAS: 447-61-0).12 39% yield
1
(34 mg) as a faint yellow oil liquid. H NMR: (400 MHz, CDCl3,
3-Bromobenzaldehyde (15, CAS: 3132-99-8).17 87% yield (80.5
ppm) δ 10.34 (1H, q, J = 2.4 Hz), 8.07−8.05 (1H, m), 7.74−7.71 (1H,
m), 7.69−7.63 (2H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ
188.7 (d, J = 2.5 Hz), 133.6, 133.5, 132.2, 130.8 (q, J = 32.3 Hz),
1
mg) as a colorless oil liquid. H NMR: (400 MHz, CDCl3, ppm) δ
9.86 (1H, s), 7.88 (1H, d, J = 3.2 Hz), 7.71 (1H, dd, J = 7.6, 1.2 Hz),
7.66 (1H, dd, J = 8.0, 0.8 Hz), 7.32 (1H, t, J = 8.0 Hz). 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 190.4, 137.7, 136.9, 131.9, 130.4, 128.1,
123.0.
129.0, 126.0 (q, J = 5.7 Hz), 123.7 (q, JCF = 272.7 Hz, CF).
3
4-Chlorobenzaldehyde (7, CAS: 104-88-1).13 75% yield (52.5 mg)
as a colorless flaky crystal. 1H NMR: (400 MHz, CDCl3, ppm) δ 9.97
(1H, s), 7.81 (2H, d, J = 8.0 Hz), 7.49 (2H, d, J = 8.4 Hz). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 190.8, 140.9, 134.7, 130.8, 129.4.
Mp 45−47 °C.
4-Methylbenzaldehyde (16, CAS: 104-87-0).12 45% yield (27.1
mg) as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ
9.95 (1H, s), 7.76 (2H, d, J = 8.0 Hz), 7.31 (2H, d, J = 8.0 Hz), 2.42
(3H, s). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 191.9, 145.5,
134.2, 129.8, 129.6, 21.8.
The same procedure was used as for 2-(4-chlorophenyl)-2-
hydroxyacetic acid 30 and gave 51.1 mg of 4-chlorobenzaldehyde 7
in 73% yield.
3-Methylbenzaldehyde (17, CAS: 620-23-5).12 71% yield (42.6
mg) as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ
9.97 (1H, s), 7.67 (2H, d, J = 6.8 Hz), 7.41 (2H, d, J = 7.2 Hz), 2.42
(3H, s). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 192.5, 138.9,
136.4, 135.2, 129.9, 128.8, 127.1, 21.1.
3-Chlorobenzaldehyde (8, CAS: 587-04-2).14 89% yield (62.3 mg)
as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ 9.93
(1H, s), 7.80 (1H, d, J = 1.2 Hz), 7.72 (1H, d, J = 7.2 Hz), 7.55 (1H,
dd, 8.4, 1.2 Hz), 7.44 (1H, 8.0 Hz). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 190.7, 137.7, 135.3, 134.2, 130.3, 129.1, 127.9.
The same procedure was used for 2-(3-chlorophenyl)-2-hydroxy-
acetic acid 31 and gave 25.2 mg of 3-chlorobenzaldehyde 8 in 36%
yield.
1-Naphthaldehyde (18, CAS: 66-77-3).10 83% yield (64.7 mg) as a
faint yellow crystal. 1H NMR: (400 MHz, CDCl3, ppm) δ 10.39 (1H,
s), 9.26 (1H, d, J = 8.8 Hz), 8.08 (1H, d, J = 8.0 Hz), 7.96 (1H, d, J =
6.2 Hz), 7.91 (1H, d, J = 8.4 Hz). 7.71−7.68 (1H, m), 7.63−7.57 (1H,
m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 193.4, 136.5, 135.2,
133.6, 131.4, 130.5, 129.0, 128.4, 126.9, 124.8 (2C).
2-Chlorobenzaldehyde (9, CAS: 89-98-5).14 72% yield (50.4 mg)
1
2-Naphthaldehyde (19, CAS: 66-99-9).14 93% yield (72.5 mg) as a
faint yellow crystal. 1H NMR: (400 MHz, CDCl3, ppm) δ 10.14 (1H,
s), 8.31 (1H, s), 7.99−7.88 (4H, m), 7.65−7.55 (2H, m). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 192.1, 136.4, 134.4, 134.4, 132.6,
129.4, 129.0 (2C), 128.0, 127.0, 122.7.
as a colorless oil liquid. H NMR: (400 MHz, CDCl3, ppm) δ 10.4
(1H, s), 7.88 (1H, dd, J = 3.2, 7.6 Hz), 7.51−7.47 (1H, m), 7.42−7.40
(1H, m), 7.37−7.33 (1H, m). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 189.6, 137.8, 135.0, 132.4, 130.5, 129.2, 127.2.
The same procedure was used for 2-(2-chlorophenyl)-2-hydroxy-
acetic acid 29 and gave 48.3 mg of 2-chlorobenzaldehyde 9 in 69%
yield.
Benzaldehyde (20, CAS: 100-52-7).10 88% yield (46.6 mg) as a
1
colorless liquid. H NMR: (400 MHz, CDCl3, ppm) δ 10.01 (1H, s),
2-Fluorobenzaldehyde (10, CAS: 446-52-6).14 62% yield (38 mg)
as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ 10.32
(1H, s), 7.84−7.80 (1H, m), 7.59−7.53 (1H, m), 7.26−7.20 (1H, m),
7.15−7.10 (1H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 187.0
7.88−7.86 (2H, m), 7.64−7.60 (1H, m), 7.54−7.50 (2H, m). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 192.3, 136.4, 134.4, 129.7, 128.9.
The same procedure was used for 2-hydroxy-2-phenylacetic acid 28
and gave 38.7 mg of benzaldehyde 20 in 73% yield.
Nicotinaldehyde (21, CAS: 500-22-1).18 70% yield (37.5 mg) as a
(d, J = 6.6 Hz), 164.5 (d, JCF = 257.1 Hz, CF3), 136.2 (d, J = 9.1 Hz),
3
1
colorless liquid. H NMR: (400 MHz, CDCl3, ppm) δ 10.03 (1H, s),
128.6 (2C), 124.5 (d, J = 3.6 Hz), 116.4 (d, J = 20.3 Hz).
The same procedure was used for 2-(2-fluorophenyl)-2-hydroxy-
acetic acid 34 and gave 28.8 mg of 2-fluorobenzaldehyde 10 in 47%
yield.
9.99 (1H, d, J = 2.0 Hz), 8.76−8.74 (1H, m), 8.10−8.07 (1H, m),
7.42−7.39 (1H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 190.3,
154.0, 151.2, 135.2, 130.8, 123.4.
Thiophene-2-carbaldehyde (22, CAS: 98-03-3).12 72% yield (40.3
4-Fluorobenzaldehyde (11, CAS: 459-57-4).15 78% yield (48.4 mg)
1
1
mg) as a pale yellow oil liquid. H NMR: (400 MHz, CDCl3, ppm) δ
as a colorless oil liquid. H NMR: (400 MHz, CDCl3, ppm) δ 9.91
9.88 (1H, d, J = 1.2 Hz), 7.74−7.71 (2H, m), 7.17−7.15 (1H, m).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 182.7, 143.7, 136.2, 134.8,
128.1.
(1H, s), 7.86 (2H, dd, J = 8.8, 5.6 Hz), 7.15 (2H, t, J = 8.4 Hz).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 190.3, 166.4 (d, JCF
=
3
2-Nitrobenzaldehyde (23, CAS: 552-89-6).19 46% yield (34.7 mg)
as a flaky crystal. 1H NMR: (400 MHz, CDCl3, ppm) δ 10.36 (1H, s),
8.07 (1H, d, J = 7.6 Hz), 7.90 (1H, d, J = 7.2 Hz), 7.80−7.73 (2H, m).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 188.1, 149.4, 134.0, 133.6,
131.2, 129.5, 124.3.
254.9 Hz, CF), 132.9 (d, J = 2.4 Hz), 116.2 (d, J = 22.1 Hz).
The same procedure was used for 2-(4-fluorophenyl)-2-hydroxy-
acetic acid 32 and gave 37.8 mg of 4-fluorobenzaldehyde 11 in 61%
yield.
3-Fluorobenzaldehyde (12, CAS: 456-48-4).14 65% yield (40.3 mg)
as a faint yellow oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ 9.98
(1H, d, J = 2.0 Hz), 7.67−7.65 (1H, m), 7.56−7.49 (2H, m), 7.34−
7.29 (1H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 190.8 (d, J =
1-Methyl-2-nitrobenzene (23-b, CAS: 88-72-2).20 52% yield (35.6
1
mg) as a yellow liquid. H NMR: (400 MHz, CDCl3, ppm) δ 7.96
(1H, d, J = 8.4 Hz), 7.49 (1H, t, J = 7.2 Hz), 7.35−7.32 (2H, m), 2.60
(3H, s). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 133.5, 132.9,
132.7, 126.8, 124.6.
1.9 Hz), 163.0 (d, JCF = 247.8 Hz, CF), 138.4 (d, J = 6.1 Hz), 130.7
3
(d, J = 7.6 Hz), 126.0 (d, J = 2.8 Hz), 121.5 (d, J = 21.5 Hz), 115.2 (d,
J = 21.7 Hz).
4-Nitrobenzaldehyde (24, CAS: 555-16-8).19 55% yield (41.5 mg)
1
The same procedure was used for 2-(3-fluorophenyl)-2-hydroxy-
acetic acid 33 and gave 35.9 mg of 3-fluorobenzaldehyde 12 in 58%
yield.
as a yellow crystal. H NMR: (400 MHz, CDCl3, ppm) δ 10.14 (1H,
s), 8.35 (2H, d, J = 8.4 Hz), 8.06 (2H, d, J = 8.4 Hz). 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 190.3, 151.0, 140.0, 130.4, 124.2.
1-Methyl-4-nitrobenzene (24-b, CAS: 99-99-0).20 44% yield (30.1
2-Bromobenzaldehyde (13, CAS: 6630-33-7).16 70% yield (64.7
1
1
mg) as a faint yellow liquid. H NMR: (400 MHz, CDCl3, ppm) δ
mg) as a yellow crystal. H NMR: (400 MHz, CDCl3, ppm) δ 8.08
(2H, d, J = 8.8 Hz), 7.29 (2H, d, J = 8.4 Hz), 2.45 (3H, s). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 145.9 (2C), 129.7, 123.4, 21.5. Mp
52−54 °C.
10.22 (1H, s), 7.78−7.76 (1H, m), 7.52−7.50 (1H, m), 7.33−7.30
(2H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 191.2, 135.0,
133.5, 133.1, 129.5, 127.6, 126.7.
D
dx.doi.org/10.1021/jo402778p | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1-(4-Isobutylphenyl)ethanone (25, CAS: 38861-78-8).21 31% yield
(27.2 mg) as a colorless liquid. H NMR: (400 MHz, CDCl3, ppm) δ
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2671−2678. (b) Shang, R.; Liu, L. Sci. China Chem. 2011, 54, 1670−
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Tunge, J. A. J. Am. Chem. Soc. 2010, 132, 9280−9282. (b) Shang, R.;
Yang, Z.-W.; Wang, Y.; Zhang, S.-L.; Liu, L. J. Am. Chem. Soc. 2010,
132, 14391−14393. (c) Shang, R.; Ji, D.-S.; Chu, L.; Fu, Y.; Liu, L.
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13, 4240−4243. (b) Shang, R.; Huang, Z.; Xiao, X.; Lu, X.; Fu, Y.; Liu,
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(b) Song, Q.; Feng, Q.; Yang, K. Org. Lett. 2014, 16, 624−627.
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1
7.83 (2H, d, J = 8.0 Hz), 7.18 (2H, d, J = 8.0 Hz), 2.51 (3H, d, J = 12.0
Hz), 2.47 (2H, s), 1.90−1.80 (1H, m), 0.87 (6H, d, J = 6.4 Hz).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 197.4, 147.3, 134.8, 129.0,
128.1, 45.1, 29.9, 26.2, 22.1
4-Propoxybenzaldehyde (41, CAS: 5736-85-6).22 66% yield (54.1
1
mg) as a colorless liquid. H NMR: (400 MHz, CDCl3, ppm) δ 9.86
(1H, s), 7.81 (2H, ddd, J = 11.2, 9.2, 4.4, 2.4 Hz), 6.98 (2H, d, J = 8.8
Hz), 3.99 (2H, t, J = 6.8 Hz), 1.83 (2H, ddd, J = 28, 21.2, 18.0, 7.2
Hz), 1.04 (3H, t, J = 7.6 Hz). 13C{1H} NMR (100 MHz, CDCl3, ppm)
δ 190.7, 164.2, 131.9, 129.7, 114.7, 69.8, 22.3, 10.4.
Cyclopentyl(phenyl)methanone (27, CAS: 5422-88-8).23 93% yield
1
(80.9 mg) as a colorless liquid. H NMR: (400 MHz, CDCl3, ppm) δ
7.98 (2H, dd, J = 6.4, 0.8 Hz), 7.55−7.51 (1H, m), 7.46−7.43 (2H,
m), 3.73−3.70 (1H, m), 1.95−1.90 (4H, m), 1.75−1.64 (4H, m).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 202.7, 137.0, 132.6, 128.5,
128.5, 46.3, 30.0, 26.3.
Benzophenone (42, CAS: 119-61-9).24 95% yield (86.5 mg) as a
colorless oil liquid. 1H NMR: (400 MHz, CDCl3, ppm) δ 7.80 (4H, d,
J = 7.2 Hz), 7.57 (2H, t, J = 7.6 Hz), 7.47 (4H, t, J = 7.6 Hz). 13C{1H}
NMR (100 MHz, CDCl3, ppm) δ 196.5, 137.5, 132.3, 129.9, 128.1.
Cyclohexyl(phenyl)methanone (43, CAS: 712-50-5).25 95% yield
(89.3 mg) as a colorless oil liquid. 1H NMR: (400 MHz, CDCl3, ppm)
δ 7.98 (2H, d, J = 8.0 Hz), 7.57 (1H, t, J = 6.8 Hz), 7.48 (2H, t, J = 7.6
Hz), 3.34−3.26 (1H, m), 1.95−1.85 (4H, m), 1.78−1.76 (1H, m),
1.59−1.25 (5H, m). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 203.6,
136.2, 132.5, 128.4, 128.1, 45.4, 29.3, 25.8, 25.7.
(10) Zhu, Y.; Zhao, B.; Shi, Y. Org. Lett. 2013, 15, 992−995.
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(12) Tang, L.; Sun, H.; Li, Y.; Zha, Z.; Wang, Z. Green Chem. 2012,
14, 3423−3428.
(13) Kawahara, R.; Fujita, K.-i.; Yamaguchi, R. Angew. Chem., Int. Ed.
2012, 51, 12790−12794.
(14) Wu, X.-F. Chem.Eur. J. 2012, 18, 8912−8915.
(15) Tang, L.; Guo, X.; Li, Y.; Zhang, S.; Zha, Z.; Wang, Z. Chem.
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(16) Hajimohammadi, M.; Safari, N.; Mofakham, H.; Deyhimi, F.
Green Chem. 2011, 13, 991−997.
ASSOCIATED CONTENT
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(17) Karimi, B.; Badreh, E. Org. Biomol. Chem. 2011, 9, 4194−4198.
(18) Korsager, S.; Taaning, R. H.; Lindhardt, A. T.; Skrydstrup, T. J.
Org. Chem. 2013, 78, 6112−6120.
S
* Supporting Information
General experimental considerations and copies of NMR
spectra for all compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(19) Sun, H.-y.; Hua, Q.; Guo, F.-f.; Wang, Z.-y.; Huang, W.-X. Adv.
Synth. Catal. 2012, 354, 569−573.
(20) Yadav, R. R.; Vishwakarma, R. A.; Bharate, S. B. Tetrahedron
Lett. 2012, 53, 5958−5960.
AUTHOR INFORMATION
■
(21) Liu, R.; Yuan, G.; Joe, C. L.; Lightburn, T. E.; Tan, K. L.; Wang,
D. Angew. Chem., Int. Ed. 2012, 51, 6709−6712.
Corresponding Author
*Email: qsong@hqu.edu.cn.
(22) Liu, W.; Wang, Y.; Sun, M.; Zhang, D.; Zheng, M.; Yang, W.
Chem. Commun. 2013, 49, 6042−6044.
Notes
(23) Li, M.; Wang, C.; Ge, H. Org. Lett. 2011, 13, 2062−2064.
(24) Basavaraju, K. C.; Sharma, S.; Maurya, R. A.; Kim, D.-P. Angew.
Chem., Int. Ed. 2013, 52, 6735−6738.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(25) Sumino, S.; Ui, T.; Ryu, I. Org. Lett. 2013, 15, 3142−3145.
■
The authors are grateful for financial support from the National
Science Foundation of China (21202049), the Recruitment
Program of Global Experts (1000 Talents Plan), Fujian
Hundred Talents Program, and Research Funds of Huaqiao
University.
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