Iron-facilitated oxidative radical decarboxylative cross-coupling between α-oxocarboxylic acids and acrylic acids: An approach to α,β-unsaturated carbonyls

Article abstract of DOI:10.1021/acs.joc.5b00267

The first Fe-facilitated decarboxylative cross-coupling reaction between α-oxocarboxylic acids and acrylic acids in aqueous solution has been developed. This transformation is characterized by its wide substrate scope and good functional group compatibility utilizing inexpensive and easily accessible reagents, thus providing an efficient and expeditious approach to an important class of α,β-unsaturated carbonyls frequently found in bioactive compounds. The synthetic potential of the coupled products is also demonstrated in subsequent functionalization reactions. Preliminary mechanism studies suggest that a free radical pathway is involved in this process: the generation of an acyl radical from α-oxocarboxylic acid via the excision of carbon dioxide followed by the addition of an acyl radical to the α-position of the double bond in acrylic acid then delivers the α,β-unsaturated carbonyl adduct through the extrusion of another carbon dioxide.

Full text of DOI:10.1021/acs.joc.5b00267

Article
pubs.acs.org/joc
Iron-Facilitated Oxidative Radical Decarboxylative Cross-Coupling
between α‑Oxocarboxylic Acids and Acrylic Acids: An Approach to
α,β-Unsaturated Carbonyls
Qing Jiang, Jing Jia, Bin Xu, An Zhao, and Can-Cheng Guo*
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
S
* Supporting Information
ABSTRACT: The first Fe-facilitated decarboxylative cross-coupling reaction between α-oxocarboxylic acids and acrylic acids in
aqueous solution has been developed. This transformation is characterized by its wide substrate scope and good functional group
compatibility utilizing inexpensive and easily accessible reagents, thus providing an efficient and expeditious approach to an
important class of α,β-unsaturated carbonyls frequently found in bioactive compounds. The synthetic potential of the coupled
products is also demonstrated in subsequent functionalization reactions. Preliminary mechanism studies suggest that a free radical
pathway is involved in this process: the generation of an acyl radical from α-oxocarboxylic acid via the excision of carbon dioxide
followed by the addition of an acyl radical to the α-position of the double bond in acrylic acid then delivers the α,β-unsaturated
carbonyl adduct through the extrusion of another carbon dioxide.
synthetic approaches for their synthesis.6−12 Traditionally, α,β-
unsaturated ketones are mainly prepared by aldol condensation
INTRODUCTION
■
Transition-metal-catalyzed decarboxylative coupling reactions
have attracted much attention in the past decade due to their
potential advantages, such as high selectivity, efficiency, and
(Claisen−Schmidt condensation) between ketones and alde-
hydes.7 Unfortunately, this process often requires relatively
strong basic reaction conditions, which place limitations on the
convenience as well as the nontoxic byproduct (CO2). Thus far,
use of functional groups that are sensitive to bases. Accordingly,
notable progress has been made in the area of decarboxylative
the development of methods to overcome this limitation would
couplings for various C−C bond and C−heteroatom bond
forming reactions.1 However, examples involving a decarbox-
ylative coupling reaction between carboxylic acids remain much
underdeveloped:2 almost all of these reactions are restricted to
Pd-catalyzed decarboxylative hetero- or homocouplings be-
tween aromatic carboxylic acids. Herein, we report the first
example of a decarboxylative cross-coupling reaction between
α-oxocarboxylic acids and acrylic acids to α,β-unsaturated
carbonyl compounds facilitated by an iron catalyst through the
extrusion of two molecules of CO2 in aqueous media (Scheme
1).
be of significant importance. In 2000, Muller reported
̈
Sonogashira coupling of electron-deficient aryl halides with
aryl 1-propargyl alcohols for the synthesis of α,β-unsaturated
ketones, even though the reaction required the use of an
expensive palladium catalyst combined with a cocatalyst.8 Later
on, the groups of Beller and Skrydstrup and Feng developed a
very efficient access to α,β-unsaturated ketones through Pd-
catalyzed carbonylative Heck coupling9 of aryl halides/boronic
acids with styrenes and carbonylative addition10 of aryl halides
to arylalkynes in the presence of CO; however, the requirement
for high CO pressure and/or the presence of halide anions
make this reaction environmentally unfavorable. Recently, Su
and Lei independently achieved the Pd-catalyzed C−H
olefination of (hetero)arenes/aryl carboxylic acids with
saturated ketones in the presence of a stoichiometric amount
of Ag2CO3 assisted by a phosphine ligand11 and the copper-
catalyzed oxidative coupling of styrenes with aromatic
aldehydes using TBHP as the oxidant12 for the preparation of
α,β-Unsaturated carbonyls are a particularly important class
of naturally occurring and manmade compounds that display
extraordinary and interesting pharmaceutical and biological
properties, including anticancer, antioxidant, antimicrobial, anti-
inflammatory, antianginal, antimutagenic, antihepatotoxic,
antimalarial, antimitotic, and antiallergic activities (Scheme
2).3Also, this class of compounds is extremely attractive as
intermediates both in the synthesis of various heterocycles4 and
in functional materials.5 Because of the important applications
of α,β-unsaturated carbonyls in biology, medicine, and materials
science, considerable efforts have been made to develop various
Received: February 4, 2015
© XXXX American Chemical Society
A
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Scheme 1. Decarboxylative Cross-Coupling Reaction between Carboxylic Acids To Form α,β-Unsaturated Carbonyls
unsaturated carbonyls is highly desirable and remains a
challenge. Toward this goal, we present an efficient and general
protocol for the synthesis of α,β-unsaturated carbonyl
compounds from carboxylic acids using a cheap iron catalyst
(Scheme 1). To the best of our knowledge, this work
demonstrates the first construction of α,β-unsaturated carbonyl
scaffolds via the decarboxylative cross-coupling between
-oxocarboxylic acids and acrylic acids. The present method is
characterized by its broad substrate scope, high functional
group compatibility, and the formation of innocuous byproduct
CO2. The generality of this approach is also demonstrated by
synthesizing an exemplary set of α,β-unsaturated carbonyl
compounds (>40 examples). Moreover, from a practical and
sustainable chemistry standpoint, the use of easily available and
stable materials and aqueous solvent represent additional
benefits. Finally, the preliminary mechanistic studies seem to
support a free radical mechanism.
Scheme 2. Biological Significance of α,β-Unsaturated
Carbonyl-Containing Compounds
α,β-unsaturated ketones, respectively. Despite formidable
advances, most methods suffer from one or more limitations
including poor substrate scope, limited functional group
tolerance, the use of stoichiometric toxic reagents, and/or the
high cost of the catalytic system. Therefore, the development of
a general, green, and practical synthetic route toward α,β-
a
Table 1. Initial Studies toward Decarboxylative Cross-Coupling Reaction between Carboxylic Acids
entry
metal source
oxidant
base
solvent (v/v)
yield (%)
1
AgNO3
AgNO3
AgNO3
AgNO3
AgNO3
Ag2CO3
CuO
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
Na2S2O8
TBHP
H2O2
−
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
DMSO/H2O (1/1)
CH3CN/H2O (1/1)
DMSO
23
41
32
28
26
43
34
trace
54
40
25
41
48
<5
69
83
76
75
0
2
HCOONa·2H2O
NaOAc
3
4
Cs2CO3
5
pyridine
6
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
HCOONa·2H2O
7
8
CuCl
9
FeCl2
Ni(OAc)2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
FeCl2
−
10
11
12
13
14
15
16
17
18
19
20
21
22
H2O
CH3CN
DMSO/H2O (5/15)
DMSO/H2O (3/17)
DMSO/H2O (2/18)
DMSO/H2O (3/17)
DMSO/H2O (3/17)
DMSO/H2O (3/17)
DMSO/H2O (3/17)
DMSO/H2O (3/17)
0
−
0
K2S2O8
21
a
Reaction conditions: benzoylformic acid (0.5 mmol, 1 equiv), cinnamic acid (1.0 mmol, 2 equiv), catalyst (10 mol %), base (2.0 equiv), oxidant (2.5
equiv), solvent (2.0 mL), 120 °C, N2, 15 h.
B
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a
Table 2. Scope of the α-Oxocarboxylic Acids Coupling Component
a
Reaction conditions: α-oxocarboxylic acid (0.5 mmol, 1 equiv), cinnamic acid (1.0 mmol, 2 equiv), FeCl2 (10 mol %), HCOONa·2H2O (2.0
equiv), K2S2O8 (2.5 equiv), H2O (1.7 mL), DMSO (0.3 mL), 120 °C, N2, 15 h.
Among the oxidants tested, K2S2O8 afforded the best result
(Table 1, entries 18−20). Control experiments showed that no
conversion to 1 occurred in the absence of K2S2O8 (Table 1,
entry 21), while, in the absence of FeCl2, a much lower
background reaction was observed (Table 1, entry 22, 21%
yield).
Scope of the α-Oxocarboxylic Acid in the Decarbox-
ylative Cross-Coupling Reaction. With the optimized
reaction conditions in hand, we sought to examine the scope
and generality of the reaction between various α-oxocarboxylic
acids and cinnamic acid, and the results are summarized in
Table 2. A series of electron-rich and -poor benzoylformic acids
readily undergo decarboxylative coupling with cinnamic acid,
delivering the corresponding products in 64−92% yield. For
example, benzoylformic acid derivatives with electron-donating
substituents (Me, MeO, EtO) afforded the desired α,β-
unsaturated ketones in yields ranging from 78% to 92% (2−
8), while benzoylformic acid derivatives bearing electron-
withdrawing substituents (F, Cl, Br, I, CF3) provided the
desired α,β-unsaturated ketones in yields ranging from 64% to
RESULTS AND DISCUSSION
■
Optimization of the Reaction Conditions. Our inves-
tigation started with the reaction of benzoylformic acid with
cinnamic acid using 10 mol % AgNO3 along with 2.5 equiv of
K2S2O8 in DMSO/H2O at 120 °C for 15 h. To our delight, the
desired chalcone product 1 was obtained in 23% yield under
these conditions (Table 1, entry 1). The efficiency of this
decarboxylation protocol was improved by adding bases to the
reaction mixture, with HCOONa·2H2O proving to be optimal
(Table 1, entries 2−5). Moreover, evaluation of other metal
salts revealed that FeCl2 was the best choice (Table 1, entries
6−10). Subsequently, we investigated the influence of the
solvent. When other solvents, such as DMSO, H2O, and
CH3CN, were employed instead of DMSO/H2O, a low or
moderate of the desired product was obtained (Table 1, entries
11−14). In addition, it was observed that varying the ratio of
DMSO to H2O also had an effect on the yield of 1 (Table 1,
entries 15−17). The best results (83%) were achieved when the
volume ratio of H2O and DMSO was 17:3. The choice of
oxidant was also found to have a dramatic effect on the yield.
C
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a
Table 3. Scope of the Acrylic Acids Coupling Component
a
Reaction conditions: benzoylformic acid (0.5 mmol, 1 equiv), acrylic acid (2.0 mmol, 4 equiv), FeCl2 (10 mol %), HCOONa·2H2O (2.0 equiv),
b
K2S2O8 (2.5 equiv), H2O (1.0 mL), DMSO (3.0 mL), 120 °C, N2, 15 h. DMSO (4.0 mL).
82% (9−15). It is noteworthy that benzoylformic acid bearing
the same substituents at different positions on the phenyl ring
had little influence on the efficiency of the reaction (2−4, 11−
13). A naphthyl oxocarboxylic acid also efficiently reacted with
cinnamic acid, giving the product 16 in 64% yield. Importantly,
heterocyclic α-keto acids were also productive reaction partners
in this transformation (17 and 18, 62% and 51% yield).
Interestingly, aliphatic α-keto acids also underwent the
decarboxylation to give the corresponding products 19 and
20 in 52% and 38% yield, respectively. In addition, oxamic acids
were also compatible, albeit affording a lower yield (21−23,
41−45% yield). Control reactions have established that no
amine acyl exchange occurred between oxamic acid and
cinnamic acid in only a H2O/DMSO system or in the absence
of an oxidant (see the Supporting Information). 2-Ethoxy-2-
oxoacetic acid reacted to afford a much lower yield of the
desired product (24, <5% yield). It is noteworthy that the
halogen groups and carboxyl group in the product are useful
handles for further synthetic functionalization.
Scope of the Acrylic Acid in the Decarboxylative
Cross-Coupling Reaction. Subsequently, we explored the
scope of the reaction between a variety of acrylic acids and
benzoylformic acid. As can be seen in Table 3, a wide range of
cinnamic acids, with either electron-donating or -withdrawing
functional groups on the aromatic ring, were compatible with
this transformation. Decarboxylation of electron-rich cinnamic
D
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acids gave the corresponding products in 43−90% yield (25−
31), whereas electron-poor cinnamic acids underwent the
decarboxylation to afford the desired products in 60−74% yield
(32−41). Notably, the variety of substituents including fluoro,
chloro, bromo, trifluoromethyl, methoxyl, hydroxyl, and nitro
were well tolerated in these cross-coupling reactions, thus
offering potential applications for further synthetic elaboration.
Particularly noteworthy was that 4-formylcinnamic acid
provided the product 40 in 63% yield. This is particularly
important, since aldehydes are susceptible to oxidation in the
presence of K2S2O8 as the oxidant. Moreover, 1,4-phenylene-
diacrylic acid only afforded monofunctionalization product 42
in 45% yield, and the attempted difunctionalization reaction
was unsuccessful. Gratifyingly, the arene ring is not limited to
benzene rings. Decarboxylation of pyridyl, thiophen-2-yl, and
furan-2-yl substituted acrylic acid proceeded to give the
corresponding products in synthetically useful yields (43−46,
42−72% yield). Interestingly, a conjugated dienoic acid also
underwent the decarboxylative cross-coupling reaction to give
the product 47 in 32% yield. In addition, β-disubstituted acrylic
acid was also a viable substrate for this reaction, delivering the
desired product 48 in 56% yield. The present protocol is not
without limitations. The α-substituted acrylic acid such as α-
methylcinnamic acid is not amenable to this procedure (49),
which is presumably due to the increased steric hindrance of
the α-position in acrylic acid. Crotonic acid, which is a substrate
with a monoalkyl substituent at the β-position of acrylic acid,
was scarcely productive, and the attempted reaction provided
only a trace amount of the desired product 50. Also,
butenedioic acid gave a complex reaction mixture.
Finally, to probe the nature of the iron cation, the reaction
between 2-oxo-2-(p-tolyl)acetic acid and cinnamic acid with
FeCl2 or FeCl3 as the precatalyst was investigated. The results
are shown in Scheme 4e. Using FeCl2 as the catalyst precursor,
the reaction provided the desired product 2 in 81% yield. The
reaction using FeCl3 as the catalyst precursor afforded a 77%
yield of 2. The similar results show that Fe(III) might be
involved in the catalytic cycle for this decarboxylative cross-
coupling reaction.
Proposed Mechanism. On the basis of the observed
experimental results and previous literature,13 a plausible
mechanism is proposed in Scheme 5. First, the acyl radical II
is generated from α-oxocarboxylates I via an oxidative radical
decarboxylative process in the presence of FeCl2 and K2S2O8.
Moreover, it is also likely that I is activated by K2S2O8 to
produce intermediate II (Table 1, entry 22). Subsequently,
addition of the benzoyl radical to the double bond of acrylic
acid III produces the alkyl radical IV. Finally, under the
reaction conditions, the intermediate IV would undergo β-
elimination to give the desired product V along with the release
of CO2.
As mentioned above, it turned out that the FeCl2/K2S2O8/
HCOONa·2H2O system is useful to the decarboxylative cross-
coupling reaction between α-oxocarboxylic acids and acrylic
acids in DMSO/H2O. Interestingly, the present method uses
stable, cheap, and readily available carboxylic acids as starting
materials and exhibits a broader substrate scope and more
excellent functional group tolerance than the classical aldol
condensation for the synthesis of α,β-unsaturated carbonyls.
The present decarboxylation proceeds via a free-radical
pathway. In addition, all the reagents (α-oxocarboxylic acids,
acrylic acids, K2S2O8, and HCOONa·2H2O) are used as
received without further purification.
Demonstration of the Scalability of the Decarbox-
ylative Coupling. To demonstrate the preparative practicality
of this new decarboxylative cross-coupling process, we
performed the reaction on a gram scale. Reaction of 1.5 g
(10 mmol) of benzoylformic acid with 2.0 equiv cinnamic acid
(2a) under the standard reaction conditions generated 1 (1.29
g) in 62% yield (Scheme 3).
CONCLUSION
■
In summary, we have developed the first Fe-facilitated
decarboxylative cross-coupling reaction between α-oxocarbox-
ylic acids and acrylic acids in aqueous solution. This
decarboxylative cross-coupling reaction is not only general
and efficient but also functional group compatible. Moreover,
this transformation could also be conducted on gram-scale, and
the synthetic utilities of these decarboxylation products have
been showcased in synthetically useful functionalization
reactions. In addition, radical-trapping experiments indicated
that this transformation proceeded through a free-radical
process. In view of the broad substrate scope, excellent
functional group compatibility, ready availability of materials,
and formation of innocuous byproduct CO2, the present
protocol provides a important complement for the synthesis of
the highly valuable enone functionality and should find some
applications in organic synthesis.
Scheme 3. Gram-Scale Reaction with Benzoylformic Acid
Mechanistic Studies. In order to gain insight into the
mechanism of the decarboxylative cross-coupling process,
several control experiments were carried out. First, when the
radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) was added to the reaction mixture, only a trace
amount of 1 was observed by GC-MS (Scheme 4a), whereas in
the presence of hydroquinone the reaction was completely
inhibited and the corresponding radical adducts were detected
by GC-MS (Scheme 4b; for details, see the Supporting
Information). The results indicate that the transformation
proceeds via a free-radical pathway. Subsequently, almost all of
the cinnamic acid remained intact when only cinnamic acid was
heated under the standard reaction conditions (Scheme 4c).
The reaction failed to give the desired product 1 when
benzoylformic acid was treated with styrene under the standard
conditions (Scheme 4d). These results described above suggest
that the initial protodecarboxylation and the following acylation
processes might not be involved in the reaction mechanism.
EXPERIMENTAL SECTION
■
General Comments. All commercially available compounds were
purchased from commercial suppliers and used without further
purification unless otherwise noted. All solvents were purified
according to the method of Grubbs.14 All kinds of substituted α-
aryketo acids were prepared from oxidation of corresponding methyl
ketones with SeO2 according to the reported procedure.15 1H NMR
and 13C NMR spectra were recorded at 400 and 101 MHz in CDCl3
or DMSO-d6 using TMS as the internal standard. Column
chromatography was performed on 200−300 mesh silica gel. Thin-
layer chromatography (TLC) was performed on Silicycle 250 mm
silica gel F-254 plates. Multiplicities are indicated as s (singlet), d
E
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Scheme 4. Control Experiments
Scheme 5. Proposed Mechanism
(doublet), t (triplet), q (quartet), and m (multiplet), and coupling
constants (J) are reported in hertz.
Na2SO4, filtered, and concentrated in vacuo. The resulting residue was
purified by column chromatography on silica gel to give the desired
product α,β-unsaturated carbonyls.
Typical Procedure for the Decarboxylative Cross-Coupling
Reaction between Various α-Oxocarboxylic Acids and
Cinnamic Acid. To a 20 mL Schlenk tube was added α-oxocarboxylic
acids (0.5 mmol, 1.0 equiv), cinnamic acid (148 mg, 1.0 mmol, 2.0
equiv), K2S2O8 (337.5 mg, 1.25 mmol), HCOONa·2H2O (104 mg, 1.0
mmol), and FeCl2 (6.3 mg, 0.05 mmol). The tube was evacuated and
backfilled with N2 three times. H2O (1.7 mL) and DMSO (0.3 mL)
were added. The reaction mixture was stirred at 120 °C for 15 h. Upon
completion, the resulting mixture was dilute by EtOAc and washed
with H2O. The organic phase was separated, dried over anhydrous
General Procedure for the Decarboxylative Cross-Coupling
Reaction between Benzoylformic Acid and Various Acrylic
Acids. To a 20 mL Schlenk tube was added benzoylformic acid (75
mg, 0.5 mmol, 1.0 equiv), acrylic acids (2.0 mmol, 4.0 equiv), K2S2O8
(337.5 mg, 1.25 mmol), HCOONa·2H2O (104 mg, 1.0 mmol), and
FeCl2 (6.3 mg, 0.05 mmol). The tube was evacuated and backfilled
with N2 three times. H2O (1.0 mL) and DMSO (3.0 mL) were added.
The reaction mixture was stirred at 120 °C for 15 h. Upon completion,
the resulting mixture was diluted by EtOAc and washed with H2O.
F
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The organic phase was separated, dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. The resulting residue was purified
by column chromatography on silica gel to give the desired product
α,β-unsaturated carbonyls.
55.6, 55.8, 98.6, 105.3, 122.2, 127.2, 128.3, 128.9, 130.0, 132.9, 135.5,
142.0, 160.5, 164.2, 190.5 ppm. Anal. Calcd for C17H16O3 Elemental
Analysis: C, 76.10; H, 6.01. Found: C, 76.02; H, 6.16.
(E)-1-(4-Ethoxyphenyl)-3-phenylprop-2-en-1-one (8):9b By
following the typical procedure, the product was isolated as a colorless
solid, 115.9 mg (92%), flash chromatography (petroleum ether/ethyl
(E)-Chalcone (1):9b By following the typical procedure, the
product was isolated as a yellow solid, 86.3 mg (83%), flash
chromatography (petroleum ether/ethyl acetate, 30/1), mp = 56−58
°C (lit.9b mp = 55−57 °C); 1H NMR (CDCl3, 400 MHz) δ 7.40−7.42
(m, 3 H), 7.48−7.60 (m, 4 H), 7.63−7.65 (m, 2 H), 7.81 (d, J = 16.0
Hz, 1 H), 8.01−8.03 (m, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
122.1, 128.4, 128.5, 128.7, 129.0, 130.6, 132.8, 134.9, 138.2, 144.9,
190.6 ppm. Anal. Calcd for C15H12O Elemental Analysis: C, 86.51; H,
5.81. Found: C, 86.47; H, 5.83.
acetate, 30/1), mp = 67−69 °C (lit.9b mp = 67−69 °C); H NMR
1
(CDCl3, 400 MHz) δ 1.45 (t, J = 8.0 Hz, 3 H), 4.12 (q, J = 8.0 Hz, 2
H), 6.97 (d, J = 8.0 Hz, 2 H), 7.40−7.42 (m, 3 H), 7.55 (d, J = 16.0
Hz, 1 H), 7.63−7.65 (m, 2 H), 7.80 (d, J = 16.0 Hz, 1 H), 8.04 (d, J =
12.0 Hz, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 14.7, 63.8, 114.3,
121.9, 128.4, 129.0, 130.3, 130.8, 130.9, 135.1, 143.9, 162.9, 188.7
ppm. Anal. Calcd for C17H16O2 Elemental Analysis: C, 80.93; H, 6.39.
Found: C, 80.90; H, 6.41.
(E)-3-Phenyl-1-(p-tolyl)prop-2-en-1-one (2):9b By following the
typical procedure, the product was isolated as a pale yellow solid, 89.9
mg (81%), flash chromatography (petroleum ether/ethyl acetate, 30/
(E)-1-(4-Fluorophenyl)-3-phenylprop-2-en-1-one (9):9b By
following the typical procedure, the product was isolated as a pale
yellow solid, 92.7 mg (82%), flash chromatography (petroleum ether/
1), mp = 48−50 °C (lit.9b mp = 47−49 °C); H NMR (CDCl3, 400
1
ethyl acetate, 30/1), mp = 72−74 °C (lit.9b mp = 71−73 °C); H
1
MHz) δ 2.31 (s, 3 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.29−7.30 (m, 3 H),
7.43 (d, J = 16.0 Hz, 1 H), 7.51−7.54 (m, 2 H), 7.70 (d, J = 16.0 Hz, 1
H), 7.84 (d, J = 8.0 Hz, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
21.7, 122.1, 128.5, 128.7, 129.0, 129.4, 130.5, 135.0, 135.7, 143.7,
144.4, 190.0 ppm. Anal. Calcd for C16H14O Elemental Analysis: C,
86.45; H, 6.35. Found: C, 86.56; H, 6.23.
NMR (CDCl3, 400 MHz) δ 7.06−7.10 (m, 2 H), 7.32−7.33 (m, 3 H),
7.41 (d, J = 16.0 Hz, 1 H), 7.53−7.56 (m, 2 H), 7.72 (d, J = 16.0 Hz, 1
H), 7.85−7.98 (m, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 115.8
(d, J = 22.0 Hz), 121.6, 128.5, 129.0, 130.7, 131.1(d, J = 9.0 Hz), 134.5
(d, J = 3.0 Hz), 134.8, 145.1, 165.6 (d, J = 253.0 Hz), 190.0 ppm. Anal.
Calcd for C15H11FO Elemental Analysis: C, 79.63; H, 4.90. Found: C,
79.76; H, 4.82.
(E)-3-Phenyl-1-(m-tolyl)prop-2-en-1-one (3):12 By following
the typical procedure, the product was isolated as a pale yellow solid,
91.0 mg (82%), flash chromatography (petroleum ether/ethyl acetate,
(E)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-one (10):9b By
following the typical procedure, the product was isolated as a pale
yellow solid, 94.4 mg (78%), flash chromatography (petroleum ether/
30/1), mp = 60−62 °C (lit.17a mp = 59−60 °C); H NMR (CDCl3,
1
400 MHz) δ 2.43 (s, 3 H), 7.38−7.42 (m, 5 H), 7.52 (d, J = 16.0 Hz, 1
H), 7.63−7.65 (m, 2 H), 7.78−7.83 (m, 3 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 21.5, 122.3, 125.8, 128.4, 128.5, 129.0, 129.1,
130.5, 133.6, 135.0, 138.3, 138.5, 144.7, 190.7 ppm. Anal. Calcd for
C16H14O Elemental Analysis: C, 86.45; H, 6.35. Found: C, 86.37; H,
6.48.
ethyl acetate, 30/1), mp = 84−86 °C (lit.9b mp = 83−85 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.30−7.32 (m, 3 H), 7.35−7.40 (m, 3 H),
7.52−7.54 (m, 2 H), 7.71 (d, J = 16.0 Hz, 1 H), 7.85 (d, J = 8.0 Hz, 2
H); 13C NMR (CDCl3, 101 MHz) δ 121.5, 128.6, 128.9, 129.0, 130.0,
130.8, 134.7, 136.5, 139.2, 145.4, 189.1 ppm. Anal. Calcd for
C15H11ClO Elemental Analysis: C, 74.23; H, 4.57. Found: C, 74.42;
H, 4.48.
(E)-3-Phenyl-1-(o-tolyl)prop-2-en-1-one (4):9b By following the
typical procedure, the product was isolated as a pale yellow oil, 86.6
mg (78%), flash chromatography (petroleum ether/ethyl acetate, 30/
1); 1H NMR (CDCl3, 400 MHz) δ 2.37 (s, 3 H), 7.06 (d, J = 16.0 Hz,
1 H), 7.17−7.21 (m, 2 H), 7.28−7.43 (m, 6 H), 7.49−7.49 (m, 2 H);
13C {1H} NMR (CDCl3, 101 MHz) δ 21.2, 125.5, 126.8, 128.1, 128.5,
129.0, 130.5, 130.7, 131.4, 134.6, 137.0, 139.1, 146.0, 196.6 ppm;
LRMS: m/z calcd for C16H14O (M+H): 223, found: 223.
(E)-1-(4-Bromophenyl)-3-phenylprop-2-en-1-one (11):9b By
following the typical procedure, the product was isolated as a pale
yellow solid, 91.5 mg (64%), flash chromatography (petroleum ether/
ethyl acetate, 30/1), mp = 98−100 °C (lit.9b mp = 90−92 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.31−7.33 (m, 3 H), 7.38 (d, J = 12.0 Hz,
1 H),7.52−7.55 (m, 4 H), 7.72 (d, J = 12.0 Hz, 1 H), 7.79 (d, J = 8.0
Hz, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 121.4, 127.9, 128.6,
129.0, 130.1, 130.8, 132.0, 134.7, 136.9, 145.4, 189.3 ppm. Anal. Calcd
for C15H11BrO Elemental Analysis: C, 62.74; H, 3.86. Found: C,
62.94; H, 3.73.
(E)-1-(4-Methoxyphenyl)-3-phenylprop-2-en-1-one (5):9b By
following the typical procedure, the product was isolated as a pale
yellow colorless solid, 103.5 mg (87%), flash chromatography
(petroleum ether/ethyl acetate, 30/1), mp = 104−106 °C (lit.9b mp
(E)-1-(3-Bromophenyl)-3-phenylprop-2-en-1-one (12):16a By
following the typical procedure, the product was isolated as a pale
yellow solid, 97.2 mg (68%), flash chromatography (petroleum ether/
1
= 94−96 °C); H NMR (CDCl3, 400 MHz) δ 3.88 (s, 3 H), 6.96−
7.00 (m, 2 H), 7.40−7.42 (m, 3 H), 7.55 (d, J = 16.0 Hz, 1 H), 7.63−
7.65 (m, 2 H), 7.80 (d, J = 16.0 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 2 H);
13C {1H} NMR (CDCl3, 101 MHz) δ 55.5, 113.9, 121.9, 128.4, 129.0,
ethyl acetate, 30/1), mp = 92−94 °C (lit.17a mp = 92−94 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.29 (t, J = 8.0 Hz, 1 H), 7.33−7.39 (m, 4
H), 7.55−7.57 (m, 2 H), 7.62 (dd, J = 4.0 Hz, 4.0 Hz, 1 H), 7.73(d, J =
16.0 Hz, 1 H), 7.85 (d, J = 8.0 Hz, 1 H), 8.05 (s, 1 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 121.4, 123.0, 127.0, 128.6, 129.1, 130.2, 130.9,
131.5, 134.6, 135.6, 140.0, 145.7, 189.0 ppm. Anal. Calcd for
C15H11BrO Elemental Analysis: C, 62.74; H, 3.86. Found: C, 62.60;
H, 3.92.
130.4, 130.9, 131.1, 135.1, 143.7, 144.0, 190.0 ppm. Anal. Calcd for
C16H14O2 Elemental Analysis: C, 80.65; H, 5.92. Found: C, 80.89; H,
5.75.
(E)-1-(3,4-Dimethoxyphenyl)-3-phenylprop-2-en-1-one
(6):9d By following the typical procedure, the product was isolated as a
yellow oil, 113.9 mg (85%), flash chromatography (petroleum ether/
ethyl acetate, 3/1); 1H NMR (CDCl3, 400 MHz) δ 3.85 (s, 3H), 3.86
(s, 3 H), 6.81 (d, J = 8.0 Hz, 1 H), 7.30−7.32 (m, 3 H), 7.46 (d, J =
16.0 Hz, 1 H), 7.53−7.55 (m, 3 H), 7.59 (dd, J = 2.0 Hz, 2.0 Hz, 1 H),
7.70 (d, J = 12.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 56.0,
56.1, 110.0, 110.8, 121.6, 123.1, 128.4, 128.9, 130.4, 131.3, 135.1,
144.0, 149.2, 153.3, 188.5 ppm; LRMS: m/z calcd for C17H16O3 (M +
H): 269, found: 269.
(E)-1-(2,4-Dimethoxyphenyl)-3-phenylprop-2-en-1-one
(7):9d By following the typical procedure, the product was isolated as a
pale yellow solid, 112.6 mg (84%), flash chromatography (petroleum
ether/ethyl acetate, 10/1), mp = 76−79 °C (lit.17b mp = 80.5−81 °C);
1H NMR (CDCl3, 400 MHz) δ 3.76 (s, 3H), 3.80 (s, 3 H), 6.40 (d, J =
(E)-1-(2-Bromophenyl)-3-phenylprop-2-en-1-one (13):16b By
following the typical procedure, the product was isolated as a pale
yellow oil, 101.5 mg (71%), flash chromatography (petroleum ether/
1
ethyl acetate, 30/1); H NMR (CDCl3, 400 MHz) δ 2.37 (s, 3 H),
7.10 (d, J = 16.0 Hz, 1 H), 7.31−7.45 (m, 7 H), 7.54−7.57 (m, 2 H),
7.64 (d, J = 8.0 Hz, 2 H); 13C NMR (CDCl3, 101 MHz) δ 119.5,
126.2, 127.4, 128.6, 129.0, 129.2, 131.0, 131.4, 133.5, 134.4, 141.2,
146.7, 194.8 ppm; LRMS: m/z calcd for C15H11BrO (M + H): 288,
found: 288.
(E)-1-(4-Iodophenyl)-3-phenylprop-2-en-1-one (14):16c By
following the typical procedure, the product was isolated as a colorless
solid, 111.9 mg (67%), flash chromatography (petroleum ether/ethyl
2.4 Hz, 1 H), 6.46 (dd, J = 2.0 Hz, 2.4 Hz, 1 H), 7.26−7.32 (m, 3 H),
7.43 (d, J = 16.0 Hz, 1 H), 7.45−7.51 (m, 2 H), 7.59 (d, J = 16.0 Hz, 1
H), 7.67 (d, J = 8.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
acetate, 30/1), mp = 112−114 °C (lit.17a mp = 112−113 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.42−7.48 (m, 4 H), 7.63−7.66 (m, 2
G
DOI: 10.1021/acs.joc.5b00267
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Article
H),7.72−7.75 (m, 2 H), 7.82 (d, J = 16.0 Hz, 1 H), 7.85−7.88 (m, 2
H); 13C {1H} NMR (CDCl3, 101 MHz) δ 100.7, 121.4, 128.6, 129.0,
130.0, 130.8, 134.7, 137.5, 138.0, 145.5, 189.7 ppm. Anal. Calcd for
C15H11IO Elemental Analysis: C, 53.92; H, 3.32. Found: C, 53.78; H,
3.41.
(CDCl3, 101 MHz) δ 119.7, 128.0, 128.9, 130.0, 134.5, 142.5, 168.1
ppm. Anal. Calcd for C9H9NO Elemental Analysis: C, 73.45; H, 6.16;
N, 9.52. Found: C, 73.62; H, 6.20; N, 9.48.
N,N-Diethylcinnamamide (22):16g By following the typical
procedure, the product was isolated as a colorless solid, 45.7 mg
(45%), flash chromatography (petroleum ether/ethyl acetate, 2/1),
(E)-3-Phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-one
(15):9b By following the typical procedure, the product was isolated as
colorless solid, 88.3 mg (64%), flash chromatography (petroleum
ether/ethyl acetate, 30/1), mp = 114−116 °C (lit.9b mp = 114−116
mp = 61−63 °C (lit.17f mp = 60−62 °C); H NMR (CDCl3, 400
1
MHz) δ 1.19−1.26 (m, 6 H), 3.48−3.50 (m, 5 H), 6.83 (d, J = 16.0
Hz, 1 H), 7.32−7.39 (m, 3 H), 7.52−7.54 (m, 2 H), 7.72 (d, J = 12.0
Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 13.3, 15.1, 41.1, 42.3,
117.8, 127.8, 128.8, 129.5, 135.5, 142.3, 165.7 ppm. Anal. Calcd for
C13H17NO Elemental Analysis: C, 76.81; H, 8.43; N, 6.89. Found: C,
76.94; H, 8.48; N, 6.73.
1
°C); H NMR (CDCl3, 400 MHz) δ 7.44−7.51 (m, 4 H), 7.65−7.67
(m, 2 H),7.78 (d, J = 12.0 Hz, 1 H), 7.84 (d, J = 16.0 Hz, 1 H), 8.11
(d, J = 8.0 Hz, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 121.6,
123.7 (d, J = 271.0 Hz), 125.7 (q, J = 2.0 Hz), 128.6, 128.8, 129.0,
131.0, 134.1 (d, J = 32.0 Hz), 134.5, 146.2, 189.7 ppm. Anal. Calcd for
C16H11F3O Elemental Analysis: C, 69.56; H, 4.01. Found: C, 69.72; H,
3.93.
N-Methyl-N-phenylcinnamamide (23):16h By following the
typical procedure, the product was isolated as a colorless solid, 52.7
mg (41%), flash chromatography (petroleum ether/ethyl acetate, 3/1),
(E)-1-(Naphthalen-2-yl)-3-phenylprop-2-en-1-one (16):12 By
following the typical procedure, the product was isolated as a pale
yellow solid, 82.6 mg (64%), flash chromatography (petroleum ether/
mp = 66−69 °C (lit.17g mp = 67−68 °C); H NMR (CDCl3, 400
1
MHz) δ 3.41 (s, 3 H), 6.37 (d, J = 16.0 Hz, 1 H), 7.22−7.38 (m, 8 H),
7.44 (t, J = 8.0 Hz, 2 H), 7.68 (d, J = 16.0 Hz, 1 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 37.6, 118.8, 127.3, 127.6, 127.9, 128.7, 129.5,
129.7, 13.5.2, 141.7, 143.6, 166.2 ppm. Anal. Calcd for C16H15NO
Elemental Analysis: C, 80.98; H, 6.37; N, 5.90. Found: C, 81.14; H,
6.44; N, 5.76.
ethyl acetate, 30/1), mp = 106−108 °C (lit.17c mp = 105 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.41−7.44 (m, 3 H), 7.54−7.61 (m, 2 H),
7.66−7.70 (m, 3 H), 7.85−7.93 (m, 3 H), 7.98 (d, J = 8.0 Hz, 1 H),
8.10 (dd, J = 4.0 Hz, 4.0 Hz, 1 H), 8.52 (s, 1 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 122.1, 124.5, 126.8, 127.9, 128.4, 128.5, 128.6,
129.0, 129.6, 130.0, 130.6, 132.6, 135.0, 135.5, 135.6, 144.8, 190.3
ppm. Anal. Calcd for C19H14O Elemental Analysis: C, 88.34; H, 5.46.
Found: C, 88.61; H, 5.28.
(E)-1-Phenyl-3-(p-tolyl)prop-2-en-1-one (25):17h By following
the general procedure, the product was isolated as a pale yellow solid,
99.9 mg (90%), flash chromatography (petroleum ether/ethyl acetate,
30/1), mp = 96−98 °C (lit.17h mp = 96−97.5 °C); 1H NMR (CDCl3,
400 MHz) δ 7.24 (t, J = 8.0 Hz, 2 H), 7.47−7.58 (m, 6 H), 7.80 (d, J =
16.0 Hz, 1 H), 8.00−8.03 (m, 2 H); 13C {1H} NMR (CDCl3, 101
MHz) δ 21.6, 121.1, 128.4, 128.5, 128.6, 129.7, 132.2, 132.7, 138.4,
141.1, 145.0, 190.7 ppm. Anal. Calcd for C16H14O Elemental Analysis:
C, 86.45; H, 6.35. Found: C, 86.31; H, 6.43.
(E)-3-Phenyl-1-(thiophen-2-yl)prop-2-en-1-one (17):12 By
following the typical procedure, the product was isolated as a pale
yellow solid, 66.3 mg (62%), flash chromatography (petroleum ether/
ethyl acetate, 30/1), mp = 82−84 °C (lit.17d mp = 82−83 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.16−7.18 (m, 1 H), 7.40−7.44 (m, 4 H),
7.62−7.65 (m, 2 H), 7.67 (dd, J = 0.8 Hz, 0.8 Hz, 1 H), 7.83−7.87 (m,
2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 121.6, 128.3, 128.5, 129.0,
130.6, 131.9, 134.0, 134.7, 144.1, 145.6, 182.1 ppm. Anal. Calcd for
C13H10OS Elemental Analysis: C, 72.87; H, 4.70. Found: C, 72.95; H,
4.64.
(E)-1-Phenyl-3-(m-tolyl)prop-2-en-1-one (26):6c By following
the general procedure, the product was isolated as a pale yellow solid,
96.6 mg (87%), flash chromatography (petroleum ether/ethyl acetate,
30/1), mp = 62−64 °C (lit.6c mp = 59−61 °C); H NMR (CDCl3,
1
400 MHz) δ 2.39 (s, 3 H), 7.23 (t, J = 8.0 Hz, 1 H), 7.30 (t, J = 8.0 Hz,
1 H), 7.43−7.59 (m, 6 H), 7.78 (d, J = 16.0 Hz, 1 H), 8.01−8.03 (m, 2
H); 13C {1H} NMR (CDCl3, 101 MHz) δ 121.9, 125.8, 128.5, 128.6,
128.9, 129.1, 131.5, 132.8, 134.9, 138.3, 138.7, 145.1, 190.6 ppm. Anal.
Calcd for C16H14O Elemental Analysis: C, 86.45; H, 6.35. Found: C,
86.59; H, 6.28.
(E)-1-(Furan-2-yl)-3-phenylprop-2-en-1-one (18):16d By fol-
lowing the typical procedure, the product was isolated as a yellow oil,
50.1 mg (51%), flash chromatography (petroleum ether/ethyl acetate,
30/1); 1H NMR (CDCl3, 400 MHz) δ 6.60 (dd, J = 1.6 Hz, 1.6 Hz, 1
H), 7.34 (d, J = 4.0 Hz, 1 H), 7.40−7.48 (m, 4 H), 7.64−7.66 (m, 3
H), 7.88 (d, J = 16.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
112.6, 117.6, 121.2, 128.6, 129.0, 130.6, 134.7, 144.0, 146.6, 153.7,
178.0 ppm; LRMS: m/z calcd for C13H10O2 (M + H), 199; found, 199.
(E)-4-Phenylbut-3-en-2-one (19):16e By following the typical
procedure, the product was isolated as a yellow solid, 38.0 mg (52%),
flash chromatography (petroleum ether/ethyl acetate, 30/1), mp =
(E)-1-Phenyl-3-(o-tolyl)prop-2-en-1-one (27):16i By following
the general procedure, the product was isolated as a pale yellow oil,
94.4 mg (85%), flash chromatography (petroleum ether/ethyl acetate,
30/1); 1H NMR (CDCl3, 400 MHz) δ 2.46 (s, 3 H), 7.21−7.31 (m, 3
H), 7.44−7.51 (m, 3 H), 7.57 (t, J = 8.0 Hz, 1 H), 7.69 (d, J = 8.0 Hz,
1 H), 8.03 (d, J = 8.0 Hz, 2 H), 8.12 (d, J = 16.0 Hz, 1 H); 13C {1H}
NMR (CDCl3, 101 MHz) δ 19.9, 123.1, 126.4, 126.5, 128.6, 128.7,
130.3, 131.0, 132.9, 133.9, 138.3, 138.4, 142.5, 190.5 ppm; LRMS: m/z
calcd for C16H14O (M + H), 223; found, 223.
40−42 °C (lit.17e mp = 40−41 °C); H NMR (CDCl3, 400 MHz) δ
1
2.37 (s, 3 H), 6.70 (d, J = 20.0 Hz, 1 H), 7.37−7.39 (m, 3 H), 7.48−
7.54 (m, 3 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 27.5, 127.1,
128.3, 129.0, 130.5, 134.4, 143.4, 198.4 ppm. Anal. Calcd for C10H10O
Elemental Analysis: C, 82.16; H, 6.89. Found: C, 82.32; H, 6.74.
(E)-4-Oxo-6-phenylhex-5-enoic acid (20). By following the
typical procedure, the product was isolated as a colorless solid, 38.8 mg
(38%), flash chromatography (petroleum ether/ethyl acetate, 1/1),
mp = 124−126 °C (lit.17o mp = 124−126 °C); 1H NMR (DMSO-d6,
400 MHz) δ 2.47 (t, J = 8.0 Hz, 2 H), 2.92 (t, J = 8.0 Hz, 2 H), 3.72
(brs, 1 H), 6.92 (d, J = 16.0 Hz, 1 H), 7.43−7.44 (m, 3 H), 7.62 (d, J =
16.0 Hz, 1 H), 7.71−7.73 (m, 2 H); 13C {1H} NMR (DMSO-d6, 101
MHz) δ 122.1, 124.5, 126.8, 127.9, 128.4, 128.5, 128.6, 129.0, 129.6,
130.0, 130.6, 132.6, 135.0, 135.5, 135.6, 144.8, 190.3 ppm. Anal. Calcd
for C12H12O3 Elemental Analysis: C, 70.57; H, 5.92. Found: C, 70.51;
H, 5.95.
(E)-3-(4-Methoxyphenyl)-1-phenylprop-2-en-1-one (28):17h
By following the general procedure, the product was isolated as a
yellow solid, 97.6 mg (82%), flash chromatography (petroleum ether/
ethyl acetate, 10/1), mp = 74−76 °C (lit.17h mp = 71−76 °C); H
1
NMR (CDCl3, 400 MHz) δ 3.84 (s, 3 H), 6.93 (d, J = 8.0 Hz, 2 H),
7.41 (d, J = 16.0 Hz, 1 H), 7.49 (d, J = 8.0 Hz, 2 H), 7.55−7.61 (m, 3
H), 7.79 (d, J = 12.0 Hz, 1 H), 8.00−8.02 (m, 2 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 55.4, 114.5, 119.8, 127.6, 128.4, 128.6, 130.3,
132.6, 138.5, 144.7, 161.7, 190.6 ppm. Anal. Calcd for C16H14O2
Elemental Analysis: C, 80.65; H, 5.92. Found: C, 80.81; H, 5.84.
(E)-3-(3-Methoxyphenyl)-1-phenylprop-2-en-1-one (29):6c
By following the general procedure, the product was isolated as a
pale yellow solid, 92.8 mg (78%), flash chromatography (petroleum
ether/ethyl acetate, 20/1), mp = 50−52 °C (lit.6c mp = 62−63 °C);
1H NMR (CDCl3, 400 MHz) δ 3.76 (s, 3 H), 6.88 (dd, J = 4.0 Hz, 4.0
Hz, 1 H), 7.07 (s, 1 H), 7.14−7.17 (m, 1 H), 7.24 (t, J = 8.0 Hz, 1 H),
7.40−7.44 (m, 3 H), 7.50 (t, J = 8.0 Hz, 1 H), 7.68 (d, J = 16.0 Hz, 1
H), 7.92−7.94 (m, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 55.4,
113.5, 116.3, 121.1, 122.4, 128.5, 128.7, 130.0, 132.8, 136.3, 138.2,
Cinnamamide (21):16f By following the typical procedure, the
product was isolated as a colorless solid, flash chromatography
(petroleum ether/ethyl acetate, 1/1), 30.9 mg (42%), mp = 144−147
°C (lit.16f mp = 148−150 °C); H NMR (CDCl3, 400 MHz) δ 5.84
1
(brs, 1 H), 5.98 (brs, 1 H), 6.43 (d, J = 16.0 Hz, 1 H), 7.29−7.30 (m, 3
H), 7.43−7.46 (m, 2 H), 7.57 (d, J = 16.0 Hz, 1 H); 13C {1H} NMR
H
DOI: 10.1021/acs.joc.5b00267
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144.8, 160.0, 190.6 ppm. Anal. Calcd for C16H14O2 Elemental Analysis:
C, 80.65; H, 5.92. Found: C, 80.52; H, 5.98.
128.7, 130.2, 130.4, 133.1, 135.0, 136.8, 137.9, 143.1, 190.1 ppm. Anal.
Calcd for C15H11FO Elemental Analysis: C, 79.63; H, 4.90. Found: C,
79.58; H, 4.95.
(E)-3-(2-Methoxyphenyl)-1-phenylprop-2-en-1-one (30):6c
By following the general procedure, the product was isolated as a
pale yellow oil, 90.4 mg (76%), flash chromatography (petroleum
(E)-3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one (37):17h By
following the general procedure, the product was isolated as a pale
yellow solid, 75.0 mg (62%), flash chromatography (petroleum ether/
ethyl acetate, 30/1), mp = 113−115 °C (lit.17h mp = 113.5−115.5
°C); 1H NMR (CDCl3, 400 MHz) δ 7.31 (d, J = 8.0 Hz, 2 H), 7.43 (t,
J = 16.0 Hz, 1 H), 7.49−7.54 (m, 3 H), 7.68 (d, J = 16.0 Hz, 1 H),
7.93−7.95 (m, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 121.4,
127.5, 127.7, 128.2, 128.6, 131.9, 132.4, 135.4, 137.0, 142.3, 189.2
ppm. Anal. Calcd for C15H11ClO Elemental Analysis: C, 74.23; H,
4.57. Found: C, 74.39; H, 4.48.
1
ether/ethyl acetate, 20/1); H NMR (CDCl3, 400 MHz) δ 3.91 (s, 3
H), 6.94 (d, J = 8.0 Hz, 1 H), 6.99 (t, J = 8.0 Hz, 1 H), 7.36−7.40 (m,
1 H), 7.49 (t, J = 8.0 Hz, 2 H), 7.55−7.64 (m, 3 H), 8.01−8.03 (m, 2
H), 8.12 (d, J = 16.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
55.6, 111.3, 120.8, 122.9, 123.9, 128.5, 128.6, 129.3, 131.8, 132.6,
138.5, 140.5, 158.8, 191.2 ppm; LRMS: m/z calcd for C16H14O2 (M +
H), 239; found, 239.
(E)-3-(4-Hydroxyphenyl)-1-phenylprop-2-en-1-one (31):16j
By following the general procedure, the product was isolated as a
yellow solid, 48.2 mg (43%), flash chromatography (hexane/acetone,
3/1), mp = 184−186 °C (lit.16j mp = 187−188 °C); 1H NMR
(DMSO-d6, 400 MHz) δ 6.85 (d, J = 8.0 Hz, 2 H), 7.57 (t, J = 8.0 Hz,
2 H), 7.64−7.68 (m, 1 H), 7.73 (dd, J = 4.0 Hz, 8.0 Hz, 4 H), 8.11−
8.14 (m, 2 H), 10.12 (brs, 1 H); 13C {1H} NMR (DMSO-d6, 101
MHz) δ 116.3, 118.9, 126.2, 128.8, 129.2, 131.5, 133.3, 138.4, 145.0,
160.0, 189.5 ppm. Anal. Calcd for C15H12O2 Elemental Analysis: C,
80.34; H, 5.39. Found: C, 80.29; H, 5.43.
(E)-3-(4-Bromophenyl)-1-phenylprop-2-en-1-one (38):16l By
following the general procedure, the product was isolated as a colorless
solid, 95.8 mg (67%), flash chromatography (petroleum ether/ethyl
acetate, 30/1), mp = 122−124 °C (lit.16l mp = 127−128 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.49−7.62 (m, 8 H), 7.74 (d, J = 16.0 Hz,
1 H), 8.00−8.03 (m, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ
122.6, 124.8, 128.5, 128.7, 129.8, 132.2, 133.0, 133.8, 138.0, 143.4,
190.3 ppm. Anal. Calcd for C15H11BrO Elemental Analysis: C, 62.74;
H, 3.86. Found: C, 62.98; H, 3.73.
(E)-3-(4-Nitrophenyl)-1-phenylprop-2-en-1-one (32):8b By
following the general procedure, the product was isolated as a yellow
solid, 75.6 mg (60%), flash chromatography (petroleum ether/ethyl
(E)-3-[(1,1′-Biphenyl)-4-yl]-1-phenylprop-2-en-1-one
(39):16m By following the general procedure, the product was isolated
as a yellow solid, 92.3 mg (65%), flash chromatography (petroleum
ether/ethyl acetate, 20/1), mp = 108−110 °C (lit.16m mp = 110−112
°C); 1H NMR (CDCl3, 400 MHz) δ 7.38 (t, J = 8.0 Hz, 1 H), 7.45−
7.56 (m, 4 H), 7.58−7.67 (m, 6 H), 7.73 (d, J = 8.0 Hz, 2 H), 7.86 (d,
J = 16.0 Hz, 1 H), 8.03−8.05 (m, 2 H); 13C {1H} NMR (CDCl3, 101
MHz) δ 121.9, 127.1, 127.6, 127.9, 128.5, 128.7, 128.9, 129.0, 132.8,
133.9, 138.3, 140.2, 143.4, 144.4, 190.6 ppm. Anal. Calcd for C21H16O
Elemental Analysis: C, 88.70; H, 5.67. Found: C, 88.46; H, 5.78.
(E)-4-(3-Oxo-3-phenylprop-1-en-1-yl)benzaldehyde (40):8b
By following the general procedure, the product was isolated as a
pale yellow solid, 74.3 mg (63%), flash chromatography (petroleum
ether/ethyl acetate, 7/1), mp = 122−124 °C (lit.8b mp = 125 °C); 1H
NMR (CDCl3, 400 MHz) δ 7.53 (t, J = 8.0 Hz, 2 H), 7.60−7.67 (m, 2
H), 7.78−7.85 (m, 3 H), 7.93 (d, J = 8.0 Hz, 2 H), 8.03−8.05 (m, 2
H), 10.5 (s, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 124.8, 128.6,
128.8, 128.9, 130.2, 133.2, 137.3, 137.8, 140.6, 142.8, 190.0, 191.5
ppm. Anal. Calcd for C16H12O2 Elemental Analysis: C, 81.34; H, 5.12.
Found: C, 81.48; H, 5.04.
(E)-1-Phenyl-3-(4-(trifluoromethyl)phenyl)prop-2-en-1-one
(41):8b By following the general procedure, the product was isolated
as a colorless solid, 102.1 mg (74%), flash chromatography (petroleum
ether/ethyl acetate, 30/1), mp = 126−128 °C (lit.8b mp = 128−129
°C); 1H NMR (CDCl3, 400 MHz) δ 7.53 (t, J = 8.0 Hz, 2 H), 7.58−
7.63 (m, 2 H), 7.68 (d, J = 8.0 Hz, 2 H), 7.75 (d, J = 8.0 Hz, 2 H), 7.81
(d, J = 16.0 Hz, 1 H), 7.82−7.84 (m, 2H); 13C {1H} NMR (CDCl3,
101 MHz) δ 123.8 (d, J = 271.0 Hz), 124.3, 125.9 (d, J = 3.0 Hz),
128.5, 128.6, 128.8, 132.0 (d, J = 33.0 Hz), 133.2, 137.8, 138.3, 142.8,
190.1 ppm. Anal. Calcd for C16H11F3O Elemental Analysis: C, 69.56;
H, 4.01. Found: C, 69.42; H, 4.08.
(E)-3-(4-((E)-3-Oxo-3-phenylprop-1-en-1-yl)phenyl)acrylic
Acid (42). To a 20 mL Schlenk tube were added benzoylformic acid
(75 mg, 0.5 mmol), 1,4-phenylenediacrylic acid (436 mg, 2.0 mmol),
K2S2O8 (337.5 mg, 1.25 mmol), HCOONa·2H2O (104 mg, 1.0
mmol), and FeCl2 (6.3 mg, 0.05 mmol). The tube was evacuated and
backfilled with N2 three times. DMSO (4.0 mL) was added. The
reaction mixture was stirred at 120 °C for 15 h. Upon completion, the
resulting mixture was diluted by EtOAc and washed with H2O. The
organic phase was separated, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. The resulting residue was purified by
column chromatography on silica gel to give the desired product 42 in
45% yield (62.6 mg). Flash chromatography (hexane/acetone, 3/2),
pale yellow solid, mp = 252−254 °C; 1H NMR (DMSO-d6, 400 MHz)
δ 6.66 (d, J = 16.0 Hz, 1 H), 7.57−7.69 (m, 4 H), 7.75−7.81 (m, 3 H),
7.96 (d, J = 8.0 Hz, 2 H), 8.03 (d, J = 16.0 Hz, 1 H), 8.18 (d, J = 8.0
Hz, 2 H), 12.47 (brs, 1 H); 13C {1H} NMR (DMSO-d6, 101 MHz) δ
120.9, 123.4, 129.1, 129.2, 129.3, 129.9, 133.7, 136.7, 136.8, 138.0,
acetate, 10/1), mp = 162−164 °C (lit.8b mp = 163−164 °C); H
1
NMR (CDCl3, 400 MHz) δ 7.54 (t, J = 8.0 Hz, 2 H), 7.62−7.67 (m, 2
H), 7.79−7.83 (m, 3 H), 8.03−8.05 (m, 2 H), 8.29 (d, J = 8.0 Hz, 2
H); 13C {1H} NMR (CDCl3, 101 MHz) δ 124.3, 125.7, 128.6, 128.9,
129.0, 133.4, 137.6, 141.1, 141.5, 148.6, 189.7 ppm. Anal. Calcd for
C15H11NO3 Elemental Analysis: C, 71.14; H, 4.38; N, 5.53. Found: C,
71.32; H, 4.41; N, 5.41.
(E)-3-(3-Nitrophenyl)-1-phenylprop-2-en-1-one (33):17i By
following the general procedure, the product was isolated as a pale
yellow solid, 77.2 mg (61%), flash chromatography (petroleum ether/
ethyl acetate, 10/1), mp = 142−144 °C (lit.17j mp = 140−142 °C); 1H
NMR (CDCl3, 400 MHz) δ 7.54 (t, J = 8.0 Hz, 2 H), 7.61−7.68 (m, 3
H), 7.84 (d, J = 16.0 Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 8.04−8.07
(m, 2 H), 8.27 (dd, J = 4.0 Hz, 4.0 Hz, 1 H), 8.52−8.53 (m, 1 H); 13C
{1H} NMR (CDCl3, 101 MHz) δ 122.4, 124.6, 124.7, 128.6, 128.8,
130.1, 130.3, 133.3, 134.4, 136.7, 141.7, 148.8, 189.7 ppm. Anal. Calcd
for C15H11NO3 Elemental Analysis: C, 71.14; H, 4.38; N, 5.53. Found:
C, 71.08; H, 4.42; N, 5.50.
(E)-3-(2-Nitrophenyl)-1-phenylprop-2-en-1-one (34):16k By
following the general procedure, the product was isolated as a pale
yellow solid, 81.0 mg (64%), flash chromatography (petroleum ether/
ethyl acetate, 10/1), mp = 112−114 °C (lit.17k mp = 111−113 °C);
1H NMR (CDCl3, 400 MHz) δ 7.32 (d, J = 12.0 Hz, 1 H), 7.50−7.63
(m, 4 H), 7.68−7.78 (m, 2 H), 8.01−8.03 (m, 2 H), 8.08 (d, J = 8.0
Hz, 1 H), 8.14 (d, J = 16.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101
MHz) δ 125.0, 127.4, 128.7, 128.8, 129.3, 130.4, 131.4, 133.2, 133.6,
137.4, 140.3, 148.6, 190.6 ppm. Anal. Calcd for C15H11NO3 Elemental
Analysis: C, 71.14; H, 4.38; N, 5.53. Found: C, 71.02; H, 4.45; N, 5.48.
(E)-3-(4-Fluorophenyl)-1-phenylprop-2-en-1-one (35):17l By
following the general procedure, the product was isolated as a colorless
solid, 79.1 mg (70%), flash chromatography (petroleum ether/ethyl
acetate, 30/1), mp = 83−85 °C (lit.17l mp = 83−84 °C); H NMR
1
(CDCl3, 400 MHz) δ 7.11 (t, J = 8.0 Hz, 2 H), 7.44−7.53 (m, 3 H),
7.58−7.66 (m, 3 H), 7.78 (d, J = 16.0 Hz, 1 H), 8.01−8.03 (m, 2 H);
13C {1H} NMR (CDCl3, 101 MHz) δ 116.1 (d, J = 22.0 Hz), 121.8 (d,
J = 3.0 Hz), 128.5, 128.7, 130.4 (d, J = 8.0 Hz), 131.2, 132.9, 138.1,
143.5, 164.1 (d, J = 251.0 Hz), 190.4 ppm. Anal. Calcd for C15H11FO
Elemental Analysis: C, 79.63; H, 4.90. Found: C, 79.78; H, 4.84.
(E)-3-(3-Fluorophenyl)-1-phenylprop-2-en-1-one (36). By
following the general procedure, the product was isolated as a
colorless solid, 76.8 mg (68%), flash chromatography (petroleum
ether/ethyl acetate, 30/1), mp = 86−88 °C (lit.17m mp = 87−89 °C);
1H NMR (CDCl3, 400 MHz) δ 7.34−7.40 (m, 2 H), 7.50−7.55 (m, 4
H), 7.58−7.64 (m, 2 H), 7.74 (d, J = 16.0 Hz, 1 H), 8.01−8.04 (m, 2
H); 13C {1H} NMR (CDCl3, 101 MHz) δ 123.3, 126.8, 127.9, 128.6,
I
DOI: 10.1021/acs.joc.5b00267
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
143.5, 143.6, 168.0, 189.6 ppm. Anal. Calcd for C18H14O3 Elemental
Analysis: C, 77.68; H, 5.07. Found: C, 77.61; H, 5.12.
resulting residue was purified by column chromatography on silica gel
to give the desired product 1 in 62% yield (1.3 g).
(E)-1-Phenyl-3-(pyridin-3-yl)prop-2-en-1-one (43):16n By fol-
lowing the general procedure, the product was isolated as a pale yellow
solid, 69.0 mg (66%), flash chromatography (petroleum ether/ethyl
acetate, 3/1), mp = 102−104 °C (lit.16n mp = 104−105 °C); 1H NMR
(CDCl3, 400 MHz) δ 7.28−7.31 (m, 1 H), 7.50−7.55 (m, 2 H), 7.59−
7.64 (m, 2 H), 7.80 (d, J = 16.0 Hz, 1 H), 7.98 (d, J = 8.0 Hz, 1 H),
8.02−8.04 (m, 2 H), 8.67 (s, 1 H), 8.91 (s, 1 H); 13C {1H} NMR
(CDCl3, 101 MHz) δ 124.0, 128.3, 128.6, 128.8, 129.9, 133.2, 135.0,
137.7, 140.8, 149.6, 150.7, 189.8 ppm. Anal. Calcd for C14H11NO
Elemental Analysis: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.60; H,
5.34; N, 6.54.
ASSOCIATED CONTENT
* Supporting Information
The screening of the reaction conditions, control experimental
■
S
1
details, radical trapping experimental details, and copies of H
and 13C {1H} NMR spectra for the products. This material is
available free of charge via the Internet athttp://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ccguo@hnu.edu.cn.
Notes
■
(E)-1-Phenyl-3-(pyridin-2-yl)prop-2-en-1-one (44):16o By fol-
lowing the general procedure, the product was isolated as a pale yellow
solid, 62.7 mg (60%), flash chromatography (petroleum ether/ethyl
The authors declare no competing financial interest.
acetate, 5/1), mp = 50−52 °C (lit.17n mp = 59−61 °C); H NMR
1
(CDCl3, 400 MHz) δ 7.30−7.33 (m, 1 H), 7.48−7.53 (m, 3 H), 7.60
(d, J = 8.0 Hz, 1 H), 7.74−7.80 (m, 2 H), 8.10−8.16 (m, 3 H), 8.69
(d, J = 4.0 Hz, 1 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 124.5,
125.5, 125.7, 128.7 128.8, 133.1, 137.0, 137.8, 142.7, 150.1, 153.2,
190.5 ppm. Anal. Calcd for C14H11NO Elemental Analysis: C, 80.36;
H, 5.30; N, 6.69. Found: C, 80.52; H, 5.36; N, 6.57.
ACKNOWLEDGMENTS
This work was supported by the National Natural Science
Foundation of China (Grant No. 21372068).
■
REFERENCES
■
(E)-1-Phenyl-3-(thiophen-2-yl)prop-2-en-1-one (45):16p By
following the general procedure, the product was isolated as yellow
solid, 77.0 mg (72%), flash chromatography (petroleum ether/ethyl
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acetate, 30/1), mp = 42−44 °C (lit.16p mp = 42−44 °C); H NMR
1
(CDCl3, 400 MHz) δ 7.00−7.02 (m, 1 H), 7.18−7.29 (m, 2 H), 7.34
(d, J = 4.0 Hz, 1 H), 7.41−7.44 (m, 2 H), 7.48−7.52 (m, 1 H), 7.87
(d, J = 16.0 Hz, 1 H), 7.92−7.94 (m, 2 H); 13C {1H} NMR (CDCl3,
101 MHz) δ 120.8, 128.3, 128.4, 128.6, 128.8, 132.1, 132.8, 137.2,
138.1, 140.4, 189.9 ppm. Anal. Calcd for C13H10OS Elemental
Analysis: C, 72.87; H, 4.70. Found: C, 72.98; H, 4.64.
(E)-3-(Furan-2-yl)-1-phenylprop-2-en-1-one (46):16n By fol-
lowing the general procedure, the product was isolated as a pale yellow
oil, 41.6 mg (42%), flash chromatography (petroleum ether/ethyl
1
acetate, 30/1); H NMR (CDCl3, 400 MHz) δ 6.52 (dd, J = 4.0 Hz,
4.0 Hz, 1 H), 6.73 (d, J = 4.0 Hz, 1 H), 7.45−7.68 (m, 6 H), 8.02−
8.04 (m, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 112.7, 116.3,
119.3, 128.4, 128.6, 130.7, 132.8, 138.2, 144.9, 151.7, 189.9 ppm;
LRMS: m/z calcd for C13H10O2 (M + H), 199; found, 199.
(2E,4E)-1-Phenylhexa-2,4-dien-1-one (47):16n By following the
general procedure, the product was isolated as a pale yellow solid, 27.5
mg (32%), flash chromatography (petroleum ether/ethyl acetate, 30/
1), mp = 45−47 °C (lit.16n mp = 45−46 °C); H NMR (CDCl3, 400
1
MHz) δ 1.90 (d, J = 4.0 Hz, 3 H), 6.24−6.38 (m, 2 H), 6.87 (d, J = 4.0
Hz, 1 H), 7.37−7.47 (m, 3 H), 7.49−7.55 (m, 1 H), 7.94 (d, J = 8.0
Hz, 2 H); 13C {1H} NMR (CDCl3, 101 MHz) δ 18.9, 123.4, 128.4,
128.5, 130.6, 132.6, 138.3, 141.2, 145.3, 191.0 ppm. Anal. Calcd for
C12H12O Elemental Analysis: C, 83.69; H, 7.02. Found: C, 83.85; H,
6.92.
Dypnone (48):16q By following the general procedure, the product
was isolated as a pale yellow oil, 62.2 mg (56%), flash chromatography
(petroleum ether/ethyl acetate, 30/1); 1H NMR (CDCl3, 400 MHz) δ
2.60 (s, 3 H), 7.17 (s, 1 H), 7.39−7.44 (m, 3 H), 7.45−7.49 (m, 2 H),
7.53−7.58 (m, 3 H), 7.98−8.00 (m, 2 H); 13C {1H} NMR (CDCl3,
101 MHz) δ 18.9, 122.1, 126.5, 128.3, 128.6, 128.7, 129.2, 132.6,
139.4, 142.8, 155.2, 191.9 ppm; LRMS: m/z calcd for C16H14O (M +
H), 223; found, 223.
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General Procedure for the Gram-Scale Reaction of
Benzoylformic Acid with Cinnamic Acid (Scheme 3). To a 100
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equiv), cinnamic acid (2.96 g, 20 mmol), K2S2O8 (2.5 equiv),
HCOONa·2H2O (2.0 equiv), and FeCl2 (10 mol %). The tube was
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J
DOI: 10.1021/acs.joc.5b00267
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DOI: 10.1021/acs.joc.5b00267
J. Org. Chem. XXXX, XXX, XXX−XXX