CuBr-promoted formal hydroacylation of 1-alkynes with glyoxal derivatives: An unexpected synthesis of 1,2-dicarbonyl-3-enes

Article abstract of DOI:10.1021/jo500199v

An efficient and concise protocol has been developed for the highly regio- and stereoselective synthesis of E-1,2-dicarbonyl-3-ene derivatives by a copper-promoted reaction of 1-alkynes with α-carbonyl aldehydes in the presence of morpholine. The products obtained are believed as the formal hydroacylation of the triple bond.

Full text of DOI:10.1021/jo500199v

Note
pubs.acs.org/joc
CuBr-Promoted Formal Hydroacylation of 1‑Alkynes with Glyoxal
Derivatives: An Unexpected Synthesis of 1,2-Dicarbonyl-3-enes
Shufeng Chen,* Xiaojie Li, Haiying Zhao, and Baoguo Li
Department of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, People’s Republic of China
S
* Supporting Information
ABSTRACT: An efficient and concise protocol has been developed for
the highly regio- and stereoselective synthesis of E-1,2-dicarbonyl-3-ene
derivatives by a copper-promoted reaction of 1-alkynes with α-carbonyl
aldehydes in the presence of morpholine. The products obtained are
believed as the formal hydroacylation of the triple bond.
uring recent years, considerable interest has focused on
the transition-metal-catalyzed Mannich-type three-com-
allene products with concomitant elimination of imine species,
́
D
were first reported by Crabbe and recently modified by Ma and
ponent coupling of an aldehyde, an alkyne, and an amine (A3-
coupling), which has been established as a convenient and
efficient approach toward propargylamines.1 Moreover, the A3-
coupling as well as different tandem reactions involving A3-
coupling has found widespread application in the synthesis of
various heterocycles, natural products, and biologically active
compounds.2 However, compared to the wide applications of
aromatic and aliphatic aldehydes in the A3-coupling reactions,
the use of glyoxals is barely documented.3 In 2005, Yamamoto
and co-workers developed a Cu-catalyzed A3-coupling route
from ethyl glyoxalate, N-benzylallylamine, and 1-alkyne to
alkynylglycinate (Scheme 1, eq 1).4 More recently, Liu and co-
co-workers.7 Our group has recently described a concise and
efficient method for the synthesis of allene ferrocenes based on
́
the modified Crabbe homologation reaction of ferrocenylace-
tylene with aromatic aldehydes in the presence of morpholine
using ZnI2 as the catalyst.8 In the context of ongoing projects
for the synthesis of allene derivatives, we envisioned that
glyoxals might also be considered as starting materials, which
can offer a series of buta-2,3-dienoates.
To test our hypothesis, we initially investigated the reaction
of phenylacetylene 1a, ethyl glyoxalate 2a, and morpholine 3a
in the presence of ZnI2 (Table 1, entry 1). To our surprise, no
expected allene product was obtained. Instead, the E-1,2-
dicarbonyl-3-ene 4a was obtained in 28% yield, as the only
stereoisomer under the reaction conditions. The configuration
of the CC bond in 4a was clearly demonstrated by the
olefinic coupling constant of 16.0 Hz. As we know, the 1,2-
dicarbonyl-3-enes are versatile building blocks in organic
synthesis;9 we decided to investigate this unexpected trans-
formation in detail.
Scheme 1
In order to obtain a maximum yield of the 1,2-dicarbonyl-3-
ene derivatives, different parameters were carefully screened,
and the results are summarized in Table 1. Interestingly, the
product 4a was increased in 55% yield when CuBr was used as
the catalyst (Table 1, entry 2). Other copper salts, such as CuI
and CuCl, also worked for this reaction, albeit with lower yields
(Table 1, entries 3 and 4). Notably, Cu(OTf)2 and AgOTf
showed no conversions (Table 1, entries 5 and 6); hence, we
used CuBr for the further optimizations. Next, diverse common
organic solvents were screened; dioxane was found to be the
most suitable solvent for this transformation, whereas a low
yield of 4a was obtained when THF, CH2Cl2, or CH3CN was
used as the solvent in this reaction (Table 1, entries 7−10).
Further investigation showed that polar solvent, such as
CH3NO2, was not suitable for this reaction (Table 1, entry
11). Next, the effect of bases on this novel reaction was
workers reported a AuBr3-catalyzed three-component coupling
reaction of phenylglyoxal derivatives, secondary amines, and
terminal alkynes for the synthesis of aminofurans (Scheme 1, eq
2).5 Lately, Hashmi and co-workers disclosed a AuCl-catalyzed
reaction of an α-ketoaldehyde and a terminal alkyne in the
presence of piperidine to afford 1,2-dicarbonyl-3-ene, which
was believed as the formal hydroacylation of the triple bond
(Scheme 1, eq 3).6
On the other hand, the A3-coupling-based tandem reactions,
followed by a 1,5-hydride shift, resulting in the formation of
Received: January 27, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo500199v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of Reaction Conditions
b
entry
cat. (mol %)
base
solvent
time (h)
yield (%)
1
2
ZnI2 (80)
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
morpholine
Et2NH
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
THF
4
7
7
7
7
7
2
4
4
4
2
4
4
4
4
2
2
2
2
28
CuBr (80)
CuI (80)
55
3
48
4
CuCl (80)
Cu(OTf)2 (80)
AgOTf (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (80)
CuBr (50)
CuBr (10)
CuBr (100)
CuBr (50)
16
5
trace
trace
75
6
7
8
58
9
CH2Cl2
CH3CN
CH3NO2
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
30
10
11
12
13
14
15
16
17
18
39
trace
20
Cy2NH
30
i-Pr2NH
32
pyrrolidine
morpholine
morpholine
morpholine
morpholine
trace
73
60
73
c
19
82
a
b
All the reactions were carried out with 1a (1.0 mmol), 2a (1.8 mmol), and base (1.7 mmol) in 3.0 mL of solvent if not otherwise indicated. Yield
c
of isolated product after chromatography. The ratio of 1a/2a/morpholine is 1.0:2.0:2.0 and in 3.0 mL of dioxane.
carefully examined. Among the bases tested, morpholine was
still found to be the most effective for this transformation. The
desired product 4a was obtained in moderate yield when
Et2NH, Cy2NH, or i-Pr2NH was employed in this reaction
(Table 1, entries 12−14). With pyrrolidine, no conversion was
detected (Table 1, entry 15). Moreover, the catalyst loading of
the reaction was evaluated, and 50 mol % was the best choice
(Table 1, entries 16−18). Furthermore, the ratio of substrates
was examined, and it was found that a 1a/2a/morpholine ratio
of 1.0:2.0:2.0 led to the highest yield of 4a (Table 1, entry 19).
With the optimized reaction conditions in hand, the scope
and generality of this new procedure using various terminal
alkynes as the substrates were studied, and the results are
summarized in Table 2. Simple ethyl glyoxalate 2a reacted with
phenylacetylene or subsitituted phenylacetylene to afford the
corresponding ethyl 2-oxo-3-butenoate derivatives in good
yields as well as high regio- and stereoselectivities (Table 2,
4a−4i). Besides, we were pleased to discover that ferroceny-
lacetylene is also compatible with this transformation, and with
excellent yield (Table 2, 4j). However, when aliphatic alkyne
was used instead of aromatic ones, no desired product was
detected (Table 2, 4k).
Table 2. CuBr-Promoted Reaction of Various Terminal
Alkynes with Ethyl Glyoxalate
a
To highlight the utility of this transformation, diverse α-
carbonyl aldehydes were subjected to the optimized reaction
conditions. The results are shown in Table 3. The reaction
tolerates a relatively small range of substituent on the
phenylglyoxals. It was found that the substrates with a phenyl
ring bearing a halogen group generally gave lower yields of the
products (Table 3, 4m−4o), whereas the substrates with an
electron-donating substituent on the phenyl ring, such as p-
CH3 and p-OCH3, resulted in slightly higher yields (Table 3, 4p
and 4q). However, 4r was obtained in only 25% yield most
probably due to the strong electron-withdrawing effect of the
a
All the reactions were carried out with 1-alkyne 1a−1k (1.0 mmol),
ethyl glyoxalate 2a (2.0 mmol), morpholine 3a (2.0 mmol), and CuBr
(0.5 mmol) in 3.0 mL of dioxane, and isolated yields were reported.
nitro group on the phenyl ring. Notably, the high regio- and
stereoselectivities were observed in all the cases, and only E-
isomers were obtained.
The corresponding 1,2-dicarbonyl-3-ene derivatives are
attractive and can be further converted in organic synthesis.9
B
dx.doi.org/10.1021/jo500199v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 3. CuBr-Promoted Reaction of Phenylacetylene 1a
with Various α-Carbonyl Aldehydes
Scheme 4. Proposed Mechanism of the Reaction
a
product 4a is afforded. The coupling constants (J = 15.5−16.5
1
Hz) in the H NMR spectrum support the E-configuration of
the vinyl motif.
In conclusion, we have established a convient CuBr-
promoted protocol for the synthesis of 1,2-dicarbonyl-3-ene
derivatives from readily available starting materials based on the
reaction of 1-alkynes and α-carbonyl aldehydes in the presence
of morpholine. Owing to the important applications of 1,2-
dicarbonyl-3-enes in the heterocycle syntheses, this reaction
will be of high interest to the scientific community.
a
All the reactions were carried out with phenylacetylene 1a (1.0
mmol), α-carbonyl aldehydes 2b−2h (2.0 mmol), morpholine 3a (2.0
mmol), and CuBr (0.5 mmol) in 3.0 mL of dioxane, and isolated yields
were reported.
EXPERIMENTAL SECTION
■
The synthetic potential of this methodology was demonstrated
by the reaction of 4a. The novel 2,3-dihydro-1H-pyrrolo[1,2-
a]indole 5a was obtained in good yield when 4a reacted with 3-
methylindole in the presence of copper(II) triflate (5 mol %) in
dichloromethane at room temperature for 10 h (Scheme 2).
General Information. All reagents were used as-received from
commercial sources, unless specified otherwise, or prepared as
described in the literature. All solvents were purified following
standard literature procedures.14 For chromatography, 200−300 mesh
silica gel (Qingdao, China) was employed. H and 13C NMR spectra
1
were recorded at 500 and 125 MHz using an FT-NMR spectrometer.
Chemical shifts are reported in parts per million (ppm) using
tetramethylsilane as internal standard when CDCl3 was used as
solvent. IR spectra were recorded on an FT-IR instrument. The
HRMS analysis was obtained on a QTOF mass spectrometer. Melting
points were determined with a melting points apparatus and are
uncorrected.
Scheme 2. Synthetic Application of 4a
General Procedure for the CuBr-Promoted Reaction of 1-
Alkynes with α-Carbonyl Aldehydes in the Presence of
Morpholine. To a solution of 1-alkynes (1.0 mmol), α-carbonyl
aldehydes (2.0 mmol), and morpholine (2.0 mmol) in dioxane (3.0
mL) was added CuBr (0.5 mmol) under a N2 atmosphere. The
resulting mixture was heated at 110 °C for the indicated time. After
completion of the reaction, the mixture was cooled to room
temperature. The solvent was removed in a vacuum, and the resulting
residue was purified on a silica gel column (petroleum ether/EtOAc)
to provide the desired 1,2-dicarbonyl-3-ene products 4.
Finally, considering the general application of this formal
hydroacylation reaction, we demonstrated the gram-scale
progress, and an example of large-scale reaction with
satisfactory yield of the product is shown in Scheme 3.
Scheme 3. Large-Scale Reaction
(E)-Ethyl 2-Oxo-4-phenyl-3-butenoate (4a).10 Yellow oil; 168 mg,
82% yield; IR (KBr) 2984, 1729, 1693, 1605, 983, 745 cm−1; 1H NMR
(500 MHz, CDCl3) δ 1.40 (t, J = 7.0 Hz, 3H), 4.38 (q, J = 7.0 Hz,
2H), 7.35 (d, J = 16.0 Hz, 1H), 7.38−7.45 (m, 3H), 7.60−7.61 (m,
2H), 7.83 (d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0,
62.4, 120.6, 129.0, 129.1, 131.6, 134.0, 148.3, 162.2, 182.8.
(E)-Ethyl 2-Oxo-4-p-tolylbut-3-enoate (4b).10 Yellow oil; 134 mg,
62% yield; IR (KBr) 2984, 1729, 1605, 983, 848 cm−1; 1H NMR (500
MHz, CDCl3) δ 1.41 (t, J = 7.0 Hz, 3H), 2.38 (s, 3H), 4.39 (q, J = 7.0
Hz, 2H), 7.22 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 16.0 Hz, 2H), 7.52 (d, J
= 7.5 Hz, 2H), 7.83 (d, J = 16.0 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 14.1, 21.6, 62.4, 119.6, 129.1, 129.9, 131.4, 142.5, 148.5,
162.4, 182.9.
On the basis of the above results and related literature,6 we
proposed a plausible mechanism to account for the CuBr-
promoted formal hydroacylation, as shown in Scheme 4. First, a
copper-catalyzed three-component coupling of a glyoxal, an
alkyne, and a morpholine occurred to afford carbonyl
propargylamine intermediate A via an A3-coupling reaction;
(E)-Ethyl 4-(4-Ethylphenyl)-2-oxobut-3-enoate (4c). Yellow oil;
1
the formation of intermediate A was further confirmed by H
1
129 mg, 56% yield; IR (KBr) 2967, 1729, 1600, 986, 831 cm−1; H
NMR analysis of the crude product. The intermediate A then
isomerizes to give the conjugated allenylamine intermediate B
in the presence of morpholine. After the hydrolysis of the
allenylamine intermediate B on silica gel, the corresponding
NMR (500 MHz, CDCl3) δ 1.25 (t, J = 7.5 Hz, 3H), 1.41 (t, J = 7.0
Hz, 3H), 2.68 (q, J = 7.5 Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H), 7.26 (d, J
= 8.0 Hz, 2H), 7.33 (d, J = 16.5 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.85
(d, J = 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 15.2, 30.0,
C
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The Journal of Organic Chemistry
Note
62.5, 119.6, 128.7, 129.2, 131.6, 148.6, 148.7, 162.4, 182.9; HRMS
(EI) calcd for C14H16O3 [M]+ 232.1099, found 232.1101.
Hz, 1H), 7.41−7.45 (m, 3H), 7.48 (d, J = 7.5 Hz, 2H), 7.60 (d, J = 7.0
Hz, 2H), 7.73 (d, J = 16.5 Hz, 1H), 8.00 (d, J = 7.0 Hz, 2H); 13C
NMR (125 MHz, CDCl3) δ 121.9, 128.9, 129.1, 129.3, 131.1, 131.6,
131.7, 133.9, 141.3, 149.0, 191.6, 191.7; HRMS (EI) calcd for
C16H11ClO2 [M]+ 270.0448, found 270.0451.
(E)-1-(4-Bromophenyl)-4-phenyl-3-butene-1,2-dione (4n). Yellow
solid; 90 mg, 29% yield; mp 65−67 °C (recrystallized from petroleum
ether and ethyl acetate at room temperature); IR (KBr) 2925, 1670,
1602, 952, 828 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.17 (d, J = 16.0
Hz, 1H), 7.41−7.47 (m, 3H), 7.60 (d, J = 6.5 Hz, 2H), 7.66 (d, J = 8.0
Hz, 2H), 7.73 (d, J = 16.5 Hz, 1H), 7.92 (d, J = 8.5 Hz, 2H); 13C
NMR (125 MHz, CDCl3) δ 121.9, 128.9, 129.1, 130.2, 131.3, 131.5,
131.7, 132.5, 133.9, 140.9, 191.6, 191.7; HRMS (EI) calcd for
C16H11BrO2 [M]+ 313.9942, found 313.9941.
(E)-Ethyl 2-Oxo-4-(4-pentylphenyl)but-3-enoate (4d).11 Yellow
oil; 169 mg, 62% yield; IR (KBr) 2929, 1729, 1601, 986, 785 cm−1; 1H
NMR (500 MHz, CDCl3) δ 0.89 (t, J = 7.0 Hz, 3H), 1.26−1.36 (m,
4H), 1.41 (t, J = 7.0 Hz, 3H), 1.62 (t, J = 7.0 Hz, 2H), 2.63 (t, J = 7.5
Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H), 7.23 (t, J = 8.0 Hz 2H), 7.33 (d, J =
16.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 16.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ 13.9, 14.0, 22.5, 29.7, 30.8, 35.9, 62.3,
119.6, 128.4, 129.2, 131.6, 147.5, 148.6, 162.4, 182.9.
(E)-Ethyl 4-(4-Methoxyphenyl)-2-oxobut-3-enoate (4e).10 Yellow
solid; 163 mg, 70% yield; mp 46−47 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
1
2991, 1724, 1596, 1002, 827 cm−1; H NMR (500 MHz, CDCl3) δ
(E)-1-(4-Iodophenyl)-4-phenyl-3-butene-1,2-dione (4o). Yellow
solid; 151 mg, 42% yield; mp 90−92 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
2923, 1664, 1604, 951, 859 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.16
(d, J = 16.5 Hz, 1H), 7.42−7.44 (m, 3H), 7.60 (d, J = 6.5 Hz, 2H),
7.72 (d, J = 16.5 Hz, 1H), 7.75 (d, J = 8.5 Hz, 2H), 7.89 (d, J = 8.5 Hz,
2H); 13C NMR (125 MHz, CDCl3) δ 103.4, 121.9, 129.0, 129.1,
131.4, 131.7, 132.1, 133.9, 138.3, 149.1, 191.7, 192.2; HRMS (ESI)
calcd for C16H12IO2 [M + 1]+ 362.9882, found 362.9871.
1.41 (t, J = 7.0 Hz, 3H), 3.86 (s,3H), 4.39 (q, J = 7.0 Hz, 2H), 6.93 (d,
J = 8.5 Hz, 1H), 7.24 (d, J = 16.0 Hz, 2H), 7.59 (d, J = 7.0 Hz, 2H),
7.83(d, J = 16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 55.5,
62.4, 114.6, 118.2, 126.8, 131.1, 148.3, 162.5, 162.6, 182.7.
(E)-Ethyl 4-(4-Chlorophenyl)-2-oxobut-3-enoate (4f).10 Yellow
solid; 135 mg, 57% yield; mp 76−78 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
2925, 1720, 1690, 1607, 1004, 832 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.42 (t, J = 7.0 Hz, 3H), 4.40 (q, J = 7.0 Hz, 2H), 7.35 (d, J
= 16.0 Hz, 1H), 7.40 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 7.81
(d, J = 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 62.6,
120.9, 129.4, 130.2, 132.5, 137.6, 146.8, 162.0, 182.5.
(E)-4-Phenyl-1-p-tolylbut-3-ene-1,2-dione (4p). Yellow oil; 154
1
mg, 62% yield; IR (KBr) 2923, 1665, 1602, 949, 834 cm−1; H NMR
(500 MHz, CDCl3) δ 2.40 (s, 3H), 7.11 (d, J = 16.5 Hz, 1H), 7.28 (d,
J = 8.0 Hz, 2H), 7.36−7.40 (m, 3H), 7.55 (d, J = 7.0 Hz, 2H), 7.68 (d,
J = 16.5 Hz, 1H), 7.93 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3) δ 21.9, 122.5, 128.8, 129.0, 129.6, 130.3, 131.5, 134.0, 145.9,
148.6, 192.9, 193.1; HRMS (EI) calcd for C17H14O2 [M]+ 250.0994,
found 250.0996.
(E)-Ethyl 4-(4-Bromophenyl)-2-oxobut-3-enoate (4g).10 Yellow
solid; 177 mg, 63% yield; mp 68−70 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
1
2922, 1720, 1606, 1004, 829 cm−1; H NMR (500 MHz, CDCl3) δ
1.42 (t, J = 7.0 Hz, 3H), 4.40 (q, J = 7.0 Hz, 2H), 7.37 (d, J = 16.5 Hz,
1H), 7.50 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 7.80 (d, J =
16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 62.6, 121.0, 126.1,
130.3, 132.4, 132.9, 146.8, 162.0, 182.6.
(E)-1-(4-Methoxyphenyl)-4-phenylbut-3-ene-1,2-dione (4q).13
Yellow solid; 151 mg, 57% yield; mp 82−84 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
2947, 1649, 1598, 944, 851 cm−1; 1H NMR (500 MHz, CDCl3) δ 3.87
(s, 3H), 6.97 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 16.0 Hz, 1H), 7.39−7.41
(m, 3H), 7.57 (d, J = 7.5 Hz, 2H), 7.69 (d, J = 16.5 Hz, 1H), 8.02 (d, J
= 9.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 55.6, 114.2, 122.6,
125.7, 128.8, 129.0, 131.4, 132.6, 134.0, 148.5, 164.8, 191.8, 193.2.
(E)-1-(4-Nitrophenyl)-4-phenylbut-3-ene-1,2-dione (4r). Yellow
solid; 70 mg, 25% yield; mp 128−130 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
2925, 1675, 1600, 959, 849 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.27
(d, J = 16.0 Hz, 1H), 7.42−7.48 (m, 3H), 7.63 (d, J = 7.0 Hz, 2H),
7.81 (d, J = 16.0 Hz, 1H), 8.24 (d, J = 9.0 Hz, 2H), 8.34 (d, J = 8.5 Hz,
2H); 13C NMR (125 MHz, CDCl3) δ 121.1, 123.9, 129.1, 129.2,
131.4, 132.0, 133.8, 137.3, 149.5, 150.9, 190.0, 190.4; HRMS (ESI)
calcd for C16H12NO4 [M + 1]+ 282.0766, found 282.0755.
(E)-Ethyl 4-(3-Bromophenyl)-2-oxobut-3-enoate (4h).12 Yellow
solid; 174 mg, 62% yield; mp 62−64 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
2983, 1724, 1612, 993, 863 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.42
(t, J = 7.0 Hz, 3H), 4.40 (q, J = 7.0 Hz, 2H), 7.30 (t, J = 8.0 Hz, 1H),
7.36 (d, J = 16.5 Hz, 1H), 7.54−7.57 (m, 2H), 7.74−7.78 (m, 2H);
13C NMR (125 MHz, CDCl3) δ 14.1, 62.7, 121.7, 123.2, 127.6, 130.6,
131.5, 134.3, 136.1, 146.4, 161.9, 182.4.
(E)-Ethyl 4-(4-Fluorophenyl)-2-oxobut-3-enoate (4i).10 Yellow
solid; 146 mg, 66% yield; mp 60−62 °C (recrystallized from
petroleum ether and ethyl acetate at room temperature); IR (KBr)
1
2989, 1723, 1592, 1004, 840 cm−1; H NMR (500 MHz, CDCl3) δ
1.42 (t, J = 7.0 Hz, 3H), 4.40 (q, J = 7.0 Hz, 2H), 7.13 (t, J = 8.5 Hz,
2H), 7.31 (d, J = 16.0 Hz 1H), 7.63−7.66 (m, 2H), 7.83 (d, J = 16.0
Hz,1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 62.6, 116.3, 116.5,
120.2, 130.3, 131.1, 147.0, 162.1, 163.7, 165.7, 182.6.
ASSOCIATED CONTENT
■
(E)-Ethyl 4-Ferrocenyl-2-oxobut-3-enoate (4j). Purple solid; 221
mg, 71% yield; mp 89−90 °C (recrystallized from petroleum ether and
ethyl acetate at room temperature); IR (KBr) 2976, 1720, 1663, 1100,
S
* Supporting Information
1
Copies of H and 13C NMR spectra for all new products. This
1
1030 cm−1; H NMR (500 MHz, CDCl3) δ 1.36 (t, J = 7.0 Hz, 3H),
material is available free of charge via the Internet at http://
pubs.acs.org.
4.23 (s, 5H), 4.31 (q, J = 7.0 Hz, 2H), 4,67 (t, J = 2.0 Hz, 2H), 4.89 (t,
J = 2.0 Hz, 2H), 6.92 (d, J = 15.5 Hz, 1H), 7.48 (d, J = 15.5 Hz, 1H);
13C NMR (125 MHz, CDCl3) δ 14.2, 61.3, 70.0, 70.4, 73.8, 79.7,
129.4, 137.3, 166.2, 191.8; HRMS (ESI) calcd for C16H17FeO3 [M +
1]+ 313.0527, found 313.0534.
AUTHOR INFORMATION
Corresponding Author
*E-mail: shufengchen@imu.edu.cn.
■
(E)-1,4-Diphenylbut-3-ene-1,2-dione (4l).6 Yellow oil; 100 mg,
43% yield; IR (KBr) 2925, 1675, 1596, 961, 863 cm−1; 1H NMR (500
MHz, CDCl3) δ 7.13 (d, J = 16.5 Hz, 1H), 7.39−7.45 (m, 3H), 7.51 (t,
J = 7.0 Hz, 2H), 7.59 (d, J = 7.0 Hz, 2H), 7.65 (t, J = 7.5 Hz, 1H), 7.71
(d, J = 16.5 Hz, 1H), 8.04 (d, J = 7.0, 2H); 13C NMR (125 MHz,
CDCl3) δ 122.4, 128.9, 129.1, 130.2, 131.6, 132.8, 134.0, 134.7, 148.9,
192.8, 193.3.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project was generously supported by the National Natural
Science Foundation of China (Nos. 21262023 and 20902044)
and the Program for Young Talents of Science and Technology
in Universities of Inner Mongolia Autonomous Region (NJYT-
12-B03).
(E)-1-(4-Chlorophenyl)-4-phenylbut-3-ene-1,2-dione (4m). Yellow
solid; 82 mg, 31% yield; mp 77−79 °C (recrystallized from petroleum
ether and ethyl acetate at room temperature); IR (KBr) 2931, 1667,
1602, 950, 837 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.17 (d, J = 16.5
D
dx.doi.org/10.1021/jo500199v | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
REFERENCES
■
(1) For selected reviews, see: (a) Wei, C. M.; Li, Z. G.; Li, C. J.
Synlett 2004, 1472. (b) Zani, L.; Bolm, C. Chem. Commun. 2006, 4263.
́
(c) Kouznetsov, V. V.; Vargas Mendez, L. Y. Synthesis 2008, 4, 491.
(d) Li, C. J. Acc. Chem. Res. 2010, 43, 581. (e) Yoo, W. J.; Zhao, L.; Li,
C. J. Aldrichimica Acta 2011, 44, 43. (f) Peshkov, V. A.; Pereshivko, O.
P.; Van der Eycken, E. V. Chem. Soc. Rev. 2012, 41, 3790.
(2) For a recent review, see: Liu, Y. Y. ARKIVOC 2014, 1, 1.
(3) For selected examples using glyoxylic acid as the substrate in A3-
coupling, see: (a) Zhang, Q.; Cheng, M.; Hu, X. Y.; Li, B. G.; Ji, J. X. J.
Am. Chem. Soc. 2010, 132, 7256. (b) Feng, H.; Ermolat’ev, D. S.; Song,
G.; Van der Eycken, E. V. Org. Lett. 2012, 14, 1942.
(4) Yamamoto, Y.; Hayashi, H.; Saigoku, T.; Nishiyama, H. J. Am.
Chem. Soc. 2005, 127, 10804.
(5) Li, J.; Liu, L.; Ding, D.; Sun, J.; Ji, Y.; Dong, J. Org. Lett. 2013, 15,
2884.
(6) During the preparation of this manuscript, one gold-catalyzed
diastereoselective hydroacylation of terminal alkynes with glyoxals for
the synthesis of 1,2-dicarbonyl-3-enes was published; see: Shi, S.;
Wang, T.; Weingand, V.; Rudolph, M.; Hashmi, A. S. K. Angew. Chem.,
Int. Ed. 2014, 53, 1148.
(7) (a) Rona, P.; Crabbe,
(b) Crabbe, P.; Fillion, H.; Andre,
Commun. 1979, 859. (c) Crabbe, P.; Andre,
Lett. 1979, 20, 893. (d) Searles, S.; Li, Y.; Nassim, B.; Lopes, M.-T. R.;
Tran, P. T.; Crabbe, P. J. Chem. Soc., Perkin Trans. 1 1984, 747.
́
P. J. Am. Chem. Soc. 1969, 91, 3289.
D.; Luche, J.-L. J. Chem. Soc., Chem.
D.; Fillion, H. Tetrahedron
́
́
́
́
́
(e) Kuang, J.; Ma, S. J. Org. Chem. 2009, 74, 1763. (f) Kuang, J.; Ma, S.
J. Am. Chem. Soc. 2010, 132, 1786.
(8) Chen, S.; Shi, J.; Wang, B.; Zhao, H.; Li, B. Appl. Organomet.
Chem. 2012, 26, 284.
(9) (a) Yusubov, M. S.; Filimonov, V. D.; Vasilyeva, V. P.; Chi, K.-W.
Synthesis 1995, 1234. (b) Katritzky, A. R.; Wang, Z.; Lang, H.; Feng,
D. J. Org. Chem. 1997, 62, 4125. (c) Hu, T. C.; Hsiao, P. I.; Wang, T.
H.; Yang, Y. W.; Chang, C. Y.; Wu, Y. H.; Sun, W. C.; Yu, M. S.; Lee,
C. Y.; Lo, Y. H. Dalton Trans. 2011, 40, 12663. (d) Belmessieri, D.;
Morrill, L. C.; Simal, C.; Slawin, A. M. Z.; Smith, A. D. J. Am. Chem.
Soc. 2011, 133, 2714. (e) Xu, Z.; Liu, L.; Wheeler, K.; Wang, H. Angew.
Chem., Int. Ed. 2011, 50, 3484. (f) Gremaud, L.; Alexakis, A. Angew.
Chem., Int. Ed. 2012, 51, 794. (g) Cheng, H.; Lu, L.; Wang, T.; Yang,
Q.; Liu, X.; Li, Y.; Deng, Q.; Chen, J.; Xiao, W. Angew. Chem., Int. Ed.
2013, 52, 3250.
(10) Meng, Q.; Zhu, L.; Zhang, Z. J. Org. Chem. 2008, 73, 7209.
(11) Srivastava, B. K.; Joharapurkar, A.; Raval, S.; Patel, J. Z.; Soni, R.;
Raval, P.; Gite, A.; Goswami, A.; Sadhwani, N.; Gandhi, N.; Patel, H.;
Mishra, B.; Solanki, M.; Pandey, B.; Jain, M. R.; Patel, P. R. J. Med.
Chem. 2007, 50, 5951.
(12) Gremaud, L.; Alexakis, A. Angew. Chem., Int. Ed. 2012, 51, 794.
(13) Kim, J.; Ryu, C. M. Bull. Korean Chem. Soc. 1987, 8, 246.
(14) Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory
Chemicals, 5th ed.; Butterworth-Heinemann: Burlington, MA, 2003.
E
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