Consecutive Alkynylation-Michael Addition-Cyclocondensation (AMAC) Multicomponent Syntheses of α-Pyrones and α-Pyridones

Article abstract of DOI:10.1055/s-0037-1610129

A novel consecutive three-component synthesis of α-pyrones is based upon an alkynylation-Michael addition-cyclocondensation (AMAC) sequence, starting from (hetero)aroyl chloride and terminal alkyne to furnish the alkynone which reacts with malonates to gi

Full text of DOI:10.1055/s-0037-1610129

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
paper
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N. Breuer, T. J. J. Müller
Paper
Synthesis
Consecutive Alkynylation–Michael Addition–Cyclocondensation
(AMAC) Multicomponent Syntheses of α-Pyrones and α-Pyridones
Natascha Breuer
Three-component
Alkynylation–Michael Addition–
Cyclocondensation (AMAC) Sequence
Thomas J. J. Müller*
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9-
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9
7-
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O
O
[PdCl2(PPh3)2, CuI]
NEt3, 1,4-dioxane, rt, 3 h
O
O
OR3
Institut für Organische Chemie und Makromolekulare Chemie,
Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1,
40225 Düsseldorf, Germany
+
R2
R1
R2
R1
Cl
then: CH2(COOR3)2
Na2CO3·10 H2O, 75 °C, 16 h
14 examples, 29–80%
ThomasJJ.Mueller@uni-duesseldorf.de
Received: 15.03.2018
Accepted after revision: 07.04.2018
Published online: 28.05.2018
keto esters to 1,2-allenyl ketones13 or alkynones14 has be-
come a general access to α-pyrones. Also, the 1,4-addition
of malonates to alkynones was studied by Kohler15 and
Barat.16
DOI: 10.1055/s-0037-1610129; Art ID: ss-2018-t0183-op
Abstract A novel consecutive three-component synthesis of α-py-
rones is based upon an alkynylation–Michael addition–cyclocondensa-
tion (AMAC) sequence, starting from (hetero)aroyl chloride and termi-
nal alkyne to furnish the alkynone which reacts with malonates to give
the α-pyrones in moderate to very good yields. By concatenating am-
monolysis of the α-pyrones, an alkynylation–Michael addition–cyclo-
condensation–ammonolysis (AMACA) synthesis of α-pyridones can be
conceived. α-Pyridone products with and without ester functionality
are obtained in moderate yields.
Interestingly, α-pyrones easily react with nucleophiles.
For instance, with ammonia or primary amines as nucleop-
hiles, they are readily transformed into α-pyridones.17 α-
Pyridones are isosteres of α-pyrones containing an amide
moiety. Like α-pyrones, α-pyridones are structural motifs
in various biologically active natural products, and some of
them find application as anticancer,18 antibacterial19 and
antiviral agents.20 Many synthetic routes to α-pyridones
have been reported, including copper(II)-catalyzed [3+2+1]
annulations of 2-aminopyridines and β-enamino esters,21
Michael addition–cyclocondensation of acetamides and
α,β-unsaturated ketones,22 nucleophilic addition of malonic
esters to alkynyl imines,23 and rhodium- and ruthenium-
catalyzed oxidative coupling of alkynes and acrylamides.24
Alkynones can be formed by catalytic alkynylation of
acid chlorides with terminal alkynes.25 Due to their en-
hanced Michael reactivity, alkynones constitute key inter-
mediates in consecutive multicomponent syntheses of het-
erocycles.26 In our group, we have developed several multi-
component syntheses with alkynones as key intermediates
for the synthesis of six-membered heterocycles, for exam-
ple pyrimidines27 and 5-acylpyridin-2(1H)-ones.28 There-
fore, a base-mediated addition of malonate to the in situ
generated alkynone could well evolve into a novel multi-
component synthesis of α-pyrones. Furthermore, their im-
mediate transformation into α-pyridones appears even
more rewarding. Herein, we report the consecutive alky-
nylation–Michael addition–cyclocondensation (AMAC)
multicomponent syntheses of α-pyrones and α-pyridones
initiated by catalytic alkynylation and subsequent reaction
with malonates, and also with amines.
Key words multicomponent reactions, C–C coupling, cyclocondensa-
tion, alkynes, heterocycles, palladium
α-Pyrones, six-membered unsaturated lactones,1 are
key motifs in many natural products, which have been iso-
lated from various animals, plants, marine organisms, bac-
teria, fungi and insects. These natural products exhibit a
wide range of biological activities, including antifungal, cy-
totoxic, neurotoxic and phytotoxic properties.2 α-Pyrones
display similar reactivity as aromatics,3 dienes4 and
enones,5 and as a consequence they have received consider-
able interest in the synthesis of polysubstituted arenes via
[4+2]/retro-[4+2] sequences.4b,6 Therefore, they have be-
come interesting building blocks for the synthesis of key in-
termediates in organic and medicinal chemistry.2a,7
Amongst various syntheses of α-pyrones, quite a number of
transition-metal-catalyzed routes have been developed.
Palladium-catalyzed methodologies employing alkynes as
key components were introduced by Larock,8 Burton9 and
Negishi.10 Also starting from alkynes, Miura11 and co-work-
ers reported a rhodium-catalyzed oxidative coupling reac-
tion of substituted acrylic acids with alkynes and alkenes,
and Ackermann12 introduced a ruthenium-catalyzed syn-
thesis towards α-pyrones. Furthermore, the addition of β-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

B
N. Breuer, T. J. J. Müller
Paper
Synthesis
The consecutive three-component synthesis of α-py-
rones commenced with Sonogashira coupling between acid
chloride 1 and terminal alkyne 2. Deviating from our stan-
dard alkynone synthesis,25 we could considerably lower the
catalyst loading to 0.25 mol% PdCl2(PPh3)2 and 0.50 mol%
CuI, as shown for the model reaction of benzoyl chloride
(1a) and phenylacetylene (2a), which upon stirring in 1,4-
dioxane at 20 °C for 3 hours furnished alkynone 3a in 89%
isolated yield (Scheme 1).
Table 1 Optimization of the Michael Addition–Cyclocondensation
Step in the Consecutive Three-Component Synthesis of α-Pyrone 5aa
Entry Base ([equiv])
Additive
([equiv])
Compound 5a
(isolated yield)b
1
2
3
4c
5
6
7
8
9
NaOEt (8.00)
–
no conversion
NaOEt (4.00)
–
no conversion
NaOEt (2.50)
–
15%
NaOEt (8.00)
–
8%
0.25 mol% PdCl2(PPh3)2
0.50 mol% CuI
NaOH (8.00)
–
traces
no conversion
35%
O
O
NaOAc (8.00)
–
1.05 equiv NEt3
Ph
Ph
+
Ph
Cl
Ph
Na2CO3·10 H2O (8.00)
Na2CO3·10 H2O (5.00)
Na2CO3·10 H2O (4.00)
Na2CO3 (4.00)
–
1,4-dioxane, 20 °C, 3 h
1a
2a
3a (89%)
–
64%
Scheme 1 Synthesis of 1,3-diphenylprop-2-yn-1-one (3a)
–
75%
10
–
2%
11
Na2CO3·10 H2O (3.00)
Na2CO3·10 H2O (3.00)
Na2CO3·10 H2O (2.50)
Na2CO3·10 H2O (3.00)
Na2CO3·10 H2O (3.00)
–
81%
With these optimized conditions for the alkynylation
step, the second Michael addition–cyclocondensation step
was directly probed en route, i.e. without isolation of the
alkynone (Scheme 2, Table 1). Therefore, directly after full
conversion into the alkynone 3a, diethyl malonate (4a) and
bases were added to the reaction mixture. Although for the
direct transformation of alkynone to α-pyrone, sodium
ethoxide has been reported to be effective,15,16 this base did
not work in a one-pot fashion. Only decreasing the amount
of sodium ethoxide to 2.50 equivalents led to a minor for-
mation of α-pyrone 5a (Table 1, entries 1–4).
12
H2O (15.0)
64%
13
–
–
–
74%
14d
15e
78%
64%
a All reactions were carried out on a 2.00 mmol scale (c0(1a) = 1.1 M,
c0(2a) = 1.0 M).
b All yields refer to isolated and purified products.
c Diethyl malonate (4a) (8.00 equiv).
d Diethyl malonate (4a) (2.00 equiv).
e Diethyl malonate (4a) (1.50 equiv).
0.25 mol% PdCl2(PPh3)2
O
O
0.50 mol% CuI
1.05 equiv NEt3
With the optimized conditions for the three-component
synthesis in hand, a variety of different acid chlorides 1, ter-
minal alkynes 2 and malonates 4 were employed (Scheme
3). The one-pot synthesis was performed to give 14 exam-
ples of α-pyrones 5 in moderate to very good isolated yields
(Table 2). The structures of the α-pyrones 5 were unambig-
uously assigned by 1H and 13C NMR and IR spectroscopy, as
well as by mass spectrometry. In addition, the constitution
was unambiguously corroborated for compound 5i by
NOESY, HSQC and HMBC NMR spectra. Electron-donating
and electron-withdrawing groups, as well as heterocyclic
substituents (5h, i), could uneventfully be introduced at the
4- and 6-position of the α-pyrone core by the alkynylation–
Michael addition–cyclocondensation sequence.
O
OEt
1,4-dioxane, 20 °C, 3 h
1a
+
2a
Ph
Ph
then: 2.50 equiv CH2(COOEt)2 (4a)
base, 75 °C, 16 h
5a
Scheme 2 Model reaction for optimization of the consecutive three-
component synthesis of α-pyrone 5a
Sodium hydroxide and sodium acetate as bases only
gave traces of α-pyrone 5a or did not lead to any product
formation at all (Table 1, entries 5 and 6). The addition of
8.00 equivalents of Na2CO3·10 H2O at least led to the forma-
tion of the desired product in 35% yield (Table 1, entry 7).
Lowering the amount of Na2CO3·10 H2O to 3.00 equivalents
enhanced the yield of compound 5a considerably (Table 1,
entries 8, 9 and 11). Further lowering, however, resulted in
a drop in yield (Table 1, entry 13). The necessity for the
presence of certain water was underlined by using anhy-
drous sodium carbonate, which only gave 2% yield (Table 1,
entry 10), while further addition of water to
3.00 equivalents of Na2CO3·10 H2O led to a reduced yield of
64% (Table 1, entry 12 vs entry 11). The amount of malonate
could be reduced to 2.00 equivalents (Table 1, entry 14),
while further lowering resulted in a drop in yield (Table 1,
entry 15).
0.25 mol% PdCl2(PPh3)2
O
O
0.50 mol% CuI
1.05 equiv NEt3
1,4-dioxane, 20 °C, 3 h
O
OR3
O
+
R2
R2
R1
Cl
R1
then: 2.00 equiv CH2(COOR3)2 (4)
3.00 equiv Na2CO3·10 H2O
75 °C, 16 h
5
1
2
14 examples, 29–80%
Scheme 3 Consecutive three-component alkynylation–Michael addi-
tion–cyclocondensation (AMAC) synthesis of α-pyrones 5 from acid
chlorides 1, terminal alkynes 2 and dialkyl malonates 4
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. Breuer, T. J. J. Müller
Paper
Synthesis
Table 2 Consecutive Three-Component Alkynylation–Michael Addition–Cyclocondensation (AMAC) Synthesis of α-Pyrones 5a
Entry
Acid chloride 1
Terminal alkyne 2
Dialkyl malonate 4
α-Pyrone 5b
O
O
O
OEt
1
R1 = Ph (1a)
R2 = Ph (2a)
R3 = Et (4a)
5a (78%)
O
O
O
OEt
2
3
4
5
6
7
8
R1 = 4-MeOC6H4 (1b)
R1 = 4-tBuC6H4 (1c)
R1 = 4-MeC6H4 (1d)
R1 = 4-FC6H4 (1e)
R1 = 2-ClC6H4 (1f)
R1 = 4-NCC6H4 (1g)
R1 = 2-furyl (1h)
2a
2a
2a
2a
2a
2a
2a
4a
4a
4a
4a
4a
4a
4a
MeO
5b (29%)
O
O
O
OEt
tBu
5c (58%)
O
O
O
OEt
Me
5d (65%)
O
O
O
OEt
F
5e (75%)
O
O
O
OEt
Cl
5f (80%)
O
O
O
OEt
NC
5g (50%)
O
O
O
OEt
O
5h (63%)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

D
N. Breuer, T. J. J. Müller
Paper
Synthesis
Table 2 (continued)
Entry
9
Acid chloride 1
Terminal alkyne 2
Dialkyl malonate 4
α-Pyrone 5b
O
O
O
OEt
R1 = 2-thienyl (1i)
2a
4a
S
5i (64%)
O
O
O
OEt
10
11
12
1a
1a
1a
R2 = 4-MeOC6H4 (2b)
R2 = 4-MeC6H4 (2c)
R2 = 4-ClC6H4 (2d)
4a
4a
4a
OMe
Me
Cl
5j (65%)
O
O
O
O
O
O
O
O
O
OEt
OEt
OEt
OMe
5k (54%)
O
5l (43%)
O
13
14
1a
1a
R2 = 4-NCC6H4 (2e)
4a
CN
5m (37%)
O
2a
R3 = Me (4b)
5n (52%)
a All reactions were carried out on a 2.00 mmol scale (c0(1) = 1.1 M, c0(2) = 1.0 M, c0(4) = 2.0 M).
b All yields refer to isolated and purified products.
The consecutive three-component synthesis of α-py-
rones 5 can be extended to a four-component synthesis of
α-pyridones by in situ reaction with ammonia. However,
two α-pyridone derivatives are formed, one with and one
without the ester substituent.29 Starting from ethyl 2-oxo-
4,6-diphenyl-2H-pyran-3-carboxylate (5a), we also ob-
served the formation of two α-pyridones, 6a and 7a
(Scheme 4, Table 3). Besides the expected ester-substituted
α-pyridone 6a (21%), the α-pyridone 7a devoid of an ester
function could be isolated in 70% yield (Table 3, entry 1).
Neither a longer reaction time (Table 3, entry 2) nor an in-
creased amount of ammonia solution (Table 3, entry 3) sig-
nificantly changed the product ratio or the yield.
O
O
O
CO2Et
Ph
CO2Et
Ph
1,4-dioxane
80 °C
O
HN
HN
+
+ NH3
Ph
Ph
Ph
Ph
5a
6a
7a
Scheme 4 Model reaction for optimization of the transformation of α-
pyrone 5a into α-pyridones 6a and 7a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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N. Breuer, T. J. J. Müller
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Synthesis
Table 3 Optimization of the Synthesis of Ethyl 2-Oxo-4,6-diphenyl-
1,2-dihydropyridine-3-carboxylate (6a) and 4,6-Diphenylpyridin-2(1H)-
one (7a) from Ethyl 2-Oxo-4,6-diphenyl-2H-pyran-3-carboxylate (5a)a
With the optimized reaction conditions in hand, two
examples of α-pyridones 6 and four examples of 7 were
synthesized, in low to moderate yields (Scheme 5, Table 5),
thereby extending the one-pot process by an additional
step to an alkynylation–Michael addition–cyclocondensa-
tion–ammonolysis sequence. Interestingly, both electron-
rich and electron-deficient substituted aroyl chlorides and
arylacetylenes only furnished the ester-cleaved products
7b–d (Table 5, entries 2, 3 and 5). However, the strongly
electron-withdrawing 4-cyanophenyl substituent at posi-
tion R1 does not allow ammonolysis and, therefore, only α-
pyrone 5g was isolated (Table 5, entry 4). All this can be ac-
counted for by a crucial influence of the electron density
distribution in α-pyrone 5 and, thereby, modulation of its
electrophilicity.
Entry
25% Aqueous ammonia Time
α-Pyridone α-Pyridone
6ab 7ab
solution (equiv)
(h)
1
2
3
64.0
64.0
128
0.5
21%
70%
3
23%
23%
70%
63%
0.5
a All reactions were carried out on a 1.00 mmol scale (c0(5a) = 1.0 M).
b All yields refer to isolated and purified products.
Next, the formation of α-pyrone 5a was concatenated
with ammonolysis to give α-pyridones 6a and 7a in an
alkynylation–Michael addition–cyclocondensation–ammo-
nolysis (AMACA) sequence. Indeed, after the addition of
aqueous ammonia and reaction at 90 °C for 3 hours, α-pyri-
dones 6a and 7a were isolated in a combined yield of 67%
(Table 4, entry 1). Increasing the reaction time to 4 hours
only slightly increased the yield of both α-pyridones (Table
4, entry 2), but a further increase in the reaction time did
not increase the yield (Table 4, entry 3). Using less ammonia
solution led to a prolonged reaction time of 24 hours and a
decreased overall yield (Table 4, entry 4). The use of ammo-
nia solution in 1,4-dioxane instead of the aqueous solution
also led to a prolonged reaction time and isolated yields of
40–50% (Table 4, entries 5 and 6).
0.25 mol% PdCl2(PPh3)2
O
0.50 mol% CuI
R4
1.05 equiv NEt3
1,4-dioxane, 20 °C, 3 h
HN
O
+
R2
R1
R2
R1
Cl
then: 2.00 equiv CH2(COOR3)2 (4)
3.00 equiv Na2CO3·10 H2O
75 °C, 16 h
6
1
2
R4 = CO2R3, 3% and 16%
then: 64.0 equiv NH3, 90 °C, 4 h
7
R4 = H, 4 examples
19–57%
Scheme 5 Consecutive four-component alkynylation–Michael addi-
tion–cyclocondensation–ammonolysis (AMACA) synthesis of α-pyri-
dones 6 and 7 from acid chlorides 1, terminal alkynes 2, dialkyl
malonates 4 and ammonia
Based upon an alkynylation–Michael addition–cyclo-
condensation (AMAC) sequence by way of a consecutive
three-component reaction, we have developed a novel one-
pot synthesis of α-pyrones. Furthermore, upon concatena-
tion of an ammonolysis, a four-component synthesis of α-
pyridones could be realized. This alkynylation–Michael ad-
Table 4 Optimization of the Ammonolysis Step in the Consecutive
Four-Component Alkynylation–Michael Addition–Cyclocondensation–
Ammonolysis (AMACA) Synthesis of Ethyl 2-Oxo-4,6-diphenyl-1,2-dihy-
dropyridine-3-carboxylate (6a) and 4,6-Diphenylpyridin-2(1H)-one (7a)
in a One-Pot Fashiona
dition–cyclocondensation–ammonolysis
(AMACA)
se-
Entry 25% Aqueous ammonia Time (h) α-Pyridone
α-Pyridone
solution (equiv)
6ab
7ab
quence interestingly gives α-pyridones, however predomi-
nantly the products without esters as a consequence of
cleavage. The dense presence of diene and lactone function-
alities is predestined for further concatenations of elemen-
tary processes. Studies directed to enhance the molecular
diversity and structural complexity based upon AMAC se-
quences are currently underway.
1
2
3
4
5
6
64.0
64.0
64.0
6.40
1.50c
3.00c
3
4
12%
55%
57%
55%
24%
30%
30%
16%
15%
4%
5
24
24
24
10%
20%
a All reactions were carried out on a 1.00 mmol scale (c0(1a) = 1.1 M, c0(2a)
= 1.0 M, c0(4a) = 2.0 M, c0(Na2CO3·10 H2O) = 3.0 M).
b All yields refer to isolated and purified products.
All reactions were performed in dried Schlenk tubes under a nitrogen
atmosphere. TLC was used to monitor the reaction progress qualita-
tively, using silica gel coated aluminum foil. For detection, UV light of
wavelengths 254 and 366 nm was employed. Commercially available
chemicals were used as received without any further purification. 1H,
13C and DEPT NMR spectra were recorded in CDCl3 or DMSO-d6 on a
300 MHz (Bruker Avance III 300) or 600 MHz (Bruker Avance III 600)
NMR spectrometer. Chemical shifts are referenced to the internal sol-
vent signal: CDCl3 (1H, δ 7.26; 13C, δ 77.2), DMSO-d6 (1H, δ 2.50; 13C,
δ 39.5). Multiplicities are stated as s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet). Coupling constants (J) are given in hertz. The
assignment of primary (CH3), secondary (CH2), tertiary (CH) and qua-
c Employed as a 0.5 M solution in 1,4-dioxane.
We also tried to cleave the ester group by addition of
concentrated sulfuric acid, aiming to obtain only α-pyri-
done 7a at the end of the sequence. However, no changes in
the yield and ratio of 6a and 7a were detected. Therefore,
we reasoned that the ester cleavage rather occurs as a con-
sequence of ring opening by ammonolysis.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

F
N. Breuer, T. J. J. Müller
Paper
Synthesis
Table 5 Consecutive Four-Component Alkynylation–Michael Addition–Cyclocondensation–Ammonolysis (AMACA) Synthesis of α-Pyridones 6 and 7a
Entry
Acid chloride 1
Terminal alkyne 2
Dialkyl malonate 4
α-Pyridone 6b
α-Pyridone 7b
O
O
O
HN
HN
OEt
1
R1 = Ph (1a)
R2 = Ph (2a)
R3 = Et (4a)
6a (16%)
7a (57%)
O
HN
2
R1 = 4-MeOC6H4 (1b)
2a
4a
–
MeO
7b (19%)
O
HN
3
4
5
R1 = 4-F3CC6H4 (1j)
R1 = 4-NCC6H4 (1g)
1a
2a
4a
4a
4a
–
–
–
F3C
7c (30%)
c
2a
–
O
HN
R2 = 4-MeOC6H4 (2b)
OMe
7d (24%)
O
O
O
HN
HN
OMe
6
1a
2a
R3 = Me (4b)
6b (3%)
7a (31%)
a All reactions were carried out on a 2.00 mmol scale (c0(1) = 1.1 M, c0(2) = 1.0 M, c0(4) = 2.0 M).
b All yields refer to isolated and purified products.
c Compound 5g (13%) was isolated instead.
ternary (Cquat) carbon nuclei was made by using DEPT-135 spectra.
Mass spectroscopic measurements were conducted on a quadrupole
(EI) analyzer (TSQ 7000, Finnigan MAT). IR spectra were measured us-
ing the ATR technique (Shimadzu IRAffinity-1). The intensities of the
IR bands are abbreviated as w (weak), m (medium), s (strong) and vs
(very strong). Elemental analyses were carried out on a Perkin Elmer
Series II Analyzer 2400 in the microanalytical laboratory of the Phar-
mazeutisches Institut of the Heinrich-Heine-Universität Düsseldorf.
Uncorrected melting points and were determined with a Reichert
Thermovar melting point microscope (heating unit: PeakTech 6000A
DC Power Supply; thermometry: Norma D2400 (digital)).
(640 mg, 4.00 mmol) were added and stirring at 75 °C was continued
for 16 h. After the addition of brine (2.00 mL), the solution was ex-
tracted with CH2Cl2 (3 × 50.0 mL). The combined organic layers were
dried (anhydrous MgSO4) and the solvent was removed in vacuo. The
residue was purified by flash chromatography on silica gel (n-hex-
ane–EtOAc, 20:1 → 10:1).
Ethyl 2-Oxo-4,6-diphenyl-2H-pyran-3-carboxylate (5a)
According to GP1 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and phenylacetylene (2a) (209 mg, 2.00 mmol), 5a (519 mg,
1.62 mmol, 78%) was obtained as a colorless solid; mp 112 °C.
IR (ATR): 3061 (w), 3005 (w), 2984 (w), 2938 (w), 1728 (m), 1715 (w),
1674 (m), 1622 (m), 1578 (w), 1530 (s), 1495 (m), 1466 (w), 1451
(m), 1439 (w), 1379 (m), 1258 (m), 1188 (w), 1121 (s), 1092 (m),
1080 (m), 1053 (w), 1024 (s), 995 (w), 949 (w), 939 (w), 845 (w), 835
(w), 762 (s), 750 (m), 710 (s), 689 (s), 667 (w), 637 (m) cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 1.05 (t, J = 7.1 Hz, 3 H), 4.16 (q, J = 7.1
Hz, 2 H), 6.78 (s, 1 H), 7.40–7.56 (m, 8 H), 7.82–7.94 (m, 2 H).
2-Oxo-2H-pyran-3-carboxylates 5; General Procedure (GP 1)
PdCl2(PPh3)2 (3.50 mg, 5.00 μmol, 0.25 mol%) and CuI (1.90 mg,
10.0 μmol, 0.50 mol%) were placed in a dry Schlenk tube under a ni-
trogen atmosphere and anhydrous 1,4-dioxane (2.00 mL) was added.
An acid chloride 1 (2.20 mmol), a terminal alkyne 2 (2.00 mmol) and
NEt3 (212 mg, 2.10 mmol) were added and the mixture was stirred at
20 °C for 3 h until complete conversion (monitored by TLC). After-
wards, Na2CO3·10 H2O (1.72 g, 6.00 mmol) and diethyl malonate (4a)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

G
N. Breuer, T. J. J. Müller
Paper
Synthesis
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 61.9 (CH2), 103.6 (CH),
116.8 (Cquat), 126.1 (CH), 127.3 (CH), 129.0 (CH), 129.2 (CH), 130.3
(CH), 130.9 (Cquat), 131.7 (CH), 136.5 (Cquat), 155.5 (Cquat), 159.5 (Cquat),
160.7 (Cquat), 164.9 (Cquat).
EI-MS (70 eV): m/z (%) = 377 ([M + H]+, 11), 376 ([M]+, 43), 349 (15),
348 ([M – CO]+, 57), 334 (25), 333 ([M – C2H3O]+, 100), 331 ([M –
C2H5O]+, 14), 291 (16), 276 ([M – C4H6O3]+, 10), 161 ([M – C13H11O3]+,
28), 144 (10), 77 ([M – C18H19O4]+, 3), 57 ([M – C20H15O4]+, 7).
EI-MS (70 eV): m/z (%) = 320 ([M]+, 43), 292 ([M – C2H6]+, 63), 276 ([M
– CO2]+, 5), 275 ([M – C2H5O]+, 23), 247 ([M – C3H5O2]+, 11), 220 (100),
191 ([M – C5H5O4]+, 34), 165 ([M – C12H9]+, 7), 129 ([M – C15H11]+, 3),
77 ([M – C14H11O4]+, 24).
Anal. Calcd for C24H24O4 (376.2): C, 76.51; H, 6.93. Found: C, 76.32; H,
6.64.
Ethyl 2-Oxo-4-phenyl-6-(p-tolyl)-2H-pyran-3-carboxylate (5d)
Anal. Calcd for C20H16O4 (320.3): C, 74.99; H, 5.03. Found: C, 75.14; H,
5.23.
According to GP1 using 4-methylbenzoyl chloride (1d) (347 mg,
2.20 mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5d
(453 mg, 1.30 mmol, 65%) was obtained as a yellow solid; mp 80–
89 °C.
Ethyl 6-(4-Methoxyphenyl)-2-oxo-4-phenyl-2H-pyran-3-carboxyl-
ate (5b)
IR (ATR): 3055 (w), 2980 (w), 2864 (w), 2729 (w), 2359 (w), 1730 (m),
1691 (m), 1622 (m), 1580 (w), 1530 (s), 1510 (m), 1462 (w), 1443 (w),
1414 (w), 1375 (m), 1260 (m), 1244 (m), 1190 (m), 1115 (m), 1107
(m), 1018 (m), 1001 (w), 949 (w), 928 (w), 851 (w), 820 (s), 766 (s),
746 (m), 700 (s), 650 (w), 637 (m), 617 cm–1 (m).
According to GP1 using 4-methoxybenzoyl chloride (1b) (344 mg,
2.20 mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5b
(199 mg, 0.570 mmol, 29%) was obtained as a yellow solid; mp 99–
100 °C.
IR (ATR): 3011 (w), 2980 (w), 2940 (w), 2901 (w), 2845 (w), 1728 (s),
1688 (s), 1618 (m), 1605 (m), 1576 (w), 1530 (m), 1504 (vs), 1445
(m), 1425 (m), 1381 (w), 1369 (w), 1300 (m), 1260 (s), 1240 (m),
1182 (s), 1119 (m), 1090 (m), 1078 (m), 1057 (m), 1026 (s), 1001 (m),
949 (w), 928 (w), 856 (m), 827 (s), 814 (m), 768 (s), 748 (m), 700 (m),
652 (m) cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 1.03 (t, J = 7.1 Hz, 3 H), 3.87 (s, 3 H),
4.14 (q, J = 7.1 Hz, 2 H), 6.66 (s, 1 H), 6.92–7.01 (m, 2 H), 7.41–7.50 (m,
5 H), 7.79–7.87 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 55.7 (CH3), 61.8 (CH2), 102.2
(CH), 114.6 (CH), 115.4 (Cquat), 123.4 (Cquat), 127.3 (CH), 128.0 (CH),
128.9 (CH), 130.1 (CH), 136.9 (Cquat), 156.1 (Cquat), 159.6 (Cquat), 161.0
(Cquat), 162.5 (Cquat), 165.1 (Cquat).
1H NMR (300 MHz, CDCl3): δ = 1.04 (t, J = 7.1 Hz, 3 H), 2.41 (s, 3 H),
4.15 (q, J = 7.1 Hz, 2 H), 6.73 (s, 1 H), 7.23–7.32 (m, 2 H), 7.42–7.50 (m,
5 H), 7.74–7.81 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 21.7 (CH3), 61.8 (CH2), 103.0
(CH), 116.2 (Cquat), 126.1 (CH), 127.3 (CH), 128.1 (Cquat), 129.0 (CH),
129.9 (CH), 130.2 (CH), 136.7 (Cquat), 142.4 (Cquat), 155.8 (Cquat), 159.6
(Cquat), 161.0 (Cquat), 165.0 (Cquat).
EI-MS (70 eV): m/z (%) = 335 ([M + H]+, 12), 334 ([M]+, 51), 307 (16),
306 ([M – CO]+, 71), 289 ([M – C2H5O]+, 23), 278 ([M – C3H4O]+, 13),
261 ([M – C3H5O2]+, 10), 235 (19), 234 ([M – C4H4O3]+, 100), 205 ([M –
C5H5O4]+, 26), 119 ([M – C13H11O3]+, 44), 91 ([M – C14H11O4]+, 24), 77
([M – C15H13O4]+, 4).
Anal. Calcd for C21H18O4 (334.1): C, 75.43; H, 5.43. Found: C, 75.17; H,
5.72.
EI-MS (70 eV): m/z (%) = 351 ([M + H]+, 23), 350 ([M]+, 99), 323 (21),
322 ([M – CO]+, 100), 305 ([M – C2H5O]+, 26), 294 ([M – C3H4O]+, 18),
277 ([M – C3H5O2]+, 11), 251 (20), 250 ([M – C4H4O3]+, 96), 221 ([M –
C5H5O4]+, 30), 178 (15), 152 (15), 135 ([M – C13H11O3]+, 81), 77 ([M –
Ethyl 6-(4-Fluorophenyl)-2-oxo-4-phenyl-2H-pyran-3-carboxylate
(5e)
C
15H13O5]+, 16).
According to GP1 using 4-fluorobenzoyl chloride (1e) (355 mg, 2.20
mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5e (509 mg,
1.50 mmol, 75%) was obtained as a yellow solid; mp 143 °C.
Anal. Calcd for C21H18O5 (350.1): C, 71.99; H, 5.18. Found: C, 72.07; H,
5.27.
IR (ATR): 3152 (w), 3094 (w), 3057 (w), 2988 (w), 2967 (w), 2899 (w),
1730 (m), 1688 (s), 1624 (m), 1599 (w), 1578 (w), 1533 (m), 1506 (s),
1464 (w), 1443 (w), 1418 (m), 1379 (m), 1301 (w), 1260 (m), 1233
(m), 1163 (m), 1121 (m), 1092 (m), 1078 (m), 1053 (w), 1024 (m),
1011 (m), 999 (m), 949 (m), 930 (m), 835 (s), 814 (w), 797 (w), 785
(w), 768 (vs), 748 (m), 702 (s), 631 cm–1 (w).
Ethyl 6-(4-tert-Butylphenyl)-2-oxo-4-phenyl-2H-pyran-3-carbox-
ylate (5c)
According to GP1 using 4-tert-butylbenzoyl chloride (1c) (439 mg,
2.20 mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5c
(437 mg, 1.16 mmol, 58%) was obtained as a yellow resin.
IR (ATR): 3088 (w), 3061 (w), 3030 (w), 2963 (w), 2905 (w), 2870 (w),
1709 (vs), 1622 (m), 1578 (w), 1530 (s), 1512 (s), 1464 (w), 1445 (w),
1414 (w), 1377 (m), 1346 (w), 1260 (s), 1200 (w), 1186 (m), 1117 (s),
1078 (w), 1047 (m), 1022 (m), 1015 (m), 945 (w), 827 (m), 787 (w),
768 (s), 743 (m), 698 (s), 640 (m), 613 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 1.05 (t, J = 7.1 Hz, 3 H), 1.35 (s, 9 H),
4.15 (q, J = 7.1 Hz, 2 H), 6.74 (s, 1 H), 7.43–7.52 (m, 7 H), 7.78–7.84 (m,
2 H).
1H NMR (300 MHz, CDCl3): δ = 1.05 (t, J = 7.1 Hz, 3 H), 4.15 (q, J = 7.1
Hz, 2 H), 6.71 (s, 1 H), 7.14–7.19 (m, 2 H), 7.43–7.49 (m, 5 H), 7.84–
7.90 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 61.9 (CH2), 103.4 (CH),
116.3 (CH), 116.6 (d, J = 2.0 Hz, Cquat), 127.2 (d, J = 3.3 Hz, Cquat), 127.3
(CH), 128.4 (d, J = 8.8 Hz, CH), 129.0 (CH), 130.3 (CH), 136.4 (Cquat),
155.6 (Cquat), 159.3 (Cquat), 159.5 (Cquat), 164.76 (d, J = 254 Hz, Cquat),
164.82 (Cquat).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 31.2 (CH3), 35.2 (Cquat), 61.9
(CH2), 103.1 (CH), 116.3 (Cquat), 126.0 (CH), 126.2 (CH), 127.4 (CH),
128.1 (Cquat), 129.0 (CH), 130.2 (CH), 136.7 (Cquat), 155.5 (Cquat), 155.8
(Cquat), 159.6 (Cquat), 161.1 (Cquat), 165.0 (Cquat).
EI-MS (70 eV): m/z (%) = 339 ([M + H]+, 12), 338 ([M]+, 49), 311 (15),
310 ([M – C2H4]+, 72), 293 ([M – C2H5O]+, 29), 282 ([M – C3H4O]+, 15),
265 ([M – C3H5O2]+, 15), 239 (19), 238 ([M – C4H4O3]+, 100), 210 (11),
209 (33), 207 ([M - C5H7O4]+, 15), 123 ([M – C13H11O3]+, 59), 95 ([M –
C
14H11O4]+, 25), 77 ([M – C14H10FO4]+, 3).
Anal. Calcd for C20H15FO4 (338.3): C, 71.00; H, 4.47. Found: C, 70.94;
H, 4.56.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

H
N. Breuer, T. J. J. Müller
Paper
Synthesis
Ethyl6-(2-Chlorophenyl)-2-oxo-4-phenyl-2H-pyran-3-carboxylate
(5f)
IR (ATR): 3146 (w), 3117 (w), 3003 (w), 2978 (w), 2963 (w), 2934 (w),
2897 (w), 2870 (w), 1724 (m), 1705 (s), 1628 (m), 1580 (w), 1562 (w),
1518 (m), 1491 (w), 1476 (m), 1464 (m), 1443 (w), 1404 (w), 1371
(m), 1346 (w), 1300 (w), 1265 (m), 1240 (m), 1231 (m), 1188 (m),
1163 (w), 1109 (s), 1080 (m), 1063 (m), 1018 (m), 1001 (m), 953 (w),
925 (w), 883 (m), 827 (m), 785 (s), 766 (s), 737 (m), 700 (s), 665 (w),
648 (w), 629 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 1.04 (t, J = 7.1 Hz, 3 H), 4.14 (q, J = 7.1
Hz, 2 H), 6.58 (dd, J = 3.6, 1.8 Hz, 1 H), 6.69 (s, 1 H), 7.09–7.13 (m, 1 H),
7.45 (d, J = 2.4 Hz, 5 H), 7.54 (dd, J = 1.8, 0.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 61.9 (CH2), 101.8 (CH),
112.9 (CH), 113.6 (CH), 116.1 (Cquat), 127.3 (CH), 129.0 (CH), 130.3
(CH), 136.4 (Cquat), 145.7 (CH), 146.2 (Cquat), 152.4 (Cquat), 155.8 (Cquat),
158.7 (Cquat), 164.9 (Cquat).
EI-MS (70 eV): m/z (%) = 311 ([M + H]+, 18), 310 ([M]+, 88), 283 (19),
282 ([M – CO]+, 94), 265 ([M – C2H5O]+, 36), 254 (20), 237 ([M –
C3H5O2]+, 12), 211 (15), 210 ([M – C4H4O3]+, 100), 197 ([M – C5H5O3]+,
14), 181 ([M – C5H5O4]+, 31), 153 (14), 152 (31), 95 ([M – C13H11O3]+,
54), 77 ([M – C12H9O5]+, 5), 67 ([M – C14H11O4]+, 2).
According to GP1 using 2-chlorobenzoyl chloride (1f) (400 mg, 2.22
mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5f (568 mg,
1.60 mmol, 80%) was obtained as an orange solid; mp 94–98 °C.
IR (ATR): 3073 (w), 2984 (w), 2936 (w), 2868 (w), 2849 (w), 2355 (w),
1738 (s), 1699 (s), 1674 (w), 1632 (m), 1616 (w), 1589 (w), 1545 (m),
1493 (w), 1470 (w), 1441 (w), 1377 (m), 1348 (w), 1271 (m), 1250
(m), 1192 (m), 1180 (w), 1121 (m), 1111 (m), 1099 (w), 1072 (w),
1020 (m), 999 (w), 980 (w), 949 (w), 922 (w), 849 (w), 841 (m), 827
(w), 766 (vs), 748 (m), 700 (vs), 685 (w), 654 (w), 638 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 1.09 (t, J = 7.1 Hz, 3 H), 4.19 (q, J = 7.2
Hz, 2 H), 6.89 (s, 1 H), 7.34–7.53 (m, 8 H), 7.65–7.80 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 62.1 (CH2), 109.4 (CH),
117.7 (Cquat), 127.4 (CH), 127.5 (CH), 129.1 (CH), 130.5 (CH), 130.6
(Cquat), 130.9 (CH), 131.1 (CH), 131.9 (CH), 132.5 (Cquat), 136.1 (Cquat),
154.6 (Cquat), 158.3 (Cquat), 159.5 (Cquat), 164.8 (Cquat).
EI-MS (70 eV): m/z (%) = 356 ([M(37Cl)]+, 14), 354 ([M(35Cl)]+, 38), 328
([M(37Cl) – C2H4]+, 28), 326 ([M(35Cl) – C2H4]+, 77), 311 ([M(37Cl) –
C2H5O]+, 11), 309 ([M(35Cl) – C2H5O]+, 30), 300 ([M(37Cl) – C3H4O]+, 4),
298 ([M(35Cl) – C3H4O]+, 13), 283 ([M(37Cl) – C3H5O2]+, 6), 281
([M(35Cl) – C3H5O2]+, 18), 256 ([M(37Cl) – C4H4O3]+, 34), 254 ([M(35Cl) –
C4H4O3]+, 100), 227 ([M(37Cl) – C5H5O4]+, 8), 225 ([M(35Cl) – C5H5O4]+,
24), 191 (16), 189 (29), 141 ([M(37Cl) – C7H4ClO4]+, 16), 139 ([M(35Cl) –
C7H4ClO4]+, 47), 111 ([M(35Cl) – C14H11O4]+, 19), 77 ([M – C14H10ClO4]+,
3).
Anal. Calcd for C18H14O5 (310.1): C, 69.67; H, 4.55. Found: C, 69.65; H,
4.76.
Ethyl 2-Oxo-4-phenyl-6-(thien-2-yl)-2H-pyran-3-carboxylate (5i)
According to GP1 using 2-thenoyl chloride (1i) (329 mg, 2.20 mmol)
and phenylacetylene (2a) (206 mg, 2.00 mmol), 5i (416 mg,
1.27 mmol, 64%) was obtained as a yellow solid; mp 90–97 °C.
Anal. Calcd for C20H15ClO4 (354.1): C, 67.71; H, 4.26. Found: C, 67.88;
H, 4.34.
IR (ATR): 3115 (w), 3090 (w), 2976 (w), 2953 (w), 1709 (s), 1614 (m),
1578 (w), 1526 (m), 1514 (m), 1506 (m), 1489 (m), 1441 (m), 1425
(m), 1377 (m), 1335 (w), 1298 (w), 1256 (m), 1238 (m), 1182 (m),
1107 (s), 1076 (m), 1061 (w), 1032 (m), 1013 (m), 922 (w), 860 (m),
849 (m), 818 (m), 804 (w), 768 (m), 735 (vs), 698 (s), 681 (w), 660
(w), 648 (m), 613 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 1.03 (t, J = 7.1 Hz, 3 H), 4.14 (q, J = 7.1
Hz, 2 H), 6.59 (s, 1 H), 7.14 (dd, J = 5.0, 3.8 Hz, 1 H), 7.40–7.49 (m, 5 H),
7.52 (dd, J = 5.0, 1.2 Hz, 1 H), 7.69 (dd, J = 3.8, 1.2 Hz, 1 H).
Ethyl 6-(4-Cyanophenyl)-2-oxo-4-phenyl-2H-pyran-3-carboxylate
(5g)
According to GP1 using 4-cyanobenzoyl chloride (1g) (374 mg, 2.20
mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol) and after
washing with hot ethanol (4.00 mL), 5g (344 mg, 1.00 mmol, 50%)
was obtained as a yellow solid; mp 150–159 °C.
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 61.9 (CH2), 102.6 (CH),
115.9 (Cquat), 127.3 (CH), 128.75 (CH), 128.77 (CH), 129.0 (CH), 130.3
(CH), 134.6 (Cquat), 136.5 (Cquat), 155.9 (Cquat), 156.4 (Cquat), 158.8
(Cquat), 164.8 (Cquat).
IR (ATR): 3103 (w), 3084 (w), 2957 (w), 2857 (w), 2226 (w), 1730 (m),
1692 (s), 1624 (m), 1607 (w), 1533 (m), 1503 (m), 1412 (m), 1373
(m), 1346 (w), 1287 (w), 1273 (w), 1248 (m), 1198 (m), 1111 (m),
1080 (m), 1063 (m), 1016 (m), 999 (w), 843 (s), 829 (m), 768 (s), 748
(m), 700 (s), 613 cm–1 (m).
1H NMR (300 MHz, CDCl3): δ = 1.07 (t, J = 7.1 Hz, 3 H), 4.17 (q, J = 7.1
Hz, 2 H), 6.87 (s, 1 H), 7.42–7.55 (m, 5 H), 7.73–8.02 (m, 4 H).
13C NMR (75 MHz, CDCl3): δ = 13.8 (CH3), 62.1 (CH2), 105.0 (CH),
114.8 (Cquat), 118.0 (Cquat), 118.5 (Cquat), 126.5 (CH), 127.3 (CH), 129.2
(CH), 130.6 (CH), 132.9 (CH), 134.7 (Cquat), 135.9 (Cquat), 154.7 (Cquat),
158.0 (Cquat), 158.7 (Cquat), 164.4 (Cquat).
EI-MS (70 eV): m/z (%) = 327 ([M + H]+, 17), 326 ([M]+, 80), 299 (18),
298 ([M – CO]+, 87), 281 ([M – C2H5O]+, 32), 270 ([M – C3H5O]+, 17),
253 ([M – C3H5O2]+, 10), 241 ([M – C4H5O2]+, 10), 227 (17), 226 ([M –
C4H4O3]+, 100), 198 (11), 197 ([M – C5H5O4]+, 40), 111 ([M –
C
13H11O3]+, 63), 83 ([M – C14H11O4]+, 6), 77 ([M – C12H9O4S]+, 3).
Anal. Calcd for C18H14O4S (326.1): C, 76.57; H, 6.93. Found: C, 76.32;
H, 6.64.
EI-MS (70 eV): m/z (%) = 345 ([M]+, 7), 317 ([M – CO]+, 14), 272 ([M –
C3H5O2]+, 4), 245 ([M – C4H4O3]+, 24), 216 ([M – C5H5O4]+, 6), 130 ([M –
C
Ethyl 4-(4-Methoxyphenyl)-2-oxo-6-phenyl-2H-pyran-3-carboxyl-
ate (5j)
13H11O3]+, 14), 113 (11), 102 ([M – C14H11O4]+, 7), 77 ([M – C15H10NO4]+,
2), 71 (15), 70 (11), 57 (20), 43 (13).
According to GP1 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and 1-ethynyl-4-methoxybenzene (2b) (264 mg, 2.00 mmol), 5j
(455 mg, 1.30 mmol, 65%) was obtained as a yellow solid; mp 101–
108 °C.
Anal. Calcd for C21H15NO4 (345.1): C, 73.04; H, 4.38; N, 4.06. Found: C,
73.05; H, 4.68; N, 3.87.
Ethyl 6-(Furan-2-yl)-2-oxo-4-phenyl-2H-pyran-3-carboxylate (5h)
IR (ATR): 2980 (w), 2972 (w), 2930 (w), 2901 (w), 2841 (w), 1749 (w),
1705 (vs), 1622 (m), 1605 (m), 1576 (w), 1533 (s), 1510 (m), 1493
(m), 1441 (m), 1393 (m), 1381 (m), 1350 (w), 1296 (m), 1258 (s),
1246 (m), 1196 (m), 1179 (m), 1123 (m), 1113 (s), 1092 (m), 1074
(m), 1038 (s), 1018 (m), 964 (w), 943 (w), 824 (m), 797 (m), 768 (s),
748 (w), 689 (s), 677 (w), 648 cm–1 (m).
According to GP1 using furan-2-carbonyl chloride (1h) (295 mg,
2.20 mmol) and phenylacetylene (2a) (206 mg, 2.00 mmol), 5h
(392 mg, 1.26 mmol, 63%) was obtained as a yellow solid; mp 111–
121 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

I
N. Breuer, T. J. J. Müller
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 1.14 (t, J = 7.1 Hz, 3 H), 3.86 (s, 3 H),
4.22 (q, J = 7.1 Hz, 2 H), 6.77 (s, 1 H), 6.93–7.01 (m, 2 H), 7.40–7.52 (m,
5 H), 7.83–7.92 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 14.0 (CH3), 55.6 (CH3), 61.9 (CH2), 103.6
(CH), 114.5 (CH), 116.0 (Cquat), 126.1 (CH), 128.5 (Cquat), 129.2 (CH),
131.0 (CH), 131.5 (Cquat), 154.8 (Cquat), 159.7 (Cquat), 160.4 (Cquat), 161.5
(Cquat), 165.4 (Cquat).
EI-MS (70 eV): m/z (%) = 350 ([M]+, 38), 323 (20), 322 ([M – C2H4]+,
85), 305 ([M – C2H5O]+, 22), 294 ([M – C3H4O]+, 14), 277 ([M –
C3H5O2]+, 13), 251 (19), 250 ([M – C4H4O3]+, 100), 221 ([M – C5H5O4]+,
20), 178 (11), 135 (10), 105 ([M – C14H13O4]+, 43), 77 ([M – C15H13O5]+,
25).
13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 62.1 (CH2), 103.2 (CH),
116.9 (Cquat), 126.2 (CH), 128.8 (CH), 129.3 (CH), 129.3 (CH), 130.7
(Cquat), 131.8 (CH), 134.9 (Cquat), 136.6 (Cquat), 154.2 (Cquat), 159.2
(Cquat), 161.0 (Cquat), 164.7 (Cquat).
EI-MS (70 eV): m/z (%) = 356 ([M(37Cl)]+, 15), 354 ([M(35Cl)]+, 41), 328
([M(37Cl) – C2H4]+, 25), 326 ([M(35Cl) – C2H4]+, 71), 311 ([M(37Cl) –
C2H4O]+, 10), 309 ([M(35Cl) – C2H5O]+, 25), 300 ([M(37Cl) – C3H4O]+, 5),
298 ([M(35Cl) – C3H5O]+, 16), 283 ([M(37Cl) – C3H5O2]+, 7), 281
([M(35Cl) – C3H5O2]+, 13), 256 ([M(37Cl) – C4H4O3]+, 33), 254 ([M(35Cl) –
C4H4O3]+, 100), 227 ([M(37Cl) – C5H5O4]+, 7), 225 ([M(35Cl) – C5H5O4]+,
21), 191 (12), 189 (24), 105 ([M – C13H10O3Cl]+, 59), 77 ([M – C14H10
ClO4]+, 33).
-
Anal. Calcd for C20H15ClO4 (354.1): C, 67.71; H, 4.26. Found: C, 67.45;
H, 4.47.
Anal. Calcd for C21H18O5 (350.1): C, 71.99; H, 5.18. Found: C, 71.96; H,
5.25.
Ethyl 4-(4-Cyanophenyl)-2-oxo-6-phenyl-2H-pyran-3-carboxylate
(5m)
Ethyl 2-Oxo-6-phenyl-4-(p-tolyl)-2H-pyran-3-carboxylate (5k)
According to GP1 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and 1-ethynyl-4-methylbenzene (2c) (260 mg, 2.00 mmol), 5k
(359 mg, 1.07 mmol, 54%) was obtained as a yellow solid; mp 116–
120 °C.
According to GP1 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and 1-cyano-4-ethynylbenzene (2e) (260 mg, 2.00 mmol) and after
washing with hot ethanol (6.00 mL), 5m (250 mg, 0.730 mmol, 37%)
was obtained as a yellow solid; mp 100–119 °C.
IR (ATR): 3030 (w), 3003 (w), 2982 (w), 2953 (w), 2934 (w), 2926 (w),
2864 (w), 1730 (s), 1690 (s), 1618 (m), 1609 (m), 1568 (w), 1526 (m),
1512 (m), 1495 (m), 1470 (w), 1449 (m), 1441 (w), 1375 (m), 1348
(m), 1294 (w), 1252 (m), 1215 (w), 1186 (m), 1113 (m), 1099 (m),
1051 (w), 1016 (m), 1001 (m), 982 (w), 945 (w), 922 (w), 837 (w), 818
(m), 785 (m), 766 (vs), 746 (m), 687 (s), 673 (w), 646 (m), 602 cm–1
(m).
1H NMR (300 MHz, CDCl3): δ = 1.11 (t, J = 7.1 Hz, 3 H), 2.42 (s, 3 H),
4.20 (q, J = 7.1 Hz, 2 H), 6.77 (s, 1 H), 7.24–7.30 (m, 2 H), 7.34–7.40 (m,
2 H), 7.42–7.54 (m, 3 H), 7.82–7.92 (m, 2 H).
IR (ATR): 2986 (w), 2972 (w), 2943 (w), 2922 (w), 2901 (w), 2230 (w),
1740 (vs), 1705 (s), 1626 (m), 1607 (w), 1558 (w), 1533 (m), 1506
(w), 1495 (w), 1449 (w), 1381 (w), 1350 (w), 1263 (m), 1242 (m),
1179 (w), 1125 (m), 1113 (m), 1078 (m), 1051 (m), 1016 (s), 1001
(m), 949 (w), 868 (w), 854 (m), 833 (m), 806 (w), 783 (m), 772 (s),
760 (m), 731 (w), 692 (s), 652 cm–1 (w).
1H NMR (300 MHz, CDCl3): δ = 1.08 (t, J = 7.1 Hz, 3 H), 4.16 (q, J = 7.1
Hz, 2 H), 6.70 (s, 1 H), 7.40–7.73 (m, 5 H), 7.73–7.80 (m, 2 H), 7.83–
7.90 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 62.2 (CH2), 102.7 (CH),
114.0 (Cquat), 117.2 (Cquat), 118.0 (Cquat), 126.2 (CH), 128.2 (CH), 129.3
(CH), 130.5 (Cquat), 132.1 (CH), 132.7 (CH), 141.0 (Cquat), 153.8 (Cquat),
158.7 (Cquat), 161.7 (Cquat), 164.1 (Cquat).
13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 21.5 (CH3), 61.9 (CH2), 103.7
(CH), 116.5 (Cquat), 126.1 (CH), 127.4 (CH), 129.2 (CH), 129.7 (CH),
131.0 (CH), 131.6 (Cquat), 133.6 (Cquat), 140.8 (Cquat), 155.4 (Cquat), 159.6
(Cquat), 160.5 (Cquat), 165.2 (Cquat).
EI-MS (70 eV): m/z (%) = 346 ([M + H]+, 11), 345 ([M]+, 47), 317 ([M –
CO]+, 83), 300 ([M – C2H5O]+, 26), 289 ([M – C3H4O]+, 24), 272 ([M –
C3H5O2]+, 15), 261 (17), 260 (38), 245 ([M – C4H4O3]+, 100), 217 (13),
216 ([M – C5H5O4]+, 31), 214 (12), 105 ([M – C14H10NO3]+, 78), 77 ([M –
EI-MS (70 eV): m/z (%) = 335 ([M + H]+, 10), 334 ([M]+, 43), 307 (16),
306 ([M – CO]+, 72), 289 ([M – C2H5O]+, 25), 278 ([M – C3H4O]+, 12),
261 ([M – C3H5O2]+, 10), 235 (20), 234 ([M – C4H4O3]+, 100), 205 ([M –
C5H5O4]+, 21), 105 ([M – C14H13O3]+, 33), 91 ([M – C14H11O4]+, 2), 77 ([M
– C15H13O4]+, 22).
C
15H10NO4]+, 38).
Anal. Calcd for C21H15NO4 (345.1): C, 73.04; H, 4.38; N, 4.06. Found: C,
73.18; H, 4.51; N, 4.21.
Anal. Calcd for C21H18O4 (334.1): C, 75.43; H, 5.43. Found: C, 75.18; H,
5.58.
Methyl 2-Oxo-4,6-diphenyl-2H-pyran-3-carboxylate (5n)
Ethyl4-(4-Chlorophenyl)-2-oxo-6-phenyl-2H-pyran-3-carboxylate
In a deviation from GP1, using benzoyl chloride (1a) (312 mg,
2.20 mmol), phenylacetylene (2a) (209 mg, 2.00 mmol) and dimethyl
malonate (4b) (528 mg, 4.00 mmol), 5n (316 mg, 1.03 mmol, 52%)
was obtained as a colorless solid; mp 124–126 °C.
(5l)
According to GP1 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and 1-chloro-4-ethynylbenzene (2d) (273 mg, 2.00 mmol), 5l
(302 mg, 0.850 mmol, 43%) was obtained as a yellow solid; mp 95–
100 °C.
IR (ATR): 3098 (w), 3065 (w), 2997 (w), 2990 (w), 2949 (w), 2901 (w),
2887 (w), 1732 (s), 1694 (s), 1674 (m), 1624 (m), 1578 (m), 1530 (s),
1495 (m), 1443 (m), 1431 (m), 1381 (m), 1352 (m), 1323 (w), 1290
(w), 1263 (m), 1246 (m), 1196 (m), 1161 (w), 1123 (m), 1101 (w),
1078 (m), 1055 (m), 1020 (s), 1001 (m), 962 (w), 920 (m), 837 (m),
804 (m), 762 (s), 748 (m), 704 (s), 687 (s), 667 (m), 635 (m), 613 cm–1
(m).
IR (ATR): 2978 (m), 2936 (w), 2901 (m), 2824 (w), 2336 (w), 2313 (w),
1732 (s), 1717 (m), 1694 (m), 1616 (m), 1593 (w), 1568 (w), 1558 (w),
1522 (m), 1491 (m), 1443 (m), 1402 (m), 1393 (w), 1379 (m), 1350
(w), 1325 (w), 1294 (w), 1256 (m), 1186 (m), 1125 (m), 1107 (m),
1090 (vs), 1078 (m), 1049 (m), 1015 (s), 1001 (m), 951 (w), 860 (w),
829 (m), 768 (s), 746 (w), 710 (w), 691 (s), 644 (w), 629 cm–1 (w).
1H NMR (600 MHz, CDCl3): δ = 3.69 (d, J = 1.3 Hz, 3 H), 6.79 (s, 1 H),
7.43–7.53 (m, 8 H), 7.85–7.91 (m, 2 H).
1H NMR (300 MHz, CDCl3): δ = 1.12 (t, J = 7.1 Hz, 3 H), 4.19 (q, J = 7.2
Hz, 2 H), 6.72 (s, 1 H), 7.38–7.53 (m, 7 H), 7.83–7.91 (m, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

J
N. Breuer, T. J. J. Müller
Paper
Synthesis
13C NMR (151 MHz, CDCl3): δ = 52.7 (CH3), 103.6 (CH), 116.4 (Cquat),
126.2 (CH), 127.3 (CH), 129.1 (CH), 129.2 (CH), 130.4 (CH), 130.8
(Cquat), 131.7 (CH), 136.4 (Cquat), 155.7 (Cquat), 159.4 (Cquat), 160.8
(Cquat), 165.5 (Cquat).
EI-MS (70 eV): m/z (%) = 307 ([M + H]+, 9), 306 ([M]+, 41), 279 (21),
278 ([M – CO]+, 100), 275 ([M – CH3O]+, 18), 247 ([M – C2H3O2]+, 35),
220 (47), 191 ([M – C4H3O4]+, 28), 189 (14), 105 ([M – C12H9O3]+, 37),
77 ([M – C13H9O4]+, 26).
IR (ATR): 3138 (w), 3075 (w), 2920 (w), 2849 (w), 2826 (w), 2758 (w),
2727 (w), 2671 (w), 1645 (s), 1634 (s), 1609 (s), 1597 (s), 1574 (s),
1531 (w), 1504 (s), 1470 (w), 1452 (m), 1431 (w), 1402 (w), 1281 (w),
1231 (w), 1155 (w), 991 (m), 924 (w), 876 (w), 858 (m), 843 (m), 820
(w), 752 (s), 719 (m), 677 (s), 665 (m), 652 (m), 621 cm–1 (w).
1H NMR (600 MHz, CDCl3): δ = 6.75–6.80 (m, 2 H), 7.43–7.51 (m, 4 H),
7.51–7.56 (m, 2 H), 7.63–7.67 (m, 2 H), 7.80–7.84 (m, 2 H), 12.62 (s, 1
H).
Anal. Calcd for C19H14O4 (306.1): C, 74.50; H, 4.61. Found: C, 74.41; H,
4.71.
13C NMR (151 MHz, CDCl3): δ = 105.1 (CH), 115.3 (CH), 127.0 (CH),
127.1 (CH), 129.1 (CH), 129.3 (CH), 129.6 (CH), 130.3 (CH), 133.8
(Cquat), 138.3 (Cquat), 147.0 (Cquat), 153.9 (Cquat), 165.7 (Cquat).
EI-MS (70 eV): m/z (%) = 247 ([M]+, 100), 219 ([M – CO]+, 13), 199 (25),
2-Oxo-1,2-dihydropyridine-3-carboxylates 6 and Pyridin-2(1H)-
ones 7; General Procedure (GP 2)
183 (16), 152 (30), 121 (22), 105 (31), 77 ([M – C11H8NO]+, 29).
PdCl2(PPh3)2 (3.50 mg, 5.00 μmol, 0.25 mol%) and CuI (1.90 mg,
10.0 μmol, 0.50 mol%) were placed in a dry Schlenk tube under a ni-
trogen atmosphere and anhydrous 1,4-dioxane (2.00 mL) was added.
An acid chloride 1 (2.20 mmol), a terminal alkyne 2 (2.00 mmol) and
NEt3 (212 mg, 2.10 mmol) were added and the mixture was stirred at
20 °C for 3 h until complete conversion (monitored by TLC). Subse-
quently, Na2CO3·10 H2O (1.72 g, 6.00 mmol) and diethyl malonate (4a)
(640 mg, 4.00 mmol) were added and stirring at 75 °C was continued
for 16 h. Aqueous ammonia (25 wt %, 2.40 mL, 128 mmol) was added
and the mixture was stirred at 90 °C for 4 h. After the addition of
brine (2.00 mL), the solution was extracted with CH2Cl2 (3 × 50.0 mL).
The combined organic layers were dried (anhydrous MgSO4) and the
solvent was removed in vacuo. The residue was purified by flash chro-
matography on silica gel (n-hexane–acetone, 3:1).
Anal. Calcd for C17H13NO (247.1): C, 82.57; H, 5.30; N, 5.66. Found: C,
82.34; H, 5.30; N, 5.51.
6-(4-Methoxyphenyl)-4-phenylpyridin-2(1H)-one (7b)
According to GP2 using 4-methoxybenzoyl chloride (1b) (344 mg,
2.20 mmol) and phenylacetylene (2a) (209 mg, 2.00 mmol), 7b
(104 mg, 0.370 mmol, 19%) was obtained as a colorless solid; mp
250–253 °C.
IR (ATR): 3078 (w), 2999 (w), 2938 (w), 2911 (w), 2899 (w), 2837 (w),
2710 (w), 1632 (s), 1605 (s), 1570 (m), 1530 (m), 1508 (s), 1499 (m),
1456 (m), 1439 (m), 1422 (m), 1402 (w), 1358 (w), 1293 (w), 1250 (s),
1119 (w), 1107 (w), 1078 (w), 1059 (w), 1030 (m), 1018 (w), 989 (m),
978 (m), 943 (m), 910 (m), 853 (m), 820 (s), 797 (m), 770 (s), 704 (m),
644 (m), 615 cm–1 (m).
Ethyl 2-Oxo-4,6-diphenyl-1,2-dihydropyridine-3-carboxylate (6a)
1H NMR (300 MHz, DMSO-d6): δ = 3.82 (s, 3 H), 6.57 (s, 1 H), 6.90 (s, 1
H), 6.99–7.09 (m, 2 H), 7.44–7.56 (m, 3 H), 7.77–7.82 (m, 2 H), 7.83–
7.90 (m, 2 H), 11.65 (s, 1 H).
13C NMR (151 MHz, DMSO-d6): δ = 55.0 (CH3), 103.4 (CH), 111.1 (CH),
113.9 (CH), 126.4 (CH), 126.9 (Cquat), 127.9 (CH), 128.5 (CH), 128.8
(CH), 137.5 (Cquat), 148.2 (Cquat), 151.5 (Cquat), 160.2 (Cquat), 163.2
(Cquat).
EI-MS (70 eV): m/z (%) = 278 ([M + H]+, 20), 277 ([M]+, 100), 276 ([M –
H]+, 20), 249 ([M – CO]+, 17), 235 ([M – CNO]+, 7), 234 ([M – CHNO]+,
39), 206 (8), 204 ([M – C2H3NO2]+, 9), 178 (8).
According to GP2 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and phenylacetylene (2a) (209 mg, 2.00 mmol), 6a (103 mg,
0.320 mmol, 16%) was obtained as a colorless solid; mp 200 °C.
IR (ATR): 3130 (w), 3057 (w), 3032 (w), 2914 (w), 2895 (w), 2849 (w),
2795 (w), 2702 (w), 2687 (w), 1721 (m), 1614 (s), 1597 (m), 1574 (m),
1559 (s), 1541 (w), 1501 (w), 1474 (w), 1441 (w), 1292 (w), 1252 (m),
1227 (w), 1138 (w), 1111 (m), 1061 (m), 1001 (w), 918 (w), 858 (w),
850 (w), 779 (w), 760 (s), 692 (s), 667 (m), 652 (w), 637 (w), 608 cm–1
(w).
1H NMR (600 MHz, CDCl3): δ = 1.03 (t, J = 7.1 Hz, 3 H), 4.15 (q, J = 7.1
Hz, 2 H), 6.63 (s, 1 H), 7.43 (m, 3 H), 7.48 (s, 5 H), 7.83–7.86 (m, 2 H),
12.77 (br s, 1 H).
Anal. Calcd for C18H15NO2 (277.1): C, 77.96; H, 5.45; N, 5.05. Found: C,
77.73; H, 5.43; N, 4.92.
13C NMR (151 MHz, CDCl3): δ = 13.9 (CH3), 61.4 (CH2), 107.2 (CH),
127.2 (CH), 127.7 (CH), 128.7 (CH), 129.2 (CH), 129.3 (CH), 130.7 (CH),
133.1 (Cquat), 138.4 (Cquat), 148.2 (Cquat), 153.5 (Cquat), 162.71 (Cquat),
162.74 (Cquat), 166.6 (Cquat).
4-Phenyl-6-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one (7c)
According to GP2 using 4-(trifluoromethyl)benzoyl chloride (1j)
(468 mg, 2.20 mmol) and phenylacetylene (2a) (209 mg, 2.00 mmol),
7c (191 mg, 0.610 mmol, 30%) was obtained as a colorless solid; mp
260–262 °C.
EI-MS (70 eV): m/z (%) = 320 ([M + H]+, 23), 319 ([M]+, 100), 275 (15),
274 ([M – C2H5O]+, 65), 273 (10), 248 (11), 247 (61), 246 ([M –
C3H5O2]+, 26), 245 (89), 224 (19), 219 (12), 218 (10), 217 ([M – C8H6]+,
42), 216 (19), 202 (16), 189 ([M – C5H8NO3]+, 12), 105 (17), 77 ([M –
IR (ATR): 3125 (w), 3082 (w), 3022 (w), 2886 (w), 2847 (w), 2802 (w),
2749 (w), 2708 (w), 2648 (w), 2525 (w), 1819 (w), 1630 (s), 1601 (s),
1574 (m), 1530 (m), 1516 (w), 1462 (m), 1422 (w), 1395 (w), 1321
(m), 1314 (m), 1287 (w), 1265 (w), 1240 (w), 1190 (w), 1159 (m),
1124 (s), 1113 (s), 1067 (s), 1057 (m), 1018 (m), 991 (m), 976 (m),
945 (w), 918 (m), 868 (m), 824 (s), 764 (s), 733 (w), 694 (s), 681 (m),
669 (w), 623 (m), 606 cm–1 (m).
C
14H12NO3]+, 15).
Anal. Calcd for C20H17NO3 (319.1): C, 75.22; H, 5.37; N, 4.39. Found: C,
75.18; H, 5.39; N, 4.37.
4,6-Diphenylpyridin-2(1H)-one (7a)
1H NMR (600 MHz, DMSO-d6): δ = 6.75–6.82 (m, 1 H), 7.30 (s, 1 H),
7.46–7.56 (m, 3 H), 7.81–7.89 (m, 4 H), 8.19 (d, J = 8.0 Hz, 2 H), 11.63
(s, 1 H).
13C NMR (151 MHz, CDCl3): δ = 106.4 (CH), 116.0 (CH), 123.9 (dq, J =
272.9 Hz, Cquat), 126.4 (q, J = 3.8 Hz, CH), 127.1 (CH), 127.4 (CH), 129.3
(CH), 130.0 (CH), 130.8 (dq, J = 392.4 Hz, Cquat), 137.1 (Cquat), 137.7
(Cquat), 145.5 (Cquat), 154.3 (Cquat), 165.4 (Cquat).
According to GP2 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and phenylacetylene (2a) (209 mg, 2.00 mmol), 7a (280 mg,
1.13 mmol, 57%) was obtained as a colorless solid; mp 206 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

K
N. Breuer, T. J. J. Müller
Paper
Synthesis
EI-MS (70 eV): m/z (%) = 315 ([M]+, 100), 314 ([M – H]+, 39), 287 ([M –
Acknowledgment
CO]+, 60), 217 (10), 115 ([M – C9H5F3NO]+, 16).
The authors cordially thank the Fonds der Chemischen Industrie for
financial support and B.Sc. Alexander Orlow and B.Sc. Selcuk Hasan
Fazlaoglu for experimental assistance.
Anal. Calcd for C18H12F3NO (315.1): C, 65.12; H, 4.16; N, 3.62. Found:
C, 65.42; H, 4.46; N, 3.39.
4-(4-Methoxyphenyl)-6-phenylpyridin-2(1H)-one (7d)
According to GP2 using benzoyl chloride (1a) (312 mg, 2.20 mmol)
and 1-ethynyl-4-methoxybenzene (2b) (264 mg, 2.00 mmol), 7d
(131 mg, 0.470 mmol, 24%) was obtained as a colorless solid; mp
197–220 °C.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610129.
S
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p
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p
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rmoaitn
IR (ATR): 3086 (w), 2955 (w), 2909 (w), 2835 (w), 1636 (s), 1609 (m),
1578 (m), 1530 (m), 1516 (m), 1498 (m), 1464 (m), 1439 (m), 1422
(w), 1400 (w), 1362 (w), 1296 (m), 1250 (m), 1236 (m), 1171 (m),
1096 (w), 1028 (m), 991 (m), 935 (w), 914 (w), 903 (m), 853 (m), 829
(s), 812 (m), 773 (m), 760 (s), 731 (w), 683 (m), 673 (m), 650 (m), 638
(m), 617 cm–1 (m).
1H NMR (300 MHz, DMSO-d6): δ = 3.82 (s, 3 H), 6.60 (s, 1 H), 6.96 (s, 1
H), 7.00–7.12 (m, 2 H), 7.38–7.57 (m, 3 H), 7.74–7.81 (m, 2 H), 7.84–
7.91 (m, 2 H), 11.61 (s, 1 H).
References
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Katritzky, A. R.; Rees, C. W., Eds.; Perga-
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13C NMR (151 MHz, DMSO-d6): δ = 55.0 (CH3), 104.2 (CH), 110.8 (CH),
114.6 (CH), 126.5 (CH), 127.8 (CH), 128.2 (CH), 129.0 (CH), 129.4
(Cquat), 134.7 (Cquat), 148.3 (Cquat), 150.9 (Cquat), 160.1 (Cquat), 163.3
(Cquat).
EI-MS (70 eV): m/z (%) = 278 ([M + H]+, 20), 277 ([M]+, 100), 276 ([M –
H]+, 45), 249 ([M – CO]+, 20), 234 ([M – CHNO]+, 38), 233 ([M – CH2-
NO]+, 8), 206 (11), 204 ([M – C2H3NO2]+, 8), 178 (9).
Anal. Calcd for C18H15NO2 (277.1): C, 77.96; H, 5.45; N, 5.05. Found: C,
77.66; H, 5.55; N, 4.92.
Methyl 2-Oxo-4,6-diphenyl-1,2-dihydropyridine-3-carboxylate
(6b) and 4,6-Diphenylpyridin-2(1H)-one (7a)
(7) Pathare, R. S.; Sharma, S.; Gopal, K.; Sawant, D. M.; Pardasani, R.
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74, 6295.
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In a deviation from GP2, using benzoyl chloride (1a) (313 mg,
2.20 mmol), phenylacetylene (2a) (209 mg, 2.00 mmol) and dimethyl
malonate (4b) (539 mg, 4.00 mmol), a mixture of 6b (18.0 mg,
60 μmol, 3%) and 7a (156 mg, 63 μmol, 31%) was obtained as a color-
less solid.
Data Below is on mixture.
IR (ATR): 3142 (w), 3053 (w), 3030 (w), 2916 (w), 2853 (w), 2359 (w),
2332 (w), 1726 (m), 1620 (s), 1608 (s), 1595 (s), 1574 (m), 1531 (m),
1497 (m), 1470 (w), 1449 (m), 1393 (w), 1265 (m), 1254 (m), 1229
(m), 1188 (w), 1140 (w), 1115 (m), 1065 (m), 995 (m), 926 (w), 855
(w), 833 (w), 806 (w), 791 (w), 758 (s), 704 (m), 689 (s), 667 (m), 635
cm–1 (w).
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2061.
1H NMR (300 MHz, DMSO-d6): δ = 3.59 (s, 3 H), 6.65 (s, 1 H), 6.71 (s, 1
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Li, K. Eur. J. Med. Chem. 2013, 67, 447.
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H), 7.00 (s, 1 H), 7.47–7.53 (m, 14 H), 7.79–7.91 (m, 6 H), 12.05 (s, 2
H).
EI-MS (70 eV): m/z (%) = 305 ([M (6b)]+, 100), 274 ([M – OCH3]+, 76),
247 ([M – C2H3O2]+, 26), 246 ([M (7a)]+, 246 ([M – C2H3O2]+, 16), 245
([M – C2H4O2]+, 69), 217 ([M – C3H4O3]+, 37), 216 ([M – C3H5O3]+, 18),
202 ([M – C3H5NO3]+, 15), 94 (13).
HRMS (ESI): m/z [M + H]+ calcd for C19H16NO3 (6b): 306.1130; found:
306.1128; m/z [M + H]+ calcd for C17H14NO (7a): 248.1075; found:
248.1072.
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41, 13027.
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Org. Lett. 2013, 15, 232.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

L
N. Breuer, T. J. J. Müller
Paper
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L