Copper-catalyzed selective synthesis of highly substituted pyridones by the reaction of enaminones with alkynes

Article abstract of DOI:10.1055/s-0032-1317178

An efficient copper-catalyzed selective synthesis of highly functionalized pyridones by the reaction of enaminones with alkynes is reported. The reactions proceed to afford polysubstituted pyridone derivatives in good to high yields using CuI as the catal

Full text of DOI:10.1055/s-0032-1317178

PAPER
▌3301
paper
Copper-Catalyzed Selective Synthesis of Highly Substituted Pyridones by the
Reaction of Enaminones with Alkynes
Synthesis of Highly Substituted Pyridones
Yushang Shao, Wenjun Yao, Jun Liu, Kai Zhu, Yanzhong Li*
Department of Chemistry, and Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University,
500 Dongchun Road, Shanghai 200241, P. R. China
Fax +86(21)54340096; E-mail: yzli@chem.ecnu.edu.cn
Received: 16.07.2012; Accepted after revision: 10.08.2012
O
CO2R3
CO2R3
CO2R3
Abstract: An efficient copper-catalyzed selective synthesis of
highly functionalized pyridones by the reaction of enaminones with
alkynes is reported. The reactions proceed to afford polysubstituted
pyridone derivatives in good to high yields using CuI as the catalyst
in MeCN under nitrogen.
H
N
O
R1
CuI (cat.)
R1
R2
+
MeCN, N2
N
O
R2
Key words: copper catalysis, pyridones, regioselective cyclization,
enaminones, cascade reactions
Scheme 1 Selective synthesis of pyridones
tal conditions, and the results are depicted in Table 1.
When the reaction was carried out using CuI (20 mol%)
as the catalyst in MeCN under nitrogen at 80 °C, the cor-
responding pyridone 3a was obtained in 90% isolated
yield as the sole product within one hour, and the structure
was fully confirmed by X-ray crystal analysis9 (Table 1,
entry 1). Lowering the catalyst loading to 5 mol% resulted
in 86% yield, yet the use of 10 mol% of CuI gave a similar
result as that of 20 mol% (entries 2, 3). Without the addi-
tion of Cu catalyst, 3a could also be produced; however,
much longer reaction time (24 h) was required, and the
yield was low (entry 4). Other Cu catalysts gave lower
yields or poor selectivity (entries 7–9). Switching to other
solvents such as MeNO2, DCE, 1,4-dioxane, toluene, and
DMF afforded unsatisfactory results (entries 10–14). It is
interesting to note that when the reaction was performed
in air, 3a was obtained in 74% yield, along with 18% yield
of pyrrole 4a (entry 15). Thus, it was clear that the opti-
mized reaction condition for the pyridone formation was
to use 10 mol% of CuI as the catalyst and MeCN as the
solvent under nitrogen at 80 °C.
Pyridones are important N-containing heterocyclic com-
pounds, which not only represent useful building blocks
in the synthesis of natural products but also are key struc-
tural units in compounds that exhibit remarkable pharma-
cological activities.1 As a result, the development of
efficient synthetic methodologies for these heterocycles
has become of great interest in organic chemistry.2 Al-
though many diverse approaches toward pyridone deriva-
tives have been reported,3 the development of mild,
selective, and efficient methods for such compounds is
highly desirable. Enaminones are versatile intermediates
for the synthesis of heterocycles.4,5 However, reports con-
cerning the preparation of pyridones starting from enami-
nones are rare,6,7 and the substrates employed were those
with two substituents at C-3 position. For example, Cac-
chi et al.7 reported an effective synthesis of pyridines from
enaminones by an intramolecular annulation of N-propar-
gylic β-enaminones. There were only two reports on the
synthesis of pyridones from the reaction of enaminones
and activated alkynes using large excess amount of strong
base6a or strong acid.6b On the other hand, metal-catalyzed
methodology for the preparation of pyridones from en-
aminones has not been disclosed. Furthermore, very little
is known about the reactivity of enaminones with a mono-
substituent at C-3 position to form heterocycles. During
the course of our ongoing study on the development of
transition metal-mediated heterocycle-forming protocols
using enaminones,8 we found that pyridones could be se-
lectively prepared from the reaction of C-3 monosubsti-
tuted enaminones with alkynes using copper catalyst.
Herein, we would like to report these results (Scheme 1).
Having established an effective catalytic system for the
selective cyclization reactions, a variety of enaminones
were synthesized next to explore the scope of the pyridone
forming reaction under the optimized conditions. The rep-
resentative results are shown in Table 2. The reaction was
applicable to various enaminones. The substituent effect
at the nitrogen was studied first. Enaminones with elec-
tron-donating (4-OMe, 4-Me) aryl groups at nitrogen re-
acted smoothly with 2a to give the corresponding
pyridones in high yields (Table 2, entries 2, 3) while elec-
tron-withdrawing (4-Cl, 4-NO2) aryl groups afforded the
desired products in good or moderate yields (entries 4, 5).
Substituents at nitrogen could also be alkyl groups, such
as benzyl, butyl, and tert-butyl (entries 6–8). It is notewor-
thy that when N-t-Bu enaminone 1h was employed, pyri-
done 3h was produced in 43% yield, along with 20% the
corresponding pyrrole (entry 8). The regioselective effect
of the substituents on carbonyl carbon was also investigat-
The reaction of (Z)-1-phenyl-3-(phenylamino)prop-2-en-
1-one (1a) with dimethyl acetylenedicarboxylate (2a) was
selected as the prototypical case to screen the experimen-
SYNTHESIS 2012, 44, 3301–3306
Advanced online publication: 23.08.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1317178; Art ID: SS-2012-F0589-OP
© Georg Thieme Verlag Stuttgart · New York

3302
Y. Shao et al.
PAPER
ed. Both the electron-donating (4-OMe, 4-Me) and elec- DMAD were added, compound 5a was converted into the
tron-withdrawing (4-NO2, 2-Br) aryl groups on carbonyl corresponding 3h in 33% yield (Scheme 2, eq. 2). This
carbon gave the desired six-membered ring compounds in may due to the formation of some active Cu-DMAD spe-
good to high yields with excellent selectivity (entries 9– cies; however, we cannot confirm it at the present stage.
12). 1-Naphthyl (1m) or 2-thienyl (1n) substrates fur-
nished the pyridone derivatives as the only products in
H
O
CO2Me
CuI (10 mol%)
H
N
O
high yields ( entries 14, 15). Alkyl substituents, such as
cyclohexyl and n-hexyl, afforded the corresponding 3o
and 3p in 97% and 85% yield, respectively (entries 15,
16). When diethyl acetylenedicarboxylate (2b) was used
instead of DMAD to react with 1a, pyridone 3q was iso-
lated in 86% yield (entry 17).
Ph
N
t-Bu
(1)
Ph
t-Bu
+
MeCN, r.t., N2
MeO2C
CO2Me
CO2Me
1h
5a: 60%
MeO2C
O
To understand the reaction mechanism, the reaction of 1h
with 2a was carried out using the optimal conditions for
pyridone formation at room temperature, and the acyclic
intermediate 5a (E/Z = 3:5) was produced in 60% yield af-
ter 20 hours (Scheme 2, eq. 1). No reaction could be de-
tected even after three hours on treatment of compound 5a
under the standard conditions for pyridone formation. No
reaction took place even at a higher reaction temperature
of up to 120 °C. Interestingly, when 1.3 equivalents of
CO2Me
CO2Me
CuI (10 mol%)
Ph
+
5a
(2)
MeCN, 120 °C
N2, 3 h
O
N
t-Bu
3h: 33%
Scheme 2 Formation of intermediate 5a
Table 1 Optimization of Reaction Conditions for the Synthesis of 3a
O
O
CO2Me
MeO2C
Ph
MeO2C
CO2Me
H
N
O
(2a)
Ph
Ph
Ph
+
catalyst
MeO2C
N
N
O
solvent, 80 °C
1a
Ph
Ph
3a
4a
Entry
Catalyst (mol%)
Solvent
Time (h)
Yield (%)a 3a
Yield (%)a 4a
1
2
CuI (20)
CuI (10)
CuI (5)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeNO2
DCE
1
1
90
92
86
58
–
–
–
–
–
–
4
7
–
5
–
9
–
7
18
3
3
4
–
24
18
6
b
5
CuI (10)
CuI (10)
CuCl (10)
CuBr (10)
CuCN (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
–
6
84c
75
7
4
8
3
81
9
7
74
10
11
12
13
14
15
24
24
24
24
12
6
42
72
1,4-dioxane
toluene
DMF
70
trace
49
MeCN
74d
a Isolated yield. Unless otherwise noted, all reactions were carried out at 80 °C under N2.
b The reaction was carried out at r.t. Product 3a was not observed.
c The reaction temperature was 50 °C.
d The reaction was carried out in air.
Synthesis 2012, 44, 3301–3306
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Highly Substituted Pyridones
3303
On the basis of the above results, a plausible reaction
mechanism for the pyridone formation is shown in
Scheme 3.10 Enaminone 1 is proposed to be activated via
copper complex 6, which is formed by the replacement of
the acidic hydrogen on the amino group. Conjugate addi-
tion of 6 with acetylene dicarboxylate affords intermedi-
ate 7, which isomerizes to enaminone 8. This is followed
by intramolecular condensation to deliver the pyridone 3.
Table 2 CuI-Catalyzed Selective Synthesis of Pyridones
O
CO2R3
CO2R3
R1
H
O
CuI (10 mol%)
MeCN, 80 °C
R1
N
R2
+
N
R2
3
O
CO2R3
1
2
Entry 1
R1
R2
R3
Time Yield
In summary, we have reported an efficient copper-cata-
lyzed synthesis of highly functional pyridones by the re-
action of enaminones with alkynes. This methodology
provides a facile route for the selective synthesis of sub-
stituted pyridones using CuI as the catalyst in MeCN un-
der nitrogen.
(h)
(%)a
1
2
1a
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
3
4
92 (3a)
85 (3b)b
91 (3c)b
81 (3d)b
52 (3e)b
65 (3f)b
77 (3g)b
43 (3h)c
94 (3i)b
81 (3j)b
67 (3k)
50 (3l)
1b
1c
1d
1e
1f
4-MeOC6H4 Me
3
4-MeC6H4
4-ClC6H4
Me
Me
4
4
12
24
6
All solvents were dried by standard methods and all reactions were
carried out under N2. Unless otherwise noted, all commercial re-
5
4-O2NC6H4 Me
1
agents were used without further purification. H and 13C NMR
6
Bn
Bu
t-Bu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
spectra were recorded at 400 MHz, in CDCl3 (with 0.03% TMS) so-
lutions. 1H NMR spectra were recorded in CDCl3 (δ = 7.25) or with
TMS (δ = 0.00) as internal reference; 13C NMR spectra were re-
corded in CDCl3 (δ = 77.00) or C6D6 (δ = 128.02) as internal refer-
ence. Mass spectrometric data were obtained by electron ionization
(EI, 70 eV), or electrospray ionization (ESI).
7
1g
1h
1i
3
8
3
9
4-MeOC6H4
4-MeC6H4
4-O2NC6H4
2-BrC6H4
3
CuI-Catalyzed Synthesis of Pyridones; Methyl 5-Benzoyl-2-
oxo-1-phenyl-1,2-dihydropyridine-4-carboxylate (3a); Typical
Procedure
10
11
12
13
14
15
16
17
1j
4
1k
1l
12
24
2
(Z)-1-Phenyl-3-(phenylamino)prop-2-en-1-one (1a; 0.5 mmol),
MeCN (5 mL), dimethyl acetylenedicarboxylate (2a; 0.65 mmol),
and CuI (10 mg, 0.05 mmol) were added successively to a Schlenk
tube under N2. The mixture was stirred and heated to 80 °C for 1 h.
After cooling to r.t., the mixture was quenched with H2O (20 mL)
and extracted with EtOAc (3 × 15 mL). The combined organic ex-
tracts were washed with brine (15 mL) and dried (Na2SO4). The sol-
vent was evaporated under vacuo and the residue was purified by
chromatography on silica gel to afford 153 mg (92%) of the pyri-
done derivative 3a as a yellow solid; mp 113–114 °C.
1H NMR (CDCl3/TMS): δ = 3.58 (s, 3 H), 6.89 (s, 1 H), 7.27–7.33
(m, 2 H), 7.34–7.45 (m, 5 H), 7.46–7.53 (m, 1 H), 7.67–7.73 (m, 3
H).
13C NMR (CDCl3/TMS): δ = 52.75, 116.85, 122.06, 126.17, 126.68,
129.04, 129.21, 129.53, 133.02, 136.94, 139.46, 142.88, 143.08,
160.97, 165.64, 191.06.
1m 1-naphthyl
94 (3m)
71 (3n)
97 (3o)
85 (3p)
86 (3q)
1n
1o
1p
1a
2-thienyl
cyclohexyl
n-hexyl
Ph
3
2
3
6
a Isolated yield.
b Trace amount of pyrrole was isolated.
c Along with the corresponding pyrrole in 20% yield.
HMRS: m/z calcd for C20H15NO4: 333.1001; found: 333.1002.
Cu+
R2
R2
R2
Cu
O
N
H
R3O2C CO2R3
conjugate addition
O
N
O
HN
CuI
R1
R1
R1
H+
R3O2C
CO2R3
1
6
7
R1
O
N
R2
Cu
O
N
R3O2C
R1
R3O2C
CO2R3
R2
H+
O
8
3
Scheme 3 Proposed reaction mechanism
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3301–3306

3304
Y. Shao et al.
PAPER
Methyl 5-Benzoyl-1-(4-methoxyphenyl)-2-oxo-1,2-dihydropyri-
dine-4-carboxylate (3b)
Yield: 0.154 g (85%); yellow solid; mp 135–136 °C.
13C NMR (CDCl3/TMS): δ = 13.44, 19.62, 30.95, 50.09, 52.55,
116.43, 120.96, 128.58, 128.90, 132.85, 137.13, 142.52, 142.66,
161.15, 165.77, 191.14.
1H NMR (CDCl3/TMS): δ = 3.57 (s, 3 H), 3.74 (s, 3 H), 6.85–6.92
(m, 3 H), 7.17–7.23 (m, 2 H), 7.35–7.42 (m, 2 H), 7.45–7.52 (m, 1
H), 7.66–7.72 (m, 3 H).
13C NMR (CDCl3/TMS): δ = 52.71, 55.48, 114.65, 116.68, 121.83,
127.27, 128.64, 129.01, 132.17, 132.97, 136.95, 142.97, 143.24,
159.88, 161.24, 165.68, 191.08.
HRMS: m/z calcd for C18H19NO4: 313.1314; found: 313.1317.
Methyl 5-Benzoyl-1-tert-butyl-2-oxo-1,2-dihydropyridine-4-
carboxylate (3h)
Yield: 0.067 g (43%); pale yellow solid; mp 121–122 °C.
1H NMR (CDCl3/TMS): δ = 1.60 (s, 9 H), 3.51 (s, 3 H), 6.70 (s, 1
H), 7.35–7.56 (m, 3 H), 7.61–7.69 (m, 2 H), 7.93 (s, 1 H).
13C NMR (CDCl3/TMS): δ = 28.16, 52.59, 63.07, 115.78, 122.62,
128.65, 128.93, 132.79, 137.53, 140.13, 141.59, 162.56, 166.07,
191.77.
HRMS: m/z calcd for C21H17NO5: 363.1107; found: 363.1109.
Methyl 5-Benzoyl-2-oxo-1-p-tolyl-1,2-dihydropyridine-4-car-
boxylate (3c)
Yield: 0.158 g (91%); pale yellow solid; mp 182–183 °C.
1H NMR (CDCl3/TMS): δ = 2.31 (s, 3 H), 3.58 (s, 3 H), 6.88 (s, 1
H), 7.14–7.24 (m, 4 H), 7.35–7.42 (m, 2 H), 7.45–7.51 (m, 1 H),
7.66–7.72 (m, 3 H).
13C NMR (CDCl3/TMS): δ = 21.05, 52.73, 116.72, 121.93, 125.88,
128.67, 129.04, 130.10, 132.98, 136.93, 136.97, 139.41, 143.03,
143.12, 161.12, 165.71, 191.10.
HRMS: m/z calcd for C18H19NO4: 313.1314; found: 313.1310.
Methyl 5-(4-Methoxybenzoyl)-2-oxo-1-phenyl-1,2-dihydropyri-
dine-4-carboxylate (3i)
Yield: 0.171 g (94%); yellow solid; mp 130–131 °C.
1H NMR (CDCl3/TMS): δ = 3.60 (s, 3 H), 3.76 (s, 3 H), 6.82–6.89
(m, 3 H), 7.25–7.42 (m, 5 H), 7.61–7.73 (m, 3 H).
13C NMR (CDCl3/TMS): δ = 52.71, 55.38, 113.84, 117.12, 122.04,
126.09, 129.04, 129.40, 129.45, 131.41, 139.42, 142.05, 143.01,
160.91, 163.50, 165.58, 189.71.
HRMS: m/z calcd for C21H17NO4: 347.1158; found: 347.1161.
Methyl 5-Benzoyl-1-(4-chlorophenyl)-2-oxo-1,2-dihydropyri-
dine-4-carboxylate (3d)
Yield: 0.149 g (81%); pale yellow solid; mp 142–143 °C.
HRMS: m/z calcd for C21H17NO5: 363.1107; found: 363.1104.
1H NMR (CDCl3/TMS): δ = 3.55 (s, 3 H), 6.85 (s, 1 H), 7.21–7.27
(m, 2 H), 7.33–7.42 (m, 4 H), 7.45–7.53 (m, 1 H), 7.62–7.70 (m, 3
H).
Methyl 5-(4-Methylbenzoyl)-2-oxo-1-phenyl-1,2-dihydropyri-
dine-4-carboxylate (3j)
Yield: 0.14 g (81%); yellow solid; mp 182–183 °C.
1H NMR (CDCl3/TMS): δ = 2.31 (s, 3 H), 3.58 (s, 3 H), 6.86 (s, 1
H), 7.14–7.20 (m, 2 H), 7.24–7.30 (m, 2 H), 7.31–7.42 (m, 3 H),
7.57–7.67 (m, 3 H).
13C NMR (CDCl3/TMS): δ = 52.71, 117.05, 121.98, 127.55, 128.65,
128.95, 129.62, 133.06, 135.11, 136.75, 137.73, 142.36, 143.08,
160.72, 165.39, 190.87.
13C NMR (CDCl3/TMS): δ = 21.46, 52.65, 116.93, 121.89, 126.08,
129.05, 129.16, 129.26, 129.39, 134.14, 139.39, 142.58, 143.05,
143.91, 160.88, 165.61, 190.65.
HRMS: m/z calcd for C20H14ClNO4: 367.0611; found: 367.0613.
Methyl 5-Benzoyl-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyri-
dine-4-carboxylate (3e)
Yield: 0.098 g (52%); pale yellow solid; mp 183–184 °C.
HRMS: m/z calcd for C21H17NO4: 347.1158; found: 347.1156.
1H NMR (CDCl3/TMS): δ = 3.57 (s, 3 H), 6.94 (s, 1 H), 7.37–7.46
(m, 2 H), 7.50–7.59 (m, 3 H), 7.65–7.74 (m, 3 H), 8.26–8.31 (m, 2
H).
Methyl 5-(4-Nitrobenzoyl)-2-oxo-1-phenyl-1,2-dihydropyri-
dine-4-carboxylate (3k)
Yield: 0.127 g (67%); yellow solid; mp 172–173 °C.
1H NMR (CDCl3/TMS): δ = 3.71 (s, 3 H), 6.99 (s, 1 H), 7.35–7.42
(m, 2 H), 7.44–7.55 (m, 3 H), 7.79 (s, 1 H), 7.94 (d, J = 8.7 Hz, 3
H), 8.30 (d, J = 8.5 Hz, 2 H).
13C NMR (CDCl3/TMS): δ = 52.93, 117.90, 122.50, 124.91, 127.53,
128.84, 129.03, 133.38, 136.72, 141.24, 143.38, 144.33, 147.72,
160.47, 165.16, 190.85.
13C NMR (CDCl3/TMS): δ = 52.94, 115.91, 122.43, 123.82, 126.07,
129.39, 129.59, 129.77, 139.16, 141.95, 142.19, 143.38, 149.99,
160.74, 165.20, 189.36.
HRMS: m/z calcd for C20H14N2O6: 378.0852; found: 378.0847.
Methyl 5-Benzoyl-1-benzyl-2-oxo-1,2-dihydropyridine-4-car-
boxylate (3f)
Yield: 0.112 g (65%); yellow solid; mp 122–123 °C.
HRMS: m/z calcd for C20H14N2O6: 378.0852; found: 378.0851.
1H NMR (CDCl3/TMS): δ = 3.52 (s, 3 H), 5.04 (s, 2 H), 6.78 (s, 1H),
7.16–7.27 (m, 5 H), 7.28–7.36 (m, 2 H), 7.42–7.48 (m, 1 H), 7.52–
7.58 (m, 2 H), 7.65 (s, 1 H).
13C NMR (CDCl3/TMS): δ = 52.39, 52.58, 116.58, 121.05, 128.18,
128.42, 128.50, 128.93, 128.97, 132.84, 134.88, 136.84, 142.52,
142.68, 161.16, 165.72, 190.86.
Methyl 5-(2-Bromobenzoyl)-2-oxo-1-phenyl-1,2-dihydropyri-
dine-4-carboxylate (3l)
Yield: 0.103 g (50%); yellow liquid.
1H NMR (CDCl3/TMS): δ = 3.87 (s, 3 H), 6.80 (s, 1 H), 7.30–7.53
(m, 8 H), 7.61–7.67 (m, 2 H).
13C NMR (CDCl3/TMS): δ = 53.02, 115.73, 120.10, 120.92, 126.21,
127.56, 129.34, 129.59, 129.92, 132.18, 133.73, 138.43, 139.26,
143.36, 145.78, 160.86, 166.37, 189.68.
HRMS: m/z calcd for C21H17NO4: 347.1158; found: 347.1159.
Methyl 5-Benzoyl-1-butyl-2-oxo-1,2-dihydropyridine-4-car-
boxylate (3g)
HRMS: m/z calcd for C20H14BrNO4: 411.0106; found: 411.0110.
Yield: 0.12 g (77%); pale yellow solid; mp 63–64 °C.
Methyl 5-(1-Naphthoyl)-2-oxo-1-phenyl-1,2-dihydropyridine-
4-carboxylate (3m)
Yield: 0.18 g (94%); yellow solid; mp 156–157 °C.
1H NMR (CDCl3/TMS): δ = 3.58 (s, 3 H), 6.88 (s, 1 H), 7.25–7.31
(m, 2 H), 7.37–7.49 (m, 4 H), 7.52–7.59 (m, 2 H), 7.66 (d, J = 7.1
Hz, 1 H), 7.77 (s, 1 H), 7.87 (d, J = 7.8 Hz, 1 H), 7.97 (d, J = 8.3 Hz,
1 H), 8.38 (d, J = 8.3 Hz, 1 H).
1H NMR (CDCl3/TMS): δ = 0.87 (t, J = 7.3 Hz, 3 H), 1.24–1.34 (m,
2 H), 1.60–1.71 (m, 2 H), 3.52 (s, 3 H), 3.88 (t, J = 7.3 Hz, 2 H),
6.76 (s, 1 H), 7.36–7.44 (m, 2 H), 7.47–7.55 (m, 1 H), 7.62–7.68 (m,
3 H).
Synthesis 2012, 44, 3301–3306
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Highly Substituted Pyridones
3305
13C NMR (CDCl3/TMS): δ = 52.70, 118.00, 121.14, 124.07, 125.26,
126.01, 126.66, 127.72, 128.19, 128.28, 129.06, 129.35, 130.55,
132.43, 133.62, 134.41, 139.16, 143.48, 144.48, 160.85, 166.13,
191.79.
Minor Isomer
1H NMR: δ = 1.34 (s, 9 H), 3.24 (s, 3 H), 3.68 (s, 3 H), 6.37 (s, 1 H),
11.03 (d, J = 12.7Hz, 1 H); other peaks were overlapped with the
major isomer.
13C NMR: δ = 29.78, 51.49, 52.07, 52.99, 99.88, 120.32, 127.41,
127.75, 129.92, 141.76, 146.47, 154.85, 166.65, 168.37, 192.78.
HRMS: m/z calcd for C19H24NO5 [M + H]+: 346.1654; found:
346.1653.
HRMS: m/z calcd for C24H17NO4: 383.1158; found: 383.1157.
Methyl 2-Oxo-1-phenyl-5-(thiophene-2-carbonyl)-1,2-dihydro-
pyridine-4-carboxylate (3n)
Yield: 0.12 g (71%); yellow solid; mp 161–162 °C.
1H NMR (CDCl3/TMS): δ = 3.77 (s, 3 H), 7.01 (s, 1 H), 7.12–7.17
(m, 1 H), 7.38–7.42 (m, 2 H), 7.43–7.56 (m, 3 H), 7.59 (d, J = 3.2
Hz, 1 H), 7.72 (d, J = 4.4 Hz, 1 H), 7.89 (s, 1 H).
13C NMR (CDCl3/TMS): δ = 52.99, 117.09, 122.64, 126.22, 128.21,
129.31, 129.63, 133.62, 134.69, 139.49, 141.87, 142.66, 142.95,
161.01, 165.50, 182.73.
Acknowledgment
We are grateful to the National Natural Science Foundation of
China (No. 20872037) for financial support.
Supporting Information for this article is available online at
HRMS: m/z calcd for C18H13NO4S: 339.0565; found: 339.0566.
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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Methyl 5-(Cyclohexanecarbonyl)-2-oxo-1-phenyl-1,2-dihydro-
pyridine-4-carboxylate (3o)
Yield: 0.164 g (97%); yellow solid; mp 166–167 °C.
References
1H NMR (CDCl3/TMS): δ = 1.19–1.31 (m, 3 H), 1.43–1.55 (m, 2
H), 1.58–1.73 (m, 1 H), 1.75–1.84 (m, 4 H), 2.76–2.85 (m, 1 H),
3.91 (s, 3 H), 6.70 (s, 1 H), 7.34–7.39 (m, 2 H), 7.46–7.57 (m, 3 H),
7.94 (s, 1 H).
13C NMR (CDCl3/TMS): δ = 25.33, 25.49, 29.06, 45.87, 52.80,
116.03, 120.90, 126.24, 129.20, 129.52, 139.54, 141.42, 143.59,
160.84, 166.72, 199.02.
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HRMS: m/z calcd for C20H21NO4: 339.1471; found: 339.1474.
Methyl 5-Heptanoyl-2-oxo-1-phenyl-1,2-dihydropyridine-4-
carboxylate (3p)
Yield: 0.145 g (85%); yellow solid; mp 88–89 °C.
1H NMR (CDCl3/TMS): δ = 0.87 (t, J = 6.6 Hz, 3 H), 1.25–1.30 (m,
6 H), 1.61–1.66 (m, 2 H), 2.68 (t, J = 7.3 Hz, 2 H), 3.91 (s, 3 H),
6.60 (s, 1 H), 7.28-7.39 (m, 2 H), 7.45–7.55 (m, 3 H), 8.03 (s, 1 H).
13C NMR (CDCl3/TMS): δ = 13.76, 22.21, 23.87, 28.51, 31.29,
37.80, 52.73, 116.16, 120.12, 126.17, 129.15, 129.43, 139.45,
142.47, 143.40, 160.75, 166.89, 194.99.
HRMS: m/z calcd for C20H23NO4: 341.1627; found: 341.1626.
Ethyl 5-Benzoyl-2-oxo-1-phenyl-1,2-dihydropyridine-4-car-
boxylate (3q)
Yield: 0.149 g (86%); yellow solid; mp 167–168 °C.
1H NMR (CDCl3/TMS): δ = 1.17 (t, J = 9.2 Hz, 3 H), 4.12 (q,
J = 9.2 Hz, 2 H), 7.00 (s, 1 H), 7.35–7.61 (m, 8 H), 7.75–7.83 (m, 3
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H).
13C NMR (CDCl3/TMS): δ = 13.55, 62.13, 116.90, 121.93, 126.11,
128.62, 129.03, 129.13, 129.46, 133.01, 136.88, 139.38, 142.57,
143.22, 160.99, 165.03, 191.04.
HRMS: m/z calcd for C21H17NO4: 347.1158; found: 347.1153.
Dimethyl (Z)-2-[1-(tert-Butylamino)-3-oxo-3-phenylprop-1-en-
2-yl]but-2-enedioate (5a)
Yield: 0.104 g (60%); yellow solid; two isomers in a ratio of 3:5.
Major Isomer
1H NMR (CDCl3/TMS): δ = 1.31 (s, 9 H), 3.56 (s, 3 H), 3.57 (s, 3
H), 5.37 (s, 1 H), 7.20–7.40 (m, 5 H), 7.48–7.52 (m, 1 H), 10.84 (d,
J = 14.2 Hz, 1 H).
13C NMR (400 MHz, CDCl3/TMS): δ = 29.61, 51.33, 52.13, 53.25,
102.87, 115.63, 127.88, 128.07, 130.33, 140.29, 148.13, 151.61,
165.88, 169.05, 193.74.
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3306
Y. Shao et al.
PAPER
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336 033;
Yao, W.; Xie, X.; Wang, C.; Shao, Y.; Li, Y. Org. Biomol.
Chem. 2012, 10, 2960.
E-mail: deposit@ccdc.cam.ac.uk.
(9) CCDC 861423 contains the supplementary crystallographic
data of 3a for this paper. This data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Data Centre, 12 Union
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R. J. Mol. Cat. 1987, 42, 115. (b) Fei, C. P.; Chan, T. H.
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DeLullo, G. C.; Landen, G. L.; Henry, R. A. J. Org. Chem.
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Synthesis 2012, 44, 3301–3306
© Georg Thieme Verlag Stuttgart · New York