Michael addition-lactonization reaction of electron-deficient alkynes with n-(Diphenylmethylene)glycinates: An efficient synthesis of 3-Amino-2-pyrone Derivatives

Article abstract of DOI:10.1055/s-0029-1217098

A mild and efficient process for the synthesis of 3-amino-2-pyrone derivatives has been developed. This approach is based on the Michael addition of N-(diphenylmethylene)glycinates to various alkynyl ketones, followed by lactonization using 10 mol% sodium hydroxide as catalyst. Aromatic and aliphatic alkynyl ketones were converted into the corresponding 3-amino-2-pyrone derivatives in moderate to high yields. When methyl propiolate was submitted to the reaction,α,β-dehydroamino acids were formed in good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217098

PAPER
211
Michael Addition–Lactonization Reaction of Electron-Deficient Alkynes with
N-(Diphenylmethylene)glycinates: An Efficient Synthesis of
3-Amino-2-pyrone Derivatives
Efficient
S
ynthesis
i
of 3-
A
n
mino-2-pyro
g
ne
D
erivativ
-
es Fa Zhou, Yong Zhu, Wei-Fang Tang, Tao Lu*
Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009, P. R. of China
Fax +86(25)86285179; E-mail: lut163@163.com
Received 6 July 2009; revised 22 September 2009
(Scheme 1).15 The reaction proceeded effectively with
Abstract: A mild and efficient process for the synthesis of 3-ami-
no-2-pyrone derivatives has been developed. This approach is based
on the Michael addition of N-(diphenylmethylene)glycinates to var-
ious alkynyl ketones, followed by lactonization using 10 mol% so-
both aliphatic and aromatic acetylenic ketones, in the
presence of triethylamine at –10 °C, to gave the corre-
sponding a,b-dehydroamino acid derivatives in good
dium hydroxide as catalyst. Aromatic and aliphatic alkynyl ketones yields. When 1-phenylhex-2-yn-1-one and methyl propi-
were converted into the corresponding 3-amino-2-pyrone deriva-
tives in moderate to high yields. When methyl propiolate was sub-
olate were tested under the above reaction conditions, no
product was found. Due to the importance of a,b-dehy-
mitted to the reaction, a,b-dehydroamino acids were formed in good
droamino acid derivatives, we re-examined the reaction
yields.
using sodium hydroxide as base, in place of triethylamine,
Key words: 3-amino-2-pyrone derivatives, alkynyl ketones,
Michael addition, lactonization, synthesis
to catalyze the reaction of 1-phenylhex-2-yn-1-one (1a)
with N-(diphenylmethylene)glycinate 2a. We were sur-
prised to find that, under these conditions, the 3-amino-2-
pyrone derivative 3a was obtained (Scheme 2). Here, we
2-Pyrones are found in numerous natural products1 and
wish to report a one-step, sodium hydroxide catalyzed
exhibit a wide range of biological activities; such com-
synthesis of 3-amino-2-pyrone derivatives from simple
pounds possess anti-HIV,2 telomerase inhibition,3 antimi-
and readily available starting materials: alkynyl ketones
crobial,4
antifungal,5
cardiotonic,6
pheromonal,7
and N-(diphenylmethylene)glycinate.
androgen-like,8 and phytotoxic9 properties. 2-Pyrones are
also versatile synthetic building blocks due to the exist-
ence of a six-membered cyclic unsaturated ester.10 Thus,
Table 1 Reactions of 1-Phenylhex-2-yn-1-one (1a) with N-(Diphe-
many ways have been developed for the synthesis of 2-py- nylmethylene)glycinate 2a under Various Conditions
rones either through traditional approaches11 or by transi-
Entry Base
(mol%)
Solvent
Temp Time
Yield of
tion-metal catalyzed procedures.7,12 Recently, 2-pyrones
were synthesized via electron-deficient allenes with ace-
tates or aldehydes substituted with electron-withdrawing
groups, in the presence of either potassium carbonate13 or
phosphine14 catalyst. Despite the plethora of these syn-
thetic processes, there is a general lack of simple proce-
dures with which to synthesize 3-amino-2-pyrone
derivatives from simple and readily available starting ma-
terials.
(°C)
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
(h)
120
120
120
16
24
6
3a (%)a
1
2
Cs2CO3 (50)
Et3N (50)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
acetone
toluene
EtOAc
THF
36
0
3
Ph3P (50)
0
4
KOH (50)
NaOH (50)
NaOH (100)
NaOH (10)
NaOH (10)
NaOH (10)
NaOH (10)
NaOH (10)
NaOH (10)
NaOH (10)
NaOH (10)
76
83
84
81
trace
86
5
6
O
N
Ph
Et3N
(100 mol%)
O
R2O
7
48
72
2
O
N
Ph
+
R2O
Ph
R1
8
R1
Ph
9
40
55
60
60
60
35
O
Scheme 1
10
11
12
13
14
40 min 70
40 min 68
Recently, Xue reported an efficient synthesis of a,b-dehy-
droamino acid derivatives from the reaction of acetylenic
3
1
51
69
ketones
with
N-(diphenylmethylene)glycinates
Et2O
50 min 89
SYNTHESIS 2010, No. 2, pp 0211–0216
x
x
.
x
x
.2
0
0
9
Advanced online publication: 03.11.2009
DOI: 10.1055/s-0029-1217098; Art ID: F13409SS
a Yield after purification by silica gel column chromatography.
© Georg Thieme Verlag Stuttgart · New York

212
Q.-F. Zhou et al.
PAPER
O
Ph
Ph
O
N
O
Ph
Ph
O
base
Ph
EtOH
+
N
+
OEt
Ph
1a
2a
3a
Scheme 2
We started our studies with the reaction of 1-phenylhex- ed, sodium hydroxide was found to be the best choice. The
2-yn-1-one (1a) with N-(diphenylmethylene)glycinate amount of sodium hydroxide employed had a significance
(2a) in the presence of cesium carbonate (50 mol%) in effect on the reaction rate, but no obvious effect on the
dichloromethane at room temperature for five days. To yield (Table 1, entries 4–6). The effect of higher tempera-
our surprise, 3-(diphenylmethyleneamino)-6-phenyl-4- tures was found to be beneficial not only to the reaction
propyl-2H-pyran-2-one (3a) was isolated from the reac- rate but also for the yield of 3a (Table 1, entries 6–8).
tion mixture. This compound was satisfactorily character- When the reaction was carried out at 0 °C, only trace
ized by NMR and MS analysis. This metal-free base- amounts of product were obtained even after a prolonged
catalyzed process thus generates a 3-amino-2-pyrone de- reaction time (72 h). The choice of solvent also had an ef-
rivative that is difficult to construct using other methods. fect on the reaction; performing the reactions in acetone,
This prompted us to explore the feasibility of constructing toluene, ethyl acetate or tetrahydrofuran afforded the tar-
3-amino-2-pyrone derivatives using readily available get product in good yields. It was interesting to observe
alkynyl ketones and N-(diphenylmethylene)glycinates. that, when the same reaction was performed in diethyl
To this end, we then carried out the reaction under various ether at 35 °C, compound 3a was obtained in excellent
conditions in order to optimize the catalyst and reaction yield after 50 minutes. Thus, the optimal reaction condi-
conditions; the results are shown in Table 1. It was found tions for this reaction were determined to be: 10 mol% so-
that the nature of the base was critical to the success of the dium hydroxide as base catalyst in diethyl ether at 35 °C.
reaction (Table 1, entries 1–4). Among the catalysts test-
Table 2 Reaction of Acetylenic Ketones 1 with N-(Diphenylmethylene)glycinates 2
O
O
Ph
Ph
O
Ph
Ph
NaOH (10 mol%)
Et2O, 35 °C
N
R3OH
R1
+
O
N
+
OR3
R2
R2
R1
1
2
3
Entry
1
R1
Ph
Ph
Ph
R2
R3
Et
Time (min)
Product
3a
3a
3a
3b
3c
Yield (%)a
Pr
Pr
Pr
Pent
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
Pr
50
30
89
91
68
86
90
92
94
92
90
92
96
81
65
62
2
Me
t-Bu
Et
3
60
4
4-FC6H4
30
5
4-ClC6H4
Et
70
6
4-BrC6H4
4-O2NC6H4
4-F3CC6H4
2-F3CC6H4
4-MeC6H4
Et
60
3d
3e
7
Et
120
30
8
Et
3f
9
Et
30
3g
3h
3i
10
11
12
13
14
Et
100
70
4-MeOC6H4
1-naphthyl
Pr
Et
Et
70
3j
Et
30
3k
3l
CH2CH2Ph
Et
30
a Yield after purification by silica gel column chromatography.
Synthesis 2010, No. 2, 211–216 © Thieme Stuttgart · New York

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Efficient Synthesis of 3-Amino-2-pyrone Derivatives
213
With these results in hand, several derivatives of glycine one, under the conditions described, gave the correspond-
esters were synthesized and tested under the reaction con- ing products 3c and 3j in 90% and 96% yields, respective-
ditions (Table 2). Methyl and ethyl glycine derivatives ly.
gave the expected products in similar yields, whereas the
corresponding bulky tert-butyl ester afforded the desired
product 3a in lower yield. A variety of electron-deficient
alkynes were then submitted to the reaction; these results
When methyl propiolate16 and dimethyl but-2-ynedioate
were submitted to the reaction conditions, the reaction
proceeded smoothly at 35 °C in two hours to afford the
corresponding a,b-dehydroamino acids in good yields
(Scheme 3).
are summarized in Table 2. It was observed that all of the
reactions proceeded smoothly under the optimized condi-
A plausible mechanism to account for the formation of the
tions, to afford the corresponding products with moderate
3-amino-2-pyrone derivatives 3 is presented in Scheme 4
to excellent yields. The results show the scope of the reac-
as follows:17 Sodium hydroxide deprotonates the active
tion with respect to a range of aromatic and aliphatic
methylene proton of the benzophenone Schiff base deriv-
alkyne ketones. Aromatic alkyne ketones show higher re-
ative of glycine ester 2 to generate intermediate 6. The in-
termediate 6 then undergoes conjugate addition to the
electron-deficient alkyne to give 7, followed by proton
transfer to give compound 8. The intermediate 8 would
activity in the reaction than the aliphatic alkyne ketones.
The substituents on the phenyl ring of the aromatic acety-
lenic ketones have no obvious effect on the yields of the
reactions. For example, the reaction of 1-(4-chlorophe-
undergo carbon–carbon double bond migration and the
nyl)hex-2-yn-1-one or 1-(4-methoxyphenyl)hex-2-yn-1-
O
N
Ph
EtO
O
NaOH (10 mol%)
Et2O, 35 °C, 2 h
O
Ph
+
R
N
Ph
R
EtO
OMe
Ph
O
OMe
4a: R = H
4b: R = COOMe
5a: 87%
5b: 85%
Scheme 3
O
R1
O
O
Ph
Ph
R2
Ph
NaOH
N
N
OR3
OR3
Ph
2
6
R2
O
O
R2
O
carbon–carbon double
bond migration
O
protonation
R3O
Ph
R1
R3O
Ph
R1
N
N
Ph
Ph
7
8
O
R2
O
O
Ph
OR3
O
base
R3O
Ph
R1
Ph
N
R2
R1
Ph
10
9
O
Ph
Ph
O
R3O
N
Ph
Ph
N
– R3O–
O
O
R2
R1
R2
R1
3
11
Scheme 4 Possible mechanism for the formation of 3-amino-2-pyrone derivatives 3
Synthesis 2010, No. 2, 211–216 © Thieme Stuttgart · New York

214
Q.-F. Zhou et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 172.4, 165.3, 157.5, 153.2, 140.6,
138.7, 137.2, 133.5, 131.3, 129.8, 129.4, 128.2, 128.1, 128.0, 127.9,
127.1, 116.1, 103.4, 31.8, 31.2, 29.8, 27.3, 22.6, 14.0.
MS (70 eV): m/z = 439 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C29H26FNO2: 440.2020;
subsequent cyclization would give the product 3-amino-
2-pyrone derivatives 3.
In summary, we have developed an efficient methodology
for the synthesis of 3-amino-2-pyrone derivatives 3 from
simple and commercially available starting materials.
High yields of a,b-dehydroamino acids were obtained
when ethyl propynoate and dimethyl but-2-ynedioate
were submitted to the reaction. Efforts are currently un-
derway in our laboratories to reveal the biological activi-
ties of 3-amino-2-pyrone derivatives 3 and to develop
their synthetic applications.
found: 440.2021.
6-(4-Chlorophenyl)-3-(diphenylmethyleneamino)-4-propyl-2H-
pyran-2-one (3c)
Yellow oil.
IR (KBr): 2930, 1710, 1634, 1575, 1446, 695 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 7.5 Hz, 2 H), 7.65 (d,
J = 8.1 Hz, 2 H), 7.50–7.24 (m, 10 H), 6.46 (s, 1 H), 2.37 (t, J = 7.5
Hz, 2 H), 1.64–1.52 (m, 2 H), 1.00 (t, J = 7.2 Hz, 3 H).
All reactions were performed in anhydrous solvents under an argon
atmosphere. THF, Et2O, and toluene were distilled from K and Na
metal, respectively. CH2Cl2, EtOAc and acetone were distilled from
CaH2. PE refers to petroleum ether (boiling range 60–90 °C). Acet-
ylenic ketones18 and N-(diphenylmethylene)glycinates19 were pre-
pared following known procedures. Methyl propiolate and dimethyl
but-2-ynedioate are commercially available. Reaction progress was
monitored using thin layer chromatography (TLC) on precoated
Merck silica gel Kiese gel 60 F254 plates; the spots were visualized
under UV light (254 nm). Flash chromatography was conducted
with silica gel 230–400 mesh. The IR spectra were measured on a
Jasco FT/IR-430 spectrophotometer. 1H and 13C NMR spectra were
recorded in CDCl3 using a Bruker Avance 300 spectrometer. Chem-
ical shifts (d, ppm) were determined with TMS as the internal refer-
ence; J values are given in Hz. GC-MS spectra were obtained on a
Fisons 8000 Trio instrument at an ionization potential of 70 eV.
High-resolution mass spectra (HRMS) were recorded on a Shimadzu
LC-IT-TOF/MS instrument.
13C NMR (75 MHz, CDCl3): d = 172.4, 157.3, 152.9, 140.3, 138.6,
137.1, 135.7, 133.9, 131.3, 130.2, 130.1, 129.8, 129.4, 129.0, 128.2,
127.9, 126.2, 103.9, 33.2, 20.9, 14.2.
MS (70 eV): m/z = 427 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C27H22ClNO2: 428.1412;
found: 428.1414.
6-(4-Bromophenyl)-3-(diphenylmethyleneamino)-4-propyl-2H-
pyran-2-one (3d)
Yellow oil.
IR (KBr): 2916, 1708, 1634, 1568, 1486, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 7.5 Hz, 2 H), 7.59 (d,
J = 8.7 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H), 7.46–7.24 (m, 8 H), 6.47
(s, 1 H), 2.37 (t, J = 7.5 Hz, 2 H), 1.64–1.50 (m, 2 H), 1.00 (t,
J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.3, 157.2, 152.9, 140.2, 138.6,
137.1, 134.0, 132.0, 131.8, 131.3, 130.6, 129.8, 129.4, 128.2, 127.9,
126.3, 124.0, 103.9, 33.1, 20.9, 14.2.
Reaction of 1-Phenylhex-2-yn-1-one (1) with N-(Diphenylmeth-
ylene)glycinate 2; General Procedure
A mixture of the benzophenone Schiff base derivative of glycine
ethyl ester (0.2 mmol), alkynyl ketone (0.3 mmol), and NaOH (0.02
mmol) in Et2O (2 mL) under argon, was heated to 35 °C with stir-
ring. When the reaction was complete (monitored by TLC), the sol-
vent was evaporated and the crude product was purified by flash
chromatography on silica gel (PE–EtOAc, 10:1→5:1), to afford the
corresponding pure product.
MS (70 eV): m/z = 473 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C27H22BrNO2: 472.0907;
found: 472.0901.
3-(Diphenylmethyleneamino)-6-(4-nitrophenyl)-4-propyl-2H-
pyran-2-one (3e)
Yellow oil.
3-(Diphenylmethyleneamino)-6-phenyl-4-propyl-2H-pyran-2-
one (3a)
Yellow oil.
IR (KBr): 2924, 1707, 1633, 1504, 1447, 693 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.73–7.71 (m, 4 H), 7.49–7.25 (m,
11 H), 6.51 (s, 1 H), 2.38 (t, J = 7.8 Hz, 2 H), 1.62–1.59 (m, 2 H),
1.01 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.2, 157.5, 154.0, 140.4, 138.6,
137.1, 133.7, 131.6, 131.2, 129.8, 129.7, 129.3, 128.8, 128.2, 128.1,
127.9, 124.9, 103.6, 33.1, 20.9, 14.1.
MS (70 eV): m/z = 393 [M+].
HRMS (ESI): m/z [M+] calcd for C27H23NO2: 393.1729; found:
IR (KBr): 2930, 1711, 1637, 1595, 1518, 1446, 694 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.24 (d, J = 9.0 Hz, 2 H), 7.87 (d,
J = 9.0 Hz, 2 H), 7.78 (d, J = 8.4 Hz, 2 H), 7.58–7.24 (m, 8 H), 6.65
(s, 1 H), 2.41 (t, J = 7.2 Hz, 2 H), 1.64–1.57 (m, 2 H), 1.02 (t,
J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.5, 156.8, 151.0, 147.9, 139.5,
138.3, 137.3, 135.4, 131.5, 129.5, 128.2, 127.8, 125.4, 124.1, 106.6,
33.1, 20.9, 14.1.
MS (70 eV): m/z = 438 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C27H22N2O4: 439.1652; found:
439.1658.
393.1732.
3-(Diphenylmethyleneamino)-4-propyl-6-[4-(trifluorometh-
yl)phenyl]-2H-pyran-2-one (3f)
Yellow oil.
3-(Diphenylmethyleneamino)-6-(4-fluorophenyl)-4-pentyl-2H-
pyran-2-one (3b)
Yellow oil.
IR (KBr): 2928, 1711, 1635, 1508, 1446, 835, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78–7.67 (m, 4 H), 7.48–7.24 (m,
8 H), 7.24–7.03 (m, 2 H), 2.37 (t, J = 6.9 Hz, 2 H), 1.58–1.51 (m,
2 H), 1.34–1.24 (m, 4 H), 0.91 (t, J = 7.2 Hz, 3 H).
IR (KBr): 2962, 1712, 1637, 1614, 1577, 1446, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.83–7.86 (m, 4 H), 7.63 (d,
J = 8.4 Hz, 2 H), 7.49–7.24 (m, 8 H), 6.57 (s, 1 H), 2.39 (t, J = 7.5
Hz, 2 H), 1.63–1.54 (m, 2 H), 1.01 (t, J = 7.2 Hz, 3 H).
Synthesis 2010, No. 2, 211–216 © Thieme Stuttgart · New York

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Efficient Synthesis of 3-Amino-2-pyrone Derivatives
215
13C NMR (75 MHz, CDCl3): d = 172.5, 157.1, 152.2, 139.9, 138.5,
137.1, 134.9, 131.5, 130.1, 129.9, 129.5, 129.0, 128.2, 127.9, 125.9,
125.8, 125.1, 105.2, 33.2, 20.9, 14.2.
MS (70 eV): m/z = 461 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C28H22F3NO2: 462.1675;
127.4, 127.1, 126.9, 126.2, 125.1, 125.0, 108.8, 104.1, 33.2, 20.9,
14.2.
MS (70 eV): m/z = 443 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C31H25NO2: 444.1958; found:
444.1956.
found: 462.1674.
3-(Diphenylmethyleneamino)-4,6-dipropyl-2H-pyran-2-one
(3k)
Yellow oil.
IR (KBr): 2932, 1712, 1645, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.77 (d, J = 7.2 Hz, 2 H), 7.46–
7.24 (m, 8 H), 5.76 (s, 1 H), 2.36 (t, J = 7.2 Hz, 2 H), 2.26 (t, J = 7.5
Hz, 2 H), 1.63–1.54 (m, 4 H), 0.95 (t, J = 7.5 Hz, 3 H), 0.90 (t,
J = 7.2 Hz, 3 H).
3-(Diphenylmethyleneamino)-4-propyl-6-[2-(trifluorometh-
yl)phenyl]-2H-pyran-2-one (3g)
Yellow oil.
IR (KBr): 2962, 1714, 1643, 1577, 1447, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.81 (d, J = 7.2 Hz, 2 H), 7.71 (d,
J = 7.5 Hz, 2 H), 7.55–7.24 (m, 10 H), 6.18 (s, 1 H), 2.36 (t, J = 7.5
Hz, 2 H), 1.59–1.52 (m, 2 H), 0.98 (t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.4, 157.4, 152.4, 139.6, 138.6,
136.9, 134.3, 131.7, 131.3, 131.0, 129.8, 129.7, 129.4, 128.2, 128.1,
128.0, 126.8, 126.4, 125.8, 108.4, 32.9, 20.7, 14.0.
13C NMR (75 MHz, CDCl3): d = 171.0, 157.7, 157.5, 139.1, 137.6,
136.0, 131.3, 130.0, 128.6, 128.1, 127.0, 126.9, 126.8, 103.7, 34.0,
31.7, 19.6, 19.2, 13.0, 12.2.
MS (70 eV): m/z = 461 [M+].
MS (70 eV): m/z = 359 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C28H22F3NO2: 462.1675;
HRMS (ESI): m/z [M+] calcd for C24H25NO2: 359.1885; found:
found: 462.1672.
359.1883.
3-(Diphenylmethyleneamino)-4-propyl-6-p-tolyl-2H-pyran-2-
one (3h)
3-(Diphenylmethyleneamino)-6-phenethyl-4-propyl-2H-pyran-
2-one (3l)
Yellow oil.
Yellow oil.
IR (KBr): 2961, 1708, 1633, 1596, 1574, 695 cm–1.
IR (KBr): 2930, 1704, 1648, 1600, 1556, 699 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 7.2 Hz, 2 H), 7.62 (d,
J = 8.1 Hz, 2 H), 7.50–7.27 (m, 8 H), 7.18 (d, J = 8.1 Hz, 2 H), 6.45
(s, 1 H), 2.37–2.32 (m, 5 H), 1.62–1.54 (m, 2 H), 1.00 (t, J = 7.5 Hz,
3 H).
1H NMR (300 MHz, CDCl3): d = 7.77 (d, J = 7.2 Hz, 2 H), 7.49–
7.31 (m, 6 H), 7.25–7.14 (m, 5 H), 7.05 (d, J = 7.8 Hz, 2 H), 5.61 (s,
1 H), 2.90 (t, J = 7.5 Hz, 2 H), 2.67 (t, J = 7.5 Hz, 2 H), 2.20 (t,
J = 7.5 Hz, 2 H), 1.47–1.37 (m, 2 H), 0.89 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 171.1, 156.5, 153.2, 139.5, 138.9,
137.6, 132.2, 130.1, 128.7, 128.2, 127.8, 127.0, 126.9, 126.8, 123.7,
101.8, 32.1, 20.3, 19.8, 13.1.
13C NMR (75 MHz, CDCl3): d = 172.3, 158.5, 157.4, 140.3, 140.1,
138.8, 137.2, 132.6, 131.2, 129.7, 128.5, 128.3, 128.2, 128.0, 127.9,
126.3, 105.6, 35.4, 33.4, 32.8, 20.7, 14.1.
MS (70 eV): m/z = 407 [M+].
MS (70 eV): m/z = 421 [M+].
HRMS (ESI): m/z [M + H]+ calcd for C28H25NO2: 408.1958; found:
HRMS (ESI): m/z [M+] calcd for C29H27NO2: 421.2042; found:
408.1958.
421.2039.
3-(Diphenylmethyleneamino)-6-(4-methoxyphenyl)-4-propyl-
2H-pyran-2-one (3i)
(Z)-1-Ethyl 5-Methyl 2-(Diphenylmethyleneamino)pent-2-ene-
dioate (5a)16
Yellow oil.
Pale-yellow oil.
IR (KBr): 2932, 1705, 1633, 1607, 1575, 697 cm–1.
IR (KBr): 2961, 1735, 1717, 1262, 1097, 695 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.80 (d, J = 7.2 Hz, 2 H), 7.69 (d,
J = 8.7 Hz, 2 H), 7.51–7.28 (m, 8 H), 6.92 (d, J = 8.7 Hz, 2 H), 6.39
(s, 1 H), 3.84 (s, 3 H), 2.38 (t, J = 7.5 Hz, 2 H), 1.66–1.52 (m, 2 H),
1.01 (t, J = 7.5 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.59 (d, J = 7.2 Hz, 2 H), 7.35–
7.23 (m, 6 H), 7.09–7.01 (m, 2 H), 6.11 (d, J = 7.2 Hz, 1 H), 3.93
(q, J = 6.9 Hz, 2 H), 3.53 (s, 3 H), 3.03 (d, J = 6.9 Hz, 2 H), 1.04 (t,
J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.1, 160.9, 157.6, 154.3, 141.0,
138.8, 137.2, 132.7, 131.2, 129.7, 129.3, 129,1, 128.1, 127.9, 126.5,
124.4, 114.2, 102.1, 55.4, 33.2, 20.9, 14.2.
MS (70 eV): m/z = 351 [M+].
HRMS (ESI): m/z [M+] calcd for C21H21NO4: 351.1471; found:
351.1473.
MS (70 eV): m/z = 423 [M+].
(Z)-1-Ethyl 2,3-Dimethyl 1-(Diphenylmethyleneamino)prop-1-
ene-1,2,3-tricarboxylate (5b)
Pale-yellow oil.
HRMS (ESI): m/z [M + H]+ calcd for C28H25NO3: 424.1907; found:
424.1905.
3-(Diphenylmethyleneamino)-6-(naphthalen-1-yl)-4-propyl-
IR (KBr): 2951, 1737, 1720, 1272, 1089, 698 cm–1.
2H-pyran-2-one (3j)
Yellow oil.
IR (KBr): 2929, 1709, 1636, 1595, 1575, 696 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.59 (d, J = 7.2 Hz, 2 H), 7.48–
7.37 (m, 8 H), 4.01 (q, J = 6.9 Hz, 2 H), 3.67 (s, 3 H), 3.56 (s, 3 H),
3.27 (s, 2 H), 1.16 (t, J = 7.2 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 8.07 (m, 1 H), 7.90–7.83 (m, 4 H),
7.63–7.61 (m, 1 H), 7.55–7.65 (m, 11 H), 6.37 (s, 1 H), 2.45 (t,
J = 7.5 Hz, 2 H), 1.66–1.59 (m, 2 H), 1.04 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 172.4, 158.0, 155.2, 140.3, 137.2,
133.8, 131.3, 130.5, 130.4, 129.8, 129.4, 128.6, 128.3, 128.2, 128.0,
13C NMR (75 MHz, CDCl3): d = 171.7, 170.7, 166.8, 165.3, 150.4,
131.1, 129.7, 128.3, 128.2, 111.5, 61.8, 52.1, 52.0, 33.1, 13.8.
MS (70 eV): m/z = 409 [M+].
Synthesis 2010, No. 2, 211–216 © Thieme Stuttgart · New York

216
Q.-F. Zhou et al.
PAPER
HRMS (ESI): m/z [M+] calcd for C23H23NO6: 409.1525; found:
409.1523.
(11) (a) Komiyama, T.; Takaguchi, Y.; Tsuboi, S. Tetrahedron
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Synthesis 2010, No. 2, 211–216 © Thieme Stuttgart · New York