PPh3-KOBut-mediated cyclization reaction of β-ketoesters with alkynyl ketones: Synthesis of functionalized 2-pyrones

Article abstract of DOI:10.1080/00397911.2010.517374

Cyclization of alkynyl ketones with β-ketoesters mediated by PPh3 and KOBu^t to synthesize 2-pyrone derivatives was systematically described. A variety of β-ketoesters reacted with alkynyl ketones to give functionalized 2-pyrones in moderate to

Full text of DOI:10.1080/00397911.2010.517374

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PPh3-KOBut–Mediated Cyclization
Reaction of β-Ketoesters with Alkynyl
Ketones: Synthesis of Functionalized 2-
Pyrones
Bin Hu a , Ling-Guo Meng a , Xiao-Li Hao a , Mao Liang a & Song Xue a
a Department of Applied Chemistry, Tianjin University of Technology,
Tianjin, China
Version of record first published: 27 Jul 2011.
To cite this article: Bin Hu , Ling-Guo Meng , Xiao-Li Hao , Mao Liang & Song Xue (2011):
PPh3-KOBut–Mediated Cyclization Reaction of β-Ketoesters with Alkynyl Ketones: Synthesis
of Functionalized 2-Pyrones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 41:21, 3147-3161
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Synthetic Communications1, 41: 3147–3161, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.517374
PPh3-KOBut–MEDIATED CYCLIZATION REACTION OF
b-KETOESTERS WITH ALKYNYL KETONES: SYNTHESIS
OF FUNCTIONALIZED 2-PYRONES
Bin Hu, Ling-Guo Meng, Xiao-Li Hao, Mao Liang, and
Song Xue
Department of Applied Chemistry, Tianjin University of Technology, Tianjin,
China
GRAPHICAL ABSTRACT
Abstract Cyclization of alkynyl ketones with b-ketoesters mediated by PPh3 and KOBut to
synthesize 2-pyrone derivatives was systematically described. A variety of b-ketoesters
reacted with alkynyl ketones to give functionalized 2-pyrones in moderate to good yields
under mild conditions.
Keywords Alkynyl ketone; cyclization reaction; b-ketoester; 2-pyrone
INTRODUCTION
2-Pyrone molecules have attracted much attention from organic chemists
because of their potential biological activity[1] and pharmaceutical significance.[2]
Moreover, they have also been used as important intermediates in organic synthesis.[3]
Consequently, many feasible methods have been developed for the synthesis of
2-pyrone derivatives.[4,5] However, most of these approaches suffer from either the
limited diversity of available starting materials or expensive catalysts. Based on these
problems, the development of a facile and efficient method for 2-pyrones has been
strongly desired.
Reaction based on nucleophilic catalysis via conjugate addition of N- and
P-nucleophiles has proven to be useful in the development of cycloaddition provid-
ing various carbo-[6] and heterocycles.[7,8] In our group, we have also been interested
in the application of organic base-catalyzed annulation reactions based on
electron-deficient alkynes in organic synthesis.[9] Recently, we have reported pyridine
Received February 20, 2010.
Address correspondence to Song Xue, Department of Applied Chemistry, Tianjin University of
Technology, Tianjin 300384, China. E-mail: xuesong@ustc.edu.cn
3147

3148
B. HU ET AL.
and potassium tert-butoxide (KOBut) cocatalyzed benzannulation of b-diketones
with dimethyl acetylenedicarboxylate to provide multifunctionalized benzenes.[10]
During the course of our study on the annuulation reaction, it was demonstrated
that KOBut is crucial for this benzannulation reaction. As a continuation of this
cocatalytic system research, we further investigated the possibility of cyclization
reaction of alkynyl ketones with b-ketoesters mediated by this cocatalytic system.
To our delight, a new cyclization reaction occurred when an alkynyl ketone was
stirred with a b-ketoester in the presence of PPh3 and KOBut. Herein, we report this
annulation reaction for the synthesis of 2-pyrones under mild conditions.
RESULTS AND DISCUSSION
Our studies were initiated by the addition 0.25 equiv PPh3 to a solution of alky-
nyl ketone 1a and ethyl 3-oxobutanoate 2a, but the reaction did not occur, which
might be ascribed to the steric effect.[11] Intrigued by our previous report,[10] we
discovered that a new cyclization reaction occurred when KOBut was added into
the reaction system, and the results are shown in Table 1. For example, treatment
of 1a with 2a in the presence of 25 mol% PPh3 and 25 mol% KOBut in CH2Cl2 at
room temperature for 24 h afforded a pale yellow solid in 40% yield, which was char-
acterized as compound 3a by NMR and high-resolution mass spectrometry (HRMS)
spectra. In the absence of PPh3, only 20% yield of 3a was obtained under similar
conditions. PPh3 is the most efficient base for the course of this reaction. The use
of other organic bases, such as tributylphosphine (Bu3P), pyridine, p-(N,N-dimethy-
lamino)pyridine (DMAP), and 1,4-diazabicyclo[2,2,2]-octane (DABCO), gave lesser
yields of the desired product than PPh3 as organic base. On the other hand, the use
of other inorganic bases, such as NaH, NaOH, and Na2CO3, also did not give sat-
isfactory yields. The amount of KOBut obviously has an effect on this cyclization
reaction. The desired product of 3a was obtained in 56% yield when 75 mol% KOBut
was used. However, when 50 mol% and 100 mol% KOBut were used for the reaction,
the product 3a was obtained in 44% and 45% yields, respectively. The yield of the
reaction could not be improved when the reaction was stirred at 0 ꢀC or at reflux.
The solvents acetonitrile (CH3CN), toluene, and dimethoxylethane (DME) gave
the desired product in relatively lesser yields.
With the reaction conditions optimized for the formation of 3a, subsequently
we investigated the scope and limitations of this reaction. Various b-ketoesters were
subjected to the reaction under the standard conditions; their representative results
are shown in Table 2. When the R2 group of substrate 2 was an aliphatic group, the
reaction worked smoothly, giving the functionalized 2-pyrones 3 in moderate to
good yields. Clearly, the R2 group has no obviously effect on the yield of the
product. For example, when R2 varied from methyl to n-propyl, isopropyl, and
tert-butyl group, the cyclization reaction gave the corresponding products in 57%,
53%, and 60% yields, respectively (entries 2–4, Table 2). However, substitutes on
the aromatic alkynyl ketones had an effect on the reaction yields. The substrate with
an electron-withdrawing group on the aromatic ring gave better yields than that of
an electron-donating group on the aromatic ring. For example, substrates containing
fluoro-, chloro-, and bromo- groups on phenyl rings afforded the corresponding
functionalized 2-pyrones 3e–g in good yields. While the methoxyl group was in

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3149
Table 1. Reaction of 1-phenylhex-2-yn-1-one 1a with ethyl 3-oxobutanoate
Entry
Lewis base (mol %)
KOBut (mol %)
Solvent
Yield (%)a
1
2
PPh3 (25)
PPh3 (25)
—
—
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
Toluene
DME
NR
40
KOBut (25)
KOBut (25)
KOBut (25)
KOBut (25)
KOBut (25)
KOBut (25)
NaH (25)
3
20
21
4
PBu3 (25)
Pyridine (25)
DMAP (25)
DABCO (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
—
5
34
36
6
7
33
26
8
9
NaOH (25)
Na2CO3 (25)
KOBut (50)
KOBut (75)
KOBut (100)
KOBut (75)
KOBut (75)
KOBut (75)
KOBut (75)
KOBut (75)
KOBut (75)
37
10
11
12
13
14
15
16
17
18
19
Trace
44
56
45
40
PPh3 (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
PPh3 (25)
39b
35c
20
33
20
aIsolated yield.
bAt 0 ꢀC.
cAt reflux.
the para position of the benzene ring, the corresponding product 3i was obtained in
58% yield, but only a trace amount of 3h was obtained when 1-(4-nitrophenyl)hex-
2-yn-1-one reacted with ethyl 3-oxobutanoate under the standard conditions. The
yield of 3h could be improved to 65% when the reaction mixture was stirred at
0 ꢀC for 8 h. Heteroaromatic alkynyl ketone used as substrate, such as 1-(thiophen-2-
yl)hex-2-yn-1-one, gave the desired product 3j in moderate yield. The corres-
ponding product 3o was obtained in 53% yield when diethyl malonate was used as
substrate.
To further evaluate the scope of this reaction, various aromatic b-ketoesters
were synthesized and tested, but the desired product 2-pyrones were obtained in les-
ser yields under the standard conditions, and these results are summarized in Table 3.
Treatment of 1-phenylhex-2-yn-1-one 1a with ethyl 3-oxo-3-phenylpropanoate in the
presence of 25 mol% PPh3 and 75 mol% KOBut in CH2Cl2 at room temperature for
24 h gave only 27% yield of the corresponding product 4a. After the reactions were
optimized for aromatic b-ketoesters, it is found that the amount of KOBut has a
remarkable effect on the yield of 2-pyrone product. For example, the yield of pro-
duct 4a was improved to 47% when decreasing the amount of KOBut to 25 mol%,

3150
B. HU ET AL.
Table 2. Reactions of alkynyl ketones with aliphatic b-ketoesters mediated by PPh3 and KOBut
Entry
R1
R2
CH3
Product
Yield (%)a
1
2
C6H5
C6H5
C6H5
C6H5
3a
3b
3c
3d
3e
3f
56
57
C3H7
3
CH(CH3)2
C(CH3)3
CH3
53
60
4
5
4-FC6H4
84
73
6
4-ClC6H4
4-BrC6H4
4-NO2C6H4
4-CH3OC6H4
2-thiophenyl
1-naphthyl
4-BrC6H4
4-BrC6H4
4-BrC6H4
C6H5
CH3
CH3
7
3g
3h
3i
69
8
CH3
CH3
<10 (65b)
58
45
9
10
11
12
13
14
15
CH3
CH3
3j
3k
3l
85
66
C3H7
CH(CH3)2
C(CH3)3
EtO
3m
3n
3o
72
75
53
aIsolated yield.
bPerformed at 0 ꢀC for 8 h.
but decreased sharply when the amount of KOBut was further reduced to 10 mol%.
The yield was successfully improved to 60% when the reaction was stirred in
toluene at 60 ꢀC for 24 h. Intrigued by the results, we submitted various aromatic
b-ketoesters to the cyclization reaction. Clearly, the substitutes on the aromatic
b-ketoesters have no obvious effect on the yields of the reaction. The substrate con-
taining a fluoro-group on its phenyl ring afforded 62% yield of 4d, which was a pale
yellow solid and is unambiguously determined by x-ray diffraction; its ORTEP
drawing is shown in Fig. 1.[12] When heteroaromatic b-ketoester was submitted to
this reaction, the corresponding product 4g was also obtained in 64% yield. Notably,
the yield of 4h was also obtained in moderate yield when (E)-ethyl 3-oxo-5-phenyl-
pent-4-enoate was used as substrate. The substrates with electron-withdrawing
groups on the aromatic ring of alkynyl ketones gave better yields than those with
electron-donating groups on the aromatic ring. Substrates containing an electron-
withdrawing group, such as fluoro and chloro, on the phenyl rings gave the
corresponding functionalized 2-pyrones 4i–j in 80% and 82% yields, respectively,
Whereas the methoxyl group on the para position of the benzene ring afforded the
corresponding product 4l in moderate yield. Aliphatic alkynyl ketone was also con-
verted to the desired product, albeit the yield of 4m was moderate (entry 15, Table 3).
In many cases, the moderate yields obtained in the reaction could be accounted
for by the formation of other by-products, which could not be isolated by column
chromatography.

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3151
Table 3. Reactions of alkynyl ketones with aromatic b-ketoesters mediated by PPh3 and KOBut
Entry
R1
Ar
Product
Yield (%)a
1
2
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4a
4a
4a
4b
4c
4d
4e
4f
27b
47c
60
55
56
62
61
49
64
52
80
82
78
46
50
3
4
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
5
6
7
4-BrC6H4
2-naphthyl
2-thiophenyl
8
9
4g
4h
4i
=
10
11
12
13
14
15
(E)-C6H4CH CH
4-BrC6H4
4-BrC6H4
4-FC6H4
4-ClC6H4
4j
4-BrC6H4
4-CH3OC6H4
C6H5CH2CH2
4-BrC6H4
4-BrC6H4
4-BrC6H4
4k
4l
4m
aIsolated yields.
bPerformed in CH2Cl2 in the presence of 75 mol% KOBut.
cPerformed in CH2Cl2 in the presence of 25 mol% KOBut.
A plausible mechanism for the formation of these 2-pyrone derivatives could
be proposed as shown in Scheme 1. PPh3 as nucleophilic trigger adds to alkynyl
ketone to generate the reactive zwitterionic intermediate 6, which deprotonates the
b-ketoester to produce 7 and 8. The intermediate 8 then undergoes a Michael-type
addition to 7 to generate 9. The intermediate 9 gives its resonance structure 10 by
Figure 1. ORTEP drawing of compound 4d.

3152
B. HU ET AL.
Scheme 1. Possible mechanism for the reaction of alkynyl ketones with b-ketoesters.
electron transfer, following by intramolecular cycloaddtion step to form 11. Finally,
the intermediate 11 is deprotonated by base to give 12, which affords product 3 or 4
by the elimination of PPh3. It is noted that KOBut probably promoted the formation
of 7 and 8 during the reaction process. Furthermore, the formation of 12 might also
be mediated by KOBut. The different amounts of KOBut was used when R2 group of
b-ketoester varied from an alkyl to an aryl group, which might be ascribed to lower
reactivity of aliphatic b-ketoester than that of aromatic b-ketoester.
In conclusion, we have described an annulation reaction of alkynyl ketones
with b-ketoesters in the presence of PPh3 and KOBut. The functionalized 2-pyrones
were obtained in moderate to good yields under mild conditions. The obvious advan-
tage of this work is that it is easier to synthesize the starting materials and it uses
more diverse substrates. The presented procedure leads to building blocks and
potential intermediates in organic synthesis. However, efforts are made to elucidate
the mechanistic details and the effect of PPh3 and KOBut character on the reactions.
EXPERIMENTAL
All reactions were conducted in oven-dried glassware with magnetic stirring.
Dichloromethane was dried and freshly distilled from calcium hydride under a nitro-
gen atmosphere. Chromatographic purification was performed on silica gel (100–200
mesh) and analytical thin-layer chromatography (TLC) on silica gel 60-F254
(Qindao), which was detected by fluorescence. 1H NMR (400 MHz) and 13C
NMR (100 MHz) spectra were measured with a Bruker AC 400 spectrometer using
tetramethylsilane (TMS) as an internal standard. 1H NMR data are reported as fol-
lows: d, chemical shift; coupling constants (J are given in hertz, Hz); and integration.
Abbreviations to denote the multiplicity of a particular signal were s (singlet), d
(doublet), t (triplet), and q (quartet). High-resolution mass spectra (HRMS) were
obtained with a Micromass GCT-TOF mass spectrometer. Infrared (IR) spectra
were recorded as thin films or as solids in KBr pellets on a Perkin-Elmer FT210

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3153
spectrophotometer. Melting points were determined on a digital melting-point
apparatus, and temperatures were uncorrected.
Reaction of Aliphatic b-Ketoesters with Alkynyl Ketones: General
Procedure
PPh3 (0.075 mmol) and KOBut (0.225 mmol) were added to a stirred solution
of the aliphatic b-ketoesters (0.4 mmol) and alkynyl ketones (0.3 mmol) in CH2Cl2
(2 mL). The reaction mixture was stirred at room temperature for 24 h. The solvent
was removed under reduced pressure, and the residue was purified by column
chromatography on silica gel using petroleum ether–EtOAc (10:1) as eluent to afford
the desired product.
3-Acetyl-6-phenyl-4-propyl-2H-pyran-2-one (3a)
Pale yellow solid, mp: 74–75 ꢀC. IR (KBr): v ¼ 3097, 2955, 2870, 1666 cmꢁ1. 1H
NMR (400 MHz, CDCl3): d ¼ 7.87–7.85 (m, 2H), 7.50–7.48 (m, 3H), 6.63 (s, 1H),
2.62–2.58 (m, 5H), 1.71–1.65 (m, 2H), 1.02 (t, J ¼ 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3): d ¼ 199.8, 161.1, 160.7, 160.6, 131.5, 130.7, 129.1, 126.0, 122.5,
104.6, 35.5, 31.3, 23.1, 14.1. HRMS (ESI): m=z calcd. for C16H16O3 [M þ H]þ:
257.1172; found: 257.1173.
3-Butyryl-6-phenyl-4-propyl-2H-pyran-2-one (3b)
1
Pale yellow oil. IR (neat): v ¼ 3093, 2953, 2925, 2871, 1683 cmꢁ1. H NMR
(400 MHz, CDCl3): d ¼ 7.87–7.85 (m, 2H), 7.50–7.48 (m, 3H), 6.63 (s, 1H), 2.92 (t,
J ¼ 7.2 Hz, 2H), 2.52 (t, J ¼ 7.6 Hz, 2H), 1.76–1.66 (m, 4H), 1.03 (t, J ¼ 7.2 Hz,
3H), 0.98 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 202.7, 160.5,
160.3, 160.0, 131.3, 130.8, 129.0, 125.9, 123.1, 104.3, 45.2, 35.4, 23.0, 17.4, 14.0,
13.8. HRMS (ESI): m=z calcd. for C18H20O3 [M þ H]þ: 285.1485; found: 285.1484.
3-Isobutyryl-6-phenyl-4-propyl-2H-pyran-2-one (3c)
Pale yellow solid, mp: 49–50 ꢀC. IR (KBr): v ¼ 2966, 2933, 2872, 1713, 1538 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.87–7.85 (m, 2H), 7.50–7.48 (m, 3H), 6.65 (s, 1H),
3.48–3.45 (m, 1H), 2.47 (t, J ¼ 7.6 Hz, 2H), 1.73–1.68 (m, 2H), 1.18 (d, J ¼ 6.8 Hz, 6H),
1.03 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 206.8, 160.5, 160.2, 160.1,
131.3, 130.8, 129.0, 125.9, 122.7, 104.1, 39.8, 35.5, 23.0, 18.1, 14.1. HRMS (ESI):
m=z calcd. for C18H20O3 [M þ H]þ: 285.1485; found: 285.1487.
6-Phenyl-3-pivaloyl-4-propyl-2H-pyran-2-one (3d)
Pale yellow solid, mp: 55–57 ꢀC. IR (KBr): v ¼ 3090, 2963, 2874, 1684,
1578 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.85–7.83 (m, 2H), 7.48–7.47 (m,
3H), 6.62 (s, 1H), 2.32 (t, J ¼ 7.6 Hz, 2H), 1.73–1.65 (m, 2H), 1.31 (s, 9H), 1.01 (t,
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 211.3, 159.9, 159.4, 155.8,
131.0, 130.9, 129.0, 125.7, 125.0, 103.0, 44.9, 35.6, 29.7, 27.2, 14.1. HRMS (ESI):
m=z calcd. for C19H22O3 [M þ H]þ: 299.1642; found: 299.1644.

3154
B. HU ET AL.
3-Acetyl-6-(4-fluorophenyl)-4-propyl-2H-pyran-2-one (3e)
Pale yellow solid, mp: 112–113 ꢀC. IR (KBr): v ¼ 3095, 2962, 2932, 2876,
1701 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.88–7.85 (m, 2H), 7.20–7.15 (m,
2H), 6.57 (s, 1H), 2.61–2.58 (m, 5H), 1.72–1.65 (m, 2H), 1.02 (t, J ¼ 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3): d ¼ 199.7, 164.7, 161.2, 159.6, 128.2, 126.9, 122.4,
116.4, 116.2, 104.4, 35.5, 31.2, 23.1, 14.1. HRMS (EI): m=z calcd. for
C16H15FO3[M]þ: 274.1005; found: 274.1009.
3-Acetyl-6-(4-chlorophenyl)-4-propyl-2H-pyran-2-one (3f)
Pale yellow solid, mp: 126–128 ꢀC. IR (KBr): v ¼ 3087, 2960, 2924, 2864,
1673 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.79 (d, J ¼ 8.3 Hz, 2H), 7.46 (d,
J¼ 8.3 Hz, 2H), 6.61 (s, 1H), 2.59–2.57 (m, 5H), 1.72–1.63 (m, 2H), 1.03 (t, J¼ 7.6 Hz,
3H). 13C NMR (100 MHz, CDCl3): d ¼ 199.6, 160.9, 160.3, 159.4, 137.7, 129.4,
128.8, 127.2, 122.9, 104.7, 35.5, 31.2, 23.1, 14.1. HRMS (EI): m=z calcd. for C16H15
35ClO3[M]þ: 290.0710; found: 290.0711.
3-Acetyl-6-(4-bromophenyl)-4-propyl-2H-pyran-2-one (3g)
1
Pale yellow solid, mp: 132–134 ꢀC. IR (KBr): v ¼ 2959, 1698, 1537 cmꢁ1. H
NMR (400 MHz, CDCl3): d ¼ 7.71 (d, J ¼ 8.8 Hz, 2H), 7.60 (d, J ¼ 8.8 Hz, 2H),
6.61 (s, 1H), 2.60–2.56 (m, 5H), 1.71–1.62 (m, 2H), 0.99 (t, J ¼ 7.2 Hz, 3H). 13C
NMR (100 MHz, CDCl3): d ¼ 199.6, 160.8, 160.3, 159.4, 132.3, 129.6, 127.3, 126.1,
122.9, 104.8, 35.5, 31.2, 23.0, 14.0. HRMS (EI): m=z calcd. for C16H15 79BrO3[M]þ:
334.0205; found: 334.0203.
3-Acetyl-6-(4-nitrophenyl)-4-propyl-2H-pyran-2-one (3h)
1
Pale yellow solid, mp: 123–125 ꢀC. IR (KBr): v ¼ 1716, 1700, 1684 cmꢁ1. H
NMR (400 MHz, CDCl3): d ¼ 8.35 (d, J ¼ 8.8 Hz, 2 H), 8.04 (d, J ¼ 8.8 Hz, 2H),
6.76 (s, 1H), 2.63–2.59 (m, 5H), 1.74–1.68 (m, 2H), 1.06 (t, J ¼ 7.6 Hz, 3H). 13C
NMR (100 MHz, CDCl3): d ¼ 198.9, 159.6, 159.4, 157.2, 149.0, 136.2, 126.8, 125.9,
124.4, 107.5, 36.3, 32.1, 24.0, 15.1. HRMS (ESI): m=z calcd. for C16H15NO5
[M þ H]þ: 302.1023; found: 302.1017.
3-Acetyl-6-(4-methoxyphenyl)-4-propyl-2H-pyran-2-one (3i)
Pale yellow solid, mp: 76–77 ꢀC. IR (KBr): v ¼ 2955, 2870, 1695 cmꢁ1
.
1H
NMR (400 MHz, CDCl3): d ¼ 7.95 (d, J ¼ 8.8 Hz, 2H), 6.98 (d, J ¼ 8.8 Hz, 2H),
6.52 (s, 1H), 3.88 (s, 3H), 2.62–2.58 (m, 5H), 1.73–1.64 (m, 2H), 0.95 (t, J ¼ 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3): d ¼ 199.1, 162.1, 161.5, 160.5, 127.8, 123.2,
121.2, 114.7, 103.5, 56.2, 36.5, 32.2, 24.1, 15.1. HRMS (ESI): m=z calcd. for
C17H18O4 [M þ H]þ: 287.1278; found: 287.1278.
3-Acetyl-4-propyl-6-(thiophen-2-yl)-2H-pyran-2-one (3j)
Pale yellow solid, mp: 82–83 ꢀC. IR (KBr): v ¼ 3082, 2962, 2930, 2871,
1
1705 cmꢁ1. H NMR (400 MHz, CDCl3): d ¼ 7.69–7.68 (m, 1H), 7.55–7.53 (m, 1H),

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3155
7.17–7.15 (m, 1H), 6.45 (s, 1H), 2.60–2.56 (m, 5H), 1.70–1.64 (m, 2H), 1.02 (t,
J ¼ 7.2 Hz, 3H). 13CNMR (100 MHz, CDCl3): d ¼ 199.6, 161.7, 160.1, 156.3, 134.4,
130.1, 128.5, 128.6, 121.7, 103.7, 35.5, 31.3, 23.1, 14.1. HRMS (EI): calcd. for
C14H14O3S [M]þ 262.0664; found: 262.0660.
3-Acetyl-6-(naphthalen-1-yl)-4-propyl-2H-pyran-2-one (3k)
Pale yellow solid, mp: 80–81 ꢀC. IR (KBr): v ¼ 2955, 2871, 1704, 1544 cmꢁ1. 1H
NMR (400 MHz, CDCl3): d ¼ 8.21 (d, J ¼ 9.2 Hz, 1H), 7.97 (d, J ¼ 8.4 Hz, 1H),
7.93–7.92 (m, 1H), 7.74–7.72 (m, 1H), 7.63–7.53 (m, 3H), 6.53 (s, 1H), 2.65 (s,
3H), 2.61 (t, J ¼ 6.8 Hz, 2H), 1.74–1.69 (m, 2H), 1.05 (t, J ¼ 7.2 Hz, 3H). 13C
NMR (100 MHz, CDCl3): d ¼ 200.0, 162.1, 161.0, 160.8, 133.8, 131.6, 130.2, 129.5,
128.8, 128.0, 127.6, 126.6, 125.0, 124.7, 122.8, 109.8, 35.4, 31.3, 23.0, 14.1. HRMS
(EI): m=z calcd. for C20H18O3[M]þ 306.1256; found: 306.1244.
6-(4-Bromophenyl)-3-butyryl-4-propyl-2H-pyran-2-one(3l)
Pale yellow solid, mp: 99–100 ꢀC. IR (KBr): v ¼ 2961, 2923, 2873, 1696,
1540 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.68 (d, J ¼ 8.8 Hz, 2H), 7.58 (d,
J ¼ 8.8 Hz, 2H), 6.57 (s, 1H), 2.87 (t, J ¼ 7.2 Hz, 2H), 2.48 (t, J ¼ 7.6 Hz, 2H),
1.70–1.64 (m, 4H), 0.99 (t, J ¼ 7.2 Hz, 3H), 0.94 (t, J ¼ 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3): d ¼ 202.7, 160.3, 159.8, 159.2, 132.3, 129.7, 127.3, 126.0, 123.5,
104.5, 45.2, 35.4, 23.0, 17.4, 14.1, 13.8. HRMS (ESI): m=z calcd. for C18H19
79BrO3 [M þ H]þ: 363.0594; found: 363.0590.
6-(4-Bromophenyl)-3-isobutyryl-4-propyl-2H-pyran-2-one (3m)
Pale yellow solid, mp: 74–75 ꢀC. IR (KBr): v ¼ 2965, 2931, 2872, 1702,
1532 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.70 (d, J ¼ 8.8 Hz, 2H), 7.60 (d,
J ¼ 8.8 Hz, 2H), 6.62 (s, 1H), 3.46–3.39 (m, 1H), 2.44 (t, J ¼ 7.2 Hz, 2H), 1.69–1.66
(m, 2H), 1.17 (d, J ¼ 7.2 Hz, 6H), 1.02 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz,
CDCl3): d ¼ 206.6, 160.1, 159.8, 159.1, 132.3, 129.7, 127.2, 126.0, 123.1, 104.2,
39.8, 35.5, 23.0, 18.0, 14.1. HRMS (EI): m=z calcd. for C18H19 79BrO3 [M]þ:
362.0518; found: 363.0545.
6-(4-Bromophenyl)-3-pivaloyl-4-propyl-2H-pyran-2-one (3n)
Pale yellow solid, mp: 78–79 ꢀC. IR (KBr): v ¼ 2963, 1701, 1546 cmꢁ1
.
1H
NMR (400 MHz, CDCl3): d ¼ 7.70 (d, J ¼ 8.8 Hz, 2H), 7.59 (d, J ¼ 8.8 Hz, 2H),
6.60 (s, 1H), 2.31 (t, J ¼ 7.2 Hz, 2H), 1.68–1.64 (m, 2H), 1.27 (s, 9H), 1.00 (t,
J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 211.0, 159.5, 158.3, 155.6,
132.2, 129.8, 127.1, 125.6, 125.3, 103.2, 44.9, 35.6, 27.2, 22.3, 14.1. HRMS (EI):
m=z calcd. for C19H21 79BrO3[M]þ: 376.0674; found: 376.0676.
Ethyl 2-Oxo-6-phenyl-4-propyl-2H-pyran-3-carboxylate (3o)
Pale yellow oil. IR (neat): v ¼ 2984, 2879, 1715, 1630 cmꢁ1
.
1H NMR
(400 MHz, CDCl3): d ¼ 7.84–7.83 (m, 2H), 7.50–7.47 (m, 3H), 6.60 (s, 1H), 4.41

3156
B. HU ET AL.
(q, J ¼ 7.2 Hz, 2H), 2.57 (t, J ¼ 7.6 Hz, 2H), 1.74–1.70 (m, 2H), 1.40 (t, J ¼ 7.2 Hz,
3H), 0.87 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 164.9, 160.5,
159.3, 159.2, 131.3, 130.8, 129.0, 125.9, 117.0, 103.4, 61.7, 35.8, 22.5, 14.2, 13.9.
HRMS (ESI): m=z calcd. for C17H18O4 [M þ H]þ: 287.1278; found: 287.1278.
Reaction of Aromatic b-Ketoesters with Alkynyl Ketones: General
Procedure
Alkynyl ketones (0.3 mmol), followed by PPh3 (0.075 mmol) and KOBut
(0.075 mmol), were added to a stirred solution of the aromatic b-ketoesters (0.4 mmol)
in toluene (2 mL). The reaction mixture was stirred at 60 ꢀC for 24 h. Then the solvent
was removed in vacuo, and the residue was purified by column chromatography on
silica gel (10:1 petroleum ether=EtOAc) to give the desired product.
3-Benzoyl-6-phenyl-4-propyl-2H-pyran-2-one (4a)
Pale yellow solid, mp: 58–59 ꢀC. IR (KBr): v ¼ 2963, 1715, 1544 cmꢁ1
.
1H
NMR (400 MHz, CDCl3): d ¼ 7.94–7.91 (m, 2H), 7.89–7.88 (m, 2H), 7.64–7.62 (m,
1H), 7.51–7.48 (m, 5H), 6.73 (s, 1H), 2.44 (t, J ¼ 7.6 Hz, 2H), 1.69–1.63 (m, 2H),
0.94 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 193.3, 160.5, 160.2,
159.1, 136.7, 133.9, 131.3, 130.9, 129.3, 129.0, 128.8, 125.9, 122.3, 103.7, 35.3,
22.5, 14.0. HRMS (EI): m=z calcd. for C21H18O3[M]þ: 318.1256; found: 318.1254.
3-(4-Methylbenzoyl)-6-phenyl-4-propyl-2H-pyran-2-one (4b)
Pale yellow solid, mp: 79–80 ꢀC. IR (KBr): v ¼ 2953, 2870, 1698 cmꢁ1. 1H NMR
(400 MHz, CDCl3): d ¼ 7.91–7.88 (m, 2H), 7.86–7.84 (m, 2H), 7.50–7.49 (m, 3H),
7.30–7.28 (m, 2H), 6.72 (s, 1H), 2.45–2.41 (m, 5H), 1.68–1.62 (m, 2H), 0.93 (t,
J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 192.9, 160.3, 160.2, 158.7, 145.1,
134.2, 131.2, 131.0, 129.53, 129.52, 129.0, 125.8, 122.6, 103.6, 35.3, 22.5, 21.8, 14.0.
HRMS (ESI): m=z calcd. for C22H20O3 [M þ H]þ: 333.1485; found: 333.1490.
3-(4-Methoxybenzoyl)-6-phenyl-4-propyl-2H-pyran-2-one (4c)
1
Pale yellow solid, mp: 110–113 ꢀC. IR (KBr): v ¼ 2956, 2872, 1716 cmꢁ1. H
NMR (400 MHz, CDCl3): d ¼ 7.94–7.87 (m, 4H), 7.51–7.47 (m, 3H), 6.95 (d,
J ¼ 8.9 Hz, 2H), 6.71 (s, 1H), 3.88 (s, 3H), 2.42 (t, J ¼ 7.2 Hz, 2H), 1.69–1.60 (m,
2H), 0.91 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 191.6, 164.4,
160.3, 160.2, 158.4, 131.9, 131.2, 131.0, 129.8, 129.0, 125.8, 122.7, 114.1, 103.6,
55.6, 35.3, 22.4, 14.0. HRMS (ESI): C22H20O4 [M þ H]þ m=z calcd. for 349.1434;
found: 349.1435.
3-(4-Fluorobenzoyl)-6-phenyl-4-propyl-2H-pyran-2-one (4d)
1
Pale yellow solid, mp: 113–114 ꢀC. IR (KBr): v ¼ 2953, 2872, 1701 cmꢁ1. H
NMR (400 MHz, CDCl3): d ¼ 7.99–7.96 (m, 2H), 7.91–7.88 (m, 2H), 7.51–7.48 (m,
3H), 7.19–7.14 (m, 2H), 6.73 (s, 1H), 2.44 (t, J ¼ 7.6 Hz, 2H), 1.69–1.64 (m, 2H),

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3157
0.94 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 191.7, 166.7, 160.6, 160.2,
159.5, 133.2, 132.1, 131.4, 129.1, 128.9, 125.9, 121.9, 116.1, 103.7, 35.3, 22.5, 14.0.
HRMS (ESI): m=z calcd. for C21H17FO3 [M þ H]þ: 337.1234; found: 337.1238.
3-(4-Bromobenzoyl)-6-phenyl-4-propyl-2H-pyran-2-one (4e)
Pale yellow solid, mp: 127–128 ꢀC. IR (KBr): v ¼ 3087, 2962, 2863, 1716,
1
1699 cmꢁ1. H NMR (400 MHz, CDCl3): d ¼ 7.88–7.85 (m, 2H), 7.76 (d, J ¼ 8.1 Hz,
2H), 7.60 (d, J ¼ 8.1 Hz, 2H), 7.50–7.47 (m, 3H), 6.69 (s, 1H), 2.42 (t, J ¼ 7.6 Hz,
2H), 1.66–1.60 (m, 2H), 0.92 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d ¼ 192.2, 160.8, 160.0, 159.7, 135.6, 132.1, 131.4, 130.9, 130.7, 129.1, 125.9, 124.8,
121.8, 103.6, 35.3, 22.5, 13.9. HRMS (EI): m=z calcd. for C21H17 79BrO3[M]þ:
396.0361; found: 396.0359.
3-(2-Naphthoyl)-6-phenyl-4-propyl-2H-pyran-2-one (4f)
Pale yellow solid, mp: 113–115 ꢀC. IR (KBr): v ¼ 2960, 2931, 2865, 1718 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 8.42 (s, 1H), 8.09–8.07 (m, 1H), 7.94–7.89 (m, 5H),
7.64–7.60 (m, 1H), 7.57–7.51 (m, 4H), 6.78 (s, 1H), 2.48 (t, J ¼ 7.6 Hz, 2H), 1.71–1.66
(m, 2H), 0.94 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 193.3, 160.5,
160.3, 159.1, 136.2, 134.1, 132.6, 131.9, 130.9, 129.8, 129.1, 128.9, 128.6, 127.9,
127.8, 126.9, 125.9, 124.3, 122.5, 103.7, 35.4, 22.5, 14.0. HRMS (ESI): m=z calcd.
for C25H20O3 [M þ H]þ: 369.1485; found: 369.1486.
6-Phenyl-4-propyl-3-(thiophene-2-carbonyl)-2H-pyran-2-one (4g)
Pale yellow solid, mp: 97–98 ꢀC. IR (KBr): v ¼ 3093, 2963, 2934, 2873, 1701 cmꢁ1
.
1H NMR (400MHz, CDCl3): d ¼ 7.90–7.89 (m, 2H), 7.74 (dd, J ¼ 4.8 Hz, J ¼ 1.2 Hz,
1H), 7.67 (dd, J ¼ 3.6 Hz, J ¼ 1.2 Hz, 1H), 7.52–7.49 (m, 3H), 7.16 (dd, J ¼ 4.8 Hz,
J ¼ 3.6 Hz, 1H), 6.71 (s, 1H), 2.47 (t, J ¼ 6.8 Hz, 2H), 1.70–1.64 (m, 2H), 0.96 (t,
J ¼ 7.6 Hz, 3H).13C NMR (100MHz, CDCl3): d ¼ 185.0, 160.5, 160.0, 158.8, 143.9,
135.4, 134.7, 131.3, 130.9, 129.1, 128.4, 125.9, 122.3, 103.5, 35.3, 22.5, 14.1. HRMS
(ESI): m=z calcd. for C19H16O3S [M þ H]þ: 325.0893; found: 325.0894.
3-Cinnamoyl-6-phenyl-4-propyl-2H-pyran-2-one (4h)
Pale yellow solid, mp: 43–45 ꢀC. IR (KBr): v ¼ 2961, 2925, 1715 cmꢁ1
.
1H
NMR (400 MHz, CDCl3): d ¼ 7.92–7.90 (m, 2H), 7.64–7.62 (m, 1H), 7.53–7.51 (m,
3H), 7.43–7.41 (m, 3H), 7.28–7.24 (m, 1H), 7.22–7.21 (m, 1H), 7.20–7.18 (m, 1H),
6.71 (s, 1H), 2.62–2.59 (t, J ¼ 6.8 Hz, 2H), 1.73–1.70 (m, 2H), 1.05–0.98 (t, J ¼ 7.6 Hz,
3H). 13C NMR (100 MHz, CDCl3): d ¼ 191.4, 160.8, 160.6, 144.5, 134.5, 131.4, 130.8,
129.5, 129.0, 128.9, 128.7, 128.0, 126.5, 126.0, 125.9, 125.1, 104.3, 35.4, 22.9, 14.1.
HRMS (ESI): m=z calcd. for C23H20O3 [M þ H]þ: 345.1485; found: 345.1486.
3-(4-Bromobenzoyl)-6-(4-fluorophenyl)-4-propyl-2H-pyran-2-one (4i)
1
Pale yellow solid, mp: 122–123 ꢀC. IR (KBr): v ¼ 2962, 2873, 1709 cmꢁ1. H
NMR (400 MHz, CDCl3): d ¼ 7.92–7.89 (m, 2H), 7.80 (d, J ¼ 8.8 Hz, 2H), 7.64 (d,

3158
B. HU ET AL.
J ¼ 8.8 Hz, 2H), 7.23–7.19 (m, 2H), 6.66 (s, 1H), 2.47–2.43 (t, J ¼ 6.8 Hz, 2H),
1.69–1.63 (m, 2H), 0.98 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d ¼ 192.2, 165.9, 163.4, 159.9, 135.4, 132.2, 130.8, 129.8, 129.3, 128.2, 127.2, 121.5,
116.3, 103.5, 35.3, 22.6, 14.0. HRMS (EI): m=z calcd. for C21H16 81BrFO3 [M]þ:
416.0246; found: 416.0273.
3-(4-Bromobenzoyl)-6-(4-chlorophenyl)-4-propyl-2H-pyran-2-one (4j)
Pale yellow solid, mp: 142–143 ꢀC. IR (KBr): v ¼ 3093, 2968, 2870, 1708 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.82 (d, J ¼ 9.0 Hz, 2H), 7.78 (d, J ¼ 8.4 Hz, 2H),
7.65 (d, J ¼ 9.0 Hz, 2H), 7.49 (d, J ¼ 8.4 Hz, 2H), 6.70 (s, 1H), 2.44 (t, J ¼ 7.6 Hz,
2H), 1.68–1.63 (m, 2H), 0.96 (t, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
d ¼ 192.1, 159.8, 159.7, 159.6, 137.7, 135.4, 132.2, 132.1, 130.7, 129.4, 129.2, 127.2,
122.0, 103.9, 35.3, 22.6, 14.0. HRMS (EI): m=z calcd. for C21H16 79Br35ClO3 [M]þ:
428.9893; found: 428.9864.
3-(4-Bromobenzoyl)-6-(4-bromophenyl)-4-propyl-2H-pyran-2-one (4k)
Pale yellow solid, mp: 141–142 ꢀC. IR (KBr): v ¼ 3094, 2955, 2869, 1706 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.75 (d, J ¼ 8.8 Hz, 2H), 7.71 (d, J ¼ 8.8 Hz, 2H),
7.60 (d, J ¼ 8.8 Hz, 4H), 6.68 (s, 1H), 2.40 (t, J ¼ 7.6 Hz, 2H), 1.64–1.59 (m, 2H),
0.91 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 192.1, 159.8, 159.6,
159.6, 135.4, 132.4, 132.2, 130.7, 129.7, 129.3, 127.3, 126.1, 122.1, 103.9, 35.3, 22.5,
14.0. HRMS (EI): m=z calcd. for C21H16 79Br81BrO3[M]þ: 475.9446; found: 475.9448.
3-(4-Bromobenzoyl)-6-(4-methoxyphenyl)-4-propyl-2H-pyran-2-one (4l)
Pale yellow solid, mp: 124–125 ꢀC. IR (KBr): v ¼ 3093, 2928, 2848, 1704 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d ¼ 7.82 (d, J ¼ 8.8 Hz, 2H), 7.76 (d, J ¼ 8.4 Hz, 2H),
7.60 (d, J ¼ 8.4 Hz, 2H), 6.97 (d, J ¼ 8.8 Hz, 2H), 6.58 (s, 1H), 3.41 (s, 3H), 2.41 (t,
J ¼ 7.6 Hz, 2H), 1.65–1.60 (m, 2H), 0.92 (t, J ¼ 7.4 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): d ¼ 192.5, 162.3, 161.0, 160.4, 160.3, 135.7, 132.1, 130.8, 129.1, 127.7,
123.2, 120.3, 114.5, 102.3, 55.5, 35.4, 22.7, 14.0. HRMS (ESI): m=z calcd. for
C22H19 79BrO4 [M þ H]þ: 427.0539; found: 427.0532.
3-(4-Bromobenzoyl)-6-phenethyl-4-propyl-2H-pyran-2-one (4m)
Pale yellow oil. IR (KBr): v ¼ 2962, 1733, 1716, 1700 cmꢁ1
.
1H NMR
(400 MHz, CDCl3): d ¼ 7.75 (d, J ¼ 8.8 Hz, 2H), 7.59 (d, J ¼ 8.8 Hz, 2H), 7.35–7.20
(m, 5H), 5.95 (s, 1H), 3.05 (t, J ¼ 7.4 Hz, 2H), 2.84 (t, J ¼ 7.4 Hz, 2H), 2.28 (t,
J ¼ 7.6 Hz, 2H), 1.50–1.47 (m, 2H), 0.85 (t, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz,
CDCl3): d ¼ 192.4, 165.1, 160.8, 159.7, 139.6, 135.4, 132.1, 130.7, 129.3, 128.7,
128.4, 126.6, 121.1, 106.1, 35.8, 34.9, 33.1, 22.3, 13.9. HRMS (ESI): m=z calcd. for
C23H21 79BrO3[M þ H]þ: 425.0747; found: 425.0744.
Crystal Data for 4d
Empirical formula: C21H17FO3, formula weight: 336.65, crystal color, habit:
pare yellow solid, prismatic, crystal dimensions: 0.20 ꢂ 0.20 ꢂ 0.20 mm, crystal

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3159
˚
system: monoclinic, lattice type: primitive, lattice parameters: a ¼ 36.446(7) A,
ꢀ
ꢀ
ꢀ
˚
˚
b ¼ 7.0874(14) A, c ¼ 14.193 (5) A, a ¼ 90.000 , b ¼ 105.36(3) , c ¼ 90.000 , V ¼
3535.2(12) A3 space group: C2=c, Z ¼ 8, Dcalc ¼ 1.264 g=cm3, F000 ¼ 1408,
˚
diffractometer: Rigaku AFC7 R, residuals: R; Rw: 0.0433, 0.1061. CCDC-753660
contains the supplementary crystallographic data for this article. These data can
be obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
ACKNOWLEDGMENTS
We are grateful to the National Natural Science Foundation of China
(20772116) and the Tianjin Natural Science Foundation (09JCZDJC24400) for
financial support.
REFERENCES
1. (a) Kupchan, S. M.; Moniot, J. L.; Sigel, C. W.; Hemingway, R. H. Tumor inhibitors,
LXV: Bersenogenin, berscillogenin, and 3-epiberscillogenin, three new cytotoxic bufadie-
nolides from Bersama abyssinica. J. Org. Chem. 1971, 36, 2611; (b) Hayashi, Y.; Yuki, Y.;
Matsumoto, T.; Sakan, T. New congeners of cytotoxic nor-diterpenoid dilactones in
podocarpus nagi: Two C19 lactones from seed extract. Tetrahedron Lett. 1977, 18,
3637; (c) Kanai, A.; Kamino, T.; Kuramochi, K.; Kobyayshi, S. Synthetic studies directed
toward the assembly of the C-glycoside fragment of the telomerase inhibitor D8646-2-6.
Org. Lett. 2003, 5, 2837; (d) Evidente, A.; Cabras, A.; Maddau, L.; Serra, S.; Andolfi,
A.; Motta, A. Viridepyronone, a new antifungal 6-substituted 2H-pyran-2-one produced
by Trichoderma viride. J. Agric. Food Chem. 2003, 51, 6957; (e) Shi, X.; Leal, W. S.; Liu,
Z.; Schrader, E.; Meinwald, J. A new synthesis of alkylated 2H-pyran-2-ones and its appli-
cation to the determination of the relative and absolute configuration of supellapyrone,
sex pheromone of the brownbanded cockroach, Supella longipalpa. Tetrahedron Lett.
1995, 36, 71; (f) Schlingmann, G.; Milne, L.; Carter, G. T. New a-pyrones produced by
fungal culture LL-11G219 function as androgen receptor ligands. Tetrahedron 1998, 54,
13013.
2. Vara Prasad, J. V. N.; Para, K. S.; Lunney, E. A.; Ortwine, D. F.; Dunbar, J. B.;
Ferguson, D.; Tummino, P. J.; Hupe, D.; Tait, B. D.; Domagala, J. M.; Humblet, C.;
Bhat, T. N.; Liu, B.; Guerin, D. A. M.; Baldwin, E. T.; Erickson, J. W.; Sawyer, T. K.
Novel series of achiral, low molecular weight, and potent HIV-1 protease inhibitors. J.
Am. Chem. Soc. 1994, 116, 6989.
3. (a) Money, T. Biogenetic-type synthesis of phenolic compounds. Chem. Rev. 1970, 70,
553; (b) Corey, E. J.; Kozikowski, A. P. 3-hydroxy-2-pyrone as a vinylketene equivalent
for the synthesis of dihydrophenols and cyclohexenones. Tetrahedron Lett. 1975, 16,
2389; (c) Bloomer, J. L.; Manir, S.; Zaidi, H.; Strupczewski, J. T.; Brosz, C. S.; Gudzyk,
L. A. New polyketide synthon. J. Org. Chem. 1974, 39, 3615; (d) Bryson, T. A.; Donelson,
D. M. Diels–Alder synthesis of hindered aromatic amines. J. Org. Chem. 1977, 42, 2930;
(e) Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Diels–Alder cycloadditions of
2-pyrones and 2-pyridones. Tetrahedron 1992, 48, 9111.
4. (a) Staunton, J. The synthesis and reactions of organic compounds. In Comprehensive
Organic Chemistry; P. G. Sammes (Eds.); Pergamon Press: Oxford, 1979; vol. 4, pp. 629;
(b) Ma, S.; Yin, S.; Li, L.; Tao, F. K2CO3-catalyzed Michael addition–lactonization reac-
tion of 1,2-allenyl ketones with electron-withdrawing group substituted acetates: An

3160
B. HU ET AL.
efficient synthesis of a-pyrone derivatives. Org. Lett. 2002, 4, 505; (c) Bickel, C. L. The
addition of malonic esters to an acetylenic ketone. J. Am. Chem. Soc. 1950, 72, 1022;
(d) Migliorese, K. G.; Miller, S. I. Skipped diynes, IV: Diacetylenic ketone reactions.
J. Org. Chem. 1974, 39, 843; (e) Harris, T. M.; Harris, C. M. Carboxylation of b-dicarbo-
nyl compounds through dicarbanions: Cyclizations to 4-hydroxy-2-pyrones. J. Org.
ˆ
Chem. 1966, 31, 1032; (f) Rousset, S.; Abarbri, M.; Thibonnet, J.; Duchene, A.; Parrain,
J.-L. Palladium-catalysed annulation reaction of allenyltins with b-iodo vinylic acids:
Selective synthesis of a-pyrones. Chem. Commun. 2000, 1987; (g) Larock, R. C.; Doty,
M. J.; Han, X. Synthesis of isocoumarins and a-pyrones via palladium-catalyzed annu-
lation of internal alkynes. J. Org. Chem. 1999, 64, 8770; (h) Kuninobu, Y.; Kawata, A.;
Nishi, M.; Takata, H.; Takai, K. Rhenium- and manganese-catalyzed insertion of acety-
lenes into b-keto esters: synthesis of 2-pyranones. Chem. Commun. 2008, 6360.
5. (a) Zhu, X.-F.; Schaffner, A.; Li, R. C.; Kown, O. Phosphine-catalyzed synthesis of 6-sub-
stituted 2-pyrones: Manifestation of E=Z-isomerism in the zwitterionic intermediate. Org.
Lett. 2005, 7, 2977; (b) Hachiya, I.; Shibuya, H.; Shimizu, M. Novel 2-pyrone synthesis via
the nucleophilic addition of active methine compounds to 2-alkynone. Tetrahedron Lett.
2003, 44, 2061; (c) Zhao, W.-G.; Hua, R. ReBr(CO)5-catalyzed sequential addition–
cyclization of 1,3-dicarbonyl compounds with electron-deficient internal alkynes affording
trisubstituted 2H-pyran-2-ones. Tetrahedron 2007, 63, 11803; (d) Liu, W.-B.; Jiang, H.-F.;
Qiao, C.-L. Hydroalkylation leading to heterocyclic compounds, part 1: New strategies
for the synthesis of polysubstituted 2H-pyran-2-ones. Tetrahedron 2009, 65, 2110; (e)
Creech, G.; Zhu, X.-F.; Fonovic, B.; Dudding, T.; Kwon, O. Theory-guided design of
Brønsted acid-assisted phosphine catalysis: Synthesis of dihydropyrones from aldehydes
and allenoates. Tetrahedron 2008, 64, 6935.
6. (a) Zhang, C.; Lu, X. Phosphine-catalyzed cycloaddition of 2,3-butadienoates or
2-butynoates with electron-deficient olefins: A novel [3 þ 2] annulation approach to cyclo-
pentenes. J. Org. Chem. 1995, 60, 2906; (b) Lu, X.; Zhang, X.; Xu, Z. Reactions of
electron-deficient alkynes and allenes under phosphine catalysis. Acc. Chem. Res. 2001,
34, 535; (c) Du, Y.; Lu, X.; Yu, Y. Highly regioselective construction of ppirocycles via
phosphine-catalyzed [3 þ 2]-cycloaddition. J. Org. Chem. 2002, 67, 8901; (d) Cowen, B.
J.; Miller, S. J. Enantioselective [3 þ 2]-cycloadditions catalyzed by a protected, multi-
functional phosphine-containing a-amino acid. J. Am. Chem. Soc. 2007, 129, 10988;
(e) Ye, L.-W.; Sun, X.-L.; Wang, Q.-G.; Tang, Y. Phosphine-catalyzed intramolecular for-
mal [3 þ 2] cycloaddition for highly diastereoselective synthesis of bicyclo[n.3.0] com-
pounds. Angew Chem., Int. Ed. 2007, 46, 5951; (f) Ye, L.-W.; Han, X.; Sun, X.-L.;
Tang, Y. PPh3-catalyzed ylide cyclization for the controllable synthesis of benzobicy-
clo[4.3.0] compounds: Base effects and scope. Tetrahedron 2008, 64, 1487; (g) Dendark,
S. E.; Beutner, G. L. Lewis base catalysis in organic synthesis. Angew Chem., Int. Ed.
2008, 47, 1560; (h) Ye, L.-W.; Zhou, J.; Tang, Y. Phosphine-triggered synthesis of func-
tionalized cyclic compounds. Chem. Soc. Rev. 2008, 37, 1140.
7. (a) Lu, C.; Lu, X. Tandem reactions to construct heterocycles via phosphine-catalyzed
umpolung addition and intramolecular conjugate addition. Org. Lett. 2002, 4, 4677; (b)
Shi, Y.-L.; Shi, M. Synthesis of substituted chromenes through the DABCO-catalyzed
reaction of but-3-yn-2-one and methyl propiolate with salicyl N-tosylimines. Chem. Eur.
J. 2006, 12, 3374; (c) Gabillet, S.; Lecercle, D.; Loreau, O.; Carboni, M.; Dezard, S.;
Gomis, J.-M.; Taran, F. Phosphine-catalyzed construction of sulfur heterocycles. Org.
Lett. 2007, 9, 3925; (d) Zhu, X.-F.; Henry, C. E.; Wang, J.; Dudding, T.; Kown, O.
Phosphine-catalyzed cynthesis of 1,3-dioxan-4-ylidenes. Org. Lett. 2005, 7, 1387.
8. (a) Zu, Z.; Lu, X. Phosphine-catalyzed [3 þ 2] cycloaddition reaction of methyl 2,3-
butadienoate and N-tosylimines: A novel approach to nitrogen heterocycles. Tetrahedron
Lett. 1997, 38, 3461; (b) Xu, Z.; Lu, X. A novel [3 þ 2] cycloaddition approach to nitrogen

SYNTHESIS OF FUNCTIONALIZED 2-PYRONES
3161
heterocycles via phosphine-catalyzed reactions of 2,3-butadienoates or 2-butynoates and
dimethyl acetylenedicarboxylate with imines: A convenient synthesis of pentabromopseu-
dilin. J. Org. Chem. 1998, 63, 5031; (c) Xu, Z.; Lu, X. Phosphine-catalyzed [3 þ 2] cycload-
dition reactions of substituted 2-alkynoates or 2,3-allenoates with electron-deficient olefins
and imines. Tetrahedron Lett. 1999, 40, 549; (d) Zhu, X.-F.; Lan, J.; Kown, O. An expedi-
ent phosphine-catalyzed [4 þ 2] annulation: Synthesis of highly functionalized tetrahydro-
pyridines. J. Am. Chem. Soc. 2003, 125, 4716; (e) Zhao, G.-L.; Huang, J.-W.; Shi, M.
Abnormal aza-Baylis–Hillman reaction of N-tosylated imines with ethyl 2,3-butadienoate
and penta-3,4-dien-2-one. Org. Lett. 2003, 5, 4737; (f) Wurz, R. P.; Fu, G. C. Catalytic
asymmetric synthesis of piperidine derivatives through the [4 þ 2] annulation of imines
with allenes. J. Am. Chem. Soc. 2005, 127, 12234; (g) Nair, V.; Menon, R. S.; Sreekanth,
A. R.; Abhilash, N.; Biju, A. T. Engaging zwitterions in carbon–carbon and carbon–
nitrogen bond-forming reactions: A promising synthetic strategy. Acc. Chem. Res. 2006,
39, 520; (h) Fang, Y.-Q.; Jacobsen, E. N. Cooperative, highly enantioselective phosphi-
nothiourea catalysis of imine–allene [3 þ 2] cycloadditions. J. Am. Chem. Soc. 2008,
130, 5660.
9. (a) Meng, L.-G.; Cai, P.; Guo, Q.; Xue, S. Cycloaddition of alkynyl ketones with N-
tosylimines catalyzed by Bu3P and DMAP: Synthesis of highly functionalized pyrrolidines
and azetidines. J. Org. Chem. 2008, 73, 8491; (b) Meng, L.-G.; Hu, B.; Wu, Q.-P.; Liang,
M.; Xue, S. PPh3-catalyzed unexpected a-addition reaction of 1-(o-hydroxyaryl)-1,3-
diketones to terminal alkynoates: A straightforward synthesis of multifunctional vinyles-
ters. Chem. Commun. 2009, 6089; (c) Zhou, Q.-F.; Yang, F.; Guo, Q.-X.; Xue, S. A new
organocatalytic process of cyclotrimerization of acetylenic ketones mediated by 2,4-penta-
nedione. Synlett 2007, 215.
10. Hu, B.; Meng, L.-G.; Liu, Y.-L.; Liang, M.; Xue, S. Pyridine and kOBut co-catalyzed
benzannulation of b-diketones with dimethyl acetylenedicarboxylate. Synthesis 2009,
4137.
11. Xue, S.; Zhou, Q.-F.; Zheng, X.-Q. a-Addition of 1,3-dicarbonyl compounds to acetylenic
ketones catalyzed by triphenylphosphine. Synth. Commun. 2005, 35, 3027.