ReBr(CO)5-catalyzed sequential addition-cyclization of 1,3-dicarbonyl compounds with electron-deficient internal alkynes affording trisubstituted 2H-pyran-2-ones

Article abstract of DOI:10.1016/j.tet.2007.09.038

The reaction of 1,3-dicarbonyl compounds such as acetoacetate, acetylacetone, dibenzoylmethane, and benzoylacetate with electron-deficient internal alkynes in the presence of catalytic amount of ReBr(CO)₅ in toluene under neutral conditions resulted in the formation of 4,5,6-trisubstituted 2H-pyran-2-ones in moderate to high yield. The reaction took place via a two-step sequence including the rhenium(I)-catalyzed addition of the activated methylenes to alkynes to give enolic 2-alkenyl derivatives, and subsequently dealcoholic cyclization to form 2H-pyran-2-one derivatives.

Full text of DOI:10.1016/j.tet.2007.09.038

Tetrahedron 63 (2007) 11803–11808
ReBr(CO)5-catalyzed sequential addition–cyclization of 1,3-
dicarbonyl compounds with electron-deficient internal
alkynes affording trisubstituted 2H-pyran-2-ones
*
Wen-Guo Zhao and Ruimao Hua
Department of Chemistry, Tsinghua University, Innovative Catalysis Program, Key Laboratory of Organic Optoelectronics and
Molecular Engineering of Ministry of Education, Beijing 100084, China
Received 27 June 2007; revised 5 September 2007; accepted 21 September 2007
Available online 23 September 2007
Abstract—The reaction of 1,3-dicarbonyl compounds such as acetoacetate, acetylacetone, dibenzoylmethane, and benzoylacetate with elec-
tron-deficient internal alkynes in the presence of catalytic amount of ReBr(CO)5 in toluene under neutral conditions resulted in the formation
of 4,5,6-trisubstituted 2H-pyran-2-ones in moderate to high yield. The reaction took place via a two-step sequence including the rhenium(I)-
catalyzed addition of the activated methylenes to alkynes to give enolic 2-alkenyl derivatives, and subsequently dealcoholic cyclization to
form 2H-pyran-2-one derivatives.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
of the functionalized 2H-pyran-2-ones have been estab-
lished.9
Catalytic C–H bond activation and its addition to unsatu-
rated hydrocarbons to construct C–C bond is one of the
most attractive and valuable reactions in organic synthesis.1
Among them, the catalytic addition of activated methylenes
in 1,3-dicarbonyl compounds to alkynes in neutral condi-
tions has attracted a great deal of focus. It has been reported
that Au(I),2 Ni(II)/Yb(III),3 Pd(II),4a and Pd(II)/Yb(III)4b
complexes may serve as efficient catalyst systems for the
intramolecular cyclic addition of C–H bonds to alkynes. In
contrast, the examples of the intermolecular addition reac-
Recently we have been interested in the application of low-
valent rhenium complexes in organic synthesis, and have
demonstrated that ReBr(CO)5 can catalyze the activation
of E–H (E¼O,10 Si11) bond and for its addition to alkynes
or alkenes. We have also found that ReBr(CO)5 can effec-
tively activate C–H bond of active methylene compounds
toward the nucleophilic attack of carbonyl compounds.12
As a continuation of this research, we have designed a new
rhenium(I)-catalyzed synthetic route to trisubstituted
2H-pyran-2-ones utilizing the reaction of 1,3-dicarbonyl
compounds with propiolates. This synthetic route includes
the rhenium(I)-catalyzed addition of activated methylenes
of 1,3-dicarbonyl compounds to propiolates to give the eno-
lic adduct 3,13 which might serve as precursor to form the
substituted 2H-pyran-2-one (30) by dealcoholic reaction
(Scheme 1).
5
tions are rather limited. Only two catalyst systems, In(OTf)3
and [ReBr(CO)3(THF)]2 have been recently reported to
6
catalyze the intermolecular addition of 1,3-dicarbonyl com-
pounds to terminal alkynes to give (enolic) 2-alkenyl deriv-
atives. Moreover, further synthetic applications of such type
of intermolecular addition reactions remain to be developed.
Development of the synthetic methods for substituted
2H-pyran-2-ones is one of the important and interesting re-
search topics in organic chemistry, because 2H-pyran-2-one
derivatives are not only valuable materials in diverse organic
synthesis,7 but also exhibit important pharmacological activ-
ities.8 Therefore, many synthetic methods for the synthesis
2. Results and discussion
On the basis of the considerations above, we performed the
reaction of phenyl propiolate 1a and 1b with 1,3-dicarbonyl
compounds to determine the catalytic reaction conditions
required for the formation of 3 in the presence of rhenium
complexes. As shown in Table 1, when a mixture of 1a
(1.0 mmol), methyl acetoacetate (1.0 mmol) (2a), and
ReBr(CO)5 (0.005 mmol) in toluene (1.0 mL) under an air
Keywords: 1,3-Dicarbonyl compounds; Internal electron-deficient alkynes;
2H-Pyran-2-ones; Rhenium complexes.
* Corresponding author. Tel./fax: +86 10 62792596; e-mail: ruimao@mail.
tsinghua.edu.cn
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.038

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W.-G. Zhao, R. Hua / Tetrahedron 63 (2007) 11803–11808
R3
R4
was assigned as 3c00. Unfortunately, attempts to isolate these
products in analytical samples by column chromatography
or preparative TLC (silica) failed.
COOR2
R3
O
δ−
δ+
O
O
δ+
O
R4
δ−
H
ReBr(CO)4
R2OOC
R1
R1
The catalytic activities of other rhenium complexes in the
reaction of 1a with 2a were also examined. ReCl(CO)5
showed a moderate catalytic activity affording 3a in 61%
GC yield (entry 4). Compound 3a was obtained in 21%
GC yield when Re2(CO)10 was used as catalyst (entry 5).
CpRe(CO)3 and (NH4)ReO4 displayed very low catalytic ac-
tivities for the same addition reaction. In these cases, the
starting materials were recovered (entries 6 and 7).
1
2
R3
O
R3
O
O
R4
HO
R2OOC
R4
O
R1
R1
R2OH
3'
3
Scheme 1.
It is of interest to note that, in contrast to the recent results of
Taran and co-workers where the reaction of 1,3-dicarbonyl
compounds with substituted propiolates in the presence
of catalytic amount of phosphine as catalyst afforded
a-(gem-dicarbonyl) acrylates,14 our catalytic system gave
onlyC–C bondformationat thecarbonbondingto estergroup
in 1 to generally form the b-(gem-dicarbonyl) acrylates 3.
Table 1. Rhenium-catalyzed addition of phenyl propiolate with 1,3-
dicarbonyl compounda
R'
O
cat. Re
(0.5 mol%)
O
O
HO
R"
Ph
COOR
+
toluene
R"
ROOC
R'
Ph
120 °C, 10 h
3
Moreover, the trans-addition of C–H bond to 1 forming the
Z-configuration in the acrylate moiety of 3 could be evi-
denced by its easy subsequent dealcoholic cyclization pro-
ducing the six-membered cycle, 2H-pyran-2-one derivative
(vide infra). In addition, the structure of 3a (shown in
Fig. 1) was finally ascertained by single-crystal X-ray dif-
fraction analysis to confirm the regio- and stereoselectivity
of the addition reaction.15
R' = Me, R" = OMe 2a
R' = Me, R" = OEt 2b
R' = Ph, R" = OEt 2c
R = Me 1a
Et 1b
Entry
Catalyst
R
R0
R00
Yieldb (%)
1
2
3
4
5
6
7
ReBr(CO)5
ReBr(CO)5
ReBr(CO)5
ReCl(CO)5
Re2(CO)10
CpRe(CO)3
(NH4)ReO4
Me
Et
Et
Me
Me
Me
Me
Me
Me
Ph
Me
Me
Me
Me
OMe
OEt
OEt
OMe
OMe
OMe
OMe
3a
3b
3c
3a
3a
3a
3a
84
87
16c
(61)
(21)
(<5)
(<5)
Table 2 summarizes the reaction results of the substituted
propiolates with 1,3-dicarbonyl compounds in the presence
of ReBr(CO)5. The formation of enolic adduct 3 and/or
2H-pyran-2-one derivative 30 depended on the structure of
the reactants. The reaction of 1a with acetylacetone (2d) at
120 ꢀC for 24 h gave a mixture of the corresponding enolic
adduct 3d and trisubstituted 2H-pyran-2-one 3d0 in 47%
and 32% isolated yields, respectively (Table 2, entry 1). A
similar result was obtained in the reaction of 1b with 2d
(Table 2, entry 2). A shorter reaction time lowered the
a
The reaction was carried out using 1.0 mmol of 1, 1.0 mmol of 2, and
0.005 mmol of catalyst in toluene (1.0 mL) at 120 ꢀC for 10 h.
Isolated yield. Number in the parenthesis was GC yield.
NMR yield.
b
c
atmosphere was heated at 120 ꢀC for 10 h, the enolic adduct
3a was isolated in 84% yield (entry 1). The formation of the
isomer of 3 and the corresponding cyclic product 30 in trace
amount (<5%) was also observed by GC and GC–MS anal-
yses of the reaction mixture. The reaction of 1b with 2b
resulted in the similar result (entry 2). However, under the
same conditions, the reaction of 1b with ethyl benzoylace-
O(4)
O(3)
1
tate (2c) afforded a mixture of products (Scheme 2). H
NMR of the reaction mixture disclosed that the correspond-
ing enolic adduct 3c was formed in only 16% yield (entry 3),
and the predominant product was the heteroannulation prod-
uct, 4,6-diphenyl-5-ethoxycarbonyl-2H-pyran-2-one (3c0)
(46% NMR yield). Another considerable amount of product
C(8)
C(7)
O(5)
C(5)
C(6)
O(1)
C(4)
double bond
C(1)
O
O
ReBr(CO)5
(0.5 mol%)
C(9)
CO2Et +
OEt
Ph
C(3)
toluene,
120 °C, 10 h
1b
2c
C(2)
O(2)
Ph
O
O
O
CO2Et
Ph
double bond
+
+
HO
EtO2C
OEt
O
OEt
Ph
3c' 46%
Ph
EtO2C
Ph
O
3c 16%
3c" 33%
Scheme 2.
Figure 1. Molecular structure of 3a. Hydrogen atoms are omitted for clarity.

W.-G. Zhao, R. Hua / Tetrahedron 63 (2007) 11803–11808
11805
Table 2. Rhenium-catalyzed addition of propiolate derivative with 1,3-dicarbonyl compounda
R3
O
R3
O
O
O
ReBr(CO)5
O
R4
HO
R2OOC
R4
+
COOR2
R1
+
toluene, 120 °C
R4
R3
O
R1
R1
1
2
3
3'
Entry
1
ReBr(CO)5 (equiv)
R1
Ph
R2
R3
R4
Time (h)
24
Product/yieldb (%)
O
O
O
HO
MeOOC
0.03
Me
Me
Me
Ph
3d (47%)
O
Ph
3d' (32%)
O
HO
EtOOC
2
3
4
5
6
7
0.03
Ph
Et
Me
Ph
Me
24
15
15
10
10
10
10
3d0 (37%)
Ph
3e (47%)
Ph
O
0.01
Ph
Me
Me
Me
Me
Et
Ph
O
O
Ph
3f' (65%)
3g' (58%)
Ph
O
O
O
0.01
Me
Me
Me
Me
Me
Me
Ph
Me
O
0.005
0.005
0.005
0.005
OMe
OMe
OEt
OEt
O
OMe
3h' (94%)
O
COOMe
O
O
n-C6H13
n-C5H11
n-C5H11
3i' (74%)
O
n-C6H13
COOEt
3j' (52%)
O
n-C5H11
Ph
O
O
O
COOEt
Ph
OEt
n-C5H11
3k" (48%)
8
Et
EtOOC
O
n-C5H11
3k' (33%)
a
The reaction was carried out using 1.0 mmol of 1 and 1.0 mmol of 2 in toluene (1.0 mL) at 120 ꢀC.
Isolated yield.
b
formation of 30. For example, if the reaction of 1a with 2d
was performed for 10 h, 3d was isolated in 55% yield
(59% GC yield) while 3d0 was obtained in only 3% yield
(6% GC yield), indicating that increasing the reaction time
from 10 h to 24 h resulted in the substantial increase in 3d0
formation. In addition, the formation of 3d0 resulting from
the dealcoholic reaction of 3d was confirmed by heating a
solution of 3d under similar reaction conditions to give
quantitative 3d0 as shown in Scheme 3.
O
O
ReBr(CO)5
HO
MeOOC
(3.0 mol%)
O
+ MeOH
toluene,
120 °C, 24 h
(not optimal)
Ph
O
Ph
3d
3d'
100%
Scheme 3.
the formation of the corresponding 2H-pyran-2-one deriva-
tives even in shorter reaction times (Table 2, entries 3–7).
In the reaction between 1e and 2c, only a small amount
of the enolic adduct was observed. For this reaction
another addition–rearrangement product 3k00 and substituted
For the examined reactions, the reaction of 1a with diben-
zoylmethane (2e), methyl 2-butynoate (1c) with 2d, 1c
with 2a, methyl 2-nonynoate (1d) with 2a, and methyl
2-octynoate (1e) with 2b gave good to high selectivity for

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W.-G. Zhao, R. Hua / Tetrahedron 63 (2007) 11803–11808
2H-pyran-2-one 3k0 were isolated in 48% and 33% yields,
respectively (Table 2, entry 8).
derivatives by dealcoholic cyclization under our reaction
conditions. Therefore, this study provides a new and practi-
cal one-pot synthesis of 4,5,6-trisubstituted 2H-pyran-
2-ones from easily available 1,3-dicarbonyl compounds
and electron-deficient internal alkynes via a sequential
addition–cyclization reaction.
In an attempt to synthesize tetrasubstituted 2H-pyran-2-one
derivatives by the present reaction, the reactions of 1a, 1c
with methyl 2-benzylacetoacetate (2f) were examined. The
addition–cyclization reactions also proceeded to furnish
the corresponding tetrasubstituted 2H-pyran-2-one deriva-
tives 4a and 4b in 66% and 35% isolated yields, respectively
(Scheme 4).
4. Experimental section
4.1. General methods
O
O
O
ReBr(CO)5
(1.0 mol%)
All the reactions were carried out under air atmosphere.
Solvents and all reagents were used as received. H and
1
O
OMe
R
COOMe +
OMe
13C NMR spectra were recorded in CDCl3 at 300 and
75 MHz, respectively. The chemical shifts (d) were refer-
enced to TMS or solvent resonance. GC–MS was obtained
using electron ionization (EI). High-resolution mass spectra
and elemental analysis data were recorded in the Department
of Chemistry of Peking University.
toluene
120 °C, 24 h
O
R
Ph
R = Ph, 1a
R = Me, 1c
2f
Ph
R = Ph, 4a 66%
Me, 4b 35%
Scheme 4.
Unlike the reactions of substituted propiolates with 1,3-
dicarbonyl compounds, which gave 3 and/or 30 as major
products, the reactions of acetylenedicarboxylates with
1,3-dicarbonyl compounds were sluggish, resulting in the
formation of complex mixtures. The corresponding products
3 and 30 were formed in the moderate total yields only,
and were isolated in low yields (Table 3). The major side-
reaction was the cyclotrimerization of acetylenedicarboxy-
lates disclosed by GC and GC–MS analyses of the reaction
mixtures.
4.2. Typical procedure for the reaction of methyl phenyl
propiolate (1a) with acetylacetone (2d) (Table 2, entry 1)
A mixture of 1a (106.2 mg, 1.0 mmol), 2d (103 ml,
1.0 mmol), and ReBr(CO)5 (12.2 mg, 0.03 mmol) in toluene
(1.0 mL) was heated with stirring in a thick-walled Pyrex
sealed tube at 120 ꢀC for 24 h. After cooling, the reaction
was diluted with toluene to 1.5 mL and n-C22H46
(28.0 mg, as internal standard) was added. The resulting
mixture was then analyzed by GC and GC–MS. Volatiles
were removed in vacuum and the residue was subjected to
isolation by preparative TLC (silica, eluted with a 3:1 petro-
leum ether–diethyl ether mixture). Compounds 3d and 3d0 as
pale yellow solids were isolated in 121.0 mg (0.47 mmol,
47%), and 74.0 mg (0.32 mmol, 32%), respectively, after
removal of the solvent.
Table 3. Rhenium-catalyzed addition of acetyldicarboxylate with 1,3-
dicarbonyl compound
ReBr(CO)5
(1.0 mol%)
O
O
O
ROOC
COOR
+
toluene
120 °C, 15 h
R'
R"
R"
R = Me, 1f
R = Et, 1g
2
The selected spectroscopic data for new products are shown
below. The characterization data for known products 3c0,
R'
O
R'
1
3d0, 3e, 3g0, 3h0, 3l and the copies of H, 13C NMR for all
the products are provided in Supplementary data.
O
R"
COOR
HO
ROOC
+
O
COOR
3
3'
4.3. Characterization data for new products
Entry
R
R0
R00
Isolated yield (%)
30
4.3.1. (Z)-4-Acetyl-3-phenyl-2-pentene-1,5-dicarboxylic
acid dimethyl 3a. Pale yellow solid, mp 73–75 ꢀC;
1H NMR (300 MHz, CDCl3) d 13.0 (s, 1H), 7.52–7.36 (m,
5H), 6.43 (s, 1H), 3.72 (s, 3H), 3.65 (s, 3H), 1.77 (s, 3H);
13C NMR (75 MHz, CDCl3) d 173.1, 172.0, 166.0, 149.7,
139.7, 129.6, 128.7, 126.9, 119.6, 100.5, 51.8, 51.4, 19.6;
GC–MS m/z (% rel inten.) 244 (M+ꢁ32, 84), 229 (8), 216
(100), 201 (47), 184 (81), 171 (14), 156 (14), 145 (8), 128
(22), 115 (36), 102 (13), 77 (8). Anal. Calcd for C15H16O5:
C, 65.22; H, 5.80. Found: C, 65.01; H, 6.01.
3
1
2
3
4
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
OMe
OEt
3l
23
23
—
—
3l0
26
—
20
18
3m
3n
3o
3m0
3n0
3o0
3. Conclusions
We have developed the ReBr(CO)5-catalyzed addition reac-
tion of activated methylene compounds with electron-
deficient internal alkynes to afford enolic adducts and/or
substituted 2H-pyran-2-ones. The selectivity for the for-
mation of enolic adducts or 2H-pyran-2-one derivatives
depended on the structure of both the reactants. Enolic
adducts can be easily converted into 2H-pyran-2-one
4.3.2. (Z)-4-Acetyl-3-phenyl-2-pentene-1,5-dicarboxylic
acid diethyl 3b. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 13.1 (s, 1H), 7.50–7.35 (m, 5H), 6.39
(s, 1H), 4.22–4.10 (2ꢂq, 4H), 1.78 (s, 3H), 1.30 (t, 3H,
J¼7.0 Hz), 1.08 (t, 3H, J¼7.0 Hz); 13C NMR (75 MHz,
CDCl3) d 172.9, 171.6, 165.8, 149.4, 140.1, 129.4, 128.7,
126.9, 126.6, 120.2, 101.0, 60.5, 60.1, 19.6, 14.3, 14.0;

W.-G. Zhao, R. Hua / Tetrahedron 63 (2007) 11803–11808
11807
GC–MS m/z (% rel inten.) 258 (M+ꢁ46, 99), 243 (3), 230
(100), 213 (43), 201 (63), 184 (79), 171 (26), 160 (18),
145 (4), 128 (23), 115 (50), 103 (10), 89 (8), 77 (9). Anal.
Calcd for C17H20O5: C, 67.09; H, 6.62. Found: C, 67.27;
H, 6.57.
4.3.9. 5-Ethoxycarbonyl-4-(n-pentyl)-6-phenyl-2H-
pyran-2-one 3k0. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 7.59–7.40 (m, 5H), 6.15 (s, 1H), 4.10
(q, 2H, J¼7.1 Hz), 2.55 (t, 2H, J¼7.6 Hz), 1.61–1.53
(m, 2H), 1.40–1.25 (m, 4H), 1.03 (t, 3H, J¼7.1 Hz), 0.91
(t, 3H, J¼6.9 Hz); 13C NMR (75 MHz, CDCl3) d 166.3,
161.0, 160.9, 158.1, 132.1, 130.9, 128.5, 128.0, 113.6,
111.5, 61.9, 33.1, 31.4, 28.1, 22.3, 13.9, 13.5; GC–MS m/z
(% rel inten.) 314 (M+, 18), 285 (3), 269 (10), 257 (39),
243 (6), 230 (34), 158 (9), 128 (7), 105 (100), 77 (35).
HRMS calcd for C19H22O4 314.1518, found 314.1518.
4.3.3. (Z)-4-Benzoyl-3-phenyl-2-pentene-1,5-dicarboxy-
1
lic acid diethyl 3c. H NMR (300 MHz, CDCl3) d 13.6
(s, 1H), 6.26 (s, 1H); GC–MS m/z (% rel inten.) 366 (M+,
5), 320 (75), 292 (75), 263 (74), 247 (44), 220 (35), 191
(25), 147 (7), 105 (100), 77 (31).
4.3.4. (Z)-2-Benzoyl-3-phenyl-2-pentene-1,5-dicarboxy-
4.3.10. (E)-2-Benzoyl-3-(n-pentyl)-2-pentene-1,5-dicarb-
1
1
lic acid diethyl 3c00. H NMR (300 MHz, CDCl3) d 4.25
oxylic acid diethyl 3k00. Pale yellow viscous oil; H NMR
(q, 2H, J¼7.0 Hz), 4.06 (s, 2H), 3.93 (q, 2H, J¼7.0 Hz);
GC–MS m/z (% rel inten.) 366 (M+, 4), 320 (82), 292
(100), 274 (24), 264 (52), 247 (66), 220 (30), 191 (40),
105 (64), 77 (35).
(300 MHz, CDCl3) d 8.05–8.02 (m, 2H), 7.58–7.45 (m,
3H), 4.24 (q, 2H, J¼7.1 Hz), 4.08 (q, 2H, J¼7.1 Hz), 3.76
(s, 2H), 2.06 (t, 2H, J¼7.9 Hz), 1.45–1.38 (m, 2H), 1.33 (t,
3H, J¼7.1 Hz), 1.25–1.10 (m, 4H), 1.02 (t, 3H, J¼7.1 Hz),
0.79 (t, 3H, J¼6.7 Hz); 13C NMR (75 MHz, CDCl3)
d 194.9, 170.2, 164.2, 152.7, 137.0, 133.5, 131.8, 129.3,
128.7, 61.0, 60.7, 38.2, 36.9, 31.7, 27.0, 22.2, 14.2, 13.8,
13.8; GC–MS m/z (% rel inten.) 360 (M+, 0.1), 315 (8),
286 (12), 273 (6), 257 (8), 243 (9), 230 (12), 211 (4), 171
(5), 158 (7), 105 (100), 77 (23). HRMS calcd for
C19H23O4 (MꢁOEt) 315.1596, found 315.1591.
4.3.5. Methyl (Z)-4-acetyl-5-oxo-3-phenyl-2-hexenoate
1
3d. Pale yellow solid, mp 56–57 ꢀC; H NMR (300 MHz,
CDCl3) d 16.7 (s, 1H), 7.54–7.42 (m, 5H), 6.58 (s, 1H),
3.74 (s, 3H), 1.91(s, 6H); 13C NMR (75 MHz, CDCl3)
d 189.9 (2C), 166.0, 151.0, 139.0, 130.2, 129.1, 127.0,
119.9, 110.6, 51.6, 23.4 (2C); GC–MS m/z (% rel inten.)
260 (M+, 32), 245 (1), 229 (13), 217 (51), 201 (100), 185
(42), 171 (16), 158 (19), 129 (18), 115 (45), 105 (7), 91
(7), 77 (10), 43 (89). Anal. Calcd for C15H16O4: C, 69.22;
H, 6.20. Found: C, 69.41; H, 6.23.
4.3.11. 5-Acetyl-4-methoxycarbonyl-6-methyl-2H-
pyran-2-one 3l0. Pale yellow solid, mp 67–68 ꢀC; 1H NMR
(300 MHz, CDCl3) d 6.70 (s, 1H), 3.91 (s, 3H), 2.43
(s, 3H), 2.31 (s, 3H); 13C NMR (75 MHz, CDCl3) d 198.7,
163.9, 161.3, 160.2, 143.6, 118.3, 115.8, 53.5, 31.7, 18.5;
GC–MS m/z (% rel inten.) 210 (M+, 39), 195 (61), 178
(40), 167 (21), 151 (100), 139 (14), 125 (51), 109 (24), 93
(20), 65 (7), 43 (75). Anal. Calcd for C10H10O5: C, 57.14;
H, 4.80. Found: C, 57.11; H, 4.74.
4.3.6. 5-Benzoyl-4-methyl-6-phenyl-2H-pyran-2-one 3f0.
1
Pale yellow solid, mp 110–112 ꢀC; H NMR (300 MHz,
CDCl3) d 7.78–7.21 (m, 10H), 6.25 (s, 1H), 2.09 (s, 3H);
13C NMR (75 MHz, CDCl3) d 194.4, 160.9, 159.0, 154.6,
136.5, 134.1, 131.4, 130.9, 129.4, 128.8, 128.5, 128.5,
118.0, 113.0, 20.3; GC–MS m/z (% rel inten.) 290 (M+,
89), 261 (100), 245 (14), 233 (7), 185 (19), 169 (3), 157
(2), 128 (5), 105 (58), 77 (57), 51 (10). Anal. Calcd for
C19H14O3: C, 78.61; H, 4.86. Found: C, 78.32; H, 4.83.
4.3.12. Ethyl (E)-4-acetyl-3-ethoxycarbonyl-5-oxo-2-hex-
enoate 3m. Pale yellow viscous oil; H NMR (300 MHz,
1
CDCl3) d 16.5 (s, 1H), 7.08 (s, 1H), 4.30 (q, 2H,
J¼7.1 Hz), 4.19 (q, 2H, J¼7.1 Hz), 1.96 (s, 6H), 1.33
(t, 3H, J¼7.1 Hz), 1.26 (t, 3H, J¼7.1 Hz); 13C NMR
(75 MHz, CDCl3) d 189.9, 166.2, 164.8, 139.5, 132.4,
107.2, 62.2, 61.2, 23.5, 14.2, 14.1; GC–MS m/z (% rel inten.)
270 (M+, 1), 227 (4), 197 (47), 181 (18), 151 (100), 109 (15),
93 (3), 82 (2), 67 (2), 53 (3), 43 (26). Anal. Calcd for
C13H18O6: C, 57.77; H, 6.71. Found: C, 57.94; H, 6.83.
4.3.7. 4-(n-Hexyl)-5-methoxycarbonyl-6-methyl-2H-
pyran-2-one 3i0. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 6.02 (s, 1H), 3.88 (s, 3H), 2.52
(t, 2H, J¼7.6 Hz), 2.36 (s, 3H), 1.52–1.42 (m, 2H), 1.38–
1.22 (m, 6H), 0.87 (t, 3H, J¼6.6 Hz); 13C NMR (75 MHz,
CDCl3) d 166.3, 164.1, 161.0, 158.3, 112.8, 110.8, 52.5,
33.8, 31.4, 28.9, 28.4, 22.5, 19.5, 14.0; GC–MS m/z (% rel
inten.) 252 (M+, 20), 237 (3), 221 (15), 182 (46), 167 (32),
154 (100), 140 (16), 122 (14), 95 (11), 79 (8), 65 (6), 55
(4). Anal. Calcd for C14H20O4: C, 66.65; H, 7.99. Found:
C, 66.43; H, 8.03.
4.3.13. 4,5-Bis(methoxycarbonyl)-6-methyl-2H-pyran-
2-one 3n0. Pale yellow solid, mp 50–52 ꢀC; 1H NMR
(300 MHz, CDCl3) d 6.48 (s, 1H), 3.89 (s, 3H), 3.84
(s, 3H), 2.48 (s, 3H); 13C NMR (75 MHz, CDCl3) d 167.0,
164.7, 164.6, 159.7, 145.8, 113.8, 109.1, 53.3, 52.8, 19.4;
GC–MS m/z (% rel inten.) 226 (M+, 26), 211 (3), 195 (43),
183 (14), 167 (100), 151 (13), 137 (10), 125 (25), 108 (7),
93 (19), 59 (7), 43 (29). Anal. Calcd for C10H10O6:
C, 53.10; H, 4.46. Found: C, 53.43; H, 4.85.
4.3.8. 5-Ethoxycarbonyl-6-methyl-4-(n-pentyl)-2H-
pyran-2-one 3j0. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 6.01 (s, 1H), 4.35 (q, 2H, J¼7.1 Hz),
2.52 (t, 2H, J¼7.8 Hz), 2.37 (s, 3H), 1.55–1.42 (m, 2H),
1.37 (t, 3H, J¼7.1 Hz), 1.32–1.25 (m, 4H), 0.89 (t, 3H,
J¼6.9 Hz); 13C NMR (75 MHz, CDCl3) d 165.8, 163.8,
161.1, 158.3, 113.1, 110.8, 61.7, 33.7, 31.4, 28.2, 22.3,
19.3, 14.1, 13.9; GC–MS m/z (% rel inten.) 252 (M+, 26),
237 (4), 224 (6), 207 (31), 196 (44), 181 (29), 168 (100),
140 (31), 122 (17), 108 (9), 95 (14), 77 (6). Anal. Calcd
for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.38; H, 8.05.
4.3.14. 4,5-Bis(ethoxycarbonyl)-6-methyl-2H-pyran-
1
2-one 3o0. Pale yellow viscous oil; H NMR (300 MHz,
CDCl3) d 6.48 (s, 1H), 4.34 (q, 2H, J¼7.0 Hz), 4.30
(q, 2H, J¼7.0 Hz), 2.48 (s, 3H), 1.36 (t, 3H, J¼7.0 Hz),
1.33 (t, 3H, J¼7.0 Hz); 13C NMR (75 MHz, CDCl3)
d 166.7, 164.3, 164.2, 159.8, 146.2, 113.6, 109.5, 62.6,

11808
W.-G. Zhao, R. Hua / Tetrahedron 63 (2007) 11803–11808
62.1, 19.3, 14.0 (2C); GC–MS m/z (% rel inten.) 254 (M+,
23), 208 (29), 187 (100), 165 (12), 153 (65), 139 (9), 111
(10), 93 (18), 65 (5), 43 (29).
6. Kuninobu, Y.; Kawata, A.; Takai, K. Org. Lett. 2005, 7, 4823–
4825.
7. Examples of recent reports, see: (a) Ram, V. J.; Srivastava, P.;
Saxena, A. S. J. Org. Chem. 2001, 66, 5333–5337; (b)
Farhanullah; Agarwal, N.; Goel, A.; Ram, V. J. J. Org. Chem.
2003, 68, 2983–2985; (c) Sil, D.; Farhanullah; Ram, V. J.
Tetrahedron Lett. 2004, 45, 9025–9027; (d) Kranjc, K.;
Kocevar, M. New J. Chem. 2005, 29, 1027; (e) Goel, A.;
Dixit, M.; Verma, D. Tetrahedron Lett. 2005, 46, 491–493;
(f) Sil, D.; Kumar, R.; Sharon, A.; Maulik, P. R.; Ram, V. J.
Tetrahedron Lett. 2005, 46, 3807–3809; (g) Sil, D.; Ram,
V. J. Tetrahedron Lett. 2005, 46, 5013–5015; (h) Pratap, R.;
Sil, D.; Ram, V. J. Tetrahedron Lett. 2005, 46, 5025–5027; (i)
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5587; (j) Goel, A.; Verma, D.; Singh, F. V. Tetrahedron Lett.
2005, 46, 8487–8491; (k) Goel, A.; Verma, D.; Dixit, M.;
Raghunandan, R.; Maulik, P. R. J. Org. Chem. 2006, 71,
804–807; (l) Pratap, R.; Kumar, R.; Maulik, P. R.; Ram, V. J.
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Pratap, R.; Kumar, R.; Maulik, P. R.; Ram, V. J. Tetrahedron
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D.; Sreng, I.; Roelofs, W. L. Proc. Natl. Acad. Sci. U.S.A. 1993,
90, 10202–10205; (b) Ram, V. J.; Haque, N.; Nath, M.; Singh,
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4.3.15. 3-Benzyl-4-phenyl-5-methoxycarbonyl-6-methyl-
2H-pyran-2-one 4a. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 7.38–6.96 (m, 10H), 3.70 (s, 2H),
3.35 (s, 3H), 2.37 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 166.2, 162.1, 160.6, 151.6, 138.9, 135.9, 128.6, 128.4,
128.3, 128.2, 127.3, 126.2, 122.7, 114.3, 52.1, 33.1, 18.8;
GC–MS m/z (% rel inten.) 334 (M+, 100), 319 (18), 306
(13), 291 (13), 275 (12), 260 (8), 247 (14), 231 (35), 202
(37), 91 (14), 77 (7), 43 (19). Anal. Calcd for C21H18O4:
C, 75.45; H, 5.39. Found: C, 75.51; H, 5.12.
4.3.16. 3-Benzyl-4,6-dimethyl-5-methoxycarbonyl-2H-
pyran-2-one 4b. Pale yellow viscous oil; 1H NMR
(300 MHz, CDCl3) d 7.28–7.16 (m, 5H), 3.90 (s, 2H), 3.87
(s, 3H), 2.33 (s, 3H), 2.16 (s, 3H); 13C NMR (75 MHz,
CDCl3) d 166.6, 162.2, 160.4, 148.7, 138.4, 128.5, 128.2,
126.4, 122.3, 114.2, 52.4, 32.3, 19.1, 17.6; GC–MS m/z
(% rel inten.) 272 (M+, 100), 244 (41), 229 (93), 213 (17),
185 (23), 167 (17), 141 (34), 128 (21), 115 (23), 91 (37),
77 (12), 43 (39). Anal. Calcd for C16H16O4: C, 70.59;
H, 5.88. Found: C, 70.11; H, 5.49.
Acknowledgements
This project (20573061) was supported by National Natural
Science Foundation of China and Specialized Research
Fund for the Doctoral Program of Higher Education
(20060003079).
Supplementary data
Characterization data for the known products, copies of 1H,
13C NMR charts of 3 and 4, and the full X-ray structural
details for 3a. Supplementary data associated with this arti-
cle can be found in the online version, at doi:10.1016/
j.tet.2007.09.038.
9. (a) Hua, R.; Tanaka, M. New J. Chem. 2001, 25, 179–184 and
references therein; (b) Rousset, S.; Abarbri, M.; Thibonnet, J.;
Parrain, J. L.; Duchene, A. Tetrahedron Lett. 2003, 44, 7633–
7636; (c) Downs, J. R.; Grant, S. P.; Townsend, J. D.; Schady,
D. A.; Pastine, S. J.; Embree, M. C.; Metz, C. R.;
Pennington, W. T.; Bailey Walsch, R. D.; Beam, C. F. Can. J.
Chem. 2004, 82, 659–664; (d) Gerus, I. I.; Tolmachova,
N. A.; Vdovenko, S. I.; Froehlich, R.; Haufe, G. Synthesis
2005, 8, 1269–1278.
References and notes
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15. Crystals for X-ray diffraction analysis were obtained by recrys-
tallization from cyclohexane. CCDC645448 contains supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk.