Synthesis of α,β-unsaturated γ-lactones via photooxygenation of 2,3-dihydrofurans followed by ferrous ion-catalyzed gem-dehydration

Article abstract of DOI:10.1016/j.tet.2006.08.085

Several alkyl and aryl substituted 2,3-dihydrofurans 1a-1e were synthesized and their reactions with singlet oxygen were investigated. Photooxygenation of 1a-1e in carbon tetrachloride at ambient temperature exclusively yields allylic hydroperoxides 4a-4e. Treatment of these hydroperoxides with aqueous ferrous sulfate solution affords the corresponding α,β-unsaturated γ-lactones 6a-6e with high yields. This work provides an efficient route to the preparation of butenolide moiety, an important functionality in the structures of many natural products that exhibit biological properties.

Full text of DOI:10.1016/j.tet.2006.08.085

Tetrahedron 62 (2006) 10688–10693
Synthesis of a,b-unsaturated g-lactones via photooxygenation
of 2,3-dihydrofurans followed by ferrous ion-catalyzed
gem-dehydration
*
Yu-Zhe Chen, Li-Zhu Wu, Ming-Li Peng, Dong Zhang, Li-Ping Zhang and Chen-Ho Tung
*
Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100080, China
Received 24 June 2006; revised 14 August 2006; accepted 15 August 2006
Available online 25 September 2006
This paper is dedicated to Professor Xihui Jiang on the occasion of his 80th birthday
Abstract—Several alkyl and aryl substituted 2,3-dihydrofurans 1a–1e were synthesized and their reactions with singlet oxygen were inves-
tigated. Photooxygenation of 1a–1e in carbon tetrachloride at ambient temperature exclusively yields allylic hydroperoxides 4a–4e. Treat-
ment of these hydroperoxides with aqueous ferrous sulfate solution affords the corresponding a,b-unsaturated g-lactones 6a–6e with high
yields. This work provides an efficient route to the preparation of butenolide moiety, an important functionality in the structures of many
natural products that exhibit biological properties.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
a,b-Unsaturated g-lactone moiety is an important function-
ality in the structures of many natural products that exhibit
interesting biological properties.1–3 For example, pyrani-
cin,4 cacospongionolide,5 lituarine,6 manoalide, rubrolide,
prunolide,7 and digitalis8 all are known to include this bute-
nolide subunit (Scheme 1). Furthermore, five-membered
lactones have a specific odoriferous impression, and a,b-
unsaturated g-lactones are advanced intermediates on the
way to naturally occurring flavoring materials such as
whisky lactone and cognac lactone (Scheme 2).9 In this
regard, the development of efficient strategies for the synthe-
sis of a,b-unsaturated g-lactones is greatly demanded, and
a number of methods have been developed.10 Among these
methods, selective oxidation of furans by singlet oxygen
holds special promise. For example, Schenck and co-
workers11 irradiated furan, 2-hydroxymethylfuran, furfural,
and 2-methylfuran in alcohol in the presence of a singlet
oxygen photosensitizer, and obtained 5-alkoxybutenolide.
The formation of butenolide was assumed to occur via the
1,4-cycloaddition of singlet oxygen to the 1,3-diene in furans
to yield ozonides, which then underwent solvolysis to give
the product. 5-Hydroxybutenolides were also synthesized
by singlet oxygen oxidation of furans.12 For 3-alkylfuran
the singlet oxygen oxidation generally produces the mixture
HO
34
O
OH
10
OH
4
15
C10H22
O
OH
O
Pyranicin
Me
O
Me
O
O
O
H
O
H
O
H
O
Me
11
14
16
O
Me
Me
Me
Me
Me
1
4
9
H
O
O
O
O
N
H
HO
(+)-cacospongionolide B
Lituarine A
O
O
Me
Me
Me
H
H
O
Me
HO
O
H
OH
O
HO
HO
O
H
Manoalide
Digitalis
O
O
Br
O
O
O
O
Ar=
OH
Ar
Ar
Ar
Br
Ar
Rubrolide A
Ar
Ar
Keywords: a,b-Unsaturated g-lactones; Photooxygenation of 2,3-dihydro-
furans; Ferrous ion-catalyzed gem-dehydration of hydroperoxides.
* Corresponding authors. Tel./fax: +86 10 82543580 (L.-Z.W.); tel./fax:
+86 10 82543578 (C.-H.T.); e-mail addresses: lzwu@mail.ipc.ac.cn;
chtung@mail.ipc.ac.cn
Prunolide A
Scheme 1. Structure of pyranicin, cacospongionolide, lituarine, manoalide,
rubrolide, prunolide, and digitalis.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.085

Y.-Z. Chen et al. / Tetrahedron 62 (2006) 10688–10693
10689
Me
dioxetanes 2 decompose to yield the dicarbonyl compounds
3, while the allylic hydroperoxides 4 can eliminate H2O2 to
give the corresponding furans 5 if the 2-position of the 2,3-
dihydrofuran is unsubstituted or monosubstituted. Although
the photooxygenation of 2,3-dihydrofurans has been exten-
sively investigated,15,16 utilization of this photooxidation
as a route to synthesize a,b-unsaturated g-lactones has not
been reported. In the present work we describe a versatile
route to butenolides. Our approach involves the singlet oxy-
gen oxidation of 2,3-dihydrofurans 1 in non-polar solvents at
room temperature to give exclusively the allylic hydroper-
oxides 4 followed by ferrous ion-catalyzed gem-dehydration
of these hydroperoxides. a,b-Unsaturated g-lactones 6 are
generally produced with excellent yields.
Me
O
n-Pent
O
n-Bu
Whisky lactone
O
O
Cognac lactone
Scheme 2. Whisky lactone and cognac lactone.
of the C-3 and C-4 isomers of 5-hydroxybutenolides. To
increase the regioselectivity of this reaction, Kernan and
Faulkner13 carried out the oxidation in the presence of a
hindered base such as 2,2,6,6-tetramethylpiperidine and
selectively obtained the C-4 isomer (Scheme 3). Lee
et al.14 introduced a trimethylsilyl group into the 5-position
of 3-alkylfurans, then performed the singlet oxygen oxi-
dation. They also obtained the regioisomer, 4-alkyl-5-
hydroxy-butenolides (Scheme 4). Recently, Snapper and
co-workers5 synthesized the 5-hydroxybutenolide function-
ality in cacospongionolides B and E via photooxygenation of
furan moiety in the presence of a hindered base. Vassiliko-
giannakis et al.7 synthesized the spirocyclic core of the
prunolides by using a double photooxygenation of a 1,2-
di-[2-(5-trimethylsilyl) furyl]-alkene (Scheme 5).
O
O
R1 R2
O
O
R1
R2
H
O
H
O
3
1O2
2
R1
R2
-H2O2
CCl4, r.t.
R1
O
1
(R2=H)
O
Fe2+
R1
R2
O
5
OOH
H
-H2O
O
R1
R2
1a: R1=R2=H
4
1b: R1=H, R2=pentyl
1c: R1=H, R2=phenyl
1d: R1=H, R2=p-tolyl
1e: R1=CH3, R2=phenyl
O
6
R
R
R
R
O
OH
1O2
O
HO
O
Scheme 6. Photooxygenation of 2,3-dihydrofurans.
O
H
R
O
O
H
O
O
OH
O
N
H
2. Results and discussion
2.1. Photooxygenation of 2,3-dihydrofuran (1a)
O
Scheme 3. Oxidation of 3-substituted furan.
As mentioned above, 2,3-dihydrofuran can undergo ene re-
action and [2+2] cycloaddition with singlet oxygen to yield
allylic hydroperoxide 4 and 1,2-dioxetane 2, respectively,
and polar solvents and low temperature favor the formation
of 2 over 4. Thus, we performed the photooxygenation of
2,3-dihydrofuran in a non-polar solvent, carbon tetrachlo-
ride, at ambient temperature in order to generate the allylic
hydroperoxide in high yield. Tetraphenylporphyrin (TPP)
was used as the sensitizer, and a 450 W Hanovia high-
pressure lamp was used as the light source. A glass filter was
employed to cut off the light with l<400 nm, thus only
the sensitizer in the irradiation sample absorbed the light.
Irradiation of oxygen-bubbling solution of 1a in carbon
tetrachloride in the presence of 10ꢀ5 M TPP exclusively
resulted in the formation of 5-hydroperoxy-2,5-dihydrofuran
4a (Scheme 6). Generally, after 30 min irradiation the
conversion of 1a was close to 100%. The assignment of the
structure of 4a mainly relies on its 1H and 13C NMR spectra,
which were extracted from those of the crude reaction mix-
ture. The 13C NMR spectrum showed four signals at d 74.6
(t), 112.0 (d), 122.8 (d), and 134.2 (d) ppm. These chemical
shifts are attributed to carbon atoms C-2, C-5, C-3, and C-4
OAc
R
OAc
1O2
R
OH
O
X
O
O
X=TMS, TES, TBDMS
Scheme 4. Oxidation of 3,5-disubstituted furan.
O
O
SiMe3
SiMe3
O
i) 1O2, MeOH, 2min
ii) silica gel 80%
Ar = p-anisyl
O
O
O
O
Ar
Ar
trans:cis = 2:1
Ar
Ar
(E) or (Z) isomer
Scheme 5. The spirocyclic core of pronolides.
The photosensitized oxidation of 2,3-dihydrofurans also
has been extensively investigated.15 These substrates can
undergo [2+2] cycloadditions and ene reaction with singlet
oxygen to give 1,2-dioxetane 2 and allylic hydroperoxides 4,
respectively16 (Scheme 6). It has been established15 that in
addition to the structure details of the substrates, the nature
of the solvent (aprotic/protic solvents; polarity) and the reac-
tion temperature may affect the extent to which the two
reaction modes compete with each other for singlet oxygen.
Generally, polar solvents and low temperature favor [2+2]
cycloaddition products over ene products. On heating, the
1
of 4a, respectively. The H NMR spectrum exhibited four
multiplets at d 4.72 (H-2), 5.58 (H-3), 6.13 (H-4), and 6.37
(H-5) and a broad singlet at 8.39 (OOH) ppm in a ratio of
2:1:1:1:1 attributed to protons H-2 through H-5 and OOH
of 4a as indicated in brackets. These 13C and 1H NMR data
are consistent with those reported in the literature.15
With the allylic hydroperoxide 4a in hand, then we con-
ducted the transformation of 4a into butenolide 6a. It has

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Y.-Z. Chen et al. / Tetrahedron 62 (2006) 10688–10693
been established17 that a-alkoxybenzyl hydroperoxides can
be converted into corresponding arylcarboxylate esters via
ferrous ion-catalyzed gem-dehydration. This prompted us
to investigate the possibility of the ferrous ion-catalyzed de-
hydration of 4. To the solution of 4a in carbon tetrachloride
immediately obtained by photooxygenation described above
was added a solution of ferrous sulfate (1 equiv) in water,
and the mixture was stirred at room temperature overnight.
a,b-Unsaturated g-lactone 6a was isolated by dichloro-
methane extraction in an overall yield of 95% based on the
consumed 1a (Table 1). This product was characterized by
1H NMR spectrum that is consistent with the literature.15 It
is suggested that this ferrous ion-catalyzed gem-dehydration
proceeds via the oxy radical generated by homolytic frag-
mentation of the O–O bond of the allylic hydroperoxide in
the presence of ferrous ion (Scheme 7).17,18
into 3-(formyloxy) propanal 3a at elevated temperature
(Scheme 6). In our study since we isolated 6a in 95% yield
after the ferrous ion-catalyzed dehydration, the formation of
2a, if any, must not be significant. Evidently, temperature is
an important factor determining the pathway in the reaction
of olefins with singlet oxygen. Furthermore, Gollnick15 re-
ported that allylic hydroperoxide 4a undergoes elimination
of hydrogen peroxide to give furan 5a rather than dehydra-
tion to give the lactone 6a. Indeed, we kept the solution of
4a in carbon tetrachloride at 50 ꢁC for 4 h, and found that
quantitative furan 5a was produced.
2.2. Photooxygenation of 2-pentyl-2,3-dihydrofuran
(1b), 2-phenyl-2,3-dihydrofuran (1c), and 2-p-tolyl-2,3-
dihydrofuran (1d)
a,b-Unsaturated g-lactone moiety is often connected to nat-
ural products at its 5-position. To exploit the possibility of
utilization of the above mentioned photooxygenation of
2,3-dihydrofurans as a tool for the synthesis of natural
products, we have investigated the ene reaction and the
subsequent ferrous ion-catalyzed dehydration of several
2,3-dihydrofurans with alkyl or aryl at its 2-position. Photo-
irradiation of oxygen-bubbling 0.1 M solution of 1b in
carbon tetrachloride at room temperature in the presence of
10ꢀ5 M TPP led to the formation of 2-pentyl-5-hydroper-
oxy-2,5-dihydrofuran 4b as evidenced by 1H NMR spectrum
of the reaction mixture. No corresponding 1,2-dioxetane 2b
was detected. After 30 min irradiation the conversion of 1b
is completed. Addition of aqueous solution of ferrous sulfate
to the reaction mixture and stirring the mixture overnight re-
sulted in the formation of 5-pentyl-substituted butenolide 6b.
The isolated yield of this product was ca. 84% based on the
consumed 1b (Table 1). As in the case of 1a, when the photo-
oxygenation mixture was treated with triethylamine, the
allylic hydroperoxide 4b transformed into the 5-pentyl-
substituted butenolide 6b with the yield of 81% (Table 1).
Table 1. The yield of a,b-unsaturated g-lactones produced by photooxyge-
nation of 2,3-dihydrofurans followed by ferrous ion-catalyzed or triethyl-
amine-catalyzed gem-dehydration
Substrate
Treatment of the
oxidation product
Product
Yield (%)
FeSO4
Et3N
>95
90
O
O
6a
O
1a
FeSO4
Et3N
84
81
O
Pentyl
Pentyl
O
1b
O
6b
Ph
O
Ph
O
FeSO4
FeSO4
FeSO4
60
67
76
O
6c
1c
p-H3CPh
Me
O
p-H3CPh
O
1d
O
6d
Me
Ph
O
Ph
O
6e
O
1e
The 2-aryl-substituted 2,3-dihydrofurans 1c and 1d also can
be used as starting materials to produce the corresponding
5-aryl-substituted butenolides via photooxygenation in non-
polar solvents at ambient temperature, followed by ferrous
ion-catalyzed gem-dehydration. Under the conditions men-
tioned above, the 5-aryl-butenolides 6c and 6d were isolated
in 60 and 67% yields, respectively (Table 1). Interestingly,
the efficiency of the photooxygenation of substrates 1c and
1d is remarkably larger than those for 1a and 1b. Generally,
irradiation of the solutions of the former substrates under
above conditions for several minutes led to complete conver-
sion to the corresponding allylic hydroperoxides.
Fe2+
O
O
R
R1
R1
OOH
H
O
OH
H2O
R2
O
4
O-O fragmentation R2
O
H
Scheme 7. Ferrous ion-catalyzed gem-dehydration.
In the efforts to transform allylic hydroperoxide 4 into bu-
tenolide 6, we also tested another method that involves the
treatment of 4 with a triethylamine.17 Addition of equivalent
amount of triethylamine to the solution of 4a in carbon tet-
rachloride immediately obtain by photooxygenation and
stirring the solution overnight led to complete conversion
of 4a into 6a, as evidenced by 1H NMR spectrum changes.
Compound 6a was isolated by chromatograph on silica in
the yield greater than 90% (Table 1).
2.3. Photooxygenation of 2-methyl-2-phenyl-2,3-di-
hydrofuran (1e)
In order to elucidate the feasibility of the synthesis of 5,5-di-
substituted butenolide by the above methods, we investigated
the photooxygenation of 2-methyl-2-phenyl-2,3-dihydro-
furan 1e. As expected, TPP-sensitized photooxygenation of
1e in carbon tetrachloride at room temperature yielded the
allylic hydroperoxide 4e exclusively. No [2+2] cycloaddition
Gollnick and co-workers15 performed the photooxygenation
of 1a under similar reaction condition described above, but
at low temperatures (ꢀ78 to 13 ꢁC). In contrast to our result,
a large amount of [2+2] cycloaddition product 2a (24% of
the products) was obtained. Compound 2a transformed
1
product was detected from the H NMR spectrum of the
reaction mixture. Treatment of the reaction mixture with
aqueous ferrous sulfate solution resulted in the conversion

Y.-Z. Chen et al. / Tetrahedron 62 (2006) 10688–10693
10691
1
of 4e to 5-methyl-5-phenyl butenolide 6e. The isolated yield
of 6e was ca. 76% (Table 1).
Compound 8c: H NMR (400 MHz, CDCl3): d¼7.40–7.10
(5H, m, Ph), 4.75 (1H, m, CHOH), 2.61 (1H, d, J¼3.3 Hz,
OH), 2.51 (2H, dd, J¼6.6, 2.6 Hz, CH2), 1.96 (1H, t,
J¼2.6 Hz, CspH).
3. Conclusion
Compound 8d: 1H NMR (400 MHz, CDCl3): d¼7.29 (2H, d,
J¼7.9 Hz, Ph), 7.18 (2H, d, J¼7.9 Hz, Ph), 4.84 (1H, t,
J¼6.3 Hz, CHOH), 2.63 (2H, dd, J¼6.2, 2.6 Hz, CH2),
2.46 (1H, br, OH), 2.37 (3H, s, –CH3), 2.07 (1H, t,
J¼2.1 Hz, CspH).
Photosensitized oxidation of 2,3-dihydrofuran and its deriv-
atives with alkyl and/or aryl substituent(s) at its 2-position in
a non-polar solvent at ambient temperature exclusively yield
the corresponding allylic hydroperoxides. 1,2-Dioxetanes
were not detected. Treatment of the photooxygenation solu-
tions with ferrous sulfate aqueous solution or triethylamine
quantitatively resulted in the conversion of the allylic hydro-
peroxides into a,b-unsaturated g-lactones. The overall
yields of the a,b-unsaturated g-lactones were in the region
of 60–95% based on the consumed 2,3-dihydrofurans. The
high product yield, mild conditions under which the reac-
tions occur, and the low cost of the reagents used make
this reaction sequence to be an efficient strategy for the
synthesis of a,b-unsaturated g-lactones.
1
Compound 8e: H NMR (400 MHz, CDCl3): d¼7.50–7.20
(5H, m, Ph), 2.78 (2H, dd, J¼15.4, 2.6 Hz, CH2), 2.62
(1H, s, OH), 2.06 (1H, t, J¼2.6 Hz, CspH), 1.66 (3H, s,
–CH3).
4.1.2. Preparation of 2,3-dihydrofurans (1). In a typical
experiment, to 0.21 g (0.78 mmol) of molybdenum hexacar-
bonyl was added 14 mL of dry triethylamine under nitrogen
atmosphere, then 12 mL of dry ether was added. The mixture
was stirred for 10–15 min until the molybdenum hexa-
carbonyl had dissolved. The solution was irradiated with
350 nm light for 1 h. To the yielded yellow solution of
Et3N$Mo(CO)5 was added the solution of alkynol (8,
6 mmol) in ether, and the mixture was stirred for 72 h at
room temperature under nitrogen. The solvent was then
removed by rotary evaporation. The remaining liquid was
chromatographed on silica with n-hexane and ether mixture
(10:1, v:v) as eluent and 2,3-dihydrofurans were obtained.
4. Experimental
4.1. Materials
Solvents of reagent grade from Beijing Chemical Works and
2,3-dihydrofuran of analytical grade from Acros Co. were
used without further purification. 2-Pentyl-2,3-dihydrofuran
1b, 2-phenyl-2,3-dihydrofuran 1c, 2-p-tolyl-2,3-dihydro-
furan 1d, and 2-methyl-2-phenyl-2,3-dihydrofuran 1e were
synthesized according to the literatures19 as shown in
Scheme 8.
1
Compound 1b: H NMR (400 MHz, CDCl3): d¼6.28 (1H,
dd, J¼4.9, 2.3 Hz, OCH]), 4.85 (1H, dd, J¼4.9, 2.2 Hz,
OCH]CH), 4.52 (1H, m, –OCH–), 2.68 (1H, m, ]CH–
CH2), 2.21 (1H, ddt, J¼15.1, 7.7, 2.2 Hz, ]CH–CH2),
1.8–1.2 (8H, m, (CH2)4), 0.9 (3H, t, J¼6.6 Hz, CH3).
R
1 R2
O
O
R1
Et3N Mo(CO)5
Et2O, r.t.
HO
C3H3MgBr
1
Compound 1c: H NMR (400 MHz, CDCl3): d¼7.40–7.20
R2
R1
R2 Et2O, -30°C
(5H, m, Ph), 6.43 (1H, dd, J¼4.9, 2.3 Hz, OCH]), 5.49
(1H, dd, J¼10.7, 8.5 Hz, CHPh), 4.92 (1H, dd, J¼4.9,
2.4 Hz, –OCH]CH), 3.05 (1H, ddt, J¼15.4, 10.7, 2.4 Hz,
CH2, H-trans), 2.58 (1H, ddt, J¼15.4, 8.4, 2.4 Hz, CH2,
H-cis).
1
7
8
7b: R1=H, R2=pentyl
7c: R1=H, R2=phenyl
7d: R1=H, R2=p-tolyl
7e: R1=CH3, R2=phenyl
Scheme 8. Preparation of 2,3-dihydrofurans.
1
Compound 1d: H NMR (400 MHz, CDCl3): d¼7.40–7.10
4.1.1. Preparation of alkynols (8). In a typical experiment
a solution of Grignard reagent, C3H3MgBr in Et2O was pre-
pared by a literature procedure.20 This solution was cooled
to ꢀ30 ꢁC and a solution of the corresponding aldehyde or
ketone 7 in Et2O was added dropwise. The mixture was
slowly warmed to room temperature and stirred for 1 h. It
was then poured into ice water. Saturated aqueous NH4Cl so-
lution was added to dissolve the precipitate and the organic
layer was separated. The aqueous layer was extracted with
ether and the extracts were combined with the above organic
layer. The combined solution was dried over MgSO4. After
evaporation of the solvent the residue was purified by distil-
lation at reduced pressure.
(4H, m, Ph), 6.45 (1H, dd, J¼4.9, 2.3 Hz, OCH]), 5.50
(1H, dd, J¼10.6, 8.6 Hz, CH3Ph–CH), 4.96 (1H, m,
OCH]CH), 3.06 (1H, m, CH2, H-trans), 2.62 (1H, m,
CH2, H-cis), 2.36 (3H, s, –CH3).
1
Compound 1e: H NMR (400 MHz, CDCl3): d¼7.50–7.20
(5H, m, Ph), 6.40 (1H, dd, J¼4.9, 2.4 Hz, OCH]), 4.86
(1H, m, –OCH]CH), 2.87 (1H, dt, J¼15.0, 2.3 Hz,
]CH–CH2), 2.80 (1H, dt, J¼15.0, 2.3 Hz, ]CH–CH2),
1.67 (3H, s, –CH3).
4.1.3. Photooxygenation and ferrous ion-catalyzed gem-
dehydration. The photooxidation of 2,3-dihydrofurans 1
was carried out in carbon tetrachloride in a Pyrex reactor
with tetraphenylporphyrin (TPP) as the sensitizer. The light
source was a 450 W Hanovia high-pressure mercury lamp
with a glass filter to cut off the light with wavelength below
400 nm, thus to ensure the absence of direct excitation of
the substrates. During irradiation, oxygen was bubbled
1
Compound 8b: H NMR (400 MHz, CDCl3): d¼3.75 (1H,
m, CHOH), 2.43 (1H, ddd, J¼16.5, 4.9, 2.6 Hz, CH2–Csp),
2.31 (1H, ddd, J¼16.5, 6.6, 2.6 Hz, CH2–Csp), 2.05 (1H, t,
J¼2.6 Hz, Csp–H), 2.05 (1H, br, OH), 1.60–1.20 (8H, m,
(CH2)4), 0.89 (3H, t, J¼6.6 Hz, CH3).

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Y.-Z. Chen et al. / Tetrahedron 62 (2006) 10688–10693
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through the solution. The photooxygenation process was
followed by H NMR of the reaction mixture. After the
1
oxidation was completed, to the reaction mixture was added
equivalent amount of ferrous sulfate aqueous solution (or
triethylamine). The mixture was stirred overnight, and
then the organic layer was separated and dried over
MgSO4. Evaporation of the solvent afforded a,b-unsatu-
rated g-lactones.
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1
Compound 6a: H NMR (400 MHz, CDCl3): d¼7.60 (1H,
m, CH2–CH]), 6.21 (1H, m, CH2CH]CH), 4.93 (2H, m,
CH2).
1
Compound 6b: H NMR (400 MHz, CDCl3): d¼7.47 (1H,
dd, J¼5.7, 1.2 Hz, CHCH]CH), 6.13 (1H, dd, J¼5.7,
1.9 Hz, CHCH]CH), 5.06 (1H, m, CHCH]CH), 1.2–1.8
(8H, m, (CH2)4), 0.92 (3H, t, J¼6.7 Hz, CH3).
ꢀ
9. (a) Frater, G.; Bajgrowicz, J. A.; Kraft, P. Tetrahedron 1998, 54,
Compound 6c: 1H NMR (400 MHz, CDCl3): d¼7.2–7.5
(5H, m, Ph), 7.52 (1H, dd, J¼5.6, 1.7 Hz, CHCH]CH),
6.23 (1H, dd, J¼5.6, 2.1 Hz, CHCH]CH), 6.03 (1H, dd,
J¼2.0, 1.7 Hz, PhCH).
7633–7703; (b) Otzuka, K.; Zenibayashi, Y.; Itoh, M.; Totsuka,
A. Agric. Biol. Chem. 1974, 38, 485–490.
10. For recent reviews on the synthesis of butenolides, see: (a)
Negishi, E.; Kotora, M. Tetrahedron 1997, 53, 6707–6738;
(b) Deshong, P.; Sidler, D. R.; Slough, G. A. Tetrahedron
Lett. 1987, 28, 2233–2236; (c) Marshall, J. A.; Wolf, M. A.
J. Org. Chem. 1996, 61, 3238–3239; (d) Yu, W.; Alper, H.
J. Org. Chem. 1997, 62, 5684–5687; (e) Xiao, W.; Alper, H.
J. Org. Chem. 1997, 62, 3422–3423; (f) Arcadi, A.;
Bernocchi, E.; Burini, A.; Cacchi, S.; Marinelli, F.; Pietroni,
B. Tetrahedron 1988, 44, 481–490; (g) Marshall, J. A.;
Bartley, G. S.; Wallace, E. M. J. Org. Chem. 1996, 61, 5729–
5735; (h) Clough, J. M.; Pattenden, G.; Wight, P. G.
Tetrahedron Lett. 1989, 30, 7469–7472; (i) Chen, J.; Sanner,
M. A.; Carlson, R. M. Synth. Commun. 1990, 20, 901–906;
(j) Marshall, J. A.; Wallace, E. M.; Coan, P. S. J. Org. Chem.
1995, 60, 796–797; (k) Yoneda, E.; Kaneko, T.; Zhang, S.;
Onitsuka, K.; Takahashi, S. Org. Lett. 2000, 2, 441–443; (l)
Renurd, M.; Ghosez, L. A. Tetrahedron 2001, 57, 2597–
2608; (m) Langer, P.; Friefold, I. Synlett 2001, 523–525; (n)
Linclau, B.; Boydell, A. J.; Clarke, P. J.; Horan, R.; Jaequet,
C. J. Org. Chem. 2003, 68, 1821–1826.
11. (a) Koch, E.; Schenck, G. O. Chem. Ber. 1966, 99, 1984–
1990; (b) Schenck, G. O.; Appel, R. Naturwissenschaften
1946, 33, 122–123; (c) Schroeter, S. H.; Brammer, R.;
Schenck, G. O. Justus Liebigs Ann. Chem. 1966, 697, 42–
61; (d) Gollnick, K.; Schenck, G. O. 1,4-Cycloaddition
Reactions: The Diels–Alder Reaction in Heterocyclic Syn-
thesis; Hammer, J., Ed.; Academic: New York, NY, 1967;
Chapter 10, p 255.
12. For recent reviews, see: (a) Feringa, B. L. Recl. Trav. Chim.
Pays-Bas 1987, 106, 469–488; (b) Wasserman, H. H.; Ives,
J. L. Tetrahedron 1981, 37, 1825–1852; (c) Mataumoto, M.
Singlet Oxygen; Frimer, A. A., Ed.; CRC: Boca Raton, FL,
1985; Vol. II.
1
Compound 6d: H NMR (400 MHz, CDCl3): d¼7.1–7.4
(4H, m, Ph), 7.51 (1H, dd, J¼5.5, 1.5 Hz, CHCH]CH),
6.22 (1H, dd, J¼5.7, 2.0 Hz, CHCH]CH), 5.99 (1H, dd,
J¼2.0, 1.5 Hz, CHCH]CH), 2.37 (3H, s, –CH3).
Compound 6e: 1H NMR (400 MHz, CDCl3): d¼7.63 (1H, d,
J¼5.6 Hz, PhCCH]CH), 7.5–7.2 (5H, m, Ph–), 6.06 (1H, d,
J¼5.6 Hz, PhC–CH]CH), 1.83 (3H, s, –CH3).
Acknowledgements
Financial support from the Ministry of Science and
Technology of China (Grant no. 2004CB719903 and
2007CB808004), the National Science Foundation of
China (nos. 20333080, 20332040, 20472091, 50473048,
20472092, 20403025), and the Chinese Academy of Sci-
ences (no. KJCX2-SW-H15) is gratefully acknowledged.
References and notes
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