Efficient synthesis of dihydrofurans with sulfide groups by ceric(IV) ammonium nitrate-mediated oxidative cycloaddition of 1,3-dicarbonyl compounds to vinyl sulfides. Application to the synthesis of benzo[b]naphtho[2,3-d]furan-6,11-dione and first total synthesis of millettocalyxins C and pongamol methyl ether

Article abstract of DOI:10.1055/s-2003-41023

Ceric(IV) ammonium nitrate-mediated oxidative cycloaddition of 1,3-dicarbonyls to vinyl sulfides afforded substituted dihydrofurans with sulfide groups in moderate yields. This new synthetic method has been applied to the synthesis of benzo[b]naphtho[2,3-d]furan-6,11-dione and furanoflavone natural products such as millettocalyxins C and pongol methyl ether.

Full text of DOI:10.1055/s-2003-41023

PAPER
1977
Efficient Synthesis of Dihydrofurans with Sulfide Groups by Ceric(IV)
Ammonium Nitrate-Mediated Oxidative Cycloaddition of 1,3-Dicarbonyl
Compounds to Vinyl Sulfides. Application to the Synthesis of Benzo[b]naph-
tho[2,3-d]furan-6,11-dione and First Total Synthesis of Millettocalyxins C
and Pongamol Methyl Ether
Dihydrofurans by
o
O
xidative Cy
n
cloaddition
o
g
f
1,3-Dicarbonyl
C
R
ompounds to
V
i
o
nyl Sulfidesk Lee,* Keon Yong Kang, Gun Joon Lee, Won Kyong Lee
School of Chemical Engineering and Technology, College of Engineering Yeungnam University, Kyongsan 712-749, Korea
Fax +82(53)8148790; E-mail: yrlee@yu.ac.kr
Received 2 April 2003; revised 30 May 2003
furanoflavone natural products such as millettocalyxins C
Abstract: Ceric(IV) ammonium nitrate-mediated oxidative cy-
and pongol methyl ether.
cloaddition of 1,3-dicarbonyls to vinyl sulfides afforded substituted
dihydrofurans with sulfide groups in moderate yields. This new
synthetic method has been applied to the synthesis of benzo[b]naph-
tho[2,3-d]furan-6,11-dione and furanoflavone natural products
such as millettocalyxins C and pongol methyl ether.
The 1,3-dicarbonyl compounds used in this study includ-
ed the commercially available cyclohexane-1,3-diones 1–
4, ethyl acetoacetate (5), 2,4-pentanedione (6), 4-hydrox-
ycoumarins 7–9, 3-hydroxy-1H-phenalen-1-one (10), and
2-hydroxy-1,4-naphthoquinone (11) (Figure 1). The vinyl
sulfides 12–15 used to react with the dicarbonyl com-
pounds were readily prepared with a known procedure
(Figure 2).8
Key words: furans, natural products, cycloadditions, oxidations,
millettocalyxins C, pongol methyl ether
Oxidative cycloaddition reactions mediated by metal salts
(MnIII, CeIV, CoII, and VV) have received considerable at-
tention in organic synthesis for the construction of car-
bon–carbon bonds.1 Among these, manganese(III) acetate
and ceric(IV) ammonium nitrate (CAN) have been used
most efficiently. CAN-mediated oxidative cycloaddition
of 1,3-dicarbonyl compounds to alkenes,2 vinyl acetates,3
enol silyl ethers,4 and enol ethers5 has been studied exten-
sively. We have reported on the CAN-mediated oxidative
cycloaddition of 1,3-dicarbonyl compounds with conju-
gated compounds.6 While continuing our work based on
the CAN-mediated oxidative cycloaddition, we have ex-
panded this work to the synthesis of dihydrofurans with
sulfide groups.7 In order to examine the breadth and gen-
erality of the reactions described in our preliminary re-
sults,7 we have reviewed additional reactions of a number
of 1,3-dicarbonyl compounds and vinyl sulfides. Here, we
report the efficient synthesis of a variety of substituted di-
hydrofurans and its application to the biologically inter-
esting benzo[b]naphtho[2,3-d]furan-6,11-dione and
R5
SPh
R6
SPh
SPh
13 R5=H
14 R5=CH3
SPh
12
16 R6=H
17 R6=CH3
15
Figure 2
Reaction of 1,3-dicarbonyl compound 1 with vinyl sulfide
13 was first examined utilizing the two oxidizing agents
Mn(OAc)3·2 H2O and Ce(NH4)2(NO3)6. Both manga-
nese(III) acetate dihydrate (80 °C, 7 h) in HOAc and cer-
ic(IV) ammonium nitrate (0 °C, 6 h) in acetonitrile
provided the dihydrofuran 18 in 65 and 79% yields, re-
spectively (Table 1). However, we found that ceric(IV)
ammonium nitrate was a much superior reagent for this
cycloaddition than manganese(III) acetate dihydrate, with
the advantage of more mild reaction conditions and a
higher yield. The formation of 18 was confirmed by the
O
O
O
O
O
R4
O
O
R1
R2
R3
O
O
O
OH
O
1 R1=R2=H
5 R3=OEt
7 R4=H
8 R4=Cl
9 R4=CH3
10
11
2 R1=H, R2=CH3 6 R3=CH3
3 R1=H, R2=Ph
4 R1=R2=CH3
Figure 1
Synthesis 2003, No. 13, Print: 18 09 2003. Web: 19 08 2003.
Art Id.1437-210X,E;2003,0,13,1977,1988,ftx,en;F03003SS.pdf.
DOI: 10.1055/s-2003-41023
© Georg Thieme Verlag Stuttgart · New York

1978
Y. R. Lee et al.
PAPER
observation of a carbonyl peak of the enone at 1638 cm–1 In order to synthesize biologically interesting dihydro-
in the IR spectrum, and the expected chemical shifts asso- furocoumarin derivatives, reaction of 4-hydroxycou-
ciated with the methine proton of the dihydrofuran ring at marins 7–9 with vinyl sulfides was next examined.
d = 3.16. In order to find the optimized reaction condi- Treatment of 7 with vinyl sulfide 12 in the presence of 2.2
tions, we surveyed several solvents in the presence of equivalents of CAN(IV) in THF gave dihydrofurocou-
Ce(NH4)2(NO3)6. The best yield was obtained in THF marins 29 (42%), without any formation of possible regio-
(86%). Other solvents included methanol (27%) and ben- isomers (entry 1, Table 3). Compound 29 has been clearly
zene (12%). Our finding was very surprising in compari- shown to be angular by spectral analysis and by compari-
son with the reported result that CAN(IV)-mediated son with reported data in the literature.10,11 With other vi-
oxidative reactions have usually been used in polar sol- nyl
sulfides
13
and
15,
the
expected
vents such as acetonitrile and methanol.1–5
dihydrofurocoumarins 30–32 were also obtained in 40–
72% yields, respectively (entries 2–4). Similarly, reaction
of 7 and 9 with acyclic vinyl sulfide 16 afforded cycload-
ducts 33 and 34 in 46% and 60% yields, respectively (en-
tries 5, 6). The results are summarized in Table 3. These
reactions provide a rapid route to the preparation of
dihydrofurocoumarin derivatives which are known to
have a number of biological activities such as anticoagu-
lant, insecticidal, anthelminthic, hypnotic, and antifun-
gal.12
Table 1 Effect of Oxidants and Solvents in the Reaction of 1 and 13
O
O
SPh
13
SPh
O
O
18
1
Oxidant
Solvent
Temperature Time
Yield
(%)
(°C)
80
0
(h)
Next, reaction of 3-hydroxy-1H-phenalen-1-one (10) with
vinyl sulfides was investigated. Treatment of 10 with vi-
nyl sulfide 12 gave dihydrofurophenalenone 35 with a
yield of 87% (entry 1, Table 4). Similarly, reaction with
sulfides 13 and 15 afforded dihydrofurophenalenone de-
rivatives 36 and 37 in 77 and 74% yields, respectively (en-
tries 2, 3). Reaction with vinyl sulfide 17 afforded
cycloadduct 39 (92%) with a 34:66 mixture of cis- and
trans-isomers (entry 5). This reaction also affords the
trans-compound as the major product, despite the fact that
the cis-vinyl sulfide was the major reagent. The results are
summarized in Table 4. Importantly, these reactions pro-
vide a rapid route for the synthesis of biologically interest-
ing dihydrofurophenalenone derivatives which are
reported to have various biological activities such as anti-
biotics, antimicrobial, antifungal, and phytoalexin.13
Mn(OAc)3·2 H2O
Ce(NH4)2(NO3)6
Ce(NH4)2(NO3)6
Ce(NH4)2(NO3)6
Ce(NH4)2(NO3)6
HOAc
MeCN
THF
7
65
79
86
27
12
6
r.t.
r.t
6
MeOH
benzene
18
24
r.t
In order to extend the utility of these oxidative cycloaddi-
tions, additional reactions of 1,3-dicarbonyl compounds
with other sulfides were next investigated. In the treat-
ment of 1 and 4 with vinyl sulfide 12 in the presence of 2.2
equiv of CAN(IV) at room temperature for 6 hours in
THF, cycloadducts 19 and 20 were obtained in 79% and
84% yields, respectively (entries 1, 2, Table 1). With the
acyclic 1,3-dicarbonyl compound, the cycloaddition reac-
tion was successful. When ethyl acetoacetate (5) was
treated with vinyl sulfide 12 in THF, dihydrofuran 21 was
obtained with 40% yield (entry 3). Vinyl sulfide 14, with
a larger ring system, gave cycloadducts 23–26 in 49–87%
yields (entries 5–8). The stereochemistry of 19–26 is as-
signed as cis by spectral analysis and by analogy with ear-
lier reported data.9 The reaction was also successful with
the acyclic vinyl sulfides 16 and 17. Treatment of 1 with
vinyl sulfide 16 in THF gave cycloadduct 27 with 74%
yield (entry 9). With vinyl sulfide 17 with a 3:2 ratio of
stereoisomers, there is a moderate solvent dependence in
yield and stereoselectivity. In acetonitrile the reaction af-
forded cycloadduct 28 in 64% yield with a 32:68 mixture
of the cis- and trans-isomers (entry 10), whereas in THF
the reaction gave 28 with a higher yield (71%) and a lower
stereoseletivity toward the trans-isomer (entry 11). The
stereochemical assignment of the cis- and trans-isomers
was defined by the observation of the coupling constants
between vicinal protons (Jcis = 8.8 Hz, Jtrans = 5.3 Hz) of
the dihydrofuran ring. The results are summarized in
Table 2.
Finally, the reaction of 2-hydroxy-1,4-naphthoquinone
(11) with vinyl sulfides was investigated. Treatment of 11
with vinyl sulfide 12 resulted in dihydrofuronaphtho-
quinone 40 (30%) and 41 (19%) as a mixture of linear and
angular regioisomers (entry 1, Table 5). The products
were easily purified by column chromatography and the
structures of the two isomers were determined by their
spectroscopic data, and by comparison with data that had
been reported in the literature.14 The clear assignments
came from the IR carbonyl absorptions at 1690 and 1647
cm–1 for the two carbonyls in 40 and at 1701and 1653
cm–1 in 41. Similarly, with other sulfides 13–16, cycload-
ducts 42–47 were obtained as a mixture of regioisomers
(entries 2–4). However, reaction with vinyl sulfide 16 at
room temperature in THF afforded solely dihydrofu-
ronaphthoquinone 48 in 53% yield, without formation of
the other possible regioisomer (entry 5). The results are
summarized in Table 5. These reactions also provided a
rapid entry to the synthesis of biologically active dihydro-
furonaphthoquinone derivatives.15
As an application of this methodology, the synthesized
adducts can be elaborated toward other biologically and
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

PAPER
Dihydrofurans by Oxidative Cycloaddition of 1,3-Dicarbonyl Compounds to Vinyl Sulfides
1979
Table 2 Reaction of Cyclic and Acyclic 1,3-Dicarbonyl Compounds 1–6 with Vinyl Sulfides
Entry
1
1,3-Dicarbonyl compound Vinyl sulfide
Solvent
THF
Product
Yield (%)
79
O
H
O
SPh
12
SPh
O
O
19
1
2
3
THF
THF
84
40
O
O
H
SPh
12
SPh
O
O
20
4
O
O
O
H
EtO
SPh
OEt
5
12
14
O
H
SPh
21
4
THF
71
O
O
SPh
O
SPh
O
4
1
22
O
5
6
THF
THF
81
87
O
H
SPh
SPh
O
O
15
15
23
O
O
H
O
SPh
SPh
O
3
24
25
7
8
THF
THF
85
49
O
O
H
SPh
SPh
SPh
O
O
15
4
6
O
O
O
O
H
15
16
O
SPh
26
O
9
THF
74
64
SPh
SPh
O
O
27
1
4
10
MeCN
O
O
O
SPh
17
SPh
(cis–trans, 60:40)
O
O
O
28
(cis:trans = 32:68)
11
THF
71
4
O
SPh
17
SPh
O
(cis–trans, 60:40)
28
2
(cis:trans = 46:54)
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

1980
Y. R. Lee et al.
PAPER
Table 3 Reaction of 4-Hydroxycoumarins 7–9 with Vinyl Sulfides
Entry
1
4-Hydroxycoumarin
Vinyl sulfide
solvent
THF
Product
Yield (%)
42
PhS
O
O
SPh
12
H
O
O
O
O
7
29
2
THF
40
O
O
PhS
O
SPh
H
O
13
O
O
7
30
Cl
3
4
5
6
THF
THF
THF
THF
41
72
46
60
PhS
O
O
Cl
SPh
H
O
13
O
O
O
8
31
PhS
O
O
O
SPh
H
O
O
15
O
7
32
33
34
SPh
O
O
SPh
O
O
16
O
O
7
9
O
O
SPh
O
SPh
O
O
16
O
pharmacologically interesting compounds. For example, (Scheme 1). When 49 was treated with Pd/C at reflux for
dihydrofuran 42 can be readily converted to benzofu- 5 hours in phenyl ether, benzofuronaphthofurandione 50
ronaphthoquinone derivative 50 which has been reported was produced in 42% yield. The structural assignment of
to have significant biological activities such as antiprurit- 50 was easily made with the new aromatic peaks in the 1H
ic, antitumor, topo II-mediate DNA cleavage.16 Although NMR spectrum.
several synthetic methods for the preparation of benzofu-
As another application, a synthetic route to furanoflavone
ronaphthoquinone derivatives have been reported, their
natural products starting from the obtained dihydrofuran
synthetic exploitation has been limited due to many reac-
was next investigated (Scheme 2). Furanoflavones are an
tion steps, low yield, and the difficulty in availability of
abundant subclass of the flavonoid and are widely distrib-
the required starting materials.17 Reaction of 42 with
uted in nature.18 Members of the furanoflavones have
been associated with a wide variety of biological activities
MCPBA in CH2Cl2 at room temperature for 24 hours af-
forded the corresponding sulfoxide, which upon refluxing
such as insecticide, pesticidal, anticancer and antiulcer,19
for 5 hours in xylene gave furan 49 in 70% yield
and are used in traditional medicines for the treatment of
O
O
O
O
Pd/C
Ph2O
42%
i) mCPBA
CH2Cl2
ii) xylene
reflux
O
SPh
O
50
O
42
49
O
O
70%
Scheme 1
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

PAPER
Dihydrofurans by Oxidative Cycloaddition of 1,3-Dicarbonyl Compounds to Vinyl Sulfides
1981
Table 4 Reaction of 3-Hydroxy-1H-phenalen-1-one (10) with Vinyl Sulfides
Entry
1
3-Hydroxy-1H-
phenalen-1-one
Vinyl sulfide
Solvent
THF
Product
Yield (%)
87
O
O
H
SPh
12
SPh
O
O
35
36
37
38
39
10
2
3
4
5
THF
THF
THF
THF
77
74
62
92
O
O
O
O
O
H
SPh
SPh
O
O
13
10
O
H
SPh
SPh
O
O
15
10
O
SPh
16
SPh
O
O
O
10
O
SPh
17
SPh
(cis–trans, 60:40)
O
10
(cis–trans, 34:66)
tumours, piles, skin diseases, wounds, ulcers, etc.20 Very In conclusion, CAN-mediated oxidative cycloaddition of
recently, new furanoflavones, millettocalyxins C 55 and 1,3-dicarbonyls to vinyl sulfides is described. This meth-
pongol methyl ether 56, were isolated from the stem bark od provides a simple and efficient synthesis of substituted
of Millettia erythrocalyx.21 Currently, the bark of this dihydrofurans. As an application of this methodology, the
plant has been used by the local people in Thailand for synthesis of benzofuronaphthoquinone and the natural
treating stomach pain. However, the total synthesis of mil- furanoflavones is carried out starting from obtained dihy-
lettocalyxins C 55 and pongol methyl ether 56 has not drofurans.
been reported.
The conversion of dihydrofuran 27 to both of these natural
products 55 and 56 was begun by syn-elimination with
MCPBA to give compound 51 (70%). Transformation of
51 into the sodium enolate with an excess of NaH in the
presence of a catalytic amount of KH was followed by
treatment with dimethyl carbonate to form 52 in 90%
yield. The DDQ-mediated oxidation of 52 in refluxing di-
All experiments were carried out under a nitrogen atmosphere. Mer-
ck precoated silica gel plates (Art. 5554) with a fluorescent indica-
tor were used for analytical TLC. Flash column chromatography
was performed using silica gel 9385 (Merck). Mps were determined
with microcover glasses on a Fisher–Johns apparatus and are uncor-
1
rected. H NMR spectra were recorded on a Bruker Model ARX
(300 MHz) spectrometer. 13C NMR spectra were recorded on a
Bruker Model ARX (75 MHz) spectrometer in CDCl3 using d =
oxane gives the compound 53 (85%), which was treated 77.0 as the solvent chemical shift. IR spectra were recorded on a
JASCO FTIR 5300 spectrophotometer. Mass and high resolution
mass spectra were obtained with a JEOL JMS-700 spectrometer at
the Korea Basic Science Institute (Daegu). Elementary analyses
were performed by the Korea Basic Science Institute (Daegu).
with the dimsyl anion in benzene to form the b-keto sul-
foxide 54 (83%).22 The b-keto sulfoxide 54 is easily con-
verted by treatment with 2,5-dimethoxybenzaldehyde and
3-methoxybenzaldehyde in the presence of piperidine,
first at 40 °C and then at 110 °C, to the corresponding
furanoflavones 55 and 56 in 78% and 88% yield, respec-
tively. The spectroscopic properties of our synthetic ma-
terials agreed well with those reported in the literature.21
Dihydrofurans; General Procedure
To a solution of 1,3-dicarbonyl compound (1.0 mmol) and vinyl
sulfide (2.0 mmol) in MeCN (20 mL) or THF (20 mmol) was added
CAN (1.206 g, 2.2 mmol) and NaHCO3 (420 mg, 5.0 mmol) at 0 °C
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

1982
Y. R. Lee et al.
PAPER
Table 5 Reaction of 2-Hydroxy-1,4-naphthoquinone (11) with Vinyl Sulfides
Entry
1
2-Hydroxy-1,4-
naphthoquinone
Vinyl sulfide
Solvent
THF
Product
40
Yield (%)
19
O
O
PhS
O
H
SPh
12
H
O
SPh
OH
O
O
O
O
O
11
40
42
41
43
45
47
2
3
4
5
THF
THF
THF
THF
45
43
44
53
23
19
23
O
PhS
O
H
SPh
H
O
13
SPh
OH
O
O
O
O
O
11
O
PhS
O
H
SPh
H
14
OH
O
O
SPh
O
O
O
O
11
44
46
PhS
O
O
H
SPh
H
O
SPh
OH
O
15
O
O
O
O
11
O
SPh
16
SPh
O
OH
O
O
11
48
or r.t. The reaction mixture was stirred for 6 h at 0 °C in MeCN or
for 6 h at r.t. in THF. The mixture was diluted with H2O and extract-
ed with EtOAc (3 × 50 mL). The combined organic extracts were
washed with brine, dried (MgSO4), and evaporated under reduced
pressure to give the residue. The residue was purified by flash col-
umn chromatography on silica gel to give product.
5a-Phenylsulfanyl-3,4,5a,6,7,8,9,9a-octahydro-2H-dibenzofu-
ran-1-one (18)
Reaction of 1,3-cyclohexanedione (1) (112 mg, 1 mmol) with vinyl
sulfide 13 (381 mg, 2 mmol) in THF (20 mL) afforded 18.
Yield: 258 mg (86%); solid; mp 96–97 °C.
IR (KBr): 3057, 2946, 2866, 1638, 1474, 1454, 1439, 1399, 1248,
1181, 1136, 1061, 999 cm–1.
O
O
O
O
mCPBA
MeO
NaH(KH)
(MeO)2CO
THF
DDQ
dioxane
85%
SPh
CH2Cl2
70%
O
O
O
51
52
27
90%
R
O
MeO
H
O
OH
R
O
S
O
OH
NaH/DMSO
MeO
OMe
piperidine
toluene
O
PhH
83%
O
53
O
O
54
O
55 R=OMe 78% millettocalyxins C
56 R=H 88% pongol methyl ether
Scheme 2
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

PAPER
Dihydrofurans by Oxidative Cycloaddition of 1,3-Dicarbonyl Compounds to Vinyl Sulfides
1983
1H NMR (300 MHz, CDCl3): d = 7.58–7.53 (2 H, m), 7.37–7.29 (3
H, m), 3.16 (1 H, dd, J = 6.7, 5.9 Hz), 2.41–2.37 (2 H, m), 2.27–2.18
(2 H, m), 1.98–1.89 (4 H, m), 1.60–1.41 (6 H).
9a-Phenylsulfanyl-1,2,3,4b,5,6,7,8,9a-decahydro-10-oxabenzo-
[a]azulen-4-one (23)
Reaction of 1,3-cyclohexanedione (1) (112 mg, 1 mmol) with vinyl
sulfide 15 (409 mg, 2 mmol) in THF (20 mL) afforded 23 (255 mg,
81%).
HRMS: m/z calcd for C18H20O2S (M+): 300.1185; found: 300.1184.
8a-Phenylsulfanyl-1,2,3,3a,5,6,7,8a-octahydro-8-oxacyclopen-
ta[a]inden-4-one (19)
Reaction of 1,3-cyclohexanedione (1) (112 mg, 1 mmol) with vinyl
sulfide 12 (353 mg, 2 mmol) in THF (20 mL) afforded 19.
Solid; mp 80–81 °C.
IR (KBr): 3057, 2930, 2853, 1642, 1453, 1439, 1397, 1362, 1277,
1256, 1225, 1179, 1136, 1063, 995, 984 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.55–7.51 (2 H, m), 7.42–7.29 (3
H, m), 3.21 (1 H, d, J = 9.2 Hz), 2.43–2.38 (2 H, m), 2.32–2.16 (2
H, m), 2.04–1.89 (4 H, m), 1.76–1.35 (8 H, m).
MS (EI): m/z = 204 (M+ – PhSH) (100), 189 (30), 176 (63), 175
(46), 148 (43), 125 (20), 105 (17), 91 (20), 77 (14), 55 (18).
Yield: 226 mg (79%); solid; mp 42–43 °C.
IR (KBr): 3057, 2946, 2868, 1638, 1476, 1439, 1399, 1364, 1258,
1213, 1181, 1138, 1055, 1003, 909 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.59–7.56 (2 H, m), 7.35–7.26 (3
H, m), 3.52 (1 H, d, J = 9.1 Hz), 2.41–1.48 (m, 12 H).
HRMS: m/z calcd for C13H16O2 (M+ – PhSH): 204.1150; found:
204.1152.
HRMS: m/z calcd for C17H18O2S (M+): 286.1028; found: 286.1025.
Anal. Calcd for C19H22O2S: C, 72.57; H, 7.05; S, 10.20. Found: C,
72.35; H, 6. 98; S, 10.42.
6,6-Dimethyl-8a-phenylsulfanyl-1,2,3,3a,5,6,7,8a-octahydro-8-
oxacyclopenta[a]inden-4-one (20)
Reaction of 5,5-dimethyl-1,3-cyclohexanedione (4) (140 mg, 1
mmol) with vinyl sulfide 12 (353 mg, 2 mmol) in THF (20 mL) af-
forded 20.
2-Phenyl-9a-phenylsulfanyl-1,2,3,4b,5,6,7,8,9,9a-decahydro-
10-oxabenzo[a]azulen-4-one (24)
Reaction of 5-phenyl-1,3-cyclohexanedione (3) (188 mg, 1 mmol)
with vinyl sulfide 15 (409 mg, 2 mmol) in THF (20 mL) afforded
24 as an inseparable diastereomer.
Yield: 264 mg (84%); solid; mp 73–74 °C.
IR (KBr): 3059, 2959, 2870, 1640, 1472, 1400, 1350, 1302, 1250,
1208, 1163, 1142, 1034, 912 cm–1.
Yield: 349 mg (87%).
1H NMR (300 MHz, CDCl3): d = 7.58–7.56 (2 H, m), 7.36–7.22 (3
H, m), 3.56 (1 H, d, J = 8.3 Hz), 2.27–1.91 (6 H, m), 1.82–1.75 (2
H, m), 1.60–1.45 (2 H, m), 1.02 (3 H, s), 0.85 (3 H, s).
1H NMR (300 MHz, CDCl3): d = 7.56–7.46 (2 H, m), 7.37, 7.40–
7.32 (5 H, m), 7.29–7.20 (3 H, m), 3.42–3.28 (1 H, m), 3.23 (1 H, d,
J = 9.3 Hz), 2.75–2.62 (2 H, m), 2.59–2.40 (2 H, m), 2.06–1.96 (3
H, m), 1.75–1.58 (5 H, m), 1.50–1.40 (2 H, m).
HRMS: m/z calcd for C19H22O2S (M+): 314.1341; found: 314.1337.
IR (KBr): 3057, 3029, 2922, 2855, 1640, 1195, 1476, 1454, 1439,
1418, 1397, 1323, 1211, 1179, 1134, 1051, 1009, 983, 966, 906,
891, 860 cm–1.
MS (EI): m/z = 280 (M+ – PhSH) (85), 256 (13), 176 (100), 148
(45), 129 (66), 110 (30), 91 (23), 71 (30), 57 (44).
HRMS: m/z calcd for C19H20O2 (M+ – PhSH): 280.1463; found:
2-Methyl-6a-phenylsulfanyl-4,5,6,6a-tetrahydro-3aH-cyclo-
penta[b]furan-3-carboxylic Acid Ethyl Ester (21)
Reaction of ethyl acetoactate (5) (130 mg, 1 mmol) with vinyl sul-
fide 12 (353 mg, 2 mmol) in THF (20 mL) afforded 21 (122 mg,
40%).
Liquid.
280.1461.
IR (neat): 2961, 1699, 1649, 1476, 1441, 1379, 1277, 1246, 1208,
1130, 1071, 1022, 972, 912, 846, 802 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.57–7.54 (2 H, m), 7.31–7.24 (3
H, m), 4.16–4.04 (2 H, m), 3.47 (1 H, d, J = 8.0 Hz), 2.09 (s, 3 H),
2.00–1.90 (2 H, m), 1.76–1.65 (2 H, m), 1.61–1.47 (2 H, m), 1.20 (3
H, t, J = 7.1 Hz).
2,2-Dimethyl-9a-phenylsulfanyl-1,2,3,4b,5,6,7,8,9a-decahydro-
10-oxabenzo[a]azulen-4-one (25)
Reaction of 5,5-dimethyl-1,3-cyclohexanedione (4) (140 mg, 1
mmol) with vinyl sulfide 15 (409 mg, 2 mmol) in MeCN (20 mL)
afforded 25.
Yield: 291 mg (85%); solid; mp 102–103 °C.
HRMS: m/z calcd for C17H20O3S (M+): 304.1134; found: 314.1136.
IR (KBr): 2943, 1640, 1481, 1440, 1394, 1222, 1178, 1058, 1021,
900, 870, 839 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.55–7.50 (2 H, m), 7.37–7.21 (3
H, m), 3.21 (1 H, d, J = 9.2 Hz), 2.29 (2 H, m), 2.16 (2 H, m), 1.98–
1.90 (4 H, m), 1.66–1.38 (6 H, m), 1.10 (3 H, s), 1.08 (3 H, s).
MS: m/z = 232 (M+ – PhSH) (81), 204 (10), 176 (33), 167 (5), 153
(24), 148 (15), 110 (27), 97 (23), 81 (20), 58 (33).
3,3,8-Trimethyl-5a-phenylsulfanyl-3,4,5a,6,7,8,9,9a-octahydro-
2H-dibenzofuran-1-one (22)
Reaction of 5,5-dimethyl-1,3-cyclohexanedione (4) (140 mg, 1
mmol) with vinyl sulfide 14 (409 mg, 2 mmol) in THF (20 mL) af-
forded 22 as an inseparable diastereommer.
Yield: 243mg (71%).
IR (KBr): 3050, 2957, 1634, 1456, 1437, 1399, 1343, 1263, 1233,
1198, 1167, 1134, 1042, 984, 957, 870, 843 cm–1.
HRMS: m/z calcd for C15H20O2 (M+ – PhSH): 232.1463; found:
232.1466.
1H NMR (300 MHz, CDCl3): d = 7.53–7.50 (2 H, m), 7.37–7.27 (3
H, m), 3.24 (0.6 H, br d, J = 3.0 Hz) and 3.06 (0.4 H, dd, J = 5.9, 5.8
Hz), 2.31–2.23 (2 H, m), 2.18–2.15 (2 H, m), 2.10–2.01 (2 H, m),
1.00–1.91 (1 H, m), 1.86–1.82 (1 H, m), 1.69–1.46 (1 H, m), 1.41–
1.34 (1 H, m), 1.15–1.10 (1 H, m), 1.07 and 1.05 (3 H, s), 1.04 and
1.01 (3 H, s), 0.89 (1.8 H, d, J = 6.6 Hz) and 0.87 (1.2 H, d, J = 7.1
Hz).
1-(2-Methyl-8a-phenylsulfanyl-4,5,6,7,8,8a-hexahydro-3aH-cy-
clohepta[b]furan-3-yl)ethanone (26)
Reaction of 2,4-pentanedione (6) (100 mg, 1 mmol) with vinyl sul-
fide 15 (409 mg, 2 mmol) in THF (20 mL) afforded 26.
Yield: 148 mg (49%); liquid.
IR (neat): 3059, 2928, 2855, 1672, 1628, 1439, 1385, 1281, 1260,
1215, 1067, 1024, 983, 947, 924 cm–1.
HRMS: m/z calcd for C21H26O2S (M+): 342.1655; found: 342.1652.
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

1984
Y. R. Lee et al.
PAPER
10a-Phenylsulfanyl-6b,7,8,9,10,10a-hexahydrobenzo[4,5]fu-
ro[3,2-c]chromen-6-one (30)
Reaction of 4-hydroxycoumarin (7) (162mg, 1 mmol) with vinyl
sulfide 13 (381 mg, 2 mmol) in THF (20 mL) afforded 30.
1H NMR (300 MHz, CDCl3): d = 7.51–7.48 (2 H, m), 7.35–7.27 (3
H, m), 3.13 (1 H, d, J = 9.5 Hz), 2.21 (3 H, s), 2.18 (3 H, s), 1.96–
1.20 (10 H, m).
HRMS: m/z calcd for C12H16O2 (M+ – PhSH): 192.1150; found:
192.1150.
Yield: 140 mg (40%); solid; mp 125–126 °C.
IR (KBr) 3061, 2942, 2865, 1725, 1647, 1609, 1566, 1499, 1456,
1406, 1306, 1161, 1028, 943, 883, 845 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.70–7.67 (1 H, m), 7.58–7.53 (3
H, m), 7.36–7.26 (5 H, m), 3.40 (1 H, t, J = 6.1 Hz), 2.07–1.96 (3 H,
m), 1.90–1.82 (1 H, m), 1.65–1.46 (4 H, m).
2-Phenylsulfanyl-3,5,6,7-tetrahydro-2H-benzofuran-4-one (27)
Reaction of 1,3-cyclohexanedione (1) (112 mg, 1 mmol) with phe-
nyl vinyl sulfide (16) (272 mg, 2 mmol) in THF (20 mL) afforded
27.
Yield: 182 mg (74%); liquid.
HRMS: m/z calcd for C21H18O3S (M+): 350.0977; found: 350.0975.
IR (neat): 2943, 1640, 1481, 1440, 1394, 1222, 1178, 1058, 1021,
900, 870, 839 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.54–7.33 (5 H, m), 6.09 (1 H, dd,
J = 9.9, 5.9 Hz), 3.25 (1 H, dd, J = 15.5, 9.9 Hz), 2.83 (1 H, dd,
J = 15.5, 5.9 Hz), 2.45 (2 H, m), 2.32 (2 H, m), 2.02 (2 H, m).
2-Chloro-10a-phenylsulfanyl-6b,7,8,9,10,10a-hexahydroben-
zo[4,5]furo[3,2-c]chromen-6-one (31)
Reaction of 6-chloro-4-hydroxycoumarin (8) (197mg, 1 mmol)
with vinyl sulfide 13 (381 mg, 2 mmol) in THF (20 mL) afforded
31.
HRMS: m/z calcd for C14H14O2S (M+): 246.0715; found: 246.0716.
Yield: 158 mg (41%); solid; mp 126–128 °C.
3,6,6-Trimethyl-2-phenylsulfanyl-3,5,6,7-tetrahydro-2H-ben-
zofuran-4-one (28)23
Method A
Reaction of 5-methyl-1,3-cyclohexanedione (2) (126 mg, 1 mmol)
with phenyl 1-propenyl sulfide (17) (308 mg, 2 mmol) in MeCN (20
mL) afforded 28 as a 32:68 mixture of cis- and trans-isomers.
IR (KBr) 3069, 2961, 2940, 2870. 1726, 1651, 1564, 1493, 1431,
1391, 1265, 1123, 1065, 1011, 966, 939, 827 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.65 (1 H, d, J = 2.5 Hz), 7.59–
7.53 (2 H, m), 7.49 (1 H, dd, J = 8.9, 2,5 Hz), 7.37–7.26 (4 H, m),
3.41 (1 H, t, J = 6.1 Hz), 2.10–1.95 (3 H, m), 1.91–1.802 (1 H, m),
1.66–1.46 (4 H, m).
Yield: 185 mg (64%).
HRMS: m/z calcd for C21H17ClO3S (M+): 384.0588; found:
384.0589.
cis-Isomer
IR (neat): 3059, 2962, 2872, 1642, 1583, 1470, 1440, 1397, 1213,
1168, 1126, 1030, 914, 864 cm–1.
11a-Phenylsulfanyl-7,8,9,10,11,11a-hexahydro-6bH-5,12-di-
oxanaphtho[2,1-a]azulen-6-one (32)
Reaction of 4-hydroxycoumarin (7) (162mg, 1 mmol) with vinyl
sulfide 15 (409 mg, 2 mmol) in THF (20 mL) afforded 32.
1H NMR (300 MHz, CDCl3): d = 7.54–7.53 (2 H, m), 7.34–7.28 (3
H, m), 6.07 (1 H, d, J = 8.8 Hz), 3.61–3.51 (1 H, m), 2.31 (2 H, q),
2.21 (2 H, s), 1.34 (3 H, d, J = 7.0 Hz), 1.09 (3 H, s), 1.07 (3 H, s).
Yield: 262 mg (72%); solid; mp 116–118 °C.
trans-Isomer
IR (KBr): 3057, 2932, 2855, 1707, 1645, 1607, 1570, 1499, 1474,
1439, 1404, 1327, 1275, 1235, 1196, 1165, 1094, 1028, 963, 895
cm–1.
IR (neat): 3059, 2959, 2872, 1644, 1584, 1470, 1441, 1399, 1277,
1215, 1167, 1109, 1030, 914, 880 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.50–7.47 (2 H, m), 7.33–7.28 (3
H, m), 5.53 (1 H, d, J = 5.3 Hz), 3.21–3.17 (1 H, m), 2.28 (2 H, s),
2.17 (2 H,s), 1.29 (3 H, d, J = 6.8 Hz), 1.06 (3 H, s), 1.05 (3 H, s).
1H NMR (300 MHz, CDCl3): d = 7.67–7.62 (1 H, m), 7.59–7.51 (3
H, m), 7.39–7.27 (5 H, m), 3.40 (1 H, dd, J = 9.6, 2.8 Hz), 2.19–2.06
(3 H, m), 2.03–1.60 (6 H, m), 1.48–1.38 (1 H, m).
HRMS: m/z calcd for C16H14O3 (M+ – PhSH): 254.0943; found:
254.0948.
Method B
Reaction of 5-methyl-1,3-cyclohexanedione (2) (126 mg, 1 mmol)
with vinyl sulfide 17 (308 mg, 2 mmol) in THF (20 mL) afforded
28 as a 46:54 mixture of cis- and trans-isomers.
Anal. Calcd for C22H20O3S: C, 72.50; H, 5.53; S, 8.80. Found: C,
72.21; H, 5.42; S, 8.75.
Yield: 205 mg (71%).
2-Phenylsulfanyl-2,3-dihydrofuro[3,2-c]chromen-4-one (33)
Reaction of 4-hydroxycoumarin (7) (162mg, 1 mmol) with phenyl
vinyl sulfide (16) (272 mg, 2 mmol) in THF (20 mL) afforded 33.
9a-Phenylsulfanyl-7,8,9,9a-tetrahydro-6bH-5,10-dioxapentale-
no[2,1-a]naphthalen-6-one (29)
Yield: 136 mg (46%); solid; mp 125–126 °C.
Reaction of 4-hydroxycoumarin (7) (162mg, 1 mmol) with vinyl
sulfide 12 (353 mg, 2 mmol) in THF (20 mL) afforded 29.
IR (KBr): 3061, 2926, 1724, 1649, 1608, 1570, 1498, 1440, 1410,
1344, 1325, 1269, 1207, 1157, 1091, 1028, 941, 895, 860 cm–1.
Yield: 141 mg (42%); solid; mp 64–66 °C.
1H NMR (300 MHz, CDCl3): d = 7.68 (1 H, d, J = 7.8 Hz), 7.60–
7.52 (3 H, m), 7.39–7.28 (5 H, m), 6.39 (1 H, dd, J = 9.8, 6.1 Hz),
3.64 (1 H, dd, J = 16.4, 9.8 Hz), 3.16 (1 H, dd, J = 16.4, 6.1 Hz).
IR (KBr): 3075, 2957, 2934, 2868, 1726, 1649, 1607, 1570, 1499,
1406, 1348, 1323, 1227, 1202, 1182, 1091, 1051, 1030, 1001, 945,
906 cm–1.
HRMS: m/z calcd for C17H12O3S (M+): 296.0508; found: 296.0505.
1H NMR (300 MHz, CDCl3): d = 7.69–7.67 (1 H, m), 7.59–7.53 (3
H, m), 7.31–7.20 (5 H, m), 3.79 (1 H, dd, J = 8.2, 2.6 Hz), 2.43–2.40
(1 H, m), 2.17–2.02 (3 H, m), 1.85–1.80 (1 H, m), 1.70–1.58 (1 H,
m).
8-Methyl-2-phenylsulfanyl-2,3-dihydrofuro[3,2-c]chromen-4-
one (34)
Reaction of 4-hydroxyl-6-methylcoumarin (7) (176mg, 1 mmol)
with phenyl vinyl sulfide (16) (272 mg, 2 mmol) in THF (20 mL)
afforded 34.
HRMS: m/z calcd for C20H16O3S (M+): 336.0821; found: 336.0824.
Yield: 186 mg (60%); solid; mp 109–110 °C.
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

PAPER
Dihydrofurans by Oxidative Cycloaddition of 1,3-Dicarbonyl Compounds to Vinyl Sulfides
1985
IR (KBr): 3076, 2982, 1714, 1649, 1610, 1577, 1494, 1439, 1394,
1271, 1203, 1095, 1035, 1006, 914, 858, 829. 798 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.58–7.54 (2 H, m), 7.44 (1 H, s),
7.37–7.26 (5 H, m), 6.37 (1 H, dd, J = 9.8, 6.3 Hz), 3.61 (1 H, d,
J = 16.4, 9.8 Hz), 3.13 (1 H, dd, J = 16.4, 6.3 Hz), 2.41 (3 H, s).
1H NMR (300 MHz, CDCl3): d = 8.59 (1 H, dd, J = 7.3, 1.2 Hz),
8.13–8.04 (3 H, m), 7.72 (1 H, dd, J = 7.5, 7.4 Hz), 7.63–7.58 (3 H,
m), 7.37–7.30 (3 H, m), 6.38 (1 H, dd, J = 9.7, 6.0 Hz), 3.67 (1 H,
dd, J = 16.6, 9.7 Hz), 3.23 (1 H, dd, J = 16.6, 6.0 Hz).
HRMS: m/z calcd for C21H14O2S (M+): 330.0715; found: 330.0714.
HRMS: m/z calcd for C18H14O3S (M+): 310.0663; found: 310.0661.
8-Methyl-9-phenylsulfanyl-8,9-dihydrophenaleno[1,2-b]furan-
7-one (39)
Reaction of 3-hydroxy-1H-phenalen-1-one (10) (196 mg, 1 mmol)
with vinyl sulfide 17 (308 mg, 2 mmol) in THF (20 mL) afforded
39 as a 34:66 mixture of cis- and trans-isomers.
Dihydrofurophenalenone 35
Reaction of 3-hydroxy-1H-phenalen-1-one (10) (196 mg, 1 mmol)
with vinyl sulfide 12 (353 mg, 2 mmol) in THF (20 mL) afforded
35.
Yield: 317 mg (92%).
Yield: 322 mg (87%); solid; mp 157–159 °C.
1H NMR (300 MHz, CDCl3): d = 8.63–8.58 (1 H, m), 8.13–8.05 (3
H, m), 7.75–7.67 (1 H, m), 7.64–7.59 (3 H, m), 7.42–7.28 (3 H, m),
6.37 (0.34 H, d, J = 8.7 Hz, cis) and 5.85 (0.66 H, d, J = 5.2 Hz,
trans), 4.06–3.96 (0.34 H, cis) and 3.66–3.58 (0.66 H, trans), 1.58
(0.34 H, d, J = 7.0 Hz, cis) and 1.52 (0.66 H, d, J = 6.9 Hz).
IR (KBr): 3063, 2957, 2936, 1630, 1591, 1508, 1472, 1431, 1418,
1381, 1327, 1308, 1206, 1069, 1020, 926, 882, 833 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.52 (1 H, d, J = 7.3 Hz), 8.10–
8.03 (3 H, m), 7.71–7.59 (4 H, m), 7.21–7.14 (3 H, m), 3.90 (1 H,
dd, J = 8.5, 2.5 Hz), 2.41–2,36 (1 H, m), 2.22–2.02 (3 H, m), 1.81–
1.79 (1 H, m), 1.67–1.56 (1 H, m).
IR (KBr): 3059, 2968, 2930, 2870, 1630, 1588, 1435, 1418, 1379,
1281, 1211, 1192, 1150, 1090, 1022, 966, 910, 870, 845 cm–1.
HRMS: m/z calcd for C22H16O2S (M+): 344.0871; found: 344.0870.
HRMS: m/z (M+) calcd for C24H18O2S: 370.1028; found: 370.1027.
11a-Phenylsulfanyl-7b,8,9,10,11,11a-hexahydro-12-oxa-inde-
no[2,1-a]phenalen-7-one (36)
Reaction of 3-hydroxy-1H-phenalen-1-one (10) (196 mg, 1 mmol)
with vinyl sulfide 13 (381 mg, 2 mmol) in THF (20 mL) afforded
36.
10a-Phenylsulfanyl-2,3,3a,10a-tetrahydro-1H-10-oxapentale-
no[1,2-b]naphthalene-4,9-dione (40) and 9a-Phenylsulfanyl-
7,8,9,9a-tetrahydro-6bH-10-oxapentaleno[2,1-a]naphthalene-
5,6-dione (41)
Reaction of 2-hydroxy-1,4-naphthoquinone (11) (174 mg, 1 mmol)
with vinyl sulfide 12 (353 mg, 2 mmol) in THF (20 mL) afforded
40 (139 mg, 40%) and 41 (66 mg, 19%) as a mixture.
Yield: 296 mg (77%); solid; mp 154–156 °C.
IR (KBr): 3063, 2946, 2864, 1628, 1589, 1508, 1468, 1433, 1418,
1383, 1318, 1292, 1225, 1194, 1150, 1101, 1020, 937, 887, 860,
839 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.57 (1 H, dd, J = 7.4, 1.1 Hz),
8.11 (1 H, dd, J = 7.8, 1.1 Hz), 8.06 (2 H, d, J = 7.8 Hz), 7.72 (1 H,
dd, J = 7.8, 7.4 Hz), 7.63 (1 H, dd, J = 7.8, 7.4 Hz), 7.60–7.56 (2 H,
m), 7.39–7.30 (3 H, m), 3.50 (1 H, dd, J = 6.7, 6.0 Hz), 2.18–2.08
(3 H, m), 1.91–1.79 (1 H, m), 1.72–1.60 (1 H, m), 1.53–1.47 (3 H,
m).
Compound 40
Mp 93–94 °C.
IR (KBr): 3054, 2957, 2866, 1690, 1647, 1628, 1595, 1572, 1391,
1364, 1252, 1204, 1071, 966, 936 880 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.03–8.01 (1 H, m), 7.99–7.94 (1
H, m), 7.69–7.59 (4 H, m), 7.26–7.22 (3 H, m), 3.82 (1 H, d, J = 9.0,
2.6 Hz), 2.44–2.35 (1 H, m), 2.21–2.02 (2 H, m), 2.01–1.80 (2 H,
m), 1.74–1.59 (1 H, m).
HRMS: m/z calcd for C25H20O2S (M+): 384.1184. found: 384.1187.
HRMS: m/z calcd for C21H16O3S (M+): 348.0820; found: 348.0818.
Dihydrofurophenalenone 37
Reaction of 3-hydroxy-1H-phenalen-1-one (10) (196 mg, 1 mmol)
with vinyl sulfide 15 (409 mg, 2 mmol) in THF (20 mL) afforded
37.
Compound 41
Mp 108–110 °C.
IR (KBr): 3057, 2963, 1701, 1653, 1620, 1574, 1439, 1402, 1346,
1221, 1082, 912, 885 cm–1.
Yield: 295 mg (74%); solid; mp 150–151 °C.
1H NMR (300 MHz, CDCl3): d = 8.00 (1 H, d, J = 7.9 Hz), 7.68–
7.65 (2 H, m), 7.59–7.54 (3 H, m), 7.28–7.17 (3 H, m), 3.77 (1 H,
dd, J = 8.4, 1.8 Hz), 2.15–2.05 (2 H, m), 1.94–1.80 (2 H, m), 1.70–
1.55 (2 H, m).
IR (KBr): 3059, 2928, 2853, 1628, 1589, 1508, 1464, 1418m 1379,
1314, 1213, 1165, 1019, 960, 931, 895, 864, 845 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.59 (1 H, d, J = 7.6 Hz), 8.11 (1
H, d, J = 7.8 Hz), 8.07 (1 H, d, J = 7.8 Hz), 8.02 (1 H, d, J = 7.4 Hz),
7.72 (1 H, dd, J = 7.8, 7.4 Hz), 7.63 (1 H, dd, J = 7.8, 7.6 Hz), 7,58–
7.53 (2 H, m), 7.39–7.26 (3 H, m), 3.57 (1 H, dd, J = 9.4, 2.9 Hz),
2.67–2.19 (1 H, m), 2.14–2.11 (2 H, m), 1.86–1.69 (5 H, m), 1.56–
1.41 (2 H, m).
HRMS: m/z calcd for C21H16O3S (M+): 348.0820; found: 348.0821.
4a-Phenylsulfanyl-1,2,3,4,4a,11b-hexahydrobenzo[b]naph-
tho[2,3-d]furan-6,11-dione (42) and 10a-Phenylsulfanyl-
6b,7,8,9,10,10a-hexahydrobenzo[b]naphtho[2,1-d]furan-5,6-di-
one (43)
Reaction of 2-hydroxy-1,4-naphthoquinone (11) (174 mg, 1 mmol)
with vinyl sulfide 13 (381 mg, 2 mmol) in THF (20 mL) afforded
42 (163 mg, 45%) and 43 (83 mg, 23%) as a mixture.
HRMS: m/z calcd for C20H16O2 (M+ – PhSH): 288.1150; found:
288.1147.
9-Phenylsulfanyl-8,9-dihydrophenaleno[1,2-b]furan-7-one (38)
Reaction of 3-hydroxy-1H-phenalen-1-one (10) (196 mg, 1 mmol)
with vinyl sulfide 16 (272 mg, 2 mmol) in THF (20 mL) afforded
38.
Compound 42
Mp 94–95 °C.
Yield: 205 mg (62%); solid; mp 113–115 °C.
IR (KBr): 3063, 2944, 2865, 1680, 1651, 1624, 1595, 1476, 1439,
1387, 1360, 1248, 1202, 1161, 951, 901, 849 cm–1.
IR (KBr): 3057, 2928, 1628, 1585, 1568, 1433, 1420, 1379, 1217,
1144, 1098, 1017, 926, 876, 851 cm–1.
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

1986
Y. R. Lee et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 8.07–7.97 (2 H, m), 7.72–7.62 (2
H, m), 7.60–7.54 (2 H, m), 7.30–7.27 (3 H, m), 3.42 (1 H, dd,
J = 6.4, 6.3 Hz), 2.18–1.97 (2 H, m), 1.69–1.47 (6 H, m).
Compound 47
Mp 143–145 °C.
IR (KBr): 3067, 2938, 2855, 1698, 1651, 1620, 1589, 1574, 1474,
1443, 1399, 1319, 1223, 1084, 960, 876 cm–1.
HRMS: m/z calcd for C22H18O3S (M+): 362.0977; found: 362.0979.
1H NMR (300 MHz, CDCl3): d = 8.06 (1 H, d, J = 7.5 Hz), 7.70–
7.50 (5 H, m), 7.39–7.26 (3 H, m), 3.48 (1 H, dd, J = 9.5, 2.9 Hz),
2.13–2.07 (3 H, m), 1.88–1.59 (7 H, m).
Compound 43
Mp 118–120 °C.
IR (KBr): 3071, 2942, 1698, 1653, 1620, 1572, 1400, 1350, 1254,
1215, 1163, 1055, 1022, 986, 862 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.05 (1 H, d, J = 8.2 Hz), 7.68–
7.66 (2 H, m), 7.57–7.52 (3 H, m), 7.35–7.15 (3 H, m), 3.41 (1 H,
dd, J = 6.1, 6.0 Hz), 2.09–1.96 (2 H, m), 1.82–1.44 (6 H, m).
HRMS: m/z calcd for C17H14O3 (M+ – PhSH): 266.0943; found:
266.0938.
Anal. Calcd for C23H20O3S: C, 73.38; H, 5.35; S, 8.52. Found: C,
73.14; H, 5.26; S, 8.56.
HRMS: m/z calcd for C22H18O3S (M+): 362.0977; found: 362.0980.
2-Phenylsulfanyl-2,3-dihydronaphtho[2,3-b]furan-4,9-dione
(48)
2-Methyl-4a-phenylsulfanyl-1,2,3,4,4a,11b-hexahydroben-
zo[b]naphtho[2,3-d]furan-6,11-dione(44) and 8-Methyl-10a-
phenylsulfanyl-6b,7,8,9,10,10a-hexahydrobenzo[b]naph-
tho[2,1-d]furan-5,6-dione (45)
Reaction of 2-hydroxy-1,4-naphthoquinone (11) (174 mg, 1 mmol)
with vinyl sulfide 14 (409 mg, 2 mmol) in THF (20 mL) afforded
44 (162mg, 43%) and 45 (72 mg, 19%) as a mixture.
Reaction of 2-hydroxy-1,4-naphthoquinone (11) (174 mg, 1 mmol)
with vinyl sulfide 16 (272 mg, 2 mmol) in THF (20 mL) afforded
48.
Yield: 163 mg (53%); mp 151–152 °C.
IR (KBr): 3059, 2955, 1678, 1645, 1593, 1485, 1391, 1289, 1173,
1092, 999, 897, 789 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.15–8.02 (2 H, m), 7.73–7.64 (2
H, m), 7.59–7.57 (2 H, m), 7.34–7.31 (3 H, m), 6.26 (1 H, dd,
J = 10.0, 6.1 Hz), 3.63 (1 H, dd, J = 18.2, 10.0 Hz), 3.18 (1 H, dd,
J = 18.2, 6.1 Hz).
Compound 44
Mp 91–93 °C.
IR (KBr): 3065, 2951, 1682, 1651, 1624, 1595, 1574, 1541, 1385,
1358, 1267, 1204, 1005, 945, 839 cm–1.
HRMS: m/z calcd for C18H12O3S (M+): 308.0508; found: 308.0508.
1H NMR (300 MHz, CDCl3): d = 8.07–7.98 (2 H, m), 7.71–7.64 (2
H, m), 7.60–7.54 (2 H, m), 7.32–7.26 (3 H, m), 3.54 (1 H, dd,
J = 6.0, 3.0 Hz), 2.21–2.02 (2 H, m), 1.68–1.53 (3 H, m), 1.26–1.16
(2 H, m), 0.94 (3 H, d, J = 6.0 Hz).
1,2,3,4-Tetrahydrobenzo[b]naphtho[2,3-d]furan-6,11-dione
(49)
To a solution of 42 (181 mg, 0.5 mmol) in CH2Cl2 (10 mL) was add-
ed MCPBA (247 mg, 70%, 1.0 mmol) at r.t. and the reaction mix-
ture was stirred under nitrogen for 24 h. Sat. aq NaHCO3 was added,
and the aq layer was extracted with CH2Cl2 (3 × 30 mL). The com-
bined organic extracts were washed with brine, dried (MgSO4), and
evaporated under reduced pressure to give the residue. The residue
was refluxed for 5 h in xylene (10 mL) and then cooled to r.t. Evap-
oration of solvent and purification by flash column chromatography
(sillica gel) gave 49.
HRMS: m/z calcd for C23H20O3S (M+): 376.1133; found: 376.1132.
Compound 45
Mp 151–153 °C.
IR (KBr): 2926, 1701, 1651, 1620, 1589, 1572, 1454, 1399, 1221,
1163, 1067, 841 cm–1.
1H NMR (300 MHz, CDCl3): d = 8. 04 (1 H, d, J = 7.6 Hz), 7.67–
7.64 (2 H, m), 7.59–7.50 (3 H, m), 7.35–7.26 (3 H, m), 3.49 (1 H,
dd, J = 6.0, 3.0 Hz), 2.30–2.21 (1 H, m), 2.15–2.07 (1 H, m), 2.03–
1.90 (1 H, m), 1.74–1.60 (2 H, m), 1.27–1.86 (2 H, m), 0.93 (3 H, d,
J = 6.0 Hz).
Yield: 88 mg (70%); solid; mp 162–164 °C.
IR (KBr): 3067, 2940, 2865, 1667, 1593, 1537, 1468, 1429, 1379,
1329, 1279, 1236, 1208, 1148, 990, 953, 930. 823 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.19–8.10 (2 H, m), 7.73–7.67 (2
H, m), 2.82–2.73 (4 H, m), 1.95–1.55 (4 H, m).
HRMS: m/z calcd for C23H20O3S (M+): 376.1133; found: 376.1135.
HRMS: m/z calcd for C16H12O3 (M+): 252.0787; found: 252.0785.
10a-Phenylsulfanyl-6,7,8,9,10,10a-hexahydro-5bH-11-oxa-
naphtho[2,3-a]azulene-5,12-dione (46) and 11a-Phenylsulfanyl-
7,8,9,10,11,11a-hexahydro-6bH-12-oxanaphtho[2,1-a]azulene-
5,6-dione (47)
Reaction of 2-hydroxy-1,4-naphthoquinone (11) (174 mg, 1 mmol)
with vinyl sulfide 15 (409 mg, 2 mmol) in THF (20 mL) afforded
46 (166 mg, 44%) and 47 (87 mg, 23%) as a mixture.
Benzo[b]naphtho[2,3-d]furan-6,11-dione (50)
To a stirred solution of 49 (100 mg, 0.4 mmol) in diphenyl ether (5
mL) was added Pd/C (100 mg, 10 wt.%). The mixture was refluxed
for 5 h and cooled to r.t. The suspension was filtered off and the in-
organic material was washed with EtOAc (3 × 25 mL). The solvent
was evaporated under reduced pressure to give the residue. The res-
idue was purified by flash column chromatography (silica gel) to
give 50.
Compound 46
Mp 135–137 °C.
Yield: 41 mg (42%); mp 247 °C.
IR (KBr): 2932, 1682, 1647, 1624, 1593, 1389, 1366, 1273, 1221,
1206, 1169, 970, 951, 804 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.09–8.02 (2 H, m), 7.73–7.63 (2
H, m), 7.58–7.54 (2 H, m), 7.32–7.28 (3 H, m), 3.50 (1 H, dd,
J = 9.5, 2.9 Hz), 2.15–2.03 (3 H, m), 1.79–1.40 (7 H, m).
HRMS: m/z calcd for C17H14O3 (M+ – PhSH): 266.0943; found:
266.0945.
IR (KBr): 3079, 2963, 1667, 1593, 1578, 1566, 1487, 1445, 1372,
1325, 1182, 1040, 1011, 990, 914, 874, 802 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.31 (1 H, d, J = 7.2 Hz), 8.27–
8.20 (2 H, m), 7.82–7.76 (2 H, m), 7.70 (1 H, d, J = 8.3 Hz), 7.58 (1
H, dd, J = 8.3, 7.2 Hz), 7.49 (1 H, dd, J = 8.2, 7.9 Hz).
HRMS: m/z calcd for C16H8O3 (M+): 248.0474; found: 248.0476.
Anal. Calcd for C23H20O3S: C, 73.38; H, 5.35; S, 8.52. Found: C,
73.11; H, 5.30; S, 8.48.
Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

PAPER
Dihydrofurans by Oxidative Cycloaddition of 1,3-Dicarbonyl Compounds to Vinyl Sulfides
1987
6,7-Dihydro-5H-benzofuran-4-one (51)24
was then stirred for 1 h and then quenched with a sat. aq NH4Cl so-
To a solution of 27 (2.10 g, 8.52 mmol) in CH2Cl2 (50 mL) was add-
ed MCPBA (1.54 g, 70%, 10.4 mmol) at 0 °C. The reaction mixture
was stirred for 24 h at r.t., and then poured into sat. aq Na2CO3. The
mixture was extracted with CH2Cl2 (3 × 50 mL), washed with brine,
and dried (MgSO4). Evapotation of solvent gave an oil which was
purified by chromatography (silica gel) to give the 51.
lution (30 mL). The combined organic layers were washed with
brine, dried (MgSO4), filtered, and evaporated under reduced pres-
sure. The resulting residue was purified by flash column chroma-
tography (silica gel; EtOAc) to give 54.
Yield: 0.751 g (83%); solid; mp 113 °C.
IR (KBr): 3435, 3115, 2993, 2905, 1632, 1614, 1474, 1435, 1335,
1298, 1214, 1135, 1092, 1045, 1027 cm–1.
Yield: 812 mg (70%); liquid.
IR (neat): 3131, 2948, 1677, 1595, 1516, 1447, 1414, 1294, 1242,
1184, 1119, 1026 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32 (1 H, d, J = 2.0 Hz), 6.67 (1
H, d, J = 2.0 Hz), 2.89 (2 H, m), 2.50 (2 H, m), 2.18 (2 H, m).
13C NMR (75 MHz, CDCl3): d = 193.9, 166.7, 142.2, 120.6, 105.9,
37.2, 22.8, 22.2.
1H NMR (300 MHz, CDCl3): d = 7.65 (1 H, d, J = 9.0 Hz), 7.60 (1
H, d, J = 2.2 Hz), 7.12 (1 H, d, J = 9.0 Hz), 7.00 (1 H, d, J = 2.2 Hz),
4.40 (2 H, q), 2.79 (3 H, s).
13C NMR (75 MHz, CDCl3): d = 196.2, 160.5, 159.7, 145.0, 127.3,
117.7, 114.2, 105.1, 104.9, 62.0, 39.5.
HRMS: m/z calcd for C11H10O4S (M+): 238.0301; found: 238.0305.
MS (EI) 136 (M+), 121, 108, 94, 80, 77, 63, 55, 52.
Millettocalyxins C (55)21
4-Oxo-4,5,6,7-tetrahydrobenzofuran-5-carboxylic Acid Methyl
Ester (52)
2,5-Dimethoxybenzaldehyde (0.157 g, 0.94 mmol) in anhyd tolu-
ene (3 mL) was slowly added to a warm solution (40 °C) of 54
(0.150 g, 0.63 mmol) in anhyd toluene (20 mL) containing a cata-
lytic amount of piperidine (4 drops) and the resulting mixture was
allowed to reflux for 3 h. After distillation of the solvent, the residue
was purified by flash column chromatogaraphy (silica gel; hexane–
EtOAc, 6:1) to give 55.
To a stirred suspension of NaH (1.175 g, 29.4 mmol, 60%) and KH
(50 mg, 35 wt% dispersion in oil) in anhyd THF (50 mL) under N2
was added 52 (800 mg, 5.9 mmol) in anhyd THF (3 mL) at 0 °C.
The mixture was stirred for 30 min and dimethyl carbonate (1.593
g, 17.7 mmol) in THF (2 mL) was added slowly over 10 min. The
ice bath was removed and the reaction mixture was heated at reflux
for 2 h. After cooling to r.t., H2O (10 mL) and sat. aq NH4Cl solution
(40 mL) were added carefully dropwise and the mixture was ex-
tracted with EtOAc (3 × 50 mL). The combined organic layers were
washed with brine, dried (MgSO4), and evaporated under reduced
pressure. The residue was purified by flash column chromatography
(silica gel; hexane–EtOAc, 3:1) to give 52.
Yield: 0.158 g (78%); solid; mp 167–168 °C.
IR (KBr): 3102, 2998, 2938, 2836, 1628, 1589, 1574, 1505, 1466,
1410, 1362, 1263, 1238, 1186, 1146, 1074, 1053, 852, 839, 814
cm–1.
1H NMR (300 MHz, CDCl3): d = 8.15 (1 H, d, J = 8.8 Hz), 7.73 (1
H, d, J = 2.1 Hz), 7.54 (1 H, d, J = 8.8 Hz), 7.50 (1 H, d, J = 2.9 Hz),
7.21 (1 H, s), 7.15 (1 H, d, J = 2.1 Hz), 7.02 (1 H, dd, J = 8.8, 2.9
Hz), 6.99 (1 H, d, J = 8.8 Hz), 3.90 (3 H, s), 3.84 (3 H, s).
Yield: 1.027 g (90%).
IR (neat): 3144, 3113, 2955, 1733, 1675, 1582, 1454, 1433, 1276,
1208, 1164, 1122, 1025, 983, 903, 861 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34 (1 H, d, J = 2.0 Hz), 6.69 (1
H, d, J = 2.0 Hz), 3.76 (3 H, s), 3.52 (1 H, t, J = 4.8 Hz), 3.05–2.91
(2 H, m), 2.56–2.38 (2 H, m).
13C NMR (75 MHz, CDCl3): d = 188.5, 170.1, 166.5, 140.0, 120.2,
106.6, 53.0, 52.3, 25.6, 21.7.
Pongol Methyl Ether (56)21
3-Methoxybenzaldehyde (0.129 g, 0.94 mmol) in anhyd toluene (3
mL) was slowly added to a warm solution (40 °C) of 54 (0.150 g,
0.63 mmol) in anhyd toluene (20 mL) containing a catalytic amount
of piperidine (4 drops) and the resulting mixture was allowed to re-
flux for 3 h. After distillation of the solvent, the residue was purified
by flash column chromatogaraphy (silica gel; hexane–EtOAc, 6:1)
to give 56.
HRMS: m/z calcd for C10H10O4 (M+): 194.0579. Found: 194.0575.
Yield: 0.162 g (88%); solid; mp 156–157 °C.
4-Hydroxybenzofuran-5-carboxylic Acid Methyl Ester (53)
A mixture of 52 (0.90 g, 4.63 mmol) and DDQ (1.261 g, 5.56 mmol)
in dioxane (30 mL) was heated under reflux for 3 h. The resulting
mixture was cooled in an ice bath and solids were removed by fil-
tration through Celite. The filtrate was evaporated under reduced
pressure and purified by flash column chromatography (silica gel;
hexane–EtOAc, 5:1) to give 53.
IR (KBr): 3055, 2988, 2949, 2843, 1651, 1607, 1491, 1451, 1433,
1402, 1358, 1296, 1273, 1254, 1215, 1165, 1140, 1067, 1043, 1030
cm–1.
1H NMR (300 MHz, CDCl3): d = 8.16 (1 H, d, J = 8.8 Hz), 7.76 (1
H, d, J = 2.2 Hz), 7.57 (1 H, d, J = 8.8 Hz), 7.54 (1 H, d, J = 7.8 Hz),
7.48 (1 H, d, J = 3.0 Hz), 7.46 (1 H, dd, J = 7.8, 7.8 Hz), 7.20 (1 H,
d, J = 2.2 Hz), 7.11 (1 H, dd, J = 7.8, 3.0 Hz), 6.86 (1 H, s), 3.90 (3
H, s).
Yield: 0.756 g (85%); solid; mp 105 °C.
IR (KBr): 3500, 3071, 2950, 1677, 1629, 1471, 1446, 1358, 1288,
1234, 1195, 1169, 1134, 1052 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.78 (1 H, d, J = 8.9 Hz), 7.57 (1
H, d, J = 2.1 Hz), 7.03 (1 H, d, J = 8.9 Hz), 6.98 (1 H, d, J = 2.1 Hz),
3.97 (3 H, s).
13C NMR (75 MHz, CDCl3): d = 171.2, 159.5, 157.4, 144.3, 125.9,
117.1, 104.9, 104.7, 103.8, 52.2.
Acknowledgment
This work was supported by the Korea Research Foundation Grant
(KRF-99-042-F00167). Dr. Ronald Tepper’s help with this work is
greatly appreciated.
HRMS: m/z calcd for C10H8O4 (M+): 192.0422; found: 192.0426.
References
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Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York

1988
Y. R. Lee et al.
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Synthesis 2003, No. 13, 1977–1988 © Thieme Stuttgart · New York