Synthesis of 3-methyl- and 3,4-dimethylfurans using alkoxide, thiolate, and phenoxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing sulfur and selenium functional groups

Article abstract of DOI:10.1016/j.tet.2011.11.096

We have reported sodium alkoxide- or aryloxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing the phenylsulfanyl group 1a-d. The reactions with diverse sodium alkoxides and aryloxide produced 4-alkoxymethyl- and 4-aryloxymethylfurans 2aa-2db in goo

Full text of DOI:10.1016/j.tet.2011.11.096

Tetrahedron 68 (2012) 1566e1580
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Synthesis of 3-methyl- and 3,4-dimethylfurans using alkoxide, thiolate, and
phenoxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing sulfur and
selenium functional groups
,
Nami Takahashi a, Yuya Nagase a, Genzoh Tanabe b, Osamu Muraoka b, Mitsuhiro Yoshimatsu a
*
a Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan
b School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 October 2011
Received in revised form 28 November 2011
Accepted 30 November 2011
Available online 8 December 2011
We have reported sodium alkoxide- or aryloxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing
the phenylsulfanyl group 1aed. The reactions with diverse sodium alkoxides and aryloxide produced
4-alkoxymethyl- and 4-aryloxymethylfurans 2aae2db in good to high yields. Although reactions with
sodium benzenethiolate yielded 3,4-bis(phenylsulfanylmethyl)furans 5aeg, they readily desulfanylated
in the presence of tributyltin hydride/AIBN to give the 3-methyl- and 3,4-dimethylfuran derivatives
6aeg. This method’s utility was demonstrated by the synthesis of tetrahydronaphthalenyl furan de-
rivatives bearing alkoxy- and aryloxymethyl substituents.
Keywords:
3-Methylfuran
3,4-Dimethylfuran
Cyclization
Ó 2011 Elsevier Ltd. All rights reserved.
4-Oxahepta-1,6-diyne
Tyrosine
1. Introduction
furan-synthesis techniques. We have reported a novel method for
synthesizing 4-methoxymethyl-3-phenylsulfanylmethyl- and 3,4-
3-Methyl- and 3,4-dimethylfurans derived from the marine
sponges, and some plants are emerging as crucial pharmacophores.1
Tanshinones (isolated from the Salvia genus) and their tetrahy-
droneotanshinlactones and tetrahydronaphthalene-1-ol de-
rivatives, which contain 3-methyl- and 3,4-dimethylfuryl functional
groups, possess antitumor, and other activities in vitro.2 Although
a variety of synthetic methods for preparing highly functionalized
furans have been developed owing to the rising demands in me-
dicinal chemistry, most require many steps involving cyclizations or
cycloisomerizations of readily available starting materials, such as
1,4-diketones,3 and alkynyl and allenyl ketones.4 Similar methods
employ starting from alkynyl alcohols (3-butyn-1-ols5 and 4-
pentyn-1-ols6), epoxides,7 2-alkynyl-2-propen-1-ols,8 and 2-
penten-4-yn-1-ols.9 However, successful syntheses of substituted
furans depend on selecting easily accessible starting materials that
are, unfortunately, reluctant to cyclization or cycloisomerization.
Annulations of 1,6-heptadiynes and 4-oxo- and 4-aza-derivatives
have received considerable attention.10 Their common reactivities
based on propargyl-allenyl interconversion have been applied to
bis(phenylsulfanylmethyl)furans by nucleophile-promoted cycliza-
tion of 4-oxahepta-1,6-diynes. These reactions may involve desul-
fanylation of phenylsulfanylmethyl group leading to 4-
alkoxymethyl-3-methyl- and 3,4-dimethylfuran synthesis.11 This
unique cyclization directly yielded the furans substituted by the
nucleophile in the 4-methyl group. Therefore, cyclizations using
alkoxides can be explored for synthesizing diverse 4-
alkoxymethylfurans and aryloxymethylfurans using other alkox-
ides or aryloxides as nucleophiles. Here we report in detail a cycli-
zation of versatile 4-oxahepta-1,6-diynes using different alkoxides
and aryloxides and the successivedesulfanylations. Wealso describe
the syntheses of 5,6,7,8-tetrahydronaphthalene derivatives as
a novel utility of our synthetic approach.
2. Results and discussion
We initially examined the reactions of 4-oxahepta-1,6-diynes
with representative alkoxides according to an established method
(Scheme 1).12 Our previous study focused on the cyclization of 4-
oxahepta-1,6-diynes using sodium methoxide or ethoxide, pro-
moting us to examine cyclizations using other alkoxides. The re-
sults are shown in Table 1.
* Corresponding author. Tel.: þ81 58 293 2251; fax: þ81 58 293 2207; e-mail
address: yoshimae@gifu-u.ac.jp (M. Yoshimatsu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.096

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1567
The reaction of 3-p-methoxyphenyl-4-oxahepta-1,6-diyne with
sodium n-propoxide (5.0 M) in a 1,4-dioxaneen-propanol (1:10)
solution was examined over 10 min under reflux conditions. The
reaction yielded 3-phenylsulfanylmethyl-4-n-propoxymethylfuran
2aa, accompanied by a small amount of 3,4-bis(phenylsulfa-
nylmethyl)furan 3a. The structure of 2aa was determined on the
basis of spectral data, which revealed two types of methylene
SPh
Ar
PhS
Ar
OR
RONa
O
O
Scheme 1. Alkoxide-promoted cyclization of 4-oxahepta-1,6-diynes.
Table 1
Sodium alkoxides-promoted cyclizations of 4-oxahepta-1,6-diynes 1
Entry
1,6-Diynes
Alkoxide
% Yield of 2
% Yield of 3
Me
Me
PhS
SPh
MeO
PhS
PhS
O
SPh
1
1a
Me(CH2)2ONa
O
O
O
MeO
3a (9)
MeO
MeO
2aa (58)
2ab (59)
O
2
3
1a
1a
Me(CH2)3ONa
O
OMe
PhS
O
MeO(CH2)2ONa
O
MeO
2ac (56)
2ad (59)
PhS
O
OH
4
5
1a
1a
NaO(CH2)2ONa
CD3ONa
O
MeO
D
D
D
D
PhS
OCD3
O
MeO
2ae (59)
2af (70)
2ag (44)
PhS
O
ONa
ONa
6
7
1a
1a
O
MeO
PhS
O
O
O
MeO
PhS
O
8
9
1a
1b
ONa
MeO
2ah (52)
PhS
O
PhS
SPh
O
O
SPh
(CH2)2Me
O
O
O
O
Me(CH2)2ONa
O
O
O
3b (10)
2ba (59)
2bb (73)
2bc (73)
PhS
PhS
O
(CH2)2OMe
O
O
10
11
1b
1b
MeO(CH2)2ONa
NaO(CH2)2ONa
O
O
(CH2)2OH
O
O
O
PhS
O
ONa
O
12
13
1b
1c
O
O
2bd (57)
Me
F
PhS
O
SPh
Me(CH2)3ONa
O
(continued on next page)
O
F
2ca (42)

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N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
Table 1 (continued )
Entry
1,6-Diynes
Alkoxide
% Yield of 2
% Yield of 3
Me
PhS
O
14
15
1c
MeO(CH2)2ONa
O
F
2cb(56)
PhS
SPh
PhS
O
OH
1c
NaO(CH2)2ONa
O
O
F
F
2cc (41)
3c (22)
PhS
O(CH2)3Me
SPh
16
17
1d
Me(CH2)3ONa
S
O
O
O
S
2da (39)
OMe
PhS
SPh
PhS
O
1d
MeO(CH2)2ONa
O
S
3d (7)
S
2db (60)
protons due to the
groups. Similarly, we determined the structure of 3,4-
bis(phenylsulfanylmethyl)furan 3a, which possesses singlet meth-
a
-position of phenylsulfanyl and propoxy
the cyclized products were moderate to good, however, we ob-
served 3,4-bis(phenylsulfanylmethyl)furan formation in the re-
actions with less nucleophilic alkoxides.
ylene protons at
d
3.98 and 4.21 ppm. Linear alkoxides, such as
Next, we reacted 4-oxahepta-1,6-diynes with aryloxides,
which have higher nucleophilicities than alkoxides, and per-
formed successive desulfanylation using tributyltin hydride/AIBN,
leading to the formation of 3-methylfurans (Table 2). The opti-
mized reaction of 1a with naphtholesodium naphthoxide, pre-
pared from 2 equiv of naphthol and 1 equiv of sodium methoxide
sodium n-butoxide and methoxyethoxide also produced the 4-
alkoxymethylfuran derivatives in moderate yields (entries 2 and
3). Surprisingly, the reaction of 1a with ethyleneglycole exclusively
produced 2ad (entry 4). We attempted the reaction with CD3ONa in
CD3OD and obtained the 4-[(trideuteriummethoxy)dideuter-
iummethyl]-3-(phenylsulfanyldeuteriummethyl)furan 2ae highly
enriched in deuterium (D:H¼97:3, the ratio was determined by the
integrations of the intensities of the methylene protons in the 1H
NMR spectrum) (entry 5). This result will be discussed below when
we consider the mechanism of the nucleophile-mediated cycliza-
tions of 4-oxahepta-1,6-diynes.
The reactions with sodium allyloxide provided 4-
allyloxymethylfuran 2af in 70% yield; however, the reaction with
propargyloxide resulted in low product yields (entries 6 and 7). The
reaction also produced 1,3-benzodioxol-5-ylated furans 2baed in
moderate yields (entries 9e12). p-Fluorophenyl and 2-thienyl
propargyl ethers 1ced reacted with almost the same alkoxides to
give furans 2cae2db. Comparing these results with the reactions
using sodium methoxide and ethoxide, we found that the yields of
in
sulfanylmethyl)furan 4aa in 68% yield (Table 2, entry 1). The
structure of 4aa exhibited two types of singlets at 4.22 and
methanol,
produced
4-naphthyloxymethyl-3-(phenyl-
d
5.04 ppm due to the characteristic methylene protons in the 1H
NMR spectrum. The complete peak assignments of the products
were performed according to the spectral data of 4dc, which was
confirmed by single crystal X-ray analysis, HMBC, and NOESY
spectral analyses (Fig. 1), were performed as shown in Fig. 2. The
13C NMR spectrum of 4dc showed four sp2-carbon signals (three
singlets at dfuryl-C2 147.7, dfuryl-C3 122.9 and dfuryl-C4 115.7, and
a doublet at dfuryl-C5 140.1) in addition to those observed for the
reactants, supporting the trisubstituted furan ring formation.
The newly appeared two methylene carbon signals were
unambiguously elucidated by HMBC correlations.
Table 2
Sodium aryloxides-promoted cyclizations of 4-oxahepta-1,6-diynes 1 and following desulfanylation
YPh
Me
Ar1
OAr2
Ar2ONa/dioxane-ArOH
reflux10-30min
PhY
Ar1
Ar1
Bu3SnH/AIBN
OAr2
O
O
O
4
5
1
Entry
1,6-Diynes
Y
Ar1
Ar2
% Yield of 4
% Yield of 5
1
2
3
4
5
6
7
8
1a
1b
1b
1c
1c
1c
1d
1d
1d
1e
1g
1h
1i
S
S
S
S
S
S
S
S
S
S
Se
Se
Se
p-MeOC6H4
2-Naphthyl
p-MeOC6H4
p-t-BuC6H4
p-t-BuC6H4
p-MeOC6H4
2-Naphthyl
p-MeOC6H4
p-t-BuC6H4
2-naphthyl
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
4aa (68)
4ba (85)
4bb (63)
4ca (54)
4cb (54)
4cc (65)
4da (67)
4db (54)
4dc (75)
4ea (26)
4ga (59)
4ha (54)
4ia (77)
5aa (61)
5ba (99)
5bb (90)
5cb (quant)
5ca (d)
5cc (97)
5da (57)
5db (83)
5dc (95)
d
1,3-Benzodioxol-5-yl
1,3-Benzodioxol-5-yl
p-FC6H4
p-FC6H4
p-FC6H4
2-Thienyl
2-Thienyl
2-Thienyl
2,4,6-Me3C6H2
1-Naphthyl
1,3-Benzodioxol-5-yl
p-FC6H4
9
10
11
12
13
5ga (80)
d
5cb (90)

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1569
cyclizations of 1,3-benzodioxol-5-yl 1b and 2-thienyl 1d using so-
dium thiolate yielded 3,4-bis(phenylsulfanylmethyl)furans 3b and
3d, respectively. The desulfanylations of 2-(p-haloaryl)-3,4-
bis(phenylsulfanylmethyl)furans 3c and 3j prevented product pu-
rification because of contamination by dehalogenated derivatives.
Therefore, we examined the desulfanylation of 3c in the presence of
1 equiv of tributyltin hydride/AIBN and obtained mono-methyl
furan 7c as a sole product. The substitution pattern of 7c was de-
termined by the NOE experiments. We further investigated the
sodium-thiolate mediated cyclizations using alkane thiolate as
shown in Scheme 2. The reaction of 1a with sodium n-dec-
anethiolate provided 4-decanesulfanylmethylfuran 3I (38%) and
no-cyclized product 8I (54%). Whether the reaction would undergo
cyclization leading to furans or addition of thiolate to the 4-
oxahepta-1,6-diynes would be due to the nucleophilicity of the
thiolate. In view of the fact the alkane thiolate found to be un-
suitable for the thiolate-promoted cyclizations. We also analyzed
the reactions of 1a with sodium 1,3-benzothiazole-2-thiolate;
however, products could not be isolated.
Fig. 1. Perspective view of compound 4dc with 50% ellipsoid probability, HMBC, and
NOESY of 4dc.
Fig. 2. Peak assignments of 4dc in the 1H and 13C NMR spectrum.
We also examined the cyclization reactions of 4-oxahepta-1,6-
diynes with other phenol-phenoxide complexes. Cyclizations of the
4-oxahepta-1,6-diyne bearing 1,3-benzodioxol-5-yl group with vari-
ous phenols produced 4ba and 4bb in good yields (entries 2 and 3).
The diynes bearing other aromatic functional groups (Ar1¼2-thienyl
and p-FC6H4) underwent cyclization to provide similar 4-
aryloxymethylfuran derivatives (entries 4e9); however, the reaction
of thesterically hindered 2,4,6-trimethylphenylanalogresultedinlow
product yield (entry 10). The selenium substituted 4-oxahepta-1,6-
diynes 1gei also worked satisfactorily. Remarkably, the aryloxide-
promoted cyclizations of 4-oxahepta-1,6-diynes proceeded in high
yields compared with the alkoxide-promoted cyclizations.
The 4-phenoxymethylfurans’ phenylsulfanyl groups underwent
CeS bond fission in the presence of tributyltin hydride/AIBN.
Desulfanylation yields were moderate to quantitative as shown in
Table 2. The two-step procedures successfully led to the synthesis
of 3-methylfurans through aryloxide-mediated cyclizations-
desulfanylations of the phenylsulfanyl group at 3-position.
Scheme 2. Sodium decanethiolate-promoted cyclization of 4-oxahepta-1,6-diyne 1a.
We therefore propose the following mechanism for this cycli-
zation. In particular, this mechanism is strongly supported by the
fact that the reaction of 1a with deuterium methoxide in CD3OD
yielded the tetradeuterated furan. Furthermore, we have reported
that quenching the reaction before completion yields mono-
deuterated 4-oxahepta-1,6-diynes 11. Scheme 3 presents all the
information supporting this mechanism. The acetyleneeallene in-
terconversion proceeding via an intermediate acetylide 10 would
take place under basic conditions to form the bis(allene) 13.
Intramolecular cyclization of 13 affords the cationic intermediate
14 (path a), easily attacked by nucleophiles, such as alkoxides,
thiolates and disulfides to form product 15 under the high regio-
selective manners. This high regioselectivity would be due to the
balance of reactivities of the substrates and nucleophilicity of the
nucleophiles. Indeed, the suitable nucleophiles, such as alkoxides,
aryloxides and arylthiolates would react with the key intermediate
14 without occurring the side reactions, however, the more nu-
cleophilic alkanethiolates, such as dodecylthiolate would be ex-
pected to attack at the center of the allene bearing sulfur functional
group to form enyne disulfide 16, accompanied by the corre-
sponding furan 15 through a differential path b. Since we are now
investigating the reactions of 4-oxahepta-1,6-diynes bearing no-
aromatic substituents at 3-position of diynes, we could not de-
scribe the details of the mechanism for this cyclizations of sulfur-
substituted 4-oxahepta-1,6-diynes.
In order to apply techniques for synthesizing 3-methylfurans to
the synthesis of 3,4-dimethylfuran derivatives, we performed cy-
clizations of 4-oxahepta-1,6-diynes with sodium thiolate.
The cyclization of 1a produced 3,4-bis(phenylsulfanylmethyl)
furan 3a in 73% yield. The successive desulfanylation of 3a with
Bu3SnHeAIBN in benzene produced 4-(3,4-dimethyl-2-furyl)-1-
methoxybenzene (6a) in 56% yield (Table 3, entry 1). The
Table 3
Sodium arylthiolate-promoted cyclizations of 4-oxa-hepta-1,6-diynes and following
Desulfanylation
To demonstrate the usefulness of this cyclization we further
investigated the tyrosine-mediated cyclization reactions of the 4-
oxahepta-1,6-diynes as shown in Scheme 4.
SPh
Me
Ar
Me
PhS
Ar
SPh
PhSNa/dioxane
reflux10-30min
Bu3SnH/AIBN
Ar
O
O
O
As O-hetaryl tyrosines are one of the useful biomarkers in
searching tumor cells, it is much significant to synthesize the
O-hetaryl tyrosines analogs. First, we performed the tyrosine-
mediated cyclizations under the similar conditions using N-Boc-
tyrosine methyl ester/NaH, however, the reaction was very com-
plicated and the products were obtained in low yields. During the
course of the reaction conditions, we found that 1,8-diazabicyclo
[5.4.0]undec-7-ene was suitable for the tyrosine additional cycli-
zation leading to 4-(O-tyrosinylmethyl)furans. The similar diynes
were served as the optimized reaction conditions: tyrosine methyl
ester (2 equiv)/DBU (1 equiv)/toluene/room temperature and the
furans 16aee in 70e90% yields.
Entry
Diynes
Ar
p-MeOC6H4
1,3-Benzodioxol-5-yl
p-FC6H4
2-Thienyl
1-Naphthyl
% Yield of 3
% Yield of 6
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1j
3a (73)
3b (99)
3c (93)
3d (91)
3e (63)
3j (96)
3k (84)
6a (56)
6b (60)
6c (d)a
6d (61)
6e (79)
6j (d)a
6k (97)
p-ClC6H4
2-Benzofuran-2-yl
1g
a
When 1 equiv of tributyltin hydride was used in both the desulfanylations of 3c
and 3j, 4-(4-methyl-3-phenylsulfanylmethylfuran-2-yl)-1-fluorobenzene (7c), and
the p-chlorophenyl derivative 7j were, respectively, obtained.

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N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
Scheme 3. Plausible mechanism for the cyclization.
aryloxide-, and thiolate- and tyrosine-mediated cyclizations of 4-
oxahepta-1,6-diynes bearing the sulfur substituent followed by
successive phenylsulfanylmethyl group desulfanylations. The cy-
clizations without the added transition metals provided 3-
phenylsulfanylmethyl-4-alkoxymethyl-, 4-aryloxymethyl-, and
3,4-bis(phenylsulfanylmethyl)furans in good to high yields. Fur-
thermore, desulfanylations were achieved by the standard radical
process using tributyltin hydride/AIBN. Further application of 4-
oxa- and 4-azahepta-1,6-diynes cyclizations using various nucleo-
philes is in progress in our laboratory.
Scheme 4. Tyrosine-mediated cyclizations of 4-oxahepta-1,6-diynes.
Finally, we applied our protocol to the syntheses of tetrahy-
dronaphthyl furan derivatives, which show interesting biological
activities.2 The results are shown in Scheme 5. Readily available
1-methoxy-2,3,4,5-tetrahydro-2-naphthalenecarboxaldehyde 17
was treated with the usual alkynylation using phenyl-
sulfanylethyne/n-BuLi at 0 ꢀC to produce propargyl alcohol 18 in
excellent yield. The direct propargylic etherification of 18 under
lanthanum triflate-catalysis yielded 4-oxahepta-1,6-diyne 19. The
reaction with sodium methoxide yielded methoxymethylfuran
derivative 20, while, that of sodium p-methoxyphenyloxide pro-
duced the phenoxymethylfuran 21 in good yield. Cyclized product
desulfanylations led to the tetrahydronaphthalene derivatives 22
and 23, respectively. This process thus provides potentially pow-
erful tools for synthesizing various useful 2-furyltetrahydro-naph-
thalene derivatives.
4. Experimental section
4.1. General
Melting points were determined on a J-Science Lab. Micro
melting point apparatus and uncorrected. Elemental analyses were
performed at the Center of Instrumentation of Gifu University. 1H
and 13C NMR spectra were determined with JEOL ECA600
(600 MHz) spectrometer at Gifu University. Chemical Shifts are
expressed in parts per million (ppm) with respect to tetrame-
thylsilane as an internal standard. Splitting patterns are designated
as follows: s, singlet; d, doublet; t, triplet; q, quartet. IR spectra were
determined on a JASCO FT-IR 460-Plus infrared spectrometer and
are expressed in reciprocal centimeters. EI mass spectra (MS) were
obtained using JEOL MS-700 spectrometer with direct-insertion
probe at 70 eV. All high resolution mass determinations were ob-
tained on the JMSD300 JMS 2000 on line system.
4.2. Preparations of 3-aryl-1-(phenylsulfanyl)-4-oxahepta-
1,6-diynes
3-Aryl-1-(phenylsulfanyl)-4-oxahepta-1,6-diynes 1aed were
prepared by the previous method from 3-phenylsulfanylpropargyl
alcohols and 2-propyn-1-ol. The selenium analogs 1feh were also
obtained from the corresponding propargyl alcohols. The spectral
data of the propargyl alcohols and the 4-oxahepta-1,6-diynes were
described in the supplement data of the previous reports.11 The
other new compounds were prepared and characterized as follows.
4.3. Preparation of 2-(benzofuran-2-yl)-3-(phenylsulfanyl)
prop-2-yn-1-ol, typical procedure
n-Butyllithium in n-hexane (2.6 M, 1.20 mL, 3.0 mmol) was
added dropwise to a THF (7.2 mL) solution of phenylsulfanylethyne
(0.40 g, 3.0 mmol) at 0 ꢀC under an Ar atmosphere. The reaction
mixture was stirred for 10 min. Then, 2-benzofurancarboxaldehyde
(0.44 g, 3.0 mmol) in THF (2.0 mL) was added dropwise to the
mixture. The whole was stirred for 30 min at room temperature
and poured into a saturated ammonium chloride (50 mL) solution.
The organic layer was separated and the aqueous layer was
Scheme 5. Sodium alkoxide-promoted cyclizations of 4-oxahepta-1,6-diynes: syn-
theses of tetrahydronaphthyl furan derivatives.
3. Conclusion
In summary, we have described a powerful technique for syn-
thesizing 3-methyl- and 3,4-dimethylfurans through alkoxide-,

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1571
extracted with ether. The combined organic layer was dried over
MgSO4. The solvent was removed under reduced pressure. The
residue was purified by preparative TLC on silica gel eluting with
AcOEt-n-hexane (1:10) to give the title compound (0.64 g, 76%) as
a yellow oil.
hexane (1:20) to give the title compound 1i (0.97 g, 86%) as a pale
yellow oil.
IR (KBr, cmꢁ1) 3443, 3296, 2360, 1604, 1577, 1509, 1439, 1225,
1158, 1067, 1021, 835, 736, 687; 1H NMR (600 MHz, CDCl3)
d 2.49
(1H, d, J¼2.4 Hz, acetylenic H), 4.31 (1H, dd, J¼2.8 and 15.8 Hz, CH2),
4.42 (1H, dd, J¼2.8 and 15.8 Hz, CH2), 5.61 (1H, s, CH), 7.02e7.08
(2H, m, ArH), 7.25e7.32 (3H, m, ArH), 7.47e7.53 (4H, m, ArH); 13C
4.3.1. 2-(Benzofuran-2-yl)-3-(phenylsulfanyl)prop-2-yn-1-ol. IR
(KBr, cmꢁ1) 3375, 3060, 2187, 1582, 1478, 1453, 1441, 1296, 1254,
1171, 1132, 1072, 1023, 988, 940, 883, 828, 812, 739, 687; 1H NMR
NMR (150 MHz, CDCl3) d 55.6 (t), 69.4 (s), 70.2 (d), 75.2 (d), 79.0 (s),
100.2 (s), 115.4 (d), 115.5 (d), 127.3 (d), 128.1 (s), 129.3 (dꢂ2), 129.4
(d), 129.5 (d), 129.6 (dꢂ2), 133. 6 (s), 162.86 (d, J¼247 Hz); MS m/z
343 (Mþ). Anal. Calcd for C18H13FOSe: C, 62.98; H, 3.82. Found: C,
62.45; H, 3.95.
(600 MHz, CDCl3)
d
2.84 (1H, br s, OH), 5.80 (1H, d, J¼6.8 Hz, CH),
6.82 (1H, s, furyl H), 7.23 (2H, t, J¼7.6 Hz, ArH), 7.29e7.33 (3H, m,
ArH), 7.45 (2H, d, J¼7.5 Hz, ArH), 7.49 (1H, d, J¼8.2 Hz, ArH), 7.55
(1H, d, J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 59.6 (d), 74.5 (s),
95.2 (s), 104.5 (d), 111.4 (d), 121.4 (d), 123.0 (d), 124.8 (d), 126.6
(dꢂ2), 126.9 (d), 127.7 (s), 129.3 (dꢂ2), 131.7 (s), 154.6 (s), 155.2 (s);
MS m/z 280 (Mþ), 263 (MþꢁOH), 171 (MþꢁSPh). Anal. Calcd for
C17H12O2S: C, 72.83; H, 4.31. Found: C, 72.86; H, 4.36.
4.4.1. 1-Fluoro-4-[1-(propargyloxy)-3-(phenylsulfanyl)prop-2-yn-1-
yl]benzene (1c). Yield 76%, a yellow oil, IR (KBr, cmꢁ1) 3298, 2180,
2118,1604, 1583, 1509,1478, 1442, 1417,1328, 1227, 1157, 1055,1023,
933, 903, 837, 790, 740, 687, 634, 565; 1H NMR (600 MHz, CDCl3)
d
2.51 (1H, t, J¼2.4 Hz, acetylenic H), 4.32 (1H, dd, J¼2.4 and 15.8 Hz,
4.3.2. 1-(1-Naphthyl)-3-(phenylselanyl)prop-2-yn-1-ol. A
yellow
CH2), 4.41 (1H, dd, J¼2.4 and 15.8 Hz, CH2), 5.63 (1H, s, CH), 7.07
(2H, t, J¼7.9 Hz, ArH), 7.22e7.25 (1H, m, ArH), 7.33 (2H, t, J¼7.9 Hz,
ArH), 7.40 (2H, d, J¼8.2 Hz, ArH), 7.53 (2H, dd, J¼5.5 and 8.9 Hz,
oil, IR (KBr, cmꢁ1) 3538, 3373, 2171, 1598, 1577, 1510, 1476, 1440,
1394, 1303, 1259, 1229, 1163, 1066, 1032, 1019, 963, 802, 780, 735,
687, 666; 1H NMR (600 MHz, CDCl3)
d
3.45 (1H, d, J¼6.6 Hz, OH),
ArH); 13C NMR (150 MHz, CDCl3)
d 55.5 (t), 70.1 (d), 75.3 (d), 76.8
6.12 (1H, d, J¼6.6 Hz, CH), 7.08e7.13 (3H, m, ArH), 7.29e7.32 (1H, m,
ArH), 7.36e7.39 (2H, m, ArH), 7.39e7.43 (2H, m, ArH), 7.67e7.71
(2H, m, ArH), 7.75e7.76 (1H, m, ArH), 8.21e8.22 (1H, m, ArH); 13C
(s), 79.0 (s), 95.4 (s), 115.4 (d), 115.6 (d), 126.4 (dꢂ2), 126.8 (d), 129.3
(dꢂ2), 129.4 (d), 129.5 (d), 132.0 (s), 133.5 (s), 162.8 (d, J¼247 Hz);
MS m/z 295 (Mþꢁ1). Anal. Calcd for C18H13FOS: C, 72.95; H, 4.42.
Found: C, 73.26; H, 4.58.
NMR (150 MHz, CDCl3) d 63.6 (d), 67.5 (s), 103.1 (s), 123.9 (d), 124.5
(d), 125.0 (d), 125.6 (d), 126.1 (d), 126.9 (d), 128.1 (s), 128.5 (d), 128.9
(dꢂ2), 129.0 (d), 129.3 (dꢂ2), 130.2 (s), 133.7 (s), 135.3 (s); MS m/z
338 (Mþ). Anal. Calcd for C19H14OSe: C, 67.66; H, 4.18. Found: C,
67.18; H, 4.36.
4.4.2. 2-[1-(Propargyloxy)-3-(phenylsulfanyl)prop-2-yn-1-yl]-1,3,5-
trimethylbenzene (1e). Yield 96%, a yellow oil, IR (KBr, cmꢁ1) 3293,
2918, 2170, 2116, 1610, 1582, 1478, 1442, 1379, 931, 903, 852, 813,
779, 740, 687, 637; 1H NMR (600 MHz, CDCl3)
d 2.26 (3H, s, Me),
4.3.3. 1-(p-Fluorophenyl)-3-(phenylselanyl)prop-2-yn-1-ol. Yield
73%, a yellow oil, IR (KBr, cmꢁ1) 3359, 1604, 1577, 1508, 1477, 1439,
1225, 1157, 1045, 978, 837, 735, 687, 560; 1H NMR (600 MHz, CDCl3)
2.47 (6H, s, Meꢂ2), 2.48 (1H, t, J¼2.0 Hz, acetylenic H), 4.20 (1H, dd,
J¼2.0 and 15.8 Hz, CH2), 4.36 (1H, dd, J¼2.0 and 15.8 Hz, CH2), 6.01
(1H, s, CH), 6.85 (2H, s, ArH), 7.21e7.22 (1H, m, ArH), 7.26e7.32 (2H,
d
2.50 (1H, br s, OH), 5.63 (1H, br s CH), 7.05 (2H, t, J¼8.9 Hz, ArH),
7.24e7.31 (3H, m, ArH), 7.50e7.51 (4H, m, ArH); 13C NMR (150 MHz,
CDCl3) 64.8 (d), 67.9 (s), 102.8 (s), 115.4 (d), 115.5 (d), 127.3 (d),
m, ArH), 7.38e7.39 (2H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 20.3
(qꢂ2), 20.9 (q), 55.1 (t), 66.4 (d), 74.3 (s), 74.9 (d), 79.6 (s), 95.9 (s),
126.5 (dꢂ2), 126.6 (d), 129.2 (dꢂ2), 129.9 (dꢂ2), 130.7 (s), 132.6 (s),
137.2 (s), 138.1 (s); 151.8 (s); MS m/z 319 (Mþꢁ1), 265
(Mþꢁpropargyloxy). Anal. Calcd for C21H20OS: C, 78.71; H, 6.29.
Found: C, 78.54; H, 6.42.
d
128.0 (s), 128.4 (d), 128.5 (d), 129.3 (dꢂ2), 129.6 (dꢂ2), 136.1 (s),
162.7 (d, J¼248 Hz); MS m/z 306 (Mþ), 286 (MþꢁF). Anal. Calcd for
C15H11FOSe: C, 59.03; H, 3.63. Found: C, 59.04; H, 3.78.
4.3.4. 1-(2,4,6-Trimethylphenyl)-3-(phenylsulfanyl)prop-2-yn-1-
ol. Yield 90%, a yellow oil, IR (KBr, cmꢁ1) 3418, 2922, 2354, 2178,
1613, 1582, 1556, 1538, 1478, 1442, 1378, 1302, 1200, 1142, 1063,
4.4.3. 2-[1-(Propargyloxy)-3-(phenylsulfanyl)prop-2-ynyl]benzofu-
ran (1k). A yellow oil, IR (KBr, cmꢁ1) 3421, 3292, 2183, 1583, 1478,
1453, 1441, 1298, 1254, 1172, 1072, 1051, 1023, 813, 740, 687; 1H
1024, 982, 852, 777, 739, 687; 1H NMR (600 MHz, CDCl3)
d
2.08 (1H,
NMR (600 MHz, CDCl3)
d
2.51 (1H, t, J¼2.4 Hz, acetylenic H), 4.36
br s, OH), 2.25 (3H, s, Me), 2.49 (6H, s, Meꢂ2), 6.08 (1H, d, J¼4.3 Hz,
(1H, dd, J¼2.9 and 15.8 Hz, CH2), 4.48 (1H, dd, J¼2.9 and 15.8 Hz,
CH2), 5.85 (1H, s, CH), 6.91 (1H, s, furyl H), 7.22e7.27 (2H, m, ArH),
7.30e7.36 (3H, m, ArH), 7.47 (2H, d, J¼8.3 Hz, ArH), 7.52 (1H, d,
J¼7.6 Hz, ArH), 7.57 (1H, d, J¼7.6 Hz, ArH); 13C NMR (150 MHz,
CH), 6.85 (2H, s, ArH), 7.18e7.20 (1H, m, ArH), 7.28e7.30 (2H, m,
ArH), 7.37 (2H, d, J¼7.5 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 20.3
(qꢂ2), 20.8 (q), 61.1 (d), 72.8 (s), 98.2 (s), 126.5 (dꢂ2), 126.6 (d),
129.1 (dꢂ2), 129.9 (dꢂ2), 132.5 (s), 133.2 (s), 136.3 (sꢂ2), 137.9 (s);
MS m/z 282 (Mþ), 267 (MþꢁMe). Anal. Calcd for C18H18OS: C, 76.56;
H, 6.42. Found: C, 77.02; H, 6.46.
CDCl3)
d 55.4 (t), 64.6 (d), 75.6 (d), 76.8 (s), 78.6 (s), 92.7 (s), 106.4
(d), 111.6 (d), 121.4 (d), 123.0 (d), 125.0 (d), 126.6 (dꢂ2), 126.9 (d),
127.5 (s), 129.3 (dꢂ2), 131.7 (s), 152.2 (s), 155.3 (s); MS m/z 318 (Mþ),
263 (Mþꢁpropargyloxy). Anal. Calcd for C20H14O2S: C, 75.45; H,
4.43. Found: C, 75.51; H, 4.72.
4.4. Preparations of 1-fluoro-4-[1-(propargyloxy)-3-
(phenylselanyl)prop-2-yn-1-yl]benzene (1i), typical procedure
4.4.4. 1-[1-(Propargyloxy)-3-(phenylselanyl)prop-2-yn-1-yl]-naph-
thalene (1g). A yellow oil, IR (KBr, cmꢁ1) 3290, 3051, 1577, 1509,
1477, 1439, 1065, 1052, 1021, 802, 781, 735, 687, 667, 638; 1H NMR
Lanthanum triflate (96 mg, 0.16 mmol) was added to a mixture
of 1-(p-fluorophenyl)-3-(phenylselanyl)prop-2-yn-1-ol (1.00 g,
3.28 mmol), propargyl alcohol (1.84 g, 32.8 mmol), and tetrabuty-
lammonium hydrogensulfate (0.11 g, 0.33 mmol) in MeNO2
(11.0 mL)eH2O (1.1 mL) at room temperature. The mixture was
stirred for 1 h and poured into a saturated NaHCO3 (50 mL). The
organic layer was separated and the aqueous layer was extracted
with ether. The combined organic layer was dried over MgSO4. The
solvent was removed under reduced pressure. The residue was
purified by preparative TLC on silica gel eluting with AcOEten-
(600 MHz, CDCl3)
d
2.55 (1H, t, J¼2.4 Hz, acetylenic H), 4.30 (1H,
dd, J¼2.8 and 15.8 Hz, CH2), 4.48 (1H, dd, J¼2.8 and 15.8 Hz, CH2),
6.23 (1H, s, CH), 7.15e7.18 (2H, m, ArH), 7.38e7.49 (3H, m, ArH),
7.51e7.52 (1H, m, ArH), 7.75e7.85 (3H, m, ArH), 8.39 (1H, d,
J¼8.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 55.4 (t), 69.5 (d),
69.6 (s), 75.3 (d), 79.0 (s), 100.4 (s), 124.2 (d), 125.0 (d), 125.8 (d),
126.3 (d), 126.4 (d), 127.0 (d), 128.1 (s), 128.5 (d), 129.0 (dꢂ2),
129.4 (dꢂ2), 129.6 (d), 130.7 (s), 132.7 (s), 133.9 (s); MS m/z 375

1572
N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
(Mþꢁ1). Anal. Calcd for C22H16OSe: C, 70.21; H, 4.55. Found: C,
was added dropwise to a mixture of 2-methoxyethanol (1.0 mL) and
1,4-dioxane (0.10 mL) of 1-methoxy-4-[4-(2-propynyloxy)-3-(phe-
nylsulfanyl)-2-propyn-1-yl]benzene (2a) (50 mg, 0.162 mmol). The
reaction mixture was stirred for 10 min at 30 ꢀC and poured into
a saturated ammonium chloride (50 mL). The organic layer was
separated and the aqueous layer was extracted with ether. The
combined organic layer was dried over MgSO4. The solvent was
removed under reduced pressure. The residue was purified by
preparative TLC on silica gel eluting with AcOEten-hexane (1:20)
to give 4-(methoxyethoxymethyl)-2-(p-methoxyphenyl)-3-(phenyl-
sulfanylmethyl)furan (2ac) (30.6 mg, 49%) as a yellow oil.
69.95; H, 4.38.
4.5. Reaction of 1-methoxy-4-[4-(2-propynyloxy)-3-
(phenylsulfanyl)-2-propyn-1-yl]benzene (2a) with sodium
butoxide, typical procedure for cyclization of 4-oxahepta-1,6-
diynes with alkoxides
Sodium n-butoxide (0.80 mL, 0.80 mmol) was added to a mix-
ture of 1-butanol (1.0 mL), 1,4-dioxane (0.10 mL) of 2aa (50 mg,
0.16 mmol) at room temperature. The reaction mixture was stirred
for 2 h and then poured into water (50 mL). The organic layer was
separated and the aqueous layer was extracted with ether. The
combined organic layer was dried over MgSO4. The solvent was
removed under reduced pressure. The residue was purified by
preparative TLC on silica gel eluting with AcOEten-hexane (1:40) to
give 4-[4-butyloxymethyl-3-(phenylsulfanylmethyl)furan-2-yl]-1-
methoxybenzene (2aa) (28 mg, 46%).
4.5.5. 4-[4-(Methoxyethoxymethyl)-3-(phenylsulfanylmethyl)furan-
2-yl]-1-methoxybenzene (2ac). IR (KBr, cmꢁ1) 2929, 1606, 1579,
1506,1480, 1464,1440,1354,1305,1253,1179,1092,1065, 1030, 951,
835, 740, 691; 1H NMR (600 MHz, CDCl3)
d 3.35 (3H, s, OCH3),
3.54e3.55 (2H, m, OCH2), 3.61e3.63 (2H, m, OCH2), 3.82 (3H, s,
OCH3), 4.20 (2H, s, OCH2), 4.49 (2H, s, SCH2), 6.92 (2H, d, J¼9.0 Hz,
ArH), 7.19 (1H, t, J¼7.6 Hz, ArH), 7.26 (2H, t, J¼7.6 Hz, ArH), 7.35 (2H,
d, J¼8.3 Hz, ArH), 7.38 (1H, s, furyl H), 7.53 (2H, d, J¼8.9 Hz, ArH);
4.5.1. 4-[4-Butyloxymethyl-3-(phenylsulfanylmethyl)furan-2-yl]-1-
methoxybenzene (2aa). A yellow oil: IR (KBr, cmꢁ1) 3434, 2925,
2853, 2359, 2341, 1653, 1607, 1507, 1457, 1306, 1253, 1179, 1092,
13C NMR (150 MHz, CDCl3)
d 28.9 (t), 55.3 (q), 59.0 (q), 63.6 (t), 69.2
(t), 71.9 (t), 114.1 (dꢂ2), 114.2 (s), 123.5 (s), 123.6 (s), 126.4 (d), 127.7
(dꢂ2), 127.7 (dꢂ2), 130.1 (dꢂ2), 136.5 (s), 139.6 (d), 151.9 (s), 159.2
(s); MS m/s 384 (Mþ), 309 (MþꢁOCH2CH2OMe), 275 (MþꢁSPh);
high resolution mass calcd for C22H24O4S; 384.1395, found m/z
384.1439.
1065, 1027, 837, 759, 691; 1H NMR (600 MHz, CDCl3)
d 0.89 (3H, t,
J¼7.6 Hz Me), 1.33e1.40 (2H, m, CH2), 1.54e1.59 (2H, m, CH2), 3.46
(2H, t, J¼6.7 Hz, OCH2), 3.82 (3H, s, OCH3), 4.19 (2H, s, OCH2), 4.40
(2H, s, SCH2), 6.92 (2H, d, J¼9.2 Hz, ArH), 7.17e7.22 (1H, m, ArH),
7.24e7.27 (2H, m, ArH), 7.35 (2H, d, J¼6.9 Hz, ArH), 7.37 (1H, s, furyl
H), 7.53 (2H, d, J¼8.7 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d
14.0 (q),
4.5.6. 2-[2-(p-Methoxyphenyl)-3-(phenylsulfanylmethyl)furan-4-
ylmethoxy]ethanol (2ad). A yellow oil: IR (KBr, cmꢁ1) 3435, 2925,
2853, 1606, 1582, 1506, 1481, 1464, 1440, 1306, 1253, 1179, 1107,
19.5 (t), 29.2 (t), 31.9 (t), 55.4 (q), 63.4 (t), 70.4 (t), 114.2 (dꢂ2), 114.3
(s), 123.6 (s), 124.1 (s), 126.5 (d), 127.9 (dꢂ2), 128.9 (dꢂ2), 130.2
(dꢂ2), 136.7 (s), 139.5 (d), 152.0 (s), 159.4 (s); MS m/s 382 (Mþ), 273
(MþꢁSPh); high resolution mass calcd for C23H26O3S: 382.1602,
found m/z 382.1613.
1065, 1028, 835, 741, 692, 621; 1H NMR (600 MHz, CDCl3)
d 2.33
(1H, br s, OH), 3.59e3.60 (2H, m, OCH2), 3.74e3.75 (2H, m, OCH2),
3.82 (3H, s, OCH3), 4.18 (2H, s, OCH2), 4.47 (2H, s, SCH2), 6.92 (2H, d,
J¼8.9 Hz, ArH), 7.19e7.22 (1H, m, ArH), 7.24e7.29 (2H, m, ArH),
7.35e7.38 (2H, m, ArH), 7.39 (1H, s, furyl H), 7.56 (2H, d, J¼6.9 Hz,
4.5.2. 1-Methoxy-4-[3-(phenylsulfanylmethyl)-4-(propyloxymethyl)
furan-2-yl]benzene (2ab). A brown oil, IR (KBr, cmꢁ1) 3424, 2962,
2933, 2874, 1764, 1608, 1508, 1480, 1463, 1440, 1306, 1255, 1177,
ArH); 13C NMR (150 MHz, CDCl3)
d 29.2 (t), 55.3 (q), 61.8 (t), 63.5 (t),
71.4 (t), 113.9 (s), 114.1 (dꢂ2), 123.3 (s), 123.5 (s), 126.6 (d), 127.7
(dꢂ2), 128.9 (dꢂ2), 130.0 (dꢂ2), 136.3 (s), 139.6 (d), 152.2 (s), 159.3
(s); MS m/z 370 (Mþ), 261 (MþꢁSPh). Anal. Calcd for C21H22O4S: C,
68.08; H, 5.98. Found: C, 67.89; H, 5.94.
1089, 1028, 953, 853, 743, 691; 1H NMR (600 MHz, CDCl3)
d 0.91
(3H, t, J¼7.3 Hz, Me), 1.58e1.64 (2H, m, CH2), 3.47 (2H, t, J¼6.5 Hz,
CH2), 3.82 (3H, s, OMe), 4.20 (2H, s, OCH2), 4.41 (2H, s, SCH2), 6.92
(2H, d, J¼8.9 Hz, ArH), 7.18e7.22 (1H, m, ArH), 7.27 (2H, t, J¼6.9 Hz,
ArH), 7.32e7.34 (2H, m, ArH), 7.37 (1H, s, furyl H), 7.53 (2H, d,
4.5.7. 1-Methoxy-4-[3-(phenylsulfanyldideuteriomethyl)-4-(trideu-
teriomethoxydideuteriomethyl)furan-2-yl]benzene (2ae). A yellow
oil, IR (KBr, cmꢁ1) 3057, 3003, 2956, 2933, 2837, 2238, 2192, 2055,
1713,1605,1578,1506,1480,1440,1306,1253,1179,1127,1101,1066,
J¼9.0 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 10.6 (q), 22.9 (t), 29.1
(t), 55.3 (q), 63.2 (t), 72.2 (t), 114.1 (dꢂ2), 114.2 (s), 123.5 (s), 124.0
(s), 126.4 (d), 127.7 (dꢂ2), 128.8 (dꢂ2), 130.1 (dꢂ2), 136.6 (s), 139.4
(d), 151.9 (s), 159.2 (s); MS m/s 368 (Mþ), 259 (MþꢁSPh); high
resolution mass calcd for C22H24O3S; 368.1446, found m/z 368.1190.
1031, 945, 835, 740, 691; 1H NMR (600 MHz, CDCl3)
d 3.82 (3H, s,
OCH3), 6.92 (2H, d, J¼9.0 Hz, ArH), 7.18e7.21 (1H, m, ArH),
7.24e7.27 (2H, m, ArH), 7.36 (2H, d, J¼6.9 Hz, ArH), 7.37 (1H, s, furyl
4.5.3. 4-[3,4-Bis(phenylsulfanylmethyl)furan-2-yl]-1-methoxybenzene
(3a). A yellow oil; IR (KBr, cmꢁ1) 3057, 3003, 2956, 2930, 2836,
1943, 1889, 1712, 1605, 1582, 1506, 1480, 1439, 1361, 1306, 1292,
1252, 1222, 1178, 1091, 1065, 1027, 950, 835, 740, 690, 613, 595, 530,
H), 7.54 (2H, d, J¼8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 55.3 (q),
114.0 (s), 114.1 (dꢂ2), 123.5 (s), 123.5 (s), 126.4 (d), 127.7 (dꢂ2),
128.9 (dꢂ2), 130.1 (dꢂ2), 136.4 (s), 139.6 (d), 151.9 (s), 159.2 (s); MS
m/s 347 (Mþ), 238 (MþꢁSPh). Anal. Calcd for C20H13O3SD7: C, 69.13;
H, 3.77. Found: C, 68.67; H, 5.74.
474, 417; 1H NMR (600 MHz, CDCl3)
d 3.80 (3H, s, OMe), 3.98 (2H, s,
CH2), 4.21 (2H, s, CH2), 6.91 (2H, d, J¼8.3 Hz, ArH), 7.17e7.26 (7H, m,
ArH), 7.31e7.34 (4H, m, ArH), 7.51 (2H, d, J¼9.0 Hz, ArH); 13C NMR
4.5.8. 4-(Allyloxymethyl)-1-methoxy-3-(phenylsulfanylmethyl)-fu-
ran-2-yl]benzene (2af). A yellow oil: IR (KBr, cmꢁ1) 3075, 3004,
2931, 2854, 2556, 2049, 1768, 1647, 1607, 1580, 1506, 1480, 1464,
1440, 1421, 1354, 1306, 1254, 1179, 1065, 1029, 930, 835, 789, 740,
(150Mz, CDCl3)
d
27.9 (t), 29.0 (t), 55.2 (q), 114.0 (s), 114.1 (dꢂ2),
122.5 (s), 123.3 (s), 126.4 (d), 126.6 (d), 127.7 (dꢂ2), 128.8 (dꢂ2),
128.9 (dꢂ2), 130.0 (dꢂ2), 130.3 (dꢂ2), 136.0 (s), 136.1 (s), 139.5 (d),
151.9 (s), 159.3 (s); MS m/z 418 (Mþ), 309 (MþꢁPhS), 200
(MþꢁPhꢂ2). Anal. Calcd for C25H22O2S2: C, 71.74; H, 5.30. Found: C,
71.48; H, 5.27.
691, 474; 1H NMR (600 MHz, CDCl3)
d 3.81 (3H, s, OCH3), 4.01 (2H, d,
J¼5.5 Hz, olefinic H), 4.19 (2H, s, SCH2), 4.42 (2H, s, OCH2), 5.16e5.19
(1H, m, olefinic H), 5.28 (1H, dt, J¼1.4 and 17.4 Hz, olefinic H),
5.89e5.95 (1H, m, olefinic H), 6.92 (2H, d, J¼9.0 Hz, ArH), 7.18e7.20
(1H, m, ArH), 7.24e7.27 (2H, m, ArH), 7.35 (2H, d, J¼6.9 Hz, ArH),
7.38 (1H, s, furyl H), 7.54 (2H, br d, J¼9.0 Hz, ArH); 13C NMR
4.5.4. Reaction
of
1-methoxy-4-[4-(2-propynyloxy)-3-(phenyl-
sulfanyl)-2-propyn-1-yl]benzene (2a) with sodium 2-methoxyethox-
ide. Sodium 2-methoxyethoxide (1 M) (prepared from 2-meth
oxyethanol and sodium) in 2-methoxyethanol (0.81 mL, 0.81 mmol)
(150 MHz, CDCl3)
114.1 (s), 117.3 (t), 123.4 (s), 123.7 (s), 126.4 (d), 127.7 (dꢂ2), 128.8
d
29.0 (t), 55.2 (q), 62.5 (t), 71.1 (t), 114.1 (dꢂ2),

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1573
(dꢂ2), 130.1 (dꢂ2), 134.6 (d), 136.5 (s), 139.6 (d), 151.9 (s), 159.2 (s);
MS m/s 366 (Mþ), 257 (MþꢁSPh). Anal. Calcd for C22H22O3S: C,
72.10; H, 6.05. Found: C, 72.32; H, 6.13.
OCH3), 3.46e3.47 (2H, m, OCH2), 3.53e3.54 (2H, m, OCH2), 4.10
(2H, s, OCH2), 4.40 (2H, s, SCH2), 5.88 (2H, s, OCH2O), 6.73 (1H, d,
J¼8.7 Hz, ArH), 6.99e7.02 (2H, m, ArH), 7.10e7.13 (1H, m, ArH),
7.16e7.69 (2H, m, ArH), 7.26e7.28 (2H, d, J¼8.2 Hz, ArH), 7.29 (1H,
4.5.9. 1-Methoxy-4-[3-(phenylsulfanylmethyl)-4-(propargylox-
s, furyl H); 13C NMR (150 MHz, CDCl3)
d 29.0 (t), 58.9 (q), 63.5 (t),
ymethyl)furan-2-yl]benzene (2ag). A yellow oil: IR (KBr, cmꢁ1
)
69.2 (t), 71.9 (t), 101.1 (t), 106.9 (d), 108.5 (d), 114.6 (s), 120.4 (d),
123.6 (s), 124.8 (s), 126.5 (d), 128.8 (dꢂ2), 130.3 (dꢂ2), 136.3 (s),
139.7 (d), 147.3 (s), 147.8 (s), 151.7 (s); MS m/z 398 (Mþ), 289
(MþꢁSPh). Anal. Calcd for C22H22O5S: C, 66.31; H, 5.56. Found: C,
65.76; H, 5.39.
3289, 3058, 2932, 2839, 2360, 2116, 2049, 1768, 1669, 1607, 1580,
1507, 1480, 1464, 1440, 1354, 1306, 1256, 1179, 1072, 1028, 951, 835,
741, 691; 1H NMR (600 MHz, CDCl3)
d
2.38 (1H, t, J¼2.0 Hz, CH), 3.82
(3H, s, OMe), 4.16 (2H, d, J¼2.7 Hz, OCH2), 4.19 (2H, s, OCH2), 4.53
(2H, s, SCH2), 6.93 (2H, d, J¼8.3 Hz, ArH), 7.18e7.21 (1H, m, ArH),
7.24e7.27 (2H, m, ArH), 7.36 (2H, d, J¼8.2 Hz, ArH), 7.42 (1H, s, furyl
4.5.14. 2-[(1,3-Benzodioxol-5-yl)-3-(phenylsulfanylmethyl)furan-4-
ylmethoxy]ethanol (2bc). A yellow oil: IR (KBr, cmꢁ1) 3437, 2892,
2360, 2342, 1583, 1503, 1487, 1450, 1355, 1299, 1237, 1154, 1106,
H), 7.54 (2H, d, J¼9.0 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 28.9 (t),
55.3 (q), 56.9 (t), 61.6 (t), 74.7 (d), 79.5 (s), 114.1 (dꢂ2), 122.8 (s),
123.4 (s), 126.5 (d), 127.7 (dꢂ2), 128.8 (dꢂ2), 130.1 (dꢂ2), 136.4 (s),
140.2 (d), 152.1 (s), 159.3 (s); MS m/s 364 (Mþ), 255 (MþꢁSPh), 216
(MþꢁSPhꢁCH2CCH); high resolution mass calcd for C22H20O3S:
364.1132, found m/z 364.1109.
1039, 935, 871, 814, 740, 692; 1H NMR (600 MHz, CDCl3)
d 2.28 (1H,
s, OH), 3.59 (2H, t, J¼4.8 Hz, OCH2), 3.74 (2H, br s, OCH2), 4.16 (2H, s,
OCH2), 4.47 (2H, s, SCH2), 5.98 (2H, s, OCH2O), 6.83 (1H, d, J¼8.3 Hz,
ArH), 7.10e7.13 (2H, m, ArH), 7.20e7.23 (1H, m, ArH), 7.26e7.29
(2H, m, ArH), 7.36 (2H, d, J¼8.2 Hz, ArH), 7.38 (1H, s, furyl H); 13C
4.5.10. 4-[4-(Cyclopropylmethoxymethyl)-3-(phenylsulfanylmethyl)
furan-2-yl]benzene (2ah). A yellow oil: IR (KBr, cmꢁ1) 3077, 3003,
2031, 2854, 1607, 1579, 1560, 1480, 1440, 1305, 1253, 1179, 1079,
NMR (150 MHz, CDCl3) d 29.3 (t), 61.8 (t), 63.5 (t), 71.4 (t), 101.2 (t),
106.9 (d), 108.6 (d), 114.4 (s), 120.5 (d), 123.6 (s), 124.6 (s), 126.7 (d),
129.0 (dꢂ2), 130.3 (dꢂ2), 136.1 (s), 139.6 (d), 147.4 (s), 147.9 (s),
152.0 (s); MS m/s 384 (Mþ), 334 (MþꢁCH2CH2OH), 258
(MþꢁSPhꢁOH); Anal. Calcd for C21H20O5S: C, 65.60; H, 5.24. Found:
C, 65.51; H, 5.21.
1030, 951, 834, 739, 691; 1H NMR (600 MHz, CDCl3)
d 0.18e0.20
(2H, m, CH2), 0.51e0.53 (2H, m, CH2), 1.05e1.08 (1H, m, CH), 3.30
(2H, d, J¼6.9 Hz, CH2), 3.82 (3H, s, OMe), 4.21 (2H, s, SCH2), 4.40 (2H,
s, OCH2), 6.92 (2H, d, J¼9.0 Hz, ArH), 7.18e7.20 (1H, m, ArH),
7.25e7.27 (2H, m, ArH), 7.35 (2H, d, J¼7.2 Hz, ArH), 7.38 (1H, s, furyl
4.5.15. 5-[4-(Allyloxymethyl)-3-(phenylsulfanylmethyl)furan-2-yl]-
1,3-benzodioxole (2bd). A yellow oil: IR (KBr, cmꢁ1) 3435, 3076,
2925, 2855, 1583, 1503, 1488, 1450, 1350, 1298, 1237, 1154, 1090,
1040, 935, 868, 815, 739, 691; 1H NMR (600 MHz, CDCl3)
H), 7.53 (2H, d, J¼8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 3.0
(tꢂ2), 10.6 (d), 29.0 (t), 55.3 (q), 62.8 (t), 75.0 (t), 114.1 (dꢂ2), 114.2
(s), 123.5 (s), 123.9 (s), 126.4 (d), 127.7 (dꢂ2), 128.8 (dꢂ2), 130.0
(dꢂ2), 136.6 (s), 139.5 (d), 151.9 (s), 159.2 (s); MS m/s 380 (Mþ), 325
(MþꢁCH2(CH2CH2CH2)), 309 (MþꢁOCH2(CH2CH2CH2)), 271
(MþꢁSPh). Anal. Calcd for C23H24O3S: C, 72.60; H, 6.36. Found: C,
72.63; H, 6.33.
d
4.00e4.02 (2H, m, CH2), 4.17 (2H, s, SCH2), 4.42 (2H, s, OCH2),
5.16e5.19 (1H, m, olefinic H), 5.28 (1H, dd, J¼1.4 and 17.2 Hz, ole-
finic H), 5.89e5.98 (1H, m, olefinic H), 5.98 (2H, s, OCH2O), 6.83 (1H,
d, J¼8.2 Hz, ArH), 7.08e7.10 (2H, m, ArH), 7.19e7.22 (1H, m, ArH),
7.25e7.28 (2H, m, ArH), 7.36 (2H, d, J¼8.3 Hz, ArH), 7.37 (1H, s, furyl
4.5.11. 5-[3-(Phenylsulfanylmethyl)-4-(propyloxymethyl)furan-2-yl]-
1,3-benzodioxole (2ba). A yellow oil: IR (KBr, cmꢁ1) 2930, 1769,
1503, 1488, 1440, 1362, 1249, 1092, 1039, 936, 866, 815, 740, 691; 1H
H); 13C NMR (150 MHz, CDCl3)
d 29.1 (t), 62.4 (t), 71.2 (t), 101.1 (t),
107.0 (d), 108.5 (d), 114.6 (s), 117.3 (t), 123.8 (s), 124.8 (s), 126.6 (d),
128.9 (dꢂ2), 130.4 (dꢂ2), 134.6 (d), 134.6 (d), 136.3 (s), 139.6 (d),
147.3 (s), 147.9 (s), 151.7 (s); MS m/s 380 (Mþ), 271 (MþꢁSPh), 215
(MþꢁSPhꢁOCH2CHCH2). Anal. Calcd for C22H20O4S: C, 69.45; H,
5.30. Found: C, 69.59; H, 5.58.
NMR (600 MHz, CDCl3)
d
0.92 (3H, t, J¼7.6 H, Me), 1.56e1.65 (2H, m,
CH2), 3.42 (2H, t, J¼6.9 Hz, CH2), 4.18 (2H, s, OCH2), 4.40 (2H, s,
SCH2), 5.97 (2H, s, OCH2O), 6.82 (1H, d, J¼7.8 Hz, ArH), 7.07e7.10
(2H, m, ArH), 7.18e7.22 (1H, m, ArH), 7.25e7.26 (2H, m, ArH), 7.35
(2H, d, J¼6.4 Hz, ArH), 7.37 (1H, s, furyl H); 13C NMR (150 MHz,
4.5.16. 4-[4-Butoxymethyl-3-(phenylsulfanylmethyl)furan-2-yl]-1-
fluorobenzene (2ca). A yellow oil, IR (KBr, cmꢁ1) 3434, 2958, 2929,
2858, 1769, 1601, 1505, 1480, 1439, 1234, 1159, 1092, 839, 739, 691;
CDCl3) d 10.7 (q), 22.9 (t), 29.1 (t), 63.2 (t), 72.3 (t),101.1 (t),107.0 (d),
108.5 (d), 114.6 (s), 120.4 (d), 124.1 (s), 124.8 (s), 126.5 (d), 128.9
(dꢂ2), 130.3 (dꢂ2), 136.3 (s), 139.5 (d), 147.3 (s), 147.9 (s), 151.7 (s);
MS m/s 382 (Mþ), 273 (MþꢁSPh). Anal. Calcd for C22H22O4S: C,
69.08; H, 5.80. Found: C, 68.84; H, 5.66.
1H NMR (600 MHz, CDCl3)
d
0.90 (3H, t, J¼7.6 Hz, OCH2), 1.33e1.40
(2H, m, CH2CH2CH3), 1.55e1.60 (2H, m, CH2CH2CH3), 3.47 (2H, t,
J¼6.7 Hz, OCH2CH2), 4.17 (2H, s, OCH2), 4.45 (2H, s, SCH2), 7.05e7.08
(2H, m, ArH), 7.19e7.22 (1H, m, ArH), 7.24e7.27 (2H, s, ArH), 7.35
(2H, d, J¼6.9 Hz, OCH2), 7.39 (1H, s, furyl H), 7.51e7.56 (2H, m, ArH);
4.5.12. 5-[3,4-Bis(phenylsulfanylmethyl)-2-furyl]-1,3-benzodioxole
(3b). A yellow oil, IR (KBr, cmꢁ1) 3058, 1767, 1667, 1582, 1487, 1440,
1335, 1299, 1249, 1156, 1100, 1039, 934, 879, 814, 743, 691, 486; 1H
13C NMR (150 MHz, CDCl3)
d 13.9 (q), 19.4 (t), 29.0 (t), 31.8 (t), 63.2
(t), 70.4 (t), 115.4 (s), 115.6 (d), 115.7 (d), 124.2 (s), 126.7 (d), 128.1
(d), 128.2 (d), 128.9 (dꢂ2), 130.4 (dꢂ2), 136.2 (s), 139.9 (d), 151.0 (s),
161.5 (s), 163.1 (s); MS m/z 370 (Mþ), 297 (MþꢁOCH2CH2CH2CH3),
261 (MþꢁSPh). Anal. Calcd for C22H23O2SF: C, 71.32; H, 6.26. Found:
C, 71.18; H, 6.25.
NMR (600 MHz, CDCl3)
d 3.96 (2H, s, SCH2), 4.18 (2H, s, SCH2), 5.91
(2H, s, OCH2O), 6.80 (1H, d, J¼7.8 Hz, ArH), 7.05e7.07 (2H, m, ArH),
7.15e7.19 (3H, m, ArH and furyl H), 7.21e7.25 (4H, m, ArH),
7.30e7.33 (4H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 27.7 (t), 29.0
(t), 101.1 (t), 106.8 (d), 108.5 (d), 114.3 (s), 120.3 (d), 122.5 (s), 124.6
(s), 126.4 (d), 126.6 (d), 128.8 (dꢂ2), 128.9 (dꢂ2), 129.9 (dꢂ2), 130.4
(dꢂ2), 135.9 (s), 135.9 (s), 139.5 (d), 147.3 (s), 147.8 (s), 151.5 (s); MS
m/z 432 (Mþ); high resolution mass calcd for C25H20O3S2: 432.0854,
found m/z 432.0848.
4.5.17. 4-[3,4-Bis(phenylsulfanylmethyl)furan-2-yl]-1-fluorobenzene
(3c). A yellow oil, IR (KBr, cmꢁ1) 3387, 1504, 1480, 1438, 1232, 1158,
1091, 1061, 1024, 838, 739, 690; 1H NMR (600 MHz, CDCl3)
d 3.99
(2H, s, SCH2), 4.19 (2H, s, SCH2), 7.05e7.08 (2H, m, ArH), 7.12e7.28
(7H, m, ArH and furyl H), 7.32e7.35 (4H, m, ArH), 7.52e7.54 (2H, m,
4.5.13. 5-[4-(Methoxyethoxymethyl)-3-(phenylsulfanylmethyl)-2-
furyl]-1,3-benzodioxole (2bb). A yellow oil: IR (KBr, cmꢁ1) 3423,
2924, 2361, 2342, 1764, 1503, 1488, 1440, 1357, 1238, 1094, 1038,
ArH); 13C NMR (150 MHz, CDCl3)
d 27.8 (t), 29.0 (t), 115.2 (s), 115.6
(d), 115.8 (d), 122.7 (s), 126.5 (d), 126.8 (d), 128.1 (d), 128.2 (d), 128.9
(dꢂ2), 129.0 (dꢂ2), 130.1 (dꢂ2), 130.6 (dꢂ2), 135.7 (s), 135.9 (s),
140.0 (d), 150.9 (s), 161.4 (s), 163.1 (s); MS m/z 406 (Mþ), 297
934, 813, 741, 691, 421; 1H NMR (600 MHz, CDCl3)
d 3.27 (3H, s,

1574
N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
(MþꢁSPh). Anal. Calcd for: C24H19FOS2; C, 70.91; H, 4.71. Found: C,
(d), 126.7 (d), 127.4 (d), 128.8 (dꢂ2), 130.8 (dꢂ2), 132.3 (s), 136.0 (s),
139.9 (d), 147.5 (s); MS m/z 360 (Mþ), 301 (MþꢁCH2CH2OMe), 251
(MþꢁSPh). Anal. Calcd for C19H20O3S2: C, 63.30; H, 5.59. Found: C,
62.92; H, 5.53.
70.77; H, 4.80.
4.5.18. 4-[4-(Methoxyethoxymethyl)-3-(phenylsulfanylmethyl)furan-
2-yl]-1-fluorobenzene (2cb). A yellow oil; IR (KBr, cmꢁ1) 3060, 2925,
2874, 1600, 1504, 1481, 1439, 1354, 1233, 1199, 1159, 1131, 1092,
1025, 951, 840, 814, 739, 691, 624, 596; 1H NMR (600 MHz, CDCl3)
4.6. Reaction of 4-[1-(propargyloxy)-3-(phenylsulfanyl)prop-
2-yn-1-yl]-1-methoxybenzene (1a) with sodium p-methoxy-
phenoxide, typical procedure
d
3.36 (3H, s, OMe), 3.54e3.56 (2H, m, OCH2), 3.62e3.63 (2H, m,
OCH2), 4.19 (2H, s, OCH2), 4.49 (2H, s, SCH2), 7.05e7.08 (2H, m, ArH),
7.18e7.27 (3H, m, ArH), 7.35 (2H, d, J¼7.6 Hz, ArH), 7.41 (1H, s, furyl
H), 7.55 (2H, dd, J¼5.5 and 9.0 Hz, ArH); 13C NMR (150 MHz, CDCl3)
Sodium 2-naphthoxide (prepared from 2-naphthol (1.44 g,
10.0 mmol) and 5 M sodium methoxide (1.0 mL, 5.0 mmol) in 1,4-
d
28.9 (t), 58.9 (q), 63.5 (t), 69.3 (t), 71.8 (t), 115.4 (s), 115.5 (d), 115.7
(d), 123.7 (s), 126.6 (d), 126.9 (s), 128.0 (d), 128.1 (d), 128.8 (dꢂ2),
dioxane (9.0 mL)) (1.76 mL) were added dropwise to
dioxane (1.0 mL) solution of 4-[1-(propargyloxy)-3-(phenyl-
sulfanyl)prop-2-yn-1-yl]-1-methoxybenzene (1a) (50 mg,
a 1,4-
130.4 (dꢂ2), 136.0 (s), 140.1 (d), 151.0 (s), 162.2 (d, J¼247 Hz); MS m/
z
372 (Mþ), 313 (MþꢁCH2CH2OMe), 297 (MþꢁOCH2
CH2OMe), 263 (MþꢁSPh). Anal. Calcd for C21H21O3SF: C, 67.72; H,
0.17 mmol) at room temperature. The reaction mixture was stirred
under reflux condition. The cooled mixture was poured into water
(50 mL). The organic layer was separated and the aqueous layer was
extracted with ether. The combined organic layer was dried over
MgSO4. The solvent was removed under reduced pressure. The
residue was purified by the preparative TLC on silica gel eluting
with AcOEten-hexane (1:20) to give 2-(p-methoxyphenyl)-4-(1-
naphthoxymethyl)-3-(phenylsulfanylmethyl)furan (4aa) (75 mg,
64%) as a brown oil.
5.68. Found: C, 67.58; H, 5.64.
4.5.19. 2-(p-Fluorophenyl)-3-(phenylsulfanylmethyl)furan-3-yl-me-
thoxyethanol (2cc). A yellow oil: IR (KBr, cmꢁ1) 3436, 2927, 2864,
1600, 1504, 1481, 1439, 1354, 1233, 1159, 1099, 1062, 1025, 951, 892,
839, 741, 691; 1H NMR (600 MHz, CDCl3)
d 2.27 (1H, s, OH),
3.60e3.61 (2H, m, OCH2), 3.75e3.76 (2H, m, OCH2), 4.17 (2H, s,
OCH2), 4.48 (2H, s, SCH2), 7.06e7.09 (2H, m, ArH), 7.21e7.23 (1H, m,
ArH), 7.25e7.29 (2H, m, ArH), 7.37 (2H, d, J¼6.8 Hz, ArH), 7.42 (1H, s,
furyl H), 7.57e7.59 (2H, m, ArH); 13C NMR (150 MHz, CDCl3)
d
29.2
4.6.1. 1-Methoxy-4-[4-(1-naphthoxymethyl)-3-(phenylsulfanylmethyl)-
furan-2-yl]benzene (4aa). A brown oil, IR (KBr, cmꢁ1) 3424, 2928,
1763, 1628, 1600, 1509, 1464, 1305, 1254, 1215, 1176, 1119, 1027, 835,
(t), 61.8 (t), 63.4 (t), 71.4 (t), 115.2 (s), 115.6 (d), 115.8 (d), 123.7 (s),
126.8 (s), 126.8 (d), 128.1 (d), 128.2 (d), 129.0 (dꢂ2), 130.4 (dꢂ2),
135.9 (s), 140.1 (d), 151.2 (s), 162.3 (d, J¼247 Hz); MS m/z 358 (Mþ),
249 (MþꢁSPh), 218 (MþꢁSPhꢁOH). Anal. Calcd for C20H19O3SF: C,
67.02; H, 5.34. Found: C, 66.99; H, 5.36.
746, 691; 1H NMR (600 MHz, CDCl3)
d 3.82 (3H, s, OMe), 4.22 (2H, s,
SCH2), 5.04 (2H, s, OCH2), 6.92 (2H, d, J¼8.9 Hz, ArH), 7.17e7.23 (4H,
m, ArH), 7.31e7.35 (3H, m, ArH), 7.42e7.45 (2H, m, ArH), 7.51 (1H, s,
furyl H), 7.55 (2H, d, J¼8.9 Hz, ArH), 7.72e7.77 (3H, m, ArH); 13C
4.5.20. 2-[4-(Butoxymethyl)-3-(phenylsulfanylmethyl)furan-2-yl]
thiophene (2da). A yellow oil: IR (KBr, cmꢁ1) 3434, 2957, 2930,
2361, 2342, 1583, 1480, 1483, 1362, 1276, 1231, 1150, 1092, 1025,
NMR (150 MHz, CDCl3) d 29.5 (t), 55.3 (q), 61.2 (t), 107.3 (d), 114.2
(dꢂ2), 114.3 (s), 118.9 (d), 122.7 (s), 123.4 (s), 123.8 (d), 126.4 (d),
126.7 (d), 126.8 (d), 127.6 (d), 127.9 (dꢂ3), 128.9 (dꢂ2), 129.2 (s),
129.4 (d), 130.8 (d), 134.5 (s), 136.0 (s), 139.9 (d), 152.2 (s), 156.6 (s),
159.4 (s); MS m/z 452 (Mþ), 343 (MþꢁSPh). Anal. Calcd for
C29H24O3S: C, 76.97; H, 5.35. Found: C, 76.76, H, 5.34.
1016, 929, 913, 848, 739, 692; 1H NMR (600 MHz, CDCl3)
d 0.89 (3H,
t, J¼7.3 Hz, CH3), 1.33e1.40 (2H, m, CH2), 1.54e1.59 (2H, m, CH2),
3.45 (2H, t, J¼6.6 Hz, OCH2), 4.22 (2H, s, OCH2), 4.34 (2H, s, SCH2),
7.03e7.04 (1H, m, ArH), 7.19e7.28 (5H, m, ArH), 7.33 (1H, s, furyl H),
7.37 (2H, d, J¼8.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d
13.9 (q),
4.6.2. 5-[4-(p-Methoxyphenoxymethyl)-3-(phenylsulfanylmethyl)fu-
ran-2-yl]-1,3-benzdioxole (4ba). White powders, mp 76e79 ꢀC, IR
(KBr, cmꢁ1) 2901, 1507, 1486, 1450, 1439, 1377, 1348, 1295, 1229,
1181, 1153, 1107, 1039, 935, 867, 822, 739, 691; 1H NMR (600 MHz,
19.4 (t), 29.0 (t), 31.7 (t), 63.1 (t), 70.3 (t), 115.7 (s), 124.2 (s), 124.3
(d), 125.2 (d), 126.7 (d), 127.4 (d), 128.8 (dꢂ2), 130.8 (dꢂ2), 132.4 (s),
136.1 (s), 139.6 (d), 147.4 (s); MS m/s 358 (Mþ), 285
(MþꢁOCH2CH2CH2CH3), 249 (MþꢁSPh). Anal. Calcd for
C20H22O2S2: C, 67.00; H, 6.18. Found: C, 66.74; H, 6.11.
CDCl3) d 3.77 (3H, s, OMe), 4.17 (2H, s, SCH2), 4.89 (2H, s, OCH2), 5.98
(2H, s, OCH2O), 6.82e6.84 (3H, m, ArH), 6.89 (2H, d, J¼9.0 Hz, ArH),
7.07 (1H, br s, ArH), 7.09 (1H, dd, J¼1.0 and 8.0 Hz, ArH), 7.19e7.25
(3H, m, ArH), 7.32 (2H, d, J¼9.0 Hz, ArH), 7.44 (1H, s, furyl H); 13C
4.5.21. 2-[3,4-Bis(phenysulfanylmethyl)furan-2-yl]thiophene
(3d). IR (KBr, cmꢁ1) 3073, 3057, 2923, 1777, 1583, 1480, 1437, 1229,
NMR (150 MHz, CDCl3) d 29.4 (t), 55.7 (q), 61.8 (t),101.2 (t),107.1 (d),
1148, 1090, 1024, 846, 738, 690; 1H NMR (600 MHz, CDCl3)
d
3.91
108.6 (d), 114.6 (s), 114.6 (dꢂ2), 116.0 (dꢂ2), 120.6 (d), 123.0 (s),
124.7 (s), 126.8 (d), 128.9 (dꢂ2), 130.8 (dꢂ2), 135.9 (s), 139.9 (d),
147.4 (s), 147.9 (s), 151.9 (s), 152.7 (s), 154.1 (s); MS m/z 446 (Mþ),
337 (MþꢁSPh), 323 (MþꢁOC6H4OMe). Anal. Calcd for C26H22O5S: C,
69.94; H, 4.97. Found: C, 69.45, H, 4.74.
(2H, s, SCH2), 4.24 (2H, s, SCH2), 7.01e7.04 (1H, m, ArH), 7.16e7.26
(9H, m, ArH and furyl H), 7.31 (2H, d, J¼6.9 Hz, ArH), 7.36 (2H, d,
J¼7.6 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 27.8 (t), 29.0 (t), 115.4
(s), 122.8 (s), 124.3 (d), 125.2 (d), 126.6 (d), 126.9 (d), 127.4 (d), 128.9
(dꢂ3), 130.2 (dꢂ3), 131.0 (dꢂ2), 132.3 (s), 135.7 (s), 135.8 (s), 139.7
(d), 147.4 (s); MS m/z 394 (Mþ), 285 (MþꢁSPh). Anal. Calcd for
C22H18OS3: C, 66.97; H, 4.60. Found: C, 66.60, H, 4.72.
4.6.3. 5-[4-(p-tert-Butylphenoxymethyl)-3-(phenylsulfanylmethyl)-
furan-2-yl]-1,3-benzodioxole (4bb). A yellow oil, IR (KBr, cmꢁ1
)
2961, 1765, 1607, 1582, 1511, 1504, 1486, 1449, 1439, 1363, 1295,
4.5.22. 2-[4-(Methoxyethoxymethyl)-3-(phenylsulfanylmethyl)fu-
ran-2-yl]thiophene (2db). An orange oil; IR (KBr, cmꢁ1) 3425, 3073,
2874, 1684, 1637, 1582, 1480, 1438, 1409, 1354, 1275, 1240, 1198,
1237, 1184, 1154, 1117, 1039, 936, 866, 829, 739, 691, 553; 1H NMR
(600 MHz, CDCl3) d 1.30 (9H, s, t-Bu), 4.17 (2H, s, SCH2), 4.92 (2H, s,
OCH2), 5.96 (2H, s, OCH2O), 6.83 (1H, d, J¼8.3 Hz, ArH), 6.90 (2H, d,
J¼8.9 Hz, ArH), 7.07 (1H, br s, ArH), 7.08 (1H, d, J¼8.2 Hz, ArH),
7.18e7.23 (3H, m, ArH), 7.29e7.31 (4H, m, ArH), 7.44 (1H, s, furyl H);
1091, 1024, 847, 739, 692; 1H NMR (600 MHz, CDCl3)
d 3.36 (3H, s,
OMe), 3.54e3.55 (2H, m, OCH2), 3.56e3.61 (2H, m, OCH2), 4.23 (2H,
s, OCH2), 4.43 (2H, s, SCH2), 7.04 (1H, dd, J¼3.4 and 4.8 Hz, ArH),
7.20e7.27 (4H, m, ArH), 7.29 (1H, d, J¼3.8 Hz, ArH), 7.35 (1H, s, furyl
13C NMR (150 MHz, CDCl3)
101.2 (t), 107.0 (d), 108.5 (d), 114.3 (dꢂ2), 114.6 (s), 120.6 (d), 123.0
(s), 124.6 (s), 126.2 (dꢂ2), 126.8 (d), 128.9 (dꢂ2), 130.8 (dꢂ2), 135.8
(s), 139.9 (d), 143.7 (s), 147.4 (s), 147.9 (s), 151.9 (s), 156.3 (s); MS m/z
d
29.3 (t), 31.5 (qꢂ3), 34.1 (s), 61.0 (t),
H), 7.37 (2H, d, J¼8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 29.0 (t),
59.0 (q), 63.4 (t), 69.2 (t), 71.9 (t), 115.6 (s), 123.8 (s), 124.4 (d), 125.2

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1575
472 (Mþ), 363 (MþꢁSPh), 323 (MþꢁOPhꢁt-Bu); high resolution
mass calcd for C29H28O4S; 472.1708; found m/z 472.1779.
7.19e7.24 (4H, m, ArH), 7.24e7.34 (5H, m, ArH), 7.42 (1H, s, furyl H);
13C NMR (150 MHz, CDCl3)
d
29.2 (t), 31.4 (qꢂ3), 34.1 (s), 60.8 (t),
114.2 (dꢂ2), 115.6 (s), 123.1 (s), 124.5 (d), 125.4 (d), 126.2 (dꢂ2),
126.9 (d), 127.4 (d), 128.9 (dꢂ2), 131.2 (dꢂ2), 132.2 (s), 135.6 (s),
140.0 (d), 143.8 (s), 147.6 (s), 156.2 (s); MS m/z 434 (Mþ), 325
(MþꢁSPh), 285(MþꢁOC6H4t-Bu). Anal. Calcd for C26H26O2S2: C,
71.85; H, 6.03. Found: C, 71.54, H, 5.87.
4.6.4. 1-Fluoro-4-[4-(p-tert-butylphenoxymethyl)-3-(phenylsulfanyl-
methyl)furan-2-yl]benzene (4ca). A brown oil, IR (KBr, cmꢁ1) 3429,
2962, 2867, 1602, 1505, 1480, 1438, 1364, 1297, 1237, 1184, 1159,
1024, 1013, 950, 836, 738, 691; 1H NMR (600 MHz, CDCl3)
d 1.31
(9H, s, t-Bu), 4.17 (2H, s, SCH2), 4.93 (2H, s, OCH2), 6.90 (2H, d,
J¼8.9 Hz, ArH), 7.05e7.09 (2H, m, ArH), 7.17e7.28 (3H, m, ArH),
7.30e7.33 (4H, m, ArH), 7.48 (1H, s, furyl H), 7.54 (2H, dd, J¼5.4 and
4.6.9. 2-[4-(2-Naphthoxymethyl)-3-(phenylsulfanylmethyl)furan-2-
yl]thiophene (4dc). Colorless prisms, mp 92 ꢀC, IR (KBr, cmꢁ1) 3056,
2926, 2854, 1714, 1628, 1599, 1509, 1465, 1438, 1389, 1255, 1215,
1177, 1150, 1119, 1008, 915, 837, 745, 704, 693, 476, 434, 416; 1H
9.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d
29.1 (t), 31.5 (qꢂ3), 34.1
(s), 60.9 (t), 114.3 (dꢂ2), 115.4 (s), 115.6 (d), 115.8 (d), 123.1 (s), 126.3
(dꢂ2), 126.9 (d), 128.2 (d), 128.3 (d), 128.9 (dꢂ2), 130.9 (dꢂ2), 135.6
(s), 140.4 (d), 143.8 (s), 151.2 (s), 156.3 (s), 161.5 (s), 163.2 (s); MS m/z
446 (Mþ), 337 (MþꢁSPh). Anal. Calcd for C28H27O2FS; C, 75.31; H,
6.09. Found: C, 74.90; H, 5.97.
NMR (600 MHz, CDCl3) d 4.24 (2H, s, SCH2), 4.96 (2H, s, OCH2), 7.06
(1H, dd, J¼4.1 and 4.8 Hz, ArH), 7.15e7.22 (5H, m, naphtyl H1 and,
H3, thiophenyl Hmeta thiophenyl Hmeta and Hpara), 7.26 (1H, d,
J¼4.2 Hz, thienyl H3), 7.31 (1H, dd, J¼1.2 and 6.2 Hz, thienyl H5),
7.31e7.38 (3H, m, thiophenyl Hortho and naphtyl H6), 7.45 (1H, ddd,
J¼1.2, 6.9, 8.0, naphtyl H7), 7.46 (1H, s, furyl H5), 7.73 (1H, d,
J¼8.3 Hz, naphtyl H8), 7.74 (1H, d, J¼9.7 Hz, naphtyl H4), 7.77 (1H,
4.6.5. 1-Fluoro-4-[4-(p-methoxyphenoxymethyl)-3-(phenyl-
sulfanylmethyl)furan-2-yl]benzene (4cb). A yellow oil, IR (KBr, cmꢁ1
)
3059, 2933, 2832, 2360, 1600, 1506, 1480, 1465, 1439, 1229, 1159,
d, J¼8.3 Hz, naphtyl H5); 13C NMR (150 MHz, CDCl3)
d 29.4 (SCH2),
1013, 838, 825, 793, 738, 691; 1H NMR (600 MHz, CDCl3)
d
3.77 (3H,
60.9 (OCH2), 107.1 (naphtyl C1), 115.7 (furyl C4), 118.9 (naphtyl C3),
122.9 (furyl C3), 123.8 (naphtyl C6), 124.6 (thienyl C2), 125.5
(thienyl C5), 126.4 (naphtyl C7), 126.8 (naphtyl C8), 127.0 (thio-
phenyl Cpara), 127.5 (thienyl C4), 127.6 (naphtyl C5), 128.9 (thio-
phenyl Cmeta), 129.1 (naphtyl C4a), 129.5 (naphtyl C4), 131.4
(thiophenyl Cortho), 132.1 (thienyl C2), 134.4 (naphtyl C8a), 135.5
(thiophenyl Cipso), 140.1 (furyl C5), 147.6 (furyl C2), 156.4 (naphtyl
C2); MS m/z 428 (Mþ), 319 (MþꢁSPh), 301 (MþꢁC10H7), 284
(MþꢁOC10H7). Anal. Calcd for C26H20O2S2: C, 72.87; H, 4.70. Found:
C, 72.77; H, 4.67.
s, OMe), 4.17 (2H, s, SCH2), 4.90 (2H, s, OCH2), 6.83 (2H, d, J¼6.9 Hz,
ArH), 6.90 (2H, d, J¼6.9 Hz, ArH), 7.07 (2H, t, J¼8.9 Hz, ArH),
7.18e7.24 (3H, m, ArH), 7.31e7.32 (2H, m, ArH), 7.47 (1H, s, furyl H),
7.54e7.56 (2H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 29.3 (t), 55.7
(q), 61.7 (t), 114.6 (dꢂ2), 115.3 (s), 115.6 (d), 115.7 (d), 116.0 (dꢂ2),
123.1 (s), 126.7 (s), 126.9 (d), 128.2 (d), 128.3 (d), 128.9 (dꢂ2), 130.9
(dꢂ2), 135.7 (s), 140.3 (d), 151.2 (s), 152.6 (s), 161.5 (s), 163.2 (s); MS
m/z 420 (Mþ), 311 (MþꢁSPh), 297(MþꢁOCH2SPh). Anal. Calcd for
C25H21O3FS; C, 71.41; H, 5.03. Found: C, 71.59, H, 5.14.
4.6.6. 1-Fluoro-4-[4-(1-naphthoxymethyl)-3-(phenylsulfanylmethyl)
4.6.10. X-ray crystallographic analysis. Single crystals of product
4dc were obtained as colorless prisms by slow crystallization from
a mixture of CH2Cl2 and n-hexane. Data of 4dc were taken on
furan-2-yl]benzene (4cc). Colorless prisms, mp 98 ꢀC; IR (KBr, cmꢁ1
)
3057, 2927, 2870, 1628, 1599, 1504, 1464, 1438, 1390, 1256, 1215,
1177, 1158, 1119, 1095, 1062, 1009, 951, 915, 837, 811, 746, 691, 620;
Rigaku RAXIS RAPID imaging plate area detector with graphite
1H NMR (600 MHz, CDCl3)
d
4.19 (2H, s, SCH2), 5.04 (2H, s, OCH2),
monochromated Mo-Ka radiation (
l
¼0.71075 A). A total of 10,416
ꢀ
7.07 (2H, t, J¼8.9 Hz, ArH), 7.16e7.22 (5H, m, ArH), 7.30e7.35 (3H,
reflections (4758 unique, Rint¼0.021) were collected at a tempera-
m, ArH), 7.43e7.45 (1H, m, ArH), 7.52 (1H, s, furyl H), 7.55e7.57 (2H,
ture of 23 ꢀC to a maximum 2 value of 55ꢀ. The structure of 4dc
q
m, ArH), 7.72e7.77 (3H, m, ArH); 13C NMR (150 MHz, CDCl3)
d
29.4
was solved by direct method with SIR97, and full-matrix least-
squares refinement on F2 was employed with anisotropic thermal
parameters for all non-hydrogen atoms. All the calculations were
performed using a CrystalStructure 3.8 crystal structure analysis
package, Rigaku and Rigaku/MSC. The ORTEP drawing of 4dc is
shown in Fig. 1.
(t), 61.0 (t), 107.2 (d), 115.5 (s), 115.6 (d), 115.8 (d), 118.9 (d), 122.8 (s),
123.8 (d), 126.4 (d), 126.7 (s), 126.8 (d), 127.0 (d), 127.6 (d), 128.2 (d),
128.3 (d), 128.9 (dꢂ2), 129.1 (s), 129.5 (d), 131.0 (dꢂ2), 134.4 (s),
135.6 (s), 140.4 (d), 151.2 (s), 156.4 (s), 161.6 (s); MS m/z 440 (Mþ),
331 (MþꢁSPh). Anal. Calcd for C28H21O2FS: C, 76.34; H, 4.80. Found:
C, 76.14, H, 4.86.
ꢀ
Crystal data for 4dc; triclinic, space group P-1, a¼5.2424(4) A,
ꢀ
ꢀ
a
b¼14.6960(12) A, c¼14.8241(15) A,
¼71.557(3)ꢀ,
b
¼89.034(3)ꢀ,
3
ꢀ
4.6.7. 2-[4-(p-Methoxyphenoxymethyl)-3-(phenylsulfanylmethyl)fu-
ran-2-yl]thiophene (4da). A brown oil, IR (KBr, cmꢁ1) 2360, 1509,
1479, 1438, 1293, 1238, 1207, 1148, 1108, 1034, 999, 988, 846, 828,
g
¼77.493(2)ꢀ, V¼1056.06(16) A , Z¼2,
m
(Mo
K
a
)¼2.73 cmꢁ1
,
F(000)¼460, Dc¼1.367 g/cm3, crystal dimensions: 0.20ꢂ0.10ꢂ
0.10 mm. Final R1 [I>2.00s>(I)], R (all reflections) and Rw2 (all re-
735, 692; 1H NMR (600 MHz, CDCl3)
d
3.78 (3H, s, OMe), 4.23 (2H, s,
flections) values were 0.0629, 0.1148 and 0.2083, respectively. The
SCH2), 4.83 (2H, s, OCH2), 6.83 (2H, d, J¼9.0 Hz, ArH), 6.88 (2H, d,
J¼8.9 Hz, ArH), 7.06 (1H, dd, J¼4.1 and 5.5 Hz, ArH), 7.19e7.26 (4H,
m, ArH), 7.31 (1H, d, J¼4.8 Hz, ArH), 7.35 (2H, d, J¼6.2 Hz, ArH), 7.41
maximum and minimum peaks in the difference map were
ꢁ ꢀꢁ3
1.17 e
ꢁ ꢀꢁ3
A
and ꢁ1.15 e
A
, respectively. The data of 4dc has been
deposited to the Cambridge Crystallographic Data Centre as sup-
plementary publication number CCDC 841797. For further details on
the crystal structure, see the CIF file of compound 4dc.
(1H, s, furyl H); 13C NMR (150 MHz, CDCl3)
d 29.3 (t), 55.7 (q), 61.7
(t), 114.6 (dꢂ2), 115.6 (s), 116.0 (dꢂ2), 123.2 (s), 124.6 (d), 125.4 (d),
127.0 (d), 127.5 (d), 128.9 (dꢂ2), 131.2 (dꢂ2), 132.2 (s), 135.6 (s),
140.0 (d), 147.6 (s), 152.6 (s), 154.2 (s); MS m/z 408 (Mþ), 299
(MþꢁSPh), 285 (MþꢁOC6H4OMe). Anal. Calcd for C23H20O3S2: C,
67.62; H, 4.93. Found: C, 67.27; H, 5.03.
4.6.11. 2-[4-(p-Methoxyphenoxymethyl)-3-(phenylsulfanylmethyl)-
2-furyl]-1,3,5-trimethylbenzene (4ea). A yellow oil, IR (KBr, cmꢁ1
)
2921, 2853, 2360, 2342, 1507, 1480, 1464, 1439, 1376, 1228, 1180,
1137, 1039, 824, 740, 690; 1H NMR (600 MHz, CDCl3)
d
2.02 (6H, s,
4.6.8. 2-[4-(4-tert-Butylphenoxymethyl)-3-(phenylsulfanylmethyl)-
furan-2-yl]thiophene (4db). Brown powders, mp 76 ꢀC, IR (KBr,
cmꢁ1) 2961, 1607, 1581, 1511, 1480, 1438, 1363, 1294, 1240, 1184,
1150, 1112, 1024, 1014, 847, 829, 738, 692; 1H NMR (600 MHz,
Meꢂ2), 2.32 (3H, s, Me), 3.77 (3H, s, OMe), 3.87 (2H, s, SCH2), 5.02
(2H, s, OCH2), 6.83 (2H, d, J¼9.0 Hz, ArH), 6.90e6.93 (4H, m, ArH),
7.12e7.15 (5H, m, ArH), 7.50 (1H, s, furyl H); 13C NMR (150 MHz,
CDCl3)
d
19.9 (qꢂ2), 21.2 (q), 28.6 (t), 55.7 (q), 62.7 (t), 114.6 (dꢂ2),
CDCl3)
d
1.30 (9H, s, t-Bu), 4.22 (2H, s, SCH2), 4.86 (2H, s, OCH2), 6.88
116.3 (dꢂ2),116.9 (s),121.8 (s),126.1 (d),126.4 (s),128.1 (dꢂ2),128.7
(dꢂ2), 129.5 (dꢂ2), 136.4 (s), 139.1 (s), 139.2 (sꢂ2), 140.6 (d), 151.3
(2H, d, J¼8.9 Hz, ArH), 7.04 (1H, dd, J¼3.4 and 4.8 Hz, ArH),

1576
N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
(s), 152.8 (s), 154.1 (s); MS m/z 444 (Mþ), 312 (MþꢁCH2SPh), 109
(MþꢁC22H23OS). Anal. Calcd for C28H28O3S: C, 75.64; H, 6.35.
Found: C, 75.31; H, 6.40.
ArH), 7.53 (1H, s, furyl H), 7.57 (2H, d, J¼8.9 Hz, ArH), 7.75e7.89 (4H,
m, ArH); 13C NMR (150 MHz, CDCl3)
9.5 (q), 55.3 (q), 61.1 (t), 107.0
d
(d), 114.0 (dꢂ2), 114.5 (s), 119.0 (d), 123.2 (s), 123.8 (d), 124.5 (s),
126.4 (d), 126.8 (d), 127.2 (dꢂ2), 127.7 (d), 129.1 (s), 129.5 (d), 134.5
(s), 139.5 (d), 150.1 (s), 156.7 (s), 158.7 (s); MS m/z 334 (Mþ), 201
(MþꢁOC10H7). Anal. Calcd for C23H20O3: C, 80.21; H, 5.85. Found: C,
79.93; H, 5.83.
4.6.12. 1-[4-(p-Methoxyphenoxymethyl)-3-(phenylselanylmethyl)fu-
ran-2-yl]naphthalene (4ga). A brown oil, IR (KBr, cmꢁ1) 3433, 2925,
2359, 2341, 1635, 1507, 1229, 1105, 1038, 1021, 825, 802, 777, 738,
469; 1H NMR (600 MHz, CDCl3)
d 3.75 (3H, s, OMe), 4.06 (2H, s,
SeCH2), 5.04 (2H, s, OCH2), 6.86 (2H, d, J¼9.0 Hz, ArH), 6.94e7.01
(4H, m, ArH), 7.08 (1H, t, J¼7.6 Hz, ArH), 7.27 (2H, d, J¼6.9 Hz, ArH),
7.36 (1H, d, J¼6.9 Hz, ArH), 7.40e7.49 (3H, m, ArH), 7.60 (1H, s, furyl
4.7.2. 5-[4-(p-Methoxyphenoxymethyl)-3-methylfuran-2-yl]-1,3-
benzodioxole (5ba). White powders, mp 134e136 ꢀC, IR (KBr, cmꢁ1
)
2901, 1507, 1487, 1471, 1387, 1289, 1258, 1228, 1039, 1012, 935, 872,
H), 7.82e7.86 (3H, m, ArH); 13C NMR (150 MHz, CDCl3)
d
21.2 (t),
819; 1H NMR (600 MHz, CDCl3)
d
2.23 (3H, s, Me), 3.77 (3H, s, OMe),
55.7 (q), 62.1 (t), 114.6 (dꢂ2), 116.0 (dꢂ2), 119.1 (s), 122.4 (s), 125.0
(d), 125.9 (d), 126.0 (d), 126.5 (d), 127.1 (d), 127.4 (s), 128.1 (d), 128.2
(d), 128.8 (dꢂ2), 129.4 (d), 129.9 (s), 132.0 (s), 133.5 (dꢂ2), 133.7 (s),
140.9 (d), 151.5 (s), 152.8 (s), 154.1 (s); MS m/z 500 (Mþ); high
resolution mass calcd for C29H24O3Se: 500.0884, found m/z
500.0487.
4.85 (2H, s, OCH2), 5.98 (2H, s, OCH2O), 6.84e6.87 (3H, m, ArH), 6.93
(2H, d, J¼9.0 Hz, ArH), 7.08e7.10 (2H, m, ArH), 7.44 (1H, s, furyl H);
13C NMR (150 MHz, CDCl3)
d 9.6 (q), 55.7 (q), 61.8 (t), 101.1 (t), 106.4
(d), 108.5 (d), 114.7 (dꢂ2), 114.9 (s), 115.9 (dꢂ2), 119.7 (d), 123.5 (s),
125.9 (s), 139.4 (d), 146.7 (s), 147.8 (s), 149.8 (s), 152.8 (s), 154.1 (s);
MS m/z 338 (Mþ), 215 (MþꢁOC6H4OMe). Anal. Calcd for C20H18O5 C,
71.00; H, 5.36. Found: C, 70.92; H, 5.32.
4.6.13. 5-[4-(p-Methoxyphenoxymethyl)-3-(phenylselanylmethyl)]-
1,3-benzodioxole (4ha). Pale yellow powders 76 ꢀC, IR (KBr, cmꢁ1
)
4.7.3. 5-[4-(p-tert-Butylphenoxymethyl)-3-methyl-2-furyl]-1ꢁ,31-
2922, 2852, 1507, 1486, 1464, 1451, 1438, 1295, 1228, 1181, 1105,
benzodioxole (5bb). White powders, mp 132e133 ꢀC, IR (KBr, cm
)
1039, 935, 876, 823, 792, 737, 691; 1H NMR (600 MHz, CDCl3)
d
3.77
2960, 2920, 2868, 1606, 1509, 1504, 1489, 1469, 1455, 1294, 1246,
(3H, s, OMe), 4.18 (2H, s, SeCH2), 4.86 (2H, s, OCH2), 5.96 (2H, s,
OCH2O), 6.80e6.84 (3H, m, ArH), 6.91 (2H, d, J¼9.0 Hz, ArH), 7.06
(2H, d, J¼8.2 Hz, ArH), 7.16e7.24 (3H, m, ArH), 7.41 (1H, s, furyl H),
1234, 1186, 1081, 1037, 1010, 1003, 936, 841, 812, 554; 1H NMR
(600 MHz, CDCl3)
d 1.31 (9H, s, t-Bu), 2.23 (3H, s, Me), 4.88 (2H, s,
OCH2), 5.98 (2H, s, OCH2O), 6.85 (1H, d, J¼8.3 Hz ArH), 6.93 (2H, d,
J¼8.9 Hz, ArH), 7.08 (1H, d, J¼8.2 Hz, ArH), 7.10 (1H, s, ArH), 7.32
(2H, d, J¼9.0 Hz, ArH), 7.45 (1H, s, furyl H); 13C NMR (150 MHz,
7.45 (2H, d, J¼6.8 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 21.6 (t),
55.7 (q), 61.7 (t), 101.1 (t), 106.9 (d), 108.5 (d), 114.6 (dꢂ2), 115.8 (s),
115.9 (dꢂ2), 120.4 (d), 122.9 (s), 124.7 (s), 127.5 (d), 129.0 (dꢂ2),
130.0 (s), 134.0 (dꢂ2), 139.8 (d), 147.2 (s), 147.9 (s), 151.3 (s), 152.7
(s), 154.1 (s); MS m/z 337 (MþꢁSePh). Anal. Calcd for C26H22O5Se: C,
63.29; H, 4.49. Found: C, 63.24; H, 4.53.
CDCl3)
d
9.6 (q), 31.5 (qꢂ3), 34.1 (s), 60.9 (t),101.1 (t),106.4 (d),108.4
(d), 114.2 (dꢂ2), 115.0 (s), 119.7 (d), 123.5 (s), 125.9 (s), 126.3 (dꢂ2),
139.5 (d), 143.7 (s), 146.7 (s), 147.8 (s), 149.8 (s), 156.4 (s); MS m/z
364 (Mþ), 231 (MþꢁC6H5-t-Bu). Anal. Calcd for C23H24O4: C, 75.80;
H, 6.64. Found: C, 76.07; H, 6.86.
4.6.14. 1-Fluoro-4-[4-(p-methoxyphenoxymethyl)-3-(phenyl-
selanylmethyl)furan-2-yl]benzene (4ia). A yellow oil, IR (KBr, cmꢁ1
)
4.7.4. 4-[40-(p-Methoxyphenoxymethyl)-3-methyl-2-furyl]-1-
fluorobenzene (5cb). White powders, mp 128e130 ꢀC, IR (KBr,
cmꢁ1) 2950, 2917, 2870, 2834, 1604, 1557, 1508, 1469, 1386, 1280,
1233, 1160, 1112, 1080, 1035, 1012, 900, 797, 622, 518; 1H NMR
2926, 2854, 2360, 2342, 1599, 1506, 1475, 1464, 1438, 1229, 1159,
1038, 1022, 837, 826, 738, 691; 1H NMR (600 MHz, CDCl3)
d
3.73
(3H, s, OMe), 4.16 (2H, s, SeCH2), 4.85 (2H, s, OCH2), 6.82 (2H, d,
J¼8.9 Hz, ArH), 6.88 (2H, d, J¼8.9 Hz, ArH), 7.03 (2H, d, J¼8.9 Hz,
ArH), 7.13e7.15 (2H, m, ArH), 7.17e7.20 (1H, m, ArH), 7.41 (1H, s,
furyl H), 7.43 (2H, d, J¼6.9 Hz, ArH), 7.48e7.50 (2H, m, ArH); 13C
(600 MHz, CDCl3)
d 2.25 (3H, s, Me), 3.77 (3H, s, OMe), 4.85 (2H, s,
OCH2), 6.86 (2H, d, J¼8.9 Hz ArH), 6.93 (2H, d, J¼9.0 Hz, ArH), 7.10
(2H, t, J¼9.0 Hz, ArH) 7.46 (1H, s, furyl H), 7.57 (2H, dd, J¼5.5 and
NMR (150 MHz, CDCl3)
d
21.3 (t), 55.5 (q), 61.5 (t), 114.5 (dꢂ2), 115.5
9.0 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 9.5 (q), 55.7 (q), 61.7 (t),
(d), 115.6 (d), 115.8 (dꢂ2), 116.5 (s), 122.9 (s), 126.8 (s), 127.5 (d),
127.9 (d), 128.0 (d), 128.9 (dꢂ2), 129.7 (s), 133.9 (dꢂ2), 140.2 (d),
150.4 (s), 152.5 (s), 154.0 (s), 161.3 (s); MS m/z 311 (MþꢁSePh); high
resolution mass calcd for C25H21O3FSe: 468.0634, found m/z
468.0717.
114.7 (dꢂ2),115.4 (d),115.6 (d),115.7 (s),115.9 (dꢂ2),123.6 (s),127.4
(d), 127.4 (d), 127.9 (s), 139.9 (d), 149.1 (s), 152.8 (s), 154.1 (s), 162.6
(s); MS m/z 312 (Mþ), 189 (MþꢁOC6H4OMe). Anal. Calcd for
C19H17O3F: C, 73.06; H, 5.49. Found: C, 72.75; H, 5.48.
4.7.5. 4-[2-(2-Naphthoxymethyl)-3-methyl-2-furyl]-1-fluorobenzene
(5cc). White powders, mp 144e147 ꢀC, IR (KBr, cmꢁ1) 3063, 2925,
2874, 2360, 1626, 1597, 1505, 1465, 1388, 1255, 1240, 1213, 1182,
1159, 1081, 1004, 825, 816, 808, 744, 626, 469; 1H NMR (600 MHz,
4.7. Desulfanylation of 1-methoxy-4-[4-(1-naphthoxymethyl)-
3-(phenylsulfanylmethyl)furan-2-yl]benzene (4aa) with
tributyltin hydride/AIBN
CDCl3)
d
2.28 (3H, s, Me), 5.03 (2H, s, CH2), 7.12 (2H, t, J¼9.0 Hz,
A
mixture of 4aa (70 mg, 0.15 mmol), tributyltin hydride
ArH), 7.20 (1H, dd, J¼2.0 and 8.9 Hz, ArH), 7.27 (1H, d, J¼2.1 Hz,
ArH), 7.35 (1H, t, J¼6.9 Hz, ArH), 7.45 (1H, t, J¼6.9 Hz, ArH), 7.54
(1H, s, furyl H), 7.60 (2H, dd, J¼5.3 and 9.0 Hz, ArH), 7.75e7.78 (3H,
(0.08 mL, 0.31 mmol), and AIBN (4.9 mg, 0.03 mmol) in toluene
(1.3 mL) was refluxed for 30 min. The cooled mixture was evapo-
rated and the residue was purified by preparative TLC on silica gel
eluting with AcOEten-hexane (1:40) to give 1-methoxy-4-[3-
(naphthoxymethyl)-4-methylfuran-2-yl]benzene (5aa) (31 mg,
60%) as white powders.
m, ArH); 13C NMR (150 MHz, CDCl3)
d 9.6 (q), 61.0 (t),107.0 (d),115.5
(d), 115.6 (d), 115.7 (s), 119.0 (d), 123.3 (s), 123.8 (d), 126.4 (d), 126.8
(d), 127.4 (d), 127.5 (d), 127.8 (s), 129.1 (s), 129.5 (dꢂ2), 134.4 (s),
140.0 (d), 149.2 (s), 156.6 (s), 161.3 (d, J¼247 Hz); MS m/z 332 (Mþ),
189 (Mþꢁnaphthoxy). Anal. Calcd for C22H17FO2: C, 79.50; H, 5.16.
Found: C, 79.82; H, 5.18.
4.7.1. 1-Methoxy-4-[3-(naphthoxymethyl)-4-methylfuran-2-yl]ben-
zene (5aa). White powders, mp 147e149 ꢀC, IR (KBr, cmꢁ1) 3445,
2925, 2854, 1762, 1713, 1630, 1601, 1512, 1463, 1362, 1254, 1216,
4.7.6. 2-[4-(p-Methoxyphenoxymethyl)-3-methylfuran-2-yl]-thio-
phene (5da). White powders, mp 97e98 ꢀC, IR (KBr, cmꢁ1) 3432,
2958, 2918, 2868, 2853, 1508, 1467, 1442, 1385, 1289, 1228, 1034,
1177, 835, 759; 1H NMR (600 MHz, CDCl3)
d 2.28 (3H, s, Me), 3.85
(3H, s, OMe), 5.03 (2H, s, OCH2), 6.96 (2H, d, J¼9.0 Hz, ArH), 7.21
(1H, dd, J¼2.8 and 8.9 Hz, ArH), 7.28 (1H, s, ArH), 7.44e7.47 (1H, m,
1012, 845, 824, 796, 771, 704; 1H NMR (600 MHz, CDCl3)
d 2.25 (3H,

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1577
s, Me), 3.77 (3H, s, OMe), 4.85 (2H, s, OCH2), 6.85 (2H, d, J¼9.0 Hz,
ArH), 6.92 (2H, d, J¼9.7 Hz, ArH), 7.08 (1H, dd, J¼4.2 and 4.8 Hz,
ArH), 7.23 (1H, d, J¼3.5 Hz, ArH), 7.26 (1H, d, J¼6.2 Hz, ArH), 7.41
4.8.1. 1-[3,4-Bis(phenylsulfanylmethyl)furan-2-yl]naphthalene
(3e). A pale yellow oil, IR (KBr, cmꢁ1) 3427, 1480, 1438, 1105, 1089,
1024, 802, 777, 738, 690; 1H NMR (600 MHz, CDCl3)
d 4.05 (2H, s,
(1H, s, furyl H); 13C NMR (150 MHz, CDCl3)
d
9.29 (q), 55.7 (q), 61.7
SCH2), 4.15 (2H, s, SCH2), 7.00e7.02 (3H, m, ArH), 7.12e7.13 (2H, m,
ArH), 7.15e7.17 (1H, m, ArH), 7.24 (2H, t, J¼7.6 Hz, ArH), 7.32e7.44
(7H, m, ArH and furyl H), 7.75 (1H, d, J¼8.9 Hz, ArH), 7.81 (2H, d,
(t), 114.7 (dꢂ2), 115.7 (s), 116.0 (dꢂ2), 123.0 (d), 123.5 (s), 124.1 (d),
127.3 (d), 133.6 (s), 139.6 (d), 146.1 (s), 152.7 (s), 154.1 (s); MS m/z
300 (Mþ), 193 (MþꢁC6H5OMe), 177 (MþꢁOC6H4OMe). Anal. Calcd
for C17H16O3S: C, 67.98; H, 5.37. Found: C, 67.75; H, 5.35.
J¼8.3 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 28.4 (t), 28.9 (t), 117.8
(s), 122.0 (s), 125.0 (d), 125.9 (d), 126.0 (d), 126.4 (d), 126.5 (d), 126.6
(d), 127.4 (s), 128.2 (dꢂ2), 128.7 (dꢂ2), 128.8 (dꢂ2), 129.4 (d), 130.3
(dꢂ2), 130.4 (dꢂ2), 132.0 (s), 133.7 (s), 135.6 (s), 135.9 (s), 140.7 (d),
151.8 (s); MS m/z 438 (Mþ), 329 (MþꢁSPh). Anal. Calcd for:
C28H22OS2: C, 76.68; H, 5.08. Found: C, 76.33, H, 5.15.
4.7.7. 2-[4-(tert-Butylphenoxymethyl)-3-methylfuran-2-yl]thio-
phene (5db). White powders, mp 99e101 ꢀC, IR (KBr, cmꢁ1) 3465,
2960, 2925, 2863, 2360, 2342, 1512, 1241, 1185, 1013, 829, 757, 697;
1H NMR (600 MHz, CDCl3)
d
1.31 (9H, s, Meꢂ3), 2.25 (3H, s, Me),
4.87 (2H, s, OCH2), 6.92 (2H, d, J¼8.9 Hz, ArH), 7.06 (1H, dd, J¼3.4
and 4.8 Hz, ArH), 7.23 (1H, d, J¼4.0 Hz, ArH), 7.26 (1H, d, J¼4.8 Hz,
ArH), 7.32 (2H, d, J¼8.9 Hz, ArH), 7.43 (1H, s, furyl H); 13C NMR
4.8.2. 4-[3,4-Bis(phenylsulfanylmethyl)furan-2-yl]-1-chlorobenzene
(3j). A pale yellow oil, IR (KBr, cmꢁ1) 3073, 3057, 2919, 2361, 2339,
1583, 1547, 1481, 1437, 1233, 1152, 1092, 1060, 1024, 1012, 947, 832,
(150 MHz, CDCl3)
d
9.3 (q), 31.5 (qꢂ3), 34.1 (s), 60.8 (t), 114.2 (dꢂ2),
737, 690, 614, 506, 487, 474; 1H NMR (600 MHz, CDCl3)
d 3.98 (2H, s,
115.8 (s), 123.0 (d), 123.5 (s), 124.1 (d), 126.3 (dꢂ2), 127.3 (d), 133.6
(s), 139.6 (d), 143.8 (s), 146.1 (s), 156.3 (s); MS m/z 326 (Mþ), 177
(MþꢁOC6H4et-Bu); high resolution mass calcd for C20H22O2S:
326.134028, found m/z 326.1330.
SCH2), 4.19 (2H, s, SCH2), 7.18e7.22 (1H, m, ArH), 7.24e7.28 (5H, m,
ArH and furyl H), 7.32e7.34 (7H, m, ArH), 7.49 (2H, d, J¼8.2 Hz,
ArH); 13C NMR (150 MHz, CDCl3)
d 27.8 (t), 29.1 (t), 116.0 (s), 122.9
(s), 126.6 (d), 127.0 (d), 127.4 (dꢂ2), 128.9 (dꢂ2), 128.9 (dꢂ2), 129.0
(dꢂ2), 130.1 (dꢂ2), 130.8 (dꢂ2), 133.6 (s), 135.6 (s), 135.8 (s), 140.3
(d), 150.6 (s); MS m/z 422 (Mþ), 313 (MþꢁSPh). Anal. Calcd for
C24H19OClS2: C, 68.15; H, 4.53. Found: C, 68.08; H, 4.56.
4.7.8. 2-[4-(1-Naphthoxymethyl)-3-methylfuran-2-yl]thiophene
(5dc). Pale yellow powders, mp 132e133 ꢀC, IR (KBr, cmꢁ1) 3113,
2918, 1625, 1596, 1508, 1461, 1378, 1256, 1213, 1183, 1158, 1117, 1003,
843, 751, 699, 475; 1H NMR (600 MHz, CDCl3)
d
2.29 (3H, s, Me),
4.8.3. 2-[3,4-Bis(phenylsulfanylmethyl)furan-2-yl]benzofuran (3k). A
pale yellow oil, IR (KBr, cmꢁ1) 3465, 3057, 2922, 1581, 1480, 1450,
1438, 1256, 1169, 1069, 1024, 881, 802, 738, 690, 477; 1H NMR
5.03 (2H, s, OCH2), 7.09 (1H, dd, J¼4.1 and 5.5 Hz, ArH), 7.20 (1H, dd,
J¼2.8 and 8.9 Hz, ArH), 7.25e7.29 (3H, m, ArH), 7.34e7.36 (1H, m,
ArH), 7.44e7.47 (1H, m, ArH), 7.50 (1H, s, furyl H) 7.75e7.79 (3H, m,
(600 MHz, CDCl3) d 3.98 (2H, s, SCH2), 4.43 (2H, s, SCH2), 6.78 (1H, s,
ArH); 13C NMR (150 MHz, CDCl3)
d
9.3 (q), 60.9 (t), 107.0 (d), 115.7
furyl H), 7.10e7.15 (3H, m, ArH), 7.18e7.22 (3H, m, ArH), 7.24e7.27
(3H, m, ArH), 7.32 (2H, d, J¼7.6 Hz, ArH), 7.36 (2H, dd, J¼1.4 and
8.3 Hz, ArH), 7.43 (1H, d, J¼7.6 Hz, ArH), 7.52 (1H, d, J¼7.6 Hz ArH);
(s), 118.9 (d), 123.1 (d), 123.3 (s), 123.8 (d), 124.1 (d), 126.4 (d), 126.8
(d), 127.3 (d), 127.7 (d), 129.1 (s), 129.5 (d), 133.6 (s), 134.4 (s), 139.7
(d), 146.2 (s), 156.6 (s); MS m/z 320 (Mþ), 269 (MþꢁC4H3S), 193
(MþꢁC10H7), 177 (MþꢁOC10H7). Anal. Calcd for C20H16O2S: C, 74.95;
H, 5.33. Found: C, 74.56; H, 5.08.
13C NMR (150 MHz, CDCl3)
d 27.7 (t), 28.6 (t), 102.7 (d), 111.1 (d),
118.8 (s), 120.9 (d), 122.9 (s), 123.1 (d), 124.5 (d), 126.6 (d), 127.0 (d),
128.1 (s), 128.7 (dꢂ2), 128.9 (dꢂ2), 130.2 (dꢂ2), 131.8 (dꢂ2), 135.1
(s),135.6 (s),141.2 (d),143.6 (s),147.6 (s),154.4 (s); MS m/z 428 (Mþ),
319 (MþꢁSPh); high resolution mass calcd for C26H20O2S2:
428.0905, found m/z 428.0919.
4.7.9. 1-[4-(p-Methoxyphenoxymethyl)-3-methyl-2-furyl]naphtha-
lene (5ga). A pale yellow oil, IR (KBr, cmꢁ1) 2948, 2925, 1507, 1464,
1441, 1379, 1224, 1010, 824, 803, 777; 1H NMR (600 MHz, CDCl3)
d
2.08 (3H, s, Me), 3.78 (3H, s, OMe), 4.93 (2H, s, OCH2), 6.87 (2H, d,
4.8.4. 4-[4-(n-Decanesulfanyl)-3-(phenylsulfanyl)-2-furyl]-1-methoxy-
benzene (3l). A yellow oil, IR (KBr, cmꢁ1) 2925, 2853,1766,1606,1584,
1507, 1480, 1465, 1440, 1306, 1253, 1177, 1064, 1033, 950, 834, 740,
J¼8.9 Hz, ArH), 6.97 (2H, d, J¼8.9 Hz ArH), 7.49e7.52 (4H, m, ArH),
7.62 (1H, s, furyl H), 7.87e7.88 (2H, m, ArH), 7.94e7.96 (1H, m, ArH);
13C NMR (150 MHz, CDCl3)
d
9.2 (q), 55.7 (q), 62.1 (t), 114.7 (dꢂ2),
690; 1H NMR (600 MHz, CDCl3)
d
0.88 (3H, t, J¼7.0 Hz, Me),1.25 (12H,
116.0 (dꢂ2), 118.0 (s), 122.9 (s), 125.1 (d), 126.0 (d), 126.1 (d), 126.3
(d), 128.1 (d), 128.3 (d), 128.5 (s), 128.9 (d), 131.9 (s), 133.8 (s), 140.6
(d), 150.0 (s), 152.9 (s), 154.1 (s); MS m/z 344 (Mþ), 221
(MþꢁOC6H4Me); high resolution mass calcd for C23H20O3:
344.1407, found m/z 344.1334.
br s, CH2), 1.35 (2H, br s, CH2), 1.54e1.57 (2H, m, CH2), 2.47 (2H, t,
J¼7.6 Hz, CH2), 3.60 (2H, s, CH2), 3.82 (3H, s, OMe), 4.25 (2H, s, CH2),
6.92 (2H, d, J¼8.9 Hz, ArH), 7.20e7.21 (1H, m, ArH), 7.25e7.28 (2H, m,
ArH), 7.31 (1H, s, ArH), 7.35e7.37 (2H, m, ArH), 7.53 (2H, d, J¼9.0 Hz,
ArH); 13C NMR (150 MHz, CDCl3)
d 14.1 (q), 22.7 (t), 24.8 (t), 28.9
(tꢂ2), 29.2 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.6 (t), 31.7 (t), 31.9 (t), 55.3
(q), 114.1 (dꢂ2), 123.0 (sꢂ2), 123.5 (s), 126.5 (d), 127.7 (dꢂ2), 128.9
(dꢂ2), 130.1 (dꢂ2), 136.4 (s), 139.1 (d),152.0 (s), 159.2 (s); MS m/z 482
(Mþ), 373 (MþꢁSPh); high resolution mass calcd for C29H38O2S2:
482.2313, found m/z 482.2288.
4.8. Preparation of 3,4-bis(phenylsulfanylmethyl)-2-(p-metho-
xyphenyl)furan (3a), typical procedure
Sodium benzenethiolateesodium methoxide solution (0.50 M,
1.20 mL, 0.58 mmol) (prepared from 5 M sodium methoxide
(1.0 mL) and benzenethiol (5.0 mmol) in MeOH (9.0 mL)) was added
4.8.5. 4-[2-(n-Decanesulfanyl)-1-(phenylsulfanyl)-3-(propargyloxy)prop-
1-en-3-yl]-1-methoxybenzene (8l). A yellow oil, IR (KBr, cmꢁ1
)
to
a
1,4-dioxane (0.80 mL) solution of 1-methoxy-4-[4-(2-
(1a)
3293, 2925, 2853, 2116, 1610, 1583, 1511, 1479, 1464, 1440, 1378,
propynyloxy)-3-(phenylsulfanyl)-2-propyn-1-yl]benzene
1304, 1249, 1173, 1086, 1036, 913, 880, 832, 744, 690, 666, 634; 1H
(71 mg, 0.23 mmol) at room temperature. The reaction mixture was
heated under refluxcondition for 13 min and thenpoured intowater
(50 mL). The organic layer was separated and the aqueous layer was
extracted with ether. The combined organic layer was dried over
MgSO4. The solvent was removed under reduced pressure. The
residue was purified by preparative TLC on silica gel eluting with
AcOEten-hexane (1:20) to give 3, 4-bis(phenylsulfanylmethyl)-2-
(4-methoxyphenyl)furan (3a) (70.3 mg, 73%) as a colorless oil.
NMR (600 MHz, CDCl3)
d
0.88 (3H, t, J¼7.0 Hz, Me), 1.24 (13H, br s,
CH2), 1.29 (2H, br s, CH2), 1.45e1.49 (2H, m, CH2), 2.43 (1H, t,
J¼2.5 Hz, acetylenic H), 2.59e2.62 (2H, m, CH2), 3.79 (3H, s, OMe),
4.09 (1H, dd, J¼2.1 and 15.8 Hz, OCH2), 4.18 (1H, dd, J¼2.1 and
15.8 Hz, OCH2), 5.17 (1H, s, OCH), 6.88 (2H, d, J¼8.9 Hz, ArH), 7.02
(1H, s, olefinic H), 7.25e7.27 (1H, m, ArH), 7.31e7.34 (3H, m, ArH),
7.43 (2H, d, J¼6.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 14.1 (q),
22.6 (t), 28.7 (t), 29.2 (t), 29.3 (t), 29.5 (t), 29.6 (t), 29.8 (t), 31.9 (t),

1578
N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
33.2 (t), 55.2 (q), 55.5 (t), 74.7 (d), 79.5 (s), 82.6 (d), 113.7 (dꢂ2),
127.0 (d), 128.8 (dꢂ2), 129.1 (dꢂ2), 130.0 (dꢂ2), 130.1 (s), 131.0 (s),
133.6 (d), 135.4 (s), 159.4 (s); MS m/z 482 (Mþ), 443
(Mþꢁpropargyl), 373 (MþꢁSPh); high resolution mass calcd for
C29H38O2S2: 482.2313, found m/z 482.2313.
139.5 (d), 148.5 (s); MS m/z 314 (Mþ), 205 (MþꢁPhS). Anal. Calcd for
C18H15ClOS: C, 68.67; H, 4.80. Found: C, 68.28; H, 4.87.
4.8.12. 2-(3,4-Dimethylfuran-2-yl)benzofuran (6k). A pale yellow
oil, IR (KBr, cmꢁ1) 3426, 2925, 2857, 1769, 1583, 1453, 1253, 1168,
1093, 1031, 880, 794, 750; 1H NMR (600 MHz, CDCl3)
d 2.00 (3H, d,
4.8.6. 4-(3,4-Dimethylfuran-2-yl)-1-methoxybenzene (6a). A pale
yellow oil, IR (KBr, cmꢁ1) 2956, 2928, 2837, 1760, 1610, 1511, 1462,
1442, 1381, 1302, 1251, 1179, 1093, 1034, 1003, 833, 608, 589, 528;
J¼1.4 Hz, Me), 2.28 (3H, s, Me), 6.79 (1H, s, furyl H), 7.20e7.26 (3H,
m, ArH), 7.50 (1H, d, J¼8.2 Hz, ArH), 7.55 (1H, d, J¼8.6 Hz, ArH); 13C
NMR (150 MHz, CDCl3) d 8.1 (q), 8.8 (q), 100.9 (d), 111.0 (d), 120.1 (s),
1H NMR (600 MHz, CDCl3)
d
1.98 (3H, s, Me), 2.14 (3H, s, Me),
120.7 (d), 122.8 (s), 123.0 (d), 123.9 (d), 129.0 (s), 139.1 (d), 141.6 (s),
149.1 (s), 152.3 (s); MS m/z 212 (Mþ); high resolution mass calcd for
C14H12O2: 212.0837, found m/z 212.0653.
3.82 (3H, s, OMe), 6.94 (2H, d, J¼7.6 Hz, ArH), 7.17 (1H, s, furyl H),
7.53 (2H, d, J¼7.5 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d 8.4 (q),
9.4 (q), 55.2 (q), 113.9 (dꢂ2), 115.3 (s), 122.6 (s), 125.1 (s), 126.8
(dꢂ2), 137.1 (d), 148.8 (s), 158.4 (s); MS m/z 202 (Mþ), 187
(MþꢁMe); high resolution mass calcd for C13H14O2: 202.0994;
found m/z 202.0921.
4.9. DBU-mediated cylization reaction of 4-oxahepta-1,6-
diyne (1a) with methyl N-Boc-L-tyrosine, typical procedure
DBU (12 mg, 0.08 mmol) was added to a solution of CH2Cl2
(1.0 mL) of 1a (20 mg, 0.06 mmol) and methyl N-Boc-tyrosine
(29 mg, 0.10 mmol) at room temperature. The reaction mixture was
heated under reflux condition for 2.5 h. The cooled mixture was
poured into water (50 mL) and the organic layer was separated. The
aqueous layer was extracted with ether. The combined organic
layer was dried over MgSO4. The solvent was removed under re-
duced pressure. The residue was separated by the preparative TLC
on silica gel eluting with AcOEten-hexane (1:5) to give O-[2-p-
methoxyphenyl-3-(phenylsulfanylmethyl)furyl-3-methyl]-N-Boc-
4.8.7. 5-(3,4-Dimethyl-2-furyl)-1,3-benzodioxole (6b). A colorless
oil: IR (KBr, cmꢁ1) 3435, 2923, 2894, 1503, 1487, 1450, 1290, 1254,
1228, 1080, 1040, 938, 871, 812, 685, 616; 1H NMR (600 MHz,
CDCl3)
d 1.98 (3H, s, Me), 2.13 (3H, s, Me), 5.97 (2H, s, OCH2O),
6.85 (1H, d, J¼8.3 Hz, ArH), 7.07 (1H, dd, J¼2.1 and 8.3 Hz, ArH),
7.09 (1H, d, J¼2.1 Hz, ArH), 7.17 (1H, s, furly H); 13C NMR
(150 MHz, CDCl3)
d 8.4 (q), 9.5 (q), 101.0 (t), 106.2 (d), 108.4 (d),
115.7 (s), 119.2 (d), 122.6 (s), 126.4 (s), 137.1 (d), 146.3 (s), 147.7
(s); MS m/z 216 (Mþ); high resolution mass calcd for C13H12O3:
216.07863, found m/z 216.0803.
L
-tyrosine methyl ester (16a) (26 mg, 72%) as a pale yellow oil.
IR (KBr, cmꢁ1) 3361, 2977, 1746, 1714, 1609, 1583, 1508, 1440,
4.8.8. 2-(3,4-Dimethylfuran-2-yl)thiophene (6d). A pale yellow oil,
IR (KBr, cmꢁ1) 3445, 2922, 2360, 2342, 1763, 1637, 1582, 1477, 1339,
1106, 1082, 1058, 1024, 849, 901, 691; 1H NMR (600 MHz, CDCl3)
1366, 1299, 1252, 1174, 1110, 1063, 1026, 951, 835, 741, 692; 1H NMR
(600 MHz, CDCl3)
d
1.42 (9H, s, Meꢂ3), 3.03 (2H, dq, J¼5.9 and
17.1 Hz, CH2), 3.71 (3H, s, Me), 3.83 (3H, s, Me), 4.19 (2H, s, CH2),
4.55 (1H, q, J¼7.6 Hz, CH), 4.92 (2H, s, CH2), 4.99 (1H, d, J¼8.2 Hz,
NH), 6.88 (2H, d, J¼8.3 Hz, ArH), 6.93 (2H, d, J¼8.9 Hz, ArH), 7.04
(2H, d, J¼8.3 Hz, ArH), 7.17e7.23 (3H, m, ArH), 7.31 (2H, d, J¼6.8 Hz,
ArH), 7.46 (1H, s, furyl H), 7.53 (2H, d, J¼8.9 Hz, ArH); 13C NMR
d
2.09 (3H, s, Me), 2.21 (3H, s, Me), 7.07 (1H, dd, J¼3.4 and 4.8 Hz,
ArH), 7.15 (1H, s, ArH), 7.22e7.25 (1H, m, ArH), 7.28e7.30 (1H, m,
ArH); high resolution mass calcd for C10H10OS: 178.0452, found m/z
178.0491.
(150 MHz, CDCl3)
d
28.3 (qꢂ3), 29.2 (t), 37.4 (t), 52.2 (q), 54.5 (d),
4.8.9. 1-(3,4-Dimethylfuran-2-yl)naphthalene (6e). A pale yellow
oil, IR (KBr, cmꢁ1) 3362, 3052, 2979, 2924, 1762, 1509, 1439, 1383,
1274, 1236, 1112, 965, 805, 778, 759; 1H NMR (600 MHz, CDCl3)
55.3 (q), 61.0 (t), 79.9 (s), 114.1 (dꢂ2), 114.9 (dꢂ2), 122.7 (s), 123.2
(s), 126.7 (d), 127.9 (dꢂ2), 128.3 (s), 128.9 (dꢂ2), 130.5 (dꢂ2), 136.0
(s), 139.9 (d), 152.2 (s), 155.1 (s), 157.6 (s), 159.3 (s), 172.4 (s); MS m/z
603 (Mþ); high resolution mass calcd for C34H37NO7S: 603.2290,
found m/z 603.2985.
d
1.98 (3H, s, Me), 2.07 (3H, s, Me), 7.35 (1H, s, furyl H), 7.47e7.51
(4H, m, ArH), 7.84e7.88 (2H, m, ArH), 7.85e7.87 (1H, m, ArH); 13C
NMR (150 MHz, CDCl3) 8.5 (q), 9.2 (q), 118.7 (s), 121.9 (s), 125.1(d),
d
125.9 (d), 126.2 (d), 126.3 (d), 127.7 (d), 128.2 (d), 128.5 (d), 129.2 (s),
132.0 (s), 133.9 (s), 138.3 (d), 149.0 (s); MS m/z 222 (Mþ). Anal. Calcd
for C16H14O: C, 86.45; H, 6.35. Found: C, 86.26; H, 6.37.
4.9.1. O-[2-p-Fluorophenyl-3-(phenylsulfanylmethyl)furyl-3-methyl]-N-
Boc- )
-tyrosine methyl ester (16c). A pale yellow oil, IR (KBr, cmꢁ1
L
3360, 2978, 2930, 1745, 1714, 1610, 1505, 1438, 1391, 1366, 1298,
1238, 1162, 1061, 1015, 951, 840, 815, 741, 692; 1H NMR (600 MHz,
4.8.10. 4-(4-Methyl-3-phenylsulfanylmethylfuran-2-yl)-1-fluoro-
CDCl3)
d
1.42 (9H, s, Meꢂ3), 3.03 (2H, dq, J¼6.2 and 17.1 Hz, CH2),
benzene (7c). Pale yellow powders, mp 47e50 ꢀC; IR (KBr, cmꢁ1
)
3.71 (3H, s, Me), 4.17 (2H, s, CH2), 4.55 (1H, q, J¼7.6 Hz, CH), 4.92
(2H, s, CH2), 4.98 (1H, d, J¼8.3 Hz, NH), 6.88 (2H, d, J¼8.2 Hz, ArH),
7.04e7.07 (2H, m, ArH), 7.18 (2H, t, J¼7.3 Hz, ArH), 7.22e7.25 (2H, m,
ArH), 7.44 (2H, d, J¼6.8 Hz, ArH), 7.47 (1H, s, furyl H), 7.50e7.52 (2H,
2925, 2854, 1585, 1557, 1505, 1481, 1438, 1233, 1157, 1077, 909, 836,
746, 692; 1H NMR (600 MHz, CDCl3)
d
2.33 (3H, s, Me), 3.93 (2H, s,
SCH), 7.08e7.11 (2H, m, ArH), 7.21e7.22 (2H, m, ArH), 7.27e7.30
(2H, m, ArH), 7.35 (2H, d, J¼8.3 Hz, ArH), 7.55 (2H, dd, J¼4.8 and
m, ArH); 13C NMR (150 MHz, CDCl3)
d
28.3 (qꢂ3), 29.3 (t), 37.5 (t),
8.9 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d
9.5 (q), 28.2 (t), 115.4 (d),
52.2 (q), 54.5 (d), 61.0 (t), 79.9 (s), 114.9 (d), 115.3 (s), 115.6 (d), 115.8
(d), 122.9 (s), 126.7 (s), 126.9 (d), 128.2 (d), 128.3 (d), 128.5 (s), 128.9
(dꢂ2), 130.3 (dꢂ2), 130.9 (dꢂ2), 135.6 (s), 140.4 (d), 151.2 (s), 157.6
(s), 163.2 (s), 172.4 (s); MS m/z 591 (small Mþ); high resolution mass
calcd for C33H34NFO6S: 591.2090, found m/z 591.2090.
115.5 (s), 115.6 (d), 123.1 (s), 126.5 (d), 127.2 (d),127.3 (d), 127.9 (s),
128.9 (dꢂ2), 130.2 (dꢂ2), 136.0 (s), 139.2 (d), 148.7 (s), 161.7 (d,
J¼247 Hz); MS m/z 298 (Mþ). Anal. Calcd for C18H15FOS: C, 72.46; H,
5.07. Found: C, 71.89; H, 5.14.
4.8.11. 4-(4-Methyl-3-phenylsulfanylmethylfuran-2-yl)-1-chloro-
benzene (7j). White powders, mp 79e81 ꢀC; IR (KBr, cmꢁ1) 3434,
2925, 2360, 1771, 1586, 1488, 1481, 1437, 1397, 1159, 1024, 1007, 910,
4.9.2. O-[2-Thienyl-3-(phenylsulfanylmethyl)furyl-3-methyl]-N-Boc-
L
-tyrosine methyl ester (16d). A pale yellow oil, IR (KBr, cmꢁ1) 3426,
2976, 1916, 1745, 1713, 1611, 1584, 1510, 1439, 1366, 1278, 1243,1169,
832, 819, 748, 731, 688; 1H NMR (600 MHz, CDCl3)
d
2.24 (3H, s,
1111, 1056, 1017, 849, 745, 693; 1H NMR (600 MHz, CDCl3)
d
1.42
Me), 3.92 (2H, s, SCH2), 7.20e7.23 (2H, m, ArH), 7.28e7.30 (2H, m,
(9H, s, Meꢂ3), 3.02 (2H, dq, J¼5.9 and 17.1 Hz, CH2), 3.71 (3H, s,
OMe), 4.22 (2H, s, CH2), 4.55 (1H, br d, J¼7.6 Hz, CH), 4.85 (2H, s,
CH2), 4.98 (1H, d, J¼8.9 Hz, NH), 6.86 (2H, d, J¼8.2 Hz, ArH),
7.03e7.06 (3H, m, ArH), 7.20e7.24 (4H, m, ArH), 7.30 (1H, br d,
ArH), 7.34e7.37 (4H, m, ArH), 7.52 (2H, d, J¼8.9 Hz, ArH); 13C NMR
(150 MHz, CDCl3)
d
9.6 (q), 28.1 (t), 116.4 (s), 123.3 (s), 126.6 (dꢂ3),
128.7 (dꢂ2), 128.9 (dꢂ2), 130.1 (s), 130.2 (dꢂ2), 132.6 (s), 136.0 (s),

N. Takahashi et al. / Tetrahedron 68 (2012) 1566e1580
1579
J¼5.4 Hz, ArH), 7.33e7.34 (2H, br d, J¼6.2 Hz, ArH), 7.42 (1H, s, furyl
H); 13C NMR (150 MHz, CDCl3)
d 1.78e1.79 (4H, m, CH2), 2.76e2.78 (4H, m, CH2), 3.38 (3H, s,
d
28.3 (qꢂ3), 29.3 (t), 37.5 (t), 52.2
OMe), 3.45 (3H, s, OMe), 4.11 (2H, s, CH2), 4.56 (2H, s, CH2), 6.85
(1H, d, J¼8 Hz, ArH), 7.05 (2H, d, J¼7.5 Hz, ArH), 7.12e7.15 (1H, m,
ArH), 7.18e7.20 (2H, m, ArH), 7.27 (2H, d, J¼4.8 Hz, ArH), 7.46 (1H,
(q), 54.5 (d), 60.9 (t), 79.9 (s), 114.9 (dꢂ2), 115.5 (s), 122.9 (s), 124.6
(d), 125.5 (d), 126.9 (d), 127.5 (d), 128.5 (s), 128.9 (dꢂ2), 130.3 (dꢂ2),
131.2 (dꢂ2), 132.1 (s), 135.5 (s), 140.0 (d), 147.6 (s), 157.5 (s), 172.4
(s); MS m/z 579 (Mþ); high resolution mass calcd for C31H33NO6S2:
579.1749, found m/z 579.1741.
s, furyl H); 13C NMR (150 MHz, CDCl3)
d 22.7 (t), 22.8 (t), 23.4 (t),
28.7 (t), 29.6 (t), 58.1 (q), 60.1 (q), 65.3 (t), 116.7 (s), 120.2 (s), 123.1
(s), 124.5 (d), 126.1 (d), 127.6 (d), 128.7 (dꢂ2), 129.7 (dꢂ2), 131.1 (s),
136.8 (s), 140.0 (s), 140.4 (d), 150.0 (s), 156.1 (s); MS m/z 394 (Mþ),
285 (MþꢁSPh). Anal. Calcd for C24H26O3S: C, 73.07; H, 6.64. Found:
C, 73.30; H, 6.70.
4.9.3. O-[1-Naphthyl-3-(phenylsulfanylmethyl)furyl-3-methyl]-N-
Boc- )
-tyrosine methyl ester (16e). A pale yellow oil, IR (KBr, cmꢁ1
L
3423, 3361, 2976, 2928, 1745, 1713, 1611, 1510, 1438, 1366, 1242,
1167, 1056, 1022, 804, 778, 743, 691; 1H NMR (600 MHz, CDCl3)
4.9.8. 2-[4-(2-Naphthoxymethyl)-3-methylfuran-2-yl]-1-methoxy-
5,6,7,8-tetrahydronaphthalene (22). Pale yellow powders, mp
51e52 ꢀC, IR (KBr, cmꢁ1) 2924, 2858, 1571, 1482, 1451, 1405, 1383,
1362, 1326, 1226, 1205, 1129, 1107, 1098, 1065, 1034, 999, 966, 823,
d
1.43 (9H, s, Meꢂ3), 3.05 (2H, dq, J¼5.5 and 17.1 Hz, CH2), 3.72 (3H,
s, Me), 4.06 (2H, s, CH2), 4.56 (1H, q, J¼7.6 Hz, CH), 4.99 (1H, d,
J¼8.2 Hz, NH), 5.11 (2H, s, CH2), 6.95 (2H, d, J¼8.2 Hz, ArH),
7.01e7.04 (2H, m, ArH), 7.07 (2H, d, J¼8.7 Hz, ArH), 7.11 (2H, dd,
J¼1.4 and 8.3 Hz, ArH), 7.39 (1H, dd, J¼1.3 and 8.2 Hz, ArH),
7.45e7.52 (3H, m, ArH), 7.64 (1H, s, ArH), 7.82 (1H, d, J¼8.3 Hz, ArH),
811, 782, 774; 1H NMR (600 MHz, CDCl3)
d 1.80 (4H, br s, CH2), 2.05
(3H, s, Me), 2.77e2.79 (4H, m, CH2), 3.39 (3H, s, Me), 3.48 (3H, s,
Me), 4,34 (2H, s, CH2), 6.88 (1H, d, J¼8.3 Hz, ArH), 7.11 (1H, d,
7.89 (2H, t, J¼7.2 Hz, ArH); 13C NMR (150 MHz, CDCl3)
d
28.3 (qꢂ3),
J¼8.2 Hz, ArH), 7.46 (1H, s, furyl H); 13C NMR (150 MHz, CDCl3)
d 8.9
29.1 (t), 37.5 (t), 52.2 (q), 54.5 (d), 61.5 (t), 79.9 (s), 114.9 (d),117.9 (s),
122.3 (s), 125.1 (d), 125.9 (d), 126.1 (d), 126.5 (d), 126.6 (d), 127.3 (s),
128.2 (d), 128.3 (d), 128.7 (dꢂ3), 129.5 (d), 130.3 (dꢂ3), 130.5 (dꢂ2),
132.1 (s), 133.7 (s), 135.5 (s), 140.9 (d), 152.1 (s), 155.1 (s), 157.7 (s),
172.4 (s); MS m/z 623 (Mþ); high resolution mass calcd for
C37H37NO6S: 623.2341, found m/z 623.2339.
(q), 22.7 (t), 22.8 (t), 23.5 (t), 29.5 (t), 57.7 (q), 59.8 (q), 65.1 (t), 117.0
(s), 121.0 (s), 123.4 (s), 124.3 (d), 127.5 (d), 131.0 (s), 139.3 (s), 140.0
(d), 148.1 (s), 156.0 (s); MS m/z 286 (Mþ). Anal. Calcd for C18H22O3:
C, 75.50; H, 7.74. Found: C, 75.13; H, 8.01.
4.9.9. 2-[4-(2-Naphthyloxymethyl)-3-(phenylsulfanylmethyl)furan-
2-yl]-1-methoxy-5,6,7,8-tetrahydronaphthalene (21). A pale yellow
oil, IR (KBr, cmꢁ1) 3442, 3056, 2934, 2859, 1628, 1599, 1510, 1480,
1463, 1450, 1438, 1403, 1390, 1326, 1256, 1215, 1176, 1119, 1076,
1003, 961, 836, 811, 745, 691, 621; 1H NMR (600 MHz, CDCl3)
4.9.4. 1-Methoxy-5,6,7,8-tetrahydronaphthyl Aldehyde (17). A col-
orless oil, 1H NMR (600 MHz, CDCl3)
2.78 (2H, br s, CH2), 2.82 (2H, br s, CH2), 3.87 (3H, s, OMe), 6.96 (1H,
d
1.81 (4H, br d, J¼3.5 Hz, CH2),
d, J¼8.3 Hz, ArH), 7.59 (1H, d, J¼7.6 Hz, ArH), 10.32 (1H, s, CHO).
d 1.79e1.80 (4H, m, CH2), 2.76e2.80 (4H, m, CH2), 3.47 (3H, s, OMe),
4.16 (2H, s, SCH2), 5.15 (2H, s, OCH2), 6.86 (1H, d, J¼7.5 Hz, ArH), 7.06
(1H, d, J¼7.6 Hz, ArH), 7.09e7.13 (3H, m, ArH), 7.18e7.25 (4H, m,
ArH), 7.33e7.36 (1H, m, ArH), 7.43e7.46 (1H, m, ArH), 7.59 (1H, s,
4.9.5. 1-(1-Methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)-3-(phenyl-
sulfanyl)prop-2-yn-1-ol (18). A yellow oil, IR (KBr, cmꢁ1) 2933,
2858, 2360, 2341, 2179, 1733, 1604, 1581, 1479, 1452, 1442, 1328,
1310, 1277, 1254, 1203, 1167, 1120, 1077, 1001, 962, 833, 810, 740,
furyl H), 7.73e7.78 (3H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 22.7
(t), 22.8 (t), 23.5 (t), 29.1 (t), 29.6 (t), 60.3 (q), 61.6 (t), 107.3 (d), 116.9
(s), 119.0 (d), 120.1 (s), 122.2 (s), 123.7 (d), 124.6 (d), 126.3 (dꢂ2),
126.8 (d), 127.6 (dꢂ2), 128.7 (dꢂ2), 129.1 (s), 129.4 (d), 130.2 (dꢂ2),
131.2 (s), 134.5 (s), 136.4 (s), 140.2 (s), 140.7 (d), 150.2 (s), 156.2 (s),
156.6 (s); MS m/z 506 (small Mþ); high resolution mass calcd for
C33H30O3S: 506.1915, found m/z 506.2359.
688; 1H NMR (600 MHz, CDCl3)
d 1.71e1.77 (4H, m, CH2), 2.68e2.73
(4H, m, CH2), 3.01 (1H, d, J¼6.1 Hz, OH), 3.79 (3H, s, OMe), 5.85 (1H,
d, J¼6.2 Hz, CHO), 6.89 (1H, d, J¼8.2 Hz, ArH), 7.19e7.21 (1H, m,
ArH), 7.29e7.32 (3H, m, ArH), 7.40 (2H, d, J¼7.5 Hz, ArH); 13C NMR
(150 MHz, CDCl3)
d 22.5 (t), 22.6 (t), 23.4 (t), 29.2 (t), 61.1 (d), 61.2
(q), 72.5 (s), 99.1 (s),124.7 (d),125.3 (d),126.2 (dꢂ2),126.4 (d),129.0
(dꢂ2), 130.3 (s), 130.8 (s), 132.3 (s), 139.6 (s), 155.2 (s); MS m/z 324
(Mþ), 307 (MþꢁOH), 293 (MþꢁOMe), 215 (MþꢁSPh); high resolu-
tion mass calcd for C20H20O2S: 324.1184, found m/z 324.1182.
4.9.10. 2-[3-Methyl-4-(2-naphthyloxymethyl)furan-2-yl]-1-
methoxy-5,6,7,8-tetrahydronaphthalene (23). White prisms, mp
51e52 ꢀC, IR (KBr, cmꢁ1) 3434, 2930, 2858, 1713, 1629, 1600, 1509,
1464, 1403, 1361, 1326, 1256, 1216, 1180, 1119, 1000, 836, 811, 748,
4.9.6. 5-Methoxy-6-[1-propargyloxy-3-(phenylsulfanyl)prop-2-yn-
1-yl]-1,2,3,4-tetrahydronaphthalene (19). A yellow oil, IR (KBr,
cmꢁ1) 3291, 2935, 2856, 2360, 2180, 1698, 1605, 1580, 1479, 1452,
1441, 1417, 1379, 1328, 1260, 1203, 1168, 1075, 1058, 1023, 1003, 963,
476, 420, 405; 1H NMR (600 MHz, CDCl3)
d 1.81 (4H, br s, CH2), 2.12
(3H, s, Me), 2.79e2.81 (4H, m, CH2), 3.51 (3H, s, OMe), 5.06 (2H, s,
OCH2), 6.91 (1H, d, J¼8.2 Hz, ArH), 7.16 (1H, d, J¼8.3 Hz, ArH), 7.22
(1H, dd, J¼2.8 and 9.0 Hz, ArH), 7.27 (1H, d, J¼2.8 Hz, ArH),
7.34e7.36 (1H, m, ArH), 7.44e7.46 (1H, m, ArH), 7.60 (1H, s, furyl H),
881, 833, 813, 786, 740, 687, 634; 1H NMR (600 MHz, CDCl3)
d 1.77
(4H, br s, CH2), 2.48 (1H, t, J¼2.4 Hz, acetylenic H), 2.76 (4H, br s,
CH2), 3.82 (3H, s, OMe), 4.33 (1H, dd, J¼2.1 and 15.8 Hz, OCH2), 4.43
(1H, dd, J¼2.1 and 15.8 Hz, OCH2), 5.98 (1H, s, CHO), 6.91 (1H, d,
J¼8.3 Hz, ArH), 7.20e7.23 (1H, m, ArH), 7.30e7.33 (2H, m, ArH),
7.75e7.79 (3H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 9.1 (q), 22.7 (t),
22.8 (t), 23.5 (t), 29.6 (t), 60.0 (q), 61.4 (t), 107.1 (d), 117.0 (s), 119.1
(d), 120.9 (s), 122.5 (s), 123.7 (d), 124.4 (d), 126.4 (d), 126.8 (d), 127.6
(d), 127.7 (d), 129.1 (s), 129.4 (d), 131.1 (s), 134.5 (s), 139.5 (s), 140.3
(d), 148.4 (s), 156.1 (s), 156.7 (s); MS m/z 398 (Mþ). Anal. Calcd for
C27H26O3: C, 81.38; H, 6.52. Found: C, 81.34; H, 6.52.
7.40e7.42 (3H, m, ArH); 13C NMR (150 MHz, CDCl3)
d 22.6 (t), 22.7
(t), 23.5 (t), 29.4 (t), 55.5 (t), 61.4 (q), 65.5 (d), 74.4 (s), 74.9 (d), 79.3
(s), 96.6 (s), 125.3 (d), 125.8 (d), 126.2 (dꢂ2), 126.5 (d), 127.7 (s),
129.2 (dꢂ2), 130.8 (s), 132.4 (s), 140.1 (s), 155.7 (s); MS m/z 362
(Mþ). Anal. Calcd for C23H22O2S: C, 76.21; H, 6.12. Found: C, 75.99;
H, 6.11.
References and notes
ꢀ
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1580
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