Mn(OAc)3-promoted sulfur-directed addition of an active methylene compound to alkenes

Article abstract of DOI:10.1016/j.tet.2012.05.003

Various alkenes substituted at the 1,2-positions by phenyl, thiophene and furan rings were reacted with 3-(4-methoxyphenyl)-3-oxopropanenitrile in the presence of Mn(OAc)₃·2H₂O. The exact structure and configuration of the dihydrofuran derivatives formed were determined. In all cases only one regioisomer was formed. The observed regioselectivity was explained on the basis of the formation of a complex between Mn(OAc) ₃, alkene, and 3-(4-methoxyphenyl)-3-oxopropanenitrile, which directs the mode of the addition to the double bond.

Full text of DOI:10.1016/j.tet.2012.05.003

Tetrahedron 68 (2012) 5838e5844
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Mn(OAc)3-promoted sulfur-directed addition of an active methylene
compound to alkenes
,
,
Murat K. Deliomeroglu a, Cagatay Dengiz a, Ras¸ it C¸ alıs¸ kan a b, Metin Balci a
*
a Middle East Technical University, Department of Chemistry, 06800 Ankara, Turkey
b
€
Department of Chemistry, Suleyman Demirel University, 32260 Isparta, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Various alkenes substituted at the 1,2-positions by phenyl, thiophene and furan rings were reacted with
3-(4-methoxyphenyl)-3-oxopropanenitrile in the presence of Mn(OAc)3$2H2O. The exact structure and
configuration of the dihydrofuran derivatives formed were determined. In all cases only one regioisomer
was formed. The observed regioselectivity was explained on the basis of the formation of a complex
between Mn(OAc)3, alkene, and 3-(4-methoxyphenyl)-3-oxopropanenitrile, which directs the mode of
the addition to the double bond.
Received 7 February 2012
Received in revised form 16 April 2012
Accepted 1 May 2012
Available online 8 May 2012
Keywords:
Manganese(III) acetate
Cyclization
Ó 2012 Elsevier Ltd. All rights reserved.
Dihydrofuran
Thiophene
Furan
1. Introduction
Radical cyclization of alkenes has emerged as a powerful re-
action for ring construction.1 It has been known for a long time that
manganese(III) acetate in acetic acid at reflux converts olefins into
g
-lactones.2 Moreover, the reaction of alkenes with 1,3-dicarbonyl
compounds 1 in the presence of Mn(OAc)3 in acetic acid forms
dihydrofurans 6 (Scheme 1).
Generally, an oxidatively or reductively generated radical 3 can
add to a double bond, forming a new radical 4, which can be
reductively or oxidatively terminated. Recently, we have proposed
that the cyclization reaction takes place after the oxidation of the
radical 4 to the cation 5 to give dihydrofuran derivative 6.3
Fristad and Peterson studied the annulation of a g-lactone ring
Scheme 1. General mechanism for addition of 1,3-dicarbonyl compounds to C]C
onto various unsymmetrically substituted alkenes.4 They showed
that a terminal alkene reacted with a regioselectivity of 40:1, which
showed the preference of a secondary radical over a primary radical
intermediate. Furthermore, Nishino et al.5 demonstrated that
acylacetonitriles were easily oxidized with manganese(III) acetate
in acetic acid to form the corresponding acylcyanomethyl radicals,
which attack alkenes to form new 4,5-dihydrofuran-3-carbonitriles
at reflux temperature (Scheme 2). More recently, Yilmaz et al.6 used
the same methodology and reported the addition of acylcyanoni-
triles to various unsymmetrically substituted alkenes.
double bonds in the presence of Mn(OAc)3.
* Corresponding author. Tel.: þ90 312 2105140; fax: þ90 312 2103200; e-mail
Scheme 2. Possible adducts formed by addition of acylacetonitriles to various alkenes
in the presence of Mn(OAc)3.
address: mbalci@metu.edu.tr (M. Balci).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.003

M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
5839
Addition of acylcyanomethyl radical to unsymmetrically
substituted alkenes may provide two regioisomers pairs, 9/10 and
11/12. Moreover, the formed regioisomers may be cis or trans
(Fig. 2). However, a clear-cut differentiation between the possible
regioisomers as well as stereoisomers was not made.5,6 Assignment
of substituent stereochemistry on a dihydrofuran moiety by NMR
coupling constant data is difficult. Generally, Jtrans>Jcis is for vicinal
hydrogen atoms; however, this is not always the case. In small rings,
especially in cyclopropane and cyclobutane, Jcis>Jtrans.7 In the case of
a five-membered ring, a conclusion can be made if the conformation
of the molecule is known. Antonioletti et al.8 made the configura-
tional assignments in similar systems using NOE measurements
between the relevant protons. A differentiation between the
regioisomers was made by the chemical shifts of the ring protons.6c
This was explained by shielding of this hydrogen by the adjacent
CeC bond. This appears to be a useful diagnostic feature. However,
a chemical shift difference of about 0.5 ppm may lead to mis-
interpretation of the spectra. In this paper, we reinvestigated the
reaction of 3-(4-methoxyphenyl)-3-oxopropanenitrile with 2-[(E)-
2-phenylvinyl]thiophene in the presence of Mn(OAc)3.6c We were
interested in the correct structure of the product and furthermore
we wanted to address the question of why one regioisomer was
formed exclusively. Moreover, it is interesting to test whether the
geometry of alkene used in the reaction has an influence on the
geometry of the substituents in the products.
nenitrile (17) in the presence of Mn(OAc)3$2H2O in acetic acid
gave the dihydrofuran adduct 18 as the sole isolable product in 47%
and 45% yields, respectively (Scheme 4). Careful examination of the
reaction mixture did not reveal the formation of any other isolable
product. Because of the asymmetric environment of the double
bonds in 15 and 16, the initially formed complex between Mn(OAc)3
and 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) can add to the
double bond in two different ways forming the compounds 18 and
19. However, the expected regioisomer 19 was not detected.
The structure and the configuration of 18 were assigned from 1H
(COSY, DEPT, HSQC, and HMBC) and 13C NMR spectroscopic data. In
particular, the HMBC spectrum was very helpful in the assignment
of the correct skeleton in 18. The most conspicuous features in the
1H NMR spectrum of this compound were the dihydrofuran ring
protons. The dihydrofuran ring protons H-4 and H-5 resonate at
4.47 and 5.67 ppm as doublets with a coupling constant of
J¼7.2 ppm. The low field resonance was assigned to alkoxy proton
H-5 due to the inductive effect of the neighboring oxygen atom. In
the HMBC spectrum, the H-5 proton resonance at 5.67 ppm cor-
relates with the carbon resonance appearing at 125.9 ppm, which
belongs to the b-carbon atom (determined from the HSQC spec-
trum) of the thiophene ring. Moreover, the C-5 carbon resonance at
87.9 ppm (determined from the HSQC spectrum) correlates with
the
alkoxy proton H-5 is closer to the thiophene ring. Furthermore,
b
-proton H-30 of the thiophene ring, clearly indicating that
Fig. 1. Optimized geometries of 18 and 19 (DFT, B3LYP at 6-31G** level).
a three bond correlation between the eCN carbon atom (117.3 ppm)
and the H-4 proton resonance appearing at 4.47 establishes the
close proximity of the proton H-4 to the nitrile group.
After establishing the correct constitution of 18, we turned our
attention to the configuration of the thiophenyl and phenyl groups.
Geometry optimization calculations (DFT, B3LYP at 6-31G** level) on
the molecules 18 and 19 show a dihedral angle
F
of 27.2ꢀ for
H4eC4eC5eH5 in 18 and 147.9ꢀ for H4eC4eC5eH5 in 19 (Fig. 1). We
calculated the corresponding coupling constants using the Kar-
pluseConroy equation10 and obtained 3J¼7.2 Hz for isomer 18 and
3J¼6.6 Hz for the trans-isomer 19. The theoretically determined value
of 3J¼7.2 is in complete agreement with the measured coupling
constant of 3J¼7.2. Since the difference between the calculated cou-
pling constants J¼7.2 and 6.6 Hz was not large enough to allow an
exact assignment, we recorded NOE-DIFF and NOESY spectra. In the
NOESY spectrum we observed a strong correlation between the
proton resonances appearing at 5.67 (H5) and 4.47 (H4). Furthermore,
the NOE-DIFF spectrum showed 4.5% and 6.7% signal enhancement of
the signals resonating at 5.67 and 4.47 ppm upon irradiation at the
resonance frequencies of 4.47 and 5.67 ppm, respectively. All these
results together confirmed the cis-configuration of the protons in 18.
After complete structural characterization of the adduct 18 we
turned our attention to the reaction with cis-styrylthiophene (16).
The cis-olefin 16 was reacted with 3-(4-methoxyphenyl)-3-
oxopropanenitrile (17) and Mn(OAc)3$2H2O in acetic acid under
Fig. 2. The structures of possible intermediates 20a/20b and 21a/21b.
2. Results and discussion
The previously known alkenes 15 and 16 were synthesized as
described in the literature.9 The reaction of benzyl-
triphenylphosphonium bromide (13) with thiophene-2-carbaldehyde
(14) gave a mixture of trans- and cis-2-styrylthiophene 15 and 16 in
51% and 38% yields, respectively (Scheme 3). The isomeric mixture
was separated on a silica gel column eluting with n-hexane. The
structural assignments were made on the basis of the measured
coupling constants between the double bond protons.
Treatment of pure isomers, trans-styrylthiophene (15) or cis-
styrylthiophene (16) with 3-(4-methoxyphenyl)-3-oxopropa-

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M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
Scheme 3. Synthesis of trans-2-styrylthiophene (15) and cis-2-styrylthiophene (16).
Scheme 4. Reactions of alkenes 15 and 16 with 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) in the presence of Mn(OAc)3$2H2O.
the same reaction conditions. The adduct 18 was formed as the sole
isolable product in 45% yield. The spectroscopic data of the product
were in agreement with those obtained from the reaction with
trans-olefin 15. The configuration of the olefins used in this reaction
did not have any effect on the constitution or on the configuration
of the final product (Fig. 2).
At this stage we postulate a radical mechanism for the formation
of 18. We assume that a radical having the structure such as 3
resulting from the electron transfer reaction between Mn(III) and
17 serves as a key intermediate and adds regiospecifically to the
double bond in 15 and 16. Oxidation of the radical can form the
carbocation 20a, which undergoes a cyclization reaction to give 18.
It is remarkable to observe that no trace of 19, which might be
derived from the cation 21a, was formed. We assume that the origin
of the observed regioselectivity of the addition of the initially
formed radical is controlled by the heteroatom in the five-
membered ring. To test the feasibility of this idea we decided to
synthesize the corresponding furan derivative 24 and study the
behavior of this compound.
trans-Styrylfuran (23) and cis-styrylfuran (24) were synthe-
sized as described in the literature.11 A mixture of two isomers, 23
and 24 was formed in 59% and 34% yields (Scheme 5). Treatment
of those isomers under the same reaction conditions with 17 in
the presence of Mn(OAc)3$2H2O resulted in the formation of only
Scheme 5. Synthesis of trans-2-styrylfuran (23) and cis-2-styrylfuran (24) and their reaction with 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) in the presence of
Mn(OAc)3$2H2O.

M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
5841
one isolable product, 25, in only 2% yield. The structure of this
product was determined using 1D- and 2D-NMR spectral mea-
surements. In particular, the HMBC spectrum of 25 supports the
correct structure. The proton signal H-4 appearing at 4.73 ppm
configuration of 30 were assigned from 1H (COSY, HSQC, HMBC)
and 13C NMR spectroscopic data. A correlation between the nitrile
carbon atom and H-4 proton in the HMBC spectrum clearly in-
dicated the correct structure and the mode of the addition as we
discussed in other cases. The second product, 31, which was formed
as a single diastereomeric isomer, derives from successive oxida-
tion of the double bond in 28 followed by capture by acetate anions.
The last isomer, 32, is formed by proton abstraction of one of the
methyl protons followed by oxidation and substitution by acetate
anion.
In all three different systems 15/16, 23/24, and 28/29, the
formation of only one regioisomer can be rationalized by
regioselective addition of the initially formed radical derived
from 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) to the
double bond in those systems followed by oxidation with
Mn(OAc)3 to a classical cation, which can undergo rapid cycli-
zation with the enol form of 17. In the case of 15/16 we assume
that the heteroatom sulfur in the thiophene ring has a directing
effect for the mode of the addition, although in the case of
the formation of the other regioisomer 19 (not observed) the
formed cation 21a and 21b would be more stabilized due to
conjugation with the benzene ring.13 When the thiophene ring in
15/16 is replaced by a furan ring, high regioselectivity was also
observed. This result shows that the oxygen atom also has
a similar directing effect. However, in the case of a mixed system
(28/29), the formation of a single regioisomer is remarkable. One
would expect competition between two different heteroatoms.
The fact that this is not the case clearly indicates the dominating
effect of the sulfur atom. On the basis of these results the
following mechanism is suggested for the addition process
(Scheme 8).
correlates with the
a-carbon resonance of the benzene ring;
furthermore, a correlation between the nitrile carbon and H-4
proton supports the presumption that 25 has a similar structure
to 18. For the formation of this compound we propose 20b as the
intermediate. However, the furan ring cannot stabilize a positive
charge as much as the benzene ring. Again, we assume that the
heteroatom (oxygen atom in furan ring in 23 and 24) has
a directing effect to determine the regiospecific addition of the
initially formed radical species having a structure like 3 to the
double bond in 23 and 24.
Comparison of these results obtained from 15/16 and
23/24 shows that the yields for the formation of dihydrofuran
ring in the case of 23 and 24 are very low (2%). We assume
that the furan ring undergoes some kind of reaction at the
position or polymerization. To prevent any reaction at the
a
a
-
-
position of the furan ring, this position was blocked with
a methyl group.
The desired olefins 28 and 29 were synthesized by Wittig re-
action of 5-methylfuran-2-carbaldehyde 27 with triphenylphos-
phonium salt 26,12 prepared from 2-(bromomethyl)thiophene with
triphenylphosphine (Scheme 6). The isomers 28 and 29 formed in
53% and 38% yields were separated by column chromatography on
silica gel. The structural assignments were made using 1H and 13C
NMR spectroscopy.
The reaction of trans-isomer 28 as well as a mixture of 28 and 29
with 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) was accom-
plished with Mn(OAc)3$2H2O in acetic acid, and three products
were isolated. In contrast to the reactions with 15/16 and 28/29,
significantly different products 31 and 32 were formed beside the
expected adduct 30, in 22%, 23% and 29% yields, respectively
We propose that the complex 33 is formed between Mn(OAc)3,
alkene, and 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) at the
first stage. The next step is the electron transfer from the alkene
to the metal center and the formation of a CeC bond between
the active methylene group in 17 and the double bond carbon
atom directly connected to the benzene ring because of close
proximity. However, the formation of a CeC bond between the
(Scheme 7). Blocking of the a-position in furan increased the yield
of the products. The major product was the expected addition
product 30. Careful examination of the reaction mixture did not
reveal the formation of any other regioisomer. The structure and
Scheme 6. Synthesis of trans- and cis-2-methyl-5-(2-(thiophen-2-yl)vinyl)furan (28) and (29).
Scheme 7. Reaction of trans-2-methyl-5-(2-(thiophen-2-yl)vinyl)furan (28) with 3-(4-methoxyphenyl)-3-oxopropanenitrile (17) in the presence of Mn(OAc)3$2H2O.

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M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
3.3. Reaction of (E)-2-styrylthiophene (15) with 3-(4-
methoxyphenyl)-3-oxopropanenitrile in the presence of
Mn(OAc)3
Mn(OAc)3$2H2O (402 mg, 1.5 mmol) was dissolved in 20 mL of
glacial acetic acid and the flask was heated to 60 ꢀC under
nitrogen. Then a mixture of 2-strylthiophene (15) (100 mg,
0.54 mmol) and 3-(4-methoxyphenyl)-3-oxopropanenitrile (13)
(185 mg, 1.06 mmol) in 5 mL of glacial acetic acid was added
dropwise to the Mn(OAc)3 solution. The reaction mixture was
stirred for 12 h at 60 ꢀC under nitrogen. Water (50 mL) was added
and the mixture was stirred additional 10 min. The reaction mix-
ture was cooled to room temperature and the solution was
extracted with methylene chloride (3ꢁ50 mL). The combined or-
ganic layers were washed with saturated NaHCO3 solution and then
with water and dried (MgSO4). Evaporation of the solvent gave the
crude compound. The chromatography of the residue on silica gel
(3:1 hexane/EtOAc) gave 89 mg (47%, isolated yield) of 18 as col-
orless solid, mp 84e86 ꢀC, (lit. 85e86 ꢀC6c), rel-(4R,5S)-2-(4-
methoxyphenyl)-4-phenyl-5-(2-thienyl)-4,5-dihydrofuran-3-carbon-
33
Scheme 8. Mechanism of formation of 18.
itrile (18): 1H NMR (400 MHz, CDCl3) 7.95e7.90 (quasi d, AA0-part
d
of AA0XX0-system, 2H, benzene), 7.32e7.21 (m, 6H, five benzene,
one thiophene), 6.99 (br d, J¼4.6 Hz, 1H, thiophene), 6.93 (dd, J¼5.1
and 4.6 Hz, 1H, thiophene), 6.91e6.86 (quasi d, XX0-part of AA0XX0-
system, 2H, benzene), 5.67 (d, J¼7.2 Hz, 1H), 4.47 (d, J¼7.2 Hz, 1H),
carbon atom connected to the thiophene ring and the active
methylene carbon in 17 is probably hindered due to geometrical
restriction.
In conclusion, the sulfur atom in 15/16 and 28/29 and the
oxygen atom in 23/24 are directing the mode of the addition re-
actions. In order to obtain further evidence about the directing
effect of heteroatoms we are currently examining different sys-
tems in which the distance between the heteroatom and alkene is
varied.
3.76 (s, 3H, OCH3); 13C NMR (400 MHz, CDCl3)
d 166.2 (C-5), 162.3
(C-4), 141.9 (C-20) 139.3 (C-1), 129.3 (C-2 and C-6) 129.2 (C-3 and C-
5), 128.2 (C-4), 127.5 (C-2 and C-6), 127.0 (C-40), 126.3 (C-50), 125.9
(C-30), 120.1 (C-1), 117.3 (C^N), 114.1 (C-3 and C-5), 87.9 (C-2), 82.3
(C-4), 55.4 (OCH3), 58.8 (C-3).6c
3.4. Reaction of (Z)-2-styrylthiophene (15) with 3-(4-
methoxyphenyl)-3-oxopropanenitrile in the presence of
Mn(OAc)3
3. Experimental section
3.1. General
Mn(OAc)3$2H2O (1.24 g, 4.65 mmol), 2-strylthiophene (15)
(293 mg, 1.55 mmol), and 3-(4-methoxyphenyl)-3-oxopropane-
nitrile (13) (550 mg, 3.14 mmol) was reacted as described above
to give 250 mg (45%, isolated yield) of 18 as orange solid, mp
84e86 ꢀC.
Infrared spectra were obtained from a solution (CHCl3) in 0.1 mm
cells or KBr pellets on an FT-IR Bruker Vertex 70 instrument. The 1H
and 13C NMR spectra were recorded on a Bruker-Biospin (DPX-400)
instrument. Apparent splitting is given in all cases. Column chro-
matography was performed on silica gel (60 mesh, Merck), TLC was
carried out on Merck 0.2 mm silica gel 60 F254 analytical aluminum
plates.
3.5. (Z)-2-Styrylfuran (24) and (E)-2-styrylfuran (23)
Benzyltriphenylphosphonium bromide (13) (7.67 g, 17.7 mmol),
sodium ethoxide solution in ethanol, prepared by addition of
metallic sodium (0.42 g, 18.3 mmol) to 50 mL of EtOH and furfural
(1.54 g, 16 mmol) was reacted as described above for the synthesis
of 15 and 16. The crude product, which was chromatographed over
silica gel (150 g) eluting with hexane gave the isomers 24 and 23.
2-[(Z)-2-phenylethenyl]furan (24) was isolated as the first fraction:
colorless liquid, 930 mg, 34% (isolated yield). 2-[(E)-2-phenyl-
ethenyl]furan (23) was isolated as the second fraction: colorless
crystals, mp 51e52 ꢀC (from n-hexane/ethyl acetate, lit.
53e54 ꢀC11e), 1.62 g, 59% (isolated yield). The spectral data of these
compounds were consistent with those reported in the
literature.11
3.2. (Z)-2-Styrylthiophene (16) and (E)-2-styrylthiophene (15)
Benzyltriphenylphosphonium bromide (13) (4.5 g, 10.4 mmol)
was added to a sodium ethoxide solution in ethanol, prepared
by addition of metallic sodium (0.29 g, 12.5 mmol) to 50 mL of
EtOH. After dissolving of all phosphine reagent, thiophene-2-
carbaldehyde (14) (1.06 g, 9.46 mmol) was added to reaction
mixture. The resulting mixture was stirred at room temperature
overnight. The reaction mixture was evaporated to dryness first.
Then water was added and the mixture was extracted with meth-
ylene chloride (2ꢁ50 mL). The combined organic extracts were
washed with water and dried over MgSO4. Removal of solvent gave
2.90 g crude product, which was chromatographed over silica gel
(150 g) eluting with hexane to give the isomers 15 and 16.
3.6. Reaction of (Z)-2-styrylfuran (15) with 3-(4-
methoxyphenyl)-3-oxopropanenitrile in the presence of
Mn(OAc)3
(Z)-2-Styrylthiophene (16) was isolated as the first fraction:
colorless liquid, 670 mg, 38% (isolated yield). (E)-2-Styrylthiophene
(15) was isolated as the second fraction: colorless crystals, mp
110e111 ꢀC (from n-hexane/ethyl acetate, lit. 111e112 ꢀC9b), 0.9 g,
51.1% (isolated yield). The spectral data of these compounds were
consistent with those reported in the literature.9
Mn(OAc)3$2H2O (2.27 mg, 8.46 mmol), 2-strylthiophene (24)
(480mg,2.82mmol),and3-(4-methoxyphenyl)-3-oxopropanenitrile
(13) (988 mg, 5.64 mmol) was reacted as described above
to give 19.4 mg (2%) of 25 as yellow oil. rel-(4R,5S)-5-(4-Methox-
yphenyl)-3-phenyl-2,3-dihydro-2,20-bifuran-4-carbonitrile (25). 1H

M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
5843
NMR (400 MHz, CDCl3)
d
8.00 (quasi d, J¼9.0 Hz, 2H, H-2 and H-6),
saturated NaHCO3 dried over MgSO4. After evaporation of solvent
the residue was chromatographed on silica gel (150 g) eluting
with hexane/EtOAc (4:1) then successive flash chromatography
eluting with hexane/EtOAc (7:1) to give three compounds in the
following order 30 (320 mg, 29.1%), 31 (200 mg, 22%), and 32
(170 mg, 23%). rel-(4R,5S)-2-(4-Methoxyphenyl)-4-(5-methylfuran-
2-yl)-5-(thiophen-2-yl)-4,5-dihydrofuran-3-carbonitrile (30) was
0
0
0
7.49 (d, J5 ,4 ¼1.8 Hz, 1H, H-5 ), 7.38e7.27 (m, 5H, benzene),06.94(quasi
0
0
d, J¼9.0 Hz, 2H, H-3 and H-5), 6.45 (d, J3 ,4 ¼3.3 Hz,1H, H-3 ), 6.39 (dd,
0
0
0
0
0
J4 ,3 ¼3.3 and J4 ,5 ¼1.8 Hz,1H, H-4 ), 5.52 (d, J2,3¼7.9 Hz,1H, H-2), 4.73
(d, J3,2¼7.9 Hz,1H, H-3), 3.85 (s, 3H, OCH3).13C NMR (100 MHz, CDCl3)
d
166.4 (C-5), 162.3 (C-4), 150.6 (C-20), 143.9 (C-50), 139.4 (C-1), 129.3
(C-2 and C-6), 129.2 (C-3 and C-5) 128.1 (C-4), 127.6 (C-2 and C-6),
120.2 (C-1),117.5 (C^N),114.1 (C-3 and C-5),110.6 (C-40),109.8 (C-30),
84.9 (C-2), 82.3 (C-4), 55.4 (OCH3), 54.5 (C-3). MS (m/z, relative in-
tensity): 343.2/344.2 (Mþ, 4/1), 314.1 (M-CHO), 135.1.
isolated as colorless oil. 1H NMR (400 MHz, CDCl3)
d 7.94 (quasi d,
AA0-part of AA0XX0-system, J¼9.0 Hz, 2H, benzene), 7.20 (dd, J¼5.0
and 1.2 Hz, 1H, thiophene), 6.96e6.95 (m, 1H, thiophene), 6.92
(dd, J¼5.1 and 3.5 Hz, 1H, thiophene), 6.88 (quasi d, XX0-part of
AA0XX0-system, J¼9.0 Hz, 2H, benzene), 6.32 (d, J¼3.2 Hz, 1H,
furan), 5.95e5.90 (m, 1H, furan), 5.44 (d, J¼8.4 Hz, 1H, H-5), 4.98
3.7. Reaction of (E)-2-styrylfuran (23) with 3-(4-
methoxyphenyl)-3-oxopropanenitrile in the presence of
Mn(OAc)3
(d, J¼8.4 Hz, 1H, H-4), 3.79 (s, 3H, eOCH3), 2.26 (s, 3H, eCH3). 13
C
NMR (100 MHz, CDCl3)
d 166.3, 162.3, 154.2, 147.9, 142.6, 129.4,
Mn(OAc)3$2H2O (470 mg, 1.77 mmol), 2-strylthiophene (24)
(480 mg, 2.82 mmol), and 3-(4-methoxyphenyl)-3-oxopropanenitrile
(13) (206 mg, 1.18 mmol) was reacted as described above to give
5.0 mg (2%) of 25 as yellow oil.
127.4, 125.7, 125.5, 120.2, 114.11, 114.07, 111.5, 106.7, 85.1, 82.4, 55.5,
49.4, 13.8. IR (ATR, cmꢂ1) 2933, 2205, 1738, 1608, 1512, 1261, 1179,
908, 732. HRMS: m/z (MþH)þ calcd for C21H17NO3S: 364.1002;
found: 364.1047. 1-(5-Methylfuran-2-yl)-2-(thiophen-2-yl)ethane-
1,2-diyl diacetate (31) was isolated as the second fraction colorless
3.8. (E)-2-Methyl-5-(2-(thiophen-2-yl)vinyl)furan (28) and
(Z)-2-methyl-5-(2-(thiophen-2-yl)vinyl)furan (29)
oil. 1H NMR (400 MHz, CDCl3)
d
7.14 (dd, J¼5.0, 1.1 Hz, 1H, thio-
phene), 6.86 (br d, J¼3.6 Hz, 1H, thiophene), 6.80 (dd, J¼5.0 and
3.6 Hz, 1H, thiophene), 6.53 (d, J¼8.5 Hz, 1H, HCeC), 6.06 (d,
J¼2.7 Hz, 1H, furan), 6.05 (d, J¼8.5 Hz, 1H, CeCH), 5.78e5.73 (m,
1H, furan), 2.18 (s, 3H, eCH3), 2.02 (s, 6H, 2ꢁ COCH3); 13C NMR
Metallic sodium (0.33 g, 14.2 mmol) was divided into small
pieces and dissolved in 50 mL of ethanol gently at room tempera-
ture. After complete dissolving, benzyltriphenylphosphonium
bromide (1) (6.21 g, 14.1 mmol) was added to sodium ethoxide
solution. Then 5-methylfurfural (27) (1.42 g, 12.9 mmol) was added
to reaction mixture. The resulting mixture was stirred overnight at
room temperature and evaporated to dryness. Then water was
added and the mixture was extracted with 50 mL of methylene
chloride (2ꢁ50 mL). The combined organic extracts were dried over
MgSO4. Removal of the solvent gave 2.23 g crude product, which
was chromatographed on silica gel (150 g) eluting with hexane give
900 mg (37%) of 29 as colorless liquid and 1.24 g of (51%) (E)-2-
methyl-5-(2-(thiophen-2-yl)vinyl)furan (5) as colorless liquid. (E)-
2-methyl-5-(2-(thiophen-2-yl)vinyl)furan (29). 1H NMR (400 MHz,
(100 MHz, CDCl3)
d 169.8, 169.6, 152.9, 146.7, 138.4, 126.9, 126.6,
126.1, 111.7, 106.4, 70.3, 70.1, 20.99, 20.95, 13.6. IR (ATR, cmꢂ1
)
2957, 1743, 1370, 1214, 1020, 729, 707. HRMS: m/z (MþNa)þ calcd
for C15H16O5S: 331.0611; found: 331.0686. (E)-(5-(2-(Thiophen-2-
yl)vinyl)furan-2-yl)methyl acetate (32) was isolated as the third
fraction. Colorless oil, 1H NMR (400 MHz, CDCl3)
d 7.13 (d,
J¼5.1 Hz, 1H, thiophene), 7.11 (d, J¼16.0 Hz, 1H, C]CH), 6.99 (br d,
J¼3.6 Hz, 1H, thiophene), 6.92 (dd, J¼5.1 and 3.6 Hz, 1H, thio-
phene), 6.60 (d, J¼16.0 Hz, 1H, HC]C), 6.35 (d, A-part of AB-
system, J¼3.3 Hz, 1H, furan), 6.21 (d, B-part of AB-system,
J¼3.3 Hz, 1H, furan), 4.99 (s, 2H, CH2), 2.04 (s, 3H, COCH3); 13C
NMR (100 MHz, CDCl3)
d 170.7, 153.5, 149.0, 142.3, 127.7, 126.4,
CDCl3)
d
7.07 (br d, J¼5.0 Hz, 1H, thiophene), 7.00 (d, J¼16.0 Hz, 1H,
124.6, 121.2, 115.7, 112.8, 109.3, 58.2, 30.9; IR (ATR, cmꢂ1) 2923,
1739, 1232, 1019, 907, 729, 699. HRMS: m/z (Mþ) calcd for
C13H12O3S: 248.0507; found: 248.0509.
C]CH), 6.94 (d, A-part of AB-system, J¼3.6 Hz, 1H, thiophene), 6.90
(dd, B-part of AB-system, J¼5.0 and 3.6 Hz, 1H, thiophene), 6.57 (d,
J¼16.0 Hz, 1H, HC]C), 6.13 (d, J¼3.1 Hz, 1H, furan), 5.95e5.90 (m,
1H, furan), 2.26 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3)
d 152.3,
3.10. Reaction of a mixture of 28 and 29 with 3-(4-
methoxyphenyl)-3-oxopropanenitrile in the presence of
Mn(OAc)3
151.2, 143.0, 127.7, 125.6, 123.8, 118.7, 116.4, 110.0, 107.9, 13.8; IR
(ATR, cmꢂ1) 3105, 2947, 2917, 1588, 1543, 1423, 1019, 940, 778, 693.
HRMS: m/z (M) calcd for C11H10OS: 190.0452. Found: 190.0444. (Z)-
2-Methyl-5-(2-(thiophen-2-yl)vinyl)furan (29). Purity 90%, a mix-
ture with (E)-isomer. 1H NMR (400 MHz, CDCl3)
d 7.23 (br d,
When a mixture of 28 and 29 was used instead of pure isomers,
the same compounds were isolated almost with same products
ratio.
J¼3.6 Hz, 1H, thiophene), 7.18 (br d, J¼5.1 Hz, 1H, thiophene), 6.93
(dd, J¼5.1 and 3.6 Hz, 1H, thiophene), 6.35 (d, A-part of AB-system,
J¼12.9 Hz, 1H, C]CH), 6.30 (d, J¼3.2 Hz, 1H, furan), 6.06 (d, B-part
of AB-system, J¼12.9 Hz, 1H, HC]C), 5.91 (br d, J¼3.2 Hz, 1H, furan)
2.29 (s, 3H, CH3).
Acknowledgements
The authors are indebted to TUBITAK (Scientific and Techno-
logical Research Council of Turkey), (Grant TBAG-110R001), and the
Departments of Chemistry at Middle East Technical University and
3.9. Reaction of (E)-2-methyl-5-(2-(thiophen-2-yl)vinyl)furan
(29) with 3-(4-methoxyphenyl)-3-oxopropanenitrile in the
presence of Mn(OAc)3
€
Ataturk University and TUBA (Turkish Academy of Sciences) for fi-
nancial support of this work. Furthermore, the authors wish to
express their gratitude to Prof. Dr. Cavit Kazaz and Barıs¸ Anıl
(Ataturk University, Erzurum) for NOESY and NOE-DIFF spectra.
Mn(OAc)3$2H2O (2.41 g, 8.99 mmol) was dissolved in 50 mL of
glacial acetic acid under nitrogen. Then a solution of (E)-olefin
(29) (570 mg,
3
mmol) and 3-(4-methoxyphenyl)-3-
oxopropanenitrile (1.05 g, 6 mmol) in 10 mL of acetic acid was
added to Mn(OAc)3 solution. The reaction mixture was stirred
12 h at 60 ꢀC and under inert atmosphere. Water (50 mL) was
added and stirred for additional 10 min. The reaction mixture was
cooled to room temperature and extracted with methylene chlo-
ride (3ꢁ50 mL). Combined organic phases were washed with
Supplementary data
These data include the 1H- and 13C NMR spectra of eleven
compounds. Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2012.05.003.

5844
M.K. Deliomeroglu et al. / Tetrahedron 68 (2012) 5838e5844
7. (a) Balci, M. Basic 1H- and 13C NMR Spectroscopy; Elsevier: 2005; (b) Gunther, H.;
Jikeli, G. Chem. Rev. 1977, 77, 599e637.
€
References and notes
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