Coupling reactions and coupling-alkylations of thiophenecarbaldehydes promoted by samarium diiodide

Article abstract of DOI:10.1021/jo980851d

The coupling reactions of 2-thiophenecarbaldehyde with aromatic or aliphatic aldehydes were promoted by samarium diiodide in the presence of hexamethylphosphoramide to give C-5 hydroxyalkylation products. The coupling reactions of 3-thiophenecarbaldehyde occurred at C-2, and the subsequent alkylations occurred at the sulfur atom, accompanied by a concurrent opening of the thiophene ring to afford γ-lactols. Double hydroxyalkylations of 2- and 3-thiophenecarbaldehydes were also carried out under appropriate reaction conditions. Synthetic applications of these thiophenecarbonyl coupling products were demonstrated, for example, by elaboration to furans, butenolides, and thiophene-fused polycyclic compounds.

Full text of DOI:10.1021/jo980851d

394
J . Org. Chem. 1999, 64, 394-399
Cou p lin g Rea ction s a n d Cou p lin g-Alk yla tion s of
Th iop h en eca r ba ld eh yd es P r om oted by Sa m a r iu m Diiod id e
Shyh-Ming Yang† and J im-Min Fang*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, Republic of China
Received May 6, 1998
The coupling reactions of 2-thiophenecarbaldehyde with aromatic or aliphatic aldehydes were
promoted by samarium diiodide in the presence of hexamethylphosphoramide to give C-5
hydroxyalkylation products. The coupling reactions of 3-thiophenecarbaldehyde occurred at C-2,
and the subsequent alkylations occurred at the sulfur atom, accompanied by a concurrent opening
of the thiophene ring to afford γ-lactols. Double hydroxyalkylations of 2- and 3-thiophenecarbal-
dehydes were also carried out under appropriate reaction conditions. Synthetic applications of these
thiophenecarbonyl coupling products were demonstrated, for example, by elaboration to furans,
butenolides, and thiophene-fused polycyclic compounds.
Ta ble 1. Sm I2-P r om oted Cou p lin g Rea ction s of
2-Th iop h en eca r ba ld eh yd e (1) in THF a
In tr od u ction
Aromatic aldehydes usually undergo reductive car-
bonyl-carbonyl coupling reactions1 to give pinacols by
using SmI2 or other suitable reducing agents. However,
we have found that the coupling reactions of benzalde-
hydes or indole-3-carbaldehydes by using SmI2/HMPA as
the combined promoter proceed in a different mode to
give aryl-carbonyl coupling products.2 This new type of
coupling reactions is further extended to the system of
2- and 3-thiophenecarbaldehydes.3 Thiophenecarbalde-
hydes are generally reduced to the thienylmethanols by
coupling
products
entry
substrates (RCHO)
additive (% yield)b
1
2
3
4
5
6
7
1
1
1
none
none
HMPA 3a (45)
HMPA 3b (49)
HMPA 3c (45)
4a (48)
4a (65)
1 + 3-thiophenecarbaldehyde
1 + 4-MeOC6H4CHO
1 + 1-methyl-2-pyrrolecarbaldehyde HMPA 3d (36)
1 + CH3CH2CHO
HMPA 3a (24) +
3e (49)
5
catalytic hydrogenation4 or with LiAlH4 or Fe/HOAc.6
a
For entry 1, the molar ratio of 1/SmI2 ) 1:1.8; for entry 2, the
molar ratio of 1/SmI2 ) 1:1.2; for entry 3, the molar ratio of 1/SmI2/
HMPA ) 1:1.8:8; for entries 4-7, the molar ratio of 1/RCHO/SmI2/
HMPA ) 1:1.2:3.6:16. The reactions were conducted by dropwise
addition of 1 (or a mixture of 1 and RCHO) to the SmI2 solution.
The mixture was stirred at 0 °C to room temperature for 0.5-1.5
On treatment with Mg/MgI2, thiophenecarbaldehydes
undergo self-coupling reactions to give pinacols.7 Elec-
trochemical reductions of acetylthiophene or benzoyl-
thiophene also give pinacols.8 Reductions of alkanoyl-
thiophenes with dissolving metals such as Li/NH3 or Na/
NH3 give the corresponding 2,5-dihydro derivatives.9
Reductions of thiophenes to tetrahydrothiophenes are
achieved by using Et3SiH/CF3CO2H.10 We report herein
b
h. The starting material 1 was recovered (13-25%).
the thiophenecarbonyl coupling reactions of 2- and
3-thiophenecarbaldehydes (1 and 2) by mediation of SmI2/
HMPA. Along this line, we also found a method for
elaboration of thiophenecarbaldehydes to furans, R,â-
unsaturated-γ-lactones, and various thiophene-fused poly-
cyclic compounds including heterocyclic analogues of
neolignans.
† A recipient of Li-Ching Graduate Thesis Scholarship.
(1) For reviews of pinacolic coupling reactions, see: (a) Kahn, B.
E.; Rieke, R. D. Chem. Rev. 1988, 88, 733. (b) Robertson, G. M. in
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds;
Pergamon: Oxford, 1991; Vol. 3, pp 563-611. (c) Pons, J .-M.; Santelli,
M. Tetrahedron 1988, 44, 4295. (d) Wirth, T. Angew. Chem., Int. Ed.
Engl. 1996, 35, 61. (e) Molander, G. A.; Harris, C. R. Chem. Rev. 1996,
96, 307. For a pioneering work on the SmI2-induced pinacolic coupling
reactions, see: (f) Namy, J . L.; Souppe, J .; Kagan, H. B. Tetrahedron
Lett. 1983, 24, 765. More references with regard to the use of SmI2 for
pinacolic couplings are cited; see: (g) Lu, L.; Fang, J .-M.; Lee, G.-H.;
Wang, Y. J . Chin. Chem. Soc. 1997, 44, 279.
(2) (a) Shiue, J .-S.; Lin, C.-C.; Fang, J .-M. Tetrahedron Lett. 1993,
34, 335. (b) Shiue, J .-S.; Fang, J .-M. J . Chem. Soc., Chem. Commun.
1993, 1277. (c) Shiue, J .-S.; Lin, M.-H.; Fang, J .-M. J . Org. Chem. 1997,
62, 4643. (d) Lin, S.-C.; Yang, F.-D.; Shiue, J .-S.; Yang, S.-M.; Fang,
J .-M. J . Org. Chem. 1998, 63, 2909.
(3) (a) Yang, S.-M.; Fang, J .-M. J . Chem. Soc., Perkin Trans. 1 1995,
2669. For the related work on the coupling reactions of methyl
thiophene-2-carboxylate, see: (b) Yang, S.-M.; Fang, J .-M. Tetrahedron
Lett. 1997, 38, 1589.
(4) Wender, I.; Levine, R.; Orchin, M. J . Am. Chem. Soc. 1950, 72,
4375.
(5) Cervinka, O.; Malon, P.; Procha´zkova´, H. Collect. Czech. Chem.
Commun. 1974, 39, 1869.
(6) (a) Emerson, W. S.; Ratrick, T. M. J . Org. Chem. 1949, 14, 790.
(b) Clarke, H. T.; Dreger, E. E. Org. Synth. 1941, 304.
(7) (a) Gomberg, M.; Bachmann, W. E. J . Am. Chem. Soc. 1927, 49,
236. (b) Kegelman, M. R.; Brown, E. V. J . Am. Chem. Soc. 1953, 75,
5961.
Resu lts a n d Discu ssion
We studied first the coupling reactions of 2-thiophene-
carbaldehyde (1) promoted by SmI2 (1.8 molar proportion)
in THF solution (Table 1). In the presence of HMPA (8
M proportion), a thiophenecarbonyl coupling product 3a
was obtained in 45% yield. A significant amount (17%)
of the starting material 1 was also recovered. No pinacolic
coupling product was observed under such reaction
conditions. The reaction was presumably initiated by
sequential electron transfers from SmI2 to 2-thiophene-
carbaldehyde to form the C-3 organosamarium interme-
diate A or the C-5 organosamarium intermediate B
(Scheme 1). The C-5 organosamarium B was presumably
(9) (a) Blenderman, W. G.; J oullie´, M. M. Tetrahedron Lett. 1979,
4985. (b) Blenderman, W. G.; J oullie´, M. M. Synth. Commun. 1981,
11, 881.
(8) Kryukova, E. V.; Tomilov, A. P. Elektrokhimiya 1969, 5, 869
(Chem. Abstr. 1969, 71, 76739j).
(10) Kursanov, D. N.; Parnes, Z. N.; Bolestova, G. I.; Belen’kii, L. I.
Tetrahedron 1975, 31, 311.
10.1021/jo980851d CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/29/1998

Coupling of Thiophenecarbaldehydes
J . Org. Chem., Vol. 64, No. 2, 1999 395
Sch em e 1
was isolated by trituration of the reaction mixture with
EtOAc/hexane. A recrystallized sample was subjected to
X-ray diffraction to reveal the (1R*,1′R*,3R*,3aS*,6aR*)
configuration of this major diastereomer. To account for
the formation of this product, the chelate organo-
samarium species A was considered to dominate over B
in the absence of HMPA. The C-3 organosamarium
intermediate A could add to a second molecule of
2-thiophenecarbaldehyde via a transition state D having
two stacked thiacycles (Scheme 1). The resulting sa-
marium enolate E was then trapped by a third molecule
of 2-thiophenecarbaldehyde, presumably following the
favored chelate form F , to give an aldehyde G. The
subsequent intramolecular hemiacetalization would occur
in a stereoselective manner to furnish (1R*,1′R*,3R*,
3aS*,6aR*)-4a .
A cross-coupling reaction between 2-thiophenecarbal-
dehyde (1.0 equiv) and 3-thiophenecarbaldehyde (1.2
equiv) was effected by SmI2 (3.6 equiv) in the presence
of HMPA (16 equiv) to afford a single product 3b (49%).
This result indicated that 2-thiophenecarbaldehyde was
more reactive toward SmI2 to form organosamarium
species. Thus, 2-thiophenecarbaldehyde functioned as a
donor, whereas 3-thiophenecarbaldehyde functioned as
an acceptor in this cross-coupling reaction. Under similar
reaction conditions, the cross-coupling reactions of
2-thiophenecarbaldehyde with other aldehydes were also
carried out (Table 1). The self-coupling of 1 was dimin-
ished except for the reaction with propionaldehyde, a
relatively unreactive substrate toward SmI2 reduction.
The coupling products 3a -e were oxidized by PDC to give
the corresponding thiophene-2,5-dicarbonyl compounds
5a -e in high yields. These compounds are potentially
useful for the preparation of macrocycles and tris-1,3-
dithiole photoelectric material.12
We then studied the coupling reactions of 3-thiophene-
carbaldehyde (2) by using SmI2 in THF solution (Table
2). Unlike the coupling reactions of 1, the thiophenecar-
bonyl coupling reaction of 2 was complicated by a
pinacolic coupling reaction. In the absence of HMPA
(entries 1 and 2), the SmI2-promoted reaction afforded
pinacols 6, dimer 7a , and trimeric products 8 in variable
yields (Scheme 2). In the presence of HMPA (entry 3),
the thiophenecarbonyl coupling product 7a became the
major product (40-46%). However, the trimeric products
8 (50%) and 9 (9%) predominated (entry 4) when
3-thiophenecarbaldehyde (1 equiv) was treated with SmI2
(1.8 equiv) and HMPA (8 equiv) in THF solution for 10
min at 0 °C followed by addition of another 0.6 equiv of
3-thiophenecarbaldehyde.
favored due to the stabilizing effect of the adjacent sulfur
atom.11a Theoretically, half of 2-thiophenecarbaldehyde
would be converted to the samarium species to function
as a donor and another half of 2-thiophenecarbaldehyde
would act as an acceptor to furnish the coupling reaction.
Thus, addition of B with a second molecule of 2-thiophene-
carbaldehyde, giving C, followed by protonation and
oxidative rearomatization upon workup, would give the
thiophenecarbonyl coupling product 3a . Otherwise, the
unreacted intermediate B (or A) might revert to the
aromatic starting material 1 upon autoxidation.2
1
According to the H NMR spectral analysis, pinacols 6
existed as a mixture of two diastereomers (1:2). Com-
pound 8 also existed as a mixture of hemiacetals, which
was subjected to oxidation with PDC to give a lactone
10. Compound 9 was isolated as a single isomer; it was
presumably derived by a hydride transfer from the
hemiacetal 8 to 3-thiophenecarbaldehyde. This deduction
was supported by isolation of 3-thienylmethanol in a
nearly equal amount. The coupling constants J 3,3a of 9
and 10 were 7.6 and 7.8 Hz, respectively. By comparison
The dipolar cosolvent HMPA is known to alter the
regioselectivity in the reactions of allylmetals.11 Interest-
ingly, the reaction of 1 with SmI2 (1.2 M proportion) in
the absence of HMPA gave a mixture of the trimeric
1
product 4a and its diastereomers, as indicated by the H
NMR analysis. The major diastereomer 4a (40% yield)
(11) The cosolvent HMPA and other factors such as substituents,
attacking electrophiles, and countercations can alter the regiochemistry
in the reactions of allylmetals and related systems; see: (a) Evans, D.
A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147. (b) Biellmann, J . F.;
Ducep, J . B. Org. React. 1982, 27, 1. (c) Ogura, K. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 1, pp 505-539. (d) Roush, W. R. In Comprehensive
Organic Synthesis, Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 2, pp 1-98.
(12) For representative examples, see: (a) Armiger, Y. L. S.-T.; Lash,
T. D. J . Heterocycl. Chem. 1992, 29, 523. (b) Benahmed-Gasmi, A. S.;
Frere, P.; Garrigues, B.; Gorgues, A.; J ubault, M.; Carlier, R.; Texier,
F. Tetrahedron Lett. 1992, 33, 6457. (c) Takimiya, K.; Otsubo, T.;
Ogura, F.; Ashitaka, H.; Morita, K.; Suehiro, T. Chem. Lett. 1994, 255.
(d) Ohta, A.; Yamashita, Y. Heterocycles 1995, 40, 123.

396 J . Org. Chem., Vol. 64, No. 2, 1999
Yang and Fang
Ta ble 2. Sm I2-P r om oted Cou p lin g Rea ction s of
3-Th iop h en eca r ba ld eh yd e (2) in THF a
Sch em e 2
coupling products
(% yield)b
entry
1
substrates (RCHO)
additive
none
2
2
2
6 (20)c + 7a (20) +
8c (<5)
2
none
6 (25)c + 7a (15) +
8c (19)
3d
4e
HMPA
HMPA
6 (9)c + 7a (46)
6 (5)c + 7a (10) +
8 (50)c + 9 (9)
7a (18) + 7b (43)
7a (17) + 7c (37)
7a (27) + 7d (21)
2 + 2
5
2 + 4-MeOC6H4CHO
2 + 4-CH3C6H4CHO
2 + 1-methyl-2-pyrrole-
carbaldehyde
HMPA
HMPA
HMPA
6
7f
8
2 + CH3CH2CHO
HMPA
7a (22) + 7e (43)
a
For entry 1, the molar ratio of 2/SmI2 ) 1:1.8; for entry 2, the
molar ratio of 2/SmI2 ) 1:1.2; for entry 3, the molar ratio of 2/SmI2/
HMPA ) 1:1.8:8; for entries 5-8, the molar ratio of 2/RCHO/SmI2/
HMPA ) 1:1.2:3.6:16. The reactions were conducted by dropwise
addition of 2 (or a mixture of 2 and RCHO) to the SmI2 solution.
The mixture was stirred at 0 °C to room temperature for 0.5-2 h.
b
The starting material 2 was recovered (14-38%). c The products
d
consisted of diastereomers. If 2 was added in one portion to the
SmI2/HMPA solution, the reaction gave 6 (21%) and 7a (40%). If
the SmI2/HMPA solution was added to the 3-thiophenecarbalde-
hyde solution, the reaction gave 6 (26%) and 7a (46%). e Another
0.6 equiv of 2 was added after the mixture of 2/SmI2/HMPA (1:
1.8:8) was stirred at 0 °C for 10 min. The reaction also gave a
13% of 3-thienylmethanol. f The side products were 3-thienyl-
methanol (14%) and 2-hydroxy-1-(1-methylpyrrol-2-yl)-2-(3-thien-
yl)ethanone (16%).
with the coupling constant of 7.0 Hz for H1-H6a of
(1R*,1′R*,3R*,3aS*,6aR*)-4a , the H-3 and H-3a of 9 and
10 also likely had the cis relationship. This result could
also account for a chelate transition state J having two
stacked thiacycles (Scheme 2). Addition of 3-thiophene-
carbaldehyde to the enolate K should occur on the less
hindered face, giving the aldehyde L, which formed the
hemiacetal 8 intramolecularly. The relative configuration
of C-1′ remained unknown, though it was likely R*
according to the mechanistic consideration.
By the promotion of SmI2/HMPA, 3-thiophenecarbal-
dehyde reacted with aromatic and aliphatic aldehydes
to give the thiophenecarbonyl coupling products 7b-e
(entries 5-8, Table 2). Nonetheless, the self-coupling of
2 (giving 7a ) also competed with these cross-couplings.
The reaction with 1-methyl-2-pyrrolecarbaldehyde also
yielded 3-thienylmethanol and 2-hydroxy-1-(1-methyl-
pyrrol-2-yl)-2-(3-thienyl)ethanone in nearly equal amounts
(ca. 15% each). This result indicated that a side reaction
of crossed pinacolic coupling between 2 and 1-methyl-
pyrrole-2-carbaldehyde occurred and the resulting pinacol
could transfer a hydride to the remaining aldehyde 2.
The key intermediate M (Scheme 3) in the coupling
reactions of 3-thiophenecarbaldehyde was also trapped
by alkylating agents. The alkylations occurred exclusively
at the sulfur atom to effect a concurrent opening of the
thiophene ring, giving the hemiacetals 11a -d (Table 3).
The double bonds of 11a -d retained the (Z) configuration
as indicated by the coupling constants (ca. 10.5 Hz) of
the two adjacent vinyl protons. As trapping of the
intermediate by alkylating agents drove the coupling
reaction through the last irreversible step, the yields of
11a -d (55-74%) were higher than those of dimers 7a -d
(21-46%). The hemiacetals 11a -d were oxidized by PDC
to give 70-82% yields of the corresponding lactones
12a -d with cis double bonds. It was noted that the
hemiacetals were unstable in CDCl3 solution containing
a small amount of DCl. Indeed, an acid-catalyzed dehy-
dration of 11b was carried out to give a quantitative yield
of the furan 13a with a cis double bond. (Z)-13a isomer-
ized in part to (E)-13a when it was subjected to chroma-
tography on a silica gel column. The hemiacetal 11c was
similarly converted to the furan 13b by acid catalysis.
This sequential thiophenecarbonyl coupling-alkylation
method thus provides a convenient route to furans and
butenolides, which often exhibit important biological
activities.13
This method is also applicable to the synthesis of
thiophene-fused polycyclic compounds. The coupling prod-
ucts 7a ,b were similarly oxidized by PDC to give
thiophene-2,3-dicarbonyl compounds 14a ,b, which re-
acted further with hydrazine to give thieno[2,3-d]pyrid-
azines 15a ,b (Scheme 4). The thienopyriazones related
to 15a ,b have been used as antiasthmatic drugs.14 The
coupling products 7a -c were treated with Lawesson’s
(13) For representative reviews and examples, see: (a) Tsuboi, S.;
Wada, H.; Muranaka, K.; Takeda, A. Bull. Chem. Soc. J pn. 1987, 60,
2917. (b) Tsubuki, M. J . Synth. Org. Chem. 1993, 51, 399. (c) Marles,
R. J .; Pazos-Sanou, L.; Compadre, C. M.; Pezzuto, J . M.; Bloszyk, E.;
Amason, J . T. Recent Adv. Phytochem. 1995, 29, 333. (d) Collins, I.
Contemp. Org. Synth. 1997, 4, 281.
(14) Yamaguchi, M.; Maruyama, N.; Koga, T.; Kamei, K. Chem.
Pharm. Bull. 1995, 43, 236.

Coupling of Thiophenecarbaldehydes
J . Org. Chem., Vol. 64, No. 2, 1999 397
Sch em e 3
Sch em e 4
a
Reagents and conditions: (i) PDC, CH2Cl2, rt, 2.5 h; (ii) N2H4,
EtOH, rt (10 min) then reflux (20 min); (iii) For 16a -c, Lawesson’s
reagent, 1,4-dioxane, reflux, 3 h; for 17, PhCH2NH2, cat. PTSA,
PhH; for 18, cat. PPTS, PhH; (iv) For 19a -c, dimethyl acetylene-
dicarboxylate, cat. PPTS, PhH, 1-2 h; for 20a -c, N-phenylmale-
imide, cat. PPTS, PhH, 2 h; for 21, maleic anhydride, cat. PPTS,
PhH, 2 h.
7a -c with N-phenylmaleimide or maleic anhydride were
also realized by similar procedures. Compounds 19a ,b
are heterocyclic analogues of 1-arylnaphthalene lignans
with antihyperlipidemic activity.16
a
Reagents and conditions: (i) PDC, CH2Cl2, sieves, 3-7 h, 12a
77%, 12b 79%, 12c 82%, 12d 70%; (ii) cat. HCl in CHCl3, 13a
100%, 13b 100%.
A previous method17 for alkylation of thiophenecarbal-
dehydes requires sequential treatments with amine (such
as N-methylpiperazine) and BuLi (several molar propor-
tions) at low temperatures to generate R-aminoalkoxide
intermediates. This procedure is tedious and the reaction
shows variable regioselectivities depending on the reac-
tion substrates and conditions. On the other hand, our
present method using SmI2/HMPA as the promoter is
relatively simple and gives the thiophenecarbonyl cou-
pling products with predictable regiochemistry. The
thiophenecarbonyl coupling products are versatile build-
ing blocks for the synthesis of thiophene-fused polycyclic
compounds such as 15-21. Furthermore, we have dem-
onstrated a novel way for the ring-opening of 3-thiophene-
carbaldehyde by sequential coupling-alkylation to cul-
minate in the formation of furans and R,â-unsaturated
γ-lactones such as 12 and 13.
Ta ble 3. Sequ en tia l Cou p lin g-Alk yla tion s of
3-Th iop h en eca r ba ld eh yd e (2)a
substrates
(R1CHO)
products
(% yield)
entry
1
R2X (equiv)
2
allyl bromide (1)
6b (18) + 7a (38) +
11a b (20)
2
3
4
5
2
2
2
2
allyl bromide (2)
benzyl bromide (1)
benzyl bromide (2)
6b (5) + 11a b (55)
6b (15) + 11bb (46)
6b (13) + 11bb (65)
dimethyl sulfate (2.5) 6b (7) + 7a (29) +
11cb (29)
6
7
2
methyl iodide (2.5)
6b (8) + 11cb (74)
11bb (22) +
2 + 4-MeOC6- benzyl bromide (2)
H4CHO
11d b (63)
a
b
Refer to Scheme
3
for these sequential reactions. The
products existed as diastereomeric mixtures.
reagent to give thieno[2,3-c]thiophenes 16a -c in 81-88%
yields. Compound 7a was heated with benzylamine in
the presence of p-TsOH to give an unstable product of
thieno[2,3-c]pyrrole 17, which displayed a characteristic
signal at δH 5.40 (2 H, s) for the N-benzyl group in
addition to other signals for aromatic protons. The acid-
catalyzed dehydration of 7a also led to an unstable
thieno[2,3-c]furan 18 of which H-1 occurred at δ 7.73 (s).
Compounds 16a -c, 17, and 18 can serve as the equiva-
lents of thiophene-2,3-quinodimethane employed as the
diene substrates in Diels-Alder reactions.15 Thus, con-
densation of 7a -c with dimethyl acetylenedicarboxylate
was carried out by the catalysis of PPTS to give benzo-
thiophenes 19a -c in 89-92% yields. Cycloadditions of
Exp er im en ta l Section
Melting points are uncorrected. 1H NMR spectra were
recorded at 200, 300, or 400 MHz; 13C NMR spectra were
recorded at 50, 75, or 100 MHz. Tetramethylsilane and CDCl3
were used as internal standards in the 1H and 13C NMR
spectra, respectively. Mass spectra were recorded at an ion-
izing voltage of 70 or 20 eV. High-resolution mass spectra were
taken using an internal PFK reference followed by a computer
(16) (a) Kuroda, T.; Takahashi, M.; Ogiku, T.; Ohmizu, H.; Nishitani,
T.; Kondo, K.; Iwasaki, T. J . Org. Chem. 1994, 59, 7353. (b) Kuroda,
T.; Takahashi, M.; Ogiku, T.; Ohmizu, H.; Kondo, K.; Iwasaki, T. J .
Chem. Soc., Chem. Commun. 1991, 1635. (c) Hutchinson, C. R.
Tetrahedron 1981, 37, 1047. (d) Cardwell, K.; Hewitt, B.; Ladlow, M.;
Magnus, P. J . Am. Chem. Soc. 1988, 110, 2242. (e) Gribble, G. W.;
Saulnier, M. G. Heterocycles 1985, 23, 1277.
(15) (a) Pindur, U.; Erfanian-Abdoust, H. Chem. Rev. 1989, 89, 1681.
(b) Sha, C.-K.; Tsou, C.-P. Tetrahedron 1993, 49, 6831. (c) Sha, C.-K.;
Tsou, C.-P. J . Chem. Soc., Perkin Trans. 1 1994, 3065.
(17) (a) Comins, D. L.; Killpack, M. O. J . Org. Chem. 1987, 52, 104.
(b) Comins, D. L. Synlett 1992, 615.

398 J . Org. Chem., Vol. 64, No. 2, 1999
Yang and Fang
search for the mass that best fit an elemental formula. Merck
silica gel 60F sheets were used for analytical thin-layer
chromatography. Column chromatography was performed on
SiO2 (70-230 mesh); gradients of EtOAc and n-hexane were
used as eluents. High-pressure liquid chromatography was
mmol) in the presence of HMPA gave pinacol 6 (47 mg, 21%)
and the self-coupling product 7a (102 mg, 46%) (40%). 7a : oil;
TLC (EtOAc/hexane, 1:4) Rf ) 0.18; IR (neat) 3378 (OH), 1658
(CdO) cm-1; 1H NMR (CDCl3, 200 MHz) δ 9.92 (1 H, s, CHO),
7.43 (1 H, d, J ) 5.1 Hz, H-5), 7.27 (2 H, m), 7.20 (1 H, d, J )
5.1 Hz, H-4), 7.08 (1 H, dd, J ) 4.4, 1.9 Hz, H-4′), 6.42 (1 H,
d, J ) 4.9 Hz), 4.43 (1 H, d, J ) 4.9 Hz, OH); 13C NMR (CDCl3,
50 MHz) δ 186.1 (d), 158.3 (s), 142.8 (s), 136.1 (s), 129.8 (d),
126.1 (d), 126.0 (d), 124.3 (d), 122.4 (d), 66.9 (d); MS m/z (rel
intensity) 224 (100, M+); HRMS calcd for C10H8O2S2 223.9966,
found 223.9961. Anal. Calcd for C10H8O2S2: C, 53.57; H, 3.60.
Found: C, 53.56, H, 3.49.
carried out on
a liquid chromatograph equipped with a
refractive index detector. The samples were analyzed and/or
separated on a Hibar Lichrosorb Si 60 (7 µm) column (25 cm
× 1 cm) with the indicated eluent with a 5 mL/min flow rate.
THF was distilled from sodium benzophenone ketyl under N2.
Gen er a l P r oced u r e for th e Rea ction s of Th iop h en e-
ca r ba ld eh yd es w ith Sm I2. Samarium metal (0.66 g, 4.4
mmol) and 1,2-diiodoethane (1.02 g, 3.6 mmol) in anhydrous
THF (40 mL) were stirred at room temperature under an argon
atmosphere for 1 h to give a deep-blue solution. HMPA (2.8
mL, 16 mmol) was added in most cases. Precaution should be
taken as HMPA is a toxic cancer suspect agent. The mixture
was cooled to 0 °C in an ice bath, and a THF solution (2 mL)
of thiophenecarbaldehyde (2.0 mmol) (for self-coupling reac-
tions) or a mixture of thiophenecarbaldehyde (1 mmol) and
an appropriate aldehyde (1.2 mmol) (for cross-coupling reac-
tions) was added dropwise over a period of 2 min. The light-
yellow mixture was stirred at 0 °C for 10 min and warmed to
room temperature over a period of 0.5-2 h. Saturated NH4Cl(aq)
(0.1 mL) was added. The mixture was filtered through a pad
of silica gel and rinsed with EtOAc/hexane (1:1). The organic
phase was concentrated under reduced pressure and chro-
matographed on a silica gel column with elution of EtOAc/
hexane to give products.
3,3a -Dih yd r o-6a -(1-h yd r oxy-(3-t h ien yl)m et h yl)-3-(3-
th ien yl)th ien o[2,3-c]fu r a n -1-on e (9) a n d 3,3a -Dih yd r o-3-
(3-th ien yl)-6a -(th iop h en e-3-ca r bon yl)th ien o[2,3-c]fu r a n -
1-on e (10). According to the general procedure, 3-thiophenecarb-
aldehyde (224 mg, 2 mmol) was added to the SmI2 (3.6 mmol)/
HMPA (16 mmol) solution. The mixture was stirred for 10 min
at 0 °C, and a second portion of 3-thiophenecarbaldehyde (135
mg, 1.2 mmol) was added. The mixture was stirred at room
temperature for 10 h to give 8 (166 mg, 50%), 9 (28 mg, 9%),
and 3-thienylmethanol (45 mg, 13%). Compound 9 existed as
a single isomer: oil; TLC (EtOAc/hexane, 3:7) Rf ) 0.36; IR
1
(neat) 3468, 1756 cm-1; H NMR (CDCl3, 200 MHz) δ 7.37-
7.31 (2 H, m), 7.24-7.20 (2 H, m), 7.04-7.00 (2 H, m), 6.28 (1
H, d, J ) 5.6 Hz, H-5), 5.66 (1 H, d, J ) 5.6 Hz, H-6), 5.25 (1
H, d, J ) 5.0 Hz, H-1), 5.22 (1 H, d, J ) 7.4 Hz, H-3), 4.18 (1
H, d, J ) 7.4 Hz, H-3a), 3.16 (1 H, d, J ) 5.0 Hz, OH); 13C
NMR (CDCl3, 75 MHz) δ 175.5 (s), 139.8 (s), 138.3 (s), 130.7
(d), 127.4 (d), 126.3 (d), 125.3 (d), 125.1 (d), 123.6 (d), 122.7
(d), 119.5 (d), 84.9 (d), 72.0 (s), 70.6 (d), 54.2 (d); MS m/z (rel
intensity) 336 (33, M+), 224 (100), 206 (73), 179 (46), 113 (65);
HRMS calcd for C15H12O3S3 335.9949, found 335.9946.
5-[1-Hyd r oxy-(2-th ien yl)m eth yl]th iop h en e-2-ca r ba ld e-
h yd e (3a ) a n d 5-(Th iop h en e-2-ca r bon yl)th iop h en e-2-ca r -
ba ld eh yd e (5a ). According to the general procedure, treat-
ment of 2-thiophenecarbaldehyde (224 mg, 2 mmol) with SmI2
(3.6 mmol) in the presence of HMPA (16 mmol) gave the self-
coupling product 3a (100 mg, 45%). By a procedure similar to
that for 10, treatment of 3a (75 mg, 0.33 mmol) with PDC (376
mg, 1.0 mmol) and molecular sieves (4 Å, 2 g) in CH2Cl2 (10
mL) at 25 °C for 2 h gave 5a (66 mg, 89%). 3a : oil; TLC
Compound 8 existed as a mixture of two isomers (3:2). The
diastereomeric mixture of 8 (38 mg, 0.11 mmol) was treated
with PDC (138 mg, 0.37 mmol) and molecular sieves (4 Å, 2 g)
in CH2Cl2 (10 mL) at 25 °C for 1 h. The mixture was filtered
through a pad of silica gel and rinsed with EtOAc/hexane (3:
7). The organic phase was concentrated under reduced pres-
sure and chromatographed on a silica gel column with elution
of EtOAc/hexane (1:9) to give the product 10 (22 mg, 59%).
10: solid; mp 109-111 °C; TLC (EtOAc/hexane, 1:9) Rf ) 0.17;
1
(EtOAc/hexane (3:7)) Rf ) 0.2; H NMR (CDCl3, 200 MHz) δ
9.74 (1H, s, CHO), 7.58 (1 H, d, J ) 3.8 Hz), 7.27-7.20 (1 H,
m), 7.03-6.90 (3 H, m), 6.22 (1 H, d, J ) 3.6 Hz), 3.95 (1 H, br
s, OH). 5a : solid; mp 102-103 °C; TLC (EtOAc/hexane, 3:7)
Rf ) 0.26; IR (KBr) 2802 (CHO), 1670 (CdO), 1599 (CdO)
cm-1; 1H NMR (CDCl3, 200 MHz) δ 9.98 (1 H, s, CHO), 7.90 (1
H, dd, J ) 3.8, 1.0 Hz), 7.88 (1 H, d, J ) 3.9 Hz), 7.79 (1 H, d,
J ) 3.9 Hz), 7.75 (1 H, dd, J ) 4.8, 1.0 Hz), 7.19 (1 H, dd, J )
4.8, 3.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 183.3 (d), 178.5 (s),
148.9 (s), 147.7 (s), 142.1 (s), 135.0 (d), 134.9 (d), 134.1 (d),
132.5 (d), 128.3 (d); MS m/z (rel intensity) 222 (10, M+), 57
(100); HRMS calcd for C10H6O2S2 221.9809, found 221.9813.
1,3,6a -Tr ih yd r o-3-h yd r oxy-3a -[1-h yd r oxy-(2-t h ien yl)-
m eth yl]-1-(2-th ien yl)th ien o[2,3-c]fu r a n (4a ). According to
the general procedure, treatment of 2-thiophenecarbaldehyde
(336 mg, 3.0 mmol) with SmI2 (3.6 mmol) gave the trimeric
product 4a and its diastereomers (220 mg, 65%). The mixture
was triturated with EtOAc/hexane (1:4) and filtered to give
the major (1R*,1′R*,3R*,3aS*,6aR*)-4a isomer (136 mg, 40%).
The configuration was established by an X-ray diffraction
analysis of a sample recrystallized from CHCl3/cyclohexane.
4a : solid; mp 157.5-158.5 °C; TLC (EtOAc/hexane, 3:7) Rf )
1
IR (neat) 1773, 1664, 1247, 1165 cm-1; H NMR (CDCl3, 200
MHz) δ 8.44 (1 H, dd, J ) 2.7, 1.2 Hz), 7.65 (1 H, dd, J ) 5.1,
1.2 Hz), 7.42-7.40 (2 H, m), 7.32 (1 H, dd, J ) 5.1, 2.7 Hz),
7.16 (1 H, dd, J ) 4.2, 2.1 Hz), 6.49 (1 H, d, J ) 5.5 Hz), 5.96
(1 H, d, J ) 5.5 Hz), 5.38 (1 H, d, J ) 7.9 Hz), 4.96 (1 H, d, J
) 7.9 Hz); 13C NMR (CDCl3, 75 MHz) δ 184.4 (s), 170.7 (s),
138.0 (s), 137.4 (s), 135.3 (d), 130.8 (d), 128.5 (d), 127.6 (d),
126.0 (d), 125.0 (d), 123.5 (d), 119.0 (d), 83.9 (s), 76.9 (d), 56.8
(d); MS m/z (rel intensity) 334 (31, M+), 257 (7), 223 (10), 206
(13), 111 (100); HRMS calcd for C15H10O3S3 333.9792, found
333.9798.
Gen er a l P r oced u r e for Seq u en t ia l Cou p lin g-Alk yl-
a tion . The THF solution (40 mL) of SmI2 (3.6 mmol) and
HMPA (2.8 mL, 16 mmol) was prepared by the described
general procedure and cooled to 0 °C in an ice bath. A THF
solution (2 mL) of 3-thiophenecarbaldehyde (224 mg, 2 mmol)
(for self-coupling reactions) or a mixture of 3-thiophenecar-
baldehyde (112 mg, 1.0 mmol) and an appropriate aldehyde
(1.2 mmol) in THF (2 mL) (for cross-coupling reactions) was
added dropwise over a period of 2 min. The mixture was stirred
for 10 min, and an alkylating agent (1-2.5 mmol) was added.
The mixture was stirred at room temperature for a period of
21-27 h and quenched by addition of saturated NH4Cl(aq) (0.1
mL). The mixture was filtered through a pad of silica gel and
rinsed with EtOAc/hexane (1:1). The organic phase was
concentrated under reduced pressure and chromatographed
on a silica gel column with elution of EtOAc/hexane to give
the γ-lactols 11a -d .
0.23; IR (KBr) 3481, 3381 cm-1 1H NMR (CD3COCD3, 200
;
MHz) δ 7.33 (2 H, dd, J ) 4.7, 1.2 Hz), 7.17 (1 H, dd, J ) 2.5,
0.8 Hz), 7.01-6.88 (3 H, m), 6.29 (1 H, d, J ) 3.3 Hz), 5.92 (1
H, dd, J ) 6.0, 1.5 Hz), 5.80 (1 H, d, J ) 7.0 Hz), 5.73 (1 H, d,
J ) 3.3 Hz), 5.57 (1 H, d, J ) 5.3 Hz), 4.83 (1 H, d, J ) 5.3
Hz), 4.59 (1 H, dd, J ) 6.0, 3.1 Hz), 3.74 (1 H, ddd, J ) 7.0,
3.1, 1.5 Hz); 13C NMR (CD3COCD3, 75 MHz) δ 146.1 (s), 142.5
(s), 127.4 (d, C-5), 126.9 (d), 126.8 (d), 126.7 (d), 126.0 (d), 125.5
(d), 125.2 (d), 121.4 (d, C-6), 104.6 (d, C-3), 78.9 (s, C-3a), 78.6
(d, C-1), 72.7 (d, C-1′), 60.9 (d, C-6a); MS m/z (rel intensity)
338 (31, M+), 113 (100). Anal. Calcd for C15H14O3S3: C, 53.25;
H, 4.17. Found: C, 52.78; H, 4.17.
3-(2-Allylsu lfa n yl)eth en yl-2-h yd r oxy-5-(3-th ien yl)-2,5-
d ih yd r ofu r a n (11a ) a n d 3-(2-Allylsu lfa n yl)eth en yl-5-(3-
th ien yl)-5H-fu r a n -2-on e (12a ). According to the general
procedure, coupling of 3-thiophenecarbaldehyde (224 mg, 2
mmol) followed by alkylation with allyl bromide (0.173 mg,
2-[1-Hyd r oxy-(3-th ien yl)m eth yl]th iop h en e-3-ca r ba ld e-
h yd e (7a ). According to the general procedure, treatment of
3-thiophenecarbaldehyde (224 mg, 2 mmol) with SmI2 (3.6

Coupling of Thiophenecarbaldehydes
J . Org. Chem., Vol. 64, No. 2, 1999 399
2.0 mmol) gave the γ-lactol 11a (145 mg, 55%) as a mixture of
two isomers (62:38). Oxidation of 11a (45 mg, 0.17 mmol) with
PDC (188 mg, 0.5 mmol) at 25 °C for 3 h by a procedure similar
to that for 10 gave 12a (35 mg, 77%). 11a : oil; TLC (EtOAc/
(289 mg, 0.714 mmol) in refluxing 1,4-dioxane (10 mL) for 3
h. The mixture was cooled, concentrated, and chromato-
graphed on a silica gel column by elution with EtOAc/hexane
(1:19) to give 16a (67 mg, 85%). 16a : oil; TLC (EtOAc/hexane,
1:9) Rf ) 0.64; IR (neat) 1367, 1092, 746 cm-1; 1H NMR (CDCl3,
200 MHz) δ 7.44-7.39 (3H, m), 7.35 (1 H, d, J ) 5.5 Hz), 7.22
(1 H, s), 6.90 (1 H, d, J ) 5.5 Hz); 13C NMR (CDCl3, 75 MHz)
δ 147.9 (s), 134.6 (s), 134.4 (s), 132.1 (d), 126.5 (d), 125.8 (d),
124.2 (s), 119.5 (d), 117.3 (d), 109.9 (d); MS m/z (rel intensity)
222 (100, M+); HRMS calcd for C10H6S3 221.9632, found
221.9635.
1
hexane (3:7)) Rf ) 0.31; IR (neat) 3402, 1570, 1037 cm-1; H
NMR (CDCl3, 200 MHz) δ 7.28-7.21 (2 H, m), 7.09 (0.62 H,
dd, J ) 4.2, 2.0 Hz), 7.00 (0.38 H, dd, J ) 4.8, 1.1 Hz), 6.38 (1
H, d, J ) 10.7 Hz), 6.26 (1 H, s), 6.08 (0.38 H, s), 6.20-6.00 (1
H, m), 5.98 (1 H, d, J ) 10.7 Hz), 5.84 (0.62 H, s), 5.89-5.72
(1 H, m), 5.24-5.13 (2 H, m), 3.38 (2 H, d, J ) 7.0 Hz), 3.11 (1
H, d, J ) 7.8 Hz, OH); 13C NMR (CDCl3, 50 MHz) δ 142.5 (s),
141.5 (s), 136.8 (s), 136.5 (s), 133.5 (d, 2 C), 131.5 (d), 131.4
(d), 130.1 (d), 130.0 (d), 126.4 (d, 2 C), 126.2 (d), 126.1 (d), 122.2
(d, 2 C), 118.2 (t, 2 C), 115.5 (d, 2 C), 103.9 (d), 103.7 (d), 82.8
(d), 82.5 (d), 37.4 (t, 2 C); MS m/z (rel intensity) 266 (10, M+),
141 (100); HRMS calcd for C13H14O2S2 266.0435, found 266.0421.
12a : oil; TLC (EtOAc/hexane, 1:9) Rf ) 0.12; IR (neat) 3498
(overtone), 1747, 1624 cm-1; 1H NMR (CDCl3, 200 MHz) δ 7.47
(1 H, d, J ) 2.0 Hz), 7.35-7.32 (2 H, m), 7.01 (1 H, dd, J )
4.0, 2.2 Hz), 6.64 (1 H, d, J ) 10.7 Hz), 6.29 (1 H, d, J ) 10.7
Hz), 6.07 (1 H, d, J ) 2.0 Hz), 5.90-5.73 (1 H, m), 5.28-5.17
(2 H, m), 3.45 (2 H, dd, J ) 7.1, 1.0 Hz); 13C NMR (CDCl3, 50
MHz) δ 172.6 (s), 145.9 (d), 136.0 (s), 134.8 (d), 133.0 (d), 128.0
(s), 127.0 (d), 125.7 (d), 123.9 (d), 118.8 (t), 112.8 (d), 78.6 (d),
37.6 (t); MS m/z (rel intensity) 264 (35, M+), 111 (100); HRMS
calcd for C13H12O2S2 264.0279, found 264.0283.
3-(2-Ben zylsu lfa n yl)et h en yl-5-(3-t h ien yl)fu r a n (13a ).
Compound 11b (85 mg, 0.27 mmol) was treated with 0.01 N
HCl in CHCl3 (5 mL) for 5 min. The solution was concentrated
under reduced pressure to give (Z)-13a (80 mg, 100%), which
isomerized in part (Z/E ) 2:3) on filtration through a pad of
silica gel. (Z)-13a : oil; TLC (EtOAc/hexane, 1:19) Rf ) 0.37;
IR (neat) 3104, 1493, 779 cm-1; 1H NMR (CDCl3, 300 MHz) δ
7.56 (1 H, s), 7.45-7.44 (1 H, m), 7.37-7.24 (7 H, m), 6.69 (1
H, s), 6.22 (1 H, d, J ) 10.4 Hz), 6.13 (1 H, d, J ) 10.4 Hz),
4.00 (2 H, s); 13C NMR (CDCl3, 75 MHz) δ 150.8 (s), 140.4 (d),
137.4.(s), 132.3 (s), 128.9 (d, 2 C), 128.7 (d, 2 C), 127.4 (d),
126.1 (d), 124.8 (d), 124.7 (d), 124.2 (s), 119.2 (d), 116.4 (d),
105.5 (d), 38.8 (t); MS m/z (rel intensity) 298 (87, M+), 91 (100);
HRMS calcd for C17H14OS2 298.0486, found 298.0481. (E)-
13a : 1H NMR (CDCl3, 300 MHz) δ 7.47 (1 H, s), 7.45-7.27 (8
H, m), 6.51 (1 H, s), 6.47 (1 H, d, J ) 15.4 Hz), 6.39 (1 H, d, J
) 15.4 Hz), 3.97 (2 H, s); 13C NMR (CDCl3, 75 MHz) δ 151.6
(s), 138.1 (d), 137.2 (s), 132.2 (s), 128.7 (d, 2 C), 128.6 (d, 2 C),
127.2 (d), 126.2 (d), 125.4 (s), 124.5 (d), 123.3 (d), 119.4 (d),
118.7 (d), 102.0 (d), 37.4 (t).
4-Hyd r oxy-5,6-bis(m eth oxyca r bon yl)-7-(3-th ien yl)ben -
zo[b]th iop h en e (19a ). A mixture of 7a (79 mg, 0.352 mmol)
and dimethyl acetylenedicarboxylate (DMAD, 50 mg, 0.352
mmol) was treated with 20 mol % PPTS (18 mg, 0.071 mmol)
in refluxing benzene (30 mL) for 2 h. A Dean-Stark apparatus
was equipped for the removal of water. The mixture was
cooled, filtered through a pad of silica gel, and rinsed with
EtOAc/hexane (1:1). The organic phase was concentrated and
chromatographed on a silica gel column by elution with EtOAc/
hexane (1:4) to give 19a (112 mg, 91%). 19a : solid; mp 108-
110 °C (lit.16a 107-109 °C); TLC (EtOAc/hexane, 1:4) Rf ) 0.26;
IR (neat) 1733, 1668 cm-1; 1H NMR (CDCl3, 300 MHz) δ 11.88
(1 H, s), 7.63 (1 H, d, J ) 5.4 Hz), 7.40-7.37 (3 H, m), 7.20 (1
H, dd, J ) 5.0, 1.2 Hz), 3.91 (3 H, s), 3.64 (3 H, s); 13C NMR
(CDCl3, 75 MHz) δ 170.1 (s), 168.8 (s), 157.7 (s), 147.9 (s), 136.8
(s), 130.1 (s), 129.3 (s), 128.3 (d), 127.5 (d), 125.6 (d), 124.8
(d), 122.0 (d), 121.3 (s), 103.8 (s), 52.9 (q), 52.1 (q); MS m/z
(rel intensity) 348 (90, M+), 316 (100).
N-P h en yl-7-(3-t h ien yl)b en zo[b]t h iop h en e-5,6-d ica r -
boxim id e (20a ). By a procedure similar to that for 19a , a
mixture of 7a (79 mg, 0.352 mmol) and N-phenylmaleimide
(61 mg, 0.352 mmol) was treated with 20 mol % PPTS (18 mg,
0.071 mmol) in refluxing benzene (30 mL) for 2 h to give 20a
(113 mg, 89%). 20a : solid; mp 250-252 °C; TLC (EtOAc/
hexane, 3:7) Rf ) 0.31; IR (neat) 1762, 1712 cm-1 1H NMR
;
(CDCl3, 200 MHz) δ 8.33 (1 H, s), 7.79-7.75 (2 H, m), 7.59 (1
H, d, J ) 5.5 Hz), 7.50-7.32 (7 H, m); 13C NMR (CDCl3, 50
MHz) δ 167.0 (s), 166.7 (s), 146.9 (s), 143.4 (s), 134.4 (s), 132.6
(d), 131.8 (s), 131.7 (s), 129.1 (s), 129.0 (d, 3 C), 128.0 (d), 126.7
(d, 2 C), 126.5 (d), 125.6 (d), 125.4 (d), 121.8 (s), 118.5 (d); MS
m/z (rel intensity) 361 (100, M+); HRMS calcd for C20H11NO2S2
361.0231, found 361.0242. Anal. Calcd for C20H11NO2S2: C,
66.48; H, 3.07; N, 3.88. Found: C, 65.85; H, 2.99; N, 3.80.
7-(4-Met h ylp h en yl)b en zo[b]t h iop h en e-5,6-d ica r b ox-
ylic a n h yd r id e (21). By a procedure similar to that for 19a ,
a mixture of 7c (90 mg, 0.388 mmol) and maleic anhydride
(38 mg, 0.388 mmol) was treated with 20 mol % PPTS (20 mg,
0.078 mmol) in refluxing benzene (30 mL) for 2 h to give 21
(76 mg, 67%). 21: solid; mp 170-172 °C; TLC (EtOAc/hexane,
2-(Th iop h en e-3-ca r b on yl)t h iop h en e-3-ca r b a ld eh yd e
(14a ). By a procedure similar to that for 10, oxidation of 7a
(120 mg, 0.53 mmol) with PDC (414 mg, 1.1 mmol) and
molecular sieves (4 Å, 2 g) in CH2Cl2 (15 mL) at 25 °C for 2.5
h gave 14a (101 mg, 86%). 14a : solid; mp 111.5-112.0 °C;
TLC (EtOAc/hexane, 3:17) Rf ) 0.24; IR (KBr) 1675, 1614 cm-1
;
3:7) Rf ) 0.40; IR (neat) 1838, 1772 cm-1 1H NMR (CDCl3,
;
1H NMR (CDCl3, 200 MHz) δ 10.21 (1 H, s, CHO), 8.13-8.11
(1 H, m), 7.66-7.61 (2 H, m), 7.50 (1 H, d, J ) 4.8 Hz), 7.42-
7.38 (1 H, m); 13C NMR (CDCl3, 50 MHz) δ 186.0 (d, CHO),
180.6 (s), 146.8 (s), 144.6 (s), 142.0 (s), 134.7 (d), 129.8 (d),
128.1 (d), 127.9 (d), 127.0 (d); MS m/z (rel intensity) 222 (100,
M+); HRMS calcd for C10H6O2S2 221.9809, found 221.9810.
4-(3-Th ien yl)th ien o[2,3-d ]p yr id a zin e (15a ). A mixture
of 14a (12 mg, 0.054 mmol) and hydrazine monohydrate (0.1
mL, 2 mmol) in EtOH (10 mL) was stirred at 25 °C for 10 min
and then heated at reflux for 20 min. The mixture was
concentrated and chromatographed on a silica gel column by
elution with EtOAc/hexane (1:1) to give 15a (11 mg, 94%).
15a : solid; mp 78-79 °C; TLC (EtOAc/hexane, 1:1) Rf ) 0.13;
300 MHz) δ 8.36 (1 H, s), 7.87 (1 H, d, J ) 5.3 Hz), 7.63 (1 H,
d, J ) 5.3 Hz), 7.50 (2 H, d, J ) 8.0 Hz), 7.35 (2 H, d, J ) 8.0
Hz), 2.46 (3 H, s); 13C NMR (CDCl3, 50 MHz) δ 163.2 (s), 162.1
(s), 148.2 (s), 144.5 (s), 140.1 (s), 138.8 (s), 134.6 (d), 130.6 (s),
129.4 (d, 2 C), 128.9 (d, 2 C), 127.9 (s), 125.4 (d), 120.7 (s),
120.0 (d), 21.5 (q); MS m/z (rel intensity) 294 (100, M+); HRMS
calcd for C17H10O3S 294.0351, found 294.0348.
Ack n ow led gm en t. We thank the National Science
Council for financial support (Grant NSC87-2113-M002-
042).
IR (KBr) 1527, 1461, 1312, 863, 782, 660 cm-1 1H NMR
;
(CDCl3, 200 MHz) δ 9.44 (1 H, s), 8.17 (1 H, dd, J ) 2.8, 1.3
Hz), 7.99 (1 H, dd, J ) 5.0, 1.3 Hz), 7.84 (1 H, d, J ) 5.4 Hz),
7.52 (1 H, d, J ) 5.4 Hz), 7.49 (1 H, dd, J ) 5.0, 2.8 Hz); 13C
NMR (CDCl3, 50 MHz) δ 151.1 (s), 144.9 (d), 138.2 (s), 137.1
(s), 136.6 (s), 132.9 (d), 127.3 (d), 126.5 (d), 126.4 (d), 122.8
(d); MS m/z (rel intensity) 218 (100, M+); HRMS calcd for
Su p p or tin g In for m a tion Ava ila ble: Additional experi-
mental procedures, ORTEP drawing and crystal data of
compound 4a , and spectral data of new compounds (52 pages).
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C
10H6N2S2 217.9973, found 217.9975.
3-(3-Th ien yl)th ien o[2,3-c]th iop h en e (16a ). Compound
7a (80 mg, 0.357 mmol) was treated with Lawesson’s reagent
J O980851D