Synthesis of polysubstituted benzothiophenes and sulfur-containing polycyclic aromatic compounds via samarium diiodide promoted three-component coupling reactions of thiophene-2-carboxylate

Article abstract of DOI:10.1021/jo0257849

By the promotion of samarium diiodide, thiophene-2-carboxylate reacted with 2 equiv of ketones at the C-4 and C-5 positions to give diols such as 2 and 9. Because the intermediary organosamarium species were oxophilic but not too basic, the double hydroxyalkylations with various ketone substrates, including alkyl aryl ketones, acetylthiophenes, cyclohexanone, α-tetralone, and α-phenylacetophenones, were realized without complication of side reactions. The diol products underwent an acid-catalyzed dehydration to give dienes such as 3 and 10, which were treated with DDQ to give either polysubstituted thiophenes (e.g., 4 and 11) or benzothiophenes (e.g., 5, 13, and 14) depending on the reaction conditions. Oxidative annulations of 4,5-diarylthiophenes 11 and 4,5,6,7-tetraphenylbenzothiophenes 14 were carried out by photochemical or chemical methods to give the sulfur-containing polycyclic aromatic compounds, such as phenanthro[9,10-b]thiophene-2-carboxylate, piceno[13,14-b]thiophene-2-carboxylate, and tribenzo[fg,ij,rst]pentapheno[15,16-b]-thiophene-2-carboxylates. This method is applicable to the preparation of polysubstituted thiophenes, benzothiophenes, and the related compounds possessing liquid crystalline, photochromic, and other functional properties.

Full text of DOI:10.1021/jo0257849

Syn th esis of P olysu bstitu ted Ben zoth iop h en es a n d
Su lfu r -Con ta in in g P olycyclic Ar om a tic Com p ou n d s via Sa m a r iu m
Diiod id e P r om oted Th r ee-Com p on en t Cou p lin g Rea ction s of
Th iop h en e-2-ca r boxyla te
Shyh-Ming Yang,† J iun-J ie Shie,† J im-Min Fang,* Sandip Kumar Nandy, Hung-Yu Chang,
Syn-Hung Lu, and Gladys Wang
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan, Republic of China
jmfang@ccms.ntu.edu.tw
Received April 1, 2002
By the promotion of samarium diiodide, thiophene-2-carboxylate reacted with 2 equiv of ketones
at the C-4 and C-5 positions to give diols such as 2 and 9. Because the intermediary organosamarium
species were oxophilic but not too basic, the double hydroxyalkylations with various ketone
substrates, including alkyl aryl ketones, acetylthiophenes, cyclohexanone, R-tetralone, and R-phe-
nylacetophenones, were realized without complication of side reactions. The diol products underwent
an acid-catalyzed dehydration to give dienes such as 3 and 10, which were treated with DDQ to
give either polysubstituted thiophenes (e.g., 4 and 11) or benzothiophenes (e.g., 5, 13, and 14)
depending on the reaction conditions. Oxidative annulations of 4,5-diarylthiophenes 11 and 4,5,6,7-
tetraphenylbenzothiophenes 14 were carried out by photochemical or chemical methods to give
the sulfur-containing polycyclic aromatic compounds, such as phenanthro[9,10-b]thiophene-2-
carboxylate, piceno[13,14-b]thiophene-2-carboxylate, and tribenzo[fg,ij,rst]pentapheno[15,16-b]-
thiophene-2-carboxylates. This method is applicable to the preparation of polysubstituted thiophenes,
benzothiophenes, and the related compounds possessing liquid crystalline, photochromic, and other
functional properties.
In tr od u ction
Benzothiophenes and the sulfur-containing polycyclic
aromatic derivatives are generally prepared by two
approaches,4 either via construction of a thiophene ring
onto an aromatic moiety5 or via annulation of an aromatic
ring onto a thiophene moiety.6 The first approach can be
exemplified by the acid-catalyzed cyclization of dimeth-
oxyethyl phenyl sulfide to give benzothiophene.5a,b Con-
densation of 9-chlorophrenthrene-10-carboxaldehyde with
mercaptoacetic acid affords phenanthro[9,10-b]thiophene.5c
The reaction of cinnamic acid with thionyl chloride gives
3-chlorobenzothiophene-2-carboxyl chloride.5d-f The zir-
conocene complexes of benzyne generated from bro-
mobenzenes are trapped by alkynes and sulfur dichloride
to furnish the skeleton of benzothiophenes.5g Alterna-
tively, the Lewis acid promoted Friedel-Crafts cycliza-
tion of 4-thienylalkenoic acid derivatives serves as an
instance of the second approach for benzothiophene
synthesis.6a,b The oxidative photocyclization of hexatriene
systems (e.g., 1-phenyl-2-thienylethene and the related
Benzothiophenes and their related sulfur-containing
polycyclic aromatic derivatives are of interest in many
aspects.1-3 A recent review1c evokes the aromaticity1a of
these sulfur-containing compounds, reminiscent of poly-
cyclic aromatic hydrocarbons (PAHs),1b according to the
theoretical approach and experimental measurements.
The polycyclic aromatic compounds provide the planar
structure suitable to DNA intercalation. Phenanthro[c]-
thiophenes with appropriate substituents have been
shown to intercalate with calf thymus DNA specifically
at the sites of A-T sequence.2 Thiophenes and their
polycyclic aromatic derivatives also exhibit remarkable
electrochemical,3a,b optical,3c physical,3d and biological3e,f
properties that render their applications in material and
pharmaceutical sciences.
† S.-M.Y. and J .-J .S. contributed equally to this work.
(1) (a) Katritzky, A. R.; J ug, K.; Oniciu, D. C. Chem. Rev. 2001, 101,
1421. (b) Watson, M. D.; Fechtenko¨tter, A.; Mu¨llen, K. Chem. Rev.
2001, 101, 1267. (c) Schleyer, P. von R. Chem. Rev. 2001, 101, 1115.
(2) (a) Wilson, W. D.; Wang, Y. H.; Kusuma, S.; Chandrasekaran,
S.; Yang, N. C.; Boykin, D. W. J . Am. Chem. Soc. 1985, 107, 4989. (b)
Wilson, W. D.; Wang, Y. H.; Kusuma, S.; Chandrasekaran, S.; Boykin,
D. W. Biophys. Chem. 1986, 24, 101.
(4) (a) Campaigne, E. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds.; Elsevier: Oxford, 1984; Vol. 4, pp
863-934. (b) Nakayama, J . In Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Elsevier:
Oxford, 1996; Vol. 2, pp 607-677.
(3) (a) Roncali, J . Chem. Rev. 1992, 92, 711. (b) Roncali, J . Chem.
Rev. 1997, 97, 173. Miller, L. L.; Mann, K. R. Acc. Chem. Res. 1996,
29, 417. (c) Larsen, J .; Bechgaard, K. Acta Chem. Scand. 1996, 50, 71.
(d) Mu¨ller, M.; Mauermann-Dull, H.; Wagner, M.; Enkelmann, V.;
Mu¨llen, K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1583. (e) Tsuji, K.;
Nakamura, K.; Ogino, T.; Konishi, N.; Tojo, T.; Ochi, T.; Seki, N.;
Matsuo, M. Chem. Pharm. Bull. 1998, 46, 279. (f) Becker, F. F.;
Mukhopadhyay, C.; Hackfeld, L.; Banik, I.; Banik, B. K. Bioorg. Med.
Chem. 2000, 8, 2693.
(5) (a) Pie´, P. A.; Marnett, L. J . J . Heterocycl. Chem. 1988, 25, 1271.
(b) Iwao, M.; Lee, M. L.; Castle, R. N. J . Heterocycl. Chem. 1980, 17,
1259. (c) Vo¨gtle, F.; Palmer, M.; Fritz, E.; Lehmann, U.; Meurer, K.;
Mannschreck, A.; Kastner, F.; Irngrtinger, H.; Huber-Patz, U.; Puff,
H.; Friedrichs, E. Chem. Ber. 1983, 116, 3112. (d) Wright, W. B., J r.;
Brabander, H. J . J . Heterocycl. Chem. 1971, 8, 711. (e) Sidorenko, T.
N.; Terent’eva, G. A.; Aksenov, V. S. Chem. Heterocycl. Compd. (Engl.
Transl.) 1983, 161. (f) Camoutsis, C.; Castle, R. N. J . Heterocycl. Chem.
1993, 30, 153. (g) Buchwald, S. L.; Fang, Q. J . Org. Chem. 1989, 54, 3.
10.1021/jo0257849 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/12/2002
5208
J . Org. Chem. 2002, 67, 5208-5215

Synthesis of Polysubstituted Benzothiophenes
metalations10a of thiophene-2-carboxylates and thiophene-
2-carbamides can only introduce substituents to their C-3
or C-5 positions. Friedel-Crafts reactions of methyl
thiophene-2-carboxylate with paraformaldehyde in the
presence of ZnCl2 give a mixture of 4-chlromethyl-,
5-chloromethyl-, and 4,5-bis(chloromethyl)thiophene-2-
carboxylates in 19%, 38%, and 15% yields, respectively.10b
Using the SmI2-promoted coupling reaction appears to
be a favorable and direct method for modification of
thiophene-2-carboxylate at the C-4 and C-5 positions. We
outlined in Scheme 1 an expedient synthesis of several
specifically substituted benzothiophenes (e.g., thieno-p-
terphenyl 5a and 4,5,6,7-tetraphenylbenzothiophene 14a )
as well as the sulfur-containing polycyclic aromatics (e.g.,
15a ), which are not easily obtained by other methods.
SCHEME 1. Sm I2-P r om oted Th r ee-Com p on en t
Cou p lin g Rea ction a s th e Key Step for th e
Tr a n sfor m a tion of Th iop h en e-2-ca r boxyla tes 1a ,b
in to Th ien o-p-ter p h en yl 5a ,
Tetr a p h en ylben zoth iop h en e 14a , a n d
Su lfu r -Con ta in in g P olycyclic Ar om a tic Com p ou n d
15a
Resu lts a n d Discu ssion
The SmI2-promoted three-component coupling reac-
tions of methyl thiophene-2-carboxylate (1a ) with 2 equiv
of acetophenones afforded diols 2a -n in 60-67% yields
(Table 1). The reaction was likely initiated by a hydroxy-
alkylation at the C-5 position of the thienyl ring (Scheme
2). The samarium dienolate intermediate A was readily
trapped by the second ketone electrophile in a regio- and
stereoselective manner. This one-pot procedure thus
introduced two substituents to the C-4 and C-5 positions
of the dihydrothiophene-2-carboxylate.
polycyclic analogues) provides a versatile method for
aromatic annulation.6c-e The Michael reaction of 2-(sul-
fonylmethyl)thiophene-2-carboxaldehyde also affords a
series of polysubstituted benzothiophenes.6f Benzothio-
phenes have been obtained by the Diels-Alder reactions
of 2-vinylthiophenes6g and thiophene-2,3-quinodimethane
equivalents7 generated from thienoisofurans6h and thieno-
pyranones.6i In one case,6j the copper-mediated coupling
of 2,3,4,5-tetraethylzirconacyclopentadiene with 2-iodo-
3-bromothiophene gives 4,5,6,7-tetraethylbenzo[b]thio-
phene in 32% yield. A palladium-catalyzed method for
multiple arylation of thiophenes has recently been
explored.6k
In addition to the above-mentioned elegant methods,
we have devised an SmI2-promoted coupling reaction8 of
thiophene-2-carboxylate in a one-pot procedure to intro-
duce two substituents to the C-4 and C-5 positions.9 SmI2
promoted the double electrophilic reactions of thiophene-
2-carboxylate with a variety of ketones, including phenyl
methyl ketones, cyclic ketones, and even the enolizable
ketones (e.g., R-phenylacetophenones). By comparison,
(6) (a) Tominaga, Y.; Teduamulia, M. L.; Castle, R. N.; Lee, M. L.
J . Heterocycl. Chem. 1983, 20, 487. (b) Kusuma, S.; Wilson, W. D.;
Boykin, D. W. J . Heterocycl. Chem. 1985, 22, 1229. (c) Tinnemans, A.
H. A.; Laarhoven, W. H. J . Am. Chem. Soc. 1974, 96, 4611. (d) Buquet,
A.; Couture, A.; Lablache-Combier, A.; Pollet, A. Tetrahedron 1981,
37, 75. (e) Larsen, J .; Bechgaard, K. Acta Chem. Scand. 1996, 50, 71.
(f) Terpstra, J . W.; van Leusen, A. M. J . Org. Chem. 1986, 51, 230. (g)
Szmuszkovicz, J .; Modest, E. J . J . Am. Chem. Soc. 1950, 72, 571. (h)
Scho¨ning, A.; Debaerdermaeker, T.; Zander, M.; Friedrichsen, W.
Chem. Ber. 1989, 122, 1119. (i) J ackson, P. M.; Moody, C. J .; Shah, P.
J . Chem. Soc., Perkin Trans. 1 1990, 2909. (j) Takahashi, T.; Hara,
R.; Nishimura, Y.; Kotora, M. J . Am. Chem. Soc. 1996, 118, 5154. (k)
Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. J . Am. Chem. Soc.
2002, 124, 5287.
Even though each diol (2a -d ) had four asymmetric
carbon centers, the diol product usually existed as a
mixture of two diastereomers. The diastereomers were
separated by silica gel column chromatography. Both
(7) (a) Chou, T.-S. Rev. Heteroatom. Chem. 1993, 8, 65. (b) Peters,
O.; Friedrichsen, W. Trends Heterocycl. Chem. 1995, 4, 217. (c) Segura,
J . L.; Martin, N. Chem. Rev. 1999, 99, 3199.
J . Org. Chem, Vol. 67, No. 15, 2002 5209

Yang et al.
TABLE 1. Syn th esis of 4,7-Dia r ylben zoth iop h en es: (i) Cou p lin g Rea ction s of Th iop h en e-2-ca r boxyla te w ith Ar yl
Meth yl Keton esa Givin g Diols 2, (ii) Deh yd r a tion b Givin g Dien es 3, a n d (iii) DDQ Oxid a tion c Givin g Tr ien es 4 or
Ben zoth iop h en es 5
thiophene
ArCOMe, Ar )
diol (yield, %)
diene (yield, %)
triene (yield, %)
benzothiophene (yield, %)
1a
1a
1a
1a
1b
1a h
1a
1b
1b
1b
1b
1a
1a
1a
1a
C6H5
4-ClC6H4
4-MeC6H4
4-MeOC6H4
2a (61)d
2b (62)d
2c (60)d
2d (67)d
2e (50)
3a (90)
3b (97)
3c (98)
3d (95)
3e (92)
5a (90)e
5b (91)e
5c (89)e
5d (72)e
5e (84)g
5f (43)h
5g (89)e
5h (81)g
5i (75)g
5j (71)g
5k (68)g
7a (38)j
7b (35)j
7c (36)j
8 (42)j
4b (89)f
2-naphthyl
4e (82)
4-ClC6H4/4-MeOC6H4
4-C17H35COOC6H4
4-(4-C10H21OC6H4COO)C6H4
4-(4-C12H25OC6H4COO)C6H4
4-(4-C14H29OC6H4COO)C6H4
4-(4-C16H33OC6H4COO)C6H4
2-thienyl
5-Br-2-thienyl
3-Me-2-thienyl
3-thienyl
3g (48)i
3h (46)i
3i (43)i
3j (38)i
3k (40)i
4h (67)
4i (78)
4j (72)
4k (70)
a
Thiophene-2-carboxylate (1a or 1b) and 2 equiv of aryl methyl ketone in THF/HMPA was treated with SmI2 at 0-25 °C for 1-2 h.
The dehydration was achieved by the catalysis of p-TsOH in refluxing benzene. c The reaction with 1.2 equiv of DDQ at 60 °C gave
b
trienes 4, whereas the reaction with 2.2 equiv of DDQ in refluxing toluene gave benzothiophenes 5. A mixture of diastereomers. e The
d
product was obtained by DDQ oxidation of dienes 3, and the yield was calculated on the basis of dienes 3. f Accompanied by 5% of 5b.
g The product was obtained by DDQ oxidation of trienes 4. The SmI2-promoted coupling reaction of 1a with 1 equiv of 4-chloroacetylphe-
h
i
j
none and then with 1 equiv of 4-methoxyacetylphenone. The overall yield of two steps from 1b. The overall yield of three steps from 1a .
diastereomers showed relatively small coupling constants
(∼3 Hz) for H-4 and H-5, indicating their trans orienta-
tions. The trans configuration could be established by an
attack of the second electrophile on the less hindered face
of the dienolate intermediate. Although the stereochem-
istry of diols 2a -d was not rigorously determined, the
more polar isomers consistently exhibited the H-5 signals
posed on DDQ oxidation.11 Under mild reaction condi-
tions, diene 3b reacted with 1 equiv of DDQ at 60 °C in
benzene to give the primary dehydrogenation product 4b
in 89% yield. Besides the quantity of DDQ, the reaction
temperature was another key factor to manipulate the
formation of triene 4b or benzothiophene 5b. The amount
of 5b increased (∼15%) at an elevated reaction temper-
ature (>70 °C), even utilizing only 1 equiv of DDQ. The
similar phenomena were observed in the DDQ oxidation
of 3e (Ar ) naphthyl). At an elevated temperature,
electrocyclization12a of triene 4b (or 4e) might occur to
give the intermediate B. Dehydrogenation of the inter-
mediate could be effected by DDQ to afford benzothiophene
5b (or 5e). Indeed, the intermediate B generated from
electrocyclization of 4e exhibited the nature of o-thiophene-
quinodimethane,7a which was successfully trapped by a
dienophile of N-phenylmaleimide to give the [4 + 2]
cycloaddition product 6 (Scheme 2). The cycloaddition
was consistent with a concerted mechanism to give
adduct 6 in the endo configuration. The NOESY correla-
tion of H-4a/H-7a (δ 4.34-4.33, m) with the ethylene-
bridge protons (δ 2.15-2.11, m) supported the stereo-
chemical assignment. Electrocyclization of triene 4e was
also achieved by irradiation with 300-nm light, and the
cyclohexadiene intermediate B could be oxidized to 5e
in the presence of oxygen.12a
at the lower fields than the less polar isomers (∆δH
≈
0.2 ppm). Under the reaction conditions (SmI2/HMPA/
THF, 25 °C, 2-10 h), the chlorophenyl groups in 2b were
not reduced. No apparent pinacolic coupling reactions of
acetophenones were found to interfere with the SmI2-
promoted three-component coupling reactions. By a
similar procedure, diol 2e was prepared in 50% yield by
coupling of ethyl thiophene-2-carboxylate (1b) with 2
equiv of 2-acetylnaphthalene.
On treatment with a catalytic amount of p-TsOH in
refluxing benzene, diols 2a -e underwent dehydrations
to yield dienes 3a -e with terminal double bonds. Dienes
3a -e retained the 4,5-trans configuration. The charac-
teristic C-5 protons appeared at lower fields (δH ≈ 6.5)
as doublets with small coupling constants (∼3 Hz). When
dienes 3a -c were treated with excess amounts of DDQ
(2.2 equiv) in refluxing toluene for 7-18 h, the corre-
sponding 4,7-diphenylbenzophenone-2-carboxylates 5a -c
were obtained as the exclusive products in high yields
(∼90%). As benzothiophenes 5a -c were formed, the H-3
signals were shifted downfield (δH ≈ 8.2). The yield of
5d (Ar ) p-MeOC6H5) was somewhat lower (72%),
presumably because the anisole moieties partly decom-
A photochromic system between the colorless trienes
4l-n and their corresponding closed-ring species of
yellow color was devised (Scheme 3).12b Trienes 4l-n
were similarly prepared from the SmI2-promoted coupling
reactions of 1b with isobutyronaphthone, isobutyrophe-
none, and 4-methoxyisobutyrophenone, followed by acid-
catalyzed dehydration and DDQ dehydrogenation. Unlike
4e, trienes 4l-n carried four methyl substituents to
prevent their closed-ring isomers from oxidative aroma-
(8) (a) Kagan, H. B.; Namy, J . L.Tetrahedron 1986, 42, 6573. (b)
Inanaga, J . J . Synth. Org. Chem. 1989, 47, 200. (c) Soderquist, J . A.
Aldrichim. Acta 1991, 24, 15. (d) Brandukova, N. E.; Vygodskii, Y. S.;
Vinogradova, S. V. Russ. Chem. Rev. 1994, 63, 345. (e) Molander, G.
A.; Harris, C. R. Chem. Rev. 1996, 96, 307. (f) Molander, G. A.; Harris,
C. R. Tetrahedron 1998, 54, 3321.
(9) (a) Yang, S.-M.; Fang, J .-M. Tetrahedron Lett.1997, 38, 1589.
(b) Yang, S.-M.; Nandy, S. K.; Selvakumar, A. R.; Fang, J .-M. Org.
Lett. 2000, 2, 3719.
(11) (a) Lemaire, M.; Guy, A.; Huynh A. H.; Guette, J . P. J anssen
Chim. Acta 1987, 5, 3. Cyclohexadiene reagents: a new approach to
selectivity control. (b) Fukase, K.; Egusa, K.; Nakai, Y.; Kusumoto, S.
Mol. Diversity 1997, 2, 182.
(10) (a) Sniekus, V. Chem. Rev. 1990, 90, 879. (b) Kozm´ık, V.;
Palee`ek, J . Collect. Czech. Chem. Commun. 1992, 57, 1483.
(12) (a) Zimmerman, H. E. Acc. Chem. Res. 1971, 4, 272. (b) Shie,
J .-J .; Yang, S.-M.; Chen, C.-T.; Fang, J .-M. Org. Lett. 2002, 4, 1099.
5210 J . Org. Chem., Vol. 67, No. 15, 2002

Synthesis of Polysubstituted Benzothiophenes
SCHEME 2. Rea ction P a th w a ys: (i) Sm I2-P r om oted
Cou p lin g Rea ction , (ii) Hyd r oxya lk yla tion of
Dien ola te In ter m ed ia te, (iii) Deh yd r a tion , (iv)
Deh yd r ogen a tion , (v) Electr ocyliza tion , (vi)
Oxid a tive Ar om a tiza tion , a n d (vii) Tr a p p in g of th e
P r op osed o-Th iop h en equ in od im eth a n e
was treated with 2.2 equiv of DDQ in refluxing toluene
to afford benzothiophene 5f in 43% overall yield. Our
present three-step procedure, via the coupling reaction
of thiophenecarboxylate with ketones, acid-catalyzed
dehydration and DDQ, oxidative cyclization, is thus
applicable to the synthesis of various thieno-p-terphe-
nyls13 5a -k having the same or different aryl groups.
Similar to common terphenyl compounds, the phenyl
rings are not coplanar with the benzothiophene ring in
these thieno-p-terphenyls. The crystal structure of 5c
showed that two tolyl rings had the dihedral angles of
54° and 133°, respectively, against the central ben-
zothiophene ring (see the Supporting Information).
By a similar procedure, dienes 3g-k , trienes 4g-k ,
and benzothiophenes 5g-k bearing long-chain substit-
uents were prepared. These compounds could be consid-
ered to have a pseudo-C2 symmetry dissected by the
carboxylate group. Among them, dienes 3h -j and trienes
4h -k possess the liquid-crystalline properties14 of smec-
tic-A type. The phase transition temperatures occur in
the ranges of 67-47 °C for 3h -j and 72-52 °C for 4h -
k . Thieno-p-terphenyls 5h -k exist as solids with rather
high melting points (197-185 °C), even though they are
equipped with soft long chains of decoxy, dodecoxy,
tetradecoxy, and hexadecoxy groups. By comparison with
the thienyl rings in 3h -j and 4h -k , the rigid core of
benzothiophene is longer to disfavor the liquid-crystal-
line property.
In ter m ed ia te B by a Dien op h ile
SCHEME 3. Electr ocycliza tion of Tr ien es 4l-n
u p on Ir r a d ia tion w ith 300-n m Ligh t in CH3CN
Solu tion To Give th e Cor r esp on d in g Closed -Rin g
Sp ecies w ith Absor p tion λMa x ∼425 n m a
a
The Interconversion between 4l-n and their corresponding
closed-ring species constitutes an interesting photochromic system.
tization. The closed-ring isomers C-E returned to the
open-ring isomers 4l-n on irradiation with 450-nm
light.12b
Diol 2f bearing two different aryl substituents was
prepared by treatment of thiophene-2-carboxylate 1a
consecutively with 1 equiv of 4-chloroacetophenone (stir-
ring for 2 h at 25 °C) and 4-methoxyacetophenone. The
acid-catalyzed dehydration of diol 2f gave diene 3f, which
Benzothiophenes bearing two thienyl substituents at
the C-4 and C-7 positions, e.g., 7a -c and 8, were also
prepared by using appropriate acetylthiophenes as the
starting materials for the similar three-step reaction
J . Org. Chem, Vol. 67, No. 15, 2002 5211

Yang et al.
sequence. Compound 7b having bromine atoms on the
thienyl rings is especially versatile because it can be
elaborated by coupling with arenes, heterocyclic arenes,
alkenes, and alkynes, e.g., via Heck, Stille, Suzuki and
Sonogashira reactions,15 to construct various useful
conjugated systems, including the oligo- and polymeric
derivatives of 7b.
R-tetralone and R-phenylacetophenones) were realized.
The SmI2-promoted reaction of 1a with tetralone gave
diol 9b as a single isomer. Its relative configuration was
determined to be (4R*,5S*,1′S*,1′′R) by X-ray analysis.
The acid-catalyzed dehydration of 9a and 9b gave the
corresponding dienes 10a and 10b. Treatment of 10a
with excess amounts (6.5 equiv) of DDQ in refluxing
xylene gave diphenylthiophene 11a (89% yield), instead
of the cyclization compound 12a . Phenanthrothiophene
12a 5b was finally obtained by irradiation (300-nm light)
of 11a in the presence of iodine.6c,d,h,17 By a similar
procedure, dehydrogenation of 10b with DDQ (4.5 equiv)
in refluxing toluene gave dinaphthylthiophene 11b (94%
yield), and the subsequent photochemical reaction (300-
nm light, 1 equiv I2) gave picenothiophene 12b (89%
yield).
A variety of 4,5,6,7-tetrasubstituted benzothiophenes
such as 13a ,b and 14a -c were also synthesized via the
following three-step reaction sequence: (i) using pro-
piophenones or R-phenylacetophenones to couple with
thiophene-2-carboxylate, (ii) using p-TsOH to catalyze
dehydration, and (iii) using excess DDQ to mediate the
consecutive processes of dehydrogenation, electrocycliza-
tion, and oxidative aromatization. In the case of 13a , a
photochemical oxidative aromatization was also applied.
Tetraphenylbenzothiophenes 14a and 14b underwent the
oxidative annulations by treatment with AlCl3/CuCl2/
18a,b
O2
or FeCl3,18c giving tribenzopentaphenothiophenes
15a and 15b in 91% and 79% yields.
Tetraanisole 14d was demethylated by BBr3 to give
tetraphenol 14e in 74% yield. Alkylation of 14e with
1-bromooctane, 1-bromodecane, and 1-bromododecane
gave acids 14f-h because of the concurrent saponifica-
tion in the presence of KOH (Scheme 4). The long alkyl
chains were introduced to the radial-type benzothiophenes
as these acids might form dimeric assembly via hydrogen
bondings to render a discotic liquid-crystalline prop-
erty.19 However, acids 14f-h turn out to be crystalline
compounds. None of them exhibit the desired liquid
crystal properties.
In summary, we have developed a three-step procedure
for the preparation of polysubstituted benzothiophenes
(e.g., 5a -k , 7a -c, 13a ,b, and 14a -d ) and the related
sulfur-containing polycyclic aromatic compounds (e.g.,
12a ,b and 15a ,b). By the promotion of SmI2, thiophene-
2-carboxylate underwent a double-electrophilic reaction
By the promotion of SmI2, 1a reacted with 2 equiv of
cyclohexanone to give diol 9a in 91% yield. The trans
configuration of 9a was confirmed by its crystal structure,
and the two hydroxyl groups were shown to have the
axial orientations. As lanthanoid ion (e.g., Sm3+) is
oxophilic and less basic than alkali and alkaline metal
ions,16 additions of organosamarium species (e.g., the
samarium dienolate A) to the enolizable ketones (e.g.,
(13) Schoning, A.; Debaerdemaeker, T.; Zander, M.; Friedrichsen,
W. Chem. Ber. 1989, 122, 1119.
(14) (a) Miyake, S.; Kusabayashi, S.; Takenaka, S. Bull. Chem. Soc.
J pn. 1984, 57, 2404. (b) Brown, J . W.; Byron, D. J .; Harwood: D. J .;
Wilson, R. C.; Tajbakhsh, A. R. Mol. Cryst. Liq. Cryst. 1989, 173, 121.
(15) (a) Kalinin, V. N. Synthesis 1992, 413. (b) Zhang, F.-J .; Cortez,
C.; Harvey, R. G. J . Org. Chem. 2000, 65, 3952.
(16) (a) Molander, G. A. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 1, pp 251-
282. (b) Molander, G. A. Chem. Rev. 1992, 92, 29. (c) Imamoto, T.
Lanthanides in Organic Synthesis; Academic Press: London, 1994.
(17) (a) Baldwin, L. J .; Tedjamulia, M. L.; Stuart, J . G.; Castle, R.
N.; Lee, M. L. J . Heterocycl. Chem. 1984, 21, 1775. (b) Fischer, E.;
Larsen, J .; Christensen, J . B.; Fourmigue, M.; Madsen, H. G.; Harrit,
N. J . Org. Chem. 1996, 61, 6997.
(18) (a) Kovacic, P.; J ones, M. B. Chem. Rev. 1987, 87, 357. (b)
Muller, M.; Mauermann-Dull, H.; Wagner, M.; Enkelmann, V.; Mu¨llen,
K. Angew. Chem., Int. Ed. Engl. 1995, 34, 1583. (c) Do¨tz, F.; Brand, J .
D.; Ito, S.; Gherghel, L.; Mu¨llen, K. J . Am. Chem. Soc. 2000, 122, 7707.
(19) Kleppinger, R.; Lillya, C. P.; Yang, C. J . Am. Chem. Soc. 1997,
119, 4097.
5212 J . Org. Chem., Vol. 67, No. 15, 2002

Synthesis of Polysubstituted Benzothiophenes
SCHEME 4. Syn th esis of
4,5,6,7-Tetr a p h en ylben zo[b]th iop h en es 14a -h , a n d
th e F a n -Sh a p ed P olycyclic Ar om a tics 15a ,b
be monitored by the change of fluorescence intensity. The
ester groups in 12a ,b and 15a ,b can be modified, e.g.,
by transformation into carboxylic acids and other func-
tional derivatives, to improve their chemical and physical
properties, e.g., the water solubility and the sequence
specificity in DNA recognition. Furthermore, incorpora-
tion of sulfur atom in these polycyclic aromatics can
provide an opportunity for photochemical activation. We
are currently exploring the interaction of picenothiophene
12b with calf thymus DNA and the possible cleavage of
DNA double helix by photochemical activation.
Heterosuperbenzenes such as the nitrogen-function-
alized graphite molecules20a are interesting research
subjects. As we have previously demonstrated that in-
dolecarbonyl coupling reactions are feasible by the pro-
motion of SmI2,20b we plan to explore further the nitrogen-
containing polyaromatic systems, such as those derived
from pyrroles, by using an approach similar to that
described in this paper.
Exp er im en ta l Section
Gen er a l Met h od s. All reactions requiring anhydrous
conditions were conducted in a flame-dried apparatus under
an atmosphere of nitrogen. Syringes and needles for the
transfer of reagents were dried at 100 °C and allowed to cool
in a desiccator over P2O5 before use. Ethers were distilled from
sodium benzophenone ketyl; (chlorinated) hydrocarbons, and
amines from CaH2. Reactions were monitored by TLC using
plates precoated with a 0.25 mm layer of silica gel containing
a fluorescent indicator (Merck Art. 5544). Column chromatog-
raphy was carried out on Kieselgel 60 (40-63 µm). The
photochemical reactions were conducted in a Rayonet photo-
chemical reactor using 300-nm lamps.
1
Melting points are uncorrected. Chemical shifts of H and
13C NMR spectra are reported relative to CHCl3 [δH 7.24, δC
(central line of t) 77.0]. Coupling constants (J ) are given in
Hz. Distortionless enhancement polarization transfer (DEPT)
spectra were taken to determine the types of carbon signals.
Rep r esen ta tive P r oced u r e for th e Sm I2-P r om oted
Cou p lin g Rea ction s of Th iop h en e-2-ca r boxyla te w ith 2
equ iv of Ar yl Keton es, Givin g Diols 2. Caution: HMPA is
suspected as a carcinogen. Handle HMPA with care. Under
an atmosphere of argon, a deep blue SmI2 solution (0.1 M) was
prepared by treatment of Sm (661 mg, 4.4 mmol) with 1,2-
diiodoethane (1.01 g, 3.6 mmol) in anhydrous HMPA (2.8 mL,
16 mmol) and THF (35 mL) for 1.5 h at room temperature (25
°C). To the SmI2 solution (cooled in an ice bath) were added a
THF solution (3 mL) of methyl thiophene-2-carboxylate (142
mg, 1.0 mmol) and acetophenone (252 mg, 2.1 mmol). The
reaction mixture was stirred at 0 °C for 20 min and then at
room temperature for 2-10 h. The reaction was quenched by
addition of saturated aqueous NH4Cl solution (1 mL). The
mixture was passed through a short silica gel column by
rinsing with EtOAc/hexane (1:1). The filtrate was concentrated
and chromatographed on a silica gel column by elution with
EtOAc/hexane (2:8) to give the desired three-component
coupling product 2a (233 mg, 61%). Two diastereomers (42:
58) were separable on the silica gel column. The less polar
isomer corresponded to the minor isomer.
effectively with a variety of ketones, including the eno-
lizable ketones (e.g., tetralone and R-phenylacetophe-
nones), to give the desired diol products (e.g., 2a -e).
Dehydration of the diol products was accomplished by
the catalysis of p-TsOH to afford a series of dialk-
enyldihydrothiophenes (e.g., 3a -k and 10a ,b). For syn-
thetic purposes, dialkenyldihydrothiophenes 3a -k were
directly converted to 4,7-diarylbenzothiophenes 5a -k by
treatment with excess amounts of DDQ in refluxing
toluene. The intermediary dialkenylthiophenes (e.g., 4b
and 4f-k ) were obtained under mild reaction conditions
(1 equiv of DDQ in benzene, 60 °C). Compounds 3h -j
and 4h -k bearing long-chain alkoxyphenyl substituents
are liquid crystals of smectic-A type. Phenanthrothiophene
12a , picenothiophene 12b , and tribenzopentapheno-
thiophenes 15a and 15b were obtained by chemical or
photochemical oxidative annulations of diphenylthio-
phene 11a , dinaphthylthiophene 11b, and tetraphenyl-
benzothiophenes 14a and 14b. The polycyclic aromatic
compounds 12a ,b and 15a ,b may be used as DNA
intercalators as they exhibit characteristic planar struc-
tures similar to those of PAHs.2 As 12a ,b and 15a ,b are
fluorescent compounds, their interactions with DNA can
Rep r esen ta tive P r oced u r e for Deh yd r a tion of Diols
2, Givin g Dien es 3. Diol 2a (300 mg, 0.78 mmol) and p-TsOH
(catalytic amount) in benzene (30 mL) were heated at reflux
for 5-12 h, while a Dean-Stark apparatus removed the
generated water azeotropically. The reaction mixture was
concentrated under reduced pressure and chromatographed
(20) (a) Draper, S. M.; Gregg, D. J .; Madathil, R. J . Am. Chem. Soc.
2002, 124, 3486. (b) Lin, S.-C.; Yang, F.-D.; Shiue, J .-S.; Yang, S.-M.;
Fang, J .-M. J . Org. Chem. 1998, 63, 2909.
J . Org. Chem, Vol. 67, No. 15, 2002 5213

Yang et al.
on a silica gel column by elution with EtOAc/hexane (1:9) to
afford the corresponding diene 3a (245 mg, 90%).
J ) 6.0, 3.2 Hz), 7.37-7.34 (6 H, m), 7.00-6.95 (4 H, m), 4.29
(2 H, q, J ) 6.2 Hz), 1.69 (3 H, s), 1.67 (3 H, s), 1.60 (3 H, s),
1.57 (3 H, s), 1.33 (3 H, t, J ) 6.2 Hz); 13C NMR (CDCl3, 75
MHz) δ 162.5, 148.1, 141.8, 139.5, 139.0, 137.9, 136.5, 134.3,
133.1, 132.0 (2×), 131.8, 131.1, 131.0, 128.8 (2×), 128.7 (2×),
128.1, 127.9, 127.8, 127.7, 127.4, 127.0, 126.8, 125.8, 125.7,
125.5, 125.4, 60.9, 22.8, 22.5, 22.3, 21.9, 14.4; FAB-MS 516.2
(M+); HRMS calcd for C35H32O2S 516.2123, found 516.2122.
Anal. Calcd for C35H32O2S: C, 81.36; H, 6.24. Found: C, 81.62;
H, 6.36.
R ep r esen t a t ive P r oced u r e for DDQ Oxid a t ion of
Dien es 3, Givin g 4,5-Dia lk en ylth iop h en es 4 a n d 4,7-
Dia r ylben zoth iop h en es 5. A mixture of diene 3b (140 mg,
0.34 mmol) and DDQ (92 mg, 0.40 mmol) in anhydrous
benzene (10 mL) was heated at 60 °C for 10-12 h. The reaction
mixture was concentrated under reduced pressure and chro-
matographed on a silica gel column by elution with EtOAc/
hexane (2:8) to give thiophene 4b (125 mg, 89%). On the other
hand, diene 3a (290 mg, 0.70 mmol) was reacted with excess
amounts of DDQ (352 mg, 1.55 mmol) in refluxing toluene (15
mL) for 7-18 h to give benzothiophene 5b (262 mg, 91%).
Rep r esen ta tive P r oced u r e for Oxid a tive Cycliza tion
u n d er P h otoch em ica l Con d ition s. Diarylthiophene 11a (30
mg, 0.1 mmol) and iodine (26 mg, 0.1 mmol) in deoxygenated
anhydrous benzene (20 mL) were placed in a quartz tube
equipped with a cooling circulation of ice-water. The solution
was irradiated by 300-nm light in a Rayonet photochemical
reactor for 20 h. The mixture was concentrated, treated with
aqueous Na2S2O3 to remove the remaining iodine, and ex-
tracted with CH2Cl2 (3×). The organic phase was dried (Na2-
SO4) and concentrated. Pure polyaromatic product 12a (86%
yield) was obtained by crystallization from CH2Cl2/hexane or
by chromatography on a silica gel column with elution of
EtOAc/hexane (1:9).
Meth yl 7-(4-Ch lor op h en yl)-4-(4-m eth oxyp h en yl)ben -
zo[b]th iop h en e-2-ca r boxyla te (5f). A mixture of methyl
thiophene-2-carboxylate (142 mg, 1.0 mmol) and 4-chloroace-
tophenone (155 mg, 1.0 mmol) in THF (2 mL) was treated with
SmI2/HMPA (3.6/16.0 mmol) at 0 °C for 10 min and at 25 °C
for 2 h. The second electrophile of 4-methoxyacetophenone (180
mg, 1.2 mmol) was added dropwise. The reaction mixture was
stirred at room temperature for 14 h and then worked up to
give the diol product 2f according to the representative
procedure. The subsequent acid-catalyzed dehydration gave
diene 3f in 51% overall yield. The reaction of diene 3k with
2.2 equiv of DDQ in refluxing toluene gave benzothiophene 5f
in 85% yield: solid; mp 201-202 °C; TLC (EtOAc/hexane, 1:9)
Rf ) 0.23; IR (KBr) 1723 cm-1; UV (CHCl3) λmax (ꢀ) 282 nm
(61600), 347 nm (24000); FL (CHCl3, c ) 2 × 10-4 M) λem 435
nm by excitation at 347 nm; 1H NMR (CDCl3, 200 MHz) δ 8.21
(1 H, s), 7.65 (2 H, dd, J ) 8.6, 2.0 Hz), 7.50-7.40 (6 H, m),
Met h yl 4,5-Bis(l-h yd r oxy-l-p h en ylet h yl)-4,5-d ih yd r o-
7.04 (2 H, dd, J ) 8.6, 2.0 Hz), 3.89 (3 H, s), 3.88 (3 H, s); 13
C
th iop h en e-2-ca r boxyla te (2a ). 2a , minor isomer: oil; TLC
1
(EtOAc/hexane, 3:7) Rf ) 0.21; IR (neat) 3452, 1710 cm-1; H
NMR (CDCl3, 75 MHz) δ 163.1, 159.5, 141.8, 138.9, 138.2,
137.9, 134.3, 134.2, 133.2, 132.2, 130.7, 130.2 (2×), 129.5 (2×),
129.4 (2×), 127.0, 125.9, 114.2 (2×), 55.4, 52.5; FAB-MS m/z
407.9 (M+); HRMS calcd for C23H17ClO3S 408.0587, found
408.0583. Anal. Calcd for C23H17ClO3S: C, 67.64; H, 4.20.
Found: C, 67.21; H, 4.36.
NMR (CDCl3, 200 MHz) δ 7.47-7.18 (10 H, m), 6.21 (1 H, d,
J ) 3.6 Hz), 4.03 (1 H, d, J ) 3.1 Hz), 3.71 (3 H, s), 3.61 (1 H,
dd, J ) 3.6, 3.1 Hz), 2.70 (1 H, br s, OH), 2.35 (1 H, br s, OH),
1.65 (3 H, s), 1.16 (3 H, s); 13C NMR (CDCl3, 75 MHz) δ 162.3,
145.2, 143.9, 135.1, 134,5, 128.2 (2×), 128.1 (2×), 127.4, 126.8,
125.9 (2×), 124.7 (2×), 76.4 (2×), 61.7, 60.7, 52.3, 27.7, 26.1;
FAB-MS m/z 367.0 (M+ + 1 - H2O); HRMS calcd for C22H24O4S
384.1396, found 384.1391. 2a , major isomer: oil; TLC (EtOAc/
hexane, 3:7) Rf ) 0.18; IR (neat) 3480 cm-1; 1H NMR (CDCl3,
200 MHz) δ 7.41-7.21 (10 H, m), 6.23 (1 H, d, J ) 3.5 Hz),
4.23 (1 H, d, J ) 3.0 Hz), 3.67 (3 H, s), 3.65 (1 H, dd, J ) 3.5,
3.0 Hz), 2.86 (1 H, s, OH), 2.41 (1 H, s, OH), 1.45 (3 H, s), 1.31
(3 H, s); 13C NMR (CDCl3, 75 MHz) δ 162.2, 145.5, 145.4, 135.4,
134.6, 128.3 (2×), 128.2 (2×), 127.2 (2×), 125.3 (2×), 125.1
(2×), 76.8, 76.3, 61.3, 60.6, 52.3, 26.6, 25.0; FAB-MS m/z 367.0
(M+ + 1 - H2O); HRMS calcd for C22H24O4S 384.1396, found
384.1398.
Eth yl 6-Aza -4,8-d i(n a p h th -2-yl)-5,7-d ioxo-6-p h en yl-1-
th ia tetr a cyclo[7.3.2.4,80.3a,8a04a,7a]tetr a d eca -2,3a (8a )-d ien e-
2-ca r boxyla te (6). A mixture of triene 4e (96 mg, 0.2 mmol)
and N-phenylmaleimide (353 mg, 2.0 mmol) in deoxygenated
anhydrous toluene (15 mL) was heated at reflux for 48 h. The
mixture was concentrated and chromatographed on a silica
gel column by elution with EtOAc/hexane (2:8) to give an
oxidative aromatization product 5e (73 mg, 80%) and a Diels-
Alder addition product 6 (15 mg, 12%). 6: oily solid; TLC
(EtOAc/hexane (1:4)) Rf ) 0.10; 1H NMR (CDCl3, 300 MHz) δ
8.44 (1 H, s), 8.33 (1 H, s), 7.97-7.79 (7 H, m), 7.78 (1 H, s),
7.52-7.48 (5 H, m), 7.21-7.18 (3 H, m), 6.69-6.66 (2 H, m),
4.34-4.33 (2 H, m), 4.27 (2 H, q, J ) 7.2 Hz), 2.15-2.11 (4 H,
m), 1.28 (3 H, t, J ) 7.2 Hz); 13C NMR (CDCl3, 100 MHz) δ
174.3, 173.8, 162.2, 147.9, 143.3, 138.1, 137.6, 133.1, 133.0,
132.7, 132.5, 131.9, 131.4, 131.3, 128.8, 128.5, 128.3, 128.2,
127.9, 127.7 (2×), 127.6, 127.5 (2×), 127.1, 126.6 (2×), 126.4,
126.3, 126.2, 126.17, 126.1, 125.3, 61.2, 49.9, 49.0, 48.3, 47.8,
38.7, 38.6, 14.4. FAB-MS m/z 633.2 (M+); HRMS calcd for
Meth yl 4,5-Bis[1-(4-octa d eca n oyloxy)p h en yleth en yl]-
4,5-d ih yd r oth iop h en e-2-ca r boxyla te (3g). According to the
representative procedure, the SmI2-promoted coupling reaction
of 1a with 4-acetylphenyl stearate, followed by the acid-
catalyzed dehydration, gave diene 3g in 48% overall yield:
solid; mp 84-85 °C; TLC (EtOAc/hexane, 1:9) Rf ) 0.34; IR
1
(KBr) 1754, 1727 cm-1; H NMR (CDCl3, 200 MHz) δ 7.22 (2
C
41H31NO4S 633.1974, found 633.1968.
H, d, J ) 8.6 Hz), 7.16 (2 H, d, J ) 8.6 Hz), 6.96 (2 H, d, J )
8.6 Hz), 6.95 (2 H, d, J ) 8.6 Hz), 6.51 (1 H, d, J ) 3.1 Hz),
5.40 (1 H, s), 5.32 (1 H, s), 5.27 (1 H, s), 5.17 (1 H, s), 4.67 (1
H, d, J ) 6.7 Hz), 4.30 (1 H, dd, J ) 6.7, 3.1 Hz), 3.78 (3 H, s),
2.52 (4 H, t, J ) 7.3 Hz), 1.71 (4 H, quint, J ) 7.3 Hz), 1.33-
1.24 (56 H, br s). 0.86 (6 H, t, J ) 6.7 Hz); 13C NMR (CDCl3,
125 MHz) δ 172.1 (2×), 162.7, 150.4 (2×), 146.9, 145.8, 137.4,
137.3, 135.0, 134.9, 128.4 (2×), 127.7 (2×), 121.6 (2×), 121.4
(2×), 115.9, 115.2, 58.1 (2×), 52.4, 34.4 (2×), 31.9 (2×), 29.67
(12×), 29.64 (2×), 29.60 (2×), 29.4 (2×), 29.3 (2×), 29.2 (2×),
29.1 (2×), 24.9 (2×), 22.6 (2×), 14.1 (2×); FAB-MS m/z 913.6
(M+ + 1). Anal. Calcd for C58H88O6S: C, 76.26; H, 9.72.
Found: C, 75.96; H, 9.74.
Meth yl 4,7-Bis(5-br om o-2-th ien yl)ben zo[b]th iop h en e-
2-ca r boxyla te (7b). According to the representative proce-
dure, the SmI2-promoted coupling reaction of 1a with 2-acetyl-
5-bromothiophene, followed by the acid-catalyzed dehydration
and DDQ oxidative cyclization, gave benzothiophene 7b in 35%
overall yield: solid; mp 145-147 °C; TLC (EtOAc/hexane, 1:19)
Rf ) 0.21; IR (KBr) 1724 cm-1; UV (CHCl3) λmax (ꢀ) 294 nm
(14700), 333 nm (12300), 368 nm (11600); FL (CHCl3, c ) 1 ×
10-5 M) λem 461 nm by excitation at 368 nm; 1H NMR (CDCl3,
200 MHz) δ 8.38 (1 H, s), 7.52 (1 H, d, J ) 7.7 Hz), 7.43 (1 H,
d, J ) 7.7 Hz), 7.33 (1 H, d, J ) 3.9 Hz), 7.12 (2 H, d, J ) 3.8
Hz), 7.07 (1 H, d, J ) 3.9 Hz), 3.94 (3 H, s); 13C NMR (CDCl3,
125 MHz) δ 162.8, 142.7, 142.6, 140.8, 137.4, 134.2, 130.8,
130.75, 130.73, 130.0, 128.6, 127.0, 126.23, 126.19, 126.0,
113.13, 113.09, 52.7; EI-MS m/z (rel intensity) 516 (13,
E t h yl 4,5-b is[1-(n a p h t h -2-yl)-2-m et h ylp r op en yl]t h io-
p h en e-2-ca r boxyla te (4l): oil; TLC (EtOAc/hexane (1:19)) Rf
) 0.13; IR (neat) 1705, 1617 cm-1; UV (CHCl3) λmax (ꢀ) 290
nm (35400), 364 nm (17100); FL (CHCl3, c ) 2 × 10-5 M) λem
C
18H10(81Br)2O2S3), 514 (17), 512 (10, C18H10(79Br)2O2S3), 91
415 nm by excitation at 364 nm; H NMR (CDCl3, 300 MHz)
(100); HRMS calcd for C18H10(81Br)2O2S3 515.8169, found
515.8168.
1
δ 7.70 (2 H, dd, J ) 6.0, 3.2 Hz), 7.57 (1 H, s), 7.54 (2 H, dd,
5214 J . Org. Chem., Vol. 67, No. 15, 2002

Synthesis of Polysubstituted Benzothiophenes
Meth yl 4,5-Dip h en ylth iop h en e-2-ca r boxyla te (11a ). Ac-
cording to the representative procedure, the reaction of diene
10a with 6.5 equiv of DDQ in refluxing xylene for 48 h gave
diphenylthiophene 11a in 89% yield: solid; mp 85-86 °C;
TLC (EtOAc/hexane, 1:9) Rf ) 0.33; IR (KBr) 1715 cm-1; UV
(CHCl3) λmax (ꢀ) 317 nm (48000); FL (CHCl3, c ) 1 × 10-5 M)
λem 410 nm by excitation at 317 nm; 1H NMR (CDCl3, 200
MHz) δ 7.81 (1 H, s), 7.31-7.19 (10 H, m), 3.90 (3 H, s); 13C
NMR (CDCl3, 50 MHz) δ 162.6, 145.6, 138.8, 136.2, 135.4 (2×),
133.3, 131.1, 129.2 (2×), 128.9 (2×), 128.6 (2×), 128.4 (2×),
128.3, 127.3; EI-MS m/z (rel intensity) 294 (100, M+); HRMS
calcd for C18H14C2S 294.0715, found 294.0721. Anal. Calcd for
nm; 1H NMR (CDCl3, 300 MHz) δ 7.86 (1 H, s), 7.28-7.16 (10
H, m), 6.89-6.80 (10 H, m), 4.31 (2 H, q, J ) 7.2 Hz), 1.32 (3
H, t, J ) 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 153.8, 139.5
(2×), 139.4 (2×), 137.7 (2×), 135.2 (2×), 134.0 (2×), 131.5 (2×),
131.3 (2×), 131.2 (2×), 130.5 (2×), 129.8 (2×), 128.1 (2×), 127.7
(2×), 127.3 (2×), 126.8 (2×), 125.8 (2×), 125.6 (2×), 61.5, 14.3;
FAB-MS m/z 510.2 (M+); HRMS calcd for C35H26O2S 510.1653,
found 510.1657.
Eth yl Tr iben zo[fg,ij,r st]pen taph en o[15,16-b]th ioph en e-
2-ca r b oxyla t e (15a ). To a solution of tetraphenylben-
zothiophene 14a (228 mg, 0.45 mmol) in CH2Cl2 (10 mL) was
added slowly a solution of FeCl3 (320 mg, 3 mmol) in CH3NO2
(5 mL). The mixture was stirred at room temperature for 5 h,
water (10 mL) was added, and and the mixture was extracted
with CH2Cl2. The organic phase was dried (Na2SO4), concen-
trated, and recrystallized from CH2Cl2/hexane to give polycyclic
aromatic compound 15a (183 mg, 81%). Alternatively, treat-
ment of 14a with excess amounts of AlCl3 and anhydrous
CuCl2 in CS2 solution under the atmosphere of oxygen for 36
h afforded 15a in 91% yield: solid; mp >300 °C; IR (KBr) 1715
cm-1; UV (CHCl3) λmax (ꢀ) 312 nm (19000), 325 nm (20300),
341 nm (21300), 380 nm (7700), 401 nm (9100), 412 nm (6900),
436 nm (5000); FL (CHCl3, c ) 1 × 10-5 M) λem 436 and 472
nm by excitation at 436 nm; 1H NMR (CDCl3, 200 MHz) δ 9.25
(1 H, dd, J ) 8.0, 2.3 Hz), 9.06 (1 H, s), 8.74-8.59 (7 H, m),
7.85-7.76 (6 H, m), 4.48 (2 H, q, J ) 7.2 Hz), 1.47 (3 H, t, J )
7.2 Hz); FAB-MS m/z 504.1 (M+); HRMS calcd for C35H20O2S
504.1184, found 504.1180. Anal. Calcd for C35H20O2S: C, 83.31;
H, 4.00. Found: C, 83.18; H, 4.24.
C
18H14O2S: C, 73.45; H, 4.80. Found: C, 73.29; H, 4.67.
Meth yl P icen o[13,14-b]th iop h en e-2-ca r boxyla te (12b).
The photochemical reaction of dinaphthylthiophene 11b in the
presence of I2, under conditions similar to that for 12a , gave
picenothiophene 12b in 89% yield: solid; mp 218-219 °C; TLC
(EtOAc/hexane, 1:9) Rf ) 0.22; IR (KBr) 1712 cm-1; UV (CHCl3)
λmax (ꢀ) 348 nm (25700), 365 nm (25200), 406 nm (8100); FL
(CHCl3, c ) 1 × 10-5 M) λem 416 and 437 nm by excitation at
1
406 nm; H NMR (CDCl3, 300 MHz) δ 9.24 (1 H, d, J ) 8.5
Hz), 9.09 (1 H, s), 8.35 (1 H, d, J ) 8.2 Hz), 8.56 (1 H, d, J )
10 Hz), 8.52 (1 H, d, J ) 10 Hz), 7.98-7.92 (3 H, m), 7.89 (1
H, d, J ) 8.5 Hz), 7.76 (1 H, td, J ) 8.0, 1.2 Hz), 7.70-7.60 (3
H, m), 4.00 (3 H, s); 13C NMR (CDCl3, 75 MHz) δ 163.2, 139.4,
134.2, 133.1, 132.8, 132.5, 131.8, 129.6, 129.3, 129.0, 128.8,
128.4, 128.3, 127.5, 127.4, 127.3, 127.2, 126.8, 126.7, 126.6,
126.2, 125.6, 125.0, 121.7, 121.3, 52.5; MS m/z (rel intensity)
392 (14, M+), 91 (100); HRMS calcd for C26H16O2S 392.0871,
found 392.0873. Anal. Calcd for C26H16O2S: C, 79.57; H 4.11.
Found: C, 79.52, H 4.08.
Ack n ow led gm en t. We thank the National Science
Council for financial support and Mr. Gene-Hsiang Lee
and Yi-Hung Liu for X-ray analyses.
Eth yl 4,5,6,7-Tetr aph en ylben zo[b]th ioph en e-2-car boxy-
la te (14a ). According to the representative procedure, the
SmI2-promoted coupling reaction of ethyl thiophene-2-carboxy-
late (1b ) with R-phenylacetophenone, followed by acid-
catalyzed dehydration and DDQ oxidative cyclization, gave
tetraphenylbenzothiophene 14a in 44% overall yield: solid; mp
>300 °C; TLC (EtOAc/hexane, 1:4) Rf ) 0.32; IR (KBr) 1715
cm-1; UV (CHCl3) λmax (ꢀ) 309 nm (50600), 345 nm (18900);
FL (CHCl3, c ) 1 × 10-5 M) λem 399 nm by excitation at 345
Su p p or tin g In for m a tion Ava ila ble: Physical and spec-
tral data, NMR spectra, and X-ray analyses of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0257849
J . Org. Chem, Vol. 67, No. 15, 2002 5215