Catalytic [2 + 2 + 2] cycloaddition of benzothiophene dioxides with α,ω-diynes for the synthesis of condensed polycyclic compounds

Article abstract of DOI:10.1021/ol5030019

A Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition of the 2,3-double bond of benzothiophene dioxides with α,ω-diynes gave sulfone-containing cycloadducts in high yields. This is the first example of a catalytic [2 + 2 + 2] cycloaddition that uses the

Full text of DOI:10.1021/ol5030019

Letter
pubs.acs.org/OrgLett
Catalytic [2 + 2 + 2] Cycloaddition of Benzothiophene Dioxides with
α,ω-Diynes for the Synthesis of Condensed Polycyclic Compounds
Yu-ki Tahara,† Manami Gake,† Riku Matsubara,† and Takanori Shibata*,†,‡
†Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo,
Shinjuku, Tokyo 169-8555, Japan
‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
S
* Supporting Information
ABSTRACT: A Rh-catalyzed intermolecular [2 + 2 + 2] cycloaddition of the 2,3-double bond of benzothiophene dioxides with
α,ω-diynes gave sulfone-containing cycloadducts in high yields. This is the first example of a catalytic [2 + 2 + 2] cycloaddition
that uses the 2,3-double bond of a heterole as an ene moiety. The consecutive reaction of benzodithiophene tetraoxide with 2,3-
naphthylene-tethered 1,7-diyne gave an 11-ring condensed polycyclic compound in one pot.
Table 1. Screening of Reaction Conditions
he transition-metal-catalyzed [2 + 2 + 2] cycloaddition of
Tunsaturated motifs, such as alkynes and alkenes, is a well-
established and atom-economical protocol for the construction
of multicyclic six-membered ring systems, and various types of
substrates have been used in this reaction.1 For example, the
intermolecular [2 + 2 + 2] cycloaddition of α,ω-diynes with
1,1-disubstituted alkenes2 gave bicyclic 5,5-disubstituted cyclo-
hexa-1,3-dienes, and that with 1,2-disubstituted alkenes3 gave
5,6-disubstituted cyclohexa-1,3-dienes (paths A and B in
Scheme 1). Their asymmetric variants have also been reported.
a
entry
X
time (h)
1.0
yield (%)
1
2
3
4
5
BF4
48
90
95
93
95
b
BF4
1.0
b
BF4
1.5
b
Scheme 1. Intermolecular [2 + 2 + 2] Cycloaddition of α,ω-
Diynes with Various Types of Ene Moieties
BARF
OTf
1.5
b
1.5
a
b
Benzothiophene dioxide/diyne was 1/3. Time taken for the
dropwise addition of diyne 1a.
However, to the best of our knowledge, there has been no
report of catalytic cycloaddition in which the 2,3-double bond
of a heterole was involved as an ene moiety (path C). This
protocol could make it easy to construct a heteroatom-
containing condensed multicyclic system.4
We have comprehensively studied the intra-5 and inter-
molecular6 [2 + 2 + 2] cycloaddition of various types of
unsaturated compounds that contain alkene motifs. We recently
Received: October 13, 2014
© XXXX American Chemical Society
A
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Table 2. [2 + 2 + 2] Cycloaddition of Various Diynes 1 with
Substituted Benzothiophene Dioxide Derivatives 2
Table 3. [2 + 2 + 2] Cycloaddition of Arylene-Tethered
Diynes 1 with Naphtho- and Antrathiophene Dioxide
Derivatives 2
a
Benzothiophene dioxide/diyne was 1/3. Diyne was added dropwise
to a solution of the Rh catalyst and benzothiophene dioxide over 1.5 h.
Scheme 2. Aromatization of Cycloadduct 3ea and
Subsequent Reduction
a
Benzothiophene dioxide/diyne was 1/3. Diyne was added dropwise
to a solution of the Rh catalyst and benzothiophene dioxide over 1.5 h.
focused on sulfur-containing substrates: consecutive inter- and
intramolecular cycloadditions of thiophenylene-tethered triynes
gave macrocyclic heteroarylenes containing thiophene rings7
and intermolecular cycloaddition of sulfanylbenzene-tethered
diynes with alkynes gave multisubstituted dibenzothiophenes.8
Against this background, we next considered the catalytic [2 + 2
+ 2] cycloaddition of α,ω-diynes with sulfur-containing
benzoheterole derivatives for the synthesis of sulfur-containing
condensed polycyclic compounds.
We chose nitrogen-tethered 1,6-diyne 1a and benzothio-
phene 1,1-dioxide (2a) as a model diyne and benzoheterole,
and examined intermolecular [2 + 2 + 2] cycloaddition using
Rh-2,2′-bis(diphenylphosphino)-1,1′-biphenyl (BIPHEP) cata-
lyst at 80 °C in 1,2-dichloroethane (DCE) (Table 1).9 The
desired cycloadduct dihydrodibenzothiophene dioxide 3aa was
obtained, but the yield was moderate due to the formation of a
self-cycloadduct of diyne 1a (entry 1). When diyne 1a was
added dropwise to a heated solution of the Rh catalyst and
benzothiophene 1,1-dioxide 2a over 1 h, the yield was
drastically improved to 90% (entry 2). A slower dropwise
addition (1.5 h) realized an excellent yield of 95% (entry 3).
This reaction was little affected by the counteranion of the
cationic rhodium catalyst, and we used BF4 for further
investigations (entries 4 and 5).
B
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Table 4. Consecutive [2 + 2 + 2] Cycloaddition of Diynes 1
and Benzodithiophene Tetraoxide 5
Scheme 3. Synthesis of a Multicyclic Compound with Sulfide
and Sulfone Moieties via Two [2 + 2 + 2] Cycloadditions
to give cycloadducts 3eb−3ed in good yield. Notably,
benzothiophene dioxide 2e with a pinacolboryl group could
also be used in this reaction: the obtained cycloadduct 3ee can
be used for further transformation. 2,3-Naphtylene-tethered
diyne 1f was also a good substrate, and hexacyclic product 3fa
was obtained quantitatively (entry 4).
Next, we examined thiophene dioxides condensed with
multicyclic aromatic hydrocarbons as ene moieties (Table 3).
Naphthothiophene-1,1-dioxide 2f worked well, and the reaction
with diynes 1e and 1f proceeded to give cycloadducts 3ef and
3ff, respectively, in high yields (entries 1 and 2). Furthermore,
the reaction of anthrathiophene-1,1-dioxide 2g also proceeded
(entries 3 and 4). The reasons for the low yield of 3fg are the
lower reactivity of 2g compared to 2f and the instability of 3fg.
We next transformed the obtained cycloadduct into a
multicyclic aromatic compounds: oxidation of pentacyclic
compound 3ea using 2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ) gave the aromatized compound 4a (Scheme 2).11
Subsequent reduction gave anthra[2,3-b]benzo[d]thiophene
(4b).
a
Benzodithiophene tetraoxide/diyne was 1/9. Diyne was added
dropwise to a solution of Rh catalyst and benzodithiophene tetraoxide
over 9 h. The value is the total yield of cycloadducts 6 and their
b
We further examined consecutive [2 + 2 + 2] cycloaddition
using benzodithiophene tetraoxide (Table 4). We introduced a
hexyl group at the 4 and 8 positions, respectively, to increase
the solubility and used it in the reaction with diynes 1 (Table
4).12 While excess amounts of diynes and their slower dropwise
addition were required, the reactions of nitrogen-tethered diyne
1a, phenylene- and naphthylene-tethered diynes 1e and 1f
proceeded to give condensed polycyclic compounds. However,
double isomerization of the 1,3-cyclohexadiene motif occurred
under the reaction conditions, and the corresponding cyclo-
adducts 6a, 6e, and 6f could not be completely isolated.
Finally, we synthesized multicyclic compounds containing
two sulfur atoms, which differ with respect to the degree of
oxidation, by a stepwise protocol including two [2 + 2 + 2]
cycloadditions (Scheme 3). Rh-catalyzed intermolecular [2 + 2
+ 2] cycloaddition of sulfanylbenzene-tethered diyne 7 with 2-
butyne-1,4-diol gave dibenzothiophene (DBT) derivative 8 in
good yield.8 Subsequent iodination and ethynylation of two
hydroxyl groups gave DBT-tethered diyne 1g. The second
double bond isomers of 1,3-cyclohexadiene motif.
Under the reaction conditions for entry 3 in Table 1, various
diynes and benzothiophene dioxides were subjected to
intermolecular [2 + 2 + 2] cycloaddition (Table 2). The
reaction of oxygen-tethered diyne 1b also proceeded, and the
cycloadduct 3ba was obtained in good yield (entry 1). When
unsymmetrical diynes, which have a methyl or phenyl group
and hydrogen on their alkyne terminus, were used, the
corresponding cycloadducts 3ca and 3da were obtained with
almost perfect regioselectivity (entry 2).10 We next examined
arylene-tethered diynes for the synthesis of condensed
multicyclic compounds and first used ortho-phenylene-tethered
diyne 1e as a substrate (entry 3). The cycloaddition with 2a
proceeded quantitatively. The reaction of 5-substituted
benzothiophene dioxide derivatives 2b−2d, which have a
chloro or bromo group as an electron-withdrawing group, and a
methoxy group as an electron-donating group, also proceeded
C
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2008, 130, 3451. (d) Shibata, T.; Otomo, M.; Endo, K. Synlett 2010, 8,
1235.
intermolecular [2 + 2 + 2] cycloaddition of diyne 1g with
benzothiophene 1,1-dioxide (2a) proceeded to give a
regioisomeric mixture of cycloadducts 10 and 11 in excellent
total yield.
In summary, we have developed a Rh-catalyzed intermo-
lecular [2 + 2 + 2] cycloaddition of benzothiophene dioxides
and benzodithiophene tetraoxide with α,ω-diynes. The present
reaction provides a new protocol for the synthesis of condensed
polycyclic compounds containing sulfone moieties. Recently,
various polyaromatic systems that include thiophene dioxide
moieties have been shown to exhibit unique photophysical
properties that are different from those of thiophene.13 We will
further synthesize various condensed polycyclic compounds
and evaluate their potential as electronic materials.
(6) (a) Shibata, T.; Arai, Y.; Tahara, Y. Org. Lett. 2005, 7, 4955.
(b) Tsuchikama, K.; Kuwata, Y.; Shibata, T. J. Am. Chem. Soc. 2006,
128, 13686. (c) Shibata, T.; Kawachi, A.; Ogawa, M.; Kuwata, Y.;
Tsuchikama, K.; Endo, K. Tetrahedron 2007, 63, 12853. (d) Shibata,
T.; Otomo, M.; Tahara, Y.; Endo, K. Org. Biomol. Chem. 2008, 6, 4296.
(7) Shibata, T.; Fujimoto, M.; Otani, T. Tetrahedron 2014, 70, 8453.
(8) Tahara, Y.; Matsubara, R.; Shibata, T. Heterocycles, in press (DOI:
10.3987/COM-14-S(K)78).
(9) The reaction of 1,6-diyne 1a and benzothiophene gave no cross-
cycloadduct at all under the same reaction conditions.
(10) These regioisomeric structures were determined by NOESY
analyses (see Supporting Information).
(11) Jia, Z.; Li, S.; Nakajima, K.; Kanno, K.; Song, Z.; Takahashi, T.
Heterocycles 2012, 86, 1495.
(12) The reaction of unsubstituted benzodithiophene tetraoxide with
diyne 1a proceeded, but the yield was very low and most of tetraoxide
was recovered due to its poor solubility in DCE.
ASSOCIATED CONTENT
■
S
* Supporting Information
(13) (a) Li, H.; Batsanov, A.; Moss, K.; Vaughan, H.; Dias, F.;
Kamtekar, K.; Bryce, M.; Monkman, A. Chem. Commun. 2010, 46,
4812. (b) Moss, K.; Bourdakos, K.; Bhalla, V.; Kamtekar, K.; Bryce,
M.; Fox, M.; Vaughan, H.; Dias, F.; Monkman, A. J. Org. Chem. 2010,
75, 6771. (c) Camurlu, P.; Durak, T.; Balan, A.; Toppare, L. Synth.
Met. 2011, 161, 1898. (d) Duan, Z.; Huang, X.; Fujii, S.; Kataura, H.;
Nishioka, Y. Chem. Lett. 2012, 41, 363. (e) Hsu, C.; Hsieh, M.; Tsai,
M.; Li, Y.; Huang, C.; Su, Y.; Whang, T. Tetrahedron 2012, 68, 5481.
(f) Xiao, H.; Yu, L.; Li, Y.; Yang, W.; Zhang, B.; Yang, W.; Wu, H.;
Cao, Y. Polymer 2012, 53, 2873. (g) Nandakumar, M.; Karunakaran, J.;
Mohanakrishnan, A. Org. Lett. 2014, 16, 3068.
Experimental procedure, characterization, and NMR copies of
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: tshibata@waseda.jp.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by ACT-C from JST (Japan) and
Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology, Japan
(No. 23655091).
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