Thiophene-Fused π-Systems from Diarylacetylenes and Elemental Sulfur

Article abstract of DOI:10.1021/jacs.6b06486

A simple yet effective method for the formation of thiophene-fused π-systems is reported. When arylethynyl-substituted polycyclic arenes were heated in DMF in the presence of elemental sulfur, the corresponding thiophene-fused polycyclic arenes were obtained via cleavage of the ortho-C-H bond. Thus, arylethynylated naphthalenes, fluoranthenes, pyrenes, corannulenes, chrysenes, and benzo[c]naphtho[2,1-p]chrysenes were effectively converted into the corresponding thiophene-fused π-systems. Apart from polycyclic hydrocarbons, thiophene derivatives are also susceptible to this reaction. The practical utility of this reaction is demonstrated by preparations on the decagram scale, one-pot two-step reaction sequences, and multiple thiophene annulations.

Full text of DOI:10.1021/jacs.6b06486

Article
pubs.acs.org/JACS
Thiophene-Fused π‑Systems from Diarylacetylenes and Elemental
Sulfur
Lingkui Meng,†,‡ Takao Fujikawa,‡ Motonobu Kuwayama,‡,§ Yasutomo Segawa,*,‡,§
and Kenichiro Itami*,†,‡,§,∥
†Integrated Research Consortium on Chemical Sciences, Nagoya University, Chikusa, Nagoya 464-8602, Japan
‡Graduate School of Science, Nagoya University, Chikusa, Nagoya, Japan
§JST, ERATO, Itami Molecular Nanocarbon Project, Nagoya University, Chikusa, Nagoya, Japan
∥Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya, Japan
S
* Supporting Information
ABSTRACT: A simple yet effective method for the formation of
thiophene-fused π-systems is reported. When arylethynyl-substituted
polycyclic arenes were heated in DMF in the presence of elemental
sulfur, the corresponding thiophene-fused polycyclic arenes were obtained
via cleavage of the ortho-C−H bond. Thus, arylethynylated naphthalenes,
fluoranthenes, pyrenes, corannulenes, chrysenes, and benzo[c]naphtho-
[2,1-p]chrysenes were effectively converted into the corresponding
thiophene-fused π-systems. Apart from polycyclic hydrocarbons, thiophene derivatives are also susceptible to this reaction.
The practical utility of this reaction is demonstrated by preparations on the decagram scale, one-pot two-step reaction sequences,
and multiple thiophene annulations.
INTRODUCTION
■
Thiophene-containing π-conjugated molecules are of great
interest on account of their diverse applications in materials
science. As thiophene-containing π-systems show high charge
transport properties, they are widely used in organic field-effect
transistors (OFETs), organic light-emitting diodes (OLEDs),
and organic photovoltaics (OPVs).1 Since thiophene-annulation
reactions, the so-called thienannulations, can produce various
thiophene-fused π-systems, a number of thienannulation
reactions have been investigated.2,3 In most cases, it is necessary
to introduce two functional groups (e.g., halogen, alkynyl, or
sulfur-containing groups) on the arenes prior to thienannulation
(Figure 1, eqs 1 and 2).2 Although several examples exist, in
which only one functional group is required, e.g. reactions
between diethoxyethylsulfanes and Lewis acids (eq 3),3a 1-
ethynylnaphthalene and super bases (eq 4),3b and carbonyl-
containing arenes and thiourea or Na2S,3c−e these methods have
not been applied to the synthesis of a wide range of thiophene-
Figure 1. Thienannulation reactions.
fused polycyclic aromatic hydrocarbons (PAHs). As the recent
C−H functionalization chemistry enables rapid synthesis and
derivatization of organic materials,4 a simple method for the
formation of thiophene rings via C−H functionalization would
thus be highly attractive.
Herein, we report a simple thienannulation protocol, in which
arylethynyl-substituted PAHs are heated in DMF in the presence
of elemental sulfur5 to afford the corresponding thiophene-fused
PAHs via cleavage of the ortho-C−H bond. This reaction requires
the presence of only one functional group, i.e., an arylethynyl
group on the PAHs.
RESULTS AND DISCUSSION
■
Thienannulation of PAHs with Elemental Sulfur. The
discovery of this thienannulation reaction was serendipitous.
During the attempted Na2S-mediated reduction6 of 9-arylethyl-
phenanthrene 1a, we obtained not only the reduced cis-alkene
Received: June 23, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/jacs.6b06486
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
but also thienannulated 2a. As the thienannulation from 1a to 2a
is redox-neutral and elemental sulfur is generated from Na2S, we
treated 1a with S8 in DMF at 140 °C under an atmosphere of
argon, which resulted in the formation of 2a in high yield.
Subsequently, we screened different reaction conditions, which
are summarized in Table 1. Treatment of 1a with 1.0 equiv of S8
pot Sonogashira coupling/thienannulation sequence (Scheme
1). After the Sonogashira coupling reaction between 4a and a
terminal alkyne in DMF, S8 was added to the mixture without any
intermediary purification step, and the resulting mixture was
heated to 140 °C for 48 h. This protocol furnished
thienannulated 2a in 70% yield. We also discovered an S8-
mediated thienannulation/reduction reaction in the presence of
functional groups containing nitrogen. While dimethylamino-
substituted arylethynylphenanthrene 1n was smoothly converted
into the corresponding thienophenanthrene (2n) in 77% yield,
the reaction of a nitro-substituted derivative (1o) generated an
amino-substituted derivative (2o), in which the nitro group was
reduced to an amino group. Cyano or methoxycarbonyl groups
on the phenyl rings also reacted to afford complex mixtures.
Multiple Thienannulations. The thienannulation de-
scribed herein can also be used for the synthesis of multiply
thienannulated PAHs. Tris(arylethynyl)benzo[c]naphtho[2,1-
p]chrysene (1p) and pentakis(arylethynyl)corannulene (1q),
which are readily available from previously reported com-
pounds,7 were subjected to the optimized thienannulation
conditions (Scheme 2). Threefold and fivefold thienannulations
furnished triple thia[5]helicene 2p and pentathienocorannulene
2q, respectively. The solid-state structure of 2p was confirmed by
single-crystal X-ray diffraction analysis (Figure 2a). The C3-
symmetric structure of 2p is chiral on account of the presence of
three thia[5]helicene moieties, and the enantioenriched fractions
could be obtained by chiral HPLC (Figure 2c). The racemization
barrier was determined by an analysis of the degradation of the
intensity of the CD spectrum. The experimentally obtained value
for the racemization barrier of 2p (ΔH‡ = 24.8 kcal·mol−1, ΔS‡ =
0.44 cal·mol−1·K−1, and ΔG‡ = 24.7 kcal·mol−1 (298.15 K, 1
atm)) is consistent with the value estimated from DFT
calculations (ΔG‡ = 25.8 kcal·mol−1; B3LYP/6-31G(d) level of
theory8,9) and slightly lower than that of a previously reported
triple[5]helicene10 (ΔG‡ = 31.0 kcal·mol−1). For pentathieno-
corannulene 2q, preliminary results of an X-ray diffraction
analysis suggested efficient π−π stacking between two molecules
in the crystalline state (Figures 2b,d), which should enable the
design of one-dimensional columnar packings.
Table 1. Thienannulation of 9-(Arylethynyl)phenanthrene
a
1a
b
entry
S8 [equiv]
solvent
DMF
T [°C]
yield [%]
1
2
3
4
5
6
7
8
1.0
140
140
140
125
140
140
140
140
92
0.50
0.25
1.0
DMF
56
DMF
34
DMF
68
1.0
DMAc
80
1.0
DMSO
1,4-dioxane
mesitylene
21
1.0
19
1.0
trace
a
DMF = N,N-dimethylformamide, DMAc = N,N-dimethylacetamide,
DMSO = dimethyl sulfoxide, mesitylene = 1,3,5-trimethylbenzene.
b
Isolated yield.
in DMF at 140 °C was identified as optimal conditions (entry 1),
which afforded 2a in 92% yield. Addition of less S8 (0.5 or 0.25
equiv; entries 2 and 3), a lower temperature (125 °C, entry 4), or
the use of other solvents (DMAc, DMSO, 1,4-dioxane, or
mesitylene; entries 5−8) afforded 2a in lower yields. This
reaction can also be carried out at the decagram scale, and it also
proceeds under atmospheric conditions (for details, see the
Supporting Information).
Substrate Scope. Then, we investigated the scope of this
simple S8-mediated thienannulation, using mono(arylethynyl)-
PAHs (1b−i) and di(arylethynyl)PAHs (1j−m) under opti-
mized conditions (Table 2). In order to increase the solubility of
the starting materials and products, para-alkylphenyl groups
(Ar1−Ar4) were incorporated. Thus, naphthalene (1b−e, 1j−l),
fluoranthene (1f), pyrene (1g,h), corannulene (1i), and
chrysene (1m) derivatives could be efficiently thienannulated.
In particular, pyrene, corannulene, and chrysene derivatives
afforded the corresponding products in good to excellent yield.
Under the applied reaction conditions, methoxy and bromo
groups were tolerated well (1d,e). Based on the reactions of 1c,j
to 2c,j, it can be concluded that the C1-position of the
naphthalenes should be more reactive than the C3-position. In
the case of di(arylethynyl)naphthalenes, not only symmetrically
(1j,k) but also unsymmetrically substituted precursors (1l) could
be used. To improve the reactions involving 1j−m, 2 or 4 equiv
of S8 were used. The structures of 2e, 2j, and 2m were
unambiguously determined by single-crystal X-ray diffraction
analysis, and all products were identified by NMR spectroscopy
and high-resolution mass spectrometry. Dichloromethane
solutions of 2f−2m exhibited blue fluorescence with low to
moderate quantum yields (ΦF): 0.24 (2g), 0.38 (2h), 0.23 (2j),
and 0.28 (2k).
Thienannulation of Thiophenes. Furthermore, this
thienannulation can also be applied to arylethynylthiophenes:
treatment of (arylbutadiynyl)phenanthrene (1r) with 4 equiv of
S8 afforded a thieno[3,2-b]thiophene-fused phenanthrene (2r),
possibly generated by sequential thienannulations via
(arylethynyl)thienophenanthrene (3r) as an intermediate. This
result indicates that arylethynylthiophenes can be used in this
thienannulation, and we therefore attempted the reaction of
diarylethnylated derivatives benzo[1,2-b:4,5-b′]dithiophene (1s)
and thiophene (1t), as shown in Scheme 3. As expected,
thienannulated products 2s and 2t were obtained in 28% and
22% yields, respectively. Interestingly, (2,6-bis(4-n-octylphenyl)-
dithieno[3,2-b:2′,3′-d]thiophene (2t) has recently been reported
by Adachi and co-workers as a high-performance organic
semiconductor that exhibits one of the highest mobilities and
on/off ratios.11 While our synthetic route to 2t involves the same
number of reaction steps as the previously reported one (three
steps from commercially available compounds), 2t can be
produced more cheaply with our method, as it does not require
the use of dithieno[3,2-b:2′,3′-d]thiophene.
Mechanistic Studies. To gain a better understanding of the
mechanism of this thienannulation, the transformation of 1a into
2a was investigated in detail. Considering that all starting
materials (1a−t) were synthesized by palladium-catalyzed
One-Pot Two-Step Transformations Including a Thie-
nannulation. This thienannulation could also be included in
one-pot two-step transformations. Initially, we attempted a one-
B
DOI: 10.1021/jacs.6b06486
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Journal of the American Chemical Society
Article
Table 2. Thienannulation of Mono- or Bis(arylethynyl)PAHs
a
b
c
0.5 equiv of S8, t = 24 h. 2 equiv of S8. 4 equiv of S8.
Scheme 1. Application of Thienannulations to Two-Step
Transformations
Scheme 2. Synthesis of the Multiply Thienannulated PAHs 2p
and 2q
Sonogashira coupling reactions, we initially examined the
influence of trace amounts of impurities, especially of transition
metals such as palladium. However, the yield of 2a did not
change when chemicals (S8 and DMF) from other suppliers were
C
DOI: 10.1021/jacs.6b06486
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Scheme 4. Mechanistic Studies on the Thienannulation of 1a
Figure 2. (a,b) ORTEP drawings of 2p (a) and 2q (b) with 50%
probability; hydrogen atoms and minor parts of disordered atoms are
omitted for clarity. (c) CD spectra of the enantiomers of 2p. (d) Packing
structure of 2q.
Scheme 3. Thienannulation of Thiophenes
Figure 3. Proposed reaction mechanism for the formation of 2a.
position of phenanthrene is doubly stabilized by benzylic and
propargylic conjugations. The elimination of elemental sulfur
(Sn−1) and H+ from A would then produce B, which is a common
intermediate in thienannulation reactions (cf. eq 2).2
A
subsequent nucleophilic attack of the sulfur anion on the alkyne
would generate carboanion C, which would be rapidly
protonated by residual H2O in DMF to afford 2a.
CONCLUSION
■
In conclusion, we have developed a simple yet effective and
versatile method for the formation of thiophene-fused π-systems.
Upon heating arylethynyl-substituted polycyclic arenes in DMF
in the presence of elemental sulfur, the corresponding thiophene-
fused polycyclic arenes are obtained via cleavage of a C−H bond.
The synthetic utility of this reaction manifests in the facile
generation of thiophene-fused naphthalene, fluoranthene,
pyrene, corannulene, and chrysene derivatives. Not only
polycyclic hydrocarbons but also thiophene derivatives are
susceptible to this reaction, which greatly increases the utility of
the reaction. The practical utility of this reaction is reflected in
the fact that it can be carried out on a decagram scale, in one-pot
two-step reaction sequences, and that multiple thienannulations
are possible.
used, or when 1a was synthesized by an alternative “palladium-
free” method.12 An inductively coupled plasma mass spectrom-
etry (ICP-MS) analysis revealed that the contamination levels of
1a, S8, and DMF with palladium were all below 1 ppm. These
results suggest that this thienannulation should not be catalyzed
by transition metals. Then, a model reaction was carried out
under the conditions shown in Scheme 4. This reaction, which
used 28 equiv of D2O, afforded 2a-D, in which the β-position of
the thiophene moiety was completely deuterated. The presence
of radical scavengers such as TEMPO (2,2,6,6-tetramethyl-
piperidine 1-oxyl) or galvinoxyl did not significantly affect the
yield of 2a, which indicates that a radical mechanism should not
be operative.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.6b06486.
Based on the substrate scope and the results of the mechanistic
studies, we propose a possible reaction mechanism for the
formation of the thiophene rings during this thienannulation
(Figure 3). Initially, elemental sulfur (Sn) should react electro-
philically13 with 1a to form A, in which the cation at the C9-
Experimental procedures, characterization data for all new
compounds (PDF)
Crystallographic data (CIF, CIF, CIF, CIF, CIF, CIF, CIF,
CIF)
D
DOI: 10.1021/jacs.6b06486
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Journal of the American Chemical Society
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Petrí
̌
ck
̌
ova,
́
H. Tetrahedron Lett. 2003, 44, 8093. (d) Ahmed, H. H.;
AUTHOR INFORMATION
■
Elmegeed, G. A.; El-Sayed, E.-S. M.; Abd-Elhalim, M. M.; Shousha, W.
G.; Shafic, R. W. Eur. J. Med. Chem. 2010, 45, 5452.
Corresponding Authors
*ysegawa@nagoya-u.jp (Y.S.)
*itami@chem.nagoya-u.ac.jp (K.I.)
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the ERATO program from JST
(K.I.) and the Funding Program for KAKENHI from MEXT
(16K05771 to Y.S.). L.M. thanks the Integrated Research
Consortium on Chemical Sciences for support. Dr. Keiko
Kuwata is acknowledged for assistance with the HRMS
measurements. We thank Ms. Akiko Gocho for measuring
photophysical properties. Computations were performed using
Research Center for Computational Science, Okazaki, Japan.
ITbM is supported by the World Premier International Research
Center (WPI) Initiative, Japan.
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DOI: 10.1021/jacs.6b06486
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