Copper-Catalyzed Double S-Arylation of Potassium Thioacetate with Dibenziodolium Triflates: Facile Synthesis of Unsymmetrical Dibenzothiophenes

Article abstract of DOI:10.1002/ejoc.201600357

Much interest has been paid to cyclic diaryliodonium salts as bis(electrophile)s in transition-metal-catalyzed annulation reactions to produce polycyclic (hetero)aromatic hydrocarbons. Herein, we report that dibenziodolium triflates smoothly react with potassium thioacetate in the presence of CuCl₂in THF or DMSO at 100–110 °C to afford the corresponding dibenzothiophenes in good-to-high yields. The coupling reaction tolerates reactive functional groups such as chloro and cyano and serves as a facile and reliable method for the synthesis of unsymmetrical dibenzothiophenes.

Full text of DOI:10.1002/ejoc.201600357

DOI: 10.1002/ejoc.201600357
Communication
Thiophene Synthesis
Copper-Catalyzed Double S-Arylation of Potassium Thioacetate
with Dibenziodolium Triflates: Facile Synthesis of
Unsymmetrical Dibenzothiophenes
Masaki Shimizu*[a] Mai Ogawa,[a] Tomokazu Tamagawa,[a] Ryosuke Shigitani,[a]
Masaki Nakatani,[a] and Yoshiki Nakano[a]
Abstract: Much interest has been paid to cyclic diaryliodonium CuCl2 in THF or DMSO at 100–110 °C to afford the correspond-
salts as bis(electrophile)s in transition-metal-catalyzed annula- ing dibenzothiophenes in good-to-high yields. The coupling re-
tion reactions to produce polycyclic (hetero)aromatic hydro- action tolerates reactive functional groups such as chloro and
carbons. Herein, we report that dibenziodolium triflates cyano and serves as a facile and reliable method for the synthe-
smoothly react with potassium thioacetate in the presence of sis of unsymmetrical dibenzothiophenes.
Introduction
nium salt as the equivalent of 2,2′-diiodobinaphthyl in a Pd-
catalyzed double Heck reaction with methyl vinyl ketone to ob-
tain the corresponding dinaphthofulvene in high yield
(Scheme 1, type A).[8] Huang, Wen, and co-workers demon-
strated that 1, terminal alkynes, and arylboronic acids could be
sequentially coupled by using Pd and Cu catalysts to afford the
corresponding dibenzofulvenes in one pot (Scheme 1,
type A).[9] Phenanthrenes were synthesized by the Pd-catalyzed
insertion of an internal alkyne into 1 (Scheme 1, type B).[10] The
coupling reaction of 1 with amines was also shown to proceed
smoothly in the presence of a Pd or Cu catalyst to provide the
corresponding carbazoles in moderate-to-high yields
(Scheme 1, type C).[11] The transformations of 1 into triazolo-
phenanthridines[12] and 2,2′-diiodobiaryls[13] were also
achieved. However, to the best of our knowledge, double S-
arylation with 1 to dibenzothiophenes 2 has not been re-
ported.[14] Herein, we report a Cu-catalyzed coupling reaction
The transition-metal-catalyzed cross-coupling reactions of 2,2′-
dihalobiaryls with dianionic reagents serve as versatile methods
for the synthesis of polycyclic (hetero)aromatic hydrocarbons.[1]
For example, Nozaki and co-workers reported that the Pd-cata-
lyzed double N-arylation of primary amines with 2,2′-dibromo-
biphenyl efficiently produced the corresponding carbazoles.[2]
We reported that the Pd-catalyzed double cross-coupling reac-
tion of 2,2′-dibromobiaryls with vic-diborylalkenes and -arenes
is a facile method for the synthesis of functionalized phenan-
threnes, triphenylenes, and dibenzo[g,p]chrysenes.[3] Xi and co-
workers synthesized dibenzothiophenes by the Cu-catalyzed
coupling of carbon disulfide with 2,2′-diiodobiaryls.[4]
Considering that readily available 2,2′-dihalobiaryls are
mostly symmetrical, annulation reactions with 2,2′-dihalobiaryls
are useful for the synthesis of cyclic products that are symmetri-
cal with regard to the short axis of the biaryl skeleton but are
not practical for unsymmetrical counterparts. To overcome such
disadvantages of the double coupling strategy by using 2,2′-
dihalobiaryls, we turned our attention to dibenziodolium salts
1 (Scheme 1).[5,6] This is because 1 in both symmetrical and
unsymmetrical forms can be prepared from the corresponding
arylboronic acids and 2-nitrobromobenzenes by Suzuki–Miya-
ura cross-coupling, reduction of the nitro group, Sandmeyer re-
action, and cyclization by oxidation.[7] Indeed, several transi-
tion-metal-catalyzed reactions with the use of 1 as a synthetic
equivalent of 2,2′-dihalobiaryls have been recently reported. For
example, Hayashi and co-workers used a binaphthaleneiodo-
[a] Faculty of Molecular Chemistry and Engineering, Kyoto Institute of
Technology,
1 Hashikami-cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
E-mail: mshimizu@kit.ac.jp
http://www.cis.kit.ac.jp/~orgsynth/en/index.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600357.
Scheme 1. Transition-metal-catalyzed coupling reactions of dibenziodolium
salts 1.
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of triflates 1 (X = OTf) with potassium thioacetate to provide a
facile synthesis of symmetrical (Ar1 = Ar2) and unsymmetrical
(Ar1 ≠ Ar2) 2.[15]
Table 1. Optimization of the reaction conditions.[a]
Results and Discussion
Entry
S source (equiv.)
Catalyst (mol-%) Solvent
Yield [%][b]
Dibenziodolium triflate (1a) was selected as the model for opti-
mization of the planned cross-coupling reaction. The results ob-
tained are summarized in Table 1. First, several Pd and Cu cata-
lysts (5 mol-%) were screened by using K2S[16] (2 equiv.) in DMF
at 110 °C (Table 1, entries 1–6). The use of CuCl2 resulted in the
highest GC yield (46 %) of 2a (Table 1, entry 6).[17] Then, several
S sources were investigated by using 5 mol-% of CuCl2 as the
catalyst (Table 1, entries 7–9). Thiourea[18] and iPr3SiSH[19] pro-
duced 2a in lower yields (Table 1, entries 7 and 8); the yield
increased to 63 % upon using AcSK as the S source (Table 1,
entries 9).[20] Furthermore, an increase in the amount of AcSK
to 5 equivalents produced 2a in 84 % GC yield, and it was iso-
lated in 85 % yield (Table 1, entry 10). Next, several solvents
were screened. The use of dimethylacetamide (DMA) resulted
in a lower yield (Table 1, entry 11); the use of dimethyl sulfoxide
(DMSO) and THF afforded 2a in slightly and significantly higher
yields, respectively, than in DMF (Table 1, entries 12 and 13).
Then, the amount of AcSK was reoptimized in THF; 2 equiva-
lents of AcSK was enough to obtain 2a in high yield (Table 1,
entry 14). Finally, the effect of temperature was investigated
(Table 1, entries 13, 16, and 17). Lowering the reaction tempera-
ture decreased the yield; therefore, 110 °C was selected as the
optimum reaction temperature.
1
2
3
4
5
6
7
8
K2S (2)
K2S (2)
K2S (2)
K2S (2)
K2S (2)
K2S (2)
H2NC(=S)NH2 (2)
iPr3SiSH (2)
AcSK (2)
AcSK (5)
AcSK (5)
AcSK (5)
AcSK (5)
AcSK (2)
AcSK (1.5)
AcSK (5)
AcSK (5)
Pd2(dba)3 (5)
Pd(OAc)2 (5)
CuCl (5)
CuBr (5)
CuI (5)
CuCl2 (5)
CuCl2 (5)
CuCl2 (5)
CuCl2 (5)
CuCl2 (5)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
CuCl2 (4)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMA
DMSO
THF
29
30
40
36
38
46
43
38
9
63
10
11
12
13
14
15
16[d]
17[e]
84 (85)[c]
74
89
>99 (93)[c]
THF
THF
THF
THF
>99 (96)[c]
75
46
5
[a] In a vial, a solution of 1a (0.5 mmol), S source (1.5–5 equiv.), and the
catalyst (4 or 5 mol-%) in solvent (2 mL) was stirred at 110 °C for 24 h. dba =
dibenzylideneacetone. [b] GC yield estimated by using dodecane as the inter-
nal standard. [c] The value in parentheses shows the yield of the isolated
product. [d] The reaction was performed at 70 °C. [e] The reaction was per-
formed at room temperature.
Next, the substrate scope of the coupling reaction was inves-
tigated. The results are shown in Figure 1. Chloro-substituted
and 1,3-dimethyl-substituted unsymmetrical 2b and 2c were
produced under the optimized conditions in yields of 92 and
84 %, respectively. Thus, the chloro functionality was tolerated
under the optimized conditions, and the steric hindrance of the
methyl group at the 1-position of 1 did not interfere with the
performance of the coupling reaction. The reactions of meth-
oxy- and cyano-substituted iodonium triflates 1c and 1d under
the optimized conditions for 1a unexpectedly produced 2c and
2d in low yields of 49 and 31 %, respectively. However, the
yields of 2c and 2d increased to 70 and 76 %, respectively, if
the solvent was changed from THF to DMSO. The same solvent
effect was observed in the reactions of 1f and 1g, and thus
7-chloro-1,3-dimethyldibenzothiophene (2f) and 2-methoxy-7-
trifluoromethyldibenzothiophene (2g) were produced in yields
of 84 and 84 %, respectively, in DMSO. At present, the suitability
between the structures of 1 and solvent is unclear. In addition
to dibenzothiophenes, thieno[3,2-b][1]benzothiophene (2h)
was synthesized in a good yield from the corresponding (thi-
enyl)benziodolium triflate. Upon using bis-iodonium triflate 1i
as a coupling partner of AcSK,[13] ladder-type product 2i was
isolated in excellent yield; the reaction involved fourfold C–S
bond formation. Finally, we performed a gram-scale coupling
reaction by using 2.55 g of 1g, which produced 1.04 g of do-
nor–π–acceptor-type dibenzothiophene 2g in 77 % yield.
Figure 1. Substrate scope of dibenzothiophenes 2 and thienobenzothiophene
2h. In the cases of 2d–g and 2i, DMSO was used as the solvent at 100 °C.
CuI/III catalytic cycle has been proposed.[21] The same catalytic
cycle was hypothesized in the CuI-catalyzed iodination of dia-
ryliodonium salts.[13] On the basis of these reports, we propose
a mechanism for this transformation, as shown in Scheme 2.
First, the CuIICl2 precatalyst is converted into the CuI(X) catalyst
by reduction with the solvent or through a disproportionation
The Cu(OTf)2-catalyzed fluorination and Cu(OAc)2-catalyzed reaction.[22] Iodonium salt 1 undergoes oxidative addition to
amination of diaryliodonium salts have been reported, and a the CuI(X) catalyst, which affords aryl–CuIII complex 3. Ligand
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exchange of 3 with AcSK provides aryl–CuIII–(I)SAc complex 4,
which produces 2-acetylthio-2′-iodobiphenyl (5) with regenera-
tion of the CuI(I) catalyst.[23] Oxidative addition of the remaining
C–I bond in 5 to the CuI(I) catalyst generates aryl–CuIII complex
6. Nucleophilic attack of I– at the acyl carbon atom of a SAc
moiety provides complex 7, which undergoes intramolecular
ligand exchange to produce cyclic aryl–CuIII–S complex 8. Fi-
nally, reductive elimination of dibenzothiophene 2 from 8 liber-
ates the CuI(I) catalyst, which completes the catalytic cycle.
Upon using CuCl instead of CuCl2 under the optimized condi-
tions, 2a was produced in 83 % yield. This result indicates that
the CuI complex could serve as a catalyst for this transforma-
tion.
was purified by column chromatography on silica gel (hexane) to
give 2.
Acknowledgments
This work was supported by Grants-in-Aid for Scientific Re-
search on Innovative Areas “π-System Figuration: Control of
Electron and Structural Dynamism for Innovative Functions”
from the Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan, and The Asahi Glass Foundation.
Keywords: Sulfur heterocycles · Fused-ring systems ·
Annulation · Copper · Hypervalent compounds
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Scheme 2. A plausible mechanism.
Conclusions
Dibenziodolium triflates smoothly reacted with AcSK in THF or
DMSO at 100–110 °C in the presence of a catalytic amount of
CuCl2. Symmetrical and unsymmetrical dibenzothiophenes
were produced in good-to-excellent yields. The cross-coupling
reaction could be used for the gram-scale synthesis of 2. Fur-
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Experimental Section
General Procedure: In a glovebox, a 15 mL vial equipped with a
stirring bar was charged with CuCl2 (2.7 mg, 20 μmol), dibenziodo-
lium salt 1 (0.50 mmol), AcSK (0.11 g, 1.00 mmol), and THF or DMSO
(2 mL). The vial was capped and removed from the glovebox. The
mixture was stirred at 100 or 110 °C for 24 h. The resulting solution
was filtered through a pad of Celite, and the filtrate was diluted
with distilled water (10 mL). The aqueous layer was extracted with
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with anhydrous Na2SO4. After Na2SO4 was removed by filtration, the
filtrate was concentrated by rotary evaporation. The crude product
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Received: March 21, 2016
Published Online: May 23, 2016
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