Thioether-Directed Peri-Selective C-H Arylation under Rhodium Catalysis: Synthesis of Arene-Fused Thioxanthenes

Article abstract of DOI:10.1021/acs.orglett.8b03675

A rhodium-catalyzed direct C-H arylation of naphthalene and anthracene was developed with the assistance of a thioether directing group. The reaction proceeded with exclusive peri-selectivity, and the series of coupling products were readily transformed i

Full text of DOI:10.1021/acs.orglett.8b03675

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Thioether-Directed Peri-Selective C−H Arylation under Rhodium
Catalysis: Synthesis of Arene-Fused Thioxanthenes
Sanghun Moon,† Yuji Nishii,‡ and Masahiro Miura*,†
‡
†Department of Applied Chemistry and Frontier Research Base for Global Young Researchers, Graduate School of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
S
* Supporting Information
ABSTRACT: A rhodium-catalyzed direct C−H arylation of
naphthalene and anthracene was developed with the
assistance of a thioether directing group. The reaction
proceeded with exclusive peri-selectivity, and the series of
coupling products were readily transformed into the
corresponding sulfur-containing polyaromatics. Charge-trans-
port properties of the provided dithiapyrenes were evaluated by computational studies.
ulfur-containing fused aromatic compounds have received
tremendous attention because of their vital use in organic
electronic materials such as field-effect transistors (OFETs),
light-emitting diodes (OLEDs), and photovoltaics (OPVs).1
To meet the increasing demand in this field, development of
efficient synthetic methods for these compounds has been a
substantial topic over the past decades.2
Recently, considerable research efforts have been focusing
on the direct functionalization of aromatic C−H bonds3 with
the assistance of thioether directing groups.4 A potential
advantage of the reaction systems is that the directing groups
can be easily converted into various other functional groups
through sulfur−lithium exchange reactions5 or transition-metal
catalyses.6 Our group has also been investigating the Rh-
catalyzed direct functionalization of aromatic compounds using
sulfur-containing directing groups7 and recently disclosed the
intriguing site-selectivity of the C−H alkenylation reactions for
the acene peri-positions7e as well as the indole C4 positions7f
(Scheme 1a). As a consequence of our interest in this area, we
herein describe a rhodium-catalyzed8 peri-selective C−H
arylation of naphthalene and anthracene using boronic acid
esters as arylating reagents (Scheme 1b). For the synthesis of
sulfur-containing polyaromatic compounds, the acid-mediated
cyclization of aromatic methyl sulfoxides has been one of the
most promising methods.9 Accordingly, the present catalytic
reaction would provide valuable synthetic precursors of the
thia-heterocycles by installing various aromatic units nearby
the thiomethyl functionality. In fact, a series of coupling
products readily underwent the cyclization to provide novel
thioxanthene and dithiapyrene derivatives, which are key
motifs in biologically active compounds10 and optoelectronic
materials.11 Additionally, we evaluated the photo- and
electrochemical properties of the provided thia-heterocycles.
We started our investigation with an optimization study for
the direct C−H arylation using 1-(methylthio)naphthalene (1)
and a boronic ester PhB(neo) (2a: neo = neopentyl glycolato)
as representative substrates (Table 1). Initially, the corre-
sponding coupling product 3a was obtained in 15% yield in the
presence of [Cp*Rh(CH3CN)3][SbF6]2 catalyst along with
Ag2O oxidant in PhCF3 (entry1). Solvent screening was then
carried out, and the yield was improved up to 67% using t-
AmOH (entries 2−4). Addition of any bases significantly
retarded the reaction (entries 5 and 6). Ag2CO3 was less
effective than Ag2O in the present reaction system (entry 7),
and no coupling product was obtained with Cu(OAc)2·H2O
oxidant (entry 8). Replacement of the cationic Rh catalyst with
a chloride complex [Cp*RhCl2]2 resulted in a negligible
outcome (entry 9). Further improvement was achieved with
the increased amounts of the boron reagent and Ag2O to
furnish the desired compound in 90% isolated yield with
exclusive peri-selectivity (entry 10). This reaction could be
carried out on a subgram scale (entry 11). Although we tested
other boron reagents, PhB(OH)2 and PhB(pin) (pin =
pinacolato), they gave lower yields (entries 12 and 13). A
[Cp*RhCl2]2/AgSbF6 catalyst gave a lower yield (entry 14).
We next investigated the substrate scope with respect to the
boronates under the optimized conditions (Table 1, entry 10),
S
Scheme 1. Sulfur-Directed Direct C−H Functionalization
Received: November 17, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03675
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization Study for the Direct Arylation
Scheme 2. Substrate Scope for the Boron Reagents
b
yield
entry
PhB(OR)2
oxidant, additive
solvent
(%)
1
2
3
4
5
6
7
8
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
PhB(neo)
Ag2O
Ag2O
Ag2O
Ag2O
PhCF3
15
21
41
dioxane
diglyme
tAmOH
tAmOH
tAmOH
tAmOH
67
Ag2O, K2CO3 (1.0 equiv)
Ag2O, K3PO4 (1.0 equiv)
Ag2CO3
11
5
34
Cu(OAc)2·H2O (2.0 equiv) tAmOH
nd
c
9
Ag2O
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
tAmOH
trace
(90)
(71)
57
d
10
Ag2O (1.5 equiv)
Ag2O (1.5 equiv)
e
11
d
12
PhB(OH)2 Ag2O (1.5 equiv)
d
13
PhB(pin)
PhB(neo)
Ag2O (1.5 equiv)
Ag2O (1.5 equiv)
65
df
,
14
60
a
Reaction conditions: 1 (0.1 mmol), PhB(OR)2 (0.1 mmol),
[Cp*Rh(MeCN)3][SbF6]2 (4.0 mol %), and oxidant (0.1 mmol) in
b
solvent (1.0 mL). Yield was determined by GC analysis. Isolated
c
yield is in parentheses. [Cp*RhCl2]2 (2.0 mol %) was used instead of
d
[Cp*Rh(MeCN)3][SbF6]2. 0.2 mmol scale: 1.5 equiv of PhB(OR)2
a
Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), Ag2O (0.3
e
was used. 2.0 mmol scale: 1.5 equiv of PhB(neo) was used, and the
t
mmol), and [Cp*Rh(MeCN)3][SbF6]2 (4.0 mol %) in AmOH (2.0
f
reaction time was for 24 h. [Cp*RhCl2]2 (2.5 mol %) and AgSbF6
mL). nd = not detected.
(10 mol %) were used instead of [Cp*Rh(MeCN)3][SbF6]2.
Scheme 3. Double C−H Arylation
and the results are summarized in Scheme 2. Aryl boronic
esters bearing various functional groups at the para position,
involving alkyl (2b), alkoxy (2c), halogen (2d and 2e), ester
(2f), nitro (2g), and cyano (2h), were well tolerated under the
present catalytic conditions to afford the corresponding peri-
arylated products. The meta and ortho substituents did not
largely decrease the reaction efficiency (2i−k). Naphthyl and
phenanthryl groups were also successfully installed to give 3l−
n in good to high yields. Importantly, heteroaromatic
substrates were also applicable to the current transformation.
Benzo[b]thiophene-3-yl (2o) and thiophene-3-yl (2p) boro-
nates reacted smoothly. However, a significant drop of the
product yield was observed with either thiophene-2-yl
boronate (2r) or furan-3-yl boronate (2s). This is probably
due to their instability under the catalytic conditions, and the
pinacol esters gave higher yields for these substrates. Pyridine-
4-yl boronate was not a suitable substrate for the present
system (not shown).
Subsequently, double C−H arylation was tested (Scheme
3).12 Two aryl groups could be introduced to 9-(methylthio)-
anthracene (4) to give the corresponding products 5a and 5b,
although the yields were low to moderate. Both of the peri
positions were successfully arylated in case two SMe directing
groups present on the periphery of naphthalene ring (6 and 8),
producing the 1,4,5,8-tetrasubstituted naphthalenes with
different molecular connectivity (7 and 9).
With the series of coupling products in hand, we turned our
attention to the construction of various fused thia-heterocycles
through acid-mediated annulation (Scheme 4). The thioether
group was oxidized by reaction with m-CPBA, and the
resulting sulfoxides were sequentially treated with TfOH (Tf
= trifluoromethanesulfonyl) and pyridine. Cyclization incor-
porating the installed aryl fragments proceeded smoothly to
afford the corresponding benzo[kl]thioxanthenes 10−12 in
high yields. This method could also be applied to the
construction of benzo-fused dithiapyrene derivatives 13 and
14 via the 2-fold C−S annulation. In the cyclic voltammetry
B
DOI: 10.1021/acs.orglett.8b03675
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Organic Letters
Letter
a
Scheme 4. Acid-Mediated Cyclization of Sulfoxides
Figure 2. Solid-state structure of 14 drawn with 40% thermal
probability. Hydrogen atoms are omitted for clarity. The values
indicate the transfer integral for each direction.
a
Isolated yields over two steps are shown.
transverse directions were rather small (T1−T4: 0.40−16.5
meV). In sharp contrast to the highly anisotropic nature of 13,
relatively large transfer integrals both in the stacking (P: 48.0
meV) and transverse directions (T1: 59.0 meV, T2: 47.2 meV)
were calculated for 14. Moreover, a relatively small
reorganization energy (λ: 185 meV) was given to 14.
As another example for the synthetic application of the
thioether directing group, we examined a catalytic trans-
formation of the SMe group on 3a (eq 1). Applying a nickel-
catalyzed cross-coupling reaction with Grignard reagent,16 the
4-methoxyphenyl group was introduced onto the naphthalene
ring to give an asymmetrically substituted 1,8-diarylnaphtha-
lene 15 in 47% yield. This type of compound has been used for
evaluating the through-space aromatic interaction.17
measurement of the doubly cyclized compounds 13 and 14,
both of them exhibited two oxidation peaks as expected,11a and
the HOMO levels were estimated to be −4.76 and −4.72 eV,
respectively (for details, see the Supporting Information).
Considering the potential application of dithiapyrene
derivatives as semiconductor materials,13 we also investigated
the solid-state structure of 13 and 14 by X-ray crystallography.
The 1,4-isomer 13 has a nonplanar shape where one sulfur
atom (S1 in Figure 1) is pointing in an out-of-plane direction
In conclusion, we have developed a rhodium-catalyzed direct
C−H arylation of naphthalene and anthracene derivatives
using a thioether directing group. The reaction system
exhibited broad functional group compatibility and exclusive
peri-selectivity. The coupling products were readily trans-
formed into the corresponding sulfur-containing poly
aromatics. Preliminary structural and computational studies
on the obtained dithiapyrene derivatives implied the unique
relationship between molecular connectivity and isotropic/
anisotropic charge-transport characteristics of them.
Figure 1. Solid-state structure of 13 drawn with 30% thermal
probability. Hydrogen atoms are omitted for clarity. The values
indicate the transfer integral for each direction.
with a torsion angle of 18.6° from the hydrocarbon body.
Weak π−π stacking (3.33−3.36 Å) and CH/π interactions are
presumably responsible for its packing structure (Figure 1c).
On the other hand, the 1,5-isomer 14 has a planar structure
and crystallizes into the well-ordered herringbone packing
mode (Figure 2). There exist two independent S···H short
interstack contacts whose distances are, respectively, 2.98 and
2.99 Å; however, no significant π−π or CH/π interactions are
observed. To estimate the charge-transport properties of these
compounds, we carried out computational studies using the
ADF (Amsterdam Density Functional package)14,15 program
for the atom coordinates obtained by the X-ray analyses. The
compound 13 showed a large transfer integral along the π-
stacking direction (P: 156 meV), whereas those of the
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b03675.
Detailed experimental procedures and computational
methods, product identification data, optical and
electrochemical measurements, ORTEP drawings, and
NMR spectra (PDF)
C
DOI: 10.1021/acs.orglett.8b03675
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Accession Codes
Letter
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CCDC 1877717 and 1877720−1877721 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: miura@chem.eng.osaka-u.ac.jp.
ORCID
(9) Selected examples: (a) Sirringhaus, H.; Friend, R. H.; Wang, C.;
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Masahiro Miura: 0000-0001-8288-6439
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by JSPS KAKENHI Grant No. JP
17H06092 (Grant-in-Aid for Specially Promoted Research) to
M.M.
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D
DOI: 10.1021/acs.orglett.8b03675
Org. Lett. XXXX, XXX, XXX−XXX