Construction of Bisbenzofuro[2,3-b:3′,2′-e]pyridines by Palladium-Catalyzed Double Intramolecular Oxidative C-H/C-H Coupling

Article abstract of DOI:10.1021/acs.orglett.7b00323

The palladium-catalyzed intramolecular oxidative C-H/C-H coupling of 2-aryloxypyridines as challenging substrates is investigated to construct an important class of N,O-mixed heteroacenes, i.e. benzofuropyridines. It is found that 2,6-diaryloxypyridines e

Full text of DOI:10.1021/acs.orglett.7b00323

Letter
pubs.acs.org/OrgLett
Construction of Bisbenzofuro[2,3‑b:3′,2′‑e]pyridines by Palladium-
Catalyzed Double Intramolecular Oxidative C−H/C−H Coupling
Hiroyuki Kaida,† Tsuyoshi Goya,‡ Yuji Nishii,§ Koji Hirano,† Tetsuya Satoh,†,∥
and Masahiro Miura*,†
†Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
‡Advanced Materials Research Center, Nippon Shokubai Co. Ltd., 5-8 Nishi Otabi-cho, Suita, Osaka 564-8512, Japan
§Frontier Research Base for Global Young Researchers, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871,
Japan
∥Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585,
Japan
S
* Supporting Information
ABSTRACT: The palladium-catalyzed intramolecular oxidative C−H/C−H coupling
of 2-aryloxypyridines as challenging substrates is investigated to construct an important
class of N,O-mixed heteroacenes, i.e. benzofuropyridines. It is found that 2,6-
diaryloxypyridines efficiently undergo double cyclization to provide bisbenzofuro[2,3-
b:3′,2′-e]pyridines of interest in materials chemistry.
olycondensed heteroacenes are increasingly important as
organic functional materials. Besides the well-established
eq 1): They appear to be particularly challenging substrates
bearing an electron-deficient pyridine moiety with coordinating
ability, while the starting ethers are readily available by
conventional substitution reactions of 2-halopyridines with
phenols and the cyclized products may be of potential utility.5,6
We herein report that 2,6-diphenoxypyridines efficiently
undergo double cyclization under palladium catalysis to provide
five-ring-condensed bisbenzofuro[2,3-b:3′,2′-e]pyridines, which
are of interest in the area of materials chemistry.6 In addition,
cardinal optoelectronic properties of the N,O-mixed hetero-
acene core are also described.
When 2,6-diphenoxypyridine (1a, 0.2 mmol) was treated
with 3.0 mol % of Pd(TFA)2 (TFA = trifluoroacetate) and 4.0
equiv of AgOAc in PivOH (pivalic acid) at 150 °C for 6 h, the
corresponding doubly cyclized bisbenzofuropyridine 2a was
successfully obtained in 61% yield (73% yield with 10 mol % of
Pd in a 1.0 mmol scale) (Table 1). Similarly, 4,4′-dimethyl-,
dipropyl-, diisopropyl-, and di-tert-butyl-substituted 2,6-
diphenoxypyridines 1b−1e gave bisbenzofuropyridines 2b−
2e. The electron-donating methoxy-substituted 1f was trans-
formed to 2f, albeit in a lower yield. It was of considerable
interest that the substitution of electron-withdrawing trifluor-
omethyl did not hamper the cyclization and bisbenzofuro-
pyridine 2g was obtained in a good yield. 3,3′- or 2,2′-Dimethyl
and 3,3′- or 2,2′-di-tert-butyl-substituted 1h−1k also cyclized to
furnish 2h−2k. It is worth noting that the reactions of 1h and
1i took place only at the less hindered 6-position.
P
benzothiophene-fused series of thienoacenes,1 benzofuran-
fused polyaromatic compounds2 and O,X-mixed heteroacenes
(X = S, N, P, etc.) such as benzofuro[3,2,b]benzothiophenes,3
-indoles,4 and -benzophospholes4 are also attracting attention
since they show intriguing photophysical and electrochemical
properties. On the other hand, benzofuropyridines are of
substantial interest owing to their significant biological
activities5 as well as physical properties.6 Among various
methods for constructing the multiring systems, the palladium-
catalyzed intramolecular cross-coupling of aryl heteroaryl ethers
is promising. In particular, the oxidative C−H/C−H coupling
appears to be potentially useful because of its simplicity and
atom-economic nature (eq 1).7
In the context of our continuous studies of direct C−H
functionalization chemistry, we recently reported that 3-
aryloxy-thiophenes and -benzothiophenes effectively undergo
palladium-catalyzed oxidative cyclization in the presence of a
silver salt as the terminal oxidant to furnish the corresponding
benzofuro[3,2-b]thiophenes (Het = 3-thienyl in eq 1).8
A
similar transformation was independently reported by Kanai
and Kuninobu.9 Under the palladium catalysis, the double and
triple cyclization reactions of diaryloxy- and triaryloxy-benzenes
to give rise to benzobis- and benzotris-benzofurans could
effectively be performed.10 We were then interested in the
oxidative cyclization of 2-aryloxypyridines (Het = 2-pyridyl in
Next, we examined the synthesis of unsymmetrically
substituted bisbenzofuropyridines (Table 2). To gain the
Received: January 30, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00323
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Letter
solubility of products, substrates 3a−3j bearing a 4-tert-butyl
group were employed. Benzyl, phenyl, chloro, benzoyl, and
nitro groups as well as methyl and methoxy groups were
tolerable to afford 4a−4i in good yield. 1-Naphthyloxy-
substituted 3j selectively gave six-ring-condensed compound
4j. The reactive functional groups in 4 may be further
manipulated to afford divergent derivatives. As an example, 4f
was subjected to the Suzuki−Miyaura coupling with 4-
pyridylboronic acid to lead to compound 5 in 81% yield (eq 2).
Table 1. Double Cyclization of 2,6-Diaryloxypyridines 1a−
a
1k
a
Reaction conditions: 1 (0.20 mmol), Pd(TFA)2 (0.006 mmol, 3 mol
%), and AgOAc (0.8 mmol, 4 equiv) in PivOH (2 mL) in a 10 mL
b
c
Schlenk tube at 150 °C for 6 h under air. Isolated yield. 1 (1.0
mmol), Pd(TFA)2 (0.1 mmol, 10 mol %), and AgOAc (4.0 mmol, 4
equiv) in PivOH (10 mL) in a 50 mL Schlenk tube at 150 °C for 6 h
under air.
Table 2. Double Cyclization of Unsymmetrically Substituted
a
2,6-Diaryloxypyridines 3a−3j
The reaction of simple 2-phenoxypyridine itself unfortu-
nately did not occur under the present conditions, and only the
substrate was recovered. However, 2-(4-tert-butylphenoxy)-
quinoline (6) underwent cyclization to produce benzofuro-
quinoline 7 in 44% yield (eq 3). 2,6-Bis(6-tert-butyl-2-
pyridinyloxy)toluene (8) could be transformed to compound
9 in 44% yield (eq 4), while only less than 10% of product was
formed from the 6-methyl-2-pyridinyloxy analog of 8 (not
shown). These results may imply that a sterically demanding
circumstance around the pyridyl nitrogen is required for the
reaction to proceed smoothly.11
Though the detailed mechanism of the present reaction is
not definitive at this stage, the cyclization may be considered to
occur through palladation on the phenyl ring followed by that
on the pyridyl ring (or its reverse order) to form a six-
membered palladacycle and the subsequent reductive elimi-
nation leads to the product. The precedence of the initial
palladation would depend on the substituent of the phenyl ring.
It should be noted that the reaction of 1e in acetic acid-d4/
a
Reaction conditions: 3 (0.20 mmol), Pd(TFA)2 (0.006 mmol, 3 mol
%), and AgOAc (0.8 mmol, 4 equiv) in PivOH (2 mL) in a 10 mL
Schlenk tube at 150 °C for 6 h under air. Isolated yield.
b
B
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pivalic acid (1:1, v/v) at 130 °C for 3 h gave the monocyclized
product 2e′ and 2e in 38% and 26% yields, respectively, with
recovery of 1e (23%) (eq 5). No incorporation of deuterium
was observed in 1e and 2e′. This suggests that the metalation
step via C−H cleavage is not reversible, which contrasted the
fact that, in the relevant reaction of 1,3,5-tris(4-tert-butyl-
phenyloxyl)benzene, significant amounts of deuterium were
introduced into the central benzene ring of the starting material
and the intermediary mono- and dicyclized products (ca. 50%
D in each central-ring hydrogen, not shown).
HOMO/LUMO energy gap and a relatively high ET value,
which may meet requirements in the application to OLED
devise materials.12,13 The X-ray crystal analysis of 2e showed
that it has a planar structure as expected (Figure 3a). One of
The synthesis of 2a and some of its derivatives as candidates
of electroluminescent and semiconducting materials was
previously described using a sequence of Suzuki−Miyaura
coupling/diazonium substitution starting from 2,6-diamino-3,5-
diiodopyridine in the patent literature.6 However, no
spectroscopic and electrochemical data were given. Con-
sequently, to provide a basic set of information about
optelectronic properties of the bisbenzofuro[2,3-b:3′,2′-e]-
pyridine core, we first measured the absorption and emission
spectra of 4,4′-di-tert-butyl-substituted 2e having substantial
solubility as the representative compound (Figure 1). The UV/
Figure 3. X-ray structure of 2e (a) and HOMO and LUMO of 2a
calculated at B3LYP/6-31G(d) level of theory (b).
the major reasons for the wide HOMO/LUMO energy gap is
the unique orbital distributions in the HOMO and LUMO: the
HOMO has a node without participation of the central
perpendicular p orbitals of N and C atoms, while those of the
two oxygen atoms are not involved in the LUMO (Figure 3b).
In summary, we have developed an effective method for the
flexible construction of N,O-mixed heteroacenes such as
bisbenzofuro[2,3-b:3′,2′-e]pyridine derivatives by means of
double intramolecular oxidative C−H/C−H coupling. The
condensed five-ring system appears to be a useful core of
organic materials such as OLED components, and fine-tuning
of the physical properties by the new synthetic method and the
construction of related mixed heteroacene systems are
underway in our laboratories.
Figure 1. Normalized absorption (left, 1.0 × 10−5 M, CHCl3),
fluorescence (center, 1.0 × 10−6 M, CHCl3), and phosphorescence
spectra (right, 1.0 × 10−4 M, CHCl3/EtOH 1:4 v/v at 77 K) spectra of
2e.
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.7b00323.
vis spectrum of 2e showed intense peaks at 340 and 347 nm,
and its fluorescence spectrum showed a band with a maximum
at 360 nm (CHCl3, ΦF = 0.70), indicating a relatively small
Stokes shift. Interestingly, the phosphorescence spectrum (77
K, CHCl3−EtOH 1:4 v/v) showed a strong peak at 431 nm.
The cyclic voltammogram of 2e indicated its ambipolar
character showing both oxidation and reduction peaks (Figure
2). Based on these data, EHOMO (EOX in CV), Eg (UV/vis), and
ET (phosphorescence spectrum) of 2e were estimated to be
−6.11, 3.44, and 2.88 eV, respectively, indicating a wide
1H and 13C{1H} spectra for products (PDF)
Crystallographic data for 2e (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: miura@chem.eng.osaka-u.ac.jp.
ORCID
Koji Hirano: 0000-0001-9752-1985
Tetsuya Satoh: 0000-0002-1792-140X
Masahiro Miura: 0000-0001-8288-6439
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported, in part, by JSPS KAKENHI Grant
Number JP 24225002 (Grant-in-Aid for Scientific Research
(S)) to M.M. and JSPS KAKENHI Grant Number
JP16H01037 (in Precisely Designed Catalysts with Customized
Scaffolding) and JST (ACT-C), Japan to T.S.
Figure 2. Cyclic voltammogram of 2e in o-dichlorobenzene/
acetonitrile (10:1, v/v) containing 0.1 M Bu4NPF6 at a scan rate of
100 mV s−1.
C
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Letter
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