Synthesis of π-Extended Fluoranthenes via a KHMDS-Promoted Anionic-Radical Reaction Cascade

Article abstract of DOI:10.1021/acs.orglett.7b01538

An unprecedented KHMDS-promoted domino reaction to furnish hydroxyfluoranthenes is described. Biaryl compounds bearing acyl and naphthylalkenyl moieties are transformed into 9-hydroxydibenzo[j,l]fluoranthenes in a single step through the formation of an aromatic and a pentagonal ring system. A variety of fluoranthenes including those with extended π-conjugation, a heteroaromatic ring, and unsymmetrical substituents could be synthesized. Mechanistic studies reveal a unique reaction cascade where KHMDS acts as both a base and a single-electron donor.

Full text of DOI:10.1021/acs.orglett.7b01538

Letter
pubs.acs.org/OrgLett
Synthesis of π‑Extended Fluoranthenes via a KHMDS-Promoted
Anionic-Radical Reaction Cascade
Naoki Ogawa, Yousuke Yamaoka, Ken-ichi Yamada,† and Kiyosei Takasu*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
S
* Supporting Information
ABSTRACT: An unprecedented KHMDS-promoted domino
reaction to furnish hydroxyfluoranthenes is described. Biaryl
compounds bearing acyl and naphthylalkenyl moieties are
transformed into 9-hydroxydibenzo[j,l]fluoranthenes in a single
step through the formation of an aromatic and a pentagonal
ring system. A variety of fluoranthenes including those with
extended π-conjugation, a heteroaromatic ring, and unsym-
metrical substituents could be synthesized. Mechanistic studies reveal a unique reaction cascade where KHMDS acts as both a
base and a single-electron donor.
diverse range of polycyclic aromatic hydrocarbons
(PAHs) have been developed and are widely applied to
Scheme 1. KHMDS-Promoted (2 + 2)-Cycloaddition and
Acid-Promoted Ring-Opening Reaction
A
organic materials. In recent years, nonalternant hydrocarbons,
which possess nonhexagonal ring systems, such as pentagon
and/or heptagon, have attracted considerable attention owing
to their unique structural, optical, and electrochemical features.1
The fluoranthenes, whose skeleton features naphthalene and
benzene rings are connected by a five-membered ring, display
interesting properties such as large Stokes shifts and resistance
to air-quenching.2 Therefore, their framework is widely used in
organic materials such as luminescent twisted nanowires,
OLEDs, and OFETs.3 The common strategies to synthesize
fluoranthenes are based on Diels−Alder reactions4 or cross-
coupling reactions.5 However, it is still desirable to develop
facile and flexible methods for the preparation of unsymmetri-
cally functionalized and/or π-extended fluoranthenes.6 We
envisioned that such compounds are of interest because the
properties of fluoranthenes can be modified by introducing
substituents or π-extended systems.7 Herein, we report a novel
synthetic method for unsymmetrical hydroxyfluoranthenes with
extended π-conjugation in which an aromatic and pentagonal
ring system is formed in one step from biaryl compounds.
Mechanistic investigations suggest that potassium hexamethyl-
disilazide (KHMDS) acts as both a base and a single-electron
donor in one reaction to enable this unique transformation. In
addition, further transformation of the so-formed hydroxy-
fluoranthenes based on the recombination of the π-system are
described.
1a possessing a 1-(2-alkoxynaphthyl)vinyl moiety in the
presence of KHMDS did not give the expected cyclobutanol
5a, but instead the heptacycles 2a and 3a were obtained in 74%
and 11% yields, respectively (Scheme 2). Gratifyingly when 3a
was heated to reflux in diglyme (bp 162 °C), a retro (2 + 2)-
cycloaddition occurred and 9-hydroxydibenzo[j,l]fluoranthene
(4a) was obtained in 60% yield. The structures of 2a, 3a, and
4a were unambiguously determined by X-ray crystallographic
studies. Compound 2a has a propellane structure connected
with naphthofuran, phenanthrene, and cyclobutane rings.
Compound 3a also has a propellane framework but fused
with a 2-hydroxynaphthalene instead of naphthofuran. Com-
pound 4a, obtained by removal of an isobutylene unit from 3a,
possesses a highly planar skeleton.
The reaction conditions giving 2a, 3a, and 4a from biaryl 1a
were explored in detail (Table 1). When the reaction of 1a with
KHMDS (5 equiv) was conducted at room temperature, the
starting biaryl 1a was fully consumed within 0.5 h and only 2a
was obtained in 79% yield (Table 1, entry 1).
Compound 3a was produced when the reaction was
conducted at reflux in diglyme. The yield of 3a increased
with prolonged reaction time, suggesting that 3a was formed
from 2a by recombination of the C−O bond as a C−C bond
(Table 1, entries 2 and 3). Considering that fluoranthene 4a
was obtained by heating 3a (Scheme 2), 4a could be obtained
We previously reported a base-promoted (2 + 2)-cyclo-
addition of biaryls possessing acyl and vinyl groups at the 2 and
2′ positions, respectively, to form areno-fused cyclobutanols
and acid-promoted rearrangement of these cyclobutanols to
provide PAHs (Scheme 1).8 The polyaromatic framework and
the substituents can be prepared by retrosynthetically designing
biaryl substrates.
During the course of our study, we found an interesting
transformation reaction giving fluoranthenes. The reaction of
Received: May 20, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01538
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Letter
a
Scheme 2. Formation of 2a, 3a, and 4a and Their
Crystallographic Structures
Scheme 3. Scope of the Reaction
a
Reaction conditions: 1 (0.05 mmol), KHMDS (3 equiv) and cis-1,2-
cyclohexanediol (20 mol %) in diglyme (2 mL). Isolated yields in
b
c
d
parentheses. R = MOM. R = Me. For 36 h.
Table 1. Optimization of Reaction Conditions for the
a
Synthesis of 2a, 3a, and 4a from 1a
and 4g in good yields. Notably, both the methyl and
methoxymethyl (MOM) groups could be used as an ether
substituent (R) on the ArC ring in the fluoranthene synthesis.
This domino reaction could also be extended to double
fluoranthene formation for constructing further extended π-
systems (Scheme 4). The reaction of terphenyl 1h, bearing two
sets of acyl and alkenyl moieties, proceeded smoothly to give
the bisfluoranthene 4h in 72% yield.
b
yield (%)
entry
base
temp
time (h)
2a
3a
4a
1
2
3
4
5
6
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
LiHMDS
rt
0.5
0.17
1
79
74
34
0
0
11
46
0
0
0
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
<5
69
69
73
0
24
c
c
24
0
0
,
d
c
24
0
0
Scheme 4. Double Fluoranthene Formation
e
c
7
24
94
75
23
0
e
8
e
NaHMDS
24
0
0
c
9
KOtBu
24
0
36
a
Reactions were performed with 1a (0.050 mmol) and base (5 equiv)
b
c
in diglyme (2 mL). Isolated yields except for entries 7−9. 3 equiv of
base were used. cis-1,2-Cyclohexanediol (20 mol %) was added as an
additive. Yields were determined by H NMR.
d
e
1
directly from 1a by prolonged reaction time. Thus, the reaction
time was extended to 24 h, providing 4a in 69% yield (Table 1,
entry 4). The yield of 4a was maintained while the amount of
KHMDS was reduced to 3 equiv (Table 1, entry 5). Addition of
cis-1,2-cyclohexanediol9 (20 mol %) slightly improved the yield
of 4a (Table 1, entry 6, vide infra). The countercation of the
base was found to play an important role in the reaction.
Neither LiHMDS nor NaHMDS afforded the desired product
4a, and only 2a was formed (Tabel 1, entries 7 and 8). When
KOtBu was used, the yields of 4a decreased (Table 1, entry 9).
With the optimized conditions for producing fluoranthene 4a
in hand, we explored the scope of the reaction (Scheme 3).
Methoxy substituents on the benzene (ArA) ring were tolerated,
giving fluoranthenes 4b in good yield. Derivative 4c, bearing a
methoxy group at the naphthalene (ArC) ring, was also
obtained but in moderate yield. The incorporation of a
heteroaryl ring was also compatible with our method, yielding
thiophene-containing fluoranthene 4d in 41% yield. The π-
system of the aromatic (ArA, ArB, and ArC) rings in 1 could be
extended to produce the unsymmetrical fluoranthenes 4e, 4f,
To gain insight into the reaction mechanism, several
analogous reactions were attempted. When 1i bearing a
benzene ring instead of a naphthalene ring (ArC) was treated
with KHMDS at room temperature, only the cycloadduct 5i
was obtained in 95% yield (Scheme 5; compare with Table 1,
entry 1, for 1a). When the reaction temperature was raised to
80 °C, 5i was transformed into benzofuran 2i (61%). These
Scheme 5. Isolation of (2 + 2)-Cycloadduct 5i
B
DOI: 10.1021/acs.orglett.7b01538
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Letter
results contrasted with the reactivity of 1a and 2a and suggested
that 2a was also formed from the corresponding cyclobutanol
5a. Additionally, the observation that the formation of furan 2i
required a higher reaction temperature than that of 2a suggests
that an SNAr reaction leads to formation of the C−O bond of
the furan ring. In this step, the alkoxide ion of 5a attacks the
ipso-carbon of the aryl (ArC) ether moiety.10
Considering that 2a has no acidic protons, it can be assumed
that KHMDS does not behave simply as a base in the
reaction.11 In fact, when a radical inhibitor was added, the
formation of 2a occurred smoothly, but conversion of 2a into
3a was interrupted. This result indicates that radical species
were involved in this process (Scheme 6, eq 1). Recently, it has
formation of radical anions.9,13 In our reaction, cis-1,2-
cyclohexanediol was also found to improve the yield of 3a by
increasing the rate of reaction (Scheme 6, eq 2). This result also
suggests that similar SET processes were involved in the
reaction. It has been demonstrated that reductive C−O bond
cleavage of naphthyl trityl ether (6) occurs in the presence of
KHMDS to give 2-naphthol (7) along with triphenylmethane
in 82% and 73% yields, respectively (Scheme 6, eq 3).
On the basis of these observations, we propose a reaction
mechanism where KHMDS acts both as a base and a single-
electron donor (Scheme 7). To the best of our knowledge, this
is the first report that shows KHMDS operating as an efficient
single-electron donor. First, a base-promoted (2 + 2)-
cycloaddition of biaryl 1a gives cyclobutanol 5a. The
intermediate 5a undergoes intramolecular nucleophilic aro-
matic substitution to give 2a. SET from KHMDS to 2a occurs
at high temperature to form radical anion I, which then
undergoes C−O bond cleavage,14 and the resulting tertiary
radical II attacks the aromatic ring to form III. Deprotonation
and SET to remaining 2a leads to formation of 3a. Finally, a
retro (2 + 2)-cycloaddition gives fluoranthene 4a. The
mechanism of the retro (2 + 2)-cycloaddition is still under
investigation, but homolytic cleavage of the C−C bond in the
cyclobutane ring is likely involved in this process.
Scheme 6. SET Pathway in the Recombination Process
Finally, we investigated the transformations of resulting
fluoranthenes. Compound 4a could readily be transformed into
its derivatives by coupling reactions after the hydroxy group at
the 9-position was transformed into the triflate (Scheme 8).
Scheme 8. Transformations of 4a
been shown that single-electron-transfer (SET) from organic
bases to aromatic rings occurs, and the resulting radical anion
species may undergo various radical reactions.9,12 In these cases,
various organic additives have been reported to accelerate the
Scheme 7. Proposed Mechanism for Formation of 9-Hydroxydibenzo[j,l]fluoranthene 4a
C
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Letter
R.; Beljonne, D.; Schollmeyer, D.; Feng, X.; Mullen, K. J. Am. Chem.
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(2) (a) Berlman, I. B.; Wirth, H. O.; Steingraber, O. J. J. Am. Chem.
̈
Reduction, cyanation, and arylation of 8 proceeded smoothly to
furnish the corresponding products 9, 10, and 11, respectively,
in high yields. Interestingly, the fluorescence spectra of these
fluoranthenes was found to be significantly affected by the
substituents at 9-position. While 4a exhibits green fluorescence
(λem = 533 nm), 11 showed orange fluorescence (λem = 591
nm). These results demonstrate the utility of our methods for
designing new dibenzofluoranthene-based materials.
In summary, we have developed a novel KHMDS-promoted
domino reaction. In this process, biaryl compounds can be
converted into hydroxyfluoranthenes through the formation of
an aromatic and pentagonal ring system by simply heating a
precursor in the presence of KHMDS. A variety of
fluoranthenes including those with extended π-conjugation,
and heteroaromatic and unsymmetrical targets could be
prepared. Mechanistic studies revealed two roles of KHMDS
as both a base and a single-electron donor in the reaction. In
addition, further modifications of optical properties of resulting
fluoranthenes were demonstrated.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b01538.
■
S
(10) Since the rate of SNAr reaction is generally governed by the
resonance stability of the aromatic ring, the lower reaction rate of 1b
compared to 1a is reasonable. For examples of SNAr reactions of
nonactivated aromatic rings, see: (a) Ong, D. Y.; Tejo, C.; Xu, K.;
Hirao, H.; Chiba, S. Angew. Chem., Int. Ed. 2017, 56, 1840.
(b) Neumann, C. N.; Hooker, J. M.; Ritter, T. Nature 2016, 534, 369.
(11) To note, no transformation of 2a into 3a proceeds in the
absence of KHMDS.
(12) (a) Liu, W.; Cao, H.; Zhang, H.; Zhang, H.; Chung, K. H.; He,
C.; Wang, H.; Kwong, F. Y.; Lei, A. J. Am. Chem. Soc. 2010, 132,
16737. (b) Shirakawa, E.; Itoh, K.; Higashino, T.; Hayashi, T. J. Am.
Chem. Soc. 2010, 132, 15537. (c) Cuthbertson, J.; Gray, V. J.; Wilden,
J. D. Chem. Commun. 2014, 50, 2575. (d) Zhang, L.; Jiao, L. J. Am.
Chem. Soc. 2017, 139, 607.
Supplementary figures, experimental procedures, charac-
1
terization data, and H and 13C NMR spectra (PDF)
Crystallographic data for compound 2a (CIF)
Crystallographic data for compound 3a (CIF)
Crystallographic data for compound 4a (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: kay-t@pharm.kyoto-u.ac.jp.
ORCID
Kiyosei Takasu: 0000-0002-1798-7919
(13) Zhang, L.; Yang, H.; Jiao, L. J. Am. Chem. Soc. 2016, 138, 7151.
(14) SET induced reductive dealkylation of anisols by alkali metal is
reported: Azzena, U.; Denurra, T.; Melloni, G. J. Org. Chem. 1992, 57,
1444.
Present Address
†(K.Y.) Graduate School of Pharmaceutical Sciences, Tokush-
ima University, Shomachi, Tokushima 770-8505, Japan.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Professor Kazunori Tsubaki (Kyoto Prefectural
University) for the valuable discussion. This work was
supported by JSPS KAKENHI Grant No. JP 16H05073,
MEXT KAKENHI Grant No. JP16H01147 in Middle
Molecular Strategy, and AMED Platform for Drug Discovery,
Informatics, and Structural Life Science.
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DOI: 10.1021/acs.orglett.7b01538
Org. Lett. XXXX, XXX, XXX−XXX