A new organic two-electron oxidant: 9,10-diaryl-9,10-dihydroanthracene-9, 10-bis(ylium)

Article abstract of DOI:10.1002/asia.201300710

Strong as an Ox: A dicationic compound with a 9,10-dihydroanthracene skeleton has been produced from the corresponding 9,10-dialkoxy-9,10- dihydroanthracene, which was readily prepared from anthraquinone. The dication functions as a powerful two-electron oxidant, comparable to aminium cation radicals, and has been employed in oxidative processes such as the self-coupling of anilines and naphthols, and oxidative deprotection of p-methoxybenzyl (PMB) ethers. Copyright

Full text of DOI:10.1002/asia.201300710

COMMUNICATION
COMMUNICATION
Oxidation
Junji Ichikawa,* Hiroyuki Tanabe,
Suguru Yoshida, Takaharu Kawai,
Masahiko Shinjo,
Takeshi Fujita
&&&& — &&&&
A New Organic Two-Electron
Oxidant: 9,10-Diaryl-9,10-dihydroan-
thracene-9,10-bisACTHUNRGTNEUNG(ylium)
Strong as an Ox: A dicationic com-
pound with a 9,10-dihydroanthracene
skeleton has been produced from the
corresponding 9,10-dialkoxy-9,10-dihy-
droanthracene, which was readily pre-
pared from anthraquinone. The dicat-
ion functions as a powerful two-elec-
tron oxidant, comparable to aminium
cation radicals, and has been employed
in oxidative processes such as the self-
coupling of anilines and naphthols, and
oxidative deprotection of p-methoxy-
benzy (PMB) ethers.
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Junji Ichikawa et al.
DOI: 10.1002/asia.201300710
A New Organic Two-Electron Oxidant: 9,10-Diaryl-9,10-dihydroanthracene-
9,10-bis(ylium)
AHCTUNGTRENNUNG
Junji Ichikawa,*[a] Hiroyuki Tanabe,[a] Suguru Yoshida,[b] Takaharu Kawai,[b]
Masahiko Shinjo,[a] and Takeshi Fujita[a]
Dedicated to Professor Teruaki Mukaiyama in celebration of the 40th anniversary of the Mukaiyama aldol reaction
Oxidations are important reactions in organic synthesis as
well as in biological processes. Most oxidation reactions are
conducted with inorganic compounds of heavy metals such
as PbIV, MnIV, CeIV, CrVI, MoVI; however, the toxicity associ-
ated with some metal oxidants has limited their appeal.[1] In
this context, organic oxidants are quite attractive reagents,
but only a few are commonly used, such as 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ),[2] phenyliodonium bis-
(trifluoroacetate) (PIFA),[3] and triarylaminium cation radi-
cals.[4] Among these reagents, triarylaminium radicals are
valuable and highly powerful oxidants (Eox =0.67–1.36 V),
although they have some drawbacks. For example, through
their function as an oxidizing agent, aminium cation radicals
are transformed into the corresponding amines, which have
the potential to initiate side reactions.
Recently, we have reported that naphthalene-1,8-diylbis-
(diphenylmethylium) A (Figure 1)[5] can serve as an organic
electron-transfer oxidant, offering potentially useful synthet-
ic applications.[6] Although dication A is suitable for the oxi-
dation of aniline derivatives, it is not strong enough to oxi-
dize compounds such as phenol derivatives. Thus, it is highly
desirable to develop related dication reagents with stronger
oxidizing properties. In this study, we report a convenient
method for the preparation of 9,10-bis(4-methoxyphenyl)-
Figure 1. First- and second-generation bis(triarylmethylium)s.
9,10-dihydroanthracene-9,10-bisACTHNUGTRNEUNG(ylium) trifluoromethanesul-
fonate (1a), a second-generation dication, and its potential
as a powerful new organic two-electron oxidant.
We designed a new dication, 9,10-diaryl-9,10-dihydroan-
thracene-9,10-bisACTHNUTRGNEUNG(ylium) (B; Figure 1), which is readily ac-
cessible from a commercial source, to improve the oxidizing
properties of related species. In dications B, two cationic
centers were fixed in a cyclohexa-1,4-diene ring that was ex-
pected to significantly enhance the oxidizing properties of
these systems. Dications B readily accepts two electrons,
and transforms into 9,10-diarylanthracenes C through aro-
matization of the central six-membered ring, thereby gaining
thermodynamic stability [Eq. (1)]. Anthracene C, the re-
duced form of B, should not affect the oxidation reaction
because of its overall stability. With these considerations in
mind, we envisioned that dication B would work as strong
and useful oxidant.
[a] Prof. Dr. J. Ichikawa, Dr. H. Tanabe, M. Shinjo, Dr. T. Fujita
Division of Chemistry
Faculty of Pure and Applied Sciences
University of Tsukuba
Tsukuba, Ibaraki 305-8571 (Japan)
Fax : (+81)29-853-4237
E-mail: junji@chem.tsukuba.ac.jp
[b] Dr. S. Yoshida,+ T. Kawai
Our plan for the preparation of dication 1a involved deal-
koxylation of diether 4 by silylation of the oxygen atoms,
starting from commercially available anthraquinone. This
route would allow the generation of dication 1a under anhy-
drous conditions without the formation of any acid
(Scheme 1).[6,7] Diether 4, the precursor of dication 1a, was
readily synthesized from 9,10-anthraquinone in a high yield
by a two-step sequence consisting of arylation and etherifi-
cation.
Department of Chemistry
Graduate School of Science
The University of Tokyo
Hongo, Bunkyo-ku 113-0033 (Japan)
[+] Present Address:
Laboratory of Bioscience
Institute of Biomaterials and Bioengineering
Tokyo Medical and Dental University
Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)
The color of the reaction mixture changed to dark red
upon treatment of diether 4 with Me3SiOTf in 1,1,1,3,3,3-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201300710.
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Junji Ichikawa et al.
To confirm that dication 1a and monocation 6 were in
equilibrium, we attempted an oxidation reaction using an
aliquot of the solution. When N,N-diethyl-3,5-dimethylani-
line 8 was treated with a small excess of the solution pre-
pared from 0.6 equivalents of 4 and 1.2 equivalents of
Me3SiOTf, the oxidation proceeded smoothly to give benzi-
dine 9 in 90% yield. Furthermore, diarylanthracene 2, the
reduced product of 1a, was isolated almost quantitatively
(Scheme 3). As this oxidative coupling reaction cannot be
Scheme 1. Synthetic route to dication 1a from anthraquinone.
hexafluoropropan-2-ol (HFIP);[6,8] this indicated the genera-
tion of triarylmethylium. Initially, we tried to isolate the tri-
flate salt of dication 1a from the reaction mixture, but failed
because of its high reactivity.[9] When this solution was
quenched with saturated aqueous NaHCO3, diol 3 and hy-
droxyether 5 were both obtained (Scheme 2).
Scheme 3. Oxidative self-coupling of aniline 8 with dication 1a.
Scheme 2. Generation and quenching of dication 1a.
effected by the trityl cation,[6b] it would follow that aniline 8
was not oxidized by monocation 6 but rather by dication 1a.
Thus, these results suggest that the dark-red solution defi-
nitely contained dication 1a as well as monocation 6 in equi-
librium, and that all of 4 was eventually transformed into di-
cation 1a, which acted as a two-electron oxidant.
To estimate the oxidizing ability of dication 1a, the elec-
trochemical behavior of diarylanthracene 2 was studied. The
cyclic voltammetry (CV) measurement of 2 was conducted
in the presence of tetrabutylammonium perchlorate as a sup-
porting electrolyte in CH2Cl2 at room temperature. The
cyclic voltammogram of 2 was consistent with a two-step
one-electron oxidation process. Reversible waves were ob-
served at E1/2 =0.68 V vs Fc/Fc+ that can be interpreted as
the first redox process of 2. The cyclic voltammogram of 2
also contained a set of quasi-reversible waves at Epa =1.00 V
and Epc ꢀ0.89 V vs. Fc/Fc+ (Figure 2a). The cathodic scan
showed the deactivation process of dication 1b into 2
The formation of alcohols 3 and 5 suggests that both di-
cation 1a and monocation 6 likely exist in the reaction mix-
ture. To gain more insight into the reactive species present
in the dark red solution, we treated it with ferrocene as
a one-electron reductant. The reaction proceeded smoothly
to give 9,10-diarylanthracene 2 in 95% yield [Eq. (2)]. The
almost quantitative formation of 2 from the mixture could
be interpreted in either of the following two ways: 1) Mono-
cation 6 reacted directly with ferrocene to yield 9,10-diary-
lanthracene 2, while dication 1a was not involved. 2) Both
cationic species 1a and 6 were in equilibrium in the solution.
As 1a was consumed, monocation 6 was converted into 1a,
which in turn was reduced by ferrocene to yield 2 through
anthracene radical cation 7a (see below). The first explana-
tion seems unlikely, judging from the lower formal oxidation
potential of the trityl monocation (triphenylmethylium;
E8’=À0.11 V vs. Fc/Fc+), compared to that of ferrocene.[1]
3
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Junji Ichikawa et al.
aromatic alcohols, respectively, were readily deprotected by
1a at 08C in only 5 min to afford the deprotected alcohols
13a–d in high to excellent yields (Table 1). However, 13a
was obtained in only 3% yield when the first-generation di-
cation A was employed instead of 1a.[14] PMB ether 12b was
smoothly cleaved by this method without racemization
(Table 1, entry 2).
Figure 2. a) Cyclic voltammogram and b) differential pulse voltammo-
gram of diarylanthrathene 2. Both measurements were performed in
CH2Cl2 with nBu4NClO4 as an electrolyte.
Table 1. Oxidative deprotection of PMB ethers 12a–d with 1a.
through radical cation 7b. Furthermore, the differential
pulse voltammetry (DPV) of 2 clearly showed two major
peaks at 0.67 V and 0.93 V (Figure 2b). The value of the
second peak, 0.93 V vs Fc/Fc+, is much higher than the
formal oxidation potential of trityl cation (E8’=À0.11 V vs
Fc/Fc+),[1] and even comparable to that of aminium radicals
(E8’=0.67–1.36 V vs Fc/Fc+),[1] which have been recognized
as the strongest organic oxidizing agents (Scheme 4).[10]
Entry
1
R
Yield [%][a]
98
13a
13b
2
92
3
4
13c
13d
91
79
[a] Yield of isolated product based on 1a.
Scheme 4. Electrochemical redox potentials of diarylanthracene
CH2Cl2 (vs Fc/Fc+).
2 in
Finally, we investigated the potential for recycling dication
1a. The process was accomplished by regeneration of dieth-
er 4, which is the precursor of dication 1a, from diarylan-
thracene 2, the reduced form of 1a. Diarylanthraene 2 was
oxidized with singlet oxygen to afford peroxide 14 in 97%
yield.[15] Peroxide 14 was then treated with palladium on
charcoal under an atmosphere of hydrogen to give diol 3 in
83% yield (Scheme 5); this was easily transformed into di-
ether 4 (Scheme 1). Thus, it was found that dication 1a can
be recycled and reused easily.
Because of the high oxidizing ability of 1a, we tried oxi-
dation reactions of phenol derivatives that did not proceed
with the first-generation dication A (see below). When
excess 2-naphthol (10) was treated with the HFIP solution
of 1a, generated from 0.25 equivalents of 4 and 0.55 equiva-
lents of Me3SiOTf, self-coupling proceeded to give binaph-
thol 11 in 73% yield [Eq. (3)],[11,12] whereas 11 was obtained
in only 4% yield when the first-generation dication A was
used.
Next, we attempted the oxidation of p-methoxybenzyl
ethers (PMB ethers) as phenol derivatives using dication 1a.
PMB ethers, widely used for the protection of hydroxy
groups in the syntheses of complex molecules,[13] are oxida-
tively cleaved to yield the corresponding alcohols by the aid
of dimethyl pyridine-2,6-dicarboxylate as a base. PMB
ethers 12a–d, derived from primary, secondary, tertiary, and
Scheme 5. Recycling of dication 1a through reoxidation of diarylanthra-
cene 2.
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Junji Ichikawa et al.
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In conclusion, we have developed a second-generation di-
cation 1a, which acts as an organic two-electron oxidant. Di-
cation 1a is readily prepared from diether 4 in HFIP and
can be regenerated from its reduced form 2. Preliminary
studies of the synthetic applications of 1a have been con-
ducted, including the self-coupling of anilines and naphthols
and the oxidative deprotection of PMB ethers.
Experimental Section
Me3SiOTf (85 mL, 0.47 mmol) was added to a solution of 4 (120 mg,
0.24 mmol) in 1,1,1,3,3,3-hexafluoropropan-2-ol (2.0 mL) at 08C. The so-
lution turned dark red and the mixture was stirred for 10 min. 3,5-Di-
methyl-N,N-diethylaniline (8, 70 mg, 0.40 mmol) was added to the reac-
tion mixture and the mixture was stirred for 1 h at the same temperature.
The reaction was quenched with water, and the organic layer was extract-
ed with CH2Cl2 three times. The combined extracts were washed with
brine and dried over Na2SO4. After removal of the solvent under reduced
pressure, the precipitate was filtered off and washed with CH2Cl2 to give
2 (86 mg, 94% based on 4) as a pale-yellow solid. After removal of the
solvent of the filtrate under reduced pressure, the resulting residue was
purified by preparative TLC (silica gel) to give N,N,N’,N’-tetraethyl-
[9] Dication 1a was NMR-silent in solution. This is probably due to the
prsence of an impurity with spin. The existence of radical species
was confirmed by ESR measurements (Figure S1, see the Supporting
Information). We speculate that a small amount of radical cation 7a
might be generated by electron transfer from the solvent to 1a.
Indeed, the gradual color change of the HFIP solution of 1a from
dark red into dark blue was observed within 1 h; this might be a con-
sequence of the reduction of 1a.
[10] A comparison between the relative oxidizing potential of a first-gen-
eration dication A and a second-generation dication B (Ar=4-me-
thoxyphenyl) can be made by comparing the oxidation process of
the corresponding reduced forms. The cyclic voltammogram of
1,1,2,2-tetraphenylacenaphthene, the reduced form of A, exhibited
irreversible one-step two-electron oxidation waves at Epa =1.10 V,
2,2’,6,6’-tetramethylbiphenyl-4,4’-diamine (9, 63 mg, 90%) as
a white
solid.
Experimental procedures for other reactions are described in the Sup-
porting Information.
E
pc =0.20 V vs Fc/Fc+ (Ref. [5]). Despite the electrochemical irre-
versibility of A, a rough approximation of its half-wave potential for
the oxidation process (E1/2) can be made by calculating the simple
average of its Epa and Epc. This estimation gives a value of E1/2
=
0.65 V vs Fc/Fc+, which is much lower than the second oxidation po-
Acknowledgements
tential of 2 (0.93 V vs Fc/Fc+).
We thank Prof. T. Nabeshima and Dr. S. Akine (University of Tsukuba)
for electrochemical analysis. We acknowledge the generous gift of
(CF3)2CHOH from Central Glass Co. This work is partly supported by
a Grant-in-Aid for Young Scientists (Start-up) from JSPS (23850005).
[11] Metal-mediated self-coupling has been applied to the synthesis of
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Keywords: dication · electron transfer · oxidation · self-
coupling · synthetic methods
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Received: May 25, 2013
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