Novel triarylimidazole redox catalysts: Synthesis, electrochemical properties, and applicability to electrooxidative C-H activation

Article abstract of DOI:10.1021/ol300195c

A new class of metal-free, easy to synthesize redox catalysts based on a triarylimidazole framework is described. With those synthesized thus far, one can access a potential range of ca. 410 mV. They proved to be useful mediators for the activation of benzylic C-H bonds under mild conditions.

Full text of DOI:10.1021/ol300195c

ORGANIC
LETTERS
2012
Vol. 14, No. 5
1314–1317
Novel Triarylimidazole Redox Catalysts:
Synthesis, Electrochemical Properties,
and Applicability to Electrooxidative
CꢀH Activation
Cheng-chu Zeng,*,† Ni-tao Zhang,† Chiu Marco Lam,‡ and R. Daniel Little*,‡
College of Life Science & Bioengineering, Beijing University of Technology,
Beijing 100124, China, and Department of Chemistry & Biochemistry, University of
California;Santa Barbara, Santa Barbara, California 93106, United States
zengcc@bjut.edu.cn; little@chem.ucsb.edu
Received January 24, 2012
ABSTRACT
A new class of metal-free, easy to synthesize redox catalysts based on a triarylimidazole framework is described. With those synthesized thus far,
one can access a potential range of ca. 410 mV. They proved to be useful mediators for the activation of benzylic CꢀH bonds under mild
conditions.
Electroorganic chemistry provides convenient access to
the chemistry of radical ions. Its unique ability to effect
charge reversal (umpolung) makes it possible to achieve
bond constructions that are otherwise very difficult to
accomplish.1 The transformations can be carried out either
directly or indirectly. In the former, the redox reaction of
interest occurs at the electrode, while the latter uses an
electron transfer mediator. When the mediator is oxidized
(or reduced) at the electrode, then it can serve as a
homogeneous electron transfer agent towardthe substrate.
Use of a mediator frequently means that the chemistry can
be carried out at a potential that is less than that needed for
the direct process. Mediators come in many varieties
including, for example, metal ions, organometallic com-
plexes, halides, and polycyclic aromatics.2
† Beijing University of Technology.
‡ University of California;Santa Barbara.
(1) For organoelectrochemical synthesis, see reviews: (a) Schafer,
€
H. J. C. R. Chimie 2011, 14, 745. (b) Yoshida, J.; Kataoka, K;
~
Horcajada, R.; Nagaki A. Chem. Rev. 2008, 108, 2265. (c) Dunach, E.;
Medeiros, M. J; Olivero, S. New J. Chem. 2006, 30, 1534. (d) Sperry,
J. B.; Wright, D. L. Chem. Soc. Rev. 2006, 35, 605. (e) Frontana-Uribe,
B. A.; Little, R. D.; Ibanez, J. G.; Palma, A.; Vasquez-Medrano, R.
Green Chem. 2010, 12, 2099. (f) Little, R. D.; Moeller, K. D. Electro-
chem. Soc. Interface 2002, 11, 36. For recent excellent examples of
organoelectrochemical synthesis, see: (g) Sperry, J. B.; Wright, D. L.
J. Am. Chem. Soc. 2005, 127, 8034. (h) Xu, H.; Moeller, K. D. J. Am.
Chem. Soc. 2008, 130, 13542. (i) Tang, F.; Moeller, K. D. J. Am. Chem.
Soc. 2007, 129, 12414. (j) Tajima, T.; Kurihara, H.; Fuchigami, T. J. Am.
Chem. Soc. 2007, 129, 6680. (k) Matsumoto, K.; Fujie, S.; Ueoka, K.;
Suga, S.; Yoshida, J.-I. Angew. Chem., Int. Ed. 2008, 47, 2506. (l)
Anderson, L. A.; Redden, A.; Moeller, K. D. Green. Chem. 2011, 13,
1652. (m) Tang, F.; Moeller, K. D. Tetrahedron 2009, 65, 10863. (n)
Madelaine, C.; Six, Y.; Buriez, O. Angew. Chem., Int. Ed. 2007, 46, 8046–
8049. (o) Ashikari, Y.; Nokami, T.; Yoshida, J. J. Am. Chem. Soc. 2011,
133, 11840.
Since Nelson and co-workers first demonstrated that
para-substituted triarylamines are electrochemically stable,3
these compounds have found applicability as photoconduc-
tors,4 light emitting devices,5 and in optical data storage.6
(2) For indirect electrolysis, see reviews: (a) Ogibin, Y. N.; Elinson,
M. N.; Nikishin, G. I. Russ. Chem. Rev. 2009, 78, 89. (b) Steckhan, E.
Angew. Chem., Int. Ed. Engl. 1986, 28, 683. (c) Steckhan, E. Top. Curr.
Chem. 1987, 142, 1.
(3) (a) Seo, E. T.; Nelson, R. F.; Fritsch, J. M.; Marcoux, L. S.;
Leedy, D. T.; Adams, R. N. J. Am. Chem. Soc. 1966, 88, 3498. (b)
Ambrose, J. F.; Carpenter, L. L.; Nelson, R. F. J. Electrochem. Soc.
1975, 122, 876.
r
10.1021/ol300195c
Published on Web 02/16/2012
2012 American Chemical Society

Triarylamines have also served as redox mediators for a
host of interesting transformations. For example, Steck-
han applied triarylamines to the deprotection of dithio-
acetals, the oxidation of alcohols and alkyl benzenes, and
so on.7 Fry and co-workers studied the anodic oxida-
tion of alkenes bearing one or more strongly electron-
withdrawing substituents.8 We have also performed the
triarylamine-mediated rearrangement of housanes and
have used the transformation as the key step in the total
synthesis of daucene.9
Despite the great success of triarylamines as redox
catalysts and in materials research, the synthesis of sub-
stituted frameworks can be problematic. Positional iso-
mers are frequently generated, and tedious chromatographic
separation may be required.10 Also, the low solubility of
nitro-substituted triarylamines in organic solvents restricts
their application.
Given these shortcomings, we sought to develop a new
class of organic redox catalysts subject to the conditions
that they be (a) easy to synthesize, (b) metal-free, and (c)
capable of providing access to a wide range of potentials.
In this manuscript we report that systems based on a
triarylimidazole framework fulfill these conditions and
demonstrate their applicability to the oxidation of methoxy-
substituted benzyl alcohols and benzyl ethers.
a mixture of benzils (1), aldehydes (2), methylamine, and
ammonium acetate in the presence of a catalytic amount
of sodium dihydrogen phosphate was heated to 150 °C
under solvent-free conditions. The reaction proceeds
smoothly to afford the desired triarylimidazoles in 85ꢀ92%
yield (see Supporting Information).
Cyclic voltammetry was performed first in order to
observe the electrochemical behavior of the aryl imida-
zoles. The cyclic voltammogram (CV) of triarylimidazole
3a exhibits three oxidation peaks at 1.26, 1.54, and 1.80 V
vs Ag/AgCl and one cathodic peak at 1.19 V when 0.1 M
LiClO4/CH3CN was usedas the supporting electrolyte (see
Supporting Information (SI)). We were pleased to discover
that the first oxidation peak and the reduction peak are
quasi-reversible with the current being slightly smaller
during the reduction scan. These observations indicate
that the initially formed cation radical is stable on the
CV time scale. Of additional interest is the fact that
following an initial decrease in current during the first
three scans, the system settles down and the curve remains
quasi-reversible; we have gone to 20 scans without obser-
ving a significant change (see SI). This behavior contrasts
sharply with that for triphenylamine since its aminium
cation radical is known to dimerize thereby leading to a
nonreversible redox couple. It is noteworthy that the
voltammogram is completely irreversible when the imida-
zole nitrogen is not alkylated (viz., NH vs NCH3); this is
reasonable since the cation radical ought to be strongly
acidic and capable of protonating the starting material.
Similar CV behaviors were also observed for N-methyl
substituted triarylimidazoles, 3bꢀ3e, and the results are
summarized in Table 1. Note that the Pox1 values can be
correlated with the electronegativity of the substituents,
viz., the more electron-donating the substituent(s), the
easier the substrate is to oxidize. Notice too that these five
systems allow access to a potential range of 410 mV;
compare, for example, structures 3c and 3e.
The synthetic route used to access the mediators is
shown in Table 1. Thus, by following a known procedure,11
Table 1. Synthesis and Peak Potentials of Imidazole Mediators
1
2
3
Pox
Pox
Pox
Pred
med.
Ar1
Ar2
(V)
(V)
(V)
(V)
We envisioned that, similar to substituted triarylamines,
our systems might be able to serve as redox catalysts. To
explore this hypothesis, the electrochemical behavior of
triarylimidazole 3a in the presence of p-methoxy benzyl
alcohol (4a) and an excess of lutidine was investigated. As
shown in Figure 1, the anodic peak current for 3a increases
slightly when an excess of 4a is present (compare curves a
and b). When lutidine is added, the anodic peak current for
3a increases dramatically while the cathodic peak current
disappears (curve c). Since the substrate (4a) and base are
not oxidizable at the potentials shown in Figure 1 (the peak
potential of p-methoxy benzyl alcohol and 2,6-lutidine are
1.52 and 1.89 V vs Ag/AgCl, respectively), the enhanced
anodic current results from its re-entering the catalytic
cycle in the manner illustrated in Scheme 1; it is referred to
as a “catalytic current”. These observations provide clear
evidence that the mediator serves as the hole carrier and
3a
3b
3c
3d
3e
p-BrPh
Ph
1.26
1.00
1.30
1.15
0.89
1.54
1.27
1.58
1.32
1.15
1.80
1.48
1.84
1.70
1.36
1.19
0.92
1.17
0.71
1.05
p-BrPh
p-MeO-Ph
p-BrPh
Ph
p-BrPh
p-MeO-Ph
p-MeO-Ph
p-MeO-Ph
(4) Stolka, M.; Yanus, J. F.; Pai, D. M. J. Phys. Chem. 1984, 88, 4707.
(5) Thomas, B.; David, C.; Muller, M. G.; Klaus, M.; Oskar, N.
Macromol. Rapid Commun. 2000, 21, 583.
(6) Moerner, W. E.; Silence, S. M. Chem. Rev. 1994, 94, 127.
(7) (a) Brinkhaus, K. G.; Steckhan, E.; Schmidt, W. Acta Chem.
Scand., Ser. B 1983, 37, 499. (b) Schmidt, W.; Steckhan, E. Angew.
Chem., Int. Ed. Engl. 1978, 17, 673. (c) Schmidt, W.; Steckhan, E. Angew.
Chem., Int. Ed. 1979, 18, 801. (d) Dapperheld, S.; Steckhan, E. Angew.
Chem., Int. Ed. Engl. 1982, 21, 780. (e) Platen, M.; Steckhan, E. Chem.
Ber. 1984, 117, 1679. (f) Haberl, U.; Steckhan, E.; Blechert, S.; Wiest, O.
Chem.;Eur. J. 1999, 5, 2859.
(8) (a) Wu, X.; Davis, A. P.; Lambert, P. C.; Steffen, L. K.; Toy, O.;
Fry, A. J. Tetrahedron 2009, 65, 2408. (b) Mayers, B. T.; Fry, A. J. Org.
Lett. 2006, 8, 411. (c) Wu, X.; Davis, A. P.; Fry, A. J. Org. Lett. 2007, 9,
5633.
(10) (a) Wu, X.; Dube, M. A.; Fry, A. J. Tetrahedron Lett. 2006, 47,
7667. (b) Lartia, R.; Allain, C.; Bordeau, G.; Schmidt, F.; Fiorini-
Debuisschert, C.; Charra, F.; Teulade-Fichou, M.-P. J. Org. Chem.
2008, 73, 1732.
(9) (a) Park, Y. S.; Wang, S. C.; Tantillo, D. J.; Little, R. D. J. Org.
Chem. 2007, 72, 4351. (b) Gerken, J. B.; Wang, S. C.; Preciado, A. B.;
Park, Y. S.; Nishiguchi, G.; Tantillo, D. J.; Little, R. D. J. Org. Chem.
2005, 70, 4598. (c) Park, Y. S.; Little, R. D. J. Org. Chem. 2008, 73, 6807.
(11) Karimi-Jaberi, Z.; Barekat, M. Chin. Chem. Lett. 2010, 21, 1183.
Org. Lett., Vol. 14, No. 5, 2012
1315

challenge for the mediator in that the oxidation potential
forthesubstrate 4b(1.68V vsAg/AgCl) isca. 420mVmore
positive than that of the mediator, 3a (1.26 V). The
chemistry also proved applicable to secondary alcohols.
Compound 4c, for example, was oxidized to the corre-
sponding ketone in a good yield (entry 3). Alkylbenzenes
can also be indirectly oxidized; for example, p-methoxy-
benzaldehyde was generated from 1-methoxy-4-methyl-
benzene, 4d, under the same reaction conditions albeit in
diminished yield (entry 4).
Table 2. Oxidation Potentials of Substrates 4aꢀ4e and Yields of
the Oxidation Products Using 3a as a Redox Mediator
Figure 1. Cyclic voltammogram of triarylimidazole 3a in the
absence and presence of p-methoxy benzyl alcohol (4a) and
lutidine at a glassy carbon working electrode, platinum wire
counter and Ag/AgCl reference electrodes, in 0.1 M of LiClO4/
CH3CN, scan rate: 0.1 V/s. (curve a) 1 mmol/L 3a; (curve b)
1 mmol/L 3a, 20 mmol/L 4a; (curve c) 1 mmol/L 3a, 20 mmol/L
4a, 50 mmol/L lutidine.
Scheme 1. Catalytic Cycle
substrate
P
OX vs
Ag/AgCl
(V)
yield
(%)
entry
substrate
product
1
2
3
4
5
4a
4b
4c
4d
4e
1.52
1.68
1.66
1.53
1.75
5a
5b
5c
5a
ꢀ
65
60
64
44
ꢀ
that the neutral form is regenerated following oxidation of
the substrate. It also indicates that the added base has a
large effect on the catalysis (vide infra).
To further demonstrate the applicability of triarylimi-
dazoles as redox catalysts, preparative scale electrolysis of
a series of benzylic alcohols, 4aꢀ4e, was performed using
10 mol % of the mediator 3a and 2,6-lutidine (5 equiv) as a
base in CH3CN/CH2Cl2 (v/v = 4:1) with lithium perchlo-
rate serving as the supporting electrolyte. The transforma-
tions were carried out at a controlled potential that
It is worth noting that, for an efficient electron transfer
to occur, the difference between the oxidation potential of
the mediator and substrate should not be “too large”.
When it is, no observable reaction takes place.7f,12 This
proved to be the case with 4e; here, the 490 mV difference
between the potentials of the mediator 3a and substrate 4e
proved to be an unsurmountable thermodynamic impasse
(entry 5).
Baseduponthe results describedthusfarandtheseminal
works of Steckhan and co-workers,7 we propose that the
products arise from the oxidative activation of benzylic
CꢀH bonds (note Scheme 2). This hypothesissuggests that
the indirect oxidation of unsymmetrically substituted
ethers, wherein one of the groups is an electron-rich benzyl
unit, ought to lead to an oxocarbenium which can then
undergo nucleophilic addition. To explore this hypothesis,
p-methoxybenzyl ethers 6 were subjected to indirect oxida-
tion in the presence of 0.1 mL of water using 10 mol % of
3a as a redox catalyst. As shown in Table 3, for all
p-methoxy substituted substrates 6aꢀ6f, differing by less
than 320 mV of the oxidation potentials of 3a, moder-
ate yields of the corresponding 4-methoxybenzoate
(42ꢀ55%) were isolated, along with a trace amount of
1
matched that of the mediator (i.e., at 1.26 V = Pox for
3a), and not that of the substrate (1.52 V vs Ag/AgCl for
4a). When charge was allowed to pass, a greenish color
appeared immediately at the surface of the working elec-
trode (Pt mesh) and diffused into the bulk solution. The
addition of substrate led to an immediate color change
from green to pink (see SI).
We were delighted to discover that the transformation
proceeded smoothly, converting 4a to p-methoxybenzal-
dehyde (5a) in a 65% isolated yield (entry 1, Table 2). To
confirm that the outcome was due to electron transfer
between the mediator and substrate, a control experiment
was performed using identical conditions, but in the
absence ofthe mediator. Onlybackground levelsofcurrent
were observed, and no reaction took place.
In order to explore the generality and scope of the
reaction, other examples were investigated. As shown in
Table 2, under the exactly same conditions, m-methoxy-
benzyl alcohol, 4b, delivered m-methoxybenzaldehyde in a
60% yield (entry 2). This exampleconstituteda meaningful
(12) Miranda, J. A.; Wade, C. J.; Little, R. D. J. Org. Chem. 2005, 70,
8017.
1316
Org. Lett., Vol. 14, No. 5, 2012

4-methoxybenzaldehyde; good to excellent yields were
obtained based on the recovered substrates (column 7 of
Table 3). The electron transfer did not occur when 6g and
6h were examined, presumably because the difference
between their oxidation potential and that of 3a was too
large (>500 mV).
Scheme 2. Plausible Mechanism for the Triarylimidazole In-
duced Oxidation of 4 and 6
Table 3. Oxidation Potentials of Benzyl Ether 6 and Yields of
Benzoate 7
accessing a reasonable range of potentials simply by
adjusting the substituent pattern on the aromatic rings.
The mediators exhibit quasi-reversibility, and a catalytic
current is observed for the oxidation of benzyl alcohol in
the presence of lutidine. The preparative scale experiments
demonstrate that they can be used to catalytically mediate
the oxidation of p-methoxybenzyl alcohols and benzyl
ethers. We are hopeful that our systems will find additional
uses in materials science and in industrial settings. Further
demonstration of their applicability to radical cation ver-
sions of [4 þ 2] and [2 þ 2] cycloaddition is currently being
developed in our laboratory.
POX
yield
(%)a
yield
(%)b
sub.
Ar1
Ar2
(V)
prod.
6a
6b
6c
6d
6e
6f
p-MeO-Ph
p-MeO-Ph
p-MeO-Ph
p-MeO-Ph
p-MeO-Ph
p-MeO-Ph
m-MeO-Ph
m-MeO-Ph
p-BrPh
p-ClPh
Ph
1.54
1.58
1.54
1.57
1.57
1.56
1.74
1.77
7a
7b
7c
7d
7e
7f
ꢀ
55
54
40
42
45
50
ꢀ
87
89
92
88
86
89
ꢀ
m-BrPh
p-MePh
p-MeO-Ph
p-BrPh
m-BrPh
6g
6h
ꢀ
ꢀ
ꢀ
a Isolated. b The yield based on the recovered starting material.
A mechanism that accounts for the formation of both 5
and 7 is shown in Scheme 2. It begins with oxidation of
triarylimidazole3atthe anode. Theresultingcation radical
then accepts an electron from the substrate, either 4 or 6, to
afford a new cation radical 8 and regenerate the mediator,
3. Subsequent deprotonation by lutidine, B, and oxidation
of the resulting benzylic radical 9 leads to 10. When X =
OH, its reaction with lutidine affords 5, while a sequence
involving capture by water, loss of two protons, and
oxidation leads to 5 when X = H and benzoate 7 when
X = OR0. The prominent influence of lutidine on the
voltametric behavior shown in Figure 1 presumably re-
flects its role in the conversion of 8 to 9. That transforma-
tion shifts the original redox equilibrium toward 9 and
facilitates catalyst turnover (3þ• to 3).
Acknowledgment. This work was supported by Grants
for C.C.Z. from the National Natural Science Foundation
of China (No. 20772010), Beijing Natural Science Foun-
dation (No. 7112008), the National Basic Research Pro-
gram of China (No. 2009CB930200), and the Beijing
City Education Committee (KM201010005009). R.D.L.
thanks Amgen for an educational donation, the UCSB
Academic Senate Council on Research and Instructional
Resources, the National Science Foundation PIRE-
ECCI Program, and Dr. Timothy Gallagher for dis-
cussions of imidazoles.
Supporting Information Available. Experimental de-
tails; spectral data for 3b and 3c; photo during reaction;
CV of 3a. This material is available free of charge via the
Internet at http://pubs.acs.org.
In summary, we have uncovered a new class of organic
redox catalysts based on a triarylimidazole framework.
The systems are easy to synthesize and are capable of
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 5, 2012
1317