O-Neophyl-type 1,2-phenyl rearrangement initiated by electron transfer: Development of kinetic probes of dissociative electron transfer

Article abstract of DOI:10.1039/a807795i

The first example of an O-neophyl-type rearrangement in a distonic radical anion was found in the electron transfer induced dissociative reduction of 9,10-diphenyl-9,10-epidioxyanthracene.

Full text of DOI:10.1039/a807795i

O-Neophyl-type 1,2-phenyl rearrangement initiated by electron transfer:
development of kinetic probes of dissociative electron transfer
Robert L. Donkers, Joseph Tse and Mark S. Workentin*
Department of Chemistry, The University of Western Ontario, London, ON, Canada N6A 5B7.
E-mail: mworkent@julian.uwo.ca
Received (in Corvallis, OR, USA) 7th October 1998, Accepted 18th November 1998
The first example of an O-neophyl-type rearrangement in a
distonic radical anion was found in the electron transfer
induced dissociative reduction of 9,10-diphenyl-9,10-epi-
dioxyanthracene.
21.12 V vs. SCE at a scan rate (n) of 0.1 V s21 and the Ep shifts
to more negative potentials with increasing scan rate. The
irreversible reduction wave is very broad, with a peak width (Ep
2 Ep/2) of 148 mV (at 0.1 V s21) and a values13 of 0.32, 0.27,
0.23 and 0.21 at 0.1, 1, 5 and 10 V s21. These voltammetric
characteristics are consistent with the reduction of DPA-O2
being dissociative.6 A representative cyclic voltammogram is
shown in Fig. 1(a). Following the dissociative reduction wave
there is a second reversible redox couple at a more negative
potential. The reduction wave of this couple14a is not well-
defined until the potential is scanned to more negative values.
This feature and the reversibility of this 1 F mol21 process14b
are illustrated in Fig. 1(b). This reversible reduction at 21.804
V vs. SCE was identified as 9-phenoxy-10-phenylanthracene
(PPA) by product isolation and characterization, and by its
standard reduction potential (E°). The amount of PPA formed in
the CV experiment depends on the scan rate and the time the
potential is held at values more negative than ca. 21.9 V. Based
on peak current measurements (ip) the formation of PPA is
quantitative on the cyclic voltammetry timescale at very slow
scan rates and when the potential is held at the negative
potentials.15 Also observed in the CV on the return cycle are two
weak oxidation waves; these disappear on addition of a weak
acid (see Fig. 1) and are assigned to electrogenerated basic
intermediates. In no case was there evidence for direct reduction
of the distonic radical anion leading to the corresponding
9,10-diol, DPA-(OH)2 (Path A in Scheme 1), contrary to that
observed in all other peroxide/endoperoxide systems studied to
date.1–5
Electron transfer (ET) to endoperoxides and peroxides results in
the cleavage of the weak oxygen–oxygen (O–O) bond.1–5 This
process proceeds in peroxides and endoperoxides generally by
a dissociative ET mechanism,1–6 in which ET and O–O bond
fragmentation are concerted [eqn. (1) or (2)]. Only in the case of
+ e–
R
O
O
R
R
O• + R O–
(1)
(2)
(3)
+ e–
+ e–
R
O
O
R
•O
R
R
O–
R
O• + R O–
2R O–
+ e–
•O
R
R
O–
–O
R
R
O–
(4)
tert-butyl-p-cyanoperbenzoate is there evidence for a transition
to a stepwise mechanism with formation of the intermediate
radical anion.5 Such mechanistic studies are important because
electron transfer processes of peroxides and endoperoxides play
a key role in their activity in chemical and biological systems.7,8
For example, FeII-promoted ET reduction of the O–O bond in
the antimalarial endoperoxide artemisinin and its semi-syn-
thetic derivatives has recently been shown to be the key step in
its antimalarial activity.9,10 In the cases studied to date using
direct electrochemical methods, the alkoxy radical fragment
produced in the dissociative reduction (R–O· for acyclic
·
peroxides or O–R–R–O2 for endoperoxides) is reduced in a
second ET [eqn. (3) or (4)]; i.e. no reactivity resulting from the
alkoxyl radical fragment is observed.1–5 Since the initial O–O
bond reduction is dissociative, the alkoxyl radical fragment is
generated at the electrode that is at a potential more negative
than the reduction potential of the R–O· fragment. Therefore,
the alkoxyl radical is reduced spontaneously because of the
large driving force. Here we report the first observed11
reactivity from the alkoxyl radical in the ·O–R–R–O2 distonic
radical anion formed in a heterogenous dissociative ET, namely
a 1,2-phenyl migration (O-neophyl rearrangement). This O-
neophyl-type rearrangement of a phenyl group to the alkoxyl
radical fragment occurs in the distonic radical anion formed by
electrochemical single ET to the O–O bond in the endoperoxide
9,10-diphenyl-9,10-epidioxyanthracene (DPA-O2). In addition
to being the first example of this type of reaction, this
rearrangement occurs at the expense of the reduction of the
alkoxyl radical portion of the distonic radical anion [eqn. (4)].
This suggests that systems such as these can be developed as
kinetic probes of the rate of the second heterogeneous ET [eqn.
(3) and (4)].
Fig. 1 (a) Cyclic voltammogram showing the reduction of a 2 m
M solution
of DPA-O2 in 0.1
M
TEAP/MeCN at 0.2 V s21. (b) CV as in (a) where the
potential was held at the negative potential limit for 30 s prior to the positive
scan. The CV shown in the dashed line is that measured after the addition
of 5 equiv. of 2,2,2-trifluorethanol. (c) Cyclic voltammogram showing the
reduction of a 2.8 mM solution of DMA-O2 in 0.1 M TEAP/MeCN at 0.1
V s21 both in the presence (solid line) and the absence (dashed line) of
2,2,2-trifluoroethanol.
Electrochemical reduction of DPA-O2 was investigated in
MeCN and DMF solutions containing 0.1
M
tetraethylammon-
ium perchlorate (TEAP) using cyclic voltammetry (CV).12 In
MeCN, DPA-O2 is reduced with a peak potential (Ep) of
Chem. Commun., 1999, 135–136
135

O•
OH
gesting that there may be a stereoelectronic effect on the
rearrangement in the DPA-O2 system.
O
–O
R
R
O
HO
R
+ e–
+ e–
In the reduction of DMA-O2 the corresponding 1,2-methyl
shift or b-scission does not compete with reduction of the
distonic radical anion. Although the b-scission reaction is not
known for Ph2MeCO· the rate constant of the 1,2-methyl shift
+ 2H+
R
R
R
DPA-O2 R = Ph
DMA-O2 R = Me
DPA-(OH)2 R = Ph
DMA-(OH)2 R = Me
rate is estimated to be 4.4 3 106 s21 17
This provides a lower
.
(A)
–O
OR
OR
rate limit to compare the second heterogenous ET.
HO
•
OR
–
+ e–
+ H+
Observation of this O-neophyl rearrangement in the reduc-
tion of DPA-O2 may provide a method to quantify the
partitioning ratio (if any) between the charge and spin in the
distonic radical anions formed on reduction of unsymmetrically
substituted endoperoxides (for example, 9-methyl-10-phenyl-
9,10-epidioxyanthracene). Studies of this type are currently in
progress. Also in progress are studies addressing the generality
of this type of rearrangement on the reduction of other
polycyclic aromatic endoperoxides and other aryl substituted
endoperoxides, in an attempt to provide ‘clock’ reactions for
secondary reduction of distonic radical anions (and its implica-
tions on the theory of dissociative ET).
– HO–
R
R
(B)
R
+ H+
+ H•
PPA R = Ph
MMA R = Me
– H2O
–O
H
OR
H
HO
OR
+ H+
R
R
1
Scheme 1
This work is supported financially by NSERC and UWO.
In contrast, reduction of 9,10-dimethyl-9,10-epidioxy-
anthracene (DMA-O2) generates the corresponding 9,10-diol
[DMA-(OH)2] quantitatively via a two-electron (2 F mol21
)
Notes and references
reduction (Path A in Scheme 1). No evidence for 9-methoxy-
10-methylanthracene (MMA) was found. Other voltammetric
characteristics are similar to DPA-O2: Ep = 21.35 V vs. SCE
1 M. S. Workentin and R. L. Donkers, J. Am. Chem. Soc., 1998, 120,
2664; R. L. Donkers and M. S. Workentin, manuscript in preparation.
2 R. L. Donkers and M. S. Workentin, J. Phys. Chem. B, 1998, 102,
4061.
3 M. S. Workentin, F. Maran and D. D. M. Wayner, J. Am. Chem. Soc.,
1995, 117, 2120.
at 0.1 V s21, a peak width (Ep 2 Ep/2) of 153 mV (at 0.1 V s21
)
yielding a values of 0.31, 0.27 and 0.25 at 0.1, 1 and 10 V s21
.
Since this is a two electron process the shift of Ep to more
negative potentials by 113 mV/(log n) gives an average a value
of 0.25.
4 S. Antonello, M. Musumeci, D. D. M. Wayner and F. Maran, J. Am.
Chem. Soc., 1997,119, 9541.
5 S. Antonello and F. Maran, J. Am. Chem. Soc., 1997, 119, 12595.
6 J.-M. Savéant, in Advances in Electron Transfer Chemistry, ed. P. S.
Mariano, 1994, vol. 4, pp. 53–116 and references cited therein.
7 Organic Peroxides, ed. W. Ando, Wiley, Chichester, England, 1992.
8 Active Oxygen in Chemistry, Search Series Vol. 2, ed. C. S. Foote, J. S.
Valentine, A. Greenberg and J. F. Lieban, Blackie, New York, 1995;
Active Oxygen in Biochemistry, Search Series Vol. 3, ed. C. S. Foote,
J. S. Valentine, A. Greenberg and J. F. Lieban, Blackie, New York,
1995.
We rationalize formation of PPA in the reduction of DPA-O2
by an O-neophyl-type rearrangement from the initially formed
distonic radical anion (path B in Scheme 1); specifically the
distonic radical anion undergoes a 1,2-phenyl migration to the
alkoxyl radical center to generate the carbon-centered radical
intermediate. At the potential where DPA-O2 is reduced (Ep =
21.12 V vs. SCE) the resulting diarylphenoxymethyl radical is
not expected to be reduced.16 This intermediate can be reduced
at more negative potentials and eventually lead to PPA via
aromatization with loss of OH2. This result is consistent with
the CV results and was verified by the constant potential
electrolysis studies. Electrolysis at 21.2 V does not result in
formation of PPA; instead it generates via a 1 F mol21 process
a product that forms PPA quantitatively after work-up of the
electrolysis mixture. However, if the electrolysis is performed at
more negative potentials (21.6 V) PPA is formed quantita-
tively consuming 2 F mol21. Likewise if the electrolyses are
performed in the presence of a weak acid like 2,2,2-tri-
fluorethanol or acetanilide, PPA is not the initial product, but it
is the only product isolated after work-up. We suggest that in
these latter experiments 1 is formed by trapping the inter-
mediate formed after the O-neophyl rearrangement. No DPA-
(OH)2, which is stable to the work-up conditions, is isolated.
The O-neophyl rearrangement occurs exclusively; no diol,
which would be generated on reduction corresponding to eqn.
(4), is observed. Thus, the rearrangement must occur with a rate
faster than the rate of the heterogeneous ET reduction of the
alkoxyl radical formed on the dissociative reduction. The
9 W.-M. Wu, Y. Wu, Y.-L. Wu, Z.-J. Yao, C.-M. Xhou, Y. Li and F. Shan,
J. Am. Chem. Soc., 1998, 120, 3316.
10 G. H. Posner, S. B. Park, L. González, D. Wang, J. N. Cumming, D.
Klinedinst, T. A. Shapiro and M. D. Bachi, J. Am. Chem. Soc., 1996,
118, 3537; J. N. Cumming, D. Wang, S. B. Park, T. A. Shapiro and G. H.
Posner, J. Med. Chem., 1998, 41, 952 and references therein; A. Robert
and B. Meunier, Chem. Soc. Rev., 1998, 27, 273.
11 The reduction of 9,10-dihydro-9,10-epidioxyanthracene was reported in
the paired electrosynthesis of anthracene and oxygen on the femtolitre
scale: C. Amatore and A. R. Brown, J. Am. Chem. Soc., 1996, 118,
1482.
12 Electrochemical experiments were performed using standard equipment
and electrodes as described in ref. 1. All potentials were calibrated
+
internally to ferrocene (E°Fc /Fc is 0.449 and 0.475 vs. SCE in MeCN and
DMF, respectively). Data in DMF is similar and will be reported in the
full account of this work.
13 The transfer coefficient (or symmetry factor) a is defined as ∂DG‡/
∂DG°, where DG‡ is the free energy of activation and DG° is the free
energy of the ET.
14 (a) The reduction of DPA-O2 is a 1 F mol21 process except under the
conditions indicated later. Full details including simulations will be
reported separately. (b) Determined by comparison of the peak current
(ip) of PPA formed in an electrolysis with that measured with a known
concentration of an authentic sample of PPA.
reduction potential of Ph3C–O· (E°Ph CO /Ph CO ) is 20.03 V vs.
·
2
3
3
SCE;4 thus the driving force for reduction of the alkoxyl radical
at 21.2 V is favorable by at least 23 kcal mol21. By analogy to
the rate constant reported by Falvey et al. for the rearrangement
of the triphenylmethoxyl radical to a-phenoxydiphenylmethyl
radical we expect the O-neophyl rearrangement to be occurring
with a rate constant in the order of 5 3 1010 s21 or greater.17
Thus, the rate of the second ET cannot compete with the O-
neophyl rearrangement. This puts an upper timescale by which
to compare the rate of the second heterogenous ET. Similar O-
neophyl rearrangements were not reported during the electro-
chemical reduction of Ph3CO–OCPh3 or Ph3CO–OBut,4 sug-
15 At higher scan rates the amount of PPA formed in the CV is less than
quantitative; its presence by CV is absent at scan rates higher than 75 V
s21. In product studies the amount of product derived from the O-
neophyl rearrangement is always quantitative. This may be due to a rate
limiting aromatization.
16 The reduction potential of the triphenylmethyl radical is at least 21.2V
vs. SCE and that of tritolylmethyl radical is 21.36 V vs. SCE (S. Bank,
C. Ehrlich and J. A. Zubieta, J. Org. Chem., 1979, 44, 1454).
17 D. E. Falvey, B. S. Khambatta and G. B. Schuster, J. Phys. Chem., 1990,
94, 1056.
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Chem. Commun., 1999, 135–136