Deffieux et al.
starting materials. Initiating these one-electron oxidation
reactions under appropriate electrochemical conditions
constitutes an attractive alternative to the use of chemi-
cal reagents, notably because of the possibility of per-
forming selective oxidation under environmentally friendly
conditions. Inspired by the work of Swenton, Thomas,
and co-workers on the electrochemical generation of
paraquinone ketals,7 we recently reported for the first
time similar anodic oxidations of 2-alkoxyphenyl alkyl
ethers of type 2 for the preparation of orthoquinone
bisketals 3 and monoketals 4 by using either methanol
or water, respectively, as a reaction cosolvent in aceto-
nitrile (i.e., 2 f III f IV f V f 3/4, Scheme 1).8a
Bisketals 3 are easily transformed into their correspond-
ing monoketals 4 by selective monohydrolysis.8a Monoket-
als can also be directly generated via anodic oxidation of
2-alkoxyphenols in methanol (i.e., 1 f I f II f 4,
Scheme 1). This approach was judiciously exploited by
Yamamura and co-workers for the synthesis of asatone
and other propenylphenol-derived asatone-type neolign-
ans,9 which were obtained by simply letting anodically
generated orthoquinone dimethyl monoketals undergo
Diels-Alder dimerizations upon standing at room tem-
perature (vide infra). To the best of our knowledge, the
only two examples of this electrochemical approach that
led to nondimerizing orthoquinone monoketals are the
ones reported by Swenton and co-workers and us.8b,c
Indeed, orthoquinone monoketals of type 4 are gener-
ally not very stable, and they rapidly succumb to Diels-
Alder dimerization processes, leading to bicyclo[2.2.2]-
octenones, because of the capability of their 2,4-dienone
unit to behave both as a diene and as a dienophile. The
lack of control over this cycloaddition chemistry is
undoubtedly one of the main reasons why the use of such
potentially useful building blocks has not yet been
generalized in organic synthesis. It is nevertheless pos-
sible to harness the reactivity of these 6,6-dioxocyclohexa-
2,4-dienone systems by choosing an appropriate substi-
tution pattern.1a,b The presence of a single substituent
on their ring system can drastically influence their
stability. For example, a bromine or an iodine substituent
at the 4-position of 6,6-dimethoxycyclohexa-2,4-dienones
(i.e., 4, R ) R′ ) Me)8b,10 or a small electron-releasing
group such as an alkyl or an alkoxy group at their
5-position10b,11 are particularly efficient at retarding
Diels-Alder dimerization. The presence of a bulky
carbon-based substituent at their 4-position also stabi-
lizes these orthoquinone monoketals.8c,11b,c,12a It has fur-
thermore been observed that their 6-acetoxy derivatives
or orthoquinol acetates (i.e., 4, R ) Me, R′ ) Ac) are much
less prone to undergo dimerization than their 6,6-
dimethoxy analogues.6,13
With this knowledge on dimerizing and nondimerizing
orthoquinone monoketals and related orthoquinols in
mind, we decided to further examine the scope of their
preparation by anodic oxidation of both 2-alkoxyphenols
of type 1 and 2-alkoxyphenyl alkyl ethers of type 2.
Herein we describe our results obtained with a series of
differently substituted 2-methoxyphenols 1a-g and a
series of spirolactonizable R-(2-methoxyphenoxy)-2-me-
thylpropionic acids 2b-f. Suggestions are also made to
explain the extremely high regioselectivity of the Diels-
Alder dimerization of orthoquinone monoketals on the
basis of the intramolecular [2 + 2] reactivity of their
dimers.
Results and Discussion
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Patai, S., Rappoport, Z., Eds.; John Wiley: New York, 1988; Vol. 2,
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of a nucleophilic entity is the most direct method of
electrochemically generating orthoquinone monoketals 4
(Scheme 1), if these reactive species can withstand the
reaction conditions used. The first series of compounds
we submitted to anodic oxidation comprised the 2-meth-
oxyphenols 1a-g. Reactions were conducted in a single
cell at a constant current in methanol containing lithium
perchlorate as a supporting electrolyte (Table 1). Metha-
nol played both the role of reaction solvent and of the
nucleophilic entities necessary to trap cation intermedi-
ates of type II into 6,6-dimethoxycyclohexa-2,4-dienones
4 (i.e., R ) R′ ) Me). We were pleased to isolate such
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