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Table 2: Oxidation of various 2-(silylmethyl)phenols 11.
cyclodimerization process required high temperatures for the
reaction to go to completion. The benzoquinone side products
9 or their reductive catechol forms could not be isolated from
these reactions, except for the oxidation of 2d. Notably,
oxidation of 2,3,6-trimethylphenol (2e) proceeded selectively
at the less hindered 6-position to give the corresponding
cyclodimer 8e in 70% yield. In contrast, the ortho-selective
oxidation of the symmetrical 2,6-disubstituted phenols 2h–
l proceeded smoothly at 408C (method B), and the corre-
sponding cyclodimers 8h–l were obtained in excellent yields.
In contrast to the low-temperature conditions (208C)
required for the site-selective oxidation of unsymmetrical
phenols, almost the same results were obtained with both 10b
and 10c at 408C.[16] Notably, in contrast to IBX-mediated
oxidations,[13] phenols substituted with electron-withdrawing
groups (2 f, 2g, and 2j–l) were oxidized smoothly with the use
of our IBS/Oxone catalysis. For example, the oxidation of 2l,
bearing two ester groups at both ortho-positions, using
a stoichiometric amount of IBX did not proceed even at
elevated temperatures.
Entry
Substrate
X
R
t [h]
8 or 12
Yield [%][a]
1
2
3
4
5
6
7
8
11c
2a
11d
2d
11e
2 f
11 f
2n
SiMe3
H
SiMe3
H
SiMe3
H
SiMe3
H
5-iPr
5-iPr
5-Me
5-Me
5-F
5-F
6-Br
6-Br
5
24
5
24
7
24
5
94 (<5)[b]
82 (15)[b]
72
65
83
62
57
27
44
[a] Yield of isolated product. [b] 1,2-Benzoquinone.
The oxidation of various 2-(silylmethyl)phenols (11) was
examined under optimized reaction conditions (Table 2). The
reaction of the silylated analogue of carvacrol 11c gave the
cyclodimer 12c exclusively (entry 1 versus entry 2). More-
over, compared to their nonsilyl counterparts 2d, 2 f, and 2n,
the phenols 11d–f, bearing electron-donating or electron-
withdrawing substituents at either the meta- or ortho-posi-
tions, gave the corresponding cyclodimers in higher yields
after shorter reaction times (entries 3, 5, and 7 versus
entries 4, 6 and 8).
The oxidation of 2-cresol (2m), as the simplest substrate,
gave a complex mixture, and the desired cyclodimer 8m was
obtained in only 20% yield (Scheme 3a). To stabilize the
In contrast, the oxidation of the 4-methylphenol 11g gave
a complex mixture of products, and neither the desired 1,2-
benzoquinol 14 nor its cyclodimer 12g could be isolated
(Scheme 4a). We speculated that, because of the acidity of
Oxone, Peterson olefination[18] of the unstable 14 might
proceed preferentially to give a 1,2-benzoquinone 2-methide
15, which readily undergoes decomposition.[19] This failure
provided us an opportunity to achieve unprecedented cascade
reactions. Indeed, the elimination of silanol could be sup-
pressed by the use of buffered Oxone, and a relatively clean
reaction was achieved in the presence of excess methyl vinyl
ketone (MVK) to give the [4+2] cycloadduct 16a in good
yield as a single diastereomer (Scheme 4b).[20] In contrast, 15
could also be trapped in the presence of electron-rich alkenes,
such as indene, under acidic conditions to give the corre-
sponding tetracyclic chroman 17a (Scheme 4c).[19] Other
examples are shown in Scheme 4d for the cascade
[4+2] cycloaddition of both 1,2-benzoquinols and 1,2-benzo-
quinone 2-methides with several dienophiles, such as MVK,
methyl acrylate, aryl alkenes, and alkyl vinyl ether.[16,21]
Notably, to accelerate the generation of ortho-quinone
methide from the stable ortho-naphthoquinol, derived from
2-naphthol 11j, a catalytic amount of para-toluene sulfonic
acid was used instead of HFIP and the cycloadducts 17c and
17d were obtained in high yield.[16] Importantly, the IBS-
catalyzed chemoselective oxidation of phenols proceeded
efficiently under these mild reaction conditions even in the
presence of an excess amount of alkenes. However, the
oxidative cascade cycloaddition of both ortho-quinols and
ortho-quinone methides with acetylenes (e.g., acetylenedi-
Scheme 3. Oxidation of 2-cresol (2m) and its silylated analogues 11.
TBAF=tetra-n-butylammonium fluoride, THF=tetrahydrofuran.
partial positive charge developing at an alkylated 2-position,
we introduced a trialkylsilylmethyl substituent at the 2-
position of phenols. To our delight, the clean oxidation of the
a-trimethylsilyl-o-cresol 11a proceeded smoothly and the
corresponding cyclodimer 12a was obtained in 64% yield
along with the quinone 13a in 33% yield (Scheme 3b). Both
the site selectivity and the reaction rate were enhanced by the
b-silicon effect.[17] Notably, oxidative desilylation was not
observed under our oxidative conditions. A variety of
trialkylsilyl groups could be easily installed at the benzylic
position,[16] and easily removed after the oxidation. For
instance, 8m could be isolated in good yield from the
oxidation of the phenol 11b followed by TBAF-mediated
desilylation (Scheme 3c).
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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