J . Org. Chem. 2000, 65, 4179-4184
4179
Regioselective In tr a m olecu la r Oxid a tion of P h en ols a n d An isoles
by Dioxir a n es Gen er a ted in Situ
Dan Yang,* Man-Kin Wong, and Zheng Yan
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong
Received March 27, 2000
A novel method for regioselective oxidation of phenols and anisoles has been developed in which
dioxiranes, generated in situ from ketones and Oxone, oxidize phenol derivatives in an intramo-
lecular fashion. A series of ketones with electron-withdrawing groups, such as CF3, COOMe, and
CH2Cl, were attached to phenols, anisoles, or aryl rings via a C2 or C3 methylene linker. In a
homogeneous solvent system of CH3CN and H2O, oxidation of phenol derivatives 1-10 afforded
spiro 2-hydroxydienones in 24-55% yields regardless of the presence of other substituents (ortho
Me, meta Me or Br) on the aryl ring and the length of the linker. Experimental evidences were
provided to support the mechanism that involves a regioselective π bond epoxidation of aryl rings
followed by epoxide rearrangement and hemiketal formation.
In tr od u ction
were employed as key intermediates in the synthesis of
antibiotic aranorosin7 (Scheme 1). A common feature of
these methods involves oxidation of phenol hydroxyl
groups and subsequent transformation to reactive elec-
trophilic intermediates which are then trapped by nu-
cleophiles. However, there is no chemical method avail-
able for regioselective π-bond oxidation of phenols and
phenol ether derivatives.8
Oxidation of phenols has been recognized as an im-
portant area in organic chemistry since phenolic oxida-
tion plays important roles in biosynthesis and total
synthesis of many natural products such as quinoline and
isoquinoline alkaloids.1 In particular, p-quinols arised
from oxidation of p-alkylphenols proved to be valuable
building blocks in synthesis.2 Thus, development of
practical methods for selective oxidation of phenols to
quinols has attracted a lot of attention.3 Recently, a
ruthenium-catalyzed oxidation method4 using t-BuOOH
as a co-oxidant was discovered to convert para-substi-
tuted phenols into tert-butyldioxy-dienones in a selective
manner. Hypervalent iodine oxidants5 such as (diac-
etoxyiodo)benzene (PIDA) and [bis(trifluoroacetoxy)iodo]-
benzene (PIFA) have also been successfully used in
selective oxidation of para-substituted phenols to p-
quinols6 and spiro cyclohexadienones,6a,d-i and the latter
Dioxiranes,9 a new class of versatile oxidants, have
been used to oxidize phenols,10 catechols,11 hydroquino-
nes,12 anisoles,13 and even aromatic hydrocarbons14 under
mild conditions. However, most of those oxidation reac-
tions lack regioselectivity, which is partially overcome
by using hindered phenols11 or performing the reaction
under acidic conditions.13 Here we report an intramo-
lecular method for regioselective oxidation of phenols and
anisoles to spirocyclohexadienones, which utilizes diox-
iranes generated in situ. These oxidation reactions may
proceed via a regioselective π bond oxidation of phenols
and anisoles followed by epoxide rearrangement and
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1, p 707. (c) Kametani, T.; Fukumoto, K. Synthesis 1972, 657. (d)
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Appl. Chem. 1979, 51, 1285. (b) Mitchell, A. S.; Russell, R. A.
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10.1021/jo000458j CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/08/2000