TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6533–6535
A new mild and rapid deprotecting method for aryl
cyclohex-2-en-1-yl ethers to phenols
Pascal Carato, Guillaume Laconde, Chehla Ladjel, Patrick Depreux* and Jean-Pierre He´nichart
Institut de Chimie Pharmaceutique Albert Lespagnol, 3 rue du Professeur Laguesse, BP83, 59006 Lille, France
Accepted 16 July 2002
Abstract—Cyclohex-2-en-1-yl ether can be used as a new protecting group of mono and disubstituted phenols. The cleavage of
the cyclohex-2-en-1-yl ether is mild, rapid with excellent yields. © 2002 Elsevier Science Ltd. All rights reserved.
Protecting groups of phenols or polyphenols have been
widely used in synthetic organic chemistry,1,2 many
hydroxy protecting groups are known, the most often
used being esters,3 carbonates,4 ethers removable in
acid or basic conditions,5 but also allyl6–9 or benzyl10
groups which can be deprotected by reductive proce-
dures, including catalytic hydrogenation or dissolved
metals.
cyclohex-2-en-1-yl ether derivatives in entries 3–4, with
electron-donating groups was rapid and easy.
In the series of disubstituted phenols (Table 1, entries
6–11), the deprotection of cyclohex-2-en-1-yl ether was
also easy in the presence of a free hydroxy group, an
other ether link and even with other protecting groups
such as esters or allyl ethers.
In this paper we report the use of cyclohex-2-en-1-yl
entity as a good protecting group for phenols as ethers
not previously described. The cleavage of cyclohex-2-
en-1-yl ether in acid medium was generally rapid and
mild. The scope of this protection method was studied
with different mono and disubstituted phenols or
catechol.
The deprotection method was applied to methyl-4-
(cyclohex-2-en-1-yloxy)-3-hydroxy benzoate12 to give
the
corresponding
methyl-3,4-dihydroxybenzoate
(Table 1, entry 6). The starting material of this reaction
was synthesized with methyl-3,4-hydroxybenzoate in
the presence of 3-bromocyclohexene and K2CO3 in
acetone at room temperature to give moderate yield of
40%.12 Increasing the temperature to reflux led to the
formation of methyl-3,4-bis (cyclohex-2-en-1-yloxy)-
benzoate with a high yield of 87%.
Hydrogen chloride in anhydrous ethyl ether was used
to cleave the cyclohex-2-en-1-yl ether link. The starting
ether derivatives (Table 1, entries 1–5) were easily
obtained in excellent yields (92–98%)11 from monophe-
nols substituted either with electron-withdrawing (2-Br,
2-CONH2, 4-NO2) or electron-donating groups (4-
C2H5, 4-OCH3). The cleavage of these cyclohex-2-en-1-
yl ether derivatives was rapid and easy, to give the
corresponding phenol products with good yields (Table
1, entries 1–5). We can notice that for the deprotection
of the nitro derivative (Table 1, entry 5), the reaction
time increased (60 min), probably caused by the
strongly electron-withdrawing effect of the nitro group
compared to bromo and acetamido groups of the corre-
sponding products in entries 1–2. The cleavage of the
The diether compounds (Table 1, entries 7–11) were
synthesized from methyl-4-(cyclohex-2-en-1-yloxy)-3-
hydroxybenzoate in the presence of an excess of 3-bro-
mocyclohexene and K2CO3 in acetone with excellent
yields (89–97%).11,13 In the same conditions cleavage
with hydrogen chloride in anhydrous ether, the diether
products gave selectively methyl-3-alkoxy-4-hydroxy
benzoate (Table 1, entries 7–9). When the substrates in
entries 1011 and 1113 (Table 1) were treated in
analogous conditions, the allyl ether and the acetate
group were not cleaved and only the cyclohex-2-en-1-yl
ether was cleaved to yield the corresponding products.
The selective cleavage of cyclohex-2-en-1-yl ether could
be due to the more stability of the corresponding
carbocation formed in acid medium.
Keywords: phenol deprotection.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01466-1