1220
Communications to the Editor
Chem. Pharm. Bull. 51(10) 1220—1221 (2003)
Vol. 51, No. 10
MeOH) (entry 5).17)
A Facile Method for Deprotection of O-
Next, we applied this procedure to various types of O-al-
lylphenols 6a—13a for confirmation of scope and limitation
(Table 2). O-Allylphenols 6a—10a were readily deprotected
to give the corresponding phenols 6b—10b, respectively,
without affecting aldehyde, amide and nitro groups. Depro-
tection of O-allylphenols 11a or 12a, bearing acid labile ac-
etal or benzyl ether, gave the corresponding phenol 11b or
12b keeping another protective group. In the case of a diether
13a, which has two kinds of allyl ethers, allyl aryl ether bond
was selectively cleaved to give the phenol 13b together with
a small amount of a benzyl propyl ether 13c. Although detail
mechanism of the reaction was not clear at this stage, we as-
sumed the reaction proceeded via the formation of p-allyl
complex. However, isomerization16) of allyl ethers to enol
ethers followed by cleavage of them could not be excluded.
Allylphenols
Makoto YAMADA, Shin-ichi WATANABE,
Osamu HOSHINO, Miyuki ISHIZAKI, Maiko HAYASHIDA,
Atsuko TANAKA, and Hiroshi HARA*
Faculty of Pharmaceutical Sciences, Tokyo University of Science;
2641, Yamazaki, Noda, Chiba 278–8510, Japan.
Received July 10, 2003; accepted August 22, 2003
Allyl aryl ethers can be easily cleaved by the use of 10% Pd/C
under the mild and basic conditions.
Key words allyl aryl ethers; deprotection; palladium on carbon
Phenolic hydroxyl groups exist in various type of chemical
compounds (e.g., natural products, drugs). The functional
group plays a very important role for increasing biological
activities in many cases. Moreover, it is introduced as a key
functional group into Host compounds with interesting prop-
erty for molecular recognition (e.g., calixarenes, cyclo-
phanes). In order to synthesize such complicated compounds,
protection and deprotection of the phenol group are crucial
steps. Among them, the allyl group is known as one of the
stable protective groups towards both acidic and basic condi-
tions. Also allyl ethers have advantage that can be readily
prepared by the reaction of a phenol with allyl halide in the
presence of base. Thus, several procedures1) have been devel-
oped for one step cleavage of the group including palladium-
catalyzed reaction. Among them, most of palladium catalysts
used were Pd(PPh3)4 together with NaBH4,2) LiBH4,3)
Bu3SnH,4) PhSiH3,5) morphorine,6) ZnCl2–polymethylhy-
drosiloxane,7) or TolSO2H.8) Also, electrochemical cleavage
using PdCl29) and Ni10) were appeared. As an alternative cata-
lyst, Boss and Scheffold reported the reaction using 10%
Pd/C with p-TsOH11) under reflux conditions. In the course
of synthetic studies on a series of host compounds 1 com-
bined with a crown ether and two orthocyclophanes,12) we
Fig. 1
found a facile reaction for deprotection of O-allylphenols Table 1. Deallylation of O-Allylvanillin
using 10% Pd/C in 10% KOH–MeOH at ambient tempera-
ture. Here, we describe preliminary results of mild and con-
venient cleavage of allyl aryl ether bond.
Tetra(O-ally1-6-bromoisovanillyl)dibenzo-18-crown-6
2a,13) prepared by condensation of dibenzo-18-crown-6 and 4
eq of O-allyl-6-bromoisovanillyl alcohol, was subjected to
hydrogenolysis on 10% Pd–C14) in 10% KOH–MeOH yield-
ing a product 2b15) instead of 2c, unexpectedly. As a result,
Entry
Conditions
Yield (%)
the ether 2a was suffered not only debromination but deally-
lation. Indeed, under weaker basic conditions (10% Pd/C, H2,
4 eq of Et3N, MeOH), the ether bond was inert and the
tetrapropyl derivative 2d13) was obtained in 45% yield. Thus,
essential conditions for this facile reaction were searched by
the use of O-allylvanillin 3 as a simple substrate (Table 1).
Without both Pd catalyst and base, the reaction did not occur
at room temperature (entries 1 and 3). Also, crown ether part
was not necessary for the reaction (entry 2). Although the re-
action proceeded in the absence of KOH under reflux, the re-
action was sluggish and isomerized enol ethers 5a, b were
produced (entry 4).16) Eventually, it was verified to be a sim-
ple combination of reagents (10% Pd/C and 10% KOH–
1
2
10% KOH–MeOH
r.t., 24 h then reflux 24 h
10% KOH–MeOH
dibenzo-18-crown-6 (1 eq)
r.t., 24 h then reflux 24 h
10% Pd/C, MeOH r.t., 72 h
10% Pd/C, MeOH reflux 24 h
10% Pd/C, 10% KOH–MeOH
r.t., 8 h
0
0
3
4
5
0
28a)
96
6
10% Pd/C, NaOMe (10 eq)
MeOH, r.t., 5 h
54
a) Starting material 3 (49%) and enol ethers 5a (9%) and 5b (5%) were also
obtained.
To whom correspondence should be addressed. e-mail: h.hara@rs.noda.tus.ac.jp
© 2003 Pharmaceutical Society of Japan