Palladium charcoal-catalyzed deprotection of O-allylphenols

Article abstract of DOI:10.1016/j.tet.2004.05.097

Allyl aryl ethers can be easily cleaved by the use of 10% Pd/C under mild and basic conditions. The present reaction would involve a SET process rather than a π-allyl-palladium complex. The scope and limitation of this new deprotective methodology is also described.

Full text of DOI:10.1016/j.tet.2004.05.097

Tetrahedron 60 (2004) 7973–7981
Palladium charcoal-catalyzed deprotection of O-allylphenols
Miyuki Ishizaki,† Makoto Yamada, Shin-ichi Watanabe,‡ Osamu Hoshino, Kiyoshi Nishitani,
*
Maiko Hayashida, Atsuko Tanaka and Hiroshi Hara
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda-shi, Chiba 278-8510, Japan
Received 20 April 2004; accepted 27 May 2004
Available online 15 July 2004
Abstract—Allyl aryl ethers can be easily cleaved by the use of 10% Pd/C under mild and basic conditions. The present reaction would
involve a SET process rather than a p-allyl-palladium complex. The scope and limitation of this new deprotective methodology is also
described.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
tection of the phenolic allyl ether of tetra(O-allyl-6-
bromoisovanillyl)dibenzo-18-crown-6 (1) which gave a
tetraphenol (2a) instead of a propyl ether (2b) under
reductive conditions (H2, 10% Pd/C in 10% KOH–MeOH)
(Scheme 1). The structure of 2a was determined as the
corresponding acetate (2c), because the high polarity of 2a
prevented extraction into organic solvents. This result
indicated that 1 suffered not only debromination but also
deallylation. We envisaged that the present reaction could
be applied to the cleavage of O-allylphenols. Here, we wish
to describe a facile and mild reaction for deprotection of
O-allylphenols using 10% Pd/C in 10% KOH–MeOH at
ambient temperature12 and discuss the reaction mechanism
(Scheme 2).
The phenolic hydroxyl group exists in various types of
chemical compounds as demonstrated by the vast number of
natural products in plant and animal life. The functional
group plays a very important role in increasing biological
activities in many cases. In developing a synthesis of any
phenol-containing products, protection is often mandatory
to prevent reaction with oxidizing agents and electrophiles
or reaction of the nucleophilic phenoxide ion with even mild
alkylating and acylating agents. Thus, many of the
protective groups have been developed for phenol protec-
tion.1 Allyl ether is known as one of the useful protective
groups because of its stability in hydrolysis towards both
acidic and basic conditions. Also, facile preparation of allyl
ethers from a phenol with an allyl halide in the presence of a
base is quite advantageous. Therefore, several one-step
deprotective methods among them have appeared,1 of which
Pd-catalyzed deprotection was one of the most interesting
features. In fact, combinations of Pd(PPh3)4 and reducing
agents such as NaBH4,2 LiBH4,3 Bu3SnH,4 PhSiH3,5
morphorine,6 ZnCl2-polymethylhydrosiloxane,7 or TolSO2H8
2. Results and discussion
At first, the essential conditions for this facile reaction were
investigated by the use of O-allylvanillin (3)13 as a model
compound (Scheme 3, Table 1). Without either a Pd catalyst
or base, the reaction did not occur at room temperature
(entries 1 and 3). The crown ether part was not necessary for
the reaction (entries 2 and 5). Although the reaction
proceeded in the absence of KOH under reflux, it was
sluggish and isomerized enol ethers (5a,b) were formed
(entry 4).14 As a base, NaOMe was also efficient (entry 6),
however, eventually, it was verified to be a simple
combination of reagents (10% Pd/C and 10% KOH–
MeOH) for cleavage of the allyl ether (entry 5).
9
were reported. Also, electrochemical cleavage using PdCl2
was investigated. As an alternative catalyst, Boss and
Scheffold reported a reaction using 10% Pd/C with
p-TsOH10 under reflux conditions. During our synthetic
studies11 on host compounds combined with a crown ether
and two orthocyclophanes, we unexpectedly found depro-
Keywords: Allyl aryl ethers; Deprotection; Palladium charcoal; SET
process.
*
Corresponding author. Tel.: þ81-4-7121-3672; fax: þ81-4-7121-3672;
e-mail address: h.hara@rs.noda.tus.ac.jp
Present address: Faculty of Pharmaceutical Sciences, Josai International
Next, we applied the present reaction to various types of
mono-substituted O-allylphenols (6a–o) for confirmation of
scope and limitation (Scheme 4, Table 2). O-Allylphenols
(6a–h), which have an electron-withdrawing or weak
†
University (JIU), 1, Gumyo, Togane-shi, Chiba 283-8555.
Present address: Faculty of Pharmaceutical Sciences, Gifu
Pharmaceutical University, 5-6-1, Mitahora-higashi, Gifu 502-8585.
‡
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.097

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M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
Scheme 1.
group, such as the methoxy or hydroxyl group, were lower
compared with those of 6a–h because of the formation of
the corresponding propyl ethers (8j–o) by reduction and
enol ethers (9j,k) by isomerization (entries 10–15).14
Interestingly, although the reason was not clear, a
substituted pattern on the benzene ring markedly affected
the reaction. For example, deallylation of 2-methoxyallyl-
phenol (6l) was faster than that of 3- and 4-methoxyallyl-
phenols (6j,k) to yield 2-methoxyphenol (7l) in 76% yield
(entries 10–12)
Scheme 2.
The reaction of more complex substrates (6p–y) also
proceeded to afford the corresponding phenols (7p–u) in
good to high yields (Table 3). Deprotection of O-allyl-
phenols (6s,t), bearing an acid labile benzyl ether or acetal
group, gave the corresponding phenols (7s,t) keeping
another protective group (entries 4 and 5). Interestingly, in
the reaction of the diether (6u), which has two kinds of allyl
Scheme 3.
Table 1. Deallylation of O-allylvanillin (3)
Entry
Conditions
Yield (%)
0
1
2
3
4
5
6
10% KOH–MeOH, rt 24 h then reflux 24 h
10% KOH–MeOH, dibenzo-18-crown-6 (1 equiv), rt 24 h then reflux 24 h
10% Pd/C, MeOH, rt 72 h
10% Pd/C, MeOH, reflux 24 h
10% Pd/C, 10% KOH–MeOH, rt 8 h
10% Pd/C, NaOMe (10 equiv), MeOH, rt 5 h
0
0
28a
96
54
a
Starting material (3; 49%) and enol ethers (5a; 9%, 5b; 5%) were also obtained.
electron-donating group on the benzene ring, were readily
deprotected to give the corresponding phenols (7a–h) in
high yields (82–98%) (entries 1–8). It is noteworthy that
the amido, cyano and nitro groups in the substrates remained
intact during the reaction. In the case of O-allyl-4-
bromophenol (6i), many by-products were observed on
TLC to result in the formation of 7i in moderate yield
(entry 9). On the other hand, yields of deprotection for
O-allylphenols (6j–o) bearing a strong electron-donating
ethers, the allyl aryl ether bond was selectively cleaved to
give phenol 7u (81%) along with a small amount of benzyl
propyl ether (8u) (10%) (entry 6). Moreover, the present
reaction could apply to the substrates (6v–y), which have a
variety of allyl ether moieties, to furnish p-nitrophenol (7a)
in high yields (entries 7–10).
During the investigation of the present reaction, we found
that the choice of the palladium catalyst was quite
Scheme 4.

M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
Table 2. Deallylation of various O-allylphenols (6a–o)
7975
Entry
Substrate
R
Time (h)
7 (%)
8 (%)
(E)-9 (%)
(Z)-9 (%)
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
6g
6h
6i
p-NO2
m-NO2
o-NO2
p-CN
p-CO2Me
p-CO2H
p-t-Bu
p-NHAc
p-Br
9
9
8
10
10
10
24
48
7
94
97
96
98
44 (44)a
82
86
3
12
86
49
9
10
11
12
13
14
15
6j
6k
6l
6m
6n
6o
p-OMe
m-OMe
o-OMe
p-OH
m-OH
o-OH
96
48
24
96
96
96
17
45
76
10
0 (45)b,c
0 (43)c
20
23b
6
53
15b
21
4b
20b
4b
12b
a
Value in parenthesis is yield of p-hydroxybenzoic acid.
Determined by 1H NMR spectroscopy.
Value in parenthesis is recovery of starting material.
b
c
important. Although the reason was not clear, different
activity in this system was observed by the use of Pd
catalysts, which were purchased from four different
suppliers, in the reaction of 7a and 7h. (Scheme 4,
Table 4).15
Next, we turned our attention to clarify the reaction
mechanism. As mentioned above, O-allylphenols were
easily cleaved to give the corresponding phenols in good
to high yields except for the substrates bearing a strong
electron-donating group. To compare the reactivity of the
Table 3. Deallylation of various O-allylphenols (6p–y)
Entry
Substrate
(R¼allyl)
Time
(h)
Product
(%)
(R¼H)
Entry
Substrate
Time
(h)
Product
(%)
1
5
7p (87%)
6
7
7u: R¼Allyl (81%)
8u: R¼Pr (10%)
6p
6q
6u
6v
2
4
7q (75%)
7
24
7a (100%)
3
13
7r (71%)
8
24
7a (97%)
6w
6r
6s
4
5
8
7
7s (95%)
7t (65%)
9
30
24
6x
7a (96%)
10
7a (95%)
6t
6y

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M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
Table 4. Effect of Pd catalysta
When the deallylation reaction was performed with
Pd(PPh3)4, vanillin (4) and allyl methyl ethers (13, 14)
were obtained in quantitative yields via the formation of
p-allyl-Pd(II) complexes. The ratio (13/14¼86/14) of the
ethers was determined by 1H NMR spectroscopy. However,
the reaction of 11 with 10% Pd/C under similar conditions
as noted above afforded vanillin (4), 4-(1-propenyl)-1,2-
methylenedioxybenzene (12), and 4-(3-methoxy-1-pro-
penyl)-1,2-methylenedioxybenzene (13). With Pd/C, trans-
formation of 13 and 14 into 12 during the reaction could not
be excluded. Thus, the reaction of 13 and 14 was carried out
under similar conditions in 10% KOH–MeOH. However,
the reaction of both 13 and 14 did not give 12 at all and
Entry Substrate Supplier of Pd Time (h) Product (%) Lot. No.
1
2
3
4
5
6
7
8
6a
6a
6a
6a
6h
6h
6h
6h
Kojima
Aldrich
Nacalai
Merck
Kojima
Aldrich
Nacalai
Merck
9
7
10
99
48
9
7a (94)
7a (96)
7a (95)
7a (68)
7h (86)
7h (87)
7h (89)
7h (2)
206047
07617PI
V2P1618
S37269
206047
07617PI
V2P1618
S37269
5d
7d
a
The reaction was performed using substrate (100 mg) and 10% Pd/C
(20 mg).
Scheme 5.
Pd catalyst in the present system, the reaction of 6m
with Pd(PPh3)4 in 10% KOH/MeOH was performed at
rt for 5 h to give p-hydroquinone (7m) in 88% yield
without the formation of 8 and 9. The result suggested
that the 10% Pd/C- and Pd(PPh3)4-catalyzed
reaction would proceed by a different mechanism.
With Pd(PPh3)4, deallylation of allyl ethers usually
occurs via the formation of p-allyl-Pd(II) complexes
followed by the reaction with nucleophiles.16 To
investigate the fate of an allyl moiety, the reaction of
styryl ether (11) was carried out with Pd/C and Pd(PPh3)4
(Scheme 5).
unexpected products (15–18) were produced. These results
clearly indicated that the reaction involved an oxidation–
reduction process by the single-electron transfer (SET)
process.15,17–19 To confirm the SET process, the reaction of
7a with Pd/C was performed in the presence of tetra-
cyanoethylene (TCE)20a,b or tetracyanoquinodimethane
(TCQM),20c,d which are known as electron-capture
reagents. As expected, the reaction of O-allyl-p-nitrophenol
(7a) with a catalytic amount of TCE or TCQM did not form
p-nitrophenol (6a) even after 24 h and the starting material
(7a) was recovered in quantitative yield in each case
(Scheme 6).
Scheme 6.

M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
7977
Scheme 7.
Scheme 8.
As a result, we proposed a plausible pathway of the present
deallylation as shown in Scheme 7. Namely, the coordi-
nation of the Pd atom on the aromatic ring facilitated the
SET process and the resulting radical anion formed a
phenoxide ion and a radical species (12a), which would
abstract the hydrogen atom from PdOMe to give 12.21
having strong electron-donating groups gave phenols in nil
to moderate yields. Moreover, we revealed that the present
reaction proceeded via the SET process. Because 10% Pd/C
was a heterogeneous catalyst, the deprotected phenol was
obtained in essentially pure form by simple filtration and
extraction procedure. We believe that the present reaction
provides a new, convenient deprotective method for
O-allylphenols due to its mild conditions and simple
procedure.
Finally, the reaction of an aliphatic allyl ether (20), which
was obtained by allylation of 19,22 was investigated
(Scheme 8). As expected, no deallylation product (19) was
produced, and an inseparable mixture of a propyl ether (21)
and an enol ether (22) was obtained by reduction and
isomerization. The result is compatible with involving the
SET process in this reaction.
4. Experimental
4.1. General
All melting and boiling points were measured on a Bu¨chi or
a Yanagimoto (hot plate) melting point apparatus and by a
bulb-to-bulb distillation apparatus, and are uncorrected. H
3. Conclusion
1
In summary, we have investigated the deprotection of
various O-allylphenols to give the corresponding phenols.
The reaction of O-allylphenols bearing electron-withdraw-
ing and weak electron-donating groups on the benzene ring
proceeded smoothly, whereas the reaction of O-allylphenols
NMR spectra were taken with a JEOL JNM AL-300
(300 MHz) spectrometer in a CDCl3 solution with tetra-
methylsilane as the internal standard. Mass spectra were
measured on a Hitachi M-80 or a JEOL JMS D-300
spectrometer. Column chromatography was performed over

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M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
1
silica gel (Merck Kiegelsel 60). Preparative TLCs were run
on Merck 5744, or Merck 5715 plates. Organic extracts
were dried over MgSO4. Ten percent Pd/C was purchased
from Kojima Co. and used as received (Lot. No. 206047).
which the H NMR spectrum was identical with that of an
authentic sample.
4.2. General procedure for synthesis of O-allylphenols
(6a–r and 6v–y)
4.1.1. 11,12,24,25-Tetra(5-allyloxy-2-bromo-4-methoxy-
benzyl)-2,5,8,15,18,21-hexaoxatricyclo[2-.4.0.09.4]he-
octahydro-5,8,11,16,19,22-hexaoxa-dibenzo[a,j]cyclo-
octadecene 9,11,13,21,23,25-hexaene (1).23 Mp 176–
177 8C (benzene–EtOH); 1H NMR d 6.39, 6.54, 7.02
(each 4H, s), 5.86–6.00 (8H, m), J¼17.8 Hz), 5.19 (4H, d,
J¼10.5 Hz), 4,37 (8H, d, J¼5.4 Hz), 4.05 (8H, m), 3.96
(8H, m), 3,84 (12H, s), 3.82 (8H, s); MS m/z 1380 (Mþ),
1382 (Mþþ2); HRMS m/z calcd for C64H68Br4O14 (Mþ)
1380.1928, found: 1380. 1957.
A suspension of a phenol (6a–r) (1 equiv), K2CO3
(1.5 equiv), and 3-bromopropene (1.15 equiv) in dry DMF
(1 mL per 1 mmol of 6) was stirred at rt for 1–18 h. The
mixture was filtered by suction and water was added to the
filtrate. The aqueous layer was extracted with Et2O. The
organic extracts were washed with brine, then dried and
evaporated under reduced pressure to give a residue, which
was purified by column chromatography to afford 6a–r25a–l
and 6v–y.25m–p
4.1.2. 11,12,24,25-Tetra(5-allyloxy-2-bromo-4-methoxy-
benzyl)-2,5,8,15,18,21-hexaoxatricyclo[2-.4.0.09.4]he-
octahydro-5,8,11,16,19,22-hexaoxadibenzo[a,j]cyclo-
octadecene 9,11,13,21,23,25-hexaene (2c). A mixture of 1
(0.050 g, 0.04 mmol) and 10% Pd/C (0.017 g) in 10%
KOH–MeOH (13 mL) was stirred at rt for 30 h. The
mixture was filtered by suction and the filtrate was
evaporated under reduced pressure. Then, acetic anhydride
was added to the residue and the mixture was stirred for 5 h.
The reaction was quenched with a NaHCO3 solution and the
mixture was extracted with CHCl3. The organic extracts
were washed with brine, then dried and evaporated under
reduced pressure to give a residue, which was purified by
TLC (CHCl3–MeOH¼100:1) to afford 2c (0.009 g, 24%) as
pale yellow crystals; mp 165–166 8C (CHCl3–MeOH); 1H
NMR d 6.86 (8H, s), 6.64, 6.65 (each 4H, s), 4.10 (8H, brs),
3.99 (8H, brs), 3.80 (12H, s), 3.76 (8H, s), 2.29 (12H, s); MS
m/z 1072 (Mþ); HRMS m/z calcd for C60H64O18 (Mþ)
1072.4093, found: 1072.4109.
4.2.1. 1-Allyloxy-4-benzyloxybenzene (6s). A suspension
of 4-benzyloxyphenol (1.0 g, 5.0 mmol), 3-bromopopene
(0.43 mL, 5.0 mmol), and K2CO3 (0.828 g, 6.0 mmol) in
acetone (10 mL) was refluxed for 20 h. Then, a saturated
aqueous NH4Cl solution was added and the mixture was
extracted with Et2O. The organic extracts were washed with
brine, dried and evaporated under reduced pressure to give a
solid, which was recrystallized from Et2O–hexane to afford
6s (0.850 g, 71%) as colorless crystals; mp 57–58 8C
(Et2O–hexane); 1H NMR d 7.28–7.44 (5H, m), 6.83–6.92
(4H, m), 5.97–6.13 (1H, m), 5.24–5.43 (1H, m), 5.01 (2H,
s), 4.48 (2H, dt, J¼5.1 Hz, 1.5 Hz); MS m/z 240 (Mþ);
HRMS m/z calcd for C16H16O2 (Mþ) 240.1152, found:
240.1145.
4.2.2. 2-Allyloxy-4-(2-tetrahydropyranyloxy)methyl-1-
methoxybenzene (6t). A solution of O-allylisovanillyl
alcohol (3.0 g, 15.5 mmol), 3,4-dihydro-2H-pyrane
(1.68 mL, 18.4 mmol), and p-TsOH (0.060 g, 3.1 mmol)
in CH2Cl2 (40 mL) was stirred at rt for 20 h. The mixture
was washed with a saturated aqueous NaHCO3 solution and
brine, successively, then dried and evaporated under
reduced pressure to give an oily residue, which was purified
by column chromatography (hexane/AcOEt¼6:1) to give 6t
(1.56 g, 36%) as a colorless oil; 1H NMR d 6.83–6.94 (3H,
m), 6.02–6.17 (1H, m), 5.25–5.45 (2H, m), 4.70, 4.02 (each
1H, d, J¼11.8 Hz), 4.60–4.63 (3H, m), 3.89–3.96 (1H, m),
3.87 (3H, s), 3.50–3.58 (1H, m), 1.50–1.91 (6H, m); MS
m/z 278 (Mþ); HRMS m/z calcd for C16H22O4 (Mþ)
278.1516, found: 278.1511.
4.1.3. Deallylation of O-allylvanillin (3) (Table 1, entry
4). A mixture of 3 (0.100 g, 0.52 mmol) and 10% Pd/C
(0.020 g) in MeOH (10 mL) was refluxed for 24 h. The
mixture was filtered by suction and the filtrate was
evaporated under reduced pressure. Purification of the
residue on preparative TLC (hexane/AcOEt¼3:1) afforded
vanilline (0.022 g, 28%), 5a24 (0.009 g, 9%), 5b (0.007 g,
5%) and 3 (0.049 g, 49%).
4.1.4. 4-Dimethoxymethyl-2-methoxy-1-propenyloxy-
1
benzene (5b). Oil; H NMR d 7.04 (1H, d, J¼1.5 Hz),
6.95–6.96 (2H, m), 6.29 (1H, dq, J¼12.9, 1.7 Hz), 5.34
(1H, s), 4.91 (1H, dt, J¼12.9, 6.9 Hz), 3.90 (3H, s), 3.33
(6H, s), 1.74 (3H, dd, J¼1.7, 6.9 Hz); MS m/z 208 (Mþ);
HRMS m/z calcd for C13H18O4 (Mþ) 238.1205, found:
238.1202.
4.2.3. 2-Allyloxy-4-allyloxymethyl-1-methoxybenzene
(6u). To a suspension of O-allylisovanillyl alcohol (1.0 g,
5.2 mmol) and 60% NaH (0.424 g, 10.6 mmol) in DMF
(10 mL) at 0 8C was added 2-bromopropene (0.45 mL,
5.15 mmol) over a period of 10 min. After being stirred at rt
for 18 h, the reaction was quenched with a saturated
aqueous NH4Cl solution. The mixture was extracted with
a mixture of AcOEt and benzene. The organic extracts were
washed with brine, then dried and evaporated in vacuo to
give an oily residue, which was purified by distillation under
reduced pressure (150 8C/4 mm Hg) to afford 6u (0.950 g,
4.1.5. Deallylation of O-allylvanillin (3) (Table 1, entry
5). A mixture of 3 (0.100 g, 0.52 mmol) and 10% Pd/C
(0.020 g) in 10% KOH–MeOH (10 mL) was stirred at rt for
8 h. The mixture was filtered by suction and the filtrate was
evaporated under reduced pressure. Water was added to the
residue and the mixture was washed with ether. After the
aqueous layer was acidified with 1 M HCl, the mixture was
extracted with AcOEt. The organic extracts were washed
with brine and dried. The solvent was evaporated under
reduced pressure to give vanillin (4) (0.076 g, 96%), of
1
79%) as a colorless oil; H NMR d 6.81–6.92 (3H, m),
5.87–6.16 (2H, m), 5.16–5.44 (4H, m) 4.61 (2H, dt, J¼5.4,
1.6 Hz), 4.43 (2H, s), 3.99 (2H, dt, J¼5.7, 1.4 Hz), 3.85 (3H,
s); MS m/z 234 (Mþ); HRMS m/z calcd for C14H18O3 (Mþ)
234.1254, found: 234.1248.

M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
7979
4.3. General procedure for deallylation of O-allylphenols
(6a–y)
97%), 1226 (0.021 g, 79%) and 1330a (0.002 g, 7%). (b)
With Pd(PPh3)4; a solution of 11 (0.050 g, 0.16 mmol) and
Pd(PPh3)4 (0.001 g) in 10% KOH–MeOH (15 mL) was
stirred at rt for 1.5 h. Evaporation of the solvent afforded a
residue, which was partitioned into a mixture of ether and
water. The organic layer was washed with brine, then dried
and evaporated in vacuo to give an inseparable mixture of
1330a and 1430b (0.031 g, 100%, 13/14¼86/14). The
aqueous layer was acidified with 3 M HCl and extracted
with AcOEt. The organic extracts were washed with brine,
then dried and evaporated in vacuo to give vanillin (0.024 g,
100%). The ratio of 13 to 14 was determined by integration
of the peaks due to the methoxyl groups in 1H NMR
spectroscopy.
A mixture of an O-allylphenol (100 mg) and 10% Pd/C
(20 mg) in 10% KOH–MeOH (10 mL) was stirred at rt for
an appropriate time. After the catalyst was filtered out, the
filtrate was concentrated in vacuo. Water was added to
the residue and the mixture was washed with ether. After the
aqueous layer was acidified with 1 M HCl, the mixture was
extracted with AcOEt. The organic extracts were washed
with brine and dried. The solvent was evaporated under
reduced pressure to give the corresponding phenol (7a–q,26
r,25l s,26 t, u). The ether layer was washed with brine, then
dried and evaporated in vacuo to give a residue, which was
purified by preparative TLC to afford the enol ethers
(8f,26g,26 j,27a k,26 l,27a m,26 n,27b o,27c u) and/or propyl
ethers (9j,28a k28b).
4.3.6. Reaction of 13 with 10% Pd/C. A mixture of 13
(0.040 g, 0.21 mmol) and 10% Pd/C (0.008 g) in 10%
KOH–MeOH (5 mL) was stirred at rt for 10 h. The usual
work-up gave a residue, which was purified by preparative
TLC (hexane/AcOEt¼5:1) to yield 1531a (0.034 g, 67%)
and 1631b (0.006 g, 10%).
4.3.1. 5-(Tetrahydropyran-2-yloxymethyl)-2-methoxy-
1
phenol (7t). Oil; H NMR d 6.92 (1H, d, J¼1.3 Hz), 6.80
(1H, dd, J¼1.3, 8.3 Hz), 6.76 (1H, d, J¼8.3 Hz), 5.71 (1H,
s), 4.65, 4.36 (each 1H, d, J¼11.6 Hz), 4.63–4.68 (1H, m),
3.86–3.93 (1H, m), 3.79 (3H, s), 3.48–3.56 (1H, m), 1.48–
1.86 (6H, m); MS m/z 238 (Mþ); HRMS m/z calcd for
C13H18O4 (Mþ) 238.1203, found: 238.1198.
4.3.7. Reaction of 14 with 10% Pd/C. A mixture of 14
(0.100 g, 0.52 mmol) and 10% Pd/C (0.020 g) in 10%
KOH–MeOH (10 mL) was stirred at rt for 22 h. The usual
work-up gave a residue, which was purified by preparative
TLC (benzene) to yield 1732 (0.052 g, 52%) and 1826
(0.011 g, 12%).
4.3.2. 5-Allyloxymethyl-2-methoxyphenol (7u). Oil; 1H
NMR d 6.93 (1H, s), 6.83 (2H, s), 5.59–6.01 (1H, m), 5.59
(1H, s), 5.20–5.33 (2H, m), 4.43 (2H, s), 4.00 (2H, dt,
J¼4.3, 1.5 Hz), 3.89 (3H, s); MS m/z 194 (Mþ); HRMS m/z
calcd for C11H14O3 (Mþ) 194.0942, found: 194.0940.
4.3.8. 4-Allyloxy-1,1-dimethylcyclohexane (20). To a
suspension of 4,4-dimethylcyclohexanol (19, 0.640 g,
5.0 mmol) and 55% NaH (0.262 g, 6.0 mmol) in DMF
(25 mL) at rt was added 2-bromopropene (0.52 mL,
6.0 mmol) over a period of 5 min. After being stirred for
1 h, the reaction was quenched with saturated aqueous
NH4Cl. The mixture was extracted with Et2O. The organic
extracts were washed with brine, then dried and evaporated
in vacuo to give an oily residue, which was purified by bulb-
to-bulb distillation (130 8C/40 mm Hg) to afford 20
1
4.3.3. 2-Methoxy-5-propoxymethylphenol (8u). Oil; H
NMR d 6.93 (1H, s), 6.82 (2H, s), 5.71 (1H, s), 4.40 (2H, s),
3.86 (3H, s), 3.40 (2H, t, J¼6.6 Hz), 1.56–1.66 (2H, m),
0.93 (3H, t, J¼7.4 Hz); m/z 196 (Mþ).
4.3.4. O-[3-(3,4-Methylenedioxyphenyl)-2-propenyl]-
vanillin (11). To
a solution of vanillin (0.456 g,
3.0 mmol), 1029 (0.535 g, 3.0 mmol), and PPh3 (0.790 g,
3.0 mmol) in THF (15 mL) at 0 8C was added DEAD
(1.312 g, 3.0 mmol). After being stirred for 2 h, PPh3
(0.395 g, 1.5 mmol) and DEAD (0.656 g, 1.5 mmol) were
added and the mixture was stirred for an additional 24 h.
Then, the solvent was evaporated under reduced pressure to
give an oily residue. Ether was added to the mixture and the
precipitates were filtered. Evaporation of the filtrate in
vacuo gave a residue, which was purified by column
chromatography (hexane/benzene/AcOEt¼5:5:1) to give 11
(0.426 g, 46%) as colorless crystals; mp 130–131 8C
(0.662 g, 79%) as a colorless oil; H NMR d 5.93 (1H,
1
ddt, J¼17.1 Hz, 10.2, 5.5 Hz), 5.27(1H, ddd, J¼1.5, 3.3,
17.1. Hz), 5.15 (1H, ddd, J¼1.5, 3.3, 10.2 Hz), 4.00 (2H, dt,
J¼5.5, 1.5 Hz), 3.22–3.31 (1H, m), 1.72–1.83 (2H, m),
1.39–1.54 (4H, m), 1.12–1.22 (2H, m), 0.92, 0.90 (each 3H,
s); MS m/z 168 (Mþ); HRMS m/z calcd for C11H20O (Mþ)
168.1512, found: 168.1505.
4.3.9. Deallylation of 20. A mixture of 20 (0.100 g,
0.60 mmol) and 10% Pd/C (0.020 g) in 10% KOH–
MeOH (10 mL) was stirred at rt for 24 h. The usual work-
up gave an inseparable mixture of 21 and 22. (0.096 g, 95%,
(E)-21/(Z)-21/22¼14/36/50). The ratio of (E)-21 to (Z)-21
was determined by integration of the peaks due to the
1
(AcOEt–hexane); H NMR d 9.82 (1H, s), 7.44 (1H, dd,
J¼1.7, 8.0 Hz), 7.42 (1H, d, J¼8.0 Hz), 7.00 (1H, d,
J¼8.0 Hz), 6.93 (1H, d, J¼1.5 Hz), 6.82 (1H, dd, J¼1.2,
8.1 Hz), 6.74 (1H, d, J¼8.1 Hz), 6.64 (1H, d, J¼15.8 Hz),
6.26 (1H, dt, J¼6.0, 15.8 Hz), 5.93 (2H, s), 4.79 (2H, d,
J¼6.0 Hz), 3.93 (3H, s); MS m/z 312 (Mþ); HRMS m/z
calcd for C18H16O5 (Mþ) 312.0998, found: 312.0990.
1
olefinic protons in H NMR spectroscopy. The ratio of 21
and 22 was determined by integration of the peaks due to C1
1
protons in H NMR spectroscopy.
1
Compound 21. H NMR d 6.08 (0.28H, brd, J¼12.3 Hz),
4.3.5. Deallylation of 11. (a) With 10% Pd/C; a mixture of
11 (0.050 g, 0.16 mmol) and 10% Pd/C (0.010 g) in 10%
KOH–MeOH (15 mL) was stirred at rt for 10 h. The usual
work-up gave a residue, which was purified by preparative
TLC (hexane/AcOEt¼10:1) to yield vanillin (0.024 g,
5.98 (0.72H, brd, J¼6.5 Hz), 4.88 (0.28H, dq, J¼6.4,
12.3 Hz), 4.38 (0.72H, qui, J¼6.5 Hz), 3.52–3.62 (1H, m),
1.40–1.82 (9H, m), 1.14–1.28 (2H, m), 0.87–0.98 (6H, m).
Compound 22. 1H NMR d 3.89 (2H, t, J¼6.8 Hz),

7980
M. Ishizaki et al. / Tetrahedron 60 (2004) 7973–7981
The 124th Annual Meeting of the Pharmaceutical Society of
Japan (Osaka), March, Abstracts 2004, 2, 64.
3.15–3.41 (1H, m), 1.73–1.79 (2H, m), 1.38–1.64 (6H, m),
1.17 (2H, brt, J¼13.3 Hz), 0.92 (3H, t, J¼6.3 Hz), 0.92,
0.91 (each 3H, s).
20. (a) Fatiadi, A. J. Synthesis 1987, 959. (b) Fatiadi, A. J.
Synthesis 1986, 249. (c) Penetta, C. A.; Heimer, N. E.; Hussey,
C. L.; Metzger, R. M. Synlett 1991, 302. (d) Aviram, A.;
Ratner, M. A. Chem. Phys. Lett. 1974, 29, 277.
Acknowledgements
21. Some recent example of Pd(I) species; Hama, T.; Liu, X.;
Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
11176. (b) Hooper, M. W.; Utsunomiya, M.; Hartwig, J. F.
J. Org. Chem. 2003, 68, 2861. (c) Abdul, J. M.; Yamada, T.;
Fujinami, S.; Honjo, T.; Nishikawa, H. Polyhedron 2001, 20,
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The authors are grateful to Mrs F. Hasegawa of this faculty
for her mass spectral measurements.
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