Palladium on carbon-diethylamine-mediated hydrodeoxygenation of phenol derivatives under mild conditions

Article abstract of DOI:10.1016/j.tet.2006.11.060

We have found that phenolic hydroxyl groups were readily deoxygenated via aryl sulfonate under the Pd/C-catalyzed hydrogenation conditions in the presence of diethylamine and the method could also be applicable to the hydrodeoxygenation of morphine to afford 3-deoxy-7,8-dihydromorphine. Diethylamine is not only a scavenger of the corresponding methanesulfonic acid derivative, which is produced during the reaction progress, but also a strong promoter of the Pd/C-catalyzed reduction of aryl sulfonates. This catalyst system could provide a general method for the deoxygenation of various phenol derivatives because of its mild reaction conditions, ease of handling, and no need of particular apparatus.

Full text of DOI:10.1016/j.tet.2006.11.060

Tetrahedron 63 (2007) 1270–1280
Palladium on carbon-diethylamine-mediated hydrodeoxygenation
of phenol derivatives under mild conditions
Akinori Mori, Tomoteru Mizusaki, Takashi Ikawa, Tomohiro Maegawa, Yasunari Monguchi
*
and Hironao Sajiki
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Received 11 October 2006; accepted 15 November 2006
Available online 12 December 2006
Abstract—We have found that phenolic hydroxyl groups were readily deoxygenated via aryl sulfonate under the Pd/C-catalyzed hydroge-
nation conditions in the presence of diethylamine and the method could also be applicable to the hydrodeoxygenation of morphine to afford
3-deoxy-7,8-dihydromorphine. Diethylamine is not only a scavenger of the corresponding methanesulfonic acid derivative, which is produced
during the reaction progress, but also a strong promoter of the Pd/C-catalyzed reduction of aryl sulfonates. This catalyst system could provide
a general method for the deoxygenation of various phenol derivatives because of its mild reaction conditions, ease of handling, and no need of
particular apparatus.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
concerns. Direct deoxygenation methods previously re-
ported in the literature could only be applied to quite re-
stricted phenol derivatives, because of the drastic reaction
conditions and low yields.6 Reductive cleavage methods of
a phenolic hydroxyl group after converting to the corre-
sponding leaving group, such as sulfonate,7–9 isourea,7,10
dimethylthiocarbamate,7 aryl ether,11 5-phenyltetrazolyl
ether,12 and phosphate ester,13 are known as deoxygenation
methods of phenol derivatives. Nevertheless, these conven-
tional methods still have some disadvantages: the lack of sta-
bility of the activated intermediates; the requirement of an
environmentally harmful phosphine ligand and/or a vast
amount of catalysts or hydride reducing agents. A Pd-cata-
lyzed hydrogenative removal of phenolic hydroxyl groups
using aryl mesylates in the presence of triethylamine, which
was carried out under comparatively mild reaction condi-
tions, was reported by Jensen and Clauss in 1973.8b How-
ever, the communication did not clarify the scope and
limitation of their method. Moreover, according to our pre-
liminary results the cleavage of the methanesulfonyloxy
group was incomplete using their conditions. Therefore, de-
veloping a general, practical, and environmentally benign
method for the deoxygenation of phenolic hydroxyl groups
is still a subject of great importance in synthetic organic
chemistry. We recently developed a Pd/C-catalyzed deoxy-
genation method of phenolic hydroxyl groups via aryl tri-
flates or mesylates using Mg metal in MeOH under an
argon atmosphere.14 Although various types of aryl triflates
could undergo deoxygenation using this method, hydrolysis
of triflates to phenol was observed when electron-deficient
aryl triflates were employed as a substrate. We also reported
a facile and effective Pd/C-catalyzed hydrodehalogenation
Many natural products containing phenol moieties isolated
from plants, animals, and bacteria are known as biologically
active compounds, such as antimicrobial essential oils1 and
antiallergic,2 antitumor,3 and antioxidant polyphenols.4
Medicinal chemists have been strongly attracted to such
natural products with phenolic hydroxyl groups, which
play an important role in the biological activities. Therefore,
a number of structure activity relationship studies on pheno-
lic hydroxyl groups of the bioactive compounds have been
carried out.5 Deoxygenated derivatives of such phenolic
hydroxyl groups containing bioactive compounds have
also been of great interest for the biological studies. For
the preparation of such deoxygenated derivatives, the con-
ventional methods in the literature are categorized into the
following two types: (1) the multistep synthetic methods
starting from small synthons without phenolic hydroxyl
groups and (2) the deoxygenation of phenolic hydroxyl
groups in a direct manner6 or through an activation of the
hydroxyl groups as a leaving group based upon chemical
modifications.7–14 While the former multistep synthetic
methods (1) have some problems in terms of time- and
cost-efficiencies, the latter methods (2) would be highly
efficient and practical.
Although some methods for the deoxygenation of phenolic
hydroxyl groups were reported, they have some drawbacks
from the aspect of practical utility and environmental
* Corresponding author. Tel.: +81 58 237 3931; fax: +81 58 237 5979;
e-mail: sajiki@gifu-pu.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.060

A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1271
of aromatic halides in the presence of triethylamine,15 and
expected that the modification and optimization of the reac-
tion conditions would make the dechlorination method ap-
plicable to the hydrodeoxygenation of aryl sulfonates. In
this paper we describe a general method for the deoxygen-
ation of phenolic hydroxyl groups by a simple and practical
Pd/C-catalyzed hydrogenolysis of aryl sulfonates, together
with the detailed mechanistic study.
To explore the scope and limitation of our method, the deoxy-
genation of a variety of phenol derivatives was examined
(Table 2). Electron-deficient substrates were readily hydro-
genolyzed under the conditions to obtain the corresponding
arene products (entries 1–3 and 5). When a reducible
Table 2. Pd/C-catalyzed hydrogenolysis of various aryl mesylatesa
Et2NH (1.2 equiv)
10% Pd/C (10 wt %)
MeOH, H2 (balloon)
time, rt
-
-
Ar OMs
Ar H
2. Results and discussion
Initially, a Pd/C-catalyzed hydrogenolysis of methyl 4-meth-
anesulfonyloxyphenylacetate (1a) was performed under an
ordinary hydrogen pressure (balloon) using 10% Pd/C
(10 wt % of 1a) and 1.2 equiv of a nitrogen-containing
base as an additive in a solvent at room temperature (Table
1). While the reductive cleavage of the methanesulfonyloxy
group did not proceed without an additive (entry 1), the ad-
dition of ammonia or ethylamine completed the hydrogeno-
lysis of 1a in 21 or 22 h, respectively (entries 2 and 3).
Furthermore, diethylamine dramatically affected the reactiv-
ity to complete the reduction within 4 h (entry 4). However,
the addition of triethylamine was not effective as already
mentioned in Section 1.8b The hydrogenolysis of mesylate
(1a) could not be completed even after 48 h (entry 11).
The addition of an aromatized heterocyclic base such as pyr-
idine and quinoline did not lead to completion of the deoxy-
genation of 1a (entries 12 and 13). According to these
results, it was found that diethylamine was the most effective
additive among the nitrogen-containing bases that we inves-
tigated. Further investigation using a variety of solvents re-
vealed that the use of an alcoholic solvent, especially
MeOH, was highly effective for the hydrogenolysis (entries
4–10). Based on these results, the optimum conditions for
the deoxygenation of 1a were determined as follows: treat-
ment of 1a with 10% Pd/C (10 wt % of 1a) and 1.2 equiv
of diethylamine at room temperature under an ordinary hy-
drogen pressure (balloon).
Entry
1
Substrate
Product
Time Yield
(h) (%)b
MsO
H
18 92
20 95
1b
2b
CO2Me
CO2Me
CO2H
2
MsO
MsO
H
1c
2c
CO2Bn
3
19 91
57 96
H
1d
2d
MsO
NO2
H
NH2
4c
1e
2e
O
OH
Ph
Ph
5
17 90
MsO
H
2f
1f
CH2Ph
CH2Ph
H
6d
24 94
OMs
1g
2g
Table 1. Optimization of the reaction conditionsa
OMe
OMe
OMe
OMe
7e
58 79
additive (1.2 equiv)
CH2CO2Me
CH2CO2Me
MsO
H
10% Pd/C (10 wt %)
1h
2h
Solvent, H2 (balloon)
MsO
H
NHAc
NHAc
1a
2a
8f
129 82
1a:2ab
MsO
H
Entry
Additive
Solvent
Time (h)
1i
2i
1
2
3
4
5
6
7
8
None
NH3
MeOH
MeOH
MeOH
MeOH
EtOH
i-PrOH
THF
AcOEt
DMF
H2O
48
21
22
4
32
24
48
48
48
48
48
48
48
100:0
0:100
0:100
0:100
3:97
0:100
32:68
80:20
19:81
68:32
63:37
23:77
100:0
MsO
H
EtNH2
Et2NH
Et2NH
Et2NH
Et2NH
Et2NH
Et2NH
Et2NH
Et3N
9g
24 88h
1j
2j
OMs
H
10
31 91
9
10
11
12
13
1k
2k
MeOH
MeOH
MeOH
Pyridine
Quinoline
OMs
H
a
The reaction was carried out using 1a (244 mg, 1.00 mmol), 10% Pd/C
(24.5 mg, 10 wt % of 1a), and an additive (1.20 mmol) in a solvent
(2 mL) under an ordinary hydrogen pressure (balloon) with vigorous stir-
ring at room temperature (ca. 20 ꢀC).
11e
29 99
N
H
N
H
1l
2l
The ratio was determined by 1H NMR analysis.
b
(continued)

1272
A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
Table 3. Pd/C-catalyzed hydrogenolysis of various aryl triflatesa
Table 2. (continued)
Et2NH (1.2 equiv)
10% Pd/C (10 wt %)
MeOH, H2 (balloon)
time, rt
Entry
Substrate
Product
Time Yield
(h) (%)b
-
-
Ar OTf
Ar H
MsO
O
O
Ph
H
O
Ph
12i
24 71
Entry
1
Substrate
Product
Time (h) Yield (%)b
O
2m
OMe
OMe
1m
6
89
82
TfO
TfO
OMe
H
OMe
OMe
OMe
3h
2h
OMe
OMe
OMe
OMe
13
48 Trace
NHAc
NHAc
MsO
H
1n
2n
2
3
4.5
H
a
2i
Unless otherwise noted, the reaction was carried out using 1.0 mmol of the
substrate in MeOH (2.0 mL) with 10% Pd/C (10 wt % of the substrate)
and Et2NH (1.2 mmol) with vigorous stirring at room temperature
(ca. 20 ꢀC) under an ordinary hydrogen pressure (balloon).
Isolated yield.
After 48 h, additional 10% Pd/C (10 wt % of the substrate) and 1.2 equiv
of Et2NH were added into the reaction mixture.
The reaction was carried out in the presence of 15 wt % of 10% Pd/C and
1.5 equiv of Et2NH.
3i
OTf
H
b
c
1
4
48c
2k
3k
d
e
f
OMe
OMe
The reaction was carried out in the presence of 30 wt % of 10% Pd/C and
3.0 equiv of Et2NH.
OMe
OMe
OMe
OMe
4c
99
The reaction was carried out in the presence of 15 wt % of 10% Pd/C and
1.5 equiv of Et2NH and after 48 h, additional 10% Pd/C (10 wt % of the
substrate) and 1.2 equiv of Et2NH were added into the reaction mixture.
The reaction was carried out in the presence of 10% Pd/C (20 wt % of the
substrate) and 2.4 equiv of Et2NH.
TfO
H
3n
2n
g
a
Unless otherwise noted, the reaction was carried out using 1.0 mmol of the
substrate in MeOH (2.0 mL) with 10% Pd/C (10 wt % of the substrate)
and Et2NH (1.2 mmol) with vigorous stirring at room temperature
(ca. 20 ꢀC) under an ordinary hydrogen pressure (balloon).
Isolated yield.
Conversion yield determined by 1H NMR.
h
i
The reaction was carried out in the presence of 10% Pd/C (30 wt % of the
substrate) and 3.6 equiv of Et2NH.
b
c
The low isolated yield of the product is due to the volatile nature.
functionality such as olefin, benzyl ester, nitro, or aromatic
ketone was contained within the substrate, the reduction of
such functionalities as well as hydrogenolysis of the mesy-
loxy group took place (entries 3–5). In the case of the sub-
strate (1e) the reduction of the nitro group proceeded in
preference to the mesyloxy group and the generated amine
diminished the catalyst activity of Pd/C to prolong the re-
action time since amines generally work as a catalyst poison
for the Pd/C-catalyzed hydrogenolysis16 (entry 4). While the
introduction of electron-donating groups on the aromatic
ring of the substrate decreased the reactivity, simple modifi-
cation of the reaction conditions, such as increasing the
amount of catalyst loading or an additive, achieved the
complete deoxygenation of even electron sufficient sub-
strates to obtain the desired arene products in good yields
(entries 6–9). Moreover, naphthalene, indole, and flavone
derivatives were also applicable (entries 10–12).
hydrogenolyses of other aryl triflates were also proceeded
smoothly (within 6 h) under these reaction conditions to
give the corresponding arenes (Table 3).
Further application of a triflate was investigated. The deoxy-
genation of a bioactive morphine derivative (3o) proceeded
smoothly accompanying the hydrogenation of the olefin
within the molecule of 3o to afford 3-deoxy-7,8-dihydro-
morphine (2o) in excellent yield (Scheme 1). Eventually, it
was revealed that our method is applicable to the deoxygen-
ation of complicated biologically active substances.
Me
Me
N
N
Et2NH (1.2 equiv)
10% Pd/C
MeOH, H2 (balloon)
24 h, rt
As a limitation, the introduction of three electron-donating
methoxy groups on the benzene ring acutely reduced the
reactivity of the substrate and no hydrogenolysis of the
mesyloxy group of 1n occurred even after any optimization
of the reaction conditions (Table 2, entry 13). In order to
apply our method to such highly electron sufficient phenol
derivative, we examined the use of the corresponding aryl
triflate (3n) in the place of aryl mesylate (1n). The Pd/C-
catalyzed reductive cleavage of the trifluoromethanesulfo-
nyloxy group of 3n in the presence of diethylamine
(1.2 equiv) under an ordinary hydrogen pressure gave the
corresponding arene (2n) within 4 h in quantitative yield
(Table 3, entry 4). It is noteworthy that the triflate was
never hydrolyzed under the reaction conditions. The
O
3o
O
2o
TfO
OH
H
OH
94%
Scheme 1. Hydrogenolysis of the morphine derivative (3o).
We next planned to clarify the reaction mechanism of the
hydrogenolysis of aryl sulfonates. Since the reactivity
significantly depended on the types of the amines used
(Table 1), the additive may work not only as a scavenger
of methanesulfonic or trifluoromethanesulfonic acid, which
is generated as the reaction progresses, but also as a strong
activator of the catalytic process. We assume that a single
electron transfer (SET) from diethylamine as an additive

A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1273
directly or indirectly (via Pd metal) to the substrate is the
initial step in the catalytic cycle.15a The reaction also
smoothly proceeded by the addition of Mg metal, which
can be a single electron donor, in lieu of diethylamine
(Scheme 2).
phenyl radical C and then, the deoxygenated product D and
a stoichiometric amount of diethylamine methanesulfonate
is generated.17
In the case of arylsulfonyloxy derivatives used as substrates,
the hydrodeoxygenation would not proceed since an initial
SET from diethylamine takes place exclusively toward the
benzene ring of the arylsulfonyl group rather than of the
phenolic moiety because of lower electron density of the
former benzene ring (Scheme 6).
Mg (0.5 equiv)
CH2CO2Me
CH2CO2Me
10% Pd/C
MeOH, H2 (balloon)
24 h, rt
MsO
H
1a
2a
99%
Scheme 2. Pd/C-catalyzed hydrogenolysis of 1a promoted by Mg metal in
lieu of Et2NH.
Et2NH Et2NH
O O
S
O O
S
Pd
O
O
On the other hand, the diethylamine-promoted hydrogeno-
lysis of aryl mesylates was thoroughly suppressed by the
addition of 0.01 equiv of TCNQ (7,7,8,8-tetracyanoquino-
dimethane) as a single electron capture to the reaction
mixture (Scheme 3).
R
R
Et2NH
Et2NH
E
F
Scheme 6. Reaction mechanism in the case of aryl sulfonates.
TCNQ (0.01 equiv)
Et2NH (1.2 equiv)
CH2CO2Me
CH2CO2Me
3. Conclusion
10% Pd/C
MeOH, H2 (balloon)
24 h, rt
MsO
H
We have developed a mild and an efficient method for the
hydrodeoxygenation of phenolic hydroxyl groups via
a methanesulfonyloxy or trifluoromethanesulfonyloxy func-
tionality under the Pd/C-catalyzed hydrogenation conditions
in the presence of diethylamine. The reaction is likely to
involve an SET mechanism from diethylamine to the aro-
matic ring of aryl mesylates or aryl triflates. All reagents
for the hydrogenation are commercially available and this
method is very simple, widely applicable, and environmen-
tally benign (e.g., heterogeneous catalyst and ligandless).
Present efforts would contribute to a wide variety of syn-
thetic organic chemistry fields including process chemistry
as well as medicinal chemistry.
1a
2a
Scheme 3. Additive effect of a single electron capture.
Furthermore, when the arylsulfonyloxy derivatives (4a–8a)
were used as substrates, the reductive cleavage of the
arylsulfonyloxy groups did not proceed and the starting
materials were entirely recovered (Scheme 4).
Et2NH (1.2 equiv)
CH2CO2Me
CH2CO2Me
10% Pd/C
O O
S
MeOH, H2 (balloon)
24 h, rt
Ar
O
H
4a : Ar = p-Me-C6H4
5a : Ar = p-Ph-C6H4
2a
i
6a : Ar = 2,4,6-tri-Pr-C6H2
7a : Ar = p-F-C6H4
8a : Ar = naphth-2-yl
4. Experimental
4.1. General
Scheme 4. Investigation of a variety of sulfonates under the hydrodeoxyge-
nation conditions.
10% Pd/C was purchased from Aldrich (catalog no. 205699).
MeOH, i-PrOH, and distilled water for HPLC, dehydrated
AcOEt and dehydrated DMF were purchased from Wako
Pure Chemical Industries, Ltd. and used without purifica-
tion. THF and CH2Cl2 were distilled from sodium benzophe-
none ketyl and calcium hydride, respectively. All other
reagents were purchased from commercial sources and
used without further purification. Flash column chromato-
graphy was performed with silica gel Merck 60 (230–
400 mesh ASTM), or Kanto Chemical Co., Inc. 60N
On the basis of these results, we speculated the reaction
mechanism of this reaction as illustrated in Scheme 5. The
reaction is initiated via an SET from diethylamine to the
benzene ring of A, which is activated by coordination of
Pd, to form an anion radical B. The subsequent elimination
of the methanesulfonyl anion of B affords the corresponding
Et2NH
H
OMs
OMs
e-
1
(63–210 mm spherical, neutral). H NMR and 13C NMR
Pd
spectra were recorded on a JEOL AL 400 spectrometer or
1
JEOL EX 400 spectrometer (400 MHz for H NMR and
A
B
D
C
100 MHz for 13C NMR). Chemical shifts (d) are expressed
in parts per million and are internally referenced
(0.00 ppm for TMS and CDCl3 and 2.49 ppm for DMSO-
MsO-
e-
Et2NH
Et2NH
H
Pd
H
MsO
1
d6 for H NMR and 77.0 ppm for CDCl3 and 39.5 ppm for
DMSO-d6 for 13C NMR). Elemental analyses were
performed by a YANAKO CHN CORDER MT-5 instrument.
EI and FAB mass spectra were taken on a JEOL
JMS-SX102A instrument.
MsOH
Et2NH·MsOH
Scheme 5. Plausible reaction mechanism of the reductive cleavage of aryl
mesylates.

1274
A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
4.2. General procedure for the synthesis of aryl
mesylates
as a colorless solid. 1H NMR (CDCl3) d 8.14 (d, 2H,
J¼8.8 Hz), 7.44–7.34 (m, 7H), 5.37 (s, 2H), 3.17 (s, 3H);
13C NMR (CDCl3) d 165.4, 152.4, 135.6, 131.7, 129.1,
128.6, 128.3, 128.1, 121.8, 66.9, 37.7; MS (EI) m/z 306
(M+, 27), 199 (100), 121 (25), 91 (53); HRMS (EI) Calcd
for C15H14O5S (M+): 306.0562. Found: 306.0552. Anal.
Calcd for C15H14O5S: C, 58.81; H, 4.61. Found: C, 58.79;
H, 4.54.
To a solution of a phenol (10.0 mmol) and triethylamine
(1.67 mL, 12.0 mmol) in dichloromethane, THF or DMF
(20 mL) was added dropwise methanesulfonyl chloride
(0.929 mL, 12.0 mmol) and the mixture was stirred at ambi-
ent temperature. After a certain reaction time the volatile was
concentrated under reduced pressure. The residue was ex-
tracted with ethyl acetate (20 mL) and water (20 mL). The
organic layer was washed with saturated aqueous sodium hy-
drogen carbonate solution (20 mL), 10% aqueous sodium
hydrogen sulfonate solution (20 mL), and brine (20 mL),
dried over MgSO4, and concentrated under reduced pressure.
If necessary, the residue was purified by flash column
chromatography on silica gel or recrystallization.
4.2.5. 4-Methanesulfonyloxy-40-nitrobiphenyl (1e). Ob-
tained from 4-hydroxy-40-nitrobiphenyl (645 mg, 3.00 mmol),
triethylamine (0.502 mL, 3.60 mmol), and methanesulfonyl
chloride (0.279 mL, 3.60 mmol) according to the general
procedure for the synthesis of aryl mesylates after 1.5 h of
the reaction without any purification, in 100% yield
1
(879 mg) as a yellow solid. H NMR (CDCl3) d 8.32 (dd,
2H, J¼2.0 and 6.7 Hz), 7.72–7.66 (m, 4H), 7.43 (dd, 2H,
J¼2.0 and 6.7 Hz), 3.21 (s, 3H); 13C NMR (CDCl3)
d 149.5, 147.3, 146.0, 138.1, 129.1, 127.8, 124.2, 122.8,
37.6; MS (EI) m/z 293 (M+, 70), 214 (100), 184 (17), 156
(29), 139 (59), 128 (23); HRMS (EI) Calcd for
C13H11NO5S (M+): 293.0358. Found: 293.0364. Anal. Calcd
for C13H11NO5S: C, 53.24; H, 3.78; N, 4.78. Found: C,
53.17; H, 3.79; N, 4.65.
4.2.1. Methyl 4-methanesulfonyloxyphenylacetate (1a).
Obtained from methyl 4-hydroxyphenylacetate (1.66 g,
10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and meth-
anesulfonyl chloride (0.929 mL, 12.0 mmol) according to
the general procedure for the synthesis of aryl mesylates af-
ter 1 h of the reaction without any purification, in 94% yield
(2.29 g) as a colorless solid. 1H NMR (CDCl3) d 7.32 (d, 2H,
J¼8.6 Hz), 7.23 (d, 2H, J¼8.6 Hz), 3.69 (s, 3H), 3.62 (s,
2H), 3.12 (s, 3H); 13C NMR (CDCl3) d 171.4, 148.3,
133.4, 131.0, 122.1, 52.2, 40.4, 37.3; MS (EI) m/z 244
(M+, 85), 185 (75), 166 (42), 107 (100), 78 (34), 44 (30);
HRMS (EI) Calcd for C10H12O5S (M+): 244.0405. Found:
244.0396. Anal. Calcd for C10H12O5S: C, 49.17; H, 4.95.
Found: C, 49.08; H, 4.99.
4.2.6. (E)-3-(4-Methanesulfonyloxyphenyl)-1-phenyl-2-
propen-1-one (1f). Obtained from 4-hydroxychalcone
(2.25 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol),
and methanesulfonyl chloride (0.929 mL, 12.0 mmol)
according to the general procedure for the synthesis of aryl
mesylates after 1 h of the reaction followed by recrystalliza-
tion (ethyl acetate–/n-hexane) in 71% yield (2.10 g) as
a yellow solid. 1H NMR (CDCl3) d 8.01 (d, 2H,
J¼8.8 Hz), 7.79 (d, 1H, J¼15.6 Hz), 7.70 (d, 2H,
J¼8.3 Hz), 7.61 (t, 1H, J¼7.3 Hz), 7.54–7.49 (m, 3H),
7.35 (d, 2H, J¼8.8 Hz), 3.19 (s, 3H); 13C NMR (CDCl3)
d 190.1, 150.3, 142.8, 137.9, 134.1, 133.0, 130.0, 129.0,
128.8, 128.7, 128.5, 123.1, 122.6, 37.6; MS (EI) m/z 302
(M+, 32), 223 (100), 195 (23), 167 (24); HRMS (EI) Calcd
for C16H14O4S (M+): 302.0613. Found: 302.0603. Anal.
Calcd for C16H14O4S: C, 63.56; H, 4.67. Found: C, 63.42;
H, 4.63.
4.2.2. 4-Methanesulfonyloxybiphenyl (1b). Obtained
from 4-hydroxybiphenyl (1.70 g, 10.0 mmol), triethylamine
(1.67 mL, 12.0 mmol), and methanesulfonyl chloride
(0.929 mL, 12.0 mmol) according to the general procedure
for the synthesis of aryl mesylates after 19 h of the reaction
followed by recrystallization (ethyl acetate/n-hexane) in
1
63% yield (1.57 g) as a colorless solid. H NMR (CDCl3)
d 7.62 (d, 2H, J¼8.8 Hz), 7.55 (d, 2H, J¼7.3 Hz), 7.45 (d,
2H, J¼7.3 Hz), 7.39–7.35 (m, 3H), 2.97 (s, 3H); 13C NMR
(CDCl3) d 148.5, 140.6, 139.7, 128.9, 128.7, 127.7, 127.1,
122.3, 37.3; MS (EI) m/z 248 (M+, 43), 169 (100), 141
(45), 115 (28); HRMS (EI) Calcd for C13H12O3S (M+):
248.0507. Found: 248.0500. Anal. Calcd for C13H12O3S:
C, 62.88; H, 4.87. Found: C, 62.79; H, 4.93.
4.2.7. 2-Benzylphenyl methanesulfonate (1g). Obtained
from 2-benzylphenol (1.84 g, 10.0 mmol), triethylamine
(1.67 mL, 12.0 mmol), and methanesulfonyl chloride
(0.929 mL, 12.0 mmol) according to the general procedure
for the synthesis of aryl mesylates after 2 h of the reaction
followed by flash column chromatography on silica gel
(n-hexane/Et2O¼10/1) in 96% yield (2.51 g) as a colorless
4.2.3. Methyl 4-methanesulfonyloxybenzoate (1c).18 Ob-
tained from methyl 4-hydroxybenzoate (1.52 g, 10.0 mmol),
triethylamine (1.67 mL, 12.0 mmol), and methanesulfonyl
chloride (0.929 mL, 12.0 mmol) according to the general
procedure for the synthesis of aryl mesylates after 20 h of
the reaction followed by flash column chromatography on
silica gel (n-hexane) in 94% yield (2.17 g) as a colorless
1
solid. H NMR (CDCl3) d 7.39 (d, 1H, J¼7.8 Hz), 7.31–
7.18 (m, 8H), 4.08 (s, 2H), 2.97 (s, 3H); 13C NMR
(CDCl3) d 147.6, 139.5, 133.8, 131.6, 128.9, 128.5, 127.8,
127.2, 126.3, 121.7, 37.7, 36.2; MS (EI) m/z 262 (M+, 52),
183 (100), 181 (85), 165 (50); HRMS (EI) Calcd for
C14H14O3S (M+): 262.0664. Found: 262.0670; Anal. Calcd
for C14H14O3S: C, 64.10; H, 5.38. Found: C, 64.00; H, 5.49.
1
solid. H NMR spectrum of 1c was identical with that in
the literature.18
4.2.4. Benzyl 4-methanesulfonyloxybenzoate (1d). Ob-
tained from benzyl 4-hydroxybenzoate (2.28 g, 10.0 mmol),
triethylamine (1.67 mL, 12.0 mmol), and methanesulfonyl
chloride (0.929 mL, 12.0 mmol) according to the general
procedure for the synthesis of aryl mesylates after 1.5 h of
the reaction without any purification, in 99% yield (3.05 g)
4.2.8. 3,4-Dimethoxyphenyl methanesulfonate (1h).
Obtained from 3,4-dimethoxyphenol (771 mg, 5.00 mmol),
triethylamine (0.836 mL, 6.00 mmol), and methanesulfonyl
chloride (0.465 mL, 6.00 mmol) according to the general
procedure for the synthesis of aryl mesylates after 1.5 h of

A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1275
the reaction followed by flash column chromatography on
silica gel (n-hexane/Et2O¼10/1/2/1) in 77% yield
(892 mg) as a colorless solid. 1H NMR (CDCl3) d 6.84 (m,
3H), 3.89 (s, 3H), 3.14 (s, 3H); 13C NMR (CDCl3)
d 149.6, 148.1, 142.7, 113.3, 111.1, 106.2, 56.2, 37.0; MS
(EI) m/z 232 (M+, 28), 153 (100), 125 (32), 110 (15);
HRMS (EI) Calcd for C9H12O5S (M+): 232.0405. Found:
232.0400. Anal. Calcd for C9H12O5S: C, 46.54; H, 5.21.
Found: C, 46.40; H, 5.24.
Et2O¼20/1/1/1) in 49% yield (1.04 g) as a colorless solid.
1H NMR (CDCl3) d 8.35 (br s, 1H), 7.36 (d, 1H, J¼8.3 Hz),
7.25 (d, 1H, J¼2.9 Hz), 7.19 (t, 1H, J¼8.1 Hz), 7.10 (d, 1H,
J¼7.8 Hz), 6.68 (br s, 1H), 3.17 (s, 3H), 2.04 (s, 3H); 13C
NMR (CDCl3) d 142.1, 138.0, 125.4, 122.2, 121.6, 112.7,
110.6, 99.5, 37.5; MS (EI) m/z 211 (M+, 39), 132 (100),
104 (43), 84 (15); HRMS (EI) Calcd for C9H9NO3S (M+):
211.0303. Found: 211.0294. Anal. Calcd for C9H9NO3S:
C, 51.17; H, 4.29; N, 6.63. Found: C, 51.39; H, 4.36; N, 6.53.
4.2.9. 4-Acetamidophenyl methanesulfonate (1i). Ob-
tained from 4-acetamidophenol (1.51 g, 10.0 mmol), triethyl-
amine (1.67 mL, 12.0 mmol), and methanesulfonyl chloride
(0.929 mL, 12.0 mmol) according to the general procedure
for the synthesis of aryl mesylates after 72 h of the reaction
followed by flash column chromatography on silica gel
(CHCl3 only /CHCl3/MeOH¼100/1) in 69% yield
4.2.13. 7-Methanesulfonyloxyflavone (1m). Obtained from
7-hydroxyflavone (1.20 g, 5.00 mmol), triethylamine
(0.836 mL, 6.00 mmol), and methanesulfonyl chloride
(0.465 mL, 6.00 mmol) according to the general procedure
for the synthesis of aryl mesylates after 24 h of the reaction
followed by flash column chromatography on silica gel
(CHCl3/MeOH¼100/1) in 65% yield (1.02 g) as a colorless
solid. 1H NMR (CDCl3) d 8.30 (d, 1H, J¼8.8 Hz), 7.92 (dd,
2H, J¼2.0 and 8.4 Hz), 7.60–7.53 (m, 4H), 7.32 (dd, 1H,
J¼2.0 and 8.4 Hz), 6.84 (s, 1H), 3.27 (s, 3H); 13C NMR
(CDCl3) d 177.2, 164.0, 156.6, 131.9, 131.2, 129.1, 127.9,
126.3, 122.8, 119.2, 111.7, 107.8, 38.1; MS (EI) m/z 316
(M+, 100), 238 (33), 209 (90); HRMS (EI) Calcd for
C16H12O5S (M+): 316.0405. Found: 316.0413.
1
(1.59 g) as a colorless solid. H NMR (DMSO-d6) d 10.09
(br s, 1H), 7.64 (d, 2H, J¼9.3 Hz), 7.27 (d, 2H, J¼9.3 Hz),
3.33 (s, 3H), 2.04 (s, 3H); 13C NMR (DMSO-d6) d 168.6,
144.3, 138.6, 122.7, 120.3, 37.3, 24.1; MS (EI) m/z 229
(M+, 24), 150 (18), 108 (100), 80 (10); HRMS (EI) Calcd
for C9H11NO4S (M+): 229.0409. Found: 229.0412. Anal.
Calcd for C9H11NO4S: C, 47.15; H, 4.84; N, 6.11. Found:
C, 46.98; H, 6.05; N, 6.05.
4.2.14. 3,4,5-Trimethoxyphenyl methanesulfonate (1n).
Obtained from 3,4,5-trimethoxyphenol (1.84 g, 10.0 mmol),
triethylamine (1.67 mL, 12.0 mmol), and methanesulfonyl
chloride (0.929 mL, 12.0 mmol) according to the general
procedure for the synthesis of aryl mesylates after 19 h of
the reaction followed by recrystallization (ethyl acetate/
4.2.10. 4-Cyclohexylphenylmethanesulfonate (1j).
Obtained from 4-cyclohexylphenol (881 mg, 5.00 mmol),
triethylamine (0.836 mL, 6.00 mmol), and methanesulfonyl
chloride (0.465 mL, 6.00 mmol) according to the general
procedure for the synthesis of aryl mesylates after 1 h of
the reaction followed by flash column chromatography on
silica gel (n-hexane) in 99% yield (1.26 g) as a colorless
1
n-hexane) in 96% yield (2.52 g) as a colorless solid. H
NMR (CDCl3) d 6.53 (s, 2H), 3.86 (s, 6H), 3.83 (s, 3H),
3.16 (s, 3H); 13C NMR (CDCl3) d 153.6, 144.9, 136.9, 99.4,
60.8, 56.2, 37.2; MS (EI) m/z 262 (M+, 32), 183 (100), 168
(27), 155 (16), 125 (11), 69 (13); HRMS (EI) Calcd for
C10H14O5S (M+): 262.0511. Found: 262.0516. Anal. Calcd
for C10H14O5S: C, 45.79; H, 5.38. Found: C, 45.63; H, 5.39.
1
solid. H NMR (CDCl3) d 7.24 (d, 2H, J¼8.5 Hz), 7.19 (d,
2H, J¼8.5 Hz), 3.12 (s, 3H), 2.55–2.48 (m, 1H), 1.90–1.85
(m, 4H), 1.79–1.73 (m, 1H), 1.45–1.32 (m, 4H), 1.30–1.22
(m, 1H); 13C NMR (CDCl3) d 147.5, 147.2, 128.3, 121.7,
44.0, 37.2, 34.4, 26.8, 26.0; MS (EI) m/z 254 (M+, 100),
198 (20), 175 (32), 131 (20), 119 (38), 107 (33), 84 (23);
HRMS (EI) Calcd for C13H18O3S (M+): 254.0977. Found:
254.0986. Anal. Calcd for C13H18O3S: C, 61.39; H, 7.13.
Found: C, 61.22; H, 7.07.
4.3. General procedure of the hydrodeoxygenation
of 1a (Table 1)
After two vacuum/H2 cycles to replace air inside the reaction
tube with hydrogen, a mixture of 1a (244 mg, 1.00 mmol),
10% Pd/C (24.5 mg, 10 wt % of 1a), and an additive
(1.20 mmol) in a solvent (2.0 mL) was vigorously stirred
at room temperature (ca. 20 ꢀC) under an ordinary hydrogen
pressure (balloon). After a certain reaction time the reaction
mixture was filtered using a membrane filter (Millipore, Mil-
lexÒ-LH, 0.45 mm) and the filtrate was partitioned between
Et2O (10 mL) and water (10 mL). The aqueous layer was
extracted with Et2O (10 mLꢁ3) and the combined organic
layers were washed with brine (10 mL), dried with
anhydrous MgSO4, filtered, and concentrated under reduced
pressure to afford a mixture of 1a and 2a. The ratio of 1a and
2a was determined by 1H NMR analysis.
4.2.11. 1-Naphthyl methanesulfonate (1k). Obtained from
1-naphthol (1.44 g, 10.0 mmol), triethylamine (1.67 mL,
12.0 mmol), and methanesulfonyl chloride (0.929 mL,
12.0 mmol) according to the general procedure for the syn-
thesis of aryl mesylates after 2 h of the reaction followed by
flash column chromatography on silica gel (n-hexane/
Et2O¼5/1) in 97% yield (2.16 g) as a colorless oil. 1H
NMR (CDCl3) d 8.14 (d, 1H, J¼8.8 Hz), 7.90 (d, 1H,
J¼7.3 Hz), 7.82 (d, 1H, J¼8.3 Hz), 7.62–7.46 (m, 4H),
6.21 (s, 3H); 13C NMR (CDCl3) d 145.2, 134.8, 128.0,
127.3, 127.2, 126.9, 125.3, 121.4, 118.3, 37.8; MS (EI)
m/z 222 (M+, 30), 143 (75), 115 (100); HRMS (EI) Calcd
for C11H10O3S (M+): 222.0351. Found: 222.0358.
4.2.12. 4-Methanesulfonyloxyindole (1l). Obtained from 4-
hydroxyindole (1.33 g, 10.0 mmol), triethylamine (1.67 mL,
12.0 mmol), and methanesulfonyl chloride (0.929 mL,
12.0 mmol) according to the general procedure for the
synthesis of aryl mesylates after 1 h of the reaction followed
by flash column chromatography on silica gel (n-hexane/
4.3.1. Methyl phenylacetate (2a). Obtained from 1a
(244 mg, 1.00 mmol), 10% Pd/C (24.5 mg, 10 wt % of 1a),
and diethylamine (0.124 mL, 1.20 mmol) according to the
general procedure of the hydrodeoxygenation after 4 h of
the reaction without any purification, in 89% yield
1
(134 mg) as a colorless oil. H NMR spectrum of 2a was

1276
A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1
identical with that of the commercial authentic sample from
Tokyo Chemical Industry Co., Ltd.
(190 mg) as a colorless oil. H NMR spectrum of 2f was
identical with that in the literature.20
4.4. General procedure for the hydrodeoxygenation
of aryl mesylates (Table 2)
4.4.6. Diphenylmethane (2g). Obtained from 1g (131 mg,
500 mmol), 10% Pd/C (26.3 mg, 20 wt % of 1g), and diethyl-
amine (0.103 mL, 1.00 mmol) according to the general
procedure of the hydrodeoxygenation after 24 h of the re-
action without any purification, in 94% yield (79.8 mg) as
a colorless oil. H NMR spectrum of 2g was identical with
that of the commercial authentic sample from Tokyo Chem-
ical Industry Co., Ltd.
After two vacuum/H2 cycles to replace air inside the reaction
tube with hydrogen, a mixture of the substrate (500 mmol),
10% Pd/C (10 wt % of the substrate) and diethylamine
(62.1 mL, 600 mmol) in MeOH (1.0 mL) was vigorously
stirred at room temperature (ca. 20 ꢀC) under an ordinary
hydrogen pressure (balloon). After a certain reaction time
the reaction mixture was filtered using a membrane filter
(Millipore, MillexÒ-LH, 0.45 mm) and the filtrate was parti-
tioned between Et2O (10 mL) and water (10 mL). The aque-
ous layer was extracted with Et2O (10 mLꢁ3) and the
combined organic layers were washed with brine (10 mL),
dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure to afford the corresponding deoxy-
genated product (2a–2m).
1
4.4.7. 1,2-Dimethoxybenzene (2h). Obtained from 1h
(101 mg, 500 mmol), 10% Pd/C (30.5 mg, 30 wt % of 1h),
and diethylamine (0.155 mL, 1.50 mmol) according to the
general procedure of the hydrodeoxygenation after 58 h of
the reaction without any purification, in 79% yield
1
(54.6 mg) as a colorless oil. H NMR spectrum of 2h was
identical with that of the commercial authentic sample
from Tokyo Chemical Industry Co., Ltd.
4.4.1. Biphenyl (2b). Obtained from 1b (248 mg,
1.00 mmol), 10% Pd/C (24.8 mg, 10 wt % of 1b), and diethyl-
amine (0.124 mL, 1.20 mmol) according to the general
procedure of the hydrodeoxygenation after 18 h of the reac-
tion without any purification, in 92% yield (141 mg) as
a colorless solid. H NMR spectrum of 2b was identical
with that of the commercial authentic sample from Tokyo
Chemical Industry Co., Ltd.
4.4.8. Acetanilide (2i). Obtained from 1i (110 mg,
500 mmol), 10% Pd/C (27.5 mg, 25 wt % of 1i), and diethyl-
amine (0.130 mL, 1.25 mmol) according to the general
procedure of the hydrodeoxygenation after 129 h of the
reaction without any purification, in 82% yield (55.4 mg)
as a colorless solid. H NMR spectrum of 2i was identical
with that of the commercial authentic sample from Tokyo
Chemical Industry Co., Ltd.
1
1
4.4.2. Methyl benzoate (2c). Obtained from 1c (115 mg,
500 mmol), 10% Pd/C (11.6 mg, 10 wt % of 1c), and diethyl-
amine (62.1 mL, 600 mmol) according to the general proce-
dure of the hydrodeoxygenation after 20 h of the reaction
without any purification, in 95% yield (64.5 mg) as a color-
less oil. 1H NMR spectrum of 2c was identical with that of
the commercial authentic sample from Tokyo Chemical
Industry Co., Ltd.
4.4.9. Cyclohexylbenzene (2j).21 Obtained from 1j
(127 mg, 500 mmol), 10% Pd/C (25.6 mg, 20 wt % of 1j),
and diethylamine (0.124 mL, 1.20 mmol) according to the
general procedure of the hydrodeoxygenation after 24 h of
the reaction in 82% conversion yield. H NMR spectrum
of 2j was identical with that in the literature.21
1
4.4.10. Naphthalene (2k). Obtained from 1k (220 mg,
1.00 mmol), 10% Pd/C (22.2 mg, 10 wt % of 1k), and
diethylamine (0.124 mL, 1.20 mmol) according to the gen-
eral procedure of the hydrodeoxygenation after 31 h of the
reaction without any purification, in 91% yield (116 mg)
4.4.3. Benzoic acid (2d). Obtained from 1d (306 mg,
1.00 mmol), 10% Pd/C (30.6 mg, 10 wt % of 1d), and di-
ethylamine (0.124 mL, 1.20 mmol) according to the general
procedure of the hydrodeoxygenation after 19 h of the
reaction without any purification, in 91% yield (111 mg)
1
as a colorless solid. H NMR spectrum of 2k was identical
with that of the commercial authentic sample from Aldrich.
1
as a colorless solid. H NMR spectrum of 2d was iden-
tical with that of the commercial authentic sample from
Aldrich.
4.4.11. Indole (2l). Obtained from 1l (105 mg, 500 mmol),
10% Pd/C (21.2 mg, 20 wt % of 1l), and diethylamine
(0.124 mL, 1.20 mmol) according to the general procedure
of the hydrodeoxygenation after 29 h of the reaction without
any purification, in 99% yield (58.5 mg) as a colorless solid.
1H NMR spectrum of 2l was identical with that of the com-
mercial authentic sample from Tokyo Chemical Industry
Co., Ltd.
4.4.4. 4-Phenylaniline (2e).19 Obtained from 1e (147 mg,
500 mmol), 10% Pd/C (14.7 mg, 10 wt % of 1e), and diethyl-
amine (62.1 mL, 600 mmol) according to the general proce-
dure of the hydrodeoxygenation after 48 h of the reaction,
followed by another 9 h of the reaction after the addition
of additional 10% Pd/C (14.7 mg, 10 wt % of 1e) and diethyl-
amine (62.1 mL, 600 mmol), without any purification, in 96%
yield (81.1 mg) as a colorless solid. 1H NMR spectrum of 2e
was identical with that in the literature.19
4.4.12. Flavone (2m). Obtained from 1m (79.1 mg,
250 mmol), 10% Pd/C (23.7 mg, 30 wt % of 1m), and
diethylamine (93.1 mL, 900 mmol) according to the general
procedure of the hydrodeoxygenation after 24 h of the reac-
tion followed by flash column chromatography on silica gel
(CHCl3) in 71% yield (39.2 mg) as a colorless solid.
1H NMR spectrum of 2m was identical with that of the
commercial authentic sample from Tokyo Chemical
Industry Co., Ltd.
4.4.5. 1,3-Diphenylpropan-1-ol (2f).20 Obtained from 1f
(302 mg, 1.00 mmol), 10% Pd/C (30.2 mg, 10 wt % of 1f),
and diethylamine (0.124 mL, 1.20 mmol) according to the
general procedure of the hydrodeoxygenation after 17 h of
the reaction without any purification, in 90% yield

A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1277
4.5. General procedure for the synthesis of aryl triflates
(Table 3)22
partitioned between Et2O (10 mL) and water (10 mL). The
aqueous layer was extracted with Et2O (10 mLꢁ3) and the
combined organic layers were washed with brine (10 mL),
dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure to afford the corresponding de-
oxygenated product.
To a cooled (0 ꢀC) biphasic mixture of toluene (10 mL), 30%
(w/v) aqueous K3PO4 (10 mL), and phenol (5.00 mmol) was
added dropwise trifluoromethanesulfonic anhydride
(1.02 mL, 6.00 mmol) at a rate to maintain the reaction tem-
perature below 10 ꢀC. The reaction was allowed to warm to
ambient temperature and the mixture was stirred for 30 min.
The layers were separated and the toluene layer was washed
with water (10 mL), dried over MgSO4, and then concen-
trated under reduced pressure. If necessary, the residue
was purified by flash column chromatography on silica gel.
4.6.1. 1,2-Dimethoxybenzene (2h). Obtained from 3h
(143 mg, 500 mmol), 10% Pd/C (14.4 mg, 10 wt % of 3h),
and diethylamine (62.1 mL, 600 mmol) according to the gen-
eral procedure of the hydrodeoxygenation of aryl triflates
after 6 h of the reaction without any purification, in 89%
1
yield (61.3 mg) as a colorless oil. H NMR spectrum of 2h
was identical with that of the commercial authentic sample
from Tokyo Chemical Industry Co., Ltd.
4.5.1. 3,4,5-Trimethoxyphenyl trifluoromethanesulfonate
(3n).23 Obtained from 3,4,5-trimethoxyphenol (921 mg,
5.00 mmol), according to the general procedure for the syn-
thesis of aryl triflates after 0.5 h of the reaction without any
4.6.2. Acetanilide (2i). Obtained from 3i (115 mg,
500 mmol), 10% Pd/C (11.5 mg, 10 wt % of 3i), and diethyl-
amine (62.1 mL, 600 mmol) according to the general proce-
dure of the hydrodeoxygenation of aryl triflates after 4.5 h
of the reaction without any purification, in 82% yield
1
purification, in 97% yield (1.54 g) as a colorless solid. H
NMR spectrum of 3n was identical with that in the litera-
ture.23
1
(55.5 mg) as a colorless solid. H NMR spectrum of 2i
was identical with that of the commercial authentic sample
from Tokyo Chemical Industry Co., Ltd.
4.5.2. 3,4-Dimethoxyphenyl trifluoromethanesulfonate
(3h). Obtained from 3,4-dimethoxyphenol (771 mg,
5.00 mmol), according to the general procedure for the syn-
thesis of aryl triflates after 2 h of the reaction followed by
flash column chromatography on silica gel (n-hexane/
4.6.3. Naphthalene (2k). Obtained from 3k (111 mg,
500 mmol), 10% Pd/C (11.2 mg, 10 wt % of 3k), and diethyl-
amine (62.1 mL, 600 mmol) according to the general proce-
dure of the hydrodeoxygenation of the aryl triflates after
1 h of the reaction without any purification, in 48% yield
1
Et2O¼10/1) in 94% yield (1.34 g) as a colorless solid. H
NMR (CDCl3) d 6.85 (d, 2H, J¼2.4 Hz), 6.78 (d, 1H,
J¼2.2 Hz), 3.90 (s, 3H), 3.89 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 149.5, 148.6, 142.7, 118.5 (q, J¼321 Hz), 112.7,
111.0, 105.1, 55.9, 49.7; MS (EI) m/z 286 (M+, 28), 153
(100), 125 (30). HRMS (EI) Calcd for C9H9O5F3S (M+):
286.0123. Found: 286.0116.
1
(30.9 mg) as a colorless solid. H NMR spectrum of 2k
was identical with that of the commercial authentic sample
from Aldrich.
4.6.4. 1,2,3-Trimethoxybenzene (2n). After two vacuum/
H2 cycles to replace air inside the reaction tube with hydro-
gen, a mixture of 3n (79.1 mg, 250 mmol), 10% Pd/C
(8.0 mg, 10 wt % of 3n) and diethylamine (31.0 mL,
300 mmol) in MeOH (1.0 mL) was vigorously stirred at
room temperature (ca. 20 ꢀC) at an ordinary hydrogen
pressure (balloon) for 4 h. The reaction mixture was filtered
using a membrane filter (Millipore, MillexÒ-LH, 0.45 mm)
and the filtrate was partitioned between Et2O (10 mL) and
water (10 mL). The aqueous layer was extracted with Et2O
(10 mLꢁ3) and the combined organic layers were washed
with brine (10 mL), dried with anhydrous MgSO4, filtered,
and concentrated under reduced pressure to afford 2n in
4.5.3. 4-Acetamidophenyl trifluoromethanesulfonate
(3i).24 Obtained from 4-acetamidophenol (756 mg,
5.00 mmol), according to the general procedure for the
preparation of aryl triflates after 0.5 h of the reaction
followed by flash column chromatography on silica gel
(CHCl3/MeOH¼100/1) in 53% yield (747 mg) as a colorless
solid. 1H NMR spectrum of 3i was identical with that in the
literature.24
4.5.4. 1-Naphthalenyl trifluoromethanesulfonate (3k).8h
Obtained from 1-naphthol (721 mg, 5.00 mmol), according
to the general procedure of the preparation for aryl triflates
after 0.5 h of the reaction followed by flash column chroma-
tography on silica gel (n-hexane) in 84% yield (1.16 g) as
a colorless oil. 1H NMR spectrum of 3k was identical with
that in the literature.8h
1
99% yield (84.1 mg) as a colorless oil. H NMR spectrum
of 2n was identical with that of the commercial authentic
sample from Tokyo Chemical Industry Co., Ltd.
4.6.5. 3-Deoxy-7,8-dihydromorphine (2o) (Scheme 1).
After two vacuum/H2 cycles to replace air inside the reaction
tube with hydrogen, a mixture of 3o (20.9 mg, 50.0 mmol),
10% Pd/C (2.1 mg, 10 wt % of 3o), and diethylamine
(6.20 mL, 60.0 mmol) in MeOH (0.5 mL) was vigorously
stirred at room hydrogen pressure (balloon) and temperature
(ca. 20 ꢀC) for 24 h. The reaction mixture was filtered using
a membrane filter (Millipore, MillexÒ-LH, 0.45 mm) and the
filtrate was partitioned between CHCl3 (10 mL) and water
(10 mL). The aqueous layer was extracted with CHCl3
(10 mLꢁ3) and the combined organic layers were washed
with brine (10 mL), dried with anhydrous MgSO4, filtered,
4.6. General procedure for the hydrodeoxygenation of
aryl triflates (Table 3)
After two vacuum/H2 cycles to replace air inside the reaction
tube with hydrogen, a mixture of the substrate (500 mmol),
10% Pd/C (10 wt % of the substrate) and diethylamine
(62.1 mL, 600 mmol) in MeOH (1.0 mL) was vigorously
stirred at room temperature (ca. 20 ꢀC) under an ordinary
hydrogen pressure (balloon). After a certain reaction time
the reaction mixture was filtered using a membrane filter
(Millipore, MillexÒ-LH, 0.45 mm) and the filtrate was

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A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
and concentrated under reduced pressure to afford 2o in 94%
yield (12.7 mg) as a colorless solid. 1H NMR (CDCl3) d 7.10
(t, 1H, J¼7.7 Hz), 6.71 (d, 2H, J¼7.7 Hz), 6.67 (d, 2H,
J¼7.7 Hz), 4.58 (d, 1H, J¼5.3 Hz), 4.09–4.05 (m, 1H),
3.34 (s, 1H), 3.06 (d, 1H, J¼18.8 Hz), 2.79 (d, 1H,
J¼8.2 Hz), 2.61–2.49 (m, 6H), 2.15–2.12 (m, 1H), 1.75–
1.72 (m, 1H), 1.58–1.45 (m, 3H), 1.22–1.16 (m, 2H); 13C
NMR (CDCl3) d 168.1, 158.9, 128.7, 118.6, 106.0, 90.0,
67.4, 60.0, 46.8, 42.8, 39.9, 36.9, 29.7, 26.9, 20.8, 19.1;
MS (EI) m/z 271 (M+, 100), 254 (14), 227 (14), 164 (15),
84 (54); HRMS (EI) Calcd for C17H21NO2 (M+):
271.1572. Found: 271.1558.
(3.61 mmol) and the mixture was stirred at ambient temper-
ature (ca. 20 ꢀC). After a certain reaction time the solvent
was concentrated under reduced pressure. The residue was
extracted with ethyl acetate (10 mL) and water (10 mL).
The organic layer was washed with saturated aqueous
sodium carbonate solution (10 mL), 10% aqueous sodium
hydrogen sulfonate solution (10 mL), and brine (10 mL),
dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by flash column chroma-
tography on silica gel to afford the corresponding arenesul-
fonates (4a–8a).
4.7.1. Methyl 4-(4-toluenesulfonyloxy)phenylacetate
(4a). Obtained from methyl 4-hydroxyphenylacetate
(3.32 g, 20.0 mmol), triethylamine (3.07 mL, 22.0 mmol),
and 4-toluenesulfonyl chloride (4.19 g, 22.0 mmol) accord-
ing to the general procedure for the synthesis of arenesulfo-
nates after 10 h of the reaction followed by flash column
chromatography on silica gel (n-hexane/ethyl acetate¼
10/1/5/1) in 90% yield (5.77 g) as a yellow oil. 1H NMR
(CDCl3) d 7.71 (d, 2H, J¼8.3 Hz), 7.31 (d, 2H, J¼8.3 Hz),
7.20 (d, 2H, J¼8.3 Hz), 6.93 (d, 2H, J¼8.3 Hz), 3.61 (s,
3H), 3.58 (s, 2H), 2.45 (s, 3H); 13C NMR (CDCl3)
d 171.5, 148.7, 145.3, 132.5, 130.5, 129.7, 128.5, 122.4,
52.1, 40.4, 21.7; MS (EI) m/z 320 (M+, 75), 261 (14), 155
(100), 91 (84); HRMS (EI) Calcd for C16H16O5S (M+):
320.0718. Found: 320.0721.
4.6.6. 3-Trifluoromethanesulfonyloxymorphine (3o).25 To
a slurry of morphine hydrochloride (100 mg, 311 mmol)
in dichloromethane (5.0 mL) was added triethylamine
(108 mL, 777 mmol). The mixture was stirred for 2 h and
then N-phenylbis(trifluoromethanesulfonimide) (133 mg,
0.373 mmol) was added. After being stirred for 48 h, 10%
aqueous sodium hydrogen carbonate (10 mL) was added
and the layers were separated. The organic layer was dried
over MgSO4 and then concentrated under reduced pressure.
The residue was purified by flash column chromatography
on silica gel (CHCl3/MeOH¼100/1/10/1) to afford 3o in
62% yield (80.2 mg) as a colorless solid. 1H NMR spectrum
of 3o was identical with that in the literature.25
4.6.7. Additive effect of Mg metal in place of Et2NH
(Scheme 2). After two vacuum/H2 cycles to replace air in-
side the reaction tube with hydrogen, a mixture of 1a
(244 mg, 1.00 mmol), 10% Pd/C (24.5 mg, 10 wt % of 1a),
and Mg metal (12.2 mg, 500 mmol) in MeOH (2.0 mL)
was vigorously stirred at room temperature (ca. 20 ꢀC) under
an ordinary hydrogen pressure (balloon) for 24 h. The reac-
tion mixture was filtered using a membrane filter (Millipore,
MillexÒ-LH, 0.45 mm) and the filtrate was partitioned
between Et2O (10 mL) and water (10 mL). The aqueous
layer was extracted with Et2O (10 mLꢁ3) and the combined
organic layers were washed with brine (10 mL), dried with
anhydrous MgSO4, filtered, and concentrated under reduced
pressure to afford 2a (99% conversion yield) in 60% isolated
yield (89.1 mg).
4.7.2. Methyl 4-(4-biphenylsulfonyloxy)phenylacetate
(5a). Obtained from methyl 4-hydroxyphenylacetate
(500 mg, 3.01 mmol), triethylamine (0.510 mL, 3.61 mmol),
and 4-biphenylsulfonylchloride(913 mg, 3.61 mmol) accord-
ing to the general procedure for the synthesis of arenesulfo-
nates after 66 h of the reaction followed by flash column
chromatography on silica gel (n-hexane/Et2O¼20/1/0/
1
100) in 47% yield (537 mg) as a colorless solid. H NMR
(CDCl3) d 7.90 (d, 2H, J¼8.6 Hz), 7.73 (d, 2H, J¼8.6 Hz),
7.62 (d, 2H, J¼6.8 Hz), 7.52–7.42 (m, 3H), 7.22 (d, 2H,
J¼8.8 Hz), 6.99 (d, 2H, J¼8.8 Hz), 3.69 (s, 3H), 3.59 (s,
2H); 13C NMR (CDCl3) d 171.5, 148.7, 147.1, 133.9, 133.1,
130.6, 129.1, 128.9, 127.7, 127.4, 122.5, 52.2, 40.4; MS (EI)
m/z 382 (M+, 46), 217 (80), 153 (100); HRMS (EI) Calcd
for C21H18O5S (M+):382.0875. Found: 382.0865. Anal. Calcd
for C21H18O5S: C, 65.95; H, 4.74. Found: C, 65.91; H, 4.74.
4.6.8. Additive effect of single electron capture (Scheme
3). After two vacuum/H2 cycles to replace air inside the
reaction tube with hydrogen, a mixture of 1a (244 mg,
1.00 mmol), 10% Pd/C (24.5 mg, 10 wt % of 1a), diethyl-
amine (0.124 mL, 1.20 mmol), and TCNQ (7,7,8,8-tetracya-
noquinodimethane) (2.1 mg, 10.0 mmol) in MeOH (2.0 mL)
was vigorously stirred at room temperature (ca. 20 ꢀC) under
an ordinary hydrogen pressure (balloon) and for 24 h. The re-
action mixturewas filtered using a membrane filter (Millipore,
MillexÒ-LH,0.45 mm)andthe filtratewaspartitionedbetween
Et2O (10 mL) and water (10 mL). The aqueous layer was ex-
tracted with Et2O (10 mLꢁ3)and the combined organic layers
were washed with brine (10 mL), dried with anhydrous
MgSO4, filtered, and concentrated under reduced pressure.
4.7.3. Methyl 4-(2,4,6-triisopropylbenzenesulfonyloxy)-
phenylacetate (6a). Obtained from methyl 4-hydroxyphe-
nylacetate (500 mg, 3.01 mmol), triethylamine (0.510 mL,
3.61 mmol), and 2,4,6-triisopropylphenylsulfonyl chloride
(911 mg, 3.61 mmol) according to the general procedure
for the synthesis of arenesulfonates after 19 h of the reaction
followed by flash column chromatography on silica gel
(n-hexane/Et2O¼10/1) in 88% yield (1.15 g) as a colorless
1
solid. H NMR (CDCl3) d 7.21 (d, 2H, J¼8.6 Hz), 7.19 (s,
2H), 6.96 (d, 2H, J¼8.6 Hz), 4.08–4.01 (m, 2H), 3.66 (s,
3H), 3.58 (s, 2H), 2.95–2.91 (m, 1H), 1.27 (d, 6H,
J¼6.8 Hz), 1.17 (d, 12H, J¼6.8 Hz); 13C NMR (CDCl3)
d 171.4, 154.2, 151.2, 148.5, 132.8, 130.4, 129.6, 123.9,
122.6, 52.1, 40.4, 34.2, 29.7, 24.5, 23.5; MS (EI) m/z 432
(M+, 13), 267 (100), 203 (14), 175 (16), 149 (8), 119 (10),
91 (12); HRMS (EI) Calcd for C24H32O5S (M+): 432.1970.
Found: 432.1978. Anal. Calcd for C24H32O5S: C, 66.64;
H, 7.46. Found: C, 66.57; H, 7.51.
4.7. General procedure for the synthesis of aryl sulfonates
To a solution of methyl 4-hydroxyphenylacetate (500 mg,
3.01 mmol) and triethylamine (0.510 mL, 3.61 mmol) in
dichloromethane (10 mL) was added arenesulfonyl chloride

A. Mori et al. / Tetrahedron 63 (2007) 1270–1280
1279
1202; (b) Sivropoulou, A.; Papanikolaou, E.; Nikolaou, C.;
Kokkini, S.; Lanaras, T.; Arsenakis, M. J. Agric. Food Chem.
1997, 45, 3197.
4.7.4. Methyl 4-(4-fluorobenzenesulfonyloxy)phenyl-
acetate (7a). Obtained from methyl 4-hydroxyphenylacetate
(500 mg, 3.01 mmol), triethylamine (0.510 mL, 3.61 mmol),
and 4-fluorobenzenesulfonyl chloride (586 mg, 3.61 mmol)
according to the general procedure for the synthesis of
arenesulfonates after 2 h of the reaction followed by
flash column chromatography on silica gel (n-hexane/
Et2O¼100/0/0/100) in 91% yield (909 mg) as a colorless
solid. 1H NMR (CDCl3) d 7.96–7.93 (m, 2H), 7.35–7.28 (m,
4H), 7.03 (dd, 2H, J¼2.0 and 6.8 Hz), 3.79 (s, 3H), 3.69 (s,
2H); 13C NMR (CDCl3) d 171.4, 167.2, 164.7, 148.5, 133.2,
131.4, 131.3, 130.6, 122.3, 116.7, 116.4, 52.1, 40.3; MS (EI)
m/z 324 (M+, 100), 265 (43), 159 (97), 121 (48), 95 (64), 78
(20), 91 (12); HRMS (EI) Calcd for C15H13O5FS (M+):
324.0468. Found: 324.0460. Anal. Calcd for C15H13O5FS:
C, 55.55; H, 4.04. Found: C, 55.39; H, 4.04.
2. Akiyama, H.; Sakushima, J.; Taniuchi, A.; Kanda, T.;
Yanagida, A.; Kojima, T.; Teshima, R.; Kobayashi, Y.; Goda,
Y.; Toyoda, M. Biol. Pharm. Bull. 2000, 23, 1370.
3. (a) Yoshida, T.; Chou, T.; Matsuda, M.; Yasuhara, T.; Yazaki,
K.; Hatano, T.; Nitta, A.; Okuda, T. Chem. Pharm. Bull.
1991, 39, 1157; (b) Miyamoto, K.; Nomura, M.; Murayama,
T.; Furukawa, T.; Hatano, T.; Yoshida, T.; Koshiura, R.;
Okuda, T. Biol. Pharm. Bull. 1993, 16, 379.
4. (a) Vinson, J. A.; Hao, Y.; Su, X.; Zubik, L. J. Agric. Food
Chem. 1998, 46, 3630; (b) Barclay, L. R. C.; Edwards, C. E.;
Vinqvist, M. R. J. Am. Chem. Soc. 1999, 121, 6226; (c)
Jovanovic, S. V.; Steenken, S.; Boone, C. W.; Simic, M. G.
J. Am. Chem. Soc. 1999, 121, 9677; (d) Wright, J. S.;
Johnson, E. R.; DiLabio, G. A. J. Am. Chem. Soc. 2001, 123,
1173.
5. For example, see: Reden, J.; Reich, M. F.; Rice, K. C.; Jacobson,
A. E.; Brossi, A.; Streaty, R. A.; Klee, W. A. J. Med. Chem.
1979, 22, 256.
6. (a) Severin, T.; Ipach, I. Synthesis 1973, 796; (b) Konieczny,
M.; Harvey, R. G. J. Org. Chem. 1979, 44, 4813; (c) Node,
M.; Nishide, K.; Ohta, K.; Fujita, E. Tetrahedron Lett. 1982,
23, 689.
4.7.5. Methyl 4-(2-naphthalenesulfonyloxy)phenylace-
tate (8a). Obtained from methyl 4-hydroxyphenyl-
acetate (831 mg, 5.00 mmol), triethylamine (0.836 mL,
6.00 mmol), and 2-naphthalenesulfonyl chloride (1.36 g,
6.00 mmol) according to the general procedure for the syn-
thesis of arenesulfonates after 65 h of the reaction followed
by flash column chromatography on silica gel (n-hexane/
1
Et2O¼10/1) in 83% yield (1.48 g) as a colorless solid. H
€
ꢀ
7. Sebok, P.; Timar, T.; Eszenyi, T. J. Org. Chem. 1994, 59, 6318
and references cited therein.
NMR (CDCl3) d 8.38 (s, 1H), 7.99 (d, 1H, J¼8.8 Hz),
7.95–7.92 (m, 2H), 7.85 (dd, 1H, J¼1.7 and 8.6 Hz), 7.7
(t, 1H, J¼6.8 Hz), 7.63 (t, 1H, J¼6.8 Hz), 7.17 (d, 2H,
J¼8.6 Hz), 6.95 (d, 2H, J¼8.6 Hz), 3.67 (s, 3H), 3.56 (s,
2H); 13C NMR (CDCl3) d 171.4, 148.7, 135.4, 133.0,
132.2, 131.8, 130.6, 130.4, 129.6, 129.5, 128.0, 127.8,
122.8, 122.4, 122.4, 52.1, 40.4; MS (EI) m/z 356 (M+, 33),
191 (53), 127 (100); HRMS (EI) Calcd for C19H16O5S
(M+): 356.0718. Found: 356.0726. Anal. Calcd for
C19H16O5S: C, 64.03; H, 4.53. Found: C, 64.01; H, 4.50.
8. (a) Rottendorf, H.; Sternhell, S. Aust. J. Chem. 1963, 16, 647;
(b) Clauss, K.; Jensen, H. Angew. Chem., Int. Ed. Engl. 1973,
12, 918; (c) Lonsky, W.; Traitler, H.; Kratzl, K. J. Chem.
Soc., Perkin Trans. 1 1975, 169; (d) Subramanian, L. R.
Synthesis 1984, 481; (e) Cacchi, S.; Ciattini, P. G.; Morera, E.;
Ortar, G. Tetrahedron Lett. 1986, 27, 5541; (f) Chen, Q.-Y.;
He, Y.-B.; Yang, Z.-Y. J. Chem. Soc., Chem. Commun. 1986,
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Bernardinis, S. D.; Francalanci, F.; Penco, S.; Santi, R. J. Org.
4.8. Investigation of the leaving group (Scheme 4)
ꢀ
Chem. 1990, 55, 350; (i) Saa, J. M.; Dopico, M.; Martorell, G.;
Garcia-Raso, A. J. Org. Chem. 1990, 55, 991; (j) Sasaki, K.;
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(k) Kotsuki, H.; Datta, P. K.; Hayakawa, H.; Suenaga, H.
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Vivian, R. W. Tetrahedron Lett. 1999, 40, 6871; (m) Lipshutz,
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Int. Ed. 2006, 45, 800.
After two vacuum/H2 cycles to replace air inside the reaction
tube with hydrogen, a mixture of the substrates (4a–8a)
(1.00 mmol), 10% Pd/C (10 wt % of the substrate), diethyl-
amine (0.124 mL, 1.20 mmol) in MeOH (2.0 mL) was vigor-
ously stirred at room temperature (ca. 20 ꢀC) under an
ordinary hydrogen pressure (balloon) for 24 h. The reaction
mixture was filtered using a membrane filter (Millipore, Mil-
lexÒ-LH, 0.45 mm) and the filtrate was partitioned between
Et2O (10 mL) and water (10 mL). The aqueous layer was ex-
tracted with Et2O (10 mLꢁ3) and the combined organic
layers werewashed with brine (10 mL), dried with anhydrous
MgSO4, filtered, and concentrated under reduced pressure.
9. Recently Pd(OAc)2-catalyzed deoxygenation methods using
perfluorated polymer-supported aromatic sulfonates, which
required a phosphine ligands and heating conditions, were
reported, see: (a) Pan, Y.; Holmes, C. P. Org. Lett. 2001, 3,
2769; (b) Cammidge, A. N.; Ngaini, Z. Chem. Commun.
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10. Vowinkel, E.; Baese, H.-J. Chem. Ber. 1974, 107, 1213.
11. (a) Sartoretto, P.; Sowa, F. J. J. Am. Chem. Soc. 1937, 59, 603;
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Acknowledgements
We sincerely thank Professor Bunji Uno at the Laboratory of
Analytical Chemistry in Gifu Pharmaceutical University for
helpful discussion.
12. (a) Musliner, W. J.; Gates, J. W., Jr. J. Am. Chem. Soc. 1966, 88,
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