Mechanistic study of a Pd/C-catalyzed reduction of aryl sulfonates using the Mg-MeOH-NH4OAc system

Article abstract of DOI:10.1002/chem.200601184

A method for the deoxygenation of phenolic hydroxy groups via aryl triflates or mesylates has been established by using a combination of Pd/ C-Mg-MeOH. The addition of NH₄OAc to the system markedly accelerated the reaction rate and expanded the scope of the reaction. Mechanistic studies suggested that a single-electron transfer process from the Pd⁰ center to the benzene ring is involved in the reduction of aryl sulfonates and that NH₄OAc works as a solubilization re agent of the Mg salt and as an accelerator of the electron transfer, thus enhancing the reaction process. Our method was also applicable to the regioselective deuteration of benzene derivatives with CH₃OD as the solvent and deuterium source: the original hydroxy group could be efficiently replaced with a deuterium atom.

Full text of DOI:10.1002/chem.200601184

DOI: 10.1002/chem.200601184
Mechanistic Study of a Pd/C-Catalyzed Reduction of Aryl Sulfonates Using
the Mg–MeOH–NH4OAc System
Akinori Mori, Tomoteru Mizusaki, Takashi Ikawa, Tomohiro Maegawa,
Yasunari Monguchi, and Hironao Sajiki*[a]
Abstract: A method for the deoxyge-
nation of phenolic hydroxy groups via
aryl triflates or mesylates has been es-
tablished by using a combination of Pd/
transfer process from the Pd0 center to
the benzene ring is involved in the re-
duction of aryl sulfonates and that
NH4OAc works as a solubilization re-
agent of the Mg salt and as an acceler-
ator of the electron transfer, thus en-
hancing the reaction process. Our
method was also applicable to the re-
gioselective deuteration of benzene de-
rivatives with CH3OD as the solvent
and deuterium source: the original hy-
droxy group could be efficiently re-
placed with a deuterium atom.
C–Mg–MeOH.
The
addition
of
NH4OAc to the system markedly accel-
erated the reaction rate and expanded
the scope of the reaction. Mechanistic
studies suggested that a single-electron
Keywords: aryl sulfonates · deoxy-
genation · heterogeneous catalysis ·
palladium · single-electron transfer
Introduction
However, these methods include disadvantages such as poor
stability of the activated phenols, severe reaction conditions,
the use of environmentally harmful phosphine ligands, and
the use more than stoichiometric quantities of metal-reduc-
ing reagents. Therefore, establishment of a generally appli-
cable method for the deoxygenation of phenol derivatives is
still a broad developing area.
Recently, we reported a method for a Pd/C–Mg-mediated
cleavage of a phenolic hydroxy group after conversion into
the corresponding aryl triflate or mesylate.[10] This reaction
was remarkably accelerated by the addition of NH4OAc to
the reaction mixture. Herein, we discuss the mechanism of
the reductive cleavage of aryl sulfonates by using the Pd/C–
Mg–MeOH system, including the effect of NH4OAc, and
report on further applications and detailed experimental
procedures.
The development of a deoxygenation method for phenol de-
rivatives is one of the most important subjects in synthetic
organic and medicinal chemistry. Many organic compounds
containing a phenolic moiety are well known as biologically
and functionally important compounds, and phenolic hy-
droxy groups frequently play a crucial role in expressing
those activities.[1] In many cases, the preparation of the cor-
responding non-phenolic derivatives as reference com-
pounds is necessary for structure–activity relationship stud-
ies. Direct deoxygenation methods require both excess
amounts of the reagents and drastic reaction conditions[2]
and have a narrow substrate scope,[2b,c] because it is difficult
to directly cleave phenolic hydroxy groups from the aromat-
ic rings as a result of their stability.
To improve the leaving ability of the phenolic hydroxy
group, it was converted into the corresponding sulfona-
te,[1a,3–5] isourea,[1a,6] dimethyl thiocarbamate,[1a] aryl ether,[7]
5-phenyltetrazolyl ether,[8] and phosphate ether group.[9]
Results and Discussion
In the course of our investigation of novel Pd/C-catalyzed
reactions, we found that the Pd/C-catalyzed reductive cleav-
age of 3,4,5-trimethoxyphenyl triflate (1a) in MeOH took
place in the presence of 0.5 equivalents of Mg metal to give
1,2,3-trimethoxybenzene (2a) in 45% yield (Scheme 1).
This result encouraged us to tune the reaction conditions
(Table 1). No reaction was observed in the absence of the
metal or Pd/C (Table 1, entries 1 and 4, respectively). More-
over, the reduction did not proceed in an oxygen atmos-
[a] A. Mori, T. Mizusaki, Dr. T. Ikawa, Dr. T. Maegawa,
Dr. Y. Monguchi, Prof. Dr. H. Sajiki
Laboratory of Medicinal Chemistry
Gifu Pharmaceutical University
Mitahora-higashi 5-6-1, Gifu 502, 8585 (Japan)
Fax : (+81)58-237-5979
E-mail: sajiki@gifu-pu.ac.jp
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
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Chem. Eur. J. 2007, 13, 1432 – 1441

FULL PAPER
important factor in the prog-
ress of the reaction. From
these experimental results, the
use of a catalytic amount of
Pd/C, a stoichiometric amount
of Mg metal, and MeOH as
the solvent was found to be in-
dispensable for the completion
of the reduction of the aryl tri-
Scheme 1. Our initial study of a Pd/C-catalyzed reductive cleavage of an aryl triflate.
Table 1. Pd/C-Catalyzed reductive cleavage of 3,4,5-trimethoxyphenyl
triflate (1a) using various metals and solvents.[a]
flates. Addition of a catalytic amount of 7,7,8,8-tetracyano-
quinodimethane (TCNQ), a single-electron capture, to the
reaction mixture thoroughly suppressed the reaction, thus
suggesting the participation of a single-electron-transfer
(SET) mechanism in the catalytic process.
To clarify the hydrogen source in this reaction, an investi-
gation was carried out with four types of deuterated metha-
nol as the solvent. It is apparent that the hydrogen (deute-
rium) source in these reactions is the acidic hydrogen (deu-
terium) atom of the methanol used as the solvent (Table 2);
thus, MeOH works as a proton donor in this reaction.
Entry
1none
Metal
Solvent
T [h]
00:0
1a/2a[b]
MeOH
24
1
2
3
Mg[c]
Mg
Mg
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
24
12
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
55:45
0:100
100:0
100:0
100:0
100:0
100:0
100:0
100:0
0:100
100:0
100:0
100:0
100:0
100:0
41:59
100:0
100:0
100:0
100:0
4[d]
5[e]
6
Mg
Mg
Zn
Al
A
7
8
9
Table 2. Determination of the hydrogen source.[a]
Fe
Ni
Mg
Mg
3
Mg
Mg
Mg
Mg
8
9
10
11
12
1
14
15
16
17
1
MeOH
dry MeOH
MeOH/H2O[f]
Mg
2O
H
EtOH
dry EtOH
Entry
Solvent
2a or [D]-2a
Yield [%][b]
EtOH/MeOH[g]
EtOH/MeOH[h]
iPrOH
1CH
3OH
CD3OH
CH3OD
CD3OD
2a
2a
[D]-2a
[D]-2a
89
80
86
76
2
3
4
Mg
Mg
1
3CHCOFH
2
20
Mg
Mg
THF
MeOH
21[i]
[a] Reaction conditions: 1a (79.1mg, 250 mmol), 10% Pd/C (8.0 mg,
10 wt% of 1a), Mg (7.3 mg, 300 mmol), and solvent (1.0 mL) in an Ar at-
mosphere at room temperature for 24 h. [b] Yield of the isolated product.
[a] Reaction conditions: 1a (158 mg, 500 mmol), 10% Pd/C (15.9 mg,
10 wt% of 1a), metal (600 mmol), and solvent (2.0 mL) in an Ar atmos-
phere at room temperature. [b] The ratio was determined by using
1H NMR spectroscopic analysis. [c] 0.5 equivalents. [d] Without 10% Pd/
C. [e] In an O2 atmosphere. [f] 4:1ratio. [g] Addition of 20 equivalents of
MeOH. [h] 1:1 ratio. [i] With TCNQ (0.01 equiv).
Recently, we reported an acceleration effect caused by
the addition of NH4OAc to the Pd/C-catalyzed monoalkyla-
tion of primary amines using nitrile compounds as the alky-
lating reagents.[11] We expected that such an enhancement of
the reactivity could be applicable to the present deoxygena-
tion of the phenolic alcohol moiety, thus leading to the
rapid formation of the deoxygenated product. Therefore, we
investigated the acceleration effect of additives by using 1a
as a substrate (Table 3). The addition of NH4OAc was very
effective for the reaction: the reaction was completed within
1h (Table 3, entries 2 and 3); furthermore, even only a cata-
lytic amount of NH4OAc produced the acceleration effect
(Table 3, entry 4). As shown in Table 3, entries 5–8, other
acetate salts were not effective as additives, as they rather
suppressed the reduction. Moreover, other ammonium salts,
such as NH4HCO3 and (NH4)2CO3, exerted a suppressive
effect on the reaction and caused the hydrolysis of the tri-
flate, thus affording a mixture of the starting material 1a,
product 2a, and hydrolyzed phenol (Table 3, entries 9 and
10).
phere, as the Mg metal surface was readily coated by a layer
of MgO (Table 1, entry 5). Whereas the use of 0.5 equiva-
lents of Mg metal did not lead to complete cleavage of the
triflate group (Scheme 1and Table 1, entry 2), an increase in
the amount of Mg metal up to 1.2 equivalents led to comple-
tion of the deoxygenation reaction (Table 1, entry 3). Nei-
ther Mg(OMe)2 nor other metals, such as Zn, Al, Fe, and
A
Ni, in the place of the Mg metal affected the reaction prog-
ress (Table 1, entries 6–10). The reaction was entirely sol-
vent specific: 1) progress of the reaction was only observed
in MeOH as the solvent (Table 1, entries 3 and 11); 2) the
reduction did not proceed at all in H2O, THF, and other al-
coholic solvents, such as EtOH, iPrOH, and CF3CH2OH
(Table 1, entries 14, 15, and 18–20, respectively); 3) H2O and
EtOH suppressed the reaction (Table 1, entries 12, 13, 16,
and 17). The Mg metal dissolved only in MeOH, thus sug-
gesting the solubility of the Mg metal in the solvent is an
Chem. Eur. J. 2007, 13, 1432 – 1441
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1433

H. Sajiki et al.
Table 3. Effect of an additive on the Pd/C-catalyzed reductive cleavage
NH4OCOCF3, and HCO2NH4 probably facilitate the dissolu-
tion of the Mg metal in MeOH. The addition of AcOH af-
forded a similar result to that of NH4OAc, thus suggesting
that AcOH would work as a solubulizing agent for Mg
metal (Table 4, entry 11).
of 1a.[a]
Next, we found that the number of substituents on the ni-
trogen atom of NH4OAc was very important in producing
the acceleration effect. Whereas Et3NHOAc or Et4NOAc
depressed the reaction progress (Table 4, entries 9 and 10),
EtNH3OAc or Et2NH2OAc afforded a comparable result to
NH4OAc (Table 4, entries 7 and 8). Furthermore, the addi-
Entry
Additive
T [h]
1a/2a/4a[b]
1
2
3
4
5
6
7
8
9
none
12
0.5
10:1
6
24
24
24
24
24
24
0:100:0
2:98:0
NH4OAc
NH4OAc
NH4OAc (0.01equiv)
NaOAc
KOAc
LiOAc
00:0
0:100:0
73:22:6
79:1
80:16:4
100:0:0
9:89:0[c]
17:81:0[c]
tion of a catalytic amount of NH3 (2 equivalents of Pd/C)
5:6
could also accelerate the reaction as well as NH4OAc, but
the same amount of Et3N suppressed the reaction (Table 4,
entries 12 and 13). During the reaction, NH4OAc or
Et3NHOAc would dissociate to NH3 and AcOH or Et3N
and AcOH, respectively. We anticipated that such a differ-
ence between NH4OAc and Et3NHOAc in the additive
effect depends on the coordination ability of the amine
moiety to Pd metal, that is, bulky Et3N should be harder to
coordinate to the Pd center (see also Scheme 2).
Cu
NH4HCO3
(NH4)2CO3
A
10
ACHTREUNG
[a] Reaction conditions: 1a (79.1mg, 250 mmol), 10% Pd/C (8.0 mg,
10 wt% of 1a), Mg (7.3 mg, 300 mmol), additive (250 mmol), and MeOH
(1.00 mL) in an Ar atmosphere at room temperature. [b] The ratio was
determined by using 1H NMR spectroscopic analysis. [c] Formation of
3,4,5-trimethoxyphenol was observed (2%).
Based on the above experimental results, we speculated
that the present reductive deoxygenation process proceeds
through the pathway outlined in Scheme 2. An initial SET[12]
from the Pd0 center to the aromatic ring of the aryl triflate
should afford an anion radical, which could be converted
into an aryl radical by the elimination of the trifluorometha-
nesulfonyloxy (OTf) anion. Then, the second SET process
from the PdI center would take place to give an aryl anion,
and protonation of the anion by MeOH would give the cor-
responding deoxygenated arene product together with PdII,
which should be reduced to Pd0 by the Mg metal. The re-
To explain the acceleration effect of NH4OAc rationally,
we investigated the difference in the reactivity on the basis
of the acidity of the acid counterpart and steric hindrance of
the additives (Table 4). The use of ammonium salts consist-
ing of more acidic counterparts, such as NH4Cl,
NH4OCOCF3, and HCO2NH4, accelerated the reaction to
an extent similar to that with NH4OAc, whereas NH4OBz
was not so effective (Table 4, entries 2–5). NH4OAc, NH4Cl,
sulting magnesium salt Mg
A
G
Table 4. Additive effect on the reductive cleavage of 1a using the deriva-
tives of NH4OAc.[a]
into Mg(OTf)(OAc) in the presence of AcOH, based on the
A
ACHTREUNG
stabilization of the salt, thus generating MeOH and NH3.
Subsequently, the generated NH3 could coordinate to the
Pd0 center to enhance the electron density of Pd; as a result,
Pd-mediated electron transfer to the benzene ring could be
accelerated. NH4OAc works as a dual activator: NH4OAc
should contribute to both the enhanced solubility of the Mg
metal by the formation of AcOH, which causes the quick re-
duction of PdII to Pd0, and the acceleration of the SET pro-
cess by the coordination of NH3 to the Pd0 center. On the
other hand, in the case of the addition of NH4OBz rather
than NH4OAc, the acceleration effect did not take place be-
cause a Pd-mediated electron transfer might have taken
place competitively at the benzene ring of NH4OBz or the
substrate (Table 4, entry 5 and Scheme 3).
To explore the scope of the method, the deoxygenation of
a variety of phenol derivatives was investigated (Table 5).
AcOH, some ammonium salts (e.g, NH4Cl), and ammonia
exhibited an acceleration effect as well as NH4OAc, but
NH4OAc was chosen as the additive because of its cost effi-
ciency and near neutrality. The addition of one equivalent
of NH4OAc (Method B) dramatically improved the reactivi-
ty of electron-sufficient aryl triflates to afford the corre-
sponding reduced products within 1h (Table 5, entries 1–
Entry
Additive
T [h]
1a/2a/4a[b]
0:100:0
1
2
3
4
5
6
7
8
9
none
NH4Cl
NH4OCOCF3
HCO2NH4 00:0
NH4OBz
12
10:1
0.5
10:1
48
10:1
2
10:99:1
24
24
1.5
1.5
00:0
0:100:0
18:82:0
0:96:4
NH4OAc 00:0
EtNH3OAc[c]
Et2NH2OAc
Et3NHOAc[c]
4NOAc
71:24:5
87:10:3
1
11
1
0
Et
AcOH
0:95:5
[d]
3
3N[d]
2
3
NH
Et
0:97:2[e]
1
24
34:65:trace[e]
[a] Reaction conditions: 1a (79.1mg, 250 mmol), 10% Pd/C (8.0 mg,
10 wt% of 1a), Mg (7.3 mg, 300 mmol), additive (250 mmol), and MeOH
(1.00 mL) in an Ar atmosphere at room temperature. [b] The ratio was
1
determined by using H NMR spectroscopic analysis. [c] The additive was
prepared in situ. [d] Reaction conditions: 1a (79.1mg, 250 mmol), 10%
Pd/C (8.0 mg, 3.00 mol% of 1a), Mg (7.3 mg, 300 mmol), additive
(6.00 mol%), and MeOH (1.00 mL) in an Ar atmosphere at room tem-
perature. [e] Formation of 3,4,5-trimethoxyphenol was observed (1%).
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Reduction of Aryl Sulfonates
FULL PAPER
Scheme 2. Plausible reaction mechanism.
presence of NH4OAc (Scheme 5). Deoxygenation did not
proceed presumably because electron transfer from the Pd0
center toward the benzene ring of the toluenesulfonyl group
occurred in preference to that of the phenolic moiety.
The reduction of methyl 4-methanesulfonyloxyphenylace-
tate (6h) did not proceed well in the absence of NH4OAc
(Table 6, entry 1), even after 24 h; however, the addition of
NH4OAc enhanced the reactivity remarkably, thus giving
the desirable methyl phenylacetate in excellent yield
(Table 6, entries 2 and 3). Other aryl mesylates are also ap-
plicable to this reductive deoxygenation process, with excess
amounts of Mg metal and NH4OAc affording the corre-
sponding reduced products in good-to-excellent yields
(Table 6, entries 3–9).
As deuterium-labeled compounds have been useful in the
analysis of drug metabolism, investigation of reaction mech-
anisms, and so forth,[13] the development of facile and regio-
selective deuteration methods is the subject of great interest.
The presented deoxygenation method with CH3OD instead
MeOH as the solvent was examined (Table 7), as the hydro-
gen source in the present method is the acidic hydrogen
atom in MeOH (Table 2). The regioselective deuteration of
the aromatic rings was achieved with a quantitative deuteri-
um efficiency (Table 7). The deuteration method with
Scheme 3. The direction of the SET in NH4OBz.
10). In the case of the electron-deficient substrates 1k and
1l (Table 5, entries 11 and 12), the addition of NH4OAc was
not necessary, and the formation of deoxygenated products
was determined by analysis with GC/MS (100% conversion,
respectively, because of the volatile nature of the products).
When the benzoic ester derivatives 1m and 1n were em-
ployed as substrates, we encountered difficulty in selective
deoxygenation under the optimized conditions (see Table 5,
entries 13 and 14; Methods A and B; and Scheme 4). After
minor tuning of the reaction conditions, an excess amount
of NH4OAc (1.2–5.0 equiv) or/and Mg metal (1.2–2.4 equiv)
achieved the selective reduction of 1m and 1n (Table 5, en-
tries 13 and 14).
We attempted to apply the present method to aryl tosy-
lates and mesylates. When aryl tosylate 5h was used as the
substrate, partial hydrolysis was only observed in the ab-
sence of NH4OAc, whereas no reaction took place in the
Scheme 4. Reductive cleavage of the triflate group of 1m.
Chem. Eur. J. 2007, 13, 1432 – 1441
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1435

H. Sajiki et al.
Table 5. Pd/C-catalyzed reductive cleavage of various aryl triflates.[a]
Entry
1
Substrate
Method
T [h]
Yield [%][b]
Entry
8
Substrate
Method
T [h]
Yield [%][b]
A
B
24
1
95
99
A
B
24
1
80
83
A
B
12
1
95
89
A
B
24
1
90
92
2
9
A
B
24
0.5
90
84
3
4
B
0.5
95
10
A
B
24
1
58
97
[c]
11
A
A
24
24
1
00
00
A
B
24
0.5
98
95
[c]
5
12
13
1
A
B
C
24
24
24
53[d]
0[d]
87
A
B
24
0.5
93
98
6
7
A
B
24
1
99
94
14
B
2.5
92[e]
[a] Method A: substrate (250 mmol), 10% Pd/C (10 wt% of the substrate), Mg (7.3 mg, 300 mmol), and MeOH (1.00 mL) in an Ar atmosphere at room
temperature. Method B: substrate (250 mmol), 10% Pd/C (10 wt% of the substrate), Mg (7.3 mg, 300 mmol), NH4OAc (19.3 mg, 250 mmol), and MeOH
(1.00 mL) in an Ar atmosphere at room temperature. Method C: substrate (250 mmol), 10% Pd/C (10 wt% of the substrate), Mg (14.6 mg, 600 mmol),
NH4OAc (96.4 mg, 1.25 mmol), and MeOH (1.00 mL) in an Ar atmosphere at room temperature. [b] Yield of the isolated product. [c] The yield was de-
termined by using GC/mass-spectrometric analysis because of the low boiling point of the product. [d] See Scheme 4. [e] NH4OAc =3.0 equivalents.
phenol derivatives as the start-
ing material and CH3OD (in-
expensive relative to CD3OD)
as the deuterium source is very
useful for acquiring the deuter-
ated compounds with generali-
ty and in
a
cost-efficient
method (Table 7, entries 1–5).
Conclusion
We have developed a facile
and mild method for the deox-
ygenation of a wide variety of
Scheme 5. Application of the methodology to an aryl tosylate.
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Reduction of Aryl Sulfonates
FULL PAPER
Table 6. Pd/C-catalyzed reductive cleavage of aryl mesylates.[a]
Entry
Substrate
Mg
[equiv]
NH4OAc
[equiv]
T
[h]
Yield
[%][b]
G
G
1
2
3
1.2
1.2
2.4
none
1.0
3.0
24
12
3
14[c]
98[d]
92
4
5
2.4
1.2
30
5
89
78
5.0
24
6
7
8
2.4
2.4
2.4
30
2
6
80
57
85
30
3.0
24
9
2.4
30
24
32[e]
[a] Reaction conditions: substrate (250 mmol), 10% Pd/C (10 wt% of the substrate), Mg (7.3 mg, 300 mmol or 14.6 mg, 600 mmol), NH4OAc, and MeOH
1
(1.00 mL) in an Ar atmosphere at room temperature. [b] Yield of the isolated product. [c] Based on H NMR spectroscopic analysis, 86% of the starting
1
material was recovered. [d] Based on H NMR spectroscopic analysis, 2% of the starting material was recovered. [e] The low yield of the isolated prod-
uct is due to its volatile nature.
hydrated EtOAc were purchased from Wako Pure Chemical Industries,
Ltd. and used without purification. THF and CH2Cl2 were distilled from
sodium benzophenone ketyl and calcium hydride, respectively. CH3OD
was obtained from Wako Pure Chemical Inc. (catalogue No. 537-7439;
99% D). All other reagents were purchased from commercial sources
and used without further purification. Flash column chromatography was
performed with silica gel Merck 60 (230–400 mesh ASTM) or Kanto
Chemical Co., Inc. 60N (63–210 mm spherical, neutral). 1H and 13C NMR
spectra were recorded on JEOL AL 400 or JEOL EX 400 spectrometers
phenol derivatives via aryl triflates or mesylates by using the
combination of Pd/C, Mg metal, and MeOH. In addition, we
also found an acceleration effect through the addition of
NH4OAc. From mechanistic studies, we speculate that
NH4OAc enhanced the reaction rate as a result of a dual ac-
tivating effect caused by AcOH and NH3: the increase in
the solubility of the Mg species by AcOH and the activation
of Pd/C by the coordination of NH3. The deoxygenation
method has the following advantages: it is hydrogen gas-
and phosphine-free, requires mild reaction conditions, is
simple, and provides ready access to the reagents. Further-
more, the present method can be applied to the regioselec-
tive deuteration of benzene rings by using CH3OD as a cost-
effective deuterium source and will be practically useful
with generality in the areas of synthetic organic, medicinal,
and process chemistry.
1
(400 and 100 MHz for the H and 13C NMR spectra, respectively). Chem-
ical shifts (d) are expressed in ppm and are internally referenced (0.00
and 77.0 ppm for TMS in CDCl3 for the 1H and 13C NMR spectra, respec-
tively). Elemental analyses were performed by
a YANAKO CHN
CORDER MT-5 instrument. EI and FAB mass spectra were taken on a
JEOL JMS-SX102 A instrument.
[14]
Generalprocedure for the preparation of aryltriafltes
:
Phenol
(5.00 mmol) was dissolved in toluene (10 mL), and 30% K3PO4 solution
(10 mL) was added. The reaction mixture was cooled to 08C and triflic
anhydride (1.0 mL, 6.00 mmol) was added dropwise with stirring to main-
tain a reaction temperature of <108C. The reaction mixture was allowed
to warm to room temperature, stirred for a further 30 minutes, and then
extracted with ethyl acetate (2”10 mL). The combined organic layers
were washed with water (30 mL), dried over MgSO4, and evaporated to
give 1a–n.
ExperimentalSection
3,4,5-Trimethoxyphenyl trifluoromethanesulfonate (1a): Following the
general procedure for the preparation of aryl mesylates, 1a was obtained
from 3,4,5-trimethoxyphenol (921mg, 5.00 mmol) after a reaction time of
Generalexperimental : 10% Pd/C was purchased from Aldrich (cata-
logue No. 205699). MeOH, iPrOH, and distilled water for HPLC and de-
Chem. Eur. J. 2007, 13, 1432 – 1441
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1437

H. Sajiki et al.
1
Table 7. Regioselective deuteration of various aryl triflates with CH3OD
as the solvent.[a]
oil. The H NMR spectrum of 1 f was identical with that given in the liter-
ature.[19]
4-Cyclohexylphenyl trifluoromethanesulfonate (1g): Following the gener-
al procedure for the preparation of aryl triflates, reaction of 4-cyclohexyl-
phenol (881mg, 5.00 mmol) for 0.5 h, followed by flash column chroma-
tography on silica gel (n-hexane), gave 1g in 94% yield (1.44 g) as a col-
Entry
1
Product
T [h]
Yield [%]
86[b]
1
orless solid. The H NMR spectrum of 1 g was identical with that given in
the literature.[20]
Methyl 4-[(trifluoromethylsulfonyl)oxy]phenylacetate (1h): Following
the general procedure for the preparation of aryl triflates, reaction of
methyl 2-(4-hydroxyphenyl)acetate (831mg, 5.00 mmol) for 0.5 h, with-
out subsequent purification, gave 1h in 72% yield (1.07 g) as a colorless
oil. The 1H NMR spectrum of 1h was identical with that given in the lit-
erature.[21]
4.5
2
3
4
24
1
81
8
4-Phenylphenyl trifluoromethanesulfonate (1i): Following the general
procedure for the preparation for aryl triflates, reaction of 4-phenylphe-
95
nol (1.70 g, 10.0 mmol) for 1 h, followed by flash column chromatography
on silica gel (n-hexane), gave 1i in 93% yield (2.81g) as a colorless solid.
1H NMR (400 MHz, CDCl3): d=7.64 (d, J=8.7 Hz, 2H), 7.55 (d, J=
7.2 Hz, 2H), 7.46 (t, J=7.2 Hz, 2H), 7.39 (t, J=7.2 Hz, 1H), 7.34 ppm (d,
J=8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): d=148.9, 141.7, 139.3,
129.0, 128.9, 128.0, 127.2, 121.6, 118.8 ppm (q, J=321Hz); MS (EI): m/z
24
84
(%): 302 (40) [M+], 169 (100), 141 (46), 115 (28); HRMS (EI): m/z:
[c]
5
1
2
83
calcd for C13H9O3F3S [M+]: 302.0225; found: 302.0213; elemental analysis
calcd (%) for C13H9O3F3S: C 51.66, H 3.00; found: C 51.44, H 3.15.
[a] Reaction conditions: substrate (250 mmol), 10% Pd/C (10 wt% of the
substrate), Mg (7.3 mg, 300 mmol), and CH3OD (1.00 mL) in an Ar at-
mosphere at room temperature. [b] 0.01equivalents of NH 4OAc were
used. [c] 2.4 equivalents of Mg were used.
1-Naphthalenyl trifluoromethanesulfonate (1j): Following the general
procedure for the preparation for aryl triflates, reaction of 1-naphthol
(721mg, 5.00 mmol) for 0.5 h, followed by flash column chromatography
on silica gel (n-hexane), gave 1j in 84% yield (1.16 g) as a colorless oil.
The 1H NMR spectrum of 1j was identical with that given in the litera-
ture.[4g]
0.5 h, without subsequent purification, in 97% yield (1.54 g) as a colorless
solid. The 1H NMR spectrum of 1a was identical with that given in the
literature.[15]
4-Fluorophenyl trifluoromethanesulfonate (1k): Following the general
procedure for the preparation for aryl triflates, reaction of 4-fluorophenol
(1.12 g, 10.0 mmol) for 0.5 h, without subsequent purification, gave 1k in
93% yield (2.26 g) as a colorless oil. 1H NMR (400 MHz, CDCl3): d=
7.24 (td, J=5.0, 2.6 Hz, 2H), 7.12 ppm (td, J=7.2, 2.1Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=161.7 (d, J=249 Hz), 145.3 (d, J=3.3 Hz), 123.1
(d, J=9.0 Hz), 118.7 (q, J=321 Hz), 117.1 ppm (d, J=24.6 Hz); MS (EI):
m/z (%): 244 (45) [M+], 111 (100), 83 (78); HRMS (EI): m/z: calcd for
C7H4O3F4S: 243.9817; found: 243.9812.
3,4-Dimethoxyphenyl trifluoromethanesulfonate (1b): Following the gen-
eral procedure for the preparation of aryl triflates, reaction of 3,4-dime-
thoxyphenol (771mg, 5.00 mmol) for 1h, followed by flash column chro-
matography on silica gel (n-hexane/Et2O 10:1), gave 1b in 94% yield
(1.34 g) as a colorless oil. 1H NMR (400 MHz, CDCl3): d=6.85 (d, J=
2.4 Hz, 2H), 6.78 (d, J=2.2 Hz, 1H), 3.90 (s, 3H), 3.89 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=149.5, 148.6, 142.7, 118.5 (q, J=
321 Hz), 112.7, 111.0, 105.1, 55.9, 49.7 ppm; MS (EI): m/z (%): 286 (28)
[M+], 153 (100), 125 (30); HRMS (EI): m/z: calcd for C9H9O5F3S [M+]:
286.0123; found: 286.0116.
4-(Trifluoromethyl)phenyl trifluoromethanesulfonate (1l): Following the
general procedure for the preparation for aryl triflates, reaction of a,a,a-
trifluoromethylphenol (1.62 g, 10.0 mmol) for 0.5 h, without subsequent
purification, gave 1l in 71% yield (630 mg) as a colorless oil. The
1H NMR spectrum of 1l was identical with that given in the literature.[22]
2-Methoxy-4-propylphenyl trifluoromethanesulfonate (1c): Following the
general procedure for the preparation of aryl triflates, reaction of 2-me-
thoxy-4-propylphenol (832 mg, 5.00 mmol) for 0.5 h, followed by flash
column chromatography on silica gel (n-hexane), gave 1c in 75% yield
Methyl 4-[(trifluoromethylsulfonyl)oxy]benzoate (1m): Following the
general procedure for the preparation of aryl triflates, reaction of methyl
4-hydroxybenzoate (761mg, 5.00 mmol) for 1h, without subsequent pu-
rification, gave 1m in 98% yield (1.40 g) as a colorless oil. 1H NMR
(400 MHz, CDCl3): d=8.15 (d, J=9.0 Hz, 2H), 7.36 (d, J=9.0 Hz, 2H),
3.95 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=165.4, 152.5, 131.9,
130.4, 121.4, 118.7 ppm (q, J=321Hz); MS (EI): m/z (%): 284 (77) [M+
], 253 (90), 189 (100), 161 (22), 123 (45), 95 (38), 69 (20); HRMS (EI):
m/z: calcd for C9H7O5F3S [M+]: 283.9966; found: 283.9971.
1
(1.11 g) as a colorless oil. The H NMR spectrum of 1c was identical with
that given in the literature.[16]
4-Acetamidophenyl trifluoromethanesulfonate (1d): Following the gener-
al procedure for the preparation of aryl triflates, reaction of 4-acetamido-
phenol (756 mg, 5.00 mmol) for 0.5 h, followed by flash column chroma-
tography on silica gel (CHCl3/MeOH 100:1), gave 1d in 53% yield
(747 mg) as a colorless solid. The 1H NMR spectrum of 1d was identical
with that given in the literature.[17]
Methyl 3-methoxy-4-[(trifluoromethylsulfonyl)oxy]benzoate (1n): Fol-
lowing the general procedure for the preparation of aryl triflates, reaction
of methyl vanillate (547 mg, 3.00 mmol) for 0.5 h, followed by flash
column chromatography on silica gel (n-hexane/Et2O 10:1), gave 1n in
93% yield (872 mg) as a colorless oil. The 1H NMR spectrum of 1n was
identical with that given in the literature.[23]
4-Benzylphenyl trifluoromethanesulfonate (1e): Following the general
procedure for the preparation for aryl triflates, reaction of 4-benzylphe-
nol (921mg, 5.00 mmol) for 1h, followed by flash column chromatogra-
phy on silica gel (n-hexane), gave 1e in 92% yield (1.45 g) as a colorless
oil. The 1H NMR spectrum of 1e was identical with that given in the lit-
erature.[18]
Generalprocedure for reductive celavage of 3,4,5-trimethoxyphenyltri-
fluoromethanesulfonate (1a) using various metals and solvents (Table 1):
After two vacuum/Ar cycles to remove air from the reaction tube, a mix-
ture of 1a (158 mg, 500 mmol), 10% Pd/C (15.9 mg, 10 wt% of 1a), and
the metal (600 mmol) in the solvent (2.0 mL) was stirred at ordinary pres-
sure (balloon) and temperature (ca. 208C) for the appropriate time. The
reaction mixture was filtered by using a membrane filter (Millipore,
2-Benzylphenyl trifluoromethanesulfonate (1 f): Following the general
procedure for the preparation for aryl triflates, reaction of 2-benzylphe-
nol (921mg, 5.00 mmol) for 1h, followed by flash column chromatogra-
phy on silica gel (n-hexane), gave 1 f in 54% yield (846 mg) as a colorless
1438
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1432 – 1441

Reduction of Aryl Sulfonates
FULL PAPER
Millex-LH, 0.45 mm), and the filtrate was partitioned between diethyl
ether (10 mL) and water (10 mL). The aqueous layer was extracted with
diethyl ether (3”10 mL), and the combined organic layers were washed
with brine (10 mL), dried with anhydrous MgSO4, filtered, and concen-
trated under reduced pressure. The ratio of the substrate 1a to the prod-
uct 2a was confirmed by 1H NMR spectroscopic analysis of the crude
mixture in CDCl3.
300 mmol) in MeOH (1.0 mL) was stirred at ordinary pressure (balloon)
and temperature (ca. 208C) for the appropriate time. The reaction mix-
ture was filtered using
a membrane filter (Millipore, Millex-LH,
0.45 mm), and the filtrate was partitioned between diethyl ether (10 mL)
and water (10 mL). The aqueous layer was extracted with diethyl ether
(3”10 mL), and the combined organic layers were washed with brine
(10 mL), dried with anhydrous MgSO4, filtered, and concentrated under
reduced pressure.
Generalprocedure for Tabel 2 : After two vacuum/Ar cycles to remove
air from the reaction tube, a mixture of 1a (79.1mg, 250 mmol), 10% Pd/
C (8.0 mg, 10 wt% of 1a), and Mg metal (7.3 mg, 300 mmol) in deuterat-
ed methanol (1.0 mL) was stirred at ordinary pressure (balloon) and tem-
perature (ca. 208C) for 24 h. The reaction mixture was filtered using a
membrane filter (Millipore, Millex-LH, 0.45 mm), and the filtrate was par-
titioned between diethyl ether (10 mL) and water (10 mL). The aqueous
layer was extracted with diethyl ether (3”10 mL), and the combined or-
ganic layers were washed with brine (10 mL), dried with anhydrous
MgSO4, filtered, and concentrated under reduced pressure. The hydrogen
source in the reaction was confirmed by 1H NMR spectroscopic analysis
of the crude mixture in CDCl3.
Method B: After two vacuum/Ar cycles to remove air from the reaction
tube, a mixture of 5h (80.1mg, 250 mmol), 10% Pd/C (8.1 mg, 10 wt% of
5h), Mg metal (7.3 mg, 300 mmol), and ammonium acetate (19.3 mg,
250 mmol) in MeOH (1.0 mL) was stirred at ordinary pressure (balloon)
and temperature (ca. 208C) for the appropriate time. The reaction mix-
ture was filtered using
a membrane filter (Millipore, Millex-LH,
0.45 mm), and the filtrate was partitioned between diethyl ether (10 mL)
and water (10 mL). The aqueous layer was extracted with diethyl ether
(3”10 mL), and the combined organic layers were washed with brine
(10 mL), dried with anhydrous MgSO4, filtered, and concentrated under
reduced pressure.
Generalprocedure for Tabels 3 and 4 : After two vacuum/Ar cycles to
remove air from the reaction tube, the mixture of 1a (79.1mg,
250 mmol), 10% Pd/C (8.0 mg, 10 wt% of 1a), Mg metal (7.3 mg,
300 mmol), and an additive (250 mmol) in MeOH (1.0 mL) was stirred at
ordinary pressure (balloon) and temperature (ca. 208C) for the appropri-
ate time. The reaction mixture was filtered by using a membrane filter
(Millipore, Millex-LH, 0.45 mm), and the filtrate was partitioned between
diethyl ether (10 mL) and water (10 mL). The aqueous layer was extract-
ed with diethyl ether (3”10 mL), and the combined organic layers were
washed with brine (10 mL), dried with anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The ratio of the substrate 1a, the
product 2a, and the homo-coupling product 4a was confirmed by
1H NMR spectroscopic analysis of the crude mixture in CDCl3.
Preparation of methyl 4-[(4-methylphenylsulfonyl)oxy]phenylacetate
(6h): 4-Toluenesulfonyl chloride (4.19 g, 22.0 mmol) was added to a solu-
tion of methyl 4-hydroxyphenylacetate (3.32 g, 20.0 mmol) and triethyla-
mine (3.07 mL, 22.0 mmol) in dichloromethane (10 mL), and the reaction
mixture was stirred at ambient temperature (ca. 208C). After 10 h, the
solvent was concentrated under reduced pressure. The residue was ex-
tracted with ethyl acetate (20 mL) and water (20 mL). The organic layer
was washed successively with saturated aqueous sodium hydrogen car-
bonate solution (20 mL), 10% aqueous sodium hydrogen sulfonate solu-
tion (20 mL), and brine (20 mL); dried over MgSO4; and concentrated
under reduced pressure. The residue was purified by flash column chro-
matography on silica gel (n-hexane/ethyl acetate 10:1!5:1) to afford 6h
in 90% yield (5.77 g) as a yellow oil. 1H NMR (400 MHz, CDCl3): d=
7.71(d, J=8.3 Hz, 2H), 7.31(d, J=8.3 Hz, 2H), 7.20 (d, J=8.3 Hz, 2H),
6.93 (d, J=8.3 Hz, 2H), 3.61(s, 3H), 3.58 (s, 2H), 2.45 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=171.5, 148.7, 145.3, 132.5, 130.5, 129.7,
128.5, 122.4, 52.1, 40.4, 21.7 ppm; MS (EI): m/z (%): 320 (75) [M+], 261
(14), 155 (100), 91 (84); HRMS (EI): m/z: calcd for C16H16O5S [M+]:
320.0718; found: 320.0721.
General procedure for reductive cleavage of various aryl triflates
(Table 5): Method A: After two vacuum/Ar cycles to remove air from the
reaction tube, a mixture of the aryl triflate (250 mmol), 10% Pd/C
(10 wt% of the aryl triflate), and Mg metal (7.3 mg, 300 mmol) in MeOH
(1.0 mL) was stirred at ordinary pressure (balloon) and temperature
(ca. 208C) for the appropriate time. The reaction mixture was filtered by
using a membrane filter (Millipore, Millex-LH, 0.45 mm), and the filtrate
was partitioned between diethyl ether (10 mL) and water (10 mL). The
aqueous layer was extracted with diethyl ether (3”10 mL), and the com-
bined organic layers were washed with brine (10 mL), dried with anhy-
drous MgSO4, filtered, and concentrated under reduced pressure.
General procedure for reductive cleavage of aryl mesylates (Table 6):
After two vacuum/Ar cycles to remove air from the reaction tube, a mix-
ture of the aryl mesylate (250 mmol), 10% Pd/C (10 wt% of the aryl me-
sylate), Mg metal (7.3 mg, 300 mmol), and ammonium acetate (19.3 mg–
5.78 g, 0.250–7.50 mmol) in MeOH (1.0 mL) was stirred at ordinary pres-
sure (balloon) and temperature (ca. 208C) for the appropriate time. The
reaction mixture was filtered using a membrane filter (Millipore, Millex-
LH, 0.45 mm), and the filtrate was partitioned between diethyl ether
(10 mL) and water (10 mL). The aqueous layer was extracted with dieth-
yl ether (3”10 mL), and the combined organic layers were washed with
brine (10 mL), dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure.
Method B: After two vacuum/Ar cycles to remove air from the reaction
tube, a mixture of the aryl triflate (250 mmol), 10% Pd/C (10 wt% of the
aryl triflate), Mg metal (7.3 mg, 300 mmol), and ammonium acetate
(19.3 mg, 250 mmol) in MeOH (1.0 mL) was stirred at ordinary pressure
(balloon) and temperature (ca. 208C) for the appropriate time. The reac-
tion mixture was filtered by using a membrane filter (Millipore, Millex-
LH, 0.45 mm), and the filtrate was partitioned between diethyl ether
(10 mL) and water (10 mL). The aqueous layer was extracted with dieth-
yl ether (3”10 mL), and the combined organic layers were washed with
brine (10 mL), dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure.
Generalprocedure for the preparation of arylmesyal tes : Methanesulfon-
yl chloride (0.929 mL, 12.0 mmol) was added dropwise to a solution of a
phenol (10.0 mmol) and triethylamine (1.67 mL, 12.0 mmol) in dichloro-
methane, THF, or N,N-dimethylformamide (DMF; 20 mL), and the reac-
tion mixture was stirred at ambient temperature. After the appropriate
reaction time, the reaction mixture was concentrated under reduced pres-
sure. The residue was extracted with ethyl acetate (20 mL) and water
(20 mL). The organic layer was washed successively with saturated aque-
ous sodium hydrogen 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 resi-
due was purified by flash column chromatography on silica gel or recrys-
tallization.
Method C: After two vacuum/Ar cycles to remove air from the reaction
tube, a mixture of the aryl triflate (250 mmol), 10% Pd/C (10 wt% of the
aryl triflate), Mg metal (14.6 mg, 600 mmol), and ammonium acetate
(96.4 mg, 1.25 mmol) in MeOH (1.0 mL) was stirred at ordinary pressure
(balloon) and temperature (ca. 208C) for the appropriate time. The reac-
tion mixture was filtered by using a membrane filter (Millipore, Millex-
LH, 0.45 mm), and the filtrate was partitioned between diethyl ether
(10 mL) and water (10 mL). The aqueous layer was extracted with dieth-
yl ether (3”10 mL), and the combined organic layers were washed with
brine (10 mL), dried with anhydrous MgSO4, filtered, and concentrated
under reduced pressure.
Methyl 4-methanesulfonyloxyphenylacetate (6h): Following the general
procedure for the preparation of aryl mesylates, reaction of methyl 4-hy-
droxyphenylacetate (1.66 g, 10.0 mmol), triethylamine (1.67 mL,
12.0 mmol), and methanesulfonyl chloride (0.929 mL, 12.0 mmol) for 1 h,
without subsequent purification, gave 6h in 94% yield (2.29 g) as a color-
Reductive cleavage of 5h (Scheme 5): Method A: After two vacuum/Ar
cycles to remove air from the reaction tube, a mixture of 5h (80.1mg,
250 mmol), 10% Pd/C (8.1 mg, 10 wt% of 5h), and Mg metal (7.3 mg,
Chem. Eur. J. 2007, 13, 1432 – 1441
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1439

H. Sajiki et al.
less solid. 1H NMR (400 MHz, CDCl3): d=7.32 (d, J=8.6 Hz, 2H), 7.23
(d, J=8.6 Hz, 2H), 3.69 (s, 3H), 3.62 (s, 2H), 3.12 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=171.4, 148.3, 133.4, 131.0, 122.1, 52.2, 40.4,
37.3 ppm; MS (EI): m/z (%): 244 (85) [M+], 185 (75), 166 (42), 107
(100), 78 (34), 44 (30); HRMS (EI): m/z: calcd for C10H12O5S: 244.0405;
found: 244.0396; elemental analysis (%) calcd for C10H12O5S: C 49.17, H
4.95; found: C 49.08, H 4.99.
the filtrate was partitioned between diethyl ether (10 mL) and water
(10 mL). The aqueous layer was extracted with diethyl ether (3”10 mL),
and the combined organic layers were washed with brine (10 mL), dried
with anhydrous MgSO4, filtered, and concentrated under reduced pres-
sure.
4-Phenylphenyl methanesulfonate (6i): Following the general procedure
for the preparation of aryl mesylates, reaction of 4-hydroxybiphenyl
(1.70 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and methanesul-
fonyl chloride (0.929 mL, 12.0 mmol) for 19 h, followed by recrystalliza-
tion (ethyl acetate/n-hexane), gave 6i in 63% yield (1.57 g) as a colorless
solid. 1H NMR (400 MHz, CDCl3): d=7.62 (d, J=8.8 Hz, 2H), 7.55 (d,
J=7.3 Hz, 2H), 7.45 (d, J=7.3 Hz, 2H), 7.39–7.35 (m, 3H), 2.97 ppm (s,
3H); 13C NMR (100 MHz, CDCl3): d=148.5, 140.6, 139.7, 128.9, 128.7,
127.7, 127.1, 122.3, 37.3 ppm; MS (EI): m/z (%): 248 (43) [M+], 169
(100), 141 (45), 115 (28); HRMS (EI): m/z: calcd for C13H12O3S [M+]:
248.0507; found: 248.0500; elemental analysis (%) calcd for C13H12O3S: C
62.88, H 4.87; found: C 62.79, H 4.93.
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43, 7247–7250; b) H. Sajiki, A. Kume, K. Hattori, H. Nagase, K.
Hirota, Tetrahedron Lett. 2002, 43, 7251–7254; c) Y. Monguchi, A.
Kume, K. Hattori, T. Maegawa, H. Sajiki, Tetrahedron 2006, 62,
7926–7933.
2-Benzylphenyl methanesulfonate (6 f): Following the general procedure
for the preparation of aryl mesylates, reaction of 2-benzylphenol (1.84 g,
10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and methanesulfonyl
chloride (0.929 mL, 12.0 mmol) for 2 h, followed by flash column chroma-
tography on silica gel (n-hexane/Et2O 10:1), gave 6 f in 96% yield
(2.51g) as a colorless solid. 1H NMR (400 MHz, CDCl3): d=7.39 (d, J=
7.8 Hz, 1H), 7.31–7.18 (m, 8H), 4.08 (s, 2H), 2.97 ppm (s, 3H); 13C NMR
(100 MHz, 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 ppm; MS (EI): m/z (%): 262 (52) [M+], 183
(100), 181 (85), 165 (50); HRMS (EI): m/z: calcd for C14H14O3S [M+]:
262.0664; found: 262.0670; elemental analysis (%) calcd for C14H14O3S: C
64.10, H 5.38; found: C 64.00, H 5.49.
Methyl 4-methylsulfonyloxybenzoate (6m): Following the general proce-
dure for the preparation of aryl mesylates, reaction of methyl 4-hydroxy-
benzoate (1.52 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and
methanesulfonyl chloride (0.929 mL, 12.0 mmol) for 20 h, followed by
flash column chromatography on silica gel (n-hexane), gave 6m in 94%
1
yield (2.17 g) as a colorless solid. The H NMR spectrum of 6m was iden-
tical with that given in the literature.[24]
Methyl 3-methylsulfonyloxybenzoate (6o): Following the general proce-
dure for the preparation of aryl mesylates, reaction of methyl 3-hydroxy-
benzoate (1.52 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and
methanesulfonyl chloride (0.929 mL, 12.0 mmol) for 20 h, followed by
flash column chromatography on silica gel (n-hexane), gave 6o in 94%
1
yield (2.17 g) as a colorless solid. The H NMR spectrum of 6o was iden-
tical with that given in the literature.[24]
4-Benzylphenyl methanesulfonate (6e): Following the general procedure
for the preparation of aryl mesylates, reaction of methyl 4-benzylphenol
(1.84 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and methanesul-
fonyl chloride (0.929 mL, 12.0 mmol) for 5 h, without subsequent purifi-
cation, gave 6e in 99% yield (2.59 g) as a colorless solid. 1H NMR
(400 MHz, CDCl3): d=7.32–7.16 (m, 9H), 3.98 (s, 2H), 3.11 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=147.6, 140.6, 140.2, 130.3, 128.9, 128.6,
126.4, 121.9, 41.3, 37.3 ppm; MS (EI): m/z (%): 262 (100) [M+], 183 (80),
155 (67); HRMS (EI): m/z: calcd for C14H14O3S [M+]: 262.0664; found:
262.0660; elemental analysis (%) calcd for C14H14O3S: C 64.10, H 5.38;
found: C 64.10, H 5.40.
1-Naphthalenyl methanesulfonate (6j): Following the general procedure
for the preparation of aryl mesylates, reaction of methyl 1-naphthol
(1.44 g, 10.0 mmol), triethylamine (1.67 mL, 12.0 mmol), and methanesul-
fonyl chloride (0.929 mL, 12.0 mmol) for 2 h, without subsequent purifi-
cation, gave 6j in 97% yield (2.16 g) as a brown oil. The 1H NMR spec-
trum of 6j was identical with that given in the literature.[4g]
Generalprocedure for Tabel 7 : After two vacuum/Ar cycles to remove
air from the reaction tube, a mixture of aryl triflate (250 mmol), 10% Pd/
C
(10 wt% of the substrate), and Mg metal (7.3 mg, 300 mmol) in
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CH3OD (1.0 mL) was stirred at ordinary pressure (balloon) and tempera-
ture (ca. 208C) for the appropriate time. The reaction mixture was fil-
tered by using a membrane filter (Millipore, Millex-LH, 0.45 mm), and
[15] D. Macmillan, D. W. Anderson, Org. Lett. 2004, 6, 4659–4662.
1440
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1432 – 1441

Reduction of Aryl Sulfonates
FULL PAPER
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Received: August 15, 2006
Published online: October 30, 2006
Chem. Eur. J. 2007, 13, 1432 – 1441
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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