Palladium-catalyzed benzylic direct arylation of benzyl sulfones with aryl halides

Article abstract of DOI:10.1016/j.tet.2009.01.030

An effective palladium catalyst system for the direct arylation of benzyl sulfones with aryl halides has been developed. The catalytic reaction provides a facile route to diarylmethyl sulfones. The products can be transformed further via desulfonylative functionalization mediated by aluminum compounds.

Full text of DOI:10.1016/j.tet.2009.01.030

Tetrahedron 65 (2009) 1971–1976
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Tetrahedron
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Palladium-catalyzed benzylic direct arylation of benzyl sulfones with aryl halides
*
*
Takashi Niwa, Hideki Yorimitsu , Koichiro Oshima
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
An effective palladium catalyst system for the direct arylation of benzyl sulfones with aryl halides has
been developed. The catalytic reaction provides a facile route to diarylmethyl sulfones. The products can
be transformed further via desulfonylative functionalization mediated by aluminum compounds.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 11 December 2008
Received in revised form 26 December 2008
Accepted 6 January 2009
Available online 14 January 2009
Keywords:
Direct arylation
Palladium catalysis
Diarylmethyl sulfone
1. Introduction
activity for the reaction, the use of P(cC6H11)3 and PtBu3 resulted in
high efficiency (entries 1 and 12). Other ligands such as triaryl-
Transition-metal-catalyzed direct arylations at sp3-hybridized
carbons having acidic hydrogens have been attracting attention in
the modern cross-coupling reaction.1–5 In light of the importance of
this transformation, we thus envisioned a new application of the
direct arylation, specifically, intermolecular benzylic arylation of
benzyl sulfones (Table 1).6 Benzyl sulfone 1, readily prepared from
benzyl halide and sodium arenesulfinate, has benzylic hydrogens of
satisfactory acidity for deprotonation.7 Palladium-catalyzed aryla-
tion of 1 with aryl halide 2 would afford diarylmethyl sulfone 3.
phosphines and bidentate phosphine ligands were much less
effective.
By using P(cC6H11)3 as the optimal ligand, the effect of bases was
examined (Table 2). Cesium carbonate showed no activity (entry 7)
t
while alkali metal hydroxides and BuOK acted as effective bases
(entries 1–6 and 8). Finally, we found that the desired product 3a
was obtained in 90% yield by a similar reaction in refluxing toluene
Table 1
Optimization of ligand for direct phenylation of benzyl sulfone 1a
2. Results and discussion
2.5 mol% [PdCl(π-allyl)]2
10 mol% ligand
H
O
S
O
1a
Ph
O
S
Treatment of benzyl sulfone 1a with bromobenzene (2a) in the
2.0 eq CsOH•H2O
presence of cesium hydroxide and catalytic amounts of
p-allyl-
palladium chloride dimer and tricyclohexylphosphine (P(cC6H11)3)
in refluxing xylene provided the corresponding arylated product 3a
in moderate yield (Table 1, entry 1). A plausible reaction mecha-
nism includes deprotonation of 1a with cesium hydroxide followed
xylene, reflux, 3 h
O
3a
+
PhBr (2a, 1.2 eq)
Entry
Ligand
1H NMR yield (%)
P(cC6H11
PPh3
)
3
68
19
Trace
24
35
Trace
6
8
31
0
by transmetalation of a-tosylbenzylcesium with an arylpalladium
1
2
bromide intermediate. Although the product should have the more
acidic hydrogen,8 we could not observe p-tolyl triphenylmethyl
sulfone, which could be derived from second arylation.9
3
P(o-tol)3
4
5
P(p-MeOC6H4)3
P(p-FC6H4)3
The effect of the phosphine ligand is summarized in Table 1.
Although a number of phosphine ligands showed poor to moderate
6
7
8
9
10
11
12
DPPE (2.5 mol %)
rac-BINAP (2.5 mol %)
DPEphos (2.5 mol %)
Xantphos (2.5 mol %)
PMe3
* Corresponding authors. Tel.: þ81 75383 2441; fax: þ81 75383 2438.
E-mail addresses: yori@orgrxn.mbox.media.kyoto-u.ac.jp (H. Yorimitsu), osh-
ima@orgrxn.mbox.media.kyoto-u.ac.jp (K. Oshima).
PnBu3
0
52
PtBu3 (2.5 mol %)
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.030

1972
T. Niwa et al. / Tetrahedron 65 (2009) 1971–1976
Table 2
Table 4
Optimization of base for direct phenylation of benzyl sulfone 1a
Pd-catalyzed phenylation of other sulfones
H
π
2.5 mol% [PdCl( -allyl)]2
H
π
cat. [PdCl( -allyl)]2
c
O
S
O
R1
O
S
O
1a
c
Ph
10 mol% P( C6H11
base
)
3
R2
cat. P( C6H11
BuOK
)
O
S
O
3a
Ph
3
O
S
t
R1
1
R2
+
xylene, reflux, 3 h
toluene, reflux
PhI (2a)
O
3
+
PhBr (2a, 1.2 eq)
Entry
R1
R2
1
Time (h)
3
Isolated
yield/%
Entry
Base (equiv)
1H NMR yield (%)
1
2
3
4
5
6
7
8
CsOH$H2O (1.2)
CsOH$H2O (2.0)
CsOH$H2O (3.0)
KOH (2.0)
KOH (3.0)
NaOH (2.0)
24
68
41
50
30
37
0
61
90b
39
0
1
2
3
p-MeC6H4
p-FC6H4
p-MeOC6H4
2-Naphthyl
1b
1c
1d
3
3
4
3h
3i
3m
77a
73a
62
4
5
p-CF3C6H4
p-MeOC6H4
Ph
1e
1f
2
2
3n
3o
77
83
Cs2CO3 (2.0)
tBuOK (2.0)
6
7
Morpholinyl
NMePh
Ph
1g
1h
1
1
3p
3q
75
71
9
10
11
tBuOK (2.0)a
tBuOK (2.0)c
tBuOK (2.0)d
a
IPr$HCl (0.030 mmol) was used as a ligand.
a
Toluene was used as a solvent.
Isolated yield.
Performed in toluene at 80 ꢀC for 15 h.
Performed in toluene at 50 ꢀC at 15 h.
b
c
d
H
Me
O
O
Me
H
S
O
O
S
S
H
(entry 9). The reaction at 80 ꢀC or lower resulted in incomplete
conversion even after 15 h (entries 10 and 11).
O
O
1i
1j
1k
With the optimal conditions, we performed the direct arylation
of a variety of aryl halides (Table 3). Iodobenzene (2b) reacted
smoothly (entry 2), although chlorobenzene (2c) gave 3a in lower
yield (entry 3). Aryl iodides having chloro- (entry 4), tri-
fluoromethyl- (entry 5), and ester groups (entry 6) could be
employed. Unfortunately, attempts on the reaction with electron-
Figure 1. Other sulfones.
rich aryl iodides resulted in incomplete conversions. For such re-
actions, it was effective to use an N-heterocyclic carbene (NHC)
precursor IPr$HCl10 instead of tricyclohexylphosphine to obtain the
corresponding product in high yield (entries 7–10). Sterically de-
manding aryl iodides 2k and 2l also participated in the reaction by
using the NHC ligand (entries 11 and 12).
Other sulfones were subjected to the arylation reaction (Table
4). The reactions of p-substituted benzyl sulfones 1b, 1c and 2-
naphthylmethyl sulfone 1d proceeded smoothly (entries 1–3). The
p-trifluoromethyl- and the p-methoxy groups of the arenesulfonyl
moieties did not interfere with the arylation (entries 4 and 5).
Benzylic sulfonamides 1g and 1h could be employed to afford the
corresponding diarylmethanesulfonamides (entries 6 and 7).11
Unfortunately, the reactions of 1-phenylethyl sulfone 1i and benzyl
methyl sulfone 1j resulted in no conversions, because of the low
acidity of the benzylic protons (Fig.1). The reaction of 2-biphenylyl-
methyl sulfone 1k also afforded no arylated product, due to the
steric hindrance.
Table 3
Pd-catalyzed arylation of benzyl sulfone 1a
cat. [PdCl( -allyl)]
π
H
2
O
S
O
1a
c
Ar
cat. P( C6H11
)
3
O
S
O
t
BuOK
toluene, reflux
3
+
ArX (2)
Entry
ArX 2
Time (h)
3
Isolated
yielda (%)
1
2
3
2a
2b
2c
X¼
Br
I
Cl
3
2
3
3a
90
99
X
I
31a
4
5
6
7
8
9
10
11
2d
2e
2f
2g
2h
2i
R¼
p-Cl
2
3
5
2
4
7
2
5
3d
3e
3f
3g
3h
3i
76
75
75
m-CF3
p-CO2tBu
p-Me
p-F
p-MeO
m-Me
o-Me
Finally, desulfonylative transformations of the product 3a were
investigated (Scheme 1). Treatment of diphenylmethyl sulfone 3a
80b
64b
67b
84b
67b
Ph
R
Ph
Ph
2j
2k
3j
3k
a
b
e
O
S
O
Ph
H
Ph
Ph
I
4a 88%
3a
4e 89%
Ph
69b
d
12
2l
5
3l
c
Ph
Ph
a
The yield was determined by 1H NMR analysis.
IPr$HCl (0.030 mmol) was used as a ligand.
Me
Ph
Ph
NC
Ph
4c 100%
b
4b 85%
4d 100%
i
i
Pr
Pr
Scheme 1. Desulfonylative transformations of diphenylmethyl sulfone 3a in the
presence of aluminum compounds: (a) AlCl3 (1.5 equiv), Et3SiH (1.5 equiv), CH2Cl2,
25 ꢀC, 1 h; (b) AlCl3 (1.5 equiv), Me3SiCH2CH]CH2 (1.5 equiv), CH2Cl2, 25 ꢀC, 1 h; (c)
AlCl3 (1.5 equiv), Me3SiCN (1.5 equiv), CH2Cl2, 25 ꢀC, 1 h; (d) AlMe3 (1.5 equiv), CH2Cl2,
25 ꢀC, 2 h; (e) AlCl3 (1.5 equiv), C6H6, 25 ꢀC, 1 h.
+
N
N
i
i
Cl–
Pr
Pr
IPr•HCl

T. Niwa et al. / Tetrahedron 65 (2009) 1971–1976
1973
with hydrosilane, allylsilane, or silyl cyanide in the presence of
aluminum chloride provided the corresponding desulfonylative
product in high yield.12 Methylation of 3a with trimethylaluminum
proceeded smoothly.13 Friedel–Crafts alkylation of benzene with
diphenylmethyl sulfone 3a was facile to yield triphenylmethane
(4e).
Aqueous H2O2 (30%, 4.5 mL, 40 mmol) was slowly added to a so-
lution of the crude sulfide and molybdenum dichloride dioxide
(0.30 g, 1.5 mmol) in acetonitrile (10 mL). After being stirred for 18 h
at room temperature, the resulting mixture was poured into aqueous
sodium thiosulfate. Extraction with ethyl acetate followed by silica
gel column purification furnished benzyl p-trifluoromethylphenyl
sulfone (1e, 0.97 g, 3.2 mmol) in 32% yield in two steps.
3. Conclusion
4.2.3. Synthesis of benzylic sulfonamides (1g and 1h)
Synthesis of sulfonamide 1g is representative. A solution of
phenylmethanesulfonyl chloride (1.9 g, 10 mmol) in tetrahydro-
furan (5 mL) was slowly added to a solution of morpholine
(0.44 mL, 5.0 mmol) and diisopropylethylamine (2.1 mL, 12 mmol)
in tetrahydrofuran (10 mL) at 0 ꢀC. After the reaction mixture was
stirred for 8 h at room temperature, the reaction mixture was
quenched with a saturated ammonium chloride solution. Extrac-
tion with ethyl acetate followed by silica gel column purification
furnished N-benzylsulfonylmorpholine (1g, 0.97 g, 4.0 mmol) in
80% yield.
In summary, we have developed an effective palladium catalyst
system for the direct arylation of benzyl sulfones with aryl halides. The
catalytic reaction provides a facile route to diarylmethane derivatives.
4. Experimental
4.1. General
4.1.1. Instrumentation
1H NMR (500 MHz) and 13C NMR (126 MHz) spectra were taken
on a Varian Unity INOVA 500 spectrometer and were recorded in
4.2.4. Typical procedure for palladium-catalyzed direct arylation
of aryl benzyl sulfones
CDCl3. Chemical shifts (d) are in parts per million relative to tetra-
methylsilane at 0.00 ppm for 1H and relative to CDCl3 at 77.2 ppm
for 13C unless otherwise noted. IR spectra were determined on
a SHIMADZU FTIR-8200PC spectrometer. TLC analyses were per-
formed on commercial glass plates bearing a 0.25-mm layer of
Merck Silica gel 60F254. Silica gel (Wakogel 200 mesh) was used for
column chromatography. Elemental analyses were carried out at
the Elemental Analysis Center of Kyoto University.
Synthesis of sulfone 3a is representative (Table 3, entry 2).
tBuOK (449 mg, 4.0 mmol) and
p-allylpalladium chloride dimer
(18 mg, 0.05 mmol) were placed in a 20-mL two-necked reaction
flask equipped with a Dimroth condenser under Ar atmosphere.
Tricyclohexylphosphine (0.5 M in toluene, 0.4 mL, 0.2 mmol), tol-
uene (10 mL), benzyl p-tolyl sulfone (1a, 493 mg, 2.0 mmol), and
iodobenzene (2a, 0.27 mL, 2.4 mmol) were sequentially added at
ambient temperature. The resulting mixture was heated at reflux
for 2 h. After the mixture was cooled to room temperature, a satu-
rated aqueous ammonium chloride solution (10 mL) was added.
The product was extracted with ethyl acetate three times. The
combined organic layer was dried over sodium sulfate and con-
centrated in vacuo. Silica gel column purification (hexane/ethyl
acetate¼5:1) gave diphenylmethyl p-tolyl sulfone (3a, 637 mg,
1.97 mmol) in 99% yield.
4.1.2. Materials
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. Toluene was
purchased from Wako Pure Chemical Co. and stored over slices of
sodium. Tricyclohexylphosphine and imidazolinium salt IPr$HCl
were purchased from Strem. Preparations of sulfones (1a–1i) are
shown below. Preparations of sulfones 1j14 and 1k15 were carried
out according to the literature. All reactions were carried out under
argon atmosphere.
4.2.5. Synthesis of 4a, 4b, and 4c
Synthesis of diphenylmethane (4a) is representative. Aluminum
trichloride (40 mg, 0.3 mmol) was added to a solution of diphenyl-
methyl p-tolyl sulfone (3a, 65 mg, 0.2 mmol) and triethylsilane
4.2. Experimental procedures
4.2.1. Synthesis of benzyl aryl sulfones (1a–1d, 1i)
(48 mL, 0.3 mmol) in dichloromethane (2.0 mL). After being stirred
Synthesis of sulfone 1a is representative. Benzyl chloride (4.6 mL,
40 mmol) was added to a suspension of sodium p-toluenesulfinate
tetrahydrate (11.0 g, 44 mmol) and tetrabutylammonium bromide
(0.64 g, 2.0 mmol) in 1,2-dimethoxyethane (40 mL) at room temper-
ature. The resulting mixture was heated at reflux for 3 h. The mixture
was poured into water and insoluble materials were collected by fil-
tration to yield benzyl p-tolyl sulfone (1a, 8.9 g, 36 mmol, 82%).
for 1 h at room temperature, the reaction mixture was quenched
with aqueous sodium hydroxide (1 M, 3 mL). The product was
extracted with ethyl acetate three times. The combined organic
layer was dried over sodium sulfate and concentrated in vacuo.
Silica gel column purification yielded diphenylmethane (4a, 30 mg,
0.18 mmol) in 88% yield.
4.2.6. Synthesis of 4d
4.2.2. Synthesis of benzyl aryl sulfones (1e and 1f)
A solution of trimethylaluminum (1.0 M in toluene, 0.4 mL,
0.4 mmol) was added to a solution of diphenylmethyl p-tolyl sul-
fone (3a, 65 mg, 0.2 mmol) in dichloromethane (2.0 mL). After
being stirred for 2 h at room temperature, the reaction mixture was
quenched with aqueous sodium hydroxide (1 M, 3 mL). The prod-
uct was extracted with ethyl acetate. The combined organic layer
was dried over sodium sulfate and concentrated in vacuo.
Chromatographic purification on silica gel gave 1,1-diphenylethane
(4d, 26 mg, 0.20 mmol) in quantitative yield.
Synthesis of sulfone 1e is representative. A solution of butyl-
lithium (1.6 M in hexane, 6.3 mL, 10 mmol) was slowly added to
a solution of p-trifluoromethylbromobenzene (1.4 mL, 10 mmol) in
tetrahydrofuran (50 mL) at ꢁ78 ꢀC and the reaction mixture was
stirred for 15 min at ꢁ78 ꢀC. Sulfur (0.32 g, 10 mmol) was added to
the reaction mixture. After the reaction mixture was stirred for
10 min at ꢁ78 ꢀC, benzyl bromide (1.2 mL, 10 mmol) was slowly
added. After being stirred for 1 h at room temperature, the reaction
mixture was quenched with a saturated ammonium chloride so-
lution. The product was extracted with ethyl acetate three times.
The combined organic layer was dried over sodium sulfate and
concentrated in vacuo. The residue containing benzyl 4-tri-
fluoromethylphenyl sulfide was used for the next step without
further purification.
4.2.7. Synthesis of 4e
Aluminum trichloride (40 mg, 0.3 mmol) was added to a solution
of diphenylmethyl p-tolyl sulfone (3a, 65 mg, 0.2 mmol) in benzene
(2.0 mL). After being stirred for 1 h at room temperature, the re-
action mixture was quenched with aqueous sodium hydroxide (1 M,

1974
T. Niwa et al. / Tetrahedron 65 (2009) 1971–1976
3 mL). Extractive workup followed by silica gel column purification
afforded triphenylmethane (4e, 43 mg, 0.18 mmol) in 89% yield.
260.0867 (
D
¼1.4 ppm), calcd for C15H16O2S [Mþ]: 260.0871. Mp
114–117 ꢀC.
4.3.10. Benzyl methyl sulfone (1j)14
1H NMR (CDCl3) 2.75 (s, 3H), 4.25 (s, 2H), 7.42 (br, 5H); 13C
NMR (CDCl3)
39.2, 61.5, 128.5, 129.3 (ꢂ2C), 129.3, 130.7.
4.3. Characterization data
d
d
4.3.1. Benzyl p-tolyl sulfone (1a)13
1H NMR (CDCl3)
d
2.41 (s, 3H), 4.29 (s, 2H), 7.08–7.10 (m, 2H),
7.22–7.28 (m, 4H), 7.30–7.33 (m, 1H), 7.49–7.51 (m, 2H); 13C NMR
(CDCl3) 21.8, 63.1, 128.5, 128.7, 128.8, 128.9, 129.7, 131.0, 135.2,
4.3.11. 2-Biphenylylmethyl p-tolyl sulfone (1k)15
1H NMR (CDCl3)
2.40 (s, 3H), 4.39 (s, 2H), 6.84–6.86 (m, 2H),
7.12–7.14 (m, 3H), 7.23–7.29 (m, 5H), 7.35–7.37 (m, 2H), 7.60–7.62
(m,1H); 13C NMR (CDCl3)
21.7, 59.1,125.8,127.3,127.7,128.2, 128.6,
d
d
144.8. Anal. Calcd for C14H14O2S: C, 68.26; H, 5.73%. Found: C, 68.51;
H, 5.71%.
d
128.7, 129.2, 129.6, 130.4, 131.7, 135.8, 139.9, 143.8, 144.6.
4.3.2. p-Fluorophenylmethyl p-tolyl sulfone (1b)
4.3.12. Diphenylmethyl p-tolyl sulfone (3a)
IR (Nujol) 2923, 2854, 1460, 1377, 1126, 1087 cmꢁ1
;
1H NMR
IR (Nujol) 2925, 2854, 1457, 1377, 1141 cmꢁ1 1H NMR (CDCl3)
;
(CDCl3)
2H), 7.25–7.27 (m, 2H), 7.50–7.52 (m, 2H); 13C NMR (CDCl3)
62.2, 115.8 (d, JC–F¼21.5 Hz), 124.3 (d, JC–F¼3.9 Hz), 129.3 (d, JC–F
127 Hz), 132.7 (d, JC–F¼8.6 Hz), 134.9, 145.0, 162.2, 164.2. HRMS
(DI-EIþ) (m/z) observed: 264.0620
¼1.9 ppm), calcd for
C14H13O2FS [Mþ]: 264.0620. Mp 161–164 ꢀC.
d
2.43 (s, 3H), 4.26 (s, 2H), 6.94–6.98 (m, 2H), 7.06–7.08 (m,
d
2.37 (s, 3H), 5.26 (s, 1H), 7.15 (d, J¼8.0 Hz, 2H), 7.30–7.33 (m, 6H),
d
21.8,
7.49 (d, J¼8.0 Hz, 2H), 7.52–7.54 (m, 4H); 13C NMR (CDCl3)
d 21.8,
¼
76.7, 128.76, 128.85, 129.2, 129.4, 130.2, 133.3, 135.5, 144.6. Anal.
Calcd for C20H18O2S: C, 74.50; H, 5.63%. Found: C, 74.20; H, 5.67%.
Mp 181–185 ꢀC.
(D
4.3.13. p-Chlorophenyl(phenyl)methyl p-tolyl sulfone (3d)
4.3.3. p-Methoxyphenylmethyl p-tolyl sulfone (1c)15
1H NMR (CDCl3)
2.42 (s, 3H), 3.79 (s, 3H), 4.23 (s, 2H), 6.79 (d,
IR (Nujol) 2924, 2854, 1655, 1457, 1377 cmꢁ1; 1H NMR (CDCl3)
d
2.38
(s, 3H), 5.24 (s, 1H), 7.17–7.18 (m, 2H), 7.29–7.32 (m, 5H), 7.47–7.50 (m,
6H); 13C NMR (CDCl3)
d
J¼8.5 Hz, 2H), 7.00 (d, J¼8.5 Hz, 2H), 7.25 (d, J¼8.5 Hz, 2H), 7.51 (d,
d
21.8, 75.8, 129.0 (ꢂ2C), 129.1, 129.2, 129.6, 130.0,
J¼8.5 Hz, 2H); 13C NMR (CDCl3)
d
21.8, 55.4, 62.4, 114.2, 120.3, 128.8,
131.4, 131.8, 132.9, 135.0, 135.2, 144.9. Anal. Calcd for C20H17ClO2S: C,
67.31; H, 4.80%. Found: C, 67.10; H, 4.90%. Mp 131–135 ꢀC.
129.7, 132.2, 135.2, 144.8, 160.1.
4.3.4. 2-Naphthylmethyl p-tolyl sulfone (1d)
4.3.14. Phenyl(m-trifluoromethylphenyl)methyl p-tolyl sulfone (3e)
IR (Nujol) 2923, 2854, 1654, 1507, 1465, 1151 cmꢁ1
;
1H NMR
IR (Nujol) 2923, 2854, 1692, 1654, 1465, 1451, 1373 cmꢁ1 1H
;
(CDCl3)
(m, 4H), 7.56 (s, 1H), 7.72–7.75 (m, 2H), 7.81–7.83 (m, 1H); 13C
NMR (CDCl3) 21.8, 63.3, 125.9, 126.6, 126.8, 127.9, 128.05,
128.14, 128.5, 128.8, 129.7, 130.7, 133.21, 133.25, 135.2, 144.9. Mp
135–137 ꢀC.
d
2.40 (s, 3H), 4.45 (s, 2H), 7.19–7.22 (m, 3H), 7.46–7.52
NMR (CDCl3) d 2.36 (s, 3H), 5.33 (s, 1H), 7.15–7.17 (m, 2H), 7.32–7.33
(m, 3H), 7.45–7.52 (m, 5H), 7.56–7.57 (m, 1H), 7.66 (s, 1H), 7.84 (d,
d
J¼8.0 Hz, 1H); 13C NMR (CDCl3)
d
21.7, 76.0, 123.9 (q, JC–F¼271 Hz),
125.5 (q, JC–F¼3.8 Hz), 127.1 (q, JC–F¼3.8 Hz), 129.0, 129.08, 129.14,
129.4, 129.6, 130.0, 131.1 (q, JC–F¼32.5 Hz), 132.5, 133.3, 134.4, 134.9,
145.1. Anal. Calcd for C21H17F3O2S: C, 64.60; H, 4.39%. Found: C,
64.61; H, 4.53%. Mp 92–95 ꢀC.
4.3.5. Benzyl p-trifluoromethylphenyl sulfone (1e)
IR (Nujol) 2922, 2854, 1655, 1457, 1378 cmꢁ1 1H NMR (CDCl3)
;
d
4.35 (s, 2H), 7.08–7.10 (m, 2H), 7.26–7.30 (m, 2H), 7.35 (tt, J¼7.0,
4.3.15. tert-Butyl p-[p-tolylsulfonyl(phenyl)methyl]benzoate (3f)
2.0 Hz,1H), 7.70–7.76 (m, 4H); 13C NMR (CDCl3)
d
63.0,123.3 (q, JC–F
¼
IR (Nujol) 2923, 2854, 1654, 1507, 1457, 1151 cmꢁ1 1H NMR
;
272 Hz), 126.2 (q, JC–F¼3.8 Hz), 127.7, 129.0, 129.3, 129.5, 131.0, 135.6
(q, JC–F¼33.0 Hz), 141.5. Anal. Calcd for C14H11F3O2S: C, 55.99; H,
3.69%. Found: C, 55.73; H, 3.81%. Mp 163–165 ꢀC.
(CDCl3)
7.31–7.32 (m, 3H), 7.49–7.51 (m, 4H), 7.59–7.60 (m, 2H), 7.92–7.94
(m, 2H); 13C NMR (CDCl3)
21.8, 28.3, 76.3, 81.5, 128.96, 128.97,
d
1.58 (s, 9H), 2.39 (s, 3H), 5.31 (s, 1H), 7.17 (d, J¼8.0 Hz, 2H),
d
129.2, 129.6, 129.86, 129.94, 130.1, 132.3, 132.8, 135.3, 137.8, 144.9,
165.4. Mp 104–107 ꢀC.
4.3.6. Benzyl p-methoxyphenyl sulfone (1f)16
1H NMR (CDCl3)
d 3.86 (s, 3H), 4.28 (s, 2H), 6.88–6.91 (m, 2H),
7.08–7.10 (m, 2H), 7.25–7.29 (m, 2H), 7.30–7.34 (m, 1H), 7.51–7.54
4.3.16. Phenyl(p-tolyl)methyl p-tolyl sulfone (3g)
(m, 2H); 13C NMR (CDCl3)
128.8, 129.6, 131.0, 163.9.
d
55.8, 63.3, 109.9, 114.2, 128.68, 128.72,
IR (Nujol) 2923, 2854, 1457, 1383, 1141 cmꢁ1 1H NMR (CDCl3)
;
d
2.32 (s, 3H), 2.37 (s, 3H), 5.23 (s, 1H), 7.12–7.16 (m, 4H), 7.29–7.31
(m, 3H), 7.41–7.43 (m, 2H), 7.48–7.52 (m, 4H); 13C NMR (CDCl3)
21.3, 22.0, 76.4, 128.7, 128.8, 129.2, 129.4, 129.6, 130.0, 130.1, 130.2,
4.3.7. N-Benzylsulfonylmorpholine (1g)6e
d
1H NMR (CDCl3)
d
3.10 (dd, J¼4.5, 4.5 Hz, 4H), 3.62 (dd, J¼4.5,
133.5, 135.6, 138.7, 144.5. Anal. Calcd for C21H20O2S: C, 74.97; H,
5.99%. Found: C, 74.93; H, 6.05%. Mp 145–148 ꢀC.
4.5 Hz, 4H), 4.24 (s, 2H), 7.39–7.43 (m, 5H); 13C NMR (CDCl3)
56.9, 66.9, 128.7, 129.0, 129.1, 130.9.
d 46.3,
4.3.17. p-Fluorophenyl(phenyl)methyl p-tolyl sulfone (3h)
4.3.8. N-Benzylsulfonyl-N-methylaniline (1h)6e
IR (Nujol) 2923, 2854, 1655, 1457, 1378 cmꢁ1 1H NMR (CDCl3)
;
1H NMR (CDCl3)
d
3.13 (s, 3H), 4.27 (s, 2H), 7.23–7.28 (m, 3H),
d
2.37 (s, 3H), 5.26 (s, 1H), 6.99–7.03 (m, 2H), 7.16 (d, J¼8.0 Hz, 2H),
7.33–7.41 (m, 7H); 13C NMR (CDCl3)
128.93, 128.94, 129.4, 131.0, 141.6.
d
39.1, 56.5, 126.1, 127.0, 128.8,
7.30–7.33 (m, 3H), 7.47–7.53 (m, 6H); 13C NMR (CDCl3)
d
21.8, 75.7,
115.8 (d, JC–F¼21.5 Hz), 128.88, 128.93, 129.1 (d, JC–F¼3.4 Hz), 129.2,
129.5, 130.0, 131.9 (d, JC–F¼8.1 Hz), 134.2 (d, JC–F¼269 Hz), 144.8,
162.0, 164.0. Anal. Calcd for C20H17FO2S: C, 70.57; H, 5.03%. Found:
C, 70.31; H, 5.20%. Mp 159–162 ꢀC.
4.3.9. 1-Phenylethyl p-tolyl sulfone (1i)
IR (Nujol) 2923, 2854, 1654, 1645, 1457, 1373 cmꢁ1
(CDCl3)
1.76 (d, J¼7.0 Hz, 3H), 2.40 (s, 3H), 4.21 (q, J¼7.0 Hz, 1H),
7.14–7.15 (m, 2H), 7.18–7.20 (m, 2H), 7.23–7.31 (m, 3H), 7.40–7.43
(m, 2H); 13C NMR (CDCl3)
14.3, 21.8, 66.2, 128.5, 128.9, 129.40,
129.44, 129.6, 134.07, 134.08, 144.6. HRMS (DI-EIþ) (m/z) observed:
;
1H NMR
d
4.3.18. p-Methoxyphenyl(phenyl)methyl p-tolyl sulfone (3i)
d
IR (Nujol) 2923, 2854,1457,1377,1141 cmꢁ1;1HNMR (CDCl3)
d
2.37
(s, 3H), 3.78 (s, 3H), 5.22 (s,1H), 6.84 (d, J¼8.5 Hz, 2H), 7.15 (d, J¼8.5 Hz,

T. Niwa et al. / Tetrahedron 65 (2009) 1971–1976
1975
2H), 7.29–7.43 (m, 3H), 7.43–7.46 (m, 2H), 7.48–7.53 (m, 4H); 13C NMR
(CDCl3) 21.8, 55.5, 76.0, 114.2, 125.1, 128.7, 128.8, 129.2, 129.4, 130.0,
131.4,133.6,135.6,144.5, 159.9. Anal. Calcd for C21H20O3S: C, 71.56; H,
5.72%. Found: C, 71.56; H, 5.77%. Mp 155–158 ꢀC.
8H), 7.58–7.61 (m, 4H); 13C NMR (CDCl3)
128.9, 129.2, 129.9, 134.2,141.6. Anal. Calcd for C20H19NO2S: C, 71.19; H,
5.68%. Found: C, 71.22; H, 5.78%. Mp 115–117 ꢀC.
d
39.7, 72.2,126.2,126.9,128.8,
d
4.3.27. Diphenylmethane (4a)17
4.3.19. Phenyl(m-tolyl)methyl p-tolyl sulfone (3j)
1H NMR (CDCl3)
d
3.98 (s, 2H), 7.18–7.21 (m, 6H), 7.26–7.30 (m,
IR (Nujol) 2923, 2854, 1655, 1457, 1379 cmꢁ1
;
1H NMR (CDCl3)
4H); 13C NMR (CDCl3)
d
42.1, 126.3, 128.7, 129.1, 141.3.
d
2.33 (s, 3H), 2.38 (s, 3H), 5.26 (s,1H), 7.13–7.18 (m, 3H), 7.23(dd, J¼7.5,
7.5 Hz, 1H), 7.31–7.39 (m, 5H), 7.50–7.55 (m, 4H); 13C NMR (CDCl3)
4.3.28. 4,4-Diphenyl-1-butene (4b)18
1H NMR (CDCl3)
d
21.6, 21.7, 76.6, 127.1, 128.7 (ꢂ2C), 128.8, 129.2, 129.4, 129.5, 130.1,
d
2.81 (dd, J¼7.5, 7.5 Hz, 2H), 4.00 (t, J¼7.5 Hz,
130.8, 133.1, 133.4, 135.5, 138.5, 144.5. Anal. Calcd for C21H20O2S: C,
74.97; H, 5.99%. Found: C, 74.96; H, 6.06%. Mp 120–122 ꢀC.
1H), 4.94 (d, J¼10.5 Hz, 1H), 5.02 (d, J¼17.0 Hz, 1H), 5.71 (ddt, J¼7.5,
10.5, 17.0 Hz, 1H), 7.16 (dd, J¼7.0, 7.0 Hz, 2H), 7.21–7.28 (m, 8H); 13C
NMR (CDCl3)
d 40.1, 51.4, 116.5, 126.4, 128.1, 128.6, 137.0, 144.7.
4.3.20. Phenyl(o-tolyl)methyl p-tolyl sulfone (3k)
IR (Nujol) 2923, 2854, 1655, 1457, 1375 cmꢁ1
;
1H NMR (CDCl3)
4.3.29. Diphenylacetonitrile (4c)19
1H NMR (CDCl3) 5.13 (s, 1H), 7.30–7.39 (m, 10H); 13C NMR
(CDCl3) 42.8, 119.8, 127.9, 128.4, 129.4, 136.2.
d
2.11 (s, 3H), 2.38 (s, 3H), 5.57 (s, 1H), 7.06 (d, J¼8.0 Hz, 1H), 7.15–
7.21 (m, 3H), 7.28–7.31 (m, 4H), 7.47–7.51 (m, 4H), 8.16 (dd, J¼8.0,
1.0 Hz, 1H); 13C NMR (CDCl3)
19.9, 21.8, 71.5, 126.6, 128.6, 128.7,
d
d
d
128.8, 129.1 (ꢂ2C), 129.5, 130.5, 130.9, 132.2, 133.1, 135.9, 137.0,
144.6. Anal. Calcd for C21H20O2S: C, 74.97; H, 5.99%. Found: C, 74.73;
H, 6.09%. Mp 125–127 ꢀC.
4.3.30. 1,1-Diphenylethane (4d)20
1H NMR (CDCl3)
1.64 (d, J¼7.0 Hz, 3H), 4.14 (q, J¼7.0 Hz, 1H),
7.15–7.19 (m, 2H), 7.21–7.24 (m, 4H), 7.25–7.29 (m, 4H); 13C NMR
(CDCl3) 22.0, 44.9, 126.2, 127.8, 128.5, 146.5.
d
d
4.3.21. 1-Naphthyl(phenyl)methyl p-tolyl sulfone (3l)
IR (neat) 3068, 2930, 2861, 2247, 1507 cmꢁ1
;
1H NMR (CDCl3)
4.3.31. Triphenylmethane (4e)21
d
2.27 (s, 3H), 6.20 (s, 1H), 7.07 (d, J¼7.0 Hz, 2H), 7.22–7.26 (m, 3H),
1H NMR (CDCl3)
d 5.55 (s, 1H), 7.11–7.12 (m, 6H), 7.19–7.22 (m,
7.35–7.39 (m, 2H), 7.48–7.56 (m, 5H), 7.76–7.81 (m, 3H), 8.48 (d,
3H), 7.27–7.30 (m, 6H); 13C NMR (CDCl3)
144.1.
d 57.0, 126.5, 128.5, 129.6,
J¼7.5 Hz, 1H); 13C NMR (CDCl3)
d 21.6, 70.9, 122.2, 125.4, 125.7,
126.8, 127.3, 128.3, 128.66, 128.72, 129.1, 129.2, 129.3, 129.4, 130.5,
131.6, 133.3, 134.1, 135.7, 144.6. HRMS (DI-EIþ) (m/z) observed:
Acknowledgements
372.1180 (
D
¼1.2 ppm), calcd for C24H20O2S [Mþ]: 372.1184.
This work was supported by Grants-in-Aid for Scientific Re-
search and GCOE Research from MEXT and JSPS. T.N. acknowledges
JSPS for financial support.
4.3.22. 2-Naphthyl(phenyl)methyl p-tolyl sulfone (3m)
IR (Nujol) 2923, 2854, 1654, 1465, 1375 cmꢁ1 1H NMR (CDCl3)
;
d
2.34 (s, 3H), 5.45 (s, 1H), 7.12 (d, J¼7.5 Hz, 2H), 7.30–7.34 (m, 3H),
7.46–7.48 (m, 2H), 7.52 (d, J¼6.5 Hz, 2H), 7.57–7.59 (m, 2H), 7.66
References and notes
(dd, J¼9.0, 2.0 Hz, 1H), 7.79–7.80 (m, 3H), 8.00 (s, 1H); 13C NMR
(CDCl3)
d 21.8, 76.7, 126.5, 126.8, 127.2, 127.7, 128.4, 128.6, 128.8,
1.
a-Arylation of carbonyls: (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36,
234–245; (b) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382–
12383; (c) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108–11109;
(d) Gaertzen, O.; Buchwald, S. L. J. Org. Chem. 2002, 67, 465–475; (e) Satoh, T.;
Inoh, J.; Kawamura, Y.; Kawamura, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc.
128.9, 129.2, 129.5, 129.7, 130.2, 130.8, 133.2, 133.3, 133.4, 135.5,
144.7. HRMS (DI-EIþ) (m/z) observed: 372.1181 (
D
¼0.8 ppm), calcd
for C24H20O2S [Mþ]: 372.1184. Mp 141–145 ꢀC.
Jpn. 1998, 71, 2239–2246; g-Arylations of a,b-unsaturated carbonyl compounds:
(f) Terao, Y.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39, 6203–
6206; (g) Muratake, H.; Natsume, M. Tetrahedron Lett. 1997, 38, 7581–7582.
4.3.23. Diphenylmethyl p-trifluoromethylphenyl sulfone (3n)
IR (Nujol) 2922, 2954, 1462, 1378 cmꢁ1 1H NMR (CDCl3)
;
d 5.31
2. Intermolecular arylation at activated benzylic or allylic positions: (a) Inoh, J.;
Satoh, T.; Pivsa-Art, S.; Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39, 4673–
4676; (b) Dyker, G.; Heiermann, J.; Miura, M.; Inoh, J.; Pivsa-Art, S.; Satoh, T.;
Nomura, M. Chem.dEur. J. 2000, 6, 3426–3433; (c) Dyker, G.; Heiermann, J.;
Miura, M. Adv. Synth. Catal. 2003, 345, 1127–1132; (d) Niwa, T.; Yorimitsu, H.;
(s, 1H), 7.31–7.34 (m, 6H), 7.53–7.55 (m, 4H), 7.61 (d, J¼8.0 Hz, 2H),
7.75 (d, J¼8.0 Hz, 2H); 13C NMR (CDCl3)
d
76.7, 123.2 (q, JC–F
¼
272 Hz),125.9 (q, JC–F¼3.9 Hz),129.0, 129.2, 129.8, 130.1,132.4, 135.2
(q, JC–F¼33.0 Hz), 142.0. Anal. Calcd for C20H15F3O2S: C, 63.82; H,
4.02%. Found: C, 63.73; H, 4.10%. Mp 130–133 ꢀC.
´
Oshima, K. Org. Lett. 2007, 9, 2373–2375; (e) Mousseau, J. J.; Larivee, A.; Char-
ette, A. B. Org. Lett. 2008, 10, 1641–1643; (f) Campeau, L.-C.; Schipper, D. J.;
Fagnou, K. J. Am. Chem. Soc. 2008, 130, 3266–3267; (g) Niwa, T.; Yorimitsu, H.;
Oshima, K. Org. Lett. 2008, 10, 4689–4691.
4.3.24. Diphenylmethyl p-methoxyphenyl sulfone (3o)
3. Intramolecular arylative cyclization at benzylic positions: (a) Ren, H.; Knochel,
P. Angew. Chem., Int. Ed. 2006, 45, 3462–3465; (b) Ren, H.; Li, Z.; Knochel, P.
Chem. Asian J. 2007, 2, 416–433; (c) Dong, C.-G.; Hu, Q.-S. Angew. Chem., Int. Ed.
2006, 45, 2289–2292; (d) Hu, Q.-S. Synlett 2007, 1331–1345; (e) Catellani, M.;
Motti, E.; Ghelli, S. Chem. Commun. 2000, 2003–2004; (f) Salcedo, A.; Neuville,
L.; Zhu, J. J. Org. Chem. 2008, 73, 3600–3603.
IR (Nujol) 2910, 2852, 1472, 1378 cmꢁ1
;
1H NMR (CDCl3)
d
3.79
(s, 3H), 5.26 (s, 1H), 6.80 (d, J¼7.0 Hz, 2H), 7.29–7.33 (m, 6H), 7.50–
7.54 (m, 6H); 13C NMR (CDCl3)
55.7, 76.8, 113.9, 128.7, 128.8, 129.9,
d
130.1, 131.3, 133.4, 163.7. Anal. Calcd for C20H18O3S: C, 70.98; H,
5.36%. Found: C, 70.91; H, 5.40%. Mp 145–149 ꢀC.
4. Arylation of N-tert-butylhydrazones as an acyl anion equivalent: Takemiya, A.;
Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 14800–14801.
5. Other C(sp3)–H arylation involving cleavage of less acidic hydrogens: (a) Zait-
sev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154–13155;
(b) Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657–3659; (c) Reddy, B. V. S.;
Reddy, L. R.; Corey, E. J. Org. Lett. 2006, 8, 3391–3394; (d) Kalyani, D.; Deprez, N.
R.; Desai, L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330–7331; (e) Giri, R.;
Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am.
Chem. Soc. 2007, 129, 3510–3511; (f) Barder, T. E.; Walker, S. D.; Martinelli, J. R.;
Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685–4696; (g) Pastine, S. J.; Gribkov,
D. V.; Sames, D. J. Am. Chem. Soc. 2006, 128, 14220–14221; (h) Lafrance, M.;
Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2007, 129, 14570–14571; (i) Wata-
nabe, T.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2008, 10, 1759–1762.
4.3.25. N-(Diphenylmethyl)sulfonylmorpholine (3p)
IR (Nujol) 2924, 2854, 1465, 1458, 1339 cmꢁ1 1H NMR (CDCl3)
;
d
3.02 (dd, J¼4.5, 4.5 Hz, 4H), 3.53 (dd, J¼4.5, 4.5 Hz, 4H), 5.29 (s,
1H), 7.33–7.41 (m, 6H), 7.63–7.65 (m, 4H); 13C NMR (CDCl3)
d
46.5,
66.9, 72.8, 128.9, 129.1, 129.7, 134.2. Anal. Calcd for C17H19NO3S: C,
64.33; H, 6.03%. Found: C, 64.54; H, 6.02. Mp 152–154 ꢀC.
4.3.26. N-Methyl-N,1,1-triphenylmethanesulfonamide (3q)
6.
a-Arylation of a-sulfonyl carbonyl compounds: (a) Grimm, J. B.; Katcher, M. H.;
IR (Nujol) 2923, 2854,1654,1457,1378 cmꢁ1;1HNMR(CDCl3)
d
3.00
Witter, D. J.; Northrup, A. B. J. Org. Chem. 2007, 72, 8135–8138; (b) Kashin, A. N.;
Mitin, A. V.; Beletskaya, I. P.; Wife, R. Tetrahedron Lett. 2002, 43, 2539–2542;
(s, 3H), 5.35 (s, 1H), 7.14–7.16 (m, 2H), 7.21–7.24 (m, 1H), 7.28–7.38 (m,

1976
T. Niwa et al. / Tetrahedron 65 (2009) 1971–1976
(c) Mitin, A. V.; Kashin, A. N.; Beletskaya, I. P. J. Organomet. Chem. 2004, 689,
1085–1090; (d) Zeevaart, J. G.; Parkinson, C. J.; de Koning, C. B. Tetrahedron Lett.
2005, 46, 1597–1599; For -arylation of methanesulfonamides, see Ref. 6d.
Synthesis of benzylic sulfonamides by Pd-catalyzed Negishi coupling of sulfo-
nylmethylzinc chlorides with aryl halides: (e) Zhou, G.; Ting, P.; Aslanian, R.;
Piwinski, J. J. Org. Lett. 2008, 10, 2517–2520.
Preville, P.; Tarazi, M.; Winocour, P. D.; Siddiqui, M. A. Bioorg. Med. Chem. Lett.
2002, 12, 1181–1184.
a
12. Substitution reactions of sulfones with carbon nucleophiles in the presence of
aluminum chloride: Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V. Tetra-
hedron 1989, 45, 4293–4308.
13. Nicolaou, K. C.; Duggan, M. E.; Hwang, C.-K. J. Am. Chem. Soc. 1986, 108, 2468–
2469.
14. Ju, Y.; Kumar, D.; Varma, R. S. J. Org. Chem. 2006, 71, 6697–6700.
15. Kuwano, R.; Kondo, Y.; Shirahama, T. Org. Lett. 2005, 7, 2973–2975.
16. Gupta, B. D.; Roy, M.; Roy, S.; Kumar, M.; Das, I. J. Chem. Soc., Perkin Trans. 2 1990,
537–543.
17. Sun, H.-B.; Li, B.; Chen, S.; Li, J.; Hua, R. Tetrahedron 2007, 63, 10185–10188.
18. Yasuda, M.; Saito, T.; Ueda, M.; Baba, A. Angew. Chem., Int. Ed. 2004, 43,1414–1416.
19. Yoshida, H.; Watanabe, M.; Morishita, T.; Ohshita, J.; Kunai, A. Chem. Commun.
2007, 1505–1507.
7. The pKa value of the benzylic protons of PhSO2CH2Ph was reported to be 23.4 in
dimethyl sulfoxide at 25 ꢀC. See: Bordwell, F. G. Acc. Chem. Res. 1988, 1, 456–463.
8. The pKa value of the benzylic proton of PhSO2CHPh2 was reported to be 22.3 in
dimethyl sulfoxide at 25 ꢀC. See Ref. 7.
9. The second arylation was observed in direct arylation of phenyl(4-pyridyl)-
methane providing the corresponding tetraarylmethane. See Ref. 2d.
10. (a) Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R.; Craig, H. A.; Goerlich, J. R.;
Marshall, W. J.; Unverzagt, M. Tetrahedron 1999, 55, 14523–14534; (b) Jafarpour,
L.; Steven, E. D.; Nolan, S. P. J. Organomet. Chem. 2000, 606, 49–54.
11. Diarylmethanesulfonamide skeletons are found in biologically active com-
pounds. See: St-Denis, Y.; Levesque, S.; Bachand, B.; Edmunds, J. J.; Leblond, L.;
20. Chasssaing, S.; Kumarraja, M.; Pale, P.; Sommer, J. Org. Lett. 2007, 9, 3889–3892.
21. Podder, S.; Roy, S. Tetrahedron 2007, 63, 9146–9152.