Palladium-catalyzed coupling reactions of (ArCH2)Ti(O-i-Pr) 3 with aromatic or heteroaromatic bromides

Article abstract of DOI:10.1016/j.tet.2012.03.072

Three benzyltitanium compounds of (ArCH₂)Ti(O-i-Pr)₃ (Ar = Ph (1a), 4-MeOC₆H₄ (1b), 4-FC₆H ₄ (1c)) were prepared and used as benzyl nucleophiles for coupling reactions with aromatic or heteroaromatic bromides. The simple catalytic system of 1 mol % Pd(OAc)₂ and 2 mol % PCy₃ worked efficiently for a wide variety of aromatic bromides, producing diarylmethanes in good to excellent yields of up to 96%. Coupling reactions of hindered aromatic bromides or aromatic bromides containing electron-withdrawing substituents were slower over longer reaction times of 3-6 h. Reactions of heteroaromatic bromides of bromopyridines, bromofurans, or bromothiophenes with benzyl reagents of 1a or 1b required either longer reaction times of 12-24 h or a higher reaction temperature of 80 °C, producing pyridyl-, furyl-, and thienyl-arylmethanes in moderate yields.

Full text of DOI:10.1016/j.tet.2012.03.072

Tetrahedron 68 (2012) 3956e3962
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed coupling reactions of (ArCH )Ti(O-i-Pr) with aromatic
2
3
or heteroaromatic bromides
Shu-Ting Chang, Qinghan Li, Ruei-Tang Chiang, Han-Mou Gau *
Department of Chemistry, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Three benzyltitanium compounds of (ArCH )Ti(O-i-Pr)3 (Ar ¼ Ph (1a), 4-MeOC H (1b), 4-FC H (1c))
2
6
4
6 4
Received 28 December 2011
Received in revised form 9 March 2012
Accepted 20 March 2012
were prepared and used as benzyl nucleophiles for coupling reactions with aromatic or heteroaromatic
bromides. The simple catalytic system of 1 mol % Pd(OAc) and 2 mol % PCy worked efficiently for a wide
2
3
variety of aromatic bromides, producing diarylmethanes in good to excellent yields of up to 96%. Cou-
pling reactions of hindered aromatic bromides or aromatic bromides containing electron-withdrawing
substituents were slower over longer reaction times of 3e6 h. Reactions of heteroaromatic bromides
of bromopyridines, bromofurans, or bromothiophenes with benzyl reagents of 1a or 1b required either
Available online 28 March 2012
Keywords:
Palladium
Benzyl coupling
Aromatic bromide
Heteroaromatic bromide
Benzyltitanium
ꢀ
longer reaction times of 12e24 h or a higher reaction temperature of 80 C, producing pyridyl-, furyl-,
and thienyl-arylmethanes in moderate yields.
Ó 2012 Elsevier Ltd. All rights reserved.
1
. Introduction
halides13 or benzylic halides.14 Yet the above study has not included
the synthesis of heteroaryl-arylmethanes.
To continue our effort in the development of organoalanes or
14
The catalytic cross-coupling reactions of organometallic nucleo-
philes with organic halides were first discovered in the late 60s and
early 70s.1 The carbonecarbon bond cross-coupling reactions,
however, have emerged as the most important synthetic processes
over the past 15 years due to a fast development of effective ligands
1
3d,14,15
organotitanium compounds as efficient coupling reagents
or
16
as addition nucleophiles in asymmetric catalysis, we report
herein a novel coupling reaction of aromatic or heteroaromatic
bromides with benzyltitanium compounds for the synthesis of both
diarylmethanes and heteroaryl-arylmethanes under considerably
mild reaction conditions.
2
and diversified metal centers. Nowadays, the coupling reactions
have been widely applied to the fields of organic synthesis and
material chemistry.3 For arylearyl coupling reaction, palladium
4
5
complexes of phosphorane or NHC-carbene ligands have been the
most studied systems. Recent studies have demonstrated that cat-
2
2
. Results and discussion
alysts of other ligands6 and of economic metals of Ni, Cu, or Fe
7
8
9
.1. Synthesis of benzyltitanium compounds
have also been effective enough. In contrast, the aryl-benzyl or
heteroaryl-benzyl coupling reactions for the synthesis of diaryl-
methanes or aryl-heteroarylmethanes have been less reported.
Diarylmethanes and heteroaryl-arylmethanes are important struc-
In this study, three representative benzyltitanium compounds of
(
ArCH
were prepared as brown liquids or semi-solids from reactions of
ClTi(O-i-Pr) with benzylic Grignard reagents in diethyl ether or
2
)Ti(O-i-Pr)
3
(Ar ¼ C
6 5 6 4 6 4
H (1a), 4-MeOC H (1b), 4-FC H (1c))
10
tural scaffolds of bioactive compounds or subunits in receptor
3
11
molecules for molecular recognition. Some arylmetallic reagents
tetrahydrofuran (Eq. 1). Compounds 1aec contained trace amounts
of dibenzyl impurity and were used directly for coupling reactions
without further purification. 1aec were stable enough and could be
stored under a dry nitrogen atmosphere for months.
12
coupled with benzyl halides have been reported. However, the
reactions required to be carried out in general at elevated temper-
atures or employing higher catalyst loadings of ꢁ1 mol %. Recent
studies have revealed that aryltitanium compounds of ArTi(O-i-Pr)
3
are highly efficient nucleophiles for coupling reactions with aromatic
*
Corresponding author. Fax: þ886 4 22862547; e-mail address: hmgau@drag-
on.nchu.edu.tw (H.-M. Gau).
0
040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.072

S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
3957
2
.2. Optimization of coupling reaction conditions
electron-withdrawing fluoro substituent, the catalytic system was
still effective enough to furnish 3e in a 74% yield (entry 5). However,
the coupling reaction of 4-(trifluoromethyl)phenyl bromide pro-
ceeded slower, producing coupling product 3f in an 88% yield over
a longer reaction time of 3 h (entry 6). The reaction of 4-
cyanophenyl bromide even required 12 h to afford product 3g in
a good 88% yield (entry 7). Coupling reactions of heteroaromatic
bromides of 2-bromopyridine or 3-bromopyridine were sub-
sequently studied; the reactions were found to be much slower,
giving corresponding products 3i and 3j over 24 h in 55% and 65%
yields (entries 8 and 9), respectively.
Coupling reactions of 4-methoxyphenyl bromide (2a) and
(
PhCH
2
)Ti(O-i-Pr)
3
(1a) were optimized in THF using a catalytic
and 2 mol % PCy (Eq. 2); the results are
system of 1 mol % Pd(OAc)
presented in Table 1. The coupling reaction was first carried out at
room temperature over 2 h, affording 1-benzyl-4-methoxybenzene
2
3
(3a) in a 79% conversion (entry 1). However, the reaction completed
ꢀ
over 1 h while raising the reaction temperature to 40 C (entry 2).
Further reducing the reaction time to 0.5 h furnished 3a in a lower
8
3 2
4% conversion (entry 3). Effects of ratios of PCy over Pd(OAc)
were then studied, and a ligand/metal ratio of 1 also furnished 3a in
a 100% conversion (entry 4). In contrast, a catalytic system with
a ligand/metal ratio of 3 shut down the coupling reaction com-
6 4 2 3
Coupling reactions of (4-MeOC H CH )Ti(O-i-Pr) (1b) with
methyl-substituted aryl bromides were subsequently studied. The
reactions of sterically less-hindered 4-methyl- or 3-methyl-phenyl
bromide afforded coupling products 4aeb in 83% and 77% yields
over 1 h (entries 10 and 11). In contrast, the reaction of sterically
hindered 2-methylphenyl bromide (2l) was somewhat slower,
affording 4l in an 81% yield over 3 h (entry 12). The highly hindered
2,6-dimethylphenyl bromide (2m) required 6 h to furnish product
pletely (entry 5). Reducing the amount of Pd(OAc) down to
2
.2 mol % revealed that the system with the PCy /Pd(OAc) ratio of 2
2
0
3
produced 3a in a higher 84% conversion (entry 6) as compared to
a 65% conversion while using the catalyst with the PCy /Pd(OAc)
ratio of 1 (entry 7). Phosphine ligands of PCy Ph, PPh , and P(p-
tolyl) were subsequently screened, affording the coupling product
3
2
2
3
3
4m in a 70% yield (entry 13). Coupling reactions of 3,5-
in lower conversions of around 70% (entries 8e10). It is worth
noting that the coupling reaction didn’t take place at all while
employing the bidentate dppe [bis(diphenylphosphino)ethane] li-
bis(trifluoromethyl)phenyl bromide, 2-bromonaphthylene and 1-
bromonaphthylene were also explored to give 4n in an 81% yield
over 6 h (entry 14), 4o in an 80% yield (3 h, entry 15), and 4p in
a 90% yield (3 h, entry 16). For coupling reactions of heteroaromatic
bromides of bromofurans or bromothiophenes, the reactions re-
gand (entry 11). Tuning the amount of (PhCH
.5 mmol to 1.3 mmol yielded 3a in a 93% conversion (entry 12). The
solvent effects were also investigated and THF was the best choice
over diethyl ether (86%), hexane (82%), toluene (80%), and CH Cl
39%).
2 3
)Ti(O-i-Pr) from
1
ꢀ
quired to be conducted at a higher temperature of 80 C over
2
2
a longer reaction time of 12 h, producing products 4qeu in yields
ranged from 44 to 70% (entries 17e20). However, the higher re-
action temperature also induced higher levels of homo-coupling
product of 1,2-bis(4-methoxyphenyl)ethane in 21e44% yields de-
(
rived from the (4-MeOC
demonstrated three examples of coupling reactions of 2a, 2d, or 2g
with (4-FC )Ti(O-i-Pr) (1c), producing compounds 5a, 5d, and
g in 94%, 63%, and 94% yields (entries 21e23), respectively. Simi-
6 4 2 3
H CH )Ti(O-i-Pr) reagent. This study also
6
H
4
3
5
larly, the coupling reaction of 4-cyanobromobenzene (2g) con-
taining the strong electron-withdrawing CN substituent required
a reaction time of 12 h (entry 23).
Table 1
a
Optimization of reaction conditions of bromobenzene and PhTi(O-i-Pr)
3
mol % Temp ( C) Time (h) Yieldb (%)
ꢀ
Entry Pd(OAc)
2
(mol %)
L
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
PCy
PCy
PCy
PCy
PCy
PCy
PCy
PCy
PPh
P(p-tolyl)
dppe
PCy
3
3
3
3
3
3
3
2
2
2
2
1
rt
2
1
0.5
1
1
1
1
1
1
79
100
84
100
0
84
65
70
67
70
0
40
40
40
40
40
40
40
40
40
40
40
In this study, lower yields of desired products and/or longer
1
3
reaction times required for coupling reactions of 4-MeSC
(entry 3), 4-Me NC Br (entry 4), or heteroaromatic bromides
entries 8, 9, 17e20) are attributed to a coordination ability of the
6 4
H Br
0.2
0.2
1
1
1
0.4
0.2
2
2
2
2
6 4
H
Ph
(
3
donor atom of the substituent in 4-substituted aryl bromides or the
heteroatom in heteroaromatic bromides toward the palladium
metal center of the catalyst and/or the titanium metal center of
benzyltitanium reagents. The coordination of substrates retard an
0
1
2
3
1
1
1
1
1
1
1
c
3
93
a
b
c
Compound 2a, 1.0 mmol; (PhCH
Yields of 3a were determined based on H NMR data.
PhCH )Ti(O-i-Pr) , 1.3 mmol.
2 3
)Ti(O-i-Pr) , 1.5 mmol; THF, 1 mL.
2
1
access of the sp CeBr bond to the palladium metal center in the
(
2
3
oxidative addition step, resulting in lower yields of coupling
products or requirements of longer reaction times. In contrast, the
reactivity of 4-FC
with BnTi(O-i-Pr)
eter with the observation of longer reaction times required for
6
H
4
Br, 4-CF
3
C
6
H
4
Br, or 4-CNC
6
H
4
Br (entries 5e7)
2
.3. Reaction scope of substrates
3
can be correlated with the Hammet
s
p
param-
17
The reaction scope of the coupling reactions of (ArCH
2
)Ti(O-i-
substituents of larger
p 3
s values, i.e., CN>CF >F.
Pr)
bromides was studied employing the optimized catalytic system of
mol % Pd(OAc) and 2 mol % of PCy (Eq. 3). The results are
summarized in Table 2. Coupling reactions of (PhCH )Ti(O-i-Pr)
1a) with aryl bromides bearing an electron-donating substituent
3
with a wide variety of aromatic bromides and heteroaromatic
2.4. Catalytic cycle of the coupling reaction
1
2
3
2
3
A likely catalytic cycle of the coupling reaction is proposed as
shown in Fig. 1. The first reaction involves replacements of both
(
of methoxy or methylthio group proceeded efficiently over 1 h to
afford coupling products 3aec in good to excellent yields (entries
acetate anions in Pd(OAc)
reductive elimination of dibenyl ArCH
PCy to furnish a Pd(0) active species of Pd(PCy
addition of aryl bromide or heteroaromatic bromide to I affords
a Pd(II) species of (Cy P) Pd(Ar/HetAr)Br (II). Transmetallation of II
2
with two benzyl groups followed by
CH Ar and coordination of
(I). Oxidative
2
2
1
e3). However, the coupling reaction with 4-(dimethylamino)
phenyl bromide (2d) produced coupling product 3d in a moderate
4% yield over 1 h (entry 4). For aryl bromides containing an
3
3 2
)
6
3
2

3958
S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
Table 2
Coupling reactions of aromatic or heteroaromatic bromides with ArTi(O-i-Pr)
a
3
catalyzed by the catalytic system of 1 mol % Pd(OAc)
2
and 2 mol % PCy
3
Entry
HetArB/ArBr
2
R
Time (h)
Product
Yieldb (%)
96%
1
2a
H
1
3a
2
3
2b
2c
H
H
1
1
3b
3c
94%
82%
4
2d
H
1
3d
64%
5
6
2e
2f
H
H
1
3
3e
3f
74%
88%
7
2g
H
12
3g
88%
8
9
2h
2i
H
H
24
24
3h
3i
55%
65%
1
1
1
0
1
2
2j
OMe
OMe
OMe
1
1
3
4j
83%
77%
81%
2k
2l
4k
4l
1
1
3
4
2m
2n
OMe
OMe
6
6
4m
4n
70%
81%
1
1
5
6
2o
2p
OMe
OMe
3
3
4o
4p
80%
90%
1
1
1
2
7c
8c
9c
0c
2q
2r
2s
2u
OMe
OMe
OMe
OMe
12
12
12
12
4q
4r
4s
4u
74%
44%
61%
70%

S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
3959
Table 2 (continued )
Entry
HetArB/ArBr
2
R
F
Time (h)
1
Product
Yieldb (%)
21
2a
5a
94%
2
2
2
3
2d
2g
F
F
1
5d
5g
63%
94%
12
a
b
c
Compound 2, 1.0 mmol; (ArCH
Isolated yield from average of two runs.
The reaction was carried out in 1 mL of toluene; reaction temperature, 80 C.
2 3
)Ti(O-i-Pr) , 1.5 mmol; THF, 1 mL.
ꢀ
time of 24 h, affording desired products in moderate yields. This
study has also demonstrated coupling reactions of bromofurans or
bromothiophenes for the synthesis of furyl- or thienyl-
arylmethanes. The reactions of bromofurans and thiophenes
ꢀ
need to be carried out at 80 C in 12 h. Further studies of coupling
reactions employing the reactive organoalanes or organotitanium
reagents are currently under way.
4
4
. Experimental section
.1. General
All syntheses and manipulations were carried out under a dry
nitrogen atmosphere using standard Schlenk techniques or in
a glovebox. Solvents were dried by refluxing for at least 24 h over
2 5
P O (dichloromethane) or sodium/benzophenone (THF, diethyl
ether, n-hexane or toluene) and were freshly distilled prior to use.
1
H NMR spectra were obtained with a Varian Mercury-400
13
(400 MHz) spectrometer, and C NMR spectra were recorded
1
with the Varian Mercury-400 (100.70 MHz) spectrometer. H and
13
C chemical shifts were measured relative to TMS as the internal
Fig. 1. Proposed catalytic cycle of Pd(OAc)
bromides or heteroaromatic bromides with (ArCH
2 3
/PCy catalyzed coupling reactions of aryl
reference. Elemental analyses were performed using a Heraeus
CHN-O-RAPID instrument. High resolution mass spectroscopy
2
)Ti(O-i-Pr)3.
(HRMS) was performed by using a Finnigan MAT 95 XL Thermo-
Quest Mass spectrometer.
with (ArCH
2
)Ti(O-i-Pr)
3
gives (Cy
3
P)
2
2
Pd(Ar/HetAr)(CH Ar) (III),
which undergoes a reductive elimination process to produce the
coupling product and to regenerate the active species I for next
cycle of reaction. Due to high reactivity of (ArCH )Ti(O-i-Pr) re-
2 3
agents, there is no need to add a base to promote the coupling
reaction.
4
Pr)
.2. General procedures for the synthesis of (ArCH
2
)Ti(O-i-
3
To a two-necked round bottom flask containing magnesium
turning (2.40 g, 0.100 mol) in 100 mL of diethyl ether and equipped
with an addition funnel and condenser, benzyl bromide
0.102 mol) in 50 mL diethyl ether was added slowly over a period
3
. Conclusion
a
(
In summary, three benzyltitanium reagents of (ArCH
Pr) were prepared, and novel and efficient coupling reactions of
3
aromatic or heteroaromatic bromides with the benzyltitanium
reagents have been established. The simple and economic cata-
2
)Ti(O-i-
of 2 h to the magnesium suspension under a dry nitrogen atmo-
sphere. The reaction mixture was stirred for another 2 h to give
a benzyl Grignard solution. The above solution was transferred via
a cannula to a solution of Ti(O-i-Pr)
(2.8 mL, 0.025 mol) in 50 mL diethyl ether cooling at 0 C. The
resulting solution was reacted for 3 h at 0 C to yield a brownish
4
(22.4 mL, 0.0750 mol) and TiCl
4
ꢀ
lytic system of 1 mol % Pd(OAc)
2
and 2 mol % PCy
3
was effective
ꢀ
enough for a variety of aromatic bromides with the reactions
ꢀ
conducting at 40 C in 1 h, affording coupling products in good to
solution. The volatile material was removed completely to afford
excellent yields. Profound electronic, steric, and heteroatom ef-
fects of aromatic or heteroaromatic bromides have been observed.
For hindered aryl bromides or aryl bromides bearing strong
electron-withdrawing substituents, the coupling reactions require
longer reaction times of 3e12 h to afford products in satisfactory
yields. The reactions of bromopyridines even require a reaction
a quantitative yield of a brownish liquid of (PhCH
or brown semi-solid of (4-FC CH )Ti(O-i-Pr)
CH )Ti(O-i-Pr)
at ꢂ20 C as a brown crystalline solid (26.0 g, 75.0%). 1aec con-
tained small amounts of dibenzyl byproduct and was used without
further purification.
2
)Ti(O-i-Pr)
3
(1a)
(1c).
a
6
H
4
2
3
(4-MeOC
6
H
4
2
3
(1b) can be crystallized from n-hexane
ꢀ

3960
S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
4
d
.2.1. (C
6
H
5
CH
2
)Ti(O-i-Pr)
3
(1a). 1
H
NMR (400 MHz, CDCl
3
):
J¼242 Hz), 140.9, 136.7 (d, J¼2.7 Hz), 130.3 (d, J¼7.3 Hz), 128.8, 128.5,
126.2, 115.2 (d, J¼20.9 Hz), 41.0 ppm.
7.16e7.10 (m, 2H), 7.05e7.00 (m, 2H), 6.87e6.81 (m, 1H), 4.45
13
1
(
sept, J¼6.0 Hz, 3H), 2.41 (s, 2H),1.14 (d, J¼6.4 Hz,18H) ppm. C{ H}
NMR (100 MHz, CDCl ): 147.3, 127.9, 127.2, 121.5, 77.2, 65.2,
3
d
4.3.6. 1-Benzyl-4-(trifluoromethyl)benzene (3f).12h Eluent: hexane/
1
2
6.5 ppm.
ethyl acetate¼100/1; colorless liquid (0.208 g, 88%). H NMR
(
400 MHz, CDCl
3
, TMS):
d
7.53 (d, J¼8.4 Hz, 2H), 7.34e7.27 (m, 4H),
(1b). 1H NMR (400 MHz, CDCl
):
7.26e7.20 (m,1H), 7.19e7.15 (m, 2H), 4.03 (s, 2H) ppm. C{ H} NMR
(100 MHz, CDCl ): 145.2, 140.0, 129.2, 128.9, 128.6, 128.5 (q,
13 1
4
d
.2.2. (4-MeOC
6
H
4
2
CH )Ti(O-i-Pr)
3
3
6.95 (d, J¼8.0 Hz, 2H), 6.72 (d, J¼8.0 Hz, 2H), 4.47 (sept, J¼6.0 Hz,
3
d
13
1
3
H), 3.75 (s, 3H), 2.51 (s, 2H), 1.20 (d, J¼6.4 Hz, 18H) ppm. C{ H}
J¼32.0 Hz), 126.5, 125.4 (q, J¼7.3 Hz), 124.3 (q, J¼270 Hz), 41.7 ppm.
NMR (100 MHz, CDCl
2
3
): 154.9, 139.6, 128.1, 113.4, 76.9, 64.5, 55.3,
d
6.6 ppm.
4.3.7. 4-Benzylbenzonitrile (3g).12h Eluent: hexane/ethyl acetate
1
¼
100/1; colorless liquid (0.170 g, 88%). H NMR (400 MHz, CDCl
3
,
4.2.3. (4-FC
6
H
4
2
CH )Ti(O-i-Pr)
3
(1c). 1H NMR (400 MHz, CDCl
3
,
TMS):
(s, 2H) ppm. C{ H} NMR (100 MHz, CDCl
129.4, 128.8, 128.6, 126.5, 118.8, 109.8, 41.7 ppm.
d 7.59e7.55 (m, 2H), 7.35e7.20 (m, 5H), 7.18e7.13 (m, 2H), 4.03
1
3
1
TMS):
d
7.01e6.90 (m, 2H), 6.88e6.79 (m, 2H), 4.47 (sept, J¼6.0 Hz,
3
): d 146.5, 139.2, 132.0,
13
1
3
(
(
H), 2.86 (s, 2H), 1.21 (d, J¼5.6 Hz, 18H) ppm. C{ H} NMR
100 MHz, CDCl ):
158.7 (d, J¼238 Hz), 136.9 (d, J¼3.6 Hz), 128.1
d, J¼7.3 Hz), 114.4 (d, J¼21 Hz), 77.2, 64.0, 26.5 ppm.
3
d
4.3.8. 2-Benzylpyridine (3h).18 Eluent: hexane/ethyl acetate¼5/1;
1
colorless liquid (0.093 g, 55%). H NMR (400 MHz, CDCl
3
, TMS):
d
8.56e8.50 (m, 1H), 7.58e7.50 (m, 1H), 7.34e7.16 (m, 5H),
13
1
4
.3. General procedures for coupling reactions of aromatic or
heteroaromatic bromide with benzyltitanium reagents of
aec
7.12e7.04 (m, 2H), 4.15 (s, 2H) ppm. C{ H} NMR (100 MHz, CDCl
160.9, 149.2, 139.4, 136.4, 129.0, 128.5, 126.3, 123.0, 121.1,
44.6 ppm.
3
):
d
1
To a reaction vessel containing Pd(OAc)
PCy (5.6 mg, 0.020 mmol), and an aromatic or a heteroaromatic
bromide (1.00 mmol) in 0.5 mL THF was added a solution of (ArCH
Ti(O-i-Pr) (1.50 mmol) in 0.5 mL THF. The mixture was reacted at
2
(2.2 mg, 0.010 mmol),
4.3.9. 3-Benzylpyridine (3i).18 Eluent: hexane/ethyl acetate¼5/1;
1
3
colorless liquid (0.110 g, 65%). H NMR (400 MHz, CDCl
3
, TMS):
2
)
d
8.52e8.50 (m, 1H), 8.47e8.44 (m, 1H), 7.53e7.46 (m, 1H),
3
ꢀ
7.34e7.28 (m, 2H), 7.27e7.20 (m, 2H), 7.20e7.15 (m, 2H) 3.99 (s, 2H)
13
1
4
0 or 80 C for a given period of time under a dry nitrogen atmo-
sphere. The solution turned dark black and was quenched with
0 mL of water. The solution was extracted with dichloromethane
ppm. C{ H} NMR (100 MHz, CDCl
3
): d 150.0, 147.4, 139.6, 136.4,
136.3, 128.8, 128.6, 126.4, 123.3, 38.9 ppm.
1
(
3ꢃ30 mL). The organic phase was dried over anhydrous magne-
4.3.10. 1-Methoxy-4-(4-methylbenzyl)benzene (4j).12f Eluent: hex-
1
sium sulfate, concentrated to dryness, and purified by column
ane/ethyl acetate¼10/1; colorless liquid (0.191 g, 90%). H NMR
chromatography.
3
(400 MHz, CDCl , TMS): d 7.12e7.04 (m, 6H), 6.84e6.79 (m, 2H),
13
1
3
.88 (s, 2H), 3.77 (s, 3H), 2.31 (s, 3H) ppm. C{ H} NMR (100 MHz,
4
.3.1. 1-Benzyl-4-methoxybenzene (3a).12h Eluent: hexane/ethyl
CDCl ): 157.9, 138.5, 135.3, 133.5, 129.7, 129.0, 128.6, 113.8, 55.1,
3
d
1
acetate¼10/1; colorless liquid (0.190 g, 96%). H NMR (400 MHz,
40.5, 20.9 ppm.
CDCl
2
3
, TMS): d 7.32e7.25 (m, 2H), 7.23e7.15 (m, 3H), 7.14e7.08 (m,
13
1
4.3.11. 1-(4-Methoxybenzyl)-3-methylbenzene (4k).19 Eluent: hex-
H), 6.87e6.80 (m, 2H), 3.93 (s, 2H), 3.78 (s, 3H) ppm. C{ H} NMR
1
(
100 MHz, CDCl
3
):
d
157.9, 141.5, 133.2, 129.8, 128.8, 128.4, 125.9,
ane/ethyl acetate¼10/1; colorless liquid (0.176 g, 83%). H NMR
113.8, 55.1, 41.0 ppm.
3
(400 MHz, CDCl , TMS): d 7.16e7.10 (m, 1H), 7.09e7.03 (m, 2H),
6
.99e6.92 (m, 3H), 6.81e6.75 (m, 2H), 3.84 (s, 2H), 3.69 (s, 3H), 2.27
13
1
4
.3.2. 1-Benzyl-3-methoxybenzene (3b).18 Eluent: hexane/ethyl
3
(s, 3H) ppm. C{ H} NMR (100 MHz, CDCl ): d 157.8, 141.4, 137.8,
133.3, 129.7, 129.5, 128.2, 126.6, 125.8, 113.7, 55.0, 40.9, 21.3 ppm.
1
acetate¼10/1; colorless liquid (0.187 g, 94%). H NMR (400 MHz,
CDCl
H), 6.75e6.70 (m, 2H), 3.93 (s, 2H), 3.72 (s, 3H) ppm. C{ H} NMR
75 MHz, CDCl ): 159.7, 142.6, 140.9, 129.4, 128.9, 128.4, 126.0,
3
, TMS): d 7.29e7.23 (m, 2H), 7.21e7.14 (m, 4H), 6.79e6.75 (m,
13
1
4.3.12. 1-(4-Methoxybenzyl)-2-methylbenzene (4l).20 Eluent: hex-
1
(
1
3
d
ane/ethyl acetate¼10/1; colorless liquid (0.163 g, 77%). H NMR
121.3, 114.7, 111.2, 55.0, 41.9 ppm.
3
(400 MHz, CDCl , TMS): d 7.13e7.08 (m, 3H), 7.07e7.03 (m, 1H),
7
.02e6.97 (m, 2H), 6.80e6.74 (m, 2H), 3.87 (s, 2H), 3.69 (s, 3H), 2.20
13
1
4
.3.3. (4-Benzylphenyl)(methyl)sulfane (3c).12c Eluent: hexane/
(s, 3H) ppm. C{ H} NMR (100 MHz, CDCl
132.3, 130.2, 129.7, 129.6, 126.3, 125.9, 113.7, 55.0, 38.5, 19.5 ppm.
3
): d 157.8, 139.3, 136.4,
1
ethyl acetate¼100/1; colorless liquid (0.176 g, 82%). H NMR
(
400 MHz, CDCl
3
, TMS): d 7.29e7.23 (m, 2H), 7.21e7.13 (m, 5H),
13
1
7.12e7.07 (m, 2H), 3.92 (s, 2H), 2.43 (s, 3H) ppm. C{ H} NMR
4.3.13. 2-(4-Methoxybenzyl)-1,3-dimethylbenzene
hexane/ethyl acetate¼10/1; colorless liquid (0.159 g, 70%). H NMR
(400 MHz, CDCl , TMS): 7.11e7.03 (m, 3H), 6.94e6.89 (m, 2H),
.81e6.75 (m, 2H), 3.99 (s, 2H), 3.76 (s, 3H), 2.23 (s, 6H) ppm.
(4m). Eluent:
1
(
100 MHz, CDCl
3
):
d
140.9, 138.2, 135.7, 129.4, 128.8, 128.4, 127.1,
126.1, 41.3, 16.2 ppm.
3
d
13
6
C
4
.3.4. 4-Benzyl-N,N-dimethylaniline (3d).12h Eluent: hexane/ethyl
1
3
{ H} NMR (100 MHz, CDCl ): d 157.6, 137.1, 136.9, 131.6, 128.6, 128.0,
1
acetate¼10/1; colorless liquid (0.136 g, 64%). H NMR (400 MHz,
126.2, 113.7, 55.0, 34.0, 20.1 ppm. HRMS: m/z calcd for C16
226.1358 [M ], found 226.1356. Anal. Calcd for C16
8.02. O, 7.07%. Found: C; 84.66, H; 8.16, O; 7.12%.
H
18
O
þ
CDCl
H), 6.62e6.56 (m, 2H), 3.78 (s, 2H), 2.78 (s, 6H) ppm. C{ H} NMR
100 MHz, CDCl ): 149.1, 142.0, 129.5, 129.2, 128.7, 128.3, 125.7,
3
, TMS):
d
7.19e7.12 (m, 2H), 7.10e7.05 (m, 3H), 6.98e6.92 (m,
H18O: C, 84.91; H,
13
1
2
(
3
d
1
12.9, 40.9, 40.7 ppm.
4.3.14. 1-(4-Methoxybenzyl)-3,5-bis(trifluoromethyl)benzene
4n). Eluent: hexane/ethyl acetate¼10/1; colorless liquid (0.271 g,
(
(3e).12g Eluent:
hexane/ethyl
81%). H NMR (400 MHz, CDCl
7.11e7.05 (m, 2H), 6.89e6.83 (m, 2H), 4.04 (s, 2H), 3.80 (s, 3H) ppm.
1
4.3.5. 1-Benzyl-4-fluorobenzene
3
, TMS): d 7.71 (s, 1H), 7.61 (s, 2H),
1
acetate¼100/1; colorless liquid (0.138 g, 74%). H NMR (400 MHz,
1
3
1
CDCl
3
, TMS):
d
7.32e7.25 (m, 2H), 7.23e7.10 (m, 5H), 7.00e6.92 (m,
C{ H} NMR (100 MHz, CDCl
3
):
d
158.6, 144.2, 131.7 (q, J¼32.7 Hz),
13
1
2H), 3.95 (s, 2H) ppm. C{ H} NMR (100 MHz, CDCl ): d 161.4 (d,
3
130.9, 129.9, 128.9 (d, J¼2.8 Hz), 123.4 (q, J¼270 Hz), 120.2 (m),

S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
3961
1
1
12 6
14.3, 55.1, 40.6 ppm. HRMS: m/z calcd for C16H F O 334.0792
7.03e6.95 (m, 2H), 4.00 (s, 2H) ppm. 13C{ H} NMR (100 MHz,
þ
[M ], found 334.0783. Anal. calcd for C16
H
12
F
6
O: C, 57.49; H, 3.62;
CDCl ):
3
d
161.6 (d, J¼244 Hz), 146.4, 135.0 (d, J¼2.7 Hz), 132.2, 130.3
O, 4.79%. Found: C, 57.33; H, 3.88; O, 4.55%.
(d, J¼8.2 Hz), 129.4, 118.8, 115.5 (d, J¼21 Hz), 110.1, 41.0 ppm.
1
4
.3.15. 2-(4-Methoxybenzyl)naphthalene (4o).2 Eluent: hexane/
Acknowledgements
1
ethyl acetate¼10/1; white solid (0.199 g, 80%). H NMR (400 MHz,
CDCl
7
2
1
3
, TMS): d 7.76e7.66 (m, 3H), 7.56 (s, 1H), 7.42e7.32 (m, 2H),
Financial support from the National Science Council of Taiwan,
ROC, under the grant number of NSC 99-2113-M-005-005-MY3 is
appreciated.
.25 (d, J¼8.4 Hz, 1H), 7.12e7.05 (m, 2H), 6.82e6.76 (m, 2H), 4.01 (s,
1
3
1
H), 3.69 (s, 3H) ppm. C{ H} NMR (100 MHz, CDCl
39.0, 133.6, 133.0, 132.0, 129.9, 128.0, 127.55, 127.52, 127.48, 126.8,
25.9, 125.2, 113.8, 55.1, 41.1 ppm.
3
): d 158.0,
1
Supplementary data
2
4
.3.16. 1-(4-Methoxybenzyl)naphthalene (4p).2 Eluent: hexane/
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.03.072. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
1
ethyl acetate¼10/1; white solid (0.223 g, 90%). H NMR (400 MHz,
CDCl , TMS): 8.03e7.97 (m, 1H), 7.89e7.83 (m, 1H), 7.75 (d,
J¼8.4 Hz, 1H), 7.49e7.38 (m, 3H), 7.30e7.24 (m, 1H), 7.15e7.08 (m,
3
d
13
1
2
H), 6.84e6.78 (m, 2H), 4.39 (s, 2H), 3.77 (s, 3H) ppm. C{ H} NMR
(
1
150 MHz, CDCl ): 157.9, 137.0, 133.9, 132.6, 132.1, 129.6, 128.6,
27.1, 127.0, 125.9, 125.50, 125.48, 124.2, 113.8, 55.1, 38.1 ppm.
3
d
References and notes
1
. (a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518; (b) Tamura, M.; Kochi, J. J. Am.
Chem. Soc. 1971, 93, 1485.
4
.3.17. 2-(4-Methoxybenzyl)furan (4q).23 Eluent: hexane/ethyl
1
2. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (b) Metal-Catalyzed Cross-
acetate¼10/1; colorless liquid (0.140 g, 74%). H NMR (400 MHz,
Coupling Reactions; de Meíjere, A., Diederích, F., Eds.; Wiley-VCH: Weinhein,
CDCl
2
3
, TMS): d 7.34e7.30 (m, 1H), 7.19e7.13 (m, 2H), 6.88e6.82 (m,
2004; Vols. 1e2; (c) Negishi, E.-i.; Wang, G.; Rao, H.; Xu, Z. J. Org. Chem. 2010,
H), 6.30e6.26 (m, 1H), 6.00e5.95 (m, 1H), 3.91 (s, 2H), 3.79 (s, 3H)
75, 3151.
13
1
ppm. C{ H} NMR (100 MHz, CDCl
3
):
d
158.2, 155.0, 141.3, 130.1,
3. (a) Wegner, H. A.; Reisch, H.; Rauch, K.; Demeter, A.; Zachariasse, K. A.; de
Meijere, A.; Scott, L. T. J. Org. Chem. 2006, 71, 9080; (b) Noguchi, H.; Hojo, K.;
Suginome, M. J. Am. Chem. Soc. 2007, 129, 758; (c) Smith, A. B., III; Razler, T. M.;
Weis, R. M.; Pettit, G. R. J. Org. Chem. 2008, 73, 1201; (d) Denmark, S. E.; Liu, J.
H.-C. Angew. Chem., Int. Ed. 2010, 49, 2978; (e) Song, J.; Kim, P.; Aratani, N.; Kim,
D.; Shinokubo, H.; Osuka, A. Chem.dEur. J. 2010, 16, 3009.
129.6, 113.8, 110.1, 105.9, 55.1, 33.5 ppm.
4
.3.18. 3-(4-Methoxybenzyl)furan (4r).24 Eluent: hexane/ethyl
1
acetate¼10/1; colorless liquid (0.083 g, 44%). H NMR (400 MHz,
4
. (a) So, C. M.; Lau, C. P.; Kwong, F. Y. Angew. Chem., Int. Ed. 2008, 47, 8059; (b)
Marin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461; (c) Fu, G. C. Acc. Chem.
Res. 2008, 41, 1555; (d) Wolf, C.; Xu, H. J. Org. Chem. 2008, 73, 162; (e) Man-
olikakes, G.; Knochel, P. Angew. Chem., Int. Ed. 2009, 48, 205; (f) Liu, Q.; Lan, Y.;
Liu., J.; Li, G.; Wu, Y.-D.; Lei, A. J. Am. Chem. Soc. 2009, 131, 10201; (g) Gooßen, L.
J.; Lange, P. P.; Rodríguez, N.; Linder, C. Chem.dEur. J. 2010, 16, 3906; (h) Wang,
X.; Liu, L.-Y.; Chang, W.-X.; Li, J. Eur. J. Org. Chem. 2010, 5391; (i) Peng, Z.-Y.;
Wang, J.-P.; Cheng, J.; Xie, X.-M.; Zhang, Z.-G. Tetrahedron 2010, 66, 8238; (j) L u€ ,
CDCl
2
3
, TMS): d 7.34e7.31 (m, 1H), 7.19e7.15 (m, 1H), 7.14e7.08 (m,
H), 6.84e6.79 (m, 2H), 6.22e6.19 (m, 1H), 3.75 (s, 3H), 3.68 (s, 2H)
13
1
3
ppm. C{ H} NMR (100 MHz, CDCl ): d 158.0, 142.9, 139.4, 132.4,
129.4, 124.7, 113.8, 111.1, 55.1, 30.2 ppm.
.3.19. 2-(4-Methoxybenzyl)thiophene (4s).25 Eluent: hexane/ethyl
4
1
B.; Fu, C.-L.; Ma, S.-M. Tetrahedron Lett. 2010, 51, 1284.
acetate¼10/1; colorless liquid (0.125 g, 61%). H NMR (400 MHz,
5. (a) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290; (b) Altenhoff, G.;
CDCl
2
3
, TMS): d 7.19e7.11 (m, 3H), 6.93e6.89 (m, 1H), 6.88e6.82 (m,
Goddard, R.; Lehmann, C. W.; Glorius, F. Angew. Chem., Int. Ed. 2003, 42, 3690;
13
1
(c) Yen, S. K.; Koh, L. L.; Huynh, H. V.; Hor, T. S. A. Dalton Trans. 2007, 3952; (d)
H), 6.80e6.76 (m, 1H), 4.10 (s, 2H), 3.79 (s, 3H) ppm. C{ H} NMR
Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440; (e) Xi, Z.-X.; Zhou, Y.-B.;
Chen, W.-Z. J. Org. Chem. 2008, 73, 8497; (f) Organ, M. G.; C¸ alimsiz, S.; Sayah,
M.; Hoi, K. H.; Lough, A. J. Angew. Chem., Int. Ed. 2009, 48, 2383.
. (a) Li, S.-H.; Lin, Y.-J.; Cao, J.-G.; Zhang, S.-B. J. Org. Chem. 2007, 72, 4067; (b)
Alacid, E.; N aꢀ jera, C. Org. Lett. 2008, 10, 5011; (c) Zhao, D.-B.; Wang, W.-H.; Yang,
(
100 MHz, CDCl
3
):
d
158.2, 144.7, 132.5, 129.5, 126.7, 124.8, 123.7,
113.9, 55.2, 35.1 ppm.
6
.3.20. 3-(4-Methoxybenzyl)thiophene (4u).18 Eluent: hexane/ethyl
4
F.; Lan, J.-B.; Yang, L.; Gao, G.; You, J.-S. Angew. Chem., Int. Ed. 2009, 48, 3296; (d)
Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 9651.
1
acetate¼10/1; colorless liquid (0.143 g, 70%). H NMR (400 MHz,
CDCl
2
3
, TMS):
d
7.20e7.16 (m, 1H), 7.11e7.06 (m, 2H), 6.88e6.84 (m,
7. (a) Ackermann, L.; Born, R.; Spatz, J. H.; Meyer, D. Angew. Chem., Int. Ed. 2005,
44, 7216; (b) Xi, Z.-X.; Liu, B.; Chen, W.-Z. J. Org. Chem. 2008, 73, 3954; (c) To-
bisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem., Int. Ed. 2008, 47, 4866; (d)
Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009, 131,
17748; (e) Miyazaki, S.; Koga, Y.; Matsumoto, T.; Matsubara, K. Chem. Commun.
13
1
H), 6.83e6.78 (m, 2H), 3.88 (s, 2H), 3.73 (s, 3H) ppm. C{ H} NMR
(
100 MHz, CDCl
3
):
d
157.9, 141.9, 132.6, 129.6, 128.3, 125.5, 120.9,
113.8, 55.1, 35.5 ppm.
2010, 1932; (f) Yu, D.-G.; Li, B.-J.; Shi, S.-J. Acc. Chem. Res. 2010, 43, 1486; (g) Xie,
L.-G.; Wang, Z.-X. Chem.dEur. J. 2010, 16, 10332.
. (a) Li, J.-H.; Wang, D.-P. Eur. J. Org. Chem. 2006, 2063; (b) Boudet, N.; Sase, S.;
Sinha, P.; Liu, C.-Y.; Krasovskiy, A.; Knochel, P. J. Am. Chem. Soc. 2007, 129, 12358;
4
.3.21. 1-Fluoro-4-(4-methoxybenzyl)benzene (5a).26 Eluent: hex-
8
1
ane/ethyl acetate¼10/1; colorless liquid (0.203 g, 94%). H NMR
(c) Mao, J.-C.; Guo, J.; Fang, F.-B.; Ji, S.-J. Tetrahedron 2008, 64, 3905; (d) Shang,
(
6
(
1
400 MHz, CDCl
.84e6.78 (m, 2H), 3.85 (s, 2H), 3.74 (s, 3H) ppm. C{ H} NMR
100 MHz, CDCl ):
161.3 (d, J¼242 Hz), 158.0, 137.2 (d, J¼2.7 Hz),
3
, TMS): d 7.12e7.02 (m, 4H), 6.96e6.89 (m, 2H),
13
1
R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. Angew. Chem., Int. Ed. 2009, 48, 9350.
. (a) Sherry, B. D.; F u€ rstner, A. Acc. Chem. Res. 2008, 41, 1500; (b) Wen, J.; Zhang, J.;
Chen, S.-Y.; Li, J.; Yu, X.-Q. Angew. Chem., Int. Ed. 2008, 47, 8897; (c) Czaplik, W.
M.; Mayer, M.; von Wangelin, A. J. Angew. Chem., Int. Ed. 2009, 48, 607; (d)
Sarhan, A. A. O.; Bolm, C. Chem. Soc. Rev. 2009, 38, 2730; (e) Hatakeyama, T.;
Hashimoto, S.; Ishizuka, K.; Nakamura, M. J. Am. Chem. Soc. 2009, 131, 11949.
9
3
d
33.0, 130.1 (d, J¼8.2 Hz), 129.7, 115.1 (d, J¼20.9 Hz), 113.9, 55.1,
4
0.1 ppm.
1
0. (a) Wai, J. S.; Egbertson, M. S.; Payne, L. S.; Fisher, T. E.; Embrey, M. W.; Tran, L.
4
.3.22. 4-(4-Fluorobenzyl)-N,N-dimethylaniline (5d).27 Eluent: hex-
O.; Melamed, J. Y.; Langford, H. M.; Guare, J. P., Jr.; Zhuang, L.; Grey, V. E.; Vacca,
J. P.; Holloway, M. K.; Naylor-Olsen, A. M.; Hazuda, D. J.; Felock, P. J.; Wolfe, A. L.;
Stillmock, K. A.; Schleif, W. A.; Gabryelski, L. J.; Young, S. D. J. Med. Chem. 2000,
43, 4923; (b) Forsch, R. A.; Queener, S. F.; Rosowsky, A. Bioorg. Med. Chem. Lett.
2004, 14, 1811; (c) Long, Y.-Q.; Jiang, X.-H.; Dayam, R.; Sanchez, T.; Shoemaker,
R.; Sei, S.; Neamati, N. J. Med. Chem. 2004, 47, 2561.
1
ane/ethyl acetate¼10/1; colorless liquid (0.145 g, 63%). H NMR
(400 MHz, CDCl
3
, TMS): d 7.14e7.08 (m, 2H), 7.05e7.00 (m, 2H),
6
.97e6.89 (m, 2H), 6.71e6.65 (m, 2H), 3.84 (s, 2H), 2.90 (s, 6H) ppm.
1
3
1
C{ H} NMR (100 MHz, CDCl
3
):
d
161.2 (d, J¼242Hz),149.1,137.7,130.1
11. Ma, J. C.; Dougherty, D. A. Chem. Rev. 1997, 97, 1303.
(d, J¼7.2 Hz), 129.4, 129.0, 115.0 (d, J¼20.9 Hz), 112.9, 40.7, 40.0 ppm.
ꢀ
1
2. (a) Vanier, C.; Lorge, F.; Wagner, A.; Mioskowski, C. Angew. Chem., Int. Ed. 2000, 39,
1679; (b) Kuwano, R.; Yokogi, M. Chem. Commun. 2005, 5899; (c) McLaughlin, M.
2
8
Org. Lett. 2005, 7, 4875; (d) Crawforth, C. M.; Fairlamb, I. J. S.; Kapdi, A. R.; Serrano, J.
L.; Taylor, R. J. K.; Sanchez, G. Adv. Synth. Catal. 2006, 348, 405; (e) Molander, G. A.;
Elia, M. D. J. Org. Chem. 2006, 71, 9198; (f) Kofink, C. C.; Knochel, P. Org. Lett. 2006, 8,
4121; (g) Burns, M. J.; Fairlamb, I. J. S.; Kapdi, A. R.; Sehnal, P.; Taylor, R. J. K. Org. Lett.
4
.3.23. 4-(4-Fluorobenzyl)benzonitrile (5g). Eluent: hexane/ethyl
1
acetate¼10/1; white solid (0.157 g, 74%). H NMR (400 MHz, CDCl
3
,
TMS): 7.59e7.54 (m, 2H), 7.28e7.23 (m, 2H), 7.14e7.08 (m, 2H),
d

3
962
S.-T. Chang et al. / Tetrahedron 68 (2012) 3956e3962
007, 9, 5397; (h) Amatore, M.; Gosmini, C. Chem. Commun. 2008, 5019; (i) Bedford,
2
Wu, K.-H.; Chen, C.-A.; Gau, H.-M. J. Org. Chem. 2009, 74, 3500; (i) Biradar, D. B.;
Zhou, S.-L.; Gau, H.-M. Org. Lett. 2009, 11, 3386; (j) Zhou, S.-L.; Chen, C.-R.; Gau,
H.-M. Org. Lett. 2010, 12, 48; (k) Li, Q.-H.; Gau, H.-M. Chirality 2011, 23, 929; (l)
Wu, K.-H.; Zhou, S.-L.; Chen, C.-A.; Yang, M.-C.; Chiang, R.-T.; Chen, C.-R.; Gau,
H.-M. Chem. Commun. 2011, 47, 11668.
R. B.; Huwe, M.; Wilkinson, M. C. Chem. Commun. 2009, 60; (j) Melzig, L.; Metzger,
A.; Knochel, P. J. Org. Chem. 2010, 75, 2131.
3. (a) Han, J. W.; Tokunaga, N.; Hayashi, T. Synlett 2002, 871; (b) Manolikakes, G.;
Dastbaravardeh, N.; Knochel, P. Synlett 2007, 2077; (c) Lee, H. W.; Lam, F. L.; So,
C. M.; Lau, C. P.; Chan, A. S. C.; Kwong, F. Y. Angew. Chem., Int. Ed. 2009, 48, 7436;
1
17. Jaff eꢀ , H. H. Chem. Rev. 1953, 53, 191.
(
2
d) Yang, H.-T.; Zhou, S.-L.; Chang, F.-S.; Chen, C.-R.; Gau, H.-M. Organometallics
009, 28, 5715.
4. Chen, C.-R.; Zhou, S.-L.; Biradar, D. B.; Gau, H.-M. Adv. Synth. Catal. 2010, 352,
718.
5. (a) Ku, S.-L.; Hui, X.-P.; Chen, C.-A.; Kuo, Y.-Y.; Gau, H.-M. Chem. Commun. 2007,
847; (b) Shu, W.-T.; Zhou, S.-L.; Gau, H.-M. Synthesis 2009, 4075; (c) Biradar, D.
B.; Gau, H.-M. Chem. Commun. 2011, 47, 10467.
6. (a) Wu, K.-H.; Gau, H.-M. J. Am. Chem. Soc. 2006, 128, 14808; (b) Chen, C.-A.; Wu,
18. Henry, N.; Enguehard-Gueiffier, C.; Thery, I.; Gueiffier, A. Eur. J. Org. Chem. 2008,
4824.
1
19. Park, S. Y.; Kang, M.; Yie, J. E.; Kim, J. M.; Lee, I.-M. Tetrahedron Lett. 2005, 46,
2849.
20. Kuwano, R.; Yokogi, M. Org. Lett. 2005, 7, 945.
21. In eꢀ s, B.; Moreno, I.; SanMartin, R.; Domínguez, E. J. Org. Chem. 2008, 73,
1
1
3
8448.
1
22. Raghunandan, S. R.; Maulik, P. R.; Panda, G. Tetrahedron Lett. 2005, 46, 5337.
23. Hashmi, A. S. K.; Schwarz, L.; Bats, J. W. J. Prakt. Chem. 2000, 342, 40.
24. Bat, D. G.; Jones, D. G.; La Greca, S. J. Org. Chem. 1991, 56, 6704.
25. Buu-Hoï, N. P.; Eckert, B.; Demerseman, P. J. Org. Chem. 1954, 19, 726.
26. Sun, G.; Wang, Z. Tetrahedron Lett. 2008, 49, 4929.
K.-H.; Gau, H.-M. Angew. Chem., Int. Ed. 2007, 46, 5373; (c) Wu, K.-H.; Chuang,
D.-W.; Chen, C.-A.; Gau, H.-M. Chem. Commun. 2008, 2343; (d) Chen, C.-A.; Wu,
K.-H.; Gau, H.-M. Adv. Synth. Catal. 2008, 350, 1626; (e) Shieh, S.-H.; Chen, C.-A.;
Chuang, D.-W.; Yang, M.-C.; Yang, H.-T.; Gau, H.-M. Chirality 2008, 20, 924; (f)
Biradar, D. B.; Gau, H.-M. Org. Lett. 2009, 11, 499; (g) Zhou, S.-L.; Chuang, D.-W.;
Chang, S.-J.; Gau, H.-M. Tetrahedron: Asymmetry 2009, 20, 1407; (h) Zhou, S.-L.;
27. Bayer Pharmaceuticals Corporation. Patent WO2006/99231 A1, 2006.
28. Metzger, A.; Piller, F. M.; Knochel, P. Chem. Commun. 2008, 5824.