Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols under ligand-, base-, and additive-free reaction conditions

Article abstract of DOI:10.1016/j.tet.2011.02.050

An effective, convenient, and mild coupling reaction of benzylic alcohols with terminal alkynes has been developed. As an effective Lewis acid, Cu(OTf)₂-catalyzed arylmethylation of terminal alkynes with benzylic alcohols generated the correspo

Full text of DOI:10.1016/j.tet.2011.02.050

Tetrahedron 67 (2011) 2753e2759
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Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with benzylic alcohols
under ligand-, base-, and additive-free reaction conditions
,
c
,
b,
Kai Ren a, Pinhua Li a, Lei Wang a , Xiuli Zhang
*
*
a Department of Chemistry, Huaibei Normal University, 100 Dongshan Road, Huaibei, Anhui 235000, PR China
b College of Science, Anhui Agricultural University, Hefei, Anhui 230036, PR China
c State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An effective, convenient, and mild coupling reaction of benzylic alcohols with terminal alkynes has been
developed. As an effective Lewis acid, Cu(OTf)2-catalyzed arylmethylation of terminal alkynes with
benzylic alcohols generated the corresponding products in BrCH2CH2Br with good yields in the absence
of ligand, base, and additive.
Received 7 December 2010
Received in revised form 12 February 2011
Accepted 18 February 2011
Available online 24 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Arylmethylation
Benzylic alcohols
CeC bond formation
Cu(OTf)2
Terminal alkynes
1. Introduction
copper-co-catalyzed coupling reaction of a terminal alkyne with an
aryl halide) (Scheme 1, Eq. 1). However, the coupling of terminal al-
Because alkyne units have been found in a wide range of natural
products,1 bioactive compounds,2 and asimportant buildingblocks in
materials science3 and organic synthesis,4 the development of new
methods for incorporating them into organic molecules is an im-
portant topic in organic synthesis. One of the practical methods for
the synthesis of alkynes is the Sonogashira reaction5 (palladium and
kynes with allylic, benzylic, and propargylic electrophiles for the
formation of CspeCsp3 bond has been less widely explored,6 most of
them, usuallyrequireastrongbaseandastoichiometricquantityofan
organometallic reagent (organo-boron,7 -zinc,8 -magnesium,9 -tin,10
or -aluminum11). Recently, Fu and co-workers described the first
applications of carbene ligands in Pd-catalyzed cross-couplings of
Pd-Cu catalyst
R1
R
HX
+
R1
R1
X
H
R
Eq. 1
+
Base, Ligand
R1
n-BuLi (2 equiv.)
Eq. 2
R
H2O
OH
X2B
H
R
+
+
ClCH2CH2Cl
R2
R1
R2
R1
NH2
CCl3
NH
Au-Ag catalyst
ClCH2CH2Cl
Eq. 3
O
R
R
+
+
CCl3
R2
O
R2
Scheme 1.
* Corresponding authors. Tel.: þ86 561 3802 069; fax: þ86 561 3090 518; e-mail address: leiwang@chnu.edu.cn (L. Wang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.050

2754
K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
Table 1
alkyl electrophiles (unactivated alkyl bromides and iodides) with
terminal alkynes.12 Although this method works well even on large
scale, often it is associated with significant drawbacks including the
use of strong base and production of large amounts of halide as by-
products. Following that, Kabalka et al. demonstrated an efficient
substitutionreaction of benzylic alcohols with alkynylborondihalides
(Scheme 1, Eq. 2).13 Benzylic alcohols as electrophiles would be quite
useful since they would be both atom efficient and more environ-
mentally sound. However, the use of alkynylboron dihalides as nu-
cleophiles and the requirement of 2 equiv of n-BuLi limit its
application. Recently, Wang’s group developed the coupling reaction
of trichloroacetimidate with terminal alkyne in the presence of
5.0 mol % of AuCl/AgOTf catalyst system, along with tri-
chloroacetamide as by-product released and precious metals used in
the reaction (Scheme 1, Eq. 3).14 Therefore, the development of
a practical and economical process for CeC (spesp3) bond formation
between terminal alkyne compounds and unmodified substrates is
more essential. In this regard, alcohols as electrophiles would be at-
tractive sinceitwouldbeanatom-economicprocesswithwaterbeing
the only by-product.
The chemistry of alcohol derivatives has received much more
attention for many years because of their plentiful and inexpensive
properties, compared to alkyl halides or esters.15 In addition, the
direct coupling reaction of alcohol with CeH bond is environ-
mentally benign, only generating H2O as the side product. Very
recently, an efficient and mild FeX3-promoted strategy for the
synthesis of various substituted alkenyl halides via intermolecular
addition of benzylic alcohols to aromatic alkynes has been de-
veloped.16 Meanwhile, a Fe(OTf)3/TfOH co-catalyzed coupling re-
action of terminal alkynes with benzylic alcohols has been also
reported.17 As Lewis acid catalyst, Cu(OTf)2 has been proved to be
Optimization of reaction conditions for the model reactiona
Ph
Ph
Ph
Catalyst
Solvent
Ph
H
Ph
OH
1a
+
Ph
3a
2a
Entry
Catalyst
Solvent
Temp (ꢀC)/time (h)
Yield b(%)
1
2
3
4
5
6
7
8
Zn(OTf)2
In(OTf)3
Cu(OTf)2
Fe(OTf)3
TfOH
H2SO4
HCl
AlCl3
FeCl3
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
DMSO
DMF
C2H5OH
CH3CN
CH3NO2
ClCH2CH2Cl
BrCH2CH2Br
BrCH2CH2Br
BrCH2CH2Br
120/12
120/12
120/12
120/12
120/12
120/12
120/12
120/12
120/12
120/12
120/12
80/24
80/24
80/24
90/24
80/12
100/12
120/12
Trace, 23c
Trace, 53c
91, 91c
52, 68c, 75d
c
Trace, 38
0, 0e
0, 0e
0
0
0
0
0
0
0
51
9
10
11
12
13
14
15
16
17
18
65
77
91f, 58g
a
Reaction
conditions:
diphenylmethanol
(1.0 equiv),
phenylacetylene
(1.1 equiv), catalyst (0.5 mol %), solvent (1.0 mL mmolꢁ1), 12 h.
b
Isolated yields.
The catalyst (2.0 mol %) was used.
Fe(OTf)3 (2.0 mol %) and TfOH (4.0 mol %) were used.
Acid (5.0 mol %) was used.
Cu(OTf)2 (1.0 mol %) was used.
Cu(OTf)2 (0.25 mol %) was used.
c
d
e
f
g
powerful alkylnophilic one to activate the
p-systems toward nu-
1, entry 4).17 When other Lewis acid, such as AlCl3 or FeCl3 was used
for the reaction, only corresponding alkenyl chloride was obtained
(Table 1, entries8 and 9).19 Withrespect tothe catalystloading, when
0.25 mol % of Cu(OTf)2 was used, the reaction did not go to com-
pletion, but that a higher loading (1.0 mol %) of the catalyst gave
a very good result (Table 1, entry 18). However, with an increased
loading of the catalyst up to 2.0 mol % there was no increase in the
isolated yield of the product (Table 1, entry 3). Thus, 0.5 mol % of Cu
(OTf)2 is enough to accomplish this reaction. Moreover, this reaction
was strongly influenced by the solvents. No any desired product was
isolated when the reaction was carried out in DMSO, DMF, C2H5OH,
CH3NO2 or CH3CN (Table 1, entries 10e14). The use of ClCH2CH2Cl to
replace BrCH2CH2Br as solvent resulted in decreasing isolated yield
of the product (Table 1, entry 15). However, in the case of
BrCH2CH2Br used as solvent, at a relative low temperature (80,
100 ꢀC), 65 and 77% yield of 3a was isolated, respectively (Table 1,
entries 16 and 17). Therefore, 0.5 mol % of Cu(OTf)2 in 1,2-dibro-
moethane was considered as an efficient catalyst system at 120 ꢀC
for this cross-coupling reaction.
To probe the generality of this reaction, a series of arylmethyla-
tion products of terminal alkynes with benzylic alcohols were then
prepared through this cross-coupling protocol. Under the optimized
reaction conditions, a variety of terminal alkynes and benzylic al-
cohols were chosen as substrates for the reaction in the presence of
0.5 mol % Cu(OTf)2 in BrCH2CH2Br at 120 ꢀC for 12 h without base,
ligand, and additive. The results in Table 2 indicated that arylalkynes
with both electron-donating and electron-withdrawing functional
groups on the benzene rings, such as CH3, t-C4H9, F, Cl, and Br groups
reacted smoothly with diphenylmethanol to afford the corre-
sponding products 3aee in excellent yields (Table 2, entries 1e5).
Fortunately, phenylacetylene also gave a high yield of the desired
product, 3f (Table 2, entry 6). However, no desired coupling product
was detected when aliphatic alkyne was used as one of the substrate
in the reaction and starting materials were unchanged. In an effort to
cleophilic attack.18 As part of our ongoing efforts devoted to the
chemistry of benzylic alcohols to alkynes by using Lewis acids,
herein we wish to report a ligand-free Cu(OTf)2 (0.5 mol %) cata-
lyzed arylmethylation of terminal alkynes with benzylic alcohols in
the absence of base and additive in BrCH2CH2Br. The reactions gen-
erated the corresponding products in good to excellent yields
(90e95%) (Scheme 2).
R1
R2
R1
R2
Cu(OTf)2 (0.5 mol%)
BrCH2CH2Br
H
+
R
OH
H2O
+
R
Scheme 2.
2. Results and discussion
For initial optimization of the reaction conditions and the iden-
tification of the best catalyst, solvent, and reaction temperature,
diphenylmethanol and phenylacetylene were chosen as model
substrates. The results were summarized in Table 1. To our delight,
91% of 3a was obtained when the model reaction was carried out in
BrCH2CH2Br and 0.5 mol % of Cu(OTf)2 was used as catalyst at 120 ꢀC
for 12 h (Table 1, entry 3). Other Lewis acids, such as In(OTf)3, Zn
(OTf)2, and Fe(OTf)3 could catalyze this transformation, but their
efficiencies were much lower than that of Cu(OTf)2, especially under
low loading of catalyst reaction conditions (Table 1, entries 1e4). In
addition, Brønsted acid, TfOH gave the desired compound 3a in 38%
yield with 2.0 mol % loading of TfOH used in the reaction, but trace
amount of 3a was obtained with 0.5 mol % loading of TfOH (Table 1,
entry 5). However, H2SO4 and HCl failed to catalyze the reaction and
no desired 3a was obtained, even in high loading of catalyst used
(Table 1, entries 6 and 7). Notably, the combination of Fe(OTf)3
(2.0 mol %) and TfOH (4.0 mol %) gave 3a in 75% isolated yield (Table

K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
2755
Table 2
Cu(OTf)2-catalyzed coupling of benzylic alcohols and alkynesa
R1
R1
R2
Cu(OTf)2 (0.5 mol%)
OH
+
H
R
R
BrCH2CH2Br
R2
1
2
3
Entry
Alcohol
Alkyne
Product
Yieldb (%)
1
p-CH3C6H4C^CH
90
C6H4CH3-p
OH
3a
2
p-FC6H4C^CH
93
C6H4F-p
OH
OH
3b
3
p-ClC6H4C^CH
91
C6H4Cl-p
3c
4
5
6
p-BrC6H4C^CH
t-C4H9C6H4C^CH
C6H5C^CH
92
91
94
C6H4Br-p
OH
OH
OH
3d
C6H4(t-C4H9)-p
3e
C6H5
3f
Cl
Cl
Cl
7
C6H5C^CH
97
C6H5
OH
3g
Cl
90
Cl
8
C6H5C^CH
C6H5
Cl
OH
3h
(continued on next page)

2756
K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
Table 2 (continued )
Entry
Alcohol
Alkyne
Product
Yieldb (%)
Cl
C6H5
9
C6H5C^CH
C6H5C^CH
C6H5C^CH
96
OH
3i
Cl
F
C6H5
10
91
OH
3j
F
Br
C6H5
11
92
OH
3k
Br
H3C
C6H5
12
C6H5C^CH
93
OH
3l
CH3
a
Reaction conditions: benzylic alcohol (1.0 mmol), alkyne (1.1 mmol), Cu(OTf)2 (0.005 mmol), BrCH2CH2Br (1.0 mL), 120 ꢀC, 12 h.
Isolated yields.
b
explore the scope of the reaction, we have screened the coupling of
presumably be first formed to a carbon cation as the intermediate
in the presence of Lewis acid, Cu(OTf)2, which probably possesses
the resonance structures of allylic cation. The ratio of two
regioisomers, 5 and 50, indicated in Table 3 accounts for the dif-
ference of the stability of two resonance structures in allylic cation
(Scheme 3).
Based on the results obtained, a plausible mechanism of Cu
(OTf)2-catalyzed coupling reaction of terminal alkynes with ben-
zylic alcohols was shown in Scheme 4. Benzyl alcohol was activated
by the Lewis acid, Cu(OTf)2, to form a carbocation intermediate A.
The formed A attacks the electron-rich aromatic alkyne to generate
vinyl cation B, followed by deprotonation to form the corre-
sponding arylmethylation product.17 When other Lewis acid, such
as FeBr3 or FeCl3 was used as promoter for the reaction of benzylic
alcohol with aromatic alkyne, the highly regio- and stereo-selective
alkenyl bromides and chlorides were obtained. It was suggested
that the sp-hybridized vinyl cation B could be attacked by a stron-
ger nucleophile Brꢁ or Clꢁ to generate the corresponding alkenyl
halide in good stereoselectivity.19
representative phenylacetylene with a variety of substituted ben-
zylic alcohols. When benzylic alcohols bearing both electron-do-
nating and electron-withdrawing functional groups on the benzene
rings, such as CH3, F, Cl, and Br groups also reacted smoothly with
phenylacetylene to afford the expected products 3gel in high yields
(Table 2, entries 7e12). Notably, sterically demanding ortho sub-
stituent did not hamper the reaction and the corresponding product
3h was isolated in goodyield (Table 2, entry 8). However, when other
secondary or tertiaryalcohols, such as tert-butyl alcohol, 2-propanol
or cyclohexanol, were treated with phenylacetylene, no desired
coupling products were obtained.
We next tried the coupling reaction of phenylacetylene with
allylic alcohols under the present reaction conditions. When 1,3-
diphenylprop-2-en-1-ol was reacted with phenylacetylene in the
presence of 0.5 mol % of Cu(OTf)2, the corresponding coupling
product 5a was isolated in good yield (Table 3, entry 1). Meanwhile,
when 3-(4-chlorophenyl)-1-phenylprop-2-en-1-ol, 3-(4-methyl-
phenyl)-1-phenylprop-2-en-1-ol, and 3-(2,4-dichlorophenyl)-1-
phenylprop-2-en-1-ol were reacted with phenylacetylene, re-
spectively, under the above reaction conditions, the corresponding
coupling products, a mixture of regioisomers, 5b/5b0, 5c/5c0, and
5d/5d0 were obtained, respectively, in good yields with different
ratios (Table 3, entries 2e4). Having the confirmed structure of 5a
in our hand, the structures of 5b and 5b0, 5c and 5c0, 5d and 5d0,
were given by 1H, 13C NMR spectroscopic analysis, and HR-MS, even
though they are new compounds. The ratios of two regioisomer
products, 5b and 5b0, 5c and 5c0, 5d and 5d0, were determined by 1H
NMR spectral analysis. 1,3-Disubstituted allylic alcohol would
3. Conclusions
In summary, we have developed an effective, convenient, and
mild direct coupling reaction of benzylic alcohols with terminal
alkynes. As an effective Lewis acid, Cu(OTf)2-catalyzed arylmethy-
lation of terminal alkynes with benzylic alcohols generated the
corresponding products in BrCH2CH2Br with good yields in the
absence of ligand, base, and additive. The successful alkynylation of
allylic alcohols also provides a new route to 1,4-enynes, which are

K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
2757
Table 3
Cu(OTf)2-catalyzed coupling of allylic alcohols to phenylacetylene a
b
c
Entry
Alcohol
Product
Yield (%)/5:50
1
78
5a
OH
C6H5
Cl
Cl
Cl
2
3
80 (5:4)
5b
5b'
OH
C6H5
C6H5
H3C
H3C
H3C
84 (5:6)
5c
5c'
OH
C6H5
C6H5
Cl
Cl
Cl
4
71 (72:27)
Cl
Cl
5d
5d'
Cl
OH
C6H5
C6H5
a
Reaction conditions: allylic alcohol (1.0 mmol), phenylacetylene (1.1 mmol), Cu(OTf)2 (0.005 mmol), BrCH2CH2Br (1.0 mL), 120 ꢀC, 12 h.
b
c
Isolated yields.
Ratios were determined by 1H NMR.
suitable for further elaboration. Furthermore, H2O as the only by-
product makes this transformation atom efficient. Further studies
to extend the scope and synthetic utility for Cu-catalyzed cross-
coupling reaction are in progress in our laboratory.
Ar
Ar'
Cu(OTf)2
Ar
Ar'
Ar
Ar'
OH
Scheme 3.
4. Experimental
4.1. General remarks
Ar1
Ar1
Ar2
H
OH
All reactions were carried out under an air atmosphere. All re-
agents were purchased from commercial suppliers and used after
further purification. Products were purified by flash chromatogra-
phy on 230e400 mesh silica gel, SiO2. All 1H NMR, 13C NMR spectra
were measured on a Bruker Avance NMR spectrometer (400 MHz
or 100 MHz, respectively) with CDCl3 as solvent and recorded in
parts per million relative to internal tetramethylsilane standard.
Ar2
A
R
H
Cu(OTf)2OH
Cu(OTf)2
Ar1
R
Ar2
4.2. Typical procedure for Cu(OTf)2-catalyzed arylmethylation
of terminal alkynes with benzylic alcohols without base,
ligand, and additive
B
Cu(OTf)
2OH
Ar1
Ar2
A 10 mL reaction tube was charged with diphenylmethanol
(1.0 mmol), phenylacetylene (1.1 mmol), Cu(OTf)2 (0.005 mmol),
and BrCH2CH2Br (1.0 mL). The reaction vessel was placed in an oil
bath at 120 ꢀC. After the reaction was carried out at this tempera-
ture for 12 h, it was cooled to room temperature, diluted with H2O,
H2O
R
+
Scheme 4. Proposed mechanism of Cu(OTf)2-catalyzed reaction of benzylic alcohol
with terminal alkyne.

2758
K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
and extracted twice with Et2O. The organic layers were combined,
dried over Na2SO4, and concentrated to yield the crude product,
which was further purified by flash chromatography on silica gel
(eluant: petroleum ether) to give the desired cross-coupling
product, 1,3,3-triphenyl-1-propyne (245 mg, 91% yield).
for C21H15Cl: C, 83.30; H, 4.99. Found: C, 83.51; H, 4.75. HR-MS (ESI):
m/z¼302.0867 ([M]þ), calcd for C21H15Cl: 302.0862.
4.3.9. 1,3-Diphenyl-3-(4-chlorophenyl)-1-propyne (3i)13
(400 MHz, CDCl3):
¼7.60e7.59 (m, 2H), 7.54e7.52 (m, 2H),
7.49e7.35 (m, 10H), 5.28 (s, 1H). 13C NMR (100 MHz, CDCl3):
¼141.3, 140.3, 132.8, 131.7, 129.3, 128.8, 128.3, 128.2, 127.9, 127.1,
123.3, 89.7, 85.3, 43.2. IR (neat):
¼3447, 1950, 1900, 1592, 1098,
753, 690 cmꢁ1
.
1H NMR
d
4.3. Analytical data for the arylmethylation of terminal
alkynes with benzylic alcohols products
d
n
.
4.3.1. 1-(4-Methylphenyl)-3,3-diphenyl-1-propyne (3a)13
(400 MHz, CDCl3):
¼7.44e7.42 (m, 4H), 7.36 (d, J¼8.4 Hz, 2H), 7.30
(t, J¼7.2 Hz, 4H), 7.23e7.19 (m, 2H), 7.09 (d, J¼7.6 Hz, 2H), 5.19 (s,1H),
2.32 (s, 3H). 13C NMR (100 MHz, CDCl3):
¼141.9, 138.0, 131.5, 128.9,
128.6, 127.8, 126.8, 120.4, 89.4, 84.9, 43.8, 21.4. IR (neat):
¼3461,
3049, 2534, 1955, 1599, 1505, 1492, 1014, 827, 749, 698 cmꢁ1
.
1H NMR
d
4.3.10. 1,3-Diphenyl-3-(4-fluorophenyl)-1-propyne (3j). 1H NMR
(400 MHz, CDCl3):
¼7.47e7.45 (m, 2H), 7.41e7.35 (m, 4H),
7.32e7.26 (m, 5H), 7.21 (t, J¼7.2 Hz, 1H), 6.98 (t, J¼8.8 Hz, 2H), 5.16
(s, 1H). 13C NMR (100 MHz, CDCl3):
d
d
n
d
¼161.8 (d, J¼243.9 Hz), 141.5,
.
137.5 (d, J¼3.2 Hz), 131.6, 129.4 (d, J¼8.0 Hz), 128.7, 128.2, 128.1,
127.8, 127.0, 123.3, 115.4 (d, J¼21.4 Hz), 89.9, 85.1, 42.6 (d, J¼2.2 Hz).
4.3.2. 1-(4-Fluorophenyl)-3,3-diphenyl-1-propyne (3b)17 1H NMR
.
IR (neat):
n
¼3443, 1953, 1902, 1590, 1088, 750, 687 cmꢁ1. Anal.
(400 MHz, CDCl3):
d
¼7.46e7.42 (m, 6H), 7.32 (t, J¼8.0 Hz, 4H),
Calcd for C21H15F: C, 88.09; H, 5.28. Found: C, 88.31; H, 5.07. HR-MS
7.25e7.23 (m, 2H), 6.99 (t, J¼8.8 Hz, 2H), 5.19 (s, 1H). 13C NMR
(ESI): m/z¼286.1163 ([M]þ), calcd for C21H15F: 286.1158.
(100 MHz, CDCl3):
d
¼162.3 (d, J¼247.4 Hz), 141.6, 133.5 (d,
J¼8.2 Hz), 128.6, 127.8, 126.9, 119.5 (d, J¼3.5 Hz), 115.4 (d,
J¼21.9 Hz), 89.9 (d, J¼1.5 Hz), 83.8, 43.6. IR (neat): ¼3463, 3052,
2536, 1954, 1592, 1507, 1490, 1017, 747, 693 cmꢁ1
4.3.11. 1,3-Diphenyl-3-(4-bromophenyl)-1-propyne (3k). 1H NMR
n
(400 MHz, CDCl3):
7.25e7.21 (m, 1H), 5.15 (s, 1H). 13C NMR (100 MHz, CDCl3):
140.8, 131.7, 131.6, 129.6, 128.7, 128.2, 128.1, 127.8, 127.1, 123.2, 120.8,
d
¼7.47e7.39 (m, 6H), 7.33e7.28 (m, 7H),
.
d
¼141.1,
4.3.3. 1-(4-Chlorophenyl)-3,3-diphenyl-1-propyne (3c). 1H NMR
(400 MHz, CDCl3):
¼7.42e7.37 (m, 6H), 7.33e7.30 (m, 4H),
7.01e6.96 (m, 4H), 5.18 (s, 1H). 13C NMR (100 MHz, CDCl3):
¼141.4,
89.5, 85.2, 43.2. IR (neat):
n
¼3448, 3061, 1953, 1599, 1580, 1485,
d
1448, 1070, 1011, 841, 727, 697 cmꢁ1. Anal. Calcd for C21H15Br: C,
72.64; H, 4.35. Found: C, 72.69; H, 4.57. HR-MS (ESI): m/z¼346.0359
([M]þ), calcd for C21H15Br: 346.0357.
d
133.9, 132.9, 128.6, 128.5, 127.8, 126.9, 121.9, 91.2, 83.7, 43.7. IR
(neat):
n
¼3461, 1952, 1589, 1510, 1489, 1014, 749, 698 cmꢁ1. Anal.
Calcd for C21H15Cl: C, 83.30; H, 4.99. Found: C, 83.48; H, 5.04. HR-
4.3.12. 1,3-Diphenyl-3-(4-methylphenyl)-1-propyne (3l). 1H NMR
MS (ESI): m/z¼302.0861 ([M]þ), calcd for C21H15Cl: 302.0862.
(400 MHz, CDCl3):
d
¼7.45e7.41 (m, 4H), 7.32e7.26 (m, 7H),
7.25e7.24 (m, 1H), 7.10 (d, J¼8.0 Hz, 2H), 5.15 (s, 1H), 2.29 (s, 3H). 13C
4.3.4. 1-(4-Bromophenyl)-3,3-diphenyl-1-propyne (3d)17
(400 MHz, CDCl3):
¼7.42e7.39 (m, 6H), 7.32e7.29 (m, 6H),
7.23e7.18 (m, 2H), 5.18 (s, 1H). 13C NMR (100 MHz, CDCl3):
¼141.4,
.
1H NMR
NMR (100 MHz, CDCl3):
d¼141.9, 138.8, 136.4, 131.6, 129.3, 128.6,
d
128.2, 127.8, 127.7, 126.8, 123.6, 90.4, 84.7, 43.3, 21.0. IR (neat):
d
n
¼3444, 3063,1950,1599,1512,1489, 1447, 1072, 841, 729, 695 cmꢁ1
.
133.1, 131.4, 128.7, 127.8, 126.9, 122.4, 122.1, 91.4, 83.8, 43.7. IR
Anal. Calcd for C22H18: C, 93.57; H, 6.43. Found: C, 93.38; H, 6.62. HR-
(neat):
n
¼3461, 1953, 1587, 1510, 1484, 1011, 756, 697 cmꢁ1
.
MS (ESI): m/z¼282.1406 ([M]þ), calcd for C22H18: 282.1409.
4.3.5. 1-(4-tert-Butylphenyl)-3,3-diphenyl-1-propyne (3e). 1H NMR
(400 MHz, CDCl3):
¼7.43 (t, J¼8.4 Hz, 6H), 7.30 (t, J¼8.0 Hz, 6H),
7.23e7.20 (m, 2H), 5.19 (s,1H), 1.30 (s, 9H). 13C NMR (100 MHz, CDCl3):
¼151.2, 141.9, 131.4, 128.6, 127.9, 126.8, 125.2, 120.4, 89.5, 84.9, 43.7,
4.3.13. (E)-1,3,5-Triphenylpent-4-yne-1-ene,
(400 MHz, CDCl3):
(E)-5a13
.
1H
NMR
d
d
¼7.49e7.47 (m, 4H), 7.38e7.32 (m, 4H),
7.30e7.25 (m, 5H), 7.23e7.16 (m, 1H), 6.76 (d, J¼15.6 Hz, 1H), 6.32
d
(dd, J¼15.6, 6.8 Hz, 1H), 4.73 (d, J¼6.4 Hz, 1H). 13C NMR (100 MHz,
34.7, 31.2. IR (neat):
n
¼3461, 1952, 1590, 1512, 1492, 1074, 763,
CDCl3):
d
¼140.3, 136.8, 131.7, 130.5, 129.6, 128.7, 128.5, 128.2, 128.0,
700 cmꢁ1. Anal. Calcd for C25H24: C, 92.54; H, 7.46. Found: C, 92.69; H,
127.7, 127.5, 127.1, 126.5, 123.4, 88.8, 85.4, 41.2. IR (neat):
n
¼3462,
7.31. HR-MS (ESI): m/z¼324.1876 ([M]þ), calcd for C25H24: 324.1878.
3053, 1951, 1665, 1597, 1512, 1489, 1448, 1112, 820, 754, 691 cmꢁ1
.
4.3.6. 1,3,3-Triphenyl-1-propyne (3f)13
.
1H NMR (400 MHz, CDCl3):
4.3.14. (E)-1,3-Diphenyl-5-(4-chlorophenyl)-4-yne-1-ene (5b) and
(E)-1,5-diphenyl-3-(4-chlorophenyl)-4-yne-1-ene (5b0), (5b/5b0¼5/
d
¼7.45e7.42 (m, 6H), 7.31e7.20 (m, 7H), 7.22e7.18 (m, 2H), 5.19 (s,
1H). 13C NMR (100 MHz, CDCl3):
d
¼141.7, 131.6, 128.6, 128.2, 127.9,
4). 1H NMR (400 MHz, CDCl3):
d
¼7.50e7.47 (m, 3H), 7.41e7.33 (m,
126.9, 123.5, 90.2, 84.9, 43.7. IR (neat):
1483, 755, 697, 525 cmꢁ1
n¼3452, 2943, 1953, 1580,
3H), 7.32e7.28 (m, 5H), 7.27e7.18 (m, 3H), 6.72 (d, J¼15.6 Hz, 1H),
.
6.31e6.24 (m, 1H), 4.73e4.68 (m, 1H). 13C NMR (100 MHz, CDCl3):
d
¼140.0, 138.8, 136.6, 135.3, 133.1, 132.9, 131.7 (d), 130.8, 130.3,
4.3.7. 1,1-Di(4-chlorophenyl)-3-phenyl-1-propyne (3g). 1H NMR
(400 MHz, CDCl3):
¼7.61e7.58 (m, 2H), 7.44e7.38 (m, 11H), 5.23 (s,
1H). 13C NMR (100 MHz, CDCl3):
¼139.8, 133.0, 129.2, 128.9, 128.4,
123.0, 89.1, 85.7, 42.6. IR (neat):
129.2, 129.1, 129.0, 128.8, 128.7, 128.6, 128.5, 128.3, 128.2, 128.1,
128.0, 127.7 (t), 127.2, 126.5, 123.3, 123.1, 88.5, 88.2, 85.7, 85.4, 41.1,
d
d
40.6. IR (neat):
n
¼3467, 3058, 1950, 1675, 1596, 1514, 1489, 1442,
n
¼3422,1950,1900,1594,1091, 756,
1090, 823, 755, 691 cmꢁ1. Anal. Calcd for C23H17Cl: C, 84.01; H, 5.21.
Found: C, 84.23; H, 5.15. HR-MS (ESI): m/z¼328.1022 ([M]þ), calcd
for C23H17Cl: 328.1019.
691 cmꢁ1. Anal. Calcd for C21H14Cl2: C, 74.79; H, 4.18. Found: C,
75.01; H, 4.02. HR-MS (ESI): m/z¼337.0471 ([M]þ), calcd for
C21H14Cl2: 337.0473.
4.3.15. (E)-1,3-Diphenyl-5-(4-methylphenyl)-4-yne-1-ene (5c) and
(E)-1,5-diphenyl-3-(4-methylphenyl)-4-yne-1-ene (5c0), (5c/5c0¼5/
4.3.8. 1,3-Diphenyl-3-(2-chlorophenyl)-1-propyne (3h). 1H NMR
(400 MHz, CDCl3):
7.50e7.42 (m, 8H), 7.32e7.28 (m, 1H), 5.96 (s, 1H). 13C NMR
(100 MHz, CDCl3):
¼140.5, 139.4, 133.3, 131.8, 130.2, 129.7, 128.7,
d¼7.86 (d, J¼1.2 Hz, 1H), 7.67e7.64 (m, 4H),
6). 1H NMR (400 MHz, CDCl3):
d
¼7.49e7.26 (m, 11H), 7.21e7.07 (m,
3H), 6.74 (dd, J¼15.6, 8.8 Hz, 1H), 6.34e6.24 (m, 1H), 4.71 (m, 1H),
d
2.33 (s, 1.64H), 2.30 (s, 1.36H). 13C NMR (100 MHz, CDCl3):
137.3 (d), 136.9, 136.7, 134.0, 131.7, 130.3, 130.2, 129.8, 129.4, 129.2,
128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.7, 127.6, 127.4, 127.0,
d
¼140.4,
128.5, 128.3, 128.2, 128.0, 127.4, 127.1, 123.4, 89.8, 84.8, 40.4. IR
(neat):
n
¼3446, 1951, 1902, 1590, 1070, 752, 692 cmꢁ1. Anal. Calcd

K. Ren et al. / Tetrahedron 67 (2011) 2753e2759
2759
1988; (b) Banthorpe, D. V. In Chemistry of Triple-Bonded Functional Groups;
Patai, S., Ed.; Wiley: New York, NY, 1994; pp 689e737.
126.5, 126.4, 126.1, 123.5, 123.4, 89.1, 89.0, 85.3, 85.2, 41.2, 40.8, 21.1,
21.0. IR (neat):
n¼3465, 3055, 1952, 1660, 1598, 1510, 1490, 1448,
3. (a) Long, N. J.; Williams, C. K. Angew. Chem., Int. Ed. 2003, 42, 2586e2617; (b)
Hwang, G. T.; Son, H. S.; Ku, J. K.; Kim, B. H. J. Am. Chem. Soc. 2003, 125,
11241e11248; (c) Bai, F.-Q.; Zhou, X.; Xia, B.-H.; Liu, T.; Zhang, J.-P.; Zhang, H.-X.
J. Organomet. Chem. 2009, 694, 1848e1860; (d) Wu, R.; Schumm, J. S.; Pearson,
D. L.; Tour, J. M. J. Org. Chem. 1996, 61, 6906e6921; (e) Bunz, U. H. F. Chem. Rev.
2000, 100, 1605e1644.
1112, 817, 756, 691 cmꢁ1. Anal. Calcd for C24H20: C, 93.46; H, 6.54.
Found: C, 93.28; H, 6.72. HR-MS (ESI): m/z¼308.1569 ([M]þ), calcd
for C24H20: 308.1565.
4. (a) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim,
Germany, 1995; (b) Chemistry of Triple-Bonded Functional Groups; Patai, S., Ed.;
Wiley: New York, NY, 1994.
5. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16,
4467e4470; (b) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46e49; (c)
Metal-catalyzed Cross-Coupling Reactions; Diederich, F., Meijere, A., Eds.; Wiley-
VCH: New York, NY, 2004; (d) Tykwinski, R. R. Angew. Chem., Int. Ed. 2003, 42,
1566e1568; (e) Uemura, M.; Yorimitsua, H.; Oshima, K. Tetrahedron 2008, 64,
1829e1833.
6. (a) Negishi, E.-i.; Anastasia, L. Chem. Rev. 2003, 103, 1979e2018; (b) Perez, I.;
Sestelo, J. P.; Sarandeses, L. A. J. Am. Chem. Soc. 2001, 123, 4155e4160; (c) Perez,
I.; Sestelo, J. P.; Sarandeses, L. A. Org. Lett. 1999, 1, 1267e1269.
7. (a) Soderquist, J. A.; Matos, K.; Rane, A.; Ramos, J. Tetrahedron Lett. 1995, 36,
2401e2402; (b) Furstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165e11176; (c)
Castanet, A.-S.; Colobert, F.; Schlama, T. Org. Lett. 2000, 2, 3559e3561; (d) Oh, C.
H.; Jung, S. H. Tetrahedron Lett. 2000, 41, 8513e8516; (e) Molander, G. A.; Ka-
tona, B. W.; Machrouhi, F. J. Org. Chem. 2002, 67, 8416e8423.
4.3.16. (E)-1,3-Diphenyl-5-(2,4-dichlorophenyl)-4-yne-1-ene
(5d)
and (E)-1,5-diphenyl-3-(2,4-dichlorophenyl)-4-yne-1-ene (5d0), (5d/
5d0¼72/27). 1H NMR (400 MHz, CDCl3):
d
¼7.63e7.46 (m, 4H),
7.38e7.34 (m, 4H), 7.30e7.22 (m, 5H), 7.19e7.11 (m, 2H), 6.30e6.22
(m, 1H), 5.18 (d, J¼6.0 Hz, 0.27H), 4.75 (d, J¼6.4 Hz, 0.72H). 13C NMR
(100 MHz, CDCl3):
d
¼139.7, 136.6, 136.5, 133.7, 133.6, 133.5, 133.4,
132.8, 131.7, 131.6, 131.2, 130.5, 129.4, 129.3, 128.8, 128.5, 128.3,
128.2, 128.1, 127.7, 127.6, 127.2, 127.1, 127.0, 126.5, 125.7, 123.2, 123.0,
88.2, 87.5, 85.9, 85.5, 41.4, 37.5. IR (neat):
n
¼3446, 3060, 1954, 1646,
1598, 1558, 1490, 1451, 1101, 867, 755, 691 cmꢁ1. Anal. Calcd for
C23H16Cl2: C, 76.04; H, 4.44. Found: C, 76.25; H, 4.27. HR-MS (ESI):
m/z¼363.0631 ([M]þ), calcd for C23H16Cl2: 363.0629.
8. (a) Anastasia, L.; Negishi, E.-i. Org. Lett. 2001, 3, 3111e3113; (b) Qian, M.; Ne-
gishi, E.-I. Tetrahedron Lett. 2005, 46, 2927e2930.
Acknowledgements
9. (a) Dang, H. P.; Linstrumelle, G. Tetrahedron Lett. 1978, 191e194; (b) Negishi, E.-
I.; Zhang, Y.; Cederbaum, F. E.; Webb, M. B. J. Org. Chem. 1986, 51, 4080e4082;
(c) Yang, L.-M.; Huang, L.-F.; Luh, T.-Y. Org. Lett. 2004, 6, 1461e1463.
10. (a) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1e652; (b)
Cui, D.-M.; Hashimoto, N.; Ikeda, S.-I.; Sato, Y. J. Org. Chem. 1995, 60,
5752e5756.
We gratefully acknowledge financial support by the National
Natural Science Foundation of China (Nos. 20972057, 20772043).
Supplementary data
11. (a) Negishi, E.-i. Acc. Chem. Res. 1982, 15, 340e348; (b) Gelman, D.; Tsveli-
khovsky, D.; Molander, G. A.; Blum, J. J. Org. Chem. 2002, 67, 6287e6290.
12. Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 13642e13643.
13. Kabalka, G. W.; Yao, M. L.; Borella, S. Org. Lett. 2006, 8, 879e881 and references
cited therein.
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.02.050. These data include MOL files and
InChIKeys of the most important compounds described in this
article.
14. Chang, K. L.; Wei, B. L.; Wang, J. B. Tetrahedron Lett. 2009, 50, 2533e2535.
15. Trost, B. M. Science 1991, 254, 1471e1477.
16. (a) Liu, Z.-Q.; Wang, J.; Han, J.; Zhao, Y.; Zhou, B. Tetrahedron Lett. 2009, 50,
1240e1242; (b) Biswas, S.; Maiti, S.; Jana, U. Eur. J. Org. Chem. 2009,
2354e2359.
References and notes
17. During the preparation of our manuscript, Jiao and co-workers reported the
same reaction, they reported that Fe(OTf)3/TfOH co-catalyzed coupling reaction
of terminal alkynes with benzylic alcohols, and the highest yield (77%) was
reached co-catalyzed by Fe(OTf)3 (5 mol %) and TfOH (10 mol %) in DCE.
Markedly, even when 2 mol % of Fe(OTf)3 and 5 mol % of TfOH were employed,
the coupling went well giving 70% yield. See: Xiang, S. K.; Zhang, L. H.; Jiao, N.
Chem. Commun. 2009, 6487e6489 for detail.
1. (a) Paterson, I.; Davies, R. D.; Marquez, R. Angew. Chem., Int. Ed. 2001, 40,
603e607; (b) Toyota, M.; Komori, C.; Ihara, M. J. Org. Chem. 2000, 65,
7110e7113; (c) Yoshimura, F.; Kawata, S.; Hirama, M. Tetrahedron Lett. 1999, 40,
8281e8285; (d) Miller, M. W.; Johnson, C. R. J. Org. Chem. 1997, 62, 1582e1583;
(e) Sakai, A.; Aoyama, T.; Shioiri, T. Tetrahedron Lett. 1999, 40, 4211e4214; (f)
Graham, A. E.; McKerrecher, D.; Davies, D. H.; Taylor, R. J. K. Tetrahedron Lett.
1996, 37, 7445e7448.
18. Huang, H.; Jiang, H. L.; Chen, K. X.; Liu, H. J. Org. Chem. 2009, 74, 5476e5480.
19. Ren, K.; Wang, M.; Wang, L. Eur. J. Org. Chem. 2010, 565e571.
2. (a) Chemistry and Biology of Naturally-Occurring Acetylenes and Related Com-
pounds; Lam, J., Breteler, H., Arnason, T., Hansen, L., Eds.; Elsevier: Amsterdam,