Stereo-selective synthesis of cis-alkenes/halo-alkenes by reaction of diphenylmethane with ethynylbenzenes via sp3 C-H bond activation promoted by iron salts

Article abstract of DOI:10.1016/j.tetlet.2012.05.083

A stereo-selective reaction for the synthesis of cis-alkenes/halo-alkenes from diphenylmethane and ethynylbenzenes was developed in the presence of iron(III) bromide or chloride. Alkenyl bromides/chlorides were obtained in comparatively good yields in chlorobenzene under mild reaction conditions.

Full text of DOI:10.1016/j.tetlet.2012.05.083

Tetrahedron Letters 53 (2012) 3984–3989
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Tetrahedron Letters
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Stereo-selective synthesis of cis-alkenes/halo-alkenes by reaction of
diphenylmethane with ethynylbenzenes via sp3 C–H bond activation
promoted by iron salts
Jianguo Yang a, , Di Chen b, Weiliang Bao c,
⇑
⇑
a School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou 317000, People’s Republic of China
b College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China
c Department of Chemistry, Zhejiang University (Xixi Campus), Hangzhou 310028, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A stereo-selective reaction for the synthesis of cis-alkenes/halo-alkenes from diphenylmethane and
ethynylbenzenes was developed in the presence of iron(III) bromide or chloride. Alkenyl bromides/chlo-
rides were obtained in comparatively good yields in chlorobenzene under mild reaction conditions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 10 April 2012
Revised 15 May 2012
Accepted 18 May 2012
Available online 24 May 2012
Keywords:
cis-Alkenes
Alkynes
Diphenylmethane
Iron tribromide
Stereo-selective
With the emergence of the concepts of ‘atom economy’ and
‘green chemistry’, great efforts have been made to use cheap and
environmentally benign metals1–3 and to develop C–H activation
reactions4 recently. The cross dehydrogenative coupling (CDC) be-
tween two different C–H bonds to form C–C bond has been known
as one of the most efficient and straightforward methodologies for
organic framework construction.5 As the metal with the biggest re-
serve on the earth and low toxicity, iron has been the research hot-
spot for many years6 and indeed, iron exhibited comparatively
good catalytic ability in many reactions. With the development
of research, some special properties have also been found for iron
catalyzed reactions. The Mao group reported a specific cis/trans
isomerism of the target products in the cross-coupling reaction
of vinyl bromides or chlorides with imidazoles catalyzed by iron
in 2009.7 In 2010 our research group reported the synthesis of
substituted 1-halo-1,4-pentadiene derivatives by the reaction of
1,3-diphenylpropenes with ethynylbenzenes promoted by iron
salts,8 which specifically formed cis-alkenes after dehalogenative
hydrogenation. Moreover, our reaction was also a convenient, effi-
cient, and simple way to synthesize alkenyl halides if FeX3 was
used as a promoter.
served as substrates or intermediates in countless transforma-
tions.10 It is a great challenge to synthesize large groups substi-
tuted cis-alkenes in organic synthesis.11 The general synthesis
methodologies of cis-alkenes are the hydrogenative reduction of
the acetylenes with special transition metal catalysts which are
usually expensive and poisonous, cis-eliminations in the gas
phase,12 carbometallation of alkynes,13 McMurry coupling,14 Wit-
ting–Peterson reaction, and Horner–Wadsworth–Emmons Olefin-
ation. In 2010, Wang reported a reaction to synthesize alkenyl
bromides and chlorides from diphenylmethanol and ethynylben-
zene,15 and their method actually was cis-alkenes selective if their
products were debrominated. But no methodology directly using
diphenylmethane and ethynylbenzene as starting substrates via
CDC reaction was reported. Herein we report a new reaction using
diphenylmethane derivatives as substrates, in order to develop a
stereo-selective and convenient path to get cis-alkenes.
Firstly diphenylmethane (1a) and ethynylbenzene (2a) were
chosen as standard substrates under a dry nitrogen atmosphere,
and the results are summarized in Table 1. Benzoquinone (BQ)
was firstly used as the oxidant and dichloroethane (DCE) was used
as a solvent, but no desired product was detected in spite of screen-
ing the reaction temperature (Table 1, entries 1–3) or solvents
(Table 1, entry 4). When 2,3-dichloro-5,6-dicyano-1,4-benzoqui-
none (DDQ) was used as the oxidant instead of BQ, a comparatively
good yield was obtained (Table 1, entry 6). According to NMR
and thereafter debromination of the product 3l (Scheme 2), the
cis-Alkenes have long intrigued organic chemists because they
are motifs of many natural products (Scheme 1),9 and usually
⇑
Corresponding authors.
E-mail addresses: yjg@tzc.edu.cn (J. Yang), wlbao@css.zju.edu.cn (W. Bao).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.083

J. Yang et al. / Tetrahedron Letters 53 (2012) 3984–3989
3985
O
R1
CO2H
O
O
R'
15-epi-PGB2
R
O
laurencenyne
pyrethrins
Scheme 1. Several natural products with motifs of cis-alkenes.
Table 1
Optimization of the reaction conditionsa
Br
Br
Br
FeX
3
+
+
+
X=Cl, Br
1a
2a
3a
4a
3a'
Entry
Metal (equiv)
Oxidant
Solv.
Temp (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
FeCl3(1.0)
FeCl3(1.0)
FeCl3(1.0)
FeCl3(1.0)
FeCl3(1.0)
FeCl3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(1.0)
FeBr3(0.1)
FeBr3(1.0)
BQ
BQ
BQ
BQ
DCE
DCE
DCE
C6H5Cl
DCE
C6H5Cl
C6H5Cl
C6H5Cl
DMF
PhNO2
CH3NO2
DCE
80
110
120
120
120
120
120
50
50
50
50
50
ND
ND
ND
ND
Trace
63
Trace
64
ND
ND
17
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
t-BuOOBu-t
PhI(OAc)2
DDQ
DDQ
9
10
11
12
13
14
15
16
17c
14
Ethykene glycol diethylether
50
50
50
50
ND
ND
ND
28
C6H5Cl
C6H5Cl
C6H5Cl
C6H5Cl
50
Trace
a
Unless otherwise specified, the reaction was carried out using 0.5 mmol of 1a, 0.6 mmol of 2a, 2.0 mL of solvent, and 0.6 mmol of oxidant under an atmosphere of dry
nitrogen.
b
Isolated yield based on the amount of diphenylmethane consumed.
The reaction was carried out in open air atmosphere.
c
Br
1) BuLi, THF, -78°C
2) H O, r.t
2
O
O
O
O
3l
5l
Scheme 2. Debromination of 3l. Reaction conditions: (1) 0.35 mmol of 3l, 1.1 mmol of BuLi, 4 mL of dry THF, ꢀ78 °C, under an atmosphere of dry nitrogen; (2) 15 mL
of H2O, rt.
configuration of the products was determined. The major isomer
was the desired cis-alkene. This was in accordance with our previ-
ous result. The minor product was the double bond shifted product
(4a). Very little trans-alkene (3a0) was detected. In consideration of
the common adhibition of bromine compound in organic reactions
for the better leaving ability of bromine atom, FeBr3 was applied to
the reaction while no desired product was detected at 120 °C (Table
1, entry 7). Considering the FeBr3 may be more active than FeCl3, the
reaction temperature was lowed to 50 °C when FeBr3 was used,
then a good yield was received (Table 1, entry 8). Then solvents
such as DMF, PhNO2, CH3NO2, DCE, and ethylene glycol diethylether
were screened (Table 1, entries 9–13), and chlorobenzene was the
preferable solvent in this condition. Moreover, t-BuOOBu-t or
PhI(OAc)2 was tested as the oxidant. However, they were unsuitable
to this system. When the amount of FeBr3 was reduced to 0.1 equiv,
the desired product was only obtained in 28% yield. If the reaction
was performed in air, acetophenone was collected together with
much starting material.
With the optimized reaction conditions established (Table 1,
entry 8), the generality and efficiency of the DDQ-mediated oxida-
tive cross-coupling reaction between various diphenylmethane
derivatives and different ethynylbenzenes were explored. The

3986
J. Yang et al. / Tetrahedron Letters 53 (2012) 3984–3989
Table 2
Cross-dehydrogenative coupling of various alkynes and diphenylmethane derivativesa
X
X
cat. FeX3
Ar3
Ar2
Ar3
Ar2
Ar3
Ar1
Ar2
+
+
DDQ
X=Cl,Br
Ar1
Ar1
1
2
3
4
Ar3
Ar1
Ar2
Entry
X
Product
Yieldb (%)
Br
Br
1
Br
64
3a:4a (1:2)
Br
Br
F
F
2
3
4
Br
Br
Br
68
56
68
F
3b:4b (1:2)
Br
Br
CF3
CF3
CF
3
3c:4c (2:1)
Br
Br
Cl
Cl
Cl
3d:4d (1:3)
Br
Br
5
Br
70c
3e:4e (4:1)
Br
Br
F
74c
F
6
Br
F
3f:4f (6:1)

J. Yang et al. / Tetrahedron Letters 53 (2012) 3984–3989
3987
Table 2 (continued)
Ar3
CF3
Ar1
Ar2
Entry
X
Product
Yieldb (%)
Br
Br
CF
CF
3
3
7
Br
60c
3g:4g (1:1)
Br
8
Br
67d
O
O
O
O
3h
Br
F
9
Br
Br
Br
73d
41d
70d
O
O
F
O
O
3i
Br
Br
CF3
CF3
CF3
10
O
O
O
O
O
O
3j:4j(1:1)
Br
Br
Br
Cl
O
11
O
O
Cl
O
O
O
3k
3l
12
Br
69d
O
O
O
13
Br
66d
O
O
O
3m
(continued on next page)

3988
J. Yang et al. / Tetrahedron Letters 53 (2012) 3984–3989
Table 2 (continued)
Ar3
Ar1
Ar2
Entry
X
Product
Yieldb (%)
Br
14
Br
62d
O
O
O
O
3n
Cl
Cl
15
Cl
63
3p:4p (2:1)
a
0.5 mmol of 1, 0.6 mmol of 2, 2.0 mL of C6H5Cl, and 0.6 mmol of DDQ, 50 °C, 24 h.
Based on diphenylmethane.
0.5 mmol of 1, 0.6 mmol of 2, 2.0 mL of C6H5Cl, and 0.6 mmol of DDQ, 50 °C, 16 h.
0.5 mmol of 1, 0.6 mmol of 2, 2.0 mL of C6H5Cl, and 0.6 mmol of DDQ, 10 °C, 12 h.
b
c
d
2a
Ph
bromide anion attacked the ethynylbenzene (2a) followed by C–C
bond formation with intermediate A to give the desired product
3a,16a and 3a may be rearranged to 4a in the acidic conditions.
In summary, we have successfully obtained stereoselective
alkenyl halides from the reaction of diphenylmethane and aro-
matic alkyne promoted by FeBr3 or FeCl3. The cis-configuration of
the alkenes was confirmed after debromination even if there were
two big groups in the same side. Further investigations of the
application of this kind of iron salt in organic reactions are under-
way in our laboratory.
FeX3
Ph
O
O
X
Cl
Cl
CN
CN
X
H
Ph
Ph
FeX2
3a
4a
Ph
Ph
Ph
Ph
Ph
X
Ph
Ph
1a
A
Acknowledgment
Ph
This work was financially supported by the Key Innovation
Team of Science & Technology in Zhejiang Province (No. 2010R
50018).
Scheme 3. Proposed Mechanism.
results were outlined in Table 2. The reaction was sensitive to elec-
tronic changes both on the phenyl group of the alkyne and meth-
ane. Ethynylbenzene with an electronic-withdrawing group
reacted well with the diphenylmethane under the standard reac-
tion conditions (Table 2, entries 3, 5, 7, 10, and 12), whereas the
low yield of o-trifluoromethylphenylacetylene (Table 2, entries 4,
8, and 11) was attributed to the relatively insensitive to the reac-
tion conditions. Little desired product was obtained when ethynyl-
benzenes with electron-donating groups such as methyl, ethyl and
propyl were used until intense electron-donating groups were at-
tached to the phenyl group of diphenylmethane (Table 2, entries
13–15). 4,40-dimethoxydiphenylmethane reacted well with ethy-
nylbenzenes with both electron-donating groups and electron-
withdrawing groups. This implied that the reaction may start from
the oxidation of methylene of the diphenylmethane. In most cases
if no electron-withdrawing groups on product no isomer 4 was
formed. Aliphatic alkynes such as n-octyne and heterocyclic al-
kynes like 2-acetylenefuran and 2-acetylenepyrrole were not ame-
nable to this system.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
05.083.
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