1242
Z.-Q. Liu et al. / Tetrahedron Letters 50 (2009) 1240–1242
Table 2 (continued)
Entry
Alcohols
Alkynes
Major product
Iron salts
FeBr3
Yield (%) E/Zb
Ph
19
1c
2a
96 (3:1)
Ph
Ph
Br
3q
Ph Ph
Br
20
1a
2a
FeBr3
75 (7:1)
3r
a
Reaction conditions: benzyl alcohol 1 (0.5 mmol), aryl alkynes 2 (0.6 mmol), FeCl3Á6H2O (0.25 mmol), or FeBr3 (0.25 mmol), 50 °C, 10 h.
Isolated yield of the E/Z isomer and the ratio were determined by 1H NMR.
b
benzyl alcohols are effective under the conditions, synthesis of var-
ious substituted alkenyl chlorides and bromides via direct C–C
bond formation by benzyl alcohols and alkynes using 50 mol %
FeCl3Á6H2O or FeBr3 makes this procedure very attractive.
A plausible mechanism for the iron-mediated C–C bond forma-
tion using benzyl alcohols and aryl alkynes is depicted in Scheme 3.
Benzyl alcohol is activated by the Lewis acid to form an intermedi-
ate 1, which is substituted by benzyl alcohol to form an ether 2.5
The ether can be easily observed and isolated. It combines with
the iron salt to generate an intermediate 3, which attacks the elec-
tron-rich aryl alkynes to give intermediate 4 and a vinyl cation 5.
The sp-hybridized vinyl cation can be attacked by halides to give
the E/Z isomer of product and the intermediate 1 which will be
run in the next cycle.
In summary, this work demonstrates an efficient and mild iron-
mediated method for synthesis of alkenyl halides via direct C–C
bond formation of benzyl alcohols and aryl alkynes. Compared
with the systems using stoichiometric Lewis acid and strong base
to prepare substituted alkenyl halides, the present procedure
would provide an excellent alternative due to the environmentally
benign system and atom efficiency. Further investigation of this
procedure is underway in our laboratory.
.
R
Ar'
50mol%FeCl3 6H2O
R
or 50mol% FeBr3
(X=Cl, Br)
X
+
R'
Ar'
Ar
Ar
OH
CH2Cl2
50
R'
20 examples
Scheme 2. Reaction of benzyl alcohols and aryl alkynes.
R
OH
H2O + FeX3
R
R
FeX3
FeX3
FeX3
OH
Ar
R
R
O
H
1
O
2
R
X
FeX3
R
R
R
O
4
FeX3
O
FeX3
R
+
Ar
3
5
Ar
Acknowledgment
Scheme 3. A plausible mechanism for reaction of benzyl alcohols and aryl alkynes.
The authors thank Gannan Normal University for financial
support.
temperature (entry 9). Further investigation of solvent effect
showed that CH2Cl2 is a more effective solvent (entries 10–16).
Various aryl alkynes and benzyl alcohols were investigated as
substrates for the reaction under the typical conditions (Table 2).
It is seen from Table 2 that aryl alkynes with electron-donating
groups gave higher yields of the desired products than those bear-
ing electron-withdrawing groups, such as fluorine (entries 1–3).
Middle alkynes such as 1-phenyl-1-propyne 2d and diphenyl eth-
yne 2e also gave moderate to good yields of the corresponding
alkenyl chlorides (entries 4 and 5). Heteroaryl alkynes such as
3-ethynyl pyridine and alkyl alkynes were inactive in this reaction
(entries 6 and 7). Benzyl alcohols gave moderate to excellent yields
of the corresponding chloroalkenes by using FeCl3Á6H2O, electronic
and steric effects were not obvious (entries 8–12). However, 1-(4-
nitro-phenyl)-ethanol gave no products under the conditions.
1,2,3,4-Tetrahydro naphthalen-1-ol 1h gave low yield of the prod-
uct (entry 13). Diaryl methanols gave good yields of the desired
products (entries 14–16). 1-(5-Chloro-thiophen-2-yl)-ethanol 1l
gave moderate yield of the corresponding product, while 1-furan-
2-yl-ethanol 1m gave a mixture (entries 17 and 18). Benzyl alco-
hols with carboxyl group and alkyl alcohols remained inactive. It
is noteworthy that both benzyl alcohols and diaryl methanols gave
good to excellent yields of the corresponding alkenyl bromides by
using 50 mol % of FeBr3 at 50 °C (entries 19 and 20). Although only
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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Liu, Zhong-Quan
