J. Park et al. / Tetrahedron Letters 54 (2013) 4414–4417
4415
Fe (cat.)
the other hand, substitution of an electron-withdrawing group
such as trifluoromethyl-, chloro-, or bromo-, on the phenyl ring re-
sulted in reasonable yields (entries 6–8). Aliphatic alkynes re-
quired longer reaction times than aromatic alkynes (entries 9
and 10). Conjugated enynes allowed hydration only at their C–C
triple bond to produce the corresponding enone (entry 11). Fur-
thermore, (bromoethynyl)-benzene was also hydrated to form 2-
bromoacetophenone in good yields (entry 12). The hydration of
internal alkynes proceeded efficiently to give the corresponding
ketones, although these reactions required longer reaction times
in comparison with those of terminal alkynes (entries 13 and
14). Notably, methylphenylacetylene gave propiophenone exclu-
sively without the formation of 1-phenyl-2-propanone (entry
15). The hydration of 1,3-diethynylbenzene exclusively gave 1,3-
diacetylbenzene (entry 16).
We then examined the reactivity of terminal vs. internal alkyne
and aromatic vs. aliphatic alkyne. The reaction of equimolar mix-
ture of phenylacetylene (1a) and diphenylacetylene (1n) with
1.1 equiv of MsOH under the optimum conditions selectively pro-
duced acetophenone (2a) in 63% yield. Furthermore, the reaction of
phenylacetylene (1a) and 1-dodecyne (1i) gave acetophenone (2a)
in 64% yield and 2-dodecanone (2i) in 9% yield, respectively,
(Scheme 3).
R2
MsOH (1.1 equiv.)
O
R1
R1
R2
or
R2
R1
O
R1, R2 = H, alkyl, aryl, halide
Scheme 2. Iron-catalyzed hydration of alkyne.
the catalysts investigated, FeCl2Á4H2O produced the desired prod-
uct with the highest yield of 92% (entry 9); however, at room tem-
perature, the reaction yield decreased to 75% (entry 10). Next, the
effects of various acids were investigated for 4-pentylphenylacety-
lene. When using p-TsOH, a relatively lower isolated yield of 78%
was obtained (entry 11). No reaction occurred when using AcOH
and CSA (entries 12 and 13, respectively). When using TfOH, slug-
gish conversion of the alkyne was achieved with 59% yield (entry
14). We confirmed that hydration was not caused by a Brønsted-
acid-mediated process, because the reaction did not occur in the
presence of MsOH without iron salts, and trace amounts of ketone
could be detected by TLC analysis (entry 15). Then, various solvents
were investigated to determine the feasibility of the reaction with
FeCl2Á4H2O. The addition of water did not lead to higher conver-
sions; in fact, the use of DCE with water led to longer reaction time
(entry 16). The use of acetonitrile, THF, dioxane, MeOH, and tolu-
ene resulted in low yields (entries 17–21); furthermore, no reac-
tion occurred when using DMF. The best results were obtained
using FeCl2ÁH2O from 4-pentylphenylacetylene; this reaction pro-
duced 4-pentylacetophenone in 92% yield in only 1 h at 60 °C (en-
try 9).
To demonstrate the utility of catalytic iron/MsOH, we also
tested the indirect hydration of the propargylic alcohol system.
1-Phenylprop-2-yn-1-ol (1q) reacted smoothly to produce cinna-
maldehyde (2q) with high yield via the Meyer–Schuster rearrange-
ment. For 1-ethynylcyclohexenol (1r), dehydration proceeded
initially following which the hydration of the alkyne occurred to
Next, we investigated the scope and limitation of this indirect
hydration reaction catalyzed by FeCl2Á4H2O in the presence of
MsOH using a variety of alkynes. The obtained results are shown
in Table 2. Electron-rich aromatic alkynes rather than phenylacet-
ylene were obtained from their corresponding aryl ketones in good
to excellent yields (entries 2 and 3). 4-Ethynylphenol as unpro-
tected alcohol was also hydrated in moderate yield (entry 4). On
produce an a,b-enone 2r as the main product via Rupe rearrange-
ment (Scheme 4).
The most plausible mechanism is that methanesulfonic acid at-
tacks the triple bond activated by the iron salts to form a vinyl sul-
fonate, and then, it undergoes in situ hydrolysis to produce the
ketone. This hypothesis was supported by NMR analysis in the
crude mixture: it was found that the alkyne 1o was readily
Table 1
Optimization of reaction conditionsa
[Fe] cat.
O
Acids
CH3
solvents
n-Pent
n-Pent
1b
2b
Entry
Iron salt
Acid
Solvent
Temp (°C)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
FeCl2
FeBr2
Fe(acac)2
FeCl3
FeBr3
MsOH
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE/H2O
CH3CN
THF
1,4-Dioxane
MeOH
Toluene
DMF
60
60
60
60
60
60
60
60
60
rt
60
60
60
60
60
60
60
60
60
60
60
60
11
3
3.5
7
7
2
3
3
1
7
1.5
18
72
18
28
24
3.5
8
72
24
24
24
72
86
88
66
73
79
75
84
92
75
78
0
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
TsOH
Fe(acac)3
Fe(OTf)3
FeCl3Á6H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
—
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
FeCl2Á4H2O
9
10
11
12
13
14
15
16
17
18
19
20
21
22
AcOH
CSA
TfOH
0
59
Trace
79
74
23
57
35
31
0
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
MsOH
a
Reaction conditions: 4-pentylphenylacetylene (1 mmol), acid (1.1 equiv), iron salt (5 mol %), and solvent (3 mL) under nitrogen atmosphere.
Isolated yield.
b