Mercuric triflate-catalyzed reaction of propargyl acetates with water leading vinyl ketones

Article abstract of DOI:10.1021/ol0527431

Reaction of propargyl acetate with water catalyzed by Hg(OTf)₂ afforded vinyl ketone as the major product along with a dimeric vinyl mercuric product and normal hydration products in small amounts. The reaction is an alternative to the Meyer-Schuster and Rupe rearrangement applicable to primary alcohols, although the mechanism is entirely different.

Full text of DOI:10.1021/ol0527431

ORGANIC
LETTERS
2
006
Vol. 8, No. 3
47-450
Mercuric Triflate-Catalyzed Reaction of
Propargyl Acetates with Water Leading
Vinyl Ketones
4
Hiroshi Imagawa, Yumiko Asai, Hiroto Takano, Hitomi Hamagaki, and
Mugio Nishizawa*
Faculty of Pharmaceutical Sciences, Tokushima Bunri UniVersity, Yamashiro-cho,
Tokushima 770-8514, Japan
mugi@ph.bunri-u.ac.jp
Received November 11, 2005
ABSTRACT
2
Reaction of propargyl acetate with water catalyzed by Hg(OTf) afforded vinyl ketone as the major product along with a dimeric vinyl mercuric
product and normal hydration products in small amounts. The reaction is an alternative to the Meyer−Schuster and Rupe rearrangement
applicable to primary alcohols, although the mechanism is entirely different.
Acid-catalyzed rearrangement of propargyl alcohol to an R,â-
unsaturated ketone is known as the Meyer-Schuster and
Rupe rearrangement. Unfortunately, this reaction has only
650 °C).2c We originally developed Hg(OTf)
2
as a highly
3
efficient olefin cyclization agent, and we applied it to the
4
synthesis of polycyclic terpenoids. Recently, we found that
1
been usable for tert- and sec-alcohols. In this communica-
2 2
the Hg(OTf) and Hg(OTf) -tetramethylurea (TMU) com-
tion, we describe the reaction of propargyl acetate and water
to give vinyl ketones under very mild conditions, catalyzed
by mercury(II) trifluoromethanesulfonate [mercuric triflate,
plexes showed highly efficient catalytic activity in several
(2) (a) Yadav, J. S.; Prahlad, V.; Muralidhar, B. Synth. Commun. 1997,
2
7, 3415-3418. (b) Olivi, N.; Thomas, E.; Peyrat, J. F.; Alami, M.; Brion,
2
hereafter referred to as Hg(OTf) ], as an alternative to the
J. D. Synlett 2004, 2175-2179. (c) Trahanovsky, W. S.; Mullen, P. M. J.
Am. Chem. Soc. 1972, 94, 5086-5087.
Meyer-Schuster and Rupe rearrangement applicable to
primary alcohols, although the mechanism is entirely dif-
ferent. Conversion of primary propargyl alcohols to vinyl
(3) (a) Nishizawa, M.; Takenaka, H.; Nishide, H.; Hayashi, Y. Tetra-
hedron Lett. 1983, 24, 2581-2584. (b) Nishizawa, M.; Morikuni, E.; Asoh,
K.; Kan, Y.; Uenoyama, K.; Imagawa, H. Synlett 1995, 169-170. (c)
Nishizawa, M. Studies in Natural Product Chemistry. In StereoselectiVe
Synthesis, Part A; Rahman, A. u., Ed.; Elsevier: Amsterdam, Holland, 1988;
Vol. 1, pp 655-676. (d) Nishizawa, M. J. Synth. Org. Chem. Jpn. 1999,
57, 677-688.
ketones was reported by Yadav using 6 equiv of Hg(OAc)
2
2a
followed by H
2
S treatment and by Alami using CF
3
CO
2
H
at 100 °C.2b Trahanovsky also reported enone synthesis by
(4) (a) Nishizawa, M.; Takenaka, H.; Hirotsu, K.; Higuchi, T.; Hayashi,
pyrolysis of propargyl esters at very high temperature (around
Y. J. Am. Chem. Soc. 1984, 106, 4290-4291. (b) Nishizawa, M.; Takenaka,
H.; Hayashi, Y. J. Am. Chem. Soc. 1985, 107, 522-523. (c) Nishizawa,
M.; Takenaka, H.; Hayashi, Y. J. Org. Chem. 1986, 51, 806-813. (d)
Nishizawa, M.; Yamada, H.; Hayashi, Y. Tetrahedron Lett. 1986, 27, 187-
190. (e) Nishizawa, M.; Yamada, H.; Hayashi, Y. J. Org. Chem. 1987, 52,
4878-4884. (f) Nishizawa, M.; Takao, H.; Kanoh, N.; Asoh, K.; Hatakeya-
ma, S.; Yamada, H. Tetrahedron Lett. 1994, 35, 5693-5696. (g) Nishizawa,
M.; Morikuni, E.; Takeji, M.; Asoh, K.; Hyodo, I.; Imagawa, H.; Yamada,
H. Synlett 1996, 927-928. (h) Nishizawa, M.; Takao, H.; Iwamoto, Y.;
Yamada, H.; Imagawa, H. Synlett 1998, 76-78. (i) Nishizawa, M.; Imagawa,
H.; Hyodo, I.; Takeji, M.; Morikuni, E.; Asoh, K.; Yamada, H. Tetrahedron
Lett. 1998, 39, 389-392.
(
1) (a) Meyer, K. H.; Schuster, K. Chem. Ber. 1922, 55, 819-821. (b)
Rupe, H.; Kambli, E. HelV. Chim. Acta 1926, 9, 672. (c) Swaminathan, S.;
Narayanan, K. V. Chem. ReV. 1971, 71, 429-438. (d) Chabardes, P.
Tetrahedron Lett. 1988, 29, 6253-6256. (e) Narasaka, K.; Kusama, H.;
Hayashi, Y. Chem. Lett. 1991, 1413-1416. (f) Narasaka, K.; Kusama, H.;
Hayashi, Y. Tetrahedron 1992, 48, 2059-2068. (g) Mercier, C.; Chabardes,
P. Pure Appl. Chem. 1994, 66, 1509-1518. (h) Suzuki, T.; Tokunaga, M.;
Wakatsuki, Y. Tetrahedron Lett. 2002, 43, 7531-7533. (i) Cadierno, V.;
Diez, J.; Garcia-Garrido, S. E.; Gimeno, J. Chem. Commun. 2004, 2716-
2
717.
1
0.1021/ol0527431 CCC: $33.50
© 2006 American Chemical Society
Published on Web 01/10/2006

reactions including hydroxylative 1,6-enyne cyclization to
mercuric product 3 (1% yield) as well as ketones 4 (4%)
and 5 (4%) (Table 1, entry 1). The effects of varying the
5
11
give exomethylene five-membered ring products, cyclization
6
of 1-alkyn-5-ones leading to 2-methylfurans, arylalkyne
7
cyclization leading to dihydronaphthalene derivatives, and
biomimetic tandem cyclization of aryl-ene-yne derivatives
to give polycarbocycles. We have also reported that Hg-
Table 1. Hg(OTf)
2
-Catalyzed Reaction of 1 and H
yield (%)b
Oa
2
8
2 2
(OTf) ‚(TMU) showed highly efficient catalytic activity for
Hg(OTf)2
the hydration of terminal alkynes to give methyl ketones
under very mild conditions. That reaction is far more
efficient than the more commonly used general procedure,
2 4
which employs a significant amount of HgO and H SO in
refluxing aqueous methanol.10 It is well-known that the
hydration of internal alkyne bonds produces a regioisomeric
mixture of ketones, and thus, it is a practically useless
reaction. Consequently, we tried to control the regioselec-
2
tivity of Hg(OTf) -catalyzed hydration of internal alkynes
by using neighboring group participation and examined the
entry
(mol %)
solvent
H O equiv
2
3
4
5
1
2
9
1
2
3
4
5
6
7
8
9
5
5
5
5
5
5
5
1
CH3CN
CH3CN
CH3CN
CH3CN
CH Cl
1.5
1.1
3.0
5.0
1.5
1.5
1.5
1.5
1.5
82
71
66
53
14
16
64
16
74
1
2
4
5
2
2
4
3
3
4
4
4
9
1
14 12
72
2
2
C6H5CH3
CH3NO2
CH3CN
CH3CN
4
68
1
4
75
5
c
5
3
3
a
b
reaction of propargyl acetate 1 with water in the presence
of a catalytic amount of Hg(OTf) (Scheme 1). Contrary to
2
Reactions were carried out at room temperature for 4 h. NMR yield
using mesitylene as the internal standard. c Reaction in the presence of TMU
(5 mol %).
Scheme 1
amount of water on the yield of vinyl ketone were investi-
gated at 1.5, 1.1, 3, and 5 equiv, and the 1.5 equiv was shown
to be the best (Table 1, entries 1-4). Water insoluble
dichloromethane and toluene were shown to be useless as
solvent affording significant amounts of starting material
(Table 1, entries 5 and 6), and nitromethane was not as good
as acetonitrile (Table 1, entry 7). One mol % of catalyst was
not enough to complete the reaction (Table 1, entry 8).
Reaction in the presence of TMU (5 mol %) produced a
higher quantity of 3, and the yield of vinyl ketone 2 was
7
4% at room temperature for 4 h (Table 1, entry 9).
Next, we investigated the reactions of a variety of
-cyclohexyl-2-butynyl esters 6a-k (Scheme 2). By com-
expectation, the major product was not the expected hydra-
tion products 4 or 5 but was vinyl ketone 2.1 A strange
dimeric vinyl mercuric product 3 was also detected in low
4
1a,b
parison with acetate 1 (Table 1, entry 1), 2-methylpropionate
6
a was converted to enone 2 in lower yield (73%) along
1
1c
yield.
To characterize the reaction, we first examined a reaction
of propargyl acetate 1 with 1.5 equiv of H O in the presence
of Hg(OTf) (5 mol %) in acetonitrile at room temperature.
with 3 (2%) and ketones 7a (5%) and 8a (5%) (Table 2,
entry 1). Pivalate 6b, methoxy acetate 6c, and monochlo-
roacetate 6d also produced enone 2 in moderate yield within
several hours (Table 2, entries 2-4). p-Methoxybenzoate 6e,
p-nitrobenzoate 6f, and pentafluorobenzoate 6g formed
product 2 only in poor to moderate yield after 24 h (Table
2
12
2
The reaction was completed within 4 h, and vinyl ketone 2
was obtained in 84% yield after column chromatography on
silica gel. The yield before purification, as measured by
NMR, was 82%. Additional products included the dimeric
2
, entries 5-7). Surprisingly, benzoate 6h and 2,4,6-
trichlorobenzoate 6i produced no trace of products at all
Table 2, entries 8 and 9). On the other hand, formate 6j
produced 2 in 51% yield along with 3 (2%) and ketones 7j
2%) and 8j (4%) (Table 2, entry 10). The mother alcohol
k was entirely inert under the standard reaction conditions,
(
(
5) Nishizawa, M.; Yadav, V. K.; Skwarczynski, M.; Takao, H.;
Imagawa, H.; Sugihara, T. Org. Lett. 2003, 5, 1609-1611.
6) Imagawa, H.; Kurisaki, T.; Nishizawa, M. Org. Lett. 2004, 6, 3679-
681.
7) Nishizawa, M.; Takao, H.; Yadav, V. K.; Imagawa, H.; Sugihara, T.
Org. Lett. 2003, 5, 4563-4565.
8) (a) Imagawa, H.; Iyenaga, T.; Nishizawa, M. Org. Lett. 2005, 7, 451-
53. (b) Imagawa, H.; Iyenaga, T.; Nishizawa, M. Synlett 2005, 703-705.
9) Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara, T. Chem.
Lett. 2002, 12-13.
10) (a) Thomas, R. J.; Campbell, K. N.; Hennion, G. F. J. Am. Chem.
Soc. 1938, 60, 718-720. (b) Stacy, G. W.; Mikulec, R. A. Org. Synth.
963, 4, 13-15.
11) (a) Murai, A.; Abiko, A.; Shimada, N.; Masamune, T. Tetrahedron
(
(
6
3
(
and all starting materials were recovered (Table 2, entry 11).
(
4
(
(12) Typical experimental procedure is as follows. To a stirred solution
of propargyl acetate 1 (194 mg, 1.0 mmol) and water (27 mg, 1.5 mmol,
1.5 equiv) in acetonitrile (9.5 mL) was added 0.5 mL of 0.1 M Hg(OTf)2
(0.5 mL, 5 mol %) in acetonitrile at room temperature under argon, and
the mixture was allowed to stir at the same temperature for 4 h. After
addition of aqueous NaHCO3, the organic material was extracted with ether.
Dried and concentrated material was subjected to a column chromatography
on silica gel using pentane and ether as eluent to give enone 2 (128 mg,
84% yield, NMR yield 82%) and a mixture of dimeric mercury compound
3 (NMR yield 1%, determined by using mesitylene as an internal standard),
ketones 4 (NMR yield 2%), and ketone 5 (NMR yield 6%).
(
1
(
Lett. 1984, 25, 4951-4954. (b) Satoh, T.; Kumagawa, T.; Yamakawa, K.
Tetrahedron Lett. 1986, 27, 2471-2474. (c) Szemenyei, D.; Steichen, D.;
Byrd, J. E. J. Mol. Cat. 1977, 2, 105-117. (d) Choudary, B. M.; Prasad,
A. D.; Swapna, V.; Valli, V. L. K.; Bhuma, V. Tetrahedron 1992, 48, 953-
9
62. (e) Cahiez, G.; Bernard, D.; Normant, J. F. Synthesis 1977, 130-133.
448
Org. Lett., Vol. 8, No. 3, 2006

Scheme 2
2 2
Table 3. Hg(OTf) -Catalyzed Reaction of Acetate with H O
Together, these results indicated that the reactions were
affected by neither electronic nor steric factors of leaving
groups, and we concluded that acetate is the leaving group
of choice.
We then examined the reaction of 2-decanoyl acetate (9)
with 1.5 equiv of water in CH
3
CN at room temperature for
1
1a
3.5 h in the presence of 5 mol % Hg(OTf) . Enone 10
2
was obtained in 70% yield (as measured by NMR; isolated
yield was 59%) along with dimeric mercuric product 11 (2%)
and a mixture of hydrated ketones (7%) (Table 3). Phenyl-
propargyl acetate 12 formed enone 132
c,11a,11d
in 51% yield
(
(
isolated yield 53%), and 3-oxo-3-phenylpropanoyl acetate
18%), but no dimeric mercuric product, was detected.
Reaction of propargyl acetate containing tert-alcohol 14
afforded only Meyer-Schuster product 15 in 76% yield
(isolated yield 74%), and the acetate group did not affect
the reaction. Reaction of secondary acetate 16 took place
smoothly to give (E)-enone 17 selectively in 84% yield
(isolated yield 80%) along with dimeric mercuric product
1
8 (2% yield). Stereochemistries of 17 and 18 were
established to be E and Z, respectively, on the basis of nuclear
Overhauser effect (NOE) experiments. When the same
reaction was carried out using 1 mol % of Hg(OTf)
2
, enone
17 was obtained in 88% yield after 114 h. The reaction of
tert-acetate 19 was completed within 6 min and afforded
enone 201 in 67% yield (isolated yield 60%) along with an
enyne 21 in 13% yield. When water was added to the mixture
1e
a
NMR yield using mesitylene as an internal standard. b NMR yield using
of 19 and Hg(OTf)
and 60%, respectively, as measured by NMR. When diacetate
2 was treated with 5 mol % of Hg(OTf) and H O (1.5
equiv), enones 23 and 24 were obtained in 70% yield
isolated yield 61%) and 18% yield (isolated yield 15%),
respectively, along with a 1:5 mixture of dimeric products
2
, the yield of 20 and 21 changed to 15%
naphthalene as an internal standard. c Isolated yield.
2
2
2
2
5 and 26 in 3% yield that was difficult to separate.
Stereochemistries of 24 and 26 were established to be E and
Z, respectively, on the basis of NOE experiments.
Taken together, these results are consistent with the
following mechanism (Scheme 3). The reaction is initiated
(
by π-complexation of alkyne with Hg(OTf)
2
, as shown in
2 2
Table 2. Hg(OTf) -Catalyzed Reaction of 6 with H
Oa
2
7. Oxonium cation 28 is attacked by water to generate
yield (%)b
intermediate 29 along with TfOH. Protonation of 29 forms
alternative oxonium cation 30, which undergoes demercu-
ration to produce the second intermediate 31 and the catalyst
time
(h)
entry
R
2
3
7
8
6
1
2
3
4
5
6
7
8
9
a: COCH(CH3)2
b: COC(CH3)3
c: COCH2OCH3
d: COCH2Cl
e: COC6H4-p-OCH3
f: COC6H4-p-NO2
g: COC6F5
h: COC6H5
i: COC6H2-2,4,6-Cl3
j: COH
2
2
4
73
67
68
61
30
53
14
2
2
3
3
5
16
4
7
5
5
6
2
1
1
2
Hg(OTf) . A 6π electrocyclic reaction should yield the enone
3
2, along with acetic acid 33. If water attacks carbon 3 of
2
8
64
18
the oxonium cation as indicated in 34, an alternate intermedi-
ate 35 could form. The corresponding ketone 36 cannot be
demercurated because protonation would convert it to an
unstable primary cation. However, 36 may react slowly with
a second propargyl acetate molecule, creating another
oxonium cation 37, which becomes the stable vinyl mer-
cury product 38. Therefore, this process contains a novel
4
24
24
24
24
24
4
3
1
10
65
100
100
14
1
1
0
1
51
2
2
4
k: H
24
100
2
suicide mechanism for the catalyst Hg(OTf) . This could
explain why we could not achieve the very high catalytic
turnover for vinyl ketone formation that we observed for
a
Reaction with 1.5 equiv of H2O in CH3CN at room temperature. b NMR
yield using mesitylene as an internal standard.
Org. Lett., Vol. 8, No. 3, 2006
449

In summary, we have developed a novel reaction between
propargyl acetate and water catalyzed by Hg(OTf) to
2
Scheme 3
produce synthetically useful conjugated ketones under very
mild conditions. The reaction behaves like a variation of the
Meyer-Schuster and Rupe rearrangement, but it is applicable
to primary alcohols. Toxicity of organomercuric compounds
is a serious concern, particularly with respect to their use in
industrial synthetic application. Although, CH
3
HgCl and
(
CH Hg are extremely dangerous and can cause serious
3 2
)
damage to the central nervous system, most organomercuric
compounds are not that toxic. Phenylmercuric acetate used
to be employed as agrochemicals for rice fields, and
mercurochrome is an excellent antiseptic for wounds. It is
important to distinguish between useful mercuric compounds
and the highly toxic methylmercuric chloride.
Acknowledgment. This study was financially supported
by a Grant-in-Aid from the Ministry of Education, Culture,
Sports, Science, and Technology of the Japanese Govern-
ment.
Supporting Information Available: Spectroscopic data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
5
7
enyne cyclization, arylyne cyclization, and biomimetic
tandem cyclization.8
OL0527431
450
Org. Lett., Vol. 8, No. 3, 2006