Carbon dioxide-mediated catalytic rearrangement of propargyl alcohols into α,β-unsaturated ketones

Article abstract of DOI:10.1021/ja074350y

In the presence of a catalytic amount of a silver salt with DBU under a CO₂ atmosphere, various tertiary and secondary propargyl alcohols were efficiently converted into the corresponding α,β-unsaturated carbonyl compounds in high yield. An iso

Full text of DOI:10.1021/ja074350y

Published on Web 10/05/2007
Carbon Dioxide-Mediated Catalytic Rearrangement of Propargyl Alcohols into
r,â-Unsaturated Ketones
Yudai Sugawara, Wataru Yamada, Shunsuke Yoshida, Taketo Ikeno, and Tohru Yamada*
Department of Chemistry, Faculty of Science and Technology, Keio UniVersity, Hiyoshi, Kohoku-ku,
Yokohama 223-8522, Japan
Received June 15, 2007; E-mail: yamada@chem.keio.ac.jp
Table 1. Examination of Various Solvents
Propargyl alcohols are readily prepared by a conventional
addition reaction of the corresponding acetylides to carbonyl
compounds and have been employed as starting compounds in
various transformation reactions. The Meyer-Schuster reaction
reported in 19221 is the rearrangement reaction of propargyl alcohol
into the corresponding R,â-unsaturated carbonyl compounds. This
reaction consists of two key steps: (1) effective enhancement of
the leaving ability of the hydroxy group to generate the carbocation
intermediate and (2) nucleophilic addition of hydroxide equivalent
to activated alkyne to afford the resulting enone. For a tertiary
propargyl alcohol, a protic acid was used as a simple reagent to
drive this reaction though the Rupe rearrangement via an enyne
intermediate, which afforded the undesired R,â-unsaturated carbonyl
compounds as byproducts. To suppress such byproduct formation
during this textbook2 reaction, oxo-metallic reagents3,4 have been
examined to remove the hydroxy group concomitantly with the
[3,3]-sigmatropic rearrangement involving the nucleophilic addition
to an alkyne; however, high temperature was required to drive these
reactions toward completion.5 The high affinity of late transition-
metals such as gold6 for acetylenic π-bonds was used to activate
propargyl alcohols under mild conditions, although their applicable
substrates were limited. For example, a ruthenium complex catalyst7
was employed for the activation of an alkyne via a vinylidene-
ruthenium intermediate derived from terminal alkynes.
yield (%)b
carbonate
entrya
solvent
time/day
enone
1
2
3
toluene
CH2Cl2
PhCl
1
1
1
74
45
79
trace
7
trace
39
11
39
73
4
DMF
DMF
DMA
formamide
3
5c
6c
7c
0.5
0.5
0.5
16
6
63
86
a Reaction conditions: The reaction was carried out in 0.5 mL of solvent
using 10 mol % silver methanesulfonate, 0.25 mmol of substrate and 0.25
mmol of DBU under atmospheric CO2 pressure at room temperture.
b Isolated yield. c The reaction was carried out under 1.0 MPa CO2 pressure.
Scheme 1. Reaction Mechanism of Propargyl Alcohol with CO2
It has been reported that propargyl alcohols also react with carbon
dioxide to afford the corresponding cyclic carbonates using various
metal salts or phosphines as a catalyst;8 however, this approach
requires high CO2 pressure and/or high temperature, and is limited
to terminal alkynes. In a previous Communication, we reported that
the combined use of a catalytic amount of silver acetate and DBU
efficiently catalyzed the incorporation of CO2 under mild reaction
conditions for a wide range of propargyl alcohols to afford the
corresponding cyclic carbonates in high-to-excellent yields.9 In this
reaction, the corresponding R,â-unsaturated carbonyl compounds
generated via a Meyer-Schuster type reaction were detected in
some polar solvents. In this Communication, we report that various
tertiary and secondary propargyl alcohols are efficiently converted
into the corresponding R,â-unsaturated carbonyl compounds in high
yield using a catalytic amount of a silver salt with DBU and carbon
dioxide under mild reaction conditions.
In a toluene solution, the silver-catalyzed reaction of propargyl
alcohol with carbon dioxide selectively afforded the corresponding
cyclic carbonate, while in dichloromethane and chlorobenzene the
corresponding R,â-unsaturated carbonyl compounds generated via
a Meyer-Schuster type reaction were obtained along with the cyclic
carbonate (entries 1-3, Table 1). We propose the following reaction
mechanism for incorporating CO2 into propargyl alcohol using this
approach: the carbonate intermediate would be generated from
propargyl alcohol and CO2, then an intramolecular ring-closing
reaction would proceed at the R-carbon of the propargyl alcohol,
which was activated by the silver salt, to afford the cyclic carbonate
(path A in Scheme 1). The â-carbon of the propargyl alcohol would
be alternatively attacked to promote the [3,3]-sigmatropic rear-
rangement into the allene-enolate. The R,â-unsaturated carbonyl
compounds would result from the release of CO2 (path B in Scheme
1). It is reasonable to assume that the polarized structure with an
elongated C-O bond in the carbonate intermediate would be
stabilized in a polar solvent, enhancing the attack on the â-carbon
in the activated propargyl alcohol. In fact, DMF and DMA solvents
improved the selectivity toward the enone (entries 4-6). It was
found that formamide was the best choice to selectively obtain the
corresponding enone (entry 7).
The proposed mechanism is supported by results from an isotopic
experiment using C18O2. The reaction was carried out under a
carbon dioxide atmosphere to afford the R,â-unsaturated ketone
with a MW of 188 when regular CO2 was used, and an R,â-
unsaturated ketone with a MW of 190 when C18O2 was used. As
shown in Figure 1, no cross-product containing 16O could be
9
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J. AM. CHEM. SOC. 2007, 129, 12902-12903
10.1021/ja074350y CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Transformation of Various Propargyl Alcohols into the
Enones
Figure 1. MS spectrum of the enone obtained from the labeled CO2.
detected by GC-MS analysis. No reaction proceeded under a
nitrogen atmosphere. These observations suggest that the present
reaction should be promoted by carbon dioxide and that the
rearrangement step should proceed in an intramolecular [3,3]-
sigmatropic manner, and not by the intermolecular addition of H2O
or carbonate anion.
Various bases along with the use of a silver catalyst were
examined. In the presence of a stoichiometric amount of pyridine,
no reaction proceeded, while DBU, DBN, and diisopropylethy-
lamine drove the reaction of the propargyl alcohol 1e at room
temperature to afford the R,â-unsaturated ketone 2e in high yield.
The amount of base could be reduced to a catalytic concentration.
For the reaction of propargyl alcohol 1a, 0.2 equiv of diisopropy-
lethylamine afforded product 2a in 59% yield at room temperature,
while at 60 °C, the yield was improved to 81%. By using 0.2 equiv
of DBU at 60 °C, the reaction rate was also improved, and the
product was obtained in 89% yield after 8 h.
a Reaction conditions: The reaction was carried out in 0.5 mL of
formamide with 10 mol % silver mathanesulfonate, 0.25 mmol of substrate
and 1.0 equiv of DBU under 1.0 MPa CO2 pressure at room temperature.
b Isolated yield. c Reaction run using 0.2 equiv of DBU at 60 °C. d Reaction
run using 3.0 equiv of DBU at 60 °C. e i-Pr2NEt was used as a base. f The
reaction was carried out in DMF. g E/Z ratio was provided in parenthesis.
The optimized system was successfully applied to various
propargyl alcohols (Table 2). In the presence of 10 mol % silver
methanesulfonate and 0.2 equiv of DBU under 1.0 MPa CO2 at 60
°C, alkyl-substituted tertiary propargyl alcohols 1a and 1b were
smoothly converted into the corresponding R,â-unsaturated ketones
2a and 2b in high yield (entries 1 and 2). Propargyl alcohol 1c,
which possesses bulky substituents, was converted into correspond-
ing enone 2c in high yield at 60 °C (entry 3) when 3.0 equiv of
DBU was employed. For propargyl alcohols 1d-f, which have five-
to-seven-membered rings, the reactions smoothly proceeded under
mild conditions using 1.0 equiv of diisopropylethylamine to afford
rearranged products 2d-f with cycloalkylidene groups in 93%,
90%, and 94% yields, respectively, without any isomerization of
the C-C double bond. Propargyl alcohols 1g-h with a phenyl
group at the propargylic position, reacted with CO2 to afford the
corresponding enones 2g in 98% yield (entry 7) and 2h in 80%
yield (in DMF, entry 8). The present catalytic system could be
applied to various tertiary and secondary propargyl alcohols to
afford products 2j and 2k in high yield at room temperature (entries
10 and 11), even though it has been reported that secondary pro-
pargyl alcohols are difficult to convert into the corresponding R,â-
unsaturated ketones under mild conditions.10 However, propargyl
alcohol 1l was less reactive, and the corresponding monosubstituted
enone 2l was obtained in 29% yield (entry 12). The ethoxy-
substituted propargylic alcohols6c,d 1m and 1n were good substrates
that afforded the corresponding ethyl ester of the R,â-unsaturated
carboxylic acids 2m and 2n in high yield (entries 13 and 14).
It is noted that in the presence of a catalytic amount of a silver
salt with DBU, the Meyer-Schuster reaction of various tertiary
and secondary propargyl alcohols were efficiently promoted by
carbon dioxide to afford the corresponding R,â-unsaturated carbonyl
compounds in high yield.
Supporting Information Available: Experimental procedure and
spectra data of the new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
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