One-step ethynylation of silyl enol ether with chlorosilylethyne

Article abstract of DOI:10.1021/ol026050l

(matrix presented) In the presence of GaCl₃, silyl enol ethers are ethynylated at the α-carbon atom with chlorotrimethylsilylethyne. This reaction can provide α-ethynylated aryl ketones possessing acidic α-protons without isomerization to conju

Full text of DOI:10.1021/ol026050l

ORGANIC
LETTERS
2002
Vol. 4, No. 13
2209-2211
One-Step Ethynylation of Silyl Enol
Ether with Chlorosilylethyne
Mieko Arisawa, Ryo Amemiya, and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku UniVersity, Aoba, Sendai 980-8578, Japan
yama@mail.pharm.tohoku.ac.jp
Received April 20, 2002
ABSTRACT
In the presence of GaCl3, silyl enol ethers are ethynylated at the r-carbon atom with chlorotrimethylsilylethyne. This reaction can provide
r-ethynylated aryl ketones possessing acidic r-protons without isomerization to conjugated allenyl ketones.
Ethynylation of enolate has been problematic due to the low
reactivity of alkynyl halides and related compounds toward
SN1 and SN2, and only a few methods have been reported.
Dichloroethylene was reacted with ketone lithium enolates,
and the adducts were subjected to reduction to generate an
ethynyl group.1 In the same paper, the reaction of lithium
enolate derived from methyl cyclohexanecarbonylate with
chlorotrimethylsilylethyne was reported to give R-silyl-
ethynylated ketone in 38% yield, although the scope of this
one-step method remains unclear. Alkynyllead triacetates and
1-alkynyl(phenyl)iodonium tetrafluorobrate were reacted with
alkali metal enolates derived from â-dicarbonyl compounds
or nitroalkanes to give the ethynylated products.2,3 All of
these methods, however, have limited applicability and were
not used for the synthesis of ethynylated ketones possessing
an acidic proton at the carbonyl R-position. Such R-ethynyl
ketones have been obtained only by the oxidation of the
corresponding acetylene alcohols4 or the acylation of allenyl-
metal reagents.5 We recently reported a one-step ethynylation
reaction of phenol catalyzed by GaCl3.6 We also developed
a one-step ethenylation reaction of silyl enol ether in the
presence of GaCl3, which involved carbometalation between
gallium enolate and ethynylgallium.7 Described here is the
reaction of silyl enol ether 1 with trimethylsilylated chloro-
ethyne 28 in the presence of GaCl3, which gives R-ethynyl
ketones 7 in one-step. The reaction proceeds via several
organogallium intermediates, gallium enolate 3, galliochloro-
ethyne 4, digallated â-enone 5, and gallated ethynyl ketone
6 (Scheme 1). It is also notable that the reaction provides 7
not only with R-quaternary centers but also those possessing
R-tertiary centers.
Scheme 1
(1) (a) Kende, A. S.; Fludzinski, P.; Hill, J. H.; Swenson, W.; Clardy, J.
J. Am. Chem. Soc. 1984, 106, 3551. (b) Kende, A. S.; Fludzinski, P.
Tetrahedron Lett. 1982, 23, 2373. (c) Kende, A. S.; Fludzinski, P. Synthesis
1982, 455.
(2) Molony, M. G.; Pinhey, J. T.; Roche, E. G. J. Chem. Soc., Perkin
Trans. 1 1989, 333.
(3) Ochiai, M.; Ito, T.; Takaoka, Y.; Masaki, Y.; Kunishima, M.; Tani,
S.; Nagao, Y. J. Chem. Soc., Chem. Commun. 1990, 118.
(4) (a) Vondervoort, L. S.; Bouttemy, S.; Padro´n, J. M.; Bras, J. L.;
Muzart, J.; Alsters, P. L. Synlett 2002, 243. (b) Singh, J.; Sharma, M.;
Chhibber, M.; Kaur, J.; Kad, G. L. Synth. Commun. 2000, 30, 3941. (c)
Down, P.; Chow, M. Synth. Commun. 1978, 8, 205.
2-Methyl-1-phenyl-1-trimethylsilyloxy-1-propene and 2
were reacted with GaCl3 at -40 °C for 5 min, and the
reaction was quenched by addition of MeOH and 6 M
sulfuric acid to give 2,2-dimethyl-1-phenyl-3-butyn-1-one in
10.1021/ol026050l CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/06/2002

Table 1. R-Ethynylation of R,R-Disubstituted Silyl Enol
Table 2. R-Ethynylation of R-Monosubstituted Silyl Enol
Ethersa
Ethersa
a See reference 9 for the experimental procedures. b 0.5 mmol of the
substrate was reacted in 4 mL of methylcyclohexane for 5 min. c Accom-
panied by a byproduct 8 (8%). d 0.5 mmol of the substrate was reacted in
a mixed solvent of methylcyclohexane and ClC6H5 (12 and 10 mL).
a See the Supporting Information for the experimental procedures. b E/
Z ) ca. 1:1.
1-one was obtained in 64% yield (Table 2, entry 1).9 The
extract was rapidly passed through a short silica gel column
to remove traces of gallium salts, and the product was
purified by flash column chromatography (neutral silica gel)
at -78 °C. Isomerization of the product to conjugate
R-allenyl ketones could be avoided by these isolation
procedures. R-Ethynyl ketones are more susceptible to
isomerization compared to R-ethenyl ketones.7 The product
was accompanied by a small amount of 3-methylene-2,4-
dipentyl-1,5-diphenyl-1,5-pentanedione 8 (8%), which may
be formed by the carbogallation of 3 and 6. The yield of 8
increased to 63%, when the reaction was conducted at 0 °C
using triethylsilylated chloroethyne (Scheme 2). In contrast,
73% yield (Table 1, entry 1). Organogallium compound
either 5 or 6 precipitated from the reaction mixture, which
was dissolved by addition of MeOH. The acid workup with
6 M sulfuric acid was critical for the effective protonation
of the organogallium intermediate, and use of acetic acid or
saturated ammonium chloride considerably lowered the yield
of the product. The reaction was applied to several silyl enol
ethers giving the R-ethynylated ketones with R-quaternary
centers in high yields (Table 1).
When (Z)-1-phenyl-1-trimethylsilyloxy-1-heptene was re-
acted under the same conditions, 2-pentyl-1-phenyl-3-butyn-
(5) (a) Dollat, J. M.; Luche, J. L.; Crabbe´, P. J. Chem. Soc., Chem.
Commun. 1977, 761. (b) Schlessinger, R. H.; Wood, J. L. J. Org. Chem.
1986, 51, 2623.
(6) Kobayashi, K.; Arisawa, M.; Yamaguchi, M. J. Am. Chem. Soc.,
submitted.
Scheme 2
(7) (a) Yamaguchi, M.; Tsukagoshi, T.; Arisawa, M. J. Am. Chem. Soc.
1999, 121, 4074. (b) Arisawa, M.; Akamatsu, K.; Yamaguchi, M. Org. Lett.
2001, 3, 789. (c) Arisawa, M.; Miyagawa, C.; Yoshimura, S.; Kido, Y.;
Yamaguchi, M. Chem. Lett. 2001, 1080. (d) Arisawa, M.; Miyagawa, C.;
Yamaguchi, M. Synthesis 2002, 138.
(8) Steingross, W.; Zeil, W. J. Organomet. Chem. 1966, 6, 109.
(9) Typical Procedures for the R-Ethynylation of R-Monosubstituted
Silyl Enol Ethers. Under an argon atmosphere, a solution of 1.0 M GaCl3
(2 mmol) in methylcyclohexane (2 mL) was added to a mixture of (Z)-1-
phenyl-1-trimethylsilyloxy-1-heptene (131 mg, 0.5 mmol) and chlorotrim-
ethylsilylethyne (132 mg, 1.0 mmol) in a mixed solvent of methylcyclo-
hexane (18 mL) and chlorobenzene (2 mL) at -40 °C. The mixture was
stirred for 30 s, when MeOH (2 mL) was added. After the mixture was
stirred for 5 min at -40 °C, 6 M sulfuric acid (7 mL) was added, and the
solution was warmed to room temperature. Stirring was continued for 1 h,
and the organic materials were extracted twice with diethyl ether. The
combined organic layers were washed with brine and dried over MgSO4.
The extracts were passed through short silica gel column (hexane/diethyl
ether ) 10) and were concentrated. The residue was purified by flash column
chromatography (Kanto Chemical, silica gel 60 N (spherical, neutral), 40-
100 µm, hexane/ethyl acetate ) 400) at -78 °C to give 2-pentyl-1-phenyl-
3-butyn-1-one (91 mg, 85%).
formation of 8 was inhibited by reacting at -40 °C under
diluted conditions in methylcyclohexane-chlorobenzene (10:
1) for 30 s, and the ethynylated product was obtained in 85%
yield (Table 2, entry 2). In the case of (Z)-1-trimethylsilyl-
oxy-1-phenyl-1-propane, a 6:5 mixed solvent of methyl-
cyclohexane and chlorobenzene gave better results (Table
2, entries 5 and 6). The different optimum solvent ratio may
reflect the solubility of the organogallium intermediates:
While solubilization of gallium enolate 3 promotes the
2210
Org. Lett., Vol. 4, No. 13, 2002

reaction, the higher amount of 5 or 6 in solution results in
the side reactions such as the formation of 8. Notably, when
1,1,1,3,3,3-hexafluoro-2-propanol was added in place of
MeOH, â-chloro-â-enones were obtained (Scheme 3). The
Scheme 4
Scheme 3
ketone in only 16% yield with the recovered ketone in 40%
yield.
Acknowledgment. M.A. thanks JSPS for a Grant-in-Aid
for Encouragement of Young Scientists (No. 13771323), the
Hayashi Memorial Foundation for Female Natural Scientists,
and the Sankio Chemical Award in Synthetic Organic
Chemistry, Japan.
result suggests that the â-elimination of γ,γ-digallio-â-enone
5 takes place on addition of MeOH to give 6 and then 7.
Formation of metalated 6 in the reaction mixture was
indicated by deuteration experiment (Scheme 4). Unfortu-
nately, this ethynylation reaction proceeded effectively only
for the aromatic ketone enolates. An aliphatic enolate,
6-trimethylsilyloxy-5-undecene, gave the R-ethynylated
Supporting Information Available: Spectroscopic data
for all new products. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL026050L
Org. Lett., Vol. 4, No. 13, 2002
2211