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J. Am. Chem. Soc. 1999, 121, 4074-4075
Table 1. R-Ethenylation of Silyl Enol Ethers
Ethenylation of Silyl Enol Ether with Silylethyne
Masahiko Yamaguchi,* Toru Tsukagoshi, and Mieko Arisawa
Graduate School of Pharmaceutical Sciences
Tohoku UniVersity
Aoba, Sendai 980-8578, Japan
ReceiVed NoVember 23, 1998
Alkylation of enolate is one of the most fundamental carbon-
carbon bond formations in organic synthesis, and it is used to
attach an sp3-carbon atom to the carbonyl R-carbon atom. Such
enolate reaction at an sp2-carbon atom, however, has been
problematic, due to the inertness of vinyl halides or acetylenes
toward metal enolates. Enolate usually does not undergo SN1 and
SN2 reactions with vinylic halides, and does not add to acetylenes.
Another serious problem is that product possessing the â-enone
structure can readily isomerize to conjugate R-enone. Of the
enolate olefinations,1,2 ethenylation, i.e. C2-olefination, is the most
underdeveloped. Very few examples are known,2 and unfortu-
nately they are applicable only to the synthesis of unenolizable
ethenylated products which do not possess an acidic proton at
the carbonyl R-position. Stepwise methods, therefore, have been
employed for enolate ethenylation. Reagents such as vinyl sulfone,
ethynyl sulfone, trichloroethylene, R-phenylselenylacetoaldehyde,
R-trimethylsilylaldehyde, or vinyl ether-iron complex were
reacted with enolates, and the adducts were subjected to subse-
quent transformations to generate the ethenyl group.3 Described
here is the direct ethenylation of silyl enol ether with trimethyl-
silylethyne in the presence of GaCl3. The reaction can be applied
to the synthesis of not only unenolizable R-ethenylated ketones
but also enolizable products.
Trimethylsilylethyne and silyl enol ether were reacted with
GaCl3 in methylcyclohexane at room temperature, and after
treatment with THF and 6 M sulfuric acid, R-ethenyl ketone was
obtained in a high yield (Table 1). Carbon-carbon bond formation
was very rapid at room temperature, and was completed within
5 min. Use of hydrocarbon solvents such as methylcyclohexane
or toluene gave better results than use of dichloromethane, THF,
or acetonitrile. The organogallium compound (Vide infra) gener-
ated in this reaction was insoluble in the nonpolar solvent, and
THF was added to form a homogeneous solution. The acidic
workup with 6 M sulfuric acid was also critical for the effective
protonation of the C-Ga bond, and use of 1 M sulfuric acid or
saturated ammonium chloride considerably lowered the yield of
the product. Employment of GaCl3 was essential, and no reaction
took place with AlCl3 and InCl3, other Lewis acids of the group
13 elements. The present reaction allowed the synthesis of
ethenylated ketones with an enolizable structure without isomer-
ization to conjugated enones. The reaction can be applied to both
(1) For examples, see: Bunnett, J. F.; Creary, X.; Sundberg, J. E. J. Org.
Chem. 1976, 41, 1707. Millard, A. A.; Rathke, M. W. J. Am. Chem. Soc.
1977, 99, 4833. Kosugi, M.; Hagiwara, I.; Migita, T. Chem. Lett. 1983, 839.
Moloney, M. G.; Pinhey, J. T. J. Chem. Soc., Chem. Commun. 1984, 965.
Hayashi, A.; Yamaguchi, M.; Hirama, M. Synlett 1995, 51.
(2) Seefelder, M. Liebigs Ann. Chem. 1962, 652, 107. Makosza, M.
Tetrahedron Lett. 1966, 5489. Formation of 2-ethenylcyclohexanone by the
reaction of cyclohexanone and pressurized ethyne in a very low yield was
reported. Shuikin, N. I.; Lebedev, B. L.; Nikol’skii, V. G. IzV. Akad. Nauk
SSSR, Ser. Khim. 1965, 369; Chem. Abstr. 1965, 62, 14519f.
a Z-isomer was used. b A mixture of isomers (E:Z ) ca. 1:1) was
used. c Yields of â-enone and R-enone are shown.
(3) Oishi, T.; Takechi, H.; Ban, Y. Tetrahedron Lett. 1974, 3757. Koppel,
G. A.; Kinnick, M. D. J. Chem. Soc., Chem. Commun. 1975, 473. Metcalf,
B. W.; Bonilavri, E. J. Chem. Soc., Chem. Commun. 1978, 914. Bruhn, J.;
Heimgartner, H.; Schmid, H. HelV. Chim. Acta 1979, 62, 2630. Chang, T. C.
T.; Rosenblum, M.; Samuels, S. B. J. Am. Chem. Soc. 1980, 102, 5930.
Kowalski, C. J.; Dung, J.-S. J. Am. Chem. Soc. 1980, 102, 7951. Steglich,
W.; Wegmann, H. Synthesis 1980, 481. Hudrlik, P. F.; Kulkarni, A. K. J.
Am. Chem. Soc. 1981, 103, 6251. Clive, D. L. J.; Russell, C. G. J. Chem.
Soc., Chem. Commun. 1981, 434. Ohnuma, T.; Hata, N.; Fujiwara, H.; Ban,
Y. J. Org. Chem. 1982, 47, 4713. Kende, A. S.; Fludzinski, P.; Hill, J. H.;
Swenson, W.; Clardy, J. J. Am. Chem. Soc. 1984, 106, 3551.
acyclic and cyclic ketones. The stereochemistry of silyl enol ether
is unimportant in the ethenylation. Exceptionally cyclic ketones
of relatively small ring number such as cyclohexanone and
cycloheptanone gave varying amounts of conjugated R-enones.
The ratio of the â-enone to the R-enone could be increased by
carefully quenching the reaction at 0 °C. The R-enone, however,
was still the major product in the case of cyclohexanone.
Alkenylation of silyl enol ethers also took place with trimethyl-
10.1021/ja984022l CCC: $18.00 © 1999 American Chemical Society
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