GaCl3-promoted ethenylation of thioester silyl enolate and dienolate with silylethyne

Article abstract of DOI:10.1246/cl.2001.1080

In the presence of GaCl₃, silyl enol ethers derived from either S-alkyl or S-aryl thioesters are ethenylated at the α-carbon atom with trimethylsilylethyne in high yields. The reactions of dienolates give α,α-diethenyl thioesters.

Full text of DOI:10.1246/cl.2001.1080

1080
Chemistry Letters 2001
GaCl3-Promoted Ethenylation of Thioester Silyl Enolate
and Dienolate with Silylethyne
Mieko Arisawa, Chie Miyagawa, Satoru Yoshimura, Yoshiyuki Kido, and Masahiko Yamaguchi*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578
(Received August 6, 2001; CL-010747)
In the presence of GaCl3, silyl enol ethers derived from
either S-alkyl or S-aryl thioesters are ethenylated at the α-car-
bon atom with trimethylsilylethyne in high yields. The reac-
tions of dienolates give α,α-diethenyl thioesters.
Previously, we developed a one step ethenylation reaction
of silyl enol ethers derived from ketones with trimethylsi-
lylethyne in the presence of GaCl3.1 The reaction involving
carbogallation between gallium enolate and ethynylgallium was
found to exhibit equatorial preferences in the ethenylation of
cyclohexanone derivatives.2 The reaction can also be applied to
the silyl enol ethers derived from β-dicarbonyl compounds giv-
ing 2-ethenylated acetoacetates and malonates.3 Notably, 2-
ethenylmalonate was obtained by this method. In order to
reveal scope of this methodology, the reactions of carboxylic
acid derivatives were examined, and described here is the
ethenylation of thioester silyl enol ethers. It is also shown that
the reactions of thioester dienolates give α,α-diethenyl deriva-
tives.
Trimethylsilylethyne (1.0 mmol) and an S-alkyl thioester
silyl enol ether (0.5 mmol) reacted with GaCl3 (2.0 mmol) in
methylcyclohexane at room temperature for 5 min. Then, the
reaction was quenched with THF and 6 M sulfuric acid, and an
α-ethenylthioester was obtained in a high yield. A broad scope
of this method is shown by the reactions of α-mono- and α,α-
disubstituted thioesters (Table 1).4 No isomerizaton to α,β-
unsaturated thioesters is observed. Acidic workup with 6 M
sulfuric acid is critical for the effective protonation of C–Ga
bond. The stereochemistry of thioester silyl enol ether is unim-
portant, and the reactions of silyl enol ethers being ca. 1:1 mix-
tures of (E)- and (Z)-isomers give the ethenylated product in
high yields. When an S-aryl thioester silyl enol ethers is used,
acidic workup with 10 M hydrochloric acid for 3 h at room
temperature gives better results than 6 M sulfuric acid, saturat-
ed aqueous ammonium chloride, or saturated aqueous triethy-
lamine hydrochloride. In some cases small amounts of
silylethenyl thioesters are formed. As for the synthesis of α-
ethenylated carboxylic acid derivatives, α-alkylation reactions
of 3-propenoate were reported.5 The present method is an alter-
native, which directly introduces the ethenyl group.
The reactions of dienolates have attracted much interest,
since the nucleophiles possess two possible reaction sites. In
general, alkylation reactions of alkali metal dienolates take
place at the α-carbon atom. In order to compare the selectivity,
the ethenylation reactions of dienolates were conducted. A
dienolate was prepared from S-ethyl 2-ethenyl-1-hexanethioate
with LDA in THF at –78 °C followed by trimethylsilyl chloride
in 78% yield (Scheme 1). Then, trimethylsilylethyne (4.0
mmol) and the dienolate (0.5 mmol) were treated with GaCl3
(2.0 mmol) in methylcyclohexane at room temperature for 5
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
1081
3, 789 (2001).
4
Typical procedures are as follows. Under an argon atmos-
phere, a solution of GaCl3 (1.0 M, 2.0 mmol) in methylcy-
clohexane (2.0 mL) was added to a mixture of S-ethyl 3-
phenylpropanethioate silyl enol ether (0.5 mmol, 133 mg)
and trimethylsilylethyne (0.14 mL, 1.0 mmol) in methylcy-
clohexane (2.0 mL) at room temperature. After being
stirred at room temperature for 5 min, THF (5.0 mL) was
added to dissolve the insoluble materials. Sulfuric acid (6
M, 5.0 mL) was added, and stirring was continued for
another 5 min. Then, the organic materials were extracted
twice with ether. The combined organic layers were
washed with water and brine, dried over magnesium sul-
fate, and concentrated. The residue was purified by flash
column chromatography to give S-ethyl 2-ethenyl-3-
phenylpropanethioate (93.5 mg, 85%).
min. This reaction was quenched with THF and 10 M
hydrochloric acid for 30 min, giving a 1:1 mixture of α,α-
diethenylated thioester and α -ethenyl-α -silylethenylated
thioester. The crude product was treated with trifluoroacetic
acid at room temperature for 1 h for desilylation, and S-ethyl 2-
ethenyl-2-butyl-3-butenethioate6 was obtained in 75% yield.
It has now become clear that, as was the dienolate alkyla-
tion, the ethenylation takes place at the α-carbon atom and not
at the γ-carbon atom. It should also be noted that such α,α-
diethenylcarboxylic acid derivatives are not easy to prepare.
For example, 5-methylbicyclo[2.1.0]pentanecarboxylates were
converted at temperatures above 300 °C to α,α-diethenyl-
propanoates.7 α,α-Bis(β-hydroxyethyl)phenylacetonitrile was
transformed to the α,α-diethenylphenylacetic acid by a step-
wise method.8 In contrast, the present synthesis provides the
α,α-diethenylated acid derivatives by simply repeating the eno-
lization and the ethenylation processes.
5
6
J. L. Herrmann, G. R. Kieczykowski, and R. H.
Schlessinger, Tetrahedron Lett., 1973, 2433; M. J. Aurell,
S. Gil, R. Mestres, M. Parra, and L. Parra, Tetrahedron, 54,
4357 (1998); C. Girard, I. Romain, M. Ahmar, and R.
Bloch, Tetrahedron Lett., 30, 7399 (1989); Also see, K.
Schank and B. Zwanenburg, J. Org. Chem., 48, 4580
(1983).
1H NMR (400 MHz, CDCl3) δ 0.89 (3H, t, J = 7.6 Hz),
1.23 (3H, t, J = 7.6 Hz), 1.21–1.34 (4H, m), 1.82–1.86 (2H,
m), 2.84 (2H, q, J = 7.6 Hz), 5.21 (2H, d, J = 17.6 Hz),
5.32 (2H, d, J = 10.8 Hz), 6.05 (2H, dd, J = 17.6, 12.4 Hz).
13C NMR (100 MHz, CDCl3) δ 14.0, 14.6, 23.3, 23.7, 26.5,
36.6, 62.3, 117.1, 138.0, 201.9. IR (neat) 1681, 1634 cm–1.
MS (EI) m/z 212 (M+, 2%), 67 (M+ – 145, 100%). HRMS
Calcd for C12H20OS, 212.1235; Found, 212.1239.
Dedicated to Prof. Hideki Sakurai on the occasion of his
70th birthday.
7
8
M. J. Jorgenson and T. J. Clark, J. Am. Chem. Soc., 90,
2188 (1968).
J. W. Wilt and R. Niinemae, J. Org. Chem., 44, 2533
(1979); Also see, V. Rautenstrauch, Helv. Chim. Acta, 70,
593 (1987); P. Martinet and G. Mousset, Bull. Soc. Chim.
Fr., 1970, 1071; P. Martinet, G. Mousset, and M. Colineau,
C. R. Acad. Sci. Ser. C, 268, 1303 (1969).
References and Notes
1
2
3
M. Yamaguchi, T. Tsukagoshi, and M. Arisawa, J. Am.
Chem. Soc., 121, 4074 (1999).
M. Arisawa, C. Miyagawa, and M. Yamaguchi, Synthesis,
in press.
M. Arisawa, K. Akamatsu, and M. Yamaguchi, Org. Lett.,