Reaction of acylsilanes with α-sulfinyl carbanions: Regioselective synthesis of silyl enol ethers

Article abstract of DOI:10.1016/j.tetlet.2011.05.041

The reaction of acylsilanes with α-sulfinyl carbanions such as α-lithioalkyl sulfoxide is described. The reaction proceeds to give silyl enol ethers preferentially through the initial formation of the α-silyl alkoxide intermediates. In particular, the products derived from enolizable acylsilanes were the regio-defined silyl enol ethers that cannot be obtained by usual enolization of the corresponding unsymmetrical ketones with base.

Full text of DOI:10.1016/j.tetlet.2011.05.041

Tetrahedron Letters 52 (2011) 3740–3742
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Tetrahedron Letters
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Reaction of acylsilanes with a-sulfinyl carbanions: regioselective synthesis
of silyl enol ethers
⇑
Mitsunori Honda , Tadashi Nakajima, Maiko Okada, Keita Yamaguchi, Mitsuhiro Suda, Ko-Ki Kunimoto,
Masahito Segi
Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of acylsilanes with
tion proceeds to give silyl enol ethers preferentially through the initial formation of the
alkoxide intermediates. In particular, the products derived from enolizable acylsilanes were the
regio-defined silyl enol ethers that cannot be obtained by usual enolization of the corresponding
unsymmetrical ketones with base.
a
-sulfinyl carbanions such as
a
-lithioalkyl sulfoxide is described. The reac-
Received 13 April 2011
Revised 6 May 2011
Accepted 11 May 2011
Available online 18 May 2011
a-silyl
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Acylsilane
a-Sulfinyl carbanion
Silyl enol ether
Silyloxypropadiene
a-Silyl alkoxides are interesting and useful species in synthetic
organic chemistry, because of the specific migration behavior of si-
lyl group on them.1 For example, Reich and co-workers have de-
scribed that the reaction of acylsilanes possessing a good leaving
group at
a position with organolithium reagents proceeded to af-
ford
a
-silyl alkoxides,2 and then the intermediates were trans-
formed into isomeric silyloxy carbanions, being isolated as silyl
enol ethers, via Brook rearrangement.3 Kuwajima and co-workers,
however, reported that
a-silyl alkoxides derived from a-chloro
acylsilanes and Grignard reagent suffered 1,2-silyl migration to
b-carbon, giving the corresponding b-ketosilanes.4 On the other
hand, we previously clarified that the reaction of acylsilanes with
sulfonium ylides proceeded to give the corresponding silyl enol
Scheme 1. Reaction of acylsilanes with sulfur ylides.
related compounds. Because,
a
-sulfinyl carbanions are less stable
ethers or b-ketosilanes via
product’s ratio can be easily controlled by manipulating the reac-
tion conditions (Scheme 1).5 As mentioned above,
-silyl alkoxides
a-silyl alkoxide intermediates, and the
than the corresponding ylides, in other words these reacting spe-
cies would have higher reactivity than the corresponding ylides
to acylsilanes. Nevertheless, it is still not well known the genera-
a
bearing the leaving group (Z) on the b-carbon2,4–6 can be generated
by the reaction of suitable acylsilanes with carbanions, and the si-
lyl group in the alkoxides undergoes both cationotropic and
anionotropic 1,2-migrations competitively. The migratory aptitude
of silyl group is dependent on the nature of Z or silyl group, and
either silyl enol ethers or b-ketosilanes can be selectively produced
by appropriate choice of Z or by control of the reaction conditions.
In this context, we were interested in migratory behavior of silyl
tion of
with
However, it is also known that
as nucleophile in the reaction with the usual carbonyl com-
pounds.8 In this Letter, the reaction of acylsilanes 1 with
-sulfinyl
carbanions 2 was studied in order to clarify the effect of leaving
a
-silyl alkoxides derived from the reaction of acylsilanes
-sulfinyl carbanions and the following reaction behavior.
-sulfinyl carbanion acts merely
a
a
a
group such as arylsulfinyl group in the
ates on the product’s selectivity.
a-silyl alkoxide intermedi-
group on
a
-silyl alkoxides derived from the reaction of acylsilanes
with
a
-sulfinyl carbanions7 instead of sulfonium ylides as its
a-Sulfinyl carbanions 2 were generated by the treatment of the
corresponding alkyl or allyl aryl sulfoxide (1.2 mmol) with LDA
(1.2 mmol) in THF at À78 °C. Then various acylsilanes 1 (1.0 mmol)
were allowed to react with a small excess of 2. The reaction was
⇑
Corresponding author. Tel.: +81 76 234 4789; fax: +81 76 234 4800.
E-mail address: honda@se.kanazawa-u.ac.jp (M. Honda).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.041

M. Honda et al. / Tetrahedron Letters 52 (2011) 3740–3742
3741
Table 1
Reaction of acylsilanes with
a
-sulfinyl carbanions
Entry
1
2
Product
R1
Ph
Ar
R2
R3
Yielda (%)
E/Zb
1
2
3
4
5
6
7
8
9
1a
1b
2a
2b
2c
2d
2a
2b
2c
2d
2a
2a
2b
2c
p-Tol
p-Tol
Ph
H
Me
Me
CH2@CH
H
Me
Me
CH2@CH
H
H
H
H
Me
H
H
H
Me
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
59
62
92
92
76
87
83
85
86
64
78
56
—
71/29
—
52/48
—
70/30
—
62/38
—
—
78/22
—
Ph
PhCH2
p-Tol
p-Tol
Ph
Ph
1c
1d
PhCH2CH2
n-C8H17
p-Tol
p-Tol
p-Tol
Ph
10
11
12
3j
3k
3l
Me
Me
H
Me
13
1e
2a
p-Tol
H
H
3m
92
—
Molar ratio: 1/2 = 1:1.2.
a
Isolated yield.
b
Determined by 1H NMR analysis.
Table 2
Reaction of acylsilanes with
completed in 2 h at that temperature.9 These results are summa-
rized in Table 1. The reaction of benzoylsilane 1a with -lithiom-
ethyl sulfoxide 2a proceeded to give the corresponding silyl enol
ether 3a in moderate yield (entry 1). In the reaction with
a-sulfinyl carbanions derived from alkenyl sulfoxides
a
a
-
lithioethyl sulfoxide 2b, a mixture of geometrical isomers was
yielded with preference for E-isomer (entry 2). On the other hand,
the stereoselectivity was almost not observed in the reaction with
Entry
1
2
Product
Yielda (%)
No Reaction
4a 85
No Reaction
4b 37
R1
R2
a-sulfinyl carbanion 2d derived from allyl sulfoxide (entry 4). It is
notable that enolizable substrates 1b, 1c, and 1d reacted to give the
corresponding silyl enol ethers in good yields (entries 5–10). It is
consequently obvious that 2 reacted as nucleophile rather than
base in these reactions. Additionally, even cyclopropyl silyl ketone
1e that was accessible by our synthetic method10 reacted to afford
3k in good yield (entry 11). In all cases the formation of
b-ketosilane derivatives, yielded in the reaction of acylsilanes with
sulfonium ylides5, was not observed at all. The products 3e–h, 3k,
and 3l derived from enolizable acylsilanes 1b and 1d were the re-
gio-defined silyl enol ethers which cannot be selectively obtained
by usual enolization of the corresponding unsymmetrical ketones
with base. The regioselective synthesis of silyl enol ethers has been
one of the important subject, especially the preparation from an
internal ketone is not easy.11 So, it is interesting to note that the
products 3e–h and 3l were obtained in good yields,
because its regioisomers are predominantly yielded in the reaction
of the corresponding ketones with base followed by the treatment
of the resulting enolates with chlorosilane. Therefore the method
mentioned above will be quite an efficient and useful procedure
for the regioselective formation of silyl enol ethers.
1
2
3
4
1a
1b
1b
1d
Ph
2e
2e
2f
H
H
Me
H
PhCH2
PhCH2
n-C8H17
2e
Molar ratio: 1/2 = 1:1.2.
Determined by 1H NMR analysis.
a
These results mentioned above suggest the following mecha-
nism (Scheme 2). The reaction of acylsilanes 1 with -sulfinyl car-
banions 2 derived from the reaction of the corresponding sulfoxide
and LDA proceeds through the initial formation of the -silyl alk-
oxide intermediates A. The oxyanion would rapidly attack silicon
(cationotropy of silicon group), followed by the elimination of sulf-
enate anion (ArSOÀ) to afford the corresponding silyl enol ethers.
a
a
The elimination of sulfenate anion from a-silyl alkoxide intermedi-
ates A in this reaction seems to be difficult compared that of neu-
tral sulfur compounds from the betaine intermediate in the
reaction of sulfonium ylides that affords silyl enol ethers and b-
ketosilanes as products (Scheme 1).5 Thus, the cationotropy of sil-
icon group to oxyanion (Brook rearrangement3) will be the driving
force to eliminate sulfenate anion from
ates A, as a consequence, silyl enol ethers were exclusively yielded.
The conformational structure of -silyl alkoxide intermediates A
would be the chair-like pseudo six-membered ring denoted as
structure B by the coordination of lithium cation to oxygen atom
of arylsulfinyl group.8 When the substituent R2 is lager than R3,
the larger group R2 and the bulky silyl group would preferably
occupy equatorial positions in six-membered ring intermediate
B. Stated another way, the substituents R1 and R3 are trans to
one another. The migration of silyl group and the formation of
Furthermore, the reaction with
a-sulfinyl carbanion 2e and 2f
derived from the corresponding vinyl and 1-propenyl sulfoxides
was investigated (Table 2). The reaction of acylsilanes 1b and 1d
with 2e proceeded to afford the corresponding 1-silyloxypropadi-
ene derivatives 4 (entries 2 and 4). However, the starting acylsilane
was recovered in the reaction of benzoylsilane 1a (entry 1). Also,
the reaction of acylsilane 1b with carbanion 2f did not proceed
at all (entry 3).12 When the same reaction was quenched with
chlorotrimethylsilane, the corresponding silyl enol ether was
a-silyl alkoxide intermedi-
a
obtained in good yield. So, it appears that
a-sulfinyl carbanion 2f
acted as base rather than nucleophile, but its cause is yet to be
identified.

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M. Honda et al. / Tetrahedron Letters 52 (2011) 3740–3742
Scheme 2. Plausible reaction mechanism of reaction of acylsilanes with a-sulfinyl carbanions.
6. For reports regarding a-silyl alkoxide bearing b-leaving group, see: (a) Fleming,
double bond would simultaneously occur to give E-silyl enol ethers
3, preferentially.
I.; Roberts, R. S.; Smith, S. C. J. Chem. Soc., Perkin Trans. 1 1998, 1215–1228; (b)
Lefebvre, O.; Brigaud, T.; Portella, C. Tetrahedron 1998, 54, 5939–5948; (c)
Brook, A. G.; Limburg, W. W.; MacRae, D. M.; Fieldhouse, S. A. J. Am. Chem. Soc.
1967, 89, 704–706; (d) Brook, A. G.; Fieldhouse, S. A. J. Organomet. Chem. 1967,
10, 235–246.
In summary, the reaction of acylsilanes with
a-sulfinyl carba-
nions proceeds through the initial formation of a
a-silyl alkoxide
intermediates, followed by the cationotropic migration of silyl
group to oxyanion and the elimination of sulfenate ion, to afford
the corresponding silyl enol ethers. Use of the enolizable acylsil-
anes allows the preparation of regio-defined silyl enol ethers,
which cannot be obtained from the usual enolization of unsym-
metrical ketones. Further studies are aimed at the stereoselectivity
control and expanding the scope of these reactions in our labora-
tory. The results will be reported in due course.
7. For reviews, see: (a) Oae, S.; Uchida, Y. In The Chemistry of Sulphones and
Sulphoxides; Patai, S., Rappoport, Z., Stirling, C. J. M., Eds.; Wiley: Chichester,
1988; pp 583–664; (b) Carreño, M. C. Chem. Rev. 1995, 95, 1717–1760.
8. For reports on the nucleophilic reaction of
a-sulfinyl carbanion to carbonyl
compounds, see: (a) Kingsbury, C. A. J. Org. Chem. 1972, 37, 102–106; (b)
Nakamura, S.; Takemoto, H.; Ueno, Y.; Toru, T.; Kakumoto, T.; Hagiwara, T. J.
Org. Chem. 2000, 65, 469–474.
9. Typical procedure for the generation of
a-sulfinyl carbanions and the following
reaction with acylsilanes: 30 ml three-necked, round-bottomed flask
A
equipped with argon inlet adapter, rubber septum, thermometer, and
magnetic stirrer bar was charged with 8 ml of dry THF and 1.2 mmol of
diisopropylamine. This solution was cooled to À78 °C and added slowly a 1.6 M
solution of n-butyllithium in hexane (1.2 mmol) over several minutes. After
stirring for 0.5 h, a solution of alkyl aryl sulfoxide (1.2 mmol) in THF (2 ml) was
added. The resulting reaction mixture was stirred for 0.5 h, and then a solution
of acylsilane (1 mmol) in THF (2 ml) was added. After stirring for 2 h, the
reaction mixture was poured into brine and allowed to warm to ambient
temperature. The aqueous layer was extracted with diethyl ether for three
times. The combined organic layers were washed with brine, dried over
anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was
purified by column chromatography on silica gel with hexane/ethyl acetate to
give E- and Z-silyl enol ether derivatives, respectively.
Acknowledgment
This work was partially supported by a Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Culture, Sports, Sci-
ence and Technology (MEXT), Japan.
References and notes
1. For recent reports on organic synthesis using a-silyl alkoxide, see: (a) Nakai, Y.;
10. (a) Nishizawa, T.; Nakae, K.; Honda, M.; Kunimoto, K.-K.; Segi, M. Tetrahedron
Lett. 2010, 51, 1294–1297; (b) Nakajima, T.; Tanabe, M.; Ohno, K.; Segi, M.;
Suga, S. Chem. Lett. 1986, 177–180.
11. For recent reports on regioselective synthesis of silyl enol ethers, see: (a)
Okada, A.; Ohshima, T.; Shibasaki, M. Tetrahedron Lett. 2001, 42, 8023–8027;
(b) Maekawa, H.; Sakai, M.; Uchida, T.; Kita, Y.; Nishiguchi, I. Tetrahedron Lett.
2004, 45, 607–609; (c) Ooguri, A.; Ikeda, Z.; Matsubara, S. Chem. Commun. 2007,
4761–4763.
Kawahata, M.; Yamaguchi, K.; Takeda, K. J. Org. Chem. 2007, 72, 1379–1387; (b)
Robertson, B. D.; Hatel, A. M. Tetrahedron Lett. 2008, 49, 2088–2090.
2. Reich, H. J.; Holtan, R. C.; Bolm, C. J. Am. Chem. Soc. 1990, 112, 5609–
5617.
3. For review on Brook rearrangement, see: Brook, M. A. Silicon in Organic,
Organometallic, and Polymer Chemistry; John Wiley & Sons: New York, 2000. and
references cited therein.
4. (a) Sato, T.; Abe, T.; Kuwajima, I. Tetrahedron Lett. 1978, 19, 259–262; (b) Sato,
T.; Matsumoto, K.; Abe, T.; Kuwajima, I. Bull. Chem. Soc. Jpn. 1984, 57, 2167–
2170.
5. Nakajima, T.; Segi, M.; Sugimoto, F.; Hioki, R.; Yokota, S.; Miyashita, K.
Tetrahedron 1993, 49, 8343–8358.
12. At this point 1-silyloxypropadiene derivatives 4 could be yielded only in the
reaction of enolizable acylsilanes with
a-sulfinyl carbanion 2e derived from
vinyl sulfoxide. An investigation of scope and limitation of the reaction is in
progress now.