Preparation of silyl enol ethers from acyloin derivatives using silyllithium reagents

Article abstract of DOI:10.1016/j.tetlet.2008.01.133

A new method for the regioselective preparation of silyl enol ethers from acyloin derivatives using silyllithium reagents has been developed. Both dimethylphenyl- and methyldiphenylsilyllithium were found to be effective, the latter providing greater stereocontrol. The reaction is believed to proceed via Brook rearrangement assisted by expulsion of the adjacent leaving group. A number of acyclic acyloin derivatives were reacted to form the corresponding silyl enol ethers in good to excellent yield.

Full text of DOI:10.1016/j.tetlet.2008.01.133

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Tetrahedron Letters 49 (2008) 2088–2090
Preparation of silyl enol ethers from acyloin derivatives
using silyllithium reagents
Bradley D. Robertson, Aaron M. Hartel *
Department of Chemistry, Winthrop University, Rock Hill, SC 29733, USA
Received 15 December 2007; revised 28 January 2008; accepted 30 January 2008
Available online 6 February 2008
Abstract
A new method for the regioselective preparation of silyl enol ethers from acyloin derivatives using silyllithium reagents has been devel-
oped. Both dimethylphenyl- and methyldiphenylsilyllithium were found to be effective, the latter providing greater stereocontrol. The
reaction is believed to proceed via Brook rearrangement assisted by expulsion of the adjacent leaving group. A number of acyclic acyloin
derivatives were reacted to form the corresponding silyl enol ethers in good to excellent yield.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Silyl enol ethers are prominent and versatile intermedi-
ates in organic synthesis.1 They are particularly useful in
carbon–carbon bond forming reactions such as the
Mukaiyama aldol addition.2 Limitations on the traditional
preparation of silyl enol ethers via the reaction of carbonyl
compounds with base and chlorosilane have given rise to
several routes that do not involve direct enolization, such
as the isomerization of allyl silyl ethers,3 and the rearrange-
ments of a-silylcarbonyls,4 silylepoxides,5 and S-a-silyl-
benzyl thioesters.6
Additionally, a number of methods for the preparation
of silyl enol ethers have been developed that utilize the
Brook rearrangement as a key step.7–9 Many of these meth-
ods involve the reaction of acylsilanes with functionalized
carbon nucleophiles.8 Comparatively, the reaction of a-
substituted ketones with silicon nucleophiles (Scheme 1)
has remained largely unexplored. Reich reported one exam-
ple of an a-phenylthioketone reacting with dimethyl-
phenylsilyllithium to give the silyl enol ether.8h Fleming
demonstrated that the reaction of acyloin derivatives with
dimethylphenylsilyllithium proceeds to give the a-reduced
Scheme 1.
ketones, evidently formed via the cleavage of initially
formed silyl enol ethers.9 The silyl enol ethers were
observed only in a few cases and in low yield. Silyl enol
ether intermediates have also been observed in the reaction
of an a,b-epoxyketone with dimethylphenylsilyllithium.10
We envisioned that the suppression of the silicon–
oxygen bond cleavage would provide a new general method
for the regioselective preparation of silyl enol ethers from
acyloin derivatives. A series of reactions using benzoin
derivative 5 was performed to determine the effect of tem-
perature, solvent, and silyllithium reagent on the relative
amounts of silyl enol ether 6 and ketone 7 formed (Scheme
2). The results are summarized in Table 1.
*
Corresponding author. Tel.: +1 803 323 4942; fax: +1 803 323 2246.
Scheme 2.
E-mail address: hartela@winthrop.edu (A. M. Hartel).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.133

B. D. Robertson, A. M. Hartel / Tetrahedron Letters 49 (2008) 2088–2090
2089
Table 1
Table 2
Reaction of 5 with silyllithium reagents (1.25 equiv)
Reaction of acyloin derivatives with 1.25 equiv of silyllithium reagent in
ether at À78 °C
Entry Substrate
Entry Silyllithium
Solvent
Temperature 6a
7a
E/Z
(°C)
(%)
(%)
Silyllithium Product
MePh2SiLi
Yielda (%) E/Z
100/0
1
2
Me2PhSiLi
Me2PhSiLi
THF
Ether
À40
À40
0
>99
22
11
9
—
76
74
91
80
84/16
81/19
83/17
74/26
—
100/0
100/0
100/0
100/0
1
82
3
4
5
6
7
8
9
10
Me2PhSilLi Toluene À40
Me2PhSiLi
Me2PhSiLi
MePh2SiLi
MePh2SiLi
MePh2SiLi
MePh2SiLi
MePh2SiLi
Ether
À78
Toluene À78
8
THF
À40
À40
Trace >99
2
3
MePh2SiLi
MePh2SiLi
86
—
—
Ether
71
84
85
77
28
8
12
17
Toluene À40
Ether
À78
Toluene À78
>99
90
Effects of temperature, silyl group, and solvent.
a
Yields determined by 1H NMR using hexamethylbenzene as an
internal standard.
4
5
6
7
MePh2SiLi
MePh2SiLi
MePh2SiLi
Me2PhSiLi
Me2PhSiLi
43/57
93/7
—
The reaction solvent had the greatest influence on prod-
uct distribution. Reactions in THF greatly favored the
undesired ketone 7. The use of the less polar solvents,
toluene and ether, provided significantly improved yields
of 6. The effect of temperature was less significant,
although colder conditions generally also enhanced the
yield. The choice of silyllithium reagent had a minimal
effect on the product distribution but showed a significant
effect on the stereoselectivity of the reaction. While the
use of dimethylphenylsilyllithium showed a preference for
the formation of the E stereoisomer, use of methyldiphen-
ylsilyllithium showed complete selectivity for the E stereo-
isomer in each case. An excellent balance of yield and
stereoselectivity was achieved using 1.25 equiv of methyl-
diphenylsilyllithium in ether at À78 °C.
66
Trace
>99b
47
89/11
96/4
8
a
Yields determined by 1H NMR using hexamethylbenzene as an
A number of protected acyloins underwent reaction with
dimethylphenyl- or methyldiphenylsilyllithium in ether at
À78 °C to form the corresponding silyl enol ethers. These
results are summarized in Table 2. Both silyloxide (entries
1–5) and carboxylate (entry 7) leaving groups were found
to be effective; however, alkoxide (entry 8) gave poor
results. We were pleased to find that both aromatic and ali-
phatic ketones reacted to give the silyl enol ether. The
Brook rearrangement of a-silylalkoxides under kinetic
conditions (complete and irreversible formation of the
alkoxide) is usually disfavored unless an anionic stabilizing
group (phenyl, vinyl, silyl) is present on the a-carbon.11 In
this case, the rearrangement of 2 is promoted by expulsion
of the adjacent leaving group, transferring the developing
negative charge from carbon to oxygen. It is unclear
whether carbanion 3 is an intermediate in the overall reac-
tion or if the migration of silicon and leaving group expul-
sion are concerted. The cyclic substrate (entry 6) gave only
a trace of the desired silyl enol ether. It is likely that the
anti-periplanar arrangement of silyl group and leaving
group necessary for fast rearrangement–elimination is
inaccessible in this rigid cyclic system.9
internal standard.
b
Yield determined using 1,4-di-tert-butylbenzene as an internal
standard.
nant (1,3-dimethyl-1,1,3,3-tetraphenyldisiloxane) or signi-
ficant decomposition. The identities of the new silyl
enol ethers (entries 1 and 3–5) were confirmed by compar-
ison to authentic samples prepared by the treatment of
the corresponding ketone with LDA followed by
chloromethyldiphenylsilane.
In conclusion, a new method for the regioselective prep-
aration of silyl enol ethers from acyloin derivatives using
silyllithium reagents has been developed. Both aryl and
alkyl ketones reacted efficiently; however, the method was
ineffective for a cyclic substrate.
2. Typical procedure
1-Trimethylsilyloxy-1,2-diphenyl-1-ethanone (0.160 g,
0.563 mmol) and hexamethylbenzene (0.016 g) were dis-
solved in 6.8 mL ether and cooled to À78 °C under argon.
A 0.46 M solution of methyldiphenylsilyllithium in THF
(1.6 mL, 1.25 equiv) was added dropwise via syringe
While the yields were often excellent, attempts to purify
the silyl enol ethers by chromatography or distillation
resulted in poor separation from the primary contami-

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B. D. Robertson, A. M. Hartel / Tetrahedron Letters 49 (2008) 2088–2090
with stirring. The reaction was immediately quenched12 at
À78 °C with an equal volume of saturated NH4Cl and
warmed to room temperature. The mixture was extracted
twice with an equal volume of CH2Cl2 and the combined
organic layers dried over Na2SO4. The dried solution was
concentrated in vacuo to give the crude E-1-methyldi-
phenylsilyloxy-1,2-diphenylethene.
Hudrlik, P. F.; Wan, C.-N.; Withers, G. P. Tetrahedron Lett. 1976, 18,
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J. Organomet. Chem. 1975, 94, C21–C25.
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Acknowledgments
This work was supported by the Department of Chem-
istry and the Research Council, Winthrop University.
Supplementary data
Spectroscopic data for the new silyl enol ethers (entries 1
and 3–5). Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.tetlet.2008.01.133.
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