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Chemistry Letters Vol.38, No.5 (2009)
Generation and Reactions of ꢀ-Silyloxiranyllithium in a Microreactor
Aiichiro Nagaki, Eiji Takizawa, and Jun-ichi Yoshidaꢀ
Department of Synthetic and Biological Chemistry, Graduate School of Engineering, Kyoto University,
Nishikyo-ku, Kyoto 615-8510
(Received February 17, 2009; CL-090169; E-mail: yoshida@sbchem.kyoto-u.ac.jp)
ꢀ-Triphenylsilyloxiranyllithium was effectively generated
O
O
O
E+
Li
R3Si
E
R3Si
BuLi
by the reaction of epoxyethyltriphenylsilane with n-BuLi in a
microflow reactor at 0 ꢁC, though it is well known that an over
reaction cannot be avoided even at lower temperatures in a con-
ventional macrobatch reactor. Subsequent reactions with various
electrophiles in the microflow reactor gave the corresponding
ꢀ-substituted epoxysilanes.
R3Si
over reaction
BuLi
OLi
Bu
R3Si
-Li2O
Li
Bu
SiR3
Epoxysilanes1 have been used as versatile synthetic inter-
mediates.2 For example, regiospecific and stereospecific opening
of epoxysilanes with a variety of nucleophiles gives diastereo-
merically pure hydroxysilanes, which undergo syn or anti elim-
ination to give the corresponding alkenes stereoselectively.3
Therefore, development of general and straightforward methods
for synthesizing epoxysilanes is very important. In general,
epoxidation of vinylsilanes with H2O2 or peroxy acids have been
utilized for this purpose.1 On the other hand, the generation of
oxiranyllithium species by the deprotonation of epoxysilanes
with BuLi also serves as a useful method for construction of var-
ious substituted epoxysilanes.4,5 However, ꢀ-silyloxiranyllithi-
ums are highly unstable and undergo an over reaction with BuLi.
Therefore, oxiranyllithiums are usually generated at very low
temperatures. This requirement limits synthetic applications of
the ꢀ-silyloxiranyllithium methodology.
Scheme 1. The generation and reaction of ꢀ-silyloxiranyllithi-
ums.
O
Bu
BuLi
O
Li
Ph3Si
Ph3Si
Ph3Si
1
M1
250 µm
3
R1
O
n-BuLi
M2
E
250 µm
Ph3Si
R2
E: electrophile
Figure 1. Microflow system for deprotonation of epoxyethyltri-
phenylsilane (1). T-shaped micromixer: M1 (inner diameter:
250 mm) and M2 (inner diameter: 250 mm), microtube reactor:
R1 and R2 (ꢁ ¼ 1000 mm, length ¼ 50 cm), a solution of epoxy-
ethyltriphenylsilane: 0.10 M in THF (6.0 mL/min), a solution of
n-BuLi: 0.60 M in hexane (1.5 mL/min), a solution of electro-
phile: 0.36 M in THF (3.0 mL/min).
We have recently reported that microflow systems6–8 are
useful for conducting reactions involving highly unstable
short-lived intermediates.9 For example, ꢀ-aryloxiranyllithiums
were effectively generated in a microflow reactor.9f We report
herein that ꢀ-silyloxiranyllithiums could be easily generated in
a microflow reactor.
We chose to study the reaction of epoxyethyltriphenylsilane
(1) with butyllithium.10 In a macrobatch reactor, it is known that
the reaction should be carried out at low temperatures such as
ꢂ78 ꢁC to avoid the over reaction.5a In fact, at higher tempera-
tures such as 0 ꢁC, the reaction of 1 with n-BuLi (1.5 equiv) fol-
lowed by treatment with chlorotrimethylsilane in a conventional
macrobatch reactor gave 1-trimethylsilyl-1-triphenylsilylepoxy-
ethane (2) only in very low yield (4% yield), and 2-triphenyl-
silyl-1-hexene (3), which was produced by reaction of ꢀ-silylox-
iranyllithium with n-BuLi (Scheme 1) in 37% yield.5c
Next, we examined the reaction in a microflow system con-
sisting of two T-shaped micromixers (M1 and M2) and two
microtube reactors (R1 and R2) shown in Figure 1. The yield
of 2 was determined by changing the residence time in R1 and
the temperature of the cooling bath in the microflow system.
The residence time was adjusted by changing the length of R1
with a fixed flow rate.
in the residence time in R1 because of the progress of the depro-
tonation of 1. The yield became maximum at a residence time of
0.377 s. Further increase in the residence time caused a decrease
in the yield of 2 presumably because of the over reaction. At
0 ꢁC, the yield of 2 reached the maximum at a residence time
of 3.14 s.
Using the optimized conditions (0 ꢁC, residence time in R1:
3.14 s), the reactions of ꢀ-silyloxiranyllithium with various elec-
trophiles were examined. As summarized in Table 1, reactions
with iodomethane, chlorotrimethylsilane, chlorodimethylsilane,
chlorodimethylphenylsilane, benzyl bromide, benzaldehyde,
chlorotributylstannane, methyl chloroformate, and dimethylcar-
bamoyl chloride were successfully carried out to give the corre-
sponding ꢀ-substituted epoxysilanes in good yields.
In conclusion, we have developed an efficient method for
synthesizing ꢀ-substituted epoxysilanes based on generation and
reactions of ꢀ-silyloxiranyllithium without the over reaction at
0 ꢁC by virtue of short residence times and efficient temperature
control in microflow reactors. The scope and limitations of the
present method and synthesis of a variety of substituted epoxy-
silanes are under investigation in our laboratory.
As profiled in Figure 2a, the yield significantly depends on
both temperature and residence time (See Supporting Informa-
tion for the details).11,12 Figure 2b shows the cross section at 0
and 24 ꢁC. At 24 ꢁC, the yield of 2 increased with an increase
Copyright ꢀ 2009 The Chemical Society of Japan
Nagaki, Aiichiro
