Studies on retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes. Observation of the formation of unusual 3,3-bissilyl enols

Article abstract of DOI:10.1016/j.tet.2012.06.005

Detailed investigations of the retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes are described. Based on control experiments and NMR studies, rationalizations are proposed for the formation of 3,3-bissilyl enols, unusual compounds that are stable

Full text of DOI:10.1016/j.tet.2012.06.005

Tetrahedron 68 (2012) 6928e6934
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Studies on retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes. Observation
of the formation of unusual 3,3-bissilyl enols
*
Zubao Gan, Ya Wu, Lu Gao, Xianwei Sun, Jian Lei, Zhenlei Song , Linjie Li
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Detailed investigations of the retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes are described.
Based on control experiments and NMR studies, rationalizations are proposed for the formation of 3,3-
bissilyl enols, unusual compounds that are stable to acidic hydrolysis but that can be transformed into
the corresponding aldehydes under basic hydrolysis conditions. These studies further show that the 3,3-
bissilyl enolates can be O-alkylated by alkyl halides with complete chemoselectivity. This reaction pro-
vides a practical entry to various 3,3-bissilyl aldehydes and enol derivatives. As a demonstration of the
synthetic utility of this approach, 3,3-bissilyl aldehyde was converted into bissilyl divinyl ketone, which
Received 2 February 2012
Received in revised form 24 May 2012
Accepted 1 June 2012
Available online 12 June 2012
Keywords:
Bissilyl compound
Retro-[1,4] Brook rearrangement
3-Silyl allyloxysilane
Enol
can undergo an SiO2-promoted Nazarov reaction to give cyclic b-silyl enone smoothly.
Ó 2012 Elsevier Ltd. All rights reserved.
s-BuLi
SiM
1. Introduction
Z
Si
THF/HMPA
SiM
O
SiM OE
OLi
H
or
Z
OSiM
retro-[1,4]
Brook
Geminal bimetallic compounds are useful building blocks that
support highly efficient formation of carbonecarbon bonds.1
Within the germinal bimetal family, bissilyl compounds2 are
a special type of organosilane3 that appear to be attractive synthons
because of their great potential for bifunctional reactivity. However,
investigations of these compounds have been limited because of
the lack of practical methods to synthesize them. Indeed, the at-
tachment of two large silyl groups to one carbon center is quite
challenging. Solving this problem requires efficient formation of
a carbonesilicon bond in a sterically bulky system. Our interest in
these compounds led us to focus on the well-known retro-Brook
rearrangement,4 which involves an intramolecular silyl group mi-
gration from an oxygen to a carbon atom. The most appealing
feature of this reaction is that functionalized organosilane can be
rapidly constructed from more accessible silyl ethers. Recently, we
communicated a facile retro-[1,4] Brook rearrangement of 3-silyl
allyloxysilanes 1 promoted by organolithium (Scheme 1).5 The re-
action not only provides a practical approach to synthesize 3,3-
bissilyl aldehydes 3 and (Z)-3,3-bissilyl enol derivatives 4, but it
also shows some unusual characteristics. Here we report detailed
studies that provide a deeper understanding of this reaction.
Si
H
Si
Si
1
2
3
4
Scheme 1. Retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes.
2. Results and discussion
Although the retro-Brook rearrangement has been studied ex-
tensively, few studies have examined the allyloxysilane system.
Mitchell et al. reported a retro-[1,4] Brook rearrangement of 3-silyl
allyloxysilane containing an (n-Bu)3Sn group at the 2-position (Eq.
1).6 This reaction suffers from two limitations. First, the (n-Bu)3Sn
group is required in order to facilitate the silyl migration, but such
a substrate is toxic and apparently difficult to prepare. Second,
when both silyl groups are bulkier than the trimethylsilyl group,
the reaction is sluggish. These disadvantages limit the usefulness of
this approach when researchers wish to use different bissilyl
groups in order to examine their steric and electronic effects on
a given transformation.
To avoid these disadvantages, we reasoned that silyl group mi-
gration in 3-silyl allyloxysilanes might be feasible in the presence of
a stronger base, such as organolithiums like s-BuLi, and polar
cosolvents like HMPA or DMPU, which would reduce aggregation of
the initially formed allyl anion. As expected, 1a containing two
triethylsilyl groups reacted completely after several seconds at
ꢀ78 ꢁC in THF (Scheme 2). After quenching with 10% aq HCl, a new
* Corresponding author. Tel.: þ86 28 85501062; e-mail address: zhenleisong@
scu.edu.cn (Z. Song).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.005

Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
6929
Table 1
compound was obtained and appeared to be stable to acidic hy-
Screening of reaction conditions
drolysis conditions, even after several hours. To our surprise, the
product proved not to be the expected aldehyde 3a, since 3a
formed in 42% yield after concentration of the original reaction
mixture and chromatography on silica gel. Since we could rule out
that the reaction product was the result of retro-[1,2] Brook rear-
rangement or a 1,3-hydrogen shift, we presumed it might be the
hydrate 5a generated by acidic hydrolysis of lithium enolate 2a
(Scheme 1).5
Et3Si
Et3Si
O
s-BuLi (1.5 equiv)
Et3Si
H
THF/HMPA, -78 °C
then basic hydrolysis
OSiEt3
3a
1a
Entry
HMPA
Workup
Tempa
Time
Yieldb
1
2
3
4
5
6
7
8
9
5.0 equiv
5.0 equiv
5.0 equiv
5.0 equiv
0.3 equiv
1.2 equiv
1.2 equiv
1.2 equiv
1.2 equiv
satd aq NH4Cl
satd aq NaHCO3
30 equiv
10 equiv
10 equiv
10 equiv
10 equiv
20 equiv/LiOH (3.0 equiv)
i-PrOH (10 equiv)
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
25 ꢁC
50 ꢁC
25 ꢁC
25 ꢁC
3 h
3 h
3 h
3 h
3 h
3 h
1 h
2 h
3 h
45%
53%
55%
62%
d
Sn(n-Bu)3
OSiMe3
Me3Si
Me3Si
O
LDA, THF, rt
then H2O
Me3Si
H
91%
30%
75%
d
1. The (n-Bu)3Sn group is necessary for silyl group migration.
2. Silyl groups bulkier than Me3Si cannot undergo migration.
a
Temperature of the basic hydrolysis step.
Isolated yields after purification by silica gel column chromatography.
b
Et3Si
Et3Si
O
Et3Si
Et3Si
5a (original
OH
Et3Si
a
b
42%
H
OH
OSiEt3
and subsequent drying and concentrating at 0 ꢁC generated the
proposed hydrate 5a. Treating 5a again with s-BuLi and quenching
with triethylsilyl chloride afforded the corresponding silyl enol
ether 4a in 90% yield. This result suggested to us that 5a was not the
proposed hydrate, but rather an enol. In fact, some stable enols of
simple ketone compounds have been observed and even isolated.7
Generally, bulky substituents on the enol are required in order to
prevent hydrolysis to the corresponding ketone. However, stable
enols of aldehydes have rarely been reported. To obtain more re-
liable evidence that our reaction had generated the unusual 3,3-
bisslilyl enol, 1H NMR analysis was performed on crude enol 5f
containing a bistriphenylsilyl group. The spectrum clearly showed
signals due to enol 5f, albeit contaminated with signals from the
corresponding aldehyde 3f (Fig. 1).
3a
1a
presumption)
a. s-BuLi (1.5 equiv), HMPA (5.0 equiv)/THF, -78 °C then 10% aq HCl. b.
concentration and chromatography on silica gel.
Scheme 2. Initial presumption that 5a is a hydrate.
To determine whether this presumption was correct, the fol-
lowing control experiments were performed (Scheme 3). In the first
Et3Si
Et3Si
Et3Si
4a
OSiEt3
Et3Si
Et3Si
OLi
s-BuLi
Et3SiCl
95%
OSiEt3 THF/HMPA
1a
2a
Because the reason why the acidic hydrolysis gives the stable
enol was not clear at the moment, we screened a series of hydro-
lysis conditions to obtain the desired 3,3-bissilyl aldehydes. Using
satd aq NH4Cl or satd aq NaHCO3 led to no obvious transformation
from the enol into aldehyde 3a, which was generated in moderate
yields upon subsequent concentration and silica gel chromatogra-
phy (Table 1, entries 1 and 2). Interestingly, quenching the reaction
with 30 equiv of H2O gave slightly higher yield, and most of the
enol was transformed into the aldehyde (entry 3). This result sug-
gests that more basic hydrolysis conditions favor tautomerization
toward the aldehyde. As expected, a higher yield of 62% was
obtained using 10 equiv of H2O with stirring at room temperature
for 3 h (entry 4). Further testing with HMPA showed that while
using a catalytic amount led to only partial [1,2]-Brook rearrange-
ment (entry 5), using 1.2 equiv gave a much higher yield (91%, entry
s-BuLi, THF/HMPA, then
10% aq. HCl
s-BuLi, THF/HMPA
5a
then Et3SiCl, 90%
drying and concentration, 0 ºC
Et3Si
Et3Si
Scheme 3. Control experiments implying that 5a is an enol.
OH
Et3Si
OH
5a:
not
Et3Si
OH
experiment, the reaction was quenched with triethylsilyl chloride,
generating silyl enol ether 4a exclusively in the Z-configuration in
95% yield. This result supports the idea that Z-lithium enolate 2a
forms through the retro-[1,4]-Brook rearrangement of 1a. In the
second experiment, the reaction was quenched with 10% aq HCl,
Fig. 1. 1H NMR spectrum of 3,3-bistriphenylsilyl enol 5f contaminated with the corresponding aldehyde 3f.

6930
Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
Table 2
Table 3
Scope of 3-silyl allyloxysilanesa
Scope of 3-silyl allyloxysilanes substituted at the 1-, 2- or 3-positiona
SiM
O
SiM
O
OSiM
s-BuLi
Si
s-BuLi/TMEDA
THF/HMPA, -78 oC,
OSiM
Si
H
Si
R1
THF/HMPA, -78 oC,
Si
R1
then H2O , 25 o
C
R2
1
1
3
R2
3
then H2O , 25 o
C
Entry
1
Allyloxysilane
Product
Yieldb
90%
Entry
1
Allyloxysilane
Product
Yieldb
67%
OSiEt3
Et3Si
Et3Si
O
O
1a-Z
3a
OSiEt3
Me
Et3Si
Et3Si
O
Et3Si
H
1l
3l
Et3Si
Me
Me3Si
Me3Si
1b
3b
2
3
4
5
6
7
8
9
74%
73%
93%
50%
75%
d
OSiMe3
Ph
O
O
OSiMe3
Me3Si
H
3m
3n
3o
1m
2
3
50%
72%
Me3Si
Me3Si
Me3Si
Ph
H
t-BuMe2Si
PhMe2Si
MePh2Si
Ph3Si
t-BuMe2Si
t-BuMe2Si
O
1c
3c
OSiMe3
Me3Si
Me3Si
OSiMe2t-Bu
H
1n
PhMe2Si
PhMe2Si
O
1d
Me
Me
O
3d
OSiMe2Ph
OSiPh2Me
OSiPh3
H
OSiMe3
Me3Si
1o
MePh2Si
MePh2Si
O
4
5
53%
23%
1e
3e
Me3Si
Me3Si
Me3Si
Me3Si
H
H
OSiMe3
OSiMe3
Ph3Si
Ph3Si
O
3f
1f
1p
3p
H
s-Bu
(i-Pr)3Si
Me3Si
(i-Pr)3Si
(i-Pr)3Si
O
1g
3g
Me3Si
Me3Si
O
H
Ph OSiMe3
3q
OSi(i-Pr)3
OSiEt3
H
1q
6
d
Me3Si
Et3Si
O
O
Ph
87%
82%
3h
1h
a
Me3Si
H
H
Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv), TMEDA
(1.5 equiv), HMPA (1.2 equiv) in THF at ꢀ78 ꢁC, then H2O (10 equiv), warmed to rt,
Me3Si
PhMe2Si
Me3Si
3 h.
1i
b
Isolated yields after purification by silica gel column chromatography.
3i
OSiMe2Ph
Me
Si
Et3Si
bistriisopropylsilyl group (entry 7). The approach could also be
used to synthesize bissilyl groups containing two different silyl
species (entries 8e11). The resulting aldehyde 3j is an attractive
compound given its potential to undergo intramolecular func-
tionalization9 and directed transformations.10 Reaction of 1k was
complex and led to only 21% yield of the aldehyde 3k, in which the
vinyl group in the 3-silyl substitution was added by s-BuLi before
or after silyl migration.
Me
Me
OSi
Me
1j
O
3j
10
60%
21%
Et3Si
H
Me
Me Si
Et3Si
Si
O
3k
1k
11
H
OSiEt3
s-Bu
Reactions of substrates with a substituent at the 1-, 2- or
3-position were further tested using the more reactive s-BuLi/
TMEDA complex to facilitate the initial deprotonation step. While
the desired 3,3-bissilyl ketone 3l was formed in 67% yield from 1l
(Table 3, entry 1), reaction of 1m led only to a 1,3-hydrogen shift
and gave ketone 3m in 50% yield after hydrolysis of the resulting
silyl enol ether (entry 2). Compounds 1n and 1o, which have
methyl and allyl substitutions at the 2-position, were also suitable
for this approach (entries 3 and 4). However, in the reaction of 1p,
only the addition of s-BuLi to the vinyl group was observed; no silyl
group migration occurred (entry 5). Further attempts to obtain the
aldehyde 3q proved unsuccessful (entry 6). It seems reasonable to
assume that the difficulty of forming a sterically constrained qua-
ternary carbon center at the 3-position suppresses the silyl mi-
gration completely.
a
Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv), HMPA
(1.2 equiv) in THF at ꢀ78 ꢁC, then H2O (10 equiv), warmed to rt, 3 h.
b
Isolated yields after purification by silica gel column chromatography.
6) than using 5.0 equiv (62%, entry 4). This result is in sharp contrast
to Tomooka’s observation8 that a large excess of HMPA is generally
necessary for the retro-[1,4] Brook rearrangement of simple ally-
loxysilanes. More vigorous workup conditions, such as stirring at
50 ꢁC (entry 7) and adding an extra 3.0 equiv of LiOH (entry 8),
resulted in lower yields, even though the hydrolysis proceeded
faster. In addition, quenching the reaction with i-PrOH gave
a complex mixture (entry 9). The lithium isopropoxide produced
probably acted as a strong base and destroyed the bissilyl or alde-
hyde groups.
The scope of this synthetic approach was examined (Table 2).
The reaction was suitable for 1aez with a Z-configuration, giving
3a in relatively high yield (Table 2, entry 1). Moreover, a wide
range of bissilyl groups could be constructed by smooth silyl mi-
gration (entries 2e6), except for the extremely bulky
Trapping the 3,3-bissilyl enolate 2a by various electrophiles,
including trialkylsilyl chlorides (Table 4, entry 1), acyl chlorides
(entries 2e6), anhydrides (entry 7), acyl imidazole (entry 8) and
PhNTf2 (entry 9) provided the corresponding 3,3-bissilyl enol de-
rivatives exclusively in the Z-configuration and in good to excellent
yields.

Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
6931
Table 4
Table 5
Synthesis of 3,3-bissilyl enol compoundsa
Synthesis of 3,3-bissilyl enol compounds by selective O-alkylationa
SiM OE
Et3Si
Et3Si
Et3Si
OE
s-BuLi (1.5 equiv)
HMPA (1.2 equiv)/THF, -78 oC,
then electrophile
s-BuLi (1.5 equiv)
HMPA (1.2 equiv)/THF, -78 oC,
then electrophile, rt
Z
OSiM
Z
Si
OSiEt3
Si
R2
b
4
R2
1a
b
1
4
Entry
1
Electrophile
Et3SiCl
Product
Yieldc
95%
Entry
Electrophile
MeI
Product
Yieldc
Et3Si
Et3Si
OSiEt3
O
4a
Et3Si
Et3Si
OMe
OBn
O
1
2
3
84%
90%
63%
4j
Et3Si
Et3Si
Et3Si
Et3Si
O
O
O
Et
2
EtCOCl
93%
92%
90%
92%
70%
4k
BnBr
4b
Et3Si
Et3Si
O
O
Br
4l
Et3Si
Et3Si
Ph
3
PhCOCl
4c
Et3Si
Et3Si
O
O
4b
60%
52%
61%
Me
Ph
Br
Br
4m
Me
4b
EtOCOCl
(i-Pr)2NCOCl
Et3Si
Et3Si
OEt
Et3Si
Et3Si
5
4d
4n
4o
Ph
O
O
Me
Me
Et3Si
Et3Si
O
6
Et3Si
Et3Si
O
O
N(i-Pr)2
5
OTs
4e
Me
Me
Et3Si
Et3Si
O
O
Me
7
61%
O
Me
OTs
OTs
4p
Et3Si
Et3Si
6
Cl
4f
Et3Si
Et3Si
8
9
45%
68%
4q
Ph
Ph
O
O
O
O
O
O
Et3Si
Et3Si
O
O
7
8
4g
52%
Et3Si
Et3Si
O
4r
I
O
OH
O
O
O
N
NEt2
NEt2
Et3Si
Et3Si
Et3Si
Et3Si
O
Br
10
75%
60%
Et3Si
Et3Si
4s
N
O
50%
60%
4h
OMe
OMe
MeO
OMe
OMe
11d
MeI
MeI
4t
Et3Si
Et3Si
OTf
Me
9
PhNTf2
4i
Me3Si
Me3Si
OMe
4u
12d
58%
a
Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv), HMPA
(1.2 equiv) in THF at ꢀ78 ꢁC, then electrophile (3.0 equiv), 15 min.
Ph
b
The stereoselectivity was determined by 1H NMR spectroscopy, and the con-
figuration was determined based on NOE experiments with 4j in Table 5.
a
Reaction conditions: allyloxysilane (0.15 M), s-BuLi (1.5 equiv), HMPA
(1.2 equiv) in THF at ꢀ78 ꢁC, then electrophile (3.0 equiv), warm to rt, 4 h.
c
Isolated yields after purification by silica gel column chromatography.
b
The stereoselectivity was determined by 1H NMR spectroscopy, and the con-
figuration was determined based on NOE experiments with 4j.
c
Isolated yields after purification by silica gel column chromatography.
TMEDA (1.5 equiv) was added.
d
Alkylation of the lithium enolate was further investigated. The
reaction could be performed with various electrophiles, such as
alkyl halides (Table 5, entries 1, 9e12), benzyl bromide (entry 2),
allyl halides and tosylates (entries 3e7), as well as propargyl
tosylate (entry 8), giving functionally diverse Z-3,3-bissilyl enol
ethers in moderate to good yields. The most surprising result
was that all reactions reliably showed exclusive O-alkylation se-
lectivity. We did not observe formation of either 10 or 11 from the
C1- or C3-alkylation of allyl anion 8, or formation of aldehyde 12
from the C2-alkylation of enolate 2 (Scheme 4). This is in marked
contrast to previous results obtained in the reaction of simple
allyloxysilane 6 with iodomethane (Eq. 2). Macdonald, Still11 and
Tomooka8 all observed that only the C3-alkylated product 7
formed and neither retro-[1,2] nor retro-[1,4] Brook rearrange-
ment occurred. To account for the unusual chemoselectivity dis-
played in our reaction, we propose the following mechanistic
explanation.

6932
Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
s-BuLi, or t-BuLi
Me
by the bulky bissilyl group, would form the desired aldehyde 3 only
OSiEt3
eq. 2
with great difficulty. However, under basic hydrolysis conditions,
there would be an equilibrium between the enol 5 and Z-enolate 2.
The Z-enolate 2 could be subsequently converted into the E-enolate
2-E via a series of tautomerizations and bond rotations. Although
this configurational conversion may be unfavorable, the sub-
sequent protonation of 2-E from the side opposite to the silyl
groups should be feasible, and this could drive the entire process
slowly toward formation of the aldehyde 3.
THF/HMPA, -78 ºC
then MeI, rt
>90%
OSiEt3
6
7
SiM OR
Et3Si
H2
Me
O
J H2-3 = 12.4 Hz; no NOE
observed
between H2 and H3
Z
H3
Si
Et3Si
4j-4u
4j
The synthetic utility of 3,3-bissilyl aldehyde was explored
by examining the silicone-assisted Nazarov reaction13 of divinyl
ketone 14. As shown in Scheme 6, Mannich reaction of 3b with
formaldehyde generated enal 13 in 85% yield,14 and this was further
transformed into 14 in overall 75% yield by addition to cyclohexenyl
lithium and IBX oxidation of the resulting allylic alcohol. While
general Lewis acids and Brønsted acids yielded complex mixtures,
SiO2 proved effective at promoting a smooth Nazarov reaction of 14,
O-alkylation
SiM
RX
O
Li
Li
Li
1
O
2
O
irreversible
SiM
1
-
H
H
H
H
H
O
H
2
3
3
SiM
Si
Si
both sides of C2 are
shielded by silyl groups Si
8
9
2
C1- and C3-alkylation
C2-alkylation
R
1
Si
R
3
Si
SiM
Si
H
giving the 5,6-membered ring-fused b-silyl enone 15 in 55% yield
and
2
and with excellent stereochemical control of both the ring junction
OSiM
R
OSiM
and exo-cyclic double bond.15
10
11
12
Scheme 4. Modeling to explain the exclusive O-alkylation of 3,3-bissilyl enolate 2 by
alkyl halides.
HCHO (aq)
Me3Si
Me3Si
O
Me3Si
Me3Si
O
pyrrolidine/C2H5CO2H
H
H
i-PrOH, 45 oC
First, we found that the 1,4-silyl migration proceeded very fast
and generally finished after several seconds. Given that the silyl
group can stabilize the a-carbanion through a ped p-bonding in-
85%
3b
13
teraction,12 the observed kinetic favorability may be because the
C3-position in allyl anion 8 is much more electron-dense than the
C1-position attached to an anion-destabilizing OSiR3 group. Sec-
ond, the entire process appears to be thermodynamically favorable,
as the resulting lithium enolate can be stored at either ꢀ78 ꢁC or
10 ꢁC for several hours and still show good reactivity with elec-
trophiles. This thermodynamic favorability implies that the re-
action involves one or more irreversible processes. Based on the
observed coupling constant (J¼12.4 Hz) and the absence of an NOE
between H2 and H3 in 4j, we propose that the Z-lithium enolate
adopts the most favorable conformation as 2, thereby minimizing
allylic strain and nonbonded interactions (Scheme 4). For this
reason, regenerating allyl anion 8 through a reverse process via the
pentacoordinated silicate 9 would be very difficult. For the same
reason, the corresponding C1- and C3-alkylation to give 10 and 11,
respectively, would be prevented. At the same time, the bulky
bissilyl moiety shields both sides of the 2-position in 2, making
C2-alkylation to give aldehyde 12 impossible. As a result, alkyl
halides are forced to approach the oxygen anion completely, gen-
erating exclusively O-alkylated products 4.
1. cyclohexenyl lithium,
Et2O, 0 o
2. IBX, EtOAc
overall 75%, 2 steps
C
O
Me3Si
Me3Si
O
H
SiO2
petroleum ether
rt, 16 h
Me3Si
H
15
14
55%
Scheme 6. An SiO2-promoted Nazarov reaction of bissilyl divinyl ketone 14.
3. Conclusion
We have described detailed studies of the retro-[1,4] Brook
rearrangement of 3-silyl allyloxysilanes. Control experiments and
NMR studies have been used to rationalize the observed formation
of unusual 3,3-bissilyl enols, which are stable to acidic hydrolysis
but can be transformed into the corresponding aldehyde by basic
hydrolysis. These studies further show that the 3,3-bissilyl enolates
can be O-alkylated by alkyl halides with complete chemoselectivity.
The synthetic utility of the 3,3-bissilyl aldehydes has been dem-
The above mechanistic analysis may also explain why the enol is
stable to acidic hydrolysis, but can be transformed into an aldehyde
by basic hydrolysis. As shown in Scheme 5, under acidic hydrolysis
conditions, protonation of the enol double bond, which is shielded
onstrated by preparing cyclic b-silyl enone from a bissilyl divinyl
ketone via an SiO2-promoted Nazarov reaction. Further applica-
tions of this methodology are being investigated.
acidic hydrolysis
H3O+
SiM
SiM
4. Experimental section
4.1. General conditions
SiM
O
OH
H
H+
OH
H
H
H
H3O+
2
2
Si
H
H
H
Si
Si
5
3
1H NMR spectra were recorded at 400 MHz (Varian) and13
C NMR spectra were recorded at 100 MHz (Varian) using CDCl3
(except where noted) with TMS or residual solvent as standard.
Infrared spectra were obtained using NaCl plates on a VECTOR22.
High-resolution mass spectral analyses were performed on a Wa-
ters Q-TOF Premier apparatus. HMPA, TMEDA, CH2Cl2 and Et3N
were distilled from CaH2. Et2O and THF were distilled from sodium.
TLC was performed on glass-backed silica plates and visualized
using UV, KMnO4 stains, H3PO4$12MoO3/EtOH stains, and H2SO4
basic hydrolysis
SiM
SiM
SiM
O
H2O
H
OH-
H2O
O
OH
H
O
H
H
H
H
H
2
Si
H
E 2
SiM
2-E
Z
Si
H
H
3
Si
Si
5
2
Scheme 5. Proposal to explain why acidic hydrolysis gives the enol, while basic
hydrolysis gives the aldehyde.

Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
6933
(concd)/EtOH stains. Column chromatography was performed
using silica gel (300e400 mesh) and a mobile phase of EtOAc/pe-
troleum ether.
4.4.1. 3,3-Bistriethylsilyl methyl enol ether (4j). 1H NMR (400 MHz,
CDCl3)
0.57 (q, 12H, J¼8.0 Hz), 0.94 (t, 18H, J¼8.0 Hz), 1.72 (d, 1H,
d
J¼12.4 Hz), 3.51 (s, 3H), 4.24 (dd, 1H, J¼6.0, 12.4 Hz), 5.80 (d, 1H,
J¼6.0 Hz); 13C NMR (100 MHz, CDCl3)
d 4.3, 7.8, 8.6, 59.0, 105.4,
4.2. General procedure for the synthesis of 3,3-bissilyl
aldehydes
143.5; IR (neat) cmꢀ1 3024w, 2953s, 2912s, 1644m, 1460m, 1415m,
1377m, 1267m, 1236m, 1107s; HRMS (MALDI, m/z) calcd for
C16H36OSi2 Na (MþNa)þ: 323.2197, found 323.2210.
To a solution of 1a (86 mg, 0.3 mmol) in anhyd THF (1.5 mL) and
anhyd HMPA (64 mL, 0.36 mmol) under argon was added s-BuLi
(0.45 mL of a 1.0 M solution in pentane, 0.45 mmol) at ꢀ78 ꢁC. After
4.5. Preparation of bissilyl divinyl ketone 14 and the
subsequent SiO2-promoted Nazarov reaction to give cyclic
stirring for 5 min, H2O (30
mL, 3.0 mmol) was added and the
resulting solution was warmed to room temperature with stirring
for another 3 h. The organic layer was diluted with Et2O (5.0 mL),
dried over Na2SO4 and concentrated under reduced pressure. Pu-
rification of the crude residue via silica gel flash column chroma-
tography (gradient eluent: 5e10% of EtOAc/petroleum ether)
afforded pure 3a (63 mg, 91%) of as a colorless oil.
b
-silyl enone 15
To a mixture of aqueous formaldehyde solution (37% form-
aldehyde in water, 24 mmol) and 3b (4 g, 20 mmol) in i-PrOH
(2 mL) were added pyrrolidine (0.5 mL, 6 mmol) and propionic
acid (0.45 mL, 6 mmol). The reaction mixture was stirred at
45 ꢁC for 10 h. The mixture was quenched with satd aq NaHCO3
(10 mL) and extracted with Et2O (3ꢂ20 mL). The combined or-
ganic layers were then dried over Na2SO4 and concentrated
under reduced pressure. Purification of the crude residue via
silica gel flash column chromatography (gradient eluent: 0e0.2%
of EtOAc/petroleum ether) afforded pure 13 (3.6 g, 85%) as
4.2.1. 3,3-Bistriethylsilyl aldehyde (3a). 1H NMR (400 MHz, CDCl3)
d
0.56 (q, 12H, J¼8.0 Hz), 0.84 (t, 1H, J¼6.0 Hz), 0.95 (t, 18H,
13
J¼8.0 Hz), 2.55 (dd, 2H, J¼1.6, 6.0 Hz), 9.73 (t, 1H, J¼1.6 Hz);
C
NMR (100 MHz, CDCl3)
d
-1.7, 4.2, 7.8, 41.0, 202.4; IR (neat) cmꢀ1
2954s, 2881s, 2734m, 1709s, 1461m, 1417m, 1380m; HRMS
(MALDI, m/z) calcd for C15H34OSi2Na (MþNa)þ: 309.2040, found
309.2047.
a yellow oil. 1H NMR (400 MHz, CDCl3)
(s, 1H), 5.86 (s, 1H), 6.07 (s, 1H), 9.42 (s, 1H); 13C NMR (100 MHz,
CDCl3)
-0.2, 16.5, 130.9, 150.8, 194.6; IR (neat) cmꢀ1 2960 (s),
d 0.01 (s, 18H), 1.87
d
4.3. General procedure for the synthesis of 3,3-bissilyl enol
derivatives in Table 4
2855 (m), 1696 (s), 1608 (m), 1256 (s), 1051 (m), 845 (s), 691 (m);
HRMS (MALDI, m/z) calcd for C10H23OSi2 (MþH)þ: 215.1282,
found 215.1286.
To a solution of 1a (86 mg, 0.3 mmol) in anhyd THF (1.5 mL)
To a solution of 13 (1.5 g, 7.0 mmol) in dry ether (10 mL) was
added cyclohexenyl lithium (14 mL of a w1.0 M solution in Et2O,
14.0 mmol)16 at 0 ꢁC. After stirring for 20 min, the reaction mixture
was quenched with satd aq NH4Cl (20 mL) and extracted with Et2O
(3ꢂ10 mL). The combined organic phases were dried over Na2SO4
and concentrated under reduced pressure. Purification of the crude
residue via silica gel flash column chromatography (gradient elu-
ent: 0.7%e0.9% of EtOAc/petroleum ether) afforded the pure alco-
hol (1.74 g, 85%) of as a colorless oil. The resulting alcohol (273 mg,
0.92 mmol) was dissolved in ethyl acetate (13.5 mL) and IBX
(386 mg, 1.38 mmol) was added. The resulting suspension was
immersed in an oil bath set to 80 ꢁC and stirred vigorously open to
the atmosphere overnight. The reaction mixture was cooled to
room temperature and filtered through a medium glass frit. The
filter cake was washed with EtOAc (3ꢂ5 mL) and the combined
filtrates were concentrated under reduced pressure. Purification of
the crude residue via silica gel flash column chromatography
(gradient eluent: 0e0.25% of EtOAc/petroleum ether) afforded pure
14 (325 mg, 88%) of as a colorless oil. 1H NMR (400 MHz, CDCl3)
and anhyd HMPA (64
mL, 0.36 mmol) under argon was added
s-BuLi (0.45 mL of a 1.0 M solution in pentane, 0.45 mmol) at
ꢀ78 ꢁC. After stirring for 5 min, triethylsilyl chloride (135 mg,
0.9 mmol) was added and the resulting solution stirred at ꢀ78 ꢁC
for another 15 min. Then the reaction was quenched with satd aq
NaHCO3 (3.0 mL) and extracted with Et2O (2ꢂ5 mL). The com-
bined organic phases were dried over Na2SO4 and concentrated
under reduced pressure. Purification of the crude residue via silica
gel flash column chromatography (gradient eluent: 5e10% of
EtOAc/petroleum ether) afforded pure 4a (114 mg, 95%) of as
a colorless oil.
4.3.1. 3,3-Bistriethylsilyl triethylsilyl enol ether (4a). 1H NMR
(400 MHz, CDCl3)
d
0.53 (q, 12H, J¼8.0 Hz), 0.63 (q, 6H, J¼8.0 Hz),
0.93 (t, 9H, J¼8.0 Hz), 0.94 (t, 9H, J¼8.0 Hz), 0.97 (t, 9H, J¼8.0 Hz),
1.89 (d, 3H, J¼12.0 Hz), 4.26 (dd, 1H, J¼5.6, 12.4 Hz), 6.15 (d, 1H,
J¼5.6 Hz); 13C NMR (100 MHz, CDCl3)
d 4.3, 4.6, 6.4, 6.6, 6.8, 7.5, 7.9,
107.2, 135.3; IR (neat) cmꢀ1 3024w, 2954s, 2910s, 2880s, 1636m,
1461m, 1414m, 1270m, 1238m, 1101s; HRMS (MALDI, m/z) calcd for
C21H48OSi3Na (MþNa)þ: 423.2905, found 423.2906.
d
0.04 (s, 18H), 1.62e1.68 (m, 4H), 1.75 (s, 1H), 2.22e2.27 (m, 4H),
5.44 (s, 1H), 5.56 (s, 1H), 6.64 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d
0.2, 21.6, 22.0, 24.5, 25.7, 121.5, 137.8, 139.4, 148.0, 199.7; IR (neat)
4.4. General procedure for the synthesis of 3,3-bissilyl enol
derivatives in Table 5
cmꢀ1 2949s, 2859w, 1640s, 1598w, 1249m, 1203w, 844m; HRMS
(MALDI, m/z) calcd for C16H30OSi2Na (MþNa)þ: 317.1727, found
317.1743.
To a solution of 1a (86 mg, 0.3 mmol) in anhyd THF (1.5 mL)
To a suspension of flame-activated silica gel (210 mg,
and anhyd HMPA (64
m
L, 0.36 mmol) under argon was added
200e300 mesh) in dry petroleum ether (5 mL) was added 14
(20 mg, 0.07 mmol). After stirring at room temperature for 16 h, the
reaction mixture was filtered. The filtrates were concentrated un-
der reduced pressure. Purification of the crude residue via silica gel
flash column chromatography (gradient eluent: 0e0.5% of EtOAc/
petroleum ether) afforded 15 (8.3 mg, 55%). 1H NMR (400 MHz,
s-BuLi (0.45 mL of a 1.0 M solution in pentane, 0.45 mmol) at
ꢀ78 ꢁC. After stirring for 5 min, CH3I (56
mL, 0.9 mmol) was added
and the resulting solution was warmed to room temperature with
stirring for another 4 h. Then the reaction was quenched with satd
aq NaHCO3 (3.0 mL) and extracted with Et2O (2ꢂ5 mL). The
combined organic phases were dried over Na2SO4 and concen-
trated under reduced pressure. Purification of the crude residue
via silica gel flash column chromatography (gradient eluent:
5e10% of EtOAc/petroleum ether) afforded pure 4j (79 mg, 84%) of
as a colorless oil.
CDCl3)
d 0.18 (s, 9H), 0.90 (m, 1H), 1.07 (m, 1H), 1.20 (m, 1H),
1.47e1.50 (m, 2H),1.56 (m,1H),1.68 (m,1H), 2.14 (m,1H), 2.28e2.33
(m, 2H), 2.42 (d, 1H, J¼16.4 Hz), 2.62 (ddd, 1H, J¼2.8, 6.0, 16.4 Hz),
6.75 (br s,1H); 13C NMR (100 MHz, CDCl3)
d 1.1, 22.6, 23.0, 24.1, 29.5,
33.3, 34.8, 48.7, 134.3, 150.6, 206.0; IR (neat) cmꢀ1 2929s, 2852m,

6934
Z. Gan et al. / Tetrahedron 68 (2012) 6928e6934
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A. Chem. Rev. 1986, 86, 857e873; (b) Panek, M.; Masse, C. E. Chem. Rev. 1995, 95,
1293e1316; (c) Langkopf, E.; Schinzer, D. Chem. Rev. 1995, 95, 1375e1408; (d)
Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063e2192.
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Stone, F. G. A., Eds.; Academic: New York, NY, 1977; Vol. 16, pp 1e31; (b) Brook,
A. G.; Bassindale, A. R. In Rearrangements in Ground and Excited States; De Mayo,
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1722s, 1616w, 1249m, 1165w, 860m, 840m; HRMS (MALDI, m/z)
calcd for C21H48OSi3Na (MþNa)þ: 245.1338, found 245.1333.
Acknowledgements
This research was supported by the National Natural Science
Foundation of China (21172150, 21021001), the National Basic Re-
search Program of China (973 Program, 2010CB833200), and
Sichuan University (Distinguished Young Scientist Program,
2011SCU04A18).
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Supplementary data
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Experimental procedures and spectral data for products (PDF)
can be found in the online version of this article. Supplementary
data associated with this article can be found, in the online version,
at http://dx.doi.org/10.1016/j.tet.2012.06.005.
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