Exploration of versatile geminal bis(silane) chemistry

Article abstract of DOI:10.1055/s-0032-1317706

Geminal bis(silyl) compounds, a special type of organosilane, are attractive synthons because of their great potential for bifunctional reactivity. This article outlines our recent efforts to develop a practical method to synthesize geminal bis(silane) compounds and to explore their interesting bifunctionality. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317706

SYNPACTS
▌139
synpacts
Exploration of Versatile Geminal Bis(silane) Chemistry
Geminal Bis(silane) Chemistry
Lu Gao, Yuebao Zhang, Zhenlei Song*
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy,
Sichuan University, Chengdu, 610041, P. R. of China
E-mail: zhenleisong@scu.edu.cn
Received: 03.09.2012; Accepted after revision: 01.11.2012
Abstract: Geminal bis(silyl) compounds, a special type of or-
ganosilane, are attractive synthons because of their great potential
for bifunctional reactivity. This article outlines our recent efforts to
develop a practical method to synthesize geminal bis(silane) com-
pounds and to explore their interesting bifunctionality.
Key words: organosilane, geminal bis(silane), bifunctional reactiv-
ity, silyl migration, Prins cyclization
Organosilane chemistry1 has remained an active and im-
portant area of research for organic chemists in recent de-
cades. Studies describing new organosilane species and
Zhenlei Song (left) was born in Jiangsu Province, China, in 1978. He
obtained his PhD in organic chemistry from Lanzhou University with
Professor Yongqiang Tu in 2005. From 2005 to 2008, he was a post-
doctoral associate in Professor Richard P. Hsung’s group at the Uni-
versity of Wisconsin at Madison. Currently he is Associate Professor
at West China School of Pharmacy, Sichuan University. His research
program focuses on organosilane chemistry, total syntheses of natural
products, and medicinal chemistry.
Lu Gao (center) was born in Xinjiang Province, China, in 1987. She
attended Sichuan University, where she received her BA in 2009.
Currently she is pursuing doctoral studies with Prof. Zhenlei Song at
West China School of Pharmacy, Sichuan University. Her research
projects focus on silyl migration to form useful organosilane species.
Yuebao Zhang (right) was born in Henan Province, China, in 1988.
He received his BA from Henan University in 2011. Currently he is a
second-year master’s student in Prof. Zhenlei Song’s group at West
China School of Pharmacy, Sichuan University. His research projects
focus on the application of bis(silyl) chemistry in natural product syn-
thesis.
exploring their unique reactivity and efficient use in natu-
ral product synthesis have led to many significant devel-
opments in this field. For example, some well-known
name reactions such as the Brook rearrangement,2 Dan-
heiser cyclopentene annulation,3 Fleming–Tamao oxida-
tion,4 Hiyama coupling,5 Peterson olefination,6 and
Sakurai allylation7 have been widely used in organic syn-
thesis. Geminal bis(silane) compounds 1,8 featuring the
attachment of two silyl groups to one carbon center, are a
special type of organosilane (Scheme 1). Similar to other
geminal bimetallic species,9 which are useful coupling re-
agents, bis(silyl) compounds also possess great potential
because of their bifunctional reactivity. For example,
Lautens10 and Williams11 reported the Sakurai reaction of
allyl bis(silane) 2 with aldehyde to generate homo allylic
alcohols 3 (Scheme 1). Elimination of one silyl group left
the second group in the form of vinylsilane, which could
be used as a functional group for the next transformation.
we wish to outline our recent efforts to develop a practical
method to synthesize geminal bis(silane) and to explore
their interesting bifunctional reactivity.
HO
R2
R3Si
R3Si
Si
Si
R2CHO
In 1997, Mitchell developed a lithium amide induced ret-
ro-[1,4] Brook rearrangement12 of 2-tributylstannyl-3-si-
lyl allyloxysilane 4 to create 3,3-bis(trimethylsilyl)
aldehyde 6a directly (Scheme 2).13 Nevertheless, the sub-
strate containing a vinyl (n-Bu)3Sn group, which is re-
quired to facilitate the silyl migration, is toxic and difficult
to prepare. In addition, the reaction is only feasible when
the less bulky trimethylsilyl group is involved, which lim-
its the usefulness of this approach.
R
L.A., CH2Cl2
56–82%
R3Si
R1
1
R1
3
geminal bis(silane)
2
Scheme 1 General structure of geminal bis(silane) (left) and the Sak-
urai reaction of allyl bis(silane) with aldehyde (right)
Despite their attractiveness as synthons, studies on gemi-
nal bis(silane) have been very limited, presumably as a re-
sult of steric considerations. Indeed, the attachment of two
large silyl groups to one carbon center is quite challenging
in such a sterically bulky system. In this SynPact article,
Inspired by this work, our group developed an improved
method in 2010.14 Using s-BuLi as base, and HMPA as
cosolvent to reduce aggregation of the initially formed al-
lyl anion, a smooth silyl group migration of 3-silyl ally-
loxysilanes 5 was achieved (Scheme 3). Through base-
mediated hydrolysis of lithium enolate, a wide range of
3,3-bis(silyl) aldehydes 6 were formed in good to excel-
SYNLETT 2013, 24, 0139–0144
Advanced online publication: 28.11.2012
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0032-1317706; Art ID: ST-2012-P0739-SP
© Georg Thieme Verlag Stuttgart · New York

140
L. Gao et al.
OSiMe3
SYNPACTS
shields both sides of the 2-position in 8, making C2-alkyl-
ation more difficult. As a result, halides are forced to react
with the oxygen anion, generating exclusively O-alkylat-
ed products 7.
Me3Si
LDA
SiMe3
Me3Si
THF, r.t.
Sn(n-Bu)3
O
H
4
6a
R2
SiM OR
Scheme 2 Mitchell’s LDA-induced retro-[1,4] Brook rearrangement
of 4 to synthesize 3,3-bis(trimethylsilyl) aldehyde 6a
s-BuLi
Z
Si
Si
THF, HMPA, –78 °C
then RX, r.t.
OSiM
R2
5
7
lent yield, including products containing the much more
sterically bulky geminal bis(silyl) group (6c and 6d) and
compounds containing two different silyl groups (6e–g).
The approach was also applicable to substrates with a sub-
stituent at the 1- or 2-position, which readily produced the
corresponding 3,3-bis(silyl) ketone 6h and 2-substituted
3,3-bis(silyl) aldehydes 6i and 6j.
Et3Si
OMe
Et3Si
OBn
Et3Si
O
Et3Si
Et3Si
7b: 90% (X = Br)
Et3Si
7a: 84% (X = I)
7c: 63% (X = Br)
Ph
Me
O
Me
R2
SiM
O
Et3Si
O
Et3Si
O
Et3Si
O
s-BuLi
Si
R1
Si
R1
THF, HMPA, –78 °C
then H2O, r.t.
Et3Si
7d: 61% (X = OTs)
Et3Si
7f: 68% (X = I)
Et3Si
7e: 45% (X = OTs)
OSiM
R2
6
5
O
O
NEt2
Et3Si
O
t-BuMe2Si
O
Ph3Si
O
O
O
Et3Si
Et3Si
OMe
Me3Si
Me3Si
OMe
Et3Si
H
t-BuMe2Si
6c: 73%
H
Et3Si
Ph3Si
H
H
H
6b: 91%
Et3Si
Me3Si
6d: 75%
Me
7h:a 60% (X = I)
Ph
7i:a 58% (X = I)
Et3Si
7g: 75% (X = Br)
O
PhMe2Si
Me3Si
O
AllMe2Si
Et3Si
H
H
Scheme 4 Selective O-alkylation with alkyl halides to generate 3,3-
bis(silyl) enol ethers. Reagents and conditions: 5 (0.15 M), s-BuLi
(1.5 equiv), HMPA (1.2 equiv), THF, –78 °C, then RX (3.0 equiv),
warmed to r.t., 4 h. a TMEDA (1.5 equiv) was added to facilitate the
initial deprotonation step.
6e: 87%
Et3Si
Et3Si
6f: 82%
Me3Si
Me3Si
6g: 60%
O
O
Me3Si
Me3Si
Me
H
Me
6i:a 72%
Li
O
Li
SiM
1
6h:a 67%
6j:a 53%
irreversible
1
O
H
OLi
H
2
-
SiM
H
H
H
2
H
3
SiM
3
Si
Scheme 3 s-BuLi-induced retro-[1,4] Brook rearrangement of 3-si-
lyl allyloxysilanes to synthesize various 3,3-bis(silyl) aldehydes and
ketones. Reagents and conditions: 5 (0.15 M), s-BuLi (1.5 equiv),
HMPA (1.2 equiv), THF, –78 °C, then H2O (10 equiv), warmed to
Si
Si
both sides of C2
are shielded by
bis(silyl) group
10
9
8
a
r.t., 3 h. TMEDA (1.5 equiv) was added to facilitate the initial de-
O-alkylation
protonation step.
R
SiM
H
Si
R
1
Si
SiM OR
3
We obtained a particularly notable result when trapping
3,3-bis(silyl) enolate 8 with alkyl halides. All reactions
proceeded through selective O-alkylation and provided
the corresponding Z-enol ethers exclusively, with no C-al-
kylated products detected at all (Scheme 4). This interest-
ing selectivity provided a deeper mechanistic insight,
especially into the unique properties of the 3,3-bis(silyl)
enolate. We proposed that the enolate adopts the Z-config-
uration and that its most favorable conformation is that
shown in 8, which minimizes allylic strain and nonbonded
interactions and which benefits from a double-hypercon-
jugation effect between the two C–Si bonds and the enol
double bond (Scheme 5). This would prevent reverse silyl
migration via the pentacoordinated silicate 9 to give allyl
anion 10, as well as further C1- and C3-alkylation of 10.
At the same time, the bulky geminal bis(silyl) moiety
2
Z
OSiM
R
OSiM
Si
O
Si
7
C1-, C2- and C3-alkylation were not observed
Scheme 5 Model to explain the exclusive O-alkylation of 3,3-bis(si-
lyl) enolate with alkyl halides
The easy accessibility of 3,3-bis(silyl) aldehyde and enol
derivatives allowed us to explore the more diverse reactiv-
ity of geminal bis(silanes). We discovered that bis(silyl)
enal 11,15 prepared by a Mannich reaction of aldehyde 6
with formaldehyde, proved to be a useful linchpin in an
efficient three-component coupling process involving an-
ion relay chemistry (Scheme 6).16 The reaction features a
[1,4]-Brook rearrangement, which is triggered by the ad-
Synlett 2013, 24, 139–144
© Georg Thieme Verlag Stuttgart · New York

SYNPACTS
Geminal Bis(silane) Chemistry
141
dition of organolithium to aldehyde, to generate the sili- by regioselective deprotonation of enol allyl ether 14-D to
con-stabilized allyl anion 13. It is noteworthy that this form allyl anion 15, which quickly undergoes a [1,5]-an-
process provides a new method for forming silyl allyl an- ion relay via a boat-shaped transition state with a six-
ions, which is generally accessed by deprotonation of allyl membered ring to generate the thermodynamically more
silane. Two transition states seem possible: endo-orientat- stable geminal bis(silyl) allyl anion 16. Next, [2,3]-Wittig
ed endo-13 features tolerable A1,3 strain between the silyl rearrangement of 16 occurs to continuously drive the re-
group and γ-H, so it appears to be more favorable than action to give bis(silyl) allylic alcohol 17-D. The reaction
exo-13, which involves severe A1,2 strain between the silyl is generally suitable for enol allyl ethers with a substituted
group and the 2-substituent. Thus, addition of electro- allyl chain, and it delivers the products in good yields.
philes to endo-13 at the more accessible γ-position gave When a substrate with one substitution at the 3-position
various E-vinylsilanes 12 both regio- and stereoselective- was used, the syn-isomer was obtained as a major product
ly in good yields.
(17d and 17e). When enol allyl ether substituted at both
the 2- and 3-positions was used, the anti-isomer formed
predominantly (17f).
OH
SiM
O
NuLi, THF
β
Si
Nu
α
γ
Si
H
E
H
HMPA, TMEDA
E+, –78 to –15 °C
then H+
Et3Si
Et3Si
17
OH
R
Et3Si
E
t-BuLi
H
12 [γ/E]
11
Et3Si
O
H
THF, HMPA
–78 °C
R
OH
OH
OH
14
H
H
Et3Si
n-Bu
Et3Si
n-Bu
Et3Si
n-Bu
Et
i-Pr
Et3Si
Et3Si
Cy
Ph
Ph
SPh
Et3Si
Et3Si
Et3Si
12a: 86% [81:6:13]a
12b: 71% [78:0:22]a
12c: 81% [65:35:0]a
Et3Si
OH
OH
OH
OH
OH
OH
17a: 74%
17b: 80%
17c: 75%
Me
Me3Si
Ph
n-Bu Me3Si
i-Pr
n-Bu Me3Si
n-Bu
Me
t-Bu
HO
Et3Si
Et3Si
17d: 80%
Et3Si
Et3Si
Me
Et3Si
Et3Si
Me Ph
OH
OH
OH
OH
12d: 82% [100:0:0]a
12e: 60% [100:0:0]a
12f: 53% [100:0:0]a
OH
17f: 58%
17e: 76%
OH
OH
N
dr = 80:20
dr = 90:10
dr = 86:14
Me3Si
HO
Me3Si
H
H
Et3Si
Et3Si
Et3Si
H
O
t-BuLi
Et3Si
D
D
O
Ph Ph
THF, HMPA
Ph
12g: 58% [91:9:0]a
12h: 62% [100:0:0]a
regioselective deprotonation
14-D
15
[1,5]-anion relay
A1,2
OSiM
Si
OSiM
Nu
α
β
Et3Si
Si
α
Et3Si
SiEt3
O1
[2,3]-Wittig
SiEt3
Nu
β
rearrangement
H
H
γ
A1,3
H
H
D
γ
H
H
H
2
80%
OH
H
D
H
1'
2'
exo-13
(unfavorable)
endo-13
(favorable)
3'
H
17-D (Z/E = 1:1)
16
Scheme 6 Geminal bis(silyl) enal as the linchpin in the synthesis of
vinylsilane species by anion relay chemistry. Reagents and condi-
tions: 11 (1.0 equiv), NuLi (1.1 equiv), THF, –78 °C, then TMEDA
(1.1 equiv), warm to –15 °C, then electrophile (3.0 equiv) and HMPA
(4.0 equiv); crude products were treated with p-TsOH (0.2 equiv) in
MeOH. a The ratio γ/E:γ/Z:α.
Scheme 7 Regioselective deprotonation/[1,5]-anion relay/[2,3]-
Wittig rearrangement of 3,3-bis(silyl) allyl enol ethers. Reagents and
conditions: 14 (1.0 equiv), t-BuLi (3.0 equiv) and HMPA (3.0 equiv),
THF, –78 °C.
Geminal bis(silyl) allylic alcohols 17 can be further trans-
formed into the more functionalized trisubstituted vinyl-
silanes 18 (Scheme 8). The process features a sequential
[1,4]-Brook rearrangement/alkylation reaction promoted
by t-BuOLi/CuCN in THF and DMF as co-solvents.18 The
reaction is suitable for a wide range of allylic and propar-
gyl electrophiles, and the leaving group can be one of sev-
eral species, such as halides and tosylate.
As part of our studies on the reactivity of 3,3-bis(silyl)
enol ethers, we focused on the deprotonation of the ex-
tremely bulky bis(silyl) group. Because initial attempts
based on either intermolecular deprotonation or directed
metalation proved unsuccessful, a conceptually new strat-
egy was designed and verified using deuterium-labeling
experiments (Scheme 7).17 The entire process is initiated
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 139–144

142
L. Gao et al.
SYNPACTS
SiMe3
R1
Me3Si
R
t-BuOLi, CuCN
Me3Si
R
Et3Si
R2CHO, TMSOTf
Z
Et3Si
Et3Si
O
RX, THF–DMF, r.t.
Et2O, –78 °C
Z/E ≥ 99:1
cis/trans ≥ 99:1
cis
R1
R
OSiEt3
OH
R2
HO
19a
17
18
20
Me3Si
Me3Si
Me3Si
O
Et3Si
Et3Si
Et3Si
Ph
OSiEt3
OSiEt3
OSiEt3
BnO
Br
18b: 69% (X = Br)
Me
O
O
O
n-Pr
n-Pr
n-Pr
Ph
Me3Si
4
20a: 86%
Me3Si
20b: 90%
20c: 81%
Me3Si
18a: 65% (X = OTs)
18c: 80% (X = OTs)
Me3Si
Et3Si
Et3Si
Et3Si
I
OSiEt3
OSiEt3
Et3Si
18e: 68% (X = OTs)
OSiEt3
Br
O
O
O
n-Pr
n-Pr
MeO
n-Pr
3
Me
Me
Et3Si
20d: 60%
20e: 69%
20f: 65%
18d: 55% (X = Br)
18f: 60% (X = Br)
i-Pr
Me3Si
Me3Si
Me3Si
Me
Et3Si
PhS
18g: 55% (X = SPh)
Et3Si
Et3Si
O
O
O
Me
Ph
n-Pr
n-Pr
n-Pr
Cy
OSiEt3
OSiEt3
OSiEt3
20g: 83%
20h: 98%
20i: 89%
18h: 75% (X = Cl)
18i: 83% (X = Cl)
Scheme 9 The Prins cyclization of geminal bis(silyl) homoallylic al-
cohols with aldehydes to generate 2,6-cis-tetrahydropyrans contain-
ing an exocyclic Z-vinylsilane. Reagents and conditions: 19 (0.1 M),
R2CHO (2.0 equiv), TMSOTf (1.5 equiv), Et2O, –78 °C, 20 min.
Scheme 8 Application of the [1,4]-Brook rearrangement/alkylation
protocol with geminal bis(silyl) allylic alcohols to synthesize trisub-
stituted vinylsilanes. Reagents and conditions: 17 (1.0 equiv), RX
(2.0 equiv), t-BuOLi (3.0 equiv), CuCN (3.0 equiv), DMF–THF (5:3)
as cosolvent at 25 °C.
groups lie in the pseudoequatorial position, could be ex-
pected to give (Z)-20 and (E)-20, respectively. Although
both feature antiperiplanar arrangements, the second silyl
group adopts a different orientation. Whereas transition
state (E)-21 suffers from a steric interaction between the
silyl group and H-2 in the pseudoaxial position, a similar
interaction between the silyl group and H-6 in transition
state (Z)-21 appears to be tolerated because H-6 points in-
ward. Thus, transition state (Z)-21 should be energetically
more favorable and should lead to the observed exclusive
Z-selectivity.
Our latest investigations have shown that bis(silyl) chem-
istry may also play a key role in the synthesis of complex
natural products such as bryostatins.19 This family of mol-
ecules has shown remarkable biological activity against a
range of cancers, and has been used extensively in clinical
trials against these diseases. The main challenge presented
by the bryostatins is the construction of cis-tetrahydropy-
ran rings B and C containing geometrically defined exo-
cyclic methyl enoates. Inspired by the bifunctionality of
geminal bis(silyl) compounds, we developed a new strat-
egy to form ring B of bryostatins.20
R1
H
R2
H
O
O
The key reaction lies in a TMSOTf-promoted Prins
cyclization21 of geminal bis(silyl) homoallylic alcohols
1922 with aldehydes to generate 2,6-cis-tetrahydropyrans
20 containing an exocyclic Z-vinylsilane (Scheme 9). This
approach is not only widely applicable to a variety of al-
dehydes and homo allylic alcohols, but is also remarkable
in that configurational control of the exocyclic vinylsilane
is independent of both the R1 and R2 groups. Thus, reliable
Z-selectivity can be achieved when the silyl group falls on
the same side as the incorporated aldehyde.
R1
H
R2
H2
H6
Me3Si
H6
SiMe3
H
SiMe3
H2
H
Me3Si
H
(Z)-21 (favorable)
(E)-21 (unfavorable)
H6: pointing inward
H2: pseudoaxial
Me3Si
SiMe3
R1
R1
R2
R2
O
O
A rationalization of this interesting stereoselectivity is
tentatively proposed in Scheme 10. Two chair-like transi-
tion states (Z)-21- and (E)-21, in which both R1 and R2
(Z)-20
(E)-20
Scheme 10 A model to explain the exclusive Z-selectivity observed
during formation of exocyclic vinylsilane
Synlett 2013, 24, 139–144
© Georg Thieme Verlag Stuttgart · New York

SYNPACTS
Geminal Bis(silane) Chemistry
143
Me3Si
Me3Si
Me3Si
Me
t-BuMe2SiO
Me
a
OH
Me Me
HO
+
OPMB
13
OAc
Me
Me
MeO2C
9
7
H
B
A
O
O
O
22
23
O
OPMB
OH
15
24
O
t-BuMe2SiO
OH
O
H
b
Me
O
Me 19
O
C
MeO2C
Br
Me
CO2Me
OH
Me
OPMB
OPMB
c
O
Me
Me
Me
O
Me
O
bryostatin 1
26
25
t-BuMe2SiO
t-BuMe2SiO
Scheme 11 Synthesis of the ring B of bryostatins. Reagents and conditions: (a) 23 (2.0 equiv), TMSOTf (1.5 equiv), Et2O, –78 °C, 92%; (b)
NBS (5.0 equiv), DMF, 0 °C, 88%; (c) [PdCl2(MeCN)2] (10 mol%), dppf (30 mol%), CO, MeOH, Et3N, DMF, 80 °C, 73%.
This methodology was then applied to the synthesis of
ring B of bryostatins to show the bifunctional role of the
bis(silyl) group (Scheme 11). Prins cyclization of bis-
(silyl) homoallylic alcohol 22 with aldehyde 23 under
standard conditions generated the desired cis-tetrahydro-
pyran 24 in 92% yield with exclusive Z-selectivity. Bro-
mination of the exocyclic vinylsilane in 24 with N-
bromosuccinimide (NBS) gave 25 in 88% yield and with
retention of the Z-configuration. A final carbonylation
step led to formation of methyl enoate and generated 26 as
the C9–C19 fragment of bryostatins in 73% yield.
References and Notes
(1) For selective reviews on organosilanes, see: (a) Overman, L.
E.; Blumenkopf, T. A. Chem. Rev. 1986, 86, 857. (b) Panek,
M.; Masse, C. E. Chem. Rev. 1995, 95, 1293. (c) Langkopf,
E.; Schinzer, D. Chem. Rev. 1995, 95, 1375. (d) Fleming, I.;
Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063.
(2) For reviews on the Brook rearrangement, see: (a) Brook, A.
G. Acc. Chem. Res. 1974, 7, 77. (b) Moser, W. H.
Tetrahedron 2001, 57, 2065.
(3) (a) Danheiser, R. L.; Carini, D. J.; Basak, A. J. Am. Chem.
Soc. 1981, 103, 1604. (b) Danheiser, R. L.; Kwasigroch, C.
A.; Tsai, Y. M. J. Am. Chem. Soc. 1985, 107, 7233.
(c) Danheiser, R. L.; Fink, D. M.; Tsai, Y. M. Org. Synth.
1988, 66, 8. (d) Danheiser, R. L.; Stoner, E. J.; Koyama, H.;
Yamashita, D. S.; Klade, C. A. J. Am. Chem. Soc. 1989, 111,
4407. (e) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J.
Org. Chem. 1992, 57, 6094.
(4) (a) Tamao, K.; Akita, M.; Kumada, M. J. Organomet. Chem.
1983, 254, 13. (b) Fleming, I.; Henning, R.; Plaut, H. J.
Chem. Soc., Chem. Commun. 1984, 29. (c) For the latest
review on Fleming–Tamao oxidation, see: Jones, G. R.;
Landais, Y. Tetrahedron 1996, 52, 7599.
In summary, we have described our recent progress in
studies of geminal bis(silane) chemistry. Our research has
involved developing practical methods to synthesize
functionalized geminal bis(silanes), discovering new re-
actions involving these compounds, and applying them to
natural product synthesis. This interesting chemistry
shows the attractive versatility of geminal bis(silyl) spe-
cies, especially their bifunctional reactivity in several
transformations. We are optimistic that research in this
field will grow and some breakthroughs can be expected.
For example, enantioselective silyl migration to generate
chiral 3,3-bis(silyl) aldehydes containing two different si-
lyl groups would be an extremely useful advance. These
compounds should be useful in all kinds of asymmetric
transformations involving selective desilylation. In addi-
tion, the steric bulk of the bis(silyl) group may be a unique
way to achieve regio- and stereoselectivity under chal-
lenging circumstances. Encouraged by the construction of
ring B of bryostatins, we expect that geminal bis(silane)
chemistry will, as additional reactivities are discovered,
play further key roles and find more efficient applications
in natural product synthesis.
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Acknowledgment
We thank the National Natural Science Foundation of China
(21172150, 21021001), the National Basic Research Program of
China (973 Program, 2010CB833200), and Sichuan University (Di-
stinguished Young Scientist Program, 2011SCU04A18; 985 project
– Science and Technology Innovation Platform for Novel Drug De-
velopment) for financial support.
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Supporting Information of ref. 15 for details.
Synlett 2013, 24, 139–144
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