Highly Regioselective Sequential 1,1-Dihydrosilylation of Terminal Aliphatic Alkynes with Primary Silanes

Article abstract of DOI:10.1002/cjoc.201900079

A regioselective double 1,1-hydrosilylation of terminal aliphatic alkynes with primary silanes catalyzed by one cobalt catalyst has been developed. gem-Bis(dihydrosilyl)alkanes containing four silicon-hydrogen bonds are efficiently constructed in an atom-economical manner. Tolerated substrates include simplest alkyne-ethyne, a complicated drug derivative and various functionalized terminal aliphatic alkynes. Asymmetric approach using two catalysts is achieved with excellent enantioselectivities to access corresponding chiral products. The transformations of Si—H bonds into Si—C, Si—O, and Si—F bonds and the synthesis of enantioriched α-hydroxysilane show synthetic utility.

Full text of DOI:10.1002/cjoc.201900079

Accepted Article
Title: Highly Regioselective Sequential 1,1-Dihydrosilylation of Terminal Aliphatic
Alkynes with Primary Silanes
Authors: Zhaoyang Cheng, Shipei Xing, Jun Guo, Biao Cheng, Lan-Fang Hu, Xing-
Hong Zhang and Zhan Lu*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2019, 37, 10.1002/cjoc.201900079.
The final Version of Record (VoR) of it with formal page numbers will soon be
published online in Early View: http://dx.doi.org/10.1002/cjoc.201900079.
ISSN 1001-604X • CN 31-1547/O6
mc.manuscriptcentral.com/cjoc
www.cjc.wiley-vch.de

Highly Regioselective Sequential 1,1-Dihydrosilylation of Terminal
Aliphatic Alkynes with Primary Silanes†
Zhaoyang Cheng,a Shipei Xing,a Jun Guo,a Biao Cheng,a Lan-Fang Hu,b Xing-Hong Zhangb and Zhan Lu*,a
a Department of Chemistry, Zhejiang University, Hangzhou 310058, China
b
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University,
Hangzhou 310027, China
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion A regioselective double 1,1-hydrosilylation of terminal aliphatic alkynes with primary silanes catalyzed by
one cobalt catalyst has been developed. gem-bis(dihydrosilyl)alkanes containing four silicon-hydrogen bonds are efficiently constructed in an
atom-economical manner. Tolerated substrates include simplest alkyne-ethyne, a complicated drug derivative and various functionalized terminal
aliphatic alkynes. Asymmetric approach using two catalysts is achieved with excellent enantioselectivities to access corresponding chiral products. The
transformations of Si-H bonds into Si-C, Si-O, and Si-F bonds and the synthesis of enantioriched α-hydroxysilane show synthetic utility.
insufficiency of
Scheme 1 Synthesis of gem-(bis)silanes
Introduction
Organosilanes are important and valuable compounds, which
have been widely used in organic synthesis,1 materials,2
biotechnology,3 and medicinal chemistry,4 due to their abundance
and useful properties.5 The development of efficient methods for
the synthesis of various organosilanes is crucial for fundamental
studies and application investigations. Geminal (bis)silanes, with
two silyl groups both connected to the same sp3-hybridized
carbon, have emerged various unique characteristics and received
increasing attentions in methodology and total synthesis.6
However, the scarcity of effective approaches to access
gem-(bis)silanes largely limit their further utility explorations. To
date, only a few studies have established synthetic methods to
synthesize gem-(bis)silanes (Scheme 1a), such as reductive
disilylation of ketones,7 retro-[1,4]-Brook rearrangement of 3-silyl
allyloxysilanes,8 carbenes insertion into Si-Si bonds,9 double
C(sp3)-Si coupling of gem-dibromides.10 However, these protocols
can only afford fully substituted silyl products. Organosilanes
containing multiple silicon-hydrogen bonds have been proven as
good candidates for further elaborations.11 Therefore, it would be
highly desirable to develop new strategies for the synthesis of
gem-(bis)silanes with multiple silicon-hydrogen bonds.
Selective sequential double hydrofunctionalization of alkynes
has emerged as an important way to prepare germinal
functionalized products.12 Sequential double hydrosilylation of a
carbon-carbon triple bond would be a straightforward and
atom-economical strategy to introduce two silyl groups into one
molecule.12d Ideally and theoretically, when primary silanes
served as silicon sources, gem-bis(dihydrosilyl)alkanes with four
silicon-hydrogen bonds could be obtained through regioselective
sequential 1,1-dihydrosilylation of alkynes. However, realization of
this reaction may have many difficulties (Scheme 1b). First, most
catalytic systems can only transform alkynes to vinylsilanes,13
which are intermediates for the sequential reaction, and no
further hydrosilylation happens presumably due to the
on
Previous studies
gem
a)
-(bis)silanes synthesis:
R2
SiR3
R'
SiMe2F
SiMe2F
Ph
R
SiMe3
SiMe3
R
SiMe2Ph
SiMe2Ph
Double C-Si
OHC
SiR3
SiR3
R
SiR3
OR3
Reductive
retro-Brook
Carbenes insertion
disilylation
rearrangement
coupling
alkyl, phenyl
M. et. al.
(2018)
=
=
=
R
H
T.N. et. al.
R
R
Ph, Me,
R. et. al.
Mitchell,
Song,
(1999)
aryl, alkenyl, alkynyl
Z. et. al.
J. et. al.
Calas,
Oestreich,
R
(1969)
(2010)
with
Wang,
(2015)
silanes:
primary
b) Sequential alkyne 1,1-dihydrosilylation
R
R
SiH2R'
SiH2R'
R'SiH3
SiH2R'
+
+
+
+
SiHR'
...
SiHR'
R
R
cat.
[M]
R
R
R
Reactivity
SiH2R'
SiH
2R'
SiH2R'
R
SiH2R' ...
+
+
R
Regioselecvity
SiH2R'
R
Chemoselectivity
1,1-dihydrosilylation
This work:
c)
IIP•CoCl
NaBHEt
-5
2 (1 mol%)
3 (3-15 mol%)
Ph
SiH2R
N
alkyl
(H, Si)
+
RSiH3
2.2
N
alkyl
(H, Si)
toluene
2 h
iPr
RT,
SiH2R
examples
(0.25 M),
one
N
Co
N
equiv.
pot
32
iPr
Cl
·
·
·
·
Cl
High regioselectivities
Products with four Si-H bonds
51-96%
iPr
yields
one
catalyst
Effective
reaction enabled
IIP•CoCl2
sequential
by
as
terminal
substrate
including ethyne
Simple
aliphatic alkynes
reactivity caused by steric hinderance. Second, regioselectivities
involved in both hydrosilylation process should be controlled
carefully.14 Third, chemoselectivities are of vital importance to
avoid over-hydrosilylation of products with alkynes15 and
competition of hydrogenation.11d,14c To our knowledge, the control
of reactivity, regio- and chemoselectivities of 1,1-dihydrosilylation
of alkynes with primary silanes enabled by only one catalyst has
not been well explored.12d,16
Our group is particularly interested in earth-abundant-metal
catalyzed asymmetric hydrofunctionalization of alkenes11c,17 and
alkynes.11d,12a,18 Here, we developed a highly regioselective
sequential 1,1-dihydrosilylation of terminal aliphatic alkynes with
primary silanes to access valuable gem-bis(dihydrosilyl)alkanes
catalyzed by single cobalt catalyst (Scheme 1c).
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.201900079
This article is protected by copyright. All rights reserved.

Chen et al.
Breaking Report
A 1,2-dihydrosilylation product was not detected, showing little
reactivity for hydrosilylation of 4a. Then, cobalt complexes were
Results and Discussion
screened.
Lb·CoCl2
with
more
sterically
hindered
Table 1 Optimizations for sequential 1,1-dihydrosilytion of terminal
aliphatic alkynesa
2,6-diisopropylphenyl imine led to slightly raise in the yield and
selectivities (entry 2). A larger imine Lc, however, seriously
damaged the result, leading to 52% yield of 3a and 22% yield of
4a (entry 3). Encouragingly, when a more electron-rich N-phenyl
protected chiral imidazoline iminopyridine (IIP) Ld18a was used,
the yield of 3a was increased dramatically to 99% yield with
excellent regioselectivity (entry 4). Neither increasing nor
decreasing of the
1
1
2
R3
H,
X
O
=
•
:
:
=
=
=
=
=
=
R2
=
i
Pr,
=
i
Pr,
=
La
CoCl2
R
R
Me,
=
CoCl2
R3
X
R3
=
X
O
•
Lb
R
i
Pr,
CHPh2 R2
X
1
N
•
:
=
=
=
Lc
CoCl2
R
R
i
X
O
R1
,
=
=
OMe,
Pr,
1
CoCl2
R2
R2
R2
R3
R3
R3
i
NPh
NPh
NPh
N
N
•
Co
:
=
=
=
Ld
i
i
Pr,
H,
H,
H,
Pr,
=
X
Bu,
R3 Le
1
•
:
Cl
CoCl2
R
t
Cl
Pr,
Pr,
R1
R2
1
•
:
=
=
=
X
Lf
R
i
CoCl2
Bn,
SiH2Ph
L.
CoCl
n
2 (5 mol%)
Bu
SiH2Ph
n
Bu
Bu
NaBHEt
3 (15 mol%)
SiH2
Ph
n
Bu
+
PhSiH3
5a
3a
Table 2 Scope of gem-(Bis)silanesa
toluene
2 h
Ar, RT,
(0.25 M),
1a
0.5 mmol
2a
SiH2Ph
SiH2Ph
SiH2Ph
N.D.
1.1 mmol
R
Ph
SiH2
SiH2
n
Bu
R
n
Bu
n
4a
R
Ph
SiH2
SiH2
H4
=
=
3i R
,
H5
,
C6
85%
=
=
=
=
3b R
4-MeOC6
90%
90%
87%
86%
,
,
Entry
1
L.CoCl2
La.CoCl2
Lb.CoCl2
Lc.CoCl2
Ld.CoCl2
Le.CoCl2
Lf.CoCl2
Ld.CoCl2
Ld.CoCl2
Ld.CoCl2
Ld.CoCl2
Ld.CoCl2
Solvent
Yield of 3a/4a/5a (%)b
72 / 12 / -
81 / 12 / 3
52 / 22 / 5
99 / <1 / -
30 / 22 / 40
97 / 3 / -
,
,
79%
84%
70%b
R
H4
2-MeC6
3-MeC6
3j
3c R
H4
,
4-ClC6
,
=
3k R
,
3l R
,
3m R
,
3n R
,
H4
,
3d R
,
Bn,
toluene
toluene
toluene
toluene
toluene
toluene
THF
=
4-MeC6
H4
,
3e R
,
CH2CH
2Pn,
1,
=
diMeC
6H
3, 74%
3,5-
,
87%b
90%b
96%b
n=
3f
Ph
SiH2
2
=
4-PhC6
H4
,
89%
n
n=
,
,
5,
3g
3h
=
=
3o R
,
89%
Ph
SiH2
1-naphthyl,
2-naphthyl,
3
n=
12,
R
,
76%
3p
4
Ph Ph
SiH2Ph
Bu SiH2Ph
Ph
Ph
SiH2
Ph
SiH2
SiH2
iPr
tBu
3
5
n
Ph
SiH2
Ph
Ph
SiH2
SiH2
c
3r
3s
, 85%
3t
, 84%
, 83%
, 96%
3q
5
6
Ph
SiH2
Ph
SiH2
Ph
SiH2
SiH2
Ph
7
75 / 5 / -
Cl
MeOOC
Et2NOC
BnO
5
5
5
Ph
Ph
SiH2
Ph
SiH2
SiH2
81%c
SiH2
8
Et2O
88 / <1 / -
90 / 3 / -
3w
3x
3u
3v
, 94%
,
, 69%
, 72%
9
dioxane
MeCN
O
Ph
SiH2
Ph
SiH2
Ph
TBSO
HO
EtO
SiH2
10
11c
- / - / 9
99 (93)d / <1 /-
O
3
Ph
Ph
SiH2
SiH2
, 78%
Ph
SiH2
O
toluene
toluene
toluene
c
3z
, 63%
Cl
3aa
3y
, 51%
12c, e Ld.CoCl2
13c, f
- / - / -
Ph
SiH2
N
Ph
SiH2
-
- / - / -
Ph
SiH2
3
N
Ph
SiH2
a
S
SiH2
Ph
The reaction was conducted using 1a (0.5 mmol), 2a (1.1 mmol), [Co]
N
Ph
SiH2
c
b
and NaBHEt3 in a solution (0.25 M) at RT under argon atmosphere for 2 h.
3ab
3ad
, 88%
, 74%
b
c
c
3ac
, 84%
Yields were determined using TMSPh as an internal standard. [Co] (3
mol%), NaBHEt3 (9 mol%). d Isolated yield. e w/o NaBHEt3. f w/o [Co].
At the beginning of optimization, 1-hexyne (1a) and
phenyl-silane (2a) were used as model substrates. Chiral
oxazoline iminopyridine (OIP) cobalt complex La·CoCl2 and
NaBHEt3 were chosen as a precatalyst and an activator,
respectively. The reaction was carried out under the atmosphere
of argon, using 1a (0.5 mmol), 2a (1.1 mmol), La·CoCl2 (5 mol%)
and NaBHEt3 (15 mol%) in a solution of toluene (0.25 M) at
ambient temperature for 2 hours. Remarkably, a sequential
double hydrosilylation occurred only using one catalyst, delivering
desired product 3a in 72% yield and Markovnikov
mono-hydrosilylation product 4a in 12% yield, without
a The standard conditions: 1 (0.5 mmol), 2 (1.1 mmol ), Ld.CoCl2 (3 mol%),
b
NaBHEt3 (9 mol%), toluene (0.25 M) at RT, Ar, 2 h. Ld.CoCl2 (1 mol%),
NaBHEt3 (3 mol%). c Ld.CoCl2 (5 mol%), NaBHEt3 (15 mol%).
steric hindrance on imidazoline improved the result (entries 5 and
6). No better result was obtained after screening various solvents
(entries 7-10). Delightedly, when the catalyst loading decreased
to 3 mol%, the reaction still processed smoothly to afford 3a in 93%
isolated yield with excellent chemo- and regioselectivities (entry
11). The control experiments indicated that precatalyst and
reductant were necessary (entries 12-13). The standard
conditions were identified as 0.5 mmol of alkynes, 1.1 mmol of
primary silanes, 3 mol% of Ld·CoCl2, and 9 mol% of NaBHEt3 in
toluene (0.25 M) at ambient temperature for 2 hours.
anti-Markovnikov mono-hydrosilylation product 5a and
a
1,2-dihydrosilylation product (entry 1, Table 1). The absence of 5a
demonstrated good reactivity for hydrosilylation of 5a. Yet, 12%
yield of 4a indicated poor regioselectivity for hydrosilylation of 1a.
With the optimal conditions established, the substrate scope
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
was investigated (Table 2). First, the scope of primary silanes was
explored briefly. For aryl silanes, both electron-donating and
electron-withdrawing groups in the para-position of phenyl ring
gave the desired products in excellent yields (3b-3c). Besides,
alkyl primary silanes could also participate to the reactions
(3d-3e). However, when diphenylsilane served as silicon source,
the reactions only delivered mono-hydrosilylation products. Next,
the scope of aliphatic alkynes was explored. The reactions were
not obviously influenced by the chain length (1f-1h), delivering
corresponding gem-bis(dihydrosilyl)alkanes (3f-3h) in 87-96%
yields. Various branched alkynes (3q-3s) could be tolerated as
well, including sterically congested quaternary substrate (1s).
Substrates with terminated aromatic rings were also competent
(3i-3p). Polycycles like 1-naphthyl, 2-naphthyl (1o-1p) were
compatible as well. Notably, alkynes with heterocycles such as
thiophene, carbazole, pyridine (1ab-1ad) were well tolerated,
affording corresponding products (3ab-3ad) in 74-88% yields.
Various functionalized substrates such as cyclopropane, halide,
ester, amide, ether, silyl protected alcohol, free alcohol and
dioxalate were well tolerated (1t-1aa), which demonstrated
were carried out successfully, delivering the corresponding chiral
products in good yields with excellent enantioselectivities,
tolerating N- (6ac-a, 6ac-b) and O-heteroatoms (6ag) (Table 3).
The absolute configure-ation was confirmed by X-ray
crystallographic analysis of 6ac-b.20
Table 3 Asymmetric Hydrosilylation of β-Vinylsilanesa
standard conditionsa
Ph
SiH2
R2
Ph
SiH2
R1
+
SiH3
R1
R2
SiH2
5
2
6
0.5 mmol
0.55 mmol
Ph
Ph
ee
SiH2
SiH2Bn
ee
SiH2
SiH2Bn
n
Bu
BnO
3
N
Ph
SiH2
SiH2R
6a
,
99%
,
98%
77%,
87%,
6ag
=
eeb
97%
77%,
6ac-a
R
Bn
,
,
=
eeb
6ac-b R
,
,
91%
73%,
1-naphthyl
a
remarkable functional group tolerance. Furthermore,
a
The same as the condition of table 2 except using 5 (0.5 mmol), 2 (0.55
mmol). b Ld.CoCl2 (5 mol%), NaBHEt3 (15 mol%).
complicated drug derivative (1ad) could be transformed
efficiently, delivering gem-(bis)dihydrosilyl modified drug
derivative 3ad in 74% yield. When phenylacetylene was tested as
substrate, the reaction afforded (α-/β-)vinylsilanes in 60%/19%
yields, presumably because of electron effects. The reaction of
5-decyne only delivered mono-hydrosilylation product in 96%
isolated yield.
The reaction could be easily scaled up. The gram scale
reaction using 1 mol% catalyst loading was successfully carried
out, delivering 3a in 92% yield (eq 1).
Furthermore, asymmetric sequential double hydrosilylation of
alkynes by one-pot two steps way was developed (Table 4). The
reaction directly using Ld.CoCl2 with two different silanes in one
pot afforded a mixture of unseparated three gem-(bis)silanes (see
SI, S138). Enlightened by the studies of cobalt-catalyzed
anti-Markovnikov hydrosilylation of alkynes using dpephos as
ligand15b,21 and our previous works,11d,12a,17 asymmetric
1,1-hydrosilylation of terminal aliphatic alkynes were achieved,
delivering 6a, 6q, 6u in 72-84% yields with 97-98% ee (Table 4). In
particularly, chloride-containing (6u) fragments of products could
be used for further downstream diversification. Moreover,
opposite chiral gem-bis(dihydrosilyl) alkanes could be prepared
Ld.
CoCl
2 (1 mol%)
3 (3 mol%)
NaBHEt
1a
+
PhSiH3
3a 1.3698
92%
yield
,
g
(1)
toluene
0 oC to
2 h
RT,
(0.25 M),
5 mmol
Table
4
Asymmetric sequential 1,1-dihydrosilylation of terminal
aliphatic alkynesa
Interestingly, ethynyltrimethylsilane could be tolerated to
deliver structurally intriguing 1,1,2-(tris)silyl ethane 3ae in 87%
yield (eq 2).16b Notably, ethyne, which is abundant and the
simplest alkyne, could be transformed to 3af in 70% yield by
simply using syringe to add ethyne gas (eq 3). To the best of our
knowledge, this is the first time to achieve sequential
dihydrosilylation of ethyne.19
3SiR2
3SiR3
H
H
cat.1,
cat.2,
(1) [Co]
(2) [Co]
R2
SiH2
R3
R1
R
toluene
Ar
RT,
(0.25 M),
SiH2
1
One
pot
6
Ph
SiH2
Bn
Ph
ee
Ph
ee
SiH2
SiH2
SiH2
n
n
Bu
6a
Bu
6a
iPr
Cl
3
5
Bn
SiH2
Ph
SiH2
Bn
SiH2
Bn
SiH2
ee
ee
6q 84%,
R
)-
6u
SiH2Ph
,
98%
S
,
98%
,
97%
,
98%
72%,
83%,
80%,
(
(
)-
standard conditions
Me3Si
Me3Si
+
PhSiH3
(2)
Ld.
CoCl
SiH2Ph
2 (5 mol%)
(1) 1 (0.5 mmol), H3SiR2 (0.5 mmol), Co(OAc)2 (2 mol%), dpephos (2.4
a
NaBHEt
3ae
3 (15 mol%)
, 87%
yield
mol%), NaBHEt3 (6 mol%), toluene (0.25 M), RT, Ar, 3 h. (2) H3SiR3 (0.5
mmol), Ld.CoCl2 (3 mol%), NaBHEt3 (9 mol%), toluene (0.25 M), RT, Ar, 3 h.
Ld.
CoCl
2 (5 mol%)
SiH2Bn
NaBHEt
+
BnSiH3
3 (15 mol%)
SiH2Bn
3af
with excellent enantioselectivities (R-6a, S-6a). Usually,
preparation of two opposite enantiomers with high
enantioselectivities should use opposite chrial sources or different
ligands.17b Through this way, the opposite enantiomers of chiral
products could be easily obtained by simply changing the adding
sequence of two different primary silanes.
(3)
toluene
(0.25 M)
0.5 mmol
(11.2 mL)
1.0 mmol
, 70%
yield
RT,
overnight
In consideration of the chirality of Ld, the possibility of
asymmetric hydrosilylation of β-vinylsilanes may exist if a
different primary silane was used. However, because primary
silanes differed only in one substitution, the asymmetric process
is highly challenging. To our delight, the asymmetric reactions
Silicon-hydrogen bonds of gem-bis(dihydrosilyl) alkanes could
be transformed to Si-X (X = Me,22 OMe,23 Ph,24 F25) in good to
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Chen et al.
Breaking Report
excellent yields (Table 5), which enriched the diversities of
gem-(bis)silanes and broadened the possibilities for further
modifications.
added PE/Et2O (1/1) (10 mL) and filtered through a pad of silica
gel. The Schlenk flask and silica gel were washed by ether (15 mL
× 3). The combined filtrate was concentrated and purified by flash
column chromatography using PE as the eluent to afford the
corresponding product.
Table 5 Transformations of Silicon-hydrogen Bonds
SiMe2Ph
n
Bu
SiMe2Ph
(a)
(b)
SiFPh2
SiHPh2
7
, 88%
yield
(d)
(c)
n
Bu
n
Bu
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2019xxxxx.
3a
Ph
SiFPh2
, 86%
Si(OMe)2
SiHPh2
, 91%
n
Bu
10
9
yield
yield
Ph
Si(OMe)2
, 65%
8
yield
a
o
b
CH2I2, ZnEt2, DCE, 0 C to RT, 30 h. KN(SiMe3)2, MeOH, toluene, 22 h.
Acknowledgement
c PhMgBr, THF, reflux, 36 h. d CuI, CuCl2, KF, THF, RT, 18 h.
Financial support was provided by NSFC (21772171), Zhejiang
Provincial Natural Science Foundation of China (LR19B020001),
Zhejiang University K. P. Chao’s High Technology Development
Foundation and the Fundamental Research Funds for the Central
Universities.
To further demonstrate synthetic utility, a selective cleavage
of carbon-silicon bond was explored, transforming a chiral
gem-(bis)silane to a useful chiral α-hydroxysilane.1b,26 Through
methylation22 and Fleming-Tamao oxidation,27 (R)-6a could be
stereospecifically converted into 11 in 72% total yields with 98%
ee (Scheme 2).
References
[1] For selected reviews, see: (a) Jones, G. R.; Landais, Y., The oxidation
of the carbon-silicon bond. Tetrahedron 1996, 52, 7599-7662; (b)
Fleming, I.; Barbero, A.; Walter, D., Stereochemical control in organic
synthesis using silicon-containing compounds. Chem. Rev. 1997, 97,
2063-2192; (c) Denmark, S. E.; Sweis, R. F., Design and
implementation of new, silicon-based, cross-coupling reactions:
Importance of silicon-oxygen bonds. Acc. Chem. Res. 2002, 35,
835-846; (d) Denmark, S. E.; Regen, C. S., Palladium-catalyzed
cross-coupling reactions of organosilanols and their salts: practical
alternatives to boron- and tin-based methods. Acc. Chem. Res. 2008,
41, 1486-1499; (e) Nakao, Y.; Hiyama, T., Silicon-based cross-coupling
reaction: an environmentally benign version. Chem. Soc. Rev. 2011,
40, 4893-4901; (f) Jensen, K. L.; Dickmeiss, G.; Jiang, H.; Albrecht, L.;
Jorgensen, K. A., The diarylprolinol silyl ether system: a general
organocatalyst. Acc. Chem. Res. 2012, 45, 248-264; (g) Zhang, H. J.;
Priebbenow, D. L.; Bolm, C., Acylsilanes: valuable organosilicon
reagents in organic synthesis. Chem. Soc. Rev. 2013, 42, 8540-8571;
(e) Komiyama, T.; Minami, Y.; Hiyama, T., Recent Advances in
Scheme 2 Selective Cleavage of Carbon-Silicon Bond
BF3•Et2O
OH
SiH2Ph
CH2 2 ZnEt
I
KF/KHCO3/H2O2
,
2
n
Bu
n
Bu
AcOH
36 h
CHCl3
0 oC to
,
MeOH/THF
SiMe2Bn
RT,
SiH2Bn DCE,
RT,
2 h
RT,
overnight
11
, 72%
total
yield
ee
98%
R
99%
6a
ee
(
)-
Conclusions
In summary, we developed
a
highly regioselective
cobalt-catalyzed sequential double hydrosilylation of terminal
aliphatic alkynes with primary silanes for efficient synthesis of
gem-bis(dihydrosilyl)alkanes. Alkynes from the simplest ethyne to
complex drug derivative, could be well transformed with excellent
functional group tolerance. This protocol could be easily scaled up.
Silicon-hydrogen bonds of gem-bis(dihydrosilyl)alkanes could be
converted to prepare various gem-(bis)silanes. Asymmetric
transformations
were
also
achieved
with
excellent
enantioselect-ivities. Different enantiomers could be obtained by
simply switching the addition order of two different primary
silanes. Chiral α-hydroxysilanes could be prepared by selective
oxidation of chiral gem-(bis)silanes. Further studies on the
mechanism and utility of gem-bis(dihydrosilyl)alkanes are
underway in our laboratory.
Transition-metal-catalyzed
synthetic
transformations
of
organosilicon Reagents. ACS Catal. 2017, 7, 631-651.
[2] (a) Kawakami, Y.; Li, Y. N., Approaches to polymers containing a
silicon-oxygen bond in the main chain. Des. Monomers. Polym. 2000,
3, 399-419. (b) Rappoport, Z. Patai, S. The Chemistry of Organic
Silicon Compounds. Wiley: Chichester, 1989; Vol. 1, Chapter 25; (c)
Brook, M. A. Silicon in Organic Organometallic and Polymer
Chemistry. Wiley: New York, 1999.
Experimental
A 25 mL Schlenk flask equipped with a magnetic stirrer and a
flanging rubber plug was dried with flame under vacuum. When
cooled to ambient temperature (10-35 oC), it was vacuumed and
flushed with Ar. This degassed procedure was repeated for three
times. To the flame-dried Schlenk flask Ld•CoCl2 complex (0.015
mmol, 3 mol%), 2.0 mL (0.25 M) of toluene and phenylsilane (98%,
1.1 mmol) were added by dropwise sequentially. After that,
NaBHEt3 (45 μL, 1.0 M in THF, 0.045 mmol) and an alkyne (0.5
mmol, 1.0 equiv.) were added to the mixture sequentially and
stirred at ambient temperature for 2 h. the resulting solution was
[3] (a) Frampton, M. B.; Zelisko, P. M., Organosilicon Biotechnology.
Silicon 2009, 1, 147-163; (b) Kan, S. B. J.; Lewis, R. D.; Chen, K.;
Arnold, F. H., Directed evolution of cytochrome c for carbon-silicon
bond formation: Bringing silicon to life. Science 2016, 354,
1048-1051.
[4] For selected reviews, see: (a) Pooni, P. K.; Showell, G. A., Silicon
switches of marketed drugs. Mini.-Rev. Med. Chem. 2006, 6,
1169-1177; (b) Franz, A. K.; Wilson, S. O., Organosilicon molecules
with medicinal applications. J. Med. Chem. 2013, 56, 388-405; (c)
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
Min, G. K.; Hernandez, D.; Skrydstrup, T., Efficient routes to
of geminal dibromides: ionic-to-radical switch in the reaction
mechanism. Org. Lett. 2018, 20, 5367-5369.
carbon-silicon bond formation for the synthesis of silicon-containing
peptides and azasilaheterocycles. Acc. Chem. Res. 2013, 46, 457-470.
[5] Driess, M.; Oestreich, M., New frontiers and challenges in silicon
chemistry: ISOS XVII in Berlin. Chem.-Eur. J. 2014, 20, 9144-9145.
[6] For selected review, see: (a) Gao, L.; Zhang, Y. B.; Song, Z. L.,
Exploration of versatile geminal vis(silane) chemistry. Synlett 2013,
24, 139-144; Selected examples for unique and useful characteristics
of gem- (bis)silanes, see: (b) Liu, Z. J.; Lin, X. L.; Yang, N.; Su, Z. S.; Hu,
C. W.; Xiao, P. H.; He, Y. Y.; Song, Z. L., Unique steric effect of geminal
bis(silane) To control the high exo-selectivity in intermolecular
Diels-Alder reaction. J. Am. Chem. Soc. 2016, 138, 1877-1883; (c)
Groll, K.; Manolikakes, S. M.; du Jourdin, X. M.; Jaric, M.; Bredihhin,
A.; Karaghiosoff, K.; Carell, T.; Knochel, P., Regioselective Metalations
of Pyrimidines and Pyrazines by Using Frustrated Lewis Pairs of
[11] For selected reviews, see: (a) Cheng, C.; Hartwig, J. F., Catalytic
silylation of unactivated C-H bonds. Chem. Rev. 2015, 115,
8946-8975; (b) Lipke, M. C.; Liberman-Martin, A. L.; Tilley, T. D.,
Electrophilic activation of silicon-hydrogen bonds in catalytic
hydrosilations. Angew. Chem. Int. Ed. 2017, 56, 2260-2294; For
selected examples, see: (c) Cheng, B.; Lu, P.; Zhang, H. Y.; Cheng, X. P.;
Lu, Z., Highly Enantioselective Cobalt-Catalyzed Hydrosilylation of
Alkenes. J. Am. Chem. Soc. 2017, 139, 9439-9442; (d) Guo, J.; Shen, X.
Z.; Lu, Z., Regio- and Enantioselective Cobalt-Catalyzed Sequential
Hydrosilylation/ Hydrogenation of Terminal Alkynes. Angew. Chem.
Int. Ed. 2017, 56, 615-618; (e) Toutov, A. A.; Liu, W. B.; Betz, K. N.;
Fedorov, A.; Stoltz, B. M.; Grubbs, R. H., Silylation of C-H bonds in
aromatic heterocycles by an Earth-abundant metal catalyst. Nature
2015, 518, 80-84.
.
BF3 OEt2 and Hindered Magnesium- and Zinc-Amide Bases. Angew.
Chem. Int. Ed. 2013, 52, 6776-6780; (d) Wu, Y.; Li, L. J.; Li, H. Z.; Gao,
L.; Xie, H. M.; Zhang, Z. G.; Su, Z. S.; Hu, C. W.; Song, Z. L.,
Regioselective nucleophilic addition of organometallic reagents to
3-geminal bis(silyl) N-acyl pyridinium. Org. Lett. 2014, 16, 1880-1883.
(e) Gao, L.; Lu, J.; Song, Z. L.; Lin, X. L.; Xu, Y. J.; Yin, Z. P., [1,5]-Brook
rearrangement: an overlooked but valuable silyl migration to
synthesize configurationally defined vinylsilane. The unique steric
and electronic effects of geminal bis(silane). Chem. Commun. 2013,
49, 8961-8963; (f) Zhang, Y. B.; Guo, Q. Y.; Sun, X. W.; Lu, J.; Cao, Y. J.;
Pu, Q.; Chu, Z. W.; Gao, L.; Song, Z. L., Total synthesis of bryostatin 8
using an organosilane-based strategy. Angew. Chem. Int. Ed. 2018,
57, 942-946; (g) Li, L. J.; Ye, X. C.; Wu, Y.; Gao, L.; Song, Z. L.; Yin, Z. P.;
Xu, Y. J., Sakurai reaction of 3,3-bis(silyl) silyl enol ethers with acetals
involving selective desilylation of the geminal bis(silane). Concise
synthesis of nematocidal oxylipid. Org. Lett. 2013, 15, 1068-1071; (h)
Li, L. J.; Chu, Y.; Gao, L.; Song, Z. L., Geminal bis(silane)-controlled
regio- and stereoselective oxidative Heck reaction of enol ethers
with terminal alkenes to give push-pull 1,3-dienes. Chem. Commun.
2015, 51, 15546-15549; (i) Fleming, I.; Lawrence, A. J.; Richardson, R.
D.; Surry, D. S.; West, M. C., 1,1-Disilyl alcohols as d1 synthons:
Harnessing the 1,2-Brook rearrangement. Helv. Chim. Acta. 2002, 85,
3349-3365; (j) Bai, X. F.; Deng, W. H.; Xu, Z.; Li, F. W.; Deng, Y.; Xia, C.
G.; Xu, L. W., Silicon-based bulky group-induced remote control and
conformational preference in the synthesis and application of
isolable atropisomeric amides with secondary alcohol or amine
moieties. Chem.-Asian J. 2014, 9, 1108-1115.
[12] For selected examples. Sequential hydrosilylation/hydroboration of
terminal alkynes, see: (a) Guo, J.; Lu, Z., Highly chemo-, regio-, and
stereoselective cobalt-catalyzed Markovnikov hydrosilylation of
alkynes. Angew. Chem. Int. Ed. 2016, 55, 10835-10838; (b) Zuo, Z. Q.;
Yang, J.; Huang, Z., Cobalt-catalyzed alkyne hydrosilylation and
aequential vinylsilane hydroboration with Markovnikov selectivity.
Angew. Chem. Int. Ed. 2016, 55, 10839-10843; Sequential
1,1-dihydroboration of terminal alkynes, see: (c) Zuo, Z. Q.; Huang, Z.,
Synthesis of 1,1-diboronate esters by cobalt-catalyzed sequential
hydroboration of terminal alkynes. Org. Chem. Front. 2016, 3,
434-438; One example for sequential double hydrosilylation of
alkynes, 1,2- dihydrosilylation enabled by Pt and Pd catalysis, see: (d)
Shimada, T.; Mukaide, K.; Shinohara, A.; Han, J. W.; Hayashi, T.,
Asymmetric synthesis of 1-Aryl-1,2-ethanediols from arylacetylenes
by palladium-catalyzed asymmetric hydrosilylation as a key step. J.
Am. Chem. Soc. 2002, 124, 1584-1585.
[13] For selected reviews, see: (a) Sun, J.; Deng, L., Cobalt
complex-catalyzed hydrosilylation of alkenes and alkynes. ACS Catal.
2016, 6, 290-300; (b) Greenhalgh, M. D.; Jones, A. S.; Thomas, S. P.,
Iron-catalysed hydrofunctionalisation of alkenes and alkynes.
Chemcatchem 2015, 7, 190-222; (c) Lim, D. S. W.; Anderson, E. A.,
Synthesis of vinylsilanes. Synlett 2012, 44, 983-1010; For selected
examples, see: (d) Molander, G. A.; Retsch, W. H., Selective
Hydrosilylation of alkynes catalyzed by an organoyttrium complex.
Organometallics 1995, 14, 4570-4575; (e) Trost, B. M.; Ball, Z. T.,
Alkyne hydrosilylation catalyzed by a cationic ruthenium complex:
Efficient and general trans addition. J. Am. Chem. Soc. 2005, 127,
17644-17655; (f) Wang, P.; Yeo, X. L.; Loh, T. P., Copper-catalyzed
highly regioselective silylcupration of terminal alkynes to form
α-vinylsilanes. J. Am. Chem. Soc. 2011, 133, 1254-1256; (g) Mo, Z. B.;
Mao, J.; Gao, Y. F.; Deng, L., Regio- and Stereoselective
hydrosilylation of alkynes catalyzed by three-coordinate cobalt(I)
alkyl and silyl complexes. J. Am. Chem. Soc. 2014, 136, 17414-17417;
(h) Rivera-Hernandez, A.; Fallon, B. J.; Ventre, S.; Simon, C.; Tremblay,
M. H.; Gontard, G.; Derat, E.; Amatore, M.; Aubert, C.; Petit, M.,
Regio- and stereoselective hydrosilylation of unsymmetrical alkynes
catalyzed by a well-defined, low-valent cobalt catalyst. Org. Lett.
2016, 18, 4242-4245; (i) Yang, X. X.; Wang, C. Y., Dichotomy of
manganese catalysis via organometallic or radical mechanism:
stereodivergent hydrosilylation of alkynes. Angew. Chem. Int. Ed.
[7] Calas, R.; Dunogues, J.; Biran, C.; Duffaut, N.; Pisciott.F; Lapouyad.P,
New methods of producing silicon-carbon bonds from chlorosilanes
II formation of gem-disily derivatives from a carbonyl group or an
(α-silyalkoxy)silane. J. Organomet. Chem. 1969, 20, 22-24.
[8] (a) Mitchell, T. N.; Schutze, M., 1,4-silyl migration from oxygen to
carbon in silyl allyl ethers: Kinetic and thermodynamic factors.
Tetrahedron 1999, 55, 1285-1294; (b) Song, Z. L.; Lei, Z.; Gao, L.; Wu,
X.; Li, L. J., Efficient approach to 3,3-bissilyl carbonyl and enol
derivatives via retro-[1,4] Brook rearrangement of 3-silyl
allyloxysilanes. Org. Lett. 2010, 12, 5298-5301.
[9] Liu, Z. X.; Tan, H. C.; Fu, T. R.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. B.,
Pd(0)-catalyzed carbene insertion into Si-Si and Sn-Sn bonds. J. Am.
Chem. Soc. 2015, 137, 12800-12803.
[10] Hazrati, H.; Oestreich, M., Copper-catalyzed double C(sp3)-Si coupling
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

Chen et al.
Breaking Report
2018, 57, 923-928.
hydroboration of 1,1-disubstituted alkenes. Org. Chem. Front. 2014,
1, 1306-1309; (c) Chen, J. H.; Guo, J.; Lu, Z., Recent Advances in
Hydrometallation of Alkenes and Alkynes via the First Row Transition
Metal Catalysis. Chin. J. Chem. 2018, 36, 1075-1109; Chen, J. H.; Xi, T.;
Lu, Z., 10 gram-scale synthesis of a chiral oxazoline iminopyridine
ligand and its applications. Org. Chem. Front. 2018, 5, 247-253.
[19] Voronin, V. V.; Ledovskaya, M. S.; Bogachenkov, A. S.; Rodygin, K. S.;
Ananikov, V. P., Acetylene in organic synthesis: recent progress and
new uses. Molecules 2018, 23, 2442-2526.
[14] Synthesis of gem-(bis)silanes via regioselective hydrosilylation has
not been well developed, see: (a) Amako, M.; Schinkel, J.; Freiburger,
L.; Brook, M. A., Siloxane-supported organometallic compounds and
their catalytic activities for the hydrosilylation of vinylsilanes and
dienes. Dalton. Trans. 2005, 74-81; (b) Fu, P. F., Formation of
branched silanes via regiospecific hydrosilylation of vinylsilanes. J.
Mol. Catal. A-Chem. 2006, 243, 253-257; (c) Lee, K. L.,
(Aminomethyl)pyridine complexes for the cobalt-catalyzed
anti-Markovnikov hydrosilylation of alkoxy- or siloxy (vinyl)silanes
with alkoxy- or siloxyhydrosilanes. Angew. Chem. Int. Ed. 2017, 56,
3665-3669.
[15] (a) Zak, P.; Bolt, M.; Pietraszuk, C., Selective synthesis of
E-vinylsilanes and E,E-divinylsilanes via platinum-catalyzed
hydrosilylation of alkynes with secondary silanes. RSC Adv. 2018, 8,
40016-40021; (b) Wu, C. Z.; Teo, W. J.; Ge, S. Z., Cobalt-aatalyzed
(E)-selective anti-Markovnikov hydrosilylation of terminal alkynes.
ACS Catal. 2018, 8, 5896-5900.
[16] (a) Small amount of 1,1-disilylalkane was detected as side product,
see: Chen, C.; Hecht, M. B.; Kavara, A.; Brennessel, W. W.; Mercado,
B. Q.; Weix, D. J.; Holland, P. L., Rapid, regioconvergent, solvent-free
alkene hydrosilylation with a cobalt catalyst. J. Am. Chem. Soc. 2015,
137, 13244-13247; (b) While this manuscript was in preparation, one
example of 1,1-dihydrosilylation with primary silane was reported.
However, the reactions were preliminarily studied and remained
low-efficient (8 days’ reaction time is needed). Nurseiit, A.; Janabel,J.;
Gudun, K. A.; Kassymbek, A.; Segizbayev, M.; Seilkhanov, T. M.;
Khalimon, A. Y. Bench-stable cobalt pre-catalysts for mild
hydrosilative reduction of tertiary amides to amines and beyond.
ChemCatChem 2019, 11, 790-798.
[17] (a) Chen, J. H.; Cheng, B.; Cao, M. Y.; Lu, Z., Iron-catalyzed
asymmetric hydrosilylation of 1,1-disubstituted alkenes. Angew.
Chem. Int. Ed. 2015, 54, 4661-4664; (b) Zhang, H. Y.; Lu, Z.,
Dual-stereocontrol asymmetric cobalt-catalyzed hydroboration of
sterically hindered styrenes. ACS Catal. 2016, 6, 6596-6600; (c) Chen,
X.; Cheng, Z. Y.; Guo, J.; Lu, Z., Asymmetric remote C-H borylation of
internal alkenes via alkene isomerization. Nat. Commun. 2018, 9,
3939-3947; (d) Cheng, B.; Liu, W. B.; Lu, Z., Iron-catalyzed highly
enantioselective hydrosilylation of unactivated terminal alkenes. J.
Am. Chem. Soc. 2018, 140, 5014−5017
[20] CCDC 1876614.
[21] Wu, G. J.; Chakraborty, U.; Jacobi Von Wangelin, A., Regiocontrol in
the cobalt- catalyzed hydrosilylation of alkynes. Chem. Commun.
2018, 54, 12322-12325.
[22] Wen, H. A.; Wan, X. L.; Huang, Z., Asymmetric synthesis of
silicon-stereogenic vinylhydrosilanes by cobalt-catalyzed regio- and
enantioselective alkyne hydrosilylation with dihydrosilanes. Angew.
Chem. Int. Ed. 2018, 57, 6319-6323.
[23] Liu, X.; Xiang, L.; Louyriac, E.; Maron, L.; Leng, X.; Chen, Y. Divalent
ytterbium complex-catalyzed homo- and cross-coupling of primary
arylsilanes. J. Am. Chem. Soc. 2019, 141, 138-142.
[24] Hirone, N.; Sanjiki, H.; Tanaka, R.; Hata, T.; Urabe, H., Acceleration of
the substitution of silanes with grignard reagents by using either LiCl
or YCl3/MeLi. Angew. Chem. Int. Ed. 2010, 49, 7762-7764.
[25] Kunai, A.; Sakurai, T.; Toyoda, E.; Ishikawa, M., Selective synthesis of
fluoro-, fluorohydro-, and chlorofluorosilanes from hydrosilanes with
the use of a CuCl2(CuI)/KF reagent. Organometallics 1996, 15,
2478-2482.
[26] Roesner, S.; Brown, C. A.; Mohiti, M.; Pulis, A. P.; Rasappan, R.; Blair,
D. J.; Essafi, S.; Leonori, D.; Aggarwal, V. K., Stereospecific conversion
of alcohols into pinacol boronic esters using lithiation-borylation
methodology with pinacolborane. Chem. Commun. 2014, 50,
4053-4055.
[27] Shin, K.; Joung, S.; Kim, Y.; Chang, S., Selective synthesis of silacycles
by borane-catalyzed domino hydrosilylation of proximal unsaturated
bonds: tunable approach to 1,n-diols. Adv. Synth. Catal. 2017, 359,
3428-3436.
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
[18] (a) Guo, J.; Cheng, B.; Shen, X. Z.; Lu, Z., Cobalt-catalyzed asymmetric
sequential hydroboration/hydrogenation of internal alkynes. J. Am.
Chem. Soc. 2017, 139, 15316-15319; (b) Chen, J. H.; Xi, T.; Ren, X.;
Cheng, B.; Guo, J.; Lu, Z., Asymmetric cobalt catalysts for
o
m
o
l
%
mo
l
%
IIP
l
(
•C C 2
5
Ph
)
n
n
iH B
S
N
2
a
N BHEt 15
N
as
+
G
(
)
3
(
)
r
iP
o
C
N
N
o ue e
r. .
t l t
,
n
iH B
S
2
r
iP
l
C
l
C
n
S
B
iH
r
e
i l
d
iP
7
0
%
3
y
o
IIP
l
•C C 2
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.