Cu-Catalyzed Reductive gem-Difunctionalization of Terminal Alkynes via Hydrosilylation/Hydroamination Cascade: Concise Synthesis of α-Aminosilanes

Article abstract of DOI:10.1002/chem.202001799

A copper-catalyzed reductive gem-difunctionalization of terminal alkynes with hydrosilanes and hydroxylamines has been developed. The reaction proceeds via hydrosilylation/hydroamination cascade, and the readily available and simple terminal alkynes can be transformed into the corresponding α-aminosilanes of medicinal interest in a single operation. Additionally, the use of chiral bisphosphine ligand successfully makes the reaction enantioselective to deliver the optically active α-aminosilanes with good enantiomeric ratios.

Full text of DOI:10.1002/chem.202001799

Accepted Article
Accepted Article
Title: Cu-Catalyzed Reductive gem-Difunctionalization of Terminal
Alkynes via Hydrosilylation/Hydroamination Cascade: Concise
Synthesis of α-Aminosilanes
Authors: Koji Hirano, Masahiro Miura, and Soshi Nishino
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To be cited as: Chem. Eur. J. 10.1002/chem.202001799
Link to VoR: https://doi.org/10.1002/chem.202001799
01/2020

10.1002/chem.202001799
Chemistry - A European Journal
COMMUNICATION
Cu-Catalyzed Reductive gem-Difunctionalization of Terminal
Alkynes via Hydrosilylation/Hydroamination Cascade: Concise
a
Synthesis of -Aminosilanes
Soshi Nishino,[a] Koji Hirano,*[a] and Masahiro Miura*[a]
Dedication ((optional))
Abstract: A copper-catalyzed reductive gem-difunctionalization of
operation (Scheme 1b). Additionally, an appropriate chiral
bisphosphine ligand makes the reaction enantioselective to form
the optically active a-aminosilanes[7] with good enantiomeric
ratio (e.r.), which are of interest in medicinal chemistry, as
exemplified by angiotensin-converting enzyme (ACE) inhibitor
and serine protease human neutrophil elastase (HNE)
inhibitor.[8] Our group and Buchwald independently reported the
related Cu-catalyzed aminoboration[7d] and hydroamination[7e] of
vinylsilanes; however, in which the starting vinylsilanes need to
be prepared from terminal alkynes in advance. In sharp contrast,
the present sequential Cu catalysis allows the terminal alkynes
to be starting platforms. We note that during the course of this
study, Engle and Liu reported the related copper-catalyzed
sequential hydroboration/hydroamination of terminal alkynes,
giving the a-aminoboronates.[9]
terminal alkynes with hydrosilanes and hydroxylamines has been
developed.
The
reaction
proceeds
via
hydrosilylation/hydroamination cascade, and the readily available
and simple terminal alkynes can be transformed into the
corresponding a-aminosilanes of medicinal interest in a single
operation. Additionally, the use of chiral bisphosphine ligand
successfully makes the reaction enantioselective to deliver the
optically active a-aminosilanes with good enantiomeric ratios.
The terminal alkyne is simple and abundant but one of the
indispensable chemical entities in modern organic synthesis
because of its high and versatile reactivity associated with two p
bonds.[1] Particularly, metal-catalyzed addition-type reactions
can add various functional groups across the alkyne platform.
Among them, the catalytic, simultaneous introduction of two
functional groups (difunctionalization) has received significant
attention because it can rapidly increase the molecular
a) Hydroboration/hydroarylation sequence (Lalic)
Ar
cat. Cu/Pd
R
+
+
X
Ar
H
Bpin
Bpin
R
complexity.
Whereas the catalytic vic-difunctionalization
b) Hydrosilylation/hydroamination sequence (this work)
reactions have been widely studied, the introduction of two
NR3
functions at the alkyne terminus (gem-difunctionalization) is less
explored.
2
cat. Cu/L*
SiR2
R
The catalytic double hydroboration[2] and
+
+
BzO
H
NR3
2
SiR2
3
R
*
3
hydrosilylation[3] were reported to form the corresponding gem-
diborylalkanes and -disilylalkanes, respectively, but only the
same functional groups (boryl or silyl) could be installed.
Buchwald[4] and Mankad[5] independently developed the copper-
Scheme 1. Metal-catalyzed reductive gem-difunctionalization of terminal
alkynes with two different non-hydrogen functional groups. pin = pinacolate.
Bz = benzoyl.
catalyzed
reductive
hydroamination
and
reductive
On the basis of the reported copper-catalyzed
hydrosilylation[10] and hydroamination,[11,12,13] our optimization
studies commenced with 5-phenyl-1-pentyne (1a; 3.0 equiv),
Ph2SiH2 (2a; 3.0 equiv), and O-benzoyl-N-benzyl-N-tert-
butylhydroxylamine (3a) as model substrates, and several
phosphine ligands were screened, in conjunction with CuCl
catalyst (10 mol%), LiOtBu base (3.0 equiv), and 1,2-
hydroacylation of terminal alkynes, respectively. However, one
of functional groups added to the terminal carbon is a hydrogen
atom. Only one successful example of gem-difunctionalization
with two different non-hydrogen functional groups is the
copper/palladium co-catalyzed hydroboration/hydroarylation
sequence with pinacolborane and aryl halides, which was
recently reported by Lalic (Scheme 1a).[6] Thus, this research
field still remains underdeveloped. Herein, we report a copper-
dichloroethane (DCE) solvent (Scheme 2).
In an early
experiment, treatment of 1a with 2a and 3a under the
catalyzed
hydrosilylation/hydroamination
sequence
with
CuCl/dppbz catalysis afforded a small but meaningful amount of
a-aminosilane 4aaa (2% H NMR yield) along with the reduced
1
hydrosilanes and hydroxylamines: the silyl and amino groups
are added in the gem-relationship, and the corresponding a-
aminosilanes are obtained from the terminal alkynes in a single
byproduct 6a.
Prompted by the preliminary result, we
investigated several dppbz-type ligands.[14] The introduction of
substituents at the ortho- or para-position on the benzene ring
gave almost negligible impact, and concomitant formation of
vinylsilane 5aa, alkene 6a, and alkylsilane 7aa byproducts were
observed. In sharp contrast, dppbz ligands modified with the
bulky tert-butyl group at the meta-position greatly increased the
reactivity and selectivity (DTBM-dppbz and tBu-dppbz).
Moreover, the more sterically demanding Me3Si-substituted
TMS-dppbz showed the best performance to form the desired
4aaa in 97% 1H NMR yield. Subsequent fine-tuning revealed
that the reaction also proceeded well with the decreased amount
[a]
S. Nishino, Prof. Dr. K. Hirano, Prof. Dr. M. Miura
Department of Applied Chemistry
Graduate School of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
Fax: (+81) 6-6879-7362
E-mail: k_hirano@chem.eng.osaka-u.ac.jp;
miura@chem.eng.osaka-u.ac.jp
Supporting information for this article is available on the WWW
under http://www.xxx.
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10.1002/chem.202001799
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COMMUNICATION
of 1a (2.0 equiv) or LiOtBu (2.0 equiv) to deliver 4aaa in 91 or
87% isolated yield, respectively. Some additional observations
are to be noted: attempts with other monodentate and bidentate
ligands suffered from much lower selectivity; LiOtBu is
indispensable for the high conversion; no reaction occurred in
the absence of any Cu salts (see the Supporting Information for
more detailed optimization studies).
isolated in an analytically pure form after conversion into the silyl
benzyl ethers (4kaa-OCH2Ar and 4laa-OCH2Ar).[15]
The
cyclohexylacetylene (1b) could also be coupled with acyclic N,N-
dibenzylamine as well as cyclic morpholine, thiomorpholine, and
Boc-protected piperazine to deliver the corresponding a-
aminosilanes 4bab–4bae in good yields.
The 4-
bromobenzylamine 2f also provided 4baf with the aryl-Br
remaining untouched. Furthermore, the reaction was conducted
on a 1.0 mmol scale without any difficulty (4aaa), indicating the
scalability and reproducibility of the copper catalysis.
tBu
CuCl/ligand
Ph
+
+
H
SiPh2H
BzO
3a
N
LiOtBu
DCE, 40 ˚C, 18 h
3
Bn
2a
1a
tBu
Bn
Me3Si
SiMe3
N
+
+
+
Ph
Ph
SiPh2H
NR3
2
Ph
SiPh2H
Ph
SiPh2H
Ar =
3
3
3
3
Me3Si
Me3Si
SiMe3
SiMe3
P
P
CuCl/TMS-dppbz
+
+
R1
4aaa
6a
7aa
5aa
SiR2
BzO
H
NR3
2
SiR2
3
R1
3
LiOtBu, DCE
40 ˚C, 18 h
SiMe3
Me3Si
Me
1
2
3
4
PAr2
PAr2
TMS-dppbz
OMe
scope of hydrosilanes 2
tBu
Bn
tBu
Bn
tBu
Bn
N
tBu
Bn
o-Me-dppbz
0/10/5/0
dppbz
2/0/7/0
MeO-dppbz
1/0/7/0
N
dppbz-type liagnd
N
N
% yields of 4aaa/5aa/6a/7aa
Ph
SiEt2H
Ph
SiPh2H
Ph
SiPhMeH
Ph
SiPhH2
3
3
3
3
t-Bu
OMe
t-Bu
F
F
F
4aca 29%[c]
4aaa 87% (82%)[a]
4aba 72%, 51:49 d.r.[b]
4ada 39%[c]
CF3
t-Bu
scope of terminal alkynes 1
tBu
Bn
tBu
Bn
tBu
Bn
tBu
Bn
tBu
Bn
p-tBu-dppbz
N
DTBM-dppbz
67/0/3/15
p-CF3-dppbz
2/0/3/0
N
N
N
N
F3-dppbz
0/0/5/0
11/0/7/1
SiPh2H
SiPh2H
SiPh2H
SiPh2H
4daa 63%
Cl
SiPh2H
3
SiMe3
t-Bu
t-Bu
4baa 80%
4caa 81%[d]
4faa 74%
CF3
4eaa 82%
tBu
Bn
tBu
Bn
tBu
Bn
tBu
Bn
N
N
N
N
SiMe3
O
CF3
PivO
SiPh2H
BnO
SiPh2H
TBSO
3
SiPh2H
3
SiPh2H
3
7
99 (91)/0/3/9[a]
96 (87)/0/3/9[b]
TMS-dppbz
97/0/5/11
tBu-dppbz
49/0/7/8
CF3-dppbz
0/0/0/0
O
4iaa 70%
4gaa 87%
4haa 84%
4jaa 69%
tBu
Bn
tBu
Bn
tBu
Bn
tBu
Bn
Scheme 2. Representative ligand optimization studies for Cu-catalyzed
hydrosilylation/hydroamination sequence of terminal alkyne 1a with
dihydrosilane 2a and hydroxylamine 3a. Conditions: 1a (0.45 mmol), 2a (0.45
mmol), 3a (0.15 mmol), CuCl (0.015 mmol), ligand (0.015 mmol), LiOtBu (0.45
mmol), DCE (1.5 mL), 40 ˚C, 18 h, N2. 1H NMR yields based on 0.15 mmol
with CH2Br2 internal standard are shown. Isolated yields are in parentheses.
[a] With LiOtBu (0.30 mmol). [b] With 1a (0.30 mmol).
N
BocN
N
N
BocN
N
O
Ar
O
Ar
Br
NC
Si
Ph2
Si
NC
SiPh2H
SiPh2H
3
3
Ph2
4kaa-OCH2Ar 32%[f]
4laa-OCH2Ar 42%[f]
4kaa 85%[e]
4laa 92%[g]
Ar = 3,5-(MeO)2C6H3
Ar = 3,5-(MeO)2C6H3
scope of hydroxylamines 3
Boc
N
Br
O
N
S
N
Bn
Bn
N
N
SiPh2H
SiPh2H
4bac 79%
SiPh2H
SiPh2H
4bae 63%
With optimal conditions in hand, we investigated the
generality of copper-catalyzed sequential process (Scheme 3).
We initially tested some hydrosilanes 2: secondary PhMeSiH2,
Et2SiH2, and primary PhSiH3 also worked to form the
corresponding a-aminosilanes 4aba–4ada, but in the latter two
cases the products were too unstable for chromatographic
purification to be isolated. On the other hand, tertiary silanes
such as Ph2MeSiH and (EtO)2MeSiH did not provide any
N
4bab 94%
4bad 74%
SiPh2H
4baf 73%
Scheme 3. Cu-catalyzed hydrosilylation/hydroamination sequence of terminal
alkynes 1 with hydrosilanes 2 and hydroxylamines 3. Conditions: 1 (0.30
mmol), 2 (0.45 mmol), 3 (0.15 mmol), CuCl (0.015 mmol), TMS-dppbz (0.015
mmol), LiOtBu (0.45 mmol), DCE (1.5 mL), 40 ˚C, 18 h, N2. Isolated yields are
shown. [a] On 1.0 mmol scale. [b] With 1 (0.45 mmol) and LiOtBu (0.30 mmol).
[c] 1H NMR yields. [d] With 1c (0.45 mmol). [e] Contaminated with 22% of
deaminated product 7ka. [f] Isolated after treatment with 3,5-dimethoxybenzyl
alcohol and K2CO3.
Contaminated with 17% of deaminated product 7la. Bn = benzyl, Boc = tert-
butoxycarbonyl, Piv = tert-butylcarbonyl, TBS = tert-butyldimethylsilyl.
products because of no hydrosilylation activity.
The
corresponding simply hydroaminated product, that is enamine,[4]
was also not detected (data not shown). The scope of terminal
See the Supporting Information for details.
[g]
alkynes
1
was substantially broad.
The more sterically
demanding cyclohexylacetylene (1b), isopropylacetylene (1c),
and tert-butylacetylene (1d) underwent the reaction smoothly to
Our next target was the enantioenriched a-aminosilane by
the enantioselective hydrosilylation/hydroamination cascade.
After the evaluation of chiral ligands and various reaction
parameters, we were pleased to find that the optically active
4aaa was obtained in 74% isolated yield with 96:4 e.r. under the
Cu(OAc)2/(R,R)-Ph-BPE catalysis combined with cyclopentyl
methyl ether (CPME) solvent (Scheme 4). The 4aaa was readily
purified by silica gel column chromatograph but unstable for
chiral HPLC analytical conditions; therefore, the e.r. value was
determined after the conversion into the corresponding silyl
form the desired 4baa–4daa in good yields.
The
cyclopropylacetylene (1e) was converted to 4eaa with the
cyclopropyl ring left intact. Moreover, the copper catalyst was
compatible with several functional groups including alkyl chloride,
benzyl ether, silyl ether, pivaloyl ester, and acetal to deliver the
gem-functionalized products 4faa–4jaa in 69–87% isolated
yields. The nitrile and NBoc moieties were also tolerated under
the standard reaction conditions, but the products were
somewhat sensitive to silica gel and partially decomposed
during purification (4kaa and 4laa); however, they could be
ether 4aaa-OCH2Ar (vide supra).[16]
Sterically hindered
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10.1002/chem.202001799
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secondary alkyl-substituted terminal alkynes also underwent the
enantioselective gem-difunctionalization to from 4caa, 4eaa, and
4bab with 88:12–95:5 e.r. The asymmetric catalysis was
tolerated with the alkyl chloride and silyl ether moieties, and the
corresponding functionalized chiral a-aminosilanes 4faa and
4haa were formed in good yields with acceptable
enantioselectivity.
Based on the aforementioned results, we are tempted to
propose that the mechanism of reaction is as follows (Scheme
6a). Initially, the active copper alkoxide species A is generated
in situ from CuCl, LiOtBu, and the ancillary ligand L.
Subsequent s-bond metathesis with the hydrosilane 2 (A to B)
and insertion of the terminal alkyne 1 form the vinylcopper
intermediate C, where the regioselectivity is controlled by steric
factors and the more bulky copper is located at the terminal
position.[19] The second s-bond metathesis with the hydrosilane
2[9] and insertion via the vinylsilane-coordinated copper hydride
D afford the alkylcopper E. In the vinylsilane insertion step,
hyperconjugation between the Cu–C s orbital and proximal Si–C
s* orbital can work well to lead to the one regioisomer E
Ph
Ph
NR2
2
P
Cu(OAc)2/(R,R)-Ph-BPE
P
R1
H
SiPh2H
NR2
BzO
2
+
+
R1
SiPh2H
LiOtBu, CPME
40 ˚C, 18 h
*
Ph
Ph
1
2a
3
4
(R,R)-Ph-BPE
tBu
Bn
tBu
Bn
tBu
Bn
tBu
Bn
N
*
N
*
N
*
N
*
selectively.[7d,e,20]
Final electrophilic amination with the
SiPh2H
Ph
SiPh2H
SiPh2H
Cl
SiPh2H
3
3
hydroxylamine 3[21] gives the a-aminosilane 4, and salt
metathesis with LiOtBu regenerates the starting copper alkoxide
A to complete the catalytic cycle. When using the chiral (R,R)-
Ph-BPE ligand, the second hydrocupration (D to E) is the
enantioselectivity-determining step, and the corresponding
enantioenriched a-silylalkylcopper E is eventually transformed
into the optically active 4. The byproducts 6 and 7 observed
during the optimization studies could arise from protonolysis of
organocopper intermediates C and E, respectively, while the
dissociation of LnCuH from p-complex D produces the vinylsilane
5. The results of control experiments with deuterium-labeled
hydrosilane [D2]2a and terminal alkyne [D]1a are also consistent
with the proposed mechanism (Scheme 6b).
4caa 63%, 88:12 e.r.[a]
4eaa 85%, 95:5 e.r.
4aaa 74%, 94:6 e.r.
4faa 80%, 90:10 e.r.
tBu
Bn
Bn
N
Bn
N
*
TBSO
SiPh2H
3
SiPh2H
*
4bab 49%, 91:9 e.r.
4haa 75%, 88:12 e.r.
Scheme 4. Cu-catalyzed enantioselective hydrosilylation/hydroamination
sequence of terminal alkynes with diphenyldihydrosilane (2a) and
1
hydroxylamines 3. Conditions: 1 (0.30 mmol), 2a (0.45 mmol), 3 (0.15 mmol),
Cu(OAc)2 (0.015 mmol), (R,R)-Ph-BPE (0.018 mmol), LiOtBu (0.45 mmol),
CPME (0.30 mL), 40 ˚C, 18 h, N2. Isolated yields of 4 are shown. The
enantiomeric ratios (e.r.) were determined by HPLC analysis on a chiral
stationary phase after conversion into 4-OCH2Ar. [a] With 1c (0.45 mmol).
To get insight into the mechanism, we then evaluated the
reactivity of potential intermediates (Scheme 5).[18] First, we
confirmed the viability of propargylbenzene (1m) under almost
a) Plausible mechanism
CuCl
L, LiOtBu
LiOBz
H
Si
1
identical conditions to form the a-aminosilane 4mab in 69% H
2
LnCuOtBu
NMR yield (Scheme 5a). Second, we independently prepared
the corresponding vinylsilane 5ma and enamine 8mb and
checked their reactivity: whereas 5ma was converted to 4mab in
73% yield (Scheme 5b), no reaction occurred with 8mb
(Scheme 5c). On the other hand, the gem-disilane 9aa[17] was
also another putative intermediate but not detected at all even
when the terminal alkyne 1a was subjected to otherwise
identical conditions without the hydroxylamine: only the terminal
alkene 6a and alkylsilane 7aa were formed (Scheme 5d). These
outcomes suggest the most plausible intermediacy of the
vinylsilane.
LiOtBu
Si OtBu
A
NR2
Si
R
LnCuOBz
LnCu
H
F
H
H
B
4
R
1
BzO NR2
CuLn
R
CuLn
3
R
Si
H
C
H
H
E
R
H
H
CuLn
Si
H
Si
H
H
R
6
2
R
Si
H
H
H
7
R
D
Si
H
5
a) Reactivity of model substrate 1m
b) Deuterium-labeling experiments
Bn
Bn
Bn
Bn
N
Cu(OAc)2/TMS-dppbz
tBu
Bn
Ph
+
+
H
SiPh2H
BzO
N
N
LiOtBu
DCE, 40 ˚C, 18 h
tBu
Ph
SiPh2H
CuCl/TMS-dppbz
Ph
+
+
D
SiPh2D
BzO
3a
N
4mab 69% (1H NMR)
2a
3b
1m
Ph
SiPh2D
LiOtBu
DCE, 40 ˚C, 18 h
3
3
D
Bn
D
(>99% D)
[D2]2a
1a
b) Reactivity of vinylsilane 5ma
(>99% D)
Bn
Bn
Bn
N
[D3]4aaa 63%
Cu(OAc)2/TMS-dppbz
+
+
H
SiPh2H
BzO
N
Ph
SiPh2H
LiOtBu
DCE, 40 ˚C, 18 h
Ph
SiPh2H
Bn
tBu
Bn
4mab 73% (1H NMR)
2a
3b
5ma
N
D
tBu
(72% D)
D
CuCl/TMS-dppbz
Ph
+
+
H
SiPh2H
BzO
3a
N
Ph
SiPh2H
c) Reactivity of enamine 8mb
LiOtBu
DCE, 40 ˚C, 18 h
3
3
Bn
2a
[D]1a
[D]4aaa 63%
Bn
Cu(OAc)2/TMS-dppbz
+
H
SiPh2H
no reaction
Ph
N
LiOtBu
DCE, 40 ˚C, 18 h
Bn
2a
8mb
Scheme
6.
a)
Plausible
mechanism
for
Cu-catalyzed
hydrosilylation/hydroamination sequence of terminal alkynes
1
with
d) Availability of gem-disilane 9aa under conditions without the hydroxylamine
hydrosilanes 2 and hydroxylamines 3; b) deuterium-labeling experiments. L =
TMS-dppbz or (R,R)-Ph-BPE.
SiPh2H
CuCl/TMS-dppbz
+
Ph
+
H
SiPh2H
Ph
SiPh2H
Ph
Ph
SiPh2H
7aa 49%
3
3
3
LiOtBu
DCE, 40 ˚C, 18 h
3
1a
2a
6a 18%
9aa not detected
In conclusion, we have developed
reductive gem-difunctionalization of terminal alkynes with
a copper-catalyzed
Scheme 5. Evaluation of potential intermediates.
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10.1002/chem.202001799
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COMMUNICATION
Hirano, M. Miura, Chem. Eur. J. 2018, 24, 10975; f) T. Takata, K.
Hirano, M. Miura, Org. Lett. 2019, 21, 4284.
hydrosilanes and hydroxylamines. The reaction proceeds via
hydrosilylation/hydroamination sequence, and the corresponding
a-aminosilanes are obtained in a single operation. Additionally,
the asymmetric synthesis is also possible to deliver the
enantioenriched a-aminosilanes of interest in medicinal
chemistry.[22] Improvement of the reaction efficiency as well as
enantioselectivity and expansion of this reaction concept to other
type alkyne difunctionalizations are currently underway.
[12] For contributions from Buchwald group, see: a) S. Zhu, N. Niljianskul, S.
L. Buchwald, J. Am. Chem. Soc. 2013, 135, 15746; b) S. Zhu, S. L.
Buchwald, J. Am. Chem. Soc. 2014, 136, 15913; c) N. Niljianskul, S.
Zhu, S. L. Buchwald, Angew. Chem. Int. Ed. 2015, 54, 1638; Angew.
Chem. 2015, 127, 1658; d) S.-L. Shi, S. L. Buchwald, Nat. Chem. 2015,
7, 38; e) Y. Yang, S.-L. Shi, D. Niu, P. Liu, S. L. Buchwald, Science
2015, 349, 62; f) D. Niu, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137,
9716; g) H. Wang, J. C. Yang, S. L. Buchwald, J. Am. Chem. Soc. 2017,
139, 8428; h) Y. Zhou, O. D. Engl, J. S. Bandar, E. D. Chant, S. L.
Buchwald, Angew. Chem. Int. Ed. 2018, 57, 6672; Angew. Chem. 2018,
130, 6782; i) S. Guo, J. C. Yang, S. L. Buchwald, J. Am. Chem. Soc.
2018, 140, 15976.
Acknowledgements ((optional))
This work was supported by JSPS KAKENHI Grant Nos. JP
18K19078 (Grant-in-Aid for Challenging Research (Exploratory))
to K.H. and JP 17H06092 (Grant-in-Aid for Specially Promoted
Research) to M.M.
[13] For related seminal work and reviews of electrophilic amination with
hydroxylamines, see: a) H. Tsutsui, Y. Hayashi, K. Narasaka, Chem.
Lett. 1997, 26, 317; b) A. M. Berman, J. S. Johnson, J. Am. Chem. Soc.
2004, 126, 5680; c) S. Liu, L. S. Liebeskind, J. Am. Chem. Soc. 2008,
130, 6918; d) E. Erdik, M. Ay, Chem. Rev. 1989, 89, 1947; e) K.
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Conflict of Interest
The authors declare no conflict of interest.
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff)
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Keywords: a-aminosilanes · asymmetric catalysis · copper ·
hydroamination · hydrosilylation
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10.1002/chem.202001799
Chemistry - A European Journal
COMMUNICATION
[22] See the Supporting Information for product derivatizations.
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10.1002/chem.202001799
Chemistry - A European Journal
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Entry for the Table of Contents (Please choose one layout)
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Page No. – Page No.
Title
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S. Nishino, K. Hirano,* M. Miura*
asymmetric catalysis
with (R,R)-Ph-BPE
NR3
2
cat. CuCl/TMS-dppbz
H
NR3
2
SiR2
R
+
+
BzO
SiR2
3
tBu
Bn
Page No. – Page No.
R
LiOtBu, DCE
3
N
up to 94%
✓ one shot manner
✓ regioselective
Cu-Catalyzed Reductive gem-
Difunctionalization of Terminal
Alkynes via
SiPh2H
*
✓ introduction of N and Si in gem-relationship
85%, 95:5 e.r.
Hydrosilylation/Hydroamination
Cascade: Concise Synthesis of
Aminosilanes
Si(lent)
N(ight)
in
Alkyne:
A
Cu/TMS-dppbz-catalyzed
a
-
hydrosilylation/hydroamination cascade of simple terminal alkynes with hydrosilanes
and hydroxylamines proceeds chemoselectively to deliver the reductive gem-
difunctionalization products, a-aminosilanes, in a single operation. Additionally, the
chiral (R,R)-Ph-BPE ligand makes the reaction asymmetric to directly form the
corresponding optically active a-aminosilanes, which are Si mimics of
enantioenriched a-amino acids and of interest in medicinal chemistry.
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