Asymmetric hydrogenation of 1-silyl-1-substituted alkenes for preparation of optically active silanes

Article abstract of DOI:10.1016/j.tetlet.2016.11.017

Asymmetric hydrogenation of 1-silyl-1-substituted alkenes has been explored, producing eight optically active silanes with good to excellent enantioselectivity (66–99% ee) and yield (74–99%). The reaction was efficiently catalyzed by the cationic N,P-Ir c

Full text of DOI:10.1016/j.tetlet.2016.11.017

Accepted Manuscript
Asymmetric Hydrogenation of 1-Silyl-1-substituted Alkenes for Preparation of
Optically Active Silanes
Dan-Dan Ma, Peiming Gu, Rui Li
PII:
S0040-4039(16)31473-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.017
TETL 48303
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
24 August 2016
23 October 2016
4 November 2016
Please cite this article as: Ma, D-D., Gu, P., Li, R., Asymmetric Hydrogenation of 1-Silyl-1-substituted Alkenes for
Preparation of Optically Active Silanes, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.
2
016.11.017
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Asymmetric Hydrogenation of 1-Silyl-1-substituted Alkenes for
Preparation of Optically Active Silanes
Dan-Dan Ma, Peiming Gu, Rui Li*
School of Chemistry & Chemical Engineering, Ningxia Engineering and Research Center for
Natural Medicines, Ningxia University, Yinchuan 750021, China
Phone: +86(951)206-2274
Fax: +86(951)206-2323
E-mail: ruili@nxu.edu.cn
Abstract: Asymmetric hydrogenation of 1-silyl-1-substituted alkenes has been explored,
producing eight optically active silanes with good to excellent enantioselectivity (66-99% ee) and
yield (74-99%). The reaction was efficiently catalyzed by the cationic N,P-Ir complexes, and the
polar solvents were found to be essential for the stereocontrol of the conversion.
Key words: Asymmetric hydrogenation, silyl alkenes, Ir catalyst.
Main Text:
The silicon-containing compounds are very important organic reagents and intermediates in
1
synthetic chemistry . Generally, the optically active silane can be produced by hydrosilylation of
2
3
an olefin , Si-H insertion of a metal carbenoid , and desymmetrization of a prochiral silane via
4
miscellaneous conversions . Asymmetric hydrogenation of the silyl alkenes should be a sensitive
approach toward the enantio enriched silanes, as the hydrogenation reaction has been
5
demonstrated to be a very reliable method for preparation of chiral materials . But the real
situation is that asymmetric hydrogenation of silyl alkenes has been significantly less explored,
6
and the conversion was only reported by Andersson’s group . In this paper, we would like to
report the asymmetric hydrogenation of the 1-silyl-1-substituted ethylenes, producing chiral
silanes with good to excellent enantioselectivity and yield.
Although the silyl group is considered as a functional group in synthetic chemistry, the
silicon will exhibit the similar chemical and physical properties to that of carbon, as they are the
same group elements. Asymmetric hydrogenation of unfunctionalized alkenes represents a very
challenging conversion as no additional chelating groups can be used during the coordination of
7
alkenes with chiral metal-complexes , therefore the analogue transformation of silyl alkenes
would also be very difficult. The most successful catalysts for the asymmetric hydrogenation of
unfunctionalized alkenes was based on the modification of Crabtree’s catalyst with N,O-ligands,
8
and the pioneering work was addressed by Pfaltz and co-workers . The chiral iridium complexes
were found to be efficient for many kinds of alkenes, but it was highly substrate-dependent. The
slight difference between the substrates could result in a large gap in enantioselectivity with some
7
a,7b
cases , and the similar phenomenon of substrate-dependent was also observed with the silyl
6
alkenes . Six silyl alkenes had been hydrogenated, and five of them had been reported with only
poor to moderate enantioselectivity. Asymmetric hydrogenation of the 1-TMS-1-phenyl ethylene

1a to silane 2a in DCM with only moderate enantioselectivity (58% ee) was unsurprising since the
asymmetric hydrogenation of the 1,1-disubstituted alkene was more striking than that of
7
a
trisubstituted alkene (Scheme 1). Thus it convinced us to extensively investigate the asymmetric
hydrogenation of 1-silyl-1-substituted ethylenes.
Andersson's work:
PPh2
[
Ir(L*)(cod)]BArF
N
S
TMS
TMS
3
0 bar H , DCM
2
Ph
1
a
(S)-2a
8% ee
L*
5
This work:
Bn Bn Me
[
Ir(L'*)(cod)]BArF
O

O
R
Si
30 bar H , MeOH
R
Si
PCy N
2
2
Ph
L'*
R = Ar, Si = TMS, 97-99% ee
Scheme 1. Previous asymmetric hydrogenation of 1-silyl-1-substituted alkene
9
Following our research on the asymmetric reduction of azido alkenes , we started the project
on the asymmetric hydrogenation of silyl alkenes. The commercially available ligands 3a-3g for
rhodium complexes and two representative iridium complexes from ligands 3h and 3i were
employed for the initial hydrogenation of 1-TMS-1-phenyl ethylene 1a (Figure 1).
Et
Et
Ph
Ph
PR'2
Bn Bn Me
R P
P
P
P
P
2
Me
Fe
MeO
MeO
PAr2
PAr2
Et
Et
Ph
Ph
O
PR2
H
O
Ph
N
L-3e: R = R' = Cy
t
L-3f: R = Ph, R' = Bu
L-3a: R = Ph
L-3b: R = 4-OMe-3,5- Bu-Ph
L-3g: R = 4-OMe-3,5-Me-Ph, L-3h: R = Ph
L-3c
L-3d
t
L-3i: R = Cy
R' = Cy
Figure 1. Ligands for asymmetric hydrogenation of 1a.
As expected, hydrogenation of silyl alkene 1a with chiral Rh catalysts could proceed with
complete conversion (>99%), but the enantioselectivity for silane 2a was unacceptable (Table 1,
entries 1-8). It was unsurprising to observe the poor control of enantioselectivity (< 23% ee) with
rhodium catalysts-catalyzed reaction, for the rhodium catalysts were generally efficient for the
functionalized alkenes, while the silyl alkene 1a is lack of a chelating group. Then the iridium
complexes were charged with the important mission for the hydrogenation of silyl alkenes. In
general, the optimal solvent for hydrogenation of alkenes with iridium complexes is
dichloromethane (DCM), therefore investigation of the reaction of 1a with iridium complexes
from ligands 3h and 3i in DCM was performed. Unfortunately, both experiments failed to control
the enantioselectivity (Table 1, entries 9 and 10), and ligand 3i gave the just passable result (43%
ee). To our great surprise, when the DCM was replaced with more polar solvents, such as
methanol, ethanol, and tetrahydrofuran (THF), the silane 2a could be obtained with excellent
enantioselectivity (Table 1, entries 11-13). These results might indicate that the solvent
participates in coordination with the Ir complex, however the full mechanism can’t be proposed at
current stage. Further evaluation of the reaction conditions revealed that the hydrogen pressure
had little effect on the conversion. Asymmetric hydrogenation of 1a with 0.2 mol %
[
F
Ir(L-3i)(COD)]BAr was also examined, and the reaction could be completed in 24 h, producing

silane 2a with only 95% ee. The configuration of 2a was assigned as R by comparison of the
1
0
rotation data ([α]
D
+18.0) with that of the previous reports ([α]
D
-8.05 for the S-enantiomer) .
a
Table 1. Optimization of the asymmetric hydrogenation of the silyl alkene 1a.
Me

M/L*, H2
TMS
TMS
b
c
entry Complex
S/C P (bar) Sol
Time (h) Conv (%) Ee (%)
1
2
3
4
5
6
7
8
9
1
[Rh(L-3a)(NBD)]BF
[Rh(L-3b)(NBD)]BF
[Rh(L-3c)(COD)]BF
4
20
30
40
40
30
30
30
30
30
MeOH 21
MeOH 15
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
5
4
20
20
1
4
DCM
21
5
[Rh(L-3c)(COD)]OTf 20
[Rh(L-3d)(COD)]OTf 20
MeOH 12
MeOH 12
MeOH 12
MeOH 21
MeOH 12
23
5
[Rh(L-3e)(NBD)]BF
[Rh(L-3f)(NBD)]BF
[Rh(L-3g)(COD)]BF
[Ir(L-3h)(COD)]BAr
4
20
20
20
9
4
22
20
<3
43
97
97
97
95
98
95
4
F
200 30
200 30
200 40
200 40
200 40
200 10
200 30
500 30
DCM
DCM
MeOH
EtOH
THF
43
43
4
0
[Ir(L-3i)(COD)]BAr
[Ir(L-3i)(COD)]BAr
[Ir(L-3i)(COD)]BAr
[Ir(L-3i)(COD)]BAr
[Ir(L-3i)(COD)]BAr
F
11
F
1
1
1
1
1
2
3
4
5
6
F
F
F
15
15
2
MeOH
MeOH
[Ir(L-3i)(COD)]BAr
[Ir(L-3i)(COD)]BAr
F
2
F
MeOH 24
a
Asymmetric hydrogenation of silyl alkene 1a (44.0 mg, 0.25 mmol) at room temperature
b
1
c
under the conditions mentioned above. Determined by H NMR. Determined by chiral GC
o
d
(
Agilent CYCLOSIL-B capillary column, 100 C). Opposite enantioselectivity of the product was
observed.
With the optimal reaction conditions (in bold, Table 1), the scope of substrates was
investigated, and the results were summarized in Table 2. First, asymmetric hydrogenation of
-TMS-1-phenyl ethylene 1a was re-examined at 1.0 mmol scale, affording enantio-enriched
1
silane 2a with 99% ee in an isolated yield of 86%. The primary results revealed that the
enantioselectivity was nearly immune to the electron-donating substituents on the aromatic ring of
the substrates. Asymmetric hydrogenation of the silyl ortho-methyl-styrene had been examined
(
not shown in Table 2), and the conversion was very poor (<10%). The electron-withdrawing
groups had been envisioned to be attached to the aromatic ring, but the substrates were difficult to
prepare. The naphthalene analogue 2e was also obtained with 97% ee in 99% yield.
Hydrogenation of 1f and 1g indicated that the alkyl substituted substrates were not very perfect for
the conversion, and it required more time to complete the reaction. Among them, the TES
substrate 2g was hydrogenated with 5 mol % catalyst at even higher temperature, and it gave
lower enantioselectivity (66% ee). Finally, hydrogenation of the triethoxyl silyl alkene 1h in
methanol could be successful, but the trimethoxyl silane 2h with transalkoxylation was observed
with only 78% ee. Fleming-Tamao oxidation of the silane 2h under several different conditions

failed to give the corresponding 1-phenylethanol, which had been expected to check the absolute
configuration of the chiral silane. The silanes 2a-2h should be considered as the volatile materials,
and purification of them by flash chromatography was eluted with light petroleum ether (30-60
o
C).
a
Table 2. Scope of conversion .
[
Ir(L-3i)(cod)]BAr , H2
F
R
Si
R Si


TMS


TMS
TMS
2a (86%, 99% ee)
2b (97%, 99% ee)
2c (83%, 99% ee)
O

TMS

TMS

TMS
2d (88%, 98% ee)
2e (99%, 97% ee)
2f (94%, 83% ee)b

TES

Si(OMe)3
2
g (77%, 66% ee)c
2h (74%, 78% ee)d
a
Asymmetric hydrogenation of silyl alkene 1 (1.0 mmol) using 0.5 mol %
[
Ir(L-1i)(COD)]BAr
F
with H
2
(30 bar) in MeOH (4 mL) at room temperature for 2 h.
b
c
Hydrogenation for 20 h. Hydrogenation of silyl alkene 1g (24.4 mg, 0.10 mmol) using 5 mol %
o
d
catalyst with H
catalyst.
2
(45 bar) in MeOH (0.4 mL) at 50 C for 24 h. Hydrogenation with 1 mol %
The experimental results here indicated that asymmetric hydrogenation of silyl alkenes with
iridium complexes was also very sensitive the structure of substrates, which kept pace with the
iridium catalyzed asymmetric hydrogenation of normal alkenes. Therefore, there must leave much
to be desired for ligand development for iridium complexes and investigation of substrate scope
for this type hydrogenation reaction.
In conclusion, the asymmetric hydrogenation of 1-TMS-1-phenyl ethylene with the chiral
Ir-complex has been realized, producing several silanes with excellent enantioselectivity. The
reaction of 1-silyl-1-alkyl ethylene exhibited a dropped enantioselectivity, and the substrate with
methoxyl group attached at the silicon would also result in a negative effect. Further investigation
on the asymmetric hydrogenation of the silyl alkenes with more substituents is underway in our
laboratory.
Acknowledgment This work was supported by the Ningxia Natural Science Foundation
(
NZ15035).
Supporting Information Available Experimental procedures and spectroscopic data and copies

of NMR spectra and copies of chiral HPLC and GC spectra for all the products.
REFERENCES
(
1) a) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063–2192; b) Brook, M. A.
Silicon in Organic, Organometallic, and Polymer Chemistry; Wiley: New York, 2000.
2) For a recent review, see: Han, J. W.; Hayashi, T. Tetrahedron: Asymmetry 2014, 25,
79–484, and cited there in.
(
4
(
(
3) For a recent review, see: Zhu, S.-F.; Zhou, Q.-L. Acc. Chem. Res. 2012, 45, 1365–1377.
4) For reviews, see: a) Xu, L.-W. Angew. Chem. Int. Ed. 2012, 51, 12932–12934; b) Shintani,
R. Asian J. Org. Chem. 2015, 4, 510–514.
(
(
5) Noyori, R. Angew. Chem., Int. Ed. 2002, 41, 2008–2022.
6) Källström, K.; Munslow, I. J.; Hedberg, C.; Andersson, P. G. Adv. Synth. Catal. 2006, 348,
2575–2578.
(
7) a) Cui, X.; Burgess, K. Chem. Rev. 2005, 105, 3272–3296; b) Källström, K.; Munslow, I.;
Andersson, P. G. Chem. Eur. J. 2006, 12, 3194–3200; c) Roseblade, S. J.; Pfaltz, A. Acc. Chem.
Res. 2007, 40, 1402–1411.
(
(
(
8) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem., Int. Ed. 1998, 37, 2897–2899.
9) Ji, Y.; Xue, P.; Ma, D.-D.; Li, X.-Q.; Gu, P.; Li, R. Tetrahedron Lett. 2015, 56, 192–194.
10) Hayashi, T.; Tamao, K.; Katsuro, Y.; Nakae, I.; Kumada, M. Tetrahedron Lett. 1980, 21,
1
871–1874

TOC:

Highlights
1
2
3
4
. Asymmetric hydrogenation of 1-silyl-1-substituted alkenes is addressed.
. Chiral silanes are produced with good to excellent enantioselectivity.
. Cationic N,P-Ir complexes are employed.
. Polar solvent contributes to the excellent enantioselectivity.