Enantioselective hydrosilylation with chiral frustrated lewis pairs

Article abstract of DOI:10.1002/chem.201200244

Frustrated partners: Based on an initial mechanistic investigation, enantioselective hydrosilylation of various imines was accomplished for the first time by using a novel chiral frustrated Lewis pair (FLP) catalyst. High enantioselectivities of up to 87

Full text of DOI:10.1002/chem.201200244

DOI: 10.1002/chem.201200244
Enantioselective Hydrosilylation with Chiral Frustrated Lewis Pairs
Dianjun Chen,[a] Valeri Leich,[a] Fangfang Pan,[b] and Jꢀrgen Klankermayer*[a]
Dedicated to Dr. Christian Bruneau on the occasion of his 60th birthday
In recent years, the chemistry of frustrated Lewis pairs
(FLP) has been greatly developed, and the carefully chosen
combination of sterically hindered Lewis acids and bases
has shown unprecedented reactivity towards the activation
of small molecules.[1] This FLP approach rapidly found ap-
plication in catalysis and effective systems for catalytic hy-
drogenation without the use of transition metals were devel-
oped.[2] Subsequently, chiral borane-based, FLP-enabled,
enantioselective hydrogenation of prochiral imines in up to
84% enantiomeric excess (ee) was demonstrated.[3] Thus, hy-
drosilylation as a comparably attractive process based on
the use of cheap and stable hydridic silanes is gaining in-
creasing interest.[4] In most cases, and especially in asymmet-
Scheme 1. Proposed mechanisms of B
carbonyl compounds.
ACHTNUGTERN(NGNU C6F5)3-catalyzed hydrosilylation of
ric transformations, effective hydrosilylation processes are
mediated by transition-metal catalysts.[4–5] As early as 2000,
Piers and co-workers reported the highly effective BACHTUNRGTNEUNG(C6F5)3-
catalyzed hydrosilylation of imines, and spectral evidence
strongly supported Si H bond activation through a FLP
Lewis basic substrates (Scheme 1).[10] Recently, Oestreich
and Rendler reinvestigated the B(C6F5)3-catalyzed hydrosi-
lylation of acetophenone with an enantiomerically enriched
chiral silane, and in their study, a diastereomeric silicon
ether was preferentially produced.[11] After stereospecific
À
mechanism.[6] Recently, Alcarazo and co-workers extended
the FLP concept for silane activation, and in their study the
FLP, incorporating hexaphenylcarbodiphosphorane and B-
ACHTUNGTRENNUNG
[7]
À
N
À
Interestingly, FLPs could also catalyze the deoxygenative
hydrosilylation of CO2 to CH4 with triethylsilane as reducing
agent, indicating the scope of this metal-free transforma-
tion.[8] In our continued interest in the application of FLP
reactivity to catalysis, the enantioselective hydrosilylation by
using chiral FLPs as catalysts is reported herein.
cleavage of the Si O bond with retention of configuration
at the Si atom, the chiral silane was recovered with com-
plete inversion of configuration at the silicon center. The
observation of Walden inversion in this catalytic experiment
suggested an SN2-Si mechanism (Scheme 1). More interest-
ingly, the product 1-phenylethanol could be obtained with
a moderate, but promising enantioselectivity of already
38% ee.[11] However, the corresponding hydrosilylation of
imines with the chiral silane resulted in only racemic prod-
ucts.[12]
The frequently used Lewis acidic component in FLPs, B-
ACHTUNGTRENNUNG(C6F5)3, is a highly active catalyst for hydrosilylation of car-
bonyl compounds and imines under ambient conditions.[6,9]
Based on systematic mechanistic studies, Piers and co-work-
ers proposed a mechanism for this transformation that in-
volves the formation of a counterion pair through abstrac-
Rather than solely using BACHTUNRGTEN(UNG C6F5)3 as a catalyst for metal-
free hydrosilylation, we recently became interested in the
catalytic activity of frustrated Lewis pairs for this reaction.
Initially, mixtures of dimethylphenylsilane (PhMe2SiH) and
typical FLPs were studied by NMR spectroscopy in solution.
tion of hydride from silane by BACHTNUTRGNE(UNG C6F5)3 in the presence of
[a] Dr. D. Chen, V. Leich, Prof. Dr. J. Klankermayer
Institut fꢀr Technische und Makromolekulare Chemie
RWTH Aachen University
When the FLPs, including Mes3P/BACHTUNGTRNE(UNG C6F5)3 and PhMe2SiH,
were stoichiometrically dissolved in [D2]-dichloromethane,
the 31P, 19F, and 11B NMR experiments revealed no obvious
evidence of silane cleavage (Scheme 2). Carrying out the
same experiment with tBu3P, a new species formed immedi-
ately in dichloromethane solution. Multinuclear NMR spec-
troscopy corroborated the product as the ionic complex
Worringerweg 1, 52074 Aachen (Germany)
E-mail: jklankermayer@itmc.rwth-aachen.de
[b] F. Pan
Institut fꢀr Anorganische Chemie
RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
[tBu3PSi(Me)2Ph][HBACTHNUTRGNEUNG
(C6F5)3] (1; Scheme 2). The 31P NMR
spectrum of the cation exhibits a resonance at d=34.2 ppm,
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200244.
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Chem. Eur. J. 2012, 18, 5184 – 5187

COMMUNICATION
loading of 4 mol%. In addition, an NMR investigation
showed that the [HBACTHNUTRGNEUNG
(C6F5)3]À anion was the only boron spe-
cies detectable in the solution. The observed significant re-
action-rate difference and exclusive formation of hydridobo-
rate in the reaction solution corroborated the assumption
that the hydrosilylation reaction rate strongly depends on
À
the activation of the Si H bond. In the absence of the Lewis
Scheme 2. Reaction of FLPs with dimethylphenylsilane in dichlorome-
thane solution.
À
acid B
U
sequently no hydrosilylation of imines takes place. Addition
of BACHTNURGTNE(UGN C6F5)3 to the silane solution results in the formation of
À
À
which is significantly high-field shifted in comparison to the
cation [tBu3PH]+ (d=56.6 ppm),[13] whereas the 19F NMR
(d=À133.6 (o), À164.5 (p), À167.3 ppm (m-C6F5)), and
11B NMR (d=À25.4 ppm) signals confirmed the [HB-
a B H dative bond and weakening of the Si H bond. This
activation is sufficient to render the addition of silane to the
imine in a fast and concerted pathway. However, heterolytic
À
cleavage of the Si H bond in the presence of the FLP
(tBu3P/B(C6F5)3), results in the rapid formation of the silyli-
um and [HB
(C6F5)3]À ions, and the hydride transfer to the
(C6F5)3]À structure of the anion.[13]
ACHTUNGTRENNUNG
Single crystals could be obtained from pentane–dichloro-
ACHTUNGTRENNUNG
methane solutions at À308C, and X-ay diffraction analysis
unambiguously confirmed the formation of 1 (Figure 1 and
the Supporting Information).
imine becomes rate determining, resulting in a slow hydrosi-
lylation reaction. Therefore, the catalytic reactions with only
the Lewis acid BACTHUNRTGNNEGU(C6F5)3 and with the FLP (tBu3P/BACHTUNGTRENNUNG(C6F5)3)
represents the two activity boundaries of the hydrosilylation
reaction pathways. Consequently, the influence of weaker
Lewis bases for this transformation should be investigated,
and indeed the FLP with the weaker Lewis base component
Mes3P provided 65% conversion after 8 min. Consequently,
by careful tuning of the Lewis acidity or basicity of FLP
partners, these experimental findings could help to optimize
the catalytic system with a focus on enantioselectivity. Based
on these findings and the successful synthesis of chiral FLPs
in a previous study,[3b] the extension of the chiral FLP con-
cept to enantioselective catalytic hydrosilylation was at-
tempted. For this purpose, a new stable chiral borane 4
(Figure 2) could be synthesized by reaction of the Piersꢂ
Figure 1. Crystal structure of 1. Hydrogen atoms are omitted for clarity,
except for the hydrogen atoms bonded to boron. Thermal ellipsoids are
set at 50% probability.
À
The interesting observation of Si H bond splitting by
FLP straightforwardly directed the investigation towards
catalytic hydrosilylation reactions. For the initial catalytic
experiments, N-(1-phenyl-ethylidene)aniline (2a) was
chosen as model substrate (Scheme 3).
Figure 2. Chiral borane 4 and phosphonium hydridoborates 5 and 6.
borane[14] with chiral alkene (1R,4R)-1,7,7-trimethyl-2-(2-
naphthyl)-bicycloACTHNUTRGNE[NUG 2.2.1]hept-2-ene. The resulting diastereo-
merically pure borane 4 was simply isolated quantitatively
after removing the solvent in vacuo. Compound 4 featured
a set of 19F NMR signals at d=À130.7 (o), À150.0 (p), and
À161.1 ppm (m-C6F5), and a broad 11B NMR signal at d=
75.2 ppm, indicating a neutral boron center. The absolute
configuration of 4 was determined as bis(perfluorophe-
nyl)[(1R,2R,3R,4S)-4,7,7-trimethyl-3-phenylbi-cyclo-
Scheme 3. Catalyzed hydrosilylation of imine by BACHTUNRGTNEUNG(C6F5)3 and FLP.
As was already illustrated by Piers, B
be a very active catalyst for the hydrosilylation of various
imines.[6] In the presence of 0.35 mol% of B
(C6F5)3, imine
ACHTNUGTNER(NGNU C6F5)3 was found to
G
ACHTUNGERTN[NUNG 2.2.1]heptan-2-yl]borane by X-ray diffraction analysis of its
2a was converted to the corresponding secondary amine 3
(after hydrolysis) in only 4 min. However, reactions with the
dihydrogen activation product 5 (see the Supporting Infor-
mation).
FLP incorporating tBu3P and B
conversion after four days of reaction time with a catalyst
(C6F5)3 only resulted in 25%
With only the enantiopure chiral borane 4, the hydrosily-
lation of imine 2a with dimethylphenylsilane in toluene at
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5185

J. Klankermayer et al.
Table 1. Hydrosilylation of imine 2a with chiral borane or FLP catalysts.
Table 2. Hydrosilylation of imine 2 by using chiral catalyst 5 or 6.
Entry[a]
Catalyst
t
Yield [%][b]
ee [%][c]
Entry[a]
Substrate
Catalyst
Yield [%][b]
ee [%][c]
1
2
3
4
4
2h
4d
4d
4d
>99
67
55
<2
63
79
83
4/Mes3P 1:1
4/tBu3P 1:1
5
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2 f
2g
2a
2e
2g
6
6
6
6
6
6
6
5
5
5
50
<5
33
38
55
74
61
61
90
82
83 (R)
–
50
84 (À)
81 (À)
81 (À)
85 (R)
87 (+)
84 (R)
84 (R)
85 (+)
[a] Reaction conditions: catalyst (0.02 mmol), imine (0.5 mmol),
PhMe2SiH (0.55 mmol), RT. [b] Determined by NMR spectroscopy.
[c] Determined by GC method by using a chiral column.
room temperature gave amine 3a in racemic form (Table 1,
entry 1). Considering the results from Oestreich with B-
ACHTUNGTRENNUNG(C6F5)3-catalyzed hydrosilylation of imines in the presence
10
[a] Reaction conditions: catalyst (0.02 mmol), imine (0.5 mmol),
PhMe2SiH (0.55 mmol), RT. [b] Determined by NMR spectroscopy.
[c] Determined by GC and HPLC methods by using a chiral column.
of a chiral silane showing only racemic product, it prompted
them to suggest a different mechanism for the imines in
comparison to the ketone substrates (Scheme 1).[12] More-
over, as the involved chiral hydridoborate intermediate has
previously shown excellent discrimination of the diastereo-
topic faces of prochiral imines in catalytic hydrogenation,
a novel design of the catalytic system based on an altered
mechanism has to be applied. The possibility of retro hydro-
boration of the chiral borane to give the achiral Piersꢂ
borane as the active catalyst could be excluded by NMR in-
vestigations (see the Supporting Information).
By using the developed modulating effect of the Lewis
base in the hydrosilylation experiment, the chiral borane 4
in combination with Lewis basic phosphines as the catalyst
slowed down the reaction dramatically, but resulted in sur-
prisingly high enantioselectivity (Table 1, entry 2 and 3). Hy-
drosilylation with the FLP Mes3P/BACTHUNTGRNEUGN(C6F5)3 showed 67%
conversion and 63% enantioselectivity (Table 1, entry 2).
Using the more basic phosphine tBu3P as the Lewis base in
combination with BACHTUNGTRENNUNG(C6F5)3 resulted in an even slower reac-
tion, albeit with clearly higher enantioselectivity (Table 1,
entry 3; 55% conversion and 79% ee). NMR experiments
did not show Si H cleavage in any of these reactions with
high enantioselectivities were obtained for most of the
imines, whereas the reactivity highly depended on the sub-
stitution pattern of the substrate. Hydrosilylation of sterical-
ly hindered imine 2-methyl-N-(1-phenylethylidene)aniline
(2b) afforded only negligible conversion (Table 2, entry 2)
and the introduction of an electron-withdrawing group to
the acetophenone moiety led to relatively low conversion
with enantioselectivities of 84 and 81% (Table 2, entry 3
and 4). However, the presence of a methoxy donor group in
N-(1-(4-methoxyphenyl) ethylidene)aniline (2e) or 4-me-
thoxy-N-(1-phenylethylidene)aniline (2 f) enhanced hydrosi-
lylation conversion strongly, and high enantioselectivities of
81 and 85% ee could be achieved (Table 2, entry 5 and 6).
The highest enantioselectivity of 87% ee (55% yield) was
obtained with the imine derivative 4-methoxy-N-(1-(naph-
thalen-2-yl)ethylidene)aniline (2g), demonstrating the effec-
tiveness of the catalytic system with the chiral FLP (Table 2,
entry 7,). A further improvement was based on the applica-
tion of the more active chiral catalyst 5 with the substrates
2a, 2e, and 2g. In these hydrosilylation experiments, around
84% enantioselectivity was achieved at nearly full conver-
sion (Table 2, entries 8–10).
Further experiments should corroborate the applicability
of the catalytic system with ketones as substrates. However,
application of the chiral borane 4 in the catalytic hydrosily-
lation of acetophenone gave only racemic product, which is
in agreement with similar results recently reported by the
group of Oestreich when using an axially chiral borane as
catalyst for this reaction.[15] However, the application of the
phosphonium hydridoborate catalysts 5 or 6 resulted in full
conversions after three days, and interestingly, (R)-config-
ured 1-phenylethanol was produced with moderate enantio-
selectivities (5, 37% ee; 6, 24% ee) demonstrating the
future possibilities of this approach.
À
the combination of chiral borane 4 and the selected phos-
phines, corroborating the close correlation between activity
and selectivity based on the selected FLP partners.
Considering that the stoichiometric mixture of borane 4
and tBu3P could be generated in situ from its dihydrogen ac-
tivation product 5 after transferring the proton and hydride
to the imine substrate, the easier-handling crystalline com-
pound 5 was used for subsequent hydrosilylation reactions.
As expected, similar activity and selectivity could be ach-
ieved by using 5 as the catalyst (Table 1, entry 4). In addi-
tion, at higher reaction temperature the reaction rate did
not increase, but enantioselectivity decreased dramatically.
Encouraged by the results achieved in the asymmetric hy-
drosilylation of 2a with chiral FLPs, various other acyclic N-
aryl imines were applied with chiral catalysts 5 or 6. All re-
actions were performed in toluene at room temperature
with a catalyst loading of 4 mol%. As shown in Table 2,
In summary, based on initial mechanistic investigation,
enantioselective hydrosilylation of various imines was ac-
complished by using a novel chiral FLP catalyst. High enan-
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Chem. Eur. J. 2012, 18, 5184 – 5187

Enantioselective Hydrosilylation
COMMUNICATION
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Experimental Section
In a glove box, a reaction vial with stirring bar was loaded with imine or
acetophenone (0.5 mmol, 1.0 equiv), catalyst (0.02 mmol), and dry tolu-
ene (1 mL). Dimethylphenylsilane (0.55 mmol, 1.1 equiv) was added to
the solution, and the reaction mixture was stirred for the indicated
period of time in the glove box at RT. The conversion of the substrate
was determined by 1H NMR spectroscopy of the crude reaction mixture.
The products were purified by flash chromatography on silica gel by
using n-pentane/ethyl acetate (10:1) as the eluent. In the case of aceto-
phenone, the product was hydrolyzed with tetrabutylammonium fluoride
at RT for 1 h before purification. The ee was determined either by HPLC
by using a chiral stationary phase column (Chiralcel OD-H) or by GC
(Chirasil-Dex CB).
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Acknowledgements
This work was performed as part of the Cluster of Excellence “Tailor-
Made Fuels from Biomass”, which is funded by the Excellence Initiative
of the German Federal and State Governments to promote science and
research at German Universities.
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Keywords: asymmetric catalysis · frustrated Lewis pairs ·
homogeneous catalysis · hydrosilylation
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Received: January 23, 2012
Published online: March 16, 2012
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www.chemeurj.org
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