Asymmetric palladium-catalyzed hydrosilylation of styrenes using efficient chiral spiro phosphoramidite ligands

Article abstract of DOI:10.1016/j.tetasy.2004.05.038

Asymmetric hydrosilylation of styrene derivatives with trichlorosilane in the presence of palladium complexes of chiral spiro phosphoramidites provided 1-aryl-1-silylalkanes as single regioisomers in high yields, which have been oxidized with hydrogen peroxide to give the corresponding chiral alcohols in up to 99.1% ee.

Full text of DOI:10.1016/j.tetasy.2004.05.038

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2231–2234
Asymmetric palladium-catalyzed hydrosilylation of styrenes
using efficient chiral spiro phosphoramidite ligands
Xun-Xiang Guo, Jian-Hua Xie, Guo-Hua Hou, Wen-Jian Shi, Li-Xin Wang
and Qi-Lin Zhou*
Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, China
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China
Received 16 March 2004;accepted 21 May 2004
Abstract—Asymmetric hydrosilylation of styrene derivatives with trichlorosilane in the presence of palladium complexes of chiral
spiro phosphoramidites provided 1-aryl-1-silylalkanes as single regioisomers in high yields, which have been oxidized with hydrogen
peroxide to give the corresponding chiral alcohols in up to 99.1% ee.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Ph
O
O
CF3
P
N
Catalytic asymmetric functionalization of alkenes has
been recognized as one of the most useful methods for
the preparation of optically active alcohols.1 In partic-
ular, the asymmetric palladium-catalyzed hydrosilyl-
ation of olefins with trichlorosilane is a highly potent
example of hydrometallation reactions that display
excellent regioselectivities and enantioselectivities for
alkyl-substituted terminal alkenes, styrene derivatives
and the other alkenes.2 In this hydrosilylation reaction,
palladium can provide only one coordination site to the
ligand, so monophosphorus ligands are essential for
achieving high reactivities and enantioselectivities. Many
well-known chelating diphosphine ligands, such as BI-
NAP and CHIRAPHOS, cannot be used in this reac-
tion.1;2a Despite the palladium-catalyzed hydrosilylation
of alkenes being a facile method for the synthesis of
chiral alcohols, only a few monophosphorus ligands
have been applied in this reaction. Efficient ligands in-
clude Hayashi’s MOP ligands2 and Feringa’s MONO-
PHOS ligands3 based on axially chiral biaryl backbones
and MOPF ligands4 based on planar chiral ferrocene
backbones. The most enantioselective ligands so far re-
ported for the palladium-catalyzed hydrosilylation of
alkenes are ligands 12 and 2,3 which afforded the alcohols
upon oxidation in up to 98% ee and 99% ee, respectively.
P
Ph
2
CF3
(R)-1
(S,R,R)-2
Recently, we designed a novel class of chiral mono-
phosphoramidite ligands (SIPHOS) 3 and 45 containing
a 1,10-spirobiindane scaffold and demonstrated that
these ligands were highly efficient for the Rh-catalyzed
asymmetric hydrogenation of functionalized olefins5a;b
and the Cu-catalyzed conjugate addition of Et2Zn to
a,b-unsaturated ketones.5c These results stimulated us to
further extend the application of these spiro mono-
phosphorus ligands in transition metal-catalyzed reac-
tions. Herein, we report the asymmetric palladium-
catalyzed hydrosilylation of styrene derivatives using
phosphoramidite ligands 3 and 4, providing 1-aryl-1-
silyalkanes and the corresponding alcohols in high yields
with excellent enantioselectivities (up to 99.1% ee).
2. Results and discussion
Asymmetric hydrosilylation of styrene 5a with trichlo-
rosilane was carried out without solvent at room tem-
perature in the presence of 0.25 mol % of catalyst
generated in situ by mixing [PdCl(g3-C3H5)]2 and chiral
* Corresponding author. Tel.: +86-22-23500011;fax: +86-22-235061-
77;e-mail: qlzhou@nankai.edu.cn
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.05.038

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X.-X. Guo et al. / Tetrahedron: Asymmetry 15 (2004) 2231–2234
Table 1. Palladium-catalyzed hydrosilylation of styrene 5a using chiral spiro monodentate phosphoramidite ligands 3 and 4a
Entry
Ligand
Sub./HSiCl3
Time (h)
Yield (%)b
Ee (%)c
1
(R)-3a
(R)-3b
(R)-3c
1:2
1:2
1:2
1:2
1:2
1:1.2
1:4
1:2
1:2
20
45
30
2
91
61
42
99
99
97
99
97
64
62 (R)
46 (R)
51 (S)
97 (R)
55 (S)
96 (R)
96 (R)
97 (R)
90 (R)
2
3
4
(R,R,R)-4
(S,R,R)-4
(R,R,R)-4
(R,R,R)-4
(R,R,R)-4
(R,R,R)-4
5
2
6
2
7
2
8d
9e
2
72
a All reactions were conducted without solvent with 5a/HSiCl3/[Pd(g3-C3H5)Cl]2/ligand, 1/2/0.00125/0.005 at room temperature (15–20 ꢁC), unless
otherwise stated.
b Isolated yield of silane by distillation.
c Ee of alcohol determined by chiral GC on a Suplco b-DEXTM 120 column. Absolute configurations were determined by comparison of specific
rotations with literature data.
d 0.1 mol % Pd was used.
e 0.025 mol % Pd was used.
spiro phosphoramidite ligands 3 or 4 (Pd/L ¼ 1:2). The
results are summarized in Table 1. It was found that the
reactivities and enantioselectivities of hydrosilylation
were strongly dependent on the alkyl groups on the
nitrogen atom of the ligand. Ligand (R)-3a, which had a
dimethylamino group, provided 91% of silane product
6a in 20 h. The oxidation of silane 6a under Tamao
conditions6 produced alcohol 7a in 62% ee with an (R)-
configuration (entry 1). Ligands (R)-3b and (R)-3c,
having pyrrolinyl and diisopropylamino groups, gave
sluggish hydrosilylation reactions, with low yields and
enantioselectivities (entries 2 and 3). It is interesting to
note that the alcohol obtained with ligand (R)-3c had an
(S)-configuration, which is opposite to those obtained
with ligands (R)-3a and (R)-3b. Ligand (R,R,R)-4, de-
rived from (R)-1,10-spirobiindane-7,70-diol and bis[(R)-
1-phenylethyl]amine, was found to be the ligand of
choice, which afforded hydrosilylation products (R)-6a
in 99% yield with 97% ee (entry 4). The reactivity of
(R,R,R)-4-Pd catalyst is noteworthy as the reaction
was complete within 2 h.7 However, the diastereomeric
ligand (S,R,R)-4 had a much lower enantioselectivity
(55% ee) (entry 5). These results clearly indicate that
ligand (R,R,R)-4 has matched configurations. The con-
figurations of the products were determined by the
configuration of 1,10-spirobiindane scaffold. The amount
of HSiCl3 used in the hydrosilylation was found to have
no obvious effect on the rate and enantioselectivity of
reaction (entries 6 and 7 vs 4). When the catalyst loading
was lowered to 0.1 mol %, the reaction still gave satis-
fying result. Reducing the catalyst loading further to
0.025 mol % led to a very slow reaction with a dramatic
decrease in the enantioselectivity (entry 9).
A variety of styrene derivatives can be efficiently hy-
drosilylated with a Pd complex of (R,R,R)-4. As shown
in Table 2, most of the substituted styrenes can react
completely with HSiCl3 within 10 h at room tempera-
ture, affording the corresponding hydrosilylation prod-
ucts in high yields and excellent enantioselectivities. The
highest enantioselectivity (99.1% ee) was achieved in the
hydrosilylation of 2-chlorostyrene (entry 4). The hy-
drosilylations of 4-methoxylstyrene 5g and 3-bromo-
styrene 5i are two exceptions;the former gave the lowest
enantioselectivity while the latter had a slow reaction
Table 2. Asymmetric hydrosilylation of styrene derivatives catalyzed
by Pd complex of (R,R,R)-4a
Entry
Substrate
Time (h)
Yield (%)b
Ee (%)c
1
5a
5b
5c
5d
5e
5f
2
3
99
90
91
88
86
90
84
94
75
93
86
97 (R)
97 (R)
98 (R)
99.1 (R)
95 (R)
96 (R)
82 (R)
96 (R)
97 (R)
95 (R)
95 (R)
Ph
2
R
3
4
N
N
R
P
O
P
O
4
7
O
O
Ph
5
9
3a: R = Me
6
7d
3
3b: R = -(CH2)4-
5g
5h
5i
3
i
3c: R = Pr
8
4
(R)-3
(R,R,R)-4
9
45
7
10
11
5j
5k
SiCl3
OH
0.25 mol% Pd-L*
36
H2O2
KF / KHCO3
R
R
R
Ar
Ar
a All reactions were conducted without solvent with 5/HSiCl3/[Pd(g3-
C3H5)Cl]2/(R,R,R)-4, 1/2/0.00125/0.005 at room temperature (15–
20 ꢁC), unless otherwise stated.
Ar
*
HSiCl3
*
7a-k
5a-k
6a-k
a: Ar = C6H5, R = H
g: Ar = 4-CH3O-C6H4, R = H
h: Ar = 4-CF3-C6H4, R = H
i: Ar = 3-Br-C6H4, R = H
j: Ar = 4-Br-C6H4, R = H
k: Ar = C6H5, R = CH3
b Isolated yields of silane by distillation.
b: Ar = 3-CH3-C6H4, R = H
c: Ar = 4-CH3-C6H4, R = H
d: Ar = 2-Cl-C6H4, R = H
e: Ar = 3-Cl-C6H4, R = H
f: Ar = 4-Cl-C6H4, R = H
c Ee of alcohol determined by chiral GC on a Suplco b-DEXTM 120
column. Absolute configurations were determined by comparison of
specific rotations with literature data.
d Reaction performed at 0 ꢁC.

X.-X. Guo et al. / Tetrahedron: Asymmetry 15 (2004) 2231–2234
2233
rate (entries 7 and 9). The low enantioselectivity (82%
ee) obtained in the hydrosilylation of 5g showed that the
strong electron-donating group on the phenyl ring of the
substrate was unfavourable for achieving high enantio-
selectivity. However, the reason for the slow reaction
rate observed in the hydrosilylation of 5i remains
unknown. b-Methylstyrene 5k can also be hydrosilyl-
ated in high yield and high enantioselectivity (95% ee),
albeit slowly (entry 11).
fused silica capillary column) and chiral HPLC per-
formed on a Hewlett Packard 1100 with Chiralcel OB
column (25 cm · 0.46 cm i.d.). All spectral data of
products were in accordance with those reported in the
literature.9
4.2. General procedure for asymmetric hydrosilylation
A dried Schlenk tube containing a stirbar was charged
with
To extend the range of substrates in the hydrosilylation
catalyzed by Pd complex of (R,R,R)-4, we next investi-
gated the hydrosilylation of cyclic substrate 1,2-dihy-
dronaphthalene 8. The hydrosilylation of 8, proceeded
at room temperature in the presence of 1 mol % of cat-
alyst for 5 days and provided alcohol 9 upon oxidation
in 61% yield with 85% ee (R). Increasing the catalyst
loading to 5 mol % improved the yield (80%) as well as
the enantiomeric excess (88% ee) of alcohol 9. The cat-
alytic asymmetric hydrosilylation of simple 1-alkenes
was much more difficult with only the Hayashi’s MOP
ligand giving satisfactory results.2a;8 We performed the
hydrosilylation of 1-hexene 10 in benzene in the presence
of 1 mol % (R,R,R)-4-Pd catalyst at 40 ꢁC for 72 h. The
hydrosilylation product was oxidized under Tamao
conditions giving the corresponding alcohol 11 in 35%
yield with 68% ee (R).
allylpalladium
chloride
dimer
(1.5 mg,
0.0041 mmol), the phosphoramidite ligand (R,R,R)-4
(8.3 mg, 0.0164 mmol) and styrene 5a (341 mg,
3.28 mmol). After 20 min stirring at room temperature,
trichlorosilane (0.66 mL, 6.56 mmol) was added at 0 ꢁC.
The reaction mixture was stirred at room temperature
for 2 h. The product was purified by distillation to yield
778 mg (99%) of 6a. The results for the asymmetric hy-
drosilylations of styrene derivatives 5b–k are summa-
rized in Table 2.
4.3. General procedure for oxidation of silanes
The silane 6a (177 mg, 0.741 mmol), KF (258 mg,
4.446 mmol), KHCO3 (445 mg, 4.446 mmol), MeOH
(15 mL) and THF (15 mL) were transferred to a 50-mL
flask. H2O2 (0.89 mL, 30%) was added and the mixture
stirred for 16 h before quenching with 4 mL saturated
Na2S2O3 solution. After stirring for an additional 1 h, the
reaction mixture was extracted with Et2O (3 · 30 mL),
and the combined organic phases dried over MgSO4,
filtered and concentrated in vacuum. The crude residue
was purified by flash column chromatography on silica
gel (pentane/ethyl acetate, 90/10), affording the alcohol
7a (76 mg, 99%) with 97% ee (R). The results for the
oxidation of silanes 6b–k, are summarized in Table 2.
OH
OH
11
8
9
10
3. Conclusion
We have demonstrated that the chiral spiro monophos-
phoramidite (R,R,R)-4 containing a 1,10-spirobiindane
scaffold is a highly effective ligand for the palladium-
catalyzed asymmetric hydrosilylation of styrene deriva-
tives, producing the chiral silanes and alcohols upon
oxidation in high yields and excellent enantioselectivities
(up to 99.1% ee). This novel ligand has a higher activity
and comparable enantioselectivity to monophosphor-
amidite ligand 2 derived from BINOL. Further appli-
cations of this ligand in other transition metal-catalyzed
asymmetric reactions are currently under investigation.
Acknowledgements
We thank the National Natural Science Foundation of
China, the Major Basic Research Development Program
(Grant G2000077506), and the Ministry of Education of
China for financial support.
References and notes
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