Highly enantioselective hydrosilylation of aromatic alkenes

Article abstract of DOI:10.1021/ja025617q

Currently, the most effective and economic way to convert an alkene into an optically active alcohol is the two-step sequence: hydrosilylation/oxidation. Much work has been devoted to elucidating effective catalysts for this process, but hitherto only one effective and highly stereoselective process has been available. Herein we present a novel catalytic system for the asymmetric hydrosilylation of aromatic alkenes, giving the products in high yields and with the highest enantioselectivity (up to 99% ee) ever observed for this reaction. The reaction works efficiently for a variety of substituted aromatic alkenes, giving access after Tamao oxidation to almost optically pure benzylic alcohols in high yields. Copyright

Full text of DOI:10.1021/ja025617q

Published on Web 04/04/2002
Highly Enantioselective Hydrosilylation of Aromatic Alkenes
Jakob F. Jensen, Bo Y. Svendsen, Thomas V. la Cour, Henriette L. Pedersen, and
Mogens Johannsen*
Department of Chemistry, Technical UniVersity of Denmark, Building 201, DK-2800 Kgs Lyngby, Denmark
Received January 16, 2002
Catalytic asymmetric functionalization of alkenes continues to
be one of the most important methods for constructing chiral units.
The palladium-catalyzed hydrosilylation of alkenes is a highly
potent example of a hydro-metalation reaction that displays excellent
regioselectivity for aryl-substituted olefins (Scheme 1).1 Addition
of a hydrosilane in the presence of an optically active palladium-
complex affords a chiral organosilane. The Tamao-Fleming
oxidation is an important example of the numerous versatile
transformations organosilanes can undergo.2 Stereospecific oxida-
tion affords a chiral alcohol with retention of configuration, making
the overall reaction sequence equivalent to an enantioselective
Markovnikov hydration of an olefin. Opposed to the hydroboration,
the hydrosilylation can be conducted with very low catalyst
loadings, applying cheap hydrosilanes as the stoichiometric reagent,
making this process outstanding in terms of synthesizing chiral
alcohols.
Figure 1. Monophosphine ligands.
p-MeO-Ph-MOPF 5 (Figure 1) displayed the highest selectivity
in the hydrosilylation of styrene, furnishing 3a with 90% ee.6 In
our continued studies we focused on other possible ligands for the
hydrosilylation.
Scheme 1
Figure 2. Phosphoramidite ligands.
Chiral phosphoramidite ligands represented by 6-8 (Figure 2)
introduced by Feringa and co-workers are interesting candidates
for application in the hydrosilylation.7 They include the axially
chiral BINOL structure in combination with a phosphorus-nitrogen
bond. Furthermore, as ligand 8 demonstrates, additional chiral
elements can be introduced, allowing facile structure modification.
The development of highly enantioselective optically active
palladium complexes for the hydrosilylation was troubled in its
infancy by the lack of activity of palladium-bisphosphine com-
plexes. Considering the excellent results obtained with C2-symmetric
bisphosphine ligands in asymmetric transition metal catalysis, the
focus put on this ligand class is not surprising. However, with the
discovery that some catalytical processes require a free coordination
site on the metal to proceed, the importance of monophosphine
ligands became clear. Despite several reports of novel monophos-
phine ligands, thus far only Hayashi’s MOP ligands have displayed
high efficiency with respect to reactivity and selectivity in the
hydrosilylation of aryl-substituted alkenes.3,4 Thus, palladium-
catalyzed hydrosilylation of styrene 1a with the MOP ligand 4
(Figure 1) affords upon oxidation 1-phenyl ethanol 3a in excellent
yield and 98% enantiomeric excess.
Table 1. Palladium-Catalyzed Hydrosilylation of Styrene (1a)
Using Phosphoramidite Ligandsa
entry
ligand
conversion [%]b
ee [%]c,d
1
2
6
7
8
100
100
100
100
100
55 (S)
20 (R)
99 (R)
99 (R)
60 (S)
3
4e
5
8
8′f
a All reactions were conducted with 1a/HSiCl3/[ClPd(C3H5)]2/ligand -
1/1.2/0.005/0.02 unless otherwise stated. b Conversion to 2a determined by
1H NMR. c Ee of 3a determined by chiral HPLC on a OD-H column.
d Absolute configuration determined by optical rotation and comparison with
literature data. e 0.25 mol % Pd and 0.5 mol % ligand was applied. f Reaction
performed with the diastereomeric (RA,RC,RC)-8′ ligand.
Initially, ligands 6-8 were tested in the hydrosilylation of styrene
(Table 1).8 The reactions proceeded smoothly at room temperature
with 1 mol % of the catalyst affording 100% conversion to the
product within 24 h. Upon oxidation under Tamao conditions, the
alcohol 3a was obtained in yields >80%. Notably, ligand 6 affords
3a with (S)-configuration in 55% ee (entry 1), whereas 7 furnishes
We became interested in the asymmetric hydrosilylation reaction
in the course of developing a novel class of aryl-monophosphino
ferrocene ligands (MOPF ligands).5
* To whom correspondence should be addressed. E-mail: mj@kemi.dtu.dk.
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J. AM. CHEM. SOC. 2002, 124, 4558-4559
10.1021/ja025617q CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
the product with opposite configuration (entry 2), albeit with low
enantiomeric excess (20%). Ligand 8 also lead to the (R)-configured
product, but with 99% enantiomeric excess, which is the highest
selectiVity eVer obserVed in the hydrosilylation of styrene (entry
3). Lowering the catalyst loading to 0.25 mol % did not affect the
excellent selectivity displayed by ligand 8 (entry 4).
Acknowledgment. We thank The Danish Technical Research
Council, Leo Pharmaceuticals, Lundbeckfonden, and Familien Hede
Nielsens Fond for generous support.
Supporting Information Available: Detailed experimental pro-
cedures (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
To evaluate the impact of the configuration of substituents on
nitrogen, the diastereomeric ligand (RA,RC,RC)-8’ was applied in
the reaction (entry 5). While retaining the activity of the Pd-ligand
complex, the absolute configuration was inversed, accenting to the
effect from the absolute stereochemistry of the binaphthol system.
The relative low enantiomeric excess of 3a (entry 5, Table 1) clearly
demonstrates that this diastereoisomer (8′) has mismatched chiral
elements.
Given the excellent performance of the Pd-8 complex in the
hydrosilylation reaction, we wanted to explore the scope of this
reaction toward diversely functionalized styrenes. Table 2 sum-
marizes the results obtained with substrates 1a-1j.
References
(1) For reviews on the hydrosilylation of olefins, see: (a) Yamamoto, K.;
Hayashi, T. In Transition Metals for Organic Synthesis: Building Blocks
and Fine Chemicals, Beller, M., Bolm, C., Eds.; Vol. 2; Wiley-VHC:
Weinheim, 1998. (b) Hayashi, T. In ComprehensiVe Asymmetric Catalyses;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin,
1999. For reviews covering all aspects of the hydrosilylation, see: (c)
Ojima, I.; Li, Z.; Zhu, J. In The Chemistry of Organic Silicon Compounds;
Rappoport, Z., Apeloig, Y., Eds.; John Wiley & Sons Ltd: New York,
1998; Vol. 2. (d) Nishiyama, H.; Itoh, K. in Catalytic Asymmetric Synthesis
(Ed. Ojima, I.) Wiley-VCH: New York, 2000.
(2) For a comprehensive review on oxidation of the carbon-silicon bond,
see: Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
(3) (a) Uozumi, Y.; Hayashi, T. J. Am. Chem. Soc. 1991, 113, 9887. (b)
Uozumi, Y.; Sang-Yong, L.; Hayashi; T. Tetrahedron Lett. 1992, 33, 7185.
(c) Uozumi, Y.; Hayashi, T. Tetrahedron Lett. 1993, 34, 2335. (d)
Kitayama, K.; Uozumi, Y.; Hayashi, T. Chem. Commun. 1995, 1533. (e)
Kitayama, K.; Tsuji, H.; Uozumi, Y.; Hayashi, T. Tetrahedron Lett. 1996,
37, 4169. (f) Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji, H.; Torii, A.;
Uozumi, Y. Chem. Lett. 2000, 1272. (g) Hayashi, T.; Hirate, S.; Kitayama,
K.; Tsuji, H.; Torii, A.; Uozumi, Y. J. Org. Chem. 2001, 66, 1441. (h)
Hayashi, T.; Han, J. W.; Takeda, A.; Tang, J.; Nohmi, K.; Mukaide, K.;
Tsuji, H.; Uozumi, Y. AdV. Synth. Catal. 2001, 343, 279. (i) Han, J. W.;
Hayashi, T. Chem. Lett. 2001, 976. For reviews on the MOP ligands in
asymmetric hydrosilylation see (j) Uozumi, Y.; Kitayama, K.; Hayashi,
T.; Yanagi, K.; Fukuyo, E. Bull. Chem. Soc. Jpn. 1995, 68, 713. (k)
Hayashi, T. Catal. Today 2000, 62, 3. (l) For a review on the MOP ligand
see, e.g.: Hayashi, T. Acc. Chem. Res. 2000, 33, 354.
Table 2. Catalytic Asymmetric Hydrosilylation of Aromatic
Alkenesa
reaction
time [h]
conversion
[%]b
yield
[%]c
ee
[%]d
entry
substrate
1e
2e,f
3g
1a
1b
1c
1d
1e
1f
1g
1h
1i
16
144
40
60
40
60
40
40
40
40
100
100
100
100
92
100
83
100
100
100
87
94
89
91
74
88
75
95
80
91
99 (R)
95 (R)
96 (R)
98 (R)
95 (R)
98 (R)
97 (R)
86 (R)
96 (R)
98 (R)
4g
5g
6f,g
7g
(4) For other examples of asymmetric hydrosilylation with palladium
complexes, see: (a) Tamao, K.; Yoshida, J.-I.; Takahashi, M.; Yamamoto,
H.; Kakui, T.; Matsumoto, H.; Kurita, A.; Kumada, M. J. Am. Chem.
Soc. 1978, 100, 290. (b) Hayashi, T.; Tamao, K.; Katsuro, Y.; Nakae, I.;
Kumada, M. Tetrahedron Lett. 1980, 21, 1871. (c) Hayashi, T.; Kabeta,
K.; Yamamoto, T.; Tamao, K.; Kumada, M. Tetrahedron Lett. 1983, 24,
5661. (d) Hayashi, T.; Kabeta, K. Tetrahedron Lett. 1985, 26, 3023. (e)
Okada, T.; Morimoto, T.; Achiwa, K. Chem. Lett. 1990, 999. (f) Marinetti,
A. Tetrahedron Lett. 1994, 35, 5861. (g) Ohmura, H.; Matsuhashi, H.;
Tanaka, M.; Kuroboshi, M.; Hiyama, T.; Hatanaka, Y.; Goda, K.-I. J.
Organomet. Chem. 1995, 499, 167. (h) Pioda, G.; Togni, A. Tetrahedron:
Asymmetry 1998, 9, 3903. (i) Bringmann, G.; Wuzik, A.; Breuning, M.;
Henschel, P.; Peters, K.; Peters, E. V. Tetrahedron: Asymmetry 1999, 10,
3025. (j) Kamikawa, T.; Hayashi, T. Tetrahedron 1999, 55, 3455. (k)
Perch, N. S.; Widenhoefer, R. A. J. Am. Chem. Soc. 1999, 121, 6960. (l)
Perch, N. S.; Pei, T. Widenhoefer, R. A. J. Org. Chem. 2000, 65, 3836.
(5) Pedersen, H. L.; Johannsen, M. Chem. Commun. 1999, 2517.
(6) Pedersen, H. L.; Johannsen, M. Manuscript submitted for publication.
(7) (a) de Vries, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2374. (b) Feringa, B. L.; Pineschi, M.; Arnold, L. A.;
Imbos, R.; de Vries, A. H. M. Angew. Chem., Int. Ed. Engl. 1997, 36,
2620.
(8) General procedure for the hydrosilylation/oxidation sequence: A dried
Schlenk tube containing a stirbar was charged with allylpalladium chloride
dimer (1.5 mg, 0.0041 mmol, 0.25 mol % Pd), 8 (8.9 mg, 0.0164 mmol,
0.5 mol %) and 2-chlorostyrene (1c) (454 mg, 3.28 mmol). After 20 min
stirring at room temperature, trichlorosilane (396 µL, 3.93 mmol) was
added. The reaction mixture was stirred and heated for the time specified
in Table 2. The product was purified by Kugelrohr distillation to yield
796 mg (89%) of 2c. The silane (200 mg, 0.741 mmol), KF (6 equiv),
KHCO3 (6 equiv), MeOH (15 mL), and THF (15 mL) were transferred to
a 50-mL flask. H2O2 (0.89 mL, 30%) was added, and the mixture was
stirred for 16 h before quenching with Na2S2O3 (saturated 4 mL). After
stirring for an additional hour the reaction mixture was extracted with
Et2O (3 × 30 mL), and the combined organic phases were dried over
MgSO4, filtered, and concentrated in vacuo. The crude residue was purified
by flash chromatography (pentane/ethyl acetate, 90/10), affording the
alcohol 3c in 86% yield and with 96% ee. All spectral data were in
accordance with literature. See, e.g.: Doucet, H.; Fernandez, E.; Layzell,
T. P.; Brown J. B. Chem. Eur. J. 2001, 5, 1320.
8g
9g
10f,g
1j
a All reactions were conducted with substrate/HSiCl3/ [ClPd(C3H5)]2/
ligand, 1/1.2/0.00125/0.005 at 20 °C, unless otherwise stated. b Conversion
to silane determined by 1H NMR. c Isolated yield of silane. d Absolute
configuration determined by optical rotation. e Ee of alcohol determined
by HPLC on a Chiralcel OD-H column. f Reaction performed at 40 °C.
g Ee of alcohol determined by GC on a Chiralsil-Dex column.
Electron-withdrawing substituents prolong the reaction time
(entry 2-6), but in all cases excellent yields and enantiomeric
excess is achieved. The positioning of these substituents on the
aromatic ring has no apparent effect on the outcome of the reaction.
The weakly electron-donating methyl substituent affords comparable
selectivity when positioned ortho to the vinyl group (entry 7).
p-Methyl-substituted alcohol 3h was obtained with the lowest ee
(entry 8). However, reconstituting the 2-methyl group enhanced
the selectivity to 96% (entry 9). â-Methyl-substituted styrene 1j
was an excellent substrate in the reaction, the silyl group was
introduced exclusively at the benzylic position, and the product
was obtained with 98% enantioselectivity (entry 10).
Herein we have presented a novel catalytic system for the
asymmetric hydrosilylation of aromatic alkenes giving the products
in high yields and with the highest enantioselectivity ever observed
for this reaction. The reaction works efficiently for a variety of
substituted aromatic alkenes, giving access to almost optically pure
benzylic alcohols in high yields after Tamao oxidation.
JA025617Q
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J. AM. CHEM. SOC. VOL. 124, NO. 17, 2002 4559