Copper-catalyzed highly enantioselective carbenoid insertion into Si-H bonds

Article abstract of DOI:10.1002/anie.200803192

(Chemical Equation Presented) Complete control: A highly efficient, copper-catalyzed, asymmetric carbenoid insertion into Si-H bonds, using chiral spiro diimine (SIDIM) ligands (see scheme, Ar=2,6-Cl₂C ₆H₃, OTf=trifluoromethanesulfonate), produces a wide range of α-silylesters, in high yields with excellent enantiomeric excesses. This catalytic system offers unprecedented levels of enantiocontrol for the Si-H bond insertion reaction.

Full text of DOI:10.1002/anie.200803192

Communications
DOI: 10.1002/anie.200803192
Asymmetric Catalysis
Copper-Catalyzed Highly Enantioselective Carbenoid Insertion into
À
Si H Bonds**
Yong-Zhen Zhang, Shou-Fei Zhu, Li-Xin Wang, and Qi-Lin Zhou*
Chiral silanes are versatile intermediates for stereoselective
transformations in organic synthesis.[1] Transition-metal-cata-
À
lyzed carbenoid insertion into Si H bonds provides a direct
and efficient method for the synthesis of silane-containing
compounds.[2] The most popular catalysts used in Si H bond-
À
insertion reactions have been copper(I) and rhodium(II)
complexes.[3] In 1996, Doyle and Moody[4] reported the first
À
asymmetric Si H bond-insertion reaction of a-diazophenyl-
acetates, catalyzed by a chiral dirhodium(II) carboxylate and
carboxamidate complexes with moderate enantioselectivities
(up to 47% ee). A year later, Davies and co-workers[5]
achieved high enantioselectivities (up to 95% ee) in the
À
Si H bond insertion of a-vinyldiazoacetates catalyzed by
rhodium(II)
N-[p-(dodecylphenyl)-sulfonyl]prolinate.
Recently, Ge and Corey[6] reported a Si H bond insertion
of an a-diazoketone with a N-nonafluorobutanesulfonylpro-
line rhodium(II) catalyst to prepare 6-silyl-2-cyclohexenones
with 94% ee. Several other chiral rhodium(II) catalysts have
À
À
Scheme 1. Copper-catalyzed insertion of a-diazoesters 3 into Si H
bonds. L=chiral spiro-bisoxazoline (spirobox) or spiro-diimine
À
also been used in the Si H bond-insertion reaction with
different diazo compounds, with no marked improvement in
(SIDIM) ligand.
enantiocontrol.[7] Although copper catalysts had been applied
to
The reaction of methyl a-diazophenylacetate (3a) and
dimethylphenylsilane (4a) was performed in CH2Cl2 at 258C
with a copper catalyst generated in situ from 5 mol% CuCl
and 6 mol% ligand. Firstly, we developed and examined
various chiral spiro-bisoxazoline ligands (1a–d) (Scheme 1).
All copper complexes of ligands 1a–d catalyzed the reaction,
Si H bond-insertion reactions before rhodium catalysts,[3] the
À
À
copper-catalyzed asymmetric Si H bond insertion has not
been widely exploited. The only example of a copper-
À
catalyzed asymmetric Si H bond-insertion reaction was
reported by Panek and Jacobsen.[8] Using a copper chiral-
À
À
Schiff-base complex as a catalyst, they obtained Si H bond-
insertion products in high yields with up to 88% ee, for the
reaction of a-diazophenylacetate with trialkylsilanes. In
affording the Si H insertion product methyl 2-dimethylphen-
ylsilyl-2-phenylacetate (5a), in high yields, with the ligand
(Ra,S,S)-1a being the most enantioselective (81% ee)
(Table 1, entry 2). Comparison of enantioselectivities of
ligands (Ra,S,S)-1a and (Sa,S,S)-1a clearly revealed that the
combination of chiralities in the ligand (Ra,S,S)-1a is matched
in terms of enantioselectivity (Table 1, entries 1 and 2). With
ligand (Ra,S,S)-1a, the reaction conditions were then carefully
optimized for maximum enantioselectivity. However, no
additional positive effect was detected.
previous studies, we accomplished highly enantioselective
[9]
À
insertions of a-diazoesters into N H bonds of anilines and
O H[10] bonds of phenols and water, using copper complexes
À
of chiral spiro-bisoxazoline ligands 1 (spirobox; Scheme 1).
We report herein a copper/chiral spiro-diimine-complex-
catalyzed asymmetric carbenoid insertion into the Si H
bond, with high yields and excellent enantioselectivities (up
À
À
to 99% ee).
To further improve the enantioselectivity of the Si H
bond-insertion reaction, we turned our attention to new
diimine ligands 2a–e, incorporating a chiral spirobiindane
backbone. The chiral spiro diimines 2a–e (abbreviated as
SIDIM) were prepared by a facile condensation of enantio-
pure (R)-1,1’-spirobiindane-7,7’-diamine (R)-6[11] with differ-
ent aromatic aldehydes (Scheme 2, for detailed synthesis of
ligands 2a–e, see the Supporting Information).
[*] Y.-Z. Zhang, Dr. S.-F. Zhu, Prof. L.-X. Wang, Prof. Q.-L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry
Nankai University, Tianjin 300071 (China)
Fax: (+86)22-2350-6177
E-mail: qlzhou@nankai.edu.cn
[**] We thank the National Natural Science Foundation of China (Grant
No. 20532010, 20702025), the Major Basic Research Development
Program (Grant No. 2006CB806106), the “111” project (B06005) of
the Ministry of Education of China and Merck Research Laborato-
ries for financial support.
Encouragingly, the SIDIM ligand (R)-2a had much higher
activity and enantioselectivity than the spirobox ligands 1a–d
À
in the Si H insertion reaction of methyl a-diazophenylace-
À
tate. The reaction was complete in 1 h at 08C, and the Si H
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803192.
insertion product was obtained in 95% yield with 93% ee
8496
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 8496 –8498

Angewandte
Chemie
À
Table 1: Copper-catalyzed asymmetric Si H insertion of methyl
À408C or À608C, the enantioselectivity was further enhanced
a-diazophenylacetate with dimethylphenylsilane: optimization of
to 97% ee and 98% ee, respectively, albeit with a longer
reaction time needed for full conversion (Table 1, entries 15
and 16). On reducing the catalyst loading to 1 mol%, the
conditions.[a]
À
Si H insertion product was obtained in 85% yield with a
slightly lower enantioselectivity (93% ee, Table 1, entry 17).
Solvents other than CH2Cl2 were also tested in this insertion
reaction. However, none of them gave results superior to
CH2Cl2 (data not shown).
Entry
Ligand
L*
[Cu]
T [8C] t [h] Yield[b] ee[c]
[%]
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17[d]
(Sa,S,S)-1a
(Ra,S,S)-1a
(Ra,S,S)-1b
(Ra,S,S)-1c
(Ra,S,S)-1d
(R)-2a
(R)-2b
(R)-2c
(R)-2d
(R)-2e
(R)-2a
(R)-2a
(R)-2a
(R)-2a
(R)-2a
(R)-2a
(R)-2a
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
CuCl/NaBArF
Cu(OTf)2/NaBArF
Cu(OTf)2
(CuOTf)2 Tol
CuPF6(MeCN)4
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
25
25
25
25
25
0
0
0
0
0
2
2
2
2
10
1
1
10
1
10
1
1
92
95
95
96
90
95
95
93
93
92
95
93
98
96
95
94
85
21
81
35
71
37
93
83
78
50
69
93
93
93
91
97
98
93
Avariety of a-diazoesters were examined as substrates for
À
the Si H insertion reaction with dimethylphenylsilane, under
the optimal reaction conditions. All substrates reacted to
produce the corresponding a-silylesters in high yields and
excellent enantioselectivities (90–99% ee), regardless of the
nature and the position of substituents on the phenyl ring of
the diazoesters (Table 2, entries 1–22). However, the reac-
tivity of the substrate was influenced by the electronic
properties of substituents on the phenyl ring of the
a-diazophenylacetates. a-Diazophenylacetates containing an
electron-withdrawing group had lower reactivities and
needed a higher reaction temperature (À408C) for complete
conversion (Table 2, entries 9–16). With the exception of
triisopropylsilane, which was too sterically bulky to undergo
0
0
0
0
1
3
5
6
À40
À60
À40
20
À
Si H insertion, other silanes, including triethylsilane, tripro-
pylsilane, and diphenylmethylsilane, can be applied as a silane
source in the reaction with a-diazoesters to afford the desired
a-silylesters in very high yields and enantiopurities. The
a-aryl group in the diazoester substrate is vital for obtaining
high yield and enantioselectivity. For example, the reactions
of methyl a-diazopropionate with PhMe2SiH and (o-Tol)-
[a] Reaction conditions: [Cu] (0.01 mmol), ligand (0.012 mmol), and
NaBArF (0.012 mmol, entries 1–11) were mixed in CH2Cl2 (2 mL) and
stirred for 2 h at 258C. Dimethylphenylsilane (0.2 mmol) and methyl
a-diazophenylacetate (0.2 mmol) were introduced and the mixture
stirred at the specified temperature for the specified time. [b] Yield of
isolated product. [c] Determined by chiral HPLC using a Chiralcel OD-H
column. [d] With 1 mol% catalyst. Tol=toluene.
À
Me2SiH gave the Si H insertion products in very low yields
and ee values (Table 2, entries 25 and 26). Similarly, the
substrate a-allyldiazoacetate afforded a complicated mixture
À
of products in the Si H insertion reaction (Table 2, entry 24).
In summary, we have developed a highly efficient copper-
À
catalyzed asymmetric carbenoid insertion into Si H bonds.
By using chiral spirodiimine ligands, a wide range of
a-silylesters were produced in excellent yields and enantio-
selectivities. The results achieved in this study represented, to
our knowledge, the highest level of enantiocontrol for a
Scheme 2. Preparation of spiro-diimine ligand 2
À
catalytic Si H bond-insertion reaction and indicated high
potential for wide-ranging applications of these novel diimine
ligands in other carbenoid-insertion reactions.
(Table 1, entry 6). Other SIDIM ligands (2b–e), with different
steric and electronic properties, however, had lower enantio-
À
selectivities in the Si H insertion reaction (Table 1, entries 7–
À
10). In our previous studies on the copper-catalyzed N H and
À
O H bond-insertion reactions using spirobox ligands 1a–d,
the additive NaBArF (NaBArF = tetrakis[3,5-bis(trifluorome-
thyl)phenyl]borate) played a crucial role for obtaining high
reactivity and enantioselectivity.[9,10] However, in the present
case, NaBArF was found to be unnecessary in the copper-
Experimental Section
Typical procedure: In a Schlenk tube, under an argon atmosphere,
Cu(OTf)2 (3.6 mg, 0.01 mmol) and (R)-2a (6.8 mg, 0.012 mmol)
dissolved in CH2Cl2 (2.0 mL). The mixture was stirred at room
temperature for 2 h, and then cooled to À608C. Dimethylphenylsi-
lane (28 mg, 0.2 mmol) and a-diazophenylacetate (35 mg, 0.2 mmol)
were added sequentially and the mixture was stirred at À608C for
approximately 6 h, until the diazo compound was consumed com-
pletely. The mixture was concentrated under reduced pressure
without further workup and purified by chromatography on silica
gel with petroleum ether/ethyl acetate (20:1, v/v). The product 5a was
isolated in 94% yield as a colorless oil. Enantiomeric excess (98%)
À
catalyzed Si H insertion reaction with SIDIM ligand (R)-2a
if an ionic catalyst-precursor was used. For example, the
reactions catalyzed by Cu(OTf)2/(R)-2a took place smoothly
with or without NaBArF and gave essentially identical results
(Table 1, entries 11 and 12). In addition to Cu(OTf)2, other
copper salts such as CuOTf and CuPF6 were also suitable
À
catalyst precursors for this Si H insertion reaction (Table 1,
entries 13 and 14). By decreasing the reaction temperature to
Angew. Chem. Int. Ed. 2008, 47, 8496 –8498
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 8497

Communications
[a]
À
Watanabe, T. Nakano, K.-I. Araki,
H. Matsumoto, Y. J. Nagai, J.
Organomet. Chem. 1974, 69, 389;
c) V. E. Baikov, L. P. Danilkina,
K. A. Oglobin, J. Gen. Chem.
1981, 51, 1858. For earlier exam-
ples of rhodium-catalyzed carbe-
Table 2: Asymmetric catalytic carbenoid insertion into Si H Bonds of silanes.
Entry
R1
R2
Silane
T [8C]
Product
Yield [%]
ee [%]
À
noid insertions into Si H bonds,
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Ph
o-MeC6H4
o-MeOC6H4
m-MeC6H4
p-MeC6H4
m-MeOC6H4
p-MeOC6H4
p-PhC6H4
o-ClC6H4
m-ClC6H4
p-ClC6H4
m-BrC6H4
p-BrC6H4
m-FC6H4
p-FC6H4
m-CF3C6H4
2-Naphthyl
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
PhMe2SiH
Et3SiH
À60
À60
À60
À60
À60
À60
À60
À60
À40
À40
À40
À40
À40
À40
À40
À40
À60
À60
À60
À60
À60
À60
0–25
0–25
À40
À40
5a
5b
5c
5d
5e
5 f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
5t
5u
5v
–
–
5w
5x
94
91
89
95
97
89
93
95
91
88
95
87
86
85
87
88
92
92
95
94
95
88
NR[b]
ND[c]
60
14
98
96
90
99
97
98
95
96
97
98
99
97
98
97
93
97
98
98
97
96
97
93
–
see: d) V. Bagheri, M. P. Doyle, J.
Taunton, E. E. Claxton, J. Org.
Chem. 1988, 53, 6158; e) O.
Andrey, Y. Landai, D. Planche-
nault, Tetrahedron Lett. 1993, 34,
2977; f) Y. Landais, D. Planche-
nault, Tetrahedron Lett. 1994, 35,
9549; g) O. Andrey, Y. Landais, D.
Planchenault, V. Weber, Tetrahe-
dron 1995, 51, 12083.
[4] R. T. Buck, M. P. Doyle, M. J.
Drysdale, L. Ferris, D. C. Forbes,
D. Haigh, C. J. Moody, N. D. Pear-
son, Q.-L. Zhou, Tetrahedron Lett.
1996, 37, 7631.
[5] H. M. L. Davies, T. Hansen, J.
Rutberg, P. R. Bruzinski, Tetrahe-
dron Lett. 1997, 38, 1741.
Ph
Ph
Ph
Ph
iPr
[6] M. Ge, E. J. Corey, Tetrahedron
Lett. 2006, 47, 2319.
Me
Me
Me
Me
Et
nPr3SiH
Ph2MeSiH
iPr3SiH
PhMe2SiH
PhMe2SiH
o-TolMe2SiH
[7] a) P. Bulugahapitiya, Y. Landais,
L. Parra-Rapado, D. Planchenault,
V. Weber, J. Org. Chem. 1997, 62,
1630; b) R. T. Buck, D. M. Coe,
M. J. Drysdale, C. J. Moody, N. D.
Pearson, Tetrahedron Lett. 1998,
39, 7181; c) S. Kitagaki, M.
Kinoshita, M. Takeba, M. Anada,
S. Hashimoto, Tetrahedron: Asym-
metry 2000, 11, 3855; d) R. T.
Buck, D. M. Coe, M. J. Drysdale,
Ph
=
PhCH CH
–
35
12
Me
Me
Et
Et
[a] Reaction conditions were the same as those in Table 1, entry 16; [Cu]=Cu(OTf)2. The reactions were
run to completion in times of 2–12 h. For the characterization and analyses of ee values of Si H
insertion products, see the Supporting Information. [b] NR=no reaction. [c] ND=not determined.
À
was determined by chiral HPLC analysis using a Daicel Chiralcel
OD-H column.
L. Ferris, D. Haigh, C. J. Moody, N. D. Pearson, J. B. Sanghera,
Tetrahedron: Asymmetry 2003, 14, 791. For examples of diaste-
À
reoselective Si H bond insertion, see: e) Y. Landais, D. Plan-
Received: July 2, 2008
Published online: September 29, 2008
chenault, Tetrahedron Lett. 1994, 35, 4565; f) Y. Landais, D.
Planchenault, V. Weber, Tetrahedron Lett. 1994, 35, 9549.
[8] a) L. A. Dakin, S. E. Schaus, E. N. Jacobsen, J. S. Panek,
Tetrahedron Lett. 1998, 39, 8947; b) L. A. Dakin, P. C. Ong,
J. S. Panek, R. J. Staples, P. Stavropoulos, Organometallics 2000,
19, 2896.
Keywords: asymmetric catalysis · carbenoids · copper ·
.
insertion · N ligands
[9] B. Liu, S.-F. Zhu, W. Zhang, C. Chen, Q.-L. Zhou, J. Am. Chem.
Soc. 2007, 129, 5834.
[10] a) C. Chen, S.-F. Zhu, B. Liu, L.-X. Wang, Q.-L. Zhou, J. Am.
Chem. Soc. 2007, 129, 12616; b) S.-F. Zhu, C. Chen, Y. Cai, O.-L.
Zhou, Angew. Chem. 2008, 120, 946; Angew. Chem. Int. Ed.
2008, 47, 932.
[1] I. Fleming, A. Barbero, D. Walter, Chem. Rev. 1997, 97, 2063.
[2] For reviews, see: a) M. P. Doyle, M. A. McKervey, T. Ye, Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds,
Wiley, New York, 1998; b) M. P. Doyle, D. C. Forbes, Chem. Rev.
1998, 98, 911.
[11] C. Chen, S.-F. Zhu, X.-Y. Wu, Q.-L. Zhou, Tetrahedron:
Asymmetry 2006, 17, 2761.
[3] For earlier examples of copper-catalyzed carbenoid insertions
À
into Si H bonds, see: a) F. Rijkens, M. J. Janssen, W. Drenth,
G. J. M. van derKerk, J. Organomet. Chem. 1964, 2, 347; b) H.
8498 www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 8496 –8498