5466
B. He et al. / Tetrahedron Letters 45 (2004) 5465–5467
Ph
Ph
N
shown in Table 2, observations accorded with those
afforded by CDAM.13e While the para-substituents
(methyl, methoxy, chloro or fluoro) on the aromatic ring
lead to lower enantioselectivities and yields than ace-
tophenone (Table 2, entries 1–5), the meta-chloro
substituted ketone gives similar enantioselectivity and
yield to acetophenone (Table 2, entry 6). a-Tetralone
and 1-indanone afford products with similar enantio-
selectivities (Table 2, entries 7 and 8). Different from
Snapper’s report,6 the a,b-saturated ketone gives a
higher ee value than the a,b-unsaturated one (Table 2,
entries 9 and 10). This is in agreement with Shibasaki’s
result.4a
OH
N
R1
N
O
R1
OH HO
R1
R2
R2
R2
(1S, 2S)-1a-f
2a-f
tBu, R2 = tBu
2a R1 = tBu, R2 = H
2b R1 = Me, R2 = H
2c R1 = Ph, R2 = H
1a R1
=
1b R1 = H, R2 = Me
1c R1 = H, R2 = Ph
1d R1 = H, R2 = tBu
1e R1 = Me, R2
1f R1 = H, R2 = H
2d R1 = tBu, R2
=
tBu
=
tBu
2e R1 = H, R2 = tBu
2f R1 = H, R2 = H
Figure 1. Screening of ligands and N-oxides.
In conclusion, by introducing phenolic N-oxides as
additives into the asymmetric cyanosilylation of
ketones, we achieved the comparable results that affor-
ded by CDAM. Moreover, the use of additives simpli-
fied the procedure and it is a method for the screening of
efficient catalyst systems. The precise function of the N-
oxide additive is not clear at present. To improve
enantioselectivity, modification of the N-oxides can be
rationally based and an investigation of the mechanism
is underway.
Table 1. Asymmetric cyanosilylation of acetophenone catalyzed by
1a-Ti(OiPr)4 complex and additivesa
Entry
Additive
Amount
of addi-
tiveb (%)
Temp
(°C)
Yieldc
(%)
Eed (%)
1
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
10
5
)2
)2
)2
)2
0
0
0
0
0
94
89
94
83
70
76
81
80
2
3
1
4
0.5
1
5
98
23
73
93
88
80
73
70
72
68
69
69
66
60
6
1
)40
0
7
1
Acknowledgements
8
1
0
9
1
0
We thank the National Natural Science Foundation of
China (No. 20225206, 20390050, and 20372050) and the
Ministry of Education, P.R. China (No. 01144, 104209,
and others) for financial support.
10
11
1
0
1
0
a All the reactions were carried out under the following conditions:
10 mol % 1a-Ti(OiPr)4 complex, concentration of acetophenone ¼
0.5 M in CH2Cl2, 96 h.
b The molar ratio of additive to acetophenone.
c Isolated yield.
d Determined by chiral GC analysis on Chirasil DEX CB.
References and notes
€
1. (a) Vogl, E. M.; Groger, H.; Shibasaki, M. Angew. Chem.,
Int. Ed. 1999, 38, 1570–1577, and references cited therein;
(b) Costa, A. M.; Jimeno, C.; Gavenonis, J.; Carrol, P. J.;
Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 6929–6941, and
references cited therein; (c) Yuan, Y.; Long, J.; Sun, J.;
Ding, K.-L. Chem. Eur. J. 2002, 8, 5033–5042; (d) Yuan,
Y.; Li, X.; Sun, J.; Ding, K.-L. J. Am. Chem. Soc. 2002,
124, 14866–14867.
Encouraged by the result obtained for acetophenone, we
investigated a number of other ketones to probe their
behavior under the current catalytic condition.14 As
Table 2. Asymmetric cyanosilylation of ketones catalyzed by 1a-
Ti(OiPr)4 complex and N-oxide additive 2aa
2. Of course, the chiral ligand itself may already accelerate
the catalytic reaction Berrisford, D. J.; Bolm, C.; Sharp-
less, K. B. Angew. Chem., Int. Ed. Engl. 1995, 34, 1059–
1070.
Entry
Ketone
Yieldb (%)
Eec (%)
1
2
3
4
5
6
7
8
9
10
Acetophenone
94
68
81
75
89
93
73
96
94
81
71
74
67
73
82
77
79
74d
52d
40-Methylacetophenone
40-Methoxyacetophenone
40-Chloroacetophenone
40-Fluoroacetophenone
30-Chloroacetophenone
a-Tetralone
3. Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North, M.;
Tararov, V. I. Tetrahedron Lett. 1999, 40, 8147–8150.
4. (a) Hamashima, Y.; Kanai, M.; Shibasaki, M. J. Am.
Chem. Soc. 2000, 122, 7412–7413; (b) Hamashima, Y.;
Kanai, M.; Shibasaki, M. Tetrahedron Lett. 2001, 42, 691–
694; (c) Yabu, K.; Masumoto, S.; Yamasaki, S.; Hama-
shima, Y.; Kanai, M.; Du, W.; Curran, D. P.; Shibasaki,
M. J. Am. Chem. Soc. 2001, 123, 9908–9909; (d) Yabu, K.;
Masumoto, S.; Kanai, M.; Curran, D. P.; Shibasaki, M.
Tetrahedron Lett. 2002, 43, 2923–2926; (e) Masumoto, S.;
Suzuki, M.; Kanai, M.; Shibasaki, M. Tetrahedron Lett.
2002, 43, 8647–8651.
1-Indanone
Benzylacetone
trans-4-Phenyl-3-buten-2-one 77
a All the reactions were carried out under the optimized conditions:
10 mol % 1a-Ti(OiPr)4, 1 mol % 2a, )20 °C, concentration of
ketones ¼ 0.5 M in CH2Cl2, 96 h.
b Isolated yield.
5. (a) Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2001, 123,
6195–6196; (b) Tian, S.-K.; Hong, R.; Deng, L. J. Am.
Chem. Soc. 2003, 125, 9900–9901.
c Determined by chiral GC analysis on Chirasil DEX CB.
d Determined by HPLC on Chiralcel OD.