I. V. P. Raj et al. / Tetrahedron Letters 48 (2007) 7211–7214
7213
Table 2. Cyanosilylation of various aldehydes using organocatalyst 4a
Bn
N+
OTMS
Br-
TMSCN
OTMS
R
CN
TMSCN, 4 (0.5 mol%)
CH2Cl2, 25 °C
RCHO
2
N
R
CN
2a-l
4
Bn
N+
Yieldb (%)
Bn
Br-
Entry
R
T (h)
Br-
N+
a
b
c
d
e
f
g
h
i
C6H5
24
24
24
24
10
3
51
52
62
57
4-MeOC6H4
4-MeC6H4
4-HOC6H4
4-FC6H4
4-NCC6H4
4-O2NC6H4
Ph(CH2)2
Ph–CH@CH
BnO(CH2)4
BnO(CH2)5
(CH3)2CH
N+
Si
N+
CN-
-
Si
R
H
73
O
7
72, 53c, 58d
RCHO
8
CN
3
92
80
60
83
81
90
10
10
10
10
10
Scheme 2. Possible pathway for the cyanosilylation of aldehydes.
j
k
l
Acknowledgements
VPRI thanks CSIR, New Delhi, for the award of
research fellowships. The authors are thankful to Dr.
B. D. Kulkarni, Head, CE-PD Division, for his constant
encouragement and support.
a Reagents and conditions: aldehyde (5.0 mmol), TMSCN (6.0 mmol),
organocatalyst 4 (0.5 mol %), CH2Cl2, 25 °C.
b Isolated yield after column chromatographic purification.
c % Yield when catalyst 3 was used.
d % Yield when catalyst 5 was used.
References and notes
Table 3. Strecker-type a-aminonitrile synthesis using 4 as catalyst and
1. (a) Purkarthofer, T.; Pabst, T.; van den Broek, C.;
Griengl, H.; Maurer, O.; Skranc, W. Org. Process Res.
Dev. 2006, 10, 618; (b) Brunel, J.-M.; Holmes, I. S. Angew.
Chem., Int. Ed. 2004, 43, 2752; (c) North, M. Tetrahedron:
Asymmetry 2003, 14, 147; (d) Nicolaou, K. C.; Vassili-
kogiannakis, G.; Kranich, R.; Baran, P. S.; Zhong, Y.-L.;
Natarajan, S. Org. Lett. 2000, 2, 1895; (e) Gregory, R. J.
H. Chem. Rev. 1999, 99, 3649.
2. Kruse, C. G. In Chirality in Industry; Collins, A. N.,
Sheldrake, G., Crosby, J., Eds.; Wiley: Chichester, 1992,
Chapter 14.
3. (a) Weber, W. P. Silicon Reagents for Organic Synthesis;
Springer: Berlin, 1983; (b) Colvin, E. W. Silicon Reagents
in Organic Synthesis; Academic Press: London, 1981, and
references cited therein.
4. (a) Sung, S. K.; Rajagopal, G. Synthesis 2007, 215; (b) De,
S. K.; Gibbs, R. A. J. Mol. Catal. A: Chem. 2005, 232,
123; (c) Bandgar, B. P.; Kamble, V. T. Green Chem. 2001,
3, 265; (d) Karimi, B.; Ma’Mani, L. Org. Lett. 2004, 6,
4813; (e) King, J. B.; Gabbai, F. P. Organometallics 2003,
22, 1275.
5. (a) Denmark, S. E.; Chung, W.-J. J. Org. Chem. 2006, 71,
4002; (b) Li, Y.; He, B.; Feng, X.; Zhang, G. Synlett 2004,
1598; (c) Kim, S. S.; Kim, D. W.; Rajagopal, G. Synthesis
2004, 213; (d) Kim, S. S.; Rajagopal, G.; Kim, D. W.;
Song, D. H. Synth. Commun. 2004, 34, 2973; (e) Kruchok,
I. S.; Gerus, I. I.; Kukhar, V. P. Tetrahedron 2000, 56,
6533.
TMSCN as cyanide sourcea
p-anisidine,MgSO4
4 (0.5 mol%), TMSCN
CH2Cl2, 25 oC, 12 h
NHPMP
RCHO
R
CN
6
Entry
R
Yield (%)b
1
2
3
4
5
6
7
8
9
C6H5
77
79
67
81
81
69
72
68
73
83c
90d
4-MeOC6H4
3,4-(MeO)2C6H3
Ph(CH2)2
4-O2NC6H4
4-ClC6H4
3-O2NC6H4
3,4-Methylenedioxyphenyl
CH3–(CH2)3
10
11
CH3–(CH2)3
CH3–(CH2)3
a Reagents and conditions: aldehyde (5.0 mmol), TMSCN (6.0 mmol),
p-anisidine (5.0 mmol),
(25 mL), 25 °C, 12 h.
4 (0.5 mol %), anhyd MgSO4, CH2Cl2
b Isolated yield after column chromatographic purification.
c Yield when morpholine was used as the amine source.
d Yield when n-butylamine was used as the amine source.
7 with aldehydes gives intermediate 8, which subse-
quently dissociates into silylated cyanohydrin 2 with
the regeneration of catalyst 4.
6. (a) Holmes, I. P.; Kagan, H. B. Tetrahedron Lett. 2000, 41,
7453; (b) Holmes, I. P.; Kagan, H. B. Tetrahedron Lett.
2000, 41, 7457.
7. (a) Hamashima, Y.; Sawada, D.; Nogami, H.; Kanai, M.;
Shibasaki, M. Tetrahedron 2001, 57, 805; (b) Kanai, M.;
Hamashima, Y.; Shibasaki, M. Tetrahedron Lett. 2000, 41,
2405; (c) Hamashima, Y.; Sawada, D.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 2641.
8. Kurono, N.; Yamaguchi, M.; Suzuki, K.; Ohkuma, T.
J. Org. Chem. 2005, 70, 6530.
In conclusion, we have shown, for the first time, the use
of ammonium salts as new Lewis base catalysts for
cyanosilylation of aldehydes and the three-component
Strecker- type a-aminonitrile synthesis under ambient
conditions.12,13 Both the methods are effective and uti-
lize the readily available cyanide source TMSCN. These
catalysts have also shown advantages in terms of chemi-
cal stability and high solubility in organic solvents.
9. The crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre as deposition
No. CCDC 651284. Copies of the data can be obtained,