A. S. Paraskar, A. Sudalai / Tetrahedron Letters 47 (2006) 5759–5762
5761
and 1,5-diazabicyclo[4.3.0]undec-7-ene (DBU) were
found to be equally effective in catalyzing the reaction.
to imine 4 generated in situ, to afford a-aminonitrile 2
along with regeneration of Et3N.
It was of interest to subject various substituted alde-
hydes 1a–r to the three-component Strecker-type
reaction using a catalytic amount of either Cu(OTf)2–
TMSCN or Et3N–acetone cyanohydrin and the results
are shown in Table 2.
In conclusion, we have shown, for the first time, the use
of either Cu(OTf)2/TMSCN or Et3N/acetone cyanohy-
drin as new catalytic systems for the three-component
Strecker-type a-aminonitrile synthesis under ambient
conditions. Both catalytic systems are effective and uti-
lize cheap available cyanide sources giving correspond-
ing a-aminonitriles in excellent yields.
As can be seen, the reaction conditions are mild
[Cu(OTf)2) (1 mol %) or Et3N (5 mol %), CH3CN, 25
°C]. Aldehydes possessing both electron-donating as well
as electron-withdrawing groups underwent condensation
to afford the corresponding a-aminonitriles 2a–r. Even
sterically hindered aldehyde 1n underwent the reaction
producing the corresponding a-aminonitriles 2n in 56–
69% yield. Aliphatic, heterocyclic and unsaturated alde-
hydes also underwent the Strecker-type reaction giving
the corresponding a-aminonitriles in moderate yields.
However, the reaction failed in the case of acetophenone
under both sets of reaction conditions.
Acknowledgements
A.S.P. thanks CSIR, New Delhi, for the award of
research fellowships. Financial Grants from DST, New
Delhi (Sanction No SR/S1/OC-22/2002) are gratefully
acknowledged. The authors thank Dr. B. D. Kulkarni,
Head, CE-PD Division, for his constant encouragement
and support.
References and notes
In our attempt to obtain optically pure a-aminonitriles,
we employed various chiral bases but reactions failed to
deliver optical induction (Table 1). However, when (S)-
(À)-a-methylbenzylamine (3) and benzaldehyde were
subjected to hydrocyanation in the presence of a cata-
lytic amount of Et3N, we obtained a 3:1 diastereomeric
mixture8b of a-aminonitrile 2c in 87% yield (Scheme 1).
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rile.9 In the case of the Et3N-catalyzed reaction, the
probable mechanistic pathway is shown in Figure 1,
wherein the adduct Et3N–HCN (A), formed by the reac-
tion of acetone cyanohydrin with Et3N, transfers CNÀ
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CH3
HN
Ph
Ph
CN
CN
OH
i
+
PhCHO
H3C
Ph
NH2
+
1a
2c
3
Yield = 87%
dr = 3:1
Scheme 1. Reagents and conditions: (i) cat. Et3N (5 mol %), CH3CN,
25 °C, 5 h, 87%.
R'
_
N
+
O
O
Et NH
CN
3
10. (a) Paras, N. A.; MacMillan, D. W. C. J. Am. Chem. Soc.
2001, 123, 4370; (b) Ahrendt, K. A.; Borths, C. J.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243;
(c) Jen, W. S.; Wiener, J. J. M.; MacMillan, D. W. C. J.
Am. Chem. Soc. 2000, 122, 9874.
R
O
4
A
R'
HN
CN
OH
Et3N
R
CN
11. (a) Nazarov, I. N.; Zavyalov, S. I. J. Gen. Chem. USSR
(Engl. Transl.) 1954, 24, 475; Chem. Abstr. 1955, 49, 6139f;
(b) Betts, B. E.; Davey, W. J. Chem. Soc. 1958, 4193; (c)
Acetone cyanohydrin is a commercially available raw
2
Figure 1. Proposed catalytic cycle for the Et3N-catalyzed hydrocya-
nation of imines.