Lithium perchlorate/diethylether-catalyzed three-component coupling reactions of aldehydes, hydroxylamines and trimethylsilyl cyanide leading to α-cyanohydroxylamines

Article abstract of DOI:10.1016/S0040-4039(00)00182-9

Three-component coupling reactions of aldehydes, hydroxylamines and trimethylsilyl cyanide proceeded smoothly in the presence of lithium perchlorate/diethylether solution (5 M) to afford α-cyanohydroxylamine derivatives in high yields. (C) 2000 Elsevier S

Full text of DOI:10.1016/S0040-4039(00)00182-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2471–2473
Lithium perchlorate/diethylether-catalyzed three-component
coupling reactions of aldehydes, hydroxylamines and
trimethylsilyl cyanide leading to α-cyanohydroxylamines
a,∗
b
a
c
Akbar Heydari, Hassan Larijani, Jalal Emami and Bahador Karami
a
Chemistry Department, Tarbiat Modarres University, PO Box 14155-4838, Tehran, Iran
b
Chemistry Department, Kordestan University, Sanandaj, Iran
Chemistry Department, Tarbiat Moallem University, Tehran, Iran
c
Received 26 October 1999; revised 24 January 2000; accepted 25 January 2000
Abstract
Three-component coupling reactions of aldehydes, hydroxylamines and trimethylsilyl cyanide proceeded smo-
othly in the presence of lithium perchlorate/diethylether solution (5 M) to afford α-cyanohydroxylamine derivatives
in high yields. © 2000 Elsevier Science Ltd. All rights reserved.
We have already reported that lithium perchlorate/diethylether (5.0 M) LPDE is an excellent catalyst
1
for the activation of nitrogen-containing compounds (for example, aldimines). Many Lewis acids are
deactivated or sometimes decomposed by nitrogen containing reactants; even when the desired reactions
proceed, more than stoichiometric amounts of the Lewis acids are needed because the acids are trapped
2
3
by nitrogen. On the other hand, it has been demonstrated that LPDE (1–5 M) retains activity in the
4
presence of nitrogen-containing compounds, for example Mannich-type reactions proceed smoothly in
the presence of the LPDE solution.
Nitrones are a particularly interesting class of compounds by virtue of their utility in organic synthesis.
They are reactive starting materials in a large number of 1,3-dipolar cycloadditions and can act as
electrophiles with a variety of both carbon and heteronucleophiles. Lewis acids are known to promote
these reactions. However, some nitrones, especially α-aliphatic nitrones, are unstable under these
5
conditions and low yields are sometimes observed. It is desirable from a synthetic point of view
that nitrones, which are prepared in situ from aldehydes and hydroxylamines, immediately react with
nucleophiles. Although a solution of aldehyde 1, phenylhydroxylamine 2a and trimethylsilylcyanide 3 in
diethylether remains unchanged after 4 h at room temperature, the reaction in 5 M ethereal LiClO4
solution, followed by hydrolysis, leads to the formation of the α-cyanohydroxylamine 4, within 15
6
min, in high yields. α-Cyanohydroxylamines are an important class of compounds. Hydrolysis of
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00182-9
tetl 16462

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α-cyanohydroxylamines gives N-hydroxylamino acids, which undergo catalytic hydrogenation to give
amino acids. N-Hydroxyamino acids are a biologically important class of compounds which are produced
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by metabolism of amino acids and act as antibiotics and growth factors. It is noteworthy that α-
cyanohydroxylamine can be converted into the corresponding nitrones upon treatment with bases with
elimination of hydrogen cyanide. It should be noted that most Lewis acids cannot be used in this
9
reaction since they are decomposed or deactivated by the amines and water which exist at the stage of
5
nitrone formation. Several examples of the present three-component coupling reactions are summarized
in Scheme 1. Not only aromatic, but also aliphatic and heterocyclic aldehydes reacted smoothly under
these conditions.
Scheme 1.
In summary, we have found that 5.0 M LPDE promotes the reaction of TMSCN with aldehydes to give
α-cyanohydroxylamines. This method has some noteworthy features: (1) excellent yields can be obtained
for aromatic, aliphatic and heterocyclic aldehydes. In particular, α-aliphatic nitrones, are stable under
these conditions and excellent yields are observed; and (2) operational simplicity at ambient temperature.
Acknowledgements
Research supported by the National Research Council of I. R. Iran as a National Research project
under the number 984 and (the Kurdestan University). A.H. thanks Alexander von Humboldt Stiftung for
the award of a University Research fellowship. We thank Prof. Dr. Paul Knochel (Ludwig-Maximilliams
University) for helpful suggestions.
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1
1
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3
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