Do aziridines require Lewis acids for cleavage with ionic nucleophiles?

Article abstract of DOI:10.1016/S0040-4039(03)01414-X

A variety of activated aziridines were cleaved by sodium azide and sodium cyanide in aqueous acetonitrile at reflux, in the absence of any Lewis acid, to provide ring-opened products in quantitative yields. However, the reaction was sluggish in the ring o

Full text of DOI:10.1016/S0040-4039(03)01414-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5839–5841
Do aziridines require Lewis acids for cleavage with ionic
nucleophiles?
Alakesh Bisai, Ghanshyam Pandey, Manoj K. Pandey and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 3 March 2003; revised 29 May 2003; accepted 5 June 2003
Abstract—A variety of activated aziridines were cleaved by sodium azide and sodium cyanide in aqueous acetonitrile at reflux, in
the absence of any Lewis acid, to provide ring-opened products in quantitative yields. However, the reaction was sluggish in the
ring opening of unactivated aziridines with sodium azide where the yields could be increased by adding 50 mol% CuCl ·2H O. The
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reaction was used to synthesize chiral diamines.
2003 Elsevier Ltd. All rights reserved.
©
Aziridines are versatile intermediates for the synthesis1
of nitrogen containing biologically active compounds.
The reactivity of this strained heterocyclic ring system is
dependent upon the substitution on the nitrogen atom.
Electron withdrawing groups on nitrogen enhance the
reactivity of the ring and these are termed as activated
azidirines. A number of nucleophilic ring-opening reac-
tions have been studied on activated and nonactivated
aziridines (N-alkyl or aryl). The ring-opening reaction
of aziridines with nitrogen nucleophiles such as the
azide ion has special significance because the products
are precursors for vicinal diamines which have varied
the 1,2-azidoamine in quantitative yield (Table 1, entry
1). In a similar fashion, the reaction of the above
aziridine with sodium cyanide gave the 1,2-cyanoamine
in 92% yield (Table 1, entry 2). The reactions were
extended to several activated aziridines and in all cases,
a high yield of the product was obtained (Table 1).
A phenyl substituted aziridine underwent the reaction
in a regioselective manner whereby the azide and cya-
nide ions attacked the benzylic position (Table 1,
entries 10 and 11). Acyclic terminal aziridines gave
products resulting from terminal attack (Table 1,
entries 12–16). It was observed that the reaction of
unactivated aziridines with sodium azide was sluggish.
For example, the yield from the cleavage of N-phenyl-
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applications in organic synthesis. This is usually done
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using TMSN as the classical protocol (NaN3 and
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NH Cl) requires a longer reaction time. Recently,
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cyclohexyl aziridine with NaN was only 40% at reflux
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cleavage of activated aziridines and epoxides with
temperature for 12 h. The reaction yield and rate were
improved by adding 50 mol% of CuCl ·2H O under the
NaN in the presence of cerium(III) chloride has been
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reported. Although this is a useful procedure, we dis-
above conditions (Table 2, entry 1). Similar results were
obtained in the cases of other N-arylcyclohexyl aziridi-
nes (Table 2, entries 2–6). It was observed that these
unactivated aziridines could not be cleaved with sodium
covered that cerium(III) chloride is not required for
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opening activated aziridines and epoxides. In fact, the
reaction is faster in the absence of this Lewis acid. In
view of this observation, we carried out a detailed study
and now report our results.
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cyanide in absence of Lewis acids. In order to increase
the scope of this reaction, it was extended to epoxides
(
Table 2, entries 7–9), which behaved like unactivated
A solution of N-tosylcyclohexyl aziridine (1 mmol) and
aziridines. The epoxides were cleaved with NaN in the
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NaN (1.5 mmol) in acetonitrile:water (5 mL; 9:1) was
3
absence of cerium chloride, but the reactions were
sluggish. However, as expected, the reaction was very
facile upon addition 50 mol% CuCl ·2H O.
refluxed for 40 min. After completion of the reaction,
the flask was cooled and the majority of the MeCN was
removed in vacuo. The crude reaction mixture was then
partitioned between EtOAc and water. Work-up and
purification by silica gel column chromatography gave
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The reaction was also extended to the cleavage of the
chiral aziridines 1. In the case of 1a (n=1), an insepara-
ble mixture (diastereomeric ratio=1:3) of cleaved
product 2a was obtained in 80% yield. However, 1b
(n=2) provided a separable mixture of 2b in a
*
Corresponding author. Fax: 91-512-597436; e-mail: vinodks@
iitk.ac.in
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01414-X

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840
A. Bisai et al. / Tetrahedron Letters 44 (2003) 5839–5841
Table 1. Cleavage of activated aziridines with NaN or NaCN in MeCN:H O (9:1) at 80°C
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Scheme 1.
diastereomeric ratio of 1:4.5. The major diastereomer
R,R,R)-2b was converted to the (R)-enantiomer of
trans-1,2-cyclohexanediamine by a known method
Acknowledgements
(
V.K.S. thanks DST for a research grant. A.B. thanks
CSIR for a junior research fellowship.
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e
(
Scheme 1).

A. Bisai et al. / Tetrahedron Letters 44 (2003) 5839–5841
5841
Table 2. Cleavage of unactivated aziridines and epoxides with NaN in MeCN:H O (9:1) at 80°C
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