J. Llaveria et al. / Tetrahedron Letters 53 (2012) 2525–2529
2529
yields and excellent regioselectivities (>95:<5), as a consequence of
Supplementary data
the preferred attack at the benzylic carbon.
The reactivity of other arylsubstituted aziridines such as p-fluo-
rophenyl- (37) and naphthyl- (38) aziridines with aniline, allyl
alcohol, and pyrrole were also explored (Table 4). The fluoro deriv-
ative 37 was completely consumed and the regioselectivity was
excellent for all three nucleophiles (Table 4, entries 1–3). Naphthy-
laziridine 38 also afforded almost complete conversion with all
three nucleophiles and, although the regioselectivity slightly de-
creased, the isolated yields of the major products remained high
(Table 4, entries 4–6). The use of pyrrole as a nucleophile afforded
a mixture of C2 and C3 compounds (Table 4, entries 3 and 6) in a
ratio similar to that previously obtained.
The sulphated zirconia used in this work was not acidic enough
to open non activated aziridines such as those derived from cyclo-
pentene or hexene; however, this fact can be advantageously used
for the selective opening of structurally different aziridines. As
proof of principle, a mixture of tosylaziridine derived from cyclo-
pentene 51 and aziridine 1 was treated with 4 equiv of allyl alcohol
and sulphated zirconia and only aziridines 11 and 19 resulting
from the exclusive opening of aziridine 1, were obtained
(Scheme 2).
Supplementary data (general experimental methods, experi-
mental details, characterization and NMR spectra for all new com-
pounds) associated with this article can be found, in the online
References and notes
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2011, 15, 1507–1538; Reviews about aziridine opening: (f) Tanner, D. Angew.
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Finally, the ring-opening reaction of aziridine 1 with allylic
alcohol was selected as model reaction to test the recovery and re-
use of the sulphated zirconia (Fig. 2).9 Full conversions were ob-
tained after four runs. However, in the fifth run, the conversion
decreased to 65% although the reaction time was longer, and in
subsequent cycles (cycle 6) a decrease of activity was observed
(40%) (Fig. 2).
In conclusion, sulphated zirconia is an efficient catalyst for the
ring-opening reaction of aziridines and the catalytic properties
can be modulated in order to improve the compatibility with a
variety of nucleophiles, including acid sensitives and slightly basic
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7. Procedure for the preparation of sulfated zirconia catalysts: Sulfuric acid (98% wt,
1 mL) was mixed with deionized water (3.5 mL). Zirconium isopropoxide
(70 wt % in 1-propanol, 20 mL) was further diluted with 1-propanol (30.5 mL).
The acid solution was dropwise added to the alkoxide solution under vigorous
stirring, until a viscous solution was obtained. The gel was heated at 80 °C to
evaporate excess alcohol. After, the dry gel was calcinated at 600 °C for 7 h in air.
8. General procedure for ring opening reaction: The nucleophile (0.7 mmol) and
hydroxyphenyl, –thioalkyl, –thiophenyl, –2-pyrrolyl, and –3-
indolyl derivatives can be obtained with high conversions and
regioselectivities. The prepared zirconia selectively opens pheny-
laziridine in the presence of dialkyl aziridines. Using allyl alcohol
as a nucleophile the reusability of the sulphated zirconia was
tested, and yields and regioselectivities do not change during the
first 4 cycles.
Acknowledgments
sulphated zirconia (0.025 g) were added to
a solution of N-tosylaziridine
(0.5 mmol) in dichloromethane (1 mL). The mixture was vigorously stirred at
room temperature for the appropriated time. The reaction mixture was filtered
and rinsed with dichloromethane (5 mL). Finally, the organic solution was
concentrated under vacuum and resulting residue was purified by column
chromatography.
Financial support of DGI-CTQ2008-01569-bqu (Ministerio de
Ciencia e Innovación, Spain) and technical assistance from the
servei de recursos cientifics (URV) are gratefully acknowledged.
J.L. thanks MICIN for a FPU fellowship, and A.E. thanks Consejo
Nacional de Ciencia y Tecnología, CONACYT for a postgradro schol-
arship (271892) in Tarragona-Spain. Authors thank Dr. Y. Díaz for
interesting suggestions.
9. Procedure for recovering and reusing the catalyst: When the reaction was finished,
the solids were filtered off and rinsed with dichloromethane and acetone. The
solid was then heated to 600 °C for 1 h and then was maintained at 110 °C
before the use in the following reaction.