Indium triflate-catalyzed ring opening of aziridines with carboxylic acids

Article abstract of DOI:10.1016/S0040-4039(02)00189-2

Aziridines react smoothly with carboxylic acids in the presence of a catalytic amount of indium triflate at ambient temperature to afford the corresponding β-aminoacetates and benzoates in high yields with high regioselectivity.

Full text of DOI:10.1016/S0040-4039(02)00189-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2099–2101
Indium triflate-catalyzed ring opening of aziridines with
carboxylic acids
J. S. Yadav,* B. V. Subba Reddy, K. Sadashiv and K. Harikishan
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 25 October 2001; revised 3 January 2002; accepted 24 January 2002
Abstract—Aziridines react smoothly with carboxylic acids in the presence of a catalytic amount of indium triflate at ambient
temperature to afford the corresponding b-aminoacetates and benzoates in high yields with high regioselectivity. © 2002 Elsevier
Science Ltd. All rights reserved.
Aziridines are versatile synthetic intermediates for the
synthesis of many biologically interesting molecules
such as amino acids,1 heterocycles2 and alkaloids.3 They
are well known carbon electrophiles capable of reacting
with various nucleophiles and their ability to undergo
regioselective ring opening reactions contributes largely
to their synthetic value.4–6 However, there are no
reports on the regioselective ring opening of aziridines
with carboxylic acids. Metal triflates are unique Lewis
acids that are currently of great research interest.7
esters in high yields. Aryl-N-tosyl aziridines underwent
cleavage by an acid with preferential attack at the
benzylic position resulting in the formation of products
2 with a trace amount of 3 (Table 1, entries g–m).
However, the treatment of alkyl-N-tosyl aziridines with
carboxylic acids gave predominantly the ring-opened
products 3 with a minor amount of 2 (entries n–p). The
1
ratios of products 2 and 3 were determined from the H
NMR spectra of the crude products. A variety of
carboxylic acids reacted well with aziridines to give the
respective b-amino esters. In all cases, the reactions
proceeded efficiently in high yields at ambient tempera-
ture. Furthermore, the treatment of cycloalkyl-N-tosyl
aziridines with acids afforded the corresponding b-
amino esters in high yields with high stereoselectivity
(Scheme 2).
In this report we wish to highlight our results on the
regioselective ring opening of aziridines with carboxylic
acids using a catalytic amount of indium triflate. Thus,
treatment of styrene-N-tosyl aziridine with acrylic acid
in the presence of 5 mol% In(OTf)3 at ambient temper-
ature resulted in the formation of b-amino acrylate
derivatives 2 and 3 in 90% yield (Scheme 1).
In the case of cycloalkyl aziridines, the stereochemistry
of the ring product 4e was found to be trans from the
coupling constants of the ring protons at l 3.47 ppm
Similarly, aryl-N-tosyl aziridines reacted smoothly with
carboxylic acids to afford the corresponding b-amino
1
(ddd, J=6.0, 8.0, and 8.0 Hz, 1H) for (NCH) in the H
NMR spectrum, similarly the peak at l 4.89 ppm for
(CHOCOR) showed a similar splitting pattern (ddd,
J=5.5, 8.0, and 10.0 Hz, 1H). The method is clean and
highly regioselective, affording b-amino esters in excel-
lent yields. The reaction conditions are mild and no side
products or decomposition of the products was
observed. All the products were fully characterized by
1H NMR, IR, 13C NMR and mass spectroscopic data.
Similar yields and selectivity were also obtained with 3
mol% scandium triflate under the present reaction con-
ditions. However, in the absence of catalyst, the reac-
tion did not yield any product even at reflux
temperature. Finally, the catalyst was recovered from
the aqueous layer on work-up and recycled in subse-
Scheme 1.
Keywords: indium reagents; aziridines; carboxylic acids; b-amino-
acetates.
* Corresponding author. Fax: 91-40-7160512; e-mail: yadav@
iict.ap.nic.in
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00189-2

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J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 2099–2101
Table 1. In(OTf)3-catalyzed ring opening of aziridines with carboxylic acids
synthesis of b-amino esters are summarized in Table
1.8
In conclusion, we have demonstrated a novel and
efficient method for the preparation of b-amino esters
from aziridines using a catalytic amount of indium
triflate. The notable features of this method are high
yields of products, short reaction times, mild reaction
conditions, greater regioselectivity, cleaner reaction
profiles, simplicity in operation and reusability of the
catalyst, which makes it a useful and attractive process
Scheme 2.
quent reactions with a gradual decrease in activity; for
example, styrene-N-tosyl aziridine and acetic acid gave
92, 85 and 80% yields over three cycles. Several exam-
ples illustrating this novel and simple method for the

J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 2099–2101
2101
for the synthesis of b-amino acetates, acrylates, propi-
L.-X. J. Org. Chem. 2000, 65, 1344.
onates, butenoates and benzoates.
6. (a) Meguro, M.; Asao, N.; Yamamoto, Y. Tetrahedron
Lett. 1994, 35, 7395; (b) Righi, G.; Franchini, T.; Bonini,
C. Tetrahedron Lett. 1998, 39, 2385; (c) Ungureanu, I.;
Klotz, P.; Mann, A. Angew. Chem., Int. Ed. Engl. 2000, 41,
4615.
Acknowledgements
7. Kobayashi, S. Eur. Org. Chem. 1999, 15 and references
cited therein.
B.V.S. and K.H. thank CSIR, New Delhi for the award
of fellowships.
8. Experimental procedure: A mixture of N-tosyl aziridine (5
mmol), acid (7 mmol) and indium triflate (5 mol%) or
scandium triflate (3 mol%) in dichloromethane (10 mL)
was stirred at ambient temperature for an appropriate time
(Table 1). After completion of the reaction, as indicated by
TLC, the reaction mixture was diluted with water and
extracted with dichloromethane (2×10 mL). The combined
organic layers were dried over anhydrous Na2SO4, concen-
trated in vacuo and the resulting product was purified by
column chromatography on silica gel (Merck, 100–200
mesh, ethyl acetate–hexane, 1:9) to afford pure b-amino
ester. Spectroscopic data for product 4e: 2-(4-
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(m, 2H), 1.70–1.77 (m, 2H), 1.83 (dd, 3H, J=1.7, 6.8 Hz),
2.40 (s, 3H), 3.47 (ddd, 1H, J=6.0, 8.0, 8.0 Hz), 4.89 (ddd,
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323 M+.