Scandium triflate-catalyzed 1,3-dipolar cycloaddition of aziridines with alkenes

Article abstract of DOI:10.1016/S0040-4039(01)02008-1

Phenyl aziridines undergo 1,3-dipolar cycloaddition efficiently with olefins such as cyclic enol ethers and allyltrimethylsilane in the presence of a catalytic amount of Sc(OTf)₃ at ambient temperature to afford the corresponding pyrrolidine derivatives in high yields with high regioselectivity.

Full text of DOI:10.1016/S0040-4039(01)02008-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9089–9092
Scandium triflate-catalyzed 1,3-dipolar cycloaddition of
aziridines with alkenes†
J. S. Yadav,* B. V. Subba Reddy, Sushil Kumar Pandey, P. Srihari and I. Prathap
Organic Chemistry Division 1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 20 August 2001; revised 9 October 2001; accepted 19 October 2001
Abstract—Phenyl aziridines undergo 1,3-dipolar cycloaddition efficiently with olefins such as cyclic enol ethers and allyltrimethyl-
silane in the presence of a catalytic amount of Sc(OTf)3 at ambient temperature to afford the corresponding pyrrolidine derivatives
in high yields with high regioselectivity. © 2001 Elsevier Science Ltd. All rights reserved.
Aziridines are versatile building blocks for the synthesis
of many nitrogen containing bioactive molecules.1 They
are known to react with various nucleophiles and their
ability to undergo regioselective ring-opening reactions
contributes largely to their synthetic value. As a result,
several procedures have been developed for the ring
opening of aziridines with various nucleophiles such as
organometallic reagents,2 silyl nucleophiles,3 Wittig
reagents,4 amines5 and hydroxyl compounds,6 but the
procedures for their opening with alkenes are scarce.7
Moreover, these methods require stoichiometric
amounts of Lewis acids, very low temperatures and
anhydrous reaction conditions to obtain the desired
products. Therefore, there is merit in developing a truly
catalytic process for the synthesis of substituted pyrro-
lidines from phenyl aziridines and alkenes. Lanthanide
triflates are unique Lewis acids that are currently of
great research interest. They are quite stable to water
and reusable, as well as highly effective for the activa-
tion of nitrogen containing compounds. Therefore, lan-
thanide triflates are unique catalysts compared to
conventional Lewis acids in several carbonꢀcarbon
bond forming reactions and have found a wide applica-
tion in organic synthesis.8 In addition, these metal
triflates can be used either in aqueous or in non-
aqueous media and the reactions can be conveniently
carried out under mild conditions and do not require
anhydrous conditions or an inert atmosphere. However,
there is no report on the use of lanthanide triflates for
the ring opening of aziridines with alkenes.
In continuation of our interest on the use of Sc(OTf)3
for various transformations,9 we herein report a novel
and efficient protocol for the cyclocondensation of aryl
aziridines with cyclic enol ethers using a catalytic
amount of scandium triflate. The starting N-tosyl aryl
aziridines were easily prepared from styrenes and chlo-
ramine-T using catalytic amounts of elemental iodine.10
The treatment11 of aryl aziridines with 2,3-dihydrofuran
in the presence of 3 mol% Sc(OTf)3 in dichloromethane
at 0°C resulted in the formation of azaoxa cycloadducts
as a mixture of 2 and 3 in good yields (Scheme 1).
In all the reactions, the product was obtained as a
mixture of 2a and 3a in a ratio of 1:1, which were
separated by column chromatography. The stereochem-
istry of the product 2a was assigned on the basis of
coupling constants and NOE studies. The coupling
constant Ja–b=5.8 Hz between Ha (l 5.97)-Hb (l 3.25)
and the presence of NOE cross peaks between Ha–Hb,
Hb–Hc and Ha–Hc indicate a structure with cis-fusion
with the phenyl ring is an exo configuration (Fig. 1). In
the product 3a, similar to product 2a, the two five-
membered rings are cis-fused. The coupling constant
J
a–b=6.0 Hz between Ha (l 5.72)-Hb (l 2.83) and the
presence of an NOE cross peak between Ha and Hb
Keywords: aziridines; scandium triflate; cycloaddition; pyrrolidines.
* Corresponding author. Fax: +91 40 7170512; e-mail: yadav@
iict.ap.nic.in
† IICT Communication No. 4859.
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02008-1

9090
J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 9089–9092
Figure 1.
Scheme 3.
Figure 2.
Scheme 4.
again shows that Ha is cis to Hb and that the phenyl
ring is in an endo configuration (Fig. 2).
presence of 5 mol% scandium triflate at ambient tem-
perature resulted in the formation of a mixture of the
highly substituted pyrrolidine 2 with a small amount of
the g-amino olefinic adduct 3 (Scheme 4).
The formation of the products may be explained by the
(3+2) cycloaddition between the aziridine and the cyclic
enol ether. Scandium triflate activates the N-tosyl
group in the aziridine to cleave the benzylic CꢀN bond
resulting in the formation of a 1,3-dipole which is
trapped by the nucleophilic olefin to afford the desired
pyrrolidine (Scheme 2).
The five-membered pyrrolidines were obtained as a
mixture of cis and trans isomers in a ratio of 1:1, which
were inseparable on TLC. Similarly, various substituted
aryl aziridines reacted well with allyltrimethylsilane to
afford the corresponding pyrrolidines. In all these cases,
the reactions proceeded smoothly at ambient tempera-
ture and the products were obtained in high yields
within 1.5–3 h. Among various metal triflates like
In(OTf)3, Yb(OTf)3, Y(OTf)3 and LiOTf, scandium
triflate was found to be the more efficient in terms of
yields and reaction time. The catalyst, Sc(OTf)3 was
recovered from the aqueous layer during work-up and
reused in subsequent reactions without any decrease in
activity. Several examples illustrating this novel and
general method for the synthesis of pyrrolidines are
listed in Table 1.
In a similar fashion, aryl aziridines reacted smoothly
with 3,4-dihydro-2H-pyran in the presence of 3 mol%
Sc(OTf)3 in dichloromethane at 0°C to give the respec-
tive azaoxa [3.2.0] cycloadducts as a mixture of 2 and 3
in good yields (Scheme 3).
In these reactions, the products were also obtained as a
mixture of 2 and 3 in a ratio of 1:1, which were
separated by column chromatography. The structure of
the products were assigned on the basis of coupling
constants and NOE cross peaks. The coupling constant
J
a–b=5.0 Hz, for 2, indicates a structure with cis-fusion
In summary, we have demonstrated Sc(OTf)3 as a novel
and highly efficient Lewis acid for the synthesis of
substituted pyrrolidines from aryl aziridines and olefins.
The method offers several advantages over conven-
tional methods, which include mild reaction conditions,
high yields of products, operational simplicity, catalytic
amounts of Sc(OTf)3, reusability of the catalyst and
simple experimental/work-up procedures. These advan-
tages make it a useful and attractive process for the
synthesis of highly substituted pyrrolidines.
and an exo phenyl ring, which is further supported by
the presence of NOE cross peaks between Ha–Hb,
Hb–Hc and Ha–Hc. In product 3, Ja–b=3.8 Hz and the
presence of an NOE between Ha and Hb shows a
structure with cis fusion and an endo phenyl ring.
Furthermore, the assigned structures of 2 and 3 are in
agreement with the literature.7b In all these cases, the
reactions proceeded efficiently at 0°C, under mild reac-
tion conditions and in good yields. Further, the treat-
ment of aryl aziridines with allyltrimethylsilane in the
Scheme 2.

J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 9089–9092
Table 1. Sc(Otf)3-catalyzed synthesis of pyrrolidine derivativesa
9091

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J. S. Yada6 et al. / Tetrahedron Letters 42 (2001) 9089–9092
mol%) in dichloromethane (10 mL) was stirred at 0°C for
Acknowledgements
the specified time required to complete the reaction. After
complete conversion, as indicated by TLC, the reaction
mixture was diluted with water (10 mL) and extracted
with dichloromethane (2×15 mL). The combined organic
layers were washed with brine, dried over anhydrous
Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 100–200 mesh,
ethyl acetate–hexane, 1:9) to afford pure exo and endo
B.V.S., P.S.H. and I.P. thank CSIR, New Delhi for the
award of fellowships.
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1
129.52, 140.46, 143.49. 2d: H NMR (CDCl3, 400 MHz):
l 1.13–1.48 (m, 4H), 2.30–2.42 (m, 1H), 2.47 (s, 3H), 3.19
(dd, 1H, J=8.3, 14.9 Hz), 3.45–3.62 (m, 2H), 3.87 (d, 2H,
J=8.3 Hz), 5.31 (d, 1H, J=4.9 Hz), 7.10 (d, 2H, J=8.0
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1
136.85, 139.37, 143.49. 3d: H NMR (CDCl3, 400 MHz):
l 1.30–1.82 (m, 4H), 2.13–2.17 (m, 1H), 2.45 (s, 3H),
3.43–3.70 (m, 4H), 3.90–3.95 (m, 1H), 5.32 (d, 1H, J=3.8
Hz), 7.18 (d, 2H, J=8.0 Hz), 7.22–7.35 (m, 5H), 7.83 (d,
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11. Experimental procedure: A mixture of aryl aziridine (2
mmol), enol ether (3 mmol) and scandium triflate (3