Angewandte
Chemie
DOI: 10.1002/anie.201203925
Aziridination
Hypoiodite-Mediated Metal-Free Catalytic Aziridination of Alkenes**
Akira Yoshimura, Kyle R. Middleton, Chenjie Zhu, Victor N. Nemykin, and Viktor V. Zhdankin*
Aziridination of alkenes is an important chemical trans-
formation and is a convenient method for accessing various
nitrogen-containing products and synthetic intermediates.[1]
Particularly useful aziridinating reagents are N-tosyliminoio-
danes (ArINTs), which are important representatives of the
rapidly growing field of hypervalent-iodine reagents.[2]
Numerous synthetically useful aziridination methods are
based on the use of metal salts or complexes as catalysts
(for example, derivatives of Cu, Mn, Fe, and Rh) and ArINTs
as nitrenium precursors.[3] However, from both environmental
and economical viewpoints, avoiding toxic metals and per-
forming reactions under metal-free conditions, is critically
important in the development of “green” synthetic method-
ologies. Recently, the research groups of Che[4a,b] and
Yudin[4c–e] reported metal-free conditions for aziridination
using (diacetoxyiodo)benzene and N-aminoheterocycles. Che
and co-workers have also reported aziridination using in situ
generated hypervalent-iodine reactive species.[4b] However,
the attempted realization of the catalytic version of aziridi-
nation was not successful. Likewise, Wirth and co-workers
were unsuccessful in their broad search for reaction con-
ditions to effect organocatalytic alkene aziridination using
N-aminophthalimide (PhthNH2) as the nitrenium source.[5] To
the best of our knowledge, the organocatalytic aziridination
of alkenes using PhthNH2 as the nitrenium precursor has not
yet been developed.
Herein we report the first metal-free catalytic aziridina-
tion using catalytic amounts of tetrabutylammonium iodide
(TBAI), m-chloroperoxybenzoic acid (mCPBA) as the ter-
minal oxidant, and PhthNH2 as the nitrenium precursor. This
new catalytic reaction has an advantage over the commonly
used reactions that employ stoichiometric amounts of
N-tosyliminoiodanes, because it employs the common inex-
pensive reagents, TBAI and mCPBA. Very recently, the
research group of Ishihara reported the use of quaternary
ammonium iodides as catalysts for the oxidative cycloether-
ification of ketophenol and intra- and intermolecular organo-
catalytic oxidative-coupling reactions mediated by the in situ
generated tetrabutylammonium hypoiodite.[6] Several other
research groups have also reported reactions using catalytic
amounts of TBAI and common oxidants.[7]
In a search for iodine-mediated organocatalytic aziridi-
nation reaction conditions, we investigated the reactions of
alkenes and PhthNH2 as a nitrenium precursor with a broad
range of oxidants (for example, Oxone, sodium perborate,
and mCPBA) in the presence of iodine-containing precata-
lysts (various aryl iodides, I2, NaI, and Bu4NI) under different
reaction conditions using various solvents and other additives
(for more details see the Supporting Information, Table S1).
In the absence of iodine-containing pre-catalysts, the
reactions of alkenes with PhthNH2 and mCPBA afford mainly
epoxides and do not produce any significant amounts of
aziridines. The addition of 0.5 equivalents of an aryl iodide
(PhI, 4-MeOC6H4I, 2,4,6-Me3C6H2I, 2-MeOC6H4I, 4-
MeC6H4I, 4-CF3C6H4I, 4-ClC6H4I, and 3-HO2CC6H4I were
tested) results in the formation of moderate amounts (below
40%) of the desired aziridines, a result, which is in agreement
with previously reported observations of Che and co-work-
ers,[4b] and is indicative of a noncatalytic reaction.
We were pleased to find that the addition of TBAI
dramatically changes the outcome of this reaction, in that the
desired aziridines were now formed in high yields. We
investigated the aziridination of styrene as a model alkene
in the presence of TBAI at 408C under different reaction
conditions (see Table 1; for more details see the Supporting
Information, Table S1). Out of several solvents tested (see the
Supporting Information, Table S1), ethyl acetate was found to
be the best solvent. In particular, the reaction of styrene (1a)
with PhthNH2 (2), mCPBA, and 0.5 equivalents of TBAI in
the presence of potassium carbonate in ethyl acetate afforded
aziridine 3a in 62% yield (Table 1, entry 1). Under these
reaction conditions, but using a longer reaction time, aziridine
3a was obtained in 71% yield (Table 1, entry 2). When the
amount of TBAI was reduced from 50 mol% to 20 mol%, 3a
was obtained in a slightly lower yield (69%; Table 1, entry 3).
Decreasing the amount of mCPBA from five to three
equivalents resulted in further improvement of the yield to
79% (Table 1, entry 6). Lower amounts of mCPBA or TBAI
and a lower reaction temperature lead to reduced yields of 3a
(Table 1, entries 9–11). A further increase in reaction time
does not improve the yields (Table 1, entries 7, 8, and 12).
Only trace amounts of 3a are observed in the absence of
TBAI (Table 1, entry 13). The presence of a base, potassium
carbonate, is critically important (also see the Supporting
Information, Table S1), probably because the aziridine prod-
uct 3a is unstable under acidic reaction conditions.
[*] Dr. A. Yoshimura, K. R. Middleton, Prof. Dr. V. N. Nemykin,
Prof. Dr. V. V. Zhdankin
Department of Chemistry and Biochemistry
University of Minnesota Duluth
Duluth, MN 55812 (USA)
E-mail: vzhdanki@d.umn.edu
C. Zhu
School of Chemical Engineering
Nanjing University of Science and Technology
Nanjing 210094 (China)
[**] This work was supported by a research grant from the National
Science Foundation (CHE-1009038).
Using the optimized reaction conditions with 20 mol%
TBAI, we investigated the conversion of various substituted
alkenes 1 into the respective aziridines 3 (Table 2). In general,
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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