N-Ar yla tion of Azir id in es
F IGURE 1. Metal-bound aziridine species.
Mikio Sasaki, Shadi Dalili, and Andrei K. Yudin*
Department of Chemistry, University of Toronto, 80 St.
George Street, Toronto, Ontario M5S 3H6, Canada
best of our knowledge, no investigation into the scope and
potential applications of this process has been docu-
mented.14
ayudin@chem.utoronto.ca
Received November 14, 2002
We prepared the aziridine starting materials using one
of the following two methods: (a) ring closure of 1-azido-
2-hydroxycyclohexane with triphenylphosphine,15 and (b)
1,4-addition of methoxylamine to R,â-unsaturated ketone
followed by ring closure.16 It was subsequently found that
Pd2(dba)3/BINAP served as an effective catalyst for
amination of N-H aziridines. Using this methodology,
several types of N-arylated products have been synthe-
sized. BINAP and 1,3-bis(diphenylphosphino)propane
(DPPP) were tried as ligands for the reaction between
o-bromopyridine (2a ) and cyclohexeneimine (1a ), which
revealed that BINAP was an effective ligand in this
process, whereas DPPP did not give the desired product.
This contrasts with the success of DPPP in the amination
of 2a with various arylamines or cyclic amines.17
In the case of pyridine substrates, direct nucleophilic
displacement of halide has been ruled out: heating the
mixture of 1a and 2a did not give the desired product.
Uncatalyzed processes in the case of the nitro- and cyano-
substituted substrates have also been ruled out: without
Pd2(dba)3 and BINAP, 1-bromo-4-nitrobenzene (2h ) and
1-bromo-4-cyanobenzene (2i) did not react with 1a in the
presence of sodium tert-butoxide at 70 °C. To our delight,
the insertion of palladium into the nitrogen-carbon bond
was not observed in any of these cases, although oxidative
addition of Ni to N-tosylaziridines has been reported18
and oxidative addition of transition metals to aziridines
has been invoked in catalytic carbonylation of aziridines
to give â-lactams.19,20
The scope of N-arylation of 1a with Pd/BINAP was
investigated (Scheme 1). The results are shown in Table
1. Both electron-withdrawing and electron-donating groups
on the aryl halide moiety can be tolerated. Electron-
withdrawing groups tend to increase reactivity (Table 1,
entry 8), while electron-rich substrates, such as 2-bro-
moanisole (2f), needed more forceful conditions to com-
plete the reaction (Table 1, entry 6). In the case of
4-bromoanisole (2g), the reaction was sluggish and did
not reach completion after 12 h at 80 °C (Table 1, entry
7). For such substrates, the copper-catalyzed amination
described below was found to be the method of choice.
Aryl chlorides did not react under the reaction conditions
(Table 1, entry 10). Thus, o-bromochlorobenzene (2d ) led
to N-(2-chlorophenyl)aziridine (3d ) with high chemo-
Abstr a ct: A range of N-arylaziridines were prepared by the
palladium or copper catalyzed amination reaction between
N-H aziridines and aryl bromides or arylboronic acids.
These results showcase the synthetic utility of metal-bound
aziridine species in nitrogen transfer processes.
Palladium-catalyzed carbon-nitrogen bond-forming
reactions have received considerable attention in recent
years.1,2 A wide range of amines, amides, indoles, and
imines participate in this useful process. Our interest in
the synthetic applications of functionalized aziridines,3,4
and more recently in metal-bound aziridine species
(Figure 1), led us to investigate the possibility of reductive
elimination of the arylated aziridines from a variety of
transition metal complexes. An intriguing question is
whether the alkylated aziridine ring can tolerate the
Lewis acidic character of some of the late transition
metal-based catalysts and resist concomitant ring-open-
ing.
Traditional routes to N-arylated aziridines are based
on (a) ring closure of N-aryl-â-amino alcohols,5-8 (b)
addition of carbenoid species to imines,9-12 and (c) nu-
cleophilic aromatic substitution reactions between aziri-
dine nucleophiles and activated aryl halides.13 Transition
metal-catalyzed amination of aryl halides is well-known
but, to the best of our knowledge, has not been applied
in the amination with aziridines. This is partly due to
the difficulties associated with the preparation of N-H
aziridines. Hartwig reported an example of the reaction
between Ar-Pd-Br complexes and parent ethyleneimine
lithium amide to produce N-arylated aziridine but, to the
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10.1021/jo020696+ CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/04/2003
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