generally applicable methods for N-trimethylsilyl or N-
arylaziridine synthesis from imines.5
Searching for an alternative to metal-based Lewis acids or
the highly electrophilic H+ species, we considered the fluoro-
nium cation, i.e., F+, as a possible alternative. The highly
electrophilic nature of F+ should allow, presumably in a process
similar to H+, imine activation and subsequent nucleophilic
attack by EDA. Importantly, the nonacidic nature of either the
N-fluoroheterocyclic salt or the fluoronium cation may allow
the use of acid-sensitive functional and/or protecting groups.
We also considered the fluoronium salts to have properties and
benefits that many currently employed Lewis and Brønsted acids
do not always have, i.e., easily handled, stable, crystalline,
nonhygroscopic, organic soluble salts which produce a relatively
benign and easily removed byproduct.
Furthermore, few innovative organocatalytic methods that
generate NH6 and N-arylaziridines7 have been reported,
despite the acknowledged potent biological activity of
N-arylaziridines.8 Thus, Kocovsky et al. detailed a two-step
procedure for the asymmetric synthesis of 2-substituted
N-arylaziridines, i.e., 4, via the asymmetric reduction of imine
2 (performed with 5 mol % of organocatalyst 1 and
trichlorosilane) affording 3, followed by its cyclization
generating 4 (Scheme 1).
Our preliminary studies focused on the reaction between
N-arylimine 5 (X ) N), EDA 6, and N-fluoropyridinium
triflate 7 (10 mol %, Scheme 2). Gratifyingly, after 5 h at
ambient temperature, TLC analysis indicated complete
consumption of 5.
Scheme 1. Organocatalytic Synthesis of N-Arylaziridines
Scheme 2
.
Efficient Synthesis of N-Arylaziridines from 5
An alternative methodology for N-arylaziridine synthesis
has focused, in the main, on employing strong Lewis acid
or transition-metal complexes. Thus, Templeton et al.9
reacted EDA with a Lewis acid, i.e., BF3OEt2, AlCl3, or TiCl4
(10 mol %) activated N-arylimine and generated racemic
mixtures of cis- and trans-C2,3-disubstituted N-arylaziridines
in variable yields (2-76%).
Furthermore, for the purposes of our research, we dis-
counted the use of triflic acid (cf. Johnston work)10 or the
application of protic salts because of their incompatibility11
with our desire to utilize N-TMS imines as precursors to
C2,3-disubstituted N-TMS-aziridines.
1
Workup (filter through alumina) and H NMR analysis
indicated that rac-8 (83% yield) was afforded cleanly and
with a coupling constant of J2,3 ) 6.8 Hz to have C2,3-cis-
stereochemistry. There was no indication that any of the
trans-isomer of rac-8 was present. Subsequent X-ray analysis
confirmed our cis-stereochemical assignment (Figure 1).
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Figure 1. X-ray crystal structure of rac-cis-8 (X ) N).
Repeating the reaction in Scheme 2 but employing 5 (X )
C), the corresponding cis-aziridine rac-8 (X ) C) was
afforded in a 47% yield.
Confident that 7 was a viable catalyst, we elected using 5
(X ) N) and 6 to screen solvents with disparate polarities
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