iodomethane occurred. The second quaternization of 1a and
diphenyliodonium triflate in the presence of a catalytic
amount of CuCl(I) successfully proceeded to furnish the
corresponding (ꢀ-trifluoromethyl)vinyl phenyl tolyl sulfo-
nium triflate 2a in 92% yield.6 Although this method itself
is highly effective and efficient, it suffers from the need to
isolate the sensitive, oily vinyl sulfonium salt 2a. To
overcome this shortcoming, we further searched for a
corresponding crystalline alternative of 2a. As a result, we
found the beneficial (ꢀ-trifluoromethyl)vinyl diphenyl sul-
fonium triflate 2b, a free-flowing, shelf-stable, and easy to
handle crystalline material.
to give the corresponding (R-trifluoromethyl)aziridine 4 in
good to excellent yields. It is noteworthy that amino- or ester-
substituted primary amines were also employed in this
reaction to afford the corresponding functionalized aziridines
(entries 6 and 7). In addition, the sodium salt of the less
nucleophilic p-toluenesulfonamide (TsNH2) also participated
in this reaction to give the N-tosyl-(R-trifluoromethyl)aziri-
dine in excellent yield (entry 8).7b
When we performed the aziridination with the optically
active primary amine (S)-1-phenethylamine 5, a mixture of
diastereomers 6a and 6b was obtained with a ratio of 54:46
in 82% combined yield. These diastereomers could be cleanly
separated by silica gel column chromatography. As one of
the diasteremers was known in the literature,7g we compared
With a facile preparation of crystalline 2b in hand, we
next paid attention to the synthetic approach to (R-trifluo-
romethyl)aziridine.7 Nonfluorinated aziridine rings have
recently received great attention due to their biological
activity and/or versatile synthetic intermediates.8 We ex-
pected that a variety of (R-trifluoromethyl)aziridines should
give the opportunity to develop new designed trifluorom-
ethylated pharmaceuticals and agrochemicals.9 According to
a reported procedure, we initially examined the preparation
of the corresponding (R-trifluoromethyl)aziridine from the
sulfonium salt 2b and benzylamine.1a,10 The reaction smoothly
proceeded to provide the N-benzyl-(R-trifluoromethyl)aziri-
dine 4a in 90% yield (Table 1, entry 1).7g Compared to a
1
the H NMR data to determine their stereochemistry. The
1H NMR spectrum of the more polar diastereomer was
identical with that of (R)-1-[(S)-1-phenethylamino]-2-trif-
luoromethylaziridine 6a. Thus, the stereochemistry of the less
polar diastereomer was assigned to (S)-1-[(S)-1-phenethy-
lamino]-2-trifluoromethylaziridine 6b (Scheme 2).
Scheme 2. Reaction of Optically Active Amine with 2b
Table 1. Substrate Scopea
We next envisioned that using an appropriate nucleophile
instead of the primary amines would create an alternative to
the aziridine synthesis mode, and such a nucleophile, phthal-
imide 7, was initially chosen. Thus, the reaction of 2b with 7
in the presence of triethylamine smoothly proceeded to afford
the corresponding N-[(R-trifluoromethyl)vinyl]phthalimide 8 in
98% yield.11 Accomplishment of this transformation suggests
that a wide range of 3,3,3-trifluoro-2-substituted propenes may
be synthesized depending on choice of nucleophile under
modified conditions. To test our hypothesis, we next examined
entry
primary amine
benzylamine
product yield (%)b
1
2
3
4
4a
4b
4c
4d
4e
4f
90
96
94
91
86
63c
78
91
2-phenylethylamine
3,5-dimethylbenzylamine
3,5-bis(trifluoromethyl)benzylamine
1-naphthylmethylamine
2-diethylaminoethylamine
glycine ethyl ester hydrochloride
p-toluenesulfonamide
5
6
7d
4g
4h
8e
a Unless otherwise noted, the reaction of 2b (1.05 equiv) with 3 (1 equiv)
was carried out in the presence of BuNH2 (3 equiv). b Isolated yield.
t
(7) For the preparation of trifluoromethylated aziridines, see: (a)
Yamauchi, Y.; Kawate, T.; Katagiri, T.; Uneyama, K. Tetrahedron 2003,
59, 9839. (b) Yamauchi, Y.; Kawate, T.; Itahashi, H.; Katagiri, T.; Uneyama,
K. Tetrahedron Lett. 2003, 44, 6319. (c) Akiyama, T.; Ogi, S.; Fuchibe, K.
Tetrahedron Lett. 2003, 44, 4011. (d) Volonterio, A.; Bravo, P.; Panzeri,
W.; Pesenti, C.; Zenda, M.; Eur, J. Org. Chem. 2002, 3336. (e) Crousse,
B.; Narizuka, S.; Bonnet-Delpon, D.; Be´gue´, J.-P. Synlett 2001, 679. (f)
Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.; Kenji, U. J. Org. Chem.
1999, 64, 7323. (g) Katagiri, T.; Ihara, H.; Takahashi, M.; Kashino, S.;
Furuhashi, K.; Uneyama, K. Tetrahedron: Asymmetry 1997, 8, 2933. (h)
Quinze, K.; Laureny, A.; Mison, P. J. Fluorine Chem. 1989, 44, 233. (i)
Tanaka, K.; Ohsuga, M.; Sugimoto, Y.; Okafuji, Y.; Mitsuhashi, K. J.
Fluorine Chem. 1988, 39, 39.
c Percent yield including a small amount of unidentified product. d The
reaction of 2b (1 equiv) with 3 (2 equiv) was conducted in the presense of
TEA (1.5 equiv). e Reaction performed in the presense of NaH (1.2 equiv)
in THF.
previous method for the preparation of related (R-trifluo-
romethyl)aziridines,7 this simple method should be more
convenient and practical. To explore the generality and scope
of the aziridination with 2b, representative primary amines
were examined. The results are summarized in Table 1. A
variety of primary amines 3 were smoothly reacted with 2b
(8) (a) Dauban, P.; Malik, G. Angew. Chem., Int. Ed. 2009, 48, 9026.
(b) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res. 2006, 39, 194.
(9) (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem.
Soc. ReV. 2008, 37, 320. (b) Kirk, K. L. Org. Process Res. DeV. 2008, 12,
305. (c) Isanbor, C.; O’Hagan, D. J. Fluorine Chem. 2006, 127, 303.
(10) Matsuo, J.; Yamanaka, H.; Kawana, A.; Mukaiyama, T. Chem. Lett.
2003, 32, 392.
(5) Hanamoto, T.; Shindo, K.; Matuoka, M.; Kiguchi, Y.; Kondo, M.
J. Chem. Soc., Perkin Trans.1 2000, 103.
(6) Kitamura, T.; Yamane, M.; Zhang, B. X.; Fujiwara, Y. Bull. Chem.
Soc. Jpn. 1998, 71, 1215.
(11) (a) Ishihara, K.; Nakano, K.; Akakura, M. Org. Lett. 2008, 10, 2893.
(b) Yamanaka, H.; Mukaiyama, T. Chem. Lett. 2003, 32, 1192.
Org. Lett., Vol. 12, No. 11, 2010
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Maeda, Ryoko
