Regioselective ring-opening reaction of 2-trifluoromethyl-N-tosylaziridine with some nucleophiles under basic conditions

Article abstract of DOI:10.1016/j.tet.2013.06.044

The ring-opening reaction of 2-trifluoromethyl-N-tosylaziridine with a variety of heteroatom- and carbon-centered nucleophiles was achieved under basic conditions in good to high yield with excellent regioselectivity. These findings enabled an easy access to useful α-trifluoromethyl-N- tosylmethylamine derivatives, such as 1,2-aminoalcohol, 1,2-diamine, 1,2-aminothiol, and distant secondary amine.

Full text of DOI:10.1016/j.tet.2013.06.044

Tetrahedron 69 (2013) 7448e7454
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective ring-opening reaction of 2-trifluoromethyl-N-
tosylaziridine with some nucleophiles under basic conditions
Yui Takehiro a, Kensuke Hirotaki a, Chihomi Takeshita a, Hiroshi Furuno b,
,
Takeshi Hanamoto a
*
a Department of Chemistry and Applied Chemistry, Graduate School of Science and Engineering, Saga University, Honjyo-machi 1, Saga 840-8502, Japan
b Institute for Materials Chemistry and Engineering (IMCE), Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The ring-opening reaction of 2-trifluoromethyl-N-tosylaziridine with a variety of heteroatom- and
Received 11 March 2013
Received in revised form 12 June 2013
Accepted 13 June 2013
carbon-centered nucleophiles was achieved under basic conditions in good to high yield with excellent
regioselectivity. These findings enabled an easy access to useful a-trifluoromethyl-N-tosylmethylamine
derivatives, such as 1,2-aminoalcohol, 1,2-diamine, 1,2-aminothiol, and distant secondary amine.
Available online 24 June 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Trifluoromethyl group
Aziridine
Ring-opening reaction
CF3-Building block
1. Introduction
basic conditions is scarce.4 The reason seems to be electrostatic
repulsion between one pair of fluorine on the trifluoromethyl
Medicinal modifications in biologically active molecules are
frequently related to replacing hydrogen with fluorine at the spe-
cific position.1 Lipitor bearing one fluorine on the benzene ring is
the most popular fluorinated drug for a cholesterol-reducer. On the
other hand, trifluoromethyl group (CF3) also plays an important
role due to its unique stereoelectronic property. Celecoxib pos-
sessing CF3 group on the pyrazole ring is well-accepted as an anti-
inflammatory drug. Accordingly, the facile preparation of selec-
tively trifluoromethylated molecules has become a great chal-
lenging task in the areas of pharmaceuticals and agrochemicals.2 In
conjunction with this area, we have been interested in an easy
group and the negative charge of nucleophiles.4c
We recently reported the easily prepared 2-trifluoromethyl-N-
tosylaziridine 1 would be a useful precursor for the synthesis of the
corresponding
cis-4-trifluoromethyl-2-substituted-N-tosyl-1,3-
oxazolidines.5 The CF3eaziridine 1 would be also a fascinating
electrophile for the ring-opening reaction due to the small steric
hindrance (no substituents on the ring except for CF3 group). We
report herein the first effective ring-opening reaction of 1 with
a variety of nucleophiles, such as alcohols, phenols, amides, imides,
thiols, and active methylene compounds under basic conditions,
providing the corresponding
amine derivatives.
a-trifluoromethyl-N-tosylmethyl-
preparation of a wide range of
a-(trifluoromethyl)methylamine
derivatives. In spite of the versatile potential of these molecules,
their expeditious preparation remains unexplored. We considered
that these molecules should be directly accessible from the regio-
controlled ring-opening reaction of 2-(trifluoromethyl)aziridine.
Aziridines are important synthetic intermediates for the synthesis
of biologically active compounds due to their inherent ring strain.
Reports on the ring-opening reaction of 2-(trifluoromethyl)azir-
idine derivatives under acidic conditions are available in the liter-
ature.3 However, the corresponding ring-opening reaction under
2. Results and discussion
2.1. Ring-opening reaction of 2-trifluoromethyl-N-tosylazir-
idine 1 with O-nucleophiles
Literature search for the ring-opening reaction of non-
fluorinated aziridines under basic conditions revealed that the
protocol by Zhou and co-workers was essentially suitable for our
purpose. They actually reported the tandem ring-opening/closing
reactions of 2-alkyl-N-tosylaziridines and aryl propargyl alcohols
* Corresponding author. Tel.: þ81 952 28 8704; fax: þ81 952 28 8548; e-mail
t
address: hanamoto@cc.saga-u.ac.jp (T. Hanamoto).
in the presence of BuOK in DMSO.6 Our investigation started by
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.044

Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
7449
using 1 and phenyl propargyl alcohol 2a as a model compound.
When the reaction of 1 was conducted with 2a using BuOK in
DMSO at room temperature, the reaction smoothly proceeded
giving not the anticipated cyclized product 3a but the simple ring-
opening product 4a as a single isomer in 80% yield (Scheme 1).
(4e) and the additional 1:2 ring-opening product (4ee) were ob-
tained in 46% and 52% yields, respectively (entry 5 and Scheme 2).
With the aim of gaining 4e exclusively, the use of 2e (2.2 equiv)
resulted in the formation of 4e (66% yield) along with 4ee (32%
yield) under the identical reaction conditions.
t
Scheme 1. Ring-opening reaction of 1 and 2a.
The reaction was highly regioselective such that other isomers
were not detected in the crude reaction mixture. Although we did
not obtain the corresponding CF3emorphorine derivative, consid-
ering the simplicity of the reaction under mild conditions, the re-
Table 2
Ring-opening reaction of 1 and various O-nucleophiles.a
sult in Scheme
1 appeared to be meaningful synthetic
transformation. To build on this result, we screened another base
and solvents shown in Table 1.
Entry
1
Product (Yield)b
Entry
6
Product (Yield)b
Table 1
Screening of reaction conditions.
2
7e
Entry
Base
Solv.
Time/h
Yield/%a
1
2
3
4
5
tBuOK
tBuOK
tBuOK
NaH
DMSO
DMF
THF
DMSO
THF
1
4.5
4
1
16
80
78
32
54
70
3
8f
NaH
a
Isolated yield.
4c
9f
The suitable base from this screening was tBuOK in DMSO. With
the aim of preparing the cyclic product 3a (see Scheme 1), the el-
evated reaction temperature (up to 80 ꢀC) and the longer reaction
time (24 h) caused 4a to partially decompose. Accordingly, room
temperature in DMSO (entry 1) was suitable for the optimal re-
action conditions of this ring-opening reaction. Once again, it is
noteworthy that this reaction proceeded affording the single
regioisomer under mild conditions. We deduced that both steric
and electronic effects of the trifluoromethyl group resulted in the
excellent regioselectivity and the high reactivity resulted from the
strong electron-withdrawing effect of tosyl group.7
With the optimal reaction conditions in hand, we examined the
substrate scope. Table 2 summarized the results of the ring-
opening reaction of 1 and a wide range of alcohols and phenol
(2). In most cases, the reaction smoothly proceeded giving the
corresponding product as a single regioisomer. When we con-
ducted the reaction of 2d, a mixture of diastereomers was obtained
in 92% combined yield (entry 4). This mixture could not be sepa-
rated to its components. When we carried out the reaction using 1
(1.0 equiv) and 2e (1.1 equiv) as a bi-functional nucleophile under
the optimized reaction conditions, the 1:1 ring-opening product
5d
10g
a
The reaction were carried out using 1 (1.0 equiv) and 2 (1.1 equiv) in the
presence of tBuOK (1.1 equiv) in DMSO at rt for 1 h unless otherwise noted.
b
Isolated yield.
c
An inseparable mixture of diastereomers was produced.
The corresponding bis-adduct was also produced (52%). See the text.
d
e
Reaction was run for 2 h.
f
Reaction was run in DMF at 0 ꢀC for 2 h.
g
Reaction was run in DMSO/THF¼1/1 at ꢁ20 ꢀC for 2 h.
2.2. Ring-opening reaction of 2-trifluoromethyl-N-tosylazir-
idine 1 with N-, S-, C-nucleophiles
We next investigated replacing the O-nucleophiles with other
nucleophiles. Table 3 shows the additional results of the ring-
opening reaction of 1 and N-, S-, and C-nucleophiles. In some
cases, we needed slightly modified reaction conditions in order to

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Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
Scheme 2. Reaction of 1 with 2-butyn-1,4-diol.
Table 3
these unsuccessful reactions is not clear at present. Although the
Ring-opening reaction of 1 and various N-, S-, C-nucleophiles.a
useable nucleophiles have some limitations for this reaction, the
ring-opening products produced here should be transformed into
the corresponding trifluoromethylated 1,2-aminoalcohols, 1,2-
diamines, 1,2-amino thiols, and distant secondary amines by ex-
posure of appropriate reaction conditions.
Finally, in addition to above findings, we happened to encounter
the formation of acceptable-yielding 2,5-bis(trifluoromethyl)-1,4-
bis(tosyl)piperazine 8 during the optimization of ring-opening re-
action.8 Thus, the reaction of 1 using each amount of tBuOTMS
(1.5 equiv) and CsF (1.5 equiv) in DMSO at 80 ꢀC for 24 h furnished
several products from which fortunately we separated 8 as a single
isomer in 33% yield after decantation repeated several times
(Scheme 3).
Entry
1
Product (Yield)b
Entry
6
Product (Yield)b
2c
7
8
3c
Scheme 3. Formation of 2,5-bis(CF3)-1,4-bis(Ts) piperazine under basic conditions.
4c
9
The structure of 8 was tentatively assigned on the basis of 1H
NMR, 13C NMR, 19F NMR, and GCeMS. The final structural de-
termination was established by its X-ray analysis. The ORTEP
drawing of 8 is shown in Fig. 1. The X-ray analysis reveals un-
ambiguous proof of the structure and stereochemistry of trans-8.
We again monitored this interesting reaction process by TLC and
GCeMS analysis, which resulted in detection and isolation of the
corresponding slightly contaminated acyclic product 9 as a pre-
cursor for 8 by column chromatography. The structure of 9 was
assigned on the basis of 1H and 19F NMR, and GCeMS analysis.9
These results let us to propose the following cyclization mecha-
nism in Scheme 4. The deprotonation of 1 with cesium tert-but-
oxide (tBuOCs) generated probably in situ resulted in the
transformation to the corresponding anion intermediate A. This
anion attacks the less hindered carbon of the remaining 1 to gen-
erate the corresponding anion intermediate B. This intermediate B
undergoes intramolecular cyclization in a 6-endo-trig fashion
yielding the trans-8.
5d
10e
a
The reaction were carried out using 1 (1.0 equiv) and NaH (1.1 equiv) in the
t
presence of BuOK (1.1 equiv) in DMSO at rt for 1 h unless otherwise stated.
b
Isolated yield.
Reaction was run for 1.5 h.
Reaction was conducted using NaH (1.1 equiv).
Reaction was run for 4 h.
c
d
e
obtain the corresponding products in good yields. As shown in
entries 1e4, N-nucleophiles smoothly reacted with 1 to afford the
corresponding adducts as a single regioisomer in high to excellent
yields. However, the reaction of 1 and N-methylaniline in the
presence of NaH in DMSO did not proceed as both starting mate-
rials were recovered intact (entry 5). The next reactions using S-
nucleophiles, such as an aliphatic thiol and an aromatic thiol (en-
tries 6 and 7) also gave the corresponding regioisomers in good and
high yields, respectively. Compared with O-, N-, and S-nucleophiles,
C-nucleophiles afforded the products in reasonable yields (entries
8e10). In addition, the useable C-nucleophiles had some limita-
tions. When we carried out the reaction using other C-nucleophiles,
such as tert-butyl acetoacetate, pentane-2,4-dione, 1,3-
dimethylbarbituric acid, phenylacetylene, the reactions resulted
in complex mixtures. In other words, the reactions did not afford
a detectable quantity of the ring-opening products. The reason for
3. Conclusion
We have developed the efficient and completely regioselective
ring-opening reaction of 2-CF3-N-Ts-aziridine 1 with a wide range
of O-, N-, S-, and C-nucleophiles in good to excellent yields under
mild conditions, affording
a-trifluoromethyl-N-tosylmethylamine
derivatives, such as 1,2-aminoalcohol, 1,2-diamine, 1,2-aminothiol,
and distant secondary amine. We also found the formation of

Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
7451
2-propyn-1-ol 2a (26.0 mL, 0.21 mmol) and tBuOK (23.4 mg,
0.21 mmol) in DMSO (1 mL). After stirring for 10 min, to this
mixture was added 2-CF3-N-Ts-aziridine 1 (50.8 mg, 0.19 mmol)
and the mixture was stirred for 1 h. The reaction was quenched by
the addition of saturated aqueous ammonium chloride solution.
The aqueous layer was extracted with hexane/EtOAc¼3/1. An ad-
ditional extraction was repeated twice. The combined organic so-
lution was dried over Na2SO4, filtered, and concentrated in vacuo.
The resulting oily residue was purified by column chromatography
(silica gel, hexane/EtOAc¼3/1) to give 4a as a white solid (61.1 mg,
80%): mp: 84.5e85.9 ꢀC; IR (KBr) 3268, 2970, 2879, 1599, 1333,
1288, 1233, 1036, 968, 694 cmꢁ1; 1H NMR (CDCl3, 300 MHz)
d 7.76
(d, J¼8.8 Hz, 2H), 7.46e7.41 (m, 2H), 7.37e7.32 (m, 3H), 7.26 (s, 2H),
5.34 (d, J¼9.5 Hz, 1H), 4.34 (d, J¼0.92 Hz, 2H), 4.12e3.98 (m, 1H),
3.83 (dd, J¼10.3, 3.1 Hz, 1H), 3.69e3.62 (dm, J¼10.3 Hz, 1H), 2.37 (s,
3H); 13C NMR (CDCl3, 75 MHz)
d 143.8, 137.4, 131.8, 129.6, 128.7,
128.3, 127.0, 123.9 (q, J¼282.1 Hz), 122.1, 87.4, 83.4, 65.7 (q,
J¼1.9 Hz), 59.4, 54.4 (q, J¼31.1 Hz), 21.4; 19F NMR (CDCl3, 283 MHz)
d
ꢁ75.1 (d, J¼7.3 Hz); GCeMS m/z 333 (1), 258 (3), 242 (100), 155
(18), 131 (6), 115 (53), 112 (28), 91 (25), 65 (6); Anal. Calcd for
19H18F3NO3S: C, 57.42; H, 4.57; N, 3.52. Found: C, 57.41; H, 4.52; N,
C
3.51%.
4.3. N-(1,1,1-Trifluoro-3-(prop-2-ynyloxy)propan-2-yl)tolue-
nesulfonamide (4b)
White solid; yield 97%; mp: 122.8e124.5 ꢀC; IR (KBr) 3319, 2970,
2125, 1598, 1384, 1337, 1262, 1146, 1090, 817, 662, 565 cmꢁ1 1H
;
NMR (CDCl3, 300 MHz)
d
7.76 (d, J¼8.1 Hz, 2H), 7.30 (d, J¼8.1 Hz,
2H), 5.29 (d, J¼9.4 Hz, 1H), 4.10 (d, J¼2.4 Hz, 2H), 4.12e3.97 (m, 1H),
3.78 (dd, J¼10.3, 3.1 Hz, 1H), 3.61 (dd, J¼10.3, 2.9 Hz, 1H), 2.45 (d,
Fig. 1. X-ray crystal structure of 8 with thermal ellipsoids shown at the 50% probability
level.
J¼2.4 Hz, 1H), 2.43 (s, 3H); 13C NMR (CDCl3, 75 MHz)
d 143.9, 137.5,
Scheme 4. . Plausible reaction mechanism of formulation of 8.
a novel trans-2,5-bis(trifluoromethyl)-1,4-bis(tosyl)piperazine 8.
Various -(trifluoromethyl)methylamine derivatives and 8 would
provide additional opportunities for valuable synthetic strategies in
129.6,127.0,123.8 (q, J¼282.7 Hz), 78.1, 75.7, 65.8 (q, J¼1.8 Hz), 58.6,
a
54.4 (q, J¼31.1 Hz), 21.5; 19F NMR (CDCl3, 283 MHz)
d
ꢁ75.1 (d,
J¼9.5 Hz); GCeMS m/z 302 (1), 282 (1), 257 (5), 242 (1), 166 (81),
the field of organofluorine chemistry.
155 (57), 139 (16), 112 (21), 91 (100), 69 (46); Anal. Calcd for
C13H14F3NO3S: C, 48.59; H, 4.39; N, 4.36. Found: C, 48.72; H, 4.35; N,
4.36%.
4. Experimental section
4.1. General information
4.4. N-(1,1,1-Trifluoro-3-(but-2-ynyloxy)propan-2-yl)toluene-
sulfonamide (4c)
1H, 13C, and 19F NMR spectra were measured in CDCl3 solutions.
Chemical shifts are reported in parts per million using an internal
Me4Si (TMS) for 1H NMR and 13C NMR spectra. Chemical shifts are
reported in ppm relative to that of CFCl3 for 19F NMR spectra using
an internal CF3C6H5 (benzotrifluoride) or C6F6. Infrared (IR) spectra
are reported in cmꢁ1. Melting points are uncorrected.
White solid; yield 93%; mp: 106.3e107.3 ꢀC; IR (KBr) 3336, 2978,
2925, 2225, 1599, 1377, 1341, 1179, 1142, 1090, 820, 661, 567 cmꢁ1
;
1H NMR (CDCl3, 300 MHz)
d
7.78 (d, J¼7.9 Hz, 2H), 7.31 (d, J¼7.9 Hz,
2H), 5.31 (d, J¼9.2 Hz, 1H), 4.14e3.93 (m, 3H), 3.76 (dd, J¼10.3,
3.1 Hz, 1H), 3.58 (dm, J¼10.3 Hz, 1H), 2.44 (s, 3H), 1.86 (t, J¼2.4 Hz,
3H); 13C NMR (CDCl3, 75 MHz)
d 143.8, 137.4, 129.5, 127.0, 123.8 (q,
4.2. N-(1,1,1-Trifluoro-3-(phenylprop-2-ynyloxy)propan-2-yl)
toluenesulfonamide (4a)
J¼282.7 Hz), 83.8, 73.7, 65.4, 59.1, 54.37 (q, J¼29.9 Hz), 21.5, 3.4; 19
F
NMR (CDCl3, 283 MHz)
d
ꢁ74.8 (d, J¼7.1 Hz); GCeMS m/z 271 (11),
252 (3), 207 (4), 180 (93), 155 (91), 139 (29), 112 (39), 91 (100), 65
(22), 53 (41); Anal. Calcd for C14H16F3NO3S: C, 50.14; H, 4.81; N, 4.18.
Found: C, 50.25; H, 4.76; N, 4.15%.
A 25 mL two-necked flask equipped with a magnetic stir bar,
a stopcock, and a three-way stopcock, was charged with 3-phenyl-

7452
Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
4.5. N-(1,1,1-Trifluoro-3-(but-3-yn-2-yloxy)propan-2-yl)tolue-
4.9. (E)-N-(1,1,1-Trifluoro-3-(1-phenylpropen-3-yloxy)
nesulfonamide (4d)
propan-2-yl)toluenesulfonamide (4g)
Mixture of diastereomers; white solid; yield 92%; mp:
White solid; yield 50%; mp: 128.8e129.1 ꢀC; IR (KBr) 3268, 2970,
73.5e75.0 ꢀC; IR (KBr) 3276, 2924, 2113, 1599, 1445, 1330, 1280,
2919, 2878, 1599, 1477, 1333, 1288, 1233, 1173, 1036, 968, 812, 754,
1186, 1153, 813, 675, 563 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
694 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
7.76 (d, J¼8.3 Hz, 2H),
d
7.79e7.77 (m, 4H), 7.32e7.25 (m, 4H), 5.30 (d, J¼9.0 Hz, 1H), 5.20
7.39e7.25 (m, 7H), 6.54 (d, J¼15.9 Hz, 1H), 6.14 (dt, J¼15.9, 6.2 Hz,
1H), 5.43 (d, J¼9.4 Hz, 1H), 4.06e4.01 (m, 2H), 4.01e3.99 (m. 1H),
3.70 (dd, J¼10.3, 2.9 Hz, 1H), 3.50 (ddd, J¼10.3, 2.9, 1.4 Hz, 1H), 2.38
(d, J¼8.8 Hz, 1H), 4.14e3.98 (m, 4H), 3.93 (dd, J¼10.1, 3.7 Hz, 1H),
3.81e3.76 (m, 1H), 3.62 (dd, J¼10.2, 2.8 Hz, 1H), 3.53e3.47 (m, 1H),
2.45e2.40 (m, 8H), 1.39e1.34 (m, 6H); 13C NMR (CDCl3, 101 MHz)
(s, 3H); 13C NMR (CDCl3, 101 MHz)
d 143.9, 137.4, 136.2, 133.6, 129.7,
d
143.9, 143.8, 129.7, 129.6, 127.1, 123.9 (q, J¼282.6 Hz), 123.8 (q,
128.6, 128.0, 127.0, 126.6, 124.4, 123.9 (q, J¼282.6 Hz), 72.2, 65.9,
J¼282.6 Hz), 82.2, 82.1, 74.2, 74.1, 66.1, 65.9, 64.7, 64.6, 64.3, 54.5 (q,
54.4 (q, J¼31.2 Hz), 21.5; 19F NMR (CDCl3, 376 MHz)
d
ꢁ75.8 (d,
J¼31.2 Hz), 54.4 (q, J¼30.4 Hz), 21.6, 21.51, 21.49; 19F NMR (CDCl3,
J¼6.8 Hz); GCeMS m/z 244 (56), 155 (26), 140 (41), 134 (10), 133
376 MHz)
d
ꢁ74.9 (d, J¼6.8 Hz, 3F), ꢁ74.8 (d, J¼6.8 Hz, 3F); GCeMS
(100), 117 (54), 115 (39), 112 (33), 91 (65), 65 (10); Anal. Calcd for
m/z 320 (1), 252 (9), 180 (54), 155 (100), 139 (27), 112 (24), 92 (23),
91 (92), 65 (20), 53 (27); Anal. Calcd for C14H16F3NO3S: C, 50.14; H,
4.81; N, 4.18. Found: C, 50.21; H, 4.78; N, 4.20%.
C19H20F3NO3S: C, 57.13; H, 5.05; N, 3.51. Found: C, 57.14; H, 5.05; N,
3.47%.
4.10. N-(1,1,1-Trifluoro-3-(benzyloxy)propan-2-yl)toluene-
4.6. N-(1,1,1-Trifluoro-3-(4-hydroxybut-2-ynyloxy)propan-2-
sulfonamide (4h)
yl)toluenesulfonamide (4e)
White solid; yield 82%; mp: 85.0e85.5 ꢀC; IR (KBr) 3248, 3036,
Colorless oil; yield 46%; IR (neat) 3491, 3278, 2926, 1599, 1447,
2950, 2862, 1600, 1333, 1290, 1240, 1180, 1091, 946, 814, 564 cmꢁ1
;
1335, 1162, 1019, 815, 665 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
7.77
1H NMR (CDCl3, 400 MHz)
d
7.73 (d, J¼7.8 Hz, 2H), 7.38e7.30 (m,
(d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H), 5.54 (d, J¼9.2 Hz, 1H), 4.32
(d, J¼5.6 Hz, 2H), 4.26e4.07 (m, 2H), 4.26e3.99 (m, 1H), 3.87e3.82
(m, 1H), 3.73e3.69 (m, 1H), 2.43 (s, 3H), 2.38e2.31 (m, 1H); 13C
3H), 7.28e7.22 (m, 4H), 5.31 (d, J¼8.4 Hz, 1H), 4.02 (s, 2H),
4.08e3.98 (m, 1H), 3.68 (dd, J¼10.4, 2.7 Hz, 1H), 3.51e3.45 (m, 1H),
2.42 (s, 3H); 13C NMR (CDCl3, 101 MHz)
d 143.9, 137.4, 136.8, 129.6,
NMR (CDCl3, 101 MHz)
d
144.0, 137.2, 129.6, 127.1, 123.8 (q,
128.5, 128.1, 127.7, 127.0, 124.0 (q, J¼282.6 Hz), 73.6, 66.1, 54.5 (q,
J¼282.6 Hz), 86.3, 80.2, 66.0, 59.1, 54.4 (q, J¼31.2 Hz), 50.8, 21.5; 19
F
J¼32.0 Hz), 21.5; 19F NMR (CDCl3, 376 MHz)
d
ꢁ74.7 (d, J¼8.1 Hz);
NMR (CDCl3, 376 MHz)
d
ꢁ74.6 (d, J¼8.2 Hz); GCeMS m/z 285 (1),
GCeMS m/z 281 (1), 266 (1), 252 (3), 218 (29), 186 (1), 155 (33), 112
(53), 92 (12), 91 (100), 65 (12); Anal. Calcd for C17H18F3NO3S: C,
54.68; H, 4.86; N, 3.75. Found: C, 54.73; H, 4.89; N, 3.77%.
266 (12), 196 (12), 178 (36), 155 (73), 139 (52), 112 (31), 91 (100), 69
(17), 65 (22); Anal. Calcd for C14H16F3NO4S: C, 47.86; H, 4.59; N,
3.99. Found: C, 47.73; H, 4.68; N, 3.93%.
4.11. N-(1,1,1-Trifluoro-3-(4-methoxybenzyloxy)propan-2-yl)
4.7. N-(1,1,1-Trifluoro-3-(4-(3,3,3-trifluoro-2-(toluenesulfony-
lamino)-propyloxy)-but-2-ynyloxy)propan-2-yl)toluenesulfo-
namide (4ee)
toluenesulfonamide (4i)
White solid; yield 74%; mp: 76.0e76.5 ꢀC; IR (KBr) 3263, 2962,
2914, 2876, 1613, 1513, 1332, 1258, 1175, 1093, 1032, 997, 948, 813,
Mixture of diastereomers; white solid; yield 52%; mp:
676, 549 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
7.72 (d, J¼7.9 Hz, 2H),
86.1e88.7 ꢀC; IR (KBr) 3270, 2926, 2254, 1927, 1599, 1444, 1277,
7.26 (d, J¼7.9 Hz, 2H), 7.16 (d, J¼8.4 Hz, 2H), 6.88 (d, J¼8.4 Hz, 2H),
5.30 (d, J¼9.4 Hz, 1H), 4.39 (s, 2H), 4.03e3.97 (m, 1H), 3.82 (s, 3H),
3.64 (dd, J¼10.2, 2.9 Hz, 1H), 3.47e3.41 (m, 1H), 2.42 (s, 3H); 13C
1128, 1020, 944, 815, 664 cmꢁ1 1H NMR (CDCl3, 400 MHz)
;
d
7.79e7.74 (m, 8H), 7.32e7.29 (m, 8H), 5.68 (d, J¼9.6 Hz, 2H), 5.52
(d, J¼9.6 Hz, 2H), 4.27e4.10 (m, 8H), 4.10e4.00 (m, 4H), 3.84e3.81
NMR (CDCl3, 101 MHz) d 159.5, 143.8, 137.4, 129.6, 129.3, 128.8,
(m, 4H), 3.76e3.70 (m, 4H), 2.43 (s,12H); 13C NMR (CDCl3,101 MHz)
127.0, 123.9 (q, J¼282.6 Hz), 113.9, 73.1, 65.6, 55.2, 54.4 (q,
d
143.90, 143.86, 129.6, 123.9 (q, J¼281.9 Hz), 82.42, 82.40, 66.11,
J¼31.2 Hz), 21.4; 19F NMR (CDCl3, 376 MHz)
d
ꢁ74.7 (d, J¼8.1 Hz);
66.06, 58.8, 54.4 (q, J¼31.1 Hz), 54.3 (q, J¼31.1 Hz), 21.5; 19F NMR
GCeMS m/z 403 (3, Mþ), 266 (1), 249 (4), 248 (33), 155 (6), 137
(CDCl3, 376 MHz)
d
ꢁ74.7-(-74.5) (m, 6F); GCeMS m/z 461 (2), 429
(100), 95 (121), 112 (13), 91 (31), 65 (8); Anal. Calcd for
C18H20F3NO4S: C, 53.59; H, 5.00; N, 3.47. Found: C, 53.36; H, 5.05; N,
3.47%.
(2), 333 (5), 281 (7), 266 (39), 207 (15), 178 (69), 155 (80), 139 (31),
91 (100); Anal. Calcd for C24H26F6N2O6S2: C, 46.75; H, 4.25; N, 4.54.
Found: C, 46.93; H, 4.18; N, 4.46%.
4.12. N-(1,1,1-Trifluoro-3-(3-methoxyphenyloxy)propan-2-yl)
4.8. N-(1,1,1-Trifluoro-3-(propen-3-yloxy)propan-2-yl)tolue-
toluenesulfonamide (4j)
nesulfonamide (4f)
White solid; yield 88%; mp: 98.5e100.0 ꢀC; IR (KBr) 3305, 2972,
White solid; yield 74%; mp: 106.3e107.5 ꢀC; IR (KBr) 3315, 3269,
1618, 1586, 1495, 1341, 1276, 1189, 1156, 972, 858, 818, 758, 676, 571,
1598, 1376, 1339, 1244, 1180, 1164, 1143, 1087, 933, 820, 661 cmꢁ1
;
545 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
7.75 (d, J¼8.0 Hz, 2H), 7.25
1H NMR (CDCl3, 400 MHz)
d
7.76 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz,
(d, J¼8.0 Hz, 1H), 7.14 (t, J¼8.2 Hz, 2H), 6.50 (ddd, J¼8.2, 2.4, 0.8 Hz,
1H), 6.33 (ddd, J¼8.2, 2.4, 0.8 Hz, 1H), 6.29 (t, J¼2.4 Hz, 1H), 5.54 (d,
J¼9.8 Hz, 1H), 4.22 (m, 1H), 4.11 (dd, J¼10.4, 3.5 Hz, 1H), 4.00e3.97
2H), 5.85e5.72 (m, 1H), 5.29 (d, J¼9.1 Hz, 1H), 5.26e5.18 (m, 2H),
4.07e3.95 (m, 1H), 3.93 (d, J¼5.7 Hz, 2H), 3.67 (dd, J¼10.3, 2.7 Hz,
1H), 3.48 (ddd, J¼10.3, 3.1, 1.2 Hz, 1H), 2.44 (s, 3H); 13C NMR (CDCl3,
(m, 1H), 3.76 (s, 3H), 2.40 (s, 3H); 13C NMR (CDCl3, 101 MHz)
d 160.8,
101 MHz)
d
143.8, 137.5, 133.4, 129.6, 126.9, 123.9 (q, J¼282.6 Hz),
158.7, 144.0, 137.3, 130.0, 129.7, 128.0, 124.1 (q, J¼282.6 Hz), 107.6,
117.9, 72.3, 65.8, 54.5 (q, J¼31.2 Hz), 21.4; 19F NMR (CDCl3, 376 MHz)
106.4, 101.2, 64.5, 55.3, 54.3 (q, J¼31.2 Hz), 21.5; 19F NMR (CDCl3,
d
ꢁ74.8 (d, J¼6.8 Hz); GCeMS m/z 323 (1, Mþ), 284 (1), 266 (33), 207
376 MHz)
d
ꢁ75.4 (d, J¼6.8 Hz); GCeMS m/z 389 (77, Mþ), 266 (76),
(5), 168 (35), 155 (100), 132 (18), 112 (32), 91 (99), 71 (13), 65 (21),
63 (4); Anal. Calcd for C13H16F3NO3S: C, 48.29; H, 4.99; N, 4.33.
Found: C, 48.54; H, 4.95; N, 4.38%.
155 (37), 139 (21), 125 (17), 124 (100), 107 (21), 92 (19), 91 (73), 77
(19); HRMS (FAB, m/z) Calcd for C17H18F3NO4S: 389.0909; Found:
389.0923.

Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
7453
4.13. N-(1,1,1-Trifluoro-3-(toluenesulfonylamino)propan-2-yl)
toluenesulfonamide (5a)
4.17. N-(1,1,1-Trifluoro-3-(dodecanylsulfanyl)propan-2-yl)tol-
uenesulfonamide (6a)
White solid; yield 91%; mp: 152.7e153.7 ꢀC; IR (KBr) 3298,
White solid; yield 80%; mp: 63.5e64.5 ꢀC; IR (KBr) 3300, 2924,
2854, 1600, 1453, 1338, 1272, 1175, 1159, 1120, 918, 814, 683 cmꢁ1
1H NMR (CDCl3, 400 MHz)
1598, 1327, 1295, 1251, 1161, 955, 925, 813, 665, 548 cmꢁ1
;
1H
;
NMR (CDCl3, 400 MHz)
d
7.76 (d, J¼8.2 Hz, 2H), 7.70 (d, J¼8.2 Hz,
d
7.75 (d, J¼8.0 Hz, 2H), 7.29 (d, J¼8.0 Hz,
2H), 7.33 (d, J¼8.2 Hz, 4H), 5.42 (d, J¼9.1 Hz, 1H), 4.88 (t, J¼6.4 Hz,
2H), 5.17 (d, J¼8.8 Hz, 1H), 4.10e4.07 (m, 1H), 2.76 (d, J¼5.9 Hz, 2H),
2.41 (t, J¼14.7 Hz, 2H), 2.41 (s, 3H), 1.52e1.46 (m, 2H), 1.31e1.29 (m,
1H), 4.00e3.93 (m, 1H), 3.30e3.20 (m, 1H), 3.20e3.10 (m, 1H),
2.45 (s, 6H); 13C NMR (DMSO-d6þCDCl3, 101 MHz)
d
141.72,
18H), 0.68 (t, J¼6.6 Hz, 3H); 13C NMR (CDCl3, 101 MHz)
d 143.9,
141.67, 137.2, 135.4, 128.2, 128.1, 125.5, 125.4, 53.4 (q, J¼29.6 Hz),
137.5, 129.6, 127.1, 124.2 (q, J¼282.6 Hz), 53.9 (q, J¼30.4 Hz), 31.9,
39.9, 20.12, 20.10, CF3 is obscure; 19F NMR (CDCl3, 376 MHz)
31.4, 29.1, 29.2, 29.3, 29.5, 29.5, 29.60, 29.61, 28.7, 22.7, 21.5, 1.41; 19
F
d
ꢁ75.1 (d, J¼6.9 Hz); GCeMS m/z 302 (1), 282 (1), 257 (5), 242
NMR (CDCl3, 376 MHz)
d
ꢁ75.7 (d, J¼6.8 Hz); GCeMS m/z 467 (3,
(1), 166 (81), 155 (57), 139 (16), 112 (21), 91 (100), 69 (46); HRMS
(FAB, m/z) Calcd for C17H20F3N2O4S2: 437.0817 (MHþ); Found:
437.0814.
Mþ), 312 (64), 215 (100), 199 (70), 172 (16), 155 (51), 91 (68); HRMS
(FAB, m/z) Calcd for C22H37F3NO2S2: 468.2218 (MHþ); Found:
468.2181.
4.18. N-(1,1,1-Trifluoro-3-(toluylsulfanyl)propan-2-yl)toluene-
sulfonamide (6b)
4.14. N-(1,1,1-Trifluoro-3-(N-phthalimidyl)propan-2-yl)tolue-
nesulfonamide (5b)
White solid; yield 94%; mp: 94.0e94.5 ꢀC; IR (KBr) 3217, 2926,
White solid; yield 89%; mp: 257.0e257.8 ꢀC; IR (KBr) 3263, 1780,
1906, 1599, 1493, 1378, 1338, 1274, 1158, 1114, 920, 810, 677,
1720, 1597, 1380, 1351, 1171, 1031, 952, 717, 667, 580, 551 cmꢁ1; 1H
559 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
7.71 (d, J¼8.5 Hz, 2H),
NMR (CDCl3, 400 MHz)
d
7.80e7.72 (m, 4H), 7.55 (d, J¼8.2 Hz, 2H),
7.25e7.20 (m, 4H), 7.10 (d, J¼7.8 Hz, 2H), 5.50 (d, J¼9.0 Hz, 1H),
6.95 (d, J¼8.0 Hz, 2H), 5.27 (d, J¼9.2 Hz, 1H), 4.37e4.22 (m, 1H),
3.96e3.85 (m, 2H), 2.13 (s, 3H); 13C NMR (DMSO-d6, 151 MHz)
4.11e4.01 (m, 1H), 3.14 (dd, J¼4.3, 14.3 Hz, 1H), 3.08e2.98 (m, 1H),
2.40 (s, 3H), 2.33 (s, 3H); 13C NMR (CDCl3, 101 MHz)
d 143.8, 137.8,
d
167.9, 143.3, 138.7, 135.1, 131.5, 123.0, 129.9, 126.0, 124.6 (q,
J¼283.9 Hz), 53.3 (q, J¼29.9 Hz), 36.7, 21.5; 19F NMR (CDCl3,
137.5, 131.5, 130.1, 130.0, 129.5, 127.0, 124.1 (q, J¼282.6 Hz), 54.3 (q,
J¼31.1 Hz), 34.8, 21.5, 21.0; 19F NMR (CDCl3, 376 MHz)
d
ꢁ75.8 (d,
376 MHz)
d
ꢁ76.4 (d, J¼6.8 Hz); GCeMS m/z 257 (57), 239 (3), 219
J¼6.8 Hz); GCeMS m/z 389 (50, Mþ), 266 (2), 218 (36), 203 (1), 155
(1), 160 (100), 155 (7), 133 (6), 104 (6), 91 (19), 77 (8), 65 (6); Anal.
Calcd for C18H15F3N2O4S: C, 52.43; H, 3.67; N, 6.79. Found: C, 52.31;
H, 3.67; N, 6.81%.
(7), 149 (4), 137 (100), 123 (8), 91 (35), 65 (10); Anal. Calcd for
C
17H18F3NO2S2: C, 52.43; H, 4.66; N, 3.60. Found: C, 52.49; H, 4.69;
N, 3.64%.
4.15. N-(1,1,1-Trifluoro-3-(2-pyrrolidonyl)propan-2-yl)tolue-
nesulfonamide (5c)
4.19. Dimethyl 2-(3,3,3-trifluoro-2-(toluenesulfonylamino)
propyl) malonate (7a)
White solid; yield 87%; mp: 244.0e244.2 ꢀC; IR (KBr) 3087,
White solid; yield 65%; mp: 92.0e93.3 ꢀC; IR (KBr) 3283, 2959,
1747, 1599, 1439, 1346, 1269, 1164, 1135, 967, 895, 816, 665 cmꢁ1; 1H
2899, 1930, 1651, 1549, 1428, 1345, 1264, 1179, 1130, 959, 821, 665,
570 cmꢁ1
;
1H NMR (CDCl3, 400 MHz)
d
7.74 (d, J¼8.0 Hz, 2H), 7.30
NMR (CDCl3, 400 MHz)
d
7.71 (d, J¼8.2 Hz, 2H), 7.28 (d, J¼8.2 Hz,
(d, J¼8.0 Hz, 2H), 5.78 (d, J¼7.6 Hz, 1H), 4.28e4.16 (m, 1H), 3.91 (dd,
J¼14.2, 10.7 Hz, 1H), 3.51 (dd, J¼8.4, 14.3 Hz, 1H), 3.37 (dd, J¼8.6,
14.3 Hz,1H), 3.19 (dd, J¼14.2, 3.3 Hz,1H), 2.42 (s, 3H), 2.39e2.30 (m,
2H), 5.21 (d, J¼9.5 Hz, 1H), 4.16e4.03 (m, 1H), 3.80 (s, 3H), 3.78 (s,
3H), 3.71 (dd, J¼8.8, 5.3 Hz, 1H), 2.42 (s, 3H), 2.11e2.01 (m, 2H); 13
C
NMR (CDCl3, 101 MHz) d 169.4, 168.7, 143.7, 137.3, 129.5,126.8, 124.3
2H), 2.09e1.90 (m, 2H); 13C NMR (CDCl3, 101 MHz)
d 175.3, 142.3,
(q, J¼281.8 Hz), 53.7 (q, J¼32.0 Hz), 52.9, 52.8, 47.1, 27.8, 21.3; 19F
137.9, 128.7, 125.7, 123.3 (q, J¼282.6 Hz), 52.3 (q, J¼29.6 Hz), 47.2,
NMR (CDCl3, 376 MHz)
d
ꢁ77.1 (d, J¼6.8 Hz); GCeMS m/z 366 (2),
40.5, 29.5, 20.5, 16.8; 19F NMR (CDCl3, 376 MHz)
d
ꢁ76.1 (d,
301 (12), 242 (75), 210 (48), 178 (32), 155 (52), 150 (12), 132 (10), 91
(100), 65 (19), 55 (10); Anal. Calcd for C15H18F3NO6S: C, 45.34; H,
4.57; N, 3.52. Found: C, 45.23; H, 4.43; N, 3.72%.
J¼6.8 Hz); GCeMS m/z 350 (1, Mþ), 253 (1), 195 (22), 179 (2), 155
(2), 99 (9), 98 (100), 91 (14), 70 (11), 65 (5); Anal. Calcd for
C
14H17F3N2O3S: C, 47.99; H, 4.89; N, 8.00. Found: C, 48.09; H, 4.92;
N, 8.09%.
4.20. Ethyl 2-(3,3,3-trifluoro-2-(toluenesulfonylamino)pro-
pyl)cyanoacetate (7b)
4.16. N-(1,1,1-Trifluoro-3-(N-indolyl)propan-2-yl)toluene-
sulfonamide (5d)
Mixture of diastereomers; colorless oil; yield 81%; IR (neat)
3272, 2987, 2257,1748,1599,1443, 1343,1266,1163,1138, 1094, 816,
White solid; yield 98%; mp: 152.5e153.5 ꢀC; IR (KBr) 3254,
665 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
d
7.77 (d, J¼8.4 Hz, 2H), 7.72
1596, 1466, 1342, 1270, 1249, 1191, 1159, 1129, 948, 725, 569 cmꢁ1
;
(d, J¼8.4 Hz, 2H), 7.35e7.29 (m, 4H), 5.40 (d, J¼10.0 Hz, 1H), 5.34 (d,
J¼10.0 Hz, 1H), 4.40e4.28 (m, J¼4H), 4.25e4.10 (m, 1H), 4.10e4.00
(m, 1H), 3.95e3.85 (m, 2H), 2.56e2.48 (m, 1H), 2.44 (s, 6H),
2.39e2.21 (m, 2H), 2.10e2.00 (m, 1H), 1.40e1.31 (m, 6H); 13C NMR
1H NMR (CDCl3, 400 MHz)
d
7.54 (d, J¼8.1 Hz, 1H), 7.42 (dd,
J¼8.2 Hz, 2H), 7.23e7.17 (m, 2H), 7.13e7.04 (m, 1H), 7.06 (d,
J¼8.2 Hz, 2H), 6.92 (d, J¼3.1 Hz, 1H), 6.39 (dd, J¼3.1, 0.8 Hz, 1H),
4.89 (d, J¼9.4 Hz, 1H), 4.50 (dd, J¼14.3, 3.7 Hz, 1H), 4.38e4.26 (m,
(CDCl3, 101 MHz) d 165.2, 165.0, 144.4, 144.3, 136.53, 136.49, 129.83,
2H), 2.35 (s, 3H); 13C NMR (DMSO-d6, 151 MHz)
d
143.8, 136.3,
129.77, 127.14, 127.06, 124.0 (q, J¼281.8 Hz), 123.9 (q, J¼282.6 Hz),
135.9, 129.5, 128.8, 128.1, 126.4, 123.0 (q, J¼282.6 Hz), 122.3, 121.1,
63.7, 63.6, 53.4 (q, J¼31.9 Hz), 53.2 (q, J¼31.9 Hz), 33.6, 31.9, 29.53,
120.0, 108.7, 102.9, 54.9 (q, J¼30.4 Hz), 45.2, 21.5; 19F NMR (CDCl3,
29.52, 21.5, 13.8; 19F NMR (CDCl3, 376 MHz)
d
ꢁ76.9 (d, J¼6.9 Hz,
376 MHz)
d
ꢁ75.4 (d, J¼6.8 Hz); GCeMS m/z 382 (26, Mþ), 383 (6),
3F), ꢁ76.8 (d, J¼6.9 Hz, 3F); GCeMS m/z 378 (12, Mþ), 333 (3), 306
(8), 268 (3), 242 (6), 223 (24), 177 (4), 155 (51), 91 (100), 65 (16);
Anal. Calcd for C15H17F3N2O4S: C, 47.62; H, 4.53; N, 7.40. Found: C,
47.30; H, 4.57; N, 7.16%.
131 (11), 130 (100), 103 (5), 91 (5), 77 (5); Anal. Calcd for
C
18H17F3N2O2S: C, 56.54; H, 4.48; N, 7.33. Found: C, 56.74; H, 4.57;
N, 7.40%.

7454
Y. Takehiro et al. / Tetrahedron 69 (2013) 7448e7454
4.21. 4,4,4-Trifluoro-3-(toluenesulfonylamino)-1,1-
Cambridge Crystallographic Data Centre, 12, Union Road, Cam-
bis(phenylsulfonyl)butane (7c)
bridge CB2 1EZ, UK; fax: þ44 1223 336033.
White solid; yield 68%; mp: 178.5e180.0 ꢀC; IR (KBr) 3313, 2926,
Acknowledgements
1586, 1449, 1332, 1163, 1091, 946, 741, 663, 576 cmꢁ1 1H NMR
;
(CDCl3, 400 MHz)
d
8.01 (d, J¼8.4 Hz, 2H), 7.92 (d, J¼8.3 Hz, 2H),
We greatly thank TOSOH F-TECH, Inc. for a gift of 2-bromo-3,3,3-
trifluoropropene and Central Glass Co., Ltd for a gift of tri-
fluoromethanesulfonic acid. We are grateful to Prof. Junji Inanaga at
Institute for Materials Chemistry and Engineering, Kyushu Univer-
sity for helpful discussion. This work was performed under the
Cooperative Research Program of ‘Network Joint Research Center
for Materials and Devices’.
7.75e7.68 (m, 4H), 7.56 (t, J¼7.7 Hz, 4H), 7.31 (d, J¼8.2 Hz, 2H), 5.14
(d, J¼7.5 Hz, 1H), 5.01 (d, J¼10.2 Hz, 1H), 4.23e4.10 (m, 1H), 2.71
(dd, J¼7.6, 2.3 Hz, 1H), 2.48e2.40 (m, 1H), 2.43 (s, 3H); 13C NMR
(CDCl3, 101 MHz)
d 144.5, 137.5, 136.8, 136.2, 134.9, 134.7, 129.8,
129.6, 129.5, 129.4, 129.2, 127.3, 123.8 (q, J¼282.6 Hz), 77.0, 54.3 (q,
J¼31.2 Hz), 25.0, 21.6; 19F NMR (CDCl3, 376 MHz)
d
ꢁ77.1 (d,
J¼7.8 Hz, 3F); GCeMS m/z 406 (10), 350 (4), 264 (100), 155 (32), 143
(32), 141 (24), 125 (72), 91 (82), 77 (61), 65 (15), 51 (11); Anal.
Calcd for C23H22F3NO6S3: C, 49.19; H, 3.95; N, 2.49. Found: C, 49.29;
H, 3.88; N, 2.49%.
Supplementary data
Spectral data for new compounds are available. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.06.044.
4.22. 1,4-Ditosyl-2,5-bis(trifluoromethyl)piperazine (8)
References and notes
A 25 mL two-necked flask equipped with a magnetic stir bar,
a stopcock, and a three-way stopcock, was charged with CsF
(27.5 mg, 0.181 mmol). After heating the flask with a heat gun
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9586e9593; (e) Crousse, B.; Narizuka, S.; Bonnet-Delpon, D.; Begue, J.-P.
Synlett 2001, 679e681; (f) Katagiri, T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.;
Uneyama, K. J. Org. Chem. 1999, 64, 7323e7329; (g) Katagiri, T.; Ihara, H.;
Takahashi, M.; Kashino, S.; Funuhashi, K.; Uneyama, K. Tetrahedron: Asym-
metry 1997, 8, 2933e2937; (h) Quinze, K.; Mison, A. J. Fluorine Chem. 1989,
44, 233e265.
under reduced pressure for 10 min, the mixture allowed to cool to
t
room temperature. To this mixture was added BuOTMS (34.8
mL,
0.181 mmol) and DMSO (1 mL) and the mixture warmed to 60 ꢀC for
30 min. To the mixture was added N-Ts-2-CF3-aziridine 1 (32.0 mg,
0.121 mmol) and the mixture warmed to 80 ꢀC for 24 h. The re-
action was quenched by the addition of saturated aqueous am-
monium chloride solution. The aqueous layer was extracted with
EtOAc. An additional extraction was repeated twice. The combined
organic solution was dried over Na2SO4, filtered, and concentrated
in vacuo. The resulting dark brown solid attached on the inner wall
of the flask was very carefully washed with hexane/EtOAc¼3/1
several times then acetone one time to give 8 as a white solid
(10.5 mg, 33%): mp: 274.2e275.8 ꢀC; IR (KBr) 1598, 1384, 1343,
1298, 1248, 1160, 971, 817, 695, 639, 575 cmꢁ1
400 MHz)
7.66 (d, J¼8.2 Hz, 4H), 7.30 (d, J¼8.2 Hz, 4H), 4.59e4.49
(m, 2H), 4.23 (d, J¼14.1 Hz, 2H), 3.55 (dd, J¼14.1, 3.4 Hz, 2H), 2.43 (s,
;
1H NMR (CDCl3,
d
6H); 13C NMR (DMSO-d6, 101 MHz)
d 144.3, 136.2,130.0, 127.3, 124.6
(q, J¼288.0 Hz), 50.1 (q, J¼29.6 Hz), 21.2, NCH2 is obscure; 19F NMR
(CDCl3, 376 MHz)
d
ꢁ70.5 (d, J¼6.8 Hz); GCeMS m/z 530 (5, Mþ),
461 (4), 429 (2), 375 (53), 355 (3), 306 (10), 281 (10), 207 (20), 155
(100), 91 (97), 65 (14); Anal. Calcd for C20H20F6N2O4S2: C, 45.28; H,
3.80; N, 5.28. Found: C, 45.11; H, 3.70; N, 5.20%.
ꢁ
ꢁ
4.23. Crystal data for 8
5. (a) Maeda, R.; Ishibashi, R.; Kamaishi, R.; Hirotaki, K.; Furuno, H.; Hanamoto, T.
Org. Lett. 2011, 13, 6240e6243; (b) Maeda, R.; Ooyama, K.; Anno, R.; Shiosaki,
M.; Azema, T.; Hanamoto, T. Org. Lett. 2010, 12, 2548e2550.
6. Wang, L.; Liu, Q.-B.; Wang, D.-S.; Li, X.; Han, X.-W.; Xiao, W.-J.; Zhou, Y.-G. Org.
Lett. 2009, 11, 1119e1122.
(C20H20F6N2O4S2): M¼530.52, T¼143 (2) K, triclinic, space group
3
ꢀ
ꢀ
ꢀ
ꢀ
Pꢁ1, a¼6.084 (5) A, b¼8.217 (9) A, c¼11.308 (9) A, V¼540.0 (9) A ,
Z¼1, Dx¼1.631 Mg mꢁ3, m¼0.330 mmꢁ1, l¼0.71073 A, qmax¼27.44ꢀ,
ꢀ
5442 measured reflection, 2453 independent reflections, 194 re-
fined parameters, GOF¼0.991, R[F2>2s(F2)]¼0.1672, wR(F2)¼0.1849.
The intensity data were collected on a Rigaku RAXIS-RAPID dif-
fractometer. The structure was solved by direct methods
(SIR200410) and the non-hydrogen atoms were refined anisotrop-
ically by full-matrix least-squares procedures on F2 for all re-
ductions (SHELXL9711). Some hydrogen atoms were determined by
difference Fourier synthesis, and others were positioned geo-
metrically and refined as riding. CCDC-919854 contains the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif,
or by emailing data_request@ccdc.cam.ac.uk, or by contacting The
7. Compared with the reactivity of the corresponding 2-isopropyl-N-Ts aziridine
with a propargyl alcohol under basic conditions, that of 2-trifluoromethyl-N-Ts
aziridine 1 is relatively high. See Ref. 6 in SD.
8. (a) Trinchera, P.; Musio, B.; Degennaro, L.; Moliterni, A.; Falcicchio, A.; Luisi, R.
Org. Biomol. Chem. 2012, 10, 1962e1965; (b) Shainyan, B. A.; Moskalik, M. Y.;
Starke, I.; Schilde, U. Tetrahedron 2010, 66, 8383e8386.
9. In the GCeMS spectrum of the crude reaction mixture that contained 9, a major
peak appeared at m/z¼375 (MþꢁTs), M¼530 (C20H20F6N2O4S2). The crude 1H
NMR spectrum showed two vinyl proton signals at 6.21 (s, 1H) and 6.14e6.12
(m, 1H), respectively. The crude 19F NMR displayed two CF3 signals at ꢁ66.2 (s,
3F) and ꢁ75.7 (d, J¼6.8 Hz, 3F), respectively.
10. Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.; Cascarano, G. L.; De Caro,
L.; Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 2005, 38, 381e388.
11. Sheldrick, G. M. SHELXL-97, Program for Refinement of Crystal Structures;
€
University of Gottingen, 1997.