Synthesis of optically active trifluoromethyl substituted diaziridines and oxaziridines

Article abstract of DOI:10.1016/j.tet.2011.05.097

(E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent. Sim

Full text of DOI:10.1016/j.tet.2011.05.097

Tetrahedron 67 (2011) 5375e5381
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Tetrahedron
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Synthesis of optically active trifluoromethyl substituted diaziridines
and oxaziridines
*
*
Laura Carroccia, Stefania Fioravanti , Lucio Pellacani , Claudia Sadun, Paolo A. Tardella
ꢀ
Dipartimento di Chimica, Universita degli Studi ‘La Sapienza’, P.le Aldo Moro 5, I-00185 Roma, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
(E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding
diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction
was strongly controlled by the N-substituent. Similar results were obtained in the epoxidation reactions
performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral
diaziridines or oxaziridines were obtained with very high enantiopurity.
Received 14 March 2011
Received in revised form 5 May 2011
Accepted 23 May 2011
Available online 30 May 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Amination
Diastereoselectivity
Small heterocycles
1. Introduction
NsONHCO2Et in CH2C12 without added base at room temperature
to give the corresponding diaziridines 2aej. The results are repor-
The presence in a molecule of fluorine atoms often leads to
relevant modifications in the chemical and biological properties
compared with unfluorinated parent compounds.1 For some years
now, a noteworthy development of methodologies to synthesize
fluorinated organic compounds was observed, focusing the atten-
tion in particular on the preparation of trifluoromethylated sys-
tems2 One of the most interesting aspects of organofluorine
chemistry is that of asymmetric reactions often coupled with the
unexpected reactivity and stereochemical outcome, due to the
strongly electronegative nature of fluorine atoms, which can
modify the asymmetric course of reactions.3
In this field, we have reported the results obtained by alkyl
nosyloxycarbamates (NsONHCO2R, Ns¼4-NO2C6H4SO2) in the di-
rect amination reaction of different trifluoromethylated com-
pounds,4 stressing the different reactivity observed with respect to
the analogous unfluorinated compounds.5
ted in Table 1.
In all cases, trifluoromethyl substituted diaziridines 2 were
obtained in high yields7 with total retention of the starting imine
configurations as confirmed by NMR spectroscopy, and no further
purifications were required after the work-up.
As we have previously reported,7 the synthesis of diaziridines 2
could be explained either by the involvement of (ethoxycarbonyl)
nitrene (:NCO2Et, via a) or by a nucleophilic addition to imine
carbon followed by a ring closure reaction (via b) involving an ionic
pathway (Scheme 1).
To gain more information, imines 1a,c were successfully tested
in the amination reactions with NsONHCO2t-Bu (Scheme 2), a car-
bamate, that is, known to give amination reactions only by an ionic
pathway involving the corresponding aza-anion.8
Furthermore, a high regioselectivity was observed in the one-
pot synthesis of the trifluoromethyl diaziridine 2k (Scheme 3),
starting from trifluoroacetaldehyde ethyl hemiacetal (90% aq so-
lution) and allylamine, strengthening the hypothesis that the re-
action proceeds by an ionic pathway.
Continuing our studies, we would like to report the reactivity of
different trifluoromethyl imines6 in the amination reaction per-
formed by using NsONHCO2Et as aminating agent, focusing on the
diastereoselective course of the reaction.
Very interesting is the diastereoselective outcome of the ami-
nation reaction, as determined by 1H NMR spectroscopy performed
on the crude products.
2. Results and discussion
As shown in Table 1, the stereoselective induction appears to
be controlled by steric or electronic effects present on the
b- or
Inspired by our previous studies performed on unfluorinated
imines,7 compounds (E)-1aej were reacted with a twofold excess of
a-carbon of the aminic residue. In fact, while the presence of a tert-
butyl group (entry 7) leads to the diastereomeric diaziridines with
a 1.7:1 dr, 2e was obtained as a 1:1 diastereomeric mixture (entry 5)
and the isopropyl group leads to an induction decrease (entry 6). In
* Corresponding authors. Fax: þ39 06490631; e-mail addresses: stefania.fior-
avanti@uniroma1.it (S. Fioravanti), lucio.pellacani@uniroma1.it (L. Pellacani).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.097

5376
L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
Table 1
contrast, the same group present in the
induction (entry 8). Finally, a very good diastereomeric induction
was observed when the phenyl group is present in the position
(entry 10), but if the same group is present in the position a re-
versal of induction was observed leading to a 1:1.7 mixture of di-
astereomers (entry 9).
g position does not give any
Synthesis of trifluoromethyl diaziridines
R
R
N
H
a
NsONHCO2Et
CH2Cl2, rt, 16 h
N
N
CO2Et
b
F3C
H
1a-j
F3C
molar ratio
2a-j
1:NsONHCO2Et = 1:2
To exclude a possible influence of the CF3 group on the stereo-
chemical outcome of the aziridination reaction, imine 3, an
unfluorinated analogue of 1g, was reacted with NsONHCO2Et
(Scheme 4), and even in this case, the corresponding diaziridines 4
were obtained as a diastereomeric mixture (dr¼1.7:1), as de-
termined by its 1H NMR spectrum.
Entry
2
R
Yield %
dra
1
2
a
48
40
d
d
Ph
b
3
4
5
c
50
50
49
d
7
4
NsONHCO2Et
CH2Cl2, rt, 16 h
N
t-Bu
N
t-Bu
N
H
CO2Et
d
e
d
H3C
H
H3C
molar ratio
3
4 (42% yield)
dr = 1.7:1
3:NsONHCO2Et = 1:2
1:1
Scheme 4. Aziridination reaction of unfluorinated imine 3.
6
7
f
37
38
1.3:1
1.7:1
Starting from these results, optically pure trifluoromethyl im-
ines (R)- and (S)-1g,j were considered as suitable substrates to
obtain the corresponding enantiopure diaziridines and the results
are reported in Table 2.
g
Table 2
Synthesis of chiral trifluoromethyl diaziridines
8
9
h
i
44
40
1:1
R*
R*
N
H
N
NsONHCO2Et
CH2Cl2, rt, 16 h
*N
*
CO2Et
F3C
H
Ph
Ph
F3C
1:1.7
molar ratio
imine:NsONHCO2Et =1:2
dra
10
j
35
100:1
Entry
1
Imine
R
Diaziridine
Yield %
a
By 1H NMR spectroscopy.
(R,S,S)-2g
(R,R,R)-2g
(R)-1g
49
44
48
2.5:1
H
N
-NsO-
a
N
CO2Et
1
NsO
CO2Et
R
R
N
H
(S,R,R)-2g
(S,S,S)-2g
N
+
N
2
3
(S)-1g
(R)-1j
2:1
CO2Et
NsO
CO2Et
b
R
H
N
EtO2C
NsO
N
1
F3C
N
F3C
H
-NsO-
Ph
Ph
(R,S,S)-2j
(R,R,R)-2j
F3C
1
2
100:1
Scheme 1. Possible pathways for the aziridination reaction.
(S,R,R)-2j
(S,S,S)-2j
4
(S)-1j
35
100:1
a
By 1H and 19F NMR spectroscopy.
R
H
R
NsONHBoc
N
N
N Boc
H
The diastereomeric mixtures were separated by HPLC and
enantiomerically pure trifluoromethyl diaziridines were obtained.
Based on data reported in the literature for trifluoromethyl
aziridines,9 the absolute configuration of the obtained compounds
was deduced from 2D-NOESY correlations performed on purified
(R,S,S)- and (R,R,R)-2g. While no NOE interactionwas observed in the
minor isomer, a significant NOE interaction between (CH3)3eC and
CH2Cl2, rt, 12 h
F3C
F3C
molar ratio
1:NsONHBoc = 1:2
1a, R = Bn
1c, R = -(CH2)7Me
2a' (42% yield)
2c' (44% yield)
Scheme 2. Amination reactions with NsONHCO2t-Bu.
Ha (at
d 3.60) was detected in the major isomer, suggesting a 2S,3S
absolute configuration for the diaziridine ring of the latter (Fig. 1).10
Consequently, the absolute configurations for all other di-
astereomers were assigned on the basis of the above reported
NOE data.
H2N
HO OEt
N
NsONHCO2Et
CH2Cl2, rt, 24 h
N
N
H
CO2Et
solvent-free
105 °C
F3C
H
F3C
H
F3C
Then, the synthesis of trifluoromethyl oxaziridines was con-
sidered, as an interesting extension of our studies. It is known that
oxaziridines exhibit a remarkable stability11 and can be used as
both oxygenating and aminating agents in reactions with a wide
2k (40% yield)
molar ratio
allyl amine:NsONHCO2Et = 1:2
Scheme 3. Regioselectivity in the amination giving trifluoromethyl diaziridine 2k.

L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
5377
Fluorinated oxaziridines are oxidants effective almost as much
as dioxiranes and certainly more effective than unfluorinated an-
alogues, as a consequence of the strong electron-withdrawing ef-
fect of fluoroalkyl groups.13a So, the optically pure oxaziridines can
be regarded as interesting enantiopure oxygenating agents to be
used in different reactions.16
3. Conclusions
In conclusion, trifluoromethyl aziridines can be prepared in
a diastereoselective manner by direct aziridination of the corre-
sponding imines. While in the past,4 we observed a significant CF3
group effect on the reactions between different trifluoromethyl
alkenes and nosyloxycarbamates, the presence of the same group
on the C]N bond does not seem to influence the outcome of the
aziridination reactions, probably due to the major polarization of
imine bond with respect to the C]C bond. A strong influence on
the diastereoselective course of the reaction seems to be exerted by
Fig. 1. Diaziridine (R,S,S)- and (R,R,R)-2g. NOE interaction and optimized geometries of
both diastereomers.
variety of nucleophiles. On the other hand, these compounds,
characterized by a reactive strained C,N,O three-membered ring,
are very interesting reagents for their potential use in asymmetric
induction,12 and especially perfluorinated oxaziridines have been
reported as effective and versatile oxidizing agents toward different
substrates.13 Recently N-unsubstituted oxaziridines were employed
as sources of electrophilic nitrogen.14
steric or electronic effects on the
b- or a-carbon of the aminic
residue. The same stereochemical trend was observed in the ep-
oxidation reactions, obtaining the synthesis, also as pure enantio-
mers, of potentially effective oxygenating agents.
The epoxidation reaction15 was tested first on the imine 1b and
then on the imines 1feh, using m-CPBA as oxidant. The results are
reported in Table 3.
4. Experimental section
4.1. General
Table 3
Synthesis of chiral trifluoromethyl diaziridines
IR spectra were recorded on a PerkineElmer 1600 FTIR spec-
trophotometer in CHCl3 as the solvent. 1H NMR and 13C NMR
spectra were recorded on a Varian XL-300 instrument at 300 and
75 MHz, respectively. CDCl3 was used as the solvent and CHCl3 as
the internal standard. 19F NMR spectra were recorded at 282.2 MHz
with a Varian XL-300 instrument, using CDCl3 as the solvent and
C6F6 as the internal standard; chemical shifts are given in parts per
million relative to CFCl3. The NOE experiments were performed at
400 MHz with a Bruker Advanced-three spectrometer using CDCl3
as the solvent and CHCl3 as the internal standard. HRMS analyses
were performed using a Micromass Q-TOF Micro quadrupole-time
of flight (TOF) mass spectrometer equipped with an ESI source and
a syringe pump. The experiments were conducted in the positive
ion mode. HPLC analyses were performed with a Varian 9002 in-
strument equipped with a Varian 9050 RI-4 differential re-
fractometer or UV/vis detector using an analytical column
(3.9ꢀ300 mm, flow rate 1.3 mL/min). Eluents were HPLC grade.
Optical rotations were recorded at the Sodium D line with a Jasco
Model DIP-370 polarimeter at room temperature, using a quartz
cell of 1 cm lenght. The diastereomers (R,S,S)- and (R,R,R)-2g were
separated by HPLC using 9:1 hexane/ethyl acetate mixture (flow
1.3 mL/min) as the eluent. The diastereomers (R,S,S)- and (R,R,R)-5g
were separated by flash chromatography (silica gel, pentane/
dichloromethane¼9.5:0.5). The synthesis of imines6 1aed,f,h, (R)-
1g,j, NsONHCO2Et,17 and NsONH/Boc18 were performed following
reported procedures.
R
R
O
H
N
N
m-CPBA
CH2Cl2, 0 °C
F3C
H
F3C
5
1
equimolar ratio
Entry
1
Imine
R
Oxaziridine
Time h
20
Yield %
76
dra
1b
5b
d
2
3
1f
5f
3
4
90
79
3.3:1
5:1
1g
5g
4
5
1h
5h
2
2
80
84
1.4:1
5:1
(R,S,S)-5g
(R,R,R)-5g
(R)-1g
(S,R,R)-5g
(S,S,S)-5g
6
(S)-1g
2
87
5:1
a
By 1H NMR spectroscopy.
4.2. General procedure for the synthesis of (E)-trifluoromethyl
imines (1)
As reported in Table 3, the expected compounds were obtained
in good yield, the diastereoselectivity observed being related to the
steric hindrance of the N-substituent (entries 2e4). In comparison
to the aziridinations, the epoxidation reactions require shorter
times and occur in all cases with a higher diastereoselectivity.
Furthermore, the epoxidation reactions performed on enantiopure
imines (R)- and (S)-1g lead to the corresponding fluorinated oxa-
ziridines (R,S*,S*)- and (S,R*,R*)-5g with very high diaster-
eoselectivity (entries 5e6). Products (R,S,S)- and (R,R,R)-5g were
obtained as pure enantiomers after an easy purification.
A stirred equimolar solution (10 mmol) of trifluoroacetaldehyde
ethyl hemiacetal (90% aq solution) and different primary amines
was heated under solvent-free conditions in a flask fitted with
a calcium chloride tube.
4.2.1. N-[(E)-2,2,2-Trifluoroethylidene]pentan-2-amine
(1e). External bath: 105 ꢁC; reaction time: 3 h; 1.22 g; 73% yield;
yellow oil; IR: 1688 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼0.88 (t,
3J¼7.3 Hz, 3H) 1.00e1.05 (m, 2H), 1.22 (d, 3J¼6.3 Hz, 3H), 1.28e1.66

5378
L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
(m, 2H), 3.31e3.42 (m, 1H), 7.60 (3JHeF¼3.4 Hz, 1H); 13C NMR
4.3.1. Ethyl 2-benzyl-3-(trifluoromethyl)diaziridine-1-carboxylate
(75 MHz, CDCl3):
d
¼13.7, 19.3, 21.6, 39.0, 65.6, 119.0 (q,
(2a). Orange oil; 0.13 g; IR: 1605, 1735 cmꢂ1 1H NMR (300 MHz,
;
2
1JCeF¼274.6 Hz, CF3), 147.3 (q, JCeF¼37.6 Hz, CCF3); 19F NMR
CDCl3):
d
¼1.27 (t, 3J¼6.6 Hz, 3H), 3.57 (q, 3J¼4.3 Hz, 1H), 3.77 (d,
3
(282.2 MHz, CDCl3):
d
¼ꢂ72.1 (d, JFeH¼3.5 Hz, 3F); HRMS: m/z
2J¼13.3 Hz, 1H), 3.97 (d, 2J¼13.3 Hz, 1H), 4.05e4.34 (m, 2H),
[MþNa]þ calcd for C7H12F3NNa: 190.0820; found: 190.0819.
7.31e7.41 (m, 5H); 13C NMR (75 MHz, CDCl3):
d
¼13.8, 58.4 (q,
2JCeF¼41.0 Hz, CeCF3), 63.6, 63.8, 121.6 (q, JCeF¼277.4 Hz, CF3),
1
4.2.2. 3,3-Dimethyl-N-[(E)-2,2,2-trifluoroethylidene]butan-2-amine
(1g). External bath: 110 ꢁC; reaction time: 30 min; 1.50 g; 83%
128.2, 128.5 (2C), 128.8 (2C), 132.2, 159.2; 19F NMR (282.2 MHz,
CDCl3):
d
¼ꢂ72.2 (d, 3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþH]þ calcd for
yield; colorless oil; IR: 1682 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
C12H14F3N2O2: 275.1007; found: 275.1009.
d
¼0.88 (s, 9H), 1.13 (d, 3J¼6.5 Hz, 3H), 3.01 (q, 3J¼6.5 Hz, 1H), 7.57
(3JHeF¼3.4 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d
¼16.7, 26.2 (3C),
4.3.2. Ethyl 2-cyclopentyl-3-(trifluoromethyl)diaziridine-1-
1
2
33.9, 74.8, 119.0 (q, JCeF¼274.9 Hz, CF3), 147.2 (q, JCeF¼38.2 Hz,
carboxylate (2b). Yellow oil; 0.10 g; IR: 1737 cmꢂ1 1H NMR
;
CeCF3); 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.4 (d, JFeH¼3.3 Hz,
(300 MHz, CDCl3):
d
¼1.29 (t, 3J¼7.1 Hz, 3H), 1.56e2.02 (m, 8H),
3
3F); HRMS: m/z [MþNa]þ calcd for C8H14F3NNa: 204.0976; found:
2.51e2.58 (m,1H), 3.45 (q, 3JHeF¼4.3 Hz,1H), 4.10e4.31 (m, 2H); 13
C
204.0981.
NMR (75 MHz, CDCl3):
d
¼13.8, 24.3, 24.6, 28.8, 31.6, 58.3 (q,
2JCeF¼39.0 Hz, CeCF3), 63.5, 70.8, 120.2 (q, JCeF¼275.0 Hz, CF3),
1
4.2.3. 1-Phenyl-N-[(E)-2,2,2-trifluoroethylidene]propan-2-amine
(1i). External bath: 105 ꢁC, reaction time: 6 h; 1.96 g; 91% yield;
159.3; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.5 (d, 3JFeH¼4.3 Hz, 3F);
HRMS: m/z [MþNa]þ calcd for C10H15F3N2NaO2: 275.0983; found:
275.0988, m/z [MþH]þ calcd for C10H16F3N2O2: 253.1164; found:
253.1170.
yellow oil; IR: 1687 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼1.35 (d,
3J¼7.0 Hz, 3H), 3.21 (sextet, 3J¼7.0 Hz, 1H), 3.73e3.77 (m, 2H),
7.15e7.36 (m, 5H), 7.38e7.42 (m, 1H); 13C NMR (75 MHz, CDCl3):
d
¼18.9, 40.0, 67.7, 118.6 (q, 1JCeF¼274.8 Hz, CF3), 126.6, 127.2 (2C),
4.3.3. Ethyl 2-octyl-3-(trifluoromethyl)diaziridine-1-carboxylate
128.5 (2C), 143.8, 149.8 (q, JCeF¼38.0 Hz, CeCF3); 19F NMR
(2c). Yellow oil; 0.15 g; IR: 1743 cmꢂ1 1H NMR (300 MHz,
;
2
3
(282.2 MHz, CDCl3):
d¼ꢂ71.9 (d, JFeH¼3.5 Hz, 3F); HRMS: m/z
CDCl3):
d
¼0.87 (t, 3J¼6.6 Hz, 3H), 1.19e1.42 (m, 13H), 1.56e1.76 (m,
[MþNa]þ calcd for C11H12F3NNa: 238.0820; found: 238.0828.
2H), 2.51e2.77 (m, 2H), 3.44 (q, JHeF¼4.3 Hz, 1H), 4.19e4.32 (m,
3
2H); 13C NMR (75 MHz, CDCl3):
d¼13.9, 14.0, 22.6, 26.8, 27.7, 29.1,
2
4.2.4. 1-Phenyl-N-[(Eꢁ)-2,2,2-trifluoroethylidene]ethanamine
29.3, 31.9, 59.2 (q, JCeF¼40.0 Hz, CeCF3), 60.6, 63.7, 121.6 (q,
(1j). External bath: 115 C; reaction time: 90 min; 1.51 g; 75% yield;
1JCeF¼277.0 Hz, CF3), 159.4; 19F NMR (282.2 MHz, CDCl3):
¼ꢂ71.8
d
yellow oil; IR: 1687 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼1.59 (d,
(d, 3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for
3J¼6.7 Hz, 3H), 4.61 (q, 3J¼6.7 Hz, 1H), 7.27e7.40 (m, 5H), 7.65
C13H23F3N2NaO2: 319.1609; found: 319.1613.
(3JHeF¼3.4 Hz,1H); 13C NMR (75 MHz, CDCl3):
¼23.8, 68.7, 119.0 (q,
d
1JCeF¼274.9 Hz, CF3), 126.6 (2C), 127.6, 128.7 (2C), 142.2, 148.0 (q,
4.3.4. Ethyl 2-pentyl-3-(trifluoromethyl)diaziridine-1-carboxylate
2JCeF¼38.2 Hz, CeCF3); 19F NMR (282.2 MHz, CDCl3):
d¼ꢂ72.0 (d,
(2d). Colorless oil; 0.13 g; IR: 1741 cmꢂ1 1H NMR (300 MHz,
;
3JFeH¼3.5 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C10H10F3NNa:
CDCl3):
d
¼0.9 (t, 3J¼7.1 Hz, 3H), 1.21e1.46 (m, 7H), 1.62e1.72 (m,
3
224.0663; found: 224.0670.
2H), 2.54e2.72 (m, 2H), 3.44 (q, JHeF¼4.4 Hz, 1H), 4.18e4.36 (m,
2H); 13C NMR (75 MHz, CDCl3):
d
¼13.8,13.9, 22.4, 27.3, 28.9, 59.2 (q,
1
4.2.5. (2S)-3,3-Dimethyl-N-[(E)-2,2,2-trifluoroethylidene]butan-2-
amine [(S)-1g]. External bath: 110 ꢁC; reaction time: 1 h; 1.28 g;
2JCeF¼40.0 Hz, CeCF3), 60.5, 63.7, 121.6 (q, JCeF¼277.0 Hz, CF3),
159.5; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ71.8 (d, 3JFeH¼4.4 Hz, 3F);
25
71% yield; colorless oil; [
a
]
þ35.8 (c 1.9, CHCl3); IR (CHCl3):
HRMS: m/z [MþNa]þ calcd for C10H17F3N2NaO2: 277.1140; found:
277.1139; m/z [MþH]þ calcd for C10H18F3N2O2: 255.1320; found:
255.1328.
D
1681 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼0.88 (s, 9H), 1.13 (d,
3J¼6.5 Hz, 3H), 3.01 (q, 3J¼6.5 Hz, 1H), 7.57 (3JHeF¼3.4 Hz, 1H); 13
C
NMR (75 MHz, CDCl3):
d
¼16.7, 26.2 (3C), 33.9, 74.8, 118 (q,
1JCeF¼274.9 Hz, CF3), 147.2 (q, JCeF¼37.8 Hz, CeCF3); 19F NMR
4.3.5. Ethyl 2-(1-methylbutyl)-3-(trifluoromethyl)diaziridine-1-
2
3
(282.2 MHz, CDCl3):
d
¼ꢂ72.6 (d, JFeH¼3.3 Hz, 3F); HRMS: m/z
carboxylate (2e). Orange oil; 0.12 g; IR: 1748 cmꢂ1 1H NMR
;
[MþNa]þ calcd for C8H14F3NNa: 204.0976; found: 204.0974.
(300 MHz, CDCl3):
d
¼0.90 (t, 3J¼7.1 Hz, 3H, diastereomer I), 0.91 (t,
3J¼7.3 Hz, 3H, diastereomer II), 1.09e1.81 (m, 20H), 1.92e2.03 (m,
3
4.2.6. (1S)-1-Phenyl-N-[(E)-2,2,2-trifluoroethylidene]ethanamine
[(S)-1j]. External bath: 115 ꢁC, reaction time: 4 h; 1.85 g; 92% yield;
2H), 3.43 (q, JHeF¼4.3 Hz, 1H, diastereomer I), 3.49 (q,
3JHeF¼4.3 Hz, 1H, diastereomer II), 4.14e4.32 (m, 4H); 13C NMR
25
yellow oil; [
a
]
ꢂ29.2 (c 1.2, CHCl3); IR: 1685 cmꢂ1
;
1H NMR
(75 MHz, CDCl32): ¼13.8 (2C), 14.1 (2C), 16.5, 18.5, 18.7, 18.8, 35.8,
d
D
(300 MHz, CDCl3):
d
¼1.59 (d, 3J¼6.7 Hz, 3H), 4.61 (q, 3J¼6.6 Hz, 1H),
37.4, 58.4 (q, JCeF¼40.2 Hz, CeCF3, diastereomer I), 59.3 (q,
2JCeF¼39.9 Hz, CeCF3, diastereomer II), 63.7 (2C), 65.1, 65.3,121.6 (q,
1JCeF¼277.3 Hz, CF3, diastereomer I), 121.7 (q, 1JCeF¼276.7 Hz, CF3,
7.27e7.40 (m, 5H), 7.65 (3JHeF¼3.3 Hz, 1H); 13C NMR (75 MHz,
CDCl3):
d
¼23.8, 68.7, 119.0 (q, 1JCeF¼274.9 Hz, CF3), 126.6 (2C), 127.6,
128.7 (2C), 142.2, 148.0 (q, JCeF¼38.2 Hz, CeCF3); 19F NMR
diastereomer II), 159.6 (2C); 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.7
2
3
3
3
(282.2 MHz, CDCl3):
d
¼ꢂ72.0 (d, JFeH¼3.5 Hz, 3F); HRMS: m/z
(d, JFeH¼4.4 Hz, 3F, diastereomer I), ꢂ70.4 (d, JFeH¼4.3 Hz, 3F,
diastereomer II); HRMS: m/z [MþNa]þ calcd for C10H17F3N2NaO2:
277.1140; found: 277.1143.
[MþNa]þ calcd for C10H10F3NNa: 224.0663; found: 224.0659.
4.3. General procedure for the synthesis of ethyl 2-alkyl-3-
(trifluoromethyl)diaziridine-1-carboxylates (2aej)
4.3.6. Ethyl 2-(1,2-dimethylpropyl)-3-(trifluoromethyl)diaziridine-1-
carboxylate (2f). Orange oil; 0.09 g; IR: 1743 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
d
¼0.93e1.04 (m, 12H), 1.12e1.20 (m, 6H),
To a stirred solution of 1 mmol of trifluoromethyl imine in 2 mL
of anhydrous CH2Cl2, 1 mmol of NsONHCO2Et was added batchwise
at room temperature. After 1 h another 1 mmol of NsONHCO2Et
was added and the mixture was kept stirring. After 16 h hexane was
added, nosylate salts were filtered and the solvents were evapo-
rated under vacuum.
1.24e1.30 (m, 6H), 1.74e1.89 (m, 2H), 1.96e2.07 (m, 2H), 3.39 (q,
3JHeF¼4.3 Hz, 1H, minor), 3.52 (q, JHeF¼4.3 Hz, 1H, major),
3
4.14e4.32 (m, 4H); 13C NMR (75 MHz, CDCl3):
d
¼12.1, 13.9 (2C),
14.9, 16.5, 17.6, 19.0, 19.3, 31.3 (major), 31.6 (minor), 58.4 (q,
2JCeF¼40.2 Hz, CeCF3, minor), 59.7 (q, JCeF¼39.8 Hz, CCF3, ma-
2
jor), 63.6 (minor), 63.7 (major), 70.0 (minor), 70.5 (major), 121.4

L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
5379
1
1
3
(q, JCeF¼277.4 Hz, CF3, minor), 121.7 (q, JCeF¼277.2 Hz, CF3,
CDCl3):
d
¼ꢂ72.5 (d, JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd
major), 157.9 (2C); 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.5 (d,
for C13H15F3N2NaO2: 311.0983; found: 311.0991.
3JFeH¼4.3 Hz, 3F, minor), ꢂ70.1 (d, JFeH¼4.3 Hz, 3F, major);
HRMS: m/z [MþNa]þ calcd for C10H17F3N2NaO2: 277.1140; found:
277.1149, m/z [MþH]þ calcd for C10H18F3N2O2: 255.1320; found:
255.1324.
3
4.4. General procedure for the synthesis of tert-butyl 2-alkyl-
3-(trifluoromethyl)diaziridine-1-carboxylates (2a0,c0)
To a stirred solution of 1 mmol of trifluoromethyl imine in 2 mL
of anhydrous CH2Cl2, 1 mmol of NsONHCO2t-Bu was added batch-
wise at room temperature. After 1 h another 1 mmol of NsONH-
CO2t-Bu was added and the mixture was kept stirring. After 24 h
hexane was added, nosylate salts were filtered and the solvents
were evaporated under vacuum.
4.3.7. Ethyl 3-(trifluoromethyl)-2-(1,2,2-trimethylpropyl)diaziridine-
1-carboxylate (2g). Brown oil; 0.10 g; IR: 1743 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
d
¼0.97 (s, 9H, major), 1.02 (s, 9H, minor), 1.18 (d,
3J¼6.5 Hz, 6H),1.27 (t, 3J¼7.1 Hz, 6H),1.78 (q, 3J¼6.5 Hz, 2H), 3.34 (q,
3JHeF¼4.4 Hz, 1H, minor), 3.59 (q, JHeF¼4.2 Hz, 1H, major),
3
4.13e4.32 (m, 4H); 13C NMR (75 MHz, CDCl3):
d¼12.9 (minor), 13.8
(minor), 13.9 (major), 14.8 (major), 26.5 (3C, major), 26.6 (3C, mi-
4.4.1. tert-Butyl 2-benzyl-3-(trifluoromethyl)diaziridine-1-
2
nor), 34.0 (major), 34.3 (minor), 57.1 (q, JCeF¼40.3 Hz, CeCF3,
carboxylate (2a0). Colorless oil; 0.13 g; IR: 1738, 1604 cmꢂ1
;
1H
2
3
minor), 61.4 (q, JCeF¼39.8 Hz, CeCF3, major), 63.5 (2C), 73.0 (mi-
NMR (300 MHz, CDCl3):
d
¼1.45 (s, 9H), 3.57 (q, JHeF¼4.3 Hz, 1H),
1
nor), 73.4 (major), 121.7 (q, JCeF¼277.9 Hz, CF3, major), 122.0 (q,
3.77 (d, 2J¼13.3 Hz, 1H), 3.97 (d, 2J¼13.3 Hz, 1H), 7.26e7.43 (m, 5H);
1JCeF¼277.1 Hz, CF3, minor), 159.9 (2C); 19F NMR (282.2 MHz,
13C NMR (75 MHz, CDCl3):
d
¼28.5 (3C), 58.3 (q, JCeF¼41 Hz,
2
3
1
CDCl3):
d¼ꢂ71.2 (d, JFeH¼4.3 Hz, 3F, minor), ꢂ70.4 (d,
CeCF3), 63.2, 80.5, 121.0 (q, JCeF¼276 Hz, CF3), 127.3, 127.8 (2C),
3JFeH¼4.3 Hz, 3F, major); HRMS: m/z [MþNa]þ calcd for
C11H19F3N2NaO2: 291.1296; found: 291.1292, m/z [MþH]þ calcd for
C11H20F3N2O2: 269.1477; found: 269.1479.
128.5 (2C), 139.2, 158.6; 19F NMR (282.2 MHz, CDCl3):
d¼ꢂ72.0 (d,
3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C14H17F3N2NaO2:
325.1140; found: 325.1137.
4.3.8. Ethyl 2-(1,3-dimethylbutyl)-3-(trifluoromethyl)diaziridine-1-
4.4.2. tert-Butyl 2-octyl-3-(trifluoromethyl)diaziridine-1-carboxylate
carboxylate (2h). Yellow oil; 0.12 g; IR: 1745 cmꢂ1
;
1H NMR
(2c0). Colorless oil; 0.14 g; IR: 1737 cmꢂ1 1H NMR (300 MHz,
;
(300 MHz, CDCl3):
d
¼0.83 (d, 3J¼6.5 Hz, 3H), 0.84 (d, 3J¼6.4 Hz, 3H),
CDCl3):
d
¼0.86 (t, 3J¼6.6 Hz, 3H), 1.20e1.41 (m, 10H), 1.46 (s, 9H),
1.91 (d, 3J¼6.5 Hz, 6H), 1.11 (d, 3J¼6.5 Hz, 3H), 1.24e1.31 (m, 9H),
1.39e1.50 (m, 2H), 1.60e1.86 (m, 4H), 1.98e2.11 (m, 2H); 3.44 (q,
1.55e1.79 (m, 2H), 2.45e2.77 (m, 2H), 3.42 (q, JHeF¼4.3 Hz, 1H);
3
13C NMR (75 MHz, CDCl3):
d
¼14.1, 22.5, 26.2, 27.4 (2C), 28.4 (3C),
3JHeF¼4.3 Hz, 1H, diastereomer I), 3.47 (q, JHeF¼4.3 Hz, 1H, di-
30.5, 32.6, 50.3, 59.1 (q, JCeF¼41 Hz, CeCF3), 80.4, 121.8 (q,
3
2
astereomer II), 4.13e4.32 (m, 4H); 13C NMR (75 MHz, CDCl3):
1JCeF¼277 Hz, CF3), 159.3; 19F NMR (282.2 MHz, CDCl3):
¼ꢂ71.9 (d,
d
d
¼13.9 (2C), 17.0, 18.8, 22.1, 22.2, 23.2, 23.3, 24.4 (2C), 42.7, 44.6,
3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C15H27F3N2NaO2:
2
58.3 (q, JCeF¼40.2 Hz, CeCF3, diastereomer I), 59.3 (q,
347.1922; found: 347.1931.
2JCeF¼40.1 Hz, CeCF3, diastereomer II), 63.4, 63.6, 63.7 (2C), 121.6
1
1
(q, JCeF¼277.4 Hz, CF3, diastereomer I), 121.7 (q, JCeF¼277.4 Hz,
4.5. Synthesis of ethyl 2-allyl-3-(trifluoromethyl)diaziridine-
1-carboxylate (2k)
CF3, diastereomer II), 159.7 (2C); 19F NMR (282.2 MHz, CDCl3):
3
d
¼ꢂ72.9 (d, JFeH¼4.4 Hz, 3F, diastereomer II), ꢂ70.5 (d,
3JFeH¼4.3 Hz, 3F, diastereomer I); HRMS: m/z [MþNa]þ calcd for
C11H19F3N2NaO2: 291.1296; found: 291.1289, m/z [MþH]þ calcd for
C11H20F3N2O2: 269.1477; found: 269.1471.
A stirred solution of 0.5 mmol of trifluoroacetaldehyde ethyl
hemiacetal (90% aq solution) and 0.5 mmol of allylamine was
heated at 105 ꢁC under solvent-free conditions in a flask fitted with
a calcium chloride tube. After the reaction was completed (1H NMR,
4 h), 2 mL of anhydrous CH2Cl2 and 0.5 mmol of NsONHCO2Et were
added batchwise at room temperature. After 1 h another 1 mmol of
NsONHCO2Et was added and the mixture was kept stirring. After
24 h hexane was added, nosylate salts were filtered and the sol-
vents were evaporated under vacuum. Orange oil; 0.04 g; IR: 1745,
4.3.9. Ethyl
2-(1-methyl-2-phenylethyl)-3-(trifluoromethyl)diazir-
idine-1-carboxylate (2i). Orange oil; 0.12 g; IR: 1608, 1743 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼1.19 (t, 3J¼7.1 Hz, 3H, major), 1.20 (t,
3J¼7.0 Hz, 3H, minor), 1.29 (d, 3J¼7.0 Hz, 3H, major), 1.41 (d,
3J¼6.9 Hz, 3H, minor), 2.49 (dd, 2J¼4.6 Hz, 3J¼11.6 Hz, 1H),
3
2.66e2.90 (m, 3H), 3.00e3.16 (m, 2H), 3.20 (q, JHeF¼4.3 Hz, 1H,
1650 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼1.30 (t, 3J¼7.1 Hz, 3H),
3
major), 3.39 (q, JHeF¼4.3 Hz, 1H, minor), 4.07e4.24 (m, 4H),
3.21 (dd, 3J¼6.5 Hz, 2J¼13.6 Hz, 1H), 3.41 (dd, 3J¼6.5 Hz, 2J¼13.6 Hz,
7.09e7.25 (m, 10H); 13C NMR (75 MHz, CDCl3):
d
¼13.8 (2C), 18.9
1H), 3.51 (q, JHeF¼4.3 Hz, 1H), 4.21e4.37 (m, 2H), 5.27e5.40 (m,
3
(minor), 19.8 (major), 39.0 (minor), 39.1 (major), 59.0 (q,
2H), 5.87e6.00 (m, 1H); 13C NMR (75 MHz, CDCl3):
d¼13.9, 58.5 (q,
2JCeF¼40.3 Hz, CeCF3, major), 59.5 (q, JCeF¼40.2 Hz, CeCF3, ma-
2JCeF¼40 Hz, CeCF3), 62.4, 62.9, 119.9, 121.6 (q, 1JCeF¼278 Hz, CF3),
2
jor), 63.7 (4C), 67.4 (minor), 67.5 (major), 121.4 (q, 1JCeF¼277.6 Hz,
130.9, 159.5; 19F NMR (282.2 MHz, CDCl3):
d¼ꢂ71.4 (d,
1
CF3, major), 121.6 (q, JCeF¼277.4 Hz, CF3, minor), 126.5 (minor),
3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C8H11F3N2NaO2:
247.0670; found: 247.0667, m/z [MþH]þ calcd for C8H12F3N2O2:
225.0851; found: 225.0849.
126.7 (major), 127.1 (4C), 128.5 (minor), 128.6 (major), 144.1, 144.2,
159.3, 159.4; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ71.2 (d,
3JFeH¼4.3 Hz, 3F, minor), ꢂ70.4 (d, JFeH¼4.3 Hz, 3F, major);
HRMS: m/z [MþNa]þ calcd for C14H17F3N2NaO2: 325.1140; found:
325.1137, m/z [MþH]þ calcd for C14H18F3N2O2: 303.1320; found:
303.1327.
3
4.6. Synthesis of N-[(E)-ethylidene]-3,3-dimethylbutan-2-
amine (3)
To a stirred solution of 1 mmol of 3,3-dimethylbutan-2-amine in
3 mL of CH2Cl2, 2 mmol of acetaldehyde was added at room tem-
perature, reaction time 10 min; 0.09 g; 68% yield; yellow oil; IR:
4.3.10. Ethyl 2-(1-phenylethyl)-3-(trifluoromethyl)diaziridine-1-
carboxylate (2j). Yellow oil; 0.10 g; IR: 1740, 1607 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
d
¼1.12 (t, 3J¼7.1 Hz, 3H), 1.41 (d, 3J¼6.8 Hz, 3H),
1668 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼0.74 (s, 9H), 0.95 (d,
3.17 (q, 3J¼6.7 Hz,1H), 3.47 (q, 3JHeF¼4.3 Hz, 1H), 3.98e4.15 (m, 2H),
3J¼6.5 Hz, 3H), 1.83 (d, 3J¼4.8 Hz, 3H), 2.61 (q, 3J¼6.5 Hz, 1H), 7.53
7.18e7.41 (m, 5H); 13C NMR (75 MHz, CDCl3):
d¼13.8, 20.0, 58.8 (q,
(q, 3J¼5.1 Hz,1H); 13C NMR (75 MHz, CDCl3):
¼19.9, 23.9, 25.7 (3C),
d
2JCeF¼40.4 Hz, CeCF3), 63.6, 68.5, 121.7 (q, JCeF¼277.3 Hz, CF3),
42.8, 70.3, 156.7; HRMS: m/z [MþNa]þ calcd for C8H17NNa:
1
127.3 (2C), 127.8, 128.3 (2C), 140.4, 159.1; 19F NMR (282.2 MHz,
150.1259; found: 150.1264.

5380
L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
3
4.7. Synthesis of ethyl 3-methyl-2-(1,2,2-trimethylpropyl)
diaziridine-1-carboxylate (4)
CDCl3):
d
¼ꢂ71.2 (d, JFeH¼4.3 Hz, 3F, minor), ꢂ70.4 (d,
3JFeH¼4.3 Hz, 3F, major); HRMS: m/z [MþNa]þ calcd for
C11H19F3N2NaO2: 291.1296; found: 291.1294.
To a stirred solution of imine 3 (1 mmol) in 2 mL in anhydrous
CH2Cl2, 1 mmol of NsONHCO2Et was added batchwise at room
temperature. After 30 min another 1 mmol of NsONHCO2Et was
added and the mixture was kept stirring. After the reaction was
completed (1H NMR, 2 h), hexane was added, nosylate salts were
filtered and the solvent was evaporated under vacuum. Colorless
4.8.4. Ethyl (2S,3S)-2-[(R)-1-phenylethyl]-3-(trifluoromethyl)diazir-
25
idine-1-carboxylate [(R,S,S)-2j]. Orange oil; 0.14 g; [
a
]
þ27.1 (c
D
2.0, CHCl3); IR: 1740, 1607 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼1.12
(t, 3J¼7.1 Hz, 3H), 1.41 (d, 3J¼6.8 Hz, 3H), 3.17 (q, 3J¼6.7 Hz, 1H), 3.47
3
(q, JHeF¼4.3 Hz, 1H), 3.98e4.15 (m, 2H), 7.18e7.42 (m, 5H); 13C
oil; 0.09 g; IR (CHCl3): 1740 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
NMR (75 MHz, CDCl3):
d
¼13.8, 20.0, 58.8 (q, 2JCeF¼40.4 Hz, CeCF3),
d
¼0.87 (s, 9H, major), 0.94 (s, 9H, minor), 1.12 (d, 3J¼6.5 Hz, 6H),
63.6, 68.5,121.7 (q, 1JCeF¼277.3 Hz, CF3),127.3 (2C),127.8,128.3 (2C),
1.26 (t, 3J¼7.1 Hz, 3H, major), 1.27 (t, 3J¼7.1 Hz, 3H, minor), 1.33 (d,
3J¼6.5 Hz, 6H), 1.58 (q, 3J¼6.4 Hz, 1H, major), 1.65 (q, 3J¼6.7 Hz, 1H,
minor), 2.92 (q, 3JHeF¼5.2 Hz, 1H, minor), 3.07 (q, 3JHeF¼5.1 Hz, 1H,
140.4, 159.1; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.6 (d,
3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C13H15F3N2NaO2:
311.0983; found: 311.0994.
major), 4.09e4.29 (m, 4H); 13C NMR (75 MHz, CDCl3):
d¼13.2
(minor), 14.2 (2C), 14.8 (major), 16.0 (major), 16.3 (minor), 26.7 (3C,
minor), 26.8 (3C, major), 33.8 (major), 34.3 (minor), 58.7 (2C), 62.5
(minor), 63.8 (major), 72.6 (minor), 73.1 (major), 162.0, 162.6;
HRMS: m/z [MþNa]þ calcd for C11H22N2NaO2: 237.1579; found:
237.1582, m/z [MþH]þ calcd for C11H23N2O2: 215.1760; found:
215.1768.
4.8.5. Ethyl (2R,3R)-2-[(S)-1-phenylethyl]-3-(trifluoromethyl)diazir-
25
idine-1-carboxylate [(S,R,R)-2j]. Orange oil; 0.10 g; [
a
]
ꢂ29.2 (c
D
1.2, CHCl3); IR: 1607, 1740 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼1.12
(t, 3J¼7.1 Hz, 3H), 1.41 (d, 3J¼6.8 Hz, 3H), 3.17 (q, 3J¼6.8 Hz, 1H), 3.47
(q, 3JHeF¼4.3 Hz,1H), 3.97e4.14 (m, 2H), 7.17e7.41 (m, 5H); 13C NMR
(75 MHz, CDCl31):
d
¼13.7, 20.0, 58.7 (q, 2JCeF¼40.3 Hz, CeCF3), 63.6,
68.5, 121.7 (q, JCeF¼277.3 Hz, CF3), 127.3 (2C), 127.8, 128.3 (2C),
4.8. General procedure for the synthesis of enantiopure ethyl
2-alkyl-3-(trifluoromethyl)diaziridine-1-carboxylate
140.4, 159.1; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.5 (d,
3JFeH¼4.3 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C13H15F3N2NaO2:
311.0983; found: 311.0989.
To a stirred solution of 1 mmol of trifluoromethyl imine in 2 mL
of anhydrous CH2Cl2, 1 mmol of NsONHCO2Et was added batchwise
at room temperature. After 1 h another 1 mmol of NsONHCO2Et
was added and the mixture was kept stirring. After 16 h hexane was
added, nosylate salts were filtered and the solvents were evapo-
rated under vacuum.
4.9. General procedure for the synthesis of 2-alkyl-3-
(trifluoromethyl)oxaziridines
Trifluoromethyl imine (1 mmol) was dissolved in 1 mL of CH2Cl2
and was added dropwise to a stirred solution of 1 mmol of m-CPBA
in 2 mL of CH2Cl2 at 0 ꢁC. When the solution becomes clear was
washed with 2 N Na2CO3 and the solvent was evaporated under
vacuum after drying over Na2SO4.
4.8.1. Ethyl (2S,3S)-3-(trifluoromethyl)-2-[(R)-1,2,2-trimethylpropyl]
25
diaziridine-1-carboxylate [(R,S,S)-2g]. Colorless oil; 0.09 g; [a]
D
ꢂ18.2 (c 1.6, CHCl3); IR: 1742 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼0.98 (s, 9H), 1.19 (d, 3J¼6.5 Hz, 3H), 1.28 (t, 3J¼7.1 Hz, 3H), 1.79 (q,
4.9.1. 2-Cyclopentyl-3-(trifluoromethyl)oxaziridine (5b). Yellow oil;
3J¼6.6 Hz,1H), 3.60 (q, 3JHeF¼4.2 Hz,1H), 4.22 (q, 3J¼7.1 Hz, 2H); 13
C
0.14 g; IR: 1412 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼1.38e2.01 (m,
3
NMR (75 MHz, CDCl3):
d
¼13.9, 14.8, 26.5 (3C), 34.0, 61.4 (q,
8H), 2.71e2.80 (m, 1H), 4.15 (q, JHeF¼3.3 Hz, 1H); 13C NMR
2JCeF¼40.0 Hz, CeCF3), 63.5, 73.4, 121.6 (q, JCeF¼277.0 Hz, CF3),
(75 MHz, CDCl3):
d
¼24.1 (2C), 31.3 (2C), 69.3, 74.6 (q, 2JCeF¼42.0 Hz,
1
159.9; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ70.4 (d, 3JFeH¼4.3 Hz, 3F);
CeCF3), 120.9 (q, 1JCeF¼277.4 Hz, CF3); 19F NMR (282.2 MHz, CDCl3):
HRMS: m/z [MþNa]þ calcd for C11H19F3N2NaO2: 291.1296; found:
d
¼ꢂ72.5 (d, JFeH¼3.4 Hz, 3F); HRMS: m/z [MþNa]þ calcd for
3
291.1291.
C7H10F3NNaO: 204.0612; found: 204.0620.
4.8.2. Ethyl (2R,3R)-3-(trifluoromethyl)-2-[(R)-1,2,2-trimethylpropyl]
4.9.2. 2-(1,2-Dimethylpropyl)-3-(trifluoromethyl)oxaziridine
(5f). Yellow oil; 0.16 g; IR: 1421 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
25
diaziridine-1-carboxylate [(R,R,R)-2g]. Colorless oil; 0.04 g; [a]
D
þ16.6 (c 1.6, CHCl3); IR: 1742 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
¼0.98 (d, 3J¼6.7 Hz, 6H, minor), 0.99 (d, 3J¼6.7 Hz, 6H, major), 1.09
d
¼1.04 (s, 9H), 1.12 (d, 3J¼6.5 Hz, 3H), 1.29 (t, 3J¼7.1 Hz, 3H), 1.79 (q,
(d, 3J¼6.6 Hz, 3H, minor), 1.24 (d, 3J¼6.2 Hz, 3H, major), 1.80e2.01
(m, 4H), 4.17 (q, 3JHeF¼3.3 Hz, 1H, minor), 4.27 (q, 3JHeF¼3.3 Hz, 1H,
3J¼6.5 Hz,1H), 3.35 (q, 3JHeF¼4.4 Hz,1H), 4.25 (q, 3J¼7.1 Hz, 2H); 13
C
NMR (75 MHz, CDCl3):
d
¼12.9, 13.8, 26.6 (3C), 34.2, 57.2 (q,
major); 13C NMR (75 MHz, CDCl3):
d
¼12.7, 16.1, 17.7, 18.5, 18.8, 19.0,
2JCeF¼40.0 Hz, CeCF3), 63.6, 72.9, 122.1 (q, JCeF¼277.0 Hz, CF3),
31.8 (major), 32.4 (minor), 71.4 (minor), 71.5 (major), 73.9 (q,
2JCeF¼42.0 Hz, CeCF3, minor), 76.2 (q, 2JCeF¼41.5 Hz, CeCF3, major),
120.9 (q, 1JCeF¼277.8 Hz, CF3, major), 121.1 (q, 1JCeF¼277.5 Hz, CF3,
1
160.3; 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ71.1 (d, 3JFeH¼4.3 Hz, 3F);
HRMS: m/z [MþNa]þ calcd for C11H19F3N2NaO2: 291.1296; found:
291.1289.
minor); 19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.4 (d, 3JFeH¼3.4 Hz, 3F,
3
minor), ꢂ70.2 (d, JFeH¼3.4 Hz, 3F, major); HRMS: m/z [MþNa]þ
4.8.3. Ethyl (2R* ,3R* )-3-(trifluoromethyl)-2-[(S)-1,2,2-
trimethylpropyl]diaziridine-1-carboxylate [(S,R*,R*)-2g]. Yellow oil;
calcd for C7H12F3NNaO: 206.0769; found: 206.0774.
0.12 g; IR: 1743 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼0.96 (s, 9H,
4.9.3. 3-(Trifluoromethyl)-2-(1,2,2-trimethylpropyl)-oxaziridine
(5g). Yellow oil; 0.16 g; IR: 1416 cmꢂ1; 1H NMR (300 MHz, CDCl3):
major), 1.02 (s, 9H, minor), 1.12 (d, 3J¼7.1 Hz, 3H, minor), 1.18 (d,
3J¼6.5 Hz, 3H, major), 1.27 (t, 3J¼7.1 Hz, 6H), 1.78 (q, 3J¼6.6 Hz, 2H),
3.35 (q, 3JHeF¼4.4 Hz, 1H, minor), 3.60 (q, 3JHeF¼4.2 Hz, 1H, major),
d
¼0.99 (s, 9H, major), 1.00 (s, 9H, minor), 1.07 (d, 3J¼6.9 Hz, 3H,
minor), 1.21 (d, 3J¼6.4 Hz, 3H, major), 1.87e1.98 (m, 2H), 4.09 (q,
4.13e4.31 (m, 4H); 13C NMR (75 MHz, CDCl3):
(minor), 13.9 (major), 14.8 (major), 26.5 (3C, major), 26.6 (3C, mi-
d¼12.9 (minor), 13.8
3JHeF¼3.3 Hz,1H, minor), 4.31 (q, 3JHeF¼3.3 Hz,1H, major); 13C NMR
(75 MHz, CDCl3):
d
¼11.9 (minor), 14.7 (major), 26.3 (3C, minor),
2
nor), 34.0 (major), 34.3 (minor), 57.1 (q, JCeF¼40.1 Hz, CeCF3, mi-
26.6 (3C, major), 34.9 (major), 36.0 (minor), 73.2 (q, 2JCeF¼42.1 Hz,
nor), 61.4 (q, 2JCeF¼39.8 Hz, CeCF3, major), 63.5 (2C), 72.9 (minor),
CeCF3, minor), 74.2 (2C) 77.5 (q, JCeF¼41.1 Hz, CCF3, major), 120.9
2
1
73.4 (major), 121.7 (q, JCeF¼277.9 Hz, CF3, major), 122.0 (q,
(q, 1JCeF¼277.5 Hz, CF3, major),121.2 (q, 1JCeF¼277.5 Hz, CF3, minor);
1JCeF¼277.1 Hz, CF3, minor), 159.9 (2C); 19F NMR (282.2 MHz,
19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ71.2 (d, 3JFeH¼3.4 Hz, 3F, minor),

L. Carroccia et al. / Tetrahedron 67 (2011) 5375e5381
5381
3
ꢂ70.4 (d, JFeH¼3.4 Hz, 3F, major); HRMS: m/z [MþNa]þ calcd for
References and notes
C8H14F3NNaO: 220.0925; found: 220.0931.
1. (a) Guest Curr. Org. Chem.; Liu, Z.-P., Ed.; 2010; Vol. 14, pp 888e999; (b) Guest
Curr. Org. Synth.; Lopez, S. E., Ed.; 2010; Vol. 7, pp 402e531; (c) Verniest, G.; Piron,
K.; Van Hende, E.; Thuring, J. W.; Macdonald, G.; Deroose, F.; De Kimpe, N. Org.
Biomol. Chem. 2010, 8, 2509e2512; (d) Kawai, H.; Kusuda, A.; Nakamura, S.; Shiro,
M.; Shibata, N. Angew. Chem., Int. Ed. 2009, 48, 6324e6327; (e) Lemal, D. M.;
Ramanathan, S. In Fluorinated Heterocyclic Compounds: Synthesis, Chemistry, and
Applications; Petrov, V. A., Ed.; John Wiley: Hoboken, 2009; (f) O’Hagan, D. Chem.
4.9.4. 2-(1,3-Dimethylbutyl)-3-(trifluoromethyl)oxaziridine
(5h). Orange oil; 0.16 g; IR: 1416 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼0.86e0.95(m, 12H), 1.15 (d, 3J¼6.6 Hz, 3H, minor), 1.26 (d,
3J¼6.2 Hz, 3H, major), 1.34e1.45 (m, 2H), 1.61e1.87 (m, 4H),
3
2.19e2.30 (m, 2H), 4.17 (q, JHeF¼3.3 Hz, 1H, minor), 4.22 (q,
ꢁ
ꢁ
Soc. Rev. 2008, 37, 308e319; (g) Begue, J.-P.; Bonnet-Delpon, D. In Bioorganic and
Medicinal Chemistry of Fluorine; J. Wiley: Hoboken, NJ, 2008; (h) Kirsch, P. In
Modern Fluoroorganic Chemistry; Wiley-VCH: Weinheim, 2004; (i) Chambers, R.
D. Fluorine in Organic Chemistry; Oxford: , Blackwell, 2004.
3JHeF¼3.2 Hz, 1H, major); 13C NMR (75 MHz, CDCl3):
¼16.6 (mi-
d
nor), 19.2 (major), 22.3, 26.6 (2C), 23.0, 24.5 (2C), 42.2 (minor), 44.9
2
(major), 64.4 (minor), 64.6 (major), 74.0 (q, JCeF¼42.1 Hz, CeCF3,
ꢁ
ꢁ
2. (a) Begue, J. P.; Bonnet-Delpon, D.; Crousse, B.; Legros, J. Chem. Soc. Rev. 2005, 34,
562e572; (b) Qiu, X.-L.; Meng, W.-D.; Qing, F.-L. Tetrahedron 2004, 60,
6711e6745; (c) Biomedical Frontiers of Fluorine Chemistry; Ojima, I., McCarthy, J.
R., Welch, J. T., Eds.; ACS Books, American Chemical Society: Washington, DC,
1996; (d) Fluorine-containing Amino Acids: Synthesis and Properties; Kukhar, V. P.,
Soloshonok, V. A., Eds.; John Wiley: Chichester, UK, 1995.
2
minor), 75.4 (q, JCeF¼41.8 Hz, CeCF3, major), 120.8 (q,
1JCeF¼277.7 Hz, CF3, minor), 120.9 (q, 1JCeF¼277.5 Hz, CF3, major);
19F NMR (282.2 MHz, CDCl3):
d
¼ꢂ72.9 (d, 3JFeH¼3.4 Hz, 3F, minor),
ꢂ70.5 (d, JFeH¼3.4 Hz, 3F, major); HRMS: m/z [MþNa]þ calcd for
3
3. (a) Mikami, K.; Itoh, Y.; Yamanaka, M. Chem. Rev. 2004, 104, 1e16; (b) Ram-
achandran, P. V., Ed. Asymmetric Fluoroorganic Chemistry. Synthesis, Applications,
and Future Directions; ACS Symposium Series 746; American Chemical Society:
Washington, DC, 2000. (c) Soloshonok, V. A. Enantiocontrolled Synthesis of
Fluoro-organic Compounds; Wiley: Chichester, UK, 1999; (d) Iseki, K. Tetrahedron
1998, 54, 13887e13914; (e) Resnati, G. Tetrahedron 1993, 49, 9385e9445; (f)
Bravo, P.; Resnati, G. Tetrahedron: Asymmetry 1990, 1, 661e692.
4. (a) Fioravanti, S.; Pellacani, L.; Ramadori, F.; Tardella, P. A. Tetrahedron Lett. 2007,
48, 7821e7824; (b) Fioravanti, S.; Colantoni, D.; Pellacani, L.; Tardella, P. A.
J. Org. Chem. 2005, 70, 3296e3298; (c) Colantoni, D.; Fioravanti, S.; Pellacani, L.;
Tardella, P. A. Org. Lett. 2004, 6, 197e200.
5. (a) Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A. Eur. J. Org. Chem.
2003, 4549e4552; (b) Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A.
Synthesis 2001, 1975e1978; (c) Fioravanti, S.; Morreale, A.; Pellacani, L.; Tar-
della, P. A. Tetrahedron Lett. 2001, 42, 1171e1173.
6. Carroccia, L.; Fioravanti, S.; Pellacani, L.; Tardella, P. A. Synthesis 2010,
4096e4100.
7. The same imine might behave like a base; therefore in these reaction condi-
tions yields up to 50% can be obtained: Fioravanti, S.; Olivieri, L.; Pellacani, L.;
Tardella, P. A. Tetrahedron Lett. 1998, 39, 6391e6392 A third hypothesis, put
forward by a referee, could be the direct addition of nosyloxycarbamate across
the imine bond.
8. (a) Fioravanti,S.;Marchetti,F.;Morreale,A.;Pellacani,L.;Tardella,P.A.Org.Lett.2003,
5,1019e1021; (b) Hanessian, S.; Johnstone, S. J. Org. Chem.1999, 64, 5896e5903.
9. De Vitis, L.; Florio, S.; Granito, C.; Ronzini, L.; Capriati, V.; Luisi, R.; Pilati, T.
Tetrahedron 2004, 60, 1175e1182.
C8H14F3NNaO: 220.0925; found: 220.0935.
4.9.5. Ethyl (2S,3S)-3-(trifluoromethyl)-2-[(R)-1,2,2-trimethylpropyl]
25
oxaziridine [(R,S,S)-5g]. Yellow oil; 0.13 g; [
a
]
D
ꢂ22.0 (c 1.2,
CHCl3); IR: 1419 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼1.0 (s, 9H),
1.21 (d, 3J¼6.4 Hz, 3H), 1.94 (q, 3J¼6.4 Hz, 1H), 4.31 (q, 3JHeF¼3.3 Hz,
1H); 13C NMR (75 MHz, CDCl3):
d
¼14.7, 26.6 (3C), 34.7, 74.3, 77.5 (q,
2JCeF¼41.1 Hz, CeCF3), 120.9 (q, JCeF¼277.5 Hz, CF3); 19F NMR
1
3
(282.2 MHz, CDCl3):
d
¼ꢂ70.4 (d, JFeH¼3.4 Hz, 3F); HRMS: m/z
[MþNa]þ calcd for C8H14F3NNaO: 220.0925; found: 220.0931.
4.9.6. Ethyl (2R,3R)-3-(trifluoromethyl)-2-[(1R)-1,2,2-
trimethylpropyl]oxaziridine [(R,R,R)-5g]. Colorless oil; 0.03 g;
25
[
a]
þ18.4 (c 1.4, CHCl3); IR: 1421 cmꢂ1
;
1H NMR (300 MHz,
D
CDCl3):
d
¼0.99 (s, 9H), 1.07 (d, 3J¼6.9 Hz, 3H), 1.90 (q, 3J¼6.9 Hz,
1H), 4.09 (q, 3JHeF¼3.3 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d¼12.0,
2
26.4 (3C), 36.1, 73.2 (q, JCeF¼42.1 Hz, CeCF3), 74.2, 121.1 (q,
1JCeF¼277.6 Hz, CF3); 19F NMR (282.2 MHz, CDCl3):
¼ꢂ71.2 (d,
d
3JFeH¼3.4 Hz, 3F); HRMS: m/z [MþNa]þ calcd for C8H14F3NNaO:
220.0925; found: 220.0929.
10. The equilibrium geometries of the two diastereomers were obtained from
B3PW91/6-311þþG** optimizations. Single-point energy calculations of
B3PW91/aug-cc-pvtz //B3PW91/6-311þþG** were accomplished to determine
a better evaluation of relative stability. Further, zero-point energy and thermal
corrections at 298 K were included to improve the energy difference value.
Quantum mechanical calculations were performed using the GAUSSIAN 03,
revision C.02 package Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.;
Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara,
M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.;
Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.;
Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Ragha-
vachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cio-
slowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez,
C.; Pople, J. A. Gaussian 03, Revision C.02; Gaussian: Wallingford CT, 2004.
11. Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919e934.
4.9.7. Ethyl (2R* ,3R* )-3-(trifluoromethyl)-2-[(S)-1,2,2-
trimethylpropyl]oxaziridine [(S,R*,R*)-5g]. Orange oil; 0.17 g; IR:
1422 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼0.99 (s, 9H, minor), 1.00
(s, 9H, major), 1.07 (d, 3J¼6.9 Hz, 3H, minor), 1.21 (d, 3J¼6.4 Hz, 3H,
major), 1.87e1.98 (m, 2H), 4.09 (q, 3JHeF¼3.3 Hz, 1H, minor), 4.31 (q,
3JHeF¼3.3 Hz,1H, major); 13C NMR (75 MHz, CDCl3):
¼11.9 (minor),
d
14.7 (major), 26.3 (3C, minor), 26.6 (3C, major), 34.8 (major), 36.1
2
(minor), 73.2 (q, JCeF¼42.1 Hz, CeCF3, minor), 74.2 (2C), 77.5 (q,
2JCeF¼41.1 Hz, CeCF3, major), 120.9 (q, 1JCeF¼277.5 Hz, CF3, major),
121.2 (q, 1JCeF¼277.5 Hz, CF3, minor); 19F NMR (282.2 MHz, CDCl3):
3
3
d
¼ꢂ71.2 (d, JFeH¼3.4 Hz, 3F, minor), ꢂ70.4 (d, JFeH¼3.4 Hz, 3F,
major); HRMS: m/z [MþNa]þ calcd for C8H14F3NNaO: 220.0925;
found: 220.0931.
Acknowledgements
12. Mishra, J. K. Synlett 2005, 543e544 and refs therein.
ꢀ
Italian MIUR; and Universita degli Studi di Roma ‘La Sapienza’
13. (a) Petrov, V. A.; Resnati, G. Chem. Rev. 1996, 96, 1809e1824; (b) DesMarteau, D. D.;
Petrov,V.A.;Montanari,V.;Pregnolato,M.;Resnati,G.J.Org.Chem.1994,59,2762e2765.
14. Blanc, S.; Bordogna, C. A. C.; Buckley, B. R.; Elsegood, M. R. J.; Page, P. C. B. Eur. J.
Org. Chem. 2010, 882e889.
are gratefully acknowledged for financial support (PRIN
2007FJC4SF_005). We thank Dr. Davide Massari for experimental
support.
15. The epoxidation of chlorinated and brominated aldimines in similar conditions
have been reported: De Kimpe, N.; De Corte, B. Tetrahedron 1992, 48, 7345e7362.
16. (a) Page, P. C. B.; Buckley, B. R. N-tert-Butoxycarbonyl(4-cyanophenyl)oxaziridine
In e-EROS, Electronic Encyclopedia of Reagents for Organic Synthesis; John Wiley:
New York, NY, 2005; (b) Metrangolo, P.; Novo, B.; Resnati, G. Oxaziridine, 3-
fluoro-3-(heptafluoropropyl)-2-(nonafluorobutyl)- In e-EROS, Electronic Ency-
clopedia of Reagents for Organic Synthesis; John Wiley: New York, NY, 2005; (c)
Beak, P.; Anderson, D. R.; Jarboe, S. G.; Kurtzweil, M. L.; Woods, K. W. Pure Appl.
Chem. 2000, 72, 2259e2264; (d) Aube, J. Chem. Soc. Rev. 1997, 26, 269e278.
17. Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87, 3630e3637.
18. (a) Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Hodgson, P. K. G.; Langridge-Smith,
P. R. R.; Millar, J. R. A.; Taylor, A. T. J. Chem. Soc., Chem. Commun. 1995, 885e886;
(b) Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Hodgson, P. K. G.; Langridge-Smith,
P. R. R.; Rankin, D. W. H. Synth. Met. 1996, 77, 77e80.
Supplementary data
Supplementary data associated with this article [1H and 13C
NMR spectra of (E)-trifluoromethyl imines 1e,g,i,j, and (S)-1g,j, 3;
diaziridines 2aek, 2a0,c0, (R,S,S)- and (R,R,R)-2g, (S,R*,R*)-2g, (R,S,S)-
and (S,R,R)-2j and 4; oxaziridines 5b,feh, (R,S,S)-5g, (S,R,R)-5g, and
(S,R*,R*)-5g] can be found. Supplementary data associated with
this article can be found in online version at doi:10.1016/
j.tet.2011.05.097.