Stereoselective aza-MIRC reactions on optically active (E)-nitro alkenes

Article abstract of DOI:10.1016/j.tetasy.2007.12.007

Optically active (E)-nitro alkenes carrying a 1,3-dioxolane or 1,3-oxazolidine residue undergo stereoselective aza-MIRC reactions, leading to the synthesis of the corresponding chiral nitro aziridines in high yields and with good diastereoselectivity. Interestingly, the stereochemical outcome of the aziridination reactions was strongly influenced by the chiral residue considered, giving stereoisomers, regardless of the reaction conditions.

Full text of DOI:10.1016/j.tetasy.2007.12.007

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 231–236
Stereoselective aza-MIRC reactions on optically active
(E)-nitro alkenes
b,
a,
a
Stefania Fioravanti,a,* Fabio Marchetti, Lucio Pellacani, Luca Ranieri
*
*
and Paolo A. Tardellaa,*
a
`
Dipartimento di Chimica, Universita degli Studi ‘La Sapienza’, P.le Aldo Moro 2, I-00185 Roma, Italy
`
Dipartimento di Chimica e Chimica Industriale, Universita degli Studi di Pisa, V. Risorgimento 35, I-56124 Pisa, Italy
b
Received 22 November 2007; accepted 18 December 2007
Abstract—Optically active (E)-nitro alkenes carrying a 1,3-dioxolane or 1,3-oxazolidine residue undergo stereoselective aza-MIRC reac-
tions, leading to the synthesis of the corresponding chiral nitro aziridines in high yields and with good diastereoselectivity. Interestingly,
the stereochemical outcome of the aziridination reactions was strongly influenced by the chiral residue considered, giving stereoisomers,
regardless of the reaction conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
For many years our research group has developed an effi-
cient direct aziridination methodology, which involves the
aza-MIRC (Michael initiated ring closure) reaction pro-
moted by inorganic bases on alkyl nosyloxycarbamates
(NsONHCO2R, Ns = 4-NO2C6H4SO2) starting from elec-
tron poor alkenes (Scheme 1).4
Aziridines are among the most fascinating intermediates in
organic synthesis, acting as precursors to complex molecules
due to the strain incorporated in their skeletons.1 Besides
their importance as reactive intermediates, many biologically
active compounds also contain these three-membered rings.2
Thus, obtaining aziridines, especially optically active aziri-
dines, has become of great importance in organic chemistry.
Our interest has been devoted to different alkenes contain-
ing different EWGs (electron withdrawing groups), the
reaction leading to mixtures of diastereomeric aziridines,
in relationship with the substituents considered. The nitro
group, which is a strong electron withdrawing group and
a well-known precursor of the important amine functional-
ity,5 promptly caught our attention.6
The chemistry of aziridines was hindered by the dearth of
suitable methods available: as a synthetic process, aziridin-
ation is poorly developed. In particular, the range of direct
synthetic methodology available to obtain aziridines start-
ing from alkenes is narrow.3
R
R
collapse
EWG
EWG
N
R
N
EWG
inorganic
base
CO2R'
NsONHCO2R'
NsONCO2R'
EWG
R'O2C
ONs
rotation/
collapse
R
N
CO2R'
Scheme 1.
*
Corresponding authors. Tel.: +39 0649913673; fax: +39 06490631 (L.P.); e-mail: lucio.pellacani@uniroma1.it
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.12.007

232
S. Fioravanti et al. / Tetrahedron: Asymmetry 19 (2008) 231–236
2. Results and discussion
CO2R'
O
O
O
O
O
O
NsONHCO2R'
R' = Et, Bn
N
R
R
R
+
We report herein novel studies in this field, extending our
methodology to the synthesis of optically active nitro azir-
idines by direct amination of nitro alkenes. Starting from
commercially available nitro alkanes, we performed a
Henry condensation reaction7 with (R)-2,2-dimethyl-
1,3-dioxolane-4-carboxaldehyde 1 and with tert-butyl
(R)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
(Garner’s aldehyde) 2 (Scheme 2), useful precursors of
important chemical functionality.8 Dehydration reaction
of the intermediate nitro aldols gives the expected nitro
alkenes 3a,b and 4a,b in the yields reported in Table 1.
H
NO2
H
NO2
H
NO2
N
CO2R'
5a',b'
5a,b
6a
(E)-3a,b
Scheme 3.
6a'
Table 2. Aziridination of (E)-nitro alkenes 3
Entry Alkene R0 Solvent Base Time Yielda Aziridineb
(h)
(%)
(dr)
1
2
3
4
5
6
7
(E)-3a Et CH2Cl2 CaO
(E)-3a Bn CH2Cl2 CaO
4
3
1
1
82
85
78
75
70
79
72
5a/5a0 (8:2)
6a/6a0 (8:2)
5a/5a0 (8:2)
6a/6a0 (8:2)
5a/5a0 (8:2)
5b/5b0 (7:3)
6b/6b0 (7:3)
(E)-3a Et THF
(E)-3a Bn THF
NaH
NaH
1. KF, r.t.
R*
R
+
RCH2 NO2
R* CHO
1 R* = O
(E)-3a Et
(E)-3b Et CH2Cl2 CaO
(E)-3b Et CaO 0.5
—
CaO 0.5
2. MsCl
3. EtNi-Pr2
H
NO2
4
O
—
a R = H
3a,b
4a,b
a After flash chromatography. The isomers could not be separated by
HPLC.
b Determined by 1H NMR spectra on crude mixtures.
b R = CH3
N Boc
O
2 R* =
The aziridination reactions occurred with complete reten-
tion of stereochemistry of the substrates, also in solvent-
free conditions (entries 5 and 7) and only stereoisomers
Scheme 2.
1
were obtained. The H NMR spectra performed on the
crude mixture showed the presence of diastereomeric azir-
idines with the same configuration of the starting alkenes,
as confirmed by the coupling constant values9 (Fig. 1).
Table 1. Synthesis of nitro alkenes at 0 °C
Alkene
R*
R
Yield (%)
77
E/Z
3a
H
>99:1
O
O
O
3b
4a
4b
CH3
75
76
82
91:9a
>99:1
>99:1
O
O
O
N
N
Boc
Boc
H
CH3
a E-Isomer was purified by flash chromatography.
We found that the dehydration reaction can be stereochem-
ically controlled by changing the temperature. In fact,
working under the reported conditions (ꢀ78 °C),7 diaste-
reomeric mixtures 70:30 of E/Z nitro olefins were obtained:
an increase of the reaction temperature (0 °C) allowed us to
obtain the single E-isomer, except that for 3b, which was
however obtained with satisfactory purity.
The chiral (E)-nitro alkenes 3 were aziridinated using dif-
ferent carbamates (NsONHCO2Et or NsONHCO2Bn)
and changing the reaction conditions. In all cases the azir-
idines were obtained in high yields and with good stereose-
lectivity (Scheme 3). The results are reported in Table 2.
Figure 1.

S. Fioravanti et al. / Tetrahedron: Asymmetry 19 (2008) 231–236
233
The stereochemical result can be explained by the involve-
ment of a dioxolane oxygen in the first step of aziridin-
ation, as in other related three-membered ring forming
reactions.10 As a result of the coordination of the nucleo-
philic attack, free rotation around the single bond of the
intermediate would be completely inhibited and the major
isomer derived by attack on the Re face of chiral olefins
(Scheme 4).
nitro aziridines, due to the expected free rotation around
the single bond of the reaction intermediates.
1
The aziridine proton b signal in the H NMR spectrum of
isomer 7a is doubled probably because of the presence of
rotamers, due to the proximity to the Boc group, differently
from the proton b signal of isomer 7a0 (Fig. 2). According
to the formation of two diastereomers 7a and 7a0, the
coupling constants for these signals are different (see
Section 4).
Mn+
ONs
O
O
N CO2R'
R
Re
Si
CO2Et
O
O
O
O
H
NO2
N
R
R
H
NO2
H
NO2
Mn+
ONs
major isomer
O
O
N CO2R'
NO2
H
R
Scheme 4.
Interestingly, a different stereochemical reaction outcome
was observed when tert-butyl (R)-4-formyl-2,2-dimethyl-
1,3-oxazolidine-3-carboxylate was used as a resident chiral
residue (Scheme 5).
As reported in Table 3, starting from alkenes 4a,b a very
high asymmetric induction leading to the formation of only
one of the possible diastereomers of aziridines was ob-
served regardless of the choice of the aminating agent, of
the inorganic base, and of the solvent.
Figure 2.
Concerning the absolute configuration of the new chiral
centres of these aziridines, X-ray analysis performed on
8a showed that the nucleophilic attack of the aza-anion
takes place on the Si face of chiral alkenes 4. In Figure 3,
the molecular structure of 8a is shown. Ellipsoids are at
50% probability.
Table 3. Aziridination of (E)-nitro alkenes 4
Entry Alkene R0 Solvent Base Time Yielda Aziridineb
(h)
(%)
(dr)
The choice between the two enantiomeric models (RRR) or
(SSS) at the atoms C(3), C(7) and C(8), respectively, has
been done on the basis of the known configuration of the
C(3) atom.
1
2
3
4
5
6
(E)-4a Et CH2Cl2 CaO
(E)-4a Bn CH2Cl2 CaO
3.5
3
1
1
4
81
84
78
79
78
72
7a/7a0 (6:4)
8a/8a0 (6:4)
7a/7a0 (6:4)
8a/8a0 (6:4)
7b/7b0 (7:3)
7b/7b0 (7:3)
(E)-4a Et THF
(E)-4a Bn THF
NaH
NaH
(E)-4b Et CH2Cl2 CaO
(E)-4b Et CaO
Finally our interest was turned towards the useful chemical
elaboration of optically active aziridines. In particular, we
were interested to open selectively the dioxolane ring with-
out affecting the aziridine.
—
0.5
a After flash chromatography. The isomers were separated by HPLC.
b Determined by 1H NMR spectra on crude mixtures.
1
The analyses of H NMR spectra performed on the crude
Starting from the diastereomers 5a,a0, a chemoselective
mixture confirmed the formation of two diastereomers of
hydrolysis of the dioxolane ring11 with HCl led to the for-
Boc
Boc
N CO2R'
Boc
N
O
N
CO2R'
O
O
NsONHCO2R'
R
N
+
N
R
NO2
H
NO2
H
NO2
H
R
R' = Et, Bn
7a,b
7a',b'
(E)-4a,b
8a
8a'
Scheme 5.

234
S. Fioravanti et al. / Tetrahedron: Asymmetry 19 (2008) 231–236
corded on a PERKIN ELMER 1600 FT/IR spectropho-
tometer in CHCl3 as the solvent, and reported in cmꢀ1
.
1H NMR and 13C NMR spectra were recorded at 300
and 75 MHz or at 200 and 50 MHz with a Varian XL-
300 or Gemini 200 NMR spectrometer, respectively, and
reported in d units. CDCl3 was used as the solvent and
CHCl3 as the internal standard. ESI MS analyses were per-
formed 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 con-
ducted in the positive ion mode. Optical rotations were
determined with a JASCO DIP-370 polarimeter. HPLC
analyses were performed with a VARIAN 9002 instrument
using an analytical column (3.9 ꢁ 300 mm, flow rate
1.3 mL/min; detector: 254 nm) equipped with a VARIAN
9040 differential refractometer, or a VARIAN 9050 UV/
VIS detector. Eluents were HPLC grade. Analytical thin-
layer chromatography (TLC) was carried out on precoated
silica gel plates. Silica gel 230–400 mesh was used for
column chromatography. All solvents were dried following
reported standard procedures.
4.1.1. Synthesis of optically active nitro alkenes. General
procedure
4.1.1.1. Formation of nitro aldols. To a solution of
enantiomerically pure aldehyde 1 or 2 (10 mmol, 1.0 equiv)
in i-PrOH (20 mL) and benzene (2 mL) a suitable nitro
alkane (50 mmol, 5.0 equiv) and KF (100 mg) were added.
The mixture was stirred at room temperature for 24 h.
Then CH2Cl2 (20 mL) was added and the solution was fil-
tered through a pad of Celite. After evaporation of the sol-
vents under reduced pressure the residue was dissolved in
CH2Cl2, washed with saturated NaCl solution and dried
with Na2SO4. Evaporation of the solvent under reduced
pressure gave crude nitro aldols as diastereomeric mixtures,
which were used in the dehydration step without further
purification.
Figure 3.
mation of diastereomers 9a,a0 in quantitative yield after
30 min (Scheme 6).
CO2R'
CO2R'
O
OH
H
O
N
HCl 10%
N
R
HO
R
MeOH, r.t., 30 min
H
NO2
NO2
4.1.1.2. Dehydration of nitro aldols. Methylsulfonyl
chloride (1.2 equiv) was added to a solution of crude nitro
aldol (3.25 mmol, 1.0 equiv) in 20 mL of dry CH2Cl2 in one
portion at 0 °C after 10 min followed by i-Pr2NEt
(2.5 equiv). The reaction mixture was allowed to warm to
room temperature and washed with water, 2 M HCl and
sat. NH4Cl-solution. After drying with Na2SO4 the solvent
was evaporated under reduced pressure and the remaining
residue was purified by flash chromatography.
5a,a'
9a,a'
Scheme 6. Chemoselective hydrolysis of the dioxolane ring.
3. Conclusion
In conclusion, we have reported the synthesis of chiral
functionalized aziridines, which can be considered useful
building blocks, potential starting materials to obtain
target molecules containing different sites of molecular
growth.12 Interestingly, the stereochemical outcome of
aziridination reactions was strongly influenced by the chi-
ral residue, giving stereoisomers, regardless of the reaction
conditions.
4.1.2. Synthesis of chiral nitro aziridines. General proce-
dures. To an equimolar stirred solution of optically active
nitro alkenes 3 and 4 and NsONHCO2R (R = Et,13a
Bn13b), CaO or NaH (2 equiv) in CH2Cl2 or THF were
added, respectively. After the reaction was complete (1–
4 h, HPLC) the crude aziridines were filtered through plugs
filled with silica gel using a 7/3 hexane/ethyl acetate eluent
and products 5–8 were obtained as oils after solvent re-
moval. The diastereomeric mixtures of nitro aziridines 7
and 8 were separated by HPLC using an 8/2 hexane/ethyl
acetate mixture as the eluent (flow 1.3 mL/min).
4. Experimental
4.1. General methods
GC–MS analyses were performed with a HP G1800A gas
chromatograph equipped with a capillary column (phenyl
methyl silicone, 30 m ꢁ 0.25 mm). IR spectra were re-
4.1.3. Solvent-free synthesis of chiral nitro aziridines.
General procedure. CaO (2 mmol), NsONHCO2Et

S. Fioravanti et al. / Tetrahedron: Asymmetry 19 (2008) 231–236
235
(1 mmol) and optically active nitro alkenes (E)-3a, (E)-3b
or (E)-4b (1 mmol) were ground together in a mortar for
30 min. The solid mixtures were dissolved with ethyl ace-
tate and filtered through plugs filled with silica gel using
a 7/3 hexane/ethyl acetate mixture. After evaporation of
the solvents under reduced pressure, diastereomeric mix-
tures of corresponding nitro aziridines were obtained.
6H), 1.45 (s, 3H), 1.48 (s, 9H) 1.93/2.03 (s, 3H), 3.44 (m,
1H), 4.12 (m, 4H), 5.29 (s, 1H). 13C NMR: 14.4, 23.1,
25.1, 26.5, 28.2, 44.2, 54.5, 63.2, 81.8, 94.5, 151.4, 156.0.
HRMS (ES Q-TOF) calcd for C16H28N3O7 (M+H)+:
374.1927; found: 374.1891.
4.1.10. tert-Butyl (4S)-4-[(20S,30R)-10-(ethoxycarbonyl)-30-
methyl-30-nitroaziridin-20-yl]-2,2-dimethyl-1,3-oxazolidine-3-
carboxylate 7b0. Yellow oil, 23%. [a]D = +2.15 (c 1.0,
4.1.4. Ethyl (2R,3S)- and (2S,3R)-2-[(40S)-20,20-dimethyl-
10,30-dioxolan-40-yl]-3-nitroaziridine-1-carboxylate
5a,a0.
CHCl3). IR: 1743, 1698, 1561 cmꢀ1 1H NMR: 1.12 (s,
.
Pale yellow oil, 70–82%. IR: 1744, 1568 cmꢀ1. H NMR:
1.28 (t, J = 10 Hz, 3H), 1.44 (s, 6H), 3.26 (d, J = 1.5 Hz,
1H), 3.32 (d, J = 1.5 Hz, 1H), 3.92 (m, 1H), 3.97 (m,
1H), 4.22 (m, 4H), 4.43 (m, 1H), 5.17 (d, J = 1.5 Hz,
1H), 5.2 (d, J = 1.5 Hz, 1H). 13C NMR: 14.2, 24.8, 26.2,
26.8, 28.1, 46.0, 46.3, 62.9, 63.2, 71.4, 71.5, 110.8, 156.4,
157.9. HRMS (ES Q-TOF) calcd for C10H17N2O6
(M+H)+: 261.1087; found: 261.1062.
6H), 1.35 (s, 9H), 1.46 (s, 3H) 2.01 (s, 3H), 3.41 (m, 1H),
4.05 (m, 5H). 13C NMR: 14.4, 23.0, 25.4, 26.8, 29.2, 44.3,
54.6, 63.2, 81.8, 97.5, 151.4, 156.0. HRMS (ES Q-TOF)
calcd for C16H28N3O7 (M+H)+: 374.1927; found:
374.1894.
1
4.1.11. tert-Butyl (4S)-4-{(20S,30S)-10-[(phenylmethoxy)car-
bonyl]-30-nitroaziridin-20-yl}-2,2-dimethyl-1,3-oxazolidine-3-
carboxylate 8a. White solid, 47%. mp 89–91 °C.
4.1.5. Benzyl (2R,3S)- and (2S,3R)-2-[(40S)-20,20-dimethyl-
[a]D = +2.7 (c 1.0, CHCl3). IR: 1743, 1702, 1566 cmꢀ1
.
10,30-dioxolan-40-yl]-3-nitroaziridine-1-carboxylate
6a,a0.
1H NMR: 1.47 (s, 3H), 1.49 (s, 3H), 3.27 (dd, J = 0.7 Hz,
7.8 Hz, 1H), 3.45/3.58 (m, 1H), 4.01/4.13 (m, 2H), 5.16
(m, 1H), 5.21/5.24 (br, 1H), 7.34 (m, 5H). 13C NMR:
22.7, 24.0, 28.2, 46.0/46.5, 56.7/57.2, 69.4/69.8, 81.3, 95.1,
128.5, 128.6, 128.7, 151.2, 152.4, 156.4. HRMS (ES Q-
TOF) calcd for C20H28N3O7 (M+H)+: 422.1927; found:
422.1866.
Yellow oil, 75–85%. IR: 1743, 1565 cmꢀ1. H NMR: 1.27
(s, 3H), 1.39 (s, 3H), 3.27 (dd, J = 1.8 Hz, 2.4 Hz, 1H),
3.35 (dd, J = 1.2 Hz, 1.5 Hz, 1H), 3.94 (m, 2H), 4.19 (m,
2H), 5.15 (m, 2H), 5.19 (s, 2H), 7.36 (m, 5H). 13C NMR:
24.7, 24.8, 26.0, 46.5, 67.2, 69.3, 71.1, 110.8, 128.5, 128.9,
134.6, 156.4, 157.8. HRMS (ES Q-TOF) calcd for
C15H17N2O6 (M+H)+: 323.1243; found: 323.1207.
1
4.1.12. X-ray crystallographic study of 8a. Colourless thin
needles of 8a were grown by slow evaporation of a satu-
rated hexane solution. In spite of the relatively good crystal
quality, their low diffracting power and the too small
dimensions prevented a diffraction study on a home diffrac-
tometer. X-ray crystallographic analysis was then per-
formed using synchrotron radiation data, collected at
ELETTRA (XRD-1 beam line), Trieste (Italy),
4.1.6. Ethyl (2S,3R)- and (2R,3S)-3-[(40S)-20,20-dimethyl-
10,30-dioxolan-40-yl]-2-methyl-2-nitroaziridine-1-carboxylate
1
5b,b0. Yellow oil, 79%. IR: 1743, 1561 cmꢀ1. H NMR:
1.33 (s, 3H), 1.42 (s, 3H), 1.97 (s, 3H), 1.98 (s, 3H), 2.78
(m, 1H), 3.32 (m, 1H), 4.18 (m, 5H). 13C NMR: 14.2,
16.8, 25.1, 26.6, 49.2, 49.6, 63.5, 63.8, 67.7, 67.8, 110.7,
156.6, 157.2. HRMS (ES Q-TOF) calcd for C11H19N2O6
(M+H)+: 275.1243; found: 275.1189.
˚
k = 0.700087 A. A marCCD detector (marUSA Inc.,
USA) and focusing optics were employed for the measure-
ments. Ninety images were collected at 100 K and a 4°
oscillation range was used for all images. The degree of lin-
ear polarization was assumed to be 0.95 and the mosaic
spread of the crystal was estimated to be 0.54°. Raw data
were indexed, integrated, scaled, and reduced using the
HKL14 package. The specimen used (15 lm ꢁ 30 lm ꢁ
280 lm) belongs to the orthorhombic system with unit cell:
a = 17.937(1), b = 5.739(1), c = 20.731(2), space group
4.1.7. tert-Butyl (4S)-4-[(2S,3S)-1-(ethoxycarbonyl)-3-nitro-
aziridin-2-yl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
7a. Yellow oil, 32%. [a]D = +2.2 (c 1.0, CHCl3). IR: 1743,
1696, 1566 cmꢀ1. 1H NMR: 1.26 (t, J = 7 Hz, 3H), 1.46 (s,
9H), 1.50 (s, 6H), 3.24 (m, 1H), 3.52 (m, 1H), 4.11 (m, 4H),
5.22/5.47 (br s, 1H). 13C NMR: 14.1, 22.9, 24.0, 28.2, 46.2,
57.3, 63.8, 81.8, 94.7, 153.6, 156.5. HRMS (ES Q-TOF)
calcd for C15H26N3O7 (M+H)+: 360.1771; found:
360.1749.
P212121, Z = 4, l = 0.120 mmꢀ1 and Dc = 1.312 g cmꢀ3
.
The intensity data were merged to give 7990 unique reflec-
tions, merging R = 0.0243, of which 6816 with I P 2r(I).
The structure was solved by SHELXS-9715 and refined by
full-matrix least-squares procedures. Hydrogen atoms were
located from a difference Fourier map. In the final refine-
ment cycle anisotropic thermal parameters were used for
all of the nonhydrogen atoms, while hydrogen ones were
refined isotropically using a riding model. The final residu-
als were R1 = 0.0507, wR2 = 0.1218 for the 6816 observed
reflections and 0.0634, 0.1298 for all data and 277 para-
4.1.8. tert-Butyl (4S)-4-[(2S,3R)-1-(ethoxycarbonyl)-3-nitro-
aziridin-2-yl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
7a0. Yellow oil, 49%. [a]D = +1.9 (c 1.0, CHCl3). IR:
1
1743, 1696, 1566 cmꢀ1. H NMR: 1.26 (t, J = 7 Hz, 3H),
1.47 (s, 9H), 1.56 (s, 6H), 3.38/3.44 (d, J = 1.1 Hz, 1H),
4.06 (m, 5H), 5.06 (d, J = 1.1 Hz, 1H). 13C NMR: 14.0,
23.3, 26.5, 28.2, 44.9, 54.5, 63.5, 81.1, 94.6, 151.0, 156.2.
HRMS (ES Q-TOF) calcd for C15H26N3O7 (M+H)+:
360.1771; found: 360.1746.
meters. Goof = 1.087, maximum Dq = 0.452 e Aꢀ3. All
˚
4.1.9. tert-Butyl (4S)-4-[(20S,30S)-10-(ethoxycarbonyl)-30-
methyl-30-nitroaziridin-20-yl]-2,2-dimethyl-1,3-oxazolidine-3-
carboxylate 7b. Yellow oil, 55%. [a]D = +1.9 (c 1.0,
calculations were performed on a microcomputer using
SHELXL-97 and WINGX programs.15,16 Crystallographic
data (excluding structure factors) for the structure reported
in this paper have been deposited with the Cambridge
CHCl3). IR: 1743, 1698, 1561 cmꢀ1 1H NMR: 1.25 (s,
.

236
S. Fioravanti et al. / Tetrahedron: Asymmetry 19 (2008) 231–236
A. S. In Aziridines and Epoxides in Organic Synthesis; Yudin,
A. K., Ed.; Wiley-VCH: Weinheim, 2006; pp 399–442.
3. (a) Olsen, C. A.; Franzyk, H.; Jaroszewski, J. W. Eur. J. Org.
Chem. 2007, 1717–1724; (b) Sweeney, J. B. Chem. Soc. Rev.
2002, 31, 247–258.
Crystallographic Data Centre as supplementary publica-
tion no. CCDC-666872. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: int. code +44(1223)336-
033; e-mail: deposit@ccdc.cam.ac.uk].
4. Colantoni, D.; Fioravanti, S.; Pellacani, L.; Tardella, P. A.
Org. Lett. 2004, 6, 197–200, and references cited therein.
5. (a) Wurz, R. P.; Charette, A. B. J. Org. Chem. 2004, 69, 1262–
1269; (b) Yun, Y. K.; Godula, K.; Cao, Y.; Donaldson, W. A.
J. Org. Chem. 2003, 68, 901–910; (c) Yashin, N. V.; Averina,
E. B.; Gerdov, S. M.; Kuznetsova, T. S.; Zefirov, N. S.
Tetrahedron Lett. 2003, 44, 8241–8244; (d) Brandl, M.;
Kozhushkov, S. I.; Loscha, K.; Kokoreva, O. V.; Yufit, D.
S.; Howard, J. A. K.; de Meijere, A. Synlett 2000, 1741–1744.
6. Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A.;
Ballini, R. Tetrahedron 1998, 54, 6169–6176.
4.1.13. tert-Butyl (4S)-4-{(20S,30R)-10-[(phenylmethoxy)car-
bonyl]-30-nitroaziridin-20-yl}-2,2-dimethyl-1,3-oxazolidine-3-
carboxylate 8a0. White solid, 32%. mp 95–97 °C.
[a]D = +2.0 (c 1.0, CHCl3). IR: 1743, 1702, 1566 cmꢀ1
.
1H NMR: 1.45 (s, 3H), 1.47 (s, 3H), 3.28 (dd, J = 0.7 Hz,
7.8 Hz, 1H), 3.82 (m, 2H), 5.08 (s, 2H), 5.16 (m, 1H),
5.21/5.24 (br, 1H), 7.34 (m, 5H). 13C NMR: 14.0, 22.5,
28.2, 54.4, 67.8/69.3, 128.4, 128.5, 128.6, 156.1. HRMS
(ES Q-TOF) calcd for C20H28N3O7 (M+H)+: 422.1927;
found: 422.1860.
7. Hubner, J.; Liebscher, J.; Pa¨tzel, M. Tetrahedron 2002, 58,
¨
10485–10500.
8. (a) Foss, F. W.; Snyder, A. H.; Davis, M. D.; Rouse, M.;
Okusa, M. D.; Lynch, K. R.; Macdonald, T. L. Bioorg. Med.
Chem. 2007, 15, 663–677; (b) Reginato, G.; Meffre, P.;
Gaggini, F. Amino Acids 2005, 29, 81–87; (c) Krief, A.;
Froidbise, A. Tetrahedron 2004, 60, 7637–7658; (d) Shin, J.;
Gerasimov, O.; Thompson, D. H. J. Org. Chem. 2002, 67,
6503–6508; (e) Dollt, H.; Zabel, V. Aust. J. Chem. 1999, 52,
259–270.
4.1.14. Ethyl (2R,3S) and (2S,3R)-2-[(10S)-10,20-dihydroxy-
ethyl]-3-nitroaziridine-1-carboxylate 9a,a0. Pale yellow oil.
IR: 3630, 1744, 1568 cmꢀ1. 1H NMR: 1.25 (s, 3 H), 1.60 (s,
1H), 3.66 (d, J = 1.5 Hz, 1H), 3.75 (d, J = 1.5 Hz, 1H), 4.14
(m, 6H), 5.35 (d, J = 1.5 Hz, 1H), 5.14 (d, J = 1.5 Hz, 1H).
13C NMR: 46.4, 46.8, 63.0, 63.2, 71.4, 71.8, 111.4, 156.7,
157.1. HRMS (ES Q-TOF) calcd for C7H13N2O6
(M+H)+: 221.0774; found: 221.0790.
9. Xie, W. H.; Fang, J. W.; Li, J.; Wang, P. G. Tetrahedron
1999, 55, 12929–12938.
10. (a) Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P.
A. Tetrahedron Lett. 1993, 34, 4353–4354; (b) Mash, E. A.;
Hemperly, S. B.; Nelson, K. A.; Hedidt, P. C.; Van Deusen,
S. J. Org. Chem. 1990, 55, 2045–2055; (c) Mash, E. A.;
Hemperly, S. B. . J. Org. Chem. 1990, 55, 2055–2060.
11. Akindele, T.; Yamamoto, Y.; Maekawa, M.; Umeki, H.;
Yamada, K.-I.; Tomioka, K. Org. Lett. 2006, 8, 5729–5732.
12. (a) Hodgson, D. M.; Humphreys, P. G.; Hughes, S. P. Pure
Appl. Chem. 2007, 79, 269–279; (b) Zhou, P.; Chen, B.-C.;
Davis, F. A. In Aziridines and Epoxides in Organic Synthesis;
Yudin, A. K., Ed.; Wiley-VCH: Weinheim, 2006; pp 73–115;
(c) McCoull, W.; Davis, F. A. Synthesis 2000, 1347–1365.
13. (a) Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87,
3630–3637; (b) Fioravanti, S.; Morreale, A.; Pellacani, L.;
Tardella, P. A. . Eur. J. Org. Chem. 2003, 4549–4552.
14. Otwinowski, Z.; Minor, W. In Methods in Enzymology;
Carter, C. W., Jr., Sweet, R. M., Eds.; Macromolecular
Crystallography, Part A; Academic Press: New York, 1997;
Vol. 276, pp 307–326.
Acknowledgements
This research was carried out within the framework of the
National Project ‘Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni’, supported by the Italian
`
Ministero dell’Istruzione dell’Universita e della Ricerca
`
(MIUR) and by the Universita degli Studi di Roma ‘La
Sapienza’.
References
1. (a) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem. Res.
2006, 39, 194–206; (b) Helten, H.; Schirmeister, T.; Engels, B.
J. Org. Chem. 2005, 70, 233–237; (c) Tetrahedron Symposia-
in-Print, Florio, S., Ed. Tetrahedron 2003, Vol. 59, 9693–
9864; (d) Dahanukar, V. H.; Zavialov, L. A. Curr. Opin. Drug
Discov. Devel. 2002, 5, 918–927.
15. Sheldrick, G. M. SHELXS-97 and SHELXL-97, Programs for
Solution and Refinement of Crystal Structures, University of
Go¨ttingen, Germany, 1997.
2. (a) Mladenovic, M.; Schirmeister, T.; Thiel, S.; Thiel, W.;
Engels, B. ChemMedChem 2007, 2, 120–128; (b) Lowden, P.
16. Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.