One-pot synthesis of aziridines from vinyl selenones and variously functionalized primary amines

Article abstract of DOI:10.1016/j.tet.2010.06.055

Variously substituted aziridines were conveniently prepared by an aza-Michael Initiated Ring Closure (aza-MIRC) reaction starting from vinyl selenones and primary amines, aminoalcohols or diamines. The reactions proceed in very high yields at room temperature in toluene or water. A significant rate acceleration was observed under aqueous conditions.

Full text of DOI:10.1016/j.tet.2010.06.055

Tetrahedron 66 (2010) 6851e6857
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Tetrahedron
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One-pot synthesis of aziridines from vinyl selenones and variously functionalized
primary amines
*
Silvia Sternativo, Francesca Marini , Francesca Del Verme, Antonella Calandriello, Lorenzo Testaferri,
Marcello Tiecco
Dipartimento di Chimica e Tecnologia del Farmaco, Sezione di Chimica Organica, Università di Perugia, 06123 Perugia, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Variously substituted aziridines were conveniently prepared by an aza-Michael Initiated Ring Closure
(aza-MIRC) reaction starting from vinyl selenones and primary amines, aminoalcohols or diamines. The
reactions proceed in very high yields at room temperature in toluene or water. A significant rate
acceleration was observed under aqueous conditions.
Received 30 March 2010
Received in revised form 3 June 2010
Accepted 21 June 2010
Available online 25 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Aziridine
Vinyl selenone
Aza-Michael reaction
Ring-closure
Water
1. Introduction
aziridines from vinyl selenones by an aza-Michael Initiated Ring
Closure reaction (aza-MIRC) (Scheme 1, path d).
Because of their high level of chemical diversity, ready avail-
ability, easy handling, and wide efficiency and applicability, orga-
noselenium compounds are considered useful reagents for many
synthetic transformations.1 Although their chemical structure is
closely related to that of the homologous sulfur analogous, the re-
activity often presents marked differences.1 An illustrative example
is that of vinyl selenones. The electron-withdrawing effect com-
bined with the excellent nucleofugal ability of the phenylselenonyl
function makes the vinyl selenones useful substrates for interesting
transformations, which have no parallel in sulfone chemistry. A
classic example is the one-pot synthesis of cyclopropanes by
treatment of vinyl selenones with enolates, a Michael Initiated Ring
Closure reaction (MIRC) in which the phenylselenonyl substituent
plays a dual role as activating group in the conjugate addition and
as leaving group in the following cyclization (Scheme 1, path a).2
Recently, as part of our study on novel synthetic applications of
vinyl selenones, we have developed organocatalyzed cascade re-
actions for the enantioselective synthesis of highly functionalized
cyclopropanes3 (Scheme 1, path b) as well as of other useful poly-
functional compounds containing quaternary stereocentres4
(Scheme 1, path c). We now report the one-pot synthesis of
Scheme 1. Some useful conversions involving vinyl selenones.
Multistep syntheses of aziridines, based on ring closure re-
actions starting from b-aminoselenides are disposable in the liter-
ature,5 but examples of direct transformation of vinyl selenones
through tandem Michael additioneintramolecular nucleophilic
* Corresponding author. Tel.: þ39 075 585 5105; fax: þ39 075 585 5116; e-mail
address: marini@unipg.it (F. Marini).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.055

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S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
substitution reactions are only sporadic.6 As a consequence of the
great synthetic and biological interest for the aziridine skeleton7
and considering the recent interest for MIRC-type approaches to
this ring,8 we decided to study the scope and limitations of this one-
pot protocol respect to amine and selenone structural variations.
The feasibility of the process under aqueous conditions9 has also
been investigated.
chromatography on a pad of silica gel. With regard to Michael
acceptors, the -substituted vinyl selenone 1E is less reactive than
the -substituted 1AeD and the unsubstituted 1F. Functionalized
a,b
b
amines containing more than one nucleophilic group, such as the
diamines 2d and 2e or the aminoalcohols 2f and 2g, react, che-
moselectively, affording the expected aziridines in high to nearly
quantitative yields (Table 1, entries 4e7). In order to access to
non-racemic aziridines the (R)-2-aminopropan-1-ol 2j, the (R)-1-
phenylethylamine 2k, and the (1R,2R)-1,2-diphenylethane-1,2-di-
amine 2l were employed. The aziridines 3jA and 3kA were formed
from 2j or 2k and 1A in good yields as mixtures of two enantio-
merically pure diastereoisomers in 1:1 and 3:1 ratio, respectively
(Table 1, entries 15 and 16). The diastereoisomers could be easily
separated by flash chromatography. On the contrary the reaction of
2l with 1A was very sluggish and even after prolonged reaction
times only traces of the diastereomeric aziridines 3lA were present
in the reaction mixture (Table 1, entry 18). The reaction of 2k with
the sterically unhindered selenone 1F went to completion within
only 1 h (Table 1, entry 17).
2. Results and discussion
Preliminary experiments were carried out on vinyl selenone 1A
and benzylamine 2a at room temperature in different organic sol-
vents, such as toluene, CH2Cl2, and CH3CN. The best results were
obtained in toluene in the presence of molecular sieves.10 The
aziridine 3aA was formed at room temperature with a good yield
and an acceptable reaction time (Table 1, entry 1). 2 equiv of 2a
were used to effect the aza-Michael addition and the trapping of
the benzenseleninic acid (PhSeO2H) released during the cyclization
step. Harsh reaction conditions or catalysts, usually employed with
other Michael acceptors,11 were not required to promote the initial
amine addition.
The reactivity of aromatic amines, such as aniline or the
more nucleophilic p-methoxyaniline, was also investigated.
Table 1
Reactions of amines 2ael with the vinyl selenones 1AeF
Entry
R1
R2
R
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
1A
1A
1A
1A
1A
1A
1A
1A
1A
1B
1C
1D
1D
1E
CH2Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
2a
2a
2a
2b
2a
24
24
24
24
24
24
48
110
72
60
3aA
3bA
3cA
3dA
3eA
3fA
3gA
3hA
3iA
3aB
3aC
3aD
3bD
3aE
80
97a
94
88
99
99
86
40b
82
75
43
83
87a
50
(CH2)3CH3
CH2CH]CH2
(CH2)4NH2
(CH2)2NH2
(CH2)5OH
(CH2)2OH
CH2CO2CH3
(CH2)2CO2CH2CH3
CH2Ph
CH2Ph
CH2Ph
(CH2)3CH3
PhCH2
9
Ph
10
11
12
13
14
p-MeeC6H4
p-CleC6H4
(CH2)5CH3
(CH2)5CH3
e(CH2)3e
72
48
24
120
82c
d.r. 50:50
15
16
17
Ph
Ph
H
H
H
H
1A
1A
1F
2j
48
60
1
3jA
54c
d.r. 75:25
2k
2k
3kA
3kF
85
18
Ph
H
1A
2l
120
3lA
traces
a
3.5 equiv of BuNH2 were used.
b
c
The reaction was carried out in dichloromethane.
Combined yield of the chromatographically separated diastereoisomers. Diastereomeric ratios were determined by 1H NMR of the crude product and confirmed after
chromatographic separation.
These reaction conditions proved to be effective for the con-
version of the variously substituted vinyl selenones 1AeF with
a wide range of primary amines. As shown in Table 1, with few
exceptions, the aziridines 3 were obtained in high yields after
evaporation of the solvent and purification by flash
Unfortunately, only starting materials were recovered from the
reactions even after prolonged reaction times, heating or addition
of promoters, such as amberlyst,11a,b CAN11c,d or DBU.11e These re-
sults are consistent with the lower nucleophilicity of the aromatic
amines in comparison with the aliphatic ones.

S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
6853
Finally we decided to test the feasibility of the process in
aqueous suspension or emulsion, without any catalyst or organic
co-solvent. Recently the use of water as a medium for organic re-
actions9 has attracted much attention not only because it is envi-
ronmentally friendly, but also because exhibits a unique reactivity
that can not be obtained with the conventional organic solvents.
Generally, conjugate additions to selenones have been carried out
in apolar or polar aprotic solvents1,6 but, to the best of our knowl-
edge, not in pure water. The results of the experiments are collected
in Table 2. Water significantly improved the process, in fact all the
aziridines were obtained in good to excellent yields in shortened
reaction times. As a significant example, the aziridines 3lA, present
only in traces when toluene was used as the solvent, could be
isolated in high yield (Table 2, entry 10). The increase in rate of the
aqueous over the solvent-free reaction of 2a with 1A (Table 2, en-
tries 1 and 2) suggests that water plays an active role on promoting
the addition and/or the cyclization step and the rate acceleration is
not only a consequence of the increased effective concentration of
the poorly soluble reacting species.9a It seems reasonable that, as
proposed for other aza-Michael additions to activated alkenes,12
water acts both as H-bond donor with the selenone group, in-
Scheme 2. Possible role of water during the aza-Michael and the cyclization step.
as catalysts for an asymmetric process. The aziridines were
obtained in good yields, but, unfortunately, with very poor asym-
metric induction. For example, the experiments carried out with
the selenones 1A or 1D and the amine 2a in the presence of cata-
lytic amounts (20 mol %) of (R)-BINOL in toluene gave the aziridines
3aA and 3aD with 76% yield, 18% ee and 92% yield, 10% ee, re-
spectively. Similar results were obtained using stoichiometric
amounts of (R)-BINOL.
creasing the electrophilic character of the
b
-carbon atom in 1, and
Table 2
Reactions of amines 2 with vinyl selenones 1 in water
Entry
R1
R2
R
Time (h)
Yield (%)
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
H
H
H
H
H
H
1A
1A
1A
1A
1D
1D
1E
CH2Ph
CH2Ph
2a
2a
2b
2c
2a
2b
2a
3
7
5
5
5
3aA
3aA
3bA
3cA
3aD
3bD
3aE
91
72a
75b
63
(CH2)3CH3
CH2CH]CH2
CH2Ph
(CH2)3CH3
CH2Ph
CH3(CH2)5
CH3(CH2)5
(CH2)3
97
5
20
80b
99
76c,d
d.r. 65:35
8
9
Ph
H
H
1A
1D
2k
2k
40
72
3kA
3kD
70c,d
d.r. 50:50
CH3(CH2)5
82c,d
d.r. 60:40
10
Ph
Ph
H
H
1A
1A
2l
72
22
3lA
61c,d
d.r. 60:40
11
2m
3mA
a
Reaction carried out under solvent-free condition, with 4 equiv of PhCH2NH2.
3.5 equiv of BuNH2 were used.
b
c
1.1 equiv of the chiral amine and 2 equiv of Et3N have been used.
d
Combined yield of the chromatographically separated diastereoisomers. Diastereomeric ratios were determined by 1H NMR of the crude product and confirmed after
chromatographic separation.
as H-bond acceptor with the amine 2, increasing its nucleophilic
3. Conclusions
properties. Similar H-bonding between water and the
b-amino-
selenone intermediate should also have beneficial effects on the
following cyclization step (Scheme 2). More generally, water may
be responsible for a faster proton transfer.12d
Finally, the observation that aziridine formation is favored in
a protic solvent prompted us to investigate the use of chiral alcohols
In conclusion a tandem Michael additioneintramolecular nu-
cleophilic substitution process for the preparation of aziridines
from vinyl selenones and primary amines has been described.
Variously functionalized aziridines have been generated in good to
excellent yields. Using a chiral amine it is possible to produce

6854
S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
a
couple of optically active, easily separable diastereomeric
(ATR): nmax 3089, 3042, 1700, 1447, 1370, 1220, 1065, 981, 928,
882 cmꢁ1. Anal. Calcd for C8H8O2Se: C, 44.67; H, 3.75; found: C,
44.93; H, 3.69.
aziridines. The process has been conveniently carried out under
aqueous conditions with shortened reaction times. The reported
aziridination confirms the potential of vinyl selenones as
valuable substrates for sequential or domino reactions. Further
investigations in this field are currently underway in our
laboratories.
4.3. General procedure for the one-pot synthesis of the
aziridines 3 in toluene
In an ordinary vial equipped with a Teflon-coated stir bar, vinyl
selenones 1AeF (0.2 mmol) and amines 2ael (0.4 mmol, 2 equiv)
were dissolved in undistilled toluene (0.4 mL) with 20 mg of 4 Å MS
under an air atmosphere. The resulting mixtures were stirred at
room temperature for the time reported in Table 1. The reaction
mixtures were directly poured into the column for the flash chro-
matographic purification (hexane/EtOAc or dichloromethane/
MeOH as eluant). Yields and diastereomeric ratios of the aziridines
3 are reported in Table 1.
4. Experimental section
4.1. General
1H and 13C NMR spectra were recorded in CDCl3 at 400 and
100 MHz, respectively, on a Bruker Avance-DRX 400 instrument.
The chemical shifts (d
) are referred to TMS as internal standard (1H
NMR) and the residual signals of the solvent (CDCl3, 77.0 ppm for
13C NMR). Coupling constants are given in hertz. The following
abbreviations are used to indicate the multiplicity: s, singlet; d,
doublet; t, triplet; q, quartet; quint, quintet; m, multiplet; br, broad
signal. GCeMS analyses were carried out with an HP 6890 gas
chromatograph (HP-5MS capillary column, 30 m, I.D. 0.25 mm, film
4.4. General procedure for the one-pot synthesis of the
aziridines 3 in water
In an ordinary vial equipped with a Teflon-coated stir bar, the
amines 2aec (0.4 mmol, 2 equiv) or the chiral amines 2kem
(0.22 mmol, 1.1 equiv) were added to the suspension or emul-
sion of the vinyl selenones 1A, DeE (0.2 mmol) in distilled water
(0.4 mL). When chiral amines were used, Et3N (0.4 mmol,
2 equiv) was also added. The resulting mixtures were vigorously
stirred at room temperature for the time reported in Table 2.
The reaction mixtures were extracted with dichloromethane
and the organic layers were dried over Na2SO4 and evaporated.
The aziridines were purified by flash chromatography. Yields
and diastereomeric ratios of the aziridines 3 are reported in
Table 2.
0.25 mm) equipped with an HP 5973 Mass Selective Detector at an
ionizing voltage of 70 eV. FTIR spectra were recorded with a Jasco
model 410 spectrometer equipped with a Pike Technologies Hori-
zontal ATR cell. Optical rotations were measured with a Jasco DIP-
1000 digital polarimeter, the concentrations (c) are reported in
gram per 100 mL. Elemental analyses were carried out on a Carlo
Erba 1106 Elemental analyzer. The melting points are uncorrected.
Thin layer chromatography (TLC) was performed on silica gel 60
F254 (Merck) on aluminum sheets. Purification of reaction products
was carried out by flash chromatography on silica gel Merck 60
(230e400 mesh).
Spectral data of aziridines 3aA,16 3bA,17 3cA,18 3aB,19 3aC,18
3aE20 are identical to those previously described in the literature.
New compounds were characterized by 1H NMR, 13C NMR, IR, and
GCeMS. It is interesting to point out that 1H NMR spectra (CDCl3) of
the 1,2-disubstituted aziridines exhibit a typical trend for the two
protons at the C3 position consisting in two doublets with
3Jy3.4 Hz and 3Jy6.5 Hz, respectively, and an apparent
2J¼0 Hz.16e19 Also the ring protons in 3kF have no apparent gem-
inal coupling constants, as already reported for a similar aziridine.21
Physical and spectral data of aziridines 3aD, 3dA, 3eA, 3fA, 3gA,
3hA, 3iA, 3bD, 3jA, 3kA, 3kF, 3lA, 3kD, 3mA are reported below.
4.2. Starting materials
Commercial grade solvents and reagents were used without
further purification. The starting amines 2aei and the chiral amines
2j (97% ee), 2l (96% ee), 2k (98% ee), and 2m (99% ee) were pur-
chased from Aldrich Inc. According to literature procedures2b,3,4 the
vinyl selenones were prepared from the corresponding commercial
or easily available vinyl bromides by nucleophilic vinylic sub-
stitution followed by oxidation with an excess of m-CPBA and
K2HPO4 in MeOH (1AeC) or from alkenes by a sequence of sele-
nobromination and dehydrobromination13,14 followed by oxidation
with an excess of m-CPBA in dichloromethane (1DeE). 1F was
prepared by oxidation of the corresponding easily accessible sele-
nide15 with an excess of m-CPBA in dichloromethane. Physical and
spectral data of (E)-vinyl selenones 1AeD were previously reported
in the literature.2b,3 Physical and spectral data of 1E, F are described
below.
4.4.1. 4-(2-Phenyl-1-aziridinyl)butylamine (3dA). Yield: (33.6 mg,
88%). Viscous oil. 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.34e7.19 (m, 5H; CH), 2.72 (t, 2H; J¼6.8 Hz, CH2), 2.53 (dt, 1H;
J¼6.8, 11.6 Hz, CH2), 2.37 (dt, 1H; J¼6.8, 11.6 Hz, CH2), 2.33 (dd,
1H; J¼3.3, 6.4 Hz, CH), 2.19 (br s, 2H; NH2), 1.92 (d, 1H; J¼3.3 Hz,
13
CH2), 1.71e1.50 (m, 5H; CH2); C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼140.3, 128.3 (2C), 126.8, 126.1 (2C), 61.5, 42.0, 41.3, 37.8, 31.4,
4.2.1. Cyclopent-1-enyl phenyl selenone (1E). Yield: (190 mg, 30%).
White solid, mp 88e91 ꢀC. 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
27.2. IR (ATR): nmax 3357, 3062, 3032, 2931, 2849, 1640, 1563,
1494, 1313, 1203, 1086, 1061, 1027, 819 cmꢁ1. MS (70 eV, EI): m/z
(%): 189 (1) [Mþꢁ1], 172 (18), 160 (14), 147 (31), 146 (44), 134
(62), 132 (60), 118 (73), 104 (43), 103 (20), 91 (100), 86 (28), 77
(23), 72 (32), 70 (30), 65 (21), 57 (16), 51 (11). Anal. Calcd for
C12H18N2: C, 75.74; H, 9.53; N, 14.72; found: C, 76.05; H, 9.34; N,
14.61.
d
¼8.03e7.96 (m, 2H; CH), 7.76e7.62 (m, 3H; CH), 6.95e6.85 (m, 1H;
CH), 2.79e2.70 (m, 2H; CH2), 2.68e2.61 (m, 2H; CH2), 2.15 (quint,
13
2H; J¼7.7 Hz, CH2); C NMR (100 MHz, CDCl3, 25 ꢀC):
¼144.9,
d
144.8, 141.1, 134.1, 130.2 (2C), 127.0 (2C), 32.6, 30.8, 23.3. IR (ATR):
nmax 3066, 2930, 1611, 1444, 1066, 930, 877 cmꢁ1. Anal. Calcd for
C11H12O2Se: C, 51.78; H, 4.74; found: C, 51.83; H, 4.86.
4.4.2. 2-(2-Phenyl-1-aziridinyl)ethylamine (3eA). Yield: (32.2 mg,
4.2.2. Vinyl phenyl selenone (1F). Yield: (450 mg, 60%). White
99%). Oil. 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.33e7.20 (m,
1
solid, mp 97e102 ꢀC. H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
5H; CH), 3.55 (br s, 2H; NH2), 2.91 (t, 2H; J¼5.9 Hz, CH2), 2.55 (dt,
d
¼8.08e7.95 (m, 2H; CH), 7.76e7.70 (m, 1H; CH), 7.70e7.63 (m,
1H; J¼5.9, 11.9 Hz, CH2), 2.50 (dt, 1H; J¼5.9, 11.9 Hz, CH2), 2.39
2H; CH), 7.03 (dd, 1H; J¼9.1, 16.5 Hz, CH), 6.75 (dd, 1H; J¼2.0,
(dd, 1H; J¼3.3, 6.5 Hz, CH), 1.92 (d, 1H; J¼3.3 Hz, CH2), 1.73 (d, 1H;
16.5 Hz, CH2), 6.47 (dd, 1H; J¼2.0, 9.1 Hz, CH2); 13C NMR (100 MHz,
J¼6.5 Hz, CH2); C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼140.0, 128.3
13
CDCl3, 25 ꢀC):
d¼141.2, 138.9, 134.3, 131.2, 130.3 (2C), 126.9 (2C). IR
(2C), 126.9, 126.1 (2C), 62.5, 41.2, 41.0, 37.6. IR (ATR): nmax 3352,

S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
6855
3063, 2928, 2847, 1648, 1575, 1497, 1455, 1307, 1204, 1088, 1027,
800 cmꢁ1. MS (70 eV, EI): m/z (%): 162 (10) [Mþ], 161 (65), 132
(100), 120 (94), 118 (83), 105 (46), 104 (63), 103 (32), 91 (97), 77
(33), 65 (23), 51 (19). Anal. Calcd for C10H14N2: C, 74.03; H, 8.70;
N, 17.27; found: C, 74.17; H, 8.89; N, 16.94.
for C15H23N: C, 82.89; H, 10.67; N, 6.44; found: C, 82.96; H, 10.91;
N, 6.13.
4.4.8. 1-Butyl-2-hexylaziridine (3bD). Yield: (32.0 mg, 87%). Oil. 1H
NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼2.30 (ddd, 1H; J¼6.6, 8.5,
11.5 Hz, CH2), 2.11 (ddd, 1H; J¼6.0, 8.3, 11.5 Hz, CH2), 1.63e1.19
4.4.3. 5-(2-Phenyl-1-aziridinyl)-1-pentanol (3fA). Yield: (40.8 mg,
(m, 15H, CH, CH2), 1.49 (d, 1H; J¼3.4 Hz, CH2), 1.17 (d, 1H;
99%). Oil. 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d¼7.35e7.21 (m,
J¼6.3 Hz, CH2), 0.92 (t, 3H; J¼7.3 Hz, CH3), 0.89 (t, 3H; J¼7.0 Hz,
13
5H; CH), 3.63 (t, 2H; J¼6.4 Hz, CH2), 2.52 (dt, 1H; J¼7.0, 11.5 Hz,
CH2), 2.39 (dt, 1H; J¼7.0, 11.5 Hz, CH2), 2.34 (dd, 1H; J¼3.4, 6.5 Hz,
CH), 2.10 (br s, 1H; OH), 1.93 (d, 1H; J¼3.4 Hz, CH2), 1.74e1.54 (m,
5H; CH2), 1.53e1.40 (m, 2H; CH2); 13C NMR (100 MHz, CDCl3,
CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼61.3, 39.5, 33.8, 33.2,
32.0, 31.8, 29.1, 27.5, 22.6, 20.5, 14.0 (2C). IR (ATR): nmax 2962,
2922, 2865, 1465, 1378, 1079 cmꢁ1. MS (70 eV, EI): m/z (%): 183
(1) [Mþ], 182 (5), 168 (5), 154 (14), 140 (86), 126 (79), 112 (30), 98
(100), 86 (24), 84 (55), 70 (70), 57 (39), 55 (29). Anal. Calcd
for C12H25N: C, 78.62; H, 13.74; N, 7.64; found: C, 78.84; H, 13.89;
N, 7.27.
25 ꢀC):
d
¼140.2, 128.3 (2C), 126.8, 126.2 (2C), 62.6, 61.6, 41.3, 37.7,
32.5, 29.4, 23.5. IR (ATR): nmax 3310, 2922, 2862, 1728, 1493, 1454,
1053 cmꢁ1. MS (70 eV, EI): m/z (%): 205 (21) [Mþ], 204 (79), 188
(18), 174 (14), 160 (23), 146 (21), 132 (100), 128 (56), 118 (78), 104
(21), 91 (93), 84 (13), 77 (23), 65 (22), 51 (11). Anal. Calcd for
C13H19NO: C, 76.06; H, 9.33; N, 6.82; found: C, 76.51; H, 9.67;
N, 6.53.
4.4.9. (2R)-2-(2-Phenyl-1-aziridinyl)-1-propanol(3jA). Yield: (14.7 mg,
17
41%). First diastereoisomer: oil. [
a
]
ꢁ41.1 (c 0.92, CHCl3); 1H NMR
D
(400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.33e7.21 (m, 5H; CH), 3.72 (dd, 1H;
J¼4.1, 11.1 Hz, CH2), 3.62 (dd, 1H; J¼5.2, 11.1 Hz, CH2), 2.56 (dd, 1H;
J¼3.4, 6.6 Hz, CH), 2.20 (br s, 1H; OH), 1.95 (d, 1H; J¼3.4 Hz, CH2),
1.87e1.78 (m, 1H; CH), 1.77 (d, 1H; J¼6.6 Hz, CH2), 1.20 (d, 3H;
4.4.4. 2-(2-Phenyl-1-aziridinyl)ethanol (3gA). Yield: (28.2 mg, 86%).
1
Oil, slightly impure. H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.40e7.19 (m, 5H; CH), 3.80 (t, 2H; J¼5.1 Hz, CH2), 3.6 (br s, 1H;
J¼6.5 Hz, CH3); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
¼139.9, 128.4 (2C),
d
OH), 2.65 (dt, 1H; J¼5.1, 12.1 Hz, CH2), 2.61 (dt, 1H; J¼5.1, 12.1 Hz,
CH2), 2.47 (dd, 1H; J¼3.4, 6.5 Hz, CH), 1.97 (d, 1H; J¼3.4 Hz, CH2),
127.0, 126.2 (2C), 67.0, 66.1, 41.5, 34.9, 16.3. IR (ATR): nmax 3342, 3039,
2975, 2847, 1727, 1607, 1499, 1448, 1373, 1263, 1203, 1169, 1052,
992 cmꢁ1. MS (70 eV, EI): m/z (%): 177 (13) [Mþ], 176 (89), 146 (22), 130
(6), 120 (15), 118 (52), 104 (15), 91 (100), 86 (10), 77 (16), 65 (10), 51 (9).
Anal. Calcd for C11H15NO: C, 74.54; H, 8.53; N, 7.90; found: C, 74.73; H,
13
1.79 (d, 1H; J¼6.5 Hz, CH2); C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼139.9, 128.3 (2C), 127.0, 126.1 (2C), 62.7, 61.9, 41.0, 37.4. IR (ATR):
nmax 3352, 2935, 2846, 1723, 1606, 1497, 1452, 1261, 1064, 928 cmꢁ1
.
MS (70 eV, EI): m/z (%): 163 (30) [Mþ], 162 (100), 144 (7), 132 (24),
119 (21), 118 (71), 117 (25), 105 (22), 104 (20), 103 (20), 91 (82), 77
(26), 65 (23), 51 (17).
8.69; N, 7.65. (14.5 mg, 41%). Second diastereoisomer: oil. [
a
]
18 þ15.3 (c
D
0.85, CHCl3); 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.40e7.22 (m,
5H; CH), 3.77 (dd, 1H; J¼4.1, 11.0 Hz, CH2), 3.66 (dd, 1H; J¼4.6, 11.0 Hz,
CH2), 2.47 (dd, 1H; J¼3.4, 6.5 Hz, CH), 2.10 (br s, 1H; OH), 1.96 (d, 1H;
4.4.5. Methyl (2-phenyl-1-aziridinyl)acetate (3hA). Yield: (15.4 mg,
J¼3.4 Hz, CH2), 1.88 (d, 1H; J¼6.5 Hz, CH2), 1.85e1.76 (m, 1H; CH), 1.22
1
13
40%). Oil, slightly impure. H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
(d, 3H; J¼6.4 Hz, CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
d¼140.1,
d
¼7.45e7.20 (m, 5H; CH), 3.75 (s, 3H; OMe), 3.35 (d, 1H; J¼16.1 Hz,
128.3 (2C), 126.9, 126.3 (2C), 66.6, 66.3, 38.8, 37.4, 16.8. IR (ATR): nmax
3353, 3040, 2964, 1727, 1457, 1263, 1102, 1050. cmꢁ1. MS (70 eV, EI): m/
z (%): 177 (18) [Mþ], 176 (100), 146 (22), 130 (6), 120 (20), 118 (62), 104
(17), 91 (95), 86 (5), 77 (16), 65 (11), 51 (8). Anal. Calcd for C11H15NO: C,
74.54; H, 8.53; N, 7.90; found: C, 74.91; H, 8.75; N, 7.47.
CH2), 3.22 (d, 1H; J¼16.1 Hz, CH2), 2.50 (dd, 1H; J¼3.6, 6.5 Hz, CH),
2.10 (d, 1H; J¼3.6 Hz, CH2), 1.81 (d, 1H; J¼6.5 Hz, CH2); 13C NMR
(100 MHz, CDCl3, 25 ꢀC):
d
¼170.6, 139.1,128.3 (2C), 127.1,126.3 (2C),
61.5, 51.9, 41.5, 37.6. IR (ATR): nmax 3066, 2923, 2852, 1740, 1476,
1445, 1331, 1152, 1079, 1019 cmꢁ1. MS (70 eV, EI): m/z (%): 191 (18)
[Mþ], 190 (100), 132 (28), 130 (19), 118 (20), 103 (12), 91 (70),
77 (13).
4.4.10. 2-Phenyl-1-[(1R)-1-phenylethyl]aziridine(3kA). Yield: (22.1 mg,
49.5%). First diastereoisomer: oil. [
a
]
19 þ78.9 (c 0.92, CHCl3); 1H NMR
D
(400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.52e7.44 (m, 2H; CH), 7.42e7.23 (m,
4.4.6. Ethyl3-(2-phenyl-1-aziridinyl)propanoate(3iA). Yield: (36.0 mg,
8H; CH), 2.70 (q,1H; J¼6.5 Hz, CH), 2.57 (dd,1H; J¼3.3, 6.5 Hz, CH),1.87
82%). Oil. 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.34e7.20 (m, 5H;
(d, 1H; J¼3.3 Hz, CH2), 1.72 (d, 1H; J¼6.5 Hz, CH2), 1.51 (d, 3H; J¼6.5 Hz,
13
CH), 4.15 (dq, 1H; J¼7.1, 10.8 Hz, CH2), 4.10 (dq, 1H; J¼7.1, 10.8 Hz, CH2),
2.88e2.78 (m, 1H; CH2), 2.72e2.61 (m, 3H; CH2), 2.42 (dd, 1H; J¼3.4,
CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
d¼144.7, 140.6, 128.3 (2C),
128.2 (2C), 127.0, 126.9 (2C), 126.8, 126.4 (2C), 70.3, 41.6, 37.2, 23.6. IR
(ATR): nmax 3025, 2973, 1604, 1494, 1448, 1350, 1218, 1162, 1093, 1029,
934 cmꢁ1. MS (70 eV, EI): m/z (%): 223 (4) [Mþ], 222 (8) 118 (100), 105
(51), 103 (24), 91 (97), 79 (23), 77 (39), 65 (23), 51 (18). Anal. Calcd for
6.5 Hz, CH), 1.92 (d, 1H; J¼3.4 Hz, CH2), 1.76 (d, 1H; J¼6.5 Hz, CH2), 1.23
13
(t, 3H; J¼7.1 Hz, CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
d¼172.3,
140.0, 128.2 (2C), 126.9, 126.1 (2C), 60.4, 56.5, 41.3, 37.7, 35.0, 14.1. IR
(ATR): nmax 3065, 2925, 1734, 1497, 1451, 1376, 1186, 1030 cmꢁ1. MS
(70 eV, EI): m/z (%): 219 (29) [Mþ], 218 (100), 190 (51), 174 (17), 132
(42), 130 (19), 118 (65), 117 (23), 104 (14), 91 (81), 77 (17), 65 (16).
Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39; found: C, 71.53; H,
7.96; N, 6.28.
C16H17N: C, 86.05; H, 7.67; N, 6.27; found: C, 86.16; H, 7.78; N, 6.06.
19
(11.9 mg, 26.5%). Second diastereoisomer: oil. [
a
]
ꢁ106.8 (c 0.84,
D
1
CHCl3); H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.41e7.35 (m, 2H;
CH), 7.32e7.17 (m, 8H; CH), 2.71 (q, 1H; J¼6.6 Hz, CH), 2.43 (dd, 1H;
J¼3.4, 6.5 Hz, CH), 2.07 (d, 1H; J¼3.4 Hz, CH2), 1.86 (d, 1H; J¼6.5 Hz,
13
CH2), 1.52 (d, 3H; J¼6.6 Hz, CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
4.4.7. 1-Benzyl-2-hexylaziridine (3aD). Yield: (42.1 mg, 97%). Vis-
d
¼144. 7, 140.1, 128.2 (2C), 128.1 (2C), 126.8, 126.7 (3C), 126.3 (2C), 70.4,
1
cous oil. H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.40e7.21 (m,
40.9, 37.5, 23.4. IR (ATR): nmax 3059, 2970, 1603, 1494, 1448, 1369, 1308,
1212, 1153, 1091, 1069, 1028, 933 cmꢁ1. MS (70 eV, EI): m/z (%): 223 (4)
[Mþ], 222 (9), 118 (100), 105 (50), 103 (25), 91 (96), 79 (22), 77 (39), 65
(23), 51 (18). Anal. Calcd for C16H17N: C, 86.05; H, 7.67; N, 6.27; found:
C, 86.17; H, 7.73; N, 6.10.
5H; CH), 3.52 (d, 1H; J¼13.2 Hz, CH2), 3.35 (d, 1H; J¼13.2 Hz, CH2),
1.63 (d, 1H; J¼3.2 Hz, CH2), 1.46e1.15 (m, 12H; CH, CH2), 0.89 (t, 3H;
13
J¼7.1 Hz, CH3); C NMR (100 MHz, CDCl3, 25 ꢀC):
d¼139.4, 128.2
(2C), 128.1 (2C), 126.9, 65.0, 39.8, 34.0, 33.4, 33.0, 29.0, 27.4, 22.5,
14.0. IR (ATR): nmax 3033, 2928, 2856, 1729, 1495, 1453, 1380, 1355,
1278, 1164, 1069, 1028 cmꢁ1. MS (70 eV, EI): m/z (%): 217 (5) [Mþ],
216 (20), 188 (23), 174 (41), 160 (76), 146 (66), 132 (23), 126 (28), 120
(46), 106 (19), 91 (100), 84 (17), 77 (12), 65 (33), 55 (46). Anal. Calcd
4.4.11. 1-[(1R)-1-Phenylethyl]aziridine (3kF). Yield: (25.1 mg, 85%).
20
1
Oil. [
TMS):
a
]
þ77.6 (c 1.1, CHCl3); H NMR (400 MHz, CDCl3, 25 ꢀC,
D
d
¼7.42e7.25 (m, 5H; CH), 2.33 (q, 1H; J¼6.5 Hz, CH), 1.93 (dd,

6856
S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
1H; J¼4.0, 5.7 Hz, CH2), 1.71 (dd, 1H; J¼4.0, 5.7 Hz, CH2), 1.47 (d, 3H;
J¼6.5 Hz, CH3), 1.32 (dd, 1H; J¼4.0, 7.1 Hz, CH2), 1.18 (dd, 1H; J¼4.0,
N, 12.95; found: C, 77.98; H, 9.46; N, 12.56. (10.5 mg, 24%). Second
21
diastereoisomer: mp 108e110 ꢀC. [
a
]
D
þ70.5 (c 0.86, CHCl3); 1H
¼7.37e7.20 (m, 5H; CH),
7.1 Hz, CH2); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼144.7, 128.3 (2C),
NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
126.9, 126.7 (2C), 70.6, 27.8, 26.9, 23.3. IR (ATR): nmax 3062, 2972,
1493, 1449, 1352, 1264, 1171, 1065, 943 cmꢁ1. MS (70 eV, EI): m/z
(%): 147 (2) [Mþ], 146 (2), 132 (15), 105 (100), 103 (12), 88 (10), 79
(14), 77 (21), 58 (9), 57 (8), 51 (9). Anal. Calcd for C10H13N: C, 81.59;
H, 8.90; N, 9.51; found: C, 81.77; H, 9.01; N, 9.22.
3.05e2.95 (m, 1H; CH), 2.77 (br s, 2H; NH2), 2.40 (dd, 1H; J¼3.4,
6.6 Hz, CH), 2.15 (d, 1H; J¼3.4 Hz, CH2), 2.10 (d, 1H; J¼6.6 Hz, CH2),
1.95e1.86 (m, 2H; CH2), 1.78e1.66 (m, 2H; CH2), 1.47e1.16 (m, 5H;
CH2); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼140.3, 128.3 (2C), 126.8,
126.5 (2C), 74.5, 56.7, 38.9, 36.6, 33.4, 31.1, 24.7, 24.5. IR (ATR): nmax
3357, 2926, 2857,1610, 1497, 1451, 1096, 1037 cmꢁ1. MS (70 eV, EI):
m/z (%): 216 (7) [Mþ], 215 (25), 199 (7), 144 (9), 120 (68), 118 (84),
111 (15), 104 (100), 97 (66), 91 (55), 81 (25), 78 (21), 77 (21), 69
(71), 56 (58). Anal. Calcd for C14H20N2: C, 77.73; H, 9.32; N, 12.95;
found: C, 77.51; H, 9.41; N, 13.08.
4.4.12. [(1R,2R)-1,2-Diphenyl-2-(2-phenyl-1-aziridinyl) ethyl]amine
(3lA). Yield: (30.8 mg, 49%). First diastereoisomer: viscous oil.
[
d
a
]
19 ꢁ31.8 (c 0.55, CHCl3); 1H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
D
¼7.38e7.05 (m, 15H; CH), 4.27 (d, 1H; J¼6.0 Hz, CH), 2.97 (d, 1H;
J¼6.0 Hz, CH), 2.51 (dd, 1H; J¼3.4, 6.5 Hz, CH), 1.96 (br s, 2H; NH2),
1.80 (d, 1H; J¼3.4 Hz, CH2), 1.57 (d, 1H; J¼6.5 Hz, CH2); 13C NMR
Acknowledgements
(100 MHz, CDCl3, 25 ꢀC):
d
¼142.8, 141.2, 140.2, 128.2 (2C), 128.1
(2C), 127.8 (2C), 127.7 (2C), 127.3 (2C), 127.1, 126.9, 126.8, 126.1 (2C),
80.9, 62.5, 44.6, 35.5. IR (ATR): nmax 3380, 3029, 1718, 1602, 1494,
1452, 1264, 1094, 1028 cmꢁ1. Anal. Calcd for C22H22N2: C, 84.04; H,
7.05; N, 8.91; found: C, 84.36; H, 7.23; N, 8.41. (20.7 mg, 33%).
Financial support from MIUR, National Projects PRIN 2007,
University of Perugia and Consorzio CINMPIS, Bari is gratefully
acknowledged.
Second diastereoisomer: viscous oil. [
a
]
19 þ58.7 (c 0.77, CHCl3); 1H
D
References and notes
NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.34e7.02 (m, 15H; CH), 4.31
(d, 1H; J¼5.3 Hz, CH), 2.99 (d, 1H; J¼5.3 Hz, CH), 2.26 (dd, 1H; J¼3.5,
1. (a) ‘Organoselenium Chemistry: Modern Developments in Organic Synthesis’.
In Top. Curr. Chem.; Wirth, T., Ed.; Springer: Berlin, 2000; Vol. 208; (b) Orga-
noselenium Chemistry. In A Practical Approach; Back, T. G., Ed.; Oxford Uni-
versity Press: Oxford, New York, NY, 2000.
2. (a) Bagnoli, L.; Scarponi, C.; Testaferri, L.; Tiecco, M. Tetrahedron: Asymmetry
2009, 20, 1506; (b) Tiecco, M.; Chianelli, D.; Testaferri, L.; Tingoli, M.; Bartoli, D.
Tetrahedron 1986, 42, 4889; (c) Kuwajima, I.; Ando, R.; Sugawara, T. Tetrahedron
Lett. 1983, 24, 4429; (d) Ando, R.; Sugawara, T.; Shimizu, M.; Kuwajima, I. Bull.
Chem. Soc. Jpn. 1984, 57, 2897; Shimizu, M.; Kuwajima, I. J. Org. Chem. 1980, 45,
2921.
6.5 Hz, CH), 2.07 (br s, 2H; NH2), 2.00 (d, 1H; J¼3.5 Hz, CH2), 1.72 (d,
13
1H; J¼6.5 Hz, CH2); C NMR (100 MHz, CDCl3, 25 ꢀC):
d¼143.1,
141.0, 140.2, 128.1 (2C), 128.0 (2C), 127.9 (2C), 127.8 (2C), 127.3 (2C),
127.0, 126.9, 126.6, 126.1 (2C), 81.0, 62.4, 41.5, 37.8. IR (ATR): nmax
3404, 3027, 1715, 1603, 1495, 1452, 1204, 1064, 1021 cmꢁ1. Anal.
Calcd for C22H22N2: C, 84.04; H, 7.05; N, 8.91; found: C, 84.27; H,
7.21; N, 8.52.
3. Marini, F.; Sternativo, S.; Del Verme, F.; Testaferri, L.; Tiecco, M. Adv. Synth. Catal.
2009, 351, 1801.
4.4.13. 2-Hexyl-1-[(1R)-1-phenylethyl]aziridine(3kD). Yield: (16.3 mg,
4. Marini, F.; Sternativo, S.; Del Verme, F.; Testaferri, L.; Tiecco, M. Adv. Synth. Catal.
2009, 351, 103.
19
35%). First diastereoisomer: oil. [
a
]
þ58.4 (c 0.64, CHCl3); 1H NMR
D
(400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.42e7.24 (m, 5H; CH), 2.42 (q, 1H;
5. (a) Demarcus, M.; Filigheddu, S. N.; Mann, A.; Taddei, M. Tetrahedron Lett. 1999,
40, 4417; (b) Boivin, S.; Outurquin, F.; Paulmier, C. Tetrahedron Lett. 2000, 41,
663; (c) Ward, V. R.; Cooper, M. A.; Ward, A. D. J. Chem. Soc., Perkin Trans. 1
2001, 944; (d) Miniejew, C.; Outurquin, F.; Pannecoucke, X. Org. Biomol. Chem.
2004, 2, 1575; (e) Miniejew, C.; Outurquin, F.; Pannecoucke, X. Tetrahedron
2005, 61, 447; (f) Miniejew, C.; Outurquin, F.; Pannecoucke, X. Tetrahedron
2006, 62, 2657.
6. These papers describe cyclizations based on conjugate additions to vinyl se-
lenones derived from nucleosides. (a) Wu, J.-C.; Chattopadhyaya, J. Tetrahedron
1989, 45, 4507; (b) Tong, W.; Sandstrom, A.; Wu, J.-C.; Chattopadhyaya, J. Tet-
rahedron 1990, 46, 3037.
7. For general reviews on the synthesis of aziridines see: (a) Pellissier, H. Tetra-
hedron 2010, 66, 1509; (b) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247; (c) Padwa,
A.; Murphree, S. S. Arkivoc 2006, iii, 6; (d) Osborn, H. M. I.; Sweeney, J. Tetra-
hedron: Asymmetry 1997, 8, 1693 For recent papers on biological properties
of natural or unnatural aziridines see: (e) Ismail, F. M. D.; Levitsky, D. O.;
Dembitsky, V. M. Eur. J. Med. Chem. 2009, 44, 3373; (f) Vicik, R.; Busemann, M.;
Baumann, K.; Schirmeister, T. Curr. Top. Med. Chem. 2006, 6, 331.
8. For recent aza-MIRC reactions for the preparation of aziridines see: (a) Ciogli, A.;
Fioravanti, S.; Gasparrini, F.; Pellacani, L.; Rizzato, E.; Spinelli, D.; Tardella, P. A. J.
Org. Chem. 2009, 40, 9314; (b) Fioravanti, S.; Morea, S.; Morreale, A.; Pellacani, L.;
Tardella, P. A. Tetrahedron 2009, 65, 484; (c) Fioravanti, S.; Colantoni, D.; Pella-
cani, L.; Tardella, P. A. J. Org. Chem. 2005, 70, 3296; (d) Colantoni, D.; Fioravanti,
S.; Pellacani, L.; Tardella, P. A. Org. Lett. 2004, 6, 197; (e) Fioravanti, S.; Morreale,
A.; Pellacani, L.; Tardella, P. A. Eur. J. Org. Chem. 2003, 4549; (f) Mekonnen, A.;
Carlson, R. Tetrahedron 2006, 62, 852; (g) Barros, M. T.; Maycock, C. D. M.;
Ventura, R. Tetrahedron Lett. 2002, 43, 4329; (h) Tranchant, M.-J.; Dalla, V.; Jabin,
I.; Decroix, B. Tetrahedron 2002, 58, 8425; (i) De Saint-Fuscien, C.; Tarrade, A.;
Dauban, P.; Dodd, R. H. Tetrahedron Lett. 2000, 41, 6393.
J¼6.5 Hz, CH), 1.62e1.25 (m, 13H), 1.46 (d, 3H; J¼6.5 Hz, CH3); 0.92 (t,
3H; J¼6.8 Hz, CH3); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
¼144. 7, 128.2
d
(2C), 126.8 (3C), 69.9, 40.7, 33.4, 33.3, 31.9, 29.2, 27.8, 23.3, 22.6, 14.1. IR
(ATR): nmax 3028, 2922, 2853, 1494, 1454, 1368, 1171, 1028 cmꢁ1. MS
(70 eV, EI): m/z (%): 231 (8) [Mþ], 230 (32), 216 (73), 202 (9), 188 (9),
174 (20), 161 (16), 160 (16), 146 (39), 134 (27), 126 (66), 105 (100), 91
(21), 84 (23), 79 (32), 77 (38), 70 (17), 55 (43). Anal. Calcd for C16H25N:
C, 83.06; H, 10.89; N, 6.05; found: C, 83.29; H, 10.97; N, 5.74. (16.2 mg,
35%). Second diastereoisomer: oil. [
a
]
20 þ46.9 (c 0.77, CHCl3); 1H NMR
D
(400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.41e7.23 (m, 5H; CH), 2.40 (q, 1H;
J¼6.6 Hz, CH), 1.69 (d, 1H; J¼3.0 Hz, CH2), 1.45 (d, 3H; J¼6.6 Hz, CH3),
1.42e1.01 (m, 12H), 0.83 (t, 3H; J¼7.1 Hz, CH3); 13C NMR (100 MHz,
CDCl3, 25 ꢀC):
d
¼144. 8, 128.2 (2C), 126.9 (3C), 70.3, 38.9, 34.2, 32.9,
31.7, 28.8, 27.2, 22.8, 22.4, 14.0. IR (ATR): nmax 3033, 2928, 2856, 1493,
1452, 1369, 1167 cmꢁ1. MS (70 eV, EI): m/z (%): 231 (7) [Mþ], 230 (31),
216 (78), 202 (9), 188 (10), 174 (20), 161 (15), 160 (17), 146 (39), 134
(27), 126 (67), 105 (100), 91 (22), 84 (23), 79 (33), 77 (38), 70 (17), 55
(43). Anal. Calcd for C16H25N: C, 83.06; H, 10.89; N, 6.05; found: C,
83.18; H, 11.01; N, 5.81.
4.4.14. [(1R,2R)-2-(2-Phenylaziridin-1-yl)cyclohexyl] amine (3mA).
21
Yield: (16.0 mg, 37%). First diastereoisomer: viscous oil. [
a]
9. (a) Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725; (b) Gruttadauria, M.;
Giacalone, F.; Noto, R. Adv. Synth. Catal. 2009, 351, 33; (c) Narayan, S.; Muldoon,
J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B. Angew. Chem., Int. Ed.
2005, 44, 3275.
10. In the absence of 4 Å molecular sieves the aziridine 3aA was isolated in 53%
yield after 32h. Molecular sieves are known to have a role as proton scavanger,
see: (a) Terada, M.; Matsumoto, Y.; Nakamura, Y.; Mikami, K. Chem. Commun.
1997, 281; (b) Hasegawa, M.; Ono, F.; Kanemasa, S. Tetrahedron Lett. 2008, 49,
5220.
D
1
ꢁ141.4 (c 0.76, CHCl3); H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.39e7.20 (m, 5H; CH), 2.92e2.83 (m, 1H; CH), 2.68 (dd, 1H;
J¼3.2, 6.5 Hz, CH), 2.00e1.63 (m, 6H; CH, CH2), 1.88 (d, 1H;
J¼3.2 Hz, CH2), 1.72 (d, 1H; J¼6.5 Hz, CH2), 1.48e1.10 (m, 5H; CH2);
13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼139.9, 128.4 (2C), 127.0, 126.2
(2C), 74.9, 56.6, 42.7, 33.7, 33.2, 30.5, 25.0, 24.8. IR (ATR): nmax
3370, 2926, 2856, 1728, 1497, 1448, 1262, 1085, 1030 cmꢁ1. MS
(70 eV, EI): m/z (%): 216 (4) [Mþ], 215 (14), 199 (4), 144 (6), 120
(52), 118 (71), 111 (10), 104 (100), 97 (55), 91 (47), 81 (19), 78 (16),
77 (16), 69 (72), 56 (53). Anal. Calcd for C14H20N2: C, 77.73; H, 9.32;
11. For some recent examples of aza-Michael additions of alkylamines to a,b-un-
saturated ketones, esters, nitriles, amides and sulfones catalyzed by acids or
bases see: (a) Esteves, A. P.; Silva, M. E.; Rodrigues, L. M.; Oliveira-Campos, A. M.
F.; Hrdina, R. Tetrahedron Lett. 2007, 48, 9040; (b) Das, B.; Chowdhuri, N. J. Mol.
Catal. A: Chem. 2007, 263, 212; (c) Duan, Z.; Xuan, X.; Li, T.; Yang, C.; Wu, Y.

S. Sternativo et al. / Tetrahedron 66 (2010) 6851e6857
6857
Tetrahedron Lett. 2006, 47, 5433; (d) Bartoli, G.; Bartolacci, M.; Giuliani, A.;
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Marcantoni, E.; Massaccesi, M.; Torregiani, E. J. Org. Chem. 2005, 70, 169; (e)
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