Chiral bidiaziridines by a two-step domino aziridination of meso-α-diimines Dedicated to Professor Paolo Antonio Tardella on the occasion of his 78th birthday.

Article abstract of DOI:10.1016/j.tet.2013.08.017

Chiral racemic α-diimines, tested in aziridination reactions with NsONHCO₂Et, for the first time led to the synthesis of (±)-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-α-diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino process. The structures of the compounds were determined using 2D NMR on purified bidiaziridines.

Full text of DOI:10.1016/j.tet.2013.08.017

Tetrahedron 69 (2013) 9507e9511
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chiral bidiaziridines by a two-step domino aziridination of
meso-a-diimines
*
Emanuele Aresu, Laura Carroccia, Stefania Fioravanti , Simona Gasbarri, Lucio Pellacani,
Fabio Sciubba
ꢀ
Dipartimento di Chimica, Universita degli Studi “La Sapienza”, Piazzale A. 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:
Received 13 June 2013
Received in revised form 25 July 2013
Accepted 12 August 2013
Available online 30 August 2013
Chiral racemic a-diimines, tested in aziridination reactions with NsONHCO2Et, for the first time led to the
synthesis of (ꢀ)-bidiaziridines, stereoselectively derived from the corresponding meso (E-s-trans-E)-
a-
diimines. Moreover, a minor bidiaziridine isomer, probably a meso form that was lost under classical
work-up conditions, can be obtained by adding water to the crude mixtures at the end of amination
reactions. The results definitively prove that the imine aziridination by carbamates is a two-step domino
process. The structures of the compounds were determined using 2D NMR on purified bidiaziridines.
Ó 2013 Published by Elsevier Ltd.
Dedicated to Professor Paolo Antonio Tar-
della on the occasion of his 78th birthday.
Keywords:
Amination
Configuration determination
NMR spectroscopy
Imines
Small ring systems
1. Introduction
As previously reported by us, the presence of a minor isomeric
amination product was observed in very few cases, as suggested by
a
-Diimines1 derived from glyoxal and primary aliphatic amines
1H NMR performed before the crude work-up.
treated with hydroxylamine-O-sulfonic acid in anhydrous methanol
in the presence of an organic base led to the formation of a complex
mixture of the corresponding diastereomeric bidiaziridines.2
This minor product was lost in all cases during the work-up
steps (hexane addition followed by filtration through plugs filled
with silica gel) and in all cases only one amination product was
obtained as pure isomer.
Recently, we reported a direct aziridination of (E-s-trans-E)-a-
diimines with ethyl nosyloxycarbamate (NsONHCO2Et; Ns¼4-
NO2C6H4SO2) promoted by CaO,3 that led only to one of the pos-
sible stereoisomers, the meso form, with total retention of the
diimine configuration. Moreover, enantiomerically pure bidiazir-
idines were obtained starting from the corresponding (R,R) or (S,S)
Interested in better understanding the stereochemical outcome
of aziridination reactions, the aminations of a-diimines that led to
the formation of the aforementioned minor product were newly
considered to examine the observed ratios between the two iso-
mers. In order to achieve this, some reaction parameters were
changed with particular emphasis on the possibility to control the
amination products distribution and to avoid the loss of minor
compounds during the reaction work-up. Moreover, as an in-
teresting extension of our studies on the bidiaziridine isomerism,
(E-s-trans-E)-a
-diimines4 (Scheme 1).
CO2Et
H
R
R
N
N
H
H
N
N
H
NsONHCO2Et, CaO
CH2Cl2, rt
new chiral racemic
a-diimines, bearing a steric hindrance in
b
-position, were tested with the aim of evaluating the possible
effects of this hindrance on the stereochemical outcome.
N
R
N
EtO2C
R
2. Results and discussion
Scheme 1. Synthesis of enantiomerically pure bidiaziridines by NsONHCO2Et.
The
a-diimines derived from glyoxal and carrying the cyclo-
hexyl5 (1a) or the pentyl6 (1b) residues7 were aziridinated with
* Corresponding author. Tel.: þ39 (0)6 49913098; fax: þ39 (0)6 490631; e-mail
address: stefania.fioravanti@uniroma1.it (S. Fioravanti).
NsONHCO2Et, in the presence of CaO in CH2Cl2,8 under different
0040-4020/$ e see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2013.08.017

9508
E. Aresu et al. / Tetrahedron 69 (2013) 9507e9511
reaction conditions. However, the variation of molar ratios between
the reactants and/or time of reaction and also the use of a different
inorganic base (NaH) did not lead to any variation of the reaction
course. On the contrary, working at low temperature (0 ꢁC) no re-
action was observed while adding metal ions (LiCl 5e10%) greatly
slowed the reaction without any alteration of the product distri-
bution even after 24 h of stirring. The only significant success was
achieved by modifying the work-up step. At the end of the reaction,
the crude mixtures were washed twice with H2O to remove the
calcium nosylate salts and the solvent was evaporated under vac-
uum (Scheme 2). The subsequent NMR analysis confirmed the ef-
fectiveness of the new work-up, showing again the presence of the
expected two amination products (ca. 25:1). An HPLC purification
(eluant: hexane/ethyl acetate¼9:1) successfully allowed us to ob-
tain the known bidiaziridines (meso)-2a,b as major products and
bidiaziridine structures 3a,b as minor products are thought to be
other meso isomers or d,l mixtures (Scheme 2).
moieties face in the opposite planes of both the diaziridine protons
and the N-alkyl substituent protons, since no correlation was
detected between the carbamic protons and the other protons of
the molecule, for example, Ha, Hc, and Hd.4,10
Compound 3 showed a much different ROESY pattern compared
to the major form 2. In fact, as reported in Fig. 1 for 3a, diaziridine
protons show only a correlation with Hc protons (interproton dis-
ꢁ
tance between 3.5 and 4.5 A) while a correlation between Hb and
ꢁ
Hd protons (interproton distance between 3.0 and 3.8 A) is clearly
present. These interproton distances indicate that both nitrogen
substituents are on the opposite plane of Ha, according to only one
of the two reported structures, meso- or d,l-3a (Fig. 1).
Considering that diimine aziridination reactions via carbamate
takes place only by the attack of aza-anion (NsONꢂCO2Et) across
the opposite faces of the conjugated system,4 the most probable
structure of 3a is a meso form, since the d,l form could only be
derived from the attack of aza-anion on the same faces.
While diaziridines in cis-configuration were already established
by NMR analysis,13 to the best of our knowledge an analogous
configuration for heterocyclic rings in bidiaziridines was never
obtained.14
CO2Et
CO2Et
H
R
N
R
N
N
RN
H
N
H
NsONHCO2Et, CaO
The formation of the minor isomers meso-3 could be explained
by the presence in the starting materials of traces (ꢃ5%) of a dif-
CH2Cl2, rt
work-up in H2O
H
N
R
H
NR
H
N
R
N
N
ferent a a
-diimine isomer,15 namely the (Z-s-trans-Z)- -diimine,16 or
EtO2C
EtO2C
(E-s-trans-E)-1a,b
meso-2a,b
3a,b
through the complete rotation around the two single CeN bonds
derived by the anti-attack of aza-anion on the (E-s-trans-E) isomer,
followed by ring closure reaction with loss of the starting diimine
configuration (Scheme 3).
major
minor
a: R = cyclohexyl
b: R = pentyl
Scheme 2. Synthesis of bidiaziridines with NsONHCO2Et.
CO2Et
H
R
N
N
N
H
H
N
To gain further insight,9,10 2D NMR ROESY experiments11 were
performed directly on the pure amination products and compari-
son were made between them (Fig. 1).12
H
N
H
R
aza-anion attack
aza-anion attack
rotation followed by
ring closure reaction
R
R
R
N
fast ring closure reaction
H
N
R
N
EtO2C
meso-3 (traces)
(Z-s-trans-Z)
(E-s-trans-E)
Scheme 3. Possible synthetic pathways for minor meso-3.
The latter hypothesis could be the first direct experimental ev-
idence that even the diaziridine synthesis by carbamate, as the
aminating agent of imines is a two-step domino process,17 which
involves an aza-anionic addition to C]N bond, similar to that ob-
served on EWG-substituted olefins.18
Continuing our studies, a-diimines carrying two racemic chiral
centers were considered as more complex substrates.
Starting from chiral racemic amines, the condensation reaction
with glyoxal obviously leads to the synthesis of diastereomeric a-
diimines 1 and 10cee, as clearly shown by NMR spectra.19 Un-
fortunately, all attempts to separate the two isomers failed,
achieving only more-or-less enriched mixtures (ca. 60:40) of one of
the two diastereomers, and the aziridination reactions were di-
rectly performed on the diastereomeric mixture (ca. 1:1). After the
work-up in water, routine NMR analysis showed the presence of
three different amination products, the meso-2 and the meso-3
forms20 and a new amination compound never seen before in this
kind of aziridination reactions, characterized by the presence of
two doublets due to magnetically non-equivalent diaziridine pro-
tons (Scheme 4).
Fig. 1. ROESY spectrum of pure meso-2a (A). Spatial correlations between Ha and Hc
and Hd are evident. On the basis of molecular models, the existence of the latter cross
peak is possible only if the diaziridine protons and those of N-alkyl substituents face
the same plane. ROESY spectrum of pure 3a (B). Spatial correlations between Ha and Hc
and between Hb and Hd are evident. On the basis of molecular models, the existence of
the latter cross peak is possible only if the carbamic moiety protons and those of N-
alkyl substituents face the same plane. Moreover, a lack of dipolar couplings between
Ha and Hd indicates that the diaziridine protons and those of nitrogen substituents are
directed toward opposite planes.
To unequivocally identify all the observed compounds, an HPLC
methodology was optimized to separate the isomers and then
ROESY NMR experiments were acquired on the purified com-
pounds (Fig. 2).
In the ROESY spectrum of pure meso-2a the most useful dipolar
couplings are the ones observed among the aziridine protons Ha,
the methylene protons of the carbamic moiety Hb and the protons
belonging to the N-alkyl substituent (Hc, Hd). The carbamic
So, 2 and 3cee were identified as the (ꢀ)-structures (A and B,
Fig. 2) and the structures 4 were confirmed by comparison between
the ROESY spectra (C, Fig. 2). In fact, the spatial correlations of the
two diaziridine protons in 4 are different in the two rings, since the

E. Aresu et al. / Tetrahedron 69 (2013) 9507e9511
CO2Et
9509
CO2Et
CO Et
ONs
CO Et
ONs
CO2Et
R
N
R
R
R
N
N
N
N
N
N
H
-
H
H
N
-
H
H
N
N
H
H
N
R
N
H
H
R
NsONHCO2Et, CaO
rotation
rotation
+
R
R
CH2Cl2, rt
H
N
R
N
H
H
N
R
N
N
work-up in H2O
N
N
N
N
N
R
CO Et
R
N
EtO C
R
EtO C
EtO2C
EtO2C
H
EtO2C
R
R
N
H
H
N
N
N
NsONCO Et
(
)-(E-s-trans-E)-1c-e
meso-(E-s-trans-E)-1'c-e
- NsO
(
)-4c-e
I
(
)-2c-e
( )-3c-e
II
N
- NsO
anti attack
minor
H
CO Et
CO Et
H
CO Et
R
N
R
;
;
(
)-4
R=
N
R
N
N
H
R
c
d
e
meso-(E-s-trans-E)-1'
-
-
H
N
H
N
N
N
Scheme 4. Aziridination of racemic mixtures of
a
-diimines.
NsO
NsO
EtO C
EtO C
R
Scheme 5. Possible pathway for the synthesis of (ꢀ)-4 starting from meso 10.
Probably, the ring closure reaction to form the second diazir-
idine ring is slowed down in the intermediate I by steric hindrance,
which is less important in the intermediate II. Moreover, consid-
ering that the optically pure
only the corresponding enantiomerically pure bidiaziridines,4
-diimine meso-10cee by a two-
a-diimines (S,S)- or (R,R)-1d,e yielded
(ꢀ)-4 must be formed only from
a
step domino process that lead to d,l structures analogous to those
obtained by an aziridination reaction of conjugated nitro alkenes
using NsONHCO2Et as aminating agent.21
3. Conclusions
In conclusion, the aziridination reaction of a-diimines promoted
by CaO with NsONHCO2Et as an aminating agent is finally dem-
onstrated to be a two-step domino process. Also, the reported
aziridination methodology is confirmed to be more stereoselective
than the other methodology reported in the literature. In fact, if the
reaction is performed on the meso-
a
-diimine and (E,E)-(ꢀ) mix-
tures, the first isomer gave stereoselectively the synthesis of only
one of several possible (ꢀ)-bidiaziridine isomers, while the second
one only led to one of the possible d,l forms, in which the diazir-
idine rings retain the (E,E)-diimine configuration, a different meso
form remaining always a highly minor compound also by changing
some parameters of the reaction.
The structural identification of all bidiaziridine isomers ach-
ieved only through the use of 2D NMR techniques on purified
amination compounds confirms the versatility of the multidimen-
sional NMR spectroscopy.22
4. Experimental
4.1. General
Fig. 2. ROESY spectrum of pure (ꢀ)-2d (A) and (ꢀ)-3d (B). Contrary to what observed
for 3a, no dipolar couplings were observed between Hb and Hd in B due to the greater
flexibility of this molecule compared to the cyclic 3a. ROESY spectrum of pure (ꢀ)-4d
IR spectra were recorded on a PerkineElmer 1600 FT/IR spec-
trophotometer in CHCl3 as the solvent.1H NMR and 13C NMR spectra
were recorded by a Bruker Avance III 400 MHz NMR spectrometer.
CDCl3 was used as the solvent and CHCl3 as the internal standard.
2D NMR techniques were recorded by a Bruker Avance III 400 MHz
NMR spectrometer and used to assist in structure elucidation.22b
HRMS analyses were performed using a Micromass Q-TOF spec-
trometer equipped with an ESI source and a syringe pump. The
experiments were conducted in the positive ion mode. HPLC anal-
yses were performed with a Varian 9002 instrument equipped with
a Varian 9050 RI-4 differential refractometer. Eluants were mixtures
0
0
(C). Spatial correlations between Ha and Hc, Ha and Hd, and Ha and Hc are evidenced.
0
Contrary to what observed for the other structures, the diaziridinic protons Ha and Ha
clearly show different spatial correlation patterns, the first interacting with Hc and Hd
0
while the latter interact only with Hc
.
Ha proton has dipolar couplings similar to the diaziridine protons of
0
meso-2a,b and (ꢀ)-2c-e, while the Ha proton has the same corre-
lation pattern of meso-3a,b and (ꢀ)-3cee structures.
To explain the formation of d,l-4, it is possible to assume that
a first aziridine ring is formed very quickly after aza-anion
(NsONꢂCO2Et) attack on the diiminic conjugated system, so
retaining the E configuration of C]N double bond, while the other
ring is formed only after rotation around the formed single CeN
bond of the intermediate I, giving an aziridine ring with complete
of HPLC grade hexane and ethyl acetate. NsONHCO2Et23 and
a-dii-
mines 14 were synthesized as previously described.
4.1.1. N,N0-(1E,2E)-Ethane-1,2-diylidenebis(4-methylpentan-2-
amine) [(ꢀ)-(E-s-trans-E)-1c and meso-(E-s-trans-E)-10c]. Orange
oil (150 mg, 67%). IR (CHCl3) 1626 cmꢂ1. 1H NMR (CDCl3):
d
¼0.84
inversion of the starting
a-diimine configuration (Scheme 5).
(d, J¼6.5 Hz, 6H), 0.85 (d, J¼6.5 Hz, 6H), 0.88 (d, J¼6.4 Hz, 6H, 10c),

9510
E. Aresu et al. / Tetrahedron 69 (2013) 9507e9511
0.89 (d, J¼6.5 Hz, 6H,10c),1.17 (d, J¼6.6 Hz, 6H,10c),1.19 (d, J¼6.6 Hz,
6H), 1.28e1.36 (m, 4H), 1.42e1.59 (m, 8H), 3.34e3.44 (m, 4H), 7.89
13C NMR (CDCl3):
d
¼12.5 (2C), 13.5 (4C), 15.8 (2C), 16.5 (2C), 19.0
(10C), 20.0 (4C), 30.8 (2C), 31.4 (4C), 41.9 (2C), 42.5 (2C), 42.8 (2C),
59.6 (2C), 61.7 (2C), 62.7 (2C), 63.1 (3C), 63.5 (3C), 69.4 (2C), 71.4
(2C), 71.8 (2C), 160.8 (2C), 161.4 (4C). HRMS-ESI (m/z) [MþH]þ calcd
for C20H39N4O4: 399.2971; found: 399.2964.
(s, 2H), 7.91 (s, 2H, 10c). 13C NMR (CDCl3):
d
¼21.4 (2C), 21.5 (2C), 21.6
(2C), 22.3 (2C), 23.0 (2C), 23.1 (2C), 24.3 (2C), 24.4 (2C), 46.5 (4C),
63.6 (4C), 159.7 (4C). HRMS-ESI (m/z) [MþH]þ calcd for C14H29N2:
225.2331; found: 225.2336.
4.2.4. Diethyl 2,20-bis(1,2,2-trimethylpropyl)-3,30-bidiaziridine-1,10-
4.1.2. N,N0-(1E,2E)-Ethane-1,2-diylidenebis(3,3-dimethylbutan-2-
dicarboxylate [(ꢀ)-3d]. Orange oil (27 mg, 7%). IR (CHCl3)
amine) [(ꢀ)-(E-s-trans-E)-1d and meso-(E-s-trans-E)-10d]. Brown
1735 cmꢂ1. 1H NMR (CDCl3):
d¼0.91 (d, J¼6.7 Hz, 6H), 0.96 (s, 18H),
solid (204 mg, 91%). IR (CHCl3) 1619 cmꢂ1. 1H NMR (CDCl3):
d
¼0.79
1.26 (t, J¼7.1 Hz, 6H), 1.72 (q, J¼6.7 Hz, 2H), 2.69 (s, 2H), 4.01e4.12
(s, 18H, 10d), 0.81 (s, 18H), 1.05e1.13 (m, 12H), 2.82e2.89 (m, 4H),
(m, 4H). 13C NMR (CDCl3):
d¼11.1 (2C),12.8 (2C), 26.1 (6C), 33.5 (2C),
7.82 (s, 2H, 10d), 7.84 (s, 2H). 13C NMR (CDCl3):
d
¼17.1 (2C, 10d), 17.2
62.8 (2C), 63.2 (2C), 72.1 (2C), 160.8 (2C). HRMS-ESI (m/z) [MþH]þ
(2C), 26.3 (6C, 10d), 26.4 (6C), 33.8 (2C, 10d), 34þ.0 (4C), 75.4 (2C), 75.6
(2C, 10d), 160.3 (2C). HRMS-ESI (m/z) [MþH] calcd for C14H29N2:
225.2331; found: 225.2333.
calcd for C20H39N4O4: 399.2971; found: 399.2974.
4.2.5. Diethyl 2,20-bis(1,2-dimethylpropyl)-3,30-bidiaziridine-1,10-di-
carboxylate [(ꢀ)-3e]. Orange oil (22 mg, 6%). IR (CHCl3) 1735 cmꢂ1
.
4.1.3. N,N0-(1E,2E)-Ethane-1,2-diylidenebis(3-methylbutan-2-amine)
1H NMR (CDCl3):
d¼0.84 (d, J¼6.9 Hz, 6H), 0.88 (d, J¼6.6 Hz, 6H),
[(ꢀ)-(E-s-trans-E)-1e and meso-(E-s-trans-E)-10e]. Brown solid
1.24 (d, J¼6.8 Hz, 6H), 1.34 (t, J¼7.1 Hz, 6H), 1.59e1.72 (m, 2H),
(151 mg, 77%). IR (CHCl3) 1619 cmꢂ1
.
1H NMR (CDCl3):
d
¼0.80 (d,
1.92e1.98 (m, 2H), 2.67 (s, 2H), 4.22e4.32 (m, 4H). 13C NMR (CDCl3):
J¼6.8 Hz, 6H), 0.83 (d, J¼6.7 Hz, 6H, 10e), 0.86 (d, J¼6.8 Hz, 6H), 0.87
(d, J¼6.7 Hz, 6H,10e),1.14 (d, J¼6.4 Hz, 6H),1.18 (d, J¼6.4 Hz, 6H,10e),
1.66e1.77 (m, 4H), 2.85e2.97 (m, 2H), 2.89e2.98 (m, 2H, 10e), 7.82
d
¼12.5 (2C), 15.8 (2C), 19.0 (4C), 31.4 (2C), 62.7 (2C), 63.1 (2C), 71.4
(2C), 160.8 (2C). HRMS-ESI (m/z) [MþH]þ calcd for C18H35N4O4:
371.2658; found: 371.2651.
(s, 2H, 10e), 7.89 (s, 2H). 13C NMR (CDCl3):
d
¼18.6 (2C, 10e), 18.7 (4C),
19.0 (2C, 10e), 19.1 (2C), 19.2 (2C), 33.5 (4C), 71.8 (2C, 10e), 71.9 (2C),
159.8 (4C). HRMS-ESI (m/z) [MþH]þ calcd for C12H25N2: 197.2018;
found: 197.2016.
4.2.6. Diethyl 2,20-bis(1,2,2-trimethylpropyl)-3,30-bidiaziridine-1,10-
dicarboxylate [(ꢀ)-4d]. Orange oil (139 mg, 35%). IR (CHCl3)
1734 cmꢂ1. 1H NMR (CDCl3):
d¼0.91 (d, J¼6.6 Hz, 6H), 0.95 (s, 18H),
1.23e1.29 (m, 6H), 1.58e1.69 (m, 2H), 2.47 (d, J¼8.5 Hz, 1H), 2.63 (d,
4.2. General for the synthesis of bidiaziridines
J¼8.5 Hz,1H), 4.15e4.24 (m, 4H). 13C NMR (CDCl3):
¼13.3 (2C), 13.9
d
(2C), 25.7 (6C), 33.4 (2C), 59.3 (2C), 62.2, 63.6, 72.8 (2C), 160.6 (2C).
HRMS-ESI (m/z) [MþH]þ calcd for C20H39N4O4: 399.2971; found:
399.2972.
To a stirred solution of a
-diimines 1a,b and 1, 10cee (1 mmol) in
CH2Cl2 (3 mL), CaO (3 mmol) and NsONHCO2Et (2 mmol) were
added at room temperature. After the reactions were completed
(1H NMR), water was added. This operation is repeated twice, the
organic layers were combined, dried over sodium sulfate. and the
solvent was removed in vacuo. Bidiaziridines 2a,b, 3a,b, 2dee,
3dee, and 4dee were separated by HPLC (hexane/ethyl
acetate¼90:10, 1.3 mL/min, RI; 2a:4 176 mg, 44%; 2b:4 236 mg, 63%;
2d:4123 mg, 32%; 2e:4 134 mg, 36%).
4.2.7. Diethyl 2,20-bis(1,2-dimethylpropyl)-3,30-bidiaziridine-1,10-di-
carboxylate [(ꢀ)-4e]. Orange oil (126 mg, 34%). IR (CHCl3)
1733 cmꢂ1
.
1H NMR (CDCl3):
d
¼0.80 (d, J¼6.9 Hz, 6H), 0.92 (d,
J¼6.6 Hz, 6H), 1.10 (d, J¼6.8 Hz, 6H), 1.34 (t, J¼7.1 Hz, 6H), 1.70e1.82
(m, 2H), 1.92e2.00 (m, 2H), 2.60 (d, J¼8.3 Hz, 1H), 2.65 (d, J¼8.3 Hz,
1H), 4.22e4.38 (m, 4H). 13C NMR (CDCl3):
d¼13.5 (2C), 16.4 (2C),
20.0 (4C), 31.4 (2C), 59.6 (2C), 62.5, 63.5, 71.8 (2C), 161.4 (2C).
HRMS-ESI (m/z) [MþH]þ calcd for C18H35N4O4: 371.2658; found:
371.2656.
4.2.1. Diethyl 2,20-dicyclohexyl-3,30-bidiaziridine-1,10-dicarboxylate
(3a). Brown oil (12 mg, 3%). IR (CHCl3) 1736 cmꢂ1. 1H NMR (CDCl3):
d
¼1.12e1.14 (m, 4H), 1.16e1.18 (m, 2H), 1.25 (t, J¼7.1 Hz, 6H),
1.37e1.40 (m, 2H), 1.42e1.44 (m, 2H), 1.50e1.54 (m, 2H), 1.70e1.72
(m, 4H), 1.73e1.77 (m, 2H), 1.77e1.81 (m, 2H), 1.86e1.90 (m, 2H),
Acknowledgements
2.78 (s, 2H), 4.10e4.25 (m, 4H). 13C NMR (CDCl3):
d¼13.2 (2C), 22.9
ꢀ
Universita degli Studi di Roma “La Sapienza” is gratefully
(2C), 23.1 (2C), 24.6 (2C), 28.3 (2C), 30.2 (2C), 60.9 (2C), 62.4 (2C),
66.9 (2C), 160.8 (2C). HRMS-ESI (m/z) [MþH]þ calcd for
C20H35N4O4: 395.2658; found: 395.2656.
acknowledged for financial support.
Supplementary data
4.2.2. Diethyl
(3b). Yellow oil (15 mg, 4%). IR (CHCl3) 1734 cmꢂ1. 1H NMR (CDCl3):
¼0.83 (t, J¼6.7 Hz, 6H), 1.22e1.31 (m, 8H), 1.26 (t, J¼7.1 Hz, 6H),
1.55e1.60 (m, 4H), 2.05e2.15 (m, 2H), 2.60e2.70 (m, 2H), 3.02 (s,
2H), 4.10e4.25 (m, 4H). 13C NMR (CDCl3):
21.4 (2C), 26.9 (2C), 27.8 (2C), 58.3 (2C), 59.6 (2C), 62.2 (2C), 160.9
(2C). HRMS-ESI (m/z) [MþH]þ calcd for C18H35N4O4: 371.2658;
found: 371.2660.
2,20-dipentyl-3,30-bidiaziridine-1,10-dicarboxylate
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.08.017.
d
d
¼12.9 (2C), 13.2 (2C),
References and notes
1. For a recent review on imines, see: Dekeukeleire, S.; D’hooghe, M.; De Kimpe, N.
Imines in Science of Synthesis Knowledge Updates 2011/3; Georg Thieme: Stutt-
gart, Germany, 2012; pp 93e150.
2. (a) Petukhova, V. Yu; Kuznetzov, V. V.; Shevtsov, A. V.; Strelenko, Yu. A.; Ma-
khova, N. N.; Lyssenko, K. A.; Antipin, M. Yu Russ. Chem. Bull., Int. Ed. 2001, 50,
440e444; (b) Makhova, N. N.; Petukhova, V. Yu; Kuznetsov, V. V. ARKIVOC 2008,
i, 128e152; (c) Kamuf, M.; Rominger, F.; Trapp, O. Eur. J. Org. Chem. 2012,
4733e4739.
3. Pellacani, L.; Fioravanti, S.; Tardella, P. A. Curr. Org. Chem. 2011, 15, 1465e1481.
4. Carroccia, L.; Delfini, M.; Fioravanti, S.; Pellacani, L.; Sciubba, F. J. Org. Chem.
2012, 77, 2069e2073.
4.2.3. Diethyl 2,20-bis(4-methylpentan-2-yl)-3,30-bidiaziridine-1,10-
dicarboxylate [(ꢀ)-2c, (ꢀ)-3c; (ꢀ)-4c]. Orange oil (259 mg, 65%). IR
(CHCl3) 1739 cmꢂ1. 1H NMR (CDCl3):
d
¼0.73 (d, J¼6.6 Hz, 6H), 0.74
(d, J¼6.6 Hz, 6H), 0.78 (d, J¼6.5 Hz, 6H), 0.82 (d, J¼6.5 Hz, 12H), 0.85
(d, J¼6.4 Hz, 6H), 1.01 (d, J¼6.7 Hz, 6H), 1.02 (d, J¼6.7 Hz, 6H), 1.18
(d, J¼6.5 Hz, 6H), 1.30e1.40 (m, 6H); 1.59e1.65 (m, 6H), 1.69e1.72
(m, 6H), 1.88e1.96 (m, 6H), 2.54 (s, 2H, 2c), 2.55 (d, J¼8.3 Hz, 1H,
4c), 2.59 (d, J¼8.3 Hz, 1H, 4c), 2.61 (s, 2H, 3c), 4.12e4.29 (m, 12H).
5. Kliegman, J. M.; Barnes, R. K. Tetrahedron 1970, 26, 2555e2560.
6. Woitha, C.; Behrens, U.; Vergopoulos, V.; Rehder, D. J. Organomet. Chem. 1990,
393, 97e109.

E. Aresu et al. / Tetrahedron 69 (2013) 9507e9511
9511
7. Only in these two cases the sensitivity of the instrument (NMR operating at
400 MHz) allowed to detect the presence of a minor isomer in the crude
amination mixtures. The presence of a similar isomer could not be excluded in
the other amination crudes due to the limited sensibility of the instrument.
8. Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A. Tetrahedron 1991, 47,
5877e5882.
9. Jones, C. R.; Butts, C. P.; Harvey, J. N. Beilstein J. Org. Chem. 2011, 7, 145e150.
10. Krishnamurthy, V. V.; Casida, J. E.; Ruzo, L. O. J. Agric. Food Chem. 1987, 35,
504e506.
11. (a) Kessler, H.; Griesinger, C.; Kersse-baum, R.; Wagner, K.; Ernst, R. R. J. Am.
Chem. Soc. 1987, 109, 607e609; (b) Neuhaus, D.; Williamson, M. P. The Nuclear
Overhauser Effect in Structural and Conformational Analysis, 2nd ed.; WILEY-VCH:
New York, NY, 2000.
protons of 1a and 1b)] are observable at very high levels of magnification, while
no other signals are detected in the 13C NMR spectrum. Even HPLC was not able
to show the presence of the supposed minor isomer. In an attempt to gain more
insight on the presence of possible minor isomers, a-diimine 1a was stirred in
CH2Cl2 in the presence of CaO for 24 h and then analyzed by 1H NMR, but no
isomerization was observed. Isomerization was not observed even by varying
the temperature up to 80 ꢁC during the NMR experiments; (b) See Ref. 4.
17. (a) Fioravanti, S.; Olivieri, L.; Pellacani, L.; Tardella, P. A. Tetrahedron Lett. 1998,
39, 6391e6392; (b) Carroccia, L.; Fioravanti, S.; Pellacani, L.; Sadun, C.; Tardella,
P. A. Tetrahedron 2011, 67, 5375e5381.
18. (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. Synlett
2004, 1083e1085; (c) Fioravanti, S.; Marchetti, F.; Pellacani, L.; Ranieri, L.;
Tardella, P. A. Tetrahedron: Asymmetry 2008, 19, 231e236.
12. For the NOESY analysis of 2b see Ref. 4.
13. Kostyanovsky, R. G.; Shustov, G. V.; Starovoitov, V. V.; Chervin, I. I. Mendeleev
19. To the best of our spectrometer sensibility and resolution, the NMR analysis
Commun. 1998, 8, 113e116.
showed the presence of only two a-diimine isomers.
14. (a) Mannschreck, A.; Seitz, W. Angew. Chem. 1969, 81, 224; Angew. Chem., Int. Ed.
Engl. 1969, 8, 212e213; (b) Al-Omari, M.; Banert, K.; Hagedorn, M. Angew. Chem.
, Int. Ed. 2006, 45, 309e311.
20. meso-2cee and meso-3cee derive from (ꢀ)-(E-s-trans-E)-
a-diimines 1cee.
21. (a) Ciogli, A.; Fioravanti, S.; Gasparrini, F.; Pellacani, L.; Rizzato, E.; Spinelli, D.;
Tardella, P. A. J. Org. Chem. 2009, 74, 9314e9318; (b) Abbate, S.; Ciogli, A.;
Fioravanti, S.; Gasparrini, F.; Longhi, G.; Pellacani, L.; Rizzato, E.; Spinelli, D.;
Tardella, P. A. Eur. J. Org. Chem. 2010, 6193e6199.
15. For other studies on the
a-diimine isomerization see: (a) De Kimpe, N.;
Moens, L.; Verhe, R.; de Buyck, L.; Schamp, N. Tetrahedron Lett. 1982, 23,
789e792; (b) De Kimpe, N.; D’Hondt, L.; Stanoeva, E. Tetrahedron Lett. 1991,
32, 3879e3882; (c) De Kimpe, N.; D’Hondt, L.; Moens, L. Tetrahedron 1992,
48, 3183e3208.
22. (a) D’Alagni, M.; Delfini, M.; Di Nola, A.; Eisenberg, M.; Paci, M.; Roda, L. G.;
Veglia, G. Eur. J. Biochem. 1996, 240, 540e549; (b) Claridge, T. D. W. High-res-
olution NMR Techniques in Organic Chemistry, 2nd ed.; Elsevier: Amsterdam, The
~
16. (a) The NMR analysis showed the presence of traces of the hypothesized minor
Netherlands, 2009; (c) Acuna-Rougier, C.; Jullian, C.; Olea-Azar, C. J. Inclusion
isomer of the
a
-diimines [in the 1H NMR spectrum a triplet at 0.79 ppm (for the
Phenom. Macrocycl. Chem. 2012, 74, 157e166.
eCH3 of the pentyl chain of 1b) and a singlet around at 6.89 ppm (for the imine
23. Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87, 3630e3637.