A. S. Pankova et al. / Tetrahedron Letters 50 (2009) 5990–5993
5991
strate by gradual heating starting from ambient temperature and
by monitoring the reaction by TLC.
c
O
N
b
NPhth
N
a
Compounds 6a and 7a gave the expected corresponding con-
densed N-phthalimidopyrrolidine derivatives 10 and 11 as mix-
tures of two diastereoisomers in the ratio ꢀ2:1 (Scheme 2). The
most important distinction between these products is the value
of the vicinal coupling constant 3J (H–3a–H–9b) in their 1H NMR
spectra, which is 5.1 Hz for the major component and 11.1 Hz for
the minor one in the mixture of compounds 10, and 5.8 Hz and
10.2 Hz in the mixture of 11, respectively. A comparison of these
values with the literature data12 for similar structures allowed us
to conclude that the major components of these mixtures are cis-
orientated at the five- and six-membered ring junctions, whereas
the minor diastereomers are trans-fused. Fractional crystallization
of the mixture of products 10 from ethanol afforded pure cis-iso-
mer 10. To our disappointment, this method failed in the case of
the mixture of 11. The low yield of tricyclic esters 10 seems to
be a consequence of the competition between 1,3-dipolar cycload-
dition and other secondary processes, for example, rearrange-
ments.5–8,18
H2
N
C6H6, 6 h
R
O
H9b
R
H3a
O
O
6a R = CO2Me
7a R = CN
150 oC
120 oC
10, 10%
11, 50%
cis : trans = 2.3:1
cis : trans = 2.2:1
Scheme 2. Thermolysis of aziridines 6a and 7a.
aminoaziridination procedure14 (Scheme 1 and Table 1). This reac-
tion affects only the styrene C@C bond of these compounds and is
in full agreement with the well-known low activity of the triple
and non-conjugated terminal double bonds in such
transformations.15
Electron-withdrawing substituents on the aziridine ring should
promote ring-opening to a 1,3-dipole with a partial negative
charge on the carbon atoms. Therefore, we chose CN, CO2Me, and
CONEt2 groups along with a phenyl group that efficiently delocal-
izes both negative and positive charges. The length of the unsatu-
rated side chain ensures the formation of an unstrained condensed
system of five- and six-membered rings. The spatial proximity of
the interacting fragments allows us to use non-activated C@C
and C„C bonds16 giving access to both saturated and unsaturated
heterocycles and also allows a study of the stereochemical aspects
of the cycloaddition process.
An important property of most N-aminoaziridine derivatives is
the high barrier to endocyclic nitrogen atom inversion, which usu-
ally leads to the co-existence of two invertomers on the NMR time
scale.17 According to 1H NMR spectra at room temperature, aziri-
dines 6–8a,b exist as a mixture of two invertomers with a strong
prevalence for one of them (the ratio is ꢀ95:5). The signals of
the aziridine protons of the main invertomer are located at higher
fields than those of the minor one. Reliable identification of the sig-
nals in the 13C NMR spectra can only be achieved for the main
invertomer. Aziridines 9a,b exist as single invertomers. According
to the small vicinal coupling constants in the aziridine rings
(3J = 5.0–5.1 Hz for the main invertomer and 5.6–6.0 Hz for the
minor one), the trans-orientation of the substituents in the starting
olefins 1–3a,b is retained in the aziridines 6–8a,b.
The characteristic features of the 13C NMR spectra of com-
pounds 10 and 11, as well as of the other sterically hindered N-
phthalimidopyrrolidine and N-phthalimidopyrroline derivatives
obtained,9,10 are the absence of C(O)N carbon signals and broaden-
ing of the C-a signals of the phthalimide moiety. This is due to slow
rotation of this group around the N–N bond resulting in non-equiv-
alent halves of the phthalimide fragment.
The orientation of the R substituents on C-2 in compounds 10
and 11 was proved from the 2D NOESY spectra, which allowed
confirmation of the signal assignment in the 1H NMR spectra as
well. Such positioning of the substituents is in accordance with a
thermally allowed conrotatory ring-opening of the trans-aziridine
into the (E,E)- or (Z,Z)-azomethine ylide followed by a concerted
cycloaddition reaction. Two different plausible cycloaddition tran-
sition states give rise to the formation of diastereoisomers with
either cis or trans ring junctions at the five- and six-membered
rings (Scheme 3).
A surprising result was obtained on thermolysis of aziridine 8a.
In this case, we observed no traces of the expected cycloadduct in
the 1H NMR spectrum of the reaction mixture after heating. The
only isolated product (apart from phthalimide and 2-(allyl-
oxy)benzaldehyde) was chromenopyridine 12 (Scheme 4).
The structure and composition of compound 12 were proved
from its mass spectrum (molecular ion peak with m/z 254), 1H
and 13C NMR data, the 2D NOESY spectrum, and elemental analy-
sis. In the 1H NMR spectrum the signals of the o-C6H4 moiety
(d = 6.92–8.06 ppm), two ethyl groups, the OCH2 group as well as
two doublets due to the pyridine ring protons (4J = 2.9 Hz) were
easily identified. The position of the NEt2 substituent was in agree-
The non-equivalence of the ethyl groups of the diethylamide
fragment in aziridines 8a,b became apparent in their NMR spectra
due to hindered rotation about the amide C–N bond.
Thermolysis of compounds 6–9a,b was carried out in benzene.
The optimal reaction temperature was determined for each sub-
NPhth
R
R
PhthN
H
H
N
N
N
H
H
NPhth
H
H
O
N
H
H
O
R
cis
10,11
-
O
NPhth
R
R
PhthN
H
H
N
6,7a
H
H
H
H
O
H
H
O
trans
10,11
-
Scheme 3. Transition states en route to cis- and trans-10, 11.
Pankova, Alena S.
