N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide as an active aminoaziridinating agent

Article abstract of DOI:10.1002/ejoc.200900326

N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide is active in the oxidative aminoaziridination reaction toward alkenes substituted with aryl-, alkyl, and electron-withdrawing groups, providing access to stable derivatives of N-aminoaz-iridine. Yields varied from 19 to 76%, and trans-substituted alkenes reacted faster and gave better yields than cis-alkenes. No products of self-aziridination were isolated.

Full text of DOI:10.1002/ejoc.200900326

FULL PAPER
DOI: 10.1002/ejoc.200900326
N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide as an Active
Aminoaziridinating Agent
Mikhail Zibinsky,[a,b] Timothy Stewart,[b] G. K. Surya Prakash,[a,b] and
Mikhail A. Kuznetsov*[c]
Dedicated to Prof. Armin de Meijere on the occasion of his 70th birthday
Keywords: Nitrogen heterocycles / Amines / Alkenes / Synthons
N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide
is
alkenes reacted faster and gave better yields than cis-
active in the oxidative aminoaziridination reaction toward al-
kenes substituted with aryl-, alkyl, and electron-withdrawing
groups, providing access to stable derivatives of N-aminoaz-
iridine. Yields varied from 19 to 76%, and trans-substituted
alkenes. No products of self-aziridination were isolated.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
cyclo[2.2.1]hept-5-ene-2,3-dicarboximide (EnN-NH2, 1)
and Pb(OAc)4 together form a good aziridinating system
despite the presence of a norbornene-type carbon–carbon
double bond in its structure[3j] (Figure 1). Herein, we report
the structurally similar N-amino-exo-3,6-epoxy-1,2,3,6-
tetrahydrophthalimide (EPTN-NH2, 2), which possesses an
exo configuration and which is also capable of oxidative
aziridination of double bonds. Our findings suggest the in-
volvement of a possibly different intermediate species for
the EPTN-NH2/PhI(OAc)2 system. Apart from its synthetic
utility, EPTN-NH2 is also a compound of interest as a re-
sult of its structural similarity to cantharidine (3), a drug
known for its antiviral and anticancer activity.[5]
Introduction
Aminoaziridines are important synthons in organic syn-
thesis capable of undergoing ring opening by nucleo-
philes.[1] They also serve as important precursors for α-hy-
drazino acids, which naturally occur in peptide antibiotics,
the inhibit amino acid utilizing enzymes, and they can be
used as metabolically stable peptide mimetics with antiviral
potential.[2] Oxidative aminoaziridination is a direct and
convenient way to access a wide range of stable derivatives
of N-aminoaziridine (Scheme 1). A variety of N-aminohet-
erocycles were tested in this reaction[3] during the last sev-
eral decades. However, only N-aminophthalimide[3a,4a–4d]
and 3-aminoquinazolin-4(3H)-ones[3a,4e–4g] have found wide
use.
Figure 1. Structures of EnN-NH2 (1), EPTN-NH2 (2), and can-
tharidine (3).
Scheme 1. Oxidative aminoaziridination of alkenes.
Aminonitrene or a nitrene-type intermediate is consid-
ered to be the key intermediate when Pb(OAc)4 is used as
the oxidant.[3,4] Recently, we showed that N-amino-endo-bi-
The first synthesis of compound 2 was reported in 1965
by Furdik and Sidoova.[6a] In the early 1970s Augustin and
Reinemann along with Title also published the synthesis of
EPTN-NH2 and its derivatives.[6b–6d] Between 1980 and
1990, several reports were published on the synthesis and
biological activity of EPTN-NH2 and related com-
pounds,[5c,7] indicating their high uptake in lungs, kidneys,
and spleen.[5b] Recently, Struga et al. reported the X-ray
structure of EPTN-NH2,[8] affirming its exo configuration.
[a] Loker Hydrocarbon Research Institute,
837 Bloom Walk, Los Angeles, CA 90089-1661, USA
[b] Department of Chemistry, University of Southern California,
Los Angeles, CA 90089, USA
[c] Saint-Petersburg State University,
Universitetskii Pr. 26, St. Petersburg, 198504, Russia
E-mail: mak@mail.wplus.net
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900326
Eur. J. Org. Chem. 2009, 3635–3642
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3635

M. Zibinsky, T. Stewart, G. K. S. Prakash, M. A. Kuznetsov
FULL PAPER
Table 1. Oxidative aminoaziridination of alkenes with EPTN-
NH2.[a]
Results and Discussion
To our best knowledge, the oxidation of 2 in the presence
of unsaturated compounds has not been investigated. For
this study we chose a series of aryl- and alkyl-substituted
alkenes, with either electron-donating or electron-with-
drawing groups at the double bond, including cyclic com-
pounds. Unless otherwise mentioned, most of the reactions
were carried out with (diacetoxyiodo)benzene (1 equiv.) as
the oxidant and unsaturated substrates 4 (1–3 equiv.) in
dichloromethane solution at ambient temperature for 16 h.
An excess amount of anhydrous potassium carbonate (3–
4 equiv.) was used as a base (Scheme 2).
Scheme 2. Oxidative aminoaziridination of alkenes with EPTN-
NH2/PhI(OAc)2 system.
Most of the alkenes were converted into the correspond-
ing aminoaziridines in yields varying from 19 to 76%
(Table 1), but the reactivity of nonconjugated terminal al-
kenes varied from very low with hex-5-en-2-one – trace
amounts of the product – to no reaction at all in the case
of 4-phenylbut-1-ene. The use of an excess amount of al-
kenes 4a, 4f, 4m, 4q, and 4s (see Table 1) did not provide
better yields. In analogy with epoxidation, the oxidative
aminoaziridination with 2 proceeded with retention of con-
figuration of the alkene, which was confirmed by NMR
spectroscopic analysis of compounds 5 and by X-ray struc-
tural data for compounds 5c and 5f (Figure 2). Configura-
tion retention has been reported for other N-aminoazirid-
ination protocols.[4g,9] All the aziridines shown in Table 1
are new compounds. Their compositions were confirmed
1
by HRMS data and their structures by H and 13C NMR
spectroscopy.
Despite the fact that 2 possesses a norbornene-type
double bond, which is generally considered more reactive
than an unstrained cis double bond, the product of inter-
molecular self-aziridination was never isolated from the re-
action mixture. Also, a sharp variation in the yields was
observed for cis and trans alkenes. For instance, aziridine
5g from trans-stilbene was obtained in 76% yield, whereas
cis-stilbene gave only 19% yield of 5h. Similar results were
obtained for dimethyl fumarate (4e; adduct 5e, 56%) and
dimethyl maleate (4f; adduct 5f, 20%). Furthermore, we re-
corded low yields for cyclohexene (4m; adduct 5m, 25%),
cyclohexenone (4p; adduct 5p, 21%), and naphthoquinone
(4n; adduct 5n, 21%). Although cyclohexenone did not give
a good yield with the EnN-NH2/Pb(OAc)4 system, cyclo-
hexene and naphthoquinone gave better results.[3j] There-
fore, the observed low reactivity of the double bond of
EPTN-NH2 in the reaction could be due to the general low
reactivity of cis double bonds with the reagent under the
reaction conditions.
[a] Yields are based on complete conversion of 2.
3636
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3635–3642

N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide in Aminoaziridinations
Figure 2. ORTEP renderings of the X-ray structures of compounds 5c (A) and 5f (B).
To elucidate our observations, we carried out a simple
experiment to determine whether the low yields for cis-sub-
stituted alkenes were due to their low reactivity and not
caused by slow crystallization rates of the corresponding
aziridines, their instability under the reaction conditions, or
any other factor. In this study trans- (4e) and cis-alkenes
(4f) were taken in excess to 2 and diacetoxyiodobenzene
[3 equiv. of each alkene to 1 equiv. of EPTN-NH2 and
1 equiv. of PhI(OAc)2] in CDCl3 (Scheme 3). Reaction pro-
1
gress was monitored by H NMR spectroscopy (Figure 3).
Formation of trans-aziridine 5e was expected to be observed
by the appearance of the aziridine proton peak at 3.53 ppm,
whereas the protons of cis-aziridine 5f have a chemical shift
of 3.46 ppm.
Scheme 3. Competitive addition of EPTN-NH2 to dimethyl fumar-
ate versus dimethyl maleate.
After 4 h at 21 °C the reaction was complete (with no
compound 2 left, Figure 3). Interestingly, no compound 5f
was formed in this experiment. These results indicate that
trans-alkene 4e is much more reactive than its cis-isomer 4f
Figure 3. 1H NMR spectroscopic study of competitive oxidative
addition of EPTN-NH2 to dimethyl fumarate (4e) versus dimethyl
maleate (4f) in CDCl3. Expansions shown: 6.6–6.4 ppm (Hc peak
of 2 disappears, Hc and HcЈ peaks of 5e appear) and 3.6–2.5 ppm
(Ha peak of 2 disappears, Ha, HaЈ and Haz peaks of 5e appear). (A)
5 min, 2% conv., (B) 62 min, 21% conv., (C) 176 min, 74% conv.,
(D) 270 min., 100% conv.
under the conditions described above.
We propose the involvement of a sterically demanding
phenyliodo group in the transition state in agreement with
a higher activation barrier for the cis alkene (Scheme 4).
Richardson and co-workers suggested that a similar reac-
tion with the N-aminophthalimide/PhI(OAc)2 system can
proceed not only via an aminonitrene or N-acetoxy deriva-
tive, but via an N-phenyliodo intermediate as well.[4g] In
order to explain the difference in reactivity between cis- and between R1 and R2 in case of the cis alkene is outweighed
trans-alkenes, one needs to compare the corresponding by the trans orientation of the EPTN substituent. Similarly,
transition states. If the reactive species is a nitrene or ni- in the case of the trans alkene, an unfavorable interaction
trenoid (N-acetoxy derivative), no significant difference in between R1 (or R2) and EPTN is offset by the trans config-
steric interactions in the generalized transition state can be uration of R1 and R2. If the reactive species is an adduct of
anticipated (Path A, Scheme 4) to explain the difference in EPTN-NH2 and PhI(OAc)2 (Paths B and C, Scheme 4), a
reactivity of cis and trans alkenes. Unfavorable interaction significant steric demand is predicted on the transition state
Eur. J. Org. Chem. 2009, 3635–3642
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3637

M. Zibinsky, T. Stewart, G. K. S. Prakash, M. A. Kuznetsov
FULL PAPER
Scheme 4. Proposed mechanisms for oxidative aminoaziridination with the EPTN-NH2/PhI(OAc)2 system.
involving the cis alkene compared with that of the trans of starting heterocycle 2 is less than 2 Hz, which is in a good
alkene. EPTN as well as phenyliodo groups are bulky, and agreement with its exo configuration. Because the value of
the presence of both of them in the transition state accounts 3Jb,c is also small, signals of pairwise enantiotopic Ha, Hb,
for the additional increment in total energy of this particu- and Hc atoms appear in the form of singlets with no visible
lar transition state. For example, in the case of cis alkene spin–spin interaction. However, for the majority of com-
(Path B, Scheme 4) this energy increment for the transition pounds 5 (except for molecules 5f, 5h, 5m, and 5n with a
state is the largest due to strong steric interactions between symmetry plane) the chirality of the aziridine fragment
R1, R2 and either EPTN or PhI. In other words, three sub- causes the diastereotopicity of initially enantiotopic atoms
stituents crowd on one side of the ring, whereas there is and groups in the tricyclic moiety. This leads to the doub-
only one substituent on the opposite side. To the contrary, ling of the corresponding signals in the NMR spectra and
in the transition state involving trans alkenes (Path C, to the visible appearance of spin–spin interaction between
Scheme 4), substituents are distributed evenly on both sides these nuclei (we observe AB or even AX spin systems in-
of the aziridine ring, which lowers the overall energy of the stead of A2). Therefore, this interaction depends on the dis-
transition state. Such an energy difference may account for tance between the centers of chirality and the atom or
the higher activation barrier and, hence, slower rate of reac- group under consideration.
tion and lower general reactivity of cis alkenes under these
When other dynamic processes, such as rotation around
conditions. This explanation also questions the nitrene/ni- the N–N bond in some sterically hindered compounds 5,
trenoid mechanism for this particular substrate/oxidant are slowed down, additional complications in the NMR
pair.
spectra are observed. This could be the reason why there
Generally, aminoaziridines are known to have a consider- are broad Ha and Hb signals along with sharp HaЈ and HbЈ
able barrier towards inversion of the endocyclic nitrogen peaks (see Scheme 2) in the spectrum of trans-stilbene ad-
atom, which usually leads to co-existence of the two in- duct 5g. It is possible that the chemical shifts for one of the
vertomers on the NMR timescale. However, most products atoms of the diastereomeric pair do not differ significantly
5 showed only one set of signals in the H NMR spectra, in both rotamers (the signal appears sharp). In the 1H
1
which indicates that one of the invertomers strongly pre- NMR spectra of chiral aziridines 5, spin–spin interactions
vails. This may be due to the bulkiness of the exo-3,6-ep- can be observed between diastereotopic Ha and HaЈ atoms
oxy-1,2,3,6-tetrahydrophthalimide fragment, which prefers (3Ja,aЈ = 6.4 Hz) and in some cases between the Hc and HcЈ
an anti position to the largest substituent in the aziridine atoms (3Jc,cЈ = 5.6–6.0 Hz) of the tricyclic fragments. The
ring. For molecules 5e and 5g with the axial symmetry of degree of nonequivalence (chemical shifts difference) can
the aziridine fragment, nitrogen inversion is a degenerate vary from case to case. At the same time, another atom of
process. However, the slow rate of inversion in these cases that pair can have rather different chemical shifts for these
causes nonequivalence of the syn and anti substituents (as rotamers, which results in a broader peak at the same rota-
related to the EPTN group) at the carbon atoms of the tion rate. In the 13C NMR spectrum of adduct 5g the peak
aziridine ring. Similar behavior is observed in the case of of a carbon atom in the aziridine moiety at 53.8 ppm is
aminoaziridine derivatives with an EnN group.[3j]
sharp, but the second one at 45.3 ppm is broadened, which
As expected, the NMR spectra pattern for the tricyclic is likely to be caused by the same reason. In contrast, the
fragment in compound 2 and in most aziridines 5 differs spectra of less sterically hindered fumarate derivative 5e
3
1
significantly. The value of Ja,b in the H NMR spectrum shows sharp peaks for all protons and carbon atoms men-
3638
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3635–3642

N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide in Aminoaziridinations
tioned above. More complicated are the NMR spectra of tural feature of both adducts 5 is the trans orientation of
adduct with β-nitrostyrene 5o. For this compound, we ob- the aziridine ring and the tricyclic fragment. NMR spectro-
served two invertomers in a ratio of about 2:1, as well as scopic data also suggests that compound 5c exists as a trans
the slow rotation around the N–N bond (same for com- isomer/anti invertomer (cis isomer/anti invertomer for 5f),
pound 5g), which causes significant broadening of many which was confirmed by X-ray studies.
signals in the 1H and 13C NMR spectra. Unexpectedly, nei-
ther low- (–20 and –50 °C) nor high-temperature (+50 °C)
1
NMR spectroscopic investigations helped to clarify the H
spectrum of 5o. At elevated temperature all peaks broad-
ened further, which indicated that at 50 °C many signals of
compound 5o are approaching their coalescence tempera-
tures for nitrogen inversion. At low temperatures, we ob-
served that some of the peaks broadened. This may be due
to a decrease in the rate of rotation around the N–N bond.
All these effects significantly complicated the peak assign-
ments, which we were able to do only partially.
No significant difference in yields was observed among
the chalcone series between adducts with electron-donating
and electron-withdrawing substituents in the para position
of the phenyl ring (compounds 4i–l). However, aminoazirid-
ines formed from alkenes with electron-donating substitu-
ents attached directly to the double bond are generally
known to be unstable.[10] The structures of their decomposi-
Figure 4. Bond lengths in compounds 2, 5c, 5f, and 7.
tion products depend on the nature of the substituents in
the alkene.[3a] In our attempt to react 2 with isobutyl vinyl
ether (4r), the corresponding aziridine was not isolated.
When furan (3 equiv.) was used as a trap instead of an al-
kene, previously unknown aldehyde 6 was isolated in 40%
yield. Formation of 6 could be explained by initial addition
of 2 to the carbon–carbon double bond of furan followed
by ring opening (Scheme 5). The cis configuration of alde-
hyde 6 was deduced from the small value of the vicinal
spin–spin constant between the olefinic protons (10 Hz),
Conclusions
N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide
is an active aminoaziridinating agent that reacts with al-
kenes containing a variety of substituents. Despite pos-
sessing its own double bond, no evidence of self-aziridina-
tion was found. A number of novel derivatives of N-amino-
aziridine were obtained in yields of 19–76%, and these de-
which is in good agreement with the proposed formation
rivatives were characterized by NMR spectroscopy, HRMS,
mechanism (Scheme 5) and the reported literature data.[10]
and single-crystal X-ray diffraction (compounds 5c and 5f).
A competitive study of the reactivity of cis versus trans al-
kenes demonstrates strong selectivity towards the trans al-
kene. Our results question the “nitrene”-based mechanism
It is interesting to note that the oxidative aminoaziridina-
tion of furan in the most often used N-aminophthalimide/
Pb(OAc)4 system produced an intractable product.[10a]
when phenyliodobenzene is used as an oxidant.
Experimental Section
1
General Remarks: H and 13C NMR spectra were recorded with a
400 MHz spectrometer in CDCl3 by using tetramethylsilane (δ =
0.00 ppm) as an internal standard for 1H NMR and CDCl3 (δ =
77.0 ppm) as an internal standard for 13C NMR spectroscopy.
High-resolution mass spectra (ESI or FAB) were obtained with a
Fourier transform mass spectrometer. Reactions were monitored
by thin-layer chromatography carried out on F254 silica gel coated
plates by using UV visualization and basic KMnO4 solution as
a developing agent. All reagents and solvents were commercially
available and were used as supplied without additional purification.
Scheme 5. Oxidative addition of EPTN-NH2 to furan.
Comparing the crystal structures of compounds 5c and
5f (Figure 4) with the crystal structures of starting heterocy-
cle 2 and N-phthalimidoaziridine 7 revealed no significant
difference in N–N bond lengths: 1.418, 1.420, 1.418, and
1.425 Å. The bond lengths in the aziridine cycle vary within
0.005 Å for compounds 5c and 5f. However, the aziridine
carbon–nitrogen and carbon–carbon bonds are somewhat
N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide (2):[6] Hy-
drazine hydrate (18 g, 0.36 mol, 1.2 equiv.) was added to exo-3,6-
epoxy-1,2,3,6-tetrahydrophthalic anhydride (50.0 g, 0.30 mol) in
isopropyl alcohol (300 mL). The mixture was heated at reflux for
3 h and then cooled down to 0 °C. The yellowish crystalline precipi-
shorter for phthalimide derivative 7.[2b,8] A noticeable struc- tate of 2 was smashed into pieces, filtered off, recrystallized from
Eur. J. Org. Chem. 2009, 3635–3642
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3639

M. Zibinsky, T. Stewart, G. K. S. Prakash, M. A. Kuznetsov
and 80.52 (C-3,6), 114.07 (Cm), 128.18 (Co), 130.82 (Ci), 136.26 and
FULL PAPER
MeOH, and then dried in the air. Yield: 32.3 g (60%). M.p. 186–
187 °C (ref.[6a] 187–188 °C). 1H NMR (400 MHz, CDCl3): δ = 2.83 136.44 (C-4,5), 159.83 (C-OMe), 172.08 (NC=O), 172.38 (NC=O),
(s, 1 H, Ha), 4.27 (s, 2 H, NH2), 5.26 (s, 2 H, Hb), 6.51 (s, 2 H, Hc)
ppm. 13C NMR (100 MHz, CDCl3): δ = 45.5 (C-1,2), 80.5 (C-3,6),
136.3 (C-4,5), 173.6 (C=O) ppm. HRMS (ESI+): calcd. for
C8H8N2O3 [M + H]+ 181.0613; found 181.0613 (–0.1 ppm error).
198.41 (C=O) ppm. HRMS (ESI+): calcd. for C19H18N2O5 [M +
H]+ 355.1288; found 355.1286 (–0.2 ppm error).
Dimethyl 1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)aziridine-
trans-2,3-dicarboxylate (5e): Yield: 1.001 g (56%). White crystals,
m.p. 156–157 °C. 1H NMR (400 MHz, CDCl3): δ = 2.73 (d, J =
6.4 Hz, 1 H, Ha), 2.80 (d, J = 6.4 Hz, 1 H, HaЈ), 3.53 (d, J = 4.4 Hz,
1 H, NCH), 3.72 (d, 1 H, NCH), 3.73 (s, 3 H, MeO), 3.82 (s, 3 H,
MeO), 5.22 (s, 1 H, Hb), 5.24 (s, 1 H, HbЈ), 6.48 (m, 2 H, Hc + HcЈ)
ppm. 13C NMR (100 MHz, CDCl3): δ = 42.44, 44.35, 45.37, 45.78,
53.13 (MeO), 53.22 (MeO), 80.35 and 80.52 (C-3 and C-6), 136.31
and 136.49 (C-4 and C-5), 165.15 (CO2Me), 166.35 (CO2Me),
171.43 (NC=O), 171.57 (NC=O) ppm. HRMS (ESI+): calcd. for
C14H14N2O7 [M + Na]+ 345.0693; found 345.0693 (–0.3 ppm er-
ror).
General Procedure for the Preparation of Compounds 5 and 6: Anhy-
drous K2CO3 (3.1 g, 22.5 mmol), PhI(OAc)2 (1.8 g, 5.6 mmol), 2
(1.0 g, 5.6 mmol), and the alkene (1–5 equiv.) were mixed and then
CH2Cl2 (30 mL) was added. The mixture was stirred at room tem-
perature for 16 h. The resulting suspension was centrifuged, and
after washing the precipitate with CH2Cl2 (30 mL) the combined
supernatant was filtered through a short plug of silica gel. The
solvent was removed under reduced pressure without heating, and
the residue was triturated with diethyl ether (15 mL). If no crystalli-
zation occurred, the crude product was purified by column
chromatography on silica gel (ethyl acetate/hexane, 1:1).
Recrystallization of the product from methanol was necessary in
some cases.
Dimethyl 1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)aziridine-
cis-2,3-dicarboxylate (5f): Yield: 361 mg (20%). White crystals, m.p.
168–169 °C. 1H NMR (400 MHz, CDCl3): δ = 2.79 (s, 2 H, Ha),
3.46 (s, 2 H, NCH), 3.83 (s, 6 H, MeO), 5.24 (s, 2 H, Hb), 6.50 (s,
2 H, Hc) ppm. 13C NMR (100 MHz, CDCl3): δ = 45.06 and 45.58
(NCH and C-1,2), 53.11 (MeO), 80.61 (C-3,6), 136.38 (C-4,5),
165.25 (CO2Me), 171.08 (NC=O) ppm. HRMS (ESI+): calcd. for
C14H14N2O7 [M + Na]+ 345.0693; found 345.0693 (–0.3 ppm er-
ror).
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-2-phenylaziridine
(5a): Yield: 854 mg (54 %). White crystals, m.p. 152–153 °C. 1H
NMR (400 MHz, CDCl3): δ = 2.67–2.72 (m, 2 H, Hcis + Htrans),
2.77 (s, 2 H, Ha + HaЈ), 3.44 (dd, J = 7.6, 6.0 Hz, 1 H, CHPh), 5.25
(s, 1 H, Hb), 5.27 (s, 1 H, HbЈ), 6.50 (s, 2 H, Hc + HcЈ), 7.29–7.41
(m, 5 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 40.00 (CH2),
44.60 (NCH), 45.54 (C-1,2), 80.60 and 80.61 (C-3,6), 127.03, 128.03
(Cp), 128.49, 136.22 (Ci), 136.33 and 136.37 (C-4,5), 172.21
(NC=O) ppm. HRMS (ESI+): calcd. for C16H14N2O3 [M + H]+
283.1077; found 283.1077 (–0.1 ppm error).
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-trans-2,3-diphen-
ylaziridine (5g): Yield: 1.525 g (76 %). White crystals, m.p. 150–
151 °C. 1H NMR (400 MHz, CDCl3): δ = 2.51 (br. s, 1 H, Ha),
2.57 (d, J = 6.8 Hz, 1 H, HaЈ), 3.89 (d, J = 6.0 Hz, 1 H, NCH),
4.64 (d, J = 5.6 Hz, 1 H, NCH), 4.83 (br. s, 1 H, Hb), 5.17 (s, 1 H,
HbЈ), 6.39 (m, 2 H, Hc + HcЈ), 7.27–7.42 (m, 8 H, Ph + Hm,p), 7.50
(m, 2 H, Ho) ppm. 13C NMR (100 MHz, CDCl3): δ = 45.37 (br. s,
NCH), 45.37 and 46.37 (C-1,2), 53.80 (NCH), 80.10 and 80.33 (C-
3,6), 127.01, 127.98, 128.04 (Cp), 128.52, 128.68 (Cp), 129.47,
130.73 (Ci), 135.86 and 136.50 (C-4,5), 136.36 (Ci), 172.49 (NC=O),
172.79 (NC=O) ppm. HRMS (ESI+): calcd. for C22H18N2O3 [M +
H]+ 359.1396; found 359.1390 (–0.1 ppm error).
Methyl 1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-phenyl-
aziridine-2-carboxylate (5b): Yield: 1.105 g (58%). White crystals,
m.p. 161–162 °C. 1H NMR (400 MHz, CDCl3): δ = 2.77 (d, J =
6.4 Hz, 1 H, Ha), 2.83 (d, J = 6.4 Hz, 1 H, HaЈ), 3.43 (d, J = 4.8 Hz,
1 H, CHCO2Me), 3.75 (s, 3 H, MeO), 4.13 (d, J = 4.8 Hz, 1 H,
CHPh), 5.25 (s, 1 H, Hb), 5.29 (s, 1 H, HbЈ), 6.49 (m, 2 H, Hc +
HcЈ), 7.30–7.42 (m, 5 H, Ph) ppm. 13C NMR (100 MHz, CDCl3):
δ = 45.33, 45.83 (2 C), 49.32, 52.84 (MeO), 80.36 and 80.51 (C-3
and C-6), 127.03 (Co or Cm) 128.58 (Cm or Co + Cp), 134.24 (Ci),
136.26 and 136.46 (C-4 and C-5), 166.57 (CO2Me), 171.94 and
172.24 (2 NC=O) ppm. HRMS (ESI+): calcd. for C18H16N2O5 [M
+ H]+ 341.1132; found 341.1132 (–0.4 ppm error).
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-cis-2,3-diphenyl-
aziridine (5h): Yield: 381 mg (19 %). White crystals, m.p. 195–
1
196 °C. H NMR (400 MHz, CDCl3): δ = 2.83 (s, 2 H, Ha), 3.93
(s, 2 H, NCH), 5.30 (m, 2 H, Hb), 6.53 (m, 2 H, Hc), 7.14–7.25 (m,
10 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 45.68 (C-1,2),
51.85 (NCH), 80.67 (C-3,6), 127.41 (Cp), 127.89, 128.13, 133.31
(Ci), 136.39 (C-4,5), 172.10 (NC=O) ppm. HRMS (ESI+): calcd.
for C22H18N2O3 [M + H]+ 359.1390; found 359.1390 (–0.3 ppm
error).
2-Acetyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-phenyl-
aziridine (5c): Yield: 1.003 g (51 %). White crystals, m.p. 153–
154 °C. 1H NMR (400 MHz, CDCl3): δ = 2.49 (s, 3 H, COMe),
2.69 (d, J = 6.4 Hz, 1 H, Ha), 2.83 (d, J = 6.4 Hz, 1 H, HaЈ), 3.60
(d, J = 4.8 Hz, 1 H, CHAc), 4.11 (d, J = 4.8 Hz, 1 H, CHPh), 5.25
(s, 1 H, Hb), 5.26 (s, 1 H, HbЈ), 6.48 (m, 2 H, Hc + HcЈ), 7.30–7.40
(m, 5 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 31.29 (Me),
45.30 and 45.79 (C-1 and C-2), 49.64 (NCHPh), 50.86 (NCHAc),
80.30 and 80.51 (C-3 and C-6), 126.91, 128.52 (Cp), 128.59, 134.72
(Ci), 136.26 and 136.43 (C-4 and C-5), 172.02 and 172.33 (2
NC=O), 198.24 (C=O) ppm. HRMS (ESI+): calcd. for
C18H16N2O4 [M + H]+ 325.1183; found 325.1183 (–0.3 ppm error).
2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-phen-
ylaziridine (5i): Yield: 1.601 g (74 %). White crystals, m.p. 177–
178 °C. 1H NMR (400 MHz, CDCl3): δ = 2.69 (d, J = 6.4 Hz, 1
H, Ha), 2.87 (d, J = 6.4 Hz, 1 H, HaЈ), 4.30 (d, J = 4.8 Hz, 1 H,
NCH), 4.42 (d, J = 4.8 Hz, 1 H, NCH), 5.23 (d, J = 1.6 Hz, 1 H,
Hb), 5.26 (d, J = 1.6 Hz, 1 H, HbЈ), 6.45 (m, 1 H, Hc), 6.50 (m, 1
H, HcЈ), 7.32–7.54 (m, 7 H, Ph + Hm), 7.58–7.64 (m, 1 H, Hp),
8.04–8.08 (m, 2 H, Ho) ppm. 13C NMR (100 MHz, CDCl3): δ =
45.29 and 45.87 (C-1,2), 48.51 (NCH), 50.37 (NCH), 80.36 and
80.60 (C-3,6), 127.06, 128.56, 128.65, 128.72, 133.61 (Cp Bz),
134.97 (Ci Bz), 136.26 and 136.47 (C-4,5), 137.12 (Ci Ph), 172.04
(NC=O), 172.13 (NC=O), 190.16 (C=O) ppm. HRMS (ESI+):
calcd. for C23H18N2O4 [M + H]+ 387.1339; found 387.1339
(–0.7 ppm error).
2-Acetyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-meth-
oxyphenyl)aziridine (5d): Yield: 793 mg (40%). White crystals, m.p.
151–152 °C. 1H NMR (400 MHz, CDCl3): δ = 2.50 (s, 3 H,
MeCO), 2.70 (d, J = 6.4 Hz, 1 H, Ha), 2.83 (d, J = 6.4 Hz, 1 H,
HaЈ), 3.59 (d, J = 4.4 Hz, 1 H, CHAc), 3.80 (s, 3 H, OMe), 4.06 (d,
J = 4.4 Hz, 1 H, ArCH), 5.25 (s, 1 H, Hb), 5.26 (s, 1 H, HbЈ), 6.49
(m, 2 H, Hc + HcЈ), 6.89 (m, 2 H, Hm), 7.30 (m, 2 H, Ho) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 31.31 (COMe), 45.30 and 45.80 (C- 2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-ni-
1 and C-2), 49.53 (NCHPh), 50.78 (NCHAc), 55.31 (MeO), 80.30 trophenyl)aziridine (5j): Yield: 1.691 g (70%). White crystals, m.p.
3640
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3635–3642

N-Amino-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide in Aminoaziridinations
171–172 °C. 1H NMR (400 MHz, CDCl3): δ = 2.71 (d, J = 6.4 Hz,
1 H, Ha), 2.88 (d, J = 6.4 Hz, 1 H, HaЈ), 4.29 (d, J = 4.4 Hz, 1 H,
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-2-nitro-3-phenyl-
aziridine (5o): Yield: 549 mg (30 %). Light-yellow crystals, m.p.
NCH), 4.48 (d, J = 4.4 Hz, 1 H, NCH), 5.24 (d, J = 1.6 Hz, 1 H, 133–134 °C (decomp.). Two invertomers ≈2:1.[4] 1H NMR
Hb), 5.26 (d, J = 1.6 Hz, 1 H, HbЈ), 6.46 (m, 1 H, Hc), 6.50 (m, 1 (400 MHz, [D6]DMSO): δ = 2.51–2.68 (br. m, 2 H, 1,2-H major),
H. HcЈ), 7.50–7.56 (m, 2 H, Hm), 7.61–7.66 (m, 3 H, HoЈ + Hp),
2.77–2.95 (br. m, 1 H, 1,2-H minor), 4.51 (br. s, 1 H), 4.68–4.74
8.04–8.09 (m, 2 H, Ho), 8.21–8.26 (m, 2 H, HmЈ) ppm. 13C NMR (br. m, 1.5 H), 5.15 (s, 1 H), 5.25–5.35 (br. m, 1 H), 5.43 (br. s, 0.5
(100 MHz, CDCl3): δ = 45.30 and 45.85 (C-1,2), 48.59 (NCH), H), 6.35–6.60 (br. m, 4 H, 4,5-H + CHNO2 major), 7.25–7.48 (br.
48.92 (NCH), 80.36 and 80.60 (C-3,6), 123.81 (p-C6H4NO2, Cm), m, 8 H, Ph + CHNO2 minor) ppm. 13C NMR (100 MHz, CDCl3):
128.05, 128.79, 128.80, 133.33 (Bz Ci), 133.91 (Bz Cp), 136.24 and
δ = 45.30, 45.72 and 46.08 (minor) (C-1,2); 49.89 (NCHPh minor),
136.43 (C-4,5), 141.45 and 142.28 (p-C6H4NO2, Ci and Cp), 171.87 51.70 (NCHPh major), 70.95 (CHNO2 major), 73.60 (CHNO2
(NC=O), 171.95 (NC=O), 189.15 (C=O) ppm. HRMS (ESI+): minor); 80.23 and 80.41 (C-3,6); 127.18, 128.65, 128.92, 129.50,
calcd. for C23H17N3O6 [M + Na]+ 454.1010; found 454.1010
(–0.4 ppm error).
130.18; 135.92, 136.39 and 136.49 (C-4,5 and Ci) ppm. HRMS
(ESI+): calcd. for C16H13N3O5 [M + H]+ 328.0928; found 328.0928
(–0.4 ppm error).
2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-chlo-
rophenyl)aziridine (5k): Yield: 1.626 g (69%). White crystals, m.p.
7-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-7-azabicy-
1
clo[4.1.0]heptan-2-one (5p): Yield: 322 mg (21%). White crystals,
179–180 °C (decomp.). H NMR (400 MHz, CDCl3): δ = 2.69 (d,
1
J = 6.4 Hz, 1 H, Ha), 2.86 (d, J = 6.4 Hz, 1 H, HaЈ), 4.25 (d, J =
4.8 Hz, 1 H, NCH), 4.38 (d, J = 4.8 Hz, 1 H, NCH), 5.22 (d, J =
1.6 Hz, 1 H, Hb), 5.26 (d, J = 1.6 Hz, 1 H, HbЈ), 6.45 (m, 1 H, Hc),
6.50 (m, 1 H, HcЈ), 7.32–7.42 (m, 4 H, p-C6H4Cl), 7.49–7.54 (m, 2
H, Hm), 7.61 (m, 1 H, Hp), 8.04–8.08 (m, 2 H, Ho) ppm. 13C NMR
(100 MHz, CDCl3): δ = 45.30 and 45.87 (C-1,2), 48.45 (NCH),
49.56 (NCH), 80.36 and 80.61 (C-3,6), 128.75, 128.77, 128.85,
133.55 (Bz, Ci or p-ClC6H4, C-Cl), 133.72 (Bz Cp), 134.48 (Bz, Ci
or p-ClC6H4, C-Cl), 136.27 and 136.46 (C-4,5), 136.99 (p-C6H4Cl,
Ci), 172.02 (NC=O), 172.05 (NC=O), 189.85 (C=O) ppm. HRMS
(ESI+): calcd. for C23H17ClN2O4 [M + H]+ 421.0950; found
421.0950 (–0.7 ppm error).
m.p. 163–164 °C. H NMR (400 MHz, CDCl3): δ = 1.62–1.71 (m,
1 H), 1.83–2.12 (m, 3 H), 2.40–2.52 (m, 2 H), 2.75 (s, 2 H, Ha),
2.87 (d, J = 7.2 Hz, H1Ј), 3.22 (dt, J = 7.2, 2.4 Hz, 1 H, H6Ј), 5.21
(m, 2 H, Hb), 6.48 (m, 2 H, Hc) ppm. 13C NMR (100 MHz,
CDCl3): δ = 17.99 (C-4Ј), 21.84 (C-5Ј), 36.87 (C-3Ј), 45.44 and
45.50 (C-1,2), 46.25 (C-6Ј), 49.09 (C-1Ј), 80.57 and 80.61 (C-3,6),
136.29 (C-4,5), 171.75 (NC=O), 202.83 (C-2Ј) ppm. HRMS (ESI+):
calcd. for C14H14N2O4 [M + H]+ 275.1032; found 275.1032 (–
0.7 ppm error).
2-Acetyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-pentyl-
aziridine (5q): Yield: 730 mg (41 %). White crystals, m.p. 124–
125 °C. 1H NMR (400 MHz, CDCl3): δ = 0.88 (m, 3 H, Me of
C5H11), 1.28–1.38 (m, 4 H), 1.48–1.58 (m, 3 H), 1.77 (m, 1 H), 2.43
(s, 3 H, COMe), 2.64 (d, J = 6.4 Hz, 1 H, Ha), 2.78 (d, J = 6.4 Hz,
1 H, HaЈ), 3.14 (m, 1 H, NCHC5H11), 3.20 (d, J = 4.8 Hz, 1 H,
NCHCOMe), 5.22 (s, 1 H, Hb), 5.25 (s, 1 H, HbЈ), 6.47 (m, 2 H,
Hc + HcЈ) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.99 (Me of
C5H11), 22.45, 25.65, 26.94, 31.09, 31.50 (4CH2 and Me of Ac),
45.17 and 45.81 (C-1,2), 48.62 (NCH), 49.35 (NCH), 80.29 and
80.50 (C-3,6), 136.29 and 136.39 (C-4,5), 172.24 (NC=O), 172.62
(NC=O), 199.37 (C=O) ppm. HRMS (ESI+): calcd. for
C17H22N2O4 [M + H]+ 319.1658; found 319.1658 (–0.3 ppm error).
2-Benzoyl-1-(exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimidyl)-3-(4-
methoxyphenyl)aziridine (5l): Yield: 1.726 g (74%). White crystals,
m.p. 179–180 °C. 1H NMR (400 MHz, CDCl3): δ = 2.69 (d, J =
6.4 Hz, 1 H, Ha), 2.86 (d, J = 6.4 Hz, 1 H, HaЈ), 3.81 (s, 3 H, OMe),
4.28 (d, J = 4.8 Hz, 1 H, NCH), 4.36 (d, J = 4.8 Hz, 1 H, NCH),
5.22 (d, J = 1 Hz, 1 H, Hb), 5.26 (d, J = 1 Hz, 1 H, HbЈ), 6.44 (m,
1 H, Hc), 6.49 (m, 1 H, HcЈ), 6.90 (m, 2 H, Hm), 7.38 (m, 2 H, Ho),
7.51 (m, 2 H, H2 Bz), 7.61 (m, 1 H, H3 Bz), 8.05 (m, 2 H, H1 Bz)
ppm. 13C NMR (100 MHz, CDCl3): δ = 45.27 and 45.86 (C-1,2),
48.43 (NCH), 50.24 (NCH), 55.35 (MeO), 80.34 and 80.58 (C-3,6),
114.11 (Cm), 126.97 (p-Anys, Ci), 128.32, 128.69, 128.71, 133.55
(2Z)-4-[(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)imino]but-2-
(Bz, Cp), 136.25 and 136.46 (C-4,5), 137.19 (Bz, Ci), 159.87 (C- enal (6): Yield: 551 mg (40%). Yellow crystals, decomposes below
OMe), 172.05 (NC=O), 172.14 (NC=O), 190.30 (C=O) ppm.
HRMS (ESI+): calcd. for C24H20N2O5 [M + H]+ 417.1445; found
417.1445 (–0.3 ppm error).
1
120 °C. H NMR (400 MHz, CDCl3): δ = 2.92 (s, 2 H, Ha), 5.36
(s, 2 H, Hb), 6.44 (ddd, J = 11.6, 6.8, 1.2 Hz, 1 H, H1), 6.55 (s, 2
H, Hc), 7.09 (dd, J = 11.6, 10.0 Hz, 1 H, H2), 10.07 (dd, J = 10.0,
1.2 Hz, 1 H, Him), 10.22 (d, J = 6.8 Hz, 1 H, Hal) ppm. 13C NMR
(100 MHz, CDCl3): δ = 45.49 (C-1,2), 81.29 (C-3,6), 135.83 (=CH),
136.54 (C-4,5), 140.97 (=CH), 154.11 (C=N), 172.55 (NC=O),
189.56 (CH=O) ppm. HRMS (ESI+): calcd. for C12H10N2O4 [M +
H]+ 247.0719; found 247.0719 (–0.4 ppm error).
7-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-7-azabicyclo[4.1.0]-
heptane (5m): Yield: 364 mg (25 %). White crystals, m.p. 170–
171 °C. 1H NMR (400 MHz, CDCl3): δ = 1.18–1.29 (m, 2 H), 1.32–
1.44 (m, 2 H), 1.84–1.94 (m, 2 H), 2.12–2.22 (m, 2 H), 2.57 (m, 2
H, H1Ј), 2.70 (s, 2 H, Ha), 5.20 (s, 2 H, Hb), 6.47 (s, 2 H, Hc) ppm.
13C NMR (100 MHz, CDCl3): δ = 19.91 (C3Ј), 23.02 (C2Ј), 43.97
and 45.53 (C1Ј and C-1,2), 80.51 (C-3,6), 136.30 (C-4,5), 172.51
(NCO) ppm. HRMS (ESI+): calcd. for C14H16N2O3 [M + H]+
261.1234; found 261.1234 (+0.1 ppm error).
Study of Competitive Oxidative Addition of EPTN-NH2 to Dimethyl
Fumarate (4e) vs. Maleate (4f) in CDCl3: Anhydrous K2CO3(2.30 g,
16.7 mmol), PhI(OAc)2 (1.79 g, 5.6 mmol), 2(1.00 g, 5.6 mmol), di-
methyl maleate (2.33 g, 16.2 mmol), and dimethyl fumarate (2.34 g,
16.3 mmol) were mixed in CDCl3 (30 mL). The mixture was stirred
at room temperature and 10 NMR spectra of 10 0.5-mL aliquots
were taken within 270 min. Reaction was complete in 4 h. Isolation
of the product was carried out as described above. Yield of trans-
aziridine 5e was 42 %.
1-(exo-3,6-Epoxy-1,2,3,6-tetrahydrophthalimidyl)-1a,7a-dihydro-
1H-naphtho[2,3-b]azirene-2,7-dione (5n): Yield: 395 mg (21%). Yel-
low crystals, m.p. 179–180 °C. 1H NMR (400 MHz, [D6]DMSO): δ
= 2.87 (s, 2 H, Ha), 3.91 (s, 2 H, Haz), 5.12 (s, 2 H, Hb), 6.53 (s, 2
H, Hc), 7.85–7.96 (m, 4 H, o-C6H4) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 45.26 (C-1,2), 48.76 (NCH), 80.23 (C-3,6), 126.35
(C-3,6, Ar), 132.64 (C-2a,6a, Ar), 134.70 (C-4,5, Ar), 136.28 (C-
4,5), 171.83 (NC=O), 188.38 (C=O) ppm. HRMS (ESI+): calcd.
Supporting Information (see also the footnote on the first page of
this article): Copies of NMR spectra of all compounds and crystal-
lographic data for compounds 5c and 5f.
for C18H12N2O5 [M + H]+ 337.0819; found 337.0819 (–0.3 ppm CCDC-733493 (for 5c) and -733494 (for 5f) contain the supplemen-
error).
tary crystallographic data for this paper. These data can be ob-
Eur. J. Org. Chem. 2009, 3635–3642
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3641

M. Zibinsky, T. Stewart, G. K. S. Prakash, M. A. Kuznetsov
FULL PAPER
V. N. Belov, Zh. Org. Khim. 1984, 20, 1786; d) M. A. Kuznet-
sov, L. M. Kuznetsova, J. G. Schantl, K. Wurst, Eur. J. Org.
Chem. 2001, 1309; e) R. S. Atkinson, J. R. Malpass, K. L. Skin-
ner, K. L. Woodthorpe, J. Chem. Soc. Perkin Trans. 1 1984,
1905; f) R. S. Atkinson, J. Fawcett, I. S. T. Lochrie, S. Ulucanli,
T. A. Claxton, J. Chem. Soc. Perkin Trans. 2 2002, 819; g) R. D.
Richardson, M. Desaize, T. Wirth, Chem. Eur. J. 2007, 13,
6745.
tained free of charge from the Cambridge Crystallographic Data
Center via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgments
This study was conducted with the support of the Loker Hydro-
carbon Institute.
[5] a) H. Dong, C. Liu, Q. He, L. Zhao, Yaoxue Shijian Zazhi
2007, 25, 276; b) T. Li, Z. Tang, G. Wang, Hejishu 1998, 21,
744; c) J.-Y. Liu, B.-X. Zhang, R.-X. Li, Yaoxue Xuebao 1980,
15, 271; d) L. Moed, T. A. Shwayder, M. W. Chang, Arch.
Dermatol. 2001, 137, 1357; e) R. Rauh, S. Kahl, H. Boechzelt,
R. Bauer, B. Kaina, T. Efferth, Chin. Med. 2007, 2, 8; f) Q.-H.
Shi, Y.-L. Wang, H.-R. Song, M.-S. J. J. Cheng, Chin. Pharma-
ceut. Sci. 2005, 14, 250; g) W.-N. Zeng, Y. Lu, Youji Huaxue
2006, 26, 579; h) J.-I. Zhou, W.-Y. Yao, Y.-Z. Yuan, Shanghai
Yixue 2007, 30, 294.
[6] a) M. Furdik, E. Sidoova, Acta Fac. Rerum Nat. Univ. Comen-
ianae, Chimia 1965, 9, 255; b) M. Augustin, P. Reinemann, Z.
Chem. 1972, 12, 101; c) M. Augustin, P. Reinemann, Z. Chem.
1973, 13, 61; d) H. Title, Fr. Demande. 1970, 15.
[7] a) S. Cheng, Wulijimuren, X. Wu, X. Zhang, Huaxue Shiji
1993, 15, 152; b) K. Narasimhan, P. R. Kumar, J. Org. Chem.
1983, 48, 1122.
[8] M. Struga, B. Miroslaw, I. Wawrzycka-Gorczyca, J. Kossakow-
ski, A. E. Koziol, Pol. J. Chem. 2007, 81, 51.
[9] a) L. B. Krasnova, R. M. Hili, O. V. Chernoloz, A. K. Yudin,
ARKIVOC 2005, 26; b) L. B. Krasnova, A. K. Yudin, Org.
Lett. 2006, 8, 2011.
[10] a) D. W. Jones, J. Chem. Soc., Chem. Commun. 1971, 1130; b)
W. Rao, P. W. H. Chan, Tetrahedron Lett. 2007, 48, 3789.
Received: March 25, 2009
[1] a) R. S. Atkinson, A. P. Ayscough, W. T. Gattrell, T. M. Rayn-
ham, J. Chem. Soc. Perkin Trans. 1 2000, 3096; b) R. S. Atkin-
son, R. D. Draycott, D. J. Hirst, M. J. Parratt, T. M. Raynham,
Tetrahedron Lett. 2002, 43, 2083.
[2] a) T. K. Chakraborty, A. Ghosh, Indian J. Chem. 2001, 40B,
895; b) J. T. Kapron, B. D. Santarsiero, J. C. Vederas, J. Chem.
Soc., Chem. Commun. 1993, 1074; c) C. Xiong, W. Wang, V.
Hruby, Abstracts of Papers, 221st ACS Meeting, San Diego,
CA, April 1–5, 2001, ORGN-129.
[3] a) D. J. Anderson, T. L. Gilchrist, D. C. Horwell, C. W. Rees, J.
Chem. Soc. C 1970, 576; b) R. S. Atkinson, C. W. Rees, Chem.
Commun. (London) 1967, 1230; c) J. De Mendoza, T. Torres,
M. D. Badia, Monatsh. Chem. 1988, 119, 1041; d) M. B. Ho-
gale, P. B. Chavan, Indian J. Chem. 1993, 32B, 581; e) J. Li, J.-
L. Liang, P. W. H. Chan, C.-M. Che, Tetrahedron Lett. 2004,
45, 2685; f) J. Li, P. W. H. Chan, C.-M. Che, Org. Lett. 2005,
7, 5801; g) K. K. Mayer, F. Schröppel, J. Sauer, Tetrahedron
Lett. 1972, 13, 2899; h) H. Person, A. Foucaud, Bull. Soc.
Chim. Fr. 1976, 1119; i) F. Schröppel, J. Sauer, Tetrahedron
Lett. 1974, 15, 2445; j) M. Zibinsky, A. N. Butkevich, M. A.
Kuznetsov, Tetrahedron Lett. 2008, 49, 5505.
[4] a) R. S. Atkinson, J. R. Malpass, J. Chem. Soc. Perkin Trans. 1
1977, 2242; b) O. A. Ignatenko, M. A. Kuznetsov, S. I. Seliv-
anov, Russ. J. Org. Chem. 2007, 43, 1042; c) M. A. Kuznetsov,
Published Online: June 8, 2009
3642
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3635–3642