Reaction of 1,6-dioxo-2,4-diene with aziridine and secondary amine

Article abstract of DOI:10.1002/jccs.200700225

The (2E,4E)- and (2E,4Z)-1-phenyl-1,6-dioxo-hepta-2,4-diene reacts with aziridine to give aziridinecyclopentenol 3. This product arises from an intermolecular Michael addition of a nitrogen lone pair to the less reactive enone, followed by an intramolecul

Full text of DOI:10.1002/jccs.200700225

Journal of the Chinese Chemical Society, 2007, 54, 1595-1600
1595
Reaction of 1,6-Dioxo-2,4-diene with Aziridine and Secondary Amine
Tsung-Hsien Sun (
Department of Chemistry, National Sun Yat Sen University, Kaohsiung, Taiwan 804, R.O.C.
) and Chi-Wi Ong* (
)
The (2E,4E)- and (2E,4Z)-1-phenyl-1,6-dioxo-hepta-2,4-diene reacts with aziridine to give aziridine-
cyclopentenol 3. This product arises from an intermolecular Michael addition of a nitrogen lone pair to the
less reactive enone, followed by an intramolecular aldol reaction of the enol with ketone. Furthermore, the
initially formed enol did not undergo nucleophilic attack onto the aziridine ring to form heterocycles. In-
terestingly, the reaction with secondary amine did not give the cyclopentenol adduct, and this only leads to
the isomerization of (2E,4Z)-1-phenyl-1,6-dioxo-hepta-2,4-diene to the more stable (2E,4E)-1-phenyl-
1,6-dioxo-hepta-2,4-diene by addition to the more reactive enone.
Keywords: 1,6-Dioxo-2,4-diene; Aziridine; Secondary amine.
INTRODUCTION
The 1,6-dioxo-2,4-diene can be readily synthesized
volved the sequential intermolecular 1,2- or 1,4-addition of
nucleophiles to the dienone followed by an intramolecular
cyclization reaction.
using the following methods: (i) transition metal-catalyzed
reaction of monosubstituted furans with aromatic diazo ke-
tones,1 (ii) electrophilic substitution of 1,4-bis(trimethyl-
silyl)buta-l,3-diene with acyl chlorides,2 and (iii) palla-
dium-catalyzed isomerization of ynone.3 Our previous
studies have demonstrated polyaromatic furan, pyrrole and
pyrrolizine and indolizine derivatives4 (Scheme I). This in-
The chemistry of aziridines continues to attract the at-
tention of the synthetic community.5-13 We were interested
in utilizing an aziridine derivative as the nucleophile for
addition to 1,6-dioxo-2,4-diene. Although there have been
no reports of this reaction, it was believed that the aziridine
adduct might undergo a further ring opening reaction by
the generated enol or enolate to form new heterocycles.
Scheme I The synthetic application of 1,6-dioxo-2,4-diene derivatives
* Corresponding author. E-mail: cong@mail.nsysu.edu.tw

1596 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sun and Ong
RESULTS AND DISCUSSION
enol or enolate, but this might undergo a further attack on
the aziridine ring. The products that might arise from the
intermolecular 1,4- and 1,6-addition of aziridine, followed
by either an intramolecular aldol or aziridine ring opening
reaction are illustrated in Scheme II and Scheme III, re-
spectively.
We have recently reported that aromatic 1,6-dioxo-
2,4-diene can be converted to 4,5-disubstituted cyclopen-
tenone by methoxide anion through a tandem intermolecu-
lar Michael addition, followed by an intramolecular Mi-
chael addition of the enolate generated.4a In light of this re-
sult, we reasoned that aziridine would undergo a similar re-
action with aromatic 1,6-dioxo-2,4-diene to generate an
The desired 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-di-
ene (1) was readily prepared as reported.4 Next, the sym-
metric 7-azabicyclo[4,1,0]heptane, (2), was prepared from
Scheme II Proposed possible products from the 1,4-addition of aziridine to 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-
diene (1)

Cyclopentanol from 1,6-Dioxo-2,4-diene and Aziridine
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1597
Scheme III Proposed products from the 1,6-addition of aziridine to 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-diene (1)
cyclohexene oxide by the ring-opening reaction with so-
dium azide followed by the ring-closure reaction with
PPh3.14 Aziridine (2) was chosen because of the ease of
preparation, and it is not volatile and thus can be easily han-
dled. Treatment of 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-
diene (1) with aziridine (2) under basic conditions using
tBuOK resulted in a great number of unidentifiable prod-
ucts and could not be separated by chromatography. Conse-
quently, the reaction was carried out in the absence of base.
Indeed, when 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-diene
(1) was used directly to react with aziridine (2) in methanol
at 0 °C, a major product in 46% yield was obtained after pu-
rifying by chromatography on an aluminum oxide column.
The 1H-NMR of this major product showed peaks at d 5.86
and 5.73 for an unconjugated double bond. Thus, we were
able to exclude those products having a a,b-unsaturated
ketone. The most likely structures were thus those contain-
ing an isolated double bond in Scheme II and Scheme III.
We were not able to unambiguously assign the structure
from the NMR data. Luckily, we were able to obtain a sin-
gle crystal suitable for an X-ray analysis. The X-ray struc-
ture is shown in Fig. 1, and this unambiguously proves the
structure of the product to be 3. Interestingly, the neutral
aziridine (2) adds to the less reactive aromatic enone to
give a more stabilized enol, which undergoes an intramo-
lecular aldol reaction to give cyclopentenol 3. We did not
isolate the enone 6 from this reaction. This is in contrast
with the methoxide anion which adds to the more reactive
nonaromatic enone to give enone 6.4a This result showed
the inertness of the aziridine ring to undergo an intramo-
lecular ring opening reaction by the enol. This is conceiv-
able as there has not yet been any report of such reactions.
Futhermore, our result excludes the 1,6-addition shown in
Scheme III.
In order to determine the generality of the above reac-
tion for 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-diene (1) with
secondary amine, several commercially available second-
Fig. 1. The X-Ray structure of the compound 3.

1598 J. Chin. Chem. Soc., Vol. 54, No. 6, 2007
Sun and Ong
Table 1. The reaction of 1-phenyl-1,6-dioxo-hepta-2,4-(E,Z)-diene (12) with aziridine (2) and
secondary amine
Entry
Reactant
Condition
Temp.
0 °C
Product
Yield
1
2
3
4
5
6
7
8
2
tBuOK / THF
CH3OH
tBuOK / THF
Aa
3
Aa
x
46%
x
2
0 °C
R=Ethyl
R=Ethyl
R=Isopropyl
R=Isopropyl
R=Phenyl
R=Phenyl
0 °C
CH3OH
tBuOK / THF
CH3OH
tBuOK / THF
0 °C or RT
0 °C
1
100%
x
Aa
1
0 °C or RT
0 °C
100%
x
Aa
CH3OH
0 °C or RT
1
100%
a A represents the great number of unidentifiable product.
ary amines were studied. The reaction of 1-phenyl-1,6-di-
oxo-hepta-2,4-(E,E)-diene (1) with secondary amines such
as diethylamine, diisopropylamine or diphenylamine under
similar conditions resulted in the recovery of (1). The fail-
ure of the desired reaction to form cyclopentenol could be
attributed to two possibilities: (i) the addition of these
amines to the less reactive aromatic enone did not undergo
an aldol reaction, or a retro-aldol took place, and this is fol-
lowed by the elimination of the secondary amine to regen-
erate the starting materials; (ii) reaction of these amine at
the more reactive enone, but this did not undergo aldol re-
action with the more stable aromatic carbonyl and undergo
elimination to regenerate starting material.
more stable 1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-diene (1).
Reaction of (E,Z)-(12) with aziridine (2) also gave the same
cycolpentenol product 3 (Scheme IV). The reaction of di-
ethylamine, diisopropylamine or diphenylamine with 1-
phenyl-1,6-dioxo-hepta-2,4-(E,Z)-diene (12) was found to
induce isomerization of the (Z)-double bond in (12) to give
1-phenyl-1,6-dioxo-hepta-2,4-(E,E)-diene (1). These re-
sults are summarized in Table 1. The possible mechanism
of this isomerization is shown in Scheme V. This strongly
suggested that these secondary amines also react at the
more reactive (Z)-enone to allow isomerization after rota-
tion of the single bond, followed by elimination of the
disubstituent amine to form the (E,E)-(1). Thus the 1,4-ad-
dition of secondary amine is similar to that of the reported
methoxide anion.4a
We decided to probe the mechanism further. It was
hoped that the use of 1-phenyl-1,6-dioxo-hepta-2,4-(E,Z)-
diene (12) could provide some insight into the reaction. We
were able to obtain the initially formed 1-phenyl-1,6-di-
oxo-hepta-2,4-(E,Z)-diene (12) from the reaction of phenyl
diazo ketone with 2-methylfuran in the presence of cata-
lyzed copper sulfate by recrystallization from ether. Purifi-
cation by chromatography on a silica gel column gave the
CONCLUSION
In conclusion, we have shown that the reaction of
aziridine with 1-phenyl-1,6-dioxo-hepta-2,4-diene differs
Scheme IV The formation of the cyclopentenol 3 from 1,6-dioxo-2,4-(E,Z)-diene (12)

Cyclopentanol from 1,6-Dioxo-2,4-diene and Aziridine
J. Chin. Chem. Soc., Vol. 54, No. 6, 2007 1599
Scheme V The isomerization of (E,Z)-12 to (E,E)-1
from the reaction with secondary amines and methoxide
anion. Aziridine was found to give cyclopentenol via an
intermolecular 1,4-addition to the less reactive aromatic
enone, followed by an intramolecular aldol reaction. The
failure of secondary amines to undergo a similar reaction
has led us to investigate the differences of their reactivities
with respect to aziridine. More work will be carried out in
the future to induce the aziridine ring opening reaction in
the presence of metal catalysis.13
(CH ´ 2), 128.6 (CH ´ 2), 84.7 (C), 75.6 (CH), 65.1 (CH),
37.8 (CH), 37.7 (CH), 24.1 (CH2 ´ 2), 23.8 (CH3), 20.4
(CH2), 20.1 (CH2). LRMS (EI+, m/z): 296 [(M-1)+]. HRMS
(EI+) calcd for C19H23NO2 [M+]: 297.1729; found C19H23NO2
[M+]: 297.1731.
ACKNOWLEDGMENT
We gratefully acknowledge the National Science
Council (NSC) of Taiwan for funding.
EXPERIMENTAL SECTION
Compounds 1, 121 and 214 were prepared according
Received April 24, 2007.
to previously reported methods.
[5-(7-Aza-bicyclo[4.1.0]hept-7-yl)-2-hydroxy-2-methyl-
cyclopent-3-enyl]-phenylmethanone 3
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