Photoreaction of some 5-alkylidene-2,5-dihydroisoxazoles: facile construction of novel unclassical β-lactam containing heterocycles

Article abstract of DOI:10.1016/j.tet.2006.12.009

The photochemical behaviour of some 5-alkylidene-2,5-dihydroisoxazoles was investigated. This reaction produced cis-4,5-dihydrofuroazetidinones in high yields.

Full text of DOI:10.1016/j.tet.2006.12.009

Tetrahedron 63 (2007) 1583–1588
Photoreaction of some 5-alkylidene-2,5-dihydroisoxazoles:
facile construction of novel unclassical b-lactam
containing heterocycles
a
a
Donato Donati,a Stefania Fusi,a, Fabio Ponticelli, Riccardo Rossi Paccani
*
and Mauro F. A. Adamob
aDipartimento di Chimica, Universitaꢀ di Siena, Via Aldo Moro, Siena 53100, Italy
bCentre for Synthesis and Chemical Biology (CSCB), Department of Pharmaceutical and Medicinal Chemistry,
The Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Dublin, Ireland
Received 3 October 2006; revised 21 November 2006; accepted 7 December 2006
Abstract—The photochemical behaviour of some 5-alkylidene-2,5-dihydroisoxazoles was investigated. This reaction produced cis-4,5-
dihydrofuroazetidinones in high yields.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
This family of compounds could be rapidly assembled from
an opportunely substituted 5-chloroisoxazole 2, an alkylat-
ing agent 3 and an enolisable compound 4 (Fig. 1). Hence
the preparation of 1 is modular and offers the advantage of
a rapid introduction of diversity.9
The synthesis of novel b-lactam cores continues to attract the
attention of the scientific community as these molecules
possess a wide range of biological activities.1 Following
initial reports on the antibacterial and anti-b-lactamase
activities of b-lactams,2,3 several accounts appeared in
which b-lactams of unusual structure were found useful in
tackling the human cytomegalovirus.4
5-Alkylidene-2,5-isoxazoles 1 hold great potentials for the
development of diversity orientated syntheses as they con-
tain a number of photochemically switchable groups that
could be used to dictate the reaction outcome. For instance,
the N–O bond in the isoxazole moiety could be reacted by
irradiation with ultraviolet light.10 The resulting diradical
species usually rearranges to a reactive acyl-azirin interme-
diate that eventually evolves to a stable oxazole.10 Com-
pounds 1 contain two conjugated carbonyl functionalities,
which could be exploited to initiate radical cascades of the
Norrish I type.11 The latter mode of reaction expands the
number of molecular types that are available from 1.
Recently, b-lactams were also found to be useful as anti-
tumour compounds.5 Aza-sugars6 or spirocyclopentenones7
were prepared from the b-lactam core demonstrating the
potential of this class of compounds to act as synthetic
precursors. As a part of our endeavours in developing syn-
thetically useful photochemical processes, we became inter-
ested in 5-alkylidene-2,5-isoxazoles 1 (Fig. 1).8
R1
R2
R1
R2
R4
We have reported that irradiation of 5-alkylidene-2,5-
dihydroisoxazole 5 resulted in the formation of the 4,5-
dihydrofuroazetidinone 6 (Scheme 1), which is a novel
heterocyclic nucleus that contains a b-lactam core.8
R4
+
+
CF3SO3CH3
N
H3C
N
O
Cl
O
O
O
R3
R3
1
2
3
4
OEt
R1-R2 = Alkyl or Aryl; R3 = Me, -OEt; R4 = CN,COMe,COOEt
CH3
CO2Et
CH3
Ph
H3C
O
CO2Et
h
Ph
Figure 1. A family of photoreactive isoxazoles.
N
365nm
O
CO2Et
N
H3C
O
Keywords: b-Lactam; Isoxazole photochemistry.
* Corresponding author. Tel.: +39 0577 234273; fax: +39 0577 234278;
e-mail: fusiste@unisi.it
5
6
Scheme 1. Photolysis of 5-alkylidene-2,5-dihydroisoxazole 5.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.009

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D. Donati et al. / Tetrahedron 63 (2007) 1583–1588
R3
While compounds 1a–e afforded b-lactams 7a–e as the
R1
R2
Cl
R4
R4
R2
exclusive products and in high yields (Table 1, entries 1–
5), compound 1f furnished 7f only in a limited amount
(Table 1, entry 6). In this reaction, lactone 8f appeared as
the principal product and was isolated in 68% yield. Com-
pound 1g furnished upon irradiation a mixture of lactone
8g and furanone 9 (Table 1, entry 7). Surprisingly, in this
reaction no b-lactam was formed. The structures of
O
h
R1
+
+
CF3SO3CH3
+
N
O
O
N
R3
H3C
O
7
2
3
4
Figure 2. A new modular approach to the preparation of 4,5-dihydrofuro-
azetidinones 7.
1
compounds 7b–f were assigned by comparison of the H
and 13C NMR data with those of 7a whose structure was
determined by X-ray crystallographic analysis.8 We also
determined the structure of compound 7c as 1,2a-di-
methyl-6a-phenyl-2a,4,5,6a-tetrahydro-1H-6-oxa-1-aza-
cyclobuta[a]pentalene-2,3-dione and of compound 7e as
1,2a,4,6-tetramethyl-7a-phenyl-1,2a,6,7a-tetrahydro-7-oxa-
1,4,6-triaza-cyclobuta[a]indene-2,3,5-trione by X-ray crys-
tallography (Fig. 3).12
We reasoned that if an alkylidene isoxazole 5 could be con-
verted efficiently to 4,5-dihydrofuroazetidinones 6, then a
novel approach to the synthesis of 7 could be envisaged that
starts from an opportunely substituted 5-chloroisoxazole 2,
an alkylating agent 3, an enolisable compound 4 and light
(Fig. 2). To confirm this hypothesis, we started a programme
of research aimed at identifying the scope for the photo-
chemical rearrangement of compounds 1. Herein we report
the results of this study, which was focused on the nature
of the alkylidene moiety.
The structures of lactones 8f,g and furanone 9 were assigned
using mono- and two-dimensional NMR spectra and also
1
by comparison of their H and 13C NMR chemical shifts
with those of known compounds.13–15 While lactones 8f,g
were isolated using column chromatography, furanone 9
did not survive exposure to silica gel and rapidly decom-
posed. For this reason, 9 was characterised without isolating
it from 8g.
2. Results and discussion
Compounds 1a–g (Scheme 2) were prepared following
a procedure established in our laboratories,8 and were subse-
quently photoreacted using a 365 nm light until complete
conversion of the starting materials was observed (Scheme 2
and Table 1). In most cases, b-lactam products 7a–f were
obtained in high yields (Table 1).
The data collected (Table 1) pointed out that more than
one reaction pathway is available for the photoreaction of
compounds 1. We believe that compounds 7, 8 and 9 arise
Me
OEt
Me
R1
O
R2
Me
Ph
Ph
Me
Me
Me
O
O
R1
R2
h
COMe
Ph
Me
Ph
+
+
N
365nm
O
O
N
N
O
N
Me
O
Me
Me
1a-g
Scheme 2. Photoreaction of isoxazoles 1a–g.
7a-f
8f-g
9
Table 1. Products obtained photoreacting isoxazoles 1a–g
Entry
Alkylidene
b-Lactam
OEt
Yielda (%)
Alternative products
CH3
Ph
CO2Et
CH3
CO2Et
O
H3C
N
Ph
O
CO2Et
1
71
—
N
1a
H3C
O
7a
CH3
OEt
Ph
CN
CO2Et
O
H3C
N
Ph
CH3
O
CN
2
3
74
78
—
—
1b
N
H3C
O
7b
CH3
Ph
O
O
O
H3C N
Ph
Me
O
N
O
Me
O
7c
(continued)

D. Donati et al. / Tetrahedron 63 (2007) 1583–1588
1585
Table 1. (continued)
Entry
Alkylidene
b-Lactam
Yielda (%)
Alternative products
CH3
Ph
H3C N
O
O
O
O
Ph
Me
4
5
6
78
—
N
O
O
Me
CH3
O
Ph
H3C N
O
N
H3C
O
CH3
N
N
CH3
O
O
N
O
74
—
O
Ph
Me
CH3
N
Me
O
7e
CH3
OEt
EtO2C
Me
Ph
H3C
COCH3
CH3
COCH3
Me
Ph
O
O
N
Ph
O
CO2Et
14
O
N
N
N
1f
Me
H3C
O
8f
7f
CH3
CH3
Me
COMe
Ph
H3C
O
H3COC
Me
COCH3
CH3
COCH3
Me
Ph
O
N
Ph
Me
Ph
O
O
COCH3
7
0
O
1g
N
O
H3C
O
7g
N
Me
Me
8g
9
a
Isolated yields of chromatographically pure material.
from a common intermediate, which we identified as cyclo-
propanone 12 (Scheme 3). The photochemical behaviour of
a 5-alkylidene isoxazole similar to 5 has been reported and
a cyclopropanone was proposed as the main product of this
reaction.10 Therefore, it is possible that upon irradiation
with an opportune wavelength, the N–O bond present in 5
opened to form a diradical species 10. Intermediate 10 then
rearranged to give the cyclopropanone intermediate 12.
this fact manifests itself as a low activation energy that
justifies the high reactivity of cyclopropanones even at low
temperatures.
We speculated that upon photolysis compounds 1a–g
rearranged to cyclopropanones 13 that at this point could
undergo two diverse kinds of rearrangements a and b
(Scheme 4).19 Rearrangement a (Scheme 4) involved photo-
lysis of the imine moiety that triggered the rearrangement of
the cyclopropanone moiety to a b-lactam diradical species
15. Intermediate 15 could either cyclise to yield the expected
azetidinone 7 or further rearrange to furnish lactone 8.
Rearrangement b (Scheme 4) involved the homolytic ring
opening of cyclopropanones 13 to give a diradical species
17, which finally cyclised to give 9.
Cyclopropanones have been extensively studied.16 They are
intermediates in important reactions such as the Favorskii
rearrangement17 or precursors of oxyallyl cations, a widely
used class of reactive synthons.18 As a result of the severe
angle strain, cyclopropanones possess large amount of en-
ergy waiting to be released by ring opening. Experimentally
C18
O7
C19
C23
C14
N4
C8
C17
O1
O1
N15
O3
C13
C9
C24
C20
C6
C22
C12
N2
C11
N4
C21
O5
C16
C10
O3
O2
Figure 3. ORTEP drawing of compounds 7c,e with 20% probability thermal ellipsoids.

1586
D. Donati et al. / Tetrahedron 63 (2007) 1583–1588
CH3
CO2Et
Ph
H3C
H3C
Ph
Me
Me
Ph
Ph
H3C
CH3
CO2Et
O
O
h
CO2Et
CO2Et
OEt
OEt
H3C N
N
N
N
365nm
O
CO2Et
CO2Et
10
O
O
O
12
11
5
Scheme 3. Photochemical rearrangement of alkylidene isoxazole 5.
O
R2
R1
R2
Ph
Ph
H3C
O
H3C
b
R1
a
a
R1
O
Ph
R1
Ph
CH3
H3C N
H3C N
R2
R2
CH3
O
O
N
N
N
O
13
O
H3C
O
7
CH3
b
14
15
R1
Me
Me
R2
Ph
H3C
CH3
R1
O
H3C
Ph
O
Ph
O
R2
R1
Ph
H3C N
R2
O
O
N
O
H3C
N
O O
R1
17
Me
Me
9
16
8
Scheme 4. Proposed reaction pathway for the rearrangement of cyclopropanones 13.
In conclusion we have studied the photochemical rearrange-
ment of some 5-alkylidene-2,5-isoxazoles to afford b-lac-
tams. With the correct choice of alkylidene moiety this
reaction could be used to assemble families of b-lactam
compounds rapidly and efficiently.
3.2.1. Cyano-(2,4-dimethyl-3-phenyl-2H-isoxazol-5-
ylidene)-acetic acid ethyl ester 1b. Yellow solid (512 mg,
60% yield), Rf¼0.6, mp 133–135 ꢁC (ethanol); nmax (film)/
cmꢂ1: 2241s, 1735s; dH (200 MHz, CDCl3) 7.61–7.30
(5H, m, Ph), 4.22 (2H, q, J¼7, OCH2CH3), 3.48 (3H, s,
N–CH3), 2.21 (3H, s, CH3), 1.31 (3H, t, J¼7, OCH2CH3);
dC (50 MHz, CDCl3) 174.0, 165.1, 159.0, 131.5, 129.6,
128.9, 125.5, 119.0, 105.5, 65.0, 60.1, 39.5, 14.5, 9.4; m/z:
285 (100%, MH+). Anal. Calcd for C16H16N2O3: C, 67.59;
H, 5.67; N, 9.85. Found: C, 67.85; H, 5.64; N, 9.82.
3. Experimental
3.1. General experimental
Melting points were measured with a Kofler apparatus and
are uncorrected. The 1H and 13C NMR spectra were recorded
with a Bruker AC200 instrument operating at 200.13 MHz
for 1H and at 50.33 MHz for 13C. The J-long range hetero-
correlations were recorded with a Bruker DRX600 instru-
ment with J in the range 0–10 Hz. ESI-MS spectra were
recorded with an LCQ-DECAThermo Finnigan instrument.
TLC was performed on precoated 4ꢀ6.7 silica gel 60 F254
plates silica gel on aluminium with detection by UV light.
Column chromatography was carried out on silica gel
(0.040–0.063). Irradiation was carried out in a Rayonet
apparatus operating at 365 nm.
3.2.2. 2-(2,4-Dimethyl-3-phenyl-2H-isoxazol-5-ylidene)-
cyclopentane-1,3-dione 1c. Yellow solid (525 mg, 65%
yield), Rf¼0.5, mp 227–230 ꢁC (ethanol); nmax (film)/
cmꢂ1: 1718s; dH (200 MHz, CDCl3) 7.65–7.36 (5H, m,
Ph), 3.95 (3H, s, N–CH3), 2.53 (4H, m, CH2CH2), 2.12
(3H, s, CH3); dC (50 MHz, CDCl3) 200.0, 170.5, 157.9,
132.1, 129.7, 128.7, 123.4, 110.8, 100.9, 38.1, 34.0, 9.1;
m/z: 270 (100%, MH+). Anal. Calcd for C16H15NO3: C,
71.36; H, 5.61; N, 5.20. Found: C, 71.02; H, 5.63; N, 5.17.
3.2.3. 2-(2,4-Dimethyl-3-phenyl-2H-isoxazol-5-ylidene)-
cyclohexane-1,3-dione 1d. Yellow solid (340 mg, 40%
yield), Rf¼0.5, mp 190–193 ꢁC (ethanol); nmax (film)/
cmꢂ1: 1721s; dH (200 MHz, CDCl3) 7.30–7.52 (5H, m,
Ph), 3.91 (3H, s, N–CH3), 2.21 (4H, t, CH2 and CH2),
1.61–1.82 (5H, m, CH2 and CH3); dC (50 MHz, CDCl3)
193.3, 175.4, 157.6, 132.1, 129.7, 128.9, 123.8, 113.5,
101.1, 38.0, 37.7, 20.6, 9.8; m/z: 284 (100%, MH+). Anal.
Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found:
C, 72.02; H, 6.07; N, 4.90.
3.2. General procedure for the preparation
of compounds 1a–g
To a stirred solution of the desired enolisable compound
(3 mmol) in anhydrous benzene (15 mL) were sequentially
added NaH 60% in oil (3 mmol) and dry Et3N (3 mmol).
To this suspension was then slowly added 5-chloro-2,4-di-
methyl-3-phenylisoxazol-2-ium trifluoromethanesulfonate
(3 mmol) and the resulting yellow solution stirred for 1 h.
After this time the reaction mixture was concentrated in va-
cuo and the residue treated with water (20 mL) and extracted
with CH2Cl2 (2ꢀ15 mL). The organic layer was dried over
Na2SO4, the solvent evaporated and the resulting oil purified
by column chromatography (eluent CH2Cl2/CH3OH 95:5) to
give compounds 1a–g. The spectral data of compounds
1a,f,g were reported in a previous communication.8
3.2.4. 5-(2,4-Dimethyl-3-phenyl-2H-isoxazol-5-ylidene)-
1,3-dimethyl-pyrimidine-2,4,6-trione 1e. Yellow solid
(688 mg, 70% yield), Rf¼0.3, mp 198–201 ꢁC (CH2Cl2);
nmax (film)/cmꢂ1: 1723s; dH (200 MHz, CDCl3) 7.23–7.64
(5H, m, Ph), 3.98 (3H, s, N–CH3), 3.30 (6H, s, N–CH3),
2.00 (3H, s, Me); dC (50 MHz, CDCl3) 173.9, 161.8,
157.9, 152.8, 132.3, 129.8, 128.8, 123.5, 112.9, 81.1, 38.0,
27.6, 10.0; m/z: 328 (100%, MH+). Anal. Calcd for

D. Donati et al. / Tetrahedron 63 (2007) 1583–1588
1587
C17H17N3O4: C, 62.38; H, 5.23; N, 12.84. Found: C, 62.13;
H, 5.24; N, 12.78.
14% yield), Rf¼0.6; nmax (film)/cmꢂ1: 1712s, 1652s,
1639s; dH (200 MHz, CD3CN) 7.48–7.30 (5H, m, Ph),
4.41 (2H, m, CH2CH3), 2.79 (3H, s, N–CH3), 2.29 (3H, s,
CH3), 1.40 (3H, t, J¼7, CH2CH3), 0.99 (3H, s, N–CH3);
dC (50 MHz, CDCl3) 192.8, 171.8, 168.7, 133.0, 131.4,
130.6, 128.5, 95.3, 84.5, 69.8, 50.0, 30.0, 24.9, 15.9, 13.9;
m/z: 302 (100%, MH+). Anal. Calcd for C17H19NO4: C,
67.76; H, 6.36; N, 4.65. Found: C, 67.68; H, 6.38; N, 4.63.
3.3. General procedure for the irradiation of 1a–g
A solution of 1a–g (1 mmol) in anhydrous CH3CN (40 mL)
˚
in the presence of activated molecular sieves (4 A, 100–
150 mg) was irradiated for 15 h in a Pyrex tube at 365 nm.
After this time the molecular sieves were decanted, washed
with further CH3CN (10 mL) and the solvent removed in
vacuo. The oil obtained was purified by column chromato-
graphy (eluent CH2Cl2/CH3OH 95:5) to give pure com-
pounds 7a–f. The spectral data of compound 7a were
reported in a previous communication.8
3.3.6. 2,4-Dimethyl-4-(methylimino-phenyl-methyl)-5-
oxo-4,5-dihydro-furan-3-carboxylic acid ethyl ester 8f.
Orange oil (183 mg, 61% yield), Rf¼0.4; nmax (film)/cmꢂ1
:
1736s; dH (200 MHz, CD3CN) 7.40–7.31 (5H, m, Ph), 4.16
(2H, q, J¼7, CH2CH3), 2.93 (3H, s, N–CH3), 2.12 (3H, s,
CH3), 1.55 (3H, s, CH3), 1.21 (3H, t, J¼7, CH2CH3); dC
(50 MHz, CDCl3) 176.5, 167.6, 163.1, 163.0, 132.0, 128.9,
128.7, 126.7, 114.4, 60.5, 58.0, 40.5, 19.9, 13.7, 13.1; m/z:
302 (100%, MH+). Anal. Calcd for C17H19NO4: C, 67.76;
H, 6.36; N, 4.65. Found: C, 67.55; H, 6.38; N, 4.68.
3.3.1. 3-Ethoxy-5,7-dimethyl-6-oxo-1-phenyl-2-oxa-
7-aza-bicyclo[3.2.0]hept-3-ene-4-carbonitrile 7b. Orange
oil (210 mg, 74% yield), Rf¼0.6; nmax (film)/cmꢂ1: 1648s,
1638s; dH (200 MHz, CDCl3) 7.51–7.38 (5H, m, Ph), 4.47
(2H, q, J¼7, OCH2CH3), 2.79 (3H, s, N–CH3), 1.37 (3H,
t, J¼7, OCH2CH3), 0.93 (3H, s, CH3); dC (50 MHz,
CDCl3) 171.4, 170.5, 131.9, 130.7, 128.4, 116.5, 102.6,
87.9, 70.5, 69.9, 25.5, 15.7, 13.7; m/z: 307 (100%, MNa+).
Anal. Calcd for C16H16N2O3: C, 67.59; H, 5.67; N, 9.85.
Found: C, 67.84; H, 5.64; N, 9.81.
3.3.7. 4-Acetyl-3,5-dimethyl-3-(methylimino-phenyl-
methyl)-3H-furan-2-one 8g. Orange oil (103 mg, 38%
yield), Rf¼0.4; nmax (film)/cmꢂ1: 1741s; dH (200 MHz,
CD3CN) 7.50–7.39 (5H, m, Ph), 3.00 (3H, s, N–CH3),
2.30 (2ꢀ3H, s, ]CCH3 and COCH3), 1.65 (3H, s, CH3);
dC (50 MHz, CDCl3) 192.5, 176.6, 166.1, 160.7, 131.7,
131.2, 129.3, 126.0, 123.1, 57.0, 41.8, 30.9, 21.1, 15.3;
m/z: 272 (100%, MH+). Anal. Calcd for C16H17NO3: C,
70.83; H, 6.32; N, 5.16. Found: C, 71.09; H, 6.29; N, 5.19.
3.3.2. 1,2a-Dimethyl-6a-phenyl-2a,4,5,6a-tetrahydro-
1H-6-oxa-1-aza-cyclobuta[a]pentalene-2,3-dione 7c.
Pale yellow solid (210 mg, 78% yield), Rf¼0.4, mp 180–
182 ꢁC (CH2Cl2); nmax (film)/cmꢂ1: 1710s, 1645s, 1634s;
dH (200 MHz, CDCl3) 7.40–7.22 (5H, m, Ph), 2.76 (3H, s,
N–CH3), 2.69–2.64 (4H, m, CH2CH2), 0.98 (3H, s, CH3);
dC (50 MHz, CDCl3) 195.4, 193.6, 168.6, 157.9, 130.3,
128.7, 126.0, 121.8, 112.8, 95.0, 69.2, 39.1, 24.1, 22.8,
11.0; m/z: 270 (100%, MH+). Anal. Calcd for C16H15NO3:
C, 71.36; H, 5.61; N, 5.20. Found: C, 71.03; H, 5.60; N, 5.23.
3.3.8. 4-Acetyl-2,5-dimethyl-2-(methylimino-phenyl-
methyl)-furan-3-one 9. Rf¼0.3; dH (200 MHz, CD3CN)
7.48 (3H, m, Ph), 6.97–6.92 (2H, m, Ph), 3.09 (3H, s, N–
CH3), 2.39 (3H, s, COCH3), 2.37 (3H, s, CH3), 1.70 (3H, s,
CH3); dC (50 MHz, CD3CN) 199.1, 196.0, 192.5, 164.1,
135.5, 133.1, 132.9, 129.0, 115.6, 94.1, 41.6, 30.3, 18.3, 15.0.
3.3.3. 1,2a-Dimethyl-7a-phenyl-1,2a,4,5,6,7a-hexahydro-
7-oxa-1-aza-cyclobuta[a]indene-2,3-dione 7d. Yellow
solid (220 mg, 78% yield), Rf¼0.4, mp 190–194 ꢁC; nmax
(film)/cmꢂ1: 1710s, 1643s, 1634s; dH (200 MHz, CDCl3)
7.22–7.38 (m, 5H, Ph), 2.72 (3H, s, N–CH3), 2.50–2.62
(2H, m, CH2), 2.35 (2H, m, CH2), 2.05 (2H, m, CH2), 1.04
(3H, s, CH3); dC (50 MHz, CDCl3) 194.3, 176.7, 170.1,
131.2, 126.5, 128.9, 129.6, 115.6, 103.2, 70.4, 37.1, 24.4,
24.2, 21.3, 11.9; m/z: 284 (100%, MH+). Anal. Calcd for
C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C, 72.01;
H, 6.04; N, 4.98.
Acknowledgements
We like to acknowledge the RCSI Research Committee and
PTRLI cycle III for a grant to M.F.A.A.
References and notes
1. Alcaide, B.; Almendros, P. Curr. Org. Chem. 2002, 6, 245.
2. Kotra, L. P.; Mobashery, S. Bull. Inst. Pasteur 1998, 96, 136.
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Sum, F.-W.; Li, Z.; Francisco, G.; Lin, Y.-I.; Petersen, P. J.;
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T. M.; Hart, G. J.; Jackson, D. L.; Parry, N. R.; Patikis, A.;
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3.3.4. 1,2a,4,6-Tetramethyl-7a-phenyl-1,2a,6,7a-tetrahy-
dro-7-oxa-1,4,6-triaza-cyclobuta[a]indene-2,3,5-trione
7e. Yellow solid (242 mg, 74% yield), Rf¼0.2, mp 203–
206 ꢁC; nmax (film)/cmꢂ1: 1701s, 1647s, 1631s; dH
(200 MHz, CDCl3) 7.23–7.64 (m, 5H, Ph), 3.42 (3H, s,
N–CH3), 3.24 (3H, s, N–CH3), 2.84 (3H, s, N–CH3), 1.20
(3H, s, CH3); dC (50 MHz, CDCl3) 170.7, 163.1, 161.2,
152.8, 132.2, 131.7, 130.7, 128.5, 106.6, 89.9, 71.7, 30.6,
28.7, 25.5, 13.1; m/z: 328 (100%, MH+). Anal. Calcd for
C17H17N3O4: C, 62.38; H, 5.23; N, 12.84. Found: C,
62.50; H, 5.21; N, 12.89.
3.3.5. 4-Acetyl-3-ethoxy-5,7-dimethyl-1-phenyl-2-oxa-7-
aza-bicyclo[3.2.0]hept-3-en-6-one 7f. Orange oil (42 mg,
8. Donati, D.; Fusi, S.; Ponticelli, F. Tetrahedron Lett. 2003, 44,
9247.

1588
D. Donati et al. / Tetrahedron 63 (2007) 1583–1588
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19. An alternative mechanism could be envisaged that involves
the heterolytic ring opening of the cyclopropanone to form
oxyallyl cations. Efforts to trap oxyallyl cations using furan
as the solvent were unsuccessful.
11. Turro, N. J.; Cole, T. Tetrahedron Lett. 1969, 10, 3451; Hart,
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12. Crystal data of compounds 7c [CCDC 278145] and 7e [CCDC
613424] were deposited and are available at deposit@ccdc.
cam.ac.uk.
13. Calter, M. A.; Sugathapala, P. M. Tetrahedron Lett. 1998, 39,
8813; Kawaguchi, T.; Yasuta, S.; Inoue, Y. Synthesis 1996,
1431.