Functionalized imides by regioselective ozonation

Article abstract of DOI:10.1002/hlca.200690101

Ozonations of alkoxy- and (acyloxy)-substituted alkylidene-lactams 1 and 5 or of the alkylidene-sultams 9 and 10 proceeded by regioselective cleavage of the exocyclic C=C bonds (Schemes 1 and 2). These bonds are part of an enamide system and, therefore, p

Full text of DOI:10.1002/hlca.200690101

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Functionalized Imides by Regioselective Ozonation
by Hermann Poschenriedera), Hans-Dietrich Stachel*a), Eduard Eckla), Sabine Jaxa), Kurt Polbornb),
and Peter Mayerb)
a) Departement Pharmazie/Zentrum für Pharmaforschung, Universität München, Butenandtstr. 7,
D-81377 München (fax: +49-89-2180-77991; e-mail: hdsta@cup.uni-muenchen.de)
b) Departement Chemie und Biochemie, Universität München, Butenandtstr. 9, D-81377 München
Ozonations of alkoxy- and (acyloxy)-substituted alkylidene-lactams 1 and 5 or of the alkylidene-sul-
tams 9 and 10 proceeded by regioselective cleavage of the exocyclic C=C bonds (Schemes 1 and 2). These
bonds are part of an enamide system and, therefore, possess considerable polarity as shown by 13C-NMR
spectra. As a result, the partly known maleimides 3 and 6 or the ꢀsulfonimidesꢁ 11 were obtained. Com-
pounds 3 and 11 reacted with diazomethane to give the highly reactive bicyclic derivatives 8 and 12,
respectively. The cinnamylidene-lactames 16a,b were converted by selective ozonolysis mainly into the
formylmethylene lactames 17a,b (Scheme 3). The amino-substituted aldehyde 20 bears a structural rela-
tionship to the lactone antibiotic basidalin 21a. The tendency of some donor-substituted maleimides to
undergo [2+2] cycloadditions was assessed (Scheme 4). The configuration of the photodimers 22a,b
and 24a,b was established by X-ray crystallography.
Introduction. – The cleavage of alkene C=C bonds by ozone to give aldehydes,
ketones, and carboxylic acids was introduced into organic chemistry at the beginning
of the 20th century by Harries [1]. Ozonolyses take place under extremely mild reaction
conditions and often with excellent yields. The individual course of an ozonization,
however, is strongly dependent on the constitution of the starting material, the solvent,
and the choice of reductive or oxidative workup conditions (for a comprehensive
review, see [2]).
A basic three-step mechanism was formulated by Criegee and is now bearing his
name [3]. In a sequence of concerted 1,3-dipolar cycloaddition and cycloreversion, ꢀcar-
bonyl oxidesꢁ [4] are formed which are captured by internally generated carbonyl com-
pounds in another 1,3-dipolar cycloaddition to yield ozonides. As a result, for unsym-
metrical alkenes, substituent rules for the regioselective OꢀO splitting in the cyclore-
version step have been formulated [5][6]. There are, however, exceptions from these
rules, and the ozonide-forming step may be bypassed due to low dipolarophilicity of
the carbonyl intermediate. Both is examplified in the ozonolysis of ketene acetals
[7]. Modifications of the original Criegee mechanism have been introduced later [8].
An alternative mechanistic concept of ozonations was recently brought up for discus-
sion [9]. According to the ꢀdonor-acceptor conceptꢁ, ozonations are regarded as oxida-
tion reactions with radical-ion intermediates.
It is well known that the C=C bond of enol ethers is readily cleaved by ozone form-
ing a carbonyl compound and a carboxylic acid ester [10–14]. Analogously, in the ozo-
nolysis of enol esters, beside a carbonyl compound, a mixed carboxylic acid anhydride is
ꢂ 2006 Verlag Helvetica Chimica Acta AG, Zürich

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formed [7][15]. The C=C bonds of enamines can be more resistant towards ozone than
those of structurally related enol ethers [15]. We made deviating observations in the
course of ozonations of the lactams 1 bearing an enol ether moiety, and the lactams
2 with an enamine partial structure. These ozonolyses were carried out for synthetic
purposes.
Results and Discussion. – Ozonation of the lactams 1 in nonparticipating solvents
furnished the maleimides 3a–c (Scheme 1). Maleimides 3a and 3b have been synthe-
sized previously on another route [16]. The lactams 1a–c contain conjugated exocyclic
and endocyclic C=C bonds. Only the former ones were attacked by ozone.
Scheme 1
Regarding the p-system of lactams 1–3 comprising the heterocycle and the exocy-
clic C=C bond, one is tempted to depict zwitterionic pyrrole resonance structures with
positive charges at the respective HC=C(5) (in short C(a)) atoms. This view, however,
is ruled out by the 13C-NMR spectra of these compounds. For instance, the signal of
C(a) of 1a was found at d 109.0. This highfield shift, indicating an increased electron
density at C(a), was present in the 13C-NMR spectra of all lactams used here. Hence,
most of all, the enamide substructures of the lactams determine their reactivity.
Because of the pyrrolidin-1-yl substituent, the lactam ring in compounds 2 is more
electron-rich than in the lactams 1. Ozonation of compounds 2 afforded no crystalline
products so that apparently both C=C bonds were cleaved by ozone. In contrast to that,
ozonation of the vinylogous esters 5a and 5b caused selective cleavage of the exocyclic

Helvetica Chimica Acta – Vol. 89 (2006)
973
C=C bond to yield the maleimides 6a,b. Both compounds reacted with diazomethane
to give the N-methylated derivatives 7a,b as already described for 7a a long time ago
[17]. With the vinylogous anhydrides 5c,d, again regioselective ozonolysis was
observed. Only the exocyclic C=C bond was cleaved to furnish the maleimides 6c,d.
The donor–acceptor-substituted maleimides 3 are starting materials for the synthe-
sis of different bicyclic compounds. Compound 3a reacted with dimethyl 3-oxopentane-
dioate in the presence of MeONa or NaH to give the red anion of the bicyclic lactam 4a
by successive ester condensation and Michael addition. When treated with diazome-
thane in excess, the enol ethers 3a–c were converted into the bicyclic imides 8a–c
by N-methylation and subsequent cyclopropanation. The imides 8a,b and their use
for the synthesis of functionalized pyridinones by ring expansion have recently been
described by us [16]. In this context we were interested to synthesize ꢀsulfonimidesꢁ
as heteroanalogs of the imides 3a and 8a.
As starting material served the sultams 9a,b (Scheme 2). Compound 9a has been
synthesized earlier [18]. N-Methylation of 9a to 9b was accomplished by diazomethane
in excess or by heating of 9a with tetramethyl orthocarbonate. Because of the structural
similarity of the alkylidene-sultams 9a,b and the alkylidene-lactam 1a, we were not sur-
prised that selective ozonolysis of 9a,b took place furnishing the ꢀsulfonimidesꢁ 11a,b.
The same compounds were obtained by ozonation of the sultams 10a,b [19] (Scheme 2).
Scheme 2
The analogous behavior of both types of sultams in this reaction is notable in the
light of the highly different polarity of the exocyclic C=C bond in the benzylidene-sul-
tams 9a,b on the one hand, and in the differently substituted alkylidene-sultams 10a,b
on the other hand. The 13C-NMR signal of C(a) in compound 9b was found at d 115.2,
i.e., a value fairly in line with the corresponding signal of lactam 1a, whereas the signal
1
of C(a) of sultam 10b was shifted further highfield to d 91.0. Concomitantly the H-

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Helvetica Chimica Acta – Vol. 89 (2006)
NMR signal of the olefinic H-atom of 10b appeared at d 5.55 [19]. This signal disap-
peared upon addition of D2O. This H/D exchange is apparently due to the high polarity
AHCTREUNG
of the ene-sulfamide partial structure. Treatment of both new imides 11a,b with diazo-
methane in excess produced the highly reactive bicyclic sultam 12.
The above described regioselective ozonolyses of readily available tetramates and
of heterologous sultams enriches the known methods for the production of functional-
ized maleimides by amination of maleic anhydrides [20] [21] or by ester condensation
[18][22]. ꢀSulfonimidesꢁ likewise have been prepared by ester condensation [18] even
though they were usually synthesized by S-oxidation of isothiazol-3(2H)-ones [23].
Regioselective ozonolysis was also observed with the easily accessible a,g-bis(alkyl-
idene)lactams 13a–c. We obtained the succinimides 14a–c in yields of 60–75%
(Scheme 2). Similarly the [(dimethylamino)methylene]lactam 13d was converted into
imide 14d. Apparently, we have at hand a useful method for the preparation of variably
substituted alkylidenepyrrolidine-2,3,5-triones. Such substances are interesting because
they can be converted into persubstituted pyridinones in a few steps, as already shown
by the conversion of the benzylidene compound 14a into the pyridine derivative 15
[24]. In addition, compounds of type 14 have been used for the preparation of different
types of heterocycles by cycloaddition or cyclocondensation reactions [25].
In all the ozonations mentioned above, a reductive or oxidative workup was unnec-
essary. The second product of the cleavage of all benzylidenelactams was benzoic acid
which originated either from oxidation of the firstly formed benzaldehyde by peroxidic
intermediates or was the result of an ꢀozonide-free reactionꢁ.
Finally, we were interested to find out how the cinnamylidenelactams 16 [26] and
ozone might interact. It turned out that in both 16a and 16b, selectively the terminal
C=C bond of the side chain was cleaved (Scheme 3). Beside benzoic acid, we obtained
the aldehydes 17a or 17b, respectively, as the main products. The (Z)-configuration of
the new compounds was assigned by the NOE data. Presumably, this configuration is
stabilized by H-bonding interactions.
If the ozonolysis of 16a was conducted in the presence of MeOH, beside aldehyde
17a, surprisingly ester 18 was isolated, although the amount was very small. Compound
18 was synthesized on an independent route [18] so that the structure of this by-product
is beyond any doubt. The (relative) ozone-resistance of the alkylidenelactam 18 con-
trasts with the ozone-sensibility of the identically substituted sultam 10a. In addition,
the ozone-resistance of compounds 17/18 in contrast to the reactivity of 1a is remark-
able. The structural similarity of both types of alkylidenelactams is reflected in the sim-
ilarity of their 13C-NMR spectra.
The aldehydes 17a,b have shown substantial antimycobacterial activity [27]. This
makes it worthwhile to emphasize the structural similarity of these compounds to the
lactone antibiotic basidalin (21a) [28]. Efforts to synthesize this compound yielded
only the stereoisomeric (E)-basidalin [29]. On the other hand, the thio analog of basi-
dalin, 21b, has been prepared and found to be cytotoxic [30]. The aldehydes 17a/b may
be useful for the preparation of ꢀazabasidalinꢁ and derivatives. An entry to this goal
offers compound 20 which was obtained from aldehyde 17a and ammonia (Scheme 3).
The configuration of the aldehydes 17 may be altered by substituents in the side
chain. Bromination of 17b led to disubstitution in two separate steps (Scheme 3). At
first, the side-chain-brominated aldehyde 19b was obtained. The (Z)-configuration

Helvetica Chimica Acta – Vol. 89 (2006)
975
Scheme 3
was established by NOE experiments. Further bromination of 19b furnished aldehyde
19c. These aldehydes or suitable derivatives may allow ring-closure reactions.
Handling the donor-substituted maleimides 6a,b and especially 7a,b, we observed
that these substances undergo changes upon influence of light. From solutions of
7a,b, we obtained the uniform photodimers 22a,b after standing for 2–3 weeks in day-
light or after a short-time exposure to UV light (Scheme 4). Single-crystal X-ray anal-
yses revealed that in both cases, head-to-head additions had taken place forming the
cyclobutanes 22a1) and 22b1) with the alkoxy substituents arranged in trans position.
The light-induced cycloaddition of a few maleic anhydrides and maleimides has
been described [31]. However, usually the presence of a radiation sensitizer was
required. Sensitizers are needed also in the photodimerization of vinyl ethers
[32][33]. So the ease of the photoreaction of the donor-substituted maleimides 7a,b
is indeed surprising. Therefore, we have looked at the behavior toward light of similar
maleimides at hand. No tendency toward dimerization in light was observed on irradi-
ation of the donor–acceptor-substituted maleimides 3 or the (acyloxy)-substituted
maleimides 6c,d. The opposite was true for maleimides 23a,b [34] with two donor sub-
G
stituents. Imide 23a in solution was converted by UV light mainly into the photodimer
24a. As established by X-ray crystallography1) all four benzyloxy groups of 24a are in
cis position to each other. However, if imide 23a was exposed to light in the presence of
traces of benzophenone as radiation sensitizer, the isomeric dimer 22c was obtained.
Irradiation of a solution of the differently substituted imide 23b without a sensitizer
1
)
CCDC-291584 (22a), CCDC-291585 (22b), CCDC-291541 (24a), and CCDC-291586 (24b) contain
the supplementary crystallographic data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 4
led to the cyclobutane 24b as head-to-tail cyclodimerization product with all MeO and
t-BuO substituents arranged in cis position1). Catalytic debenzylation of compound 24a
yielded the all-cis tetrahydroxy derivative 24c.
Experimental Part
General. Ozone was generated by the Ozongenerator Fischer 5028, capacity: 4.3 g ozone/h at an O2
flow rate of 60 l/h. Photochemical reactions were run in a reactor equipped with a high-pressure mercury
vapor immersion lamp (HPK 125, Philips), 125 W. CC: Flash column 250 ml (Baker); silica gel
0.040–0.063 mm (Merck). M.p.: Büchi-B-540 apparatus; uncorrected. UV Spectra: MeOH soln. if not
stated otherwise; Perkin-Elmer-Lambda-20 or Jasco-V-530 spectrometer; lmax(log e) in nm. IR Spectra:
G
KBr plates; Paragon-1000 a FT-IR spectrometer; n in cmꢀ1. NMR Spectra: Jeol-Elipse-400 or Jeol-Elipse-
500 FT spectrometer; in (D6)DMSO if not indicated otherwise; d in ppm rel. to SiMe4 as internal stan-
dard, J in Hz. MS: Hewlett-Packard-5989A (EI (70 eV) and CI), Jeol-JMS-GCMATE-II (HR), and Sciex-
API-2000 (ESI) spectrometer; in m/z. Microanalyses: CHN Analyzer Elementar Vario EL.
~
Ozonation: General Procedure (G.P.). A stream of O3 (60 l/h) was passed through a soln. of the
respective substance (2–5 mmol) in 100 ml of CH2Cl2 (G.P. A) or in CH2Cl2/MeOH 1:1 (G.P. B) at
ꢀ158 for 4 min (ca. 6 mmol O3). The solvent was partly evaporated at a temp. not exceeding 108 (caution:
potential decomposition of highly explosive by-products). The residue (5–10 ml) was diluted with an
equal volume of Et2O or AcOEt and kept in the refrigerator for crystallization.
G
5-Benzylidene-2,5-dihydro-4-methoxy-2-oxo-1H-pyrrole-3-carboxylic Acid Methyl Ester (1a) [26].
1H-NMR: 10.19 (s, 1 H); 7.61–7.32 (m, 5 H); 6.41 (s, 1 H); 4.08 (s, MeO); 3.76 (s, COOMe). 13C-
NMR: 167.8 (C(4)); 164.6, 163.1 (C=O); 133.5–128.3 (C(5), arom. C); 109.0 (CH=); 100.1 (C(3));
61.0 (MeO); 52.1 (COOMe).
3-Benzoyl-5-benzylidene-1,5-dihydro-4-methoxy-2H-pyrrol-2-one (1c). An Et2O soln. of diazome-
G
thane (excess) was added to a suspension of 3-benzoyl-5-benzylidene-1,5-dihydro-4-hydroxy-2H-pyr-
rol-2-one [35] (0.58 g, 2 mmol) in MeOH (5 ml). After the evolution of N2 had ceased, the soln. was
evaporated and the residue crystallized from MeOH: 0.45 g (74%) of 1c. Light yellow crystals. M.p.

Helvetica Chimica Acta – Vol. 89 (2006)
977
1978. UV: 337 (4.392). IR: 3218, 1675, 1642, 1577. 1H-NMR (CDCl3): 8.62 (s, 1 H); 8.05–7.90 (m, 2 H);
7.65–7.15 (m, 8 H); 6.50 (s, 1 H); 3.95 (s, 3 H). Anal. calc. for C19H15NO3 (305.33): C 74.74, H 4.95, N 4.58;
found: C 74.62, H 4.87, N 4.49.
5-Benzylidene-2,5-dihydro-2-oxo-4-(pyrrolidin-1-yl)-1H-pyrrole-3-carboxylic Acid Methyl Ester
(2a). Pyrrolidine (0.5 ml) was added to a soln. of 1a [26] (0.26 g, 1 mmol) in MeOH (30 ml). Shortly there-
after, yellowish crystals started to separate: 0.24 g (80%) of 2a. M.p. 1498 (MeOH). UV: 326 (4.347). IR:
3201, 1659, 1622, 1551. 1H-NMR: 9.21 (br., 1 H); 7.55–7.28 (m, 5 H); 6.56 (s, 1 H); 3.66 (s, 3 H); 3.59 (m, 4
H); 1.94 (m, 4 H). 13C-NMR: 168.7 (C(4)); 164.6, 154.7 (C=O); 134.7–127.5 (C(5), arom. C); 112.1 (CH=);
93.6 (C(3)); 53.7 (CH2N); 51.1 (MeO); 25.3 (CH2). Anal. calc. for C19H15NO3 (298.34): C 68.44, H 6.08, N
9.39; found: C 68.34, H 6.27, N 9.24.
5-Benzylidene-1,5-dihydro-4-(pyrrolidin-1-yl)-2H-pyrrol-2-one (2d). Under stirring, compound 2a
(0.90 g, 3 mmol) was heated with freshly prepared t-BuOK (2.8 g, 25 mmol) in DMSO (15 ml) to 808
for 1 h. The precipitate was filtered off and then dissolved in H2O, the soln. acidified with 2N HCl, and
i
the crude product collected and recrystallized from Pr2O/MeOH: 0.57 g (80%) of 2d. Yellow crystals.
1
M.p. 1868. UV: 226 (4.220), 317 (4.355), 375 (br.). IR: 3250, 2960, 2860, 1655, 1535. H-NMR: 8.87 (s, 1
H); 7.58–7.25 (m, 5 H); 6.31 (s, 1 H); 4.64 (s, 1 H); 3.46 (m, 4 H); 1.97 (m, 4 H). 13C-NMR: 172.4
(C(4)); 156.0 (C=O); 134.9–127.0 (C(5), arom. C); 108.6 (CH=); 88.4 (C(3)); 50.8 (CH2N); 25.1
(CH2). Anal. calc. for C15H16N2O (240.31): C 74.97, H 6.71, N 11.66; found: C 75.08, H 6.50, N 11.38.
2,5-Dihydro-4-methoxy-2,5-dioxo-1H-pyrrole-3-carboxylic Acid Methyl Ester (3a). According to the
G.P. A, from 1a [26] (1.0 g, 3.8 mmol). Crystallization started after addition of AcOEt: 0.37 g (52%) of
3a. M.p. 1558 (AcOEt) ([16]: 1558). 1H-NMR: 11.07 (s, 1 H); 4.19 (s, 3 H); 3.74 (s, 3 H). 13C-NMR:
167.9 (C(4)); 165.5, 161.3, 159.9 (C=O); 103.0 (C(3)); 61.6 (MeO); 52.5 (COOMe). MS: 185 (M+).
Anal. calc. for C7H7NO3 (185.14): C 45.41, H 3.81, N 7.57; found: C 45.27, H 3.80, N 7.47.
2,5-Dihydro-4-methoxy-2,5-dioxo-1H-pyrrole-3-carbonitrile (3b). According to the G.P. A, from 1b
[16] (1.0 g, 4.4 mmol): 0.36 g (60%) of 3b. M.p. 189–1908 ([22]: 1908).
3-Benzoyl-4-methoxy-1H-pyrrole-2,5-dione (3c). According to G.P. A, from 1c (0.90 g, 3 mmol).
Crystallization started after addition of Et
2O: 0.30 g (43%) of 3c. M.p. 1488 (iPr2O/EtOH). UV: 247
A
1
(3.679), 308 (3.481). IR: 3227, 1788, 1740, 1655. H-NMR (CDCl3): 10.56 (s, 1 H); 7.95–7.87 (m, 2 H);
7.72–7.50 (m, 3 H); 4.01 (s, 3 H). Anal. calc. for C12H9NO4 (231.21): C 62.34, H 3.92, N 6.06; found: C
62.24, H 3.92, N 5.93.
1,2,4,5-Tetrahydro-2,5-dioxocyclopenta[b]pyrrole-3,4,6-tricarboxylic Acid Trimethyl Ester (4a). NaH
(0.80 g, 60%, 20 mmol) was added to a stirred soln. of 3-oxopentanedioic acid dimethyl ester (1.74 g, 10
mmol) in THF (50 ml). After the evolution of H2 had ceased, 3a (1.81 g, 10 mmol) was added in portions.
The red suspension obtained within 30 min was evaporated. The aq. soln. of the residue (75 ml) was acidi-
fied with 2N HCl (10 ml) and extracted twice with CH2Cl2 (75 ml). The org. phase was dried (Na2SO4) and
evaporated and the oily residue dissolved in Et2
erator: 0.66 g (22%) of 4a. Beige crystals. M.p. 2208 (dec.). UV: 223 (4.195), 279 (4.388), 325 (4.158).
IR: 3220, 2970, 2925, 1750, 1730, 1670, 1640. 1H-NMR: 11.96 (s, exchange with D2
O, 1 H); 4.56 (s,
exchange with D
2O, 1 H); 3.94 (s, 6 H); 3.81 (s, 3 H). MS: 309 (M+). Anal. calc. for C13H11NO8
(309.23): C 50.49, H 3.59, N 4.53; found: C 50.56, H 3.71, N 4.70.
O (20 ml) and set aside for crystallization in the refrig-
AHCTREUNG
AHCTREUNG
5-Benzylidene-1,5-dihydro-4-methoxy-2H-pyrrol-2-one (5a) [26]. 1H-NMR: 9.73 (br., 1 H);
7.55–7.23 (m, 5 H); 6.16 (s, 1 H); 5.33 (d, J=1.5, 1 H); 3.89 (s, 3 H). 13C-NMR: 171.7 (C(4)); 167.1
(C=O); 133.8–127.5 (C(5), arom. C); 105.5 (CH=); 92.5 (C(3)); 58.4 (MeO).
5-Benzylidene-4-(benzyloxy)-1,5-dihydro-2H-pyrrol-2-one (5b). A soln. of 5-benzylidene-1,5-dihy-
dro-4-hydroxy-2H-pyrrol-2-one [26] (1.87 g, 10 mmol) in toluene (50 ml) and benzyl alcohol (10 ml)
were refluxed in the presence of TsOH (0.34 g, 2 mmol). After 3 h, the mixture was evaporated and
the residue recrystallized from AcOEt: 1.50 g (54%) of 5b. Light yellow crystals. M.p. 1568. UV: 321
1
(4.416). IR: 3206, 1694, 1587. H-NMR (CDCl3): 7.65 (s, 1 H); 7.43–7.23 (m, 10 H); 6.37 (s, 1 H); 5.26
(d, J=1, 1 H); 5.09 (s, 2 H). Anal. calc. for C18H15NO2 (277.33): C 77.96, H 5.45, N 5.05; found: C
77.73, H 5.53, N 5.18.
5-Benzylidene-1,5-dihydro-4-{[(4-methylphenyl)sulfonyl]oxy}-2H-pyrrol-2-one (5c). The 5-benzyl-
ACHTREUNG

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Helvetica Chimica Acta – Vol. 89 (2006)
TsCl (2.1 g, 11 mmol) was added in portions. After a short time, the product started to crystallize: 2.90 g
(85%) of 5c. Yellowish crystals. M.p. 1478. UV: 228 (4.352), 338 (4.405). IR: 3200, 1705, 1651, 1594. 1H-
NMR (CDCl3): 8.05 (s, 1 H); 7.90–7.86 (m, 2 H); 7.42–7.30 (m, 7 H); 6.21 (s, 1 H); 5.86 (d, J=2, 1 H);
2.45 (s, 3 H). Anal. calc. for C18H15NO4S (341.39): C 63.33, H 4.43, N 4.10; found: C 63.74, H 4.58, N 4.00.
4-(Benzoyloxy)-5-benzylidene-1,5-dihydro-2H-pyrrol-2-one (5d) [36]. 1H-NMR: 10.26 (s, 1 H); 8.26
(d, J=8, 2 H); 7.81 (s, 1 H); 7.70–7.64 (m, 5 H); 7.42–7.33 (m, 3 H); 6.53 (s, 1 H); 6.23 (s, 1 H). 13C-NMR:
170.6, 161.9 (C=O); 155.6 (C(4)); 134.9–127.7 (C(5), arom. C); 108.1 (CH=); 105.6 (C(3)).
3-Methoxy-1H-pyrrole-2,5-dione (6a). According to the G.P. A, from 5a [26] (1.0 g, 5 mmol): 0.28 g
(50%) of 6a. M.p. 1688 ([17a]: 1698). 1H-NMR: 5.73 (d, J=1.5, 1 H); 3.87 (s, 3 H). 13C-NMR: 171.3 (C(4));
166.7, 160.9 (C=O); 97.7 (C(3)); 59.1 (MeO).
3-(Benzyloxy)-1H-pyrrole-2,5-dione (6b). According to the G.P. A, from 5b (1.0 g, 3.6 mmol): 0.30 g
(41%) of 6b. Colorless crystals. M.p. 1608 (MeOH). UV: 226 (4.227). IR: 3107, 1764, 1742, 1702, 1635. 1H-
NMR (CDCl3): 7.45–7.35 (m, 5 H); 5.44 (d, J=1.5, 1 H); 5.10 (s, 2 H). Anal. calc. for C11H9NO3 (203.20):
C 65.02, H 4.46, N 6.89; found: C 65.22, H 4.57, N 6.98.
3-{[(4-Methylphenyl)sulfonyl]oxy}-1H-pyrrol-2,5-dione (6c). According to the G.P. B, from 5c (1.0 g,
3 mmol): 0.40 g (50%) of 6c. Colorless crystals. M.p. 1608 (MeOH). UV: 224 (4.391). IR: 3210, 1803, 1729,
1627. 1H-NMR: 11.14 (br., 1 H); 8.02/7.56 (d, J=8, 4 H); 6.45 (d, J=2, 1 H); 2.45 (s, 3 H). Anal. calc. for
C11H9NO5S (267.26 ): C 49.44, H 3.39, N 5.24; found: C 49.21, H 3.71, N 5.13.
4-(Benzoyloxy)-1H-pyrrol-2,5-dione (6d). According to the G.P. B, from 5d [36] (1.0 g, 3 mmol): 0.40
g (52%) of 6d. Colorless crystals. M.p. 1948 (MeOH). UV: 232 (4.347). IR: 3201, 1786, 1756, 1718, 1619.
1H-NMR: 11.10 (br., 1 H); 8.18 (m, 2 H); 7.82–7.62 (m, 3 H); 6.66 (d, J=2, 1 H). 13C-NMR: 170.5, 166.5,
161.8 (C=O); 149.8 (C(4)); 134.9–127.1 (arom. C); 111.9 (C(3)). Anal. calc. for C11H7NO4 (217.18): C
60.83, H 3.25, N 6.45; found: C 60.96, H 3.31, N 6.41.
3-Methoxy-1-methyl-1H-pyrrole-2,5-dione (7a). An Et2O soln. of diazomethane (excess) was added
G
to a soln. of 6a (0.13 g, 1 mmol) in MeOH (5 ml). After 4 h, the mixture was evaporated and the residue
crystallized from MeOH: 0.11 g (80%) of 7a. M.p. 1308 ([17b]: M.p. 129–1308).
3-(Benzyloxy)-1-methyl-1H-pyrrole-2,5-dione (7b). As described for 7a, from 6b (0.20 g, 1 mmol)
and diazomethane: 0.40 mg (60%) of 7b. Colorless crystals. M.p. 1218 (MeOH). UV: 230 (4.238). IR:
1
3110, 1712, 1629. H-NMR (CDCl3): 7.39 (m, 5 H); 5.41 (s, 1 H); 5.11 (s, 2 H); 2.99 (s, 3 H). Anal. calc.
for C12H11NO3 (217.22): C 66.35, H 5.10, N 6.45; found: C 66.05, H 5.21, N 6.65.
1-Benzoyl-5-methoxy-3-methyl-3-azabicyclo[3.1.0]hexane-2,4-dione (8c). An Et2
A
thane (excess) was added to a soln. of 3c (70 mg, 0.3 mmol) in MeOH (5 ml). After the evolution of N2
had ceased, the soln. was evaporated and the residue recrystallized from Et2O: 25 mg (32%) of 8c. Color-
U
less crystals. M.p. 1108. UV: 206 (4.247), 250 (4.046). IR: 2926, 1782, 1709, 1677, 1597. 1H-NMR (CDCl3):
7.85–7.75 (m, 2 H); 7.65–7.55 (m, 1 H); 7.53–7.43 (m, 2 H); 3.63 (s, 3 H); 3.02 (s, 3 H); 2.85 (d, J=5.5,
1 H); 2.85 (d, J=5.5, 1 H); 2.00 (d, J=5.5 Hz, 1 H). HR-MS. 259.0856 (C
3-Benzylidene-2,3-dihydro-4-methoxy-2-methylisothiazole-5-carboxylic Acid Methyl Ester 1,1-Diox-
ide (9b). An Et2O soln. of diazomethane (excess) was added at 08 to a stirred suspension of 9a [18] (0.59 g,
2 mmol) in Et2O (10 ml). As soon as a clear soln. was obtained, the mixture was evaporated: 9b (nearly
A
G
AHCTREUNG
AHCTREUNG
quant.). A mixture of 9a [18] (0.59 g, 2 mmol) and tetramethyl orthocarbonate (10 ml) was refluxed for 15
min. Then the mixture was evaporated and the residue crystallized: 0.41 g (80%) of 9b. Yellow crystals.
M.p. 1328 (MeOH). UV: 236 (4.918), 331 (4.218). IR: 3030, 1710, 1590, 1344, 1179. 1H-NMR: 7.57–7.35
(m, 5 H); 6.90 (s, 1 H); 4.25 (s, MeO); 3.87 (s, COOMe); 2.78 (s, MeN). 13C-NMR: 163.2 (C(4)); 158.8
(C=O); 132.4–128.6 (C(5), arom. C); 115.2 (CH=); 106.7 (C(3)); 63.9 (MeO); 52.8 (COOMe); 34.1
(MeN). MS: 309 (M+). Anal. calc. for C14H15NO5 (309.30): C 54.39, H 4.85, N 4.50, S 10.37; found: C
54.45, H 4.88, N 4.45, S 10.17.
2,3-Dihydro-4-methoxy-3-(2-methoxy-2-oxoethylidene)-2-methylisothiazole-5-carboxylic Acid Meth-
yl Ester 1,1-Dioxide (10b) [19]. 13C-NMR: 165.5, 158.6, 158.1 (C(4), C=O); 139.2 (C(5)); 108.7 (C(3));
91.0 (CH=); 64.0 (MeO); 53.1, 51.4 (COOMe); 32.4 (MeN).
2,3-Dihydro-4-methoxy-3-oxoisothiazole-5-carboxylic Acid Methyl Ester 1,1-Dioxide (11a). Accord-
ing to the G.P. A, from 9a [18] (0.59 g, 2 mmol) or 10a [19] (0.56 g, (2 mmol): 0.25 g (57%) or 0.33 g (75%)

Helvetica Chimica Acta – Vol. 89 (2006)
979
of 11a, resp. Colorless crystals. M.p. 1828 (Et2O). UV: 208 (3.943), 243 (4.340). IR: 3121, 1750, 1703, 1626.
G
1H-NMR ((D6)DMSO/CDCl3): 9.27 (s, 1 H); 4.45 (s, 3 H); 3.95 (s, 3 H). Anal. calc. for C6H7NO6S
(221.18): C 32.58, H 3.19, N 6.33: found: C 32.63, H 3.28, N 6.29.
2,3-Dihydro-4-methoxy-2-methyl-3-oxoisothiazole-5-carboxylic Acid Methyl Ester 1,1-Dioxide (11b).
According to the G.P. A, from 9b (0.62 g, 2 mmol) or 10b [19] (0.58 g, 2 mmol): 0.36 g (76%) of 11b. Col-
orless crystals. M.p. 1208 (Et
2O). UV: 236 (4.376), 285 (4.196). IR: 2970, 1748, 1704, 1614. 1H-NMR: 4.39
E
(s, 3 H); 3.85 (s, 3 H); 3.04 (s, 3 H). 13C-NMR: 165.1, 160.9, 157.5 (C(4), C=O); 111.3 (C(3)); 63.2 (MeO);
52.9 (COOMe); 23.3 (MeN). Anal. calc. for C7H9NO6S (235.21): C 35.75, H 3.86, N 5.96; found: C 35.77,
H 3.96, N 5.93.
5-Methoxy-3-methyl-4-oxo-2-thia-3-azabicyclo[3.1.0]hexane-1-carboxylic Acid Methyl Ester 2,2-
Dioxide ( 12). As described for 8c, from 11a (0.22 g, 1 mmol) and excessive diazomethane: 0.22 g
(88%) of 12. Colorless crystals. M.p. 958 (MeOH). UV: 210 (3.890), 234 (sh). IR: 3100, 3015, 1760,
1
1730. H-NMR (CDCl3): 4.02 (s, 3 H); 3.62 (s, 3 H); 3.07 (s, 3 H); 2.72 (d, J=8, 1 H); 2.28 (d, J=8, 1
H). Anal. calc. for C8H11NO6S (249.23): C 38.55, H 4.49, N 5.62; found: C 39.12, H 4.49, N 5.51.
5-Benzylidene-3-(4-methoxybenzylidene)-pyrrolidine-2,4-dione (13b). A soln. of 5-benzylidene-1,5-
dihydro-4-hydroxy-2H-pyrrol-2-one [26] (1.87 g, 10 mmol) in AcOH (20 ml) was heated to reflux for
10 min in the presence of ammonium acetate (1.15 g, 15 mmol) and 4-methoxybenzaldehyde (1.63 g,
12 mmol). The product crystallized after cooling: 2.0 g (65%) of 13b, (E)/(Z) mixture 4 :1. Orange crys-
1
tals. M.p. 2128 (dec.; dioxane/H2O). UV: 307 (4.298), 381 (4.549). IR: 3186, 1718, 1664, 1634, 1583. H-
NMR (main isomer): 11.03 (s, 1 H); 8.77–8.57 (m, 2 H); 7.85–7.15 (m, 8 H); 6.50 (s, 1 H); 3.96 (s, 3
H). Anal. calc. for C19H15NO3 (305.33): C 74.74, H 4.95, N 4.59; found: C 74.29, H 4.91, N 4.58.
5-Benzylidene-3-(3-phenylprop-2-enylidene]pyrrolidine-2,4-dione (13c). As described for 13b, from
5-benzylidene-1,5-dihydro-4-hydroxy-2H-pyrrol-2-one [26] (1.87 g, 10 mmol) and cinnamaldehyde
(=3-phenylprop-2-enal; 1.60 g, 12 mmol): 1.5 g (50%) of 13c. Red crystals. M.p. 237–2398. UV: 377
(4.669). IR: 3299, 1714, 1701, 1635. 1H-NMR ((E)/(Z) 1:1): 11.01 (s, 0.5 H); 10.98 (s, 0.5 H); 8.35–8.23
(m, 1 H); 7.80–7.30 (m, 12 H); 6.41 (s, 0.5 H); 6.40 (s, 0.5 H). Anal. calc. for C20H15NO2 (301.39): C
79.87, H 4.99, N 4.66; found: C 79.51, H 4.87, N 4.32.
5-Benzylidene-3-[(dimethylamino)methylene]pyrrolidine-2,4-dione (13d). Dimethylformamide
diethyl acetal (3 ml) was added to a hot soln. of 5-benzylidene-1,5-dihydro-4-hydroxy-2H-pyrrol-2-one
[26] (1.87 g, 10 mmol) in dioxane (20 ml). After a short time, yellowish crystals started to precipitate:
1
1.70 g (70%) of 13d. M.p. 2658 (dec.). UV: 315 (4.454). IR: 3300, 1702, 1676, 1633. H-NMR: 9.95 (s, 1
H); 7.56–7.24 (m, 6 H); 6.17 (s, 1 H); 3.72 (s, 3 H); 3.36 (s, 3 H). 13C-NMR: 179.7, 172.0 (C=O); 153.7
(NꢀCH=); 134.4–126.9 (C(3), C(5), arom. C); 102.8 (CH=); 47.2 (MeN). Anal. calc. for C14H14N2O2
(242.57): C 69.84, H 5.78, N 11.56; found: C 69.31, H 5.76, N 11.67
4-Benzylidenepyrrolidine-2,3,5-trione (14a). According to the G.P. B, from 13a [37] (0.55 g, 2 mmol):
0.18 g (45%) of 14a, (E)/(Z) mixture 7:3. Yellow crystals. M.p. 2188 (dec.; MeOH). UV: 339 (4.040). IR:
3056, 1789, 1697, 1610. 1H-NMR (main isomer): 12.32 (s, 1 H); 8.47–8.39 (m, 2 H); 7.87 (s, 1 H);
7.69–7.54 (m, 3 H). MS: 201 (M+). Anal. calc. for C11H7NO3 (201.18): C 65.67, H 3.51, N 6.96; found:
C 64.62, H 3.63, N 6.95.
4-(4-Methoxybenzylidene)pyrrolidine-2,3,5-trione (14b). According to the G.P. B, from 13b (0.91 g, 3
mmol): 0.48 g (70%) of 14b, (E)/(Z) mixture 7:3. Yellow crystals. M.p. 2158 (dec.; MeOH). UV: 252
1
(3.902), 387 (4.383). IR: 3259, 1779, 1745, 1690. H-NMR (main isomer): 12.18 (s, 1 H); 8.60–8.47 (m,
2 H); 7.84 (s, 1 H); 7.20–7.07 (m, 2 H); 3.91 (s, 3 H). Anal. calc. for C7H8N2O3 (168.15): C 50.00, H
4.79, N 16.66; found: C 50.16, H 4.99, N 16.26.
4-(3-Phenylprop-2-enylidene)pyrrolidine-2,3,5-trione (14c). According to the G.P. B, from 13c (0.60
g, 2 mmol): 0.28 g (61%) of 14c, (E)/(Z) mixture 7:3. Yellow crystals. M.p. 2308 (dec.; MeOH). UV:
250 (3.901), 382 (4.471). IR: 3432, 3234, 1780, 1704, 1686. 1H-NMR (main isomer): 12.18 (s, 1 H);
8.15–8.05 (m, 1 H); 7.85–7.65 (m, 4 H); 7.55–7.45 (m, 3 H). Anal. calc. for C13H9NO3 (227.22): C
68.72, H 3.99, N 6.16; found: C 68.52, H 4.11, N 6.07.
4-[(Dimethylamino)methylene]pyrrolidine-2,3,5-trione (14d). According to the G.P. B, from 13d
(0.97 g, 4 mmol): 0.50 g (74%) of 14d. Colorless crystals. M.p. 2538 (dec.; MeOH). UV: 277 (4.235),
1
336 (3.860). IR: 3129, 1770, 1731, 1673, 1636. H-NMR: 7.58 (s, 1 H); 3.61 (s, 3 H); 3.42 (s, 3 H). Anal.
calc. for C7H8N2O3 (168.15): C 50.00, H 4.79, N 16.66; found: C 50.16, H 4.99, N 16.26.

980
Helvetica Chimica Acta – Vol. 89 (2006)
(5Z)-2,5-Dihydro-4-methoxy-2-oxo-5-(2-oxoethylidene)-1H-pyrrole-3-carboxylic Acid Methyl Ester
(17a). According to the G.P. B, from 16a [26] (1.0 g, 3.4 mmol): 0.15 g (21%) of 17a. Yellow crystals.
M.p. 808 (MeOH). From the mother liquor, 18 was obtained (see below). 17a: UV: 297 (4.168). IR:
1
3197, 1720, 1673. H-NMR (CDCl3): 9.69 (d, J=1.2, 1 H); 9.23 (br. s, 1 H); 6.05 (d, J=1.2, 1 H); 4.19
(s, 3 H). 3.89 (s, 3 H). NOE: MeOꢀC(4) (4.19)/HC=C(5) (6.05). Anal. calc. for C9H9NO5 (211.17): C
51.19, H 4.29, N 6.63; found: C 51.25, H 4.49, N 6.55.
[(2Z)-1,5-Dihydro-3-methoxy-5-oxo-2H-pyrrol-2-ylidene]acetaldehyde (17b). According to the G.P.
A, from 16b [26] (1.0 g, 4.5 mmol): 0.23 g (33%) of 17b. Yellow crystals. M.p. 1488 (dec.; MeOH). UV:
1
294 (4.211). IR: 3109, 1708, 1670, 1603. H-NMR (CDCl3): 9.67 (d, J=1.4, 1 H); 9.07 (br., 1 H); 5.91
(dd, J=0.4, J=1.4, 1 H); 5.23 (dd, J=0.4, 1.8, 1 H); 3.89 (s, 3 H). NOE: MeOꢀC(3) (3.89)/HC=C(2)
(5.91) and HꢀC(4) (5.23). 13C-NMR (CDCl3): 190.9 (CH=O); 171.3, 167.3 (C(3), C=O); 145.5 (C(2));
97.9 (CH=C(2)); 94.1 (C(4)); 60.4 (MeO). Anal. calc. for C7H7NO3 (153.14): C 54.90, H 4.61, N 9.15;
found: C 54.91, H 4.65, N 8.81.
(5Z)-2,5-Dihydro-4-methoxy-5-(2-methoxy-2-oxoethylidene)-2-oxo-1H-pyrrole-3-carboxylic
Acid
Methyl Ester (18). Compound 18 crystallized from the mother liquor obtained on preparing 17a: 50
mg (6%) of 18. Colorless crystals. M.p. 1468 (MeOH). UV: 291 (4.296). IR: 3240, 1738, 1720, 1702,
1
1620. H-NMR: 10.12 (s, 1 H); 5.51 (s, 1 H); 4.09 (s, 3 H); 3.81 (s, 3 H); 3.70 (s, 3 H). 13C-NMR: 166.9,
165.1 (C=O); 163.2 (C(4)); 162.1 (C=O); 143.7 (C(5)); 100.9 (CH=); 93.8 (C(3)); 61.2 (MeO); 52.4
(COOMe); 51.5 (COOMe). Anal. calc. for C10H11NO6 (241.20): C 49.79, H 4.56, N 5.80; found: C
49.59, H 4.67, N 5.77.
Bromo[(2Z)-1,5-dihydro-3-methoxy-5-oxo-2H-pyrrol-2-ylidene]acetaldehyde (19b). Five drops of
Br2 were added to a suspension of 17b (0.15 g, 1 mmol) in AcOH (3 ml). After a short time of stirring,
the product began to crystallize. The precipitate was collected and washed with petroleum ether: 80
mg (35%) of 19b.Yellowish crystals. M.p. 2608 (dec.; MeOH). UV: 308 (4.289). IR: 3176, 3113, 1705,
1660, 1593. 1H-NMR: 10.41 (br. s, 1 H); 9.52 (s, 1 H); 5.79 (s, 1 H); 3.95 (s, 3 H). NOE: MeOꢀC(3)
(3.95)/HꢀC=O (9.52) and HꢀC(4) (5.79). Anal. calc. for C7H6BrNO3 (232.03): C 36.24, H 2.61, N
6.04; found: C 36.07, H 2.47, N 5.94.
Bromo[4-bromo-1,5-dihydro-3-methoxy-5-oxo-2H-pyrrolylidene]acetaldehyde (19c). Ten drops of
Br2 were added to a soln. of 17b (0.15 g, 1 mmol) in AcOH (15 ml). After 30 min of stirring, the mixture
was evaporated and the residue crystallized from iPr2O/EtOH (1:1): 70 mg (22%) of 19c. Yellowish crys-
tals. M.p. 2078 (dec.; AcOH). UV: 319 (4.376). IR: 3155, 1718, 1664, 1591. 1H-NMR: 10.87 (s, 1 H); 9.96 (s,
1 H); 4.34 (s, 3 H). Anal. calc. for C7H5Br2NO3 (310.93): C 27.04, H 1.62, N 4.50; found: C 27.14, H 1.87, N
4.42.
4-Amino-2,5-dihydro-2-oxo-5-(2-oxoethylidene)-1H-pyrrole-3-carboxylic Acd Methyl Ester (20). A
soln. of NH3 (1 ml, 25%) was added to a soln. of 17a (0.11 g, 0.5 mmol) in MeOH (5 ml). After a
short time of stirring, the product began to crystallize: 80 mg (81%) of 20. Colorless crystals. M.p.
1
1938 (dec.; MeOH). UV: 230 (4.014), 314 (4.145). IR: 3398, 1719, 1638, 1560. H-NMR: 10.66 (s, 1 H);
9.97 (d, J=8, 1 H); 8.71 (br. s, 1 H); 8.21 (br. s, 1 H); 6.14 (d, J=8, 1 H); 3.68 (s, 3 H). MS-HR:
196.0522 (C
A
G
N
rel-(3aR,3bR,6aS,6bS)-Tetrahydro-3a,3b-dimethoxy-2,5-dimethylcyclobuta[1,2-c:3,4-c’]dipyrrole-1,
3,4,6(2H,5H)-tetrone (22a). A soln. of 7a (0.12 g, 0.8 mmol) in CHCl3 (100 ml) was irradiated for 2 h and
then evaporated. The residue was recrystallized: 0.11 g (90%) of 22a. Colorless crystals. M.p. 2158
(EtOH/iPr2O). The structure was confirmed by X-ray crystallography1). UV: 260 (2.756). IR: 2953,
1
1780, 1721. H-NMR (CDCl3): 3.45 (s, 6 H); 3.12 (s, 6 H); 3.09 (s, 2 H). 13C-NMR (CDCl3): 172.5 (C=
O); 83.5 (CꢀO); 55.1 (MeO); 40.8 (CꢀH); 25.6 (MeN). MS: 286 (M+). Anal. calc. for C12H14N2O6
(282.26): C 51.07, H 5.00, N 9.92; found: C 50.92, H 5.05, N 9.79.
rel-(3aR,3bR,6aS,6bS)-3a,3b-Bis(benzyloxy)-tetrahydro-2,5-dimethylcyclobuta[1,2-c:3,4-c’]dipyrrole-
1,3,4,6(2H,5H)-tetrone (22b). As described for 22a, from 7b (0.11 g, 0.5 mmol): 50 mg (45%) of 22b. Col-
orless crystals. M.p. 1438 (MeOH). The structure was confirmed by X-ray crystallography1). UV: 210
1
(4.409). IR: 3473, 1778, 1799. H-NMR: 7.40–7.19 (m, 10 H); 4.64 (d, J=11.3, 4 H); 3.63 (d, J=4, 2
H); 2.98 (s, 6 H). 13C-NMR : 172.9, 170.7 (C=O); 136.6–127.2 (arom. C); 82.9 (CꢀO); 67.8 (CH2ꢀO);
25.1 (MeN). Anal. calc. for C24H22N2O6 (434.45): C 66.35, H 5.10, N 6.45; found: C 66.08, H 5.09, N 6.25.

Helvetica Chimica Acta – Vol. 89 (2006)
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rel-(3aR,3bR,6aS,6bS)-3a,3b,6a,6b-Tetrakis(benzyloxy)tetrahydro-2,5-dimethylcyclobuta[1,2-c:3,4-
c’]dipyrrole-1,3,4,6(2H,5H)-tetrone (22c). A soln. of 23a [34] (0.32 g, 1 mmol) and benzophenone (0.1 g)
1
in AcOEt/hexane 1:10 (150 ml) was irradiated for 1.5 h. After concentration of the soln. to = of the
10
original volume, the product precipitated upon cooling: 0.21 g (65% of 22c). Colorless powder. M.p.
1968. IR: 3088, 3065, 2942, 2883, 1782, 1721, 1610. 1H-NMR (CDCl3): 7.26–7.20 (m, 20 H); 5.04 (d,
J=10.6, 4 H); 4.98 (d, J=10.6, 4 H); 3.06 (s, 6 H). 13C-NMR (CDCl3): 170.9 (C=O); 136.6–127.8
(arom. C); 81.4 (CꢀO); 70.5 (CH2ꢀO); 23.2 (MeN). MS: 646 (M+). Anal. calc. for C38H34N2O8
(646.70): C 70.58, H 5.30, N 4.33; found: C 70.54, H 5.29, N 4.38.
3-(tert-Butoxy)-4-methoxy-1-methyl-1H-pyrrole-2,5-dione (23b). An Et2O soln. of diazomethane
G
(excess) was added to the soln. of 3-(tert-butoxy)-4-methoxy-1H-pyrrole-2,5-dione [38] (0.4 g, 2 mmol)
in MeOH (10 ml). After the evolution of N2 had ceased, the soln. was evaporated and the residue purified
by CC (petroleum ether). The initially oily substance crystallized slowly: 0.27 g (63%) of 23b. Yellow
crystals. M.p. 358. UV: 234 (4.127). IR: 2981, 1778, 1724, 1673. 1H-NMR (CDCl3): 4.11 (s, 3 H); 2.95 (s,
3 H); 1.44 (s, 9 H). Anal. calc. for C10H15NO4 (213.24): C 56.33, H 7.09, N 6.57, found: C 56.36, H 7.07,
N 6.91.
rel-(3aR,3bS,6aR,6bS)-3a,3b,6a,6b-Tetrakis(benzyloxy)-tetrahydro-2,5-dimethylcyclobuta[1,2-c:3,4-
c’]dipyrrole-1,3,4,6(2H,5H)-tetrone (24a). As described for 22a, from 23a [34] (0.32 g, 1 mmol) by irradi-
ation for 6 h: 0.28 g (43%) of 24a. Colorless crystals. M.p. 1298 (AcOEt/hexane). The structure was con-
firmed by X-ray crystallography1). IR: 3059, 3030, 2890, 1783, 1726. 1H-NMR (CDCl3): 7.51–7.24 (m, 20
H); 5.02 (d, J=10.2, 4 H); 4.97 (d, J=10.2, 4 H); 3.05 (s, 6 H). 13C-NMR (CDCl3): 170.8 (C=O);
136.6–127.9 (arom. C); 80.5 (CꢀO); 70.42 (CH2ꢀO); 25.14 (MeN). MS: 465 ([MꢀC14H14]+). Anal.
calc. for C38H34N2O8 (646.70): C 70.58, H 5.30, N 4.33; found: C 70.54, H 5.29, N 4.38.
rel-(3aR,3bS,6aR,6bS)-3a,6a-Di(tert-butoxy)-tetrahydro-3b,6b-dimethoxy-2,5-dimethylcyclobuta[1,
2-c:3,4-c’]dipyrrole-1,3,4,6(2H,5H)-tetrone (24b). As described for 22a, from 23b (0.11 g, 0.5 mmol): 35
mg (32%) of 24b. Colorless crystals. M.p. 1758 (MeOH). The structure was confirmed by X-ray crystal-
lography1). UV: 207 (4.222). IR: 2976, 2953, 1778, 1731. 1H-NMR: 3.80 (s, 6 H); 2.89 (s, 6 H); 1.37 (s, 18
H). 13C-NMR (CDCl3): 172.9, 170.8 (C=O); 80.0 (quart. C); 56.8 (MeO, CꢀO); 29.2 (Me3
C
rel-(3aR,3bS,6aR,6bS)-Tetrahydro-3a,3b,6a,6b-tetrahydroxy-2,5-dimethylcyclobuta[1,2-c:3,4-c’]-
dipyrrole-1,3,4,6(2H,5H)-tetrone (24c). A suspension of 24a (0.39 g, 0.6 mmol) and 10% Pd/C (50 mg) in
MeOH (50 ml) was stirred at r.t. for 18 h under H2 (1 bar). The mixture was filtered through ꢀKieselguhrꢁ
(diatomaceous earth), and the filtrate was evaporated: 0.15 g (95%) of 24c. Colorless powder. M.p. 1878.
IR: 3417, 3317, 2961, 1774. 1H-NMR: 6.93 (s, 4 OH); 2.78 (s, 6 H). MS: 286 (M+). Anal. calc. for
C10H10N2O8 (286.20): C 41.97, H 3.52, N 9.79; found: C 41.99, H 3.58, N 9.63.
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Received December 14, 2005