Tri- and tetrasubstituted N-phthalimidoaziridines in 1,3-dipolar cycloaddition reactions

Article abstract of DOI:10.1002/hlca.200900466

The thermal reactions of the 2,2,3-trisubstituted N-phthalimidoaziridine 1a with dimethyl acetylenedicarboxylate (DMAD), thioketones 4a - 4d, and dimethyl azodicarboxylate (5) proceed even at room temperature leading to the five-membered cycloadducts 2a, 6 - 8, and 12, respectively, with retention of the spatial arrangement of the aziridine substituents, in contrast to the expectation based on the conservation of orbital symmetry in concerted reactions. The analogous reactions of the tetrasubstituted phthalimidoaziridine 1b with thioketones at 40° lead to the 1,3-thiazolidine derivatives 10 and 11 as mixtures of diastereoisomers. These unexpected results may be explained by either the isomerization of the intermediate azomethine ylides or a non-concerted stepwise cycloaddition reaction of these ylides with the dipolarophiles. The structures of some adducts have been determined by X-ray crystallography.

Full text of DOI:10.1002/hlca.200900466

Helvetica Chimica Acta – Vol. 93 (2010)
847
Tri- and Tetrasubstituted N-Phthalimidoaziridines in 1,3-Dipolar
Cycloaddition Reactions
by Alexander V. Ushkov1)a), Mikhail A. Kuznetsov*a), Anthony Lindenb), and Heinz Heimgartner*b)
a) Department of Organic Chemistry, Saint-Petersburg State University, Universitetskiy pr. 26,
RU-198504 Saint-Petersburg
(phone: þ 7-812-4286779; fax: þ 7-812-4286939; e-mail: mak@mail.wplus.net)
b) Organisch-chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstrasse 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354282; fax: þ 41-44-6356812; e-mail: heimgart@oci.uzh.ch)
Dedicated to Professor Manfred Hesse on the occasion of his 75th birthday
The thermal reactions of the 2,2,3-trisubstituted N-phthalimidoaziridine 1a with dimethyl
acetylenedicarboxylate (DMAD), thioketones 4a – 4d, and dimethyl azodicarboxylate (5) proceed even
at room temperature leading to the five-membered cycloadducts 2a, 6 – 8, and 12, respectively, with
retention of the spatial arrangement of the aziridine substituents, in contrast to the expectation based on
the conservation of orbital symmetry in concerted reactions. The analogous reactions of the
tetrasubstituted phthalimidoaziridine 1b with thioketones at 408 lead to the 1,3-thiazolidine derivatives
10 and 11 as mixtures of diastereoisomers. These unexpected results may be explained by either the
isomerization of the intermediate azomethine ylides or a non-concerted stepwise cycloaddition reaction
of these ylides with the dipolarophiles. The structures of some adducts have been determined by X-ray
crystallography.
Introduction. – As far back as in the sixties of the past century, the reaction of
aziridines, e.g., A, with active dipolarophiles, e.g., a ꢀ b, leading to five-membered N-
containing heterocycles C was discovered [1 – 3] (Scheme 1). The process is considered
to start with a thermally (conrotatory) or photochemically (disrotatory) induced
cleavage of the aziridine CꢁC bond to give azomethine ylides B, which are named
Scheme 1
1
)
Part of the Ph.D. thesis of A. V. U., University of Saint-Petersburg, 2009; stay at the University of
Zꢁrich, July – September, 2005.
ꢂ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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ꢃoctet-stabilized 1,3-dipolesꢄ [4]. These reactive intermediates, which can be repre-
sented by various mesomeric structures, formally bear a positive charge on the N-atom
and negative partial charges on both C-atoms, suggesting that the opening of aziridines
A to azomethine ylides B should be accelerated by electron-withdrawing substituents,
which are able to stabilize negative charges on the terminal C-atoms of the formed
dipoles. This proposal is supported by experimental data [1 – 3][5][6]. The reactive 1,3-
dipoles B subsequently undergo cycloaddition to dipolarophiles or stabilize via various
other inter- or intramolecular transformations [3 – 8].
If both reactions of this process are concerted – the conrotatory CꢁC bond cleavage
is thermally allowed according to the Woodward – Hoffmann rules [9], and the
disrotatory one under photolysis conditions – and no stereoisomerization of the
intermediate azomethine ylides B takes place, the adduct formation proceeds
stereospecifically, and the spatial arrangement of the substituents of the product is
determined by that of the starting compounds (see, e.g., [10]). However, sometimes
these conditions are not fulfilled, and mixtures of stereo(and regio-)isomers resulted
[3][5 – 7].
The number of publications on the cycloaddition of azomethine ylides generated
from aziridines thermally or photochemically grows rapidly. More and more often, this
transformation is used in the synthesis of complex natural and biologically active
compounds [7][8]. The use of N-aminoaziridine derivatives could open a direct way to
various N-aminoheterocycles; however, only a few examples were described by
Foucaud et al. in the seventies and eighties of the past century [11]. It was shown that,
upon heating (or even at room temperature!), some N-phthalimidoaziridines with
three or four electron-withdrawing substituents in the presence of dipolarophiles give
products, which can be considered as the result of inter- (pyrrolines, azetidines) or
intramolecular (oxazolines, oxazoles) transformations of the corresponding azome-
thine ylides. Similar intramolecular transformations were also described for some N-
succinimidoaziridines [12].
Nevertheless, all of the few known examples of [2 þ 3] cycloadditions with N-
phthalimidoazomethine ylides were carried out with a single dipolarophile, the very
reactive dimethyl acetylenedicarboxylate (DMAD), and the reports are very scarce
and partly contradictory. It was reported in the first communication [11a] that briefly
boiling trans-aziridine 1a and DMAD in benzene gives a mixture of 2,5-dihydro-1H-
pyrrole 2a (25%) as a single stereoisomer and oxazole 3 (65%), which can be
considered as the product of a 1,5-dipolar electrocyclization of the intermediate
acylazomethine ylide and its subsequent aromatization by loss of phthalimide
(Scheme 2). If the same reaction was carried out at room temperature in CH2Cl2 for
two weeks, the yield of 2,5-dihydro-1H-pyrrole 2a, isolated again as a single
1
stereoisomer (according to the H-NMR data), increased to 85%, and the yield of
oxazole 3 decreased to 15% [11b]. But, in the latest article of the same group [11c], it
was reported that boiling of the tetrasubstituted N-phthalimidoaziridine 1b in the
presence of DMAD in CH2Cl2 led to the corresponding 2,5-dihydro-1H-pyrrole 2b
(84%) as a 1:1 mixture of diastereoisomers, and the authors affirmed that they had
obtained a mixture of diastereoisomers of dihydropyrrole 2a in the earlier described
experiment [11b] too! Furthermore, no determination of the relative configuration of
any of these 2,5-dihydro-1H-pyrroles was carried out.

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849
Scheme 2
Meanwhile, we reported on the inter- [13 – 15] and intramolecular [16] cyclo-
addition of several 2,3-disubstituted N-phthalimidoaziridines to a number of dipolaro-
philes with C,C multiple bonds under forced thermolysis conditions (80 – 2208), which
proceeded in a stereospecific and diastereoselective manner. Therefore, the aim of the
present work was to investigate [2 þ 3] cycloaddition reactions of N-phthalimidoaziri-
dines 1a and 1b, which are activated with three and four electron-withdrawing
substituents, respectively, to shed light on the spatial regularities of this process.
The aziridines 1a and 1b were obtained by oxidative ꢃphthalimidoaziridinationꢄ of
the corresponding unsaturated compounds [17][18]. As far as this reaction occurs
completely stereospecifically, the trans configuration of compound 1a follows from the
(E) configuration of the starting acrylate, which was established by its NOESY
spectrum (see Exper. Part). The trans configuration of 1b is in agreement with the non-
1
equivalence of the two MeO groups in the H-NMR spectrum as a result of the well-
known slow inversion of the ring N-atom in N-aminoaziridine derivatives [19].
2. Results and Discussion. – 2.1. Reaction of Aziridine 1a with DMAD. First, we
have repeated the reaction of 1a with DMAD [11]. Preliminary microscale (ca.
35 mmol) experiments in benzene and in CH2Cl2 were performed at room temperature.
The 1H- and 13C-NMR spectra of the reaction mixture, recorded immediately after the
reaction had ceased, revealed the presence of 2,5-dihydro-1H-pyrrole 2a, as a single
stereoisomer, and of oxazole 3 in a ratio of ca. 1:1 in both cases (Scheme 3). The
separation of the mixture by chromatography on silica gave ca. 60% of 2a, but only
traces (ca. 5%) of oxazole 3a, indicating the low stability of the latter under the
separation conditions.
Scheme 3

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The preparative-scale reaction of 1a with DMAD in benzene at room temperature
gave, after column chromatography, only 2a in 60% yield. Its melting point and
1H-NMR spectrum were in a good agreement with the data published earlier [11b], and
its structure was unambiguously established as the trans-isomer (rel-(2R,5R)-isomer)
by X-ray crystallography (Fig. 1). Concerning its 13C-NMR spectrum, it should be
noted that all signals of the phthalimide C-atoms are broad or even cannot be detected
(NꢁC¼O) in the spectrum. This indicates slow rotation of this substituent about the
sterically crowded NꢁN bond.
Fig. 1. ORTEP Plot [20] of the molecular structure of 2a (arbitrary numbering of atoms; 50% probability
ellipsoids)
The crystal structure of 2a clearly shows that the Ph and C ꢀ N groups have the
same relative configuration (cis orientation) as in the starting aziridine 1a. This result
was unexpected taking into account our experience with 2,3-disubstituted N-
phthalimidoaziridines [13 – 16]: we have shown that the thermal ring opening of these
aziridines to give N-phthalimidoazomethine ylides always proceeded stereospecifically,
in full agreement with the Woodward – Hoffmann rules, as a conrotatory process, and it
led to the reverse spatial arrangement of the aziridine substituents in the final
cycloadducts. In contrast, the reaction of 1a with DMAD unequivocally led to 2a with
retention of the relative configuration!
With the aim of investigating the general character of this change of the
stereochemical outcome of this process by going from disubstituted N-phthalimido-
aziridines to the thermally less stable three- and tetrasubstituted 1a and 1b, we have
carried out reactions with very active dipolarophiles, i.e., thioketones 4a – 4d, and, in
the case of 1a, also with dimethyl azodicarboxylate (5).

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2.2. Reactions of Aziridines 1a and 1b with Thioketones 4a – 4d. All reactions of 1a
with the deeply colored thioketones 4 were carried out in the same manner as described
above with DMAD, i.e., by stirring a solution of the reagents in dry benzene under Ar
at room temperature for several days. The progress of the reactions was followed by
TLC. In addition, the intense color of the initial reaction mixtures faded or disappeared
completely indicating the completion of the reaction.
The reaction of 1a with bis(4-methoxyphenyl)methanethione (4a) after 6 d gave the
1,3-thiazolidine 6 (85%) as a single regio- and diastereoisomer (Scheme 4). The
product appeared to be a heat-sensitive compound, and decomposed completely by
recrystallization from MeOH or by the determination of the melting point. Suitable
crystals of 6 were obtained from CH2Cl2/hexane, and the structure was determined by
single-crystal X-ray diffraction (Fig. 2). It shows the conservation of the spatial
arrangement of the aziridine substituents in the cycloadduct, i.e., the trans-isomer 1a
yielded the trans-isomer 6.
Scheme 4
The 1H-NMR spectrum of 6 in (D6)benzene displays a low-field signal at 7.21 ppm
for the single H-atom of the thiazolidine ring, which serves as an indication that this H-
atom is at C(2). It could be also noted that the change of the solvent from CDCl3 to
(D6)benzene causes a strong high-field shift of all signals of the phthalimide H-atoms:
instead of the usual 7.7 – 8.0 ppm, the multiplet of HꢁC(b) appears at 7.1 – 7.2 ppm, and
the signal of HꢁC(c) even at 6.6 – 6.7 ppm. The remarkable feature of the 13C-NMR
spectrum of this sterically overcrowded compound (as well as of other polysubstituted
3-phthalimido-1,3-thiazolidines obtained in this work; see Exper. Part) is a doubling of
all signals of the phthalimide C-atoms, which demonstrates the hindered rotation of this
fragment about the NꢁN bond.
The analogous reaction of 1a and adamantane-2-thione (4b) in benzene was
sluggish, and, after 16 d at room temperature, 60% of 4b were recovered (Scheme 5).
The cycloadduct 7, which was expected on the basis of the experiment with 4a, was
isolated in only 8% yield (calculated on consumed 4b). The main product of this
reaction was thiazolidine 8 (23%), which could be considered as the result of secondary
transformations of 7 with loss of the phthalimide unit. It is remarkable that both 7 and 8
were formed as single diastereoisomers. The relative configurations of both molecules
were assumed to be trans taking into account the structures of 2a and 6, which were
established by X-ray crystallography. It is essential to note that the reactions of the
unsymmetrical 1a with also unsymmetrical dipolarophiles 4a and 4b, respectively,
proceeded regioselectively affording 2-phenyl-1,3-thiazolidines exclusively.

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Fig. 2. ORTEP Plot [20] of the molecular structure of 6 (arbitrary numbering of atoms; 50% probability
ellipsoids)
Scheme 5
Beside 7 and 8, a mixture of phthalimide (18%) and a third product 9 (23%) was
1
isolated. The H-NMR spectrum of the latter displayed a singlet at 4.07 ppm (MeO)
and a characteristic multiplet of the phthaloyl H-atoms at 7.85 – 8.10 ppm. The same
product was isolated in pure form from the reaction of 1a with dimethyl azodicarboxy-
late (5; see Sect. 2.3). Its ESI-MS showed a quasimolecular-ion peak at m/z 312 (100,
[M þ Na þ MeOH]þ) that corresponds to the molecular weight of 257. Therefore, the
product might be considered as being formed by loss of the benzylidene fragment from
the starting aziridine 1a. Taking into account this information as well as the IR-, and 1H-
and 13C-NMR spectra, we assume that this product has the structure of hydrazono-
acetate 9 with unknown configuration of the C¼N bond. Its formation could be
explained as depicted in Scheme 6.

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853
Scheme 6
The formed 1,3-thiazolidine could undergo a [2 þ 3] cycloreversion under the
reaction conditions or during the separation of the reaction mixture, which led to 9 and
a thiocarbonyl ylide. This ylide apparently decomposed further, e.g., by hydrolysis, to
give, in particular, benzaldehyde, whose presence in the mixture was indicated by its
characteristic odor. It is worth mentioning that, after some time, the 1H- and 13C-NMR
spectra of a solution of 9 showed a second set of signals, which perhaps belong to the
second stereoisomer of this hydrazone (the ESI-MS of this mixture was identical with
the previous one).
In the course of the analogous reaction of 1a with xanthenethione (4c), TLC
control showed the weakening of the spots of the reagents and an increase of the
intensity of the spot of a new product. But, all attempts to separate the mixture after the
complete conversion of the starting compounds by CC on SiO2 failed, and only small
amounts of 4c and its hydrolysis product, i.e., xanthone, were isolated. This may be the
result of the instability of the corresponding 1,3-thiazolidine(s).
Under the same reaction conditions, the sterically crowded C¼S bond of 2,2,4,4-
tetramethyl-3-thioxocyclobutanone (4d; formula not shown) was inert. The generated
azomethine ylide underwent the known intramolecular 1,5-electrocyclization
[11b][21], instead of the 1,3-dipolar cycloaddition, and after long stirring of a mixture
of 1a and 4d in benzene and chromatographic workup, 1,3-oxazole 3 was obtained in
low yield because of its low stability on silica. In addition, phthalimide was isolated.
Furthermore, the reactions of thioketones 4a – 4d with aziridine 1b were carried out
for 6 – 7 h in boiling CH2Cl2 under Ar. Formation of cycloadducts was observed only in
the cases of 4a and 4c. Both reactions gave a pair of diastereoisomeric 1,3-thiazolidines
10a/10b and 11a/11b, respectively (Scheme 7). We could separate the mixture 10a/10b
and obtained both isomers in pure form (31 and 23%), but from the mixture of 11a and
11b, which, according to the 1H-NMR spectrum of the reaction mixture, were present in
a ca. 3 :1 ratio, only 11a could be isolated in pure form.
The structures of 10a and 11a were established unequivocally by X-ray crystal-
structure determinations (Figs. 3 and 4). In both cases, the molecule is trans-
configured. In the case of 10a, the ester group at C(2) is disordered, and the two
conformers differ by a ca. 1808 rotation about the C(2)ꢁC(6) bond.

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Scheme 7
Fig. 3. ORTEP Plot [20] of the molecular structure of one of the conformers of 10a (arbitrary numbering
of atoms; 50% probability ellipsoids)
It is remarkable that, in both cases, the main product is the ꢃanomalousꢄ one with the
same configuration of the substituents as in the starting aziridine 1b. It should be
mentioned that the reaction of 1b with DMAD was reported to lead to the mixture of
two diastereoisomers too, but in a ratio of ca. 1:1 [11d].
2.3. Reaction of Aziridine 1a with Dimethyl Azodicarboxylate (5). The reaction was
carried out in benzene at room temperature for two weeks, and the products were

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855
Fig. 4. ORTEP Plot [20] of the molecular structure of 11a (arbitrary numbering of atoms; 50%
probability ellipsoids)
separated by column chromatography on SiO2. In addition to phthalimide (41%), the
expected trimethyl 3-cyano-5-phenyl-4-phthalimido-1,2,4-triazolidine-1,2,3-tricarboxy-
late (12; 12%) and 9 (4%) were isolated (Scheme 8). The identity of 9 with the product
obtained from the reaction of 1a and 4b was established by the comparison of the 1H-
and 13C-NMR spectra. The configuration of 12 was not determined, but, in analogy to
products 2a and 6 of the other reactions with 1a, we propose the trans configuration for
12 too.
Scheme 8
2.4. Mechanism of the Reactions. Because of the low thermal stability of the starting
aziridines 1a and 1b, generally low yields of cycloadducts, and an appreciable sensitivity
of the processes under consideration to steric factors, the mechanisms can be discussed
only with great care.
First, it was established that the reactions of the trisubstituted aziridine 1a with
DMAD, thioketones 4a and 4b, and dimethyl azodicarboxylate (5) occur in a

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stereoselective way, affording only one of two possible diastereoisomers. Moreover, in
two cases it has been shown by X-ray crystallography that the reaction proceeds with
the conservation of the spatial arrangement of the aziridine substituents in the final
cycloadducts 2a and 4. The same stereoselectivity, but to a far less extent, is observed
for the reactions with the tetrasubstituted aziridine 1b. In addition, it can be noted that
the cycloaddition of the ꢃasymmetricꢄ aziridine 1a onto the C¼S bond of thioketones
occurs regioselectively, i.e., the S-atom is connected with the less substituted aziridine
C-atom.
These observations can be explained in different ways. Provided that the opening of
aziridines 1 to the corresponding azomethine ylides and the subsequent cycloaddition
are concerted, the rate of the generation of the ylides must be significantly higher than
the rate of their cycloaddition. In this case, the initially generated W-type (trans,trans)
dipoles (or the less probable U-type (cis,cis) dipoles) have enough time to isomerize
completely (or partially, if the cycloaddition rates for the stereoisomers are different)
into the more stable S-type (trans,cis) dipoles, which are usually more active in the
subsequent cycloadditions [3]. This mechanism is supported by the observation that the
pure trans-aziridine 1b in solution, in the absence of a dipolarophile, is slowly
transformed to a mixture of cis- and trans-stereoisomers already at room temperature,
which can be explained as the result of the stereoisomerization of the intermediate
ylide [11d].
On the other hand, one can assume that the cycloaddition of the tri- and
tetrasubstituted azomethine ylides onto dipolarophiles is not concerted, but proceeds
as a stepwise nucleophilic addition. In this case, the stereoselectivity of the whole
transformation could be determined by the relative stability of the products, which is in
agreement with our results too.
In principle, it is necessary to take into account a third possibility, namely that the S-
atom of the C¼S bond plays the role of an active nucleophilic centre. A priori, one
cannot exclude that the reaction of thioketones with 1a and 1b could start with the
attack of the S-atom onto one of the C-atoms of the electron-poor aziridine ring,
leading to the opening of the three-membered ring and subsequent ring closure of the
five-membered chain. Again, the stereoselectivity of the product formation should
mainly be determined by steric factors. But, in this case, the opening of the aziridine
should proceed by the cleavage of a CꢁN bond, and the following ring closure would
give 1,3-thiazolidines with the thioketone-derived substituents at C(2), in contrast to
the outcome of our experiments.
We thank the analytical sections of our institutes for spectra and analyses, and F. Hoffmann-La
Roche AG, Basel, for financial support. A. V. U. is very grateful for the warm hospitality he experienced
at the University of Zꢁrich.
Experimental Part
1. General. All reagents and solvents were of reagent-grade and were used without further
purification unless otherwise specified. Column chromatography (CC): flash chromatography, Merck
silica gel 60 (particle size 0.040 – 0.063 mm) packed in glass columns; for each chromatography, the
eluting solvent was optimized by TLC. Anal. TLC: Macherey-Nagel POLYGRAM SIL G/UV 254 or
ALUGRAM SIL G/UV 254. M.p.: Bꢀchi B-540 apparatus; uncorrected. IR Spectra: Perkin-Elmer-1600
(FT-IR) spectrophotometer; in KBr; absorptions in cmꢁ1 1H- (300 or 600 MHz) and 1H-decoupled
.

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13C-NMR (75.4 or 150.8 MHz) spectra: Bruker DPX-300, ARX-300 or AMX-600 instruments; in CDCl3
or (D6)benzene; d in ppm (TMS ¼ 0 ppm), coupling constants J in Hz. ESI-MS: Finnigan TSQ-700
instrument. Elemental analyses were performed at the Institute of Organic Chemistry, University of
Zꢁrich.
Bis(4-methoxyphenyl)methanethione (4a) [22], adamantane-2-thione (4b) [23], 9H-xanthene-9-
thione (4c) [24], and 2,2,4,4-tetramethyl-3-thioxocyclobutanone (4d) [25] were prepared by thionation of
the corresponding ketones according to literature procedures. Dimethyl acetylenedicarboxylate
(DMAD) and dimethyl azodicarboxylate (5) were commercially available (Fluka).
2. Preparation of 1-Phthalimidoaziridines 1a and 1b. 2.1. Methyl (E)-2-Cyano-3-phenylprop-2-enoate
was prepared from PhCHO and NCCH2COOMe on basic Al2O3 according to [26]. Yield: 80%. M.p. 91 –
1
928 ([26]: 89 – 908). H-NMR (CDCl3): 3.92 (s, MeO); 7.45 – 7.60 (m, 2 Hm, 1 Hp); 7.90 – 8.05 (m, 2 Ho);
8.25 (s, CH). Two cross-peaks in the 2D-NOESY spectrum corresponded to the NOE between the vinyl
CH and Ho of Ph and the MeO group, resp., establishing the (E) configuration of this compound.
2.2. Methyl trans-2-Cyano-3-phenyl-1-phthalimidoaziridine-2-carboxylate (1a). N-Aminophthali-
mide (486 mg, 3 mmol) and Pb(OAc)4 (1.33 g, 3 mmol) were added portionwise (10 – 15 mg) within
40 min to a stirred suspension of dry K2CO3 (1.3 g, 9.4 mmol) in a soln. of methyl (E)-2-cyano-3-
phenylprop-2-enoate (561 mg, 3 mmol) in dry CH2Cl2 (40 ml) at 08. After the completion of the addition,
the stirring was continued for 30 min. The mixture was filtered through a short plug of SiO2, which was
then washed with CH2Cl2, and the combined filtrates were concentrated in vacuo. The oily residue was
mixed with Et2O (5 ml) and left overnight at ꢁ 48. White crystals of 1a were separated by filtration.
Yield: 720 mg (69%). M.p. 165 – 1668 ([17]: 1658). 1H-NMR (CDCl3): 3.87 (s, MeO); 4.95 (s, CH); 7.40 –
7.60 (m, 5 H, Ph); 7.70 – 7.90 (m, 4 H, PiN).
2.3. Dimethyl trans-2,3-Dicyano-1-phthalimidoaziridine-2,3-dicarboxylate (1b). As described in 2.2,
N-aminophthalimide (486 mg, 3 mmol), Pb(OAc)4 (1.33 g, 3 mmol), K2CO3 (1.3 g, 9.4 mmol), and
dimethyl (2E)-2,3-dicyanobut-2-enedioate [27] (582 mg, 3 mmol) gave 365 mg (34%) of 1b. M.p. 114 –
1168 ([18]: 1308). 1H-NMR (C6D6): 3.18 (s, 2 MeO); 6.55 – 6.65 (m, 2 H, PiN); 7.00 – 7.10 (m, 2 H, PiN).
1H-NMR (CDCl3): 4.02, 4.10 (2s, 2 MeO); 7.80 – 8.00 (m, 4 H, PiN).
3. Reactions of 1a with Dipolarophiles. 3.1. Reaction with DMAD. Trimethyl trans-2-Cyano-2,5-
dihydro-5-phenyl-1-phthalimido-1H-pyrrole-2,3,4-tricarboxylate (2a) was obtained from 1a and DMAD
according to [11b] (1/3 scale) in dry benzene under Ar within 7 d at r.t. The solvent was evaporated in
vacuo, and the residue was separated by CC (hexane/AcOEt, gradient). Yield: 60%. M.p. 202 – 2038
1
([11b]: 2088). H-NMR (CDCl3): 3.64, 3.84, 3.86 (3s, 3 MeO); 6.24 (s, HꢁC(5)); 7.27 – 7.35 (m, 2 Hm,
1 Hp); 7.40 – 7.50 (m, 2 Ho); 7.70 – 7.85 (m, 4 H, PiN). 13C-NMR (CDCl3): 52.83, 53.14, 54.66 (3 MeO);
70.18, 71.74 (C(2), C(5)); 114.23 (CN); 123 – 124 (br., 2 C(b), PiN); 126.37 (C(3)); 128.51, 128.79 (2 Co,
2 Cm); 129.82 (Cp); 129 – 130 (br., 2 C(a), PiN); 132.74 (Cipso); 134.90 (br., 2 C(c), PiN); 148.40 (C(4));
159.70, 162.31, 163.13 (3 CO). The signals of the phthalimide CO could not be detected because of the
strong broadening.
Suitable crystals for the X-ray crystal-structure determination were obtained from CH2Cl2/hexane by
slow evaporation of the solvent.
3.2. Reactions with Thioketones. General Procedure. A soln. of 1a (347 mg, 1 mmol) and the
thioketone (1 mmol) in dry benzene (10 ml) was stirred at r.t. under Ar, until 1a disappeared in the
mixture (TLC control). The solvent was evaporated in vacuo, the residue was treated with hexane/
AcOEt 1:1 (10 ml), and the precipitated phthalimide was filtered off. The filtrate was evaporated in
vacuo, and the residue was separated by CC on SiO2 (45 g) with hexane/AcOEt (gradient elution).
3.2.1. Reaction of 1a with 4a. Methyl trans-4-Cyano-5,5-bis(4-methoxyphenyl)-2-phenyl-3-phthal-
imido-1,3-thiazolidine-4-carboxylate (6). After 6 d at r.t., the mixture of 1a and 4a was diluted with
AcOEt (40 ml) and filtered through a short plug of SiO2, which was washed with AcOEt (50 ml). The
solvent was evaporated in vacuo, and the residue was diluted with Et2O (3 ml). The precipitate formed
was filtered and dried. Yield: 513 mg (85%) of 6. M.p. 149 – 1508 (dec.). IR (KBr): 3067, 3036, 3002
(Carom.ꢁH), 2953, 2935, 2836 (OCꢁH), 1793, 1758 (NC¼O), 1737 (OC¼O), 1607, 1580, 1509, 1457,
1350, 1297, 1254, 1206, 1186. 1H-NMR (C6D6): 3.28 (s, 2 MeO); 3.38 (s, MeO); 6.59 – 6.69 (m, 2 HꢁC(c),
PiN); 6.70, 7.06 (AA’ of AA’BB’, J ¼ 8.7, 9.3, 4 arom. Hm); 6.79 (t, J ¼ 7.5, 1 Hp, Ph); 6.91 (t, J ¼ 7.5, 2 Hm,
Ph); 7.10 – 7.20 (m, 2 HꢁC(b), PiN); 7.21 (s, HꢁC(5)); 7.77 (d, J ¼ 7.2, 2 Ho, Ph); 7.93, 8.48 (BB’ of

858
Helvetica Chimica Acta – Vol. 93 (2010)
AA’BB’, J ¼ 8.7, 9.0, 4 arom. Ho). 13C-NMR (C6D6): 53.21, 54.75, 54.84 (3 MeO); 66.13, 69.03, 79.97
(C(2), C(3), C(5)); 113.83, 114.05 (4 arom. Cm); 115.49 (CN); 123.17, 123.99 (2 C(b), PiN); 128.90 (2 Cm,
Ph); 129.20, 129.25 (2 C(a), PiN); 130.05 (Cp, Ph); 130.44 (2 Co, Ph); 131.12 (4 arom. Co); 132.18, 134.82
(2 arom. Cipso); 134.26, 134.59 (2 C(c), PiN); 140.72 (Cipso, Ph); 159.53, 159.85 (2 arom. Cp); 163.57, 165.31,
167.56 (5 CO). ESI-MS: 628 (100, [M þ Na]þ), 370 (36), 223 (8), 170 (5). Anal. calc. for C34H27N3O6S
(605.66): C 67.42, H 4.49, N 6.94, S 5.29; found: C 67.16, H 4.44, N 6.86, S 5.26.
Suitable crystals for the X-ray crystal-structure determination were obtained from CH2Cl2/hexane by
slow evaporation of the solvent.
3.2.2. Reaction of 1a with Adamantane-2-thione (4b). Reaction time 16 d. The separation of the
mixture provided 100 mg (60%) of 4b, 110 mg of a mixture (molar ratio 2.5 :1) of phthalimide
(calculated: 65 mg, 44%) and methyl 2-cyano-2-(phthaloylhydrazono)acetate (9; calc.: 45 mg, 18%),
85 mg (23%) of methyl trans-4-cyano-2-phenylspiro[1,3-thiazolidine-5,2’-tricyclo[3.3.1.13,7]decane]-4-
carboxylate (8), and 40 mg (8%) of methyl trans-4-cyano-2-phenyl-3-phthalimidospiro[1,3-thiazolidine-
5,2’-tricyclo[3.3.1.13,7]decane]-4-carboxylate (7).
Data of 7. M.p. 201 – 2028. IR (KBr): 3063, 3030, 3010 (n(Carom.ꢁH)), 2914, 2861 (CꢁH), 1795
(NC¼O), 1738 (OC¼O), 1608, 1456, 1353, 1211. 1H-NMR (CDCl3): 1.65 – 2.35 (m, 11 H, Ad); 2.69 (d,
J ¼ 12.3, 1 H, Ad); 3.06 (s, 1 H, Ad); 3.39 (d, J ¼ 12.3, 2 H, Ad); 4.00 (s, MeO); 6.38 (s, HꢁC(2)); 7.10 –
7.40 (m, 2 Hm, 1 Hp); 7.40 – 7.60 (m, 2 Ho); 7.60 – 7.90 (m, 4 H, PiN). 13C-NMR (CDCl3): 26.04, 26.61,
34.31, 34.63, 36.19, 36.76, 37.07, 38.37 (Ad); 53.87 (MeO); 65.60, 67.39, 75.32 (C(2), C(4), C(5)); 116.55
(CN); 123.51, 124.24 (2 C(b), PiN); 128.48, 129.47 (5 arom. C); 129.20, 129.29 (2 C(a), PiN); 134.62,
134.84 (2 C(c), PiN); 135.98 (Cipso); 164.56, 164.76, 167.52 (3 CO). ESI-MS: 536 (100, [M þ Na]þ). Anal.
calc. for C29H27N3O4S (513.62): C 67.82, H 5.30, N 8.18, S 6.24; found: C 67.12, H 5.17, N 7.91, S 6.13.
Data of 8. M.p. 142 – 1438. IR (KBr): 3319 (n(NH)), 3064, 3030, 2998 (Carom.ꢁH)), 2925, 2906, 2869,
2855 (CꢁH), 2230 (C ꢀ N), 1743 (C¼O), 1624, 1494, 1475, 1457, 1441, 1262. 1H-NMR (CDCl3): 1.45 –
2.40 (m, 13 H, Ad); 2.68 (s, 1 H, Ad); 3.70 (br. s, NH); 3.91 (s, MeO); 5.67 (s, HꢁC(2)); 7.30 – 7.45
(m, 2 Hm, 1 Hp); 7.45 – 7.55 (m, 2 Ho). 13C-NMR (CDCl3): 25.90, 26.58, 33.58, 34.39, 36.41, 37.42, 38.10,
39.43, 41.08 (Ad); 54.40 (MeO); 66.85, 75.05, 79.55 (C(2), C(4), C(5)); 115.52 (CN); 127.71, 128.94 (Co,
Cm); 129.14 (Cp); 137.37 (Cipso); 167.13 (CO). ESI-MS: 391 (100, [M þ Na]þ), 364 (5), 225 (42).
Data of 9 (mixture with phthalimide). 1H-NMR (CDCl3): 4.07 (s, MeO); 7.85 – 8.10 (m, 4 H, PiN).
3.2.3. Reaction of 1a with 9H-Xanthene-9-thione (4c). The reaction was followed by TLC. After 7 d,
starting material 1a (Rf 0.3, hexane/AcOEt 2 :1 (v/v)) had almost disappeared, and a new product with Rf
0.35 has formed. After CC on SiO2, only 4c (135 mg, 64%) and traces of xanthone were obtained.
3.2.4. Reaction of 1a with 2,2,4,4-Tetramethyl-3-thioxocyclobutanone (4d). After 7 d, CC on SiO2
gave starting material 4d (64 mg, 41%), phthalimide (75 mg, 51%), and 5-methoxy-2-phenyl-1,3-oxazole-
4-carbonitrile (3). Yield: 45 mg (23%). M.p. 106 – 1078 ([11d]: 1068). 1H-NMR (CDCl3): 4.30 (s, MeO);
7.40 – 7.55 (m, 3 arom. H); 7.80 – 7.95 (m, 2 arom. H). 13C-NMR (CDCl3): 60.03 (MeO); 88.86 (C(4));
112.89 (CN); 125.66 (Cipso); 125.66, 128.95 (Co, Cm); 131.05 (Cp); 152.26 (C(2)); 164.49 (C(5)).
3.3. Reaction of 1a with 5. Reaction time 2 weeks. After CC, phthalimide (60 mg, 41%), trimethyl 3-
cyano-5-phenyl-4-phthalimido-1,2,4-triazolidine-1,2,3-tricarboxylate (12; 60 mg, 12%), and 9 (10 mg, 4%)
were isolated.
Methyl 2-Cyano-2-(phthaloylhydrazono)acetate (9). M.p. 201 – 2028. IR (KBr): 3087 (Carom.ꢁH),
2963 (OCꢁH), 1795, 1765 (NC¼O), 1714 (OC¼O), 1600, 1570, 1466, 1441, 1363, 1344, 1251. 1H-NMR
(CDCl3): 4.07 (s, MeO); 7.85 – 8.10 (m, 4 H, PiN). 13C-NMR (CDCl3, 150.8 MHz): 54.82 (MeO); 109.78
(CN); 125.46 (2 C(b), PiN); 130.33 (2 C(a), PiN); 133.56 (2 C(c), PiN); 136.11 (C¼N); 158.70 (COO);
161.25 (CON). ESI-MS: 312 (100, [M þ Na þ MeOH]þ), 285 (19).
Data of 12. M.p. 209 – 2108. IR (KBr): 3066, 3009 (Carom.ꢁH), 2985, 2958 (CꢁH), 1799 (NC¼O),
1
1750 (OC¼O), 1610, 1443, 1371, 1332, 1284, 1213. H-NMR (CDCl3, 600 MHz): 3.79, 3.90, 3.94 (3s,
3 MeO); 6.55 (s, HꢁC(5)); 7.30 – 7.40 (m, 2 Hm, 1 Hp); 7.69 – 7.75 (m, 2 Ho); 7.75 – 7.88 (m, 4 H, PiN).
13C-NMR (CDCl3, 150.8 MHz): 54.54, 54.58, 55.09 (3 MeO); 65.97 (C(3)); 80.13 (br. s, C(5)); 111.33 (br.
s, CN); 124.32 (2 C(b), PiN); 127.72, 128.81 (2 Co, 2 Cm); 129.04 (Cp); 129.86 (2 C(a), PiN); 133.78 (br. s,
Cipso); 135.17 (2 C(c), PiN); 161.20 (COO); 165.07 (br. s, CON). ESI-MS: 548 (7, [M þ Na þ MeOH]þ),
532 (17, [M þ K]þ), 516 (100, [M þ Na]þ), 432 (10), 259 (14).

Helvetica Chimica Acta – Vol. 93 (2010)
859
4. Reactions of 1b with Thioketones. General Procedure. A soln. of 1b (354 mg, 1 mmol) and the
thioketone (1 mmol) in dry CH2Cl2 (5 ml) was heated under reflux with stirring under Ar, until 1b
disappeared (TLC control). The solvent was evaporated in vacuo, and the residue was separated by CC
on SiO2 (45 g) with hexane/AcOEt (gradient elution).
4.1. Reaction of 1b with 4a. After 6 h under reflux, the mixture was left overnight at r.t. After CC on
SiO2, 4a (80 mg, 31%) and 1b (30 mg, 9%) were isolated as well as dimethyl trans-2,4-dicyano-5,5-bis(4-
methoxyphenyl)-3-phthalimido-1,3-thiazolidine-2,4-dicarboxylate (10a; 187 mg, 31%) and dimethyl cis-
2,4-dicyano-5,5-bis(4-methoxyphenyl)-3-phthalimido-1,3-thiazolidine-2,4-dicarboxylate (10b; 143 mg,
23%). Taking into account the recovered 4a, the total yield of the two adducts is 78%.
Data of 10a. M.p. 222 – 2238 (dec). IR (KBr): 3079, 3008 (Carom.ꢁH), 2956, 2910, 2840 (CꢁH), 1802,
1
1775 (NC¼O), 1750 (OC¼O), 1607, 1511, 1466, 1434, 1351, 1299, 1258, 1218, 1188. H-NMR (C6D6):
3.20, 3.22, 3.23, 3.63 (4s, 4 MeO); 6.60, 6.90 (AA’ of AA’BB’, J ¼ 9.0, 9.3, 4 Hm); 6.71, 6.77 (2t, J ¼ 7.2,
2 HꢁC(c), PiN); 7.15 (1 HꢁC(b), PiN, overlapped by solvent signal); 7.36 (d, J ¼ 6.6, 1 HꢁC(b), PiN);
7.55, 8.13 (BB’ of AA’BB’, J ¼ 9.0, 9.3, 4 Ho). 13C-NMR (C6D6): 53.08, 54.37, 54.76, 54.88 (4 MeO); 67.35,
67.53, 81.25 (C(2), C(4), C(5)); 113.82, 114.01 (CN, 4 Cm); 115.38 (CN); 124.03, 124.34 (2 C(b), PiN);
128.84, 128.90, 129.12, 137.44 (2 C(a), PiN, 2 Cipso); 130.95, 131.08 (4 Co); 134.87, 134.93 (2 C(c), PiN);
159.99, 160.37 (2 Cp); 163.50, 163.85, 165.01, 165.40 (2 COO, 2 CON). ESI-MS: 667 (17, [M þ Na þ
MeOH]þ), 635 (100, [M þ Na]þ), 377 (26), 258 (7). Anal. calc. for C31H24N4O8S (612.61): C 60.78, H
3.95, N 9.15, S 5.23; found: C 60.71, H 4.06, N 8.94, S 5.17.
Suitable crystals for the X-ray crystal-structure determination were obtained from CH2Cl2/hexane/
benzene by slow evaporation of the solvent.
Data of 10b. M.p. 208 – 2098 (dec). IR (KBr): 3070, 3038, 3000 (Carom.ꢁH), 2956, 2908, 2840 (CꢁH),
1800 (NC¼O), 1749 (OC¼O), 1607, 1580, 1511, 1467, 1434, 1359, 1300, 1259, 1217, 1187. 1H-NMR
(C6D6): 3.20, 3.21, 3.23, 3.25 (4s, 4 MeO); 6.54, 7.01 (AA’ of AA’BB’, J ¼ 9.0, 4 Hm); 6.70 – 6.85 (m,
2 HꢁC(c), PiN); 7.25 – 7.40 (m, 2 HꢁC(b), PiN); 7.53, 8.30 (BB’ of AA’BB’, J ¼ 9.0, 4 Ho). 13C-NMR
(C6D6): 53.22, 54.24, 54.78, 54.85 (4 MeO); 66.68, 68.19, 78.97 (C(2), C(4), C(5)); 113.71, 115.24 (2 CN);
113.90, 114.28 (4 Cm); 123.66, 124.52 (2 C(b), PiN); 128.86, 136.10 (2 Cipso); 129.16, 129.37 (2 C(a), PiN);
130.81 (4 Co); 134.72, 134.95 (2 C(c), PiN); 160.27, 163.22, 164.57, 166.65 (2 COO, 2 CON). ESI-MS: 635
(100, [M þ Na]þ), 377 (29), 258 (7). Anal. calc. for C31H24N4O8S (612.61): C 60.78, H 3.95, N 9.15, S 5.23;
found: C 60.89, H 4.11, N 8.91, S 5.32.
4.2. Reaction of 1b with 4c. After 7 h under reflux, the mixture was left at r.t. overnight. After CC on
SiO2, 4c (95 mg, 45%), dimethyl trans-2,4-dicyano-3-phthalimidospiro[1,3-thiazolidine-5,9’-xanthene]-
2,4-dicarboxylate (11a; 50 mg, 9%), and a mixture (ca. 2 :1) of 11a and dimethyl cis-2,4-dicyano-3-
phthalimidospiro[1,3-thiazolidine-5,9’-xanthene]-2,4-dicarboxylate (11b; 180 mg, 32%) were isolated.
Taking into account the recovered 4c, the total yield of the two adducts is ca. 75%.
Data of 11a. M.p. 195 – 1968 (dec). IR (KBr): 3038, 3072 (Carom.ꢁH), 2954, 2927, 2847 (CꢁH), 1803,
1
1772 (NC¼O), 1749 (OC¼O), 1598, 1475, 1445, 1361, 1315, 1286, 1246, 1220. H-NMR (CDCl3): 3.41,
4.10 (2s, 2 MeO); 7.10 – 7.26 (m, HꢁC(4’,5’)); 7.36 – 7.53 (m, HꢁC(2’,3’,6’,7’)); 7.70 – 8.00 (m, Hꢁ(1’,8’),
2 HꢁC(c), PiN); 8.55 – 8.35 (m, 1 HꢁC(b), PiN); 8.60 (d, J ¼ 7.8, 1 HꢁC(b), PiN). 13C-NMR (CDCl3):
54.12, 55.40 (2 MeO); 112.99, 113.96 (2 CN); 115.96, 116.53 (C(4’), C(5’)); 116.93, 117.91 (C(8a’),
C(9a’)); 123.52, 124.25 (C(2’), C(7’)); 124.73 (br., 2 C(b), PiN); 131.81, 132.51, 132.85 (C(1’), C(3’),
C(6’), C(8’)); 135.20 (br., 2 C(c), PiN); 150.80, 152.87 (C(4a’), C(10a’)); 161.04, 163.61 (2 COO). The
signals of the phthalimido CO(N) and C(a) atoms could not be detected because of a strong broadening.
ESI-MS: 589 (100, [M þ Na]þ), 540(8), 393(16), 377(48), 355(8), 327(8), 213(16).
Suitable crystals for the X-ray crystal-structure determination were obtained from CH2Cl2/hexane by
slow evaporation of the solvent.
Data of 11b (in a mixture with 11a). 1H-NMR (CDCl3): 3.40, 3.97 (2s, 2 MeO); 7.15 – 7.32, 7.40 – 7.56
(2m, HꢁC(2’ – 7’)); 7.70 – 7.95 (m, HꢁC(1’,8’), 2 HꢁC(c), PiN); 8.25, 8.53 (2d, J ¼ 9.6, 9.3, 2 HꢁC(b),
PiN). 13C-NMR (CDCl3): 54.14, 55.32 (2 MeO); 111.75, 114.37 (2 CN); 116.35, 116.79, 118.51 (C(4’),
C(5’), C(8a’), C(9a’)); 123.67, 124.10 (C(2’), C(7’)); 124.25, 124.67 (2 C(b), PiN); 131.30, 131.58, 131.73,
132.50 (C(2’), C(3’), C(6’), C(7’)); 135.21 (2 C(c), PiN); 152.10, 152.48 (C(4a’), C(10a’)); 162.46, 162.75
(2 COO). The signals of the phthalimido CO(N) and C(a) atoms could not be detected because of a
strong broadening. Probably, some signals overlapped with the signals of the main stereoisomer.

860
Helvetica Chimica Acta – Vol. 93 (2010)
Table. Crystallographic Data for Compounds 2a, 6, 10a, and 11a
2a
6
10a
11a
Crystallized from
Empirical formula
Formula weight
CH2Cl2/hexane
C25H19N3O8
489.44
CH2Cl2/hexane
C34H27N3O6S
605.66
CH2Cl2/hexane/benzene CH2Cl2/hexane
C31H24N4O8S · CH2Cl2
697.54
C29H18N4O7S
566.54
Crystal color, habit
colorless, prism
colorless, prism
colorless, prism
colorless, tablet
0.08 ꢂ 0.20 ꢂ 0.32
160(1)
Crystal dimensions [mm] 0.12 ꢂ 0.20 ꢂ 0.25 0.12 ꢂ 0.20 ꢂ 0.22 0.20 ꢂ 0.25 ꢂ 0.30
Temp. [K]
Crystal system
Space group
Z
160(1)
160(1)
monoclinic
P21/n
160(1)
triclinic
triclinic
triclinic
ꢀ
ꢀ
ꢀ
P1
P1
P1
2
4
2
2
Reflections for cell
determination
2q Range for cell
determination [8]
Unit cell parameters:
a [ꢅ]
b [ꢅ]
c [ꢅ]
a [8]
b [8]
6595
43412
57549
26942
4 – 60
4 – 55
4 – 55
4 – 55
9.0440(5)
10.7822(6)
12.9930(5)
90.033(3)
95.431(3)
111.387(2)
1173.6(1)
1.385
12.0555(2)
15.4406(4)
15.7613(4)
90
92.980(2)
90
2929.9(1)
1.373
0.163
9.4698(2)
10.4545(2)
17.2477(3)
106.768(1)
90.070(1)
104.585(1)
1577.23(5)
1.469
10.3444(2)
11.2660(3)
12.8331(3)
97.802(1)
113.232(1)
107.099(2)
1258.45(6)
1.495
g [8]
V [ꢅ3]
Dx [g cmꢁ3
]
m(MoKa) [mmꢁ1
Scan type
]
0.105
f and w
60
0.331
f and w
55
0.188
f and w
55
f and w
55
2q(max) [8]
Transmission factors
(min; max)
–
0.910; 0.980
0.784; 0.977
0.909; 0.986
Total reflections
measured
Symmetry-independent
reflections
29572
6817
62124
6722
37891
7211
29228
5756
Reflections with
I > 2s(I)
3941
4501
5441
4910
Reflections used in
refinement
6812
6720
7208
5753
Parameters refined;
restraints
328; 0
0.0592
401; 0
0.0487
468; 34
0.0470
372; 0
0.0398
Final R(F) (I > 2s(I)
reflections)
wR(F2) (all data)
Weighting parameters
(a; b)a)
0.1656
0.0796; 0.021
0.1225
0.0568; 0.7841
0.1278
0.0610; 0.7728
0.1031
0.0469; 0.6911
Goodness-of-fit
Secondary extinction
coefficient
1.035
–
1.039
0.0026(6)
1.038
0.006(2)
1.028
–
Final Dmax/s
D1 (max; min) [e ꢅꢁ3
0.010
0.34; ꢁ 0.35
0.001
0.26; ꢁ 0.36
0.001
0.52; ꢁ 0.48
0.001
0.30; ꢁ 0.33
]
a) wꢁ1 ¼ s2(F2o ) þ (aP)2 þ bP, where P ¼ (Fo2 þ 2F2c )/3.

Helvetica Chimica Acta – Vol. 93 (2010)
861
Elemental analysis for the mixture of 11a and 11b (ca. 2 :1). Anal. calc. for C29H18N4O7S (566.54): C
61.48, H 3.20, N 9.89, S 5.66; found: C 61.30, H 3.47, N 9.62, S 5.55.
5. X-Ray Crystal-Structure Determination of 2a, 6, 10a, and 11a (Table and Figs. 1 – 4)2). All
measurements were performed on a Nonius KappaCCD diffractometer [28] using graphite-monochro-
mated MoKa radiation (l 0.71073 ꢅ) and an Oxford Cryosystems Cryostream 700 cooler. The data
collection and refinement parameters are given in the Table, and views of the molecules are shown in
Figs. 1 – 4. Data reduction was performed with HKL Denzo and Scalepack [29]. The intensities were
corrected for Lorentz and polarization effects, and, in the cases of 6, 10a, and 11a, an absorption
correction based on the multi-scan method [30] was applied. Equivalent reflections were merged. The
structures were solved by direct methods using SIR92 [31], which revealed the positions of all non-H-
atoms. In the case of 10a, the asymmetric unit contains one molecule of 10a plus one molecule of CH2Cl2.
The CH2Cl2 molecule is disordered. Two sets of overlapping positions were defined for the atoms of
CH2Cl2, and the site occupation factor of the major position refined to 0.509(8). One of the ester groups
in 10a is disordered through a ca. 1808 rotation of the parent CꢁC bond. This manifests itself in two
positions being detected for the terminal Me group. These two positions were included in the model, and
the site occupation factor of the major position refined to 0.510(6). Similarity restraints were applied to
the chemically equivalent bond lengths and angles involving all disordered atoms. Neighboring atoms
within and between each conformation of the disordered CH2Cl2 molecule were restrained to have
similar atomic displacement parameters. The non-H-atoms were refined anisotropically. All of the H-
atoms in all of the structures were placed in geometrically calculated positions and refined using a riding
model where each H-atom was assigned a fixed isotropic displacement parameter with a value equal to
1.2 Ueq of its parent C-atom (1.5 Ueq for Me groups). The refinement of each structure was carried out on
F2 using full-matrix least-squares procedures, which minimized the function Sw(Fo2 ꢁ F2c )2. Corrections
for secondary extinction were applied in the cases of 6, 10a, and 11a. In the cases of 2a, 6, 10a, and 11a,
five, two, three, and three reflections, resp., whose intensities were considered to be extreme outliers,
were omitted from the final refinement. Neutral atom scattering factors for non-H-atoms were taken
from [32a], and the scattering factors for H-atoms were taken from [33]. Anomalous dispersion effects
were included in Fc [34]; the values for f’ and f’’ were those of [32b]. The values of the mass attenuation
coefficients were those of [32c]. All calculations were performed using the SHELXL97 [35] program.
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Org. Chem. 1966, 31, 3924.
[2] A. Padwa, L. Hamilton, Tetrahedron Lett. 1965, 6, 4363.
[3] J. W. Lown, in ꢃ1,3-Dipolar Cycloaddition Chemistryꢄ, Ed. A. Padwa, Wiley-Interscience, New York,
1983, Vol. 1, pp. 653 – 732.
[4] R. Huisgen, Angew. Chem., Int. Ed. 1963, 2, 565; R. Huisgen, in ꢃ1,3-Dipolar Cycloaddition
Chemistryꢄ, Ed. A. Padwa, Wiley-Interscience, New York, 1983, Vol. 1, pp. 1 – 176.
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Received December 22, 2009