Synthesis of 6- to 10-membered ring (E)- hydroxyiminohydroazaazoniabenzocycloalkenes derivative from cyclization of 2-nitromethylene-1-(ω-phenylalkyl)imidazolidine or 2-nitromethylene-1- (ω-phenylalkyl)hexahydropyrimidine in trifluoromethanesulfonic acid

Article abstract of DOI:10.1016/j.tet.2006.01.057

In trifluoromethanesulfonic acid, 2-nitromethylene-1-(ω-phenylalkyl) imidazolidine or 2-nitromethylene-1-(ω-phenylalkyl)hexahydropyrimidine derivatives undergo an intramolecular cyclization to afford (E)- hydroxyiminohydroazaazoniabenzocycloalkenes, in th

Full text of DOI:10.1016/j.tet.2006.01.057

Tetrahedron 62 (2006) 3320–3328
Synthesis of 6- to 10-membered ring
(E)-hydroxyiminohydroazaazoniabenzocycloalkenes
derivative from cyclization of
2-nitromethylene-1-(u-phenylalkyl)imidazolidine
or 2-nitromethylene-1-(u-phenylalkyl)hexahydropyrimidine
in trifluoromethanesulfonic acid
b
b
a
c
Jean-Marie Coustard,a, Yaya Soro, Sorho Siaka, Fante Bamba and Alain Cousson
*
´
a
` ´ ´
Laboratoire ‘Synthese et Reactivite des Substances Naturelles’, UMR 6514 40, Avenue du Recteur Pineau, F-86022 Poitiers, France
b
´ ´ `
Laboratoire des Procedes Industriels de Synthese et d’Environnement, Institut National Polytechnique
´ ˆ
¨
Felix Houphouet-Boigny, BP 991 Yamoussoukro, Cote d’Ivoire
c
´
Laboratoire Leon Brillouin-CEA Saclay, 91191 Gif-sur-Yvette Cedex, France
Received 8 December 2005; revised 11 January 2006; accepted 17 January 2006
Available online 13 February 2006
Abstract—In trifluoromethanesulfonic acid, 2-nitromethylene-1-(u-phenylalkyl)imidazolidine or 2-nitromethylene-1-(u-phenylalkyl)hexa-
hydropyrimidine derivatives undergo an intramolecular cyclization to afford (E)-hydroxyiminohydroazaazoniabenzocycloalkenes, in their
trifluoromethanesulfonate salt form. The reaction probably occurres via the formation of an electrophilic transient hydroxynitrilium ion (or O-
protonated nitrile oxide). The yields are generally good, except for the higher-membered ring derivatives.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
other biomolecules, particularly in regions bearing anionic
and hydrogen bonding groups such as those found in DNA.9
This kind of association plays a key role in their
physiological activity10 and explains why they are present
in many drugs.
Amidines have long been regarded as useful intermediates
in the synthesis of heterocyclic compounds,1 characteristic
structural feature of many natural substances2 and important
pharmacophore in the active ingredients of drugs.3,4
Because of these activities, substituted amidine-containing
compounds have found frequent application in medicinal
chemistry.5,6
From a structural point of view, amidines 1 have two
nitrogen atoms in the 1,3-position of an allylic system
(Fig. 1). This arrangement is particularly favorable for n-p
heteroallylic nitrogen conjugation, which confers a highly
basic character to the group. Because of this strong basic
character, they are easily N-protonated to give resonance-
stabilized amidinium cations with mesomeric formulas 2
and 37 or they form strong interactions with proteins8 and
Figure 1.
Numerous synthetic methods have been developed for the
preparation of amidines, the first of which is the classical
Pinner’s reaction, dating back to the 1800’s.11 Amidine-
containing compounds are generally prepared from nitriles,
amides (with the help of PCl5 or Et3OCBF4K or P2O5) or
thioamides involving highly acidic,12 alkaline13 or strongly
reducing conditions.14 For complex molecules with sensi-
tive functions, a mild method starting from nitriles and
N-acetylcysteine as a catalyst has also been described.15
Keywords: 2-Nitromethyleneimidazolidine derivatives; 2-Nitromethylene-
hexahydropyrimidine derivatives; Trifluoromethanesulfonic acid; Cyclic
hydroxyiminoamidines; Cyclization.
*
Corresponding author. Tel.: C33 549 454 100; fax: C33 549 453 501;
e-mail: jmcousta@univ-poitiers.fr
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.057

J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
3321
In previous papers, we reported the behavior and reactivity
of 1-arylamino-1-methylthio-2-nitroethene derivatives 4
(Fig. 2) and acyclic nitroketene S,S-acetals 5 in superacidic
media in HF–SbF5 and trifluoromethanesulfonic acid.16,17
S,N-acetals. Thus, nucleophilic substitution between
one molar equivalent of diamine 9 or 10 and 1,1-
bis(methylthio)-2-nitroethene 11 afforded the expected nitro-
ketene aminals, either in the imidazolidine series 12 (nZ1) or
hexahydropyrimidine series 13 (nZ2) with yields varying
from 33 to 78% (Table 1).
Compounds 12 and 13 were isolated by flash chromato-
graphy, followed by crystallization from a mixture of
dichloromethane–petroleum ether. These compounds were
characterized by NMR spectroscopy and HRMS.
Figure 2.
For the imidazoline series 12, a vinylic proton resonates in the
range dH 6.48–6.52 ppm, the nitromethylene carbon
]CH–NO2 at dC 96.4–96.6 ppm and the OC]C ethylene
carbon at dC 159.0–159.3 ppm. In the hexahydropyrimidine
series 13, the observed chemical shifts are similar for the
vinylic proton at dH 6.61–6.70 ppm and the nitromethylene
carbon: dC 97.8–98.6 ppm but somewhat different for the
ethylene carbon, which resonates at higher field due to a cycle
effect: dC 153.8–154.5 ppm.22
In this paper, we present a new method for the synthesis of
tricyclic (E)-hydroxyiminohydroazaazoniabenzocyclo-
alkene derivatives in their triflate salt forms, starting from
new cyclic nitroketene aminals, which were cyclized in
trifluoromethanesulfonic acid.
2. Results and discussion
2.1. Starting material
In organic solvent solution, these compounds exist as sole
isomers, as shown by a single set of signals in the 13C NMR
spectra. They are probably all (E)-isomers since this
conformation allows the formation of an intramolecular
hydrogen bond between the N–H and the –NO2 groups, as
previously reported for the 1-arylamino-1-methylthio-2-
nitroethenes 4.20
Firstly, the appropriate linear monosubstituted diamines 9 and
10 bearing a tethered phenyl group were prepared, by reacting
the corresponding 1-bromo-u-phenyl derivatives 6 with
excess 1,2-ethylenediamine 7 or 1,3-diaminopropane 8
(Scheme 1).
A potential synthon for the synthesis of nitroketene aminals
derivatives is 1,1-bis(methylthio)-2-nitroethene 11. In this
compound, both methylthio groups are easily substituted
by amino groups in mild conditions.18,19 Reactions with
aromatic20 or non-aromatic amines21 afford nitroketene
2.2. Reactions in trifluoromethanesulfonic acid
The reactions were carried out in trifluoromethanesulfonic
acid at 60 8C under nitrogen atmosphere (Scheme 2).
Scheme 1. Synthesis of imidazolidine and hexahydropyrimidine derivatives 12 and 13.
Table 1. Yields of imidazolidine 12a–d and hexahydropyrimidine 13a–d
Starting diamine
9a
9b
9c
9d
10a
10b
10c
10d
Product
Yield (%)
12a
78
12b
62
12c
33a
12d
56
13a
76
13b
64
13c
69
13d
82
a With 25% of unreacted 11.

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J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
Scheme 2. Preparation of cyclic hydroxyiminoamidine derivatives 14 and 15 from the corresponding imidazoline and hexahydropyrimidine 12 and 13,
respectively.
Table 2. Yields of triflate salts 14a–d and 15a–d
Starting compound
12a
12b
12c
12d
13a
13b
13c
13d
Triflate salt
Yield (%), isolated product
14a
62
14b
79
14c
89
14d
13
15a
90
15b
85
15c
72
15d
12
Figure 3. X-ray analysis of 14c and 15b.23
The molar ratio of trifluoromethanesulfonic acid/imidazo-
lidine 12 or hexahydropyrimidine 13 molar was 50:1. At the
end of the reaction, the acidic solution is poured into a
mixture of ice (15 g) and anhydrous Na2CO3 (6 g) and the
extraction is carried out promptly at approximately 0 8C
with dichloromethane–methanol (95/5). The reactions were
generally clean and the starting materials were fully
transformed after 24 h reaction time, with yields varying
from 12 to 90% (Table 2).
is that in the amidine group, the CN bond distance
between the central carbon and both nitrogen atoms are
˚
very similar (1.312/1.317 A for 14c and 1.335/1.325 for
15b). This observation is in agreement with the
delocalized character of the ‘double bond0. These bonds
are longer than in the localized CN double bond of the
˚
hydroxyimino group (1.291 and 1.289 A for 14c and 15b,
respectively).
The formation of compounds 14 and 15 may be explained
by a similar mechanism as reported for acyclic nitroketene
S,S-acetals 5 (Scheme 3).17
The structure of compounds 14 and 15 was determined by
NMR and was corroborated by X-ray crystallographic
analysis of 15b and 15c (Fig. 3).
In this mechanism, compounds 12 and 13 undergo multiple
protonation16 and loss of a molecule of water, leading to the
formation of transient conjugated hydroxynitrilium cations,
22 and 23, which immediately react with the tethered phenyl
ring by way of an electrophilic aromatic substitution
mechanism, to afford the observed cationic compounds 24
and 25.
Crystal data for 14c and 15d were recorded at room
temperature with a Nonius Kappa CDD difractometer
equipped with a graphite monochromator and X-ray tube
˚
with a Mo anticathode (lZ0.71069 A). The structure was
solved using direct methods24 and refined using least square
calculation.25
The X-ray analysis indicated that the hydroxyl group of
the formed hydroxyimino group adopts a cis configur-
ation relative to the aromatic ring. This assignment is in
agreement with previous observations16,17,26 and is also
as expected on a theoretical point of view27 from an
addition step on a triple bond. Another interesting feature
The formation of cationic compounds 24 and 25 occurs
through a rate-limiting step that requires heating at 60 8C.
This may be explained by the fact that (poly)protonation of
the starting molecule on both nitrogen atoms, slows down
the water elimination step. In agreement with this
assumption is the fact that with the less basic sulfur atom

J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
3323
Scheme 3. Suggested mechanism for the formation of 14 and 15.
in series 4 or 5, formation of the stable hydroxynitrilium
ions occurs even at low temperature.17,28
The influence of the imidazoline ring or hexahydro-
pyrimidine ring on the yield of this cyclization reaction is
not very clear-cut.
At the end of the reaction, even when the acidity was
quenched, compounds 14 and 15 were isolated as salts due
to the strong basicity of the amidine group.7
NMR spectroscopy shows a sole (E)-isomer for the seven to
nine-membered ring products 14a–c and 15a–c, but two sets
of signals are observed for the 10-membered ring products
14d and 15d. These two sets of signals can be due to either
(i) (E) and (Z) isomers or (ii) to a mixture of two
conformers, formation of which would occur due to
hampering of the flexing of the 10-membered ring by the
presence of both the phenyl ring and the imidazoline, or
hexahydropyrimidine, ring.30
In the imidazoline series, the yields of isolated
cyclization products 14a–c varies, depending on the size
of the formed ring; ranging from 62% for a seven-
membered ring (14a) to 89% for the nine-membered ring
(14c). As expected for reason of entropy, the yield in
intramolecular cyclization drops to 13% for the 10-
membered ring product 14d.29 The hexahydropyrimidine
series 15a–c follows the same pattern, with the yield
decreasing regularly from 90% (seven-membered ring
15a) to 72% (nine-membered ring 15c) and dropping to
12% in the 10-membered ring product 15d. In this case,
the formed hydroxynitrilium ion can also either react
(i) to afford degradation products or (ii) with triflate
anion to form the nucleophilic addition compound, as
previously observed in situ, with 1-amino-2-nitroethylene
derivatives, affording ions 26 or 27 that easily decom-
posed during the hydrolysis step of the reaction medium
(Scheme 4).28
3. Conclusion
The present study constitutes an extension of the use of
acyclic 1-arylalkyl-substituted-2-nitroethylene diamino-
acetals in the field of heterocyclic synthesis. Tricyclic
hydroxyiminohydroazaazoniabenzocycloalkene trifluoro-
methanesulfonate derivatives can be easily prepared from
2-nitromethylene-1-(phenylalkyl)imidazolidine or 2-nitro-
methylene-1-(phenylalkyl)hexahydropyrimidine deriva-
tives in trifluoromethanesulfonic acid. These derivatives
Scheme 4. Other suggested reactions for the formed hydroxynitrilium ions.

3324
J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
may be used in the field of natural products synthesis and
work is in progress in this field.
137.6 (ipso-C), 159.1 [OC]CH(NO2)]. HRMS for
C12H15N3O2 ([MC]): calcd 233.1164, found 233.1155.
HRMS for C12H15N2O ([MCKNO]): calcd 203.1184,
found 203.1181.
4. Experimental
4.2.2. 2-Nitromethylene-1-(3-phenylpropyl)imidazo-
lidine (12b). From N0-10-(3-phenylpropyl)ethane-1,2-
diamine (1.44 g, 8 mmol) and 1,1-bis(methylthio)-2-
nitroethene (1.76 g, 8 mmol) in refluxed acetonitrile
(25 mL) for 12 h. The desired compound 12b crystallized
as white crystals (1.25 g, 62%). Mp 117–118 8C (CH2Cl2/
petroleum ether). 1H NMR (CDCl3): dZ1.90 (q, JZ7.5 Hz,
2H, –CH2–CH2–CH2–), 2.63 (t, JZ7.5 Hz, 2H, –CH2-Ph),
3.12 (t, JZ7.4 Hz, 2H, –CH2–N!), 3.59 (m, 2H,
imidazolidine –CH2–N!), 3.70 (m, 2H, imidazolidine
–HN–CH2–), 6.48 (s, 1H, vinylic H), 7.16 (cd, JZ7.2 Hz,
2H, aromatic o-H), 7.20 (ct, JZ7.3 Hz, 1H, aromatic p-H),
7.29 (ct, JZ6.7 Hz, 2H, aromatic m-H), 8.59 (br s, 1H,
N–H). 13C NMR (CDCl3): dZ28.3 (CH2), 32.6 (CH2-Ph),
42.1 (–CH2–N!), 45.0 and 48.3 (imidazolidine CH2), 96.4
(]CH–NO2), 126.1, 128.0 and 128.4 (aromatic CH), 140.1
(ipso-C), 159.0 [OC]CH(NO2)]. HRMS for C13H17N3O2
([M%C]): calcd 247.13208, found 247.1334. HRMS for
C13H17N2O ([MKNO]C): calcd 217.1341, found 217.1335.
4.1. General remarks
Melting points were determined with a Bu¨chi Melting
point B545 apparatus using capillary tubes (temperature rate
2 8C/min) and were not corrected. A Brucker DPX 300
spectrometer, equipped with a low temperature probe, was
1
9
used for H, F and 13C NMR spectra recorded at 300.13,
282.37 and 75.47 MHz, respectively. NMR spectra were
recorded at room temperature and chemical shifts reported
relative to Me4Si or CFCl3 for fluorine. The reproducibility
of 13C NMR shift was about G0.05 ppm, depending on cell
and concentration. Chemical assignments were made using
DEPT135 technic and usual chemical shift assignments
rules. Electron-impact ionization (70 eV) mass spectra were
obtained with a Finnigan Incos 500 Instrument. High
Resolution Mass Spectrometry was performed by the
´
‘Centre Regional de Mesures Physiques de l’Ouest—
Universite de Rennes, France’. Flash chromatography was
´
achieved on silica gel (20–45 mm particle size). HPLC was
used to check the purity or to identify the various
compounds described below. A Waters 600 pump equipped
with a Rheodyne 7125 injector valve (20 mL loop) and an
Applied Biosystem 785A programmable or Waters 486 UV
detector at 254 nm, column 250!4 mm I.D., 5 mm
Spherisorb silica or equivalent, were used with eluent
CH3CN:H2O (with 1.5% AcOH) 70:30 and a 1 mL minK1
flow rate.
4.2.3. 2-Nitromethylene-1-(4-phenylbutyl)imidazolidine
(12c). From N0-10-(4-phenylbutyl)ethane-1,2-diamine
(2.41 g, 12.5 mmol) and 1,1-bis(methylthio)-2-nitroethene
(2.12 g, 12.8 mmol) in refluxed acetonitrile (25 mL) for
72 h. The resulting products were separated by flash
chromatography: unreacted 1,1-bis(methylthio)-2-
nitroethene (0.53 g, 25%) was first separated using
CH2Cl2 as eluent, then compound 12c (1.10 g, 33%) as
1
white crystals. Mp 96–97 8C (CH2Cl2/petroleum ether). H
Trifluoromethanesulfonic acid was purchased from across
and 1,1-bis(methylthio)-2-nitroethene from Lancaster and
were used without further purification. No attempt was
made to optimize the yields.
NMR (CDCl3): dZ1.60 (m, 4H, –CH2–CH2–), 2.63 (t, JZ
6.9 Hz, –CH2-Ph), 3.10 (t, JZ6.9 Hz, –CH2–N!), 3.58
(complex t, JappZ9.0 Hz, 2H, imidazolidine –CH2–N!),
3.71 (ct, JappZ9.0 Hz, 2H, imidazolidine –HN–CH2–), 6.52
(s, 1H, vinylic H), 7.12–7.22 (m, 3H, aromatic o-H and
p-H), 7.30 (m, 2H, aromatic m-H), 8.60 (br s, H, N–H). 13C
NMR (CDCl3): dZ26.6 (CH2), 28.4 (CH2), 35.4 (CH2-Ph),
42.3 (–CH2–N!), 45.6 and 48.5 (imidazolidine CH2), 96.6
(]CH–NO2), 126.1, 128.3 and 128.5 (aromatic CH), 141.4
(ipso-C), 159.3 [OC]CH(NO2)]. HRMS for C14H19N3O2
([MC]): calcd 261.1477, found 261.1482. HRMS for
C14H19N2O ([MCKNO]): calcd 231.1497, found
231.1507. HRMS for C14H19N2 ([MCKNO2]): calcd
215.1548, found 215.1545.
4.2. Starting material
4.2.1. 2-Nitromethylene-1-phenethylimidazolidine (12a).
Typical procedure. N0-10-Phenethylethane-1,2-diamine
(1.75 g, 10.7 mmol) and 1,1-bis(methylthio)-2-nitroethene
(1.76 g, 10.7 mmol) were heated at 60 8C in acetonitrile
(30 mL) for 14 h under N2. The advancement of the reaction
was checked by thin-layer chromatography on silica gel
deposited on aluminum sheet. The solution was concen-
trated under vacuum and the resulting residue was separated
by flash chromatography with CH2Cl2–EtOH (97/3) and
then crystallized from CH2Cl2/petroleum ether to afford
compound 12a as white crystals (1.92 g, 78%). Mp
99–98 8C (CH2Cl2/petroleum ether). 1H NMR (CDCl3):
dZ2.87 (t, JZ7.3 Hz, 2H, –CH2-Ph), 3.39 (t, JZ7.3 Hz,
2H, –CH2–N!), 3.46 (dd, JZ10.4, 1.2 Hz, 1H, imidazo-
lidine –CH2–N!), 3.48 (br d, JZ9.5 Hz, 1H, imidazolidine
–CH2–N!), 3.67 (d, JZ9.7 Hz, 1H, imidazolidine
–HN–CH2–), 3.70 (br d, JZ11.1 Hz, 1H, imidazolidine
–HN–CH2–), 6.54 (s, 1H, vinylic H), 7.10–7.25 (m, 3H,
aromatic o-H and p-H), 7.30–7.39 (m, 2H, aromatic m-H),
8.60 (br s, 1H, N–H). 13C NMR (CDCl3): dZ33.7 (CH2-
Ph), 42.4 (–CH2–N!), 47.2 and 49.1 (imidazolidine CH2),
96.4 (]CH–NO2), 127.0, 128.6 and 128.8 (aromatic CH),
4.2.4. 2-Nitromethylene-1-(5-phenylpentyl)imidazo-
lidine (12d). From N0-10-(4-phenylpentyl)ethane-1,2-di-
amine (2.21 g, 10.7 mmol) and 1,1-bis(methylthio)-2-
nitroethene (1.69 g, 10.2 mmol) at 50 8C in acetonitrile
(30 mL) for 23 h was obtained on cooling compound 12d
(1.58 g, 56%) as light white crystals. Mp 115.8 8C (CH2Cl2/
petroleum ether). 1H NMR (CDCl3): dZ1.33 (m, 2H,
–CH2–CH2–CH2–), 1.59–1.67 (m, 4H, –CH2–CH2–CH2–
CH2–), 2.62 (ct, JZ7.64, 7.49 Hz, 2H, –CH2-Ph), 3.09 (ct,
JZ7.49, 7.33 Hz, 2H, –CH2–N!), 3.61 (m, 2H, imidazo-
lidine –CH2–N!), 3.73 (m, 2H, imidazolidine –HN–CH2–),
6.52 (s, 1H, vinylic H), 7.15–7.21 (m, 3H, aromatic o-H and
p-H), 7.26–7.31 (m, 2H, aromatic m-H), 8.62 (br s, H, N–H).
13C NMR (CDCl3): dZ26.6 (CH2), 27.1 (CH2), 30.9 (CH2),

J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
3325
35.6 (CH2-Ph), 42.3 (–CH2–N!), 45.6 and 48.6 (imidazo-
lidine CH2), 96.6 (]CH–NO2), 125.9 and 128.4 (aromatic
CH), 141.9 (ipso-C), 159.3 [OC]CH(NO2)]. C15H21N3O2
(275.35): calcd C 65.49, H 7.63, N 15.34, found C 65.43, H
7.69, N 15.26.
2H, hexahydropyrimidine –CH2–N!), 3.38 (m, 2H,
hexahydropyrimidine –HN–CH2–), 6.62 (s, 1H, vinylic
H), 7.13–7.23 (m, 3H, aromatic o-H and p-H), 7.25–7.34 (m,
2H, aromatic m-H), 10.70 (br s, 1H, N–H). 13C NMR
(CDCl3): dZ20.0 (CH2), 26.8 (CH2), 28.2 (CH2), 35.2
(CH2-Ph), 37.6 (–CH2–N!), 46.7 and 50.9 (hexahydropyr-
imidine CH2), 97.9 (]CH–NO2), 125.8, 128.1 and 128.2
(aromatic CH), 141.2 (ipso-C), 153.8 [OC]CH(NO2)].
HRMS for C15H21N3O2 ([MC]): calcd 275.1634, found
275.1636. HRMS for C14H19N2O ([MCKNO]): calcd
245.1654, found 245.1652.
4.2.5. 2-Nitromethylene-1-phenethylhexahydropyrim-
idine (13a). Typical procedure. N0-10-Phenethylpropane-
1,3-diamine (1.27 g, 7.1 mmol) and 1,1-bis(methylthio)-2-
nitroethene (1.19 g, 7.2 mmol) were heated at 40 8C in
acetonitrile (30 mL) for 18 h under N2. The solution was
concentrated under vacuum and the resulting product was
purified by flash chromatography with CH2Cl2–EtOH (97/3)
and then crystallized from CH2Cl2/petroleum ether to afford
13a as light yellow crystals (1.33 g, 76%). Mp 113–114 8C
4.2.8. 2-Nitromethylene-1-(5-0phenypentyl)hexahydro-
pyrimidine (13d). From N0-1 -(5-phenylpentyl)propane-
1,3-diamine (1.0 g, 4.5 mmol) and 1,1-bis(methylthio)-2-
nitroethene (0.75 g, 4.5 mmol) at 55 8C in acetonitrile
(15 mL) for 17 h. Compound 13d (0.99 g, 82%) was
obtained as yellow crystals. Mp 112.8 8C (CH2Cl2/
petroleum ether). 1H NMR (CDCl3): dZ1.30 (m, 2H,
–CH2–), 1.62 (m, 4H, –CH2–CH2–CH2–CH2–), 2.01 (q, JZ
5.95 Hz, 2H, hexahydropyrimidine –CH2–), 2.62 (t, JZ
7.57 Hz, 2H, –CH2-Ph), 3.13 (dd, JZ7.87, 7.77 Hz, 2H,
–CH2–N!), 3.33 (ct, JappZ5.75 Hz, 2H, hexahydro-
pyrimidine –CH2–N!), 3.40 (m, 2H, hexahydropyrimidine
–HN–CH2–), 6.62 (s, 1H, vinylic-H), 7.15–7.22 (m, 3H,
aromatic o-H and p-H), 7.29–7.61 (m, 2H, aromatic m-H),
10.75 (br s, 1H, N–H). 13C NMR (CDCl3): dZ20.6 (CH2),
26.5 (CH2), 27.8 (CH2), 31.4 (CH2), 36.1 (CH2-Ph), 38.2
(–CH2–N!), 47.4 and 51.7 (hexahydropyrimidine CH2),
98.6 (]CH–NO2), 126.2 and 128.7 (aromatic CH), 142.3
(ipso-C), 154.4 [OC]CH(NO2)]. HRMS for C16H23N3O2
([MC]): calcd 289.1790, found 289.1797. HRMS for
C16H23N2O ([MCKNO]): calcd 259.1810, found
259.1802. HRMS for C16H23N2 ([MCKNO2]): calcd
243.1861, found 243.1863.
1
(CH2Cl2/petroleum ether). H NMR (CDCl3): dZ1.86 (q,
JZ8.8 Hz, 2H, hexahydropyrimidine –CH2–), 2.89 (t, JZ
7.2 Hz, 2H, –CH2-Ph), 3.13 (t, JZ5.8 Hz, 2H, –CH2–N!),
3.34 (dd, JZ5.6, 3.1 Hz, 2H, hexahydropyrimidine –CH2–
N!), 3.43 (t, JZ7.2 Hz, 2H, hexahydropyrimidine
–HN–CH2–), 6.70 (s, 1H, vinylic H), 7.16–7.23 (m, 2H,
aromatic o-H and p-H), 7.25–7.36 (m, 3H, 2 aromatic m-H
and aromatic o-H), 10.72 (br s, 1H, N–H). 13C NMR
(CDCl3): dZ19.7 (CH2), 33.7 (CH2-Ph), 37.5 (–CH2–N!),
47.4 and 52.5 (hexahydropyrimidine CH2), 97.8
[]CH(NO2)], 126.7, 128.4 and 128.5 (aromatic CH),
137.0 (ipso-C), 153.8 [OC]CH(NO2)]. HRMS for
C13H17N3O2 ([MC]): calcd 247.1321, found 247.1309.
HRMS for C13H17N2O ([MCKNO]): calcd 217.1341,
found 217.1356.
4.2.6. 2-Nitromethylene-1-(3-phenylpropyl)hexahydro-
pyrimidine (13b). From N0-10-(3-phenylpropyl)propane-
1,3-diamine (2.23 g, 11.6 mmol) and 1,1-bis(methylthio)-2-
nitroethene (1.99 g, 12 mmol) at 40 8C in acetonitrile
(30 mL) for 18 h. Compound 13b (1.95 g, 64%) was
obtained as light yellow crystals. Mp 126–127 8C
4.3. Cyclic compounds. Typical procedure
1
(CH2Cl2/petroleum ether). H NMR (CDCl3): dZ1.87 (m,
2H, hexahydropyrimidine –CH2–), 2.00 (m, 2H, CH2–CH2–
CH2), 2.62 (t, JZ7.6 Hz, 2H, –CH2-Ph), 3.16 (d, JZ8.0 Hz,
1H, –CH2–N!), 3.19 (d, JZ7.8 Hz, 1H, –CH2–N!), 3.30–
3.40 (m, 4H, hexahydropyrimidine –HN–CH2– and –CH2–
N!), 6.61 (s, 1H, vinylic H), 7.12–7.24 (m, 3H, aromatic o-
H and p-H), 7.26–7.32 (m, 2H, aromatic m-H), 10.70 (br s,
1H, N–H). 13C NMR (CDCl3): dZ20.6 (CH2), 29.2 (CH2),
33.1 (CH2-Ph), 38.2 (–CH2–N!), 47.3 and 51.2 (hexa-
hydropyrimidine CH2), 98.5 []CH(NO2)], 126.7, 128.5
and 129.0 (aromatic CH), 140.6 (ipso-C), 154.5 [O
C]CH(NO2)]. HRMS for C14H19N3O2 ([MC]): calcd
261.1477, found 261.1480. HRMS for C14H19N2O
([MCKNO]): calcd 231.1497, found 231.1496. HRMS for
C14H19N2 ([MCKNO2]): calcd 215.1548, found 215.1537.
4.3.1. 4-[(E)-Hydroxyimino]-2,4,9,10-tetrahydro-1H-
10a-aza-3-azoniabenzo[f]azulene trifluoromethanesulfo-
nate (14a). 2-Nitroethylene-1-(4-phenethyl)imidazolidine
(233 mg, 1.0 mmol) was dissolved in trifluoromethane-
sulfonic acid (4.4 mL, 50 mmol). The solution was heated to
60 8C for 24 h. After cooling, the solution was poured over
ice (15 g) and anhydrous Na2CO3 (6.0 g, 56.6 mmol). The
aqueous phase was quickly extracted with CH2Cl2–MeOH
(95/5) (4!50 mL). The organic phases were dried over
MgSO4 and the solvent evaporated under reduced pressure.
The resulting product was purified by flash chromatography
with CH2Cl2–MeOH (95/5) and then crystallized from
CH2Cl2/petroleum ether to afford 14a (227 mg, 62%) as
white crystals. Mp 191–192 8C (CH2Cl2/petroleum). 1H
NMR (CDCl3-[d6]DMSO): dZ3.13 (s, 2H, –CH2-Ph), 3.59
(br s, 2H, –CH2–N!), 3.83 (t, JZ10.8 Hz, 2H, imidazo-
lidine –CH2–N!), 4.05 (t, JZ10.5 Hz, 2H, imidazolidine
–CH2–N]), 7.41 (m, 3H, aromatic H), 7.52 (d, JZ7.5 Hz,
1H, aromatic H), 9.87 (br s, 1H, ]NH–), 13.03 (br s, 1H, O
]N–OH). 13C NMR (CDCl3-[d6]DMSO): dZ31.6 (CH2-
4.2.7. 2-Nitromethylene-1-(4-phenylbutyl)hexahydro-
pyrimidine (13c). From N0-10-(4-phenylbutyl)propane-
1,3-diamine (3.63 g, 17.8 mmol) and 1,1-bis(methylthio)-
2-nitroethene (2.81 g, 17.0 mmol) at 52 8C in acetonitrile
(30 mL) for 15 h. Compound 13c (2.40 g, 69%) was
obtained as light yellow crystals. Mp 127–128 8C
Ph), 42.4 (CH2), 49.7 (CH2), 54.3 (CH2), 121.5 (q, JC1 F
Z
1
(CH2Cl2/petroleum ether). H NMR (CDCl3): dZ1.61 (m,
321 Hz, CF3SOK3 ), 127.6 and 128.6 (aromatic CH), 129.9
and 130.9 (aromatic CH), 132.0 (ipso-C), 137.6 (ipso-C),
142.2 (OC]N–H), 160.1 (OC]N–OH). 19F NMR
(282.37 MHz, CDCl3-[d6]DMSO): dZK78.40 (CF3SOK3 ).
4H, –CH2–CH2–), 1.98 (q, JZ5.9 Hz, 2H, hexahydro-
pyrimidine –CH2–), 2.63 (ct, JZ6.9 Hz, 2H, –CH2-Ph),
3.15 (ct, JZ7.3 Hz, 2H, –CH2–N!), 3.33 (t, JZ5.8 Hz,

3326
J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
HRMS for C12H13N3O ([MCKCF3SO3H]): calcd
215.1057, found 215.1070.
43.4* (CH2), 46.7*, 46.7 (CH2), 51.8*, 50.7 (CH2), 127.7 and
127.9* (aromatic CH), 131.0* and 131.5 (aromatic CH),
131.8, 131.7* (ipso-C), 144.2*, 142.6 (ipso-C), 145.0, 144.6*
(OC]N–H), 162.5, 163.8* (OC]N–OH) {* signals from
the second isomer}. 19F NMR (282.37 MHz, [d6]acetone):
dZK78.47 (CF3SOK3 ). HRMS for C15H18N3 ([MCKCF3-
SO3H–OH]): calcd 240.1501, found 240.1494.
4.3.2. 11-[(E)-Hydroxyimino]-2,3,4,5,6,11-hexahydro-
3a-aza-1-azoniabenzo[a]cyclopenta[d]cyclooctene tri-
fluoromethanesulfonate (14b). From 2-nitroethylene-1-
(4-phenylpropyl)imidazolidine (247 mg, 1.0 mmol) was
obtained cyclic compound as the triflate salt 14b (299 mg,
79%), white crystals. Mp 160.7 8C (CH2Cl2/petroleum). 1H
NMR ([d6]acetone): dZ1.86 (m, 2H, –CH2–CH2–CH2–),
2.68 (t, JZ6.5 Hz, 2H, –CH2-Ph), 3.18 (m, 2H, CH2–N!),
3.88 (t, JZ10.3 Hz, 2H, imidazolidine –CH2–N!), 4.26 (t,
JZ11.0 Hz, imidazolidine –CH2–N]), 7.26 (t, JZ7.5 Hz,
2H, aromatic H), 7.40 (t, JZ8.0 Hz, 2H, aromatic H), 9.11
(br s, 1H, ]N–H), 12.40 (vbs, 1H, O]N–OH). 13C NMR
([d6]acetone): dZ29.9 (CH2), 30.1 (CH2-Ph), 43.5 (CH2),
45.2 (CH2), 55.4 (CH2), 122.9 (q, JCFZ321 Hz, CF3SOK3 ),
128.5 and 128.8 (aromatic CH), 130.9 and 132.9 (aromatic
CH), 133.3 (ipso-C), 139.5 (ipso-C), 144.8 (OC]N–H),
162.9 (OC]N–OH). 19F NMR (282.37 MHz, [d6]acetone):
dZK77.29 (CF3SOK3 ). MS (70 eV); m/z (%): 229 (50)
[MCKCF3SO3H], 228 (70) [MCKCF3SO3H–H], 212 (25)
[MCKCF3SO3H–OH], 184 (20), 69 (100). HRMS for
C13H15N3O ([MCKCF3SO3H]): calcd 229.1215, found
229.1205.
4.3.5. 5-[(E)-Hydroxyimino]-1,2,3,5,10,11-hexahydro-
11a-aza-4-azoniadibenzo[a,d]cycloheptene trifluoro-
methanesulfonate (15a). From 2-nitroethylene-1-(4-phen-
ethyl) hexahydropyrimidine (247 mg, 1.0 mmol) was
obtained compound 15a (342 mg, 90%) as white crystals.
Mp 193–195 8C (CH2Cl2/petroleum). 1H NMR ([d6]-
acetone): dZ2.23 (q, JZ5.8 Hz, 2H, hexahydropyrimidine
–CH2–), 3.33 (t, JZ5.6 Hz, 2H, CH2-Ph), 3.62 (t, JZ
5.5 Hz, –CH2–N!), 3.88 (t, JZ5.7 Hz, 2H, hexahydro-
pyrimidine CH2–N!), 4.03 (t, JZ5.6 Hz, 2H, hexahydro-
pyrimidine CH2–N]), 7.34 (dt, JZ7.4, 1.5 Hz, 1H,
aromatic H), 7.37 (dd, JZ7.0, 1.4 Hz, 1H, aromatic H),
7.45 (dt, JZ7.4, 1.4 Hz, 1H, aromatic H), 7.71 (dd, JZ7.8,
1.4 Hz, 1H, aromatic H), 9.42 (br s, 1H, ]N–H), 12.14 (br
s, 1H, ]N–OH). 13C NMR ([d6]acetone): dZ20.6 (CH2),
32.6 (CH2-Ph), 40.3 (CH2), 48.8 (CH2), 53.0 (CH2), 122.8
(q, J1CFZ321 Hz, CF3SOK3 ), 127.7 and 127.7 (aromatic
CH), 131.9 and 132.3 (aromatic CH), 132.5 (ipso-C), 138.3
(ipso-C), 148.0 (OC]N–H), 159.7 (OC]N–OH). 19F
NMR (282.37 MHz, [d6]acetone): dZK79.56 (CF3SOK3 ).
MS (70 eV); m/z (%): 229 (35) [MCKCF3SO3H], 228 (70)
[MCKCF3SO3H–H], 213 (55), 212 (100) [MCKCF3SO3-
H–OH], 184 (80). HRMS for C13H15N3O ([MCK
CF3SO3H]): calcd 229.1215, found 229.1210.
4.3.3. 12-[(E)-Hydroxyimino]-2,4,5,6,7,12-hexahydro-
3H-3a-aza-1-azoniabenzo[a]cyclopenta[d]cyclononene
trifluoromethanesulfonate (14c). From 2-nitroethylene-1-
(4-phenylbutyl)imidazolidine (261 mg, 1.0 mmol) was
obtained compound 14c (351 mg, 89%) as white crystals.
1
Mp 197.5 8C (CH2Cl2/petroleum). H NMR ([d6]acetone):
dZ1.82 (m, 4H, –CH2–CH2–), 2.81 (br t, JZ6.3 Hz, 2H,
–CH2-Ph), 3.40 (br t, JZ5.5 Hz, 2H, CH2–N!), 4.12 (ddd,
JZ12.5, 2.50, 1.56 Hz, 2H, imidazolidine –CH2–N]), 4.30
(ddd, JZ12.5, 2.50, 1.56 Hz, 2H, imidazolidine –CH2–N!),
7.26–7.32 (m, 1H, aromatic H), 7.36–7.42 (m, 2H,
aromatic H), 7.44–7.48 (m, 1H, aromatic H), 10.92 (br s,
2H, ]N–H and O]N–OH). 13C NMR ([d6]acetone): dZ
25.4 (CH2), 27.6 (CH2), 33.6 (CH2-Ph), 44.7 (CH2), 45.8
(CH2), 53.4 (CH2), 123.0 (q, JCFZ321 Hz, CF3SOK3 ), 128.4
and 130.38 (aromatic CH), 130.41 and 132.1 (aromatic CH),
132.5 (ipso-C), 143.1 (ipso-C), 146.7 (OC]N–H), 163.7
(OC]N–OH). 19F NMR (282.37 MHz, [d6]acetone):
dZK79.28 (CF3SOK3 ). MS (70 eV); m/z (%): 243 (42)
[MCKCF3SO3H], 225 (98) [MCKCF3SO3H–OH], 197
(45), 116 (75) [C7H6CNC], 56 (100). HRMS for C14H15N3
([MCKCF3SO3H–OH]): calcd 225.1266, found 225.1256.
4.3.6. 12-[(E)-Hydroxyimino]-3,4,5,6,7,12-hexahydro-
2H-4a-aza-1-azoniadibenzo[a,d]cyclooctene trifluoro-
methanesulfonate (15b). From 2-nitroethylene-1-(4-
phenylpropyl)hexahydropyrimidine (261 mg, 1.0 mmol)
was obtained compound 15b (334 mg, 85%) as white
crystals. Mp 154–155 8C (acetone/petroleum ether). 1H
NMR ([d6]acetone): dZ2.04 (m, 2H, hexahydropyrimi-
dine –CH2–), 2.19 (q, JZ5.8 Hz, 2H, –CH2–CH2–CH2–),
2.87 (t, JZ6.1 Hz, –CH2-Ph), 3.64 (t, JZ5.6 Hz, –CH2–
N!), 3.69 (t, JZ5.3 Hz, 2H, hexahydropyrimidine
–CH2–N!), 3.84 (t, JZ5.6 Hz, 2H, hexahydropyrimidine
–CH2–N]), 7.34 (d, JZ7.6 Hz, 1H, aromatic H), 7.35
(dt, JZ7.6, 1.5 Hz, 1H, aromatic H), 7.45 (dt, JZ7.4,
1.5 Hz, 1H, aromatic H), 7.59 (d, JZ7.9 Hz, 1H,
aromatic H), 9.54 (br s, 1H, ]N–H), 12.10 (br s, 1H,
]N–OH). 13C NMR ([d6]acetone): dZ20.7 (CH2), 29.8
(CH2), 33.5 (CH2-Ph) (br and weak signal), 40.7 (CH2),
50.9 (CH2), 54.2 (CH2) (br and weak signal), 123.0 (q,
JCFZ321 Hz, CF3SOK3 ), 127.4 and 130.5 (aromatic CH),
130.6 and 130.8 (aromatic CH), 131.7 (ipso-C), 139.6
(ipso-C), 147.9 (OC]N–H), 158.2 (OC]N–OH). 19F
NMR (282.37 MHz, [d6]acetone): dZK81.27 (CF3SOK3 ).
MS (70 eV); m/z (%): 243 (45) [MCKCF3SO3H], 242
(87) [MCKCF3SO3H–H], 226 (30) [MCKCF3SO3-
H–OH], 98 (100). HRMS for C14H17N3O ([MCK
CF3SO3H]): calcd 243.1372, found 243.1368. Analysis:
C15H18F3N3SO4 (393.38): calcd C 46.89, H 4.78, N
10.49, S 8.19; found C 45.80, H 4.58, N 10.7, S 8.14.
4.3.4.
2-Hydroxyimino-7-aza-4-azoniatricyclo-
[11.4.0.0.3,7]heptadeca-1(17),3,13,15-tetraene trifluoro-
methanesulfonate (14d) From 2-nitromethylene-1-(5-
phenylpentyl)imidazolidine (276 mg, 1 mmol) was obtained
compound 14d (54 mg, 13%) as white crystals. Mp 149.1 8C
(CH2Cl2/petroleum). 1H NMR ([D6]acetone): dZ1.16
(massif, 2H, –CH2–CH2–CH2–), 1.64 (m, 2H, –CH2–CH2–
N!), 1.73 (m, 2H, Ph-CH2–CH2–), 2.56 (dd, JZ5.8 Hz, 2H,
–CH2-Ph), 3.40 (dd, JZ5.9 Hz, 2H, CH2–N!), 4.03 (m, 2H,
imidazolidine –CH2–N!), 4.10 (m, 2H, imidazolidine,
–CH2–N]), 7.23–7.32 (m, 2H, aromatic H), 7.34–7.40 (m,
1H, aromatic H), 7.53 (m, 1H, aromatic H). 13C NMR
([d6]acetone):dZ22.7*,21.8(CH2), 27.9, 25.8*(CH2), 30.6*,
30.4 (CH2), 31.2*, 32.6 (CH2-Ph), 34.7*, 34.2 (CH2), 43.9,

J.-M. Coustard et al. / Tetrahedron 62 (2006) 3320–3328
3327
2. Hida, T.; Tsubotani, S.; Funabashi, Y.; Ono, H.; Harada, S.
Bull. Chem. Soc. Jpn. 1993, 66, 863–869.
4.3.7. 13-[(E)-Hydroxyimino]-2,3,4,5,6,7,8,13-octahydro-
4a-aza-1-azoniadibenzo[a,d]cyclononene trifluoro-
methanesulfonate (15c). From 2-nitroethylene-1-(4-phenyl-
propyl)hexahydropyrimidine (275 mg, 1.0 mmol) was
obtained compound 15c (294 mg, 72%) as white crystals.
3. Buschi, C. A.; Pomilio, A. B. Phytochemistry 1987, 26,
863–865.
4. De la Rosa, R.; Martinez-Barraza, V.; Burgos, C.; Alvarez-
Builla, J. Tetrahedron Lett. 2000, 41, 5837–5840.
5. Naka, M.; Nanbu, T.; Kobayashi, K.; Kamanaka, Y.;
Komeno, M.; Yanasa, R.; Fukutomi, T.; Fujimura, S.;
Seo, N. G.; Fujiwara, N.; Ohuchida, S.; Suzuki, K.;
Kondo, K.; Taniguchi, N. Biochem. Biophys. Res.
Commun. 2000, 270, 663–667.
1
Mp 182.9 8C (CH2Cl2/petroleum). H NMR ([d6]acetone):
dZ1.77 (br s, 4H, –CH2–CH2–), 2.28 (quintuplet, JZ
6.0 Hz, 2H, hexahydropyrimidine –CH2–), 2.87 (m, 2H,
–CH2-Ph), 3.72 (br t, JZ4.5 Hz, 2H, CH2–N!), 3.87 (m,
4H, hexahydropyrimidine CH2–N! and –CH2–N]), 7.35–
7.45 (m, 2H, aromatic H), 7.45–7.55 (m, 2H, aromatic H),
8.56 (br s, 1H, ]N–H), 10.57 (br s, 1H, ]N–OH). 13C
NMR ([d6]acetone): dZ19.6 (CH2), 26.4 (CH2), 27.6
(CH2), 29.1 (CH2-Ph), 39.8 (CH2), 48.4 (CH2), 50.4
(CH2), 122.1 (q, JCFZ321 Hz, CF3SOK3 ), 127.5 and 129.1
(aromatic CH), 130.6 and 130.9 (aromatic CH), 131.4 (ipso-
C), 141.9 (ipso-C), 148.4 (OC]N–H), 158.2 (O
C]N–OH). 19F NMR (282.37 MHz, [d6]acetone): dZK
74.14 (CF3SOK3 ). MS (70 eV); m/z (%): 257 (8) [MCK
CF3SO3H], 240 (75) [MCKCF3SO3H–OH], 116 (80), 98
(100). HRMS for C15H19N3O ([MCKCF3SO3H]): calcd
257.1528, found 257.1547. HRMS for C15H18N3 ([MCK
CF3SO3H–OH]): calcd 240.1501, found 240.1494.
6. Tucker, J. A.; Clyton, T. L.; Chidester, C. G.; Schulz,
M. W.; Harrington, L. E.; Conrad, S. J.; Yagi, Y.; Oien,
N. L.; Yurek, D.; Kuo, M.-S. Bioorg. Med. Chem. 2000,
8, 601–615.
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7. Hafelinger, G.; Kuske, F. K. H. In The Chemistry of Amidine
and Imidate; Patai, S., Rappoport, Z., Eds.; Wiley: New York,
1991; pp 1–93; and references cited therein.
8. (a) Wendt, M. D.; Rockway, T. W.; Geyer, A.; McClellan, W.;
Weitzberg, M.; Zhao, X.; Mantei, R.; Nienaber, V. L.; Stewart,
K.; Klinghofer, V.; Giranda, V. L. J. Med. Chem. 2004, 47,
303–324. (b) Kahan, F. M.; Kropp, H.; Sundelof, J. G.;
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1999, 40, 4847–4850.
4.3.8.
2-Hydroxyimino-8-aza-4-azoniatricyclo-
[12.4.0.0.3,8]octadeca-1(18),3,14,16-tetraene trifluoro-
methanesulfonate (15d) From 2-nitroethylene-1-(5-phe-
nylpentyl)hexahydropyrimidine (289 mg, 1 mmol) was
obtained compound 15d (50 mg, 12%) as white crystals.
Mp 201.2 8C (CH2Cl2/petroleum). 1H NMR ([d6]methanol):
dZ1.17 (m, 2H, –CH2–CH2–CH2–), 1.80–1.84 (massif,
4H, –CH2–CH2–CH2–), 2.08–2.10 (ct, JZ5.77 Hz, 2H,
hexahydropyrimidine, –CH2–), 2.70–2.75 (dd, JZ6.5 Hz,
2H, –CH2-Ph), 3.51–3.61 (m, 4H, –CH2–N! and hexahy-
dropyrimidine –CH2–N!), 3.90 (dd, JZ5.8 Hz, 2H, hexa-
hydropyrimidine –CH2–N]), 7.30–7.35 (m, 2H, aromatic
H), 7.37–7.44 (m, 1H, aromatic H), 7.95 (m, 1H, aromatic
H). 13C NMR ([d6]methanol) mixture of isomers: dZ
19.89*, 19.71 (CH2), 24.86, 24.86* (CH2), 28.19, 26.38*
(CH2), 33.47, 33.38* (CH2), 37.67, 37.67* (CH2-Ph), 40.46,
40.11* (CH2), 48.18*, 46.82 (CH2), 54.64*, 53.65 (CH2),
125.98, 123.93* and 127.83*, 127.64 (aromatic CH),
131.20, 130.92* and 131.47, 131.34* (aromatic CH),
132.84*, 131.83 (ipso-C), 145.95, 142.66* (ipso-C),
149.39*, 148.35 (OC]N–H), 159.26, 159.01* (O
C]N–OH) {* signals from the second isomer}. 19F NMR
(282.37 MHz, [d6]acetone): dZK77.00 (CF3SOK3 ). HRMS
for C16H20N3 ([MCKCF3SO3H–OH]): calcd 254.1657,
found 254.1672.
11. Pinner, A. Ber. 1885, 18, 2845–2852.
12. Stilz, H. U.; Jablonka, B.; Just, M.; Knoll, J.; Paulus, E. F.;
Zoller, G. J. Med. Chem. 1996, 39, 2118–2122.
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123–128.
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Sardharwala, T. A. Synth. Commun. 1996, 26,
4351–4367.
¨
15. Lange, U. E. W.; Schafer, B.; Baucke, D.; Buschmann, E.;
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16, 149–172.
20. Kearney, T.; Harris, P. A.; Jackson, A.; Joule, J. A. Synthesis
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Acknowledgements
23. (a) The atomic coordinates for 14c (deposition number CCDC
291924) and 15b (deposition number CCDC 291923) are
available upon request from the Cambridge Crystallographic
Data Centre, University Chemical Laboratory, Lensfield Road,
Cambridge CB2 1EW, UK. The crystallographic numbering
system differs from that used in the text; therefore, any request
should be accompanied by the full literature citation of this
paper. (b) The crystal representations in this paper were
produced using the Mercury 1.4.1 software from the
Cambridge Crystallographic Data Centre. http://www.ccdc.
cam.ac.uk/mercury/.
`
Thanks to CNRS for financial support and to ‘Ministere des
Affaires Etrangeres’ for fellowship fund for some of us.
´
`
References and notes
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3328
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¨ ¨
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