Diastereoselective nitrilimine cycloaddition to the C=N bond of enantiopure 1,4-benzodiazepinones

Article abstract of DOI:10.1016/S0957-4166(02)00663-8

Enantiopure 1,4-benzodiazepin-4-one 1 and 1,4-benzodiazepin-6-ones 2 were reacted with hydrazonoyl chloride 8 in the presence of various basic agents. The diastereoselective 1,3-dipolar cycloaddition between the C=N double bond of 1 or 2 and the nitrilimi

Full text of DOI:10.1016/S0957-4166(02)00663-8

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2491–2495
Diastereoselective nitrilimine cycloaddition to the CꢀN bond of
enantiopure 1,4-benzodiazepinones
Giorgio Molteni,a,* Gianluigi Brogginib and Tullio Pilatic
aUniversita` degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, via Golgi 19, 20133 Milano, Italy
bUniversita` dell’Insubria, Dipartimento di Scienze Chimiche, Fisiche e Matematiche, via Lucini 3, 22100 Como, Italy
cConsiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
Received 27 September 2002; accepted 16 October 2002
Abstract—Enantiopure 1,4-benzodiazepin-4-one 1 and 1,4-benzodiazepin-6-ones 2 were reacted with hydrazonoyl chloride 8 in the
presence of various basic agents. The diastereoselective 1,3-dipolar cycloaddition between the CꢀN double bond of 1 or 2 and the
nitrilimine intermediate 9 gave the enantiopure [1,2,4]triazolo[4,3-a][1,4]benzo diazepinones 10–13. © 2002 Elsevier Science Ltd.
All rights reserved.
1. Introduction
2. Results and discussion
Due to the increasing demand for single-enantiomer
pharmaceuticals and bioactive molecules, organic
chemists are increasingly required to synthesise new
compounds in enantiopure form rather than as racemic
mixtures.1 For instance, stereoselective 1,3-dipolar
The synthesis of 1,4-benzodiazepin-5-ones 2 is outlined
in Scheme 1, while that of 1,4-benzodiazepin-4-one 1
was performed as previously reported by us.5 The key
step was the intramolecular cycloaddition of the
alkenylazides 6 via the labile 1,2,3-triazole cycloadduct
7, whose intervention and fate has been discussed else-
where.6a,12 With enantiopure 1 and 2 in hand, the
subsequent step was concerned with their behaviour as
dipolarophiles towards nitrilimine 9. The generation of
the latter 1,3-dipolar intermediate was accomplished in
situ by treatment of the corresponding hydrazonoyl
chloride 813 with a suitable base in the presence of 1 or
2 (Scheme 2). The reaction times and bases, as well as
product yields and diastereoisomeric ratio data, are
collected in Table 1. Simple silica gel column chro-
matography of the reaction mixtures allows the facile
separation of the pure diastereoisomeric cycloadducts
10–13. Structural assignments of the above cycload-
cycloaddition is now
a well-established synthetic
methodology which enables the construction of a vari-
ety of heterocyclic systems in enantiopure form.2,3
Recently, our group has published several papers
describing the diastereoselective cycloadditions of
nitrilimines4 and azides5 in both the inter- and
intramolecular version. It is known that the CꢀN bond
of some benzodiazepines6 and benzotriazepines7
behaves as a dipolarophile toward nitrilimines, but the
literature precedents are only concerned with racemic
syntheses.8 We present herein the first diastereoselective
cycloaddition of nitrilimine to the CꢀN bond of enan-
tiopure 1,4-benzodiazepin-4-one 1 and 1,4-benzodi-
azepin-6-ones 2 (Fig. 1). The resulting [1,2,4]triazolo-
[4,3-a][1,4]benzodiazepine skeleton, obtained in non-
racemic form, represents a valuable target due to its
close structural similarity with the anti-anxiety agents
Alprazolam,9 Estazolam10 and the anti-depressant
Flumazenil.11
* Corresponding author. E-mail: giorgio.molteni@unimi.it
Figure 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00663-8

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G. Molteni et al. / Tetrahedron: Asymmetry 13 (2002) 2491–2495
Scheme 1.
Scheme 2.
Table 1. Cycloadditions between nitrilimine 9 and enantiopure 1,4-benzodiazepinones 1 and 2 in dry chloroforma
Entry
Time (h)
Base (equiv.)
Products and yields (%)b
Product ratioc
12:13
10
11
12
13
10:11
1
1
1
2a
2a
2a
2b
2b
2b
24
22
3.5
48
16
6
24
16
7
Et3N (5)
22
36
40
–
–
–
–
–
–
22
36
40
–
–
–
–
–
–
–
–
–
39
53
59
33
58
69
–
–
–
19
22
19
22
12
6
50:50
50:50
50:50
–
–
–
–
–
–
–
–
–
(−)-Sparteine (3)
AcOAg (1.5)
Et3N (5)
(−)-Sparteine (3)
AcOAg (1.5)
Et3N (5)
67:33
70:30
75:25
75:25
83:17
92:8
(−)-Sparteine (3)
AcOAg (1.5)
a At room temperature.
b Isolation yields.
c Deduced from 1H NMR of reaction crude.

G. Molteni et al. / Tetrahedron: Asymmetry 13 (2002) 2491–2495
2493
the reaction site, and the incoming nitrilimine 9 can
hardly discriminate between the two diastereofaces of
the CꢀN fragment. On the other hand, the seven-mem-
bered ring of 2 can assume a boat-like conformation
which enables the chiral auxiliary to hide preferentially
one of the CꢀN diastereofaces from dipolar attack.
Finally, the diastereoselectivity of the cycloaddition was
scarcely influenced by the base (chiral or not).
ducts rely upon analytical and spectroscopic data. As
far as the H NMR spectra are concerned, one of the
1
cycloadducts arising from 1 show a marked upfield shift
in the resonance of the aromatic hydrogen in the 7-
position of the [1,2,4]triazolo[4,3-a][1,4]benzodiazepine
skeleton (5.98 l, see Section 3). This anomalous value
may be related to the shielding effect exerted by the
phenyl ring of the pendant chiral group, and depends
upon the absolute configuration of the stereogenic cen-
tre in the 3a-position, in close analogy with structurally
similar
pyrazolo[1,5-a][1,4]benzodiazepin-4-ones.4d
3. Experimental
Based on our previous results we were confident to
assign the R absolute configuration to the 3a-position
of diastereoisomer 10. Some useful considerations can
also be made about the hydrogen bonded to the stereo-
genic carbon of the chiral pendant group of 13a, which
resonates at 4.65 l. The typical chemical shift value for
such a proton encompasses the range between 6.13 and
6.38 l,4b as is found for major 12a. Careful inspection
of the Dreiding stereomodels indicated that the phenyl
group in the 3-position is responsible for the observed
shielding effect, which is possible provided that the
absolute configuration at the 3a-position is S. Similar
statements allowed us to assign tentatively the S abso-
lute configuration to the 3a-position of 13b. These
expectations were proved unambiguously by X-ray dif-
fractometric analysis of the major isomer 12a, which
shows the R configuration at the newly-formed stereo-
genic centre at C-3a (Fig. 2 and Section 3).
Melting points were determined with a Bu¨chi apparatus
in open tubes and are uncorrected. IR spectra were
recorded with a Perkin–Elmer 1725 X spectrophotome-
ter. Mass spectra were determined with a VG-70EQ
1
apparatus. H NMR spectra were taken with a Bruker
AC 300 or a Bruker AMX 300 instrument (in CDCl3
solutions at room temperature). Chemical shifts are
given as ppm from tetramethylsilane and J values are
given in Hz. Optical rotations were recorded on a
Perkin–Elmer model 241 polarimeter at the sodium D
line. Compounds 3a–5a4b are known in the literature.
3.1. Synthesis of N-[(2S)-3,3-dimethyl-2-butyl]-2-
nitrobenzamide, 3b
A solution of (2S)-3,3-dimethyl-2-aminobutane (5.00 g,
0.05 mol) in dry toluene (150 mL) was added with
K2CO3 (27.6 g, 0.20 mol). 2-Nitrobenzoyl chloride (9.25
g, 0.05 mol) in dry toluene (10 mL) was slowly added
and the mixture was heated under reflux for 4 h under
vigorous stirring. The undissolved material was filtered
off, and the solvent was evaporated under reduced
pressure. Crystallisation of the residue from hexane–
benzene gave analytically pure 3b (11.0 g, 88%); mp
153°C; [h]2D5=+3.3 (c 0.55, CHCl3); IR (Nujol): 1640
As can be inferred from Table 1, the stereoselectivity of
the cycloaddition varies from nil to good depending
upon: (i) the dipolarophile environment and (ii) the
steric bulk of the chiral auxiliary employed. Since the
conjugated imino–amide moiety of 1 is essentially pla-
nar, the 1-(S)-phenylethyl group is forced away from
1
cm−1; H NMR: l 0.91 (9H, s), 1.13 (3H, d, J=6.8),
4.03 (1H, dq, J=7.9, 6.8), 5.50 (1H, br d, J=7.9),
7.4–7.6 (3H, m), 7.99 (1H, dd, J=8.1, 1.0); MS: m/z
250 (M+). Anal. calcd for C13H18N2O3: C, 62.38; H,
7.25; N, 11.19. Found: C, 62.44; H, 7.28; N, 11.24%.
3.2. Synthesis of N-prop-2-enyl-N-[(2S)-3,3-dimethyl-2-
butyl]-2-nitrobenzamide, 4b
A solution of 3b (4.50 g, 18.0 mmol) in dry toluene (75
mL) was treated with K2CO3 (3.04 g, 22.0 mmol),
NaOH (2.80 g, 70.0 mmol) and Bu4N+HSO4 (0.85 g,
−
2.5 mmol). Allyl bromide (0.85 g, 27.0 mmol) in dry
toluene (7.0 mL) was added dropwise at 60°C. The
mixture was warmed to 75°C for 6 h, then the undis-
solved material was filtered off. The solvent was
removed under reduced pressure and the residue was
chromatographed on a silica gel column with light
petroleum–ethyl acetate 1:3 affording 4b as undistillable
oil (3.29 g, 63% yield); [h]2D5=+27 (c 1.60, CHCl3); IR
(Nujol): 1640 cm−1; H NMR: l 0.95 (9H, s), 1.14 (3H,
1
Figure 2. ORTEPIII plot of 12a at 90 K with the crystallo-
graphic numbering scheme. The carbomethoxy group bonded
to C6 is rotationally disordered around the C6ꢁC31 bond:
only the b conformation is reported. Ellipsoids at 50% proba-
bility level. H atoms not to scale.
d, J=7.0), 3.60–3.80 (2H, m), 4.90 (1H, q, J=7.0),
5.20–5.60 (3H, m), 7.3–7.7 (3H, m), 8.20 (1H, dd,
J=8.4, 1.0); MS: m/z 290 (M+). Anal. calcd for
C16H22N2O3: C, 66.18; H, 7.64; N, 9.65. Found: C,
66.21; H, 7.68; N, 9.70%.

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G. Molteni et al. / Tetrahedron: Asymmetry 13 (2002) 2491–2495
3.5. General procedure for the cycloaddition between
hydrazonoyl chloride 8 and enantiopure 1,4-benzodi-
azepinones 1 and 2
3.3. Synthesis of N-prop-2-enyl-N-[(2S)-3,3-dimethyl-2-
butyl]-2-amino benzamide, 5b
A solution of 4b (2.60 g, 10.0 mmol) in ethanol (16 mL)
was treated with iron powder (4.47 g, 80 mmol) and
20% aqueous acetic acid (5.0 mL), and then heated
under reflux for 5 h under vigorous stirring. The mix-
ture was extracted with ethyl acetate (100 mL) and the
extract filtered through Celite. The organic layer was
washed firstly with 5% aqueous sodium hydrogencar-
bonate (60 mL), then with water (2×50 mL), and dried
over sodium sulfate. Evaporation of the solvent gave 5b
as undistillable oil (2.31 g, 89% yield); [h]2D5=+56.3 (c
0.78, CHCl3); IR (Nujol): 3450, 3350, 3245, 1620 cm−1;
1H NMR: l 1.00 (9H, s), 1.30 (3H, d, J=7.3), 4.20–
4.40 (5H, m), 5.00–5.80 (3H, m), 6.6–7.1 (4H, m); MS:
m/z 260 (M+). Anal. calcd for C16H24N2O: C, 73.81; H,
9.29; N, 10.76. Found: C, 73.77; H, 9.31; N, 9.34%.
A solution of 1 (1.36 g, 6.0 mmol) and 2 (5.0 mmol) in
dry dichloromethane (60 mL) was treated with base (see
Table 1) under stirring at room temperature for the
time indicated in Table 1. The undissolved material was
filtered off, the solvent was removed under reduced
pressure and the residue was chromatographed on a
silica gel column with ethyl acetate–hexane–
dichloromethane 12:4:1. First fractions contained
cycloadduct 10 or major 12, further elution gave
cycloadduct 11 or minor 13 (see Table 1).
Compound 10: mp 185°C (from diisopropyl ether);
[h]2D5=+79 (c 0.06, CHCl3); IR (Nujol): 1730, 1640
1
cm−1; H NMR (CDCl3): l 1.44 (3H, d, J=7.0), 1.57
(3H, s), 2.33 (3H, s), 3.70 (1H, d, J=14.7), 3.75 (3H, s),
4.58 (1H, d, J=14.7), 5.98 (1H, dd, J=8.1, 1.1), 6.08
(1H, q, J=7.0), 6.93 (1H, dd, J=8.1, 7.9), 7.1–7.5
(11H, m); 13C NMR (CDCl3): l 13.98 (q), 17.74 (q),
20.85 (q), 43.77 (t), 52.22 (d), 53.67 (q), 90.32 (s),
121.0–129.7, 133.68 (s), 137.36 (s), 139.51 (s), 168.56 (s),
173.77 (s); MS: m/z 468 (M+). Anal. calcd for
C28H28N4O3: C, 71.77; H, 6.02; N, 11.96. Found: C,
71.81; H, 6.05; N, 12.02%.
3.4. Synthesis of 2-methyl-4-[(S)-1-phenylethyl]-1,4-ben-
zodiazepin-5(3H)-one, 2a and 2-methyl-4-[(2S)-2,3,3-
trimethyl-2-butyl]-1,4-benzodiazepin-5(3H)-one, 2b
A solution of 5a or 5b (8.0 mmol) in 6 M aqueous
hydrochloric acid (6.0 mL) and acetic acid (3.0 mL) was
treated with sodium nitrite (1.10 g, 16.0 mmol) under
stirring and cooling at 0°C. After 30 min, the mixture
was treated with cold diethyl ether (35 mL) and sodium
azide (2.60 g, 0.04 mol) was added portionwise under
vigorous stirring and ice-cooling. After 1 h, the organic
layer was separated, washed with 5% aqueous sodium
hydrogencarbonate (25 mL), then with water (50 mL),
and dried over sodium sulfate. Evaporation of the
solvent gave crude 6a and 6b as brown oily residues,
which were used without further purification: 6a (2.52
g, 97%), IR (neat): 2120, 1660 cm−1; 6b (2.20 g, 96%) IR
(neat): 2130, 1650 cm−1.
Compound 11: mp 125°C (from diisopropyl ether);
[h]2D5=+7 (c 0.53, CHCl3); IR (Nujol): 1730, 1660 cm−1;
1H NMR (CDCl3): l 1.42 (3H, d, J=7.2), 1.62 (3H, s),
2.37 (3H, s), 3.68 (1H, d, J=15.0), 3.75 (3H, s), 4.38
(1H, d, J=15.0), 5.84 (1H, q, J=7.0), 7.0–7.4 (13H, m);
13C NMR (CDCl3): l 14.16 (q), 18.21 (q), 20.68 (q),
43.60 (t), 51.91 (d), 54.16 (q), 90.13 (s), 121.0–129.0,
133.27 (s), 137.20 (s), 140.11 (s), 167.59 (s), 172.98 (s);
MS: m/z 468 (M+). Anal. calcd for C28H28N4O3: C,
71.77; H, 6.02; N, 11.96. Found: C, 71.74; H, 5.99; N,
12.01%.
Compound 12a: mp 195°C (from diisopropyl ether);
[h]2D5=−6.3 (c 0.25, CHCl3); IR (Nujol): 1730, 1640
Crude 6a or 6b (7.8 mmol) were dissolved in toluene (30
mL) and then heated under reflux for 1 h. The solvent
was evaporated and the residue was crystallised from
diisopropyl ether affording pure 2a or 2b.
1
cm−1; H NMR (CDCl3): l 1.38 (3H, d, J=7.2), 1.43
(3H, s), 2.26 (3H, s), 2.86 (1H, d, J=16.0), 3.47 (1H, d,
J=16.0), 3.65 (3H, s), 6.13 (1H, q, J=7.2), 7.0–7.8
(13H, m); 13C NMR (CDCl3): l 17.13 (q), 20.43 (q),
22.35 (q), 50.84 (t), 52.06 (d), 52.32 (q), 92.75 (s), 115.17
(s), 127.1–131.9, 134.68 (s), 136.46 (s), 139.39 (s), 140.26
(s), 169.63 (s); MS: m/z 468 (M+). Anal. calcd for
C28H28N4O3: C, 71.77; H, 6.02; N, 11.96. Found: C,
71.73; H, 5.96; N, 11.94%.
Compound 2a: 1.52 g, 70%; mp 118°C; [h]2D5=−475 (c
1
0.50, CHCl3); IR (Nujol): 1635 cm−1; H NMR: l 1.50
(3H, d, J=7.2), 1.71 (3H, s), 3.25 (1H, d, J=14.5), 3.34
(1H, d, J=14.5), 6.19 (1H, q, J=7.2), 7.1–7.3 (7H, m),
7.42 (1H, dd, J=8.4, 1.3), 8.03 (1H, dd, J=8.4, 8.0);
MS: m/z 278 (M+). Anal. calcd for C18H18N2O: C,
77.67; H, 6.52; N, 10.06. Found: C, 77.62; H, 6.55; N,
10.10%.
Compound 13a: mp 125°C (from diisopropyl ether);
[h]2D5=+78 (c 0.45, CHCl3); IR (Nujol): 1730, 1645
1
cm−1; H NMR (CDCl3): l 1.57 (3H, s), 1.75 (3H, d,
Compound 2b: 1.41 g, 70%; mp 178°C; [h]2D5=−730 (c
J=7.0), 2.28 (3H, s), 3.35 (1H, d, J=16.6), 3.73 (3H, s),
3.80 (1H, d, J=16.6), 4.65 (1H, q, J=7.0), 6.9–7.8
(13H, m); 13C NMR (CDCl3): l 17.28 (q), 20.48 (q),
22.80 (q), 50.21 (t), 51.96 (d), 52.37 (q), 92.68 (s), 115.77
(s), 127.3–131.6, 134.59 (s), 136.80 (s), 138.91 (s), 140.36
(s), 168.38 (s); MS: m/z 468 (M+). Anal. calcd for
C28H28N4O3: C, 71.77; H, 6.02; N, 11.96. Found: C,
71.74; H, 6.05; N, 12.02%.
1
0.50, CHCl3); IR (Nujol): 1630 cm−1; H NMR: l 1.00
(9H, s), 1.30 (3H, d, J=7.5), 2.40 (3H, s), 3.50 (1H, d,
J=12.3), 3.75 (1H, d, J=12.3), 4.90 (1H, q, J=7.5),
7.15–7.25 (2H, m), 7.50 (1H, dd, J=8.3, 8.0), 7.96 (1H,
dd, J=8.3, 0.9); MS: m/z 258 (M+). Anal. calcd for
C16H22N2O: C, 74.38; H, 8.58; N, 10.84. Found: C,
74.34; H, 8.54; N, 10.76%.

G. Molteni et al. / Tetrahedron: Asymmetry 13 (2002) 2491–2495
2495
Compound 12b: mp 80°C (from diisopropyl ether); [h]2D5=
References
+125.5 (c 0.50, CHCl3); IR (Nujol): 1730, 1650 cm−1; 1H
NMR (CDCl3): l 0.85 (9H, s), 1.40 (3H, d, J=7.2), 1.65
(3H, s), 2.25 (3H, s), 2.54 (1H, q, J=7.2), 3.20 (1H, d,
J=15.8), 3.68 (3H, s), 3.75 (1H, d, J=15.8), 7.0–7.7 (8
H, m); 13C NMR (CDCl3): l 14.76 (q), 20.51 (q), 24.62
(q), 28.21 (q), 37.30 (s), 52.44 (q), 57.00 (t), 69.29 (d),
93.77 (s), 115.57 (s), 129.1–132.2, 130.01 (s), 134.86 (s),
138.22 (s), 139.81 (s), 140.48 (s), 158.25 (s), 168.24 (s);
MS: m/z 448 (M+). Anal. calcd for C26H32N4O3: C, 69.62;
H, 7.19; N, 12.49. Found: C, 69.58; H, 7.23; N, 12.54%.
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Compound 13b: mp 61°C (from diisopropyl ether); [h]2D51=
−18.6 (c 0.25, CHCl3); IR (Nujol): 1730, 1645 cm−1; H
NMR (CDCl3): l 0.83 (9H, s), 1.44 (3H, d, J=7.0), 1.64
(3H, s), 2.16 (1H, q, J=7.0), 2.30 (3H, s), 3.15 (1H, d,
J=15.5), 3.70 (3H, s), 3.94 (1H, d, J=15.5), 7.0–7.7 (8
H, m); 13C NMR (CDCl3): l 14.88 (q), 20.40 (q), 23.12
(q), 30.11 (q), 37.46 (s), 52.49 (q), 55.39 (t), 69.21 (d),
91.75 (s), 115.75 (s), 129.0–132.0, 129.89 (s), 133.532 (s),
138.63 (s), 139.11 (s), 140.328 (s), 159.69 (s), 169.86 (s);
MS: m/z 448 (M+). Anal. calcd for C26H32N4O3: C, 69.62;
H, 7.19; N, 12.49. Found: C, 69.66; H, 7.26; N, 12.54%.
3.6. Crystal data for compound 12a
C28H28N4O3, Fw=468.54, orthorhombic, space group
P212121, T=90 K, a=10.215(3), b=14.519(4),
c
3
,
,
16.098(4) A, V=2387.5(11) A , Z=4, Dcalcd=1.304 Mg
m−3, v (Mo Ka)=0.086 mm−1; crystal dimensions 0.35×
,
0.32×0.28 mm, u=0.71073 A (Mo Ka radiation, graphite
monochromator, Bruker SMART-APEX CCD diffrac-
tometer, equipped with KRIO-FLEX low temperature
device and software). Data collection: ꢀ and € scan
mode, 2q<55.00°; 16463 collected reflections, 3091
unique [2645 with Io>2|(Io)], merging R=0.0425. The
structure was solved by SIR-9214 and refined by
SHELXL-9715 by full-matrix least-squares based on Fo ,
2
with weights w=1/[|2(Fo)2+(0.0522P)2], where P=(Fo +
2
2
2Fc )/3. H atoms were refined with isotropic atomic
displacement parameters proportional to those of the
connected atoms. The carboxymethyl group was rota-
tionally disordered and it was modelled by two confor-
mations with ratio 0.649:0.351; the H atoms of the
disordered methyl were put in calculated position. The
final consistency index were R=0.0536 and Rw=0.0949
(0.0440 and 0.0916, respectively, for observed reflec-
tions), goodness-of-fit=0.993. The final map ranges
3
12. (a) Fusco, R.; Garanti, L.; Zecchi, G. J. Org. Chem.
1975, 40, 1906; (b) Bourgois, J.; Bourgois, M.; Texier,
F. Bull. Soc. Chim. Fr. 1978, 485.
13. El-Abadelah, M. M.; Hussein, A. Q.; Kamal, M. R.;
Al-Adhami, K. H. Heterocycles 1988, 27, 917.
14. Altomare, A.; Cascarano, G.; Giacovazzo, G.;
Guagliardi, A.; Burla, M. C.; Polidori, G.; Camalli, G.
J. Appl. Crystallogr. 1994, 27, 435.
,
between −0.18 and 0.27 e A . The absolute configuration
was determined on the base of known one at C15 (see
Fig. 2). Detailed crystallographic data were deposited as
CCDC 190381 with the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
Acknowledgements
15. Sheldrick, G. M. SHELX-97: Program for the Refine-
ment of Crystal Structures; University of Go¨ttingen,
Germany, 1997.
The authors thank MURST and CNR for financial
support.