Diastereoselective synthesis of bis(3,5)pyrazolophanes by sequential inter- and intramolecular cycloadditions of homochiral nitrilimines

Article abstract of DOI:10.1016/S0957-4166(00)00132-4

Starting from ethyl (S)-lactate as the chiral unit, we have developed the synthesis of the enantiopure bis(3,5)pyrazolophanes 9 and 19 by means of sequential inter- and intramolecular cycloadditions of nitrilimine intermediates. Copyright (C) 2000 Elsevie

Full text of DOI:10.1016/S0957-4166(00)00132-4

Tetrahedron: Asymmetry 11 (2000) 1975±1983
Diastereoselective synthesis of bis(3,5)pyrazolophanes by
sequential inter- and intramolecular cycloadditions of
homochiral nitrilimines
Gianluigi Broggini,b Giorgio Moltenia,* and Tullio Pilatic
a
Á
Dipartimento di Chimica Organica e Industriale, Universita di Milano, Via Golgi 19, 20133 Milano, Italy
b
Á
Dipartimento di Scienze Chimiche, Fisiche e Matematiche, Universita dell'Insubria, via Lucini 3, 22100 Como, Italy
Consiglio Nazionale delle Ricerche, Centro per lo Studio delle Relazioni tra Struttura e Reattivita Chimica, via Golgi 19,
c
Á
20133 Milano, Italy
Received 16 March 2000; accepted 31 March 2000
Abstract
Starting from ethyl (S)-lactate as the chiral unit, we have developed the synthesis of the enantiopure
bis(3,5)pyrazolophanes 9 and 19 by means of sequential inter- and intramolecular cycloadditions of
nitrilimine intermediates. # 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
Intramolecular cycloadditions of homochiral nitrilimines have been recently brought to light
by our group as a fruitful tool in the synthesis of a variety of enantiopure pyrazole derivatives.1 4
On the other hand, the sequential inter- and intramolecular nitrilimine cycloaddition methodology
was successfully exploited by us in the synthesis of macrocyclic (1,5)- and (3,5)pyrazolophanes.5,6
Hence, we perceived the opportunity to join these research lines aimed at the ®rst synthesis of
enantiopure bis(3,5)pyrazolophanes, which may be of interest as non-conventional chiral ligands
towards metal cations.7 9 In doing so, we devised the cheaper ethyl (S)-lactate as the chiral
building block.
2. Results and discussion
Enantiopure hydrazonoyl chlorides 5 and 16, which were devised as the suitable precursors of
the desired nitrilimines 6 and 17, were synthesised through the sequences depicted in Schemes 1
* Corresponding author. E-mail: giorgio.molteni@unimi.it
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00132-4

1976
G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
and 2. The in situ generation of the dipolar intermediates was accomplished by treating a 0.02 M
solution of 5 or 15 with a twofold molar excess of silver carbonate in dry dioxane at room tem-
perature. Column chromatography followed by crystallisation gave the pure macrocyclic com-
pounds 9 or 19, in 66 and 32% yield, respectively. The intermediate hydrazonoyl chloride 18 was
also isolated, and its subsequent reaction with silver carbonate gave 19 in almost quantitative
yield.
Scheme 1.
Both products 9 and 19 were fully characterised by analytical and spectroscopic data. In the
case of 9, X-ray di€ractometric analysis elucidated unequivocally the absolute con®gurations of
the newly formed stereocentres in the 5-position of the pyrazolinic rings as (8S,18R) (Fig. 1).

G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
1977
Scheme 2.
Unfortunately, the macrocycle 19 was obtained as an amorphous solid which precluded its
di€ractometric analysis, and the absolute con®gurations of the newly formed stereocentres may
only be tentatively assigned by analogy with 9. Such analogy is reinforced by the lack of symmetry
as evidenced by the NMR data for 19. This means that the intermolecular cycloaddition leading
to the intermediate 7 is fully diastereoselective, although we are not able to determine whether the
formation of the (8S) or the (18R) stereocentre occurs in this step. This behaviour could arise
from the asymmetric induction due to the pre-existing stereocentres reinforced by some kind of
coordination between the silver ion and the ethereal oxygens of the reactants. Analogous
considerations could also be applied to the subsequent intramolecular cycloaddition leading from
8 to 9. The replacement of the allylic dipolarophile of 6 with the more reactive acrylic one of 17
(Scheme 2) did not produce better results since, despite a single diastereoisomer again being

1978
G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
Figure 1. ORTEPIII16 projection of 9, with the crystallographic numbering scheme. Ellipsoids at 50% probability
level. H atoms not to scale
obtained, the extent of the double cycloaddition process was far less e€ective. It may be that the
ester oxygens of 17 and 18 are less prone to coordination with the silver ion in comparison to the
ether oxygens of 6 and 7.
3. Experimental
Melting points were determined with a Buchi apparatus and are uncorrected. IR spectra were
recorded with a Perkin±Elmer 1725X spectrophotometer. Mass spectra were determined with a
1
VG-70EQ apparatus. H NMR and 13C NMR spectra were taken with a Bruker AC 300 or a
Bruker AMX 300 instrument (in CDCl3 solutions). Chemical shifts are given as ppm from tetra-
methylsilane and J values are given in hertz. Optical rotations were recorded on a Perkin±Elmer
Model 241 polarimeter at the sodium D line at 25ꢀC. Compound 1110 was prepared according to
the literature method.
3.1. Preparation of ethyl [2-(S)-allyloxy]propanoate 1
Ag2O (6.96 g, 30.0 mmol) was added portionwise, under vigorous stirring, to a solution of ethyl
2-(S)-lactate (3.50 g, 30.0 mmol) and allyl bromide (5.45 g, 45.0 mmol) in anhydrous diethyl ether
(60 mL) at room temperature. The mixture was re¯uxed for 2 h, then it was cooled and ®ltered
over Celite. The organic layer was dried over sodium sulfate, the solvent was evaporated and the
residue was distilled in vacuo giving 1 (4.30 g, 93%): bp 50±53ꢀC (15 mmHg); ‰ꢀŠD25=^70.7 (c 2.68,
1
MeOH); H NMR ꢁ: 1.23 (3H, t, J=6.7), 1.35 (3H, d, J=6.7), 3.41±3.97 (2H, m), 4.05 (1H, q,
J=6.7), 4.17 (2H, q, J=6.7), 5.12±6.12 (3H, m). IR (neat) 1750 cm^1. MS m/z: 158 (M+). Anal.
calcd for C8H14O3: C, 60.72; H, 8.92. Found: C, 60.77; H, 8.94.

G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
1979
3.2. Preparation of 2-(S)-allyloxypropan-1-ol 2
A solution of 1 (4.00 g, 25.3 mmol) in anhydrous diethyl ether (25 mL) was added dropwise to
a suspension of LiAlH4 (1.40 g, 35.4 mmol) in anhydrous diethyl ether (35 mL) at 0ꢀC under a
nitrogen atmosphere and vigorous stirring. The mixture was allowed to warm to room temperature;
after 2 h it was poured onto crushed ice (120 mL) and 2.5 M sodium hydroxide (60 mL) was
added. The bulky precipitate was ®ltered o€ over Celite and washed with diethyl ether (50 mL).
The organic layer was dried over sodium sulfate and evaporated. Distillation of the residue under
reduced pressure gave 2 (1.70 g, 58%): bp 78±80ꢀC (30 mmHg); ‰ꢀŠ2D5=+32.2 (c 0.50, MeOH); 1H
NMR ꢁ: 1.05 (3H, d, J=6.0), 2.46 (1H, br s), 3.42±3.49 (1H, m), 3.54±3.62 (2H, m), 3.96 (1H, dd,
J=13.0, 6.0), 4.10 (1H, dd, J=13.0, 6.0), 5.15±5.98 (3H, m). IR (neat) 3400 cm^1. MS m/z: 116
(M+). Anal. calcd for C6H12O2: C, 62.02; H, 10.42. Found: C, 62.10; H, 10.46.
3.3. Preparation of 2-(S)-allyloxypropyl 3-oxobutanoate 3
A solution of 2 (1.60 g, 13.8 mmol) in xylene (5 mL) was treated with 2,2,6-trimethyl-4H-1,3-
dioxin-4-one11 (1.90 g, 13.8 mmol). The mixture was re¯uxed for 1 h. Evaporation of the solvent
under reduced pressure and subsequent in vacuo distillation of the residue gave 3 (2.50 g, 92%):
bp 75±77ꢀC (0.1 mmHg); ‰ꢀŠ2D5=+8.6 (c 1.75, MeOH); 1H NMR ꢁ: 1.12 (3H, d, J=5.7), 2.25 (3H,
s), 3.45 (2H, s), 3.66±3.74 (1H, m), 4.02±4.17 (4H, m), 5.18±5.92 (3H, m). IR (neat) 1750,
1720 cm^1. MS m/z: 200 (M+). Anal. calcd for C10H16O4: C, 59.97; H, 8.06. Found: C, 60.03; H,
8.02.
3.4. Preparation of 2-(S)-allyloxypropyl 2-chloro-3-oxobutanoate 4
A solution of sulfuryl chloride (1.60 g, 12.0 mmol) in dry dichloromethane (8 mL) was slowly
added (1 h) to a solution of 3 (2.40 g, 12.0 mmol) in dry dichloromethane (15 mL), while keeping
the temperature in the range 0±5ꢀC. After 1 h at room temperature, dichloromethane (75 mL)
was added and the organic solution was washed with 5% aqueous sodium hydrogencarbonate (25
mL). The organic layer was then washed with water (100 mL) and dried over sodium sulfate.
Evaporation of the solvent gave 4 (2.80 g, 99%) as a thick oil not analytically pure: ‰ꢀŠ2D5=+8.8 (c
1
2.50, MeOH); H NMR ꢁ: 1.16 (3H, d, J=5.8), 2.36 (3H, s), 3.52±3.72 (1H, m), 3.95±4.20 (4H,
m), 4.78 (1H, s), 5.18±6.03 (3H, m). IR (neat) 1760, 1735 cm^1. MS m/z: 234 (M+).
3.5. Preparation of hydrazonoyl chloride 5
A cold aqueous solution of 4-chlorobenzenediazonium chloride (10.7 mmol) was added drop-
wise to a solution of 4 (2.50 g, 10.7 mmol) in tetrahydrofuran (70 mL) under vigorous stirring and
ice-cooling. During the addition, the pH was adjusted to 5 by adding sodium acetate. The mixture
was stirred for 2 h at 0ꢀC, then 2 h at room temperature. The solvent was partly removed under
reduced pressure and the resulting mixture was extracted with diethyl ether (100 mL). The organic
layer was washed ®rstly with 5% aqueous sodium hydrogencarbonate (25 mL), then with water
(100 mL), and dried over sodium sulfate. Evaporation of the solvent gave 5 (2.30 g, 65%): mp
25
ꢀ
1
87 C (from diisopropyl ether); ‰ꢀŠD =+16.6 (c 0.40, MeOH); H NMR ꢁ: 1.25 (3H, d, J=6.1),
3.78±3.89 (1H, m), 4.13 (2H, d, J=6.4), 4.22±4.35 (2H, m), 5.17 (1H, dd, J=10.8, 2.0), 5.31 (1H,
dd, J=16.5, 10.8), 5.93 (1H, dd, J=16.5, 10.8), 7.12±7.35 (4H, m), 8.32 (1H, br s). IR (nujol) 3270,

1980
G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
1730 cm^1. MS m/z: 330 (M+). Anal. calcd for C14H16Cl2N2O3: C, 50.90; H, 4.89; N, 8.49. Found:
C, 50.93; H, 4.93; N, 8.44.
3.6. Treatment of 5 with silver carbonate
A solution of 5 (2.00 g, 6.0 mmol) in dry dioxane (120 mL) was treated with silver carbonate
(3.31 g, 12.0 mmol) and stirred in the dark at room temperature for 30 h. The undissolved
material was ®ltered o€, the solvent was evaporated, and then the residue was chromatographed
on a silica gel column with diethyl ether:hexane (4:1). The ®rst fraction contained unreacted
5 (0.30 g, 15%). Further elution gave 9,19-bis-(4-chlorophenyl)-5,15-bis-(S)-methyl-8-(S)-18-
(R)-3,6,13,16-tetraoxa-9,10,19,20-tetraaza-tricyclo[16.2.1.18,11]docosa-1(20),10-diene-2,12-dione 9
(0.84 g, 66%): mp 121ꢀC (from diisopropyl ether±dichloromethane); ‰ꢀŠ2D5=^310.0 (c 0.16,
1
CHCl3); H NMR ꢁ: 1.06 (3H, d, J=6.7), 1.18 (3H, d, J=6.7), 3.19±3.38 (5H, m), 3.53 (1H, dd,
J=9.9, 2.8), 3.63±3.78 (3H, m), 3.82 (1H, dd, J=8.9, 3.4), 3.99 (1H, dd, J=11.8, 6.3), 4.08 (1H,
dd, J=12.0, 8.4), 4.18 (1H, dd, J=11.9, 2.4), 4.31 (1H, dd, J=11.7, 2.4), 4.66±4.75 (2H, m), 7.05±
7.30 (8H, m); 13C NMR ꢁ: 16.3 (q), 16.6 (q), 35.0 (t), 35.9 (t), 60.9 (d), 61.2 (d), 66.0 (t), 66.9 (t),
67.2 (t), 68.7 (t), 72.9 (d), 74.7 (d), 116.0±129.9, 139.7 (s), 140.3 (s), 141.1 (s), 141.2 (s), 162.4 (s),
162.6 (s). IR (nujol) 1725 cm^1. MS m/z: 588 (M+). Anal. calcd for C28H30Cl2N4O6: C, 57.13; H,
5.14; N, 9.52; Cl, 11.89. Found: C, 57.17; H, 5.11; N, 9.49; Cl, 11.95.
3.7. Preparation of 2-(S)-hydroxypropyl propenoate 13
Propenoyl chloride (2.30 g, 25.0 mmol) in anhydrous toluene (15 mL) was added dropwise to a
solution of 11 (4.00 g, 25.0 mmol) and triethylamine (5.10 g, 50.0 mmol) in anhydrous toluene (80
mL) under vigorous stirring and ice-cooling. The mixture was stirred for 1 h at 0ꢀC, then for 3 h
at room temperature. Water (200 mL) was added, the organic layer was dried over sodium sulfate
and the solvent was evaporated giving crude 2-(S)-(tetrahydropyranyl)oxypropyl propenoate 12
(3.2 g, 78%) as a thick oil which was used without any further puri®cation: 1H NMR ꢁ: 1.21 (3H,
d, J=6.3), 1.42±1.80 (6H, m), 3.96±4.11 (5H, m), 5.78 (1H, d, J=10.1), 6.08 (1H, dd, J=17.2,
10.1), 6.36 (1H, d, J=17.2). IR (neat) 1730 cm^1.
A solution of 12 (3.00 g, 14.0 mmol) in methanol (15 mL) and water (5 mL) was added with
37% aqueous hydrochloric acid (0.05 mL) and stirred for 0.5 h at room temperature. The mixture
was poured into water-ice (50 mL) and extracted with dichloromethane (2Â50 mL). The organic
layer was washed with 5% aqueous sodium hydrogencarbonate (25 mL), then with water (25
mL), and dried over sodium sulfate. The solvent was evaporated and subsequent in vacuo
distillation of the residue gave 13 (1.62 g, 90%): bp 50±52ꢀC (3.0 mmHg); ‰ꢀŠD25=+18.8 (c 1.96,
1
MeOH); H NMR ꢁ: 1.18 (3H, d, J=6.0), 2.25 (1H, br s), 3.96±4.14 (3H, m), 5.82 (1H, d,
J=10.4), 6.12 (1H, d, J=17.3, 10.4), 6.40 (1H, d, J=17.3). IR (neat) 3435, 1725 cm^1. MS m/z:
130 (M+). Anal. calcd for C6H10O3: C, 55.36; H, 7.75. Found: C, 55.40; H, 7.79.
3.8. Preparation of 2-(S)-(1,3-dioxobutyl)oxypropyl propenoate 14
A solution of 13 (0.75 g, 4.7 mmol) in xylene (5 mL) was treated with 2,2,6-trimethyl-4H-1,3-
dioxin-4-one11 (0.67 g, 4.7 mmol). The mixture was re¯uxed for 2 h. Evaporation of the solvent
under reduced pressure and subsequent in vacuo distillation of the residue gave 14 (0.90 g, 89%):
25
ꢀ
1
bp 70±72 C (0.1 mmHg); ‰ꢀŠD =+10.2 (c 1.40, CH3OH); H NMR ꢁ: 1.05 (3H, d, J=7.0), 2.00

G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
1981
(3H, s), 3.22 (2H, s), 3.80±4.20 (3H, m), 5.58 (1H, dd, J=8.3, 3.0), 5.96 (1H, dd, J=16.8, 3.0),
6.28 (1H, dd, J=16.8, 8.3). IR (neat) 1750, 1720 cm^1. MS m/z: 214 (M+). Anal. calcd for
C10H14O5: C, 56.05; H, 6.59. Found: C, 55.99; H, 6.56.
3.9. Preparation of 2-(S)-(1,3-dioxo-2-chlorobutyl)oxypropyl propenoate 15
A solution of sulfuryl chloride (0.60 g, 4.4 mmol) in dry dichloromethane (2 mL) was slowly
added (1 h) to a solution of 14 (0.96 g, 4.4 mmol) in dry dichloromethane (8 mL), while keeping
the temperature in the range 0±5ꢀC. After 1.5 h at room temperature, dichloromethane (50 mL)
was added and the organic solution was washed with 5% aqueous sodium hydrogencarbonate (30
mL). The organic layer was then washed with water (80 mL) and dried over sodium sulfate.
Evaporation of the solvent gave 15 (1.10 g, 99%) as a thick oil not analytically pure: ‰ꢀŠ2D5=+12.4
(c 1.50, MeOH); 1H NMR ꢁ: 1.25 (3H, d, J=6.5), 2.30 (3H, s), 4.10 (2H, d, J=6.7), 4.70 (1H, s),
4.70±4.76 (1H, m), 5.50 (1H, dd, J=8.5, 2.8), 6.00 (1H, dd, J=16.6, 2.8), 6.48 (1H, dd, J=16.6,
2.8). IR (neat) 1750, 1735, 1730 cm^1. MS m/z: 248 (M+).
3.10. Preparation of hydrazonoyl chloride 16
A cold aqueous solution of 4-chlorobenzene diazonium chloride (4.4 mmol) was added drop-
wise to a solution of 15 (1.08 g, 4.4 mmol) in tetrahydrofuran (20 mL) under vigorous stirring and
ice-cooling. During the addition, the pH was adjusted to 5 by adding sodium acetate. The mixture
was stirred for 1 h at 0ꢀC, then 0.5 h at room temperature. The solvent was partly removed under
reduced pressure and the resulting mixture was extracted with diethyl ether (80 mL). The organic
layer was washed ®rstly with 5% aqueous sodium hydrogencarbonate (25 mL), then with water
(100 mL), and dried over sodium sulfate. Evaporation of the solvent gave 16 (1.27 g, 84%): mp
25
ꢀ
1
94 C (from diisopropyl ether); ‰ꢀŠD =+93.4 (c 0.22, MeOH); H NMR ꢁ: 1.40 (3H, d, J=6.5),
4.26 (2H, d, J=6.7), 4.30±4.38 (1H, m), 5.85 (1H, dd, J=10.5, 1.4), 6.11 (1H, dd, J=17.2, 10.5),
6.64 (1H, dd, J=17.2, 1.4), 7.13±7.30 (4H, m), 8.33 (1H, br s). IR (nujol) 3250, 1720 cm^1. MS
m/z: 344 (M+). Anal. calcd for C14H14Cl2N2O4: C, 48.83; H, 4.10; N, 8.14. Found: C, 48.85; H,
4.07; N, 8.14.
3.11. Treatment of 16 with silver carbonate
A solution of 16 (1.20 g, 3.0 mmol) in dry dioxane (60 mL) was treated with silver carbonate
(1.66 g, 6.0 mmol) and stirred in the dark at room temperature for 48 h. The undissolved material
was ®ltered o€, the solvent was evaporated, and then the residue was chromatographed on a
silica gel column with diethylether:toluene (7:1). The ®rst fraction contained unreacted 16 (0.24 g,
20%). The second fraction contained 9,19-bis-(4-chlorophenyl)-4,14-bis-(S)-methyl-3,6,13,16-
tetraoxa-9,10,19,20-tetraaza-tricyclo[16.2.1.18,11]docosa-1(20),10-diene-2,7,12,17-dione 19 (0.18 g,
25
ꢀ
1
32%): mp 130 C (from diisopropyl ether±methanol); ‰ꢀŠD =^424.4 (c 0.20, CHCl3); H NMR ꢁ:
1.25 (6H, d, J=6.4), 3.43 (2H, dd, J=18.3, 13.2), 3.59 (2H, dd, J=18.3, 4.8), 3.82 (2H, dd,
J=12.0, 9.9), 4.47 (2H, dd, J=12.0, 2.1), 4.91 (2H, dd, J=13.2, 4.8), 5.56±5.60 (2H, m), 7.00±
7.25 (8H, m); 13C NMR ꢁ: 16.2 (q), 16.5 (q), 36.0 (t), 36.9 (t), 61.9 (d), 67.8 (d), 68.0 (d), 68.0 (d),
68.5 (t), 69.2 (t), 106.0 (s), 115.0±118.0, 127.3 (s), 128.0±130.2, 139.1 (s), 140.0 (s), 141.1 (s), 162.2
(s), 169.5 (s). IR (nujol) 1740, 1725 cm^1. MS m/z: 616 (M+). Anal. calcd for C28H26Cl2N4O8: C,
54.54; H, 4.25; N, 9.09; Cl, 11.35. Found: C, 54.60; H, 4.28; N, 9.12; Cl, 11.41.

1982
G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
Further elution gave the intermediate hydrazonoyl chloride 18 (0.16 g, 26%) as a thick oil not
25
1
analytically pure: ‰ꢀŠD =^216.2 (c 0.28, CHCl3); H NMR ꢁ: 1.25 (6H, d, J=6.5), 3.42 (1H, dd,
J=18.6, 13.5), 3.59 (1H, dd, J=18.6, 5.0), 3.81 (1H, dd, J=11.8, 9.8), 4.29 (1H, dd, J=12.0, 6.5),
4.37 (1H, dd, J=12.0, 3.8), 4.47 (1H, dd, J=11.8, 2.0), 4.90 (1H, dd, J=13.5, 5.0), 5.31±5.39 (1H,
m), 5.50±5.60 (1H, m), 5.84 (1H, dd, J=10.4, 1.3), 6.12 (1H, dd, J=17.3, 10.4), 6.42 (1H, dd,
J=17.3, 1.3), 7.00±7.30 (8H, m), 8.30 (1H, br s); 13C NMR ꢁ: 16.2 (q), 16.5 (q), 36.0 (t), 36.9 (t),
60.9 (d), 61.2 (d), 66.0 (t), 66.9 (t), 67.2 (t), 68.7 (t), 72.9 (d), 74.7 (d), 116.0±129.9, 139.7 (s), 140.3
(s), 141.1 (s), 141.2 (s), 162.4 (s), 162.6 (s). IR (nujol) 3160, 1740, 1730 cm^1. MS m/z: 652 (M+).
3.12. Treatment of 18 with silver carbonate
A solution of 18 (0.10 g, 0.15 mmol) in dry dioxane (15 mL) was treated with silver carbonate
(83 mg, 0.30 mmol) and stirred in the dark at room temperature for 96 h. The undissolved
material was ®ltered o€, the solvent was evaporated, and then the residue was chromatographed
on a silica gel column with diethyl ether. The ®rst fraction contained the macrocyclic compound
19 (85 mg, 90%).
3.13. X-Ray structure determination of 9
.
C28H30Cl2N4O6 1/2(CH2Cl2), Mr=631.92, monoclinic, a=14.553(2), b=11.776(2), c=17.699(2)
A, ꢂ=92.699(11)ꢀ, V=3029.8(7) A3, space group C2, T=291(1) K, Z=4, dcalc=1.385 gcm^1,
ꢃ(Mo-Ka)=0.350 mm^1. Crystal data were collected with a Bruker P4 di€ractometer, using
graphite monochromated Mo-Ka radiation l=0.71073 A; !/2ꢄ scans, 4<2ꢄ<55ꢀ; 0<h<18,
^15<k<15, ^22<l<22; data corrected for absorption on the basis of -scan data12; 6963 unique
re¯ections collected were used for all calculations [5742 with I>ꢅ(I)]. The structure was solved by
SIR92,13 and re®ned on F2 by full-matrix least-squares by using SHELX97.14 Heavy atoms were
anisotropic, H atoms isotropic; H atoms of methyl groups were ®xed in calculated positions.
Final discrepancy index on all re¯ections R=0.0554 and wR(F2)=0.1164, g.o.f. 1.015,
^0.26<Áꢆ<0.20 eA^3. The (S) con®guration at atoms C6 and C14, known on the basis of the
reactants knowledge, was con®rmed by Flack15 parameter [0.04(5)]; the con®guration at atoms
C3 is (R) while at C9 is (S). The dichloromethane molecule lies on a crystallographic C2 axis.
Bond distances and bond angles are in the expected range. Crystallographic data of 9 have been
deposited with the Cambridge Crystallographic Data Centre as Supplementary Publication no.
138143.
Acknowledgements
Thanks are due to MURST and CNR for ®nancial support. G.B. and G.M. are grateful to
Professor Luisa Garanti and Professor Gaetano Zecchi for helpful suggestions.
References
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3. Molteni, G.; Pilati, T. Tetrahedron: Asymmetry 1999, 10, 3873.

G. Broggini et al. / Tetrahedron: Asymmetry 11 (2000) 1975±1983
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4. Broggini, G.; Casalone, G.; Garanti, L.; Molteni, G.; Pilati, T.; Zecchi, G. Tetrahedron: Asymmetry 1999, 10,
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