A novel enantiopure tricyclic β-lactam via stereoselective intramolecular nitrilimine cycloaddition

Article abstract of DOI:10.1016/j.tetasy.2010.10.018

Starting from the Staudinger [2+2] cycloaddition between the 1-azadiene 1 and acetoxyacetylketene, generated in situ from acetoxyacetyl chloride, we developed a seven-step synthesis of the novel azeto[3′,4′:2,3] pyrano[4,5-c]pyrazole skeleton 9 in both ra

Full text of DOI:10.1016/j.tetasy.2010.10.018

Tetrahedron: Asymmetry 21 (2010) 2607–2611
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A novel enantiopure tricyclic b-lactam via stereoselective intramolecular
nitrilimine cycloaddition
Paola Del Buttero a, , Giorgio Molteni a, Tullio Pilati b
⇑
a Università degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, via Golgi 19, 20133 Milano, Italy
b Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133 Milano, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Starting from the Staudinger [2+2] cycloaddition between the 1-azadiene 1 and acetoxyacetylketene,
generated in situ from acetoxyacetyl chloride, we developed a seven-step synthesis of the novel
azeto[30,40:2,3]pyrano[4,5-c]pyrazole skeleton 9 in both racemic and enantiopure forms. Silver carbonate
treatment of the functionalised hydrazonoyl chloride 7 promoted in situ generation of the corresponding
nitrilimine 8, which underwent a clean, stereoselective cycloaddition to the target tricyclic b-lactam 9.
The key step of the synthetic pathway leading to enantiopure 9 was the production of the enantiopure
azetidinone (3R,4S)-3 by enzymatic resolution with Amano Lypase PS of the racemic precursor
(3S*,4R*)-2.
Received 20 September 2010
Accepted 20 October 2010
Available online 20 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Since the early days of modern treatment of infective diseases,
it became apparent that b-lactam antibiotics play a major role
against bacterial infections.1 It is well-known that among the var-
ious families of b-lactam antibiotics, there are some relevant differ-
ences in both the ranges of anti-bacterial activity with the
tolerance towards b-lactamase enzymes.2 This latter aspect is
strictly concerned to the phenomenon of antibacterial resistance,
namely the enzyme-catalysed ring opening of b-lactams to give
ineffective b-aminoacids,3 which is caused by the extensive clinical
use of b-lactam antibiotics over the last decades. The synthesis of
new types of b-lactams that are able to overcome the defence
mechanisms of the bacteria would be a valuable target. Tricyclic
b-lactam antibiotics seem to be particularly suitable for this pur-
pose, since some representatives of these structures featured good
resistance towards b-lactamases and dehydropeptidase enzymes.4
Recently, an approach to tricyclic b-lactams involving a nitrone-
olefin cycloaddition as the key step has been successfully
exploited.5 Other types of 1,3-dipoles, such as nitrilimines, have re-
ceived less attention since the only contribution in this field comes
from a couple of papers from our laboratory.6 In a continuation of
our research within this field, we decided to synthesise the unre-
ported azeto[30,40:2,3]pyrano[4,5-c]pyrazole skeleton 9 (Scheme 1)
via the stereoselective intramolecular cycloaddition of a suitably
functionalised nitrilimine.
The racemic synthesis illustrated in the Scheme 1 starts with
the Staudinger [2+2] cycloaddition between the known azadiene
1 and acetoxyacetylketene which was generated in situ by treating
acetoxyacetyl chloride with triethylamine at 0 °C in dichlorometh-
ane. Compound (3S*,4R*)-2 was obtained in high yield (90%) as the
only diastereoisomer and showed the expected cis-arrangement at
the 3- and 4-positions of the four-membered ring.7 Further steps
involved the hydrazinolysis of the acetoxy group, the O-alkylation
of 3 and subsequent ester hydrolysis to give 5. Next, acyl hydrazine
6 was obtained through carboxyl activation with oxalyl chloride
and subsequent treatment with phenylhydrazine. Hydrazonoyl
chloride 7 was obtained from 6 by treatment with triethylphos-
phine and carbon tetrachloride as the chlorinating agent.8 Nitrili-
mine 8 was generated in situ by treating the corresponding
hydrazonoyl chloride 7 with a twofold molar excess of silver car-
bonate as an unconventional basic agent, following a procedure
established by Garanti et al.9 After 24 h, the tricyclic b-lactam 9
was obtained with 60% yield.
Analytical and spectroscopic data of the final cycloaddition
product were consistent with the above formula 9 but deserve
some comments. As far as the 1H NMR is concerned, the hydrogens
at the 6- and 9-positions of the tricyclic core show a scalar coupling
constant of 4.8 Hz, which suggests a cis-arrangement.7 On the
other hand, the value of 12.0 Hz found for the two hydrogens at
the 10- and 11-positions is typical for the trans-arrangement of
the hydrogens, which lies on the saturated portion of the 4,5-dihy-
dro pyrazole ring.10 Thus, it is apparent that the b-lactam stereo-
chemistry is retained through the dipolar cycloaddition, whereas
⇑
Corresponding author. Tel.: +39 02 50314140; fax: +39 02 50314139 (P.D.B.).
E-mail address: paola.delbuttero@unimi.it (P. Del Buttero).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.10.018

2608
P. D. Buttero et al. / Tetrahedron: Asymmetry 21 (2010) 2607–2611
Ph
Ph
Ph
H
H
N
H
H
N
O
AcO
O
HO
O
1) NaH/DME
2) BrCH2COOEt
N2H4
Et3N
CH2Cl2, Δ
(90%)
+
O
COCl
MeOH
(90%)
N
PMP
PMP
(quant.)
PMP
1
2
3
(3S*,4R*)-
EtOOC
Ph
HOOC
Ph
H
H
N
H
H
N
1) (COCl)2/toluene
2) PhNHNH2
O
O
1) aq. NaOH/dioxane
2) aq. HCl
O
O
(50%)
(83%)
PMP
PMP
4
5
_
N
Ph
+
N
NHPh
NHPh
HN
N
Ph
Ph
Ph
H
H
N
H
H
H
H
N
O
O
O
O
O
O
O
Cl
Ag2CO3
CCl4/Ph3P
dioxane
(60%)
N
MeCN
(85%)
PMP
PMP
PMP
8
6
7
2
N
1
N
Ph
3
4
11
10
H
H
5
O
OMe
Ph
PMP =
H
H
9
6
N
7
8
O
PMP
9
Scheme 1.
the trans-4,5-dihydropyrazole ring stereochemistry is dictated by
the stereoconservative nature of the concerted cycloaddition reac-
tions. Furthermore, the cycloaddition diastereoselectivity was
complete since the tricyclic b-lactam 9 was obtained as a single
diastereoisomer.
pure azetidinone (3R,4S)-2 by enzymatic resolution of the racemic
precursor (3S*,4R*)-2 (Scheme 2). This target was pursued by using
Amano Lypase PS in 0.2 M phosphate buffer (pH 7.5)/acetone,
which is known to show a (3S,4R)-stereochemical preference to-
wards simple b-lactams.14 The enantiomeric excess of (3R,4S)-2
was >95:5, as determined by 1H NMR in the presence of tris[hepta-
fluoropropyl-hydroxymethylene-(+)-camphorato]europium-(III).
Hydrazinolysis of (3R,4S)-2 gave deprotected (3R,4S)-3. It should
be noted that the ee of (3R,4S)-3 did not change with respect to
that of the precursor. The synthetic sequence 3?9 outlined in
the Scheme 1 was repeated with (3R,4S)-3. The reaction conditions
and yields were almost identical to those reported in Scheme 1,
while the ee’s of all products were determined in each step. Fol-
lowing this route, we were confident in assigning the absolute con-
figurations of the final tricyclic b-lactam as (6R,9S,10S,11S)-9.
In order to elucidate the relative configurations of the two ste-
reocentres at the 9- and 10-positions, we performed NOESY exper-
iments which showed mutual NOE enhancements between the
pair of hydrogens at the 9- and 11-positions. This observation sug-
gests their cisoid arrangement, which implies a trans-relationship
between the hydrogens at the 9- and the 10-positions. The distance
between these hydrogens calculated11 with the AM 1 semi-empir-
ical method12 was 2.33 Å, thus justifying the observed mutual NOE
enhancements. Slow evaporation of a dichloromethane solution of
9 gave crystals in a suitable form for X-ray diffractometric analysis
(Fig. 1),13 which confirmed unequivocally the relative configura-
tion at the 6-, 9-, 10- and 11-positions, which is in agreement with
our expectations on the basis of proton resonance spectra and
NOESY experiments.
3. Conclusion
The synthesis of the novel azeto[30,40:2,3]pyrano[4,5-c]pyrazolo
skeleton 9 in both the racemic and the enantiopure forms of poten-
tial interest as a b-lactamase-resistant antibiotic has been carried
In order to exploit the synthesis of tricyclic b-lactam 9 in the
enantiopure form, the first step was the obtainment of the enantio-

P. D. Buttero et al. / Tetrahedron: Asymmetry 21 (2010) 2607–2611
2609
out via a nitrilimine-alkene cycloaddition as the key step. The
above tricyclic system was obtained with good overall yields and
complete diastereoselectivity.
4. Experimental
Melting points were determined with a Büchi apparatus in open
tubes and are uncorrected. IR spectra were recorded with a Perkin–
Elmer 1725 X spectrophotometer. Mass spectra were determined
with a VG-70EQ apparatus. 1H NMR (300 MHz) and 13C NMR
(75 MHz) spectra were taken with a Bruker AMX 300 instrument
(in CDCl3 solutions at room temperature). Chemical shifts are given
as ppm from tetramethylsilane. Coupling constants (J) values are
given in hertz and are quoted to 0.1 Hz consistently with NMR
machine accuracy. NOE experiments were performed by setting
the following parameters: relaxation delay (d1) 2 s, irradiation
power (dl2) 74 dB and total irradiation time (for each signal)
1.8 s. Optical rotations were recorded on a Perkin–Elmer 241 polar-
imeter at the sodium D-line at 25 °C. Cinnamaldehyde imine 1 was
prepared as described in the literature.15 Amano Lipase PS from
Pseudomonas cepacia was used as purchased from Aldrich.
4.1. Synthesis of 1-(4-methoxyphenyl)-3-acetoxy-4-[2-(E)-
phenyl]ethylidene-(3S*,4R*)-azetidin-2-one 2
A solution of 1 (2.37 g, 10.0 mmol) and triethylamine (4.85 g,
48.0 mmol) in dry dichloromethane (50.0 mL) was cooled to 0 °C
and acetoxyacetyl chloride (4.10 g, 30.0 mmol) in dry dichloro-
methane (15 mL) was added under nitrogen with stirring and
ice-cooling. After 5 h at room temperature water (100 mL) was
added and the mixture was extracted with dichloromethane
(3 ꢀ 33 mL). The organic layer was washed with brine, (25 mL)
dried over sodium sulfate and evaporated under reduced pressure.
Crystallisation of the residue with ethanol gave pure (3S*,4R*)-2
(3.03 g, 90% yield). White powder; mp 163 °C; IR (nujol): 1750,
1730 cmꢁ1 1H NMR d 2.12 (3H, s, CH3–CO–), 3.74 (3H, s, CH3O–),
;
4.98 (1H, dd, J = 8.0, 4.9, >CH–N<), 5.92 (1H, d, J = 4.9, –O–CH<),
6.20 (1H, dd, J = 16.0, 8.0, –CH@CHPh), 6.85 (1H, d, J = 16.0,
PhCH@), 6.9–7.4 (9H, m, aromatics). MS: m/z 337 (M+). Anal. Calcd
Figure 1. ORTEPIII plot of compound (6S*,9R*,10R*,11R*)-9. Atomic displacement
parameters at 50% probability level, H atoms not to scale. In spite of the data
collection temperature (103 K) the solvate dichloromethane shows high ADPs.
Colour code: C, H, black; O, red; N, blue.
Ph
Ph
H
H
N
H
H
N
AcO
HO
O
0.2 M phosphate buffer/acetone
(quantit.)
2
(3S*,4R*)-
+
O
PMP
PMP
2
3
(3S,4R)-
(3R,4S)-
N2H4
MeOH
(90%)
2
N
1
N
Ph
Ph
3
4
Ph
H
H
N
11
HO
10
H
H
5
O
H
H
9
6
O
PMP
N
7
8
O
PMP
(3R,4S)-3
(6R,9S,10S,11S)-9
Scheme 2.

2610
P. D. Buttero et al. / Tetrahedron: Asymmetry 21 (2010) 2607–2611
for C20H19NO4: C, 71.20; H, 5.68; N, 4.15. Found: C, 71.24; H, 5.63;
N, 4.21.
and 2 M aqueous hydrochloric acid was added until pH 2. The
mixture was extracted with ethyl acetate (3 ꢀ 35 mL), after which
the organic layer was dried over sodium sulfate and evaporated
under reduced pressure. Crystallisation of the residue with etha-
nol gave pure 5 (1.16 g, 50% yield). White powder; mp 159–
4.2. Enzymatic resolution of (3S*,4R*)-2 with Amano Lypase PS
A
solution of (3S*,4R*)-2 (3.50 g, 10.4 mmol) in acetone
160 °C; IR (nujol): 3340, 1750, 1720 cmꢁ1 1H NMR d 3.75 (3H,
;
(18.0 mL) and 0.2 M phosphate buffer at pH 7.5 (150.0 mL,
30.0 mmol) was treated with Amano Lipase PS (3.50 g) and stirred
for 10 h at 37 °C. Water (100 mL) was added and the mixture was
extracted with ethyl acetate (3 ꢀ 50 mL). The organic layer was
dried over sodium sulfate and evaporated under reduced pressure.
The residue was chromatographed on a silica gel column with
ethyl acetate–light petroleum (1:1). The first fractions contained
(3R,4S)-2 (1.70 g, 97% yield). Further elution gave (3S,4R)-3
s, CH3O–), 4.33 (2H, AB, J = 15.8, –CH2O–), 5.04 (1H, dd, J = 8.5,
5.0, >CH–N<), 5.19 (1H, d, J = 5.0, –O–CH<), 6.46 (1H, dd,
J = 16.0, 8.5, –CH@CHPh), 7.03 (1H, d, J = 16.0, PhCH@), 7.1–7.6
(9H, m, aromatics), 10.8 (1H, br s, –COOH). MS: m/z 353 (M+).
Anal. Calcd for C20H19NO5: C, 67.98; H, 5.42; N, 3.96. Found: C,
68.04; H, 5.38; N, 4.02.
The same procedure was repeated with (3R,4S)-4 to give
(3R,4S)-5, which was used crude without further crystallisation.
(1.06 g, 69%), ½a D25
¼ ꢁ293:0 (c 1.25, CHCl3).
ꢂ
4.6. Synthesis of 1-(4-methoxyphenyl)-3-(1-phenylhydrazino-
carbonyl)hydroxy methylene-4-[2-(E)-phenyl]ethylidene-
azetidin-2-ones 6 and (3R,4S)-6
4.3. Synthesis of 1-(4-methoxyphenyl)-3-hydroxy-4-[2-(E)-
phenyl]ethylidene-azetidin-2-ones 3 and (3R,4S)-3
A solution of 2 (2.50 g, 7.4 mmol) in methanol (125.0 mL) was
cooled to 0 °C and hydrazine monohydrate (0.37 g, 7.4 mmol) in
methanol (35 mL) was added under stirring and ice-cooling. The
solution was then warmed to 40 °C for 4 h. After cooling at room
temperature, water (160 mL) was added and the mixture was ex-
tracted with ethyl acetate (3 ꢀ 50 mL). The organic layer was dried
over sodium sulfate and evaporated under reduced pressure. Crys-
tallisation of the residue with ethanol gave pure 3 (2.14 g, 98%
yield). White powder; mp 163–165 °C; IR (nujol): 3260,
A solution of 5 (1.10 g, 3.1 mmol) in dry toluene (45 mL) was
treated with oxalyl chloride (1.97 g, 15.5 mmol) in dry toluene
(15 mL) under nitrogen at room temperature. The solution was
warmed to 50 °C for 7 h, and then evaporated under reduced
pressure. Dry toluene (45 mL) was added under nitrogen and
the solution was cooled to 0 °C. Freshly distilled phenylhydrazine
(0.67 g, 6.2 mmol) in dry toluene (4.5 mL) was added dropwise
under stirring and ice-cooling. The mixture was allowed to reach
room temperature, after which it was stirred for 15 h. Water
(50 mL) was added and the mixture was extracted with dichloro-
methane (4 ꢀ 30 mL). The organic layer was dried over sodium
sulfate and evaporated under reduced pressure. Crystallisation
of the residue with diisopropyl ether gave pure 6 (1.15 g, 83%
yield). Pale yellow powder; mp 120 °C; IR (nujol): 3250, 1750,
1750 cmꢁ1 1H NMR d 3.60 (1H, br s, –OH), 3.75 (3H, s, CH3O–),
;
4.88 (1H, dd, J = 7.7, 5.0, >CH–N<), 5.18 (1H, d, J = 5.0, HO–CH<),
6.39 (1H, dd, J = 16.1, 7.7, –CH@CHPh), 6.84 (1H, d, J = 16.1,
PhCH@), 6.9–7.4 (9H, m, aromatics). MS: m/z 295 (M+). Anal. Calcd
for C18H17NO3: C, 73.20; H, 5.80; N, 4.74. Found: C, 73.16; H, 5.84;
N, 4.81.
1630 cmꢁ1
; d 3.75 (3H, s, CH3O–), 4.40 (2H, AB,
1H NMR
The same procedure was repeated with (3R,4S)-2 to give
J = 15.4, –CH2O–), 4.80 (1H, dd, J = 8.2, 4.8, >CH–N<), 5.04 (1H, d,
J = 4.8, –O–CH<), 6.40 (1H, dd, J = 15.9, 8.2, –CH@CHPh), 6.79
(1H, d, J = 15.9, PhCH@), 6.9–7.5 (15H, m, aromatics and –NHPh),
8.50 (1H, br s, –CONH–N<). MS: m/z 443 (M+). Anal. Calcd for
(3R,4S)-3, ½a 2D5
¼ þ257:3 (c 1.09, CHCl3).
ꢂ
4.4. Synthesis of 1-(4-methoxyphenyl)-3-(1-metoxycarbonyl)
hydroxymethylene-4-[2-(E)-phenyl]ethylidene-azetidin-2-ones
4 and (3R,4S)-4
C
26H25N3O4: C, 70.41; H, 5.68; N, 9.47. Found: C, 70.37; H, 5.66;
N, 9.53.
The same procedure was repeated with (3R,4S)-5 to give
Sodium hydride (0.25 g, 10.2 mmol) was added portionwise to
a solution of 3 (2.00 g, 6.8 mmol) and ethyl bromoacetate (1.70 g,
10.2 mmol) in dry dimetoxyethane (120.0 mL) under nitrogen at
room temperature. After stirring for 2.5 h, water (30 mL) was
added and the mixture was extracted with ethyl acetate
(3 ꢀ 35 mL). The organic layer was dried over sodium sulfate
and evaporated under reduced pressure. Crystallisation of the res-
idue with diisopropyl ether gave pure 4 (2.87 g, 90% yield). White
(3R,4S)-6, which was used crude without further crystallisation.
4.7. Synthesis of 1-(4-methoxyphenyl)-3-(2-chloro-2-phenyl-
hydrazinimino) hydroxyethylene-4-[2-(E)-phenyl]ethylidene-
azetidin-2-ones 7 and (3R,4S)-7
A solution of 6 (1.10 g, 2.5 mmol) in dry acetonitrile (50 mL)
and carbon tetrachloride (2.77 g, 18.0 mmol) was treated with
triphenylphosphine (4.72 g, 18.0 mmol) under nitrogen and stir-
red at room temperature for 24 h. Brine (25 mL) was added to
reaction mixture, after which the organic layer was separated,
dried over sodium sulfate and evaporated under reduced pres-
sure. The dark red residue was chromatographed on a silica
gel column with ethyl acetate–dichloromethane (1:1) to give
hydrazonoyl chloride 7 (1.01 g, 85% yield). Pale yellow powder;
mp 154 °C (from diisopropyl ether); IR (nujol): 3270,
powder; mp 128–130 °C; IR (nujol): 1760, 1740 cmꢁ1 1H NMR d
;
1.25 (3H, t, J = 7.3, CH3–CH2–), 3.76 (3H, s, CH3O–), 4.25 (2H, q,
J = 7.3, CH3–CH2–), 4.33 (2H, AB, J = 16.0, –CH2O–), 4.86 (1H, dd,
J = 8.5, 5.0, >CH–N<), 5.07 (1H, d, J = 5.0, –O–CH<), 6.42 (1H, dd,
J = 16.0, 8.5, –CH@CHPh), 6.8–7.4 (10H, m, aromatics and PhCH@).
MS: m/z 381 (M+). Anal. Calcd for C22H23NO5: C, 69.28; H, 6.08; N,
3.67. Found: C, 69.34; H, 6.11; N, 3.73. The same procedure was
repeated onto (3R,4S)-3 giving (3R,4S)-4, ½a D25
¼ þ140:5 (c 1.04,
ꢂ
CHCl3).
1760 cmꢁ1 1H NMR
; d 3.80 (3H, s, CH3O–), 4.54 (2H, AB,
J = 12.5, –CH2O–), 4.80 (1H, dd, J = 8.9, 4.8, >CH–N<), 5.04 (1H,
d, J = 4.8, –O–CH<), 6.40 (1H, dd, J = 16.0, 8.9, –CH@CHPh),
6.84 (1H, d, J = 16.0, PhCH@), 6.9–7.5 (14H, m, aromatics), 7.85
(1H, br s, –NHPh). MS: m/z 477 (M+). Anal. Calcd for
4.5. Synthesis of 1-(4-methoxyphenyl)-3-(1-hydroxycarbonyl)
hydroxymethylene-4-[2-(E)-phenyl]ethylidene-azetidin-2-ones
5 and (3R,4S)-5
C26H24ClN3O4: C, 65.34; H, 5.06; N, 8.79. Found: C, 65.30; H,
A solution of 4 (2.50 g, 6.6 mmol) in dioxane (65 mL) and 2 M
aqueous sodium hydroxide (16.5 mL, 33.0 mmol) was stirred for
2 h at room temperature. The solution was then cooled to 0 °C
5.02; N, 8.84.
The same procedure was repeated with (3R,4S)-6 to give
(3R,4S)-7, which was used crude without further crystallisation.

P. D. Buttero et al. / Tetrahedron: Asymmetry 21 (2010) 2607–2611
2611
4.8. Synthesis of 1,11-diphenyl-7-oxo-8-(4-methoxyphenyl)-(6S*,
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9S,10S,11S)-9
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A solution of 7 (0.90 g, 1.9 mmol) in dry dioxane (13.0 mL) was
treated with silver carbonate (1.05 g, 3.8 mmol) under nitrogen in
the dark and stirred at room temperature for 24 h. The undissolved
material was filtered off and the solvent was evaporated under re-
duced pressure. The residue was chromatographed on a silica gel
column with dichloromethane–ethyl acetate (95:5) to give cycload-
duct 9 (0.50 g, 60% yield). White powder; mp 136–140 °C (from
diisopropyl ether/dichloromethane); IR (nujol): 1750 cmꢁ1
;
1H
NMR d 3.57 (1H, dd, J = 12.0, 3.2, –CH<), 3.78 (3H, s, CH3O–), 4.29
(1H, dd, J = 4.8, 3.2, >CH–N<), 4.69 (2H, AB, J = 13.8, –CH2O–), 4.87
(1H, d, J = 12.0, PhCH@), 5.11 (1H, d, J = 4.8, –O–CH<), 6.7–7.5
(14H, m, aromatics); 13C NMR d 55.4 (q), 56.2 (d), 62.1 (t), 73.4
(d), 78.9 (d), 114–130 (m), 140.3 (s), 145.6 (s), 146.1 (s), 156.7 (s),
162.5 (s). MS: m/z 441 (M+). Anal. Calcd for C26H23N3O4: C, 70.74;
H, 5.25; N, 9.52. Found: C, 70.78; H, 5.25; N, 9.48.
The same procedure was repeated with (3R,4S)-7 to give
(6R,9S,10S,11S)-9, ½a D25
¼ ꢁ292:0 (c 0.11, CHCl3).
ꢂ
13. Crystallographic data (excluding structure factors) for structure
(6S*,9R*,10R*,11R*)-9 have been deposited with the Cambridge
Crystallographic data Centre as supplementary publication number CCDC
779769.
Acknowledgements
14. (a) Carr, J. A.; Al-Azemi, T. F.; Long, T. E.; Shim, J.-Y.; Coates, C. M.; Turos, E.;
Bisht, K. S. Tetrahedron 2003, 59, 9147; (b) Brieva, R.; Crich, J. Z.; Sih, C. J. J. Org.
Chem. 1993, 58, 1068.
Thanks are due to MURST (FIRST) for financial support. We are
grateful to Dr. Lara de Benassuti, University of Milan, for NOESY
experiments.
15. Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org. Chem. 1982, 47, 2765.