[2+2] Cycloaddition reactions of 1-benzyl-2,4-diphenyl-1,3-diazabuta-1,3-diene with chiral ketenes

Article abstract of DOI:10.1016/S0040-4020(01)00675-5

The [2+2] cycloaddition reactions of 1-benzyl-2,4-diphenyl-1,3-diaza-1,3-butadiene with β-(dimethylphenylsilyl)ketene, β-menthoxyketene and Evans-Sjo?gren ketene were investigated. The results and some chemical transformations of the obtained cycloadducts

Full text of DOI:10.1016/S0040-4020(01)00675-5

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 7205±7212
[212] Cycloaddition reactions of
1-benzyl-2,4-diphenyl-1,3-diazabuta-1,3-diene with chiral ketenes
Giorgio Abbiatip and Elisabetta Rossi
Á Á
Istituto di Chimica Organica della Facolta di Farmacia, Universita di Milano, Via Venezian 21, I-20133 Milano, Italy
Received 14 March 2001; revised 31 May 2001; accepted 20 June 2001
AbstractÐThe [212] cycloaddition reactions of 1-benzyl-2,4-diphenyl-1,3-diaza-1,3-butadiene with b-(dimethylphenylsilyl)ketene,
È
b-menthoxyketene and Evans±Sjogren ketene were investigated. The results and some chemical transformations of the obtained
cycloadducts are reported. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
ments, performed for azetidinones 3a,c,d,f, showing the
presence of a single diastereomer with cis relationship
between the benzylidene-amino group at C-4 and the
hydrogen at C-3.
Recently, we reported that cycloaddition reactions of
1-benzyl-1,3-diazabuta-1,3-diene 1a with ketenes 2a±h
proceed directly to [212] cycloaddition products giving
rise to the 1-benzyl-4-(benzylidene-amino)-4-phenyl-
azetidin-2-ones 3a±h in good yields, Scheme 1, Table 1.1
The diastereoselectivity achieved in these reactions
prompted us to extend our investigations to the enantio-
selective synthesis of azetidin-2-ones as potential useful
building blocks for natural products and the preparation of
biologically active compounds.2
Moreover, diastereoselectivity for the cycloaddition reac-
tions involving monosubstituted ketenes was demonstrated
by H NMR spectra analysis and NOE-difference experi-
1
2. Results and discussion
Over the past years exciting results have been obtained in
the enantioselective synthesis of b-lactams, performing the
Staudinger3 reaction with imines and different monosubsti-
tuted chiral ketenes.4 Among these we choose to test the
reactivity of b-silylalkylketene 2i5, b-menthoxyketene 2j6
7
and Evans±Sjogren ketenes 2k,l with 1a in order to obtain
È
Scheme 1. Reagents and conditions: (a) TEA, toluene, 08C to rt, 3±24 h.
Table 1. Compounds 3a±h
b-lactams bearing a trisubstituted stereogenic center at the
C(3) position and a quaternary stereogenic center at C(4),
Scheme 2.
R1
R2
Yield (%)
The reaction between 1a and ketene 2i, generated in situ
from the corresponding acid chloride and triethylamine, was
performed in dry toluene at 08C, Scheme 2. The reaction
products were separated by ¯ash chromatography and
further puri®ed by crystallization.
3a
3b
3c
3d
3e
3f
Ph
Ph
Cl
CHvCH2
Me
OMe
Cl
N3
H
Ph
H
H
Me
H
57
64
71
78
54
73
65
95
1-Benzyl-4-(benzylidene-amino)-3-[(dimethyl-phenyl-silanyl)-
phenyl-methyl]-4-phenyl-azetidin-2-ones 3j and k were
obtained with a total yield of 75% and with a de of 10%.
The absolute con®gurations around C3 and C4 of 3j and k
were tentatively assigned as (3R,4R,30R) and (3S,4S,30R),
respectively, through combined NMR spectroscopy (1H
NMR, COSY and NOESY) and conformational analysis
experiments,8 Fig. 1.
3g
3h
Cl
H
Keywords: [212] cycloaddition; 1,3-diaza-1,3-butadiens; chiral ketenes;
azetidin-2-ones.
Corresponding author. Tel.: 139-2-70633800; fax: 139-2-70638473;
e-mail: giorgio.abbiati@unimi.it
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00675-5

7206
G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
The 1H NMR spectrum of compound 3k showed two
doublets at 3.70 and 2.53 ppm with Jˆ6.6 Hz, which can
be easily attributed, on the basis of COSY analysis, to C3±H
and Ca±H, respectively. Moreover, proton±proton NOE
interactions were observed between C3±H and Ca±H and
C3±H and CHvN. Conformational analysis, performed for
the rotation around the C3±Ca bond with AM1 semi-
empirical SCF computational method,9 predicts a minimum
for a set of conformers with dihedral angle H±C3±Ca±H
ranging from 2110 to 2708, Fig. 1. These values applied to
3
the Karplus equation provide a theoretical JH±C3±Ca±H of
0±7 Hz.
In contrast, the 1H NMR of compound 3j showed for C3±H
and Ca±H two doublets centered at 3.68 and 2.43 ppm,
respectively, with Jˆ13.4 Hz. However, for 3j, proton±
proton NOE interactions were observed only between
C3±H and CHvN. Moreover, conformational analysis
performed for the rotation around the C3±Ca bond predicts
a minimum for a set of conformers with dihedral angle
H-C3-Ca-H ranging from 140 to 1808, corresponding to a
calculated 3JH±C3±Ca±H of 7±15 Hz, Fig. 1. All the obtained
results are in agreement with the reported structures for 3j
and k.
Similar results were obtained when 1a was reacted, under
the same conditions, with ketene 2j, Scheme 2. The reaction
affords, after usual puri®cation procedures, 1-benzyl-4-
(benzylidene-amino)-3-menthoxy-4-phenyl-azetidin-2-ones
3l and m in 65% yield and with a de of 10%. However, due
to the complexity of the menthoxy substituent, stereo-
chemical assignments have been made, by means of
NOESY experiment, only for C3±H and CHvN sub-
stituents which also in this case result in a cis relationship.
Finally, the reactions of 1a with (4S) and (4R)-3-(2-oxo-
vinyl)-4-phenyl-oxazolidin-2-ones 2k and l, run under the
usual reaction conditions, gave in both cases a single
Scheme 2. Reagents and conditions: (a) TEA, toluene, 08C to rt, 24 h.
Figure 1. C3H±CaH rotational energy chart for the diastereoisomers 3j and k.

G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
7207
1
b-lactam product as demonstrated by H NMR spectro-
scopic analysis of the corresponding crude reaction
mixtures. After usual puri®cation procedures, the azetidin-
2-ones 3n (from 2k) and 3o (from 2l) were obtained in
73±75% yields and with a de.99.5%. Also in this case,
the NOESY experiment showed a cis relationship between
C3±H and CHvN moiety, Scheme 2.
yields, the N-benzyl-3-benzylamino-2-(2-oxo-4-phenyl-
oxazolidin-3-yl)-3-phenyl-acrylamide 5a when the reaction
was performed with anhydrous ammonium formate in
methanol13, and the 3-amino-N-benzyl-2-(2-oxo-4-phenyl-
oxazolidin-3-yl)-3-phenyl-acrylamide 5b when the reaction
was performed under hydrogen atmosphere in methylene
chloride, Scheme 4. Failing the NOE experiments, the cis
relationship between amino and amido groups in the phenyl-
acrylamides 5a and b was assigned on the basis of the likely
hydrogen bond. This assumption was con®rmed by the
unexpectedly high chemical shift of amino group for 5a
(dˆ10.18) and 5b (dˆ6.83±7.14, obscured by aromatic
protons).
È
As reported in the literature, the Evans±Sjogren ketene has
been widely used to perform highly diastereoselective
cycloadditions,10 moreover this chiral auxiliary acts also
as a N-protecting group, yielding by reductive Birch
cleavage, enantiomerically pure 3-amino-azetidin-2-
ones.11 Thus, starting from 3n and o, our goal was to synthe-
size enantiomerically pure 3-amino-1-benzyl-4-(benzyl-
idene-amino)-4-phenyl-azetidin-2-one 3i which was
already obtained as a racemate by treatment of 3h with
Triphenylphosphine,12 Scheme 3.
Both reactions proceed through the intermediacy of an
unstable gem-diamine as demonstrated by the NaBH4
selective reduction of the CvN double bond14 of 3o
which also affords 5b, Scheme 5.
Scheme 3. Reagents and conditions: (i) Ph3P, THF, rt; (ii) H2O, 65%.
Scheme 5. Reagents and conditions: (a) NaBH4, THF, rt, 48%.
However, Birch reduction of 3o yields, by CvN double
bond reduction and 4-phenyl-oxazolidinone elimination,
the N-benzyl-3-benzylamino-3-phenylpropionamide 4a
and 4-phenyl-oxazolidinone as a mixture of inseparable
compounds, Scheme 4.
Moreover, Birch reduction of 5b results in the
isolation of 2,3-diamino-N-benzyl-3-phenyl-propionamide
4b, Scheme 6.
As reported in the literature,7,11a catalytic CvC double bond
reduction as well as Birch cleavage of both the N-benzyl
group and the oxazolidinone moiety can be successfully
performed for some 1-benzyl-3-(4-phenyloxazolidinyl)-4-
styryl-azetidin-2-ones. However, in our case, catalytic
hydrogenation of 3n or o gave, in nearly quantitative
Scheme 6. Reagents and conditions: (a) Li, NH3, THF/t-BuOH 10:1,
2788C, 2 min, 98%.
The instability of azetidin-2-ones 3n,o to reductive condi-
tions prompted us to extend our investigations to other
simple techniques for removing the chiral auxiliary.
Easy removal of the oxazolidinone with trimethylsilyliodide
has been described15 for sensitive b-lactams. Thus treatment
of 3o with TMSI/HMDS and DBU yielded exclusively the
3-benzyl-5-(2-oxo-4-phenyl-oxazolidin-3-yl)-2,6-diphenyl-
2,3-dihydro-1H-pyrimidin-4-one 6a, as a single diastereo-
mer (see below), Scheme 7.
Scheme 4. Reagents and conditions: (a) Li, NH3, THF/t-BuOH 10:1,
2788C, 2 min., 62%. (b) HCO2NH4, Pd/C, MeOH, re¯ux, 94%. (c) H2
(760 Torr), Pd/C, CH2Cl2, rt, 90±95%.
Scheme 7. Reagents and conditions: (i) TMSI, HMDS, CH3CN, rt; (ii)
DBU, 08C to rt, 90%.

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G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
The structure of 6a was assigned on the basis of analytical
and spectroscopic data. In particular, elemental analysis and
EI-MS are in agreement with a molecular formula of
the presence on the nitrogen atom of a bulky TMS group,
which induces the formation of a single diastereoisomer.
1
C32H27N3O3 and a molecular weight of 501 Da. The H
An alternative reaction pathway involving C3±C4 bond
breaking was ruled out by performing the TMSI mediated
reaction with the azetidin-2-one 3p bearing a 4-methyl-
phenyl substituent at the imino residue. As depicted in
Scheme 9, the pyrimidinone 6c was the sole reaction
product.
NMR spectrum showed the disappearance of the azo-
methinic proton at dH 8.26 and a doublet for C2±H centred
at ±H 5.49, with Jˆ1.1 Hz, which collapse to a singlet by
treatment with D2O. 13C APTshowed the presence of seven
quaternary Csp2 carbons and NOESY and HMBC inter-
actions (Fig. 2) are consistent with the proposed structure.
Finally, COSY and HETCOR experiments permit the
complete assignment of both 1H and 13C NMR
spectroscopic resonances.
Scheme 9. Reagents and conditions: (i) TMSI, HMDS, CH3CN, rt; (ii)
DBU, 08C to rt, 83%.
Although our goal of synthesizing new optically active
b-lactams has not been completely achieved, we consider
noteworthy the new features accomplished in the ®eld of
b-lactams and oxazolidinone substituted b-lactams.
Figure 2.
Moreover, we tested the reactivity of 3n,o under oxidative
(CAN16, K2S2O817) and hydrolytic (LiOH, HCl) conditions.
However, both CAN and K2S2O8 gave complex reaction
mixtures, whereas the reaction performed with LiOH in
H2O/THF afforded, starting from 3o, by base catalyzed
hydrolysis of the CvN double bond and azetidinone ring
opening, the 3-phenylpropenamide 5b, Scheme 8.
3. Experimental
3.1. General details
All chemicals and solvents are commercially available and
were used after distillation or treatment with drying agents.
`PE' refers to the fraction of petroleum ether with boiling
point of 40±608C. `EtOAc' means ethyl acetate. `TEA'
means triethylamine. All organic solutions from work-ups
were dried by exposure to anhydrous sodium sulfate for
20 min. Merck silica gel 60 F254 thin-layer plates were
employed for thin layer chromatography. Merck silica gel
(230±400 mesh) was employed for ¯ash column chromato-
graphy. Melting points, measured with a Stuart Scienti®c
SMP3 apparatus, are uncorrected. Infrared spectra were
recorded on a FT-IR Perkin Elmer 16 PC spectro-
photometer, using thin ®lms between NaCl plates in the
cases of liquid samples and KBr tablets for solid samples.
NMR chemical shifts are reported in parts per million
(ppm). Coupling constants (J) are reported in Hertz (Hz).
Unless otherwise stated, proton NMR spectra were recorded
in CDCl3, on Varian-Gemini 200 or Bruker 300 Avance
spectrometers, at 200 or 300 MHz, with residual chloroform
as the internal reference (dHˆ7.27 ppm). Jvic is referred to a
vicinal coupling. Jgem is referred to as geminal coupling.
Unless otherwise stated, 13C NMR spectra were recorded
in CDCl3, on the same spectrometers, at 50.3 or
75.4 MHz, with the central peak of chloroform as the inter-
nal reference (dCˆ77.3 ppm). The APT sequence was used
to distinguish the methine and methyl carbon signals from
those due to methylene and quaternary carbons. Two-
dimensional NMR experiments (COSY, HETCOR,
HMBC and NOESY) were used, where appropriate, to
aid in the assignment of signals in the proton and 13C
NMR spectra. Low-resolution mass spectra were run on a
Finally, hydrolysis of 3o with 6N HCl results in the isolation
(80%) of a 1:1 diastereomeric mixture of 6a and b, which
were easily separated by ¯ash chromatography, Scheme 8.
Scheme 8. Reagents and conditions: (a) CAN, H2O/THF,rt. (b) K2S2O8,
THF, rt. (c) LiOH, H2O/THF, rt, 93%. (d) HCl 6N, rt, 81%.
In our opinion, the mechanism involved in the HCl or TMSI
mediated reactions involves, starting from azetidin-2-one
3o, proton or TMSI addition to the CvN double bond
followed by cleavage of the N±C4 bond and cyclization
of an open chain intermediate. Finally, appropriate work-
up of the reaction mixture resulted in the isolation of
pyrimidinones 6. It is worth noting that, in the reaction
performed with TMSI, the cyclization step is affected by

G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
7209
Finnigam TSQ-700 spectrometer using CI method. The
speci®c rotations were performed on a Perkin±Elmer 241
polarimeter. 1,3-Diaza-1,3-butadiene 1a,b, ketenes 2a±g
and azetidinones 3a±g are known compounds and were
prepared according to described methods1. b-silylalkyl-
chromatography (PE/EtOAc 95:5); yield 40%; yellow oil;
1H NMR (200 MHz): 0.06 (s, 3H, CH3±Si), 0.32 (s, 3H,
CH3±Si), 2.53 (d, 1H, CH±Si, Jvicˆ6.6 Hz), 3.84 (d, 1H,
CH2, Jgemˆ15.0 Hz), 3.70 (d, 1H, CH±CvO, Jvicˆ6.6 Hz),
4.63 (d, 1H, CH2, Jgemˆ15.0 Hz), 6.71 (m, 2H, arom.),
7.00±7.04 (m, 3H, arom.), 7.22±7.51 (m, 20H, arom.),
7.81 (s, 1H, CHvN); 13C NMR (50.3 MHz): 24.1, 23.0
(CH3), 35.0 (CH±Si), 45.0 (CH2), 66.8 (CH±CvO), 87.1
(N±C±N), 124.9, 127.7, 127.9, 128.0, 128.3, 128.7, 128.8,
128.9, 129.0, 129.4, 131.5, 134.6 (CH arom.; three signals
obscured), 135.7, 136.6, 137.0, 137.6, 139.7 (C arom.; one
signal obscured), 158.0 (CHvN), 170.1 (CvO); IR (KBr,
cm21): 1644 (n CvN), 1750 (n CvO); elem. anal., found
(calcd for C38H36N2OSi): C 80.31 (80.81), H 6.28 (6.42), N
4.58 (4.96).
È
ketene 2i, b-menthoxyketene 2j and Evans±Sjogren ketenes
2k,l formally derived from, respectively, 3(S)-(dimethyl-
phenylsilyl)-3-phenyl-propionyl chloride4, menthoxy-acetyl
chloride5
and
(2-oxo-4-phenyl-oxazolidin-3-yl)-acetyl
chloride6 were synthesized in agreement to reported literature.
3.2. 1-Benzyl-4-1benzylidene-amino)-4-phenyl-azetidin-
2-ones 3h,i±p
A solution of appropriate acyl chloride (1.2 mmol) in dry
toluene (8 mL) was added slowly (over a period of 1 h) to a
nitrogen ¯ushed, well stirred and ice-water cooled solution
of 1,3-diaza-1,3-butadiene 1a or b (1.0 mmol) and triethyl-
amine (2.3 mmol) in dry toluene (14 mL). After complete
addition of acyl chloride, the reaction mixture was stirred
for 3±24 h at room temperature. It was then thoroughly
washed ®rst with a cold saturated solution of NaHCO3
(14 mL) and then with cold water (15 mL). The organic
layer was dried over anhydrous Na2SO4 and freed from solvent
under reduced pressure at 408C. The crude product was
puri®ed by crystallisation and/or by ¯ash chromatography.
3.2.4. 1-Benzyl-4-1benzylidene-amino)-3-menthoxy-4-
phenyl-azetidin-2-one 3l. Reaction time: 24 h; puri®ed by
¯ash chromatography (PE/EtOAc 95:5); yield 29%; yellow
oil; H NMR (200 MHz): 0.76 (d, 6H, CH3±CH±CH3 and
1
CH3±CH(CH2)2, Jvicˆ7.0 Hz), 0.84 (d, 3H, CH3±CH±CH3,
Jvicˆ7.0 Hz), 0.90±1.30 (m, 4H, CH2 menthoxy), 1.40±1.60
(m, 4H, CH2 and CH menthoxy), 2.19 (d sept., 1H, CH3±
CH±CH3, Jvicˆ7.0 and 2.2 Hz), 3.19 (dt, 1H, CH±O
menthoxy, Jvicˆ10.4 and 4.2 Hz), 3.71 (d, 1H, CH2±Ph,
Jgemˆ14.8 Hz), 4.38 (s, 1H, CH±CvO), 4.85 (d, 1H,
CH2±Ph, Jgemˆ14.8 Hz), 7.20±7.60 (m, 13H, arom.),
7.60±7.70 (m, 2H, arom.), 7.83 (s, 1H, Ph±CHvN); 13C
NMR (50.3 MHz): 16.8, 21.3, 22.5 (CH3), 23.7, 34.6, 41.2
(CH2 menthoxy), 25.9, 31.9, 48.5, (CH menthoxy), 45.0
(CH2±Ph), 82.4 (CH±O menthoxy), 89.2 (N±C±N), 94.6,
(CH±CvO), 128.2, 128.4, 128.7, 129.1, 129.3, 129.7,
129.9, 131.7 (CH arom.; one signal obscured), 136.0,
136.8, 137.4 (C arom.), 158.5 (CHvN), 168.5 (CvO); IR
(NaCl, cm21): 1646 (n CvN), 1766 (n CvO), 1062 (n C±
O); elem. anal., found (calcd for C33H38N2O2): C 80.01
(80.13), H 7.89 (7.74), N 5.13 (5.66).
3.2.1. 3-Azido-1-benzyl-4-1benzylidene-amino)-4-phenyl-
azetidin-2-one 3h. Reaction time: 3 h; puri®ed by crystal-
lization; yield 86%; white solid; mp 112±1138C (PE); H
1
NMR (200 MHz): 3.93 (d, 1H, CH2, Jgemˆ15.0 Hz), 4.93 (d,
1H, CH2, Jgemˆ15.0 Hz), 4.55 (s, 1H, CH) 7.17±7.59 (m,
13H, arom.), 7.60±7.66 (m, 2H, arom.), 7.92 (s, 1H,
CHvN); 13C NMR (50.3 MHz): 45.3 (CH2), 77.1 (CH),
87.9 (N±C±N), 128.1, 128.6, 128.7, 128.8, 128.9, 129.0,
129.3, 129.4, 131.9 (CH arom.), 134.9, 135.0, 136.4 (C
arom.), 159.8 (CHvN), 164.3 (CvO); IR (KBr, cm21):
1642 (n CvN), 1756 (n CvO), 2108 (n N3); elem. anal.,
found (calcd for C23H19N5O): C 72.25 (72.42), H 4.96
(5.02), N 18.39 (18.36).
3.2.5. 1-Benzyl-4-1benzylidene-amino)-3-menthoxy-4-
phenyl-azetidin-2-one 3m. Reaction time: 24 h; puri®ed
by ¯ash chromatography (PE/EtOAc 95:5); yield 36%;
yellowish oil; H NMR (200 MHz): 0.25 (d, 3H, CH3±
1
3.2.2.
13R,4R,30R)-1-Benzyl-4-1benzylidene-amino)-3-
CH±CH3, Jvicˆ6.9 Hz), 0.60 (d, 3H, CH3±CH± CH3,
Jvicˆ7.1 Hz), 0.86 (d, 3H, CH3±CH(CH2)2, Jvicˆ6.4 Hz),
0.70±1.70 (m, 4H, CH2 menthoxy), 1.40±1.60 (m, 4H,
CH2 and CH menthoxy), 2.06 (m, 1H, CH3± CH(CH2)2),
3.01 (dt, 1H, CH±O menthoxy, Jvicˆ10.6 and 4.2 Hz), 3.76
(d, 1H, CH2±Ph, Jgemˆ15.0 Hz), 4.47 (s, 1H, CH±
CvO),4.86 (d, 1H, CH2±Ph, Jgemˆ15.0 Hz), 7.22±7.57
(m, 13H, arom.), 7.65±7.70 (m, 2H, arom.), 7.84 (s, 1H,
CHvN); 13C NMR (50.3 MHz): 16.2, 21.3, 22.7 (CH3),
23.3, 34.7, 40.9 (CH2 menthoxy), 25.1, 31.9, 48.0, (CH
menthoxy), 44.9 (CH2±Ph), 81.4 (CH±O menthoxy), 89.4
(N±C±N), 92.7, (CH±CvO), 128.2, 128.6, 128.7, 129.1,
129.2, 129.5, 129.7, 129.8, 131.7 (CH arom.), 136.0,
136.6, 137.4 (C arom.), 158.5 (CHvN), 169.2 (CvO); IR
(NaCl, cm21): 1062 (n C±O), 1644 (n CvN), 1766 (n
CvO); elem. anal., found (calcd for C33H38N2O2): C
80.54 (80.13), H 7.95 (7.74), N 5.50 (5.66).
[1dimethyl-phenyl-silanyl)-phenyl-methyl]-4-phenyl-
azetidin-2-one 3j. Reaction time: 24 h; puri®ed by ¯ash
chromatography (PE/EtOAc 95:5); yield 35%; white solid;
1
mp 154±1558C (diisopropyl ether); H NMR (200 MHz):
0.19 (s, 3H, CH3±Si), 0.46 (s, 3H, CH3±Si), 2.43 (d, 1H,
CH±Si, Jvicˆ13.4 Hz), 3.68 (d, 1H, Jvicˆ13.4 Hz, CH±
CvO), 3.84 (d, 1H, CH2, Jgemˆ15.0 Hz), 4.91 (d, 1H,
CH2, Jgemˆ15.0 Hz), 6.22 (d, 2H, Jˆ6.4 Hz, arom.), 6.80±
7.01 (m, 4H, arom.), 7.12±7.43 (m, 19H, arom.), 7.74 (s,
1H, CHvN); 13C NMR (50.3 MHz): 22.6, 22.1 (CH3),
34.2 (CH±Si), 44.8 (CH2), 68.8 (CH±CvO), 87.4 (N±C±
N), 124.7, 127.5, 127.6, 127.8, 127.9, 128.1, 128.2, 128.5,
128.7, 128.9, 129.2, 129.5, 131.2, 135.0 (CH arom.; one signal
obscured), 135.9, 136.9, 137.6, 140.6 (C arom.; one signal
obscured), 157.9 (CHvN), 169.7 (CvO); IR (KBr, cm21):
1648 (n CvN), 1748 (n CvO); elem. anal., found (calcd for
C38H36N2OSi): C 80.40 (80.81), H 6.37 (6.42), N 5.03 (4.96).
3.2.3. 13S,4S,30R)1-Benzyl-4-1benzylidene-amino)-3-[1di-
methyl-phenyl-silanyl)-phenyl-methyl]-4-phenyl-azeti-
din-2-one 3k. Reaction time: 24 h; puri®ed by ¯ash
3.2.6. 11)-1-Benzyl-4-1benzylidene-amino)-3-12-oxo-4-
phenyl-oxazolidin-3-yl)-4-phenyl-azetidin-2-one 3n.
Reaction time: 24 h; puri®ed by ¯ash chromatography

7210
G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
(PE/EtOAc 7:3); yield 75%; white solid; mp 1608C;
(200 MHz): 1.49 (bs, 2H, NH2), 3.87 (d, 1H, CH2,
Jgemˆ15.0 Hz), 4.96 (d, 1H, CH2, Jgemˆ15.0 Hz), 4.09 (s,
1H, CH) 7.20±7.58 (m, 13H, arom.), 7.60±7.67 (m, 2H,
arom.), 7.91 (s, 1H, CHvN); 13C NMR (50.3 MHz): 44.9
(CH2), 75.8 (CH), 90.0 (N±C±N), 127.5, 127.9, 128.1,
128.5, 128.7, 128.9, 129.1, 129.4, 131.3 (CH arom.),
135.5, 136.9, 137.1 (C arom.), 158.1 (CHvN), 170.5
(CvO); IR (KBr, cm21): 1645 (n CvN), 1756 (n CvO),
3302, 3366 (n NH2); elem. anal., found (calcd for
C23H21N3O): C 77.54 (77.72), H 5.78 (5.96), N 11.95
(11.82).
[a]21 ˆ11358 (c 0.006, CHCl3); 1H NMR (200 MHz):
D
4.00 (dd, 1H, CH2 oxazolidinone, Jvicˆ7.3 Hz and
Jgemˆ8.9 Hz), 4.33 (t, 1H, CH2 oxazolidinone, Jvicˆ
Jgemˆ8.9 Hz), 4.39 (d, 1H, CH2±Ph, Jgemˆ15.4 Hz), 4.47
(s, 1H, CH±CvO), 4.77 (m, 2H, CH2±Ph and CH oxazoli-
dinone), 7.00±7.06 (dd, 2H, arom.), 7.19±7.44 (m, 16H,
arom.), 7.53±7.58 (dd, 2H, arom.), 8.26 (s, 1H, CHvN);
13C NMR (50.3 MHz): 45.5 (CH2±Ph), 60.0 (CH oxazoli-
dinone), 70.9 (CH2 oxazolidinone), 72.6, (CH±CvO), 88.8
(N±C±N), 128.0, 128.2, 128.6, 128.9, 129.0, 129.1, 129.1,
129.2, 129.3, 129.4, 129.6, 132.0 (CH arom.), 135.2, 135.7,
137.2 (C arom.; one signal obscured), 157.6 (CvO oxa-
zolidinone), 160.9 (CHvN), 169.2 (CvO); IR (NaCl,
cm21): 1644 (n CvN), 1756, 1775 (n CvO); elem. anal.,
found (calcd for C32H27N3O3): C 76.54 (76.63), H 5.39
(5.43), N 8.42 (8.38).
3.4. Birch reduction7;11a of 3o and 5b
To a well stirred dark-blue solution of lithium shots
(0.033 g, 4.8 mmol) in liquid ammonia (9 mL), cooled at
2788C, a solution of 3o or 5b (0.40 mmol) in But±OH/
THF 1:10 (3 mL) was added, and the mixture was stirred
at 2788C for 3 min. The lithium excess was quenched
with solid ammonium chloride (12 equiv., 0.26 g)
whereas the ammonia was allowed to distil from the
reaction mixture at room temperature. The residual
solvents were then removed under reduced pressure and
the reaction mixture treated with water (8 mL), acidi®ed
with HCl 3N to pH 3 for 3 min, basi®ed with NaOH 2N
to pH 10 and ®nally extracted with methylene chloride. The
organic layer was dried and freed from solvent under
reduced pressure at 408C giving rise to crude propionamides
4a or b.
3.2.7. 12)-1-Benzyl-4-1benzylidene-amino)-3-12-oxo-4-
phenyl-oxazolidin-3-yl)-4-phenyl-azetidin-2-one 3o.
Reaction time: 24 h; puri®ed by ¯ash chromatography
(PE/EtOAc 7:3); yield 73%; white solid; mp 1598C;
1
[a]21 ˆ21338 (c 0.006, CHCl3); H NMR, 13C NMR and
D
IR data are identical to 3n; elem. anal., found (calcd
for C32H27N3O3): C 76.24 (76.63), H 5.36 (5.43), N 8.35
(8.38).
3.2.8. 11)-1-Benzyl-4-[14-methyl-benzylidene-amino]-3-
12-oxo-4-phenyl-oxazolidin-3-yl)-4-phenyl-azetidin-2-
one 3p. Reaction time: 24 h; puri®ed by ¯ash chromato-
graphy (PE/EtOAc 7:3); yield 83%; white solid; mp 85±
3.4.1. N-Benzyl-3-benzylamino-3-phenylpropionamide
4a. Puri®ed by ¯ash chromatography (PE/AcOEt/TEA
6:2:2); yield 62%; yellowish oil (lit. 92±938C);18 1H NMR
(200 MHz): 2.00 (bs, 1H, NH amine), 2.45±2.69 (m, 2H,
2nd order system, CH±CH2±CvO), 3.48 (d, 1H, Ph±CH2±
NH±CH, Jgemˆ12.7 Hz), 3.61 (d, 1H, Ph±CH2±NH±CH,
Jgemˆ12.7 Hz), 4.04 (dd, 1H, CH, Jvicˆ4.1 and 9.8 Hz),
4.40 (m, 2H, Ph±CH2±NH±CvO), 7.20±7.50 (m, 15H,
arom.), 7.84 (bs, 1H, NH amide); 13C NMR (50.3 MHz):
43.5, 44.2, 51.3 (CH2), 59.3 (CH), 126.8, 127.2, 127.4,
127.7, 128.0, 128.4, 128.8, 129.3 (CH arom.; one signal
obscured), 138.5, 139.6, 142.5 (C arom.), 171.1 (CvO
amide); IR (NaCl, cm21): 1650 (n CvO), 3290 (n NH);
m/z 345 (M11H, 100%).
888C; [a]21 ˆ11498 (c 0.006, CHCl3); 1H NMR
D
(200 MHz): 2.40 (s, 3H, CH3), 4.00 (dd, 1H, CH2 oxazoli-
dinone, Jvicˆ7.3 Hz and Jgemˆ8.8 Hz), 4.34 (t, 1H, CH2
oxazolidinone, JvicˆJgemˆ8.8 Hz), 4.41 (d, 1H, CH2±Ph,
Jgemˆ15.4 Hz), 4.49 (s, 1H, CH±CvO), 4.73 (d, 1H,
CH2vPh, Jgemˆ15.4 Hz), 4.80 (dd, 1H, CH oxazolidinone,
Jvicˆ7.3 and 8.8 Hz), 7.02±7.07 (dd, 2H, arom.), 7.17±7.38
(m, 16H, arom.), 7.47 (d, 2H, arom. p-tolyl, Jˆ8.1 Hz), 8.24
(s, 1H, CHvN); 13C NMR (50.3 MHz): 21.6 (CH3), 45.1
(CH2±Ph), 59.7, (CH oxazolidinone), 70.5 (CH2 oxazoli-
dinone), 72.2, (CH±CvO), 88.4 (N±C±N), 127.6, 127.8,
128.3, 128.5, 128.6, 128.7, 128.8, 128.9, 129.0, 129.2, 129.4
(CH arom.), 132.9, 135.0, 136.8, 139.9, 142.1 (C arom.),
157.3 (CvO oxazolidinone), 160.4 (CHvN), 163.5
(CvO); IR (NaCl, cm21): 1637 (n CvN), 1759, 1779 (n
CvO); elem. anal., found (calcd for C33H29N3O3): C 76.81
(76.87), H 5.61 (5.67), N 8.22 (8.15).
3.4.2. 2,3-Diamino-N-benzyl-3-phenyl-propionamide 4b.
The resulting crude product was characterized without
1
further puri®cation; yield 98%; yellowish oil; H NMR
(200 MHz, benzene): 1.67 (bs, 4H, NH2), 3.57 (d, 1H,
CH, Jvicˆ5.9 Hz), 4.37 (m, 2H, CH2), 5.47 (d, 1H, CH,
Jvicˆ5.9 Hz), 7.10±7.14 (m, 2H arom.), 7.20±7.47 (m, 8H,
arom.), 7.50 (bs, 1H, NH); 13C NMR (50.3 MHz, CDCl3):
43.5, (CH2±NH), 58.9 (CH), 61.3 (CH), 127.7, 127.9, 128.1,
128.2, 129.0 (CH arom.; one signal obscured), 138.7, 141.5
(C arom.), 173.5 (CvO); IR (NaCl, cm21): 1650 (n CvO),
3264, 3280 (n NH); m/z 270 (M11H, 100%).
3.3. 3-Amino-1-benzyl-4-1benzylidene-amino)-4-phenyl-
azetidin-2-one 3i
Triphenylphosphine12 (0.068 g, 0.26 mmol) was added to a
solution of 3h (0.1 g, 0.26 mmol) in THF (0.5 mL) contain-
ing one little boiling-stone to regularize the effervescence
(N2). When the effervescence ceased, water (0.02 mL,
1.11 mmol) was added and the reaction mixture left at
room temperature overnight. The reaction crude was then
diluted with ethyl acetate (10 mL) and washed with a satu-
rated solution of NaHCO3 (3£15 mL). The organic layer
was dried and freed from solvent under reduced pressure
at 408C. The crude product was puri®ed by ¯ash chromato-
3.5. N-Benzyl-3-benzylamino-2-12-oxo-4-phenyl-oxa-
zolidin-3-yl)-3-phenyl-acrylamide 5a
To a well stirred suspension of azetidinone 3n (0.1 g,
0.2 mmol) and an equal weight of 10% Pd/C in dry metha-
nol (5 mL), anhydrous ammonium formate13 (0.063 g,
1
graphy (PE/EtOAc 4:6); yield 65%; yellow oil; H NMR

G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
7211
1 mmol) was added in a single portion under nitrogen. The
3.8. 3-Benzyl-5-12-oxo-4-phenyl-oxazolidin-3-yl)-2,6-
diphenyl-2,3-dihydro-1H-pyrimidin-4-one 6a and 3-
benzyl-5-12-oxo-4-phenyl-oxazolidin-3-yl)-2-tolyl-6-
phenyl-2,3-dihydro-1H-pyrimidin-4-one 6c
reaction mixture was stirred under re¯ux and monitored by
TLC (PE/AcOEt 1:1). After 2 h, the catalyst was removed
by ®ltration through a celite pad washing with methanol and
chloroform. The combined organic ®ltrate was dried and
freed from solvent under reduced pressure. The crude
product was puri®ed by ¯ash chromatography (PE/AcOEt
To a stirred solution of azetidinone 3o or p (0.4 mmol) in
acetonitrile (5 mL), hexamethyldisilazane (0.210 mL,
1 mmol) and trimethylsilyl iodide (TMSI)15 (0.142 mL,
1 mmol) were added at room temperature. The reaction
mixture was stirred for 4±6 h, then cooled at 08C and treated
with DBU (0.149 mL, 2.5 mmol). Stirring was continued
overnight at room temperature, then the mixture was
quenched with 5 equiv. of HCl 1N (2 mL, 2 mmol), diluted
with water (10 mL) and extracted with ethyl acetate
(3£15 mL). The aqueous phase was adjusted to pH 10
with NaOH 1N then extracted again with ethyl acetate
(2£15 mL). The organic layer was ®nally dried and the
solvent evaporated in vacuo to give crude 6a and c, respec-
tively, which were puri®ed by ¯ash chromatography (PE/
AcOEt 7:3).
1
8:2); yield 94%; white solid; mp 71±738C (PE); H NMR
(200 MHz): 3.62 (t, 1H, CH2 oxazolidinone, Jvicˆ
Jgemˆ8.7 Hz), 3.86 (dd, 1H, CH oxazolidinone, Jvicˆ5.0
and 8.7 Hz), 4.05±4.18 (m, 5H, CH2 benzylics and one H
of CH2 oxazolidinone), 5.56 (brt, 1H, NH, Jvicˆ6.0 Hz),
6.93±6.99 (m, 2H, arom.), 7.10±7.54 (m, 18H, arom.),
10.18 (brt, 1H, NH, Jvicˆ6.1 Hz); 13C NMR (50.3 MHz):
43.0, (CH2±N), 48.5 (CH2±N), 63.0 (CH), 69.0 (CH2 oxa-
zolidinone), 96.2 (Csp2), 127.0, 127.2, 127.3, 127.5, 127.7,
128.2, 128.5, 128.7, 129.3, 129.4, 129.6, 129.7 (CH arom.),
133.3, 138.3, 138.6, 138.8 (C arom.), 159.1 (CvO oxa-
zolidinone), 162.5 (Csp2), 169.3 (CvO amide); IR (KBr,
cm21): 1608 (n CvO amide), 1742 (n CvO oxazolidi-
none), 3396 (n NH); m/z 504 (M11H, 100%).
3.8.1. 6a. yield 90%; white solid; mp 217±2188C (PE/
AcOEt); 1H NMR (300 MHz): 3.58 (d, 1H, CH2±Ph,
Jgemˆ15.3 Hz), 4.07 (t, 1H, CH2 oxazolidinone, Jvicˆ
Jgemˆ9.0 Hz), 4.32 (bd, 1H, NH, Jvicˆ1.1 Hz), 4.68 (t, 1H,
CH2 oxazolidinone, JvicˆJgemˆ9.0 Hz), 5.26 (t, 1H, CH
oxazolidinone, JvicˆJgemˆ9.0 Hz), 5.35 (d, 1H, CH2±Ph,
Jgemˆ15.3 Hz), 5.49 (d, 1H, CH, Jvicˆ1.1 Hz), 6.74 (d,
2H, arom. Jˆ7.3 Hz), 7.03 (t, 2H, arom., Jˆ7.3 Hz),
7.14±7.45 (m, 16H, arom.); 13C NMR (75.4 MHz): 46.7,
(CH2±Ph), 63.5 (CH), 70.2 (CH2), 71.9 (CH), 101.4
(Csp2), 127.7, 128.2, 128.3, 128.4, 128.6, 128.8, 129.3,
129.5, 130.4, 130.6, (CH arom.; two signals obscured),
133.6, 137.1, 137.6, 138.1 (C arom.), 155.4 (CvO), 160.8
(Csp2), 163.4 (CvO); IR (KBr, cm21): 1616 (n CvO
pyrimidinone), 1742 (n CvO oxazolidinone), 3286 (n
NH); m/z 501 (M11H, 55%); elem. anal., found (calcd
for C32H27N3O3): C 75.92 (76.63), H 4.46 (5.43), N 8.25
(8.38).
3.6. 3-Amino-N-benzyl-2-12-oxo-4-phenyl-oxazolidin-3-
yl)-3-phenyl-acrylamide 5b
To a solution of azetidinone 3n or p (0.2 mmol) in dry
methylene chloride (10 mL), a catalytic amount of 10%
Pd/C (0.01 g) was added and the reaction mixture was
shaken under hydrogen7,11a at atmospheric pressure for
4 h. The catalyst was then removed by ®ltration through a
celite pad washing carefully with methylene chloride.
The combined organic ®ltrate was dried and freed from
solvent under reduced pressure. The resulting crude
product was puri®ed by ¯ash chromatography (PE/AcOEt
1
75:25); yield 90±95%; white solid; mp 2248C (PE); H
NMR (200 MHz, benzene): 3.32 (t, 1H, one H of CH2
oxazolidinone, JvicˆJgemˆ11.2 Hz), 3.55±3.64 (m, 2H, CH
and one H of CH2 oxazolidinone), 4.16 (dd, 1H, Ph±CH2±
NH, Jvicˆ6.2 Hz and Jgemˆ15.0 Hz), 4.45 (dd, 1H,
Ph±CH2±NH, Jvicˆ6.2 Hz and Jgemˆ15.0 Hz), 6.14 (brt,
1H, NH, Jvicˆ6.2 Hz), 6.83±7.14 (m, 15H, arom. and
NH2), 7.35±7.42 (m, 2H, arom.); 13C NMR (50.3 MHz,
CDCl3): 43.3, (CH2±N), 62.8 (CH), 69.5 (CH2 oxazolidi-
none), 96.7 (Csp2), 127.4, 127.5, 127.7, 128.0, 128.8, 129.6,
130.5 (CH arom.; two signals obscured), 137.1, 137.9, 139.0
(C arom.), 159.1 (Csp2), 159.1 (CvO oxazolidinone), 168.8
(CvO amide); IR (KBr, cm21): 1636 (n CvO amide), 1728
(n CvO oxazolidinone), 3264, 3394 (n NH).
1
3.8.2. 6c. yield 83%; white solid; mp 178±1828C (PE); H
NMR (200 MHz): 2.36 (s, 3H, CH3) 3.58 (d, 1H, Ph±CH2±
Ph, Jgemˆ15.4 Hz), 4.08 (t, 1H, CH2 oxazolidinone, Jvicˆ
Jgemˆ9.0 Hz), 4.28 (bs, 1H, NH), 4.69 (t, 1H, CH2 oxazoli-
dinone, JvicˆJgemˆ9.0 Hz), 5.26 (bt, 1H, CH oxazolidinone,
JvicˆJgemˆ9.0 Hz), 5.36 (d, 1H, CH2±Ph, Jgemˆ15.4 Hz),
5.46 (d, 1H, CH, Jvicˆ1.3 Hz), 6.76 (d, 2H, arom.
Jˆ7.0 Hz), 7.01±7.43 (m, 17H, arom.); 13C NMR
(50.3 MHz): 21.3 (CH3), 46.3 (CH2±Ph), 63.1 (CH), 69.9
(CH2), 71.3 (CH), 100.8 (Csp2), 127.3, 127.8, 128.0, 128.1,
128.2, 128.5, 128.9, 129.2, 129.8, 130.3 (CH arom.; one
signal obscured), 133.4, 134.9, 136.9, 137.3, 140.1 (C
arom.), 155.2 (CvO), 160.5 (Csp2), 163.2 (CvO); IR
(KBr, cm21): 1614, (n CvO pyrimidinone) 1747 (n
CvO oxazolidinone), 3253 (n NH); m/z 501 (M11H,
55%); elem. anal., found (calcd for C32H27N3O3): C 75.92
(76.63), H 4.46 (5.43), N 8.25 (8.38).
14
3.7. Selective reduction with NaBH4
To a solution of 3o (0.05 g, 0.1 mmol) in THF (3 mL),
NaBH4 (0.003 g, 0.06 mmol) was added. The mixture was
stirred at room temperature and the progress monitored by
TLC (EP/AcOEt 1:1). After 24 h, the solution was diluted
with water (30 mL) and extracted with AcOEt (3£15 mL).
The combined organic layers were dried and freed from
solvent at reduced pressure. The crude product was puri®ed
by ¯ash chromatography (EP/AcOEt 75:25) to afford 5b
(0.03 g, 48%).
3.9. Alkaline hydrolysis of 3o
A suspension of azetidinone 3o (0.1 g, 0.2 mmol) and LiOH
(0.084 g, 2 mmol) in H2O/THF 3:1 (10 mL) was stirred at
room temperature for 4 h. The reaction mixture was then

7212
G. Abbiati, E. Rossi / Tetrahedron 57 .2001) 7205±7212
183±205. (g) Southgate, R. Contemp. Org. Synth. 1994, 1,
417±432. (h) Mascaretti, O. A.; Boschetti, C. E.; Danelon,
G. O.; Mata, E. G.; Roveri, O. A. Curr. Med. Chem. 1995,
1, 441±470. (i) Kidwai, M.; Sapra, P.; Bhusham, K. R. Curr.
Med. Chem. 1999, 6, 195±215.
diluted with HCl 0.1N to neutral pH and extracted with ethyl
acetate (3£15 mL). The organic layer was dried and the
solvent evaporated in vacuo yielding pure 5b (0.076 g,
93%).
3. Staudinger, H. Liebigs Ann. Chem. 1907, 356, 51.
4. (a) Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiarbide, M. Eur.
J. Org. Chem. 1999, 3223±3235 and citations therein.
(b) Palomo, C.; Aizpurua, J. M.; Garcia, J. M.; Galarza, R.;
Legido, M.; Urchegui, R.; Roman, P.; Luque, A.; Servercarrio,
J.; Linden, A. J. Org. Chem. 1997, 62, 2070±2079 and
citations therein.
3.10. Acidic hydrolysis of 3o
A suspension of azetidinone 3o (0.1 g, 0.2 mmol) in HCl 6N
(10 mL) was stirred at room temperature for 4 h. The reac-
tion mixture was then diluted with NaHCO3 to neutral pH
and extracted with ethyle acetate (3£15 mL). The organic
layer was dried and the solvent evaporated in vacuo. Puri-
®cation by ¯ash chromatography (PE/AcOEt 7:3) yields
progressively 6a (0.039 g, 39%) and 6b (0.042 g, 42%).
5. (a) Palomo, C.; Aizpurua, J. M.; Iturburu, M.; Urchegui, R.
J. Org. Chem. 1994, 59, 240±244 and citations therein. (b)
Fleming, I.; Newton, T. W. J. Chem. Soc., Perkin Trans. 1
1984, 1805±1808. (c) Buckle, M. J. C.; Fleming, I.; Gil, S.
Tetrahedron Lett. 1992, 33, 4479±4482. (d) Fleming, I.;
Roberts, R. S.; Smith, S. C. J. Chem. Soc., Perkin Trans. 1
1998, 1209±1214.
3.10.1. 3-Benzyl-5-12-oxo-4-phenyl-oxazolidin-3-yl)-2,6-
diphenyl-2,3-dihydro-1H-pyrimidin-4-one 6b. White
solid; mp 1978C (PE/AcOEt); H NMR (200 MHz): 3.66
1
(d, 1H, CH2±Ph, Jgemˆ15.1 Hz), 3.94 (t, 1H, CH2 oxazoli-
dinone, JvicˆJgemˆ9.0 Hz), 4.55 (t, 1H, CH2 oxazolidinone,
JvicˆJgemˆ9.0 Hz), 4.95 (t, 1H, CH oxazolidinone, Jvicˆ
Jgemˆ9.0 Hz), 5.01 (d, 1H, NH, Jvicˆ5.3 Hz), 5.47 (d, 1H,
CH, Jvicˆ5.3 Hz), 5.55 (d, 1H, CH2±Ph, Jgemˆ15.1 Hz),
6.49 (d, 2H, arom. Jˆ7.5 Hz), 6.85 (t, 2H, arom.,
Jˆ7.5 Hz), 7.05±7.45 (m, 16H, arom.); 13C NMR
(50.3 MHz): 47.5, (CH2±Ph), 63.7 (CH), 68.7 (CH), 70.2
(CH2), 102.2 (Csp2), 126.6, 128.0, 128.3, 128.4, 128.6,
128.7, 128.8, 128.9, 129.1, 129.2, 129.3, 130.9 (CH
arom.), 133.5, 137.1, 137.4, 139.8 (C arom.), 154.1
(CvO), 160.7 (Csp2), 162.7 (CvO); IR (KBr, cm21):
1610 (n CvO pyrimidinone), 1756 (n CvO oxazolidi-
none), 3262, 3396 (n NH); elem. anal., found (calcd for
C32H27N3O3): C 76.18 (76.63) H 4.35 (5.43) N 8.22 (8.38).
6. Lef¯er, M. T.; Calkins, E. Organic Synthesis Collected
Volume III; Wiley: New York, 1955; pp 547±548.
7. Evans, D. A.; Sjogren, E. B. Tetrahedron Lett. 1985, 32,
3783±3786.
8. Calculations were done with the HyperCheme program (6.0
release) and performed on a Hewlett Packardw (Pentiumw III,
500 MHz) computer. Energy minimizations were done with
AM19 method using Polak±Ribiere algorithm. All calcula-
tions were carried out assuming the gas phase.
9. Dewar, M. J. S.; Zoebish, E. G.; Healy, E. F.; Stewart, J. J. P.
J. Am. Chem. Soc. 1985, 107, 3902.
10. (a) Boger, D. L.; Myers, Jr., B. J. J. Org. Chem. 1991, 56,
5385±5390. (b) Alcaide, B.; Polanco, C.; Sierra, M. A. Eur. J.
Org. Chem. 1998, 2913±2921. (c) Burwood, M.; Davies, D.;
Diaz, I.; Grigg, R.; Molina, P.; Sridharan, M.; Hughes, M.
Tetrahedron Lett. 1995, 36, 9053±9056. (d) Duczek, W.;
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