Diazoketones as precursors in β-lactam synthesis. New insights into the mechanism of the photochemically induced Staudinger reaction

Article abstract of DOI:10.1039/b105748k

Diazoketones 1-3, derived from suitably protected amino acids (Ala, Val and Tle), have been photochemically rearranged in the presence of imines leading exclusively to trans-arranged 4-aryl- and cinnamoyl-substituted β-lactams 17-33 with up to 84% yield. Selectivities were dependent on the steric demand of the amino acid side-chain ranging from 65:35 to 90:10. The relative configurations were proved by several X-ray crystal structures and comparison of NMR spectra. Further reactions of the azetidinones at position C-4 have been performed: electron-rich aryl substituents (e.g., 4-methoxyphenyl, furyl and thienyl) could be degraded to carboxylic acids 34 and 35 which were further transformed to acetoxy derivatives (compounds 36 and 37) in a Kolbe reaction of type II. The cinnamoyl group could be oxidized to the formyl group by ozonolysis (→38,39). The mechanism of the photochemically induced β-lactam formation is discussed in detail.

Full text of DOI:10.1039/b105748k

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Diazoketones as precursors in ꢀ-lactam synthesis. New insights
into the mechanism of the photochemically induced Staudinger
reaction
1
Michael R. Linder, Wolfgang U. Frey and Joachim Podlech*
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55,
70569 Stuttgart, Germany. E-mail: joachim.podlech@po.uni-stuttgart.de;
Fax: ϩ711 685 4269; Tel: ϩ711 685 4335
Received (in Cambridge, UK) 27th June 2001, Accepted 13th August 2001
First published as an Advance Article on the web 27th September 2001
Diazoketones 1–3, derived from suitably protected amino acids (Ala, Val and Tle), have been photochemically
rearranged in the presence of imines leading exclusively to trans-arranged 4-aryl- and cinnamoyl-substituted
β-lactams 17–33 with up to 84% yield. Selectivities were dependent on the steric demand of the amino acid
side-chain ranging from 65 : 35 to 90 : 10. The relative configurations were proved by several X-ray crystal
structures and comparison of NMR spectra. Further reactions of the azetidinones at position C-4 have been
performed: electron-rich aryl substituents (e.g., 4-methoxyphenyl, furyl and thienyl) could be degraded to
carboxylic acids 34 and 35 which were further transformed to acetoxy derivatives (compounds 36 and 37)
in a Kolbe reaction of type II. The cinnamoyl group could be oxidized to the formyl group by ozonolysis
(
38, 39). The mechanism of the photochemically induced β-lactam formation is discussed in detail.
Introduction
β-Lactams (azetidin-2-ones) are one crucial structural element
of natural products with antibiotic properties.1 The resistance
of bacteria to some β-lactam antibiotics can be overcome, e.g.,
by using trans-configured β-lactam moieties in drugs which
show much higher stability towards these resistant bacteria.2
Thienamycin,2 as well as the recently discovered trinems,3
bear—contrary to the classical antibiotics like penicillin
and cephalosporin—a trans-configured β-lactam moiety and
contain a hydroxyalkyl substituent in position C-3 (Fig. 1).
The most frequently used method for the synthesis of
β-lactams is the Staudinger reaction in which in situ generated
ketenes—preferentially prepared from acid chlorides—are
reacted with imines.4 While several methods for the preparation
of hydroxyalkyl-substituted β-lactams using the Staudinger
reaction have been published,5 direct methods for the stereo-
selectivesynthesisofaminoalkyl-substitutedβ-lactamsusingthis
transformation have, to the best of our knowledge, not been
reported prior to our work. However, alternative routes to this
class of compounds are known.6 Recently, we presented a new
method for the preparation of β-lactams using diazoketones
prepared from amino acids as precursors for ketenes:7 in a
diastereoselective, photochemically induced reaction, exclus-
ively trans-configured 3-aminoalkyl-substituted β-lactams were
formed. This trans-substitution pattern is otherwise hard to
achieve. In this paper we present a method for the preparation
of 4-acetoxy- and 4-formyl-substituted β-lactams which should
be possible precursors for the synthesis of bicyclic β-lactams.
Fig. 1 Antibiotics bearing a trans-substituted β-lactam moiety.
formates led to the formation of β-lactams. Consequently we
made a virtue from necessity and used imines 4–16 prepared
from substituted benzaldehydes in our reaction. Both electron-
rich (e.g. 4-methoxy-substituted) and electron-deficient (e.g.
4-nitro-substituted) benzaldimines, as well as heteroaromatic
(thienyl- or furyl-) carbaldimines could be successfully used
(Table 1). Again, exclusively trans-configured β-lactams were
obtained; the substitution pattern could be proved by the
coupling constants between the hydrogen atoms attached at
positions C-3 and C-4 of the β-lactam ring. The selectivities are
obviously dependent on the steric demands of the side chain
introduced with the amino acid derived diazoketones 1–3
(derived from alanine, valine and tert-leucine, respectively). The
selectivities ranged from 65 : 35 (R = Me, derived from alanine)
to 90 : 10 (R = tBu, derived from tert-leucine). All isomers
(except lactams 25, 26 and 33, entries 9, 10 and 17, respectively;
see Experimental section) were separated by medium pressure
liquid chromatography (MPLC) and were fully characterized.
The configuration of the isomers could be proved by X-ray
crystallographic analyses of 18b, 19b, 20b, 21a (Fig. 2), 22b, 23a,
26a and 30b8 and by comparison of their NMR data.
We were especially interested in compounds with electron-
rich aromatic substituents, since these can be easily degraded
oxidatively to carboxylic acids with ruthenium tetraoxide
(prepared in situ from RuCl3–H5IO6 or RuCl3–NaIO4).9 Under
these conditions the electron-rich aromatic substituent is
oxidized first, the product migrates into the aqueous phase and
neither the benzyl group at the amide nitrogen, nor the Z group
is attacked. Utilization of periodic acid instead of sodium
periodate as the oxidizing agent seems to give slightly better
Results and discussion
In our previous papers, we presented the synthesis of β-lactams
bearing a phenyl substituent in position C-4.7 Since this is not
very advantageous for further reactions at this position, we
looked for alternative substituents. Surprisingly, all attempts
to use imines which are not derived from aromatic alde-
hydes failed. None of the aliphatic aldimines, imines or
imidoesters prepared from crotonic aldehyde, glyoxalates or
2566
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105748k

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Table 1 Photochemically induced β-lactam synthesis starting with diazoketones
Entry
R1
Diazoketone
R2
R3
Imine
Product
Yield (%)
dra
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
iPr
iPr
iPr
iPr
tBu
tBu
tBu
1
1
1
1
1
1
1
1
1
1
2
2
2
2
3
3
3
p-C6H4-NMe2
p-C6H4-OMe
p-C6H4-Cl
p-C6H4-NO2
2-Furyl
2-Thienyl
3-Thienyl
(E)-Styryl
Ph
Mesityl
2-Furyl
2-Thienyl
(E)-Styryl
(E)-Styryl
2-Furyl
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
tBu
tBu
Bn
Bn
Bn
Allyl
Bn
Allyl
Bn
4
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
72
50
55
44
76
54
67
70 : 30
70 : 30
70 : 30
65 : 35
65 : 35
65 : 35
65 : 35
65 : 35
70 : 30
70 : 30
80 : 20
75 : 25
80 : 20
75 : 25
90 : 10
90 : 10
87 : 13
5
6
7
9
10
11
12
13
14
9
58
b
60
72
72
70
44
84
84
60
10
12
15
9
16
12
2-Furyl
(E)-Styryl
a Determined from the crude product by HPLC and NMR analysis. b Crude product was not purified.
Table 2 Oxidative degradation of aromatic and heteroaromatic
substituents
Starting Reaction
material time/min Product (%)
Yield
Entry R1
R2
1
2
3
4
5
6
7
8
Me p-C6H4-OMe 18
Me p-C6H4-OMe 18
25a
60b
10a
15b
20b
10a
10a
15b
34
34
34
34
34
35
35
35
70
50
Quant.
90
80
90
80
80
Me 2-Furyl
Me 2-Furyl
Me 2-Thienyl
iPr 2-Furyl
iPr 2-Thienyl
iPr 2-Thienyl
21
21
22
27
28
28
Fig. 2 Major isomer of the 2-furyl-substituted β-lactam 21a (X-ray).8
a Oxidant: H5IO6. b Oxidant: NaIO4.
results (Table 2, entries 1, 3 and 7). The best results were
obtained, when furan or thiophene derivatives were used. The
corresponding carboxylic acids 34 and 35 could be obtained in
almost quantitative yield (e.g., entries 3 and 6).
Azetidinecarboxylic acids are known to be suitable for a
Kolbe reaction of type II,10 leading to cyclic acyliminium com-
pounds as intermediates which are usually trapped by acetate,
yielding acetoxy-substituted β-lactams. This reaction can be
performed electrochemically or with oxidizing agents such as
lead tetraacetate11 or peracids.12 We oxidized the azetidine-
carboxylic acids using lead tetraacetate and obtained trans-
substituted 4-acetoxyazetidines 36 and 37 in 82 and 83%
yield, respectively (Scheme 1, Fig. 3).8 Obviously, the reaction
proceeds stereoselectively with attack from the less hindered
face of the iminium carbon (opposite to the substituent in
position C-3). These acetoxy-substituted β-lactams are known
to be well-suited for nucleophilic substitution with enolates13 or
organometallic compounds.14 They have been used, e.g., for the
preparation of bicyclic β-lactams.15
Scheme 1 Kolbe reaction of type II starting with azetidinecarboxylic
acids.
considered as vinylogous benzaldimines. Accordingly, β-lactam
formation could be achieved under our reaction conditions.
The resulting styryl-substituted β-lactams were formed in 55–
70% yield. Selectivities were again ruled by the amino acid
derivative employed in the reaction (Table 1). Cleavage of the
double bond in styryl-substituted β-lactam 29a by ozonolysis16
led to the corresponding aldehyde 38 in 60% yield after
reductive workup (dimethyl sulfide). in situ Formation of
the corresponding dimethyl acetal 39 with trimethyl ortho-
formate facilitated purification by chromatography, leading
to a slightly improved yield and analytically pure material
(Scheme 2).
Because the photochemical reaction of diazoketones with
imines derived from crotonaldehyde did not lead to the form-
ation of β-lactams, we used cinnamaldimines, which can be
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
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Fig. 4 Cyclic imines and a formal [2ϩ2ϩ2]-cycloadduct.
Table 3 Activation energy for the β-lactam formation
Fig. 3 The acetoxy-substituted β-lactam 36.8
Activation
energy/
Entry
Substrate
R1
R2
kJ molϪ1 a
1
2
3
4
5
C
D
E
F
Ph
Vinyl
Me
Me
Me
—
61.6
61.7
67.4
75.3
73.3
2,4,6-Trimethoxyphenyl
—
—
Scheme 2 Ozonolysis of styryl-substituted β-lactams.
G
—
a Calculated with AM1.24 Force field calculations for the starting
materials, transition states, and products, respectively, confirmed that
these are extrema on the hypersurface.
Mechanistic considerations
The mechanism of the Staudinger reaction is well understood.4
A ketene (usually generated by elimination of hydrogen chloride
from an acid chloride) is attacked by the lone pair of an imine.
The intermediate iminium enolate A is subsequently ring-closed
to the corresponding β-lactam. The helical conformation of the
iminium enolate (the double bonds are not co-planar, the
dihedral angle is about 50Њ) allows—in accordance to the least-
motion-principle—ring-closure to the cis-substituted β-lactams
only (Scheme 3). The exclusive trans-substitution observed
(which are necessarily cis-substituted). Unfortunately, we could
not achieve β-lactam formation with 5-methyl-3,4-dihydro-2H-
pyrrole 40,19 3,3-dimethyl-3H-indole 4120 or 1-methyl-1H-
isoindole 4221 (Fig. 4). With 3,4-dihydroisoquinoline 4319 we
observed the product of a [2ϩ2ϩ2]-cyclisation, pentacycle
44,22 with incorporation of two equivalents of imine (Fig. 4), a
mode of reaction which has been observed previously by
Padwa et al.23
We calculated the activation energies of the iminium enolate
ring-closure (with a simplified substitution pattern) using
semi-empirical methods (AM1,24 Table 3). Interestingly, we
found that the activation energies of acyclic iminium enolates C
or D are about 12 kJ molϪ1 lower than for the corresponding
cyclic substrates F and G. Obviously these imines are too rigid
to allow an unhindered ring-closure to β-lactams, which would
explain why the cyclic imines did not yield any β-lactams.
Consequently, we tested imines, that should be too sterically
hindered for isomerization to cis-imines. However, with N-tert-
butylmesitylenecarbaldimine, again exclusively trans-configured
β-lactams were observed. It might be possible that the aromatic
ring is not fully co-planar with the imine double bond, which
would effectively reduce the steric hindrance. This seems to be
rational, since even in trans-N-benzyl-2,4,6-trimethoxybenz-
aldimine 8, an inclination of 27Њ of the aromatic ring is
observed in the crystal (Fig. 5).8 Nevertheless, β-lactam form-
ation was not possible employing imine 8 (cf. entry 3 in Table 3).
Hegedus et al. performed photochemically induced
Staudinger reactions starting with chromium carbene com-
Scheme 3 Proposed mechanism for the formation of trans-β-lactams.
with our reaction conditions might be explained by a trans
cis-isomerization of the imines, which is well known to occur
during irradiation or heating.17 The intermediacy of an
isomeric iminium enolate B would consequently give rise to a
trans-substituted β-lactam.18
To prove the proposed mechanism, we used cyclic imines
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Scheme 4 Intramolecular stabilization of acyl-substituted aminoalkyl-
ketenes.
the proposed cis-substituted imines (which should be much
more reactive than the trans-substituted imines, even if present
only in a small fraction) react fast enough to avoid this oxaz-
inone formation. Aliphatic aldimines are not isomerized by
irradiation (in the solvents used in our reaction) and thus might
be not reactive enough to compete with the intramolecular
reaction (K L).
In conclusion, we consider the isomerization of the respective
imines most likely. This would further explain why the selectiv-
ities are somewhat lower than in other Staudinger reactions in
which the ketenes had been generated from acid chlorides.
Evans et al. and other groups reported that with glycine-derived
acid chlorides attached to a chiral auxiliary, selectivities of
up to 97 : 3 were observed.16,30 Here a large substituent (R1
in Scheme 3) approaches the stereogenic centre of the inter-
mediate ketene. In the present case only a small hydrogen atom
interacts with the ketene, consequently leading to reduced
selectivities.
Fig. 5 Structure of imine 8 as determined by X-ray crystallographic
analysis.8
Table 4 Bond order of C–N double bonds in iminium compounds
The presented Staudinger reaction in conjunction with
the degradation of aromatic substituents supplies useful inter-
mediates, e.g., in the synthesis of bicyclic β-lactam antibiotics.
Work in this direction is currently ongoing in our laboratories.
Bond ordera
Excited state27
Experimental
Entry
Substrate
X
Ground state
General
1
2
3
4
5
6
H
H
H
I
H
1.70
1.54
1.76
1.18
1.63
1.28
1.24
1.36
1.23
NMe2
NO2
O
S
—
Solvents for chromatography and for workup, e.g. ethyl acetate
(EA) and light petroleum (PE) were distilled prior to use,
diethyl ether (ether) was distilled over KOH–FeSO4. Ether and
THF used for reactions were distilled over Na–benzophenone.
Amino acid derivatives were prepared by standard procedures.31
Common amino acid abbreviations are used.32 Diazoketones
1–3 were prepared in accordance with published procedures.33
Moisture-sensitive reactions were performed in dried vessels
(150 ЊC, 24 h) under a nitrogen atmosphere using syringe
techniques. Flash column chromatography: Merck silica gel 60
(230–400 mesh). TLC: precoated sheets, Alugram SIL G/UV254
Macherey-Nagel; detection by UV extinction or by heating
after dipping in a cerium molybdate solution [phosphomolyb-
dic acid (25 g), Ce(SO4)2ؒH2O (10 g), conc. H2SO4 (60 ml),
H2O (940 ml)]. MPLC: detection with a UV detector. HPLC:
analyses of diastereoisomer distribution were carried out with a
Pharmacia LKB, RSD 2140 apparatus with a Pharmacia LKB,
RSD 2249 mixer and diode-array detection (Pharmacia RSD
2140) on a LiChrosorb Si 60, Merck (hexane–EA, flow: 2.0 ml
minϪ1) chromatographic column. 1H and 13C NMR spectra
were recorded at rt in CDCl3 unless otherwise indicated; δ is
given in ppm relative to internal TMS (0 ppm) or to resonances
of the solvent (1H: CHCl3, 7.24 ppm; 13C: CDCl3, 77.0 ppm),
J in Hz. Mass spectra were recorded using FAB or EI
techniques. IR spectra were recorded with a FTIR instrument.
Elemental analyses were performed by the service of the
Institut für Organische Chemie, Stuttgart. Melting points are
not corrected.
1.64/1.64b
1.65/1.66b
1.67/1.66b
I
J
a Calculated with PM3.28 b Values for both planar conformations result-
ing from rotation around the C–C single bond are given.
plexes.25 In their opinion, the phenyl substituent in the
employed N-benzylbenzaldimine is responsible for the observed
trans-substitution. The weakening of the double bond in the
intermediate iminium enolate A (cf. Scheme 3) should allow
rotation to the less hindered trans-intermediate B, which, after
ring closure, should give rise to the trans-substituted β-lactam.26
Other reactions employing N-benzylbenzaldimine, however,
yielded cis-substituted β-lactams—obviously no isomerization
A
B had occurred.4,16
In addition, if an isomerization of the iminium enolates
occurred, we should observe a dependency of the cis/trans-
selectivity on the substituents at the imine. These have an effect
on the bond orders of the C–N double bond as has been shown
by semi-empirical calculations (Table 4). In fact, although bond
orders range from 1.54 to 1.76 for the ground state and from
1.18 to 1.63 for the excited state,27 exclusively trans-substituted
β-lactams were observed.28
It is quite astonishing that 3-aminoalkyl-substituted β-
lactams have not been prepared via the Staudinger reaction
before our work. A reason for this might be an intramolecular
stabilization of the intermediate ketenes K. With acyl substitu-
ents at the nitrogen (e.g. protection as carbamates) attack of the
acyl carbonyl on the electrophilic ketene centre leads to stable
4,5-dihydro-1,3-oxazin-6-ones L (Scheme 4).29 With no nucleo-
phile present, these are essentially stable; with protic nucleo-
philes they are ring-opened to the corresponding β-amino acid
derivatives. Obviously, these heterocycles are not able to react
with imines in a Staudinger reaction. It might be possible that
General procedure for the preparation of imines34
One equivalent of aldehyde was mixed with alumina (activity
grade 1, 500 mg mmolϪ1 aldehyde) and one equivalent of
amine. The mixture was sealed with a stopper, shaken and kept
for 12 h. Elution with CH2Cl2, filtration over Celite and evap-
oration yielded essentially pure imine (quantitative) which was
used without further purification.
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
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N-Benzyl-4-dimethylaminobenzaldehyde imine 4.35 δH (250
MHz; CDCl3) 3.00 [6 H, s, N(CH3)2], 4.76 (2 H, d, CH2), 6.69
(2 H, d, J 8.9, H-3, H-5), 7.19–7.33 (5 H, m, Ph), 7.66 (2 H, d,
N-tert-Butylbenzaldehyde imine 13.39 Deviating from the
general procedure, benzaldehyde (531 mg, 5.00 mmol) and
tert-butylamine (439 mg, 6.20 mmol) were heated for 10 h in
benzene (8 mL) with a Dean–Stark trap filled with molecular
sieve (4 Å). The solvent was removed via a rotary evaporator
and subsequently in vacuo (with partial evaporation of the
product) to yield the imine (484 mg, 60%) as a colourless oil: δH
(500 MHz; CDCl3) 1.30 [9 H, s, C(CH3)3], 7.38–7.40, 7.73–7.75
J 8.9, H-2, H-6) and 8.26 (1 H, s, N᎐CH); δ (63 MHz; CDCl )
᎐
C
3
40.2, 40.3 [2 q, N(CH3)2], 65.1 (t, CH2), 111.1, 126.9, 128.0,
128.5, 129.8 (5 d, ar.), 124.5, 140.2, 152.2 (3 s, ar.) and 162.1
(d, N᎐C).
᎐
N-Benzylanisaldehyde imine 5.36 δH (250 MHz; CDCl3) 3.83
(3 H, s, OCH3), 4.79 (2 H, s, CH2), 6.92 (2 H, d, J 4.8, H-3, H-5),
7.21–7.37 (5 H, m, Ph), 7.73 (2 H, d, J 4.8, H-2, H-6) and 8.32
(5 H, 2 m, Ph) and 8.23 (1 H, s, N᎐CH); δ (126 MHz; CDCl )
᎐
C
3
30.1 [3 q, C(CH3)3], 57.6 [s, C(CH3)3], 128.3, 128.9, 130.1 (3 d,
Ph), 137.6 (s, ipso-Ph) and 155.6 (s, N᎐C).
᎐
(1 H, s, N᎐CH); δ (63 MHz; CDCl3) 55.4 (q, OCH3), 65.1
(t, CH2), 114.1, 127.0, 128.1, 128.6, 129.3, 130.0 (5 d, 1 s, ar.),
᎐
C
N-tert-Butylmesitylenecarbaldehyde imine 14. Deviating from
the general procedure, mesitylenecarbaldehyde (889 mg, 6.00
mmol) and tert-butylamine (527 mg, 7.20 mmol) were heated
for 10 h in benzene (10 mL) with a Dean–Stark trap filled with
molecular sieve (4 Å). The solvent was removed via a rotary
evaporator and subsequently in vacuo to yield the imine (1.22 g,
quant.) as a colourless oil: δH (500 MHz; CDCl3) 1.31 [9 H, s,
C(CH3)3], 2.26 (3 H, s, CH3), 2.31 (6 H, s, 2 CH3), 6.83 (2 H, s,
139.7, 161.8 (2 s, ar.) and 161.4 (d, N᎐C).
᎐
N-Benzyl-4-chlorobenzaldehyde imine 6.35 δH (250 MHz;
CDCl3) 4.81 (2 H, s, CH2), 7.26–7.35 (5 H, m, Ph), 7.38 (2 H, d,
J 8.5, H-3, H-5), 7.71 (2 H, d, J 8.5, H-2, H-6) and 8.34 (1 H, s,
N᎐CH); δ (63 MHz; CDCl ) 65.1 (t, CH ), 127.2, 128.1, 128.7,
᎐
C
3
2
129.0, 129.6 (5 d, ar.), 134.8, 136.8, 139.2 (3 s, ar.) and 160.6
H-3, H-5) and 8.50 (1 H, s, N᎐CH); δ (126 MHz; CDCl ) 20.5
(d, N᎐C).
᎐
C
3
᎐
(2 q, 2 CH3), 21.9 (q, CH3), 30.1 [q, C(CH3)3], 58.3 [s, C(CH3)3],
N-Benzyl-4-nitrobenzaldehyde imine 7.34 δH (250 MHz;
CDCl3) 4.89 (2 H, s, CH2), 7.30–7.41 (5 H, m, Ph), 7.94 (2 H, d,
J 8.8, H-2, H-6), 8.27 (2 H, d, J 8.8, H-3, H-5) and 8.46 (1 H, s,
129.4 (d, C-3, C-5), 133.0 (s, C-1), 136.9 (s, C-2, C-6), 138.3 (s,
C-4) and 156.2 (N᎐C).
᎐
N-Allylcinnamaldehyde imine [(E,E )-4-aza-1-phenylhepta-
1,3,6-triene 15].40 N-Allylcinnamaldehyde imine was prepared
as described in the general procedure and purified by bulb-to-
bulb distillation (60%): δH (500 MHz; CDCl3) 4.14 (2 H, dd,
J 5.8 and 1.3, H-5), 5.14 (1 H, dd, J 10.7 and 1.5 Hz, Hb-7), 5.20
(1 H, dd, J 17.2 and 1.5, Ha-7), 6.03 (1 H, ddt, J 17.1, 10.4 and
5.9, H-6), 6.93 (1 H, d, J 5.4, H-2), 6.94 (1 H, m, H-1), 7.30–7.47
(5 H, m, Ph) and 8.02 (1 H, dd, J 5.5 and 1.2, H-3); δC (126
MHz; CDCl3) 65.5 (t, C-5), 116.1 (t, C-7), 127.2, 128.6, 129.1,
131.2 (4 d, C-2, Ph), 135.7, 135.8 (1 s, 1 d, ipso-Ph, C-6), 141.8
(d, C-1) and 163.5 (d, C-3).
N᎐CH); δ (63 MHz; CDCl ) 65.2 (t, CH ), 123.8, 127.3, 128.0,
128.6, 128.9 (5 d, ar.), 138.5, 141.6, 149.0 (3 s, ar.) and 159.5
᎐
C
3
2
(d, N᎐C).
᎐
N-Benzyl-2,4,6-trimethoxybenzaldehyde imine 8.37 Mp 83–85
ЊC (Found: C, 71.15; H, 6.7; N, 4.85; C17H19NO3 requires C,
71.55; H, 6.7; N, 4.9%); νmax (KBr)/cmϪ1 2910 (CH), 2860 (CH),
2810 (CH), 1595 (C᎐N), 1215 (CO), 790 (aryl–CH); δ (500
᎐
H
MHz; CDCl3) 3.83 (9 H, s, CH3), 4.83 (2 H, s, CH2), 6.13 (2 H,
s, H-3, H-5), 7.31–7.37 (5 H, m, Ph) and 8.63 (1 H, s, N᎐CH);
᎐
δC (126 MHz; CDCl3) 55.5, 56.0 (3 q, CH3), 66.7 (t, CH2), 90.6
(d, C-3, C-5), 107.4 (s, C-1), 126.5, 127.9, 128.5 (3 d, Ph), 140.3
N-Allylfuran-2-carbaldehyde imine 16.41 δH (500 MHz;
CDCl3) 4.21 (2 H, d, J 5.9, H-3), 5.15 (1 H, dd, J 10.2 and 1.6,
Hb-5), 5.21 (1 H, dd, J 15.4 and 1.7, Ha-5), 6.04 (1 H, m, H-4),
6.46 (1 H, dd, J 3.3 and 1.7, H-4Ј), 6.75 (1 H, d, J 3.4, H-3Ј),
7.50 (1 H, d, J 1.6, H-5Ј) and 8.09 (1 H, s, H-1); δC (126 MHz;
CDCl3) 63.6 (t, C-3), 110.2, 114.0 (2 d, C-3Ј, C-4Ј), 116.5
(t, C-5), 135.6 (d, C-4), 144.7 (d, C-5Ј), 150.6 (d, C-1) and 151.6
(s, C-2Ј).
(s, ipso-Ph), 157.3 (d, N᎐C), 160.9 and 162.5 (2 s, C-2, C-4, C-6);
᎐
m/z (FAB): 286 (100%, [M ϩ H]ϩ) and 91 (18, C7H7ϩ).
N-Benzylfuran-2-carbaldehyde imine 9.38 δH (500 MHz;
CDCl3) 4.77 (2 H, s, CH2), 6.45 (1 H, dd, J 3.5 and 1.3, H-4),
6.76 (1 H, d, J 3.5, H-3), 7.30–7.34 (5 H, m, Ph), 7.49 (1 H, d,
J 1.3, H-5) and 8.15 (1 H, s, N᎐C-H); δ (63 MHz; CDCl )
᎐
C
3
64.4 (t, CH2), 127.0, 127.3, 128.0, 128.5, 129.0, 130.6 (6 d,
C-3–C-5, C-2Ј–C-6Ј), 139.0 (s, C-1Ј), 142.5 (s, C-2) and 155.2
General procedure for the preparation of azetidinones
(d, N᎐C).
᎐
In
a quartz photo-reactor diazoketone and imine were
N-Benzylthiophene-2-carbaldehyde imine 10.38 δH (250 MHz;
CDCl3) 4.79 (2 H, s, CH2), 7.07 (1 H, dd, J 5.0 and 5.0, H-4),
7.22–7.41 (7 H, m, Ph, H-3, H-5) and 8.45 (1 H, d, J 1.0,
dissolved in Et2O (300 mL), the mixture was cooled to Ϫ15 ЊC
and irradiated for 90 min. The mixture was stirred for further
30 min at this temperature and then warmed to rt. The solvent
was removed and the diastereomeric ratio was determined by
HPLC and H NMR spectroscopy. The diastereoisomers were
separated by flash column chromatography or MPLC.
N᎐C-H); δ (63 MHz; CDCl ) 64.4 (t, CH ), 127.0, 127.3, 128.0,
᎐
C
3
2
1
128.5, 129.0, 130.6 (6 d, C-3–C-5, C-2Ј–C-6Ј), 139.0 (s, C-1Ј),
142.5 (s, C-2) and 155.2 (d, N᎐C).
᎐
N-Benzylthiophene-3-carbaldehyde imine 11. δH (500 MHz;
CDCl3) 4.75 (2 H, s, CH2), 7.26–7.35 (6 H, m, Ph, H-2),
7.55–7.60 (2 H, m, H-4, H-5) and 8.35 (1 H, s, N᎐C-H); δ (126
MHz; CDCl3) 64.9 (t, CH2), 125.8, 126.4, 126.9, 127.9, 128.4,
128.6 (6 d, C-2, C-4, C-5, Ph), 139.2 (s, C-1Ј), 140.4 (s, C-3) and
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)ethyl]-4-(4-dimethylaminophenyl)azetidin-2-one
17a,b. Following the general procedure, diazoketone 1 (495 mg,
2.00 mmol) and imine 4 (953 mg, 4.00 mmol) were irradiated to
give a mixture of 17a and 17b (720 mg, 79%, 70 : 30), which was
separated by MPLC (PE–i-PrOH 9 : 1) yielding 17a (456 mg,
50%) and 17b (200 mg, 22%) as colourless solids. Compound
17a: mp 148–149 ЊC; [α]2D0 Ϫ31 (c 1, CHCl3) (Found: C, 73.35; H,
6.95; N, 9.15; C28H31N3O3 requires C, 73.5; H, 6.85; N, 9.2%);
νmax (KBr)/cmϪ1 3260 (NH), 1700 (CO), 1240 and 680; δH (500
MHz; CDCl3) 1.31 (3 H, d, J 6.8, H-2Ј), 2.97 [6 H, s, N(CH3)2],
3.11 (1 H, dd, J 2.8 and 2.8, H-3), 3.66 (1 H, d, J 15.0,
NCH2Ph), 4.16 (2 H, m, H-4, H-1Ј), 4.81 (1 H, d, J 15.0,
NCH2Ph), 4.86 (1 H, d, J 8.8, NH), 4.92 (1 H, d, J 12.3,
᎐
C
156.2 (d, N᎐C).
᎐
N-Benzylcinnamaldehyde imine [(E,E )-4-aza-1,5-diphenyl-
penta-1,3-diene 12].34 δH (500 MHz; CDCl3) 4.71 (2 H, s, H-5),
6.96 (1 H, d, J 4.9, H-2), 6.98 (1 H, s, H-1), 7.31–7.49 (10 H, m,
2 Ph) and 8.13 (dd, 1 H, J 5.0 and 1.4, H-3); δC (126 MHz;
CDCl3) 65.3 (t, C-5), 127.2, 127.8, 128.1, 128.5, 128.8, 129.1,
129.2 (7 d, C-2, Ph), 135.7 (s, ipso-Ph), 139.2 (s, ipso-Ph), 142.0
(d, C-1) and 163.4 (d, C-3).
2570
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577

View Article Online
OCH2Ph), 5.11 (1 H, d, J 12.3, OCH2Ph), 6.70 [2 H, d,
J 7.5, p-C6H4-N(CH3)2] and 7.12–7.37 [12 H, m, 2 Ph, p-C6H4-
N(CH3)2]; δC (126 MHz; CDCl3) 19.9 (q, C-2Ј), 40.5
[q, N(CH3)2], 44.0 (t, NCH2Ph), 45.2 (d, C-1Ј), 56.7 (d, C-4),
64.9 (d, C-3), 66.7 (t, OCH2Ph), 112.6 [d, C6H4-N(CH3)2], 123.9
[s, C6H4-N(CH3)2], 127.5, 127.7, 127.9, 128.1, 128.3, 128.5 [7 d,
2 Ph, C6H4-N(CH3)2, partly covered], 135.7, 136.5 (2 s, 2 Ph),
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxy-
carbonylamino)ethyl]-4-(4-chlorophenyl)azetidin-2-one 19a,b.
Following the general procedure, diazoketone 1 (495 mg, 2.00
mmol) and imine 6 (915 mg, 4.00 mmol) were irradiated to give
a mixture of 19a and 19b (707 mg, 79%, 70 : 30), which was
separated by MPLC (PE–i-PrOH 97 : 3) yielding 19a (304 mg,
34%) and 19b (188 mg, 21%) as colourless solids. Compound
19a: mp 134–135 ЊC; [α]2D0 Ϫ25 (c 1, CHCl3) (Found: C, 69.65; H,
5.65; N, 6.2; C26H25ClN2O3 requires C, 69.55; H, 5.6; N, 6.25%);
νmax (KBr)/cmϪ1 3270 (NH), 1725 (CO), 1700 (CO), 1535, 1240,
1045 and 680; δH (500 MHz; CDCl3) 1.33 (3 H, d, J 6.9, H-2Ј),
3.10 (1 H, s, H-3), 3.71 (1 H, d, J 14.9, NCH2Ph), 4.18 (1 H, mc,
H-1Ј), 4.22 (1 H, s, H-4), 4.82 (1 H, d, J 14.9, NCH2Ph), 4.85
(1 H, d, J 9.4, NH), 4.91 (1 H, d, J 12.2, OCH2Ph), 5.11 (1 H, d,
J 12.2, OCH2Ph) and 7.09–7.38 (14 H, m, 2 Ph, p-C6H4-Cl);
δC (126 MHz; CDCl3) 19.8 (q, C-2Ј), 44.5 (t, NCH2Ph), 45.1 (d,
C-1Ј), 56.1 (d, C-4), 65.4 (d, C-3), 66.9 (t, OCH2Ph), 127.7,
127.9, 128.0, 128.2, 128.3, 128.6, 128.8, 129.2, 134.3, 135.1,
150.6 [s, C H -N(CH ) ], 155.5 (s, NH-C᎐O), 167.6 (s, C-2); m/z
᎐
6
4
3 2
(FAB) 458 (100%, [M ϩ 1]ϩ). Compound 17b: mp 115–116 ЊC;
[α]2D0 ϩ27 (c 1, CHCl3) (Found: C, 73.55; H, 6.95; N, 9.15;
C28H31N3O3 requires C, 73.5; H, 6.85; N, 9.2%); νmax (KBr)/cmϪ1
3295 (NH), 1735 (CO), 1680 (CO), 1605, 1515, 1350, 1230 and
680; δH (500 MHz; CDCl3) 1.27 (3 H, d, J 6.7, H-2Ј), 2.96 [6 H,
s, N(CH3)2], 3.04 (1 H, dd, J 7.8 and 1.3, H-3), 3.70 (1 H,
d, J 15.0, NCH2Ph), 4.13 (1 H, m, H-1Ј), 4.23 (1 H, s, H-4),
4.78 (1 H, d, J 15.0, NCH2Ph), 4.85 (1 H, d, J 8.9, NH), 5.04
(1 H, d, J 12.3, OCH2Ph), 5.10 (1 H, d, J 12.3, OCH2Ph),
6.67 [2 H, d, J 7.5, p-C6H4-N(CH3)2] and 7.14–7.36 [12 H,
m, 2 Ph, p-C6H4-N(CH3)2]; δC (126 MHz; CDCl3) 18.6 (q,
C-2Ј), 40.5 [2 q, N(CH3)2], 44.1 (t, NCH2Ph), 46.4 (d, C-1Ј),
57.9 (d, C-4), 65.2 (d, C-3), 66.6 (t, OCH2Ph), 112.6 [d,
p-C6H4-N(CH3)2], 124.1 [s, p-C6H4-N(CH3)2], 127.5, 127.6,
128.1, 128.4, 128.5, 128.7 [7 d, 2 Ph, p-C6H4-N(CH3)2, partly
covered], 135.7, 136.5 (2 s, 2 Ph), 150.6 [s, p-C6H4-N(CH3)2],
135.8, 136.2 (8 d, 4 s, 2 Ph, p-C H -Cl), 156.1 (s, NH-C᎐O)
᎐
6
4
and 167.5 (s, C-2); m/z (EI, 70 eV) 448 (3%, Mϩ), 357 (23, [M Ϫ
C7H7]ϩ), 270 (22, [M Ϫ C10H12NO2]ϩ), 224 (9, [C10H12NO2 Ϫ
C2H4N]ϩ), 163 (12, [C10H12NO2 Ϫ C7H7O]ϩ) and 91 (100,
C7H7ϩ). Compound 19b: mp 125–126 ЊC; [α]2D0 ϩ22 (c 1, CHCl3)
(Found: C, 69.55; H, 5.6; N, 6.15; C26H25ClN2O3 requires C,
69.55; H, 5.6; N, 6.25%); νmax (KBr)/cmϪ1 3320 (NH), 1740
(CO), 1680 (CO), 1515, 1230, 685 and 485; δH (500 MHz;
CDCl3) 1.29 (3 H, d, J 6.6, H-2Ј), 2.99 (1 H, dd, J 8.0 and 1.7,
H-3), 3.78 (1 H, d, J 14.9, NCH2Ph), 4.14 (1 H, mc, H-1Ј), 4.37
(1 H, s, H-4), 4.76 (1 H, d, J 14.8, NCH2Ph), 4.78 (1 H, d, J 6.3,
NH), 5.02 (1 H, d, J 12.2, OCH2Ph), 5.11 (1 H, d, J 12.2,
OCH2Ph), 7.03 (2 H, d, J 8.0, p-C6H4-Cl), 7.10 (2 H, m, p-C6H4-
Cl) and 7.24–7.35 (10 H, m, 2 Ph); δC (126 MHz; CDCl3) 18.6
(q, C-2Ј), 44.6 (t, NCH2Ph), 46.4 (d, C-1Ј), 57.7 (d, C-4), 65.9
(d, C-3), 66.7 (t, OCH2Ph), 127.8, 127.9, 128.2, 128.3, 128.5,
128.6, 128.8, 129.2, 134.2, 135.1, 135.9, 136.3 (8 d, 4 s, 2 Ph,
155.5 (s, NH-C᎐O) and 167.6 (s, C-2); m/z (FAB) 458 (100%,
᎐
[M ϩ 1]ϩ).
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)ethyl]-4-(4-methoxyphenyl)azetidin-2-one
18a,b.
Following the general procedure, diazoketone 1 (495 mg, 2.00
mmol) and imine 5 (897 mg, 4.00 mmol) were irradiated to give
a mixture of 18a and 18b (719 mg, 81%, 70 : 30), which was
separated by MPLC (PE–i-PrOH 96 : 4) yielding 18a (320 mg,
36%) and 18b (128 mg, 14%) as colourless solids. Compound
18a: mp 125–126 ЊC; [α]2D0 Ϫ5 (c 0.5 in CHCl3) (Found: C, 72.95;
H, 6.4; N, 6.25; C27H28N2O4 requires C, 72.95; H, 6.35; N,
6.3%); νmax (KBr)/cmϪ1 3270 (NH), 1720 (CO), 1700 (CO),
1535, 1505, 1240, 1045 and 682; δH (500 MHz; CDCl3) 1.32
(3 H, d, J 6.8, H-2Ј), 3.11 (1 H, s, H-3), 3.68 (1 H, d, J 15.0,
NCH2Ph), 3.82 (3 H, s, OCH3), 4.19 (2 H, m, H-4, H-1Ј), 4.81
(1 H, d, J 15.0, NCH2Ph), 4.87 (1 H, d, J 8.5, NH), 4.92 (1 H, d,
J 12.2, OCH2Ph), 5.11 (1 H, d, J 12.2, OCH2Ph), 6.88 (2 H, d,
J 8.0, C6H4-OCH3) and 7.10–7.38 (12 H, m, 2 Ph, C6H4-OCH3);
δC (126 MHz; CDCl3) 19.9 (q, C-2Ј), 44.3 (t, NCH2Ph), 45.1
(d, C-1Ј), 55.3 (q, OCH3), 56.4 (d, C-4), 65.1 (d, C-3), 66.8
(t, OCH2Ph), 114.3 (d, C6H4-OCH3), 127.6, 127.8, 127.9, 128.1,
128.3, 128.5, 128.7, 128.9, 135.5, 136.3 (7 d, 3 s, 2 Ph, C6H4-
p-C H -Cl), 155.1 (s, NH-C᎐O) and 167.1 (s, C-2); m/z (EI, 70
᎐
6
4
eV) 448 (1%, Mϩ), 420 (21, [M Ϫ CO]ϩ), 357 (12, [M Ϫ C7H7]ϩ),
270 (21, [M Ϫ C10H12NO2]ϩ), 224 (6, [C10H12NO2 Ϫ C2H4N]ϩ),
163 (9, [C10H12NO2 Ϫ C7H7O]ϩ) and 91 (100, C7H7ϩ).
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)ethyl]-4-(4-nitrophenyl)azetidin-2-one 20a,b. Follow-
ing the general procedure, diazoketone 1 (495 mg, 2.00 mmol)
and imine 7 (957 mg, 4.00 mmol) were irradiated to give a
mixture of 20a and 20b (620 mg, 67%, 65 : 35), which was
separated by MPLC (PE–i-PrOH 97 : 3) yielding 20a (255 mg,
28%) and 20b (144 mg, 16%) as colourless solids. Compound
20a: mp 163–164 ЊC; [α]2D0 Ϫ45 (c 1, CHCl3) (Found: C, 67.7; H,
5.45; N, 9.1; C26H25N3O5 requires C, 67.95; H, 5.5; N, 9.15%);
νmax (KBr)/cmϪ1 3360 (NH), 1730 (CO), 1710 (CO), 1505, 1340,
1235, 1045 and 680; δH (500 MHz; CDCl3) 1.36 (3 H, d, J 7.0,
H-2Ј), 3.14 (1 H, s, H-3), 3.80 (1 H, d, J 14.9, NCH2Ph), 4.21
(1 H, mc, H-1Ј), 4.37 (1 H, d, J 1.6, H-4), 4.83 (1 H, d, J 14.9,
NCH2Ph), 4.89 (1 H, d, J 8.3, NH), 4.91 (1 H, d, J 12.2,
OCH2Ph), 5.11 (1 H, d, J 12.2, OCH2Ph), 7.09 (2 H, mc,
p-C6H4-NO2), 7.20, 7.30–7.42 (10 H, 2 m, 2 Ph) and 8.19 (2 H,
d, J 8.2, p-C6H4-NO2); δC (126 MHz; CDCl3) 19.6 (q, C-2Ј), 45.0
(t, NCH2Ph), 45.0 (d, C-1Ј), 56.0 (d, C-4), 65.8 (d, C-3), 67.0
(t, OCH2Ph), 124.2, 127.3, 127.9, 128.0, 128.3, 128.4, 128.6,
128.9, 134.7, 136.3 (8 d, 2 Ph, p-C6H4-NO2), 145.1, 147.9 (2 s,
OCH ), 156.1 (s, NH-C᎐O), 159.8 (s, C H -OCH ) and 167.7 (s,
᎐
3
6
4
3
C-2); m/z (FAB) 445 (100%, [M ϩ 1]ϩ), 353 (10, [M Ϫ C7H7]ϩ),
337 (5, [M Ϫ C7H7O]ϩ), 268 (100, [M Ϫ C10H12NO2]ϩ), 226 (10,
[C10H12NO2 Ϫ C2H4N]ϩ), 161 (20, [C10H12NO2 Ϫ C7H7O]ϩ) and
91 (80, C7H7ϩ). Compound 18b: mp 102–103 ЊC; [α]2D0 ϩ4 (c 0.5,
CHCl3) (Found: C, 72.65; H, 6.35; N, 6.3; C27H28N2O4 requires
C, 72.95; H, 6.35, N, 6.3%); νmax (KBr)/cmϪ1 3320 (NH), 1740
(CO), 1700 (CO), 1520, 1505, 1235, 1020 and 680; δH (500 MHz;
CDCl3) 1.28 (3 H, d, J 6.6, H-2Ј), 3.03 (1 H, dd, J 8.2 and 1.0,
H-3), 3.73 (1 H, d, J 15.0, NCH2Ph), 3.81 (3 H, s, OCH3), 4.14
(1 H, mc, H-1Ј), 4.27 (1 H, s, H-4), 4.77 (1 H, d, J 15.0,
NCH2Ph), 4.83 (1 H, d, J 8.8, NH), 5.03 (1 H, d, J 12.3,
OCH2Ph), 5.10 (1 H, d, J 12.3, OCH2Ph), 6.83 (2 H, d, J 8.7,
C6H4-OCH3), 7.05 (2 H, d, J 8.2, C6H4-OCH3), 7.11–7.13 and
7.25–7.36 (10 H, 2 m, 2 Ph); δC (126 MHz; CDCl3) 18.6 (q,
C-2Ј), 44.3 (t, NCH2Ph), 46.3 (d, C-1Ј), 55.3 (q, OCH3), 57.8 (d,
C-4), 65.5 (d, C-3), 66.7 (t, OCH2Ph), 114.4 (d, C6H4-OCH3),
127.7, 128.1, 128.4, 128.5, 128.8, 129.0, 135.5, 136.4 (7 d, 3 s,
p-C H -NO ), 156.2 (s, NH-C᎐O) and 167.2 (s, C-2); m/z (EI, 70
᎐
6
4
2
eV) 459 (16%, Mϩ), 368 (9, [M Ϫ C7H7]ϩ), 281 (20, [M Ϫ
C10H12NO2]ϩ), 236 (3, [C10H12NO2 NO2]ϩ), 174 (3,
Ϫ
[C10H12NO2 Ϫ C7H7O]ϩ), 91 (100, C7H7ϩ) and 44 (3, NO2ϩ).
Compound 20b: mp 160–161 ЊC; [α]2D0 ϩ52 (c 1, CHCl3) (Found:
C, 67.9; H, 5.55; N, 9.05; C26H25N3O5 requires C, 67.95; H, 5.5;
N, 9.15%); νmax (KBr)/cmϪ1 3305 (NH), 1740 (CO), 1680 (CO),
1505, 1340, 1235 and 680; δH (500 MHz; CDCl3) 1.33 (3 H, d,
J 6.8, H-2Ј), 2.98 (1 H, dd, J 8.9 and 2.2, H-3), 3.91 (1 H, d,
J 14.9, NCH2Ph), 4.16 (1 H, mc, H-1Ј), 4.54 (1 H, d, J 1.5, H-4),
2 Ph, C H -OCH , partly covered), 155.5 (s, NH-C᎐O), 159.8 (s,
᎐
6
4
3
C6H4-OCH3) and 167.4 (s, C-2); m/z (FAB) 445 (67%, [M ϩ
1]ϩ), 353 (13, [M Ϫ C7H7]ϩ), 268 (100, [M Ϫ C10H12NO2]ϩ), 226
(11, [C10H12NO2 Ϫ C2H4N]ϩ), 161 (25, [C10H12NO2 Ϫ C7H7O]ϩ)
and 91 (92, [C7H7]ϩ).
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
2571

View Article Online
4.73 (1 H, d, J 14.9, NCH2Ph), 4.78 (1 H, d, J 8.7, NH), 4.99
(1 H, d, J 12.2, OCH2Ph), 5.15 (1 H, d, J 12.2, OCH2Ph), 7.09
(2 H, mc, p-C6H4-NO2), 7.26–7.35 (10 H, 2 Ph) and 8.06 (2 H, d,
J 8.5, p-C6H4-NO2); δC (126 MHz; CDCl3) 18.7 (q, C-2Ј), 45.1
(t, NCH2Ph), 46.6 (d, C-1Ј), 58.0 (d, C-4), 66.5 (d, C-3), 66.8
(t, OCH2Ph), 124.1, 127.2, 128.1, 128.3, 128.4, 128.5, 128.6,
128.9, 134.7, 136.3 (8 d, 2 s, Ph, p-C6H4-NO2), 145.2, 147.8 (2 s,
cmϪ1 3320 (NH), 1760 (CO), 1690 (CO), 1525, 1240 and 680; δH
(500 MHz; CDCl3) 1.27 (3 H, d, J 6.7, H-2Ј), 3.19 (1 H, dd, J 8.1
and 1.5, H-3), 3.83 (1 H, d, J 15.1, NCH2Ph), 4.14 (1 H, mc,
H-1Ј), 4.65 (1 H, s, H-4), 4.77 (1 H, d, J 15.1, NCH2Ph), 4.93
(1 H, d, J 8.5, NH), 5.04 (1 H, d, J 12.3, OCH2Ph), 5.08 (1 H, d,
J 12.3, OCH2Ph), 6.82 (1 H, s, thienyl), 6.92 (1 H, mc, thienyl)
and 7.15–7.33 (m, 11 H, 2 Ph, thienyl); δC (126 MHz; CDCl3)
18.4 (q, C-2Ј), 44.4 (t, NCH2Ph), 46.3 (d, C-1Ј), 53.9 (d, C-4),
66.2 (d, C-3), 66.7 (t, OCH2Ph), 125.7, 126.1, 127.3, 127.8,
128.1, 128.2, 128.4, 128.5, 135.3, 136.3 (9 d, 2 s, 2 Ph, thienyl,
p-C H -NO ), 155.6 (s, NH-C᎐O) and 166.8 (s, C-2); m/z
᎐
6
4
2
(EI, 70 eV) 459 (14%, Mϩ), 368 (12, [M Ϫ C7H7]ϩ), 281 (19,
[M Ϫ C10H12NO2]ϩ), 236 (1, [C10H12NO2 Ϫ NO2]ϩ), 174 (3,
[C10H12NO2 Ϫ C7H7O]ϩ), 91 (100, C7H7ϩ) and 44 (3, NO2ϩ).
partly covered), 141.2 (s, thienyl), 155.5 (s, NH-C᎐O) and 166.9
᎐
(s, C-2); m/z (FAB) (100%, [M ϩ 1]ϩ).
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[(1-benzyloxycarb-
onylamino)ethyl]-4-(2-furyl)azetidin-2-one 21a,b. Following the
general procedure, diazoketone 1 (989 mg, 4.00 mmol) and
imine 9 (1.48 g, 8.00 mmol) were irradiated to give a mixture of
21a and 21b (1.43 g, 88%, 65 : 35), which was separated by
MPLC (PE–i-PrOH 97 : 3) yielding 21a (803 mg, 50%) and 21b
(415 mg, 26%) as colourless solids. Compound 21a: mp 109–
110 ЊC; [α]2D0 ϩ25 (c 1, CHCl3) (Found: C, 71.05; H, 6.0; N, 6.8;
C24H24N2O4 requires C, 71.25; H, 6.0; N, 6.95%); νmax (KBr)/
cmϪ1 3300 (NH), 1750 (CO), 1675 (CO), 1525, 1240, 1040, 990,
730 and 680; δH (500 MHz; CDCl3) 1.35 (3 H, d, J 6.9, H-2Ј),
3.51 (1 H, s, H-3), 3.78 (1 H, d, J 15.1, NCH2Ph), 4.18 (1 H, mc,
H-1Ј), 4.30 (1 H, s, H-4), 4.69 (1 H, d, J 15.1, NCH2Ph), 4.89
(1 H, d, J 8.7, NH), 4.94 (1 H, d, J 12.3, OCH2Ph), 5.11 (1 H, d,
J 12.3, OCH2Ph) and 7.12–7.38 (13 H, m, 2 Ph, furyl); δC (126
MHz; CDCl3) 19.8 (q, C-2Ј), 44.7 (t, NCH2Ph), 45.0 (d, C-1Ј),
50.2 (d, C-4), 61.3 (d, C-3), 66.9 (t, OCH2Ph), 109.8, 110.5 (2 d,
furyl), 127.6, 128.0, 128.2, 128.6, 128.7, 135.4, 136.3 (6 d, 2 s, 2
Ph, partly covered), 143.2 (s, furyl), 149.8 (d, furyl), 156.1 (s,
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)ethyl]-4-(3-thienyl)azetidin-2-one 23a,b. Following
the general procedure, diazoketone 1 (989 mg, 4.00 mmol) and
imine 11 (1.61 g, 8.00 mmol) were irradiated to give a mixture
of 23a and 23b (1.41 g, 84%, 65 : 35), which was separated by
MPLC (PE–i-PrOH 95 : 5) yielding 23a (720 mg, 43%) and 23b
(398 mg, 24%) as colourless solids. Compound 23a: mp 140–
141 ЊC; [α]2D0 ϩ18 (c 1, CHCl3) (Found: C, 68.45; H, 5.75; N, 6.6;
C24H24N2O3S requires C, 68.55; H, 5.75; N, 6.65%); νmax (KBr)/
cmϪ1 3250 (NH), 1730 (CO), 1715 (CO), 1545, 1240, 1050, 725
and 680; δH (500 MHz; CDCl3) 1.33 (3 H, d, J 6.9, H-2Ј), 3.21 (1
H, dd, J 2.6 and 2.6, H-3), 3.74 (1 H, d, J 15.0, NCH2Ph), 4.19
(1 H, mc, H-1Ј), 4.36 (1 H, s, H-4), 4.78 (1 H, d, J 15.0,
NCH2Ph), 4.93 (2 H, m, NH, OCH2Ph), 5.11 (1 H, d, J 12.2,
OCH2Ph), 6.98 (1 H, d, J 3.8, thienyl) and 7.11–7.34 (12 H, m,
2 Ph, thienyl); δC (126 MHz; CDCl3) 19.8 (q, C-2Ј), 44.4 (t,
NCH2Ph), 45.1 (d, C-1Ј), 52.7 (d, C-4), 64.3 (d, C-3), 66.8 (t,
OCH2Ph), 123.2, 125.3, 127.1, 127.6, 128.0, 128.2, 128.3, 128.5,
128.7, 135.4, 136.3 (9 d, 2 s, 2 Ph, thienyl), 138.8 (s, thienyl),
NH-C᎐O) and 167.1 (s, C-2); m/z (FAB) 404 (100%, [M ϩ 1]ϩ).
᎐
Compound 21b: mp 110–111 ЊC; [α]2D0 Ϫ40 (c 1, CHCl3) (Found:
C, 71.15; H, 6.0; N, 6.85; C24H24N2O4 requires C, 71.25; H, 6.0;
N, 6.95); νmax (KBr)/cmϪ1 3315 (NH), 1760 (CO), 1695 (CO),
1520, 1230, 1050, 700 and 680; δH (500 MHz; CDCl3) 1.28 (3 H,
d, J 6.7, H-2Ј), 3.42 (1 H, d, J 6.6, H-3), 3.85 (1 H, d, J 15.0,
NCH2Ph), 4.13 (1 H, mc, H-1Ј), 4.38 (1 H, s, H-4), 4.65 (1 H, d,
J 15.0, NCH2Ph), 4.93 (1 H, d, J 8.5, NH), 5.06 (2 H, s,
OCH2Ph), 6.15 (1 H, s, furyl), 6.29 (1 H, mc, furyl) and 7.25–
7.36 (11 H, m, 2 Ph, furyl); δC (126 MHz; CDCl3) 18.2 (q, C-2Ј),
44.8 (t, NCH2Ph), 46.0 (d, C-1Ј), 51.3 (d, C-4), 61.7 (d, C-3),
66.7 (t, OCH2Ph), 109.5, 110.5 (2 d, furyl), 127.7, 128.1, 128.2,
128.3, 128.5, 128.7, 135.4, 136.4 (6 d, 2 s, 2 Ph), 143.2 (s, furyl),
156.1 (s, NH-C᎐O) and 167.4 (s, C-2); m/z (FAB) 420 (100%,
᎐
[M ϩ 1]ϩ). Compound 23b: mp 91–92 ЊC; [α]2D0 Ϫ14 (c 1, CHCl3)
(Found: C, 68.45; H, 5.85; N, 6.55; C24H24N2O3S requires C,
68.55; H, 5.75; N, 6.65%); νmax (KBr)/cmϪ1 3310 (NH), 1760
(CO), 1690 (CO), 1525, 1240, 725 and 680; δH (500 MHz;
CDCl3) 1.29 (3 H, d, J 6.8, H-2Ј), 3.09 (1 H, dd, J 8.2 and 2.0,
H-3), 3.82 (1 H, d, J 15.0, NCH2Ph), 4.14 (1 H, mc, H-1Ј), 4.46
(1 H, d, J 2.0, H-4), 4.72 (1 H, d, J 15.0, NCH2Ph), 4.87 (1 H, d,
J 8.7, NH), 5.03 (2 H, m, NH, OCH2Ph), 5.10 (1 H, d, J 12.3,
OCH2Ph), 6.87 (1 H, d, J 4.7, thienyl), 6.97 (1 H, s, thienyl),
7.12–7.14 and 7.25–7.35 (11 H, 2 m, 2 Ph, thienyl); δC (126
MHz; CDCl3) 18.5 (q, C-2Ј), 44.5 (t, NCH2Ph), 46.3 (d, C-1Ј),
54.1 (d, C-4), 64.8 (d, C-3), 66.7 (t, OCH2Ph), 123.0, 125.1,
125.9, 127.2, 127.8, 128.2, 128.4, 128.5, 128.8, 135.4, 136.4 (9 d,
149.9 (d, furyl), 155.5 (s, NH-C᎐O) and 167.0 (s, C-2); m/z
᎐
(FAB) 404 (100%, [M ϩ 1]ϩ).
2 s, 2 Ph, thienyl), 138.9 (s, thienyl), 155.5 (s, NH-C᎐O), 167.2
᎐
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)ethyl]-4-(2-thienyl)azetidin-2-one 22a,b. Following
the general procedure, diazoketone 1 (989 mg, 4.00 mmol) and
imine 10 (1.61 g, 8.00 mmol) were irradiated to give a mixture
of 22a and 22b (991 mg, 59%, 65 : 35), which was separated by
MPLC (PE–i-PrOH 96 : 4) yielding 22a (594 mg, 35%) and 22b
(320 mg, 19%) as colourless solids. Compound 22a: mp 134–
135 ЊC; [α]2D0 ϩ26 (c 1, CHCl3) (Found: C, 68.4; H, 5.85; N, 6.7;
C24H24N2O3S requires C, 68.55; H, 5.75; N, 6.65%); νmax (KBr)/
cmϪ1 3250 (NH), 1730 (CO), 1715 (CO), 1545, 1240, 1050, 725
and 680; δH (500 MHz; CDCl3) 1.34 (3 H, d, J 6.8, H-2Ј), 3.30
(1 H, dd, J 2.9 and 2.9, H-3), 3.77 (1 H, d, J 15.1, NCH2Ph),
4.21 (1 H, mc, H-1Ј), 4.54 (1 H, d, J 1.1, H-4), 4.80 (1 H, d,
J 15.1, NCH2Ph), 4.87 (1 H, d, J 8.5, NH), 4.92 (1 H, d, J 12.3,
OCH2Ph), 5.11 (1 H, d, J 12.3, OCH2Ph), 6.96 (2 H, s, thienyl)
and 7.14–7.37 (m, 11 H, 2 Ph, thienyl); δC (126 MHz; CDCl3)
19.8 (q, C-2Ј), 44.3 (t, NCH2Ph), 45.1 (d, C-1Ј), 52.6 (d, C-4),
65.8 (d, C-3), 66.8 (t, OCH2Ph), 125.8, 126.5, 127.3, 127.7,
128.0, 128.2, 128.3, 128.5, 128.7, 135.3, 136.2 (9 d, 2 s, 2 Ph,
(s, C-2); m/z (FAB) 421 (100%, [M ϩ 1]ϩ).
(E,3R,4R,1ЈS)- and (E,3S,4S,1ЈS)-1-Benzyl-3-[1-(benzyloxy-
carbonylamino)ethyl]-4-(2-phenylethenyl)azetidin-2-one 24a,b.
Following the general procedure, diazoketone 1 (495 mg, 2.00
mmol) and imine 12 (885 mg, 4.00 mmol) were irradiated to
give a mixture of 24a and 24b (66 : 34), which was separated by
MPLC (PE–i-PrOH 95 : 5) yielding 24a (340 mg, 39%) and 24b
(171 mg, 19%) as colourless solids. Compound 24a: mp 120–
121 ЊC; [α]2D0 Ϫ2 (c 0.6, CHCl3) (Found: C, 76.2; H, 6.45; N, 6.3;
C28H28N2O3 requires C, 76.35; H, 6.4; N, 6.35%); νmax (KBr)/
cmϪ1 3260 (NH), 1725 (CO), 1702 (CO), 1545 and 1245; δH (500
MHz; CDCl3) 1.34 (3 H, d, J 6.8, H-2Ј), 3.11 (1 H, dd, J 2.5 and
2.5, H-3), 3.91 (1 H, d, J 8.1, H-4), 3.96 (1 H, d, J 15.1,
NCH2Ph), 4.18 (1 H, mc, H-1Ј), 4.67 (1 H, J 15.1, NCH2Ph),
4.91 (1 H, d, J 8.6, NH), 4.95 (1 H, d, J 12.3, OCH2Ph), 5.11
(1 H, d, J 12.2, OCH2Ph), 6.04 (1 H, dd, J 15.5 and 8.7,
CH᎐CHPh), 6.55 (1 H, d, J 15.8, CH᎐CHPh) and 7.21–7.36
᎐
᎐
(15 H, m, 3 Ph); δC (126 MHz; CDCl3) 19.9 (q, C-2Ј), 44.6
(t, NCH2Ph), 45.0 (d, C-1Ј), 56.3 (d, C-4), 62.5 (d, C-3), 66.8
(t, OCH Ph), 126.0 (d, CH᎐CHPh), 126.6, 127.6, 128.0, 128.2,
thienyl), 141.1 (s, thienyl), 156.1 (s, NH-C᎐O) and 167.1 (s, C-
᎐
2); m/z (FAB) 420 (100%, [M ϩ 1]ϩ). Compound 22b: mp 105–
106 ЊC; [α]2D0 Ϫ35 (c 1, CHCl3) (Found: C, 68.75; H, 5.85; N, 6.8;
C24H24N2O3S requires C, 68.55; H, 5.75; N, 6.65%); νmax (KBr)/
᎐
2
128.3, 128.4, 128.5, 128.7, 128.7, 135.7, 135.8, 136.3 (9 d, 3 s, 3
Ph), 134.8 (d, CH᎐CHPh), 156.1 (s, NH-C᎐O), 167.0 (s, C-2);
᎐
᎐
2572
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577

View Article Online
m/z (FAB) 882 (3%, [2(M ϩ 1)]ϩ), 441 (68 [M ϩ 1]ϩ), 264 (78)
and 91 (100, C7H7ϩ). Compound 24b: mp 109–110 ЊC; [α]2D0 ϩ10
(c 0.5, CHCl3) (Found: C, 76.15; H, 6.45; N, 6.3; C28H28N2O3
requires C, 76.35; H, 6.4; N, 6.35%); νmax (KBr)/cmϪ1 3300
(NH), 1745 (CO), 1680 (CO), 1525 and 1233; δH (500 MHz;
CDCl3) 1.28 (3 H, d, J 6.7, H-2Ј), 3.05 (1 H, d, J 7.5, H-3), 4.00
(1 H, d, J 8.5, H-4), 4.03 (1 H, d, J 15.1, NCH2Ph), 4.13 (1 H, q,
J 7.2, H-1Ј), 4.64 (1 H, d, J 15.0, NCH2Ph), 4.94 (1 H, d, J 7.8,
NH), 5.04–5.12 (2 H, m, OCH2Ph), 5.99 (1 H, dd, J 15.7 and
dd, J 2.9 and 2.9, H-3), 3.76 (1 H, d, J 15.2, NCH2Ph), 3.83
(1 H, ddd, J 10.4, 7.3 and 2.9, H-1Ј), 4.26 (1 H, d, J 2.4, H-4),
4.67 (1 H, d, J 15.1, NCH2Ph), 4.95 (1 H, d, J 10.1, NH), 4.96
(1 H, d, J 12.3, OCH2Ph), 5.14 (1 H, d, J 12.3, OCH2Ph), 6.25
(1 H, d, J 3.1, C4H3O), 6.32 (1 H, dd, J 2.9 and 1.9, C4H3O),
7.13 (2 H, m, C4H3O, Ph), 7.18 and 7.34–7.40 (9 H, m, Ph); δC
(126 MHz; CDCl3) 18.9, 19.7 [2 q, CH(CH3)2], 32.0 (d, C-2Ј),
44.6 (t, NCH2Ph), 50.8 (d, C-4), 54.9 (d, C-1Ј), 58.6 (d, C-3),
66.9 (t, OCH2Ph), 110.0 (d, C4H3O), 110.5 (d, C4H3O), 127.5,
127.8, 128.1, 128.2, 128.5, 128.6 (6 d, Ph), 135.4, 136.4 (2 s, ipso-
Ph), 143.2 (d, C4H3O), 149.7 (s, ipso-C4H3O), 156.8 (s, NHCO)
8.7, CH᎐CHPh), 6.48 (1 H, d, J 15.8, CH᎐CHPh), 7.22–7.33
᎐
᎐
(15 H, m, 3 Ph); δC (126 MHz; CDCl3) 18.4 (q, C-2Ј), 44.7 (t,
NCH2Ph), 46.1 (d, C-1Ј), 57.5 (d, C-4), 62.7 (d, C-3), 66.7 (t,
OCH Ph), 126.3 (d, CH᎐CHPh), 126.6, 127.8, 128.1, 128.1,
and 166.9 (s, C-2); m/z (FAB) 455 (9%, [M ϩ Na]ϩ), 433 (75,
ϩ
[M ϩ H]ϩ), 228 (98, [M ϩ H Ϫ C12H15NO2]ϩ), 91 (100, C7H7
)
᎐
2
128.3, 128.5, 128.5, 128.7, 128.8, 135.7, 135.8, 136.3 (9 d, 3 s, 3
and 77 (8, C6H5ϩ). Compound 27b: mp 129–130 ЊC; [α]2D0 Ϫ39
(c 1, CHCl3) (Found: C, 72.45; H, 6.6; N, 6.35; C26H28N2O4
requires C, 72.2; H, 6.55; N, 6.5%); νmax (KBr)/cmϪ1 3358 (NH),
Ph), 134.6 (d, CH᎐CHPh), 155.5 (s, NH-C᎐O), 166.8 (s, C-2);
᎐
᎐
m/z (FAB) 441 (100%, [M ϩ 1]ϩ), 264 (43) and 91 (59, C7H7ϩ).
3130 (CH), 2940 (CH), 1742 (C᎐O), 1710 (C᎐O, amide I), 1520
᎐
᎐
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-3-[1-(Benzyloxycarbonyl-
amino)ethyl]-1-tert-butyl-4-phenylazetidin-2-one 25a,b. Follow-
ing the general procedure, diazoketone 1 (268 mg, 1.08 mmol)
and imine 13 (1.02 g, 4.32 mmol) were irradiated to give a
mixture of 25a and 25b. The ratio of isomers was determined
from the crude product (25a : b 74 : 26). Compound 25a,b:
δH (500 MHz; CDCl3; index a: major isomer, index b: minor
isomer) 1.17 [9 H, s, C(CH3)3], 1.31 (3 H, d, J 6.9, H-2Ј), 2.78
(1 H, dd, J 8.9 and 2.1, Hb-3), 2.87 (1 H, dd, J 3.2 and 2.2,
Ha-3), 4.22 (1 H, m, Hb-1Ј), 4.23 (1 H, m, Ha-1Ј), 4.38 (1 H, d,
J 2.2 Hz, Ha-4), 4.52 (1 H, d, J 2.3, Hb-4), 4.83 (1 H, d, J 9.0,
NHb), 4.88 (1 H, d, J 9.0, NHa), 5.07–5.19 (2 H, m, CH2) and
7.29–7.37 (10 H, m, Ph).
(NHCO, amide II), 1230 (CO), 750 and 680 (Ph); δH (500 MHz;
CDCl3) 0.88 [3 H, d, J 6.9, CH(CH3)2], 0.93 [3 H, d, J 6.8,
CH(CH3)2], 2.20 (1 H, mc, J 6.7, H-2Ј), 3.46 (1 H, dd, J 9.3 and
2.2, H-3), 3.90 (1 H, d, J 15.1, NCH2Ph), 4.08 (1 H, ddd, J 9.7,
9.7 and 4.0, H-1Ј), 4.43 (1 H, d, J 2.3, H-4), 4.61 (1 H, d, J 14.9,
NCH2Ph), 4.63 (1 H, d, J 8.6, NH), 5.02 (1 H, d, J 12.2,
OCH2Ph), 5.14 (1 H, d, J 12.3, OCH2Ph), 6.07 (1 H, d, J 3.1,
C4H3O), 6.27 (1 H, dd, J 3.0 and 2.0, C4H3O), 7.12–7.14 (2 H,
m, C4H3O, Ph) and 7.23–7.39 (9 H, m, Ph); δC (126 MHz;
CDCl3) 19.3, 19.8 [2 q, CH(CH3)2], 30.1 (d, C-2Ј), 44.8 (t,
NCH2Ph), 51.7 (d, C-4), 55.3 (d, C-1Ј), 59.7 (d, C-3), 66.8 (t,
OCH2Ph), 109.4 (d, C4H3O), 110.5 (d, C4H3O), 127.6, 128.1,
128.2, 128.3, 128.5, 128.7 (6 d, Ph), 135.4, 136.4 (2 s, ipso-Ph),
143.1 (d, C4H3O), 150.0 (s, ipso-C4H3O), 156.3 (s, NHCO) and
166.9 (s, C-2); m/z (FAB) 455 (25%, [M ϩ Na]ϩ), 433 (50, [M ϩ
H]ϩ), 228 (75, [M ϩ H Ϫ C12H15NO2]ϩ) and 91 (100, C7H7ϩ).
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-3-[1-(Benzyloxycarbonyl-
amino)ethyl]-1-tert-butyl-4-mesitylazetidin-2-one 26a,b. Follow-
ing the general procedure, diazoketone 1 (495 mg, 2.00 mmol)
and imine 14 (1.02 g, 5.00 mmol) were irradiated to give a
mixture of 26a and 26b (550 mg, 65%, 66 : 34). Purification by
MPLC (PE–i-PrOH 97 : 7) yielded 26a (320 mg, 38%) as a
colourless solid, whilst isomer 26b could not be isolated dia-
stereomerically pure. Compound 26a: mp 122–124 ЊC; [α]2D0 ϩ34
(c 0.5, CHCl3) (Found: C, 73.9; H, 8.15; N, 6.65; C26H34N2O3
requires C, 73.9; H, 8.1; N, 6.65%); νmax (KBr)/cmϪ1 3300 (NH),
2950 (CH), 1730 (C᎐O), 1705 (C᎐O, amide I), 1525 (NHCO,
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)-2-methylpropyl]-4-(2-thienyl)azetidin-2-one 28a,b.
Following the general procedure, diazoketone 2 (1.10 g, 4.00
mmol) and imine 10 (1.61 g, 8.00 mmol) were irradiated to give
a mixture of 28a and 28b (82 : 18), which was separated by
MPLC (PE–iPrOH 95 : 5) yielding 28a (1.03 g, 57%) and 28b
(275 mg, 15%) as colourless solids. Compound 28a: mp 119–
121 ЊC; [α]2D0 ϩ53 (c 1, CHCl3) (Found: C, 69.4; H, 6.2; N, 6.25;
C26H28N2O3S requires C, 69.6; H, 6.3; N, 6.25%); νmax (KBr)/
᎐
᎐
amide II), 1330 [C(CH3)3], 1230 (CO) and 680 (Ph); δH (500
MHz; CDCl3) 1.26 [9 H, s, C(CH3)3], 1.33 (3 H, d, J 7.0, H-2Ј),
2.25, 2.39, 2.45 [9 H, 3 s, C6H2(CH3)3], 3.17 (1 H, dd, J 2.6 and
2.6, H-3), 4.21 (1 H, ddq, J 9.4, 7.0 and 2.6, H-1Ј), 4.82 (1 H, d,
J 2.5, H-4), 4.89 (1 H, d, J 9.6, NH), 5.04 (1 H, d, J 12.3,
CHAHB), 5.21 (1 H, d, J 12.3, CHAHB), 6.81, 6.83 (2 H, 2 s,
H-3Љ, H-5Љ) and 7.32–7.38 (5 H, m, Ph); δC (126 MHz; CDCl3)
20.5 [q, C6H2(CH3)3], 20.9 (q, C-2Ј), 21.1, 21.6 [2 q,
C6H2(CH3)3], 27.8 [q, C(CH3)3], 45.7 (d, C-1Ј), 52.6 (d, C-4),
55.1 [s, C(CH3)3], 59.8 (d, C-3), 67.1 (t, OCH2Ph), 128.5, 128.7,
128.9 (3 d, Ph), 130.2 (d, C-3Љ or C-5Љ), 131.5 (s, ipso-Ph), 132.1
(d, C-3Љ or C-5Љ), 136.9 (s, C-1Љ), 137.5, 137.6, 137.7 (3 s, C-2Љ,
C-4Љ, C-6Љ), 156.6 (s, NHCO) and 168.9 (s, C-2); m/z (EI, 70 eV)
422 (30%, Mϩ) and 91 (95, C7H7ϩ).
cmϪ1 3250 (NH), 3025 (CH), 2940 (CH), 1725 (C᎐O), 1710
᎐
(C᎐O, amide I), 1590 (NHCO, amide II), 1240 (CO), 690 and
᎐
680 (Ph); δH (500 MHz; CDCl3) 0.95 [3 H, d, J 6.8, CH(CH3)2],
0.97 [3 H, d, J 6.7, CH(CH3)2], 1.94 (1 H, q, J 6.8, H-2Ј), 3.44
(1 H, dd, J 2.7 and 2.7, H-3), 3.77 (1 H, d, J 15.1, NCH2Ph),
3.88 (1 H, ddd, J 10.3, 7.5 and 3.0, H-1Ј), 4.49 (1 H, d, J 2.3,
H-4), 4.79 (1 H, d, J 15.1, NCH2Ph), 4.88 (1 H, d, J 10.2, NH),
4.93 (1 H, d, J 12.3, OCH2Ph), 5.15 (1 H, d, J 12.3, OCH2Ph),
6.97 (2 H, m, C4H3S), 7.12–7.41 (11 H, m, Ph, C4H3S); δC (126
MHz; CDCl3) 18.9, 19.7 [2 q, CH(CH3)2], 32.0 (d, C-2Ј), 44.4 (t,
NCH2Ph), 53.2 (d, C-1Ј), 54.9 (d, C-4), 63.3 (d, C-3), 66.9 (t,
OCH2Ph), 125.9, 126.7, 127.3, 127.6, 127.8, 128.1, 128.3, 128.6,
128.7 (9 d, Ph, C4H3S), 135.3, 136.3 (2 s, ipso-Ph), 141.1 (s, ipso-
C4H3S), 156.7 (s, NHCO) and 166.9 (s, C-2); m/z (EI, 70 eV) 448
(1%, Mϩ), 377 (95, [MϪ CO Ϫ C3H7]ϩ), 91 (100, C7H7ϩ). Com-
pound 28b: mp 137–139 ЊC; [α]2D0 Ϫ32 (c 1, CHCl3) (Found: C,
69.5; H, 6.3; N, 6.2; C26H28N2O3S requires C, 69.6; H, 6.3; N,
(3R,4S,1ЈS)- and (3S,4R,1ЈS)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)-2-methylpropyl]-4-(2-furyl)azetidin-2-one
27a,b.
Following the general procedure, diazoketone 2 (1.38 g, 5.00
mmol) and imine 9 (1.85 g, 10.0 mmol) were irradiated to give a
mixture of 27a and 27b (8 : 20), which was separated by MPLC
(PE–i-PrOH 97 : 3) yielding 27a (1.17 g, 54%) as a slightly
yellow oil and 27b (380 mg, 18%) as a colourless solid. Com-
pound 27a: [α]2D0 ϩ44 (c 1, CHCl3) (Found: C, 72.1; H, 6.6; N,
6.5; C26H28N2O4 requires C, 72.2; H, 6.5; N, 6.5%); νmax (film)/
6.25%); νmax (KBr)/cmϪ1 3340 (NH), 2950 (CH), 1740 (C᎐O),
᎐
1710 (C᎐O, amide I), 1525 (NHCO, amide II), 1230 (CO), 730
᎐
and 680 (Ph); δH (500 MHz; CDCl3) 0.86 [3 H, d, J 6.9,
CH(CH3)2], 0.93 [3 H, d, J 6.9, CH(CH3)2], 2.20 (1 H, m, H-2Ј),
3.24 (1 H, dd, J 9.4 and 2.0, H-3), 3.87 (1 H, d, J 15.1,
NCH2Ph), 3.88 (1 H, m, H-1Ј), 4.60 (1 H, d, J 10.0, NH), 4.67
(1 H, d, J 1.5, H-4), 4.75 (1 H, d, J 15.1, NCH2Ph), 5.04 (1 H, d,
J 12.2, OCH2Ph), 5.16 (1 H, d, J 12.2, OCH2Ph), 6.74 (1 H, d,
J 3.0, C4H3S), 6.91 (1 H, dd, J 5.0 and 3.6, C4H3S), 7.13–7.15
(2 H, m, Ph, C4H3S), 7.26 and 7.31–7.34 (9 H, m, Ph); δC (126
cmϪ1 3313 (NH), 3032 (CH), 2962 (CH), 1746 (C᎐O), 1713
᎐
(C᎐O, amide I), 1531 (NHCO, amide II), 1237 (CO), 739 and
᎐
698 (Ph); δH (500 MHz; CDCl3) 0.96 [3 H, d, J 6.9, CH(CH3)2],
0.99 [3 H, d, J 6.7, CH(CH3)2], 1.97 (1 H, m, H-2Ј), 3.68 (1 H,
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
2573

View Article Online
MHz; CDCl3) 16.3, 19.8 [2 q, CH(CH3)2], 30.0 (d, C-2Ј), 44.4
(d, C-1Ј), 54.2 (t, NCH2Ph), 55.5 (d, C-4), 64.2 (d, C-3), 66.9 (t,
OCH2Ph), 125.7, 126.0, 127.3, 127.7, 128.2, 128.3, 128.5, 128.8
(9 d, Ph, C4H3S, partly covered), 135.3, 136.4 (2 s, ipso-Ph),
141.4 (s, ipso-C4H3S), 156.2 (s, NHCO) and 166.8 (s, C-2); m/z
(FAB) 471 (45%, [M ϩ Na]ϩ), 449 (95, [M ϩ H]ϩ), 244 (84,
[M ϩ 2 H Ϫ C12H16NO2]ϩ) and 91 (100, C7H7ϩ).
dd, J 15.8 and 6.8, H-1Ј), 3.88 (1 H, ddd, J 10.4, 7.5, and 2.8,
H-1Ј), 3.99 (1 H, dd, J 8.8 and 2.4, H-4), 4.03 (1 H, dd, J 15.8
and 5.1, H-1Љ), 4.92 (1 H, d, J 10.2, NH), 5.13 (1 H, d, J 12.3,
OCH2Ph), 5.07 (1 H, d, J 10.2, H-3Љ), 5.14 (1 H, dd, J 17.2 and
1.0, H-3Љ), 5.18 (1 H, d, J 12.3, OCH2Ph), 5.65 (1 H, dddd,
J 17.2, 10.3, 6.6 and 5.2, H-2Љ), 6.10 (1 H, dd, J 15.8 and 8.8,
H-1ٞ), 6.66 (1 H, d, J 15.8, H-2ٞ) and 7.25–7.42 (10 H, m, Ph);
δC (126 MHz; CDCl3) 19.0, 19.8 [2 q, CH(CH3)2], 32.0 (d, C-2Ј),
42.9 (t, C-1Љ), 54.9 (d, C-1Ј), 57.2 (d, C-4), 59.8 (d, C-3), 66.9 (t,
OCH2Ph), 118.2 (t, C-3Љ), 126.1 (d, C-1ٞ), 126.6, 128.0, 128.1,
128.3, 128.5, 128.7 (6 d, Ph), 131.7 (d, C-2Љ), 134.8, 135.8 (2 s,
ipso-Ph), 136.5 (d, C-2ٞ), 156.8 (s, NHCO) and 166.8 (s, C-2);
m/z (FAB) 441 (6%, [M ϩ Na]ϩ), 419 (58, [M ϩ H]ϩ), 214 (100,
[M ϩ H Ϫ C12H15NO2]ϩ), 91 (100, C7H7ϩ). Compound 30b: mp
100–101 ЊC; [α]2D0 Ϫ94 (c 1, CHCl3) (Found: C, 74.55; H, 7.3; N,
6.65; C26H30N2O3 requires C, 74.6; H, 7.2; N, 6.7%); νmax (film)/
(E,3R,4R,1ЈS)- and (E,3S,4S,1ЈS)-1-Benzyl-3-[1-(benzyloxy-
carbonylamino)-2-methylpropyl]-4-(2-phenylethenyl)azetidin-2-
one 29a,b. Following the general procedure, diazoketone 2
(551 mg, 2.00 mmol) and imine 12 (885 mg, 4.00 mmol) were
irradiated to give a mixture of 29a and 29b (80 : 20), which was
separated by MPLC (PE–i-PrOH 95 : 5 and PE–EA 4 : 1) yield-
ing 29a (530 mg, 57%) as a colourless oil and 29b (126 mg, 13%)
as a colourless solid. Compound 29a: [α]2D0 ϩ29 (c 1, CHCl3)
(Found: C, 76.15; H, 6.95; N, 5.8; C30H32N2O3 requires C, 76.9;
H, 6.9; N, 6.0%); νmax (film)/cmϪ1 3313 (NH), 3062 (CH), 3030
cmϪ1 3320 (NH), 3031 (CH), 2950 (CH), 1745 (C᎐O), 1680
᎐
(C᎐O, amide I), 1525 (NHCO, amide II), 1237 (CO), 732 and
᎐
(CH), 2962 (CH), 2930 (CH), 1746 (C᎐O), 1650 (C᎐O, amide I),
675 (Ph); δH (500 MHz; CDCl3) 0.89, 0.96 [6 H, 2 d, J 6.8,
CH(CH3)2], 2.24 (1 H, dsept, J 6.9 and 3.6, H-2Ј), 3.02 (1 H, dd,
J 10.1 and 2.1, H-3), 3.55 (1 H, dd, J 15.8 and 6.7, H-1Љ), 4.00
(1 H, dd, J 15.8 and 5.4, H-1Љ), 4.09 (1 H, ddd, J 10.1, 10.1, 3.7,
H-1Ј), 4.19 (1 H, dd, J 8.8 and 2.0, H-4), 4.78 (1 H, d, J 10.1,
NH), 5.03 (1 H, d, J 12.2, OCH2Ph), 5.18 (1 H, d, J 10.2, H-3Љ),
5.19 (1 H, d, J 17.1, H-3Љ), 5.20 (1 H, d, J 12.2, OCH2Ph), 5.74
(1 H, dddd, J 17.1, 10.2, 6.9 and 5.5, H-2Љ), 6.06 (1 H, dd, J 15.7
and 8.8, H-1ٞ), 6.52 (1 H, d, J 15.8, H-2ٞ) and 7.23–7.41 (10 H,
m, Ph); δC (126 MHz; CDCl3) 16.0, 19.9 [2 q, CH(CH3)2], 29.9
(d, C-2Ј), 43.3 (t, C-1Љ), 55.7 (d, C-1Ј), 58.4 (d, C-4), 60.6 (d,
C-3), 66.9 (t, OCH2Ph), 118.5 (t, C-3Љ), 126.6 (d, C-1ٞ), 126.8,
128.1, 128.2, 128.3, 128.6, 128.7 (6 d, Ph), 131.8 (d, C-2Љ), 134.2,
135.8 (2 s, ipso-Ph), 136.4 (d, C-2ٞ), 156.4 (s, NHCO) and 166.7
(s, C-2); m/z (FAB) 441 (13%, [M ϩ Na]ϩ), 419 (38, [M ϩ H]ϩ),
214 (90, [M ϩ H Ϫ C12H15NO2]ϩ), 91 (100, C7H7ϩ).
᎐
᎐
1531 (NHCO, amide II), 1236 (CO) and 969 (C᎐C); δ (500
᎐
H
MHz; CDCl3) 0.96 [3 H, d, J 6.7, CH(CH3)2], 0.99 [3 H, d, J 6.8,
CH(CH3)2], 1.95 (1 H, m, H-2Ј), 3.25 (1 H, dd, J 2.2 and 2.2,
H-3), 3.83 (1 H, ddd, J 10.4, 7.5 and 2.9, H-1Ј), 3.87 (1 H, dd,
J 8.8 and 1.8, H-4), 3.97 (1 H, d, J 15.1, NCH2Ph), 4.66 (1 H, d,
J 15.1, NCH2Ph), 4.89 (1 H, d, J 10.2, NH), 4.97 (1 H, d, J 12.3,
OCH2Ph), 5.15 (1 H, d, J 12.3, OCH2Ph), 6.05 (1 H, dd, J 15.8
and 8.8, H-1Љ), 6.56 (1 H, d, J 15.8, H-2Љ) and 7.20–7.41 (15 H,
m, Ph); δC (126 MHz; CDCl3) 19.0, 19.6 [2 q, CH(CH3)2], 32.0
(d, C-2Ј), 44.6 (t, NCH2Ph), 54.9 (d, C-1Ј), 57.0 (d, C-4), 59.8
(d, C-3), 66.9 (t, OCH2Ph), 126.0 (d, C-1Љ), 127.6, 127.8, 128.0,
128.1, 128.3, 128.4, 128.5, 128.6, 128.7 (9 d, Ph), 134.9 (d, C-2Љ),
135.7, 135.8, 136.4 (3 s, ipso-Ph), 156.7 (s, NHCO) and 166.8 (s,
C-2); m/z (FAB) 469.2490; 12C30 H3314N216O3 requires 469.2491;
1
m/z (FAB) 491 (4%, [M ϩ Na]ϩ), 469 (38, [M ϩ H]ϩ), 264 (60,
[M ϩ H Ϫ C12H15NO2]ϩ) and 91 (100, C7H7ϩ). Compound 29b:
mp 64–66 ЊC; [α]2D0 ϩ26 (c 0.5, CHCl3) (Found: C, 76.5; H, 6.9;
N, 6.0; C30H32N2O3 requires C, 76.9; H, 6.9; N, 6.0%); νmax
(KBr)/cmϪ1 3322 (NH), 3062 (CH), 3030 (CH), 2961 (CH),
(3R,4S,1ЈR)- and (3S,4R,1ЈR)-1-Benzyl-3-[1-(benzyloxycarb-
onylamino)-2,2-dimethylpropyl]-4-(2-furyl)azetidin-2-one 31a,b.
Following the general procedure, diazoketone 3 (2.03 g, 7.00
mmol) and imine 9 (2.59 g, 14.0 mmol) were irradiated to give
a mixture of 31a and 31b (90 : 10), which was separated
by MPLC (PE–i-PrOH 98 : 2) yielding 31a (2.35 g, 75%) as
a colourless oil and 31b (270 mg, 9%) as a colourless solid.
Compound 31a: [α]2D0 ϩ61 (c 1, CHCl3) (Found: C, 72.5; H, 6.85;
N, 6.2; C27H30N2O4 requires C, 72.6; H, 6.75; N, 6.25%); νmax
2930 (CH), 1717 (C᎐O), 1637 (C᎐O, amide I), 1496 (NHCO,
᎐
᎐
amide II), 1237 (CO), 750 and 696 (Ph); δH (500 MHz; CDCl3)
0.88 [3 H, d, J 6.9, CH(CH3)2], 0.95 [3 H, d, J 6.8, CH(CH3)2],
2.18 (1 H, dsept, J 6.8 and 4.3, H-2Ј), 3.08 (1 H, dd, J 9.4 and
1.5, H-3), 4.04 (1 H, ddd, J 10.4, 9.3 and 4.4, H-1Ј), 4.05 (1 H,
dd, J 8.9 and 1.5, H-4), 4.10 (1 H, d, J 15.0, NCH2Ph), 4.59
(1 H, d, J 15.3, NCH2Ph), 4.61 (1 H, d, J 10.6, NH), 5.03 (1 H,
d, J 12.2, OCH2Ph), 5.17 (1 H, d, J 12.2, OCH2Ph), 5.96 (1 H,
dd, J 15.8 and 8.9, H-1Љ), 6.42 (1 H, d, J 15.8, H-2Љ) and 7.19–
7.43 (15 H, m, Ph); δC (126 MHz; CDCl3) 16.3, 19.8 [2 q,
CH(CH3)2], 30.1 (d, C-2Ј), 44.7 (t, NCH2Ph), 55.3 (d, C-1Ј),
57.9 (d, C-4), 60.6 (d, C-3), 66.9 (t, OCH2Ph), 126.5 (d, C-1Љ),
127.7, 128.2, 128.4, 128.5, 128.8 (9 d, Ph, partly covered), 134.9
(d, C-2Љ), 135.9, 136.4 (3 s, ipso-Ph, partly covered), 156.3 (s,
NHCO) and 166.7 (s, C-2); m/z (FAB) 491 (2%, [M ϩ Na]ϩ),
469 (12, [M ϩ H]ϩ), 264 (36, [M ϩ H Ϫ C12H15NO2]ϩ) and 91
(100, C7H7ϩ).
(film)/cmϪ1 3317 (NH), 3031 (CH), 2962 (CH), 1750 (C᎐O),
᎐
1713 (C᎐O, amide I), 1504 (NHCO, amide II), 1234 (CO), 736
᎐
and 698 (Ph); δH (500 MHz; CDCl3) 0.97 [9 H, s, C(CH3)3], 3.74
(1 H, dd, J 2.5 and 2.5 Hz, H-3), 3.76 (1 H, d, J 15.1, NCH2Ph),
3.87 (1 H, dd, J 10.7 and 2.4, H-1Ј), 4.25 (1 H, d, J 2.5, H-4),
4.66 (1 H, d, J 15.1, NCH2Ph), 4.96 (1 H, d, J 12.3, OCH2Ph),
5.04 (1 H, d, J 10.7, NH), 5.17 (1 H, d, J 12.3, OCH2Ph), 6.26
(1 H, d, J 3.3, C4H3O), 6.33 (1 H, dd, J 3.3 and 1.8, C4H3O),
7.12 (2 H, m, C4H3O, Ph), 7.18, 7.20–7.41 (9 H, m, Ph); δC (126
MHz; CDCl3) 26.8 [q, C(CH3)3], 34.8 (s, C-2Ј), 44.7 (t,
NCH2Ph), 51.6 (d, C-4), 57.4 (d, C-3), 58.0 (d, C-1Ј), 66.9 (t,
OCH2Ph), 110.2 (d, C4H3O), 110.5 (d, C4H3O), 127.5, 127.8,
128.1, 128.2, 128.5, 128.8 (6 d, Ph), 135.4, 136.4, 143.3, 149.6
(1 d, 3 s, C4H3O, ipso-C4H3O, ipso-Ph), 156.8 (s, NHCO) and
166.6 (s, C-2); m/z (FAB) 469 (8%, [M ϩ Na]ϩ), 447 (50, [M ϩ
H]ϩ), 228 (100, [M ϩ 2 H Ϫ C13H18NO2]ϩ), 91 (100, C7H7ϩ).
Compound 31b: mp 160–161 ЊC; [α]2D0 Ϫ103 (c 1, CHCl3)
(Found: C, 72.55; H, 6.8; N, 6.25; C27H30N2O4 requires C, 72.6;
H, 6.75; N, 6.25%); νmax (KBr)/cmϪ1 3315 (NH), 2940 (CH),
1735 (C᎐O), 1705 (C᎐O, amide I), 1523 (NHCO, amide II),
(E,3R,4R,1ЈS)- and (E,3S,4S,1ЈS)-1-Allyl-3-[1-(benzyloxy-
carbonylamino)-2-methylpropyl]-4-(2-phenylethenyl)azetidin-2-
one 30a,b. Following the general procedure, diazoketone 2
(851 mg, 3.09 mmol) and imine 15 (793 mg, 4.63 mmol) were
irradiated to give a mixture of 30a and 30b (720 mg, 56%,
75 : 25), which was separated by MPLC (PE–i-PrOH 98 : 2)
yielding 30a (460 mg, 36%) as a colourless oil and 30b (109 mg,
8%) as a colourless solid. Compound 30a: [α]2D0 ϩ125 (c 1.02,
CHCl3) (Found: C, 74.6; H, 7.35; N, 6.7; C26H30N2O3 requires
C, 74.6; H, 7.2; N, 6.7%); νmax (film)/cmϪ1 3306 (NH), 3031
᎐
᎐
1235 (CO), 750 and 680 (Ph); δH (500 MHz; CDCl3) 0.88 [9 H, s,
C(CH3)3], 3.70 (1 H, dd, J 4.7 and 2.6, H-3), 3.72 (1 H, d, J 15.2,
NCH2Ph), 4.15 (1 H, dd, J 10.6 and 4.7 Hz, H-1Ј), 4.17 (1 H, d,
J 2.4, H-4), 4.65 (1 H, d, J 10.6, NH), 4.72 (1 H, d, J 15.2,
NCH2Ph), 5.11 (1 H, d, J 12.1, OCH2Ph), 5.19 (1 H, d, J 12.1,
OCH2Ph), 6.13 (1 H, d, J 3.0, C4H3O), 6.31 (1 H, dd, J 3.0 and
(CH), 2961 (CH), 1732 (C᎐O), 1644 (C᎐O, amide I), 1538
᎐
᎐
(NHCO, amide II), 1237 (C-O), 749 and 695 (Ph); δH (500
MHz; CDCl3) 0.97, 1.00 [6 H, 2 d, J 6.7, CH(CH3)2], 1.95 (1 H,
sept, J 6.8, H-2Ј), 3.22 (1 H, dd, J 2.7 and 2.7, H-3), 3.46 (1 H,
2574
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577

View Article Online
1.8, C4H3O), 7.10 (2 H, m, C4H3O, Ph), 7.16 (3 H, m, Ph) and
7.33–7.38 (6 H, m, Ph); δC (126 MHz; CDCl3) 26.7 [q, C(CH3)3],
34.7 (s, C-2Ј), 44.6 (t, NCH2Ph), 50.0 (d, C-4), 57.1 (d, C-3),
58.0 (d, C-1Ј), 67.1 (t, OCH2Ph), 109.6 (d, C4H3O), 110.5 (d,
C4H3O), 127.6, 128.2, 128.3, 128.4, 128.6, 128.7 (6 d, Ph), 135.5,
136.4, 143.3, 149.8 (1 d, 3 s, C4H3O, ipso-C4H3O, ipso-Ph), 156.0
(s, NHCO) and 167.4 (s, C-2); m/z (EI, 70 eV) 446 (1%, Mϩ), 91
(100, C7H7ϩ).
dd, J 10.7 and 2.5, H-1Ј), 3.99 (1 H, d, J 15.1, NCH2Ph), 4.64
(1 H, d, J 15.1, NCH2Ph), 4.96 (1 H, d, J 12.3, OCH2Ph), 5.02
(1 H, d, J 10.7, NH), 5.18 (1 H, d, J 12.4, OCH2Ph), 6.04 (1 H,
dd, J 15.8 and 8.9, H-1Љ), 6.58 (1 H, d, J 15.8, H-2Љ) and 7.19–
7.40 (15 H, m, Ph); δC (major isomer, 126 MHz; CDCl3) 27.1 [q,
C(CH3)3], 35.2 (s, C-2Ј), 45.0 (t, NCH2Ph), 58.1, 58.3 (2 d, C-4,
C-1Ј), 59.1 (d, C-3), 67.2 (t, OCH2Ph), 125.9 (d, C-1Љ), 127.6,
127.8, 128.1, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8 (9 d, Ph),
135.5 (d, C-2Љ), 136.2, 136.2, 136.8 (3 s, ipso-Ph), 157.2 (s,
NHCO) and 166.9 (s, C-2); m/z [(33a : b, 87 : 13), FAB] 483
(48%, [M ϩ H]ϩ), 264 (70, [M ϩ H Ϫ C13H17NO2]ϩ) and 91
(100, C7H7ϩ).
(3R,4S,1ЈR)- and (3S,4R,1ЈR)-1-Allyl-3-[1-(benzyloxycarb-
onylamino)-2,2-dimethylpropyl]-4-(2-furyl)azetidin-2-one 32a,b.
Following the general procedure, diazoketone 3 (700 mg, 2.42
mmol) and imine 16 (426 mg, 3.15 mmol) were irradiated to
give a mixture of 32a and 32b (90 : 10), which was separated
by MPLC (PE–i-PrOH 98 : 2) yielding 32a (730 mg, 76%) as
a colourless solid and 32b (80 mg, 8%) as a colourless oil. Com-
pound 32a: mp 138–141 ЊC; [α]2D0 ϩ105 (c 1, CHCl3) (Found: C,
69.65; H, 7.1; N, 6.9; C23H28N2O4 requires C, 69.65; H, 7.1; N,
(3ЈR,4ЈS,1ЉS)-1-Benzyl-3-[1-(benzyloxycarbonylamino)ethyl]-2-
oxoazetidine-4-carboxylic acid 34
(a) β-Lactam 21a (402 mg, 1.00 mmol) and periodic acid
(3.42 g, 15.0 mmol) were dissolved in a mixture of acetonitrile,
CCl4 and H2O (2 : 2 : 3, 14 mL) and stirred, until a clear solu-
tion had formed (5 min). RuCl3ؒH2O (4.5 mg, 20 µmol) was
added and the mixture was stirred at room temperature. After
the evolution of gas stopped (10 min), the black mixture was
cooled (0 ЊC) and Et2O (5 mL) was added. The organic phase
was separated and the aqueous phase was extracted with Et2O
(2 × 5 mL). The combined organic layers were washed with
brine (2 × 5 mL), dried (MgSO4) and concentrated. The residue
was triturated with saturated NaHCO3 solution (10 mL) and
extracted with Et2O (3 × 10 mL). The aqueous phase was
acidified to pH 2 with 6 M HCl and extracted with Et2O (3 × 10
mL). The combined organic layers were dried (MgSO4) and
concentrated to yield the carboxylic acid 34 (383 mg, quant.) as
a colourless foam.
7.05%); νmax (KBr)/cmϪ1 3250 (NH), 2915 (CH), 1750 (C᎐O),
᎐
1705 (C᎐O, amide I), 1540 (NHCO, amide II), 1235 (CO), 725
᎐
and 680 (Ph); δH (500 MHz; CDCl3) 0.98 [9 H, s, C(CH3)3], 3.30
(1 H, dd, J 15.9 and 6.8, H-1Љ), 3.69 (1 H, dd, J 2.5 and 2.5,
H-3), 3.91 (1 H, dd, J 10.7 and 2.5, H-1Ј), 3.99 (1 H, dd, J 15.9
and 5.0, H-1Љ), 4.37 (1 H, d, J 2.5, H-4), 5.01 (1 H, d, J 10.7,
NH), 5.01 (1 H, dd, J 10.2 and 1.5, H-3Љ), 5.06 (1 H, dd, J 17.1
and 1.5, H-3Љ), 5.12 (1 H, d, J 12.2, OCH2Ph), 5.17 (1 H, d,
J 12.2, OCH2Ph), 5.54 (1 H, dddd, J 17.1, 10.2, 6.8 and 5.0,
H-2Љ), 6.35 (2 H, m, C4H3O) and 7.33–7.41 (6 H, m, C4H3O,
Ph); δC (126 MHz; CDCl3) 26.8 [q, C(CH3)3], 34.7 (s, C-2Ј), 43.1
(t, C-1Љ), 51.9 (d, C-4), 57.5 (d, C-3), 58.1 (d, C-1Ј), 66.9 (t,
OCH2Ph), 110.0 (d, C4H3O), 110.5 (d, C4H3O), 118.1 (t, C-3Љ),
128.0, 128.2, 128.5 (3 d, Ph), 131.3 (s, ipso-Ph), 136.4 (d, C-2Љ),
143.2, 149.8 (d, s, C4H3O, ipso-C4H3O), 157.0 (s, NHCO)
and 166.6 (s, C-2); m/z (FAB) 419 (33%, [M ϩ Na]ϩ), 397 (36,
[M ϩ H]ϩ), 220 (50, C13H18NO2ϩ), 178 (50, [M ϩ 2 H Ϫ
C13H18NO2]ϩ), 91 (100, C7H7ϩ). Compound 32b: [α]2D0 Ϫ80
(c 0.35, CHCl3) (Found: C, 69.75; H, 7.2; N, 6.7; C23H28N2O4
requires C, 69.65; H, 7.1; N, 7.0%); νmax (film)/cmϪ1 3250 (NH),
(b) Utilization of sodium periodate as oxidation agent
(further experimental details as described above) led within
15 min to the carboxylic acid 34 (344 mg, 90%).
(c) Further starting materials for the preparation of carb-
oxylic acid 34 are summarized in Table 2. Compound 34:
softening range 40–50 ЊC; νmax (KBr)/cmϪ1 3400 (NH), 3020
(CH), 2920 (CH), 1740 (C᎐O), 1715 (C᎐O), 1515 (NHCO,
᎐
᎐
2940 (CH), 1745 (C᎐O), 1735 (C᎐O, amide I), 725 and 680 (Ph);
᎐
᎐
amide II), 1230 (CO) and 680 (Ph); δH (500 MHz; CDCl3) 1.22
(1 H, d, J 6.7, H-2Љ), 3.34 (1 H, dd, J 2.8 and 2.8, H-3Ј), 3.77
(1 H, d, J 2.6, H-4Ј), 3.99 (1 H, d, J 15.0, NCH2Ph), 4.14 (1 H,
m, H-1Љ), 4.77 (1 H, d, J 15.0, NCH2Ph), 4.83 (1 H, d, J 12.3,
OCH2Ph), 5.01 (1 H, d, J 12.3, OCH2Ph), 5.18 (1 H, d, J 8.9,
NH), 7.13–7.28 (10 H, m, Ph) and 8.86 (1 H, br s, COOH);
δC (126 MHz; CDCl3) 19.0 (q, C-2Љ), 45.2 (d, C-1Љ),
45.3 (t, NCH2Ph), 52.6 (d, C-4Ј), 60.1 (d, C-3Ј), 67.2 (t,
OCH2Ph), 128.0, 128.3, 128.4, 128.6, 128.9, 130.0 (6 d, 2 Ph),
134.5, 136.0 (2 s, ipso-Ph), 156.4 (s, NHCO), 166.6 (s, C-2Ј)
and 173.4 (s, C-1); m/z (EI, 70 eV) 382 (1%, Mϩ) and 91 (42,
C7H7ϩ).
δH (500 MHz; CDCl3) 0.92 [9 H, s, C(CH3)3], 3.35 (1 H, dd,
J 15.6 and 6.9, H-1Љ), 3.69 (1 H, dd, J 5.6 and 2.4, H-3), 4.01 (1
H, dd, J 15.8 and 5.5 Hz, H-1Љ), 4.10 (1 H, dd, J 10.6 and 5.7,
H-1Ј), 4.36 (1 H, d, J 2.5, H-4), 4.76 (1 H, d, J 10.6, NH), 5.01
(1 H, dd, J 10.2 and 1.5, H-3Љ), 5.08 (1 H, dd, J 17.1 and 1.4,
H-3Љ), 5.08 (1 H, d, J 12.2, OCH2Ph), 5.18 (1 H, d, J 12.2,
OCH2Ph), 5.54 (1 H, dddd, J 17.1, 10.2, 7.0 and 5.1, H-2Љ), 6.20
(1 H, d, J 3.2, C4H3O), 6.33 (1 H, dd, J 3.3 and 1.9, C4H3O) and
7.33–7.40 (6 H, m, C4H3O, Ph); δC (126 MHz; CDCl3) 26.7
[q, C(CH3)3], 34.6 (s, C-2Ј), 43.2 (t, C-1Љ), 50.6 (d, C-4), 57.4
(d, C-3), 58.2 (d, C-1Ј), 67.0 (t, OCH2Ph), 109.6 (d, C4H3O),
110.6 (d, C4H3O), 118.3 (t, C-3Љ), 128.3, 128.6 (3 d, Ph,
partly covered), 131.3 (s, ipso-Ph), 136.4 (d, C-2Љ), 143.2,
150.1 (d, s, C4H3O, ipso-C4H3O), 156.1 (s, NHCO) and 167.2
(s, C-2); m/z (FAB) 397 (17%, [M ϩ H]ϩ) and 91 (100,
C7H7ϩ).
(3ЈR,4ЈS,1ЉS)-1-Benzyl-3-[1-(benzyloxycarbonylamino)-2-
methylpropyl]-2-oxoazetidine-4-carboxylic acid 35
Carboxylic acid 35 was obtained as described for compound 34.
Starting azetidinones, reaction conditions and yields for these
syntheses are summarized in Table 2. Compound 35: softening
range 65–67 ЊC; [α]2D0 Ϫ28 (c 1, CHCl3) (Found: C, 66.3; H, 6.4;
N, 6.55; C23H26N2O5 requires C, 67.3; H, 6.4; N, 6.8%); νmax
(KBr)/cmϪ1 3300 (NH), 2950 (CH), 1740 (C᎐O), 1720 (C᎐O),
(E,3R,4R,1ЈR)- and (E,3S,4S,1ЈR)-1-Benzyl-3-[1-(benzyloxy-
carbonylamino)-2,2-dimethylpropyl]-4-(2-phenylethenyl)azetidin-
2-one 33a,b. Following the general procedure, diazoketone 3
(579 mg, 2.00 mmol) and imine 12 (885 mg, 4.00 mmol) were
irradiated to give a mixture of 33a and 33b (87 : 13), which
was purified by MPLC (PE–i-PrOH 99 : 1). Separation of the
isomers could not be achieved (579 mg, 60%). Compound 33a/b
(87 : 13): [α]2D0 ϩ54 [(33a : b, 87 : 13), c 0.5, CHCl3] (Found: C,
77.0; H, 7.15; N, 5.75; C31H34N2O3 requires C, 77.15; H, 7.1; N,
5.8%); νmax [film, (33a : b, 87 : 13)]/cmϪ1 3300 (NH), 3020 (CH),
᎐
᎐
1525 (NHCO, amide II), 1225 (CO), 720 and 680 (Ph); δH (500
MHz; CDCl3) 0.95 [3 H, d, J 6.8, CH(CH3)2], 0.98 [3 H, d, J 6.7,
CH(CH3)2], 1.94 (1 H, dsept, J 7.7 and 6.8, H-2Љ), 3.57 (1 H, dd,
J 3.0 and 3.0, H-3Ј), 3.81 (1 H, d, J 2.5, H-4Ј), 3.88 (1 H, ddd,
J 10.6, 7.8 and 3.2, H-1Љ), 4.07 (1 H, d, J 14.9, NCH2Ph), 4.84
(1 H, d, J 15.1, NCH2Ph), 4.92 (1 H, d, J 12.4, OCH2Ph), 5.13
(1 H, d, J 12.4, OCH2Ph), 5.21 (1 H, d, J 10.1, NH), 7.20–7.36
(10 H, m, Ph) and 8.84 (1 H, br s, COOH); δC (126 MHz;
CDCl3) 19.4, 20.2 [2 q, CH(CH3)2], 32.1 (d, C-2Љ), 45.7
(t, NCH2Ph), 53.8 (d, C-4Ј), 55.7 (d, C-1Љ), 57.8 (d, C-3Ј), 67.6
3000 (CH), 2970 (CH), 1745 (C᎐O), 1625 (C᎐O, amide I), 1500
᎐
᎐
(NHCO, amide II), 1220 (CO), 730 and 680 (Ph); δH (major
isomer, 500 MHz; CDCl3) 0.98 [9 H, s, C(CH3)3], 3.30 (1 H, dd,
J 2.4 and 2.4, H-3), 3.85 (1 H, dd, J 9.2 and 2.5, H-4), 3.86 (1 H,
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577
2575

View Article Online
(t, OCH2Ph), 128.2, 128.3, 128.5, 128.6, 128.7, 129.0 (6 d, Ph),
134.5, 136.1 (2 s, ipso-Ph), 156.9 (s, NHCO), 166.0 (s, C-2Ј)
and 173.5 (s, C-1); m/z (FAB) 433 (12%, [M ϩ Na]ϩ), 411 (83,
[M ϩ H]ϩ) and 91 (100, C7H7ϩ).
H-2Ј), 1.94 (3 H, s, COCH3), 3.41 (1 H, d, J 3.3, H-3), 3.97 (1 H,
ddd, J 10.4, 7.6 and 3.3, H-1Ј), 4.25 (1 H, d, J 15.2, NCH2Ph),
4.43 (1 H, d, J 15.2, NCH2Ph), 4.75 (1 H, d, J 10.2, NH), 4.96
(1 H, d, J 12.3, OCH2Ph), 5.10 (1 H, d, J 12.3, OCH2Ph), 5.72
(1 H, d, J 1.3, H-4) and 7.20–7.38 (10 H, m, Ph); δC (126 MHz;
CDCl3) 18.6, 19.6 [2 q, CH(CH3)2], 20.0 (q, COCH3), 31.7 (d,
C-2Ј), 45.0 (t, NCH2Ph), 54.0 (d, C-1Ј), 60.3 (d, C-3), 66.9 (t,
OCH2Ph), 79.3 (d, C-4), 127.6, 127.9, 128.1, 128.2, 128.5, 128.7
(6 d, Ph), 135.8, 136.4 (2 s, ipso-Ph), 156.5 (s, NHCO), 165.7 (s,
C-2) and 170.5 (s, COCH3); m/z (FAB) 447 (100%, [M ϩ Na]ϩ),
387 (100, [M ϩ Na Ϫ C2H3O2]ϩ) and 91 (32, C7H7ϩ).
Methyl (3ЈR,4ЈS,1ЉS)-1-benzyl-3-[1-(benzyloxycarbonylamino)-
ethyl]-2-oxoazetidine-4-carboxylate 45
To enable purification a solution of carboxylic acid 34 (80 mg,
209 µmol) in THF (5 mL) was treated with a 0.4 M solution of
CH2N2 in Et2O until the yellow colour persisted. The solution
was stirred for a further 5 min, concentrated and purified by
MPLC (PE–EA 80 : 20) to yield the methyl ester 45 (82 mg,
99%) as a colourless solid. Compound 45: mp 134–135 ЊC; [α]2D0
ϩ18 (c 1, CHCl3) (Found: C, 66.7; H, 6.2; N, 7.0; C22H24N2O5
requires C, 66.65; H, 6.1; N, 7.05%); νmax (KBr)/cmϪ1 3280
(3R,4S,1ЈS)-1-Benzyl-3-[1-(benzyloxycarbonylamino)-2-methyl-
propyl]-2-oxoazetidine-4-carbaldehyde 38
Ozone was passed for 2 min through a cooled (Ϫ78 ЊC) solution
of β-lactam 29a (797 mg, 1.70 mmol) in CH2Cl2 (40 mL). Me2S
(311 mg, 5.00 mmol) was added to the deep-blue solution and
stirring was continued for 30 min at Ϫ78 ЊC and 1 h at room
temperature. The solvents were removed on a rotary evaporator
and the crude product was purified by chromatography (PE–
EA 3 : 1) to yield carbaldehyde 38 (402 mg, 60%) as a colourless
oil: νmax (film)/cmϪ1 3321 (NH), 3064 (CH), 3032 (CH), 2962
(NH), 3021 (CH), 3004 (CH), 2980 (CH), 1740 (C᎐O), 1729
᎐
(C᎐O), 1695 (C᎐O, amide I), 1535 (NHCO, amide II), 1240
᎐
᎐
(CO), 720 and 680 (Ph); δH (500 MHz; CDCl3) 1.34 (3 H, d,
J 6.7, H-2Љ), 3.38 (1 H, s, H-3Ј), 3.70 (3 H, s, OCH3), 3.85 (1 H,
s, H-4Ј), 4.09 (1 H, d, J 14.9, NCH2Ph), 4.22 (1 H, br s, H-1Љ),
4.82 (1 H, d, J 15.0, NCH2Ph), 4.86 (1 H, d, J 8.7, NH), 4.91
(1 H, d, J 12.3, OCH2Ph), 5.09 (1 H, d, J 12.3, OCH2Ph) and
7.19–7.37 (10 H, m, Ph); δC (126 MHz; CDCl3) 19.8 (q, C-2Љ),
45.5 (d, C-1Љ), 45.7 (t, NCH2Ph), 52.8 (q, OCH3), 53.2 (d, C-4Ј),
60.6 (d, C-3Ј), 67.3 (t, OCH2Ph), 128.3, 128.4, 128.6, 128.8,
129.0, 129.2 (6 d, Ph), 135.2, 136.6 (2 s, ipso-Ph), 156.4 (s,
NHCO), 166.5 (s, C-2Ј) and 171.0 (s, C-1); m/z (EI, 70 eV) 396
(14%, Mϩ) and 91 (100, C7H7ϩ).
(CH), 1731 (C᎐O), 1538 (NHCO, amide II), 1239 (CO), 736
᎐
and 697 (Ph); δH (500 MHz; CDCl3) 0.98, 1.01 [6 H, 2 d, J 6.8,
CH(CH3)2], 1.97 (1 H, m, H-2Ј), 3.19 (1 H, dd, J 7.0, 2.2, H-3),
3.74 (1 H, m, H-1Ј), 3.85 (1 H, d, J 1.9, H-4), 4.22 (1 H, d,
J 14.8, NCH2Ph), 4.69 (1 H, d, J 14.8, NCH2Ph), 4.88 (1 H, d,
J 10.2, NH), 4.96 (1 H, d, J 12.1, OCH2Ph), 5.13 (1 H, d, J 12.4,
OCH2Ph), 7.13–7.40 (10 H, m, Ph) and 9.57 (1 H, d, J 1.7,
CHO); δC (126 MHz; CDCl3) 19.1, 19.8 [2 q, CH(CH3)2], 31.8
(d, C-2Ј), 45.9 (t, NCH2Ph), 55.3 (d, C-1Ј), 55.4 (d, C-3), 59.8
(d, C-4), 67.1 (t, OCH2Ph), 128.2, 128.3, 128.4, 128.6, 128.7,
128.9 (6 d, Ph), 134.6, 136.1 (2 s, ipso-Ph), 156.7 (s, NHCO),
(3R,4R,1ЈS)-4-Acetoxy-1-benzyl-3-[1-(benzyloxycarbonyl-
amino)ethyl]azetidin-2-one 36
To a solution of carboxylic acid 34 (1.30 g, 3.40 mmol) in DMF
(70 mL) were added at 70 ЊC in 10 portions within 1 h Pb(OAc)4
(10.2 g, 23.0 mmol) and HOAc (27 mL). The reaction was
terminated by addition of H2O (140 mL). The mixture was
extracted with Et2O (3 × 50 mL) and the organic layers were
washed with saturated NaHCO3 solution (3 × 30 mL) and brine
(30 mL), dried (MgSO4), concentrated and filtrated through a
short SiO2 pad. Purification by MPLC (PE–EA 90 : 10) yielded
the acetoxy-substituted β-lactam 36 (1.12 g, 83%) as a colour-
less oil: mp 89–91 ЊC; [α]2D0 ϩ15 (c 1, CHCl3) (Found: C, 66.55;
H, 6.1; N, 7.05; C22H24N2O5 requires C, 66.65; H, 6.1; N,
7.05%); νmax (KBr)/cmϪ1 3280 (NH), 3000 (CH), 2960 (CH),
165.3 (s, C-2) and 197.8 (d, CHO); m/z (EI, 70 eV) 394.1892;
12
C
1H2614N216O4 requires 394.1893; m/z (EI, 70 eV) 394
23
(5%, Mϩ) and 91 (100, C7H7ϩ).
(3R,4S,1ЈS)-1-Benzyl-3-[1-(benzyloxycarbonylamino)-2-methyl-
propyl]-4-dimethoxymethylazetidin-2-one 39
Ozone was passed for 2 min through a cooled (Ϫ78 ЊC) solution
of β-lactam 29a (220 mg, 470 µmol) in MeOH (8 mL). Me2S (51
mg, 0.82 mmol), trimethyl orthoformate (578 mg, 5.45 mmol)
and 1 M HCl in MeOH (0.8 mL) were added to the deep-blue
solution and stirring was continued for 12 min with warming to
room temperature. The solvents were removed on a rotary
evaporator and the crude product was triturated in saturated
NaHCO3 solution (50 mL). The mixture was extracted with
Et2O (3 × 50 mL) and the organic layers were dried (MgSO4),
concentrated and purified by chromatography (PE–EA 3 : 1) to
yield acetal 39 (137 mg, 66%) as a colourless oil: [α]2D0 ϩ35 (c 1,
CHCl3) (Found: C, 68.15; H, 7.25; N, 6.35; C25H32N2O5 requires
C, 68.15; H, 7.3; N, 6.35%); νmax (film)/cmϪ1 3315 (NH), 3054
1760 (C᎐O), 1680 (C᎐O, amide I), 1535 (NHCO, amide II), 740
᎐
᎐
and 680 (Ph); δH (500 MHz; CDCl3) 1.27 (3 H, d, J 6.9, H-2Ј),
1.97 (3 H, s, COCH3), 3.28 (1 H, d, J 3.3, H-3), 4.20 (1 H, d,
J 15.1, NCH2Ph), 4.26 (1 H, m, H-1Ј), 4.52 (1 H, d, J 15.1,
NCH2Ph), 4.96 (1 H, d, J 12.2, OCH2Ph), 5.08 (1 H, d, J 11.8,
OCH2Ph), 5.71 (1 H, s, H-4) and 7.23–7.38 (10 H, m, Ph);
δC (126 MHz; CDCl3) 19.0 (q, C-2Ј), 20.6 (q, COCH3), 44.0 (d,
C-1Ј), 44.9 (t, NCH2Ph), 62.8 (d, C-3), 66.8 (t, OCH2Ph), 79.1
(d, C-4), 127.8, 128.1, 128.1, 128.3, 128.5, 128.7 (6 d, Ph), 135.6,
136.3 (2 s, ipso-Ph), 155.8 (s, NHCO), 165.5 (s, C-2) and 170.7
(s, COCH3); m/z (FAB) 419 (4%, [M ϩ Na]ϩ), 397 (7, [M ϩ
H]ϩ), 337 (100, [M Ϫ C2H3O2]ϩ) and 91 (58, C7H7ϩ).
(CH), 2962 (CH), 2834 (OCH ), 1745 (C᎐O), 1719 (C᎐O, amide
᎐
᎐
3
I), 1509 (NHCO, amide II), 1265 (CO), 736 and 680 (Ph);
δH (500 MHz; CDCl3) 0.96 [3 H, d, J 6.8, CH(CH3)2], 1.01
[3 H, d, J 6.7, CH(CH3)2], 1.96 (1 H, sept, J 6.9, H-2Ј), 3.24
(3 H, s, OCH3), 3.30 (1 H, dd, J 2.5 and 2.5, H-3), 3.31 (3 H,
s, OCH3), 3.47 (1 H, dd, J 6.1 and 2.3, H-4), 3.77 (1 H, ddq,
J 10.3, 7.6 and 2.8, H-1Ј), 4.12 (1 H, d, J 15.0, NCH2Ph),
4.30 (1 H, d, J 6.1, H-1Љ), 4.57 (1 H, d, J 15.0, NCH2Ph),
4.77 (1 H, d, J 10.2, NH), 4.91 (1 H, d, J 12.3, OCH2-
Ph), 5.11 (1 H, d, J 12.3, OCH2Ph) and 7.16–7.39 (10 H, m,
Ph); δC (126 MHz; CDCl3) 18.9, 19.8 [2 q, CH(CH3)2],
31.7 (d, C-2Ј), 45.2 (t, NCH2Ph), 53.6 (d, C-3), 54.1 (2 q,
OCH3), 54.3 (d, C-4), 55.0 (d, C-1Ј), 66.7 (t, OCH2Ph), 104.4
(d, C-1Љ), 127.8, 128.1, 128.2, 128.5, 128.6, 128.9 (6 d, Ph),
136.2, 136.4 (2 s, ipso-Ph), 156.6 (s, NHCO) and 167.2 (s, C-2);
m/z (EI, 70 eV) 440 (1%, Mϩ), 91 (100, C7H7ϩ) and 75 (65,
C3H7O2ϩ).
(3R,4R,1ЈS)-4-Acetoxy-1-benzyl-3-[1-(benzyloxycarbonyl-
amino)-2-methylpropyl]azetidine-2-one 37
Carboxylic acid 35 (410 mg, 1.00 mmol) was dissolved in DMF
(20 mL) and reacted with Pb(OAc)4 (3.13 g, 7.07 mmol) and
HOAc (8 mL) as described for compound 36, yielding the
acetoxy-substituted β-lactam 37 (348 mg, 82%) as a colourless
oil: [α]2D0 ϩ35 (c 1, CHCl3) (Found: C, 67.75; H, 6.7; N, 6.6;
C24H28N2O5 requires C, 67.9; H, 6.65; N, 6.6%); νmax (film)/cmϪ1
3334 (NH), 3065 (CH), 3034 (CH), 2966 (CH), 1768 (C᎐O),
᎐
1729 (C᎐O), 1712 (C᎐O, amide I), 1538 (NHCO, amide II),
᎐
᎐
1236 (CO), 736 and 698 (Ph); δH (500 MHz; CDCl3) 0.95, 0.99
[6 H, 2 d, J 6.7, CH(CH3)2], 1.93 (1 H, dsept, J 7.3 and 6.7,
2576
J. Chem. Soc., Perkin Trans. 1, 2001, 2566–2577

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11 H. Ishibashi, C. Kameoka, H. Iriyama, K. Kodama, T. Sato and
M. Ikeda, J. Org. Chem., 1995, 60, 1276.
12 M. Shiozaki, Synthesis, 1990, 691.
13 M. Endo and R. Droghini, Can. J. Chem., 1988, 66, 1400; W.-B.
Choi, J. Lee, J. E. Lynch, R. P. Volante, P. J. Reider and R. A.
Reamer, Chem. Commun., 1998, 1817.
14 D. H. Hua and A. Verma, Tetrahedron Lett., 1985, 26, 547.
15 See e.g. T. J. Sowin and A. I. Meyers, J. Org. Chem., 1988, 53, 4154.
16 D. A. Evans and E. B. Sjogren, Tetrahedron Lett., 1985, 26, 3783.
17 G. Wettermark and E. Wallström, Acta Chem. Scand., 1968, 22, 675;
G. Wettermark, in The Chemistry of the Carbon–Nitrogen Double
Bond, ed. S. Patai, Interscience, London, 1970, p. 565.
Acknowledgements
The generous support of Professor Dr V. Jäger and Professor
Dr Dr h.c. F. Effenberger (Universität Stuttgart) is gratefully
acknowledged. This work was further supported by the Fonds
der Chemischen Industrie, the Deutsche Forschungsgemein-
schaft, BASF AG (donation of laboratory equipment), and
Degussa (gift of amino acids).
References
18 Unfortunately
a
photochemically
induced
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8 Crystallographic data (excluding structure factors) for the structures
in this paper have been deposited with the Cambridge
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165006 (18b), 165007 (19b), 165008 (20b), (21a), 168278 (22b),
165010 (23a), 165011 (26a), 165012 (30b) and 165013 (36). See http:/
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