Highly stereoselective synthesis of β-lactams utilizing α-chloroimines as new and powerful chiral inductors

Article abstract of DOI:10.1002/chem.200800845

A study was conducted to demonstrate stereoselective synthesis of βlactams by using α-chloroimines as chiral inductors. The study is based on the mechanistic rationale of the [2 + 2]-cycloaddition of ketenes and imines, and used α-chloroimines as chiral inductors for the synthesis of azetidin-2-ones. The study found that α-chloroimines are the powerful chiral inductors for the stereoselective Staudinge synthesis of β-lactams. The study applied (S)-α-chloroaldimines for the synthesis for novel 4-(1-chloroethyl)-β-lactams in high diastereomeric and enantiomeric excess. N-(2-chloro-1-methylpropylidene)-amines was prepared in the study through condensation of racemic 3-chloro-2-butanone and primary amines with addition of titanium (IV) chloride in THF.

Full text of DOI:10.1002/chem.200800845

DOI: 10.1002/chem.200800845
Highly Stereoselective Synthesis of b-Lactams Utilizing a-Chloroimines as
New and Powerful Chiral Inductors
Matthias Dꢀhooghe,[a] Willem Van Brabandt,[a] Stijn Dekeukeleire,[a, b]
Yves Dejaegher,[a] and Norbert De Kimpe*[a]
Due to the biological relevance of b-lactams as antibiotics
and their usefulness as synthons for further functionaliza-
tion, the b-lactam skeleton can be considered as one of the
most important azaheterocyclic frameworks in organic
chemistry.[1] In recent years, the development of chiral ap-
proaches (often catalytic methodologies) towards these at-
tractive compounds has become a key issue and challenge in
organic synthesis. The Staudinger reaction, in which a
ketene and an imine react in a [2+2]-cycloaddition, is gen-
erally acknowledged as the method of choice for the asym-
metric synthesis of b-lactams.[2] A first approach in this re-
spect consists of the cycloaddition of a chiral ketene,[3] for
example, the Evans–Sjçgren ketene,[4] and an achiral imine.
Alternatively, chirality can be induced by using a chiral
imine and an achiral ketene. However, the application of
chiral imines derived from chiral amines for the Staudinger
synthesis of b-lactams generally results in low levels of dia-
stereoselectivity,[2a] and only in some exceptional cases (e.g.
when imines derived from d-glucosamine or d-threonine
and cinnamaldehyde are used) high diastereoselectivities (de
>90) have been reported.[5,6] On the other hand, high ste-
reoselectivities are attained when chiral imines derived from
chiral aldehydes (usually a-oxy- or a-aminoaldehyde de-
rived imines) are used.[7,8] Chiral a-alkylimines, derived
from chiral a-alkylaldehydes, are known to be unreactive in
terms of both chemical reactivity and diastereoselectivity in
the Staudinger reaction towards b-lactams.[2a]
The origin of the asymmetric induction in the Staudinger
synthesis of b-lactams has been rationalized on the basis of
the magnitude of the stereoelectronic effect exerted by the
À
s*(C X) orbital (X being an electronegative atom and C a
stereogenic carbon atom) over the HOMO in the transition
G
states.[8] The angular disposition between C3 and the C X
À
bond in transition state 5 minimizes the steric interaction
between R3 and the forming b-lactam ring, but at the cost of
loss of efficiency of the stabilizing interaction between the
À
HOMO and the s*(C X) orbital. In the case of transition
E
state 3, the aforementioned steric interaction does not
À
occur, and therefore the HOMO–s*
takes place more efficiently, favored by the linear arrange-
A
À
ment between C3 and the exocyclic C X bond. Consequent-
ly, the latter transition state 3 has a lower energy and is pre-
ferred (Scheme 1).[8]
Scheme 1. AM1-calculated transition states for the asymmetric Stauding-
er synthesis of b-lactams by Palomo et al.[8]
[a] Dr. M. Dꢀhooghe, Dr. W. Van Brabandt, S. Dekeukeleire,
Dr. Y. Dejaegher, Prof. Dr. N. De Kimpe
Department of Organic Chemistry, Ghent University
Coupure Links 653, 9000 Ghent (Belgium)
Fax : (+32)9-2646243
According to a theoretical study on the hyperconjugative
acceptor ability of s bonds, the s*
À
(C X) acceptor abilities
E-mail: norbert.dekimpe@UGent.be
increase by at least 30% when X is a halogen atom in com-
parison with X being an oxygen or a nitrogen atom.[9] In
other words, the use of chiral a-chloroimines might lead to
higher stereoselectivities compared with those obtained with
a-oxy- or a-aminoaldehyde derived imines. However, the
[b] S. Dekeukeleire
Aspirant of the Fund for Scientific Research–Flanders (FWO-Vlaan-
deren)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200800845.
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Chem. Eur. J. 2008, 14, 6336 – 6340

COMMUNICATION
use of chiral a-haloimines for the asymmetric Staudinger
synthesis of b-lactams comprises an unexplored field of re-
search up to now. In addition, the presence of a halogenated
side chain at C4 in the resulting b-lactams would allow fur-
ther elaboration towards interesting heterocyclic target com-
pounds.[10]
Herein, a-chloroimines are used for the first time as pow-
erful inductors for the stereoselective synthesis of azetidin-
2-ones. This approach is inspired by the mechanistic ration-
ale of the [2+2]-cycloaddition of ketenes and imines de-
rived from a-oxy and a-amino substituted aldehydes,[8] and
a predicted higher hyperconjugative acceptor ability of halo-
gens in comparison with both oxygen and nitrogen as the a-
heteroatom.[9]
lithium aluminum hydride in diethyl ether at 08C for two
hours, affording pyrrolidines 10a,b (Scheme 3) in accord-
ance with the previously described reactivity of 4-(1-chloro-
1-methylethyl)-b-lactams towards LiAlH4.[10] Subsequently,
NOE experiments performed on the latter pyrrolidines 10
resulted in NOE effects of 2–4% between the C4 proton
and the C3 methyl group, and NOE effects of 3–5% be-
tween the C2 and C3 methyl substituents (Scheme 3). On
the other hand, treatment of b-lactam 9 f (less bulky at ni-
trogen) with five molar equivalents of LiAlH4 in diethyl
ether afforded aziridine 11 after four hours at room temper-
ature (Scheme 3), again in accordance with previously re-
ported transformations of 4-(1-chloro-1-methylethyl)-b-lac-
tams.[10] For aziridine 11, a distinct NOE effect of 10% be-
tween the proton at the a-position of the benzyloxy substitu-
ent and the aziridine C3 methyl substituent was measured
(Scheme 3), affording strong evidence for the trans-relation-
ship of the two methyl substituents on the aziridine ring.
Furthermore, a new approach towards (S)-a-chloroald-
imines starting from (2S)-chloro-1-propanol is disclosed as
an improved alternative over known enantioselective a-
chlorination procedures for short-chain aldehydes. The
latter (S)-a-chloroaldimines were applied successfully for
the synthesis of novel 4-(1-chloroethyl)-b-lactams in high
diastereomeric (84–89%) and enantiomeric excess (90%).
As no information is available regarding the use of chiral
a-haloimines for the Staudinger synthesis of b-lactams, the
attainability of the concept was first evaluated starting from
racemic substrates. Thus, N-(2-chloro-1-methylpropylidene)-
amines 8, prepared via condensation of racemic 3-chloro-2-
butanone (7) and different primary amines in the presence
of titanium(IV) chloride in THF,[11] were treated with 1.3
equivalents of benzyloxy- or phenoxyacetyl chloride in re-
fluxing benzene in the presence of three equivalents of tri-
3
Furthermore, the observed JCH coupling of 3.5 Hz between
the aziridine C2 methyl substituent and the aziridine C3
proton is in accordance with literature data,[12,13] as coupling
constants between a cis-oriented C2 methyl substituent and
a C3 proton are usually between 2 and 4 Hz. On the other
hand, this type of coupling constants is barely observable in
aziridines with a C2-methyl group and a C3-hydrogen atom
in a trans-configuration. Based on the observed NOE effects
and coupling constants in pyrrolidines 10 and aziridine 11,
the relative stereochemistry of b-lactams 9 could be assigned
as depicted in Schemes 2 and 3.
A
obtained in an excellent diastereomeric excess (96–100%,
1
determined by H NMR and GC), pointing to a strong in-
ducing effect of the a-chloro atom (Scheme 2, Table 1).
Scheme 2. Diastereoselective synthesis of rac-4-(1-chloroethyl)-4-methyl-
b-lactams 9.
Scheme 3. Transformations of 4-(1-chloroethyl)-b-lactams 9 into pyrroli-
dines 10 and aziridine 11.
Table 1. Diastereoselective synthesis of rac-4-(1-chloroethyl)-4-methyl-b-
lactams 9a–f.
Due to these encouraging results, the development of an
asymmetric version using chiral a-haloimines was envisaged.
To obtain 4-(1-chloroethyl)azetidin-2-ones, 2-chloropropa-
nal was chosen as a substrate for imination and further lac-
tamization. To date, only two methods leading towards
chiral a-chloroaldehydes bearing an a-hydrogen are avail-
able in the literature.[14,15] Both approaches are based on the
enantioselective organocatalytic a-chlorination of aldehydes,
either by means of 2,3,4,5,6,6-hexachlorocyclohexa-2,4-dien-
one in the presence of (S)-5-benzyl-2,2,3-trimethylimidazoli-
din-4-one[14] or by NCS (N-chlorosuccinimide) in the pres-
Product
R1
R2
Yield [%]
de [%]
9a
9b
9c
9d
9e
9 f
iPr
Bn
Bn
Bn
Bn
Ph
Bn
75
80
70
72
76
72
>99
>99
>99
>99
>99
96
tBu
cHex
Et
iPr
allyl
To confirm the relative configuration of b-lactams 9, azeti-
din-2-ones 9a,b were treated with two molar equivalents of
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6337

N. De Kimpe et al.
ence of l-prolinamide.[15] The synthesis of chiral 2-chloro-
propanal has only been described by the second method in
low ee (75%). As a possible and convenient alternative, the
oxidation of chiral 2-chloro-1-propanol, readily available
from a-amino acids,[16] towards chiral 2-chloropropanal was
examined. Thus, treatment of the commercially available
(2S)-chloro-1-propanol (12) with five equivalents of PCC
(pyridinium chlorochromate) in dichloromethane at room
temperature afforded the premised (2S)-chloropropanal
(13). Filtration of the reaction mixture over silica gel and
subsequent treatment with one equivalent of benzylamine
and 1.5 equivalents of MgSO4 yielded (S)-N-(2-chloropropy-
lidene)benzylamine (14a) after one hour at room tempera-
ture. Due to the high volatility, 13 was not isolated from the
solvent dichloromethane and used in solution for the next
step. The imine 14a appeared to be unstable in pure form at
room temperature, as all attempts to purify the compound
failed.
It should be noted that the application of Swern oxidation
conditions or the use of pyridinium sulfur trioxide in DMSO
instead of PCC did not afford the anticipated aldehyde 13.
Due to the instability, 14a was used as such in the next
step and treated with 1.3 equivalents of benzyloxyacetyl
chloride in dichloromethane under Staudinger conditions to
afford the corresponding b-lactam 15a, albeit in a very low
overall yield (2%, based on alcohol 12). However, the dia-
stereomeric excess appeared to be excellent (98% based on
1H NMR and GC), pointing to the very high stereoinduction
by a-chloroimines in the Staudinger reaction. In addition,
allylamine was used to perform the imination of 13 and sub-
sequent lactamization of the intermediate imine 14b to-
wards N-allylazetidin-2-one 15b. Again, the latter b-lactam
15b was obtained in a high diastereomeric excess (98%) but
in a low overall yield (3%, based on alcohol 12). The ex-
pected cis-diastereoselectivity during b-lactamization to-
wards azetidin-2-ones 15 could be confirmed based on a
coupling constant of 5 Hz between the C3 and C4 protons
(1H NMR, CDCl3). From these results, it was already clear
that the high stereocontrol by the halogen in favor of the
syn-isomer comprised a useful tool in organic synthesis.
An optimization of the reaction conditions for the synthe-
sis of b-lactams 15 appeared necessary due to the excellent
stereoinduction. Whereas the reaction of 14a with benzyl-
Scheme 4. One-pot synthesis of chiral 4-(1-chloroethyl)-b-lactams 15
from (2S)-chloro-1-propanol.
Table 2. Stereoselective synthesis of 4-(1-chloroethyl)azetidin-2-ones
15a–f.
Product
R1
R2
Overall yield [%][a]
de [%]
15a
15b
15c
15d
15e
15 f
Bn
Allyl
Bu
iBu
iPr
Bu
Bn
Bn
Bn
Bn
Bn
Me
27
31
30
43
19
6
86
85
88
84
89
80
[a] Yields after column chromatography and with respect to alcohol 12.
The generality of this methodology was demonstrated by
the one-pot synthesis of different 3-benzyloxy-4-(1-chloro-
A
43% after purification by column chromatography) and
high diastereomeric excesses of 84–89% (Scheme 4,
Table 2). It should be noted that the overall yields of 19–
43% were obtained after purification by column chromatog-
raphy on silica gel in order to obtain analytically pure sam-
ples. The crude overall yields of these b-lactams 15 were
considerably higher (32–61%). Only for the synthesis of 3-
methoxyazetidin-2-one (15 f), a lower overall yield (6%
after purification) was obtained.
To determine the enantiomeric excess of the b-lactams 15,
which can be influenced by the stability of the intermediate
a-chloroimines 14 towards racemization upon imine–enam-
ine tautomerism, the coupling of b-lactam 15c, after O-de-
benzylation, with a chiral acid chloride was envisaged. Hy-
drogenolysis of the benzyloxy group of azetidin-2-one 15c in
methanol at room temperature, followed by esterification of
the resulting 3-hydroxy-b-lactam 16 with one equivalent of
(R)-a-methoxy-a-trifluoromethyl phenylacetic acid chloride
in dichloromethane at room temperature, afforded the cor-
responding 3-(3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl-
A
at room temperature was unsuccessful, the addition of 1.3
equivalents of benzyloxyacetyl chloride to a refluxing solu-
tion of 14a and triethylamine in benzene afforded the corre-
sponding b-lactam 15a in a satisfying 27% overall yield
(after purification by column chromatography) and 86%
diastereomeric excess (Scheme 4). Although lower as com-
pared to the reaction in dichloromethane, the diasteromeric
excess of 86% is still very high and comparable to the de
values obtained when chiral a-oxy- or a-aminoaldehyde de-
rived imines are used in the Staudinger reaction.[2a] The in-
corporation of a chlorinated side chain in the resulting b-lac-
tams enables further elaboration towards chiral azaheterocy-
clic target compounds with potential biological interest.[10]
A
excess. This conclusion was based on the presence of 3 iso-
mers upon GC-analysis, that is, the (3S,4S,4’S)-isomer
(93%), the (3R,4R,4’R)-isomer (3%) and the (3R,4R,4’S)-
isomer (3%). Thus, it can be concluded that the starting b-
lactam 15c was prepared in an enantiomeric excess of 90%.
The high diastereomeric excess points to the fact that little
epimerization of the intermediate a-chloroaldehyde 13 or a-
chloroimines 14 occurs during the three-step sequence lead-
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Chem. Eur. J. 2008, 14, 6336 – 6340

Stereoselective Synthesis of b-Lactams
COMMUNICATION
further transformed into b-lactam 15a in 79% ee (GC) ap-
plying the one-pot reaction conditions as described above.
The observed decrease in ee (from 92% to 79%) during the
Staudinger reaction is in correspondence with the observa-
tions made for the synthesis of b-lactam 15c, which was ob-
tained in an ee of 90% starting from an enantiomerically
pure substrate.
From these results, it can be concluded that the new
method for the stereoselective preparation of 4-(1-chloro-
A
Scheme 5. Synthesis of 3-(3,3,3-trifluoro-2-methoxy-2-phenylpropanoy-
loxy)-b-lactam (17) starting from azetidin-2-one (15c).
provides an improved alternative in terms of enantiomeric
excess as compared to the synthesis starting from propanal
via known organocatalytic a-chlorination procedures. For
higher aldehydes, the known a-chlorination procedures
remain an attractive approach in this respect.
In continuation of the successful use of chiral a-oxy and
a-amino substituted aldehydes for the stereoselective syn-
thesis of b-lactams,[8] the application of chiral a-chloroimines
can be considered as an additional tool useful for the stereo-
selective synthesis of 4-(1-chloroalkyl)-b-lactams in a con-
venient way. The latter azetidin-2-ones have been demon-
strated previously to be suitable synthons for the prepara-
tion of other azaheterocyclic compounds such as aziridines
and pyrrolidines.[10]
ing to b-lactams 15. These data provide the first information
on the stability of chiral a-chloroaldimines under these reac-
tion conditions.
As previously mentioned, only two methods for the prep-
aration of chiral a-haloaldehydes are available in the litera-
ture. The enantioselective organocatalytic chlorination of
propanal by means of NCS in the presence of l-prolinamide
has been described to afford (R)-2-chloropropanal in an ee
of 75%.[15] The asymmetric chlorination of propanal by
2,3,4,5,6,6-hexachlorocyclohexa-2,4-dienone in the presence
of (5S)-benzyl-2,2,3-trimethylimidazolidin-4-one, however,
has not been described so far (the McMillan method has
been applied for higher aldehydes, for example, octanal, 3-
phenylpropanal).[14] In order to compare both approaches
with the newly developed methodology, the a-chlorination
of propanal by means of one equivalent of 2,3,4,5,6,6-hexa-
chlorocyclohexa-2,4-dienone (C6Cl6O) in the presence of 5
mol% of (5S)-benzyl-2,2,3-trimethylimidazolidin-4-one was
evaluated. In this way, 13 was obtained after 2 h at À308C
in acetone (Scheme 6). To evaluate the chiral purity of alde-
that a-haloimines are powerful inductors for the stereoselec-
tive Staudinger synthesis of b-lactams. In particular, a new
and efficient one-pot approach towards chiral azetidin-2-
ones has been developed starting from (2S)-chloro-1-propa-
nol, affording novel b-lactams in high diastereomeric (80–
89%) and enantiomeric excess (90%). In this case, the oxi-
dation of (2S)-chloro-1-propanol towards (2S)-chloropropa-
nal constitutes an improved alternative over known enantio-
selective a-chlorination procedures. Furthermore, the first
data on the stability of chiral a-chloroimines were provided,
pointing to the observation that the latter compounds are
relatively stable towards epimerization under Staudinger re-
action conditions.
hyde 13, condensation with (R)-a-methylbenzyl
amine[17] was
G
performed by means of standard reaction conditions in di-
chloromethane towards the corresponding imine 19
(Scheme 6). The latter imine was obtained in a diastereo-
1
meric excess of 92% (based on H NMR and GC), which
corresponds well with the ee values reported for the enantio-
selective chlorination of other aldehydes using the same
methodology (91–95%).[14] (2S)-Chloropropanal 13 was then
Experimental Section
1H NMR spectra were recorded at 270 MHz (JEOL JNM-EX 270) or at
300 MHz (JEOL ECLIPSE+) with CDCl3 as solvent and tetramethylsi-
lane as internal standard. 13C NMR spectra were recorded at 68 MHz
(JEOL JNM-EX 270) or at 75 MHz (JEOL ECLIPSE+) in CDCl3. Mass
spectra were obtained with a mass spectrometer (70 eV) using a GC-MS
coupling (20 m glass capillary column, i.d. 0.53 mm, He carrier gas) or
were recorded using a direct inlet system (70 eV). Elemental analyses
were performed with a PerkinElmer Series II CHNS/O Analyzer 2400.
Dichloromethane was dried over calcium hydride, while diethyl ether
and THF were dried by distillation over sodium/benzophenone. All other
solvents were used as received from the supplier.
General procedure for the synthesis of 4-(1-chloroethyl)-4-methylazeti-
din-2-ones 9: To a refluxing solution of imine 8 (10 mmol) and triethyla-
mine (30 mmol) in benzene (50 mL) was added dropwise a solution of
acid chloride (13 mmol) in benzene (50 mL). The resulting mixture was
heated under reflux for 30 min and stirred at room temperature for 16 h.
The reaction mixture was then diluted with chloroform (100 mL) and
washed with a saturated solution of sodium bicarbonate (150 mL) and
Scheme 6. Synthesis of b-lactam 15a starting from propanal 18.
Chem. Eur. J. 2008, 14, 6336 – 6340
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6339

N. De Kimpe et al.
brine (150 mL). Drying (MgSO4) and evaporation of the solvent afforded
the crude 9, which was purified by means of column chromatography on
silica gel (hexane/EtOAc).
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cis-3-Benzyloxy-4-(1-chloroethyl)-1-isopropyl-4-methylazetidin-2-one
(9a): 75% yield, white crystals, m.p. 69.0–70.38C; TLC Rf
= 0.27
(hexane/EtOAc 4:1); 1H NMR (270 MHz, CDCl3): d = 1.35, 1.44 (2”d,
J=6.6 Hz, 2”3H), 1.43 (s, 3H), 1.53 (d, J=6.6 Hz, 3H), 3.59 (septet, J=
6.6 Hz, 1H), 4.23 (s, 1H), 4.46 (q, J=6.6 Hz, 1H), 4.69 (d, J=11.9 Hz,
1H), 4.93 (d, J=11.9 Hz, 1H), 7.29–7.36 ppm (m, 5H); 13C NMR
(68 MHz, CDCl3): d
= 15.9, 21.4, 21.7, 21.8, 45.9, 63.0, 66.4, 72.8,
87.1,127.7, 127.9, 128.5, 137.1, 166.2 ppm. IR (NaCl): n=1735 cmÀ1 (C=
O); MS (70 eV): m/z (%): no M+, 227 (34), 143 (74), 128 (35), 57 (100);
elemental analysis calcd (%) for C16H22ClNO2: C 64.97, H 7.50, N 4.74;
found: C 65.19, H 7.78, N 4.53.
General method for the synthesis of (3S,4S)-3-alkoxy-4-((1S)-1-chloroe-
thyl)azetidin-2-ones 15: As a representative example, the synthesis of
(3S,4S)-1-benzyl-3-benzyloxy-4-((1S)-1-chloroethyl)azetidin-2-one (15a)
is described. Pyridinium chlorochromate (26.5 mmol) was added to a so-
lution of (2S)-chloro-1-propanol (12; 5.3 mmol) in dry dichloromethane
(200 mL). The reaction mixture was stirred overnight (16 h), filtered over
silica gel and the filter cake was washed two times with dichloromethane
(25 mL). Benzylamine (5.3 mmol) and MgSO4 (8.0 mmol) were added to
the combined organic fractions and the resulting mixture was stirred at
room temperature for 1.5 h. After filtration of the drying agent, the sol-
vent was evaporated under reduced pressure until approximately 10 mL
of reaction mixture remained in the flask. Then, benzene was added
(100 mL), and the residual dichloromethane was evaporated under re-
duced pressure. Subsequently, a solution of benzyloxyacetyl chloride
(6.8 mmol) in benzene (10 mL) was added dropwise to the refluxing solu-
tion in benzene. After complete addition, the reaction mixture was
stirred overnight (16 h) at room temperature. Subsequently, the reaction
mixture was poured into water (100 mL) and extracted with dichlorome-
thane (2”10 mL). After evaporation of the solvent, the crude reaction
mixture was purified by column chromatography on silica gel, affording
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pure
15a in 27% overall yield.
(3S,4S)-1-Benzyl-3-benzyloxy-4-((1S)-1-chloroethyl)azetidin-2-one (15a):
(3S,4S)-1-benzyl-3-benzyloxy-4-((1S)-1-chloroethyl)azetidin-2-one
ACHTREUNG
27% overall yield, white crystals, m.p. 928C; TLC Rf = 0.1 (hexane/
EtOAc 9:1); [a]2D0 =À10 (c=1 in CH2Cl2), de: 86%; 1H NMR (300 MHz,
CDCl3): d = 1.49 (d, J=6.6 Hz, 3H), 3.60 (d”d, J=9.9 Hz, J=5.0 Hz,
1H), 4.33 (d”q, J=9.9 Hz, J=6.6 Hz, 1H), 4.38 (d, J=14.9 Hz, 1H),
4.59 (d, J=5.0 Hz, 1H), 4.71 (d, J=11.9 Hz, 1H), 4.86 (d, J=14.9 Hz,
1H), 4.95 (d, J=11.9 Hz, 1H), 7.25–7.38 ppm (m, 10H); 13C NMR
(75 MHz, CDCl3): d
= 22.0, 45.1, 58.5, 62.3, 72.9, 80.9, 127.8, 127.9,
128.1, 128.5, 128.6, 128.8, 135.6, 136.8, 167.9 ppm; IR (NaCl): n=
1759 cmÀ1 (C=O); MS (70 eV): m/z (%): 330/2 (100) [M+ +H]; elemental
analysis calcd (%) for C19H20ClNO2: C 69.19, H 6.11, N 4.25; found: C
69.32; H 6.01; N 4.40.
Acknowledgements
The authors are indebted to the “Fund for Scientific Research - Flanders
(Belgium)” (F.W.O.-Vlaanderen) and to Ghent University (GOA) for fi-
nancial support.
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Schley, J. Liebscher, Eur. J. Org. Chem. 2007, 2945.
Keywords: chloroimines · azetid-2-ones · beta-lactams ·
heterocycles · Staudinger reaction · stereostereoselectivity
[1] a) I. Ojima, Acc. Chem. Res. 1995, 28, 383; b) I. Ojima, F. Delaloge,
Chem. Soc. Rev. 1997, 377; c) B. Alcaide, P. Almendros, Synlett 2002,
Received: May 5, 2008
Published online: June 11, 2008
6340
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