Rhodium-catalysed hydroformylation of N-(2-propenyl)-β-lactams as a key step in the synthesis of functionalised N-[4-(2-oxoazetidin-1-yl)but-1-enyl] acetamides

Article abstract of DOI:10.1039/c0nj00146e

Biologically relevant functionalised N-[4-(2-oxoazetidin-1-yl)-but-1-enyl] acetamides have been prepared in a two-step approach starting from N-(2-propenyl)-β-lactams, involving initial rhodium-catalysed hydroformylation followed by subjection of the obta

Full text of DOI:10.1039/c0nj00146e

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LETTER
www.rsc.org/njc | New Journal of Chemistry
Rhodium-catalysed hydroformylation of N-(2-propenyl)-b-lactams as a
key step in the synthesis of functionalised N-[4-(2-oxoazetidin-1-yl)but-1-
enyl]acetamidesw
a
Stijn Dekeukeleire,z Matthias D’hooghe,a Christian Mu
¨
ller,b Dieter Vogt*b and
Norbert De Kimpe*a
Received (in Montpellier, France) 23rd February 2010, Accepted 6th April 2010
First published as an Advance Article on the web 26th April 2010
DOI: 10.1039/c0nj00146e
Biologically relevant functionalised N-[4-(2-oxoazetidin-1-yl)-
but-1-enyl]acetamides have been prepared in a two-step approach
starting from N-(2-propenyl)-b-lactams, involving initial rhodium-
catalysed hydroformylation followed by subjection of the
obtained aldehydes to Staudinger reaction conditions after initial
imination.
In the present report, the application of catalytic hydro-
formylation in the synthesis of functionalised b-lactams is
disclosed, thus providing a useful example of the successful
integration of homogeneous catalysis within b-lactam chemistry.
In particular, the unprecedented rhodium-catalysed hydro-
formylation of N-(2-propenyl)-b-lactams is employed as a
key step in the synthesis of functionalised N-[4-(2-oxoazetidin-
1-yl)but-1-enyl]acetamides. The latter compounds are of interest
in the framework of anticancer research, as the presence of an
enamido moiety embedded in a larger molecular architecture
constitutes a relevant pharmacophore in that respect. The
interest in this type of compounds stems from the isolation
of different natural products with pronounced antitumor
activities, such as the marine lipopeptide Somocystinamide A7
and the macrolides Apicularen A, isolated from the
myxobacterial genus Chondromyces,8 and lobatamide C,
isolated from southwestern Pacific tunicates.9 All of these
natural compounds accommodate an enamide functionality
as an essential part of their structure. Apart from a few reports
on the hydroformylation of 4-vinyl-b-lactams,10 the catalytic
hydroformylation of b-lactams remains an unexplored field of
research to date.
In the past decade, the catalytic hydroformylation of alkenes
has acquired a prominent position in the field of homogeneous
catalysis.1 The general interest in metal-catalysed hydro-
formylation reactions is due to their high atom efficiency and
the availability of active and selective catalysts. In addition, the
transformation of alkenes into aldehydes creates a significant
added value, as the latter functional group represents an
enormous synthetic potential towards the preparation of a
variety of relevant target compounds. Nevertheless, the catalytic
hydroformylation of alkenes is mainly considered as a valuable
industrial process, and applications in the small-scale synthesis
of fine chemicals2 are rather limited. However, in recent years,
metal-catalysed hydroformylations have found their way
towards useful applications in organic synthesis, for example
for the construction of interesting oxa- and azaheterocycles.3
These examples illustrate the fact that the integration of
catalytic hydroformylations in the design of novel organic
syntheses constitutes an emerging area with promising
prospects in terms of efficiency and selectivity.
Initially, a synthetic concept was devised based on the
preparation of N-allyl-b-lactams, followed by metal-catalysed
hydroformylation as a key step and finally subjection of the
obtained aldehydes to classical Staudinger reaction conditions.
Thus, N-(2-propenyl)- and N-(2-methyl-2-propenyl)imines 2
were synthesised via condensation of benzaldehydes 1 with
allylamine or 2-methylallylamine in CH2Cl2 in the presence of
MgSO4 (Scheme 1).11 In case of N-(2-methyl-2-propenyl)-
imines 2 (R2 = Me), the hydrochloride salt of 2-methylallyl-
amine was used in the presence of Et3N. Subsequently, the
obtained N-(arylmethylidene)amines 2 were used as such for
the Staudinger synthesis of b-lactams 3, affording cis-3-
(alkoxy or phenoxy)-4-arylazetidin-2-ones12 3a–j in 81–90%
yield upon treatment with methoxy-, phenoxy- or benzyl-
oxyacetyl chloride in CH2Cl2 in the presence of Et3N (Scheme 1,
Table 1). The observed cis-selectivity is in accordance with the
known cis-selectivity associated to the use of Bose–Evans
ketenes13 and could be deduced from the 1H NMR spectra
of b-lactams 3, as the coupling constants between the protons
at C3 and C4 varied between 4.4 and 4.7 Hz (CDCl3).14
As stated earlier, metal-catalysed hydroformylations
comprise a powerful tool in organic synthesis. Up to now,
Within medicinal chemistry, the synthesis and transformation
of b-lactams comprises an important field of research, as the
class of b-lactam antibiotics is generally recognised as a
cornerstone of human health care due to their unparalleled
clinical efficacy and safety.4 Furthermore, b-lactams have
proven to be excellent substrates for further elaboration,
which has led to the introduction of the term ‘‘b-lactam
synthon method’’ in 1997.5,6
a Department of Organic Chemistry, Faculty of Bioscience
Engineering, Ghent University, Coupure links 653, B-9000 Ghent,
Belgium. E-mail: norbert.dekimpe@UGent.be
b Schuit Institute of Catalysis, Laboratory for Homogeneous
Catalysis, Eindhoven University of Technology,
5600 M B Eindhoven, The Netherlands. E-mail: d.vogt@tue.nl
w Electronic supplementary information (ESI) available: Spectro-
scopic data for compounds 4b–j, 6b–f and 7b–f. See DOI: 10.1039/
c0nj00146e
z Aspirant of the Fund for Scientific Research—Flanders (FWO-
Vlaanderen).
ꢀc
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Scheme 1
Subsequently, N-(2-methyl-2-propenyl)-b-lactams 3f–j
Table 1 Synthesis of b-lactams 3a–j
(R2 = Me) were studied as substrates for rhodium-catalysed
hydroformylation. Initial attempts using triphenylphosphine
as a ligand applying a range of reaction conditions (20 bar
CO/H2, substrate/Rh = 500, PPh3/Rh = 20, 80–120 1C,
16–40 h) always led to partial conversion (12–71%). On the
other hand, the use of tris(2,4-di-tert-butylphenyl)phosphite as
a bulky p-acceptor ligand expectedly led to full conversion of
b-lactams 3f–j (R2 = Me) under the given reaction conditions
(20 bar CO/H2 (1/1), substrate/Rh = 1000, ligand/Rh = 10,
toluene, cS = 0.25 M, preformation: 1 h, 100 1C, reaction:
16 h, 100 1C). As foreseen, only the corresponding linear
aldehydes 4f–j (R2 = Me) were obtained in good yields
(Scheme 2, Table 2), as 1,1-disubstituted alkenes are known
to afford linear aldehydes in high regioselectivity upon hydro-
formylation according to Keulemans’ empirical rule.17
Entry
R1
R2
R3
b-Lactam 3 (yield)
1
2
3
4
5
6
7
8
9
10
H
H
H
4-Cl
2-Br
H
H
H
H
H
H
H
Ph
Me
Bn
Ph
Bn
Ph
Me
Bn
Ph
Bn
3a (89%)
3b (90%)
3c (86%)
3d (81%)
3e (85%)
3f (86%)
3g (86%)
3h (89%)
3i (85%)
3j (84%)
H
Me
Me
Me
Me
Me
4-Cl
2-Br
this transformation has not been applied to (2-oxoazetidin-1-
yl)methyl-substituted alkenes, although this approach would
constitute a convenient alternative for the conventional
synthesis involving the preparation of 1-(4-hydroxybutyl)-b-
lactams (via alcohol protection/deprotection)15 and a final
oxidation step.
The relative cis-stereochemistry of the substituents attached
to the b-lactam nucleus did not affect the diastereoselectivity
during hydroformylation, as a 1/1 mixture of syn and anti
isomers—concerning the position of the methyl group
(R2 = Me) with respect to the b-lactam substituents at C3
and C4—was obtained. Furthermore, it is worth mentioning
that a Rh-catalysed isomerisation of the double bond in
N-(2-methyl-2-propenyl)-b-lactams towards N-(2-methyl-1-
propenyl)-b-lactams took place as well under the given reaction
Consequently, N-(2-propenyl)-b-lactams 3 were evaluated
as substrates for catalytic hydroformylation towards the
corresponding aldehydes. At first, N-allyl-b-lactams 3a–e
(R2 = H) were subjected to standard hydroformylation
conditions, i.e. treatment with syngas (20 bar CO/H2, 1/1)
using (acetylacetonato)dicarbonylrhodium(I) [Rh(acac)(CO)2]
as a catalyst precursor (substrate/Rh = 500) and xantphos16
as a ligand (xantphos/Rh = 2) in toluene (cS = 0.25 M) at
80 1C (preformation: 1 h, reaction: 16 h). Gratifyingly, complete
conversion of b-lactams 3a–e occurred under the given reaction
conditions as monitored by GC analysis using n-decane as an
internal standard, furnishing a mixture of linear and branched
aldehydes 4a–e (R2 = H) and 5a–e (R2 = H) in good yields
(Scheme 2, Table 2). Spectroscopic analysis (1H NMR) of the
reaction mixtures revealed the presence of linear N-(4-oxobutyl)-
azetidin-2-ones 4a–e as the major regioisomers (83–93%). In
addition, a diastereomeric mixture of branched isomers 5a–e
was formed as the minor regioisomers (7–17%, dr E 1/1).
Attempts to improve the regioselectivity by increasing the
xantphos/Rh ratio from 2 to 4 or 8 were not successful. The
major isomers 4a–e were isolated in pure form through column
chromatography on silica gel.
1
conditions, albeit to a limited extent (o5%, H NMR).
The introduction of an aldehyde functionality within
b-lactams 4 creates a variety of synthetic opportunities for
further elaboration such as alcohol synthesis, a-halogenation
or a-alkylation, formation of imines and subsequent
a-functionalisation or reduction. In light of the known reactivity
of imines towards ketenes under Staudinger reaction conditions,
our initial plan comprised imination of aldehydes 4, followed
by [2+2]-cycloaddition with different Bose–Evans ketenes
to form novel bis-b-lactams. Whereas the condensation of
aldehydes 4 with a variety of primary amines proceeded
smoothly under standard imination conditions, subsequent
reaction with methoxy-, phenoxy- or benzyloxyacetyl chloride
in benzene in the presence of Et3N did not afford the
contemplated bis-azetidin-2-ones. Nonetheless, full and selective
substrate conversion occurred, furnishing novel products in
Scheme 2
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Table 2 Catalytic hydroformylation of N-(2-propenyl)azetidin-2-ones 3a–j
Entry
Substrate
R1
R2
R3
Liganda
Conditionsb
4, 5 (yield, ratio 4/5)c,d
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
4-Cl
2-Br
H
H
H
H
H
H
H
Ph
Me
Bn
Ph
Bn
Ph
Me
Bn
Ph
Bn
Xantphos
Xantphos
Xantphos
Xantphos
Xantphos
P(OR)3
P(OR)3
P(OR)3
P(OR)3
P(OR)3
A
A
A
A
A
B
B
B
B
B
4a, 5a (79%, 89/11)
4b, 5b (89%, 88/12)
4c, 5c (86%, 93/7)
4d, 5d (97%, 89/11)
4e, 5e (81%, 83/17)
4f, 5f (82%, >99/1)
4g, 5g (95%, >99/1)
4h, 5h (92%, >99/1)
4i, 5i (89%, >99/1)
4j, 5j (77%, >99/1)
H
Me
Me
Me
Me
Me
4-Cl
2-Br
3j
a
b
Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; P(OR)3 = tris(2,4-di-tert-butylphenyl)phosphite. A: 20 bar CO/H2 (1/1),
substrate/Rh = 500, xantphos/Rh = 2, cS = 0.25 M, preformation: 1 h, 80 1C, reaction: 16 h, 80 1C; B: 20 bar CO/H2 (1/1), substrate/Rh = 1000,
c
d
P(OR)3/Rh = 10, cS = 0.25 M, preformation: 1 h, 100 1C, reaction: 16 h, 100 1C. Yield of the mixtures of b-lactams 4 and 5. Ratio determined
by 1H NMR analysis.
Scheme 3
Table 3 Synthesis of 1-(4-iminobutyl)-b-lactams 6a–f and N-[4-(2-
oxoazetidin-1-yl)-but-1-enyl]acetamides 7a–f
As described in the introduction, b-lactams 7 bearing an
enamido moiety are of interest within the framework of
anticancer research. Given the medicinal importance of
functionalised azetidin-2-ones, the combination of the b-lactam
entity with an enamido moiety might create new opportunities
for the development of novel lead compounds.
Entry R1 R2 R3 R4
R5 Imine 6 (yield) Enamide 7 (yield)a
1
2
3
4
5
6
H
H
H
H
Ph Bn
Bn iPr
Me 6a (97%)
Ph 6b (92%)
7a (59%)
7b (68%)
7c (63%)
7d (35%)
7e (33%)
7f (31%)
4-Cl H Ph nPr Bn 6c (95%)
H
H
Me Bn cHex Ph 6d (96%)
Ph 6e (93%)
Bn 6f (98%)
In conclusion, biologically relevant functionalised N-[4-(2-
oxoazetidin-1-yl)-but-1-enyl]acetamides have been prepared
starting from N-(2-propenyl)-b-lactams in a two-step approach,
involving (i) the unprecedented catalytic hydroformylation of
the olefinic moiety in the latter b-lactams and (ii) treatment of
the obtained aldehydes with alkoxyacetyl chlorides under
Staudinger reaction conditions after initial imination.
Me Me Bn
4-Cl Me Ph iPr
a
Yields after column chromatography on silica gel.
good yields. Detailed spectroscopic analysis finally revealed
the molecular structure of the latter products to be enamides 7,
which can be explained considering the formation of inter-
mediate iminium species 8, followed by a-deprotonation with
respect to the iminium moiety (Scheme 3, Table 3). It is known
that N-(alkylmethylidene)amines are less reactive towards
[2+2]-cycloaddition reactions as compared to N-(arylmethyl-
idene)amines, sometimes resulting in the formation of enamides
instead of azetidin-2-ones.18 The E-stereochemistry assigned
to the carbon–carbon double bond in enamides 7 is supported
by the observed vicinal coupling constants between both
Experimental
Hydroformylation of N-(2-propenyl)-b-lactams 3a–j
General procedure for the hydroformylation of N-(2-propenyl)-
b-lactams 3a–e: in a typical experiment, a stainless steel
standard autoclave was dried under vacuum at 100 1C over-
night and filled with argon. Afterwards, the autoclave was
flushed 20 times with argon to remove oxygen traces and was
charged with a solution of Rh(acac)(CO)2 (0.03 mmol) and
xantphos (0.06 mmol) in degassed toluene (10 mL) under
argon. The atmosphere was further exchanged with a 1 : 1
mixture of CO/H2 and the reactor was heated to 80 1C and
1
olefinic protons (J = 13.8 Hz, H NMR, CDCl3). It should
be noted that in case of enamides 7d–f (R2 = Me) only one
diastereoisomer could be isolated in pure form after column
chromatography on silica gel, hence the lower yields.
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pressurised with CO/H2 to 20 bar. The catalyst was preformed
at 20 bar (CO/H2) and 80 1C for 1 h at 2000 rpm (mechanical
stirring). Subsequently, the substrate 3 (7.5 mmol), dissolved
in degassed toluene (20 mL), was added from a dropping
funnel, followed by hydroformylation at 20 bar (CO/H2) and
80 1C for 16 h at 2000 rpm. The reaction was stopped by
cooling the reactor to room temperature and venting. The
catalyst was removed by filtration through neutral alumina,
the solvent was evaporated and the crude reaction mixture was
purified by means of column chromatography on silica gel
(hexane/EtOAc 1/1).
Synthesis of N-[4-(2-oxoazetidin-1-yl)but-1-enyl]acetamides
7a–f
General procedure: to a solution of imine 6 (2 mmol) and
triethylamine (6 mmol, 3 equiv.) in benzene (10 mL) was added
dropwise a solution of alkoxyacetyl chloride (2.6 mmol,
1.3 equiv.) in benzene (5 mL) under reflux. After complete
addition, the reaction mixture was stirred for 15 h at room
temperature. Subsequently, benzene was evaporated under
reduced pressure and the reaction mixture was re-dissolved
in dichloromethane (10 mL) and washed with water (10 mL).
After extracting the aqueous phase with dichloromethane
(2 ꢁ 10 mL), the combined organic fractions were dried
(MgSO4). Filtration of the drying agent and removal of the
solvent afforded crude N-[4-(2-oxoazetidin-1-yl)but-1-enyl]-
acetamide 7, which was purified by column chromatography
on silica gel (hexane/EtOAc 1/1). Due to hindered rotation
across the amido moiety, a major and minor isomer was
observed upon spectroscopic analysis.
The hydroformylation of N-(2-methyl-2-propenyl)-b-
lactams 3f–j was performed applying similar reaction conditions
using Rh(acac)(CO)2 (substrate/Rh = 1000) and tris(2,4-di-
tert-butylphenyl)phosphite as a ligand (ligand/Rh = 10) in
degassed toluene (cS = 0.25 M). The catalyst was preformed at
20 bar (CO/H2) and 100 1C for 1 h at 2000 rpm, and
hydroformylation took place at 20 bar (CO/H2) and 100 1C
for 16 h at 2000 rpm.
N-Benzyl-2-methoxy-N-[4-(cis-2-oxo-3-phenoxy-4-phenyl-
azetidin-1-yl)but-1-enyl]acetamide 7a. Light-yellow oil. Rf =
0.14 (hexane/EtOAc 1/1). 1H NMR (300 MHz, CDCl3): d
2.11–2.34 (4H, m, major + minor); 2.94 (2H, d ꢁ d ꢁ d,
J = 14.3, 6.9, 6.9 Hz, major + minor); 3.41 (3H, s, minor); 3.49
(3H, s, major); 3.39–3.54 (2H, m, major + minor); 4.13 (2H, s,
minor); 4.31 (2H, s, major); 4.63 (1H, d, J = 4.4 Hz, major);
4.72 (2H, s, minor); 4.80–4.97 (5H, m, major + minor); 5.26
and 5.31 (2 ꢁ 1H, 2 ꢁ d, J = 4.4 Hz, major + minor);
6.60–6.73, 6.85–6.90 and 7.10–7.36 (32H, 3 ꢁ m, major +
minor). 13C NMR (75 MHz, ref = CDCl3): d 28.7; 40.4; 40.8;
46.7; 47.9; 59.4; 62.3; 62.8; 71.5; 71.8; 81.9; 109.0; 109.5; 115.6;
122.1; 125.6; 127.0; 127.3; 127.7; 127.9; 128.3; 128.6; 128.8;
129.3; 133.1; 136.9; 156.9; 166.1; 168.1. IR (NaCl, cmꢂ1):
nCQO = 1752; nCQC = 1681; nmax = 2932, 1651, 1406,
1233, 1194, 752, 736, 699. MS (70 eV): m/z (%) 471 (M+ + 1,
100). Anal. Calcd. for C29H30N2O4: C 74.02, H 6.43, N 5.95.
Found C 73.83, H 6.61, N 5.68.
cis-1-(4-Oxobutyl)-3-phenoxy-4-phenylazetidin-2-one
4a.
Light-brown crystals. Mp 79.5 1C. Rf = 0.16 (hexane/EtOAc
1
1/1). H NMR (300 MHz, CDCl3): d 1.65–1.88 (2H, m); 2.47
(2H, t ꢁ d, J = 6.9, 3.9 Hz); 2.96 (1H, d ꢁ d ꢁ d, J = 14.2,
6.8, 6.7 Hz); 3.43 (1H, d ꢁ d ꢁ d, J = 14.2, 7.2, 7.2 Hz); 4.88
(1H, d, J = 4.4 Hz); 5.34 (1H, d, J = 4.4 Hz); 6.63–6.65,
6.77–6.82 and 7.01–7.25 (10H, 3 ꢁ m); 9.69 (1H, s). 13C NMR
(75 MHz, ref = CDCl3): d 20.0; 40.1; 41.5; 62.4; 81.9; 115.6;
122.1; 128.4; 128.7; 128.9; 129.3; 133.0; 156.9; 166.4; 201.2. IR
(ATR, cmꢂ1): nNCQO = 1750; nHCQO = 1716; nmax = 1492,
1240, 1089, 750, 688. MS (70 eV): m/z (%) 310 (M+ + 1, 100).
Anal. Calcd. for C19H19NO3: C 73.77, H 6.19, N 4.53. Found
C 73.58, H 6.37, N 4.32.
Synthesis of N-(4-iminobutyl)-b-lactams 6a–f
General procedure: to a solution of aldehyde 4 (2.5 mmol) in
dry CH2Cl2 (15 mL) was added anhydrous MgSO4 (5 mmol,
2 equiv.) and the appropriate primary amine (2.5 mmol,
1 equiv.), and the resulting suspension was stirred for one
hour at room temperature. Afterwards, MgSO4 was removed
through filtration and the solvent was evaporated under
vacuum, affording the corresponding imine 6 in high purity
(>95% based on 1H NMR). Imines 6 were used as such in the
next step due to their hydrolytic instability.
The authors are indebted to Ghent University (GOA) and
the Fund for Scientific Research—Flanders (FWO-Vlaanderen)
for financial support. C. M. gratefully acknowledges a personal
grant (VIDI) from the Netherlands Organization for Scientific
Research (NWO-CW).
References
1 P. W. N. M. van Leeuwen and C. Claver, Rhodium
Catalyzed Hydroformylation, Kluwer Academic Publishers,
Dordrecht, 2000; P. W. N. M. van Leeuwen, Homogeneous
Catalysis: Understanding the Art, Kluwer Academic Publishers,
Dordrecht, 2004.
2 For a recent review on the palladium-catalysed synthesis of fine
chemicals, see: C. Torborg and M. Beller, Adv. Synth. Catal., 2009,
351, 3027.
cis-1-(4-Benzyliminobutyl)-3-phenoxy-4-phenylazetidin-2-one
6a. Yellow oil. 1H NMR (300 MHz, CDCl3): d 1.78–1.89
(2H, m); 2.33 (2H, t ꢁ d, J = 7.6, 4.2 Hz); 3.01 (1H, d ꢁ d ꢁ d,
J = 14.0, 6.9, 6.9 Hz); 3.56 (1H, d ꢁ d ꢁ d, J = 14.0, 7.3,
7.3 Hz); 4.54 (2H, s); 4.92 (1H, d, J = 4.4 Hz); 5.37 (1H, d,
J = 4.4 Hz); 6.68–6.71, 6.83–6.88 and 7.08–7.31 (15H, 3 ꢁ m);
7.78 (1H, t, J = 4.2 Hz). 13C NMR (75 MHz, ref = CDCl3):
d 23.7; 33.2; 40.2; 62.2; 65.0; 81.8; 115.6; 122.0; 126.8; 127.2;
128.0; 128.3; 128.6; 128.7; 129.3; 133.3; 139.4; 157.0; 164.2;
166.0. IR (ATR, cmꢂ1): nCQO = 1753; nCQN = 1666;
nmax = 2922, 1494, 1234, 751, 734, 698. MS (70 eV): m/z
(%) 399 (M+ + 1, 100).
3 For
M. Rodriquez and M. Taddei, Synlett, 2009, 1562;
(b) P. S. Bauerlein, I. Arenas Gonzalez, J. J. M. Weemers,
a few recent examples, see: (a) E. Cini, G. Giorgi,
¨
M. Lutz, A. L. Spek, D. Vogt and C. Muller, Chem. Commun.,
¨
2009, 4944; (c) E. Airiau, N. Girard, A. Mann, J. Salvadori and
M. Taddei, Org. Lett., 2009, 11, 5314; (d) P. Dubon, A. Farwick
¨
and G. Helmchen, Synlett, 2009, 1413; (e) T. Spangenberg, B. Breit
and A. Mann, Org. Lett., 2009, 11, 261.
4 (a) Chemistry and Biology of b-Lactam Antibiotics, ed. R. B. Morin
and M. Gorman, Academic Press, New York, 1982, vol. 1–3;
ꢀc
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(b) G. I. Georg and V. T. Ravikumar, in The Organic Chemistry of
b-Lactams, ed. G. I. Georg, VCH, New York, 1993, ch. 6, p. 295;
(c) C. Palomo, J. M. Aizpurua, I. Ganboa and M. Oiarbide, Eur. J.
Org. Chem., 1999, 3223; (d) C. Palomo, J. M. Aizpurua, I. Ganboa
and M. Oiarbide, Curr. Med. Chem., 2004, 11, 1837; (e) N. De
Kimpe, in Comprehensive Heterocyclic Chemistry II, ed. A. Padwa,
Elsevier, Oxford, 1996, vol. 1B, p. 507; (f) G. S. Singh,
M. D’hooghe and N. De Kimpe, in Comprehensive Heterocyclic
Chemistry III, ed. A. Katritzky, C. Ramsden, E. Scriven and
R. Taylor, Elsevier, Oxford, 2008, vol. 2, p. 1.
5 I. Ojima and F. Delaloge, Chem. Soc. Rev., 1997, 26, 377.
6 (a) I. Ojima, Acc. Chem. Res., 1995, 28, 383; (b) J. F. Fisher,
S. O. Meroueh and S. Mobashery, Chem. Rev., 2005, 105, 395;
(c) B. Alcaide and P. Almendros, Synlett, 2002, 381;
(d) G. S. Singh, Tetrahedron, 2003, 59, 7631; (e) B. Alcaide,
P. Almendros and C. Aragoncillo, Chem. Rev., 2007, 107,
4437; (f) N. Fu and T. T. Tidwell, Tetrahedron, 2008, 64,
10465; (g) M. T. Aranda, P. Perez-Faginas and R. Gonzalez-
Muniz, Curr. Org. Synth., 2009, 6, 325; (h) A. R. A.
S. Deshmukh, B. M. Bhawal, D. Krishnaswamy, V. V. Govande,
B. A. Shinkre and A. Jayanthi, Curr. Med. Chem., 2004, 11, 1889;
(i) I. Ojima and F. Delaloge, Chem. Soc. Rev., 1997, 26, 377;
(j) S. France, A. Weatherwax, A. E. Taggi and T. Lectka, Acc.
Chem. Res., 2004, 37, 592.
10 (a) K. Nozaki, W. Li, T. Horiuch, H. Takaya, T. Saito, A. Yoshida,
K. Matsumura, Y. Kato, T. Imai, T. Miura and H. Kumobayashi,
J. Org. Chem., 1996, 61, 7658; (b) H. S. Park, E. Alberico and
H. Alper, J. Am. Chem. Soc., 1999, 121, 11697; (c) E. Cesarotti and
I. Rimoldi, Tetrahedron: Asymmetry, 2004, 15, 3841.
11 (a) P. Sulmon, N. De Kimpe, R. Verhe, L. De Buyck and N. Schamp,
´
Synthesis, 1986, 192; (b) P. Sulmon, N. De Kimpe, N. Schamp,
B. Tinant and J.-P. Declercq, Tetrahedron, 1988, 44, 3653.
12 (a) M. D’hooghe, S. Dekeukeleire and N. De Kimpe, Org. Biomol.
Chem., 2008, 6, 1190; (b) M. D’hooghe, S. Dekeukeleire, K. Mollet,
C. Lategan, P. J. Smith, K. Chibale and N. De Kimpe, J. Med.
Chem., 2009, 52, 4058.
13 (a) G. I. Georg and V. T. Ravikumar, in The Organic Chemistry of
b-Lactams, ed. G. I. Georg, Verlag Chemie, New York, 1993,
pp. 295–368 and references therein; (b) X. Huang and J. X. Xu,
Heteroat. Chem., 2003, 14, 564; (c) L. Jiao, Y. Liang and J. Xu,
J. Am. Chem. Soc., 2006, 128, 6060.
14 (a) K. D. Barrow and T. M. Spotswood, Tetrahedron Lett., 1965, 6,
3325; (b) J. Decazes, J. L. Luche and H. B. Kagan, Tetrahedron
Lett., 1970, 11, 3365.
15 S. Dekeukeleire, M. D’hooghe and N. De Kimpe, J. Org. Chem.,
2009, 74, 1644.
16 P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek and
P. Dierkes, Chem. Rev., 2000, 100, 2741.
7 L. M. Nogle and W. H. Gerwick, Org. Lett., 2002, 4, 1095.
8 B. Kunze, R. Jansen, F. Sasse, G. Hofle and H. Reichenbach,
J. Antibiot., 1998, 51, 1075.
9 T. C. McKee, D. L. Galinis, L. K. Pannell, J. H. II Cardellina,
J. Laasko, C. M. Ireland, L. Murray, R. J. Capon and M. R. Boyd,
J. Org. Chem., 1998, 63, 7805.
17 (a) A. I. M. Keulemans, A. Kwantes and T. van Bavel, Recl. Trav.
Chim. Pays-Bas, 1948, 67, 298; (b) M. L. Clarke and G. J. Roff,
Chem.–Eur. J., 2006, 12, 7978; (c) M. L. Clarke and G. J. Roff,
Green Chem., 2007, 9, 792.
18 M. D’hooghe, Y. Dejaegher and N. De Kimpe, Tetrahedron, 2008,
64, 4575.
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