Synthesis of new polycyclic β-lactams via one-pot enyne metathesis and Diels-Alder reactions

Article abstract of DOI:10.1055/s-2004-834877

One-pot ring-closing enyne metathesis and Diels-Alder reactions led to efficient synthesis of tricyclic and tetracyclic β-lactams.

Full text of DOI:10.1055/s-2004-834877

PAPER
2665
Synthesis of New Polycyclic b-Lactams via One-Pot Enyne Metathesis and
Diels–Alder Reactions
a
a
a
a
a
b
N
ew
P
olycylic b-L
i
actams
c
via Enyne
o
Metathesis
a
l
ndDie
a
ls–Alder
R
s
e
actions Desroy, Fabien Robert-Peillard, Julie Toueg, Charlotte Hénaut, Romain Duboc, Marie-Noëlle Rager,
a
a
Monique Savignac,* Jean-Pierre Genêt*
a
Ecole Nationale Supérieure de Chimie de Paris, Laboratoire de Synthèse Sélective Organique et Produits Naturels, UMR 7573, 11 rue
Pierre et Marie Curie, 75231 Paris cedex 05, France
Fax +33(144)071062; E-mail: genet@ext.jussieu.fr; savignac@ext.jussieu.fr
Service de RMN de l’ENSCP, Ecole Nationale Supérieure de Chimie de Paris, 11 rue Pierre et Marie Curie, 75231 Paris cedex 05, France
b
Received 1 June 2004
+H3N
-O2C
Abstract: One-pot ring-closing enyne metathesis and Diels–Alder
reactions led to efficient synthesis of tricyclic and tetracyclic b-lac-
tams.
Bn
HN
O
O
3
HN
S
S
Key words: metathesis, Diels–Alder cycloaddition, one-pot reac-
tions, polycycles, lactams
N
N
O
Me
O
O
1
CO2H
2
CO2H
O
OH
OH
One-pot processes are of considerable interest for the syn-
thetic chemist due to the convenient experimental proce-
dure, which does not require the isolation and purification
of intermediates. Such processes have been widely inves-
tigated in the last decade due to their ecological and eco-
nomic advantages when compared to stepwise
S
NH
N
N
OMe
O
O
3
CO H
NMe2
2
CO2R
4
5
: R = H
: R =
O
O
1
procedures. Consecutive ring-closing enyne metathesis
C6H11
and Diels–Alder reactions provide an attractive route to
O
2
polycyclic compounds. Variation of the size of the ring
Figure 1
3
formed by enyne metathesis and appropriate choice of di-
4
enophiles for the Diels–Alder cycloaddition allow for the
9
to form the functionalized carbapenem skeleton. More
recently a preliminary reportdescribed our strategy for the
synthesis of polycyclic 4/5/6 b-lactams based on enyne
synthesis of a broad diversity of molecules. In this article
we describe the synthesis of new polycyclic b-lactams via
one-pot enyne metathesis and Diels–Alder reactions.
1
0
metathesis and Diels–Alder reactions. Herein we report
an extension of this strategy applied to the synthesis of
new 4/6/6 and 4/7/6 polycyclic b-lactams via one-pot
enyne metathesis and Diels–Alder reactions (Scheme 1).
For comparison, metathesis and cycloaddition were first
realised in separate steps.
Although Penicillin G (1) and Cephalosporin C (2) were
discovered more than fifty years ago, b-lactams still play
5
a major role in current antibiotherapy.
Whereas the early antibiotics were from natural sources,
synthetic compounds with enhanced stability and activity
against resistant bacteria have been developed in the last
two decades. In 1984 researchers at Merck discovered 1b-
methylcarbapenem (3) and in 1988 scientists at Glaxo in-
troduced the class of trinems (tricyclic carbapenems), of
which sanfetrinem (GV104326) (4) and sanfetrinem
cilexetil (GV118819) (5) were until recently undergoing
phase II clinical trials (Figure 1). Many research groups,
both academic and industrial, have then devoted efforts
Starting from the commercially available acetoxyazetidi-
11
none 6, condensation of the anion of trimethylsilylacet-
ylene was performed in 85% yield with retention of
configuration (Scheme 2). Alkylation of 7 with suitable
bromide under phase transfer conditions also led to desi-
OTBS
X
6
,7
towards the synthesis of polycyclic b-lactams.
X
As part of our ongoing program dedicated to the synthesis
of biologically relevant molecules, we reported a few
years ago our efforts towards the synthesis of 1b-methyl-
carbapenems using p-allylpalladium ring-closure strategy
N
8
OTBS
O
n = 1
X
OTBS
n = 2
X
N
O
n
SYNTHESIS 2004, No. 16, pp 2665–2672
x
x.
x
x
.
2
0
0
4
N
Advanced online publication: 11.10.2004
DOI: 10.1055/s-2004-834877; Art ID: Z11304SS
Georg Thieme Verlag Stuttgart · New York
O
Scheme 1
©

2
666
N. Desroy et al.
PAPER
OTBS
OTBS
Diels-Alder
cycloadducts
(see Table 1)
d
TMS
N
87%
N
OTBS
OAc
OTBS
O
O
O
8
10
b
9
5%
a
OTBS
OTBS
NH
NH
c
85%
O
O
95%
6
7
Diels-Alder
cycloadducts
(see Table 2)
e
N
N
7
5%
O
9
11
Scheme 2 Reagents and conditions: a) trimethylsilylacetylene, BuLi, THF, –10 °C, then 6, –50 °C→ –30 °C; b) 4-bromobut-1-ene,
Bu NHSO , NaI, KOH, THF, r.t.; c) 5-bromopent-1-ene, Bu NHSO , NaI, KOH, THF, r.t.; d) RuCl (=CHPh)(PCy ) (A), CH Cl , 50 °C, 22 h;
4
4
4
4
2
3
2
2
2
e) RuCl (=CHPh)(PCy ) (A), CH Cl , 80 °C, 24 h
2
3
2
2
2
lylation of the alkyne to give the desired enynes 8 and 9 in A single diastereomer was obtained with para-benzo-
high yields. Ring-closing enyne metathesis with 5% of quinone and PTAD, whereas reactions with DMAD and
1
2
Grubbs’ first generation catalyst (A) afforded the bicy- maleimide yielded a mixture of diastereomers.
clic compounds 4/6 10 and 4/7 11 in 87% and 75% yields,
The stereochemistry of the products was elucidated by
respectively. These dienes were next engaged in Diels–
NOESY. In all cases, the adduct or major product arose
Alder reactions with various dienophiles. Cycloadditions
from an approach of the dienophile on the opposite side of
of diene 10 in dichloromethane at 80 °C with dimethyl-
the b-lactam ring in order to avoid the steric hindrance of
acetylene dicarboxylate (DMAD), para-benzoquinone
the bent structure of the fused bicyclic system (Scheme 3).
Cycloadditions with diene 11 were performed with
DMAD, maleic anhydride and PTAD as dienophiles in
dichloromethane (Table 2). Moderate to excellent yields
and maleimide led to high yields (90–99%) of the cy-
cloadducts 12–14 (Table 1). Due to the high reactivity of
4
-phenyl-1,2,4-triazoline-3,5-dione (PTAD), the cycload-
dition with this dienophile had to be performed at room
temperature to prevent decomposition of the product 15.
(
57–95%) of the cycloadducts 16–18 were obtained. As in
Table 1 Diels–Alder Reactions with Diene 10
Temp (°C) (equiv) Yield (%)b
a
Products
Entry
1
Dienophile
CO Me
2
80 (4 equiv)
80 (4 equiv)
92
90
CO Me
2
CO Me
2
OTBS
OTBS
CO2Me
CO2Me
CO2Me
O
N
N
+
O
O
(
1.8 : 1)
1
2a
12b
2
3
4
a
OH
OTBS
O
N
OH
O
O
1
3
O
80 (3 equiv)
25 (2 equiv)
99
90
O
OTBS
OTBS
NH
NH
NH
O
+
O
O
O
N
N
(
5.6 : 1)
O
O
1
4a
14b
O
OTBS
N
N
N
N
N
N
Ph
O
O
N
O
1
5
Reactions run in CH Cl for 20 h in screw-cap tubes.
Isolated yields.
2
2
b
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

PAPER
New Polycyclic b-Lactams via Enyne Metathesis and Diels–Alder Reactions
2667
OTBS
N
yield (Figure 2). Formation of hexamethyl mellitate 19
might involve enyne metathesis or [2 + 2 + 2] cycloaddi-
tion catalyzed by the ruthenium complex as possible
OTBS
X
X
O
H
13,14
H
N
mechanistic pathways.
O
CO2Me
MeO2C
MeO2C
CO2Me
major side of approach of the dienophile
Scheme 3
CO2Me
CO2Me
the case of diene 10, a preferential approach of the dieno-
phile on the opposite side of the b-lactam ring was ob-
served.
1
9
Figure 2
However, in order to avoid the isolation and purification
of dienes 10 and 11, one-pot ring-closing enyne metathe- One-pot metathesis–Diels–Alder reactions of enyne 9
sis and subsequent Diels–Alder reactions were carried out gave better yields of the 4/7/6 products 16–18 (Scheme 5).
consecutively (Schemes 4 and 5). Experimentally, reac- Surprisingly, and in contrast with the result obtained with
tions between enynes 8 and 9 and Grubbs’ catalyst were diene 8 and DMAD, the one-pot sequence of 9 with
first run in dichloromethane at 50 or 80 °C, respectively, DMAD was more efficient than the stepwise procedure,
for 20 h. The dienophile was then added and the tempera- although the formation of hexamethyl mellitate 19 was
ture was set to perform the cycloaddition.
again observed.
Interestingly, one-pot metathesis–cycloaddition of enyne The selectivity of the Diels–Alder reactions with enyne 8
8
4
with maleimide and PTAD gave better yields of the and 9 in the one-pot sequence was the same as with dienes
/6/6 cycloadducts 14, 15 than the stepwise procedure, 10 and 11 in the stepwise procedure.
with a remarkable 97% yield in 14 (Scheme 4). On the
contrary, better yields were obtained via the stepwise se-
quence with para-benzoquinone and DMAD due to the
formation of side-products resulting from the side-reac-
tions of the Grubbs’ catalyst with the cycloadducts or the
dienophile. In one example, one-pot sequence with
DMAD afforded by-product 19 in approximately 10%
In conclusion, we have devised an atom economical route
to new polycyclic 4/6/6 and 4/6/7 b-lactams via enyne
metathesis and Diels–Alder reactions. These two key
steps could be performed consecutively in a one-pot fash-
ion. In most cases this one-pot procedure not only avoided
the isolation of intermediate dienes, but also gave in-
Table 2 Diels–Alder Reactions with Diene 11
a
Yield (%)b
Entry
1
Dienophile
Temp (°C) (equiv)
Products
CO Me
2
80 (4 equiv)
95
CO Me
2
2
CO Me
OTBS
OTBS
CO2Me
CO2Me
CO2Me
N
+
N
O
O
(
2.1 : 1)
1
6a
16b
2
3
O
O
65 (4 equiv)
57
O
O
OTBS
O
O
N
O
1
7
O
25 (2 equiv)
86
O
N
N
N
Ph
N
N
OTBS
N
O
O
N
O
1
8
a
Reactions run in CH Cl for 20 h in screw-cap tubes.
Isolated yields.
2
2
b
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

2
668
N. Desroy et al.
PAPER
O
O
O
OTBS
OTBS
OTBS
N
N
Ph
NH
NH
N
+
O
O
O
N
N
N
(
5.6 : 1)
O
O
O
OTBS
1
5
14a
14b
a
b
8
4% (78%)
9
7% (86%)
OTBS
OH
b
N
b
O
CO2Me
CO2Me
CO2Me
2
OTBS
8
OTBS
CO Me
5
0% (78%)
5
4% (80%)
N
OH
N
N
+
O
O
O
1
3
12a
(1.8 : 1)
12b
Scheme 4 For comparison, overall yields for the reactions run in separate steps are indicated in brackets. Reagents and conditions: a)
RuCl (=CHPh)(PCy ) (A), CH Cl , 50 °C, 20 h, then PTAD, r.t., 20 h; b) RuCl (=CHPh)(PCy ) (A), CH Cl , 50 °C, 20 h, then dienophile,
2
3
2
2
2
2
3
2
2
2
8
0 °C, 20 h
O
Ph
N
N
OTBS
N
O
CO2Me
CO2Me
OTBS
OTBS
OTBS
N
a
CO2Me
CO2Me
O
82% (65%)
18
c
O
N
N
+
N
b
76% (71%)
O
O
(2.1 : 1)
O
O
9
16a
16b
OTBS
59% (43%)
O
N
O
17
Scheme 5 For comparison, overall yields for the reactions run in separate steps are indicated in brackets. Reagents and conditions: a)
RuCl (=CHPh)(PCy ) (A), CH Cl , 80 °C, 20 h, then PTAD, r.t., 20 h; b) RuCl (=CHPh)(PCy ) (A), CH Cl , 80 °C, 20 h, then maleic anhy-
2
3
2
2
2
2
3
2
2
2
dride, 65 °C, 20 h; c) RuCl (=CHPh)(PCy ) (A), CH Cl , 80 °C, 20 h, then DMAD, 80 °C, 20 h
2
3
2
2
2
creased overall yields of polycyclic compounds. Exten-
sion of this methodology and biological evaluation of
these new compounds is envisaged in our laboratory.
These results will be presented in due course.
on a Stuart Scientific or on Kofler apparatus. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter.
(3S,4S)-3-[(R)-1-(tert-Butyldimethylsilanyloxy)ethyl]-4-trimeth-
ylsilanylethynylazetidin-2-one (7)
Under argon, to a solution of trimethylsilylacetylene (8.83 mL, 62.5
mmol, M = 98.22, d = 0.695, 2.5 equiv) in THF (150 mL) at –15 °C
was added dropwise a solution of BuLi in hexane (2.14 M; 29.2 mL,
All the reactions were performed in oven-dried glassware under an
atmosphere of argon. THF was freshly distilled from sodium and
benzophenone, and CH Cl was distilled over calcium hydride prior
to use. All other reagents and solvents were used as supplied. Col-
umn chromatography and TLC were performed on Merck silica gel
2
2
6
2.5 mmol, 2.5 equiv). The solution was stirred for 1 h, then cooled
to –50 °C, and a solution of acetoxyazetidinone 6 (7.181 g, 25
mmol, M = 287.24, 1 equiv) in THF (50 mL) was slowly added via
cannula. The reaction mixture was allowed to warm up slowly to
6
0 (0.040–0.063 mm) and 60 F254, respectively.
IR spectra were recorded using a Nicolet 210 spectrophotometer us-
ing a thin film supported on NaCl plates or KBr discs where stated.
–30 °C (5 h) and was then quenched with sat. aq NH
4
Cl. Extraction
with Et O and EtOAc followed by drying (Na SO ), concentration
2
2
4
–
1
1
13
Details are reported as nmax in cm . H and C NMR spectra were
recorded on Bruker Avance 400, Avance 300 or AC 200 apparatus.
The chemical shift in ppm is quoted relative to the residual signals
in vacuo and purification by flash chromatography (500 g of silica
gel; cyclohexane–EtOAc, 9:1) gave 7.
15
Yield: 6.932 g (85%); white solid; mp 137 °C (Lit. not reported);
1
of non-deuterated NMR solvent. Multiplicities in the H NMR spec-
29
15
21
[
a]D +37 (c 1.05, CHCl ) {Lit. [a]D +39.0 (c 1.016, CHCl )}.
3
3
tra are described as: s = singlet, d = doublet, t = triplet, q = quartet,
quint = quintuplet, m = multiplet and br = broad. Coupling con-
stants (J) are reported in Hz.
–
1
IR (KBr): 3165, 2953, 2927, 2857, 2182, 1765, 1251 cm .
1
H NMR (400 MHz, CDCl ): d = 0.05 (s, 3 H), 0.06 (s, 3 H), 0.15
3
(
s, 9 H), 0.85 (s, 9 H), 1.23 (d, 3 H, J = 6.3 Hz), 3.24–3.28 (m, 1 H),
Mass spectra were recorded on a Nermag R10-10C or on a API
4
.21 (qd, 1 H, J = 6.2, 3.8 Hz), 4.33 (d, 1 H, J = 2.4 Hz).
3
000 PE Sciex apparatus. Mps are uncorrected and were measured
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

PAPER
New Polycyclic b-Lactams via Enyne Metathesis and Diels–Alder Reactions
2669
1
3
C NMR (50.3 MHz, CDCl ): d = –5.3, –4.4, –0.4, 17.8, 22.1, 25.5,
Anal. Calcd for C H NO Si (321.53): C, 67.24; H, 9.72; N, 4.36.
Found: C, 67.20; H, 9.76; N, 4.39.
3
18 31
2
3
9.4, 64.5, 67.6, 89.9, 103.2, 167.7.
+
+
MS (CI, NH ): m/z = 343 [M + NH ] , 326 [M + H] , 268 [M –
3
4
+
Diene 10
C(CH ) ] .
3
3
In a screw-cap tube flushed with argon, enyne 8 (315 mg, 1.02
mmol, M = 307.50, 1 equiv), degassed CH Cl (20 mL), and
Anal. Calcd for C H NO Si (325.59): C, 59.02; H, 9.60; N, 4.30.
Found: C, 59.02; H, 9.55; N, 4.30.
16
31
2
2
2
2
Grubbs’ first generation catalyst A (42.2 mg, 51.3 mmol,
M = 822.96, 0.05 equiv) were successively introduced. The solu-
tion was heated at 50 °C (oil bath temperature) for 22 h, then con-
centrated in vacuo. Purification by flash chromatography (15 g of
silica gel; cyclohexane–EtOAc, 9:1) gave 10.
(
3S,4S)-1-(3-Butenyl)-3-[(R)-1-(tert-butyldimethylsilanyl-
oxy)ethyl]-4-ethynylazetidin-2-one (8)
Under argon, to a solution of 7 (2.28 g, 7 mmol, M = 325.59, 1
equiv) in THF (70 mL) at r.t., were successively added 4-bromobut-
Yield: 274.8 mg (87%); brownish–yellow oil which crystallised
1
-ene (1.42 mL, 14 mmol, M = 135.0, d = 1.33, 2 equiv), tetrabutyl-
ammonium hydrogen sulfate (950.7 mg, 2.8 mmol, M = 339.54,
.4 equiv), sodium iodide (105 mg, 0.7 mmol, M = 150, 0.1 equiv)
2
5
(
mp 20–30 °C) when kept below 0 °C; [a]D –180 (c 1.05, CHCl3).
–
1
0
IR (NaCl film): 2954, 2930, 2857, 1757, 1257 cm .
and freshly crushed potassium hydroxide (982 mg, 17.5 mmol,
M = 56.11, 2.5 equiv). The solution was stirred vigorously for 3 h
1
H NMR (200 MHz, CDCl ): d = 0.08 (s, 3 H), 0.09 (s, 3 H), 0.89
3
(
(
(
(
6
13
s, 9 H), 1.32 (d, 3 H, J = 6.2 Hz), 2.05–2.18 (m, 1 H), 2.45–2.62
m, 1 H), 2.73 (dd, 1 H, J = 13.4, 5.2 Hz), 2.77–2.86 (m, 1 H), 3.88
dd, 1 H, J = 13.4, 7.4 Hz), 3.97 (br s, 1 H), 4.12–4.25 (m, 1 H), 5.03
d, 1 H, J = 11.0 Hz), 5.48 (d, 1 H, J = 17.9 Hz), 5.83–5.85 (m, 1 H),
and then quenched with sat. aq NH Cl. The aq layer was extracted
4
several times with Et O, the combined organic extracts were dried
2
(
MgSO ) and concentrated in vacuo. Purification by flash chroma-
4
tography (45 g of silica gel; cyclohexane–EtOAc, 9:1) afforded 8.
.23 (dd, 1 H, J = 17.9, 11.0 Hz).
2
5
Yield: 2.049 g (95%); pale yellow oil; [a]D –20 (c 1.00, CHCl3).
C NMR (50.3 MHz, CDCl ): d = –4.6, 18.0, 23.2, 24.2, 25.7, 35.3,
3
IR (NaCl film): 3311, 3084, 2954, 2929, 2857, 2117, 1766, 1645,
49.2, 64.3, 67.7, 114.0, 127.6, 135.9, 136.3, 170.3.
–
1
1
259 cm .
+
+
MS (CI, NH ): m/z = 325 [M + NH ] , 308 (M + H) .
3
4
1
H NMR (400 MHz, CDCl ): d = 0.05 (s, 3 H), 0.06 (s, 3 H), 0.86
3
Anal. Calcd for C H NO Si (307.50): C, 66.40; H, 9.51; N, 4.55.
Found: C, 66.31; H, 9.60; N, 4.56.
1
7
29
2
(
s, 9 H), 1.21 (d, 3 H, J = 6.3 Hz), 2.31–2.37 (m, 2 H), 2.44 (d, 1 H,
J = 2.0 Hz), 3.13–3.20 (m, 2 H), 3.38–3.45 (m, 1 H), 4.19 (m, 1 H),
.23 (dd, 1 H, J = 2.2, 2.0 Hz), 5.05 (dd, 1 H, J = 10.3, 1.4 Hz), 5.12
4
Diene 11
(dd, 1 H, J = 17.1, 1.4 Hz), 5.79 (ddt, 1 H, J = 17.0, 10.2, 6.7 Hz).
In a screw-cap tube flushed with argon, enyne 9 (165.8 mg, 0.52
mmol, M = 321.53, 1 equiv), degassed CH Cl (10 mL), and
1
3
C NMR (50.3 MHz, CDCl ): d = –5.0, –4.5, 17.8, 22.2, 25.6, 32.0,
3
2
2
4
0.1, 42.5, 64.5, 65.9, 74.2, 80.4, 116.8, 134.8, 166.8.
Grubbs’ first generation catalyst A (20.6 mg, 25 mmol, M = 822.96,
0.05 equiv) were successively introduced. The solution was heated
at 80 °C (oil bath temperature) for 24 h, then concentrated in vacuo.
Purification by flash chromatography (10 g of silica gel; cyclohex-
ane–EtOAc, 85:15) gave 11.
+
+
MS (CI, NH ): m/z = 325 [M + NH ] , 308 [M + H] , 250 [M –
3
4
+
C(CH ) ] .
3
3
Anal. Calcd for C H NO Si (307.50): C, 66.40; H, 9.51; N, 4.55.
1
7
29
2
Found: C, 66.50; H, 9.45; N, 4.42.
2
5
Yield: 124.6 mg (75%); yellow oil; [a]D –133.6 (c 1.14, CHCl3).
(
3S,4S)-3-[(R)-1-(tert-Butyldimethylsilanyloxy)ethyl]-4-ethy-
IR (NaCl film): 2952, 2928, 2856, 1755, 1634, 1255, 1142, 1063,
835, 777 cm .
–
1
nyl-1-pent-4-enylazetidin-2-one (9)
Under argon, to a solution of 7 (1.63 g, 5 mmol, M = 325.59, 1
equiv) in THF (50 mL) at r.t., were successively added 5-bro-
mopent-1-ene (97%, 1.07 mL, 9 mmol, M = 149.04, d = 1.259, 1.8
equiv), tetrabutylammonium hydrogen sulfate (679 mg, 2 mmol,
M = 339.54, 0.4 equiv), sodium iodide (75 mg, 0.5 mmol, M = 150,
1
H NMR (300 MHz, CDCl ): d = 0.07 (s, 3 H), 0.09 (s, 3 H), 0.89
3
(
(
s, 9 H), 1.28 (d, 3 H, J = 6.4 Hz), 1.81–1.86 (m, 2 H), 2.23–2.32
m, 2 H), 2.89 (d, 1 H, J = 4.0 Hz), 3.12 (dt, 1 H, J = 13.0, 4.4 Hz),
3
.79 (ddd, 1 H, J = 13.0, 8.7, 8.3 Hz), 4.15–4.23 (m, 1 H), 4.34 (br
s, 1 H), 4.97 (d, 1 H, J = 11.0 Hz), 5.37 (d, 1 H, J = 17.5 Hz), 5.87–
.91 (m, 1 H), 6.18 (dd, 1 H, J = 17.5, 11.0 Hz).
0
.1 equiv) and freshly crushed potassium hydroxide (701 mg, 12.5
5
mmol, M = 56.11, 2.5 equiv). The solution was stirred vigorously
1
3
C NMR (75.5 MHz, CDCl ): d = –4.7, –4.4, 17.9, 23.2, 25.8, 26.0,
for 3 h and then quenched with sat. aq NH Cl. The aq layer was ex-
3
4
2
6.6, 41.4, 55.8, 65.1, 66.3, 113.6, 129.7, 137.1, 139.1, 167.9.
tracted several times with Et O, the combined organic extracts were
2
dried (MgSO ) and concentrated in vacuo. Purification by flash
+
+
4
MS (CI, NH ): m/z = 339 [M + NH ] , 322 [M + H] , 264 [M –
3 4
C(CH ) ] .
chromatography (50 g of silica gel; cyclohexane–EtOAc, 9:1) af-
forded 9.
+
3
3
Anal. Calcd for C H NO Si (321.53): C, 67.24; H, 9.72; N, 4.36.
Found: C, 67.29; H, 9.61; N, 4.28.
1
8
31
2
2
5
Yield: 1.530 g (95%); pale yellow oil; [a]D –24.5 (c 1.26, CHCl3).
IR (NaCl film): 3310, 3078, 2954, 2929, 2857, 2117, 1762, 1641,
–
1
Diels–Alder Cycloadduct 12a
White solid; mp 105 °C; [a]D – 43.5 (c 0.85, CHCl3).
1
257, 1142, 1061, 837, 779 cm .
2
5
1
H NMR (300 MHz, CDCl ): d = 0.05 (s, 3 H), 0.07 (s, 3 H), 0.86
3
IR (NaCl film): 2974, 2954, 2934, 2896, 2882, 2853, 1751, 1726,
(
(
s, 9 H), 1.22 (d, 3 H, J = 6.2 Hz), 1.65–1.74 (m, 2 H), 2.04–2.17
m, 2 H), 2.44 (d, 1 H, J = 1.9 Hz), 3.07–3.20 (m, 1 H), 3.19 (t, 1 H,
–
1
1
649, 1269, 1153, 1065, 841, 830, 776 cm .
J = 2.6 Hz), 3.28–3.44 (m, 1 H), 4.15–4.26 (m, 2 H), 4.99 (d, 1 H,
J = 10.4 Hz), 5.04 (dd, 1 H, J = 16.8, 1.5 Hz), 5.75 (dddd, 1 H,
J = 16.8, 10.4, 6.6, 6.4 Hz).
1
H NMR (400 MHz, CDCl ): d = 0.07 (s, 6 H), 0.87 (s, 9 H), 1.23
3
(
d, 3 H, J = 6.2 Hz), 1.58–1.67 (m, 1 H), 2.08–2.15 (m, 1 H), 2.90–
3
.00 (m, 1 H), 2.94 (dd, 1 H, J = 4.6, 1.9 Hz), 3.08–3.21 (m, 3 H),
3.76 (s, 3 H), 3.77–3.87 (m, 1 H), 3.79 (s, 3 H), 4.18–4.23 (m, 2 H),
.63 (br s, 1 H).
1
3
C NMR (75.5 MHz, CDCl ): d = –4.9, –4.5, 17.9, 22.3, 25.7, 26.8,
3
5
3
1.1, 40.3, 42.2, 64.3, 65.8, 74.2, 80.6, 115.3, 137.3, 167.0.
1
3
+
+
C NMR (100.6 MHz, CDCl ): d = –4.8, –4.2, 18.0, 22.8, 25.8,
3
MS (CI, NH ): m/z = 339 [M + NH ] , 322 [M + H] , 264 [M –
3
4
+
27.8, 29.1, 34.2, 38.0, 52.5, 52.8, 65.2, 65.9, 117.6, 131.1, 136.0,
C(CH ) ] .
3
3
1
36.6, 167.5, 168.3, 170.0.
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

2
670
N. Desroy et al.
PAPER
+
+
MS (CI, NH ): m/z = 467 [M + NH ] , 450 [M + H] , 392 [M –
IR (KBr): 3171, 3075, 2955, 2929, 2887, 2856, 1741, 1714, 1647,
1352, 1250, 1144, 1057, 835, 811, 778 cm .
3
4
+
–1
C(CH ) ] .
3
3
1
Anal. Calcd for C H NO Si (449.61): C, 61.44; H, 7.85; N, 3.12.
Found: C, 61.37; H, 8.03; N, 2.98.
H NMR (400 MHz, CDCl ): d = 0.04 (s, 3 H), 0.06 (s, 3 H), 0.86
2
3
35
6
3
(s, 9 H), 1.24 (d, 3 H, J = 6.2 Hz), 1.90–2.10 (m, 2 H), 2.22–2.34
(m, 1 H), 2.58–2.81 (m, 2 H), 2.88–2.94 (m, 1 H), 3.00 (dd, 1 H,
Diels–Alder Cycloadduct 12b
White solid; mp 131 °C; [a]D +84.5 (c 2.155, CHCl3).
J = 5.1, 2.0 Hz), 3.15 (td, 1 H, J = 8.2, 2.7 Hz), 3.24 (t, 1 H, J = 8.2
Hz), 3.88 (dt, 1 H, J = 13.3, 5.1 Hz), 4.01 (br s, 1 H), 4.17 (quint, 1
H, J = 5.9 Hz), 5.72–5.79 (m, 1 H).
2
5
IR (NaCl film): 2952, 2928, 2934, 2893, 2856, 1747, 1732, 1651,
–
1
13
1
258, 1140, 1072, 836, 777 cm .
C NMR (100.6 MHz, CDCl ): d = –4.4, –5.1, 17.8, 21.8, 22.8,
3
1
26.0, 27.0, 32.2, 38.0, 40.1, 43.4, 52.2, 65.2, 65.4, 120.5, 137.0,
H NMR (400 MHz, CDCl ): d = 0.05 (s, 3 H), 0.07 (s, 3 H), 0.86
3
1
67.8, 177.9, 178.9.
(
s, 9 H), 1.26 (d, 3 H, J = 6.3 Hz), 1.53 (qd, 1 H, J = 12.5, 5.5 Hz),
+
+
1
.88 (dt, 1 H, J = 12.5, 2.9 Hz), 2.89–2.99 (m, 2 H), 3.13 (ddd, 1 H,
J = 7.4, 3.0, 2.0 Hz), 3.19 (dd, 1 H, J = 5.5, 1.9 Hz), 3.19–3.28 (m,
H), 3.77 (s, 3 H), 3.80 (s, 3 H), 3.88–3.93 (m, 1 H), 3.91 (br s, 1
H), 4.19 (quint, 1 H, J = 5.9 Hz), 5.60 (br s, 1 H).
MS (CI, NH ): m/z = 422 [M + NH ] , 405 [M + H] , 347 [M –
3
4
+
C(CH ) ] .
3
3
1
Anal. Calcd for C H N O Si (404.58): C, 62.34; H, 7.97; N, 6.92.
2
1
32
2
4
Found: C, 62.32; H, 7.98; N, 6.76.
1
3
C NMR (100.6 MHz, CDCl ): d = –5.0, –4.1, 18.0, 23.0, 25.7,
3
2
1
7.3, 32.8, 36.9, 38.8, 52.5, 53.6, 64.6, 65.6, 117.0, 130.8, 133.9,
36.4, 167.0, 167.5, 168.5.
Diels–Alder Cycloadduct 15
White solid; mp 245 °C; [a]D –19.4 (c 0.89, CHCl3).
2
5
+
+
MS (CI, NH ): m/z = 467 [M + NH ] , 450 [M + H] , 392 [M –
IR (KBr): 2954, 2929, 2895, 2856, 1769, 1753, 1713, 1420, 1139,
839, 779, 767 cm .
3
4
+
–1
C(CH ) ] .
3
3
1
Anal. Calcd for C H NO Si (449.61): C, 61.44; H, 7.85; N, 3.12.
Found: C, 61.34; H, 7.90; N, 3.30.
H NMR (400 MHz, CDCl ): d = 0.10 (s, 6 H), 0.89 (s, 9 H), 1.27
2
3
35
6
3
(d, 3 H, J = 6.2 Hz), 1.76–1.88 (m, 1 H), 2.99–3.05 (m, 1 H), 3.02
(
dd, 1 H, J = 4.5, 2.0 Hz), 3.18 (ddd, 1 H, J = 13.1, 8.4, 1.3 Hz), 3.97
Diels–Alder Cycloadduct 13
White solid; mp 249–254 °C; [a]D –62.0 (c 0.71, CHCl3).
(ddd, 1 H, J = 13.1, 10.7, 8.9 Hz), 4.17–4.20 (m, 2 H), 4.22–4.28
(m, 1 H), 4.34–4.40 (m, 1 H), 4.39 (br s, 1 H), 5.85–5.87 (m, 1 H),
2
5
7
.36–7.40 (m, 1 H), 7.45–7.50 (m, 4 H).
IR (KBr): 3324, 2956, 2928, 2887, 2857, 1726, 1704, 1686, 1654,
–
1
13
1
251, 1146, 1059, 832, 776 cm .
C NMR (100.6 MHz, CDCl ): d = –4.8, –4.2, 18.0, 22.8, 25.8,
3
1
26.4, 36.4, 42.8, 52.2, 52.7, 65.1, 66.4, 115.5, 125.5, 128.4, 129.3,
31.0, 136.3, 152.2, 152.5, 168.9.
H NMR (400 MHz, DMSO-d ): d = 0.12 (s, 6 H), 0.91 (s, 9 H),
6
1
1
.26 (d, 3 H, J = 6.2 Hz), 1.45–1.52 (m, 1 H), 2.66–2.74 (m, 1 H),
+
+
3
.02–3.08 (m, 2 H), 3.28–3.30 (m, 2 H), 3.40–3.46 (m, 1 H), 3.85
MS (CI, NH ): m/z = 500 [M + NH ] , 483 [M + H] , 426 [M –
3 4
+
(
dt, 1 H, J = 12.9, 9.6 Hz), 4.24–4.29 (m, 1 H), 4.29 (br s, 1 H),
C(CH ) ] .
3 3
5
.88–5.89 (m, 1 H), 6.56 (s, 2 H).
HRMS: m/z calcd for C H N O Si (M + H): 483.2428; found:
483.2434.
2
5
35
4
4
1
3
C NMR (100.6 MHz, DMSO-d ): d = –4.8, –4.3, 18.4, 22.7, 25.7,
6
2
1
6.0, 31.9, 32.7, 38.6, 55.3, 65.7, 66.3, 113.2, 113.4, 118.9, 122.4,
24.5, 138.4, 148.2, 148.4, 170.8.
Diels–Alder Cycloadduct 16a
2
5
+
+
White solid; mp 94 °C; [a]
D
–67.0 (c 1.01, CHCl ).
3
MS (CI, NH ): m/z = 433 [M + NH ] , 416 [M + H] , 358 [M –
C(CH ) ] .
3
4
+
IR (NaCl film): 2999, 2956, 2929, 2897, 2885, 1738, 1721, 1648,
3
3
–
1
1
256, 1154, 1073, 835, 754 cm .
Anal. Calcd for C H NO Si (415.60): C, 66.47; H, 8.00; N, 3.37.
Found: C, 66.32; H, 8.18; N, 3.49.
2
3
33
4
1
H NMR (400 MHz, CDCl ): d = 0.07 (s, 6 H), 0.86 (s, 9 H), 1.19
3
(
d, 3 H, J = 6.3 Hz), 1.14–1.26 (m, 1 H), 1.60–1.80 (m, 2 H), 2.05–
Diels–Alder Cycloadduct 14a
White solid; mp 85 °C; [a]D –46.6 (c 1.03, CHCl3).
2.12 (m, 1 H), 2.55–2.62 (m, 1 H), 2.83 (dd, 1 H, J = 4.2, 2.1 Hz),
2.90–3.15 (m, 3 H), 3.78 (s, 3 H), 3.79 (s, 3 H), 3.84–3.90 (m, 1 H),
2
5
4
.22–4.27 (m, 2 H), 5.75–5.76 (m, 1 H).
IR (KBr): 3224, 3077, 2956, 2930, 2885, 2856, 1777, 1724, 1655,
–
1
13
1
352, 1321, 1257, 1142, 1056, 835, 810, 777 cm .
C NMR (100.6 MHz, CDCl ): d = –4.9, –4.2, 18.0, 22.6, 25.8,
3
1
28.4, 28.6, 36.0, 37.4, 41.7, 52.5, 52.6, 58.2, 63.7, 65.2, 120.6,
33.5, 137.2, 139.0, 167.6, 167.8, 168.4.
H NMR (400 MHz, CDCl ): d = 0.04 (s, 3 H), 0.06 (s, 3 H), 0.85
3
1
(
(
s, 9 H), 1.23 (d, 3 H, J = 6.2 Hz), 1.95–2.06 (m, 1 H), 2.09–2.21
m, 1 H), 2.29–2.40 (m, 1 H), 2.59 (qd, 1 H, J = 13.8, 5.5 Hz), 2.76–
+
+
MS (Electrospray, CI): m/z = 486 [M + Na] , 481 [M + NH ] , 464
[M + H] .
4
+
2
.82 (m, 2 H), 3.19–3.24 (m, 2 H), 3.25–3.35 (m, 1 H), 3.41–3.48
(
(
1
m, 1 H), 3.94 (br s, 1 H), 4.13 (quint, 1 H, J = 5.9 Hz), 5.74–5.80
m, 1 H).
Anal. Calcd for C H NO Si (463.64): C, 62.17; H, 8.04; N, 3.02.
Found: C, 62.03; H, 8.22; N, 2.86.
2
4
37
6
3
C NMR (100.6 MHz, CDCl ): d = –4.1, –5.1, 18.0, 22.7, 22.9,
3
2
1
4.1, 25.7, 35.1, 39.0, 41.4, 44.5, 49.4, 65.0, 65.4, 121.1, 141.2,
68.7, 177.6, 179.3.
Diels–Alder Cycloadduct 16b
2
5
White solid; mp 92 °C; [a]D +147.9 (c 0.545, CHCl3).
+
+
MS (CI, NH ): m/z = 422 [M + NH ] , 405 [M + H] , 347 [M –
IR (NaCl film): 2951, 2928, 2855, 1738, 1721, 1650, 1258, 1143,
1066, 836 cm .
3
4
+
–1
C(CH ) ] .
3
3
1
HRMS: m/z calcd for C H N O Si (M + H): 405.2210; found:
H NMR (400 MHz, CDCl ): d = 0.04 (s, 3 H), 0.06 (s, 3 H), 0.84
2
1
33
2
4
3
4
05.2213.
(s, 9 H), 1.16 (d, 3 H, J = 6.3 Hz), 1.15–1.32 (m, 1 H), 1.65–1.82
(
m, 1 H), 1.94–2.03 (m, 1 H), 2.11–2.18 (m, 1 H), 2.91–3.15 (m, 3
Diels–Alder Cycloadduct 14b
White solid; mp 163 °C; [a]D +35.3 (c 0.85, CHCl3).
H), 3.19–3.28 (m, 1 H), 3.22 (br s, 1 H), 3.41 (dt, 1 H, J = 13.0, 4.3
Hz), 3.77 (s, 3 H), 3.87 (s, 3 H), 4.09 (br s, 1 H), 4.25 (qd, 1 H,
J = 6.3, 3.7 Hz), 5.73 (br s, 1 H).
2
5
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

PAPER
New Polycyclic b-Lactams via Enyne Metathesis and Diels–Alder Reactions
2671
1
3
C NMR (100.6 MHz, CDCl ): d = –5.0, –4.1, 17.9, 22.7, 25.7, References
3
2
1
5.8, 27.9, 34.0, 41.8, 43.3, 52.4, 52.5, 56.2, 57.6, 64.8, 118.7,
31.0, 135.5, 138.1, 167.3, 167.7, 168.7.
(1) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
3
2, 131.
+
+
MS (Electrospray, CI): m/z = 486 [M + Na] , 481 [M + NH ] , 464
[
4
(
2) For recent examples of one-pot enyne metathesis and Diels–
Alder reactions, see: (a) Kotha, S.; Sreenivasachary, N.;
Brahmachary, E. Tetrahedron Lett. 1998, 39, 2805.
+
M + H] .
HRMS: m/z calcd for C H NO Si (M + H): 483.2468; found:
2
4
38
6
4
64.2470.
(b) Schürer, S. C.; Blechert, S. Tetrahedron Lett. 1999, 40,
1877. (c) Stragies, R.; Voigtmann, U.; Blechert, S.
Diels–Alder Cycloadduct 17
White solid; mp 58–65 °C; [a]D –7.3 (c 1.745, CHCl3).
Tetrahedron Lett. 2000, 41, 5465. (d) Bentz, D.; Laschat, S.
Synthesis 2000, 1766. (e) Rodriguez, J. R.; Castedo, L.;
Mascareñas, J. L. Chem.–Eur. J. 2002, 8, 2923. (f) Banti,
D.; North, M. Adv. Synth. Catal. 2002, 344, 694.
2
5
IR (KBr): 2955, 2930, 2897, 2856, 1847, 1751, 1777, 1750, 1631,
–
1
1
251, 1139, 1085, 965, 834, 777 cm .
(
g) Rosillo, M.; Dominguez, G.; Casarrubios, L.; Amador,
1
H NMR (400 MHz, CDCl ): d = 0.02 (s, 3 H), 0.05 (s, 3 H), 0.82
3
U.; Perez-Castells, J. J. Org. Chem. 2004, 69, 2084.
(
(
s, 9 H), 1.20 (d, 3 H, J = 6.2 Hz), 1.47–1.72 (m, 1 H), 1.91–2.04
(
(
3) (a) Katz, T. J.; Sivavec, T. M. J. Am. Chem. Soc. 1985, 107,
m, 3 H), 2.30–2.36 (m, 1 H), 2.50–2.53 (m, 1 H), 2.70–2.81 (m, 2
737. (b) Kinoshita, A.; Mori, M. Synlett 1994, 1020. (c) For
H), 2.99 (dd, 1 H, J = 5.6, 1.0 Hz), 3.36 (dd, 1 H, J = 9.8, 5.4 Hz),
.42–3.47 (m, 1 H), 3.85–3.89 (m, 1 H), 4.06 (br s, 1 H), 4.11–4.19
a recent review on enyne metathesis, see: Poulsen, C. S.;
Madsen, R. Synthesis 2003, 1.
3
(
m, 1 H), 5.84–5.86 (m, 1 H).
4) (a) Fringuelli, F.; Taticchi, A. The Diels–Alder Reaction:
Selected Pratical Methods; Wiley and Sons: Chichester,
1
3
C NMR (100.6 MHz, CDCl ): d = –5.0, –4.2, 17.8, 22.9, 23.7,
3
2
002. (b) Corey, E. J. Angew. Chem. Int. Ed. 2002, 41,
2
1
5.7, 28.3, 29.1, 39.7, 40.3, 41.9, 46.7, 57.3, 63.3, 65.7, 123.8,
42.4, 167.3, 172.0, 173.8.
1650. (c) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.;
Vassilikogiannakis, G. Angew. Chem. Int. Ed. 2002, 41,
668.
+
+
MS (CI, NH ): m/z = 437 [M + NH ] , 420 [M + H] , 362 [M –
3
4
1
+
C(CH ) ] .
3
3
(
5) (a) Dürckheimer, W.; Blumbach, J.; Lattrell, R.;
Scheunemann, K. H. Angew. Chem., Int. Ed. Engl. 1985, 24,
180. (b) Cabri, W.; Di Fabio, R. From Bench to Market;
Oxford University Press: Oxford, 2000. (c)RecentProgress
in the Chemical Synthesis of Antibiotics; Lukacs, G.; Ohno,
M., Eds.; Springer: Berlin, 1990. (d) Mann, J. The Elusive
Magic Bullet: The Search for the Perfect Drug; Oxford
University Press: Oxford, 1999. (e) Hamilton-Miller, J. M.
T. J. Antimicrob. Chemother. 1999, 44, 729.
HRMS: m/z calcd for C H NO Si (M + H): 420.2206; found:
2
2
34
5
4
20.2208.
Diels–Alder Cycloadduct 18
White solid; mp 192–194 °C; [a]D –180.0 (c 1.03, CHCl3).
2
5
IR (KBr): 2952, 2928, 2934, 2895, 2882, 2855, 1777, 1746, 1732,
–
1
1
708, 1652, 1504, 1455, 1429, 1140, 1060, 989, 830, 776, 765 cm .
1
H NMR (400 MHz, CDCl ): d = 0.09 (s, 6 H), 0.88 (s, 9 H), 1.24
3
(6) For a review, see: Alcaide, B.; Almendros, P. Curr. Org.
(
d, 3 H, J = 6.3 Hz), 1.61–1.71 (m, 1 H), 1.71–1.80 (m, 1 H), 1.85–
Chem. 2002, 6, 245.
1
2
.95 (m, 1 H), 2.19–2.25 (m, 1 H), 2.65 (ddd, 1 H, J = 14.1, 11.0,
.9 Hz), 2.95 (dd, 1 H, J = 4.0, 2.0 Hz), 3.89 (dt, 1 H, J = 14.1, 4.0
(
7) For other syntheses of bi- and tricyclic b-lactams via
metathesis, see: (a) Barrett, A. G. M.; Baugh, S. P. D.;
Braddock, D. C.; Flack, K.; Gibson, V. C.; Giles, M. R.;
Marshall, E. L.; Procopiou, P. A.; White, A. J. P.; Williams,
D. J. J. Org. Chem. 1998, 63, 7893. (b) Barrett, A. G. M.;
Ahmed, M.; Baker, S. P.; Baugh, S. P. D.; Braddock, D. C.;
Procopiou, P. A.; White, A. J. P.; Williams, D. J. J. Org.
Chem. 2000, 65, 3716. (c) Alcaide, B.; Almendros, P.;
Alonso, J. M.; Aly, M. F.; Redondo, M. C. Synlett 2001, 773.
8) Recent references: (a) Desroy, N.; Le Roux, R.; Phansavath,
P.; Chiummiento, L.; Bonini, C.; Genêt, J.-P. Tetrahedron
Lett. 2003, 44, 1763. (b) Labeeuw, O.; Phansavath, P.;
Genêt, J. P. Tetrahedron Lett. 2003, 44, 6383. (c) Michelet,
V.; Adiey, K.; Tanier, S.; Dujardin, G.; Genêt, J.-P. Eur. J.
Org. Chem. 2003, 2947. (d) Mordant, C.; Caño de Andrade,
C.; Touati, R.; Ratovelomanana-Vidal, V.; Ben Hassine, B.;
Genet, J. P. Synthesis 2003, 2405.
Hz), 4.00–4.04 (m, 1 H), 4.29 (qd, 1 H, J = 6.3, 4.0 Hz), 4.37 (br s,
H), 4.44 (dd, 1 H, J = 16.9, 4.2 Hz), 4.54–4.56 (m, 1 H), 5.91–5.92
1
(
m, 1 H), 7.35–7.39 (m, 1 H), 7.45–7.53 (m, 4 H).
1
3
C NMR (100.6 MHz, CDCl ): d = –4.9, –4.1, 18.0, 22.7, 25.8,
3
2
1
6.3, 33.0, 41.5, 43.9, 53.5, 55.8, 64.8, 65.0, 117.9, 125.4, 128.3,
29.3, 131.1, 138.1, 151.3, 153.4, 166.7.
+
+
MS (CI, NH ): m/z = 514 [M + NH ] , 497 [M + H] , 439 [M –
3
4
(
(
+
C(CH ) ] .
3
3
Anal. Calcd for C H N O Si (496.67): C, 62.87; H, 7.31; N, 11.28.
26
36
4
4
Found: C, 62.97; H, 7.26; N, 11.04.
Hexamethyl Mellitate (19)
White solid; mp 179–184 °C (Lit. 180–184 °C).
1
6
–
1
IR (KBr): 2958, 2928, 2855, 1729, 1575 cm .
9) (a) Roland, S.; Durand, J. O.; Savignac, M.; Genêt, J.-P.
Tetrahedron Lett. 1995, 36, 3007. (b) Roland, S.; Savignac,
M.; Durand, J. O.; Genêt, J.-P. Bull. Soc. Chim. Fr. 1996,
1
H NMR (300 MHz, CDCl ): d = 3.88 (s, 18 H).
3
1
3
C NMR (75.5 MHz, CDCl ): d = 51.1, 131.5, 162.7.
3
1
33, 945. (c) Galland, J. C.; Roland, S.; Malpart, J.;
Savignac, M.; Genêt, J.-P. Eur. J. Org. Chem. 1999, 621.
d) For a recent discussion of syntheses of carbapenams
+
+
MS (CI, NH ): m/z = 461 [M + N H ] , 444 [M + NH ] .
3
2
7
4
(
using transition metals, see: Mori, M.; Kozawa, Y.;
Takimoto, M. J. Synth. Org. Chem. Jpn. 2003, 61, 1065.
Acknowledgment
The authors are grateful to Pr Murahashi and Dr Saito (Takasago In-
ternational Corporation) for their generous gift of azetidinone 6. N.
D. Thanks the Ministère de la Recherche for financial support.
(10) Duboc, R.; Hénaut, C.; Savignac, M.; Genêt, J.-P.;
Bhatnagar, N. Tetrahedron Lett. 2001, 42, 2461.
(11) (a) For a review on the synthesis of the azetidinone, see:
Berks, A. H. Tetrahedron 1996, 52, 331. (b) Noyori, R.;
Ikeda, T.; Okhuma, T.; Widhalm, M.; Kitamura, M.; Takaya,
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York

2
672
N. Desroy et al.
PAPER
H.; Akutagawa, S.; Sayo, N.; Saito, T.; Taketomi, T.;
Kumobayashi, H. J. Am. Chem. Soc. 1989, 111, 9134.
(13) For a review on non-metathetic behavior of Grubbs’ catalyst,
see: Alcaide, B.; Almendros, P. Chem.–Eur. J. 2003, 9,
1258.
(
c) Murahashi, S. I.; Naota, T.; Kuwabara, T.; Saito, T.;
Kumobayashi, H.; Akutagawa, S. J. Am. Chem. Soc. 1990,
(14) Reaction between DMAD and 5 mol% of Grubbs’ catalyst or
112, 7820.
other ruthenium(II) sources {(cod)Ru(Met) , [(p-
2
(
12) (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
cymene)RuCl] } in CH Cl at 80 °C also led to low yields
2
2
2
18. (b) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
(10–15%) of hexamethyl mellitate 19.
Soc. 1996, 118, 100.
(15) Nakai, T.; Chiba, T. U.S. Patent 4845210, 1989.
(
16) Moseley, K.; Maitlis, P. M. J. Chem. Soc., Dalton Trans.
1974, 169.
Synthesis 2004, No. 16, 2665–2672 © Thieme Stuttgart · New York