Ruthenium catalysts for carbenoid intramolecular C-H insertion of 2-diazoacetoacetamides and diazomalonic ester amides

Article abstract of DOI:10.1016/j.tet.2007.09.053

The intramolecular carbenoid C-H insertion of 2-diazoacetoacetamides, leading to γ- and/or β-lactams, is catalyzed effectively by dinuclear Ru(I,I) complexes of the type [Ru₂(μ-L¹)₂(CO)₄L²₂], where L¹ is a bidentate bridging acetate, calix[4]arenedicarboxylate, saccharinate or 6-chloropyridin-2-olate ligand. By comparison with rhodium catalysts, namely dirhodium tetraacetate and dirhodium calix[4]arenedicarboxylate complexes, product yields are similarly high and the regioselectivity of the insertion reaction is the same. Surprisingly, even the ruthenium(0) cluster Ru₃(CO)₁₂ was found to be an effective catalyst for carbenoid C-H insertion of 2-diazoacetoacetamides and also of some diazoacetamides. In terms of diastereoselectivity, trans-isomers of β- and γ-lactams are obtained. However, the β-lactam obtained from diazomalonic ester amide 2 yields the cis-isomer stereoselectively, which slowly rearranges to the trans-isomer.

Full text of DOI:10.1016/j.tet.2007.09.053

Tetrahedron 63 (2007) 12172–12178
Ruthenium catalysts for carbenoid intramolecular C–H insertion
of 2-diazoacetoacetamides and diazomalonic ester amides
*
Markus Grohmann and Gerhard Maas
Institute for Organic Chemistry I, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany
Received 20 August 2007; revised 20 September 2007; accepted 20 September 2007
Available online 26 September 2007
Abstract—The intramolecular carbenoid C–H insertion of 2-diazoacetoacetamides, leading to g- and/or b-lactams, is catalyzed effectively
by dinuclear Ru(I,I) complexes of the type [Ru2(m-L1)2(CO)4L22], where L1 is a bidentate bridging acetate, calix[4]arenedicarboxylate,
saccharinate or 6-chloropyridin-2-olate ligand. By comparison with rhodium catalysts, namely dirhodium tetraacetate and dirhodium
calix[4]arenedicarboxylate complexes, product yields are similarly high and the regioselectivity of the insertion reaction is the same. Surpris-
ingly, even the ruthenium(0) cluster Ru3(CO)12 was found to be an effective catalyst for carbenoid C–H insertion of 2-diazoacetoacetamides
and also of some diazoacetamides. In terms of diastereoselectivity, trans-isomers of b- and g-lactams are obtained. However, the b-lactam
obtained from diazomalonic ester amide 2 yields the cis-isomer stereoselectively, which slowly rearranges to the trans-isomer.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
effectively catalyze intramolecular carbenoid C–H insertion
reactions as well. Thus, Che et al. have identified ruthenium
porphyrins as effective catalysts for this reaction type,
including the formation of b-lactams from the anion of 2-
(tosylhydrazono)acetoacetamides.11 Furthermore, they have
reported that [RuCl2(p-cymene)]2 effectively catalyzes the
formation of lactams from diazomalonic ester amides and
2-diazo-3-oxocarboxamides.12
Transition-metal catalyzed intramolecular carbenoid C–H
insertion of appropriate a-diazocarbonyl compounds is a
modern tool for the convenient construction of carbo- and
heterocyclic compounds. The versatility of this approach has
been documented in several reviews.1–5 Dinuclear Rh(II,II)
complexessuchas Rh2(OAc)4, other dirhodium tetracarboxy-
lates and structurally similar dirhodium tetraamidates are
the current catalysts of choice for these transformations. A
notable application of the rhodium-mediated carbenoid
intramolecular C–H insertion strategy is the conversion of
a variety of a-diazoacetamides, 2-diazoacetoacetamides,
diazomalonic ester amides, a-diazo-a-(phenylsulfonyl)acet-
amides, and a-diazo-a-(dialkoxyphosphoryl)acetamides
into b- and g-lactams.6 The influence of different factors,
such as electronic properties of the catalyst, constitution of
the diazo compound, and substitution pattern at the amide
nitrogen atom, on the regio- and stereoselectivity of lactam
formation has been reviewed.7,8
We have found that dinuclear Ru(I,I) complexes of the type
[Ru2(m-L1)2(CO)4L22], where L1 is a bidentate bridging carb-
oxylate or amidate ligand and L2 represents a weakly co-
ordinating neutral axial ligand, catalyze effectively the
conversion of a-diazoacetamides into g- and/or b-lactams
by carbenoid C–H insertion.13 In particular, complexes
with bridging 6-chloropyridin-2-olate or saccharinate
ligands emerged as interesting alternatives to Rh2(OAc)4
and related rhodium catalysts. We have now turned our
attention to ruthenium-catalyzed carbenoid reactions of
2-diazoacetoacetamides and diazomalonic ester amides.
Due to the presence of a second electron-withdrawing sub-
stituent at the diazo function, the diazo carbon atom is less
nucleophilic than in a-diazoacetamides, and we wondered
whether our Ru(I,I) complexes, which appear to be some-
what less electrophilic than dirhodium tetraacetate, would
be able to induce effectively the elimination of dinitrogen
en route to the reactive ruthenium carbene intermediates.
We report now that dinuclear Ru(I,I) carboxylate and ami-
date complexes catalyze very effectively the conversion of
the mentioned 3-oxo-2-diazoacetamides into lactams; more-
over, we show for the first time that the trinuclear ruthenium
cluster Ru3(CO)12 catalyzes intramolecular carbenoid C–H
Recently, several types of ruthenium complexes are emerg-
ing as potential alternatives to the established rhodium cata-
lysts for carbenoid transformations of diazo compounds.
While most attention has been paid so far to ruthenium-
catalyzed olefin cyclopropanation reactions,9,10 some reports
have indicated lately that certain ruthenium complexes
Keywords: C–H insertion; Diazo compounds; Diazoacetoacetamides;
Lactams; Ruthenium.
* Corresponding author. Tel.: +49 (0)731 5022790; fax: +49 (0)731
5022803; e-mail: gerhard.maas@uni-ulm.de
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.053

M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
12173
insertion of diazoacetamides, 2-diazoacetoacetamides, and
diazomalonic ester amides.
(existing as a coordination polymer in the solid state) and
6–8 are suitable catalysts for the conversion of a-diazoacet-
amides into lactams by intramolecular C–H insertion.13 The
Ru(II)-p-cymene complex 9 is less suited for this particular
transformation, but was included here because it converts,
e.g., the ethylester analog of 2 into a b-lactam in excellent
yield.12 The results obtained with the ruthenium catalysts
were compared with those obtained with the benchmark
catalyst Rh2(OAc)4 (3). In addition, dirhodium bis(calix[4]-
arenedicarboxylate) 5 was included for comparison with the
diruthenium calix[4]arenecarboxylate complex 6; in both
cases, it was interesting to learn whether the calixarene
ligands would exert a steric influence on the regioselectivity
of the intramolecular carbenoid C–H insertion.
2. Results and discussion
2-Diazoacetoacetamides 1a–d were prepared, with some
modifications, along known procedures14,15 by reaction of
a sec-amine with diketene followed by a diazo transfer reac-
tion using tosyl azide.16 Diazomalonic ester amide 2 was
also obtained by diazo group transfer (Fig. 1).
The catalysts used in this work are shown in Figure 2. We
have reported before that dinuclear Ru(I,I) complexes 4
The results of the catalytic decomposition of diazoamides
1a–d and 2 are presented in Tables 1–5. In each case, the
reaction with at least one of the catalysts was worked up,
and the products were fully characterized. In all other cases,
the yields were determined after complete conversion of the
diazo compound by 1H NMR analysis of the crude reaction
mixture using naphthalene as an internal reference.
O
O
O
O
R2
N
O
N
N2 R1
N2
Ph
1
2
a: R1 = R2= Et; b: R1 = R2= Bu;
c: R1 = R2= iPr; d: R1 = CH2Ph, R2 = tBu
Thefollowing general observations were made: (a) the dinuc-
lear Ru(I,I) carboxylate and amidate complexes 4 and 6–8 are
excellent catalysts for the conversion of diazoacetoaceta-
mides into g- and/or b-lactams by carbenoid C–H insertion.
In many cases, yields above 90% are achieved, which are
practically the same as with the two rhodium catalysts 3
and 5. Only in the case of diethylamide 1a, the rhodium cat-
alysts are the better choice, because they catalyze the carbe-
noid insertion into the non-activated methyl C–H bond,
leading to g-lactam 12a, more effectively than the ruthenium
catalysts. Nevertheless, it should be noted that the ruthenium
catalysts convert 1a into lactams 11a and 12a in a much
higher combined yield (65–87%) than in the case of N,N-
diethyl-2-diazoacetamide, where the g-lactam was obtained
in 5–28% yield and no b-lactam was formed.13 (b) The reac-
tions were fast and high-yielding under the chosen standard
conditions (toluene, 70 ꢀC, 3 mol % of catalyst). When the
reactions with 1b were run in dichloromethane at 40 ꢀC,
Figure 1.
CH3
CH3
CO CO
CO CO
Ru Ru
O
O
O
O
Rh Rh
O
O
O
O
O
O
O
O
H3C
H3C
CH3
CH3
3
4
Br
CO
OC
CO
Br
OC
Pr
Pr
O
O
Ru Ru
O
O
O
Pr
O
O
O
O
O
O
Rh
Rh
Pr
O
O
O
O
Br
O
O
Br
Pr
O
Pr
Pr
O
O
Pr
Br
Br
O
Pr
O
Pr
O
Pr
O
Pr
5
6
Table 1. Catalytic decomposition of N,N-diethyl-2-diazoacetoacetamide
(1a) in toluene at 70 ꢀC
O
O
O
O
cat.,
toluene
O
O
CO
CO
Et
Et
SO2
+
N
N
O
N
O2S
Cl
CH3CN Ru
N
O
N
N2 Et
O
Ru Ru CO
N
N
O
Et
Cl
Ru NCCH3
OC
CO CO
OC Ru Ru
N
OC
O
11a
12a
1a
N
OC
CO
SO2
O
CO CO
O2S
Catalysta Time
[h]
Yieldb [%]
12a
17 (11c) 77 (68c) 4.5
Ratio of Total yield of
12a/11a lactams [%]
CO CO
11a
7
8
3
4
5
6
7
8
9
1
12
1
12
12
5
94 (79c)
66
90
18
13
20
15
17
9
48
77
48
50
70
19
2.7
5.9
2.4
3.3
4.1
2.1
OC CO
OC Ru CO
OC
68
65
87
28
Cl
Cl
Ru Ru
Cl
CO
Ru CO
CO
Cl
OC Ru
OC
12
COOC
a
b
c
Catalyst loading was 3 mol % (1 mol % for 11).
Yields were determined by 1H NMR analysis of the reaction mixture.
Isolated yield after purification by column chromatography over basic
alumina.
9
10
Figure 2. Catalysts used in this study.

12174
M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
Table 2. Catalytic decomposition of N,N-dibutyl-2-diazoacetoacetamide (1b)
O
O
O
O
O
cat.,
toluene
O
Bu
Bu
N
N
+
N
N2 Bu
Pr
Bu
Et
1b
11b
12b
Catalyst
Catalyst
loading [mol %]
Solvent
T [ꢀC]
Time [h]
Yielda [%]
12b
Ratio of
12b/11b
Total yield of
lactams [%]
11b
3
4
5
6
7
8
9
3
3
3
3
1
1
3
3
3
3
3
3
3
3
Toluene
CH2Cl2
Toluene
CH2Cl2
Toluene
CH2Cl2
Toluene
CH2Cl2
Toluene
CH2Cl2
Toluene
CH2Cl2
Toluene
CH2Cl2
70
40
70
40
70
40
70
40
70
40
70
40
70
40
1
1
12
72
1
1
1
1
1
1
1
1
8
144
3
2
5
3
91
90
83
92
30.3
45.0
16.6
30.7
6.8
18.8
20.0
47.0
44.5
41.5
98.0
98.0
11.0
26.5
94
92
88
95
12 (7b)
81(70b)
75
80
93 (77b)
79
84
4
4
2
2
2
1
1
4
2
94
89
83
98
98
44
53
96
91
85
99
99
48
55
Yields were determined by 1H NMR analysis of the reaction mixture.
Isolated yield after purification by column chromatography over basic alumina.
a
b
however, almost the same reaction time and yields were
generally observed (Table 2). Furthermore, the use of only
1 mol % of catalyst somewhat enhances the reaction time,
but does not affect the yields significantly (Table 5). (c) By
comparison with catalysts 4 and 6–8, [RuCl2(p-cymene)]2
(9) is much less suited to catalyze carbenoid C–H insertion
of N,N-dialkyl-diazoacetoacetamides 1a–c; high catalytic ef-
fectiveness is only observed when b-lactam formation by in-
sertion into the activated N-benzyl C–H bond can occur (1d,
2), in agreement with reported examples.12
a discussion of results obtained with Rh2(OAc)4 as catalyst,
see Refs. 7,14,15,17), but in the case of diethylamide 1a,
a lower preference for the g-lactam in the ruthenium-cata-
lyzed reactions can be noted. Whether this is related to elec-
tronic17 or steric properties of the metal fragment in the
intermediate metal–carbene complexes is not clear. It was
also interesting to see whether rhodium complex 5, bearing
two dibromocalix[4]arenedicarboxylate ligands, would give
rise to a particular regioselectivity. As Tables 1 and 2 show,
the effect appears to be contradictory, giving the highest g/
b ratio in the case of 1a, but the lowest one in the case of
1b (reaction in toluene). However, considering the absolute
In terms of regioselectivity (formation of b- vs g-lactam),
the ruthenium catalysts studied here show the same general
trends as the two rhodium carboxylate catalysts (for
Table 4. Catalytic decomposition of N-benzyl-N-tert-butyl-2-diazoaceto-
acetamide (1d) in toluene at 70 ꢀC
O
Table 3. Catalytic decomposition of N,N-diisopropyl-2-diazoacetoacet-
amide (1c) in toluene at 70 ꢀC
O
O
cat.,
toluene
O
tBu
N
O
N
N2
O
O
cat.,
toluene
tBu
O
N
N
1d
N2
11d
Catalysta
Time [h]
Yieldb of
11d [%]
1c
11c
Catalysta
Time
[h]
Yieldb of
11c [%]
3
4
5
6
7
8
9
1
1
1
1
1
1
1
93 (93c,d
81
99
)
3
4
5
6
7
8
9
1
5
1
1
5
1
8
96 (91c,d
)
87
96
90
84
78
46
90
93e
90e
91
a
Catalyst loading was 3 mol % (1 mol % for 5).
Yields were determined by 1H NMR analysis of the reaction mixture.
Isolated yield after purification by column chromatography over basic
alumina.
b
c
a
Catalyst loading was 3 mol % (1 mol % for 5).
Yields were determined by 1H NMR analysis of the reaction mixture.
Isolated yield after purification by column chromatography over basic
alumina.
b
c
d
e
A
98% yield has been reported (benzene, 80 ꢀC, 1 mol % of
Rh2(OAc)4).14
Cis/trans mixture, see text.
A yield of 89% has been reported (benzene, rt, 1 mol % of Rh2(OAc)4).14
d

M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
12175
Table 5. Catalytic decomposition of N-benzyl-N-tert-butyl-2-methoxy-
carbonyl-2-diazoacetamide (2) in toluene at 70 ꢀC
In contrast to the acetyl-substituted diazocarboxamides 1,
the methoxycarbonyl-substituted analog 2 yields cis/trans-
mixtures of b-lactam 13 in ratios which are strongly catalyst-
dependent (Table 5). With catalyst 9, the cis-isomer is
formed almost exclusively, similar to the corresponding
ethoxycarbonyl analog.12 With all other catalysts, the
amount of trans-13 increases markedly under identical reac-
tion conditions, the highest yield being 39 and 27% for the
two calixarenedicarboxylate complexes 5 and 6, respec-
tively. An unusual dependence of the cis/trans ratio on the
catalyst concentration was observed for some of the ruthe-
nium catalysts: a reduction of the catalyst concentration
from 3 to 1 (and eventually 0.1) mol % caused a strong de-
crease of the cis/trans ratio for the ruthenium acetate (4)
and saccharinate (7) catalysts, but an increase of that ratio
for ruthenium-calixarenedicarboxylate catalyst 6. The ob-
served diastereoselectivities are likely to represent the orig-
inal results of the respective reaction, because control
experiments showed that the cis/trans ratio was not a function
of the reaction time (which was longer with lower catalyst
concentrations), in contrast to the decomposition of 11d by
ruthenium saccharinate 7, as described above. The reason
for this correlation between catalyst concentration and
diastereoselectivity is not known so far.
O
O
O
O
cat.,
toluene
O
O
O
O
tBu
+
O
N
N
N
N2
tBu
tBu
2
cis-13
trans-13
Catalyst Catalyst Time
loading [h]
[mol %]
Yielda [%]
Ratio of Total
cis/trans yield [%]
cis-13 trans-13
3
4
3
1
3
1
1
3
1
3
1
0.1
3
1
3
1
2
8
14
1
1
86
86
78
22
58
72
11
12
14
70
39
27
13
8
30
35
18
19
4
7.8
7.2
5.6
0.3
1.5
2.7
6.5
10.8
2.0
1.2
4.3
4.8
23.2
23.8
97 (96b)
98
92
92
97
99
97
94
91
77
96
96
97
5
6
1.5 84
86
1.5 61
7
1
168
1
1.5 77
1
1
42
78
8
9
93
95
1
4
99
Yields were determined by 1H NMR analysis of the reaction mixture.
Isolated yield after purification by column chromatography over basic
alumina.
a
b
The readily available19 complex Ru3(CO)12 has largely been
neglected as a catalyst for diazo decomposition reactions so
far. Doyle et al.20 have reported that this complex catalyzes
two carbenoid reactions of ethyl diazoacetate, namely cyclo-
propanation of the electron-rich double bond of butyl vinyl
ether in 65% yield, and S-ylide chemistry with allyl methyl
sulfide in 96% yield. We were pleased to find that Ru3(CO)12
also catalyzes the lactam formation from 2-diazo-3-oxocarb-
oxamides 1a–d and 2 (Table 6). Although the reactions pro-
ceed significantly slower in most cases, yields are similar or
not much lower than with the other ruthenium carbonyl cat-
alysts used in this study. The regio- and stereoselectivity of
the carbenoid cyclization reaction places this catalyst in
the neighborhood of 4 and 7.
yields of the two lactams in both cases, the deviations from
reactions using the other catalysts are not large.
b-Lactams 11a,b,d were obtained with complete trans-
3
selectivity (1H NMR: JH,H¼2.0–2.3 Hz for ring protons)
in most cases, which confirms results already reported.14,17
However, we observed that treatment of 1d with the ruthe-
nium saccharinate complex 7 produced a cis/trans mixture
of 11d, the ratio of which varied in different runs. Control
experiments showed an approximate 1:1 ratio immediately
after complete conversion of the diazo compound (ca. 1 h),
whereas an almost complete cis/trans isomerization had
taken place after the reaction mixture had been kept at
70 ꢀC for 12 h. Similar observations were made when cata-
lyst 8 was used. It has been reported that related b-lactams
bearing phosphoryl groups6k undergo this epimerization in
the presence of basic alumina, and for 3-methoxycarbonyl-
azetidinones, epimerization ‘under the reaction conditions’
has been suggested.18
Encouraged by these results, we investigated also the
Ru3(CO)12-catalyzed decomposition of 2-diazoacetamides
14a–e (Table 7). Again, the reactions proceeded more slowly
than with the other ruthenium carbonyl catalysts. The
product distribution is similar to that obtained with catalysts
4, 6, 8, and 9,13 but the total yields of lactams are generally
lower.
Table 6. Decomposition of 2-diazo-3-oxocarboxamides 1a–d and 2 with Ru3(CO)12 (10)
Diazoamide
Catalyst
loading
[mol %]
Solvent
T [ꢀC]
Time [h]
Products (yield,a %)
b-Lactam
g-Lactam
1a
1b
3
3
3
3
3
3
Toluene
Toluene
CH2Cl2
Toluene
Toluene
Toluene
70
70
40
70
70
70
12
12
30
5
1
4
11a (16)
11b (4)
11b (2)
11c (75)
11d (84)
cis-13 (77),
trans-13 (9)
cis-13 (80),
trans-13 (7)
12a (58)
12b (73)
12b (93)
1c
1d
2
1
Toluene
70
6
Yields were determined by 1H NMR analysis of the reaction mixture.
a

12176
M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
Table 7. Ru3(CO)12-catalyzed decomposition of 2-diazoacetamides 14a–ea
basic, activity I, 0.063–0.2 mm, Merck) with distilled cyclo-
hexane and ethyl acetate as eluents. NMR spectra were
recorded at 400.1 MHz (1H) or 100.6 MHz (13C) in CDCl3
solution with tetramethylsilane (TMS) as the internal stan-
dard (mc¼centered multiplet). Infrared spectra were
recorded on a Bruker Vector 22 spectrometer. Mass spectra
were obtained on a Finnigan MAT SSQ 7000 spectrometer
in the CI mode. Elemental analyses were carried out with
an Elementar Vario EL elemental analyzer.
Diazoacetamide
Products (yield,b %)
O
O
O
H
R2
R2
N
N
N
R1
R2
N2
R1'
R1
14a: R1 = Me, R2 = Et
16a (24%) (R1' = H)
15a (0%)
15b (0%)
14b: R1 = Pr, R2 = Bu
16b (63%) (R1' = Et)
O
N
O
O
N
H
4.2. Materials
N
N2
Diazo compounds 1a,21 1c,14 and 1d14 have been prepared
before, but details of the synthesis and/or spectroscopic
data have not been communicated. The catalysts [Ru2-
(m-OAc)2(CO)4]n (4),22 5,23 6,24 7,25 and 826 were prepared
as described in the literature. The activity of catalyst 8
decreases on storing; therefore, it was re-activated prior to
use by dissolution in dry acetonitrile, warming at 60 ꢀC for
10 min, and evaporation of the solvent in a flow of argon.
15c (49%)
16c (22%)
O
14c
O
H
O
N
N
N
Ph
Ph
Ph
N2
Ph
Ph
15d (2%)
14d
17 (45%)
O
O
4.3. Synthesis of diazoacetoacetamides 1; general
procedure
N
N
Ph
O
2,2,6-Trimethyl-1,3-dioxen-4-one (50 mmol) and a sec-
amine (50 mmol) were dissolved in m-xylene (10 mL).
The mixture was heated at 120 ꢀC. After the elimination of
acetone had ceased, the mixture was kept at 150 ꢀC for
30 min. Then, m-xylene was evaporated at 120 ꢀC/80 mbar.
The remaining crude acetoacetamide was used for the
following diazo transfer reaction. Per 10 mmol of aceto-
acetamide, 20 mL of acetonitrile was added, followed
by triethylamine (2 equiv) and p-toluenesulfonyl azide
(1.1 equiv). The reaction mixture was stirred for 12 h before
the solvent was evaporated. The crude product was dissolved
in dichloromethane and pentane was added to precipitate
most of the by-product (p-tosylamide). The solution was
concentrated and the residue was subjected to column
chromatography on silica gel.
15e (1%)
18 (45%)
H
N
O
N
O
N2
Ph
N
Ph
Ph
14e
15f (9%)
16e (17%)
a
Conditions: dichloromethane, 40 ꢀC, 12 h (14a: 24 h), 3 mol % of cata-
lyst; the reactions were carried out by analogy to the procedure given in
Section 4.4.
Yields were determined by 1H NMR analysis of the reaction mixture; see
Ref. 13 for characterization of the products.
b
3. Conclusion
We have found that diruthenium(I,I)-tetracarbonyl com-
plexes bearing chelating carboxylate, saccharinate, and
6-chloropyridin-2-olate ligands are excellent catalysts for the
carbenoidC–H insertion by whichN,N-disubstituted 2-diazo-
acetoacetamides and malonic ester amides are converted into
g-and/orb-lactams.Withrespecttoyieldsandregioselectivity,
large differences between the various catalysts were not
observed. For the first time, the trinuclear ruthenium(0) clus-
ter Ru3(CO)12, which is a practical synthetic precursor for
complexes 4 and 6–8, was identified as a catalyst for intra-
molecular carbenoid C–H insertion; although it reacts more
sluggishly than the latter catalysts, the lactam yields are
(almost) the same and regio- and stereoselectivity are similar.
Considering the much higher prize of rhodium compared to
ruthenium, some of the ruthenium catalysts are in general at-
tractive alternatives to the established rhodium catalysts for
the carbenoid transformations described in this study.
4.3.1. N,N-Diethyl-2-diazo-3-oxobutanamide (1a). After
column chromatography (chloroform as eluent), a yellow
oil was obtained; yield: 74%. 1H NMR: d 1.21 (t, 6H,
3
3J¼7.1 Hz, CH3), 2.34 (s, 2H, COCH3), 3.38 (q, 4H, J¼
7.2 Hz, CH2). 13C NMR: d 13.1 (CH3), 27.3 (COCH3),
41.9 (CH2) 72.4 (CN2), 160.4 (CO-amide), 190.1 (CH3CO).
IR (neat): n 2104 (s), 1653 (s), 1457 (m), 1361 (m) cmꢁ1
.
MS (100 eV): m/z (%) 184 (21), 156 (100). Anal. Calcd
for C8H13N3O2 (183.21): C 52.45, H 7.15, N 22.94. Found:
C 52.26, H 7.21, N 23.01.
4.3.2. N,N-Dibutyl-2-diazo-3-oxobutanamide (1b). Col-
umn chromatography with cyclohexane/ethyl acetate (2:1)
as eluent afforded a yellow oil; yield: 81%. 1H NMR:
3
d 0.94 (t, 6H, J¼7.3 Hz, CH3), 1.33 (m, 4H, CH3CH2),
1.57 (m, 4H, NCH2CH2), 2.33 (s, 3H, COCH3), 3.32 (q,
4H, 3J¼7.6 Hz, CH2). 13C NMR: d 13.6 (CH3), 19.9
(CH3CH2), 27.1 (COCH3), 29.8 (NCH2CH2), 47.2
(NCH2), 72.3 (CN2), 160.6 (CO-amide), 189.9 (CH3CO).
IR (neat): n 2099 (s), 1635 (s), 1457 (m), 1422 (m), 1361
(m) cmꢁ1. MS (100 eV): m/z (%) 240 (37), 212 (100).
Anal. Calcd for C12H21N3O2 (239.16): C 60.23, H 8.84, N
17.56. Found: C 60.22, H 8.77, N 17.24.
4. Experimental
4.1. General methods
Column chromatography was performed on silica gel 60
(0.063–0.2 mm, Merck) or alumina (aluminum oxide 90

M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
12177
4.3.3. N,N-Diisopropyl-2-diazo-3-oxobutanamide (1c).
Column chromatography with cyclohexane/ethyl acetate
(2:1) as eluent afforded a yellow oil; yield: 62%. 1H NMR:
details). The solvent was evaporated, and the residue was
separated by column chromatography over basic alumina
(85–110 g). Elution with cyclohexane/ethyl acetate mixtures
furnished the b-lactam. When g-lactam was also formed, it
was isolated by subsequent elution with methanol and
isolated either by a second column chromatography (cyclo-
hexane/ethyl acetate, 3:1) or by vacuum distillation in a
Kugelrohr apparatus.
3
d 1.35 (d, 12H, J¼6.6 Hz, CH3), 2.31 (s, 3H, COCH3),
3
3.68 (sept, 2H, J¼6.6 Hz, CH). 13C NMR: d 20.7 (CH3),
27.0 (COCH3), 49.2 (CH), 72.8 (CN2), 159.2 (CO-amide),
189.9 (CH3CO). IR (neat): n 2098 (s), 1639 (s), 1434
(m), 1362 (m), 1331 (m) cmꢁ1. MS (100 eV): m/z (%)
212 (66), 184 (34). Anal. Calcd for C10H17N3O2 (211.13):
C 56.85, H 8.11, N 19.89. Found: C 56.69, H 8.02,
N 19.78.
For experiments without product isolation, the solvent was
evaporated at 60 ꢀC/60 mbar, and the crude product mixture
was analyzed by 1H NMR spectroscopy, whereby the prod-
uct yields were determined by integration using naphthalene
as an internal standard.
4.3.4. N-Benzyl-N-tert-butyl-2-diazo-3-oxobutanamide
(1d). Column chromatography with cyclohexane/ethyl ace-
tate (2:1) as eluent gave a yellow oil; yield: 91%. 1H
NMR: d 1.43 (s, 9H, CH3) 2.23 (s, 3H, COCH3), 4.59 (s,
2H, CH2), 7.18–7.32 (m, 10H, HPh). 13C NMR: d 27.0
(COCH3), 28.6 (CH3), 51.0 (CH2), 58.9 (Cq), 75.8 (CN2),
126.2, 127.5, 128.8, 138.9 (all CPh), 163.2 (CO-amide),
189.5 (CH3CO). IR (neat): 2102 (s), 1652 (s), 1453 (m),
1385 (m), 1362 (s) cmꢁ1. MS (100 eV): m/z (%) 274
(22), 246 (9), 218 (100). Anal. Calcd for C15H19N3O2
(273.15): C 65.91, H 7.01, N 15.37. Found: C 65.90, H
7.02, N 15.30.
4.4.1. trans-3-Acetyl-1-ethyl-4-methylazetidin-2-one
1
(11a). Colorless oil, bp 110 ꢀC/0.06 mbar (Kugelrohr). H
NMR: d 1.17 (t, 3H, 3J¼7.3 Hz, CH3), 1.37 (d, 3H,
3J¼6.3 Hz, 4-CH3), 2.30 (s, 3H, COCH3), 3.07 (mc, 1H,
3
3J¼7.1 Hz, NCH), 3.36 (mc, 1H, J¼7.2 Hz, NCH), 3.72
3
3
(d, 1H, J¼2.0 Hz, 3-H), 4.07 (dq, 1H, J¼2.1 and 6.2 Hz,
4-H). 13C NMR: d 13.1 (CH3 (Et)), 17.6 (4-CH3) 29.7
(COCH3), 35.1 (NCH2), 48.4 (C-4), 69.3 (C-3), 162.2
(CO-ring), 200.5 (CO). IR (neat): n 1752 (s), 1711 (s),
1448 (m), 1382 (m) cmꢁ1. MS (100 eV): m/z (%) 156 (9).
Anal. Calcd for C8H13NO2 (155.19): C 61.91, H 8.44, N
9.03. Found C 61.90, H 8.48, N 9.14. This compound was
prepared before by irradiation of 1a.21
4.3.5. N-Benzyl-N-tert-butyl-2-methoxycarbonyl-2-di-
azoacetamide (2). A solution of N-benzyl-N-tert-butyl-
amine (10.7 mL, 59 mmol) in dichloromethane was added
to a solution of malonic acid methylester chloride (6 mL,
56.2 mmol) in dichloromethane (30 mL). After 10 min 2 N
aq NaOH (6 mL) was added and the solution was stirred
for 4 h. The reaction mixture was extracted four times with
a satd aq NH4Cl solution. After drying (Na2SO4) and evap-
oration of the solvent, the crude malonic ester amide was
used without further purification. The amide (9.07 g,
34.4 mmol) was dissolved in acetonitrile (90 mL), triethyl-
amine (9.6 mL, 68.9 mmol) and p-toluenesulfonyl azide
(7.46 g, 37.8 mmol) were added, and the mixture was stirred
for 36 h at 20 ꢀC. The solvent was evaporated, the crude
product was dissolved in dichloromethane, and pentane
was added in order to precipitate most of the by-product (to-
sylamide). After column chromatography over silica gel
(220 g) with petroleum ether/ethyl acetate (9:1) as eluent,
a yellow solid was obtained; yield: 4.46 g (45%), mp:
4.4.2. 3-Acetyl-1-ethylpyrrolidin-2-one (12a). Colorless
1
oil, bp 140 ꢀC/0.11 mbar (Kugelrohr). H NMR: d 1.11 (t,
3
3H, J¼7.2 Hz, CH2CH3), 1.99–2.08 (m, 1H, 4-H), 2.42
3
(s, 3H, CH3), 2.49–2.58 (m, 1H, 4-H2), 3.32 (q, 2H, J¼
7.3 Hz, CH2CH3), 3.32 (mc, 1H, 5-H), 3.42 (dt, 1H,
3
3J¼9.1 and 5.6 Hz, 5-H) 3.58 (dd, 1H, J¼9.3 and 6.1 Hz,
3-H). 13C NMR: d 12.3 (CH2CH3), 19.5 (C-4), 29.9
(COCH3), 37.5 (NCH2), 44.7 (C-5), 55.9 (C-3), 169.2
(CO-ring), 203.8 (CO). IR (neat): n 1717 (s), 1683 (s),
1459 (m), 1380 (m) cmꢁ1. MS (100 eV): m/z (%) 156
(100). Anal. Calcd for C8H13NO2 (155.19): C 61.91, H
8.44, N 9.03. Found: C 61.86, H 8.44, N 9.02.
4.4.3. trans-3-Acetyl-1-butyl-4-propylazetidin-2-one
1
(11b). Colorless oil, bp 110 ꢀC/0.09 mbar (Kugelrohr). H
1
80.2–81.9 ꢀC. H NMR: d 1.39 (s, 9H, C(CH3)3), 3.77 (s,
NMR: d 0.92 (t, 3H, 3J¼7.3 Hz, CH3), 0.96 (t, 3H,
3J¼7.2 Hz, CH3), 1.26–1.56 (m, 7H, CH2), 1.75–1.85 (m,
1H, CH2), 2.30 (s, 3H, COCH3), 2.99 (mc, 1H, NCH), 3.34
3H, OCH3), 4.62 (s, 2H, CH2), 7.19–7.34 (m, 5H, HPh).
13C NMR: d 28.7 (CH3), 51.4 (CH2), 52.1 (OCH3), 58.9
(Cq), 68.0 (br, C]N2), 126.7, 127.3, 128.6, 139.5 (CPh),
162.9 (CO), 163.1 (CO). IR (neat): n 2128 (s), 1714 (s),
1612 (s), 1435 (br, m), 1363 (m) cmꢁ1. MS (100 eV): m/z
(%) 290 (100), 262 (18), 234 (93). Anal. Calcd for
C15H19N3O3 (289.33): C 62.27, H 6.62, N 14.52. Found: C
62.20, H 6.59, N 14.46.
3
(mc, NCH), 3.74 (d, 1H, J¼2.0 Hz, 3-H), 3.92–3.96 (m,
1H, 4-H). 13C NMR: d 13.5 (CH3), 13.9 (CH3), 18.9
(CH2), 20.1 (CH2), 29.7 (COCH3), 30.0 (CH2), 34.0 (4-
CH2), 40.4 (NCH2), 53.0 (C-4), 67.8 (C-3), 162.8 (CO-
ring), 200.7 (CO). IR (neat): n 1753 (s), 1712 (s), 1409
(m), 1360 (m) cmꢁ1. MS (100 eV): m/z (%) 212 (5), 113
(100). Anal. Calcd for C12H21NO2 (211.16): C 68.21, H
10.02, N 6.63. Found C 68.36, H 10.01, N 6.60.
4.4. Catalytic decomposition of diazocarboxamides
1a–d and 2; general procedure
4.4.4. trans-3-Acetyl-1-butyl-4-ethylpyrrolidin-2-one
1
The catalyst (1 or 3 mol %) was added to dry toluene
(25 mL). At 70 ꢀC a solution of diazocarboxamides 1a–
d or 2 (2–6 mmol) in dry toluene (4 mL) was added via a sy-
ringe pump during a period of 1 h. After complete addition,
the mixture was kept stirring at 70 ꢀC until the diazo com-
pound had been consumed (IR control, see Tables 1–6 for
(12b). Colorless oil, bp 155 ꢀC/0.17 mbar (Kugelrohr). H
3
NMR: d 0.90 (t, 3H, J¼7.6 Hz, CH2CH3), 0.92 (t, 3H,
3J¼7.6 Hz, (CH2)3CH3), 1.25–1.34 (m, 2H, CH2), 1.40–
1.52 (m, 4H, 2 CH2), 2.41 (s, 3H, COCH3), 2.69–2.78 (mc,
1H, 4-H), 2.95 (dd, 1H, j Jj¼9.6 Hz, J¼6.1 Hz, 5-HA),
2
3
3
3
3.25 (t, 2H, J¼7.2 Hz, NCH2), 3.26 (d, 1H, J¼7.1 Hz,

12178
M. Grohmann, G. Maas / Tetrahedron 63 (2007) 12172–12178
2
3
3-H), 3.50 (dd, 1H, j Jj¼9.6 Hz, J¼8.3 Hz, 5-HB). 13C
NMR: d 11.4 (CH3), 13.6 (CH3), 19.8 (CH2), 27.0 (4-CH2),
29.1 (CH2), 30.2 (COCH3), 34.7 (C-4), 42.5 (NCH2), 50.8
(C-5), 62.1 (C-3), 169.3 (CO-ring), 203.9 (CO). IR (neat):
n 1717 (s), 1685 (s), 1459 (m), 1356 (m) cmꢁ1. MS
(100 eV): m/z (%) 212 (100). Anal. Calcd for C12H21NO2
(211.16): C 68.21, H 10.02, N 6.63. Found: C 67.91, H
9.98, N 6.77.
4. Pfaltz, A. Comprehensive Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York,
NY, 1999; Vol. 2, pp 513–538.
5. Davies, H. M. L.; Beckwith, R. E. Chem. Rev. 2003, 103, 2861–
2903.
6. Recent publications on rhodium-catalyzed carbenoid syntheses
of b- and g-lactams: (a) Candeias, N. R.; Gois, P. M. P.; Afonso,
C. A. M. J. Org. Chem. 2006, 71, 5489–5497; (b) Wee,
A. G. H.; Duncan, S. C.; Fan, G. Tetrahedron: Asymmetry
2006, 17, 297–307; (c) Chen, Z.; Chen, Z.; Jiang, Y.; Hu, W.
Tetrahedron 2005, 61, 1579–1586; (d) Liu, W.-J.;
Chen, Z.-L.; Chen, Z.-Y.; Hu, W.-H. Tetrahedron: Asymmetry
2005, 16, 1693–1698; (e) Gois, P. M. P.; Candeias, N. R.;
Afonso, C. A. M. J. Mol. Catal. A 2005, 227, 17–24; (f)
Muroni, D.; Saba, A. ARKIVOC 2005, xiii, 1–7; (g) Flanigan,
D. L.; Yoon, C. H.; Jung, K. W. Tetrahedron Lett. 2005, 46,
143–146; (h) Chen, Z.-L.; Chen, Z.-Y.; Jiang, Y.-H.; Hu, W.
Synthesis 2004, 1763–1764; (i) Doyle, M. P.; Hu, W.; Wee,
A. G. H.; Wang, Z.; Duncan, S. C. Org. Lett. 2003, 5, 407–
410; (j) Yoon, C. H.; Niagle, A.; Chen, C.; Gandhi, D.; Jung,
K. W. Org. Lett. 2003, 5, 2259–2262; (k) Gois, P. M. P.;
Afonso, C. A. M. Eur. J. Org. Chem. 2003, 3798–3810.
7. Gois, P. M. P.; Afonso, C. A. M. Eur. J. Org. Chem. 2004, 3773–
3788.
4.4.5. 3-Acetyl-1-isopropyl-4,4-dimethylazetidin-2-one
1
(11c). Colorless oil, bp 120 ꢀC/0.09 mbar (Kugelrohr). H
3
NMR: d 1.33 (d, 6H, J¼6.8 Hz, CH3), 1.39 (s, 3H, CH3),
1.49 (s, 3H, CH3), 2.29 (s, 3H, COCH3), 3.52 (sept, 1H,
3J¼6.8 Hz, NCH), 3.65 (s, 1H, 3-H). 13C NMR: d 21.7 and
21.8 (CH(CH3)2), 22.8 (4-CH3), 27.3 (4-CH3), 30.9
(COCH3), 44.4 (NCH), 59.9 (C-4), 69.8 (C-3), 162.3 (CO-
ring), 202.1 (CO). IR (neat): n 1746 (s), 1711 (s), 1412
(m), 1373 (m) cmꢁ1. MS (100 eV): m/z (%) 184 (17).
Anal. Calcd for C10H17NO2 (183.25): C 65.54, H 9.35, N
7.64. Found: C 65.29, H 9.49, N 7.63.
4.4.6. 3-Acetyl-1-tert-butyl-4-phenylazetidin-2-one (11d);
trans-11d. White solid, mp 84.9–89.7 ꢀC. NMR (1H, 13C)
and IR data agree with reported14 values. Anal. Calcd for
C15H19NO2 (245.32): C 73.44, H 7.81, N 5.71. Found: C
73.31, H 7.82, N 5.71. cis-11d (in admixture with trans-
isomer): dH 4.18 and 4.86 (AB system, 3J¼6.0 Hz).
8. Merlic, C. A.; Zechman, A. L. Synthesis 2003, 1137–1156.
9. Maas, G. Chem. Soc. Rev. 2004, 33, 183–190.
10. Nishiyama, H. Ruthenium in Organic Synthesis; Murahashi,
S.-I., Ed.; Wiley-VCH: Weinheim, 2004; Chapter 7.
11. (a) Zheng, S.-L.; Yu, W.-Y.; Che, C.-M. Org. Lett. 2002, 4,
889–892; (b) Cheung, W.-H.; Zheng, S.-L.; Yu, W.-Y.; Zhou,
G.-C.; Che, C.-M. Org. Lett. 2003, 5, 2535–2538.
12. Choi, M. K.-W.; Yu, W. Y.; Che, C.-M. Org. Lett. 2005, 7,
1081–1084.
€
13. Grohmann, M.; Buck, S.; Schaffler, L.; Maas, G. Adv. Synth.
Catal. 2006, 348, 2203–2211.
14. Doyle, M. P.; Shanklin, M. S.; Oon, S.-M.; Pho, H. Q.; van der
Heide, F. J. Org. Chem. 1988, 53, 3384–3386.
15. Doyle, M. P.; Pieters, R. J.; Taunton, J.; Pho, H. Y.; Padwa, A.;
Hertzog, D. L.; Precedo, L. J. Org. Chem. 1991, 56, 820–829.
16. Regitz, M.; Hocker, J.; Liedhegener, A. Org. Prep. Proced.
1969, 1, 99–104.
17. Padwa, A.; Austin, D. J.; Price, A. T.; Semones, M. A.; Doyle,
M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A. J. Am.
Chem. Soc. 1993, 115, 8669–8680.
4.4.7. cis- and trans-N-tert-Butyl-3-methoxycarbonyl-4-
phenylazetidin-2-one (13). White solid, obtained as a dia-
stereomeric mixture. 1H NMR, cis-13: d 1.31 (s, 9H,
3
C(CH3)3), 3.72 (s, 3H, OCH3), 4.23 (d, 1H, J¼6.3 Hz,
4-H), 4.91 (d, 1H, 3J¼6.3 Hz, 3-H), 7.29–7.39 (m, 5H,
HPh); trans-13: d 1.27 (s, 9H, C(CH3)3), 3.71 (d, 1H,
3J¼2.3 Hz, 4-H), 3.78 (s, 3H, OCH3), 4.86 (d, 1H,
3J¼2.3 Hz, 3-H), 7.29–7.39 (m, 5H, HPh). 13C NMR, cis-
13: d 28.0 (C(CH3)3), 51.8 (OCH3), 55.2 (C(CH3)3), 56.6
(C-3), 59.9 (C-4), 127.0, 128.4, 128.7, 136.6 (all CPh),
162.8 (CO), 166.4 (CO); trans-13: d 28.0 (C(CH3)3), 52.6
(OCH3), 55.2 (C(CH3)3) 56.5 (C-3), 62.3 (C-4), 126.6,
128.4, 128.9, 139.1 (all CPh), 162.0 (CO), 166.4 (CO). IR
(neat): n 1762 (s), 1735 (s) cmꢁ1. MS (100 eV): m/z (%)
262 (31), 163 (100). Anal. Calcd for C8H15NO (261.32): C
68.94, H 7.33, N 5.36. Found: C 68.87, H 7.38, N 5.32.
18. Wee, A. G. H.; Duncan, S. C. Tetrahedron Lett. 2002, 43, 6173–
6176.
19. (a) Mantovani, A.; Cenini, S. Inorg. Synth. 1976, 16, 47–48; (b)
Eady, C. R.; Jackson, P. F.; Johnson, B. F. G.; Lewis, J.;
Malatesta, M. C.; McPartlin, M.; Nelson, W. J. H. J. Chem.
Soc., Dalton Trans. 1980, 383–392.
20. Tamblyn, W. H.; Hoffmann, S. R.; Doyle, M. P. J. Organomet.
Chem. 1981, 216, C64–C68.
Acknowledgements
The support and sponsorship contributed by COST
Action D24 ‘Sustainable Chemical Processes: Stereo-
selective Transition-Metal Catalyzed Reactions’ is kindly
acknowledged.
21. Tomioka, H.; Kondo, M.; Izawa, Y. J. Org. Chem. 1981, 46,
1090–1094.
References and notes
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