Ruthenium- and rhodium-catalyzed carbenoid reactions of diazoesters in hexaalkylguanidinium-based ionic liquids

Article abstract of DOI:10.1515/znb-2012-0408

Hexaalkylguanidinium-based room-temperature ionic liquids were investigated as solvents for the cyclopropanation of styrene with diazoacetates catalyzed by Rh₂(OAc)₄ or [Ru₂(μ-OAc) ₂(CO)₄]_n. While the yields of the formed cyclopropanes are much lower compared to the reactions performed in dichloromethane, the diastereomeric ratio is not significantly affected by the change of the reaction medium. Immobilization of the catalysts is only partially successful. In contrast to this intermolecular reaction, the Ru-catalyzed formation of a β-lactam by an intramolecular carbenoid C-H insertion of an α-methoxycarbonyl-α-diazoacetamide occurs in high yield, similar to the Rh₂(OAc)₄-catalyzed reaction. The cis → trans isomerization of the resulting 1-tert-butyl-3-methoxycarbonyl-4-phenyl-azetidin- 2-one is accelerated in the ionic liquid N,N-dibutyl-N',N'-diethyl-N'',N''- dihexylguanidin-ium triflate.

Full text of DOI:10.1515/znb-2012-0408

Ruthenium- and Rhodium-catalyzed Carbenoid Reactions of Diazoesters
in Hexaalkylguanidinium-based Ionic Liquids
Torsten Large, Tobias Mu¨ller, Helene Kunkel, Stefan Buck, and Gerhard Maas
Institute of Organic Chemistry I, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Reprint requests to Prof. Dr. Gerhard Maas. Fax: +49 731 5022803.
E-mail: gerhard.maas@uni-ulm.de
Z. Naturforsch. 2012, 67b, 347 – 353; received February 3, 2012
Dedicated to Professor Ernst Anders on the occasion of his 70th birthday
Hexaalkylguanidinium-based room-temperature ionic liquids were investigated as solvents for the
cyclopropanation of styrene with diazoacetates catalyzed by Rh2(OAc)4 or [Ru2(µ-OAc)2(CO)4]n.
While the yields of the formed cyclopropanes are much lower compared to the reactions performed
in dichloromethane, the diastereomeric ratio is not significantly affected by the change of the reaction
medium. Immobilization of the catalysts is only partially successful. In contrast to this intermolecular
reaction, the Ru-catalyzed formation of a β-lactam by an intramolecular carbenoid C–H insertion of
an α-methoxycarbonyl-α-diazoacetamide occurs in high yield, similar to the Rh2(OAc)4-catalyzed
reaction. The cis → trans isomerization of the resulting 1-tert-butyl-3-methoxycarbonyl-4-phenyl-
azetidin-2-one is accelerated in the ionic liquid N,N-dibutyl-Nꢀ,Nꢀ-diethyl-Nꢀꢀ,Nꢀꢀ-dihexylguanidin-
ium triflate.
Key words: Diazoacetates, Cyclopropanation, C–H Insertion, Ionic Liquids, Rhodium, Ruthenium
Introduction
α-diazo-α-phosphonoacetamides in a hexaalkylguani-
dinium ionic liquid [16].
Ionic liquids (ILs) have recently been introduced
as novel solvents for the purposes of organic synthe-
sis [1]. Catalytic transformations have emerged as an
attractive area of application [2], mainly for two rea-
sons: a) many of the catalytically active (transition)
metal salts and complexes have a good solubility in
ionic liquids, and b) catalysts can be immobilized and
re-used in the ionic liquid while the other components
of the reaction mixture are extracted into a solvent that
is not miscible with the ionic liquid.
Metal-catalyzed transformations of diazo com-
pounds constitute an important strategy in contem-
porary organic synthesis [3]. Several typical transfor-
mations of diazo compounds, such as cyclopropana-
tion, aziridination, C–H and X–H (X = O, N) in-
We have recently developed an interest in the syn-
thesis and properties of hexaalkylguanidinium-based
ionic liquids [17]. In continuation of our preceding
work on carbenoid transformations of diazo com-
pounds catalyzed by dinuclear ruthenium(I,I) com-
plexes [Ru(CO)2-(µ-L2)-Ru(CO)2], where L repre-
sents a bidentate acetate or amidate ligand [18, 19], we
have now studied such reactions in hexaalkylguanidin-
ium-based ionic liquids. A comparison is made with
analogous rhodium-catalyzed reactions and with reac-
tions in an imidazolium-based ionic liquid as well.
Results and Discussion
The molecular structures of the hexaalkylguanidin-
sertion, and ylide formation, in the presence of cop- ium-based r. t. ionic liquids used in this study are
per [4 – 8], rhodium [4d, 9 – 12], palladium [13], iron shown in Fig. 1. While [N11N22N44]OTf [17],
porphyrin [14], or gold [15] catalysts, have been car- [N22N44N66]OTf [17] and [N16N22N44]I [20] are
ried out in ionic liquids, mostly under the aspect of known compounds, [N16N22N44]OTf has been syn-
catalyst immobilization. Almost all of these studies thesized from the iodide by anion exchange with sil-
used ionic liquids based on 1-alkyl-3-methylimidazol- ver triflate in acetonitrile. 1-Butyl-3-methylimidazol-
ium ions. Afonso and coworkers briefly mentioned the ium hexafluorophosphate ([bmim]PF6), a widely used
rhodium- catalyzed intramolecular C–H insertion of ionic liquid, was taken for a comparison in some cases.
c
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T. Large et al. · Ruthenium- and Rhodium-catalyzed Carbenoid Reactions
Table 1. Rhodium- and ruthenium-catalyzed cyclopropanation of styrene in ionic liquids or CH2Cl2 (see Scheme 1)a.
Entry Solvent
Catalyst: [Ru2(µ-OAc)2(CO)4]n (1 mol-%)
Diazoacetateb Temperature (◦C) Yield of Z −+E-1 (%) Ratio Z-1 : E-1 Yield of 2 (%) Reference
1
2
3
4
5
6
7
8
CH2Cl2
[N11N22N44]OTf
MDA
MDA
20
40
60
80
40
40
22
40
95
30
49
38 : 62
34 : 66
34 : 66
35 : 65
34 : 66
42 : 58
43 : 57
42 : 58
[18a]
this work
not determ.
21
“
“
“
57
45
22
39
14
n.d.
15 – 18
20
[N16N22N44]I
[N16N22N44]OTf
[bmim]PF6
MDA
MDA
MDA
“
“
47 – 52
12 – 14
Catalyst: [Rh2(µ-OAc)4] (1 mol-%)
9
10
11
12
13
14
15
16
CH2Cl2
EDAc
EDA
EDA
22
40
27
27
50
50
27
50
92
38
88
42
49
quant.
56
58
40 : 60
43 : 57
10 : 90
42 : 58
41 : 59
38 : 62
38 : 62
39 : 61
[21]
[N11N22N44]OTf
[bmim]PF6
11
12
[10]
this work
this work
[12]
this work
this work
10
n.d.
11
d
[hmim]PF6
EDA
MDA
[bmim]PF6
17
a
A mixture of diazoester (1 mmol) and styrene (2 mmol) was gradually added to a solution of styrene (3 mmol) in the solvent (3 mL);
b
c
MDA = methyl diazoacetate; EDA = ethyl diazoacetate; 0.5 mol-% of catalyst was used; d hmim = 1-hexyl-3-methylimidazolium.
Scheme 1. Cyclopropanation of styrene
with diazoacetates.
turally related dinuclear complexes [Ru2(µ-OAc)2-
(CO)4]n and Rh2(OAc)4 as catalysts, we have now
checked the suitability of hexaalkylguanidiniumILs as
novel reaction media. A solution of the diazoacetate
in styrene was added gradually to the IL containing
styrene and the catalyst. The reactions were allowed to
go to complete consumption of the diazo compound.
After extraction of the organic products into diethyl
ether, the product yields and the diastereomeric ratios
of cyclopropanes 1 were determined from the 1H NMR
spectra as well as by GC of the crude product mixtures.
The results are shown in Table 1, together with some
data from the literature.
For both the rhodium- and the ruthenium-catalyzed
Fig. 1. Ionic liquids used in this study.
reactions, the cyclopropane yields obtained in ionic
liquids as reaction media fall far behind those of the
reactions in dichloromethane. This may be due in part
to the limited solubility of the catalysts in the ionic
Catalytic cyclopropanation of styrene with diazo-
acetates
The catalytic cyclopropanation of styrene with liquids. At the given concentration, Rh2(OAc)4 was
◦
methyl or ethyl diazoacetate (Scheme 1) affords 2- found to be only partly disssolved even at 50 C in
phenylcyclopropanecarboxylates 1 and usually the di- both the guanidinium ILs and in [bmim]PF6. [Ru2-
alkyl fumarates and maleates 2 as by-products. This (µ-OAc)2(CO)4]n is a coordination polymer which is
benchmark reaction has been used in the past to eval- insoluble in all solvents without Lewis base charac-
uate the effectiveness and efficiency of virtually all ter. However, we had observed earlier that it is eas-
available catalysts. For this reaction and with the struc- ily depolymerized when exposed to an alkyl diazo-
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T. Large et al. · Ruthenium- and Rhodium-catalyzed Carbenoid Reactions
349
Table 2. Re-use of the Ru-catalyst/ionic liquid solution (see
Table 1, entries 3 and 4).
acetate in dichloromethane solution [18a]. In liquid
[N11N22N44]OTf, complete dissolution is achieved in
the presence of MDA only at 60 ◦C, but not at r. t. An-
other reason for the reduced yields could be the rela-
tively high viscosity of the ionic liquids, which slows
down the diffusion rate of the solute molecules and
causes a decreased yield for the intermolecular car-
benoid reaction. The viscosity of many ionic liquids
decreases strongly at higher temperature. For exam-
ple, th◦e viscosity of [N11N22N44]OTf is 263 mPa s
Reaction cycle
1
2
3
4
5
T = 60 ◦C
Yield of E/Z-1, % 49
45
37
28
22
Ratio Z-1 : E-1
34 : 66 32 : 68 35 : 65 36 : 64 37 : 63
T = 80 ◦C
Yield of E/Z-1, %
Ratio Z-1 : E-1
57
36
23
20
22
35 : 65 42 : 58 39 : 61 38 : 62 39 : 61
[N11N22N44]OTf and the catalyst/IL combination
could be re-used, we removed the organic products
of the cyclopropanation reaction by several extractions
with ether. The IL/catalyst combination was then re-
used in five successive reaction cycles. The reactions
were performed at a temperature where the catalyst
was completely dissolved in the presence of the di-
azoester (see above). As Table 2 shows, the cyclo-
propane yields dropped sharply already in the second
and third reaction cycle. This is partly due to leaching
of the catalyst in the ether phase and partly to decom-
position of the catalyst under the reaction conditions,
as was indicated by a progressive dark coloration of the
IL from one cycle to the next. Significant leaching has
already been reported for Rh2(OAc)4 in [hmim]PF6
upon extraction with ether and toluene [12].
◦
at 23 C, and 44 mPa s at 60 C [17]; the viscosity
◦
of [bmim]PF6 was reported as 312 mPa s at 25 C
◦
and 40 mPa s at 60 C [22]. In fact, we observed an
almost doubled yield of 1 for the reaction performed
in [N11N22N44]OTf, when the reaction temperature
◦
was raised from 40 to 80 C (Table 1, entries 2 – 4).
Enhanced cyclopropane yields at higher temperature
were also observed for reactions performed in liquid
[bmim]PF6 (Table 1, entries 7/8 and 12/13). On the
other hand, the yield of 1 was significantly higher in
[N16N22N44]I (entry 5) than in [N16N22N44]OTf
(entry 6) at the same temperature, although the former
is a much more viscous oil. All these observations may
result from the combined influence of catalyst solubil-
ity and viscosity of the reaction medium.
For all reactions, the diastereomeric ratio cis-
1 : trans-1 (Z-1 : E-1) is found in a rather narrow range
(from 34 : 66 to 43 : 57), i. e., almost independent of
the solvent and the reaction temperature. This is in
agreement with a large body of literature data, show-
ing that the diastereoselectivity of cyclopropanation
can be controlled to some extent by the catalyst (lig-
ands and structure) [23, 24], but not so much by the
choice of solvent. Therefore, we were intrigued by a
publication, in which the Rh2(OAc)4-catalyzed cyclo-
propanation of styrene in the ionic liquid [bmim]PF6
was reported to give cyclopropanes 1 with an unusu-
ally high trans-selectivity of cis : trans = 10 : 90 (Ta-
ble 1, entry 11) [10]. We cannot confirm these data; un-
der the reported conditions, we found a diastereomeric
ratio of 42: 58 (Table 1, entry 12), in agreement with
the general experience, the results of our ruthenium-
catalyzed reactions, and another recent study [12],
where [hmim]PF6 was used as the ionic liquid. Exper-
iments with MDA instead of EDA (entries 15 and 16)
made sure that this minor change of the ester group
does not affect the diastereomeric ratio, as was already
known for reactions in traditional organic solvents.
In order to learn whether the ruthenium cat-
Intramolecular carbenoid C–H insertion of an
α-methoxycarbonyl-α-diazoacetamide
The rhodium- or ruthenium-catalyzed decomposi-
tion of◦α-diazocarboxamide 3 (Scheme 2) in toluene
at 70 C yields β-lactam 4 in high yield [19b, 25].
The lactam results from an intramolecular carbenoid
C–H insertion. With the hypothesis in mind that the
Scheme 2. β-Lactam formation by intramolecular carbenoid
alyst could be immobilized in the ionic liquid C–H insertion.
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350
T. Large et al. · Ruthenium- and Rhodium-catalyzed Carbenoid Reactions
Table 3. Carbenoid formation of β-lactam 4 (see Scheme 2).
Entry
Catalyst (3 mol-%)
Rh2(OAc)4
Solvent
toluene
Conditionsa
70 ◦C/1 h
Total yield of lactamsb
Ratio cis- : trans-4
90 : 10 (89 : 11)
11 : 89
82 : 18
91 : 9 (74 : 26)
3 : 97
1
2
3
4
5
6
97c,d (83d,e
98
)
Rh2(OAc)4
Rh2(OAc)4
[Ru2(µ-sac)2(CO)5]2
[Ru2(µ-sac)2(CO)5]2
Ru3(CO)12
[N22N44N66]OTf
toluene/[N22N44N66]OTf (14 : 1)
toluene
[N22N44N66]OTf
[N22N44N66]OTf
70 ◦C/2.5 h
70 ◦C/2.5 h
70 ◦C/1 h
94c (72d,e
)
70 ◦C/2.5 h
70 ◦C/4.5 h
72
66
0 : 100
a
The reactions were run up to complete consumption of the diazo compound; b if not stated otherwise, yields were determined by 1H NMR
analysis of the reaction mixture; c ref. [19b]; d yield of isolated product; e see Experimental Section for chromatographic purification.
◦
effectiveness of an intramolecular carbenoid reaction Rh2(OAc)4 (70 C/22 h, correspondig to the reaction
would not be affected by the viscosity of the reac- conditions for the formation of 4). Partial isomeriza-
tion medium as much as an intermolecular reaction, tion took place during chromatography over silica gel
we studied the outcome of these reactions using the or neutral alumina (toluene as eluent), as well as in
guanidinium-IL [N22N44N66]OTf (Fig. 1) as the sol- the solid state (from 90 : 10 to a stable ratio of 68 : 32
vent. The same catalysts as in our previous study [19b] after 150 h). The effect of the ionic liquid was con-
were used. The results are shown in Table 3. It can firmed on a 90 : 10 mixture of cis- and trans-4, which
be seen that replacement of toluene by the ionic liq- was obtained by Rh2(OAc)4-catalyzed decomposition
uid entails longer reaction times, although the cata- of diazoamide 3 in toluene (see Experimental Sec-
lysts were completely dissolved at the reaction tem- tion). When this mixture was dissolved in an ionic liq-
◦
perature of 70 ◦C and in the presence of the diazo com- uid, the cis : trans ratio after 2.5 h at 70 C was 3 : 97
pound. Notably, as in the reaction in toluene as the in [N22N44N66]OTf, 22 : 78 in 1-ethyl-3-methylimid-
solvent, the yield of the rhodium-catalyzed reaction is azolium ethylsulfate, but 82 : 18 in 1-ethyl-3-methyl-
still almost quantitative, and the decrease in yield of imidazolium methanesulfonate. It appears that both the
the ruthenium-catalyzed reactions is much less severe ionic liquid itself and, as the results with the two emim-
than in the case of the intermolecular cyclopropana- based ILs show, the nature of the anion have an influ-
tion reaction discussed above. Interestingly, the com- ence on the epimerization process. A straightforward
plex Ru3(CO)12, a synthetic precursor for the sacchari- explanation cannot be given. It is plausible that the cis
nate complex, can also be used as a catalyst in the ionic → trans isomerization of 4 is the result of an epimer-
liquid with moderate success.
ization at C-3, either via the enol or the enolate form
of the 1,3-dicarbonyl moiety. Proton catalysis does not
seem to be at work, and general base catalysis by the
anion of the ionic liquid can likely by excluded because
the triflate-contanining IL gives the highest amount
of trans-4 unter the conditions described above, al-
though the triflate anion is a weaker base than the
ethyl sulfate and methanesulfonate anions. In this con-
text, studies of the keto/enol equilibrium [27] and of
the base-catalyzed keto/enol tautomerization [28] of 2-
nitrocyclohexanone in ionic liquids compared to com-
mon organic solvents are of interest. For example, the
authors have concluded that the considerable rate ac-
celeration of the keto-enol interconversion in certain
ionic liquids is not due to a special ionic liquid ef-
fect. Taking into account not only the permittivity of
the solvent, but also the additional solvent parameters
of dipolarity/polarizability, hydrogen bond acidity, and
cohesive pressure, a reasonable linear correlation be-
tween experimental and calculated rate constants could
be found for all investigated solvents [28].
The most interesting detail in Table 3 is the in-
fluence of the ionic liquid on the cis : trans ratio
of the methoxycarbonyl-substituted β-lactam 4. The
initial formation of cis-3-alkoxycarbonyl-azetidin-2-
ones in the course of the carbenoid reaction is well
known [19b, 25, 26]. We have reported earlier that the
cis : trans ratio depends somewhat on the catalyst, and
that the amount of the trans-isomer increases with ex-
tended reaction times [19b]. Surprisingly, the cis : trans
ratio is completely reversed in favor of a high trans-
selectivity, when the reaction is carried out in the ionic
liquid [N22N44N66]OTf. Even the addition of a small
amount of this IL to toluene as the reaction medium
apparently causes the amount of the trans-isomer to
increase (entry 3). Additional experiments were made
to shed light on the particular role of this ionic liq-
uid on the isomerization cis-4 → trans-4. No isomer-
◦
ization occurred in CDCl3 or C6D6 (25 C/9 h), af-
ter addition of a drop of triflic acid (HOTf) or wa-
ter to the CDCl3 solution, or in toluene that contained
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T. Large et al. · Ruthenium- and Rhodium-catalyzed Carbenoid Reactions
351
termolecular reaction are much lower, while the in-
tramolecular reactions give high yields in both types
of reaction media. This difference may be related to
the higher viscosity of the IL hampering the effective-
ness of the intermolecular carbenoid reaction.
The immobilization of the catalyst in the ionic liq-
uid is not complete, as the recycling experiments show.
Even when the ionic liquid is extracted with the very
unpolar solvent pentane, leaching of both the rhodium
and the ruthenium catalysts into the pentane phase
(probably due to complexation to an organic product)
is significant. For the ruthenium catalysts in particu-
lar, after a few cycles the amount of catalyst no longer
suffices for an efficient transformation of the diazo sub-
strate. These results suggest to modify the rhodium and
ruthenium complexes used in this study by the intro-
duction of a hexaalkylguanidinium moiety in order to
increase their affinity to the ionic liquid containing the
same cation type. However, in a related study [12] it
was found that complexation of the dirhodium core to
an imidazolium-carboxylate and use of this catalyst in
[hmim]PF6 was less efficient and could not completely
suppress the leaching into the organic phase on extrac-
tive work-up.
Fig. 2. Use of the catalyst/ionic liquid combination in six
reaction cycles (3 → 4, ionic liquid = [N22N44N66]OTf,
◦
3 mol-% of [Ru2(µ-sac)2(CO)5]2, 70 C, 2.5 h); ꢀ = yield
of 4; ꢁ = conversion of diazoamide 3.
For the transformation 3 → 4, the possibility to re-
use the catalyst immoblized in [N22N44N66][OTf was
also investigated. To this end, the reac◦tion was car-
ried out with 3 mol-% of catalyst at 70 C for a fixed
time of 2.5 h; after cooling, the ionic liquid was ex-
tracted ten times with pentane. This procedure was
repeated in five successive reaction cycles. As indi-
cated by a slight coloration of the pentane extracts –
green in the case of Rh2(OAc)4 and yellow in the case
of [Ru2(µ-sac)2(CO)5]2 – some leaching from the IL
in the pentane phase took place with both catalysts.
As the pure catalysts are not soluble in pentane, the
leaching is likely caused by their complexation with
the extracted β-lactam. With Rh2(OAc)4, however, the
yield of β-lactam 4 remained the same over all reac-
tion cycles. This suggests that the original amount of
Rh2(OAc)4 was more than enough for an effective car-
benoid reaction. With the ruthenium catalyst, on the
other hand, the yield of 4 diminished to half of its
initial value over the six reaction cycles, and a sim-
ilar trend was observed for the conversion of the di-
azo compound (Fig. 2). These results indicate that the
amount of [Ru2(µ-sac)2(CO)5]2 decreased from one
cycle to the next (primarily due to leaching, but to some
extent also by catalyst deacitvation), so that the avail-
able amount of catalyst was no longer sufficient for a
fast and effective dediazoniation of the diazoamide.
Experimental Section
N,N-Dibutyl-Nꢀ,Nꢀ-diethyl-Nꢀꢀ,Nꢀꢀ-dimethylguanidinium
triflate ([N11N22N44]OTf) and N,N-dibutyl-Nꢀ,Nꢀ-dieth-
yl-Nꢀꢀ,Nꢀꢀ-dihexylguanidinium triflate ([N22N44N66]OTf)
were synthesized by a published procedure [17]. N,N-Dibut-
yl-Nꢀ,Nꢀ-diethyl-Nꢀꢀ-hexyl-Nꢀꢀ-methylguanidinium iodide
([N16N22N44]I) was obtained from Prof. W. Kantlehner
(Hochschule Aalen, Aalen (Germany)) [20]. 1-Butyl-
3-methylimidazolium hexafluorophosphate ([bmim]PF6
was synthesized from [bmim]Cl by anion exchange with
KPF6 [29]. 1-Ethyl-3-methylimidazolium ethylsulfate and
methanesulfonate were obtained from Solvent Innovation
GmbH. In order to keep the water content of the ionic liquids
low, they were treated at 60 ◦C/0.05 mbar for several hours,
then stored under argon. Diazoamide 3 was prepared as
published [19b].
Conclusion
N,N-Dibutyl-Nꢀ,Nꢀ-diethyl-Nꢀꢀ-hexyl-Nꢀꢀ-methylguanidinium
triflate ([N16N22N44]OTf)
Two ruthenium- or rhodium-catalyzed carbenoid
reactions – the intermolecular cyclopropanation of
styrene with alkyl diazoacetates and the intramolec-
ular β-lactam formation from 3-oxo-2-diazocarbox-
amides – have been performed in hexaalkylguanidin-
ium-based ionic liquids. Compared to tradional or-
A solution of N,N-dibutyl-Nꢀ,Nꢀ-diethyl-Nꢀꢀ-hexyl-Nꢀꢀ-
methylguanidinium iodide ([N16N22N44]I) [20] (1.09 g,
2.4 mmol) in acetonitrile (10 mL) was placed in a reac-
tion vessel protected from light, and a solution of silver(I)
trifluoromethanesulfonate (0.663 g, 2.58 mmol) in acetoni-
ganic solvents (CH2Cl2, toluene), the yields of the in- trile (5 mL) was added gradually. Precipitation of AgI be-
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352
T. Large et al. · Ruthenium- and Rhodium-catalyzed Carbenoid Reactions
gan immediately, but after complete addition the mixture was For the recycling experiments the ionic liquid after
stirred magnetically overnight to improve the crystallinity of completed reaction was extracted with diethyl ether (5 ×
the solid. The solvent was replaced by a mixture of ace- 7 mL). Phase separation was supported by centrifugation.
tonitrile and diethyl ether (25 mL, 1 : 4 by volume). The Before the next reaction cycle, the ionic liquid was kept
undissolved solid was filtered off, the solvent was evapo- at 50 ◦C/40 mbar to remove traces of diethyl ether.
rated (800 mbar), and the remaining ionic liquid was kept
at 80 ◦C/0.05 mbar to remove residual volatiles. Yield: 1.08 g
Catalytic decomposition of diazoamide 3
a) in the ionic liquid [N22N44N66]OTf
(93 %). The NMR spectra indicate the presence of hindered
1
rotation in the cation: – H NMR (CDCl3): δ = 0.85 – 0.98
N-Benzyl-N-tert-butyl-2-methoxycarbonyl-2-diazoacet-
amide (3, 50 mg, 0.173 mmol) was dissolved in
[N22N44N66]OTf (0.5 mL), and the catalyst (3 mol-%;
2.3 mg of Rh2(OAc)4; 3.7 mg of [Ru2(µ-sac)2(CO)5]2) was
added. The solution was heated at 70 ◦C until the diazo com-
pound was consumed (2.5 h, IR control). After cooling, the
ionic liquid was stirred with n-pentane (2 mL) for 8 min,
and after phase separation the pentane layer was pipetted off.
The extraction procedure was repeated nine times. The pen-
tane extracts were combined, and the solvent was evaporated.
The yield and diastereomeric ratio of N-tert-butyl-3-meth-
oxycarbonyl-4-phenylazetidin-2-one (cis- and trans-4) was
determined by integration of characteristic 1H NMR signals
(cis-4: δ = 4.23 ppm, 3J = 6.3 Hz; trans-4: δ = 3.71 ppm,
3J = 2.3 Hz [19b]) (Table 3); for the determination of yields,
a weighed amount of naphthalene was added as an internal
reference.
(several t, partly broadened, 9 H, CH3-hexyl, -butyl), 1.18 –
1.80 (m, 22 H, 8 CH2, 2 CH3-ethyl); 2.99, 3.00 (2 s, 3 H to-
gether, NCH3); 2.97 – 3.50 (m, 10 H, 5 NCH2). – 13C NMR
(CDCl3): δ = 12.69 – 13.90 (all (CH2)nCH3); 19.86 (br),
20.09 (br), 22.49, 26.46, 26.51, 27.23, 27.32, 29.41 (br),
29.57, 31.25 (CH2); 38.35, 38.55 (NCH3); 43.22, 43.60,
43.81, 43.86 (NCH2CH3), 48.86, 49.25 (br), 49.46 (NCH2-
butyl, -hexyl); 52.90, 52.95 (NCH2); 163.9 (CN3), CF3 not
observed. – IR (NaCl): ν = 1558 (m), 1544 (m), 1459 (m),
1442 (m), 1264 (s), 1225 (s), 1156 (s), 1032 (s) cm−1. –
C21H44F3N3O3S (475.65): calcd. C 53.03, H 9.32, N 8.83;
found C 52.79, H 9.56, N 9.13.
Catalytic cyclopropanation of styrene with methyl diazoac-
etate in an ionic liquid (Table 1)
Under an argon atmosphere, the catalyst (1 mol-% rela-
tive to the diazoacetate; 4.4 mg of Rh2(OAc)4, 7.1 mg of
[Ru2(µ-sac)2(CO)5]2) and styrene (199 mg, 2.0 mmol) were
added to the magnetically stirred ionic liquid (3 mL), which
was then brought to the desired temperature. A solution of
methyl diazoacetate (101 mg, 1.0 mmol) in styrene (298 mg,
3.0 mmol) was gradually added via a syringe pump dur-
ing 4 h. The reaction was allowed to continue until IR con-
trol (ν(CN2) = 2115 cm−1) indicated the complete con-
sumption of the diazoacetate. The products were extracted
with dry diethyl ether (3 × 10 mL). The ether extracts were
b) in toluene
The reported procedure [19b] was carried out on a smaller
scale and with a chromatographic work-up that avoids the
partial epimerization of azetidinone 4. A solution of diazo-
amide 3 (282 mg, 1 mmol) in dry toluene (2 mL) was added
within 45 min to toluene (13 mL) containing the catalyst
(3 mol-%; 13.3 mg of Rh2(OAc)4, 21.2 mg of [Ru2(µ-sac)2-
(CO)5]2). The mixture was heated at 70 ◦C for 1 h. The sol-
vent was evaporated in vacuo, and azetidinone 4 was pu-
rified by threefold column chromatography over charcoal
(1 g)/cellulose (2 g) using toluene as eluent. Yield of 4, with
Rh2(OAc)4 as catalyst: 83 %, cis-4 : trans-4 = 90 : 10; with
[Ru2(µ-sac)2(CO)5]2: 72 %, cis-4 : trans-4 = 74 : 26.
◦
combined, and the solvent was removed at 60 C/800 mbar.
For product analysis, the residue was dissolved in CH2Cl2
(3 mL) and a weighed amount of naphthalene (20 – 36 mg)
was added as an internal standard. The mixture was analyzed
1
by H NMR spectroscopy (for NMR data of cis- and trans-
Acknowledgement
methyl 2-phenylcyclopropane-1-carboxylate see lit. [18a]
and lit. cit.) and by GC (column: Varian CP-WAX 52, 25 m ×
0.32 mm; film thickness: 1.2 µm; helium as carrier gas, flow
rate 1 mL/min). The results obtained from the two methods
were in good agreement.
This work was supported financially by the Bundesminis-
terium fu¨r Bildung und Forschung (BMBF), project “Novel
Ionic Liquids as Innovative Reaction Media for Technical Or-
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