Gold-catalyzed ethylene cyclopropanation

Article abstract of DOI:10.3762/bjoc.15.7

Ethylene can be directly converted into ethyl 1-cyclopropylcarboxylate upon reaction with ethyl diazoacetate (N₂CHCO₂Et, EDA) in the presence of catalytic amounts of IPrAuCl/NaBAr^F₄ (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene; BAr^F₄ = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate).

Full text of DOI:10.3762/bjoc.15.7

Gold-catalyzed ethylene cyclopropanation
Silvia G. Rull, Andrea Olmos* and Pedro J. Pérez*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 67–71.
Laboratorio de Catálisis Homogénea, Unidad Asociada al CSIC,
CIQSO-Centro de Investigación en Química Sostenible and
Departamento de Química, Universidad de Huelva, Campus de El
Carmen 21007 Huelva, Spain
doi:10.3762/bjoc.15.7
Received: 17 October 2018
Accepted: 11 December 2018
Published: 07 January 2019
Email:
Andrea Olmos* - andrea.olmos@dqcm.uhu.es; Pedro J. Pérez* -
perez@dqcm.uhu.es
This article is part of the thematic issue "Cyclopropanes and
cyclopropenes: synthesis and applications".
* Corresponding author
Guest Editor: M. Tortosa
Keywords:
© 2019 Rull et al.; licensee Beilstein-Institut.
License and terms: see end of document.
carbene transfer; cyclopropane; cyclopropylcarboxylate; ethylene
cyclopropanation; ethyl diazoacetate; gold catalysis
Abstract
Ethylene can be directly converted into ethyl 1-cyclopropylcarboxylate upon reaction with ethyl diazoacetate (N2CHCO2Et, EDA)
in the presence of catalytic amounts of IPrAuCl/NaBArF4 (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene; BArF4 =
tetrakis(3,5-bis(trifluoromethyl)phenyl)borate).
Introduction
Nowadays the olefin cyclopropanation through metal-catalyzed
carbene transfer starting from diazo compounds to give olefins
constitutes a well-developed tool (Scheme 1a), with an
exquisite control of chemo-, enantio- and/or diastereoselectiv-
ity being achieved [1,2]. Previous developments have involved
a large number of C=C-containing substrates but, to date, the
methodology has not been yet employed with the simplest
olefin, ethylene, for synthetic purposes [3]. Since diazo
compounds bearing a carboxylate substituent are the most
commonly employed carbene precursors toward olefin cyclo-
propanation, their use with ethylene leads to cyclopropane
(Scheme 1b). De Bruin and co-workers have described [4] such
Scheme 1: (a) General metal-catalyzed olefin cyclopropanation reac-
tion with diazo compounds. (b) The ethylene cyclopropanation with
diazoacetates leads to cyclopropanecarboxylates.
product in a minor, secondary reaction (yields <12%) while Ethyl cyclopropanecarboxylate has been prepared in several
studying the copolymerization of ethylene and ethyl diazoace- ways, alternative to the direct carbene addition to ethylene
tate with rhodium-based catalysts (Scheme 2a).
(Scheme 2b): ring contraction of 2-halocyclobutanone [5],
67

Beilstein J. Org. Chem. 2019, 15, 67–71.
Scheme 2: Routes toward ethyl cyclopropanecarboxylate (1). (a) Ethylene cyclopropanation described by De Bruin and co-workers as secondary
reaction. (b) Stoichiometric transformations. (c) Gold-catalyzed ethylene cyclopropanation described in this work.
cyclization of alkyl 4-halobutanoates [6], electroreductive Results and Discussion
dehalogenation [7] and decarboxylation of diethyl 1,1-cyclo- Diazo compounds N2=CRR’ usually react with metal com-
propyldicarboxylate [8]. Other methods include the transesteri- plexes of groups 8–11 with formation of electrophilic
fication of other alkyl cyclopropanecarboxylates [9] and the metal–carbene intermediates LnM=CRR’ [1,2] that further react
esterification with ethanol of the cyclopropanecarboxylic acid with nucleophiles such as olefins en route to cyclopropanes.
[10]. This product finds applications as lubricant additives [11], However, these intermediates can also react with another mole-
alkylating reagent in the Friedel–Crafts synthesis of indanones cule of the diazo reagent promoting the formation of olefins
[12] or as synthon toward the introduction of cyclopropyl RR’C=CRR’ [17]. This side reaction frequently is avoided upon
moieties in compounds with medicinal or biological interest maintaining a low diazo compound/catalyst ratio, employing
[13,14].
slow addition devices to incorporate a solution of the diazo
reagent into the reaction mixture containing the olefin and the
In view of the lack of examples of direct conversions of ethyl- catalyst. Unfortunately, the use of ethylene as the olefin
ene into cyclopropanecarboxylates, and given our experience requires a pressure vessel and thus the diazo reagent must be
with group 11 metal-based catalysts for carbene-transfer reac- added in one portion before pressurizing the system. This fact
tions from diazoacetates [15,16], we have investigated this constitutes the main drawback when working with this alkene,
transformation and found that the gold complex IPrAuCl (IPr = and a highly chemoselective catalyst toward cyclopropanation
1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene) along with over carbene dimerization is needed to enhance the former
one equivalent of NaBArF4 (BArF4 = tetrakis(3,5-bis(trifluoro- transformation.
methyl)phenyl)borate) catalyzes the ethylene cyclopropanation
with ethyl diazoacetate as the carbene precursor, under mild In a first array of experiments, we tested several group 11
conditions, with moderate yields (ca. 70%, EDA-based).
metal-based catalysts that have been described in our group for
68

Beilstein J. Org. Chem. 2019, 15, 67–71.
the catalytic transfer of the CHCO2Et group from ethyl diazo- [20,21]. Therefore, we moved onto gold-based catalysts that
acetate (N2=CHCO2Et, EDA), as well as a rhodium-based cata- had already been validated for EDA decomposition and
lyst. The experimental procedure started upon placing the carbene-transfer reactions [22,23]. Neutral IPrAuCl was not
catalyst (0.02 mmol) into a Fischer–Porter vessel and addition effective (Table 1, entry 4), assessing the need of a cationic,
of an EDA solution in 10 mL of dichloromethane via cannula halide-free gold species toward that end. The choice of the
under ethylene atmosphere, and then it was pressurized to 8 bar halide scavenger is not innocent: on the other hand, it is key for
with the same gas. The mixture was stirred for 14 h and then the success of this search. Thus, addition of one equiv of
investigated by GC (see the experimental section). The results AgOTf with respect to the gold complex resulted in low
are collected in Table 1. The complex TpMsCu(thf), previously consumption of EDA, and minor amounts of 1, olefins 2 and
described as an excellent catalyst for olefin cyclopropanation cyclopropane 3 derived from carbene addition to 2 were
[18], led to negative results, since only the olefins 2 (mixtures detected. The use of AgSbF6 led to different results: the yield
of diethyl fumarate and maleate) were detected at the end into desired 1 increased up to 25% but the functionalization of
of the reaction. The second copper-based catalyst tested the solvent (4) constituted the main transformation. This is
Tp(CF3)2,BrCu(thf) [19] gave some of the desired product 1 probably the effect of the silver in the reaction medium, since
(Table 1, entry 2), albeit in low yield (15%). Olefins 2 were also simple silver salts promote such reaction. The use of NaBArF4
formed, although mass balance was not verified by GC studies. delivered ethyl cyclopropanecarboxylate (1) in 62% yield, with
When the crude was analyzed by NMR, broad signals character- only 2% of olefins 2 as byproducts, the remaining 36% of initial
istic of polymeric materials were observed. Given that our goal EDA appearing unreacted at the end of the 14 h period. When
was the development of a catalytic route for cyclopropane 1, we the dirhodium complex Rh2(CF3COO)4 was submitted to the
have not invested efforts in the characterization of such materi- same experimental conditions, compound 1 was detected in
als.
41% yield, along with 14% of olefins 2. Again, the analysis of
the crude mixture through NMR revealed the presence of poly-
The silver complex Tp(CF3)2,BrAg(thf) [19] (Table 1, entry 3) meric material.
was not effective toward the aforementioned target, since only
5% of 1 was formed. In this case, the product derived from the Once the IPrAuCl/NaBArF4 was identified as the best choice
insertion of the carbene CHCO2Et group into the C–Cl of the toward the catalytic formation of 1, several reaction conditions
solvent was the major one, accordingly with previous work were explored. As shown in Table 2, and plotted in Figure 1,
from this and other laboratories using silver-based catalysts four experiments carried out at 1, 2, 4 and 8 bar of ethylene
Table 1: Catalyst screening for the reaction of ethylene and ethyl diazoacetate.a
Entry
Catalyst
% 1
% 2
% 3
% 4
% EDA
1
2
3
4
5
6
7
8
TpMsCu(thf)
0
>95
15
nd
4
nd
nd
nd
0
nd
nd
>75
0
nd
Tp(CF3)2,BrCu(thf)
Tp(CF3)2,BrAg(thf)
IPrAuCl
15
5
ndb
13
0
40b
80
IPrAuCl + AgOTf
IPrAuCl + AgSbF6
IPrAuCl + NaBArF4
Rh2(CF3COO)4
2
2
9
nd
>70
nd
nd
25
62
41
0
nd
nd
nd
nd
2
36
14
ndb
aReaction carried out with 0.02 mmol of catalyst, 0.2 mmol of EDA except with the rhodium catalyst, which was run with 0.4 mmol of EDA. Ethylene
pressure = 8 bar. Solvent: 10 mL of dichloromethane. Room temperature. Product determination and quantification by GC with calibration curves,
yields based on initial EDA. nd = not detected. bNMR studies show broad signals characteristic of polymeric materials accounting for 100% of initial
EDA.
69

Beilstein J. Org. Chem. 2019, 15, 67–71.
Table 2: Catalytic activity of IPrAuCl/NaBArF4 in the reaction of ethylene and ethyl diazoacetate.a
Entry
P(C2H4) (bar)
V(CH2Cl2) (mL) % 1
% 2
% 3
% EDA
1
1
2
4
8
8
8
5
5
>90
2
nd
35
33
15
0
nd
2
5
39
66
73
70
62
12
3
5
0
nd
4
5
0
ndb
ndb
36
5c
6
5
0
10
2
0
aConditions and product numbering as described in Table 1. nd = not detected. bNMR studies show broad signals characteristic of polymeric materi-
als accounting for 100% of initial EDA. cReaction performed at 40 °C.
(Table 2, entries 1–4) revealed that the latter was the optimal is the first example of a direct cyclopropanation of ethylene by
value. This is clearly the effect of the need of a high concentra- this methodology with significant conversions.
tion of the olefin in the reaction mixture, which is proportional
Experimental
to the partial pressure above the solution. Also, the use of a 5
mL volume of the solvent instead of 10 mL not only allowed to General methods
increase the yield up to 73% but also to induce complete All preparations and manipulations were carried out under an
consumption of ethyl diazoacetate. The effect of the tempera- oxygen-free nitrogen atmosphere using conventional Schlenk
ture when moving from ambient (Table 2, entry 4) to 40 °C techniques. Solvents were rigorously dried prior to use. The
(Table 2, entry 5) was negligible, albeit in the former the cyclo- substrates as well as compound 1 (for calibration curves) were
propane 3 was observed. Again, some polymeric material was purchased from Aldrich. The catalysts were prepared according
detected by NMR spectroscopy. It is worth mentioning that to literature procedures, as well as NaBArF4 [24]. NMR spectra
when diethyl diazomalonate or ethyl 2-phenyldiazoacetate were were performed on Agilent 400 MR and 500 DD2. GC data
employed as the carbene precursor, no cyclopropanes were were collected with an Agilent 7820A equipped with an FID
detected, only olefins formed from carbene dimerization as well detector and an Agilent HP-5 column of 30 m × 320 μm ×
as unreacted diazo compounds were identified at the end of the 0.25 μm. Method: 50 °C × 1.5 min, 10 °C/min, 250 °C ×
reaction.
25 min.
Catalytic experiments
Ethylene cyclopropanation with EDA. A 175 mL high pres-
sure Fischer–Porter vessel equipped with a manometer and a
valve was charged with 0.02 mmol of IPrAuCl (24 mg) and
0.02 mmol of NaBArF4 (17 mg). The vessel was deoxygenated
and filled with ethylene. A solution of 0.2 mmol of EDA
(24 μL) in 5 mL anhydrous dichloromethane was added via
cannula and the ethylene pressure was increased up to 8 bar.
The reaction mixture was stirred for 14 hours and the pressure
was released.
Reaction mixture analysis. The crude reaction mixture was
diluted to 10 mL and directly analyzed by GC. The amounts of
ethyl cyclopropanecarboxylate (1), EDA, diethyl maleate and
diethyl fumarate (2) were determined using calibration curves
ranging from 2 mM to 20 mM, previously prepared using com-
mercially available products. Retention times of products: 1,
5.78 min; EDA, 5.90 min; diethyl maleate, 10.73 min; diethyl
Figure 1: Effect of the pressure of ethylene on the yields of ethyl
cyclopropanecarboxylate in the reaction of ethylene and EDA cata-
lyzed by IPrAuCl/NaBArF4.
Conclusion
We have found that the complex IPrAuCl in the presence of one fumarate, 10.93 min. To determine the quantity of triethyl 1,2,3-
equivalent of NaBArF4 catalyzes the reaction of ethyl diazoace- cyclopropanetriscarboxylate (3) formed, the solution was evap-
tate and ethylene, at room temperature, leading to ethyl cyclo- orated and analyzed by NMR using CDCl3 as solvent and ethyl
propanecarboxylate with yields of ca. 70% (EDA-based). This chloroacetate as internal standard.
70

Beilstein J. Org. Chem. 2019, 15, 67–71.
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Acknowledgements
Support for this work was provided by the MINECO
(CTQ2017-82893-C2-1-R and CTQ2015-73693-JIN).
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ORCID® iDs
Andrea Olmos - https://orcid.org/0000-0002-1871-6395
Pedro J. Pérez - https://orcid.org/0000-0002-6899-4641
21.Urbano, J.; Braga, A. A. C.; Maseras, F.; Álvarez, E.;
Díaz-Requejo, M. M.; Pérez, P. J. Organometallics 2009, 28,
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