New catalytic system Cu(OAc)2-2,4-lutidine-ZnCl2 for olefin cyclopropanation with methyl diazoacetate

Article abstract of DOI:10.1007/s11172-008-0238-x

A new efficient catalytic system consisting of Cu(OAc)₂, 2,4-lutidine, and ZnCl₂ was found for the cyclopropanation of unsaturated compounds with methyl diazoacetate. In the case of conjugated dienes, the process occurs regioselectively at the most alkylated C=C bond.

Full text of DOI:10.1007/s11172-008-0238-x

Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1784—1786, August, 2008
1784
Brief Communications
New catalytic system Cu(OAc)2—2,4ꢀlutidine—ZnCl2
for olefin cyclopropanation with methyl diazoacetate
V. F. Gareev,a R. M. Sultanova,a R. Z. Biglova,a V. A. Dokichev,a and Yu. V. Tomilovb
aInstitute of Organic Chemistry, Ufa Scientific Center of the Russian Academy of Sciences,
71 prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Fax: +7 (347) 235 6066. Eꢀmail: dokichev@anrb.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Eꢀmail: tom@ioc.ac.ru
A new efficient catalytic system consisting of Cu(OAc)2, 2,4ꢀlutidine, and ZnCl2 was found
for the cyclopropanation of unsaturated compounds with methyl diazoacetate. In the case of
conjugated dienes, the process occurs regioselectively at the most alkylated C=C bond.
Key words: olefins, diazo esters, dienes, cyclopropane carboxylates, catalytic systems,
cyclopropanation.
In the present work, we showed for the first time that
Olefin cyclopropanation with alkyl diazoacetates is
widely used in organic synthesis as a convenient method for
the preparation of cyclopropanecarboxylic acid derivaꢀ
tives,1—6 many of which are practically important compounds
(cilastatin, pyrethroids, dictyopterenes, etc.). It is noteꢀ
worthy that the majority of the known catalysts for cycloꢀ
propanation3—8 based on Cu, Со, Ru, Pd, and Rh provide
no high regioselectivity in the case of dienes and, as a
rule, require the application of a 5—10ꢀfold excess of an
unsaturated compound for the suppression of alkoxyꢀ
carbonylcarbene dimerization. The repeated use of these
catalysts is usually impossible and, hence, search for new highly
efficient catalysts for the cyclopropanation of unsaturated
compounds remains to be an urgent problem.
the Cu(OAc)2—2,4ꢀlutidine—ZnCl2 threeꢀcomponent
system with a molar ratio of 6 : 5 : 1 is an efficient catalyst
for the cyclopropanation of olefins and conjugated dienes
(1a—h, Scheme 1, Table 1) with methyl diazoacetate
(MDA). The reaction is carried out at 40 °C by the
addition of a solution of MDA in CH2Cl2 to the unꢀ
saturated compound and the catalyst, with the molar ratio
MDA : olefin : catalyst (based on Cu(OAc)2) being 1 : 1 : 0.06.
The study of the effect of the nature of pyridinium comꢀ
pounds (Py, 2,4ꢀlutidine, 2,6ꢀlutidine, 2ꢀpicoline, 2ꢀcyanoꢀ
pyridine, 2,6ꢀdiaminopyridine, 3ꢀ and 4ꢀaminoꢀ
pyriꢀdines, 3,5ꢀdibromoꢀ2ꢀaminopyridine), Lewis acids
(AlCl3, KBF4, ZnCl2), and various copper, palladium,
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1750—1752, August, 2008.
1066ꢀ5285/08/5708ꢀ1784 © 2008 Springer Science+Business Media, Inc.

Cyclopropanation of olefins
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1785
Scheme 1
R3
R4
R3
R4
R2
R1
CO2Me
H
R2
R1
R2
R1
R3
R4
H
MeO2C
H
Cat.
+
+
N2CHCO2Me
+
CHCO2Me
CH2Cl2
CO2Me
1a—h
3
trans-2a—h
cis-2a—h
Table 1. Yields of the products and the ratio of the transꢀ and
cisꢀisomers of compound 2
lates from methyl diazoacetate and unsaturated comꢀ
pounds.
Comꢀ
pounds
2a—h
R1 R2 R3
R4
Yield (%)
Ratio
of isomers
trans/cis
Experimental
2
3
The structures of compounds 2a—h were confirmed by the
1Н and 13С NMR spectral data. 1Н and 13С NMR spectra
were recorded on a Bruker AMꢀ300 spectrometer (300.13 and
75.47 mHz, respectively) in CDCl3 using Me4Si as an internal
standard. GLC analysis was carried out on a Chromꢀ5 chroꢀ
matograph with a flameꢀionization detector (column 1200×3 mm
with 5% SEꢀ30 on Chromatone NꢀAWꢀHMDS) using helium as
a carrier gas. 2,5ꢀDimethylhexaꢀ2,4ꢀdiene (1g), 2,4ꢀlutidine,
[CuOTf]2•С6H6, and Cu(OTf)2 (Aldrich) and Сu(OAc)2 (ZAO
Vekton, Russia) were used. Unsaturated compounds 1а—h were
distilled under an argon flow and stored over hydroquinone. The
solvents used (CH2Cl2 and petroleum ether) were purified using
standard procedures.9
a
b
c
d
e
f
g
g*
g**
h
H
H
H
H
H
H
H
H
H
H
H
H
Bu
Ph
CH=CH2
28
72
49
52
50
50
25
26
9
9
8
—
20
9
11
—
1.9
2.0
1.3
1.3
1.3
1.3
1.9
1.9
2.0
1.5
Me CH=CH2
Me H CH=CH2
CH=CH2
Me H
H
Me Me H CH=CMe2 65
Me Me H CH=CMe2 81
Me Me H CH=CMe2 72
Me Me H CH=CCl2
48
*Sixth cycle of the catalyst use.
**Seventh cycle.
Catalytic cyclopropanation of olefins 1a—h with methyl
diazoacetate (general procedure). Unsaturated compound 1a—h
(18 mmol) was added to a stirred solution containing anhydrous
ZnCl2 (4.1 mg, 0.03 mmol), 2,4ꢀlutidine (16.0 mg, 0.15 mmol),
and Сu(OAc)2 (32.7 mg, 0.18 mmol) in СH2Cl2 (5 mL). Then
at 40 °С (in the case of diene 1с, the reaction was carried out at
room temperature) methyl diazoacetate (1.80 g, 18 mmol) in
СH2Cl2 (7 mL) was slowly added until gas evolution has ceased.
The solvent was removed in vacuo, petroleum ether (b.p. 40—70 °С)
was added to the residue, and the catalytic system was separated
as a dark brown oil (the catalytic system obtained for the
cyclopropanation of diene 1g was used seven times more in
experiments on cyclopropanation). The petroleum ether solution
was concentrated in vacuo, and the residue was analyzed by
GLC and 1Н NMR spectroscopy. The yields of compounds 2a—h
were determined by GLC using tetradecane as an internal
standard calibrated by an authentic sample of methyl chrysantꢀ
hemate 2g. The isomers were characterized in a mixture by
NMR spectroscopy, and their ratio was determined on the basis
of the integral intensity of signals of the methinic protons at the
C(1) atom for compounds 2a—c,g,h and the vinylic protons for
compounds 2d—f in the 1Н NMR spectra. The physicochemical
and spectral characteristics of compounds 2a—h corresponded
to the published data.4,10,11
and rhodium compounds (Cu(OAc)2, [CuOTf]•C6H6,
Cu(OTf)2, Pd(OAc)2, Rh2(CF3CO2)4, Rh2(OAc)4) on the
reaction products showed that a combination of the comꢀ
ponents Cu(OAc)2—2,4ꢀlutidine—ZnCl2 provided the best
results. In the absence of at least one of the components
of this system, MDA does not interact with unsaturated
compounds 1a—h. When this system is used, the cycloꢀ
propanation of 1,3ꢀdienes 1с—h with MDA occurs regioꢀ
selectively at the most alkylated С=С bond to form mixtures of
diastereomeric methyl vinylcyclopropanecarboxylates
2c—h with prevailing of transꢀisomers in 49—81% yields
(see Scheme 1). It should be mentioned that for diene 1g
no double cyclopropanation products were observed even
when using a twofold molar excess of MDA. The double
bond of chrysanthemate 2g is not subjected to cycloꢀ
propanation under these conditions.
It was found for the cyclopropanation of 2,5ꢀdimethylꢀ
hexaꢀ2,4ꢀdiene (1g) as an example that the Cu(OAc)2—
2,4ꢀlutidine—ZnCl2 catalytic system did not lose its acꢀ
tivity even being used eight times. Moreover, it turned out
that recycling of the catalyst increased the yield of methyl
chrysanthemate (2g) up to 81%. The obtained catalytic
system is an oily dark brown substance soluble in methylꢀ
ene chloride and insoluble in petroleum ether, which
allows easy isolation of the catalyst from the reaction
mixture for repeated use.
This work was financially supported by the Presidium
of the Russian Academy of Sciences (Program for Fundaꢀ
mental Research “Development of Methods for the
Synthesis of Chemical Substances and Design of New
Materials,” Subprogram “Development of Methodology
of Organic Synthesis and Design of Compounds with
Valuable Applied Properties”).
Thus, we proposed a new rather simple and effiꢀ
cient catalyst for the synthesis of cyclopropanecarboxyꢀ

1786
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
Gareev et al.
6. T. Werle, G. Maas, Adv. Synth. Catal., 2001, 343, 37.
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Received April 23, 2008;
in revised form May 30, 2008