Stereoselective electrocatalytic transformation of malonate and alkylidenecyanoacetates into (E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates

Article abstract of DOI:10.1016/j.tet.2006.02.027

Electrolysis of malonate and alkylidenecyanoacetates in alcohols in an undivided cell in the presence of NaBr results in stereoselective formation of (E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates in 75-90% yields.

Full text of DOI:10.1016/j.tet.2006.02.027

Tetrahedron 62 (2006) 3989–3996
Stereoselective electrocatalytic transformation of malonate
and alkylidenecyanoacetates into (E)-3-substituted
2
-cyanocyclopropane-1,1,2-tricarboxylates
a,
a
b
*
Sergey K. Feducovich, Zoya A. Starikova, Anatolii N. Vereshchagin,
a
Michail N. Elinson,
a
Pavel A. Belyakov and Gennady I. Nikishin
a
a
N.D. Zelinsky Institute of Organic Chemistry, Leninsky prospect 47, 119991 Moscow, Russian Federation
A.N. Nesmeyanov Institute of Organoelement compounds, ul. Vavilova 28, 119991 Moscow, Russian Federation
b
Received 10 November 2005; revised 19 January 2006; accepted 10 February 2006
Available online 9 March 2006
Abstract—Electrolysis of malonate and alkylidenecyanoacetates in alcohols in an undivided cell in the presence of NaBr results in
stereoselective formation of (E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates in 75–90% yields.
q 2006 Published by Elsevier Ltd.
1
. Introduction
The present study continues investigations on electro-
chemical transformations of CH-acids, such as malononitr-
ile, cyanoacetic ester, and malonic ester, into functionalized
cyclopropanes in the presence of mediators, viz., alkali
metal halides. In our earlier studies of electrocatalytic
oxidation of organic compounds in the presence of
mediators, we have performed electrochemical cyclotrimer-
Functionalized cyclopropanes possess a wide spectrum of
1
physiological activities and belong to an important class of
compounds used in the synthesis of natural biologically
–3
1
active substances.
Cyclopropanecarboxylic acid deriva-
tives are successfully used in medicine and agriculture.
Naturally occurring and synthetic pyrethroids have found
wide application as insecticides.
8
9
ization of malonic and cyanoacetic esters, transformations
of aldehydes and cyanoacetic ester into functionalized
1
,4
10
cyclopropanes, and ketones and malononitrile into 3,3-
disubstituted tetracyanocyclopropanes.
1
1
Due to extensive research into electrochemistry of organic
compounds conducted over the past three decades,
electrosynthesis has become a competitive method of
The latter process is an electrochemical variant of the
Wideqvist reaction, i.e., the reaction of bromomalononitrile
with ketones in the presence of stoichiometric amounts of
5
modern organic chemistry. Electrochemical synthesis is
assuming increasing importance because of its great and,
in some cases, unique possibilities for performing various
1
2
sodium iodide.
6
transformations of organic compounds.
The electrochemical modification of this reaction is
performed with the use of malononitrile instead of
bromomalononitrile and catalytic amounts of sodium
bromide, which is completely regenerated during the
The use of mediators and mediator systems for electro-
reduction and electrooxidation of organic compounds was
an important stage in the development of electrosynthesis.
Among numerous mediators, a halide anion—halogen
system is one of the most promising mediator systems for
1
3
reaction.
7
Several years ago, we developed a new procedure for the
synthesis of functionalized cyclopropanes based on simul-
application in organic synthesis.
1
4,15
taneous electrolysis of CH-acids and activated olefins
Scheme 1).
(
Keywords: Electrolysis; Stereoselectivity; Electrocatalytic transformation;
Malonate;
Mediators;
cyclopropanes.
Alkylidenecyanoacetates;
Substituted
Recently, we have performed the ‘one-pot’ electrocatalytic
transformation of malonic ester and alkylidenemalononi-
triles into 3-substituted 2,2-dicyanocyclopropane-1,1-
*
Corresponding author. Tel. C7 95 137 38 42; fax: C7 95 135 53 28;
e-mail: elinson@ioc.ac.ru
0040–4020/$ - see front matter q 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.02.027

3990
M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
Scheme 1.
Scheme 2.
Scheme 3.
dicarboxylic acid esters. This process was carried out in
alcohols in an undivided cell with the use of NaBr as
mediator (Scheme 2).
2. Results and discussion
1
6
Electrolysis of methyl malonate 1a or ethyl malonate 1b in
the presence of alkylidenecyanoacetic esters 2a–k in
methanol or ethanol, respectively, was carried out under
constant current mode in an undivided cell equipped with a
graphite anode and an iron cathode until complete
conversion of malonic and alkylidenecyanoacetic esters
was achieved.
In the present paper, we describe our results on investigation
of the stereoselective ‘one-pot’ electrocatalytic transform-
ation of malonic ester and alkylidenecyanoacetic esters into
(
E) isomers of trialkyl esters 3-substituted 2-cyanocyclo-
propane-1,1,2-tricarboxylic acids (3a–k). This reaction was
carried out in alcohols (methanol or ethanol) in an undivided
cell with the use of NaBr or NaI as a mediator (Scheme 3,
Table 1); for a preliminary communication, see Ref. 17.
The optimum temperature for simultaneous electrolysis
of malonic ester and alkylidenecyanoacetic esters, as in
a
Table 1. Electrocatalytic transformation of malonic esters 1a,b and alkylidenecyanoacetic esters 2a–k into cyclopropanes 3a–k
1
R
2
R
b
Malonic ester
Alkylidenecyanoacetic
ester
Temperature (8C)
Mediator
Cyclopropane
Yield (%)
c
1a
1a
1a
1b
1a
1a
1a
1a
1a
1b
1a
1a
1a
1a
1a
Me
Me
Me
Et
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Me
2a
2a
2a
2b
2a
2c
2d
2e
2f
2g
2h
2i
2i
2j
2k
Ph
Ph
Ph
Ph
Ph
4-MeC
4-MeOC
2-ClC
4-ClC
4-ClC
20
10
0
0
0
0
0
0
0
0
0
0
0
0
0
NaBr
NaBr
NaBr
NaBr
NaI
NaBr
NaBr
NaBr
NaBr
NaBr
NaBr
NaBr
NaI
3a
3a
3a
3b
3a
3c
3d
3e
3f
3g
3h
3i
3i
3j
3k
(35)
c
(61)
81 (92)
c
82
67
83
87
81
87
83
93
88
71
79
75
6
H
4
6
H
4
6
6
6
H
H
H
4
4
4
3-BrC
Me
Me
Et
6
H
4
NaBr
NaBr
n-Pr
a
2
Malonic ester (10 mmol), alkylidenecyanoacetic ester (10 mmol), mediator (5 mmol), alcohol (20 ml), Fe cathode, C anode, current density 100 mA/cm ,
.0 F/mol of electricity was passed.
3
b
c
Based on the isolated cyclopropane.
The yields given in parentheses were determined from H NMR spectroscopic and GLC data.
1

M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
3991
the case of co-electrolysis of malonic ester and alkylidene-
malononitrile, is 0 8C. An increase in the temperature up to
C10 or C20 8C (at C20 8C, electrolysis of malonic ester in
ester and alkylidenecyanoacetic esters into (E)-3-substituted
2-cyanocyclopropane-1,1,2-tricarboxylic acid esters.
1
4
the presence of alkylidenemalonates was performed) leads
to a substantial decrease in the yield of cyclopropanes 3a–k,
and the reaction gives a considerable amount of oligomeric
compounds, which hinders isolation of cyclopropanes 3a–k.
Reactions at electrodes are usual for the mediator system
consisting of the halide anion and molecular halogen in
alcohols. These reactions involve the formation of halogen
at the anode and liberation of hydrogen at the cathode
resulting in the generation of alkoxide ions (Scheme 4):
As in the analogous reactions of malonic ester with
1
4
16
alkylidenemalonates
reactions of cyanoacetic ester with alkylidenecyanoacetic
or alkylidenemalononitriles,
1
5
esters, and reactions of malononitrile with alkylidene-
malononitriles, sodium bromide is a more efficient as
mediator than NaI for the electrocatalytic process studied.
Thus, with the use of NaBr as a mediator the cyclopropanes
1
8
Scheme 4.
Then malonate anions appear in solution as a result of the
reaction of the electrogenerated alkoxide ions with malonic
ester (Scheme 5):
3
a–k were obtained in higher yields.
In co-electrolysis of ester 1a and benzylidenecyanoacetic
ester 2a when a quantity of electricity was less than the
optimum value of 3 F/mol (0.5 and 1.0 F/mol), trimethyl
Scheme 5.
3
3
-cyanopropane-2-phenyl-1,1,3-tricarboxylate (4) (57 and
6% yields, respectively) was detected by H NMR
1
The reaction of the malonate anion with activated olefin 2
yields the anion (A) (Scheme 6):
spectroscopy along with cyclopropane 3a (16 and 37%
yields, respectively).
The formation of only one of two possible isomers of
13
1
cyclopropanes 3a–k was established by the H and
C
NMR spectroscopic data. The structures of 3a and 3i were
1
7
established by X-ray diffraction. Taking into account the
factor of the minimum steric hindrance in the cyclopropane
ring formation, all cyclopropanes 3 should have a structure
containing the cyano group and R -substituent in cis
arrangement (Fig. 1).
Scheme 6.
2
Subsequent halogenation of the anion A and cyclization
under the action of alkoxide ions could afford functionalized
cyclopropane 3 (Scheme 7).
However, this mechanism could provide the observed
stereoselectivity of the cyclopropane 3 formation only if
halogenation of the anion A occurred stereoselectively.
The more probable is the existence of another process
involving the initial halogen transfer by the Hal transfer
C
T
1
mechanism giving rise to an anion (B) followed by
9
thermodynamically controlled cyclization (Scheme 8).
Stereoselective thermodynamically controlled cyclization
was also observed in electrocatalytic cyclotrimerization of
cyanoacetic ester into trans-1,2,3-tricyanocyclopropane-
9
1,2,3-tricarboxylic acid ester.
Earlier, NaI was shown to be a more efficient mediator for
electrocatalytic cyclization of 2-substituted propane-
2
,1,3,3-tetracarboxylic acid esters than NaBr. This fact
0
1
is associated with the higher selectivity of iodine as an
oxidant of the 2-substituted propane-1,1,3,3-tetracarboxylic
acid esters anion in the presence of alkoxide ions compared
to bromine.
Figure 1. Molecule structure of 3a.
Based on our results and the data on the electrochemical
transformation of malonic ester and alkylidenemalonic
esters or alkylidenemalononitriles into functionalized
cyclopropanes, we suggest the following mechanism for the
stereoselective electrocatalytic transformation of malonic
In the electrocatalytic process under consideration, NaBr is
a more efficient mediator for the stereoselective transform-
ation of malonic ester and alkylidenecyanoacetic esters into
(E)-3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylic
acid esters 3a–k compared to NaI.
1
4
16

3992
M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
Scheme 7.
Scheme 8.
Scheme 9.
Most likely, this result is attributed to the presence of
another way of the electrocatalytic process (Scheme 9).
Table 2. Stereoselective electrocatalytic transformation of methyl
cyanoacete and alkylidenemalonic esters 5a,b into cyclopropanes 3a,j
a
Alkylide-
nemalonic
ester
R
Temperature Mediator
(8C)
Cyclopropane Yield
b
(%)
The fact that electrolysis of malonic ester in alcohols in the
presence of NaBr in an undivided cell produces the
bromomalonate anion has been established previously.
2
1
5
5
5
5
5
5
a
a
a
a
b
b
Ph
Ph
Ph
Ph
Et
Et
Et
Et
0
K10
K20
K20
0
NaBr
NaBr
NaBr
NaI
NaBr
NaBr
NaBr
NaI
3a
3a
3a
3a
3j
26
35
43
34
33
45
51
43
The high efficiency of NaBr as a mediator for the reaction
pathway shown in Scheme 9 is associated with the fact that
bromomalonic ester is a stronger CH-acid compared to
iodomalonic ester due to which the step (2) involving the
proton abstraction by the alkoxide ion occurs more rapidly
in bromomalonic ester than in iodomalonic ester. Besides, it
is also probable that the addition of the bromomalonate
anion to activated olefin 2 occurs more rapidly in the
step (3).
K10
K20
K20
3j
3j
3j
5b
5
b
a
Methyl cyanoacete (10 mmol), 5a or 5b (10 mmol), a mediator (5 mmol)2,
MeOH (20 ml), Fe cathode, C anode, the current density 100 mA/cm ,
3.0 F/mol of electricity was passed.
The H NMR spectroscopic and GLC data.
1
b
The formation of 3-substituted-2-cyanocyclopropane-1,1,2-
tricarboxylic acid esters 3a,j was also investigated by
performing the alternative electrolysis of cyanoacetic ester
and alkylidenemalonic esters 5 (Table 2, Scheme 10).
electrolysis of malonic ester and alkylidenecyanoacetic
esters at 0 8C.
The lower yields of cyclopropanes 3 prepared according to
the second approach (Table 2) are, apparently, attributable
to the following facts: (1) alkylidenemalonic esters are more
However, as it follows from the data of Table 2, in this case
the synthesis of cyclopropanes 3 requires that the
electrolysis was performed at lower temperature
2
2
prone to reductive dimerization compared to the competi-
tive addition of cyanoacetate or halocyanoacetate anions;
(2) the oligomerization of cyanoacetic ester in the presence
(
at K20 8C rather than at 0 8C, see Tables 1 and 2).
9
,23
of bases,
unlike malonic ester, which is stable under
It should also be noted that the reaction performed
according to Scheme 10, even at K20 8C, produces cyclic
esters 3a,j (Table 2) in 30–50% lower yields than those
obtained as described above (Table 1) by simultaneous
these conditions; (3) the reaction proceeds through the
intermediate formation of the anion (C), which can undergo
the transformation and decomposition giving rise to the
malonate anion according to the Scheme 11.

M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
3993
Scheme 10.
Scheme 11.
Scheme 12.
Transformations analogous to those presented in Scheme 11
have been described earlier for the reactions of substituted
benzylidenemalononitriles with the cyanoacetate anion.
halomalonic ester to the double bond of alkylidenecyano-
acetic ester followed by cyclization.
2
5
2
4
Thus, we developed a convenient and simple electrocata-
lytic procedure for the stereoselective transformation of
malonic ester and alkylidenecyanoacetic esters into (E)-3-
substituted 2-cyanocyclopropane-1,1,2-tricarboxylic acid
esters. This method requires the use of standard and
commercially available reagents, inexpensive apparatus,
and an undivided cell. The techniques for electrolysis and
isolation of the reaction products are simple and convenient
to use both under laboratory conditions and in large-scale
apparatus.
Electrolysis of malonate anions thus generated and alkyl-
idenemalonic ester produces cyclic ester 6 (Scheme 12).
Electrolysis of methyl cyanoacetate and benzylidenemalo-
nic ester 5a at 0, K10, and K20 8C afforded a mixture, in
which cyclic ester 3a (26, 35, and 43% yields, respectively),
ester 6 (RZPh) (23, 17, and 7%, respectively), and
tetramethyl 2,3-diphenylbutane-1,1,4,4-tetracarboxylate
1
7) (18, 13, and 6%, respectively) were detected by H
(
NMR spectroscopy and GLC analysis.
4. Experimental
3. Conclusion
All melting points were measured on a Gallenkamp melting
point apparatus and are uncorrected. GLC analyses were
carried out on a LKhM-80 chromatograph with a flame-
ionisation detector, 3 m!3 mm glass columns packed with
5% OV-17 on Inerton (0.16–0.20 mm) or 10% FFAP on
To summarize, we have performed simultaneous electro-
lysis of malonic ester and alkylidenecyanoacetic esters in an
undivided cell in the presence of a sodium halide as
mediator. With this method was realized the ‘one-pot’
stereoselective synthesis of (E)-3-substituted 2-cyanocyclo-
propane-1,1,2-tricarboxylic acid esters in 75–90% yields.
These compounds can be synthesized according to
conventional methods of organic chemistry in two steps:
1
Chromaton N-Super (0.13–0.16 mm), respectively. H and
C NMR spectra were recorded on Bruker WM-250,
1
3
Bruker AM-300 and Varian Unity 500-PLUS spectrometer
instruments operating at 250, 300 and 500 MHz, respec-
tively. The chemical shifts were measured on the d scale
(
1) halogenation of malonic ester and (2) the addition of

3994
M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
relative to Me Si. Mass-spectra (70 eV) were determined
4
directly using Finningan MAT INCOS 50 spectrometer.
CH O), 3.79 (s, 3H, CH O), 3.88 (s, 3H, CH O), 3.96 (s, 1H,
3 3 3
CH), 7.38 (m, 5H, C H ). C NMR (CDCl ), d: 30.6 (C),
6 5 3
1
3
3
(CH O), 112.4 (CN), 128.5, 128.7, 128.8, 129.3 (Ph), 162.7
9.6 (CH), 47.7 (C), 53.5 (CH O), 53.7 (CH O), 54.5
3 3
X-ray diffraction experiments were carried out on CAD4
Siemens P3/PC (3a) and Enraf-Nonius (3i) difractometers
3
(OC]O), 164.27 (OC]O), 164.8 (OC]O). MS (70 eV):
m/z (relative intensity %): 317 (M , 8), 286 (9), 258 (100),
C
(
T 293 K, graphite monochromated Mo Ka radiation,
qmaxZ258) The structures 3a and 3i were solved by direct
methods and refined by the full-matrix least-squares
198 (71), 121 (52), 59 (72). IR (KBr): nmax 2252, 1772,
1756, 1436, 1232. Anal. Calcd for C H NO : C, 60.57; H,
4.76; N, 4.41. Found: C, 60.39; H, 4.61; N, 4.25.
1
6
15
6
2
hkl
technique on F
in the anisotropic approximation. H
atoms were located from the difference Fourier synthesis
and then refined isotropically. The final values of R factors
Crystal data for 3a: C H NO , MZ317.29, rhombic,
1
6
15
6
˚
˚
were as follows: R Z0.039 (912 observed reflections),
space group P2 2 2 , aZ9.715(5) A, bZ10.693(5) A, cZ
1 1 1
3 K3
1
˚
˚
wR Z0.2348 (for all 1547 reflections) for 3a, and R Z
15.013(8) A, VZ1559.9(14) A , ZZ4, D Z1.351 g cm
.
2
1
c
0
.0580 (1704 observed reflections), wR Z0.1278 (for all
2
2226 reflections used in refinement) for 3i. All calculations
were carried out with the complex of programs SHELXTL.
4.1.2. (E)-Triethyl 2-cyanocyclopropane-3-phenyl-1,1,2-
tricarboxylate (3b). Yield 3.05 g (85%), colourless oil. H
1
NMR (CDCl ), d: 1.12 (t, CH , JZ7.1 Hz), 1.29 (t, CH ,
3
3
3
PLUS 5 [Sheldrick, G. M. SHELXTL Software Reference
Manual, Version 5, Siemens Industrial Automation, Inc.:
Madison, 1994].
JZ7.1 Hz), 1.38 (t, CH , JZ7.1 Hz), 3.93 (s, 1H, CH), 4.12
3
(q, 2H, CH O, JZ7.1 Hz), 4.20–4.45 (m, 4H, CH O), 7.25–
2
2
1
7.51 (m, 5H, C H ). C NMR (CDCl ), d: 13.4 (CH ), 13.6
3
6
5
3
3
(CH ), 13.8 (CH ), 30.6 (C), 39.0 (CH), 47.7 (C), 62.7
3 3
Crystallographic data for 3a and 3i (excluding structure
factors) have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication numbers
CCDC 284947 and CCDC 284948. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: C44 1223
(CH O), 62.8 (CH O), 64.0 (CH O), 112.5 (CN), 128.5,
2 2 2
128.6, 128.9, 129.6 (Ph), 162.3 (OC]O), 163.7 (OC]O),
164.2 (OC]O). MS (70 eV): m/z (relative intensity %): 359
(M , 3), 314 (5), 286 (100), 258 (32), 212 (23), 140 (32),
C
105 (17). IR (KBr): nmax 2256, 1752, 1448, 1264, 1232.
Anal. Calcd for C H NO : C, 63.50; H, 5.89; N, 3.90.
Found: C, 63.32; H, 5.93; N, 3.81.
1
9
21
6
3
36033 or e-mail: deposit@ccdc.cam.ac.uk].
Malonic and cyanoacetic esters were purchased from
Aldrich. Alkylidenecyanoacetic esters 2a–k and benzyl-
idene- and propylidenemalonic esters 5a,b were prepared by
Knoevenagel condensation of the corresponding alde-
hydes and cyanoacetic or malonic esters (Merck and
Aldrich).
4.1.3. (E)-Trimethyl 2-cyanocyclopropane-3-(4-methyl-
phenyl)-1,1,2-tricarboxylate (3c). Yield 2.75 g (83%),
1
white solid, mp 72–74 8C. H NMR (CDCl ), d: 2.34 (s,
3
2
6
3H, CH ), 3.72 (s, 3H, CH O), 3.83 (s, 3H, CH O), 3.89 (s,
3
3
3
1H, CH), 3.91 (s, 3H, OCH ), 7.18 (d, 2H, JZ8.3 Hz), 7.25
3
1
3
(d, 2H, JZ8.3 Hz). C NMR (CDCl ), d: 21.0 (CH ), 30.5
3
3
(C), 39.4 (CH), 47.6 (C), 53.4 (CH O), 53.6 (CH O), 54.4
(CH O), 112.4 (CN), 127.0, 128.2, 129.4, 138.5 (Ar), 162.6
3 3
4.1. General procedure for simultaneous electrolysis
of malonic ester and alkylidenecyanoacetic esters
3
(OC]O), 164.2 (OC]O), 164.8 (OC]O). MS (70 eV): m/
z (relative intensity %): 331 (M , 13), 300 (7), 272 (68),
C
A solution of malonic ester 1a,b (10 mmol), alkylidene-
cyanoacetic ester 2a–k (10 mmol), and a mediator (5 mmol)
in MeOH or EtOH (20 ml) was electrolyzed in an undivided
cell equipped with C-anode and Fe-cathode (the electrode
212 (100), 135 (52), 59 (76). IR (KBr): nmax 2252, 1756,
1748, 1436, 1232. Anal. Calcd for C H NO : C, 61.63; H,
5.17; N, 4.23. Found: C, 61.44; H, 4.98; N, 4.14.
1
7
17
6
2
surface area was 5 cm ) thermometer, external cooling and
magnetic stirring at a constant current density of 100 mA/
4.1.4. (E)-Trimethyl 2-cyanocyclopropane-3-(4-methoxy-
phenyl)-1,1,2-tricarboxylate (3d). Yield 3.01 g (87%),
2
cm by passing 3.0 F/mol of electricity. At the end of
1
white solid, mp 110–112 8C. H NMR (CDCl ), d: 3.72 (s,
3
electrolysis, the solution was additionally cooled to
K10 8C. The precipitate of cyclopropane 3 that formed
was filtered off and washed with cooled to 5 8C alcohol. An
additional amount of cyclopropane 3 was isolated as
follows. The reaction mixture was concentrated, extracted
with chloroform, washed with water, and dried over
Na SO . The chloroform was distilled off. The residue
was crystallised from an acetone–hexane or diethyl ether–
hexane mixture, and cyclopropane 3 was isolated. After
evaporation of the reaction mixture, cyclopropanes 3b,c,g
were isolated by flash chromatography (eluent chloroform/
hexane 1:1) and cyclopropanes 3j,k were isolated by
vacuum distillation.
3H, CH O), 3.80 (s, 3H, CH O), 3.82 (s, 3H, CH O), 3.87 (s,
3
3
3
1H, CH), 3.91 (s, 3H, CH O), 6.88 (d, 2H, Ar, JZ8.2 Hz),
3
1
3
7.29 (d, 2H, Ar, JZ8.2 Hz). C NMR (CDCl ), d: 30.7 (C),
3
39.3 (CH), 47.8 (C), 53.5 (CH O), 53.7 (CH O), 54.5
(CH O), 55.2 (CH O), 112.5 (CN), 114.2, 124.2, 129.7,
3
3
3
3
159.7 (Ar), 162.7 (OC]O), 164.3 (OC]O), 164.8
(OC]O). MS (70 eV): m/z (relative intensity %): 347
(M , 57), 316 (3), 288 (13), 228 (100), 170 (39), 151 (38),
2
4
C
59 (82). IR (KBr): nmax 2252, 1756, 1752, 1440, 1240. Anal.
Calcd for C H NO : C, 58.79; H, 4.93; N, 4.03. Found: C,
58.61; H, 4.84; N, 3.92.
1
7
17
7
4.1.5. (E)-Trimethyl 3-(2-chlorophenyl)-2-cyanocyclo-
propane-1,1,2-tricarboxylate (3e). Yield 2.85 g (81%),
1
white solid, mp 97–99 8C. H NMR (CDCl ), d: 3.78 (s, 3H,
4
1
.1.1. (E)-Trimethyl 2-cyanocyclopropane-3-phenyl-
,1,2-tricarboxylate (3a). Yield 2.57 g (81%), white
3
CH O), 3.83 (s, 3H, CH O), 3.88 (s, 1H, CH), 3.94 (s, 3H,
3
3
1
13
CH O), 7.25–7.48 (m, 4H, Ar). C NMR (CDCl ), d: 31.4
3 3
solid, mp 140–142 8C. H NMR (CD CN), d: 3.70 (s, 3H,
3

M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
3995
(
C), 38.6 (CH), 47.4 (C), 53.6 (CH O), 53.7 (CH O), 54.7
3
Calcd for C H NO : C, 51.77; H, 5.13; N, 5.49. Found: C,
11 13 6
3
(
CH O), 112.2 (CN), 127.1, 127.5, 129.9, 130.1, 134.9 (Ar),
3
51.55; H, 4.98; N, 5.38.
1
(
62.9 (OC]O), 164.2 (OC]O), 164.8 (OC]O). MS
70 eV): m/z (relative intensity %): 351 (M , 8), 320 (7),
C
Crystal data for 3i: C H NO , MZ255.22, monoclinic,
1
13
6
˚
˚
2
1
5
92 (100), 232 (36), 155 (33), 59 (89). IR (KBr): nmax 2256,
760, 1748, 1440, 1236. Anal. Calcd for C H ClNO : C,
4.64; H, 4.01; Cl, 10.08; N, 3.98. Found: C, 54.43; H, 3.95;
space group P2 /n, aZ8.972(3) A, bZ15.159(7) A, cZ
1
3
˚
˚
9.732(4) A, bZ106.89(3)8, VZ1266.5(9) A , ZZ4, D Z
c
K3
1
6
14
6
1.339 g cm
.
Cl, 9.87; N, 3.84.
4.1.10. (E)-Trimethyl 2-cyano-3-ethylcyclopropane-
1,1,2-tricarboxylate (3j). Yield 2.13 g (79%), colourless
4.1.6. (E)-Trimethyl 3-(4-chlorophenyl)-2-cyanocyclo-
propane-1,1,2-tricarboxylate (3f). Yield 3.06 g (87%),
1
oil, bp 131–143 8C (0.10 Torr). H NMR (CDCl ), d: 1.03 (t,
3
1
white solid, mp 73–75 8C. H NMR (CDCl ), d: 3.76 (s, 3H,
3H, CH , JZ7.3 Hz), 1.68–1.84 (m, 2H, CH ), 2.61 (t, 1H,
3
3
2
CH O), 3.84 (s, 3H, CH O), 3.87 (s, 1H, CH), 3.93 (s, 3H,
3
CH, JZ7.3 Hz), 3.72 (s, 3H, CH O), 3.81 (s, 6H, CH O).
C NMR (CDCl ), d: 12.2 (CH ), 18.0 (CH ), 30.4 (C),
3 3 2
3
3 3
1
CH O), 7.23–7.45 (m, 4H, Ar). C NMR (CDCl ), d: 30.5
3
13
3
3
(
(
(
C), 38.6 (CH), 47.5 (C), 53.5 (CH O), 53.6 (CH O), 54.6
3
CH O), 112.1 (CN), 127.7, 129.0, 129.8, 134.8 (Ar), 162.4
3
38.2 (CH), 46.8 (C), 53.5 (CH O), 53.7 (CH O), 54.3
3 3
(CH O), 112.5 (CN), 163.25 (OC]O), 164.4 (OC]O),
3
3
OC]O), 164.0 (OC]O), 164.5 (OC]O). MS (70 eV): m/
164.8 (OC]O). MS (70 eV): m/z (relative intensity %): 269
(M , 5), 238 (12), 210 (63), 178 (57), 146 (29), 133 (37), 59
C
C
z (relative intensity %): 351 (M , 8), 320 (6), 292 (72), 232
(
1
51), 174 (21), 155 (36), 59 (100). IR (KBr): nmax 2256,
756, 1744, 1440, 1232. Anal. Calcd for C H ClNO : C,
(100). IR (KBr): nmax 2252, 1755, 1748, 1436, 1238. Anal.
Calcd for C H NO : C, 53.53; H, 5.62; N, 5.20. Found: C,
53.35; H, 5.48; N, 5.31.
1
6
14
6
12 15
6
5
4.64; H, 4.01; Cl, 10.08; N, 3.98. Found: C, 54.71; H, 4.09;
Cl, 10.15; N, 3.75.
.1.7. (E)-Triethyl 3-(4-chlorophenyl)-2-cyanocyclopro-
pane-1,1,2-tricarboxylate (3g). Yield 3.27 g (83%), col-
4.1.11. (E)-Trimethyl 2-cyanocyclopropane-3-propyl-
1,1,2-tricarboxylate (3k). Yield 2.18 g (77%), colourless
4
1
oil, bp 140–142 8C (0.08 Torr). H NMR (CDCl ), d: 0.98 (t,
3
1
ourless oil. H NMR (CDCl ), d: 1.08 (t, CH , JZ7.1 Hz),
3H, CH , JZ7.3 Hz), 1.46–1.58 (m, 2H, CH ), 1.73–1.83
3
3
3
2
1
.24 (t, CH , JZ7.1 Hz), 1.35 (t, CH , JZ7.1 Hz), 3.91 (s,
(m, 2H, CH ), 2.62 (t, 1H, CH, JZ7.3 Hz), 3.73 (s, 3H,
2
13
3
3
1
H, CH), 4.15–4.45 (m, 6H, CH O), 7.20–7.45 (m, 4H, Ar).
C NMR (CDCl ), d: 13.47 (CH ), 13.53 (CH ), 13.8
CH O), 3.82 (s, 6H, CH O). C NMR (CDCl ), d: 13.3
3 3 3
2
1
3
3
3
3
(CH ), 21.2 (CH ), 26.2 (CH ), 30.4 (C), 36.7 (CH), 46.6
3 2 2
(
CH ), 33.1 (C), 38.2 (CH), 46.7 (C), 62.8 (CH O), 62.9
3
(C), 53.4 (CH O), 53.5 (CH O), 54.2 (CH O), 112.6 (CN),
3 3 3
2
(
CH O), 64.1 (CH O), 112.4 (CN), 128.9, 129.4, 129.9,
2
163.3 (OC]O), 164.4 (OC]O), 164.9 (OC]O). MS
(70 eV): m/z (relative intensity %): 283 (M , 2), 252 (17),
2
C
1
33.8 (Ar), 163.4 (OC]O), 166.1 (OC]O), 167.5
OC]O). MS (70 eV): m/z (relative intensity %): 393
(
(
224 (71), 192 (65), 160 (28), 132 (88), 59 (100). IR (KBr):
nmax 2252, 1748, 1742, 1436, 1236. Anal. Calcd for
C H NO : (%): C, 55.12; H, 6.05; N, 4.94. Found: C,
C
M , 6), 348 (7), 320 (100), 246 (98), 202 (91), 174 (78),
1
Anal. Calcd for C H ClNO : (%): C, 57.95; H, 5.12; Cl,
69 (78). IR (KBr): nmax 2252, 1752, 1736, 1440, 1260.
13
17
6
1
9
20
6
54.93; H, 6.11; N, 4.71.
9
.00; N, 3.56. Found: C, 57.74; H, 5.15; Cl, 8.91; N, 3.43.
4
.1.12. Trimethyl 2-phenyl-3-cyanopropane-1,1,3-tri-
4.1.8. (E)-Trimethyl 3-(3-bromophenyl)-2-cyanocyclo-
propane-1,1,2-tricarboxylate (3h). Yield 3.88 g (98%),
carboxylate (4). The solution of Na (1 mmol) in 5 ml of
methanol was added to solution of dimethyl malonate
(10 mmol) and methyl benzylidenecyanoacetate (10 mmol)
at room temperature. After 30 min the resulting solid was
filtered off. The solvent was evaporated, the residue was
extracted with 30 ml of chloroform, washed with water and
dried over Na SO . Chloroform was removed under reduced
1
yellow solid, mp 89–91 8C. H NMR (CDCl ), d: 3.73 (s,
3
3
3
H, CH O), 3.80 (s, 3H, CH O), 3.87 (s, 1H, CH), 3.89 (s,
3 3
H, CH O), 7.20–7.33 (m, 2H, Ar), 7.40–7.50 (m, 2H, Ar).
3
1
3
C NMR (CDCl ), d: 30.4 (C), 38.4 (CH), 47.3 (C), 53.6
3
(
CH O), 53.7 (CH O), 54.6 (CH O), 111.9 (CN), 122.4,
3 3 3
2
4
1
1
28.1, 130.3, 131.46, 131.53, 131.7 (Ar), 162.4 (OC]O),
63.8 (OC]O), 164.4 (OC]O). MS (70 eV): m/z (relative
pressure and the residue together with the first solid part
were crystallised from methanol. After crystallization 4 was
obtained as a mixture of two diastereomers (ratio 10:1),
2.55 g, 85% yield, white solid, mp 87–89 8C. Main
C
C
intensity %): 397 (M , 15), 395 (M , 14), 364 (3), 366 (2),
38 (61), 336 (78), 278 (28), 276 (34), 201 (25), 199 (27), 59
100). IR (KBr): nmax 2268, 1756, 1746, 1440, 1232. Anal.
Calcd for C H BrNO : C, 48.51; H, 3.56; Br, 20.17; N,
3
(
1
diastereomer H NMR (CDCl ), d: 3.52 (s, 3H, OCH ),
3
3
1
6
14
6
3.77 (s, 3H, CH O), 3.82 (s, 3H, CH O), 4.16 (dd, 1H, CH,
3
3
3
.54. Found: C, 48.35; H, 3.47, Br, 19.93; N, 3.29.
J Z5 Hz, J Z11 Hz), 4.25 (d, 1H, CH, JZ5 Hz), 4.38 (d,
1 2
1
H, CH, JZ11 Hz), 7.30–7.40 (m, 5H, Ph). Minor
1
4
1
.1.9. (E)-Trimethyl 2-cyanocyclopropane-3-methyl-
,1,2-tricarboxylate (3i). Yield 2.24 g (88%), white solid,
diastereomer H NMR (CDCl ), d: 3.47 (s, 3H, OCH ),
3 3
3.63 (s, 3H, CH O), 3.86 (s, 3H, CH O), 4.14 (dd, 1H, CH,
3 3
J Z5 Hz, J Z11 Hz), 4.18 (d, 1H, CH, JZ11 Hz), 4.54 (d,
1 2
1
mp 87–89 8C. H NMR (CDCl ), d: 1.45 (d, 3H, CH , JZ
3
3
6
3
.7 Hz), 2.67 (q, 1H, CH, JZ6.7 Hz), 3.70 (s, 3H, CH O),
1H, CH, JZ5 Hz), 7.30–7.40 (m, 5H, Ph). Main diaster-
3
1
.79 (s, 6H, CH O). C NMR (CDCl ), d: 9.6 (CH ), 31.0
3
13
eomer C NMR (CDCl ), d: 41.86 (CH), 44.81 (CH),
3
3
3
3
(
(
C), 31.8 (CH), 47.0 (C), 53.61 (CH O), 53.8 (CH O), 54.4
3
CH O), 112.6 (CN), 163.2 (OC]O), 164.4 (OC]O),
3
52.68, 53.10, 53.49, 54.17 (3OCH and CH), 115.07 (CN),
3
3
128.02, 128.75, 128.93, 136.20 (Ph), 165.20 (OC]O),
167.12 (OC]O), 168.00 (OC]O). Minor diastereomer C
1
3
164.9 (OC]O). MS (70 eV): m/z (relative intensity %): 255
M , 2), 224 (8), 196 (51), 164 (32), 137 (7), 92 (11), 59
C
(
NMR (CDCl ), d: 41.89 (CH), 43.97 (CH), 53.08, 53.25,
3
(
100). IR (KBr): nmax 2256, 1756, 1744, 1444, 1240. Anal.
53.33, 53.75 (3OCH3 and CH), 114.85 (CN), 128.48,

3996
M. N. Elinson et al. / Tetrahedron 62 (2006) 3989–3996
1
(
28.66, 128.71, 134.68 (Ph), 164.86 (OC]O), 166.85
OC]O), 167.97 (OC]O). IR (KBr): nmax 2260, 1732,
6. Organic Electrochemistry; Lund, H., Ed. 4th ed. (revised and
expanded); Marcel Dekker: New York, 2000.
1
6
456, 1252, 1228. Anal. Calcd for C H NO : (%): C,
1
0.18; H, 5.37; N, 4.39. Found: C, 60.25; H, 5.26; N, 4.28.
7. Shono, T. Electroorganic Chemistry as a New Tool in Organic
Synthesis; Springer: Berlin, 1994.
6
17
6
8
. Nikishin, G. I.; Elinson, M. N.; Feducovich, S. K. Izv. Acad.
Nauk SSSR, Ser. Khim. 1986, 1919–1920.
4
.1.13. Tetramethyl 3-phenylcyclopropane-1,1,2,2-tetra-
carboxylate (6). The title compound was prepared
9
. Elinson, M. N.; Lizunova, T. L.; Dekaprilevich, M. O.;
Struchkov, Yu. T.; Nikishin, G. I. Mendeleev Commun. 1993,
1
according to a known procedure, mp 85–86 8C (cf. lit.
4
2
7
1
data: mp 87 8C). H NMR (CDCl ), d: 3.66 (s, 6H, CH O),
1
91–192.
3
3
1
1
0. Elinson, M. N.; Lizunova, T. L.; Ugrak, B. I.; Dekaprilevich,
M. O.; Nikishin, G. I. Tetrahedron Lett. 1993, 33, 5795–5798.
1. Nikishin, G. I.; Elinson, M. N.; Lizunova, T. L.; Ugrak, B. I.
Tetrahedron Lett. 1991, 32, 2655–2656.
3
.78 (s, 1H, CH), 7.20–7.35 (m, 5H, Ph).
4.1.14. Tetramethyl 2,3-diphenylbutane-1,1,4,4-tetra-
carboxylate (7). The title compound was prepared
2
2
1
2. Wideqvist, S. Arkiv. Kemi 1945, 20B, 8–14.
3. Elinson, M. N.; Feducovich, S. K.; Lizunova, T. L.; Nikishin,
G. I. Tetrahedron 2000, 56, 3063–3069.
according to a known procedure in 58% yield as a
mixture of meso and D,L isomers in a ratio of 2:1. The meso
form was isolated by crystallization from methanol. The D,L
form was isolated by column chromatography of the residue
obtained after crystallization; a 2:1 diethyl ether/hexane
mixture was used as the eluent. The meso form 7 was also
isolated by crystallization from the reaction mixture, which
was obtained by simultaneous electrolysis of methyl
cyanoacetate and benzylidenemalonic ester 5a at 0 8C
1
1
1
1
1
1
4. Elinson, M. N.; Feducovich, S. K.; Bushuev, S. G.;
Zakharenkov, A. A.; Pashchenko, D. V.; Nikishin, G. I.
Mendeleev Commun. 1998, 15–17.
5. Elinson, M. N.; Feducovich, S. K.; Bushuev, S. G.;
Pashchenko, D. V.; Nikishin, G. I. Izv. Acad. Nauk, Ser.
Khim. 1998, 1165–1168.
6. Elinson, M. N.; Feducovich, S. K.; Zaimovskaya, T. A.;
Vereshchagin, A. N.; Nikishin, G. I. Izv. Acad. Nauk, Ser.
Khim. 2005, 1547–1552.
(Table 2), in 9% yield. The physicochemical and spectro-
scopic characteristics of the meso- and D,L-7 forms were
analogous to those described earlier.
2
2
7. Elinson, M. N.; Feducovich, S. K.; Starikova, Z. A.; Olessova,
O. S.; Vereshchagin, A. N.; Nikishin, G. I. Tetrahedron Lett.
2
000, 41, 4937–4941.
Acknowledgements
8. Elinson, M. N.; Feducovich, S. K.; Vereshchagin, A. N.;
Dorofeev, A. S.; Dmitriev, D. E.; Nikishin, G. I. Izv. Acad.
Nauk, Ser. Khim. 2003, 2117–2121.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 03-03-32068)
and the Program for Support of Leading Scientific Schools
1
2
2
9. Bordwell, F. G.; Clemens, A. H.; Smith, D. E.; Begemann, J.
J. Org. Chem. 1985, 50, 1151–1156.
(
Grant No. 2121.2003.3).
0. Elinson, M. N.; Feducovich, S. K.; Nikishin, G. I. Izv. Acad.
Nauk, Ser. Khim. 1990, 2783–2789.
1. Elinson, M. N.; Feducovich, S. K.; Nikishin, G. I. Izv. Acad.
Nauk, Ser. Khim. 1989, 352–355.
References and notes
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Yu. T. Tetrahedron 1995, 51, 5035–5046.
1
2
Tsiklopropani s funktsionalnimi gruppami. Sintez i primene-
nie. (Cyclopropanes with Functional Groups. Synthesis and
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. Tsuji, S.; Nishida, S. The Chemistry of the Cyclopropyl Group;
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