Synthesis of Substituted β-Styrylmalonates by Sequential Isomerization of 2-Arylcyclopropane-1,1-dicarboxylates and (2-Arylethylidene)malonates

Article abstract of DOI:10.1055/a-1348-4311

A method has been developed for the synthesis of substituted β-styrylmalonates by conversion of 2-arylcyclopropane-1,1-dicarboxylates (ACDCs) in the presence of gallium trichloride into the corresponding- 1,2-zwitterionic intermediates or (2-arylethyl-idene)malonates, followed by treatment with pyridine at room temperature leading to an isomerization of the emerging double bond. This method allows one to expand these reactions to include ACDCs with acceptor substituents at the aromatic ring.

Full text of DOI:10.1055/a-1348-4311

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–G
paper
A
en
D. D. Borisov et al.
Paper
Synthesis
Synthesis of Substituted -Styrylmalonates by Sequential Isomeri-
zation of 2-Arylcyclopropane-1,1-dicarboxylates and (2-Arylethyl-
idene)malonates
Denis D. Borisova
Grigorii R. Chermashentseva,b
Roman A. Novikov*a
R
R
CO2Me
Y
1) GaCl3 (1.4 equiv)
CH2Cl2, 0–40 °C
CO2Me
CO2Me
Ar
CO2Me
2) Pyridine (10 equiv)
CH2Cl2, 25 °C
12 examples
22–72%
Yury V. Tomilov*a
R = H; Y = H, 4-Me, 4-F, 3-Br, 2-Cl, 4-NO2, 3-NO2,
4-CF3, 3,5-(CF3)2, 2-Cl-6-F, 1-naphthyl
R = Ph; Y = H
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
novikovfff@bk.ru
tom@ioc.ac.ru
b Department of Chemistry, Lomonosov Moscow State University,
1 Leninskie Gory, 119991 Moscow, Russian Federation
YRNeMuo. mDrai.iCaVlZnont.eorToAlrmiovne.miNss@kpkioiolyovonciIfvknfd.afosi@cntv.ibrgtukuA.trueutohfoOrsrganic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation
Received: 06.12.2020
Accepted after revision: 08.01.2021
Published online: 08.01.2021
on the reactions of -styrylmalonates 1 with aromatic alde-
hydes in the presence of various Lewis acids and under di-
verse reaction conditions. We also suggested new ways for
synthesizing indene3a and dihydropyranone structures,3b
polycyclic lactones,3a,c as well as asymmetrically substituted
1,4-(cyclopentathienyl)benzenes.3d
DOI: 10.1055/a-1348-4311; Art ID: ss-2020-t0626-op
Abstract A method has been developed for the synthesis of substi-
tuted -styrylmalonates by conversion of 2-arylcyclopropane-1,1-dicar-
boxylates (ACDCs) in the presence of gallium trichloride into the
corresponding 1,2-zwitterionic intermediates or (2-arylethylidene)-
malonates, followed by treatment with pyridine at room temperature
leading to an isomerization of the emerging double bond. This method
allows one to expand these reactions to include ACDCs with acceptor
substituents at the aromatic ring.
We can explain the fact that information on the use of
-styrylmalonates 1 is fragmentary by the hard availability
of these compounds. Only a few examples of preparative
methods for synthesizing -styrylmalonates are reported in
the literature. The main method for the synthesis of unsub-
stituted -styrylmalonates 1 was reported by Trushkov’s
group10 who studied the isomerization of ACDC 2 on treat-
ment with TMSOTf or Sn(OTf)2 (Scheme 2). It should be
noted that the reported process has a number of limita-
tions: as a rule, it occurs at high temperatures of about 130
°C, TMSOTf is used in equimolar amounts, and only a limit-
ed number of ACDCs can be used in these processes. Simi-
larly, -styrylmalonates containing halogens or donor
groups at the aromatic ring can be prepared, as well as
some -heteroaryl-substituted vinylmalonates. Yet another
way to obtain -styrylmalonates 1 involves the cross-cou-
pling of -bromostyrene with malonic ester catalyzed by
copper salts.11 However, only a few examples were present-
ed in that work. The process was also considerably affected
by the electronic effects of the aromatic substituent in the
original -bromostyrene. Thus, styrylmalonates containing
only donor groups or halogen atoms at the aromatic ring
were mainly obtained.
Key words donor-acceptor
malonates, -styrylmalonates, gallium trichloride, isomerization
cyclopropanes,
(2-arylethylidene)-
-Styrylmalonates 1 are isomers of 2-arylcyclopropane-
1,1-dicarboxylates (ACDCs) 2, which, in turn, constitute the
most popular and accessible class of donor-acceptor cyclo-
propanes (DACs). The latter are widely used as versatile
building blocks allowing the use of both a three-membered
ring and donor as well as acceptor substituents.1 At present,
DACs have proven to be useful synthons in total syntheses
of natural compounds. Using DACs, various functionally
substituted compounds with a broad spectrum of chemical
and biological activity can be obtained.2 In view of this,
studies on the chemical transformations of -styryl-
malonates can become a continuation of the ACDC chemis-
try and a relevant area of organic chemistry since their be-
havior often differs from the reactions of ACDC them-
selves.3
Strangely enough, so far, the chemistry of -styryl-
malonates 1 remains a poorly studied area of organic syn-
thesis, even though these substrates have been known since
the late 1980s.4 Data on the chemical properties of -styryl-
malonates are very fragmentary. As a rule, they act either as
dipolarophiles in cycloaddition reactions or as CH acids
(Scheme 1A).4–9 Our team has published a series of works
Methods for the synthesis of -styrylmalonates with ad-
ditional substituents at the double bond were also report-
ed. They were based on the opening of donor-acceptor cy-
clopropenes on treatment with trimethylaluminum and
7
Fe(acac)3 or the cross-coupling of iodobenzenes with vinyl-
silanes.12 These methods also allow -styrylmalonates com-
prising only donor groups at the aromatic ring to be obtained.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
D. D. Borisov et al.
Paper
Synthesis
(A) Styrylmalonates as alkenes and CH-acids
Ph
RO2C
CO2R
CO2R
TsO
Ph
MeO
Me
MeO
Me
Ar1
NHTs
Ph
Ph
AlCl3
t-BuOK
Org. Lett. 2014, 16, 1856
CO2R
CO2R
1,2-DCE
J. Org. Chem. 1989, 54, 688
Ar1
styrylmalonates 1
CO2R
CO2R
Ph
MgI2
Ts
RO2C
Sn(OTf)2
PhCl
N
CO2R
Ts
N
CO2R
RO2C
RO2C
RO2C
Ph
Ph
Ph
Chem. Commun. 2013, 49, 11482
Ph
Adv. Synth. Cat. 2018, 360, 3687
(B) Reactions of styrylmalonates with aromatic aldehydes
Ar2
CO2Me
CO2Me
Ar2
Ar1
O
O
CO2Me
BF3·OEt2
Ar2
+
O
Ar1
S
CO2Me
1
CO2Me
Ar1
ref. 3b: Org. Lett. 2017, 19, 3731.
GaCl3
GaCl3
Ar2
Ar2
H
S
Ar2
Ar1
Ar1
O
O
H
CO2R
CO2Me
CO2Me
MeO2C
Ar1
CO2Me
ref. 3a: Angew. Chem. Int. Ed. 2016, 55, 12233
ref. 3d: Tetrahedron Lett. 2019, 60, 746
Scheme 1 Some known reactions of -styrylmalonates 1
In this work, we expanded the method for the synthesis
of -styrylmalonates by including the conversion of ACDCs
containing electron-acceptor substituents at the aromatic
ring. The essence of this approach involves the initial con-
version of ACDCs to (2-arylethylidene)malonates in the
presence of GaCl3 by the method that we have developed
previously,13 followed by isomerization of the resulting (2-
arylethylidene)malonates 3 to isomeric -styrylmalonates
1. For this purpose, anhydrous GaCl314 was added at the first
stage to an ACDC solution in dichloromethane to give 1,2-
zwitterionic gallium intermediates 4,8a which are precur-
sors of ethylidenemalonates 3. Further, the reaction mix-
ture was treated with 10% HCl solution. The organic layer
was separated, and the isomerization of the resulting
ethylidenemalonates 3 to the corresponding -styryl-
malonates 1 (Scheme 3) was studied. To determine the suit-
able isomerization conditions, we first optimized the pro-
cess using ACDC 2a as a model substrate. The reaction gave
dimethyl (2-phenylethylidene)malonate (3a) (Scheme 3,
Table 1).
Br
Ar
CO2Me
CO2Me
CO2Me
(i) or (ii)
(iii)
+
CO2Me
Ar
CO2Me
Ar
1
2
CO2Me
(i) TMSOTf (1.2 equiv), MS 4Å, PhCl, 130 °C
(ii) Sn(OTf)2 (10%), CH2Cl2 or C6H6 or MeNO2, 20–80 °C
(iii) CuI (5%), L-proline (10%), Cs2CO3, DMSO, 90 °C
Ar = Ph; 4-ClC6H4; 4-MeC6H4;
MeO
4-FC6H4; 4-Me2NC6H4; 2,4,6-(MeO)3C6H2;
1-naphthyl; 2-naphthyl; 4-MeOC6H4;
2-MeO-5-O2NC6H3; 2-thienyl
O
O
CO2Me
CO2Me
GaCl3
δ+
MeO
δ-
GaCl3
CH2Cl2
0 °C
Ph
Ph
2a
4
CO2Me
CO2Me
CO2Me
Py
HCl (10%)
CO2Me
CO2Me
CO2Me
CO2Me
TMSOTf
1) GaCl3
CO2Me
2) pyridine
CH2Cl2, r.t.
PhCl, Δ
Ar
CO2Me
CO2Me
Ar
Ar
Additive
2
1
2
known method
this work
Ar with EWG
Ph
Ph
25 °C
Ar with EDG
3a
1a
Scheme 2 The main known methods for the synthesis of -styryl-
malonates 1
Scheme 3 Sequential isomerization of ACDC 2a to -styrylmalonate
1a
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

C
D. D. Borisov et al.
Paper
Synthesis
pyridine without preliminary treatment with aqueous HCl.
It was found that, in this case, -styrylmalonate 1a was also
formed, again with a low content of ethylidenemalonate 3a
(ca. 7%). Their overall yield after chromatography on SiO2
reached 72%.
Once the optimum isomerization conditions were de-
termined, we synthesized a number of substituted -styryl-
malonates and studied the influence of the electronic ef-
fects of substituents at the aromatic ring on the course of
the reaction (Table 2). The reactions occurred rather suc-
cessfully with ACDCs containing a p-tolyl moiety (Table 2,
entry 2) or halogen atoms at various positions of the ben-
zene ring (entries 4–6). It is important to note that a num-
ber of ACDCs with acceptor substituents at the aromatic
ring, in particular with nitro- and trifluoromethyl groups
(entries 7–10), reacted successfully in this process.
A similar process also occurred efficiently in the case of
2,2-diphenylcyclopropane-1,1-dicarboxylate 2n. In con-
trast, the isomerization of p-methoxy-ACDC 2c containing a
strong electron-donor group (Table 2, entry 3) occurred in a
low yield. The reason for this lies in the first process stage
since compound 2c does not successfully generate the in-
termediate 4c with polarized double bond but undergoes
dimerization and significant polymerization, as we noted
previously.8a We also failed to perform the isomerization of
ACDCs that contained 4-CN and 4-CO2Me substituents at
the benzene ring. In this case, the CN or CO2Me groups
themselves were actively involved in various transforma-
tions with the 1,2-zwitterionic intermediates being gener-
ated, to give compounds of unknown structure among
which neither the corresponding -styrylmalonates nor
ethylidenemalonates were found. We also noted that the
experimentally determined time of formation of the inter-
mediates 4 strongly correlated with the results for the for-
mation and reactivity of the 1,3-zwitterionic intermediates
in reaction with 4-fluorobenzaldehyde in the presence of
SnCl4.15
It should be noted that steric factors have a considerable
effect on the degree of conversion of ethylidenemalonates
to isomeric -styrylmalonates. In fact, in the case of naph-
thyl-substituted ACDC 2m, the ratio of malonates 1m/3m
after treatment with pyridine was about 65:35 and nearly
did not change with an increase in the reaction time. ortho-
Halo-substituted ACDCs were found to behave similarly. In
the case of monochloro derivative 2f, the corresponding -
styrylmalonate 1f was obtained rather successfully, while
in the case of the 2-chloro-6-fluorophenyl substituent, the
ratio of malonates 3k to 1k was already ~2:1 in favor of
ethylidenemalonate 3k (Scheme 4). 2-(2,6-Dichlorophe-
nyl)cyclopropane-1,1-dicarboxylate 2l selectively gave only
ethylidenemalonate 3l that did not undergo isomerization
even after keeping for one month in a dichloromethane and
pyridine solution.
Table 1 Optimization of the Isomerization Process of Ethylidenemalonate
3a to -Styrylmalonate 1a
Additive
Time (h)
NMR yields (%)а
1a
3a
96
–
0.1
0.5
1
0
12
10
7
AcOH (1.5 equiv)
36% HCl (1.5 equiv)
20% H2SO4
20
80
84
60
80
52
40
82
62
70
52
35
7
1
TfOH (1 equiv)
SiO2 (15 equiv)
SiO2 (15 equiv)
SiO2 (15 equiv)
K2CO3 (1.1 equiv)
DBU (1.1 equiv)
pyridine (1 equiv)
pyridine (3 equiv)
pyridine (5 equiv)
pyridine (10 equiv)
1
9
1
12
30
40
7
12
24
1
1
26
23
42
58
86
1
24
18
24
a NMR yields were measured relative to 1,4-dinitrobenzene as standard.
It was found that, in the presence of acids of various na-
tures, the isomerization of ethylidenemalonate 3a is rather
inefficient, and although -styrylmalonate 1a is formed, its
amount is small. In certain cases, dimeric products8 and
products of acid addition to -styrylmalonate were formed,
especially in the presence of acetic and trifluoromethane-
sulfonic acids.
Prolonged stirring of ethylidenemalonate 3a with silica
gel resulted in the isomerization of about half of ethyliden-
emalonate 3a to -styrylmalonate 1a. The use of excess pyr-
idine as the base proved to be the most efficient; the yield
of the target -styrylmalonate 1a in the presence of 10
equivalents of pyridine was 85% (according to NMR data).
Unfortunately, even under these conditions, we failed to
achieve the complete conversion of ethylidenemalonate 3a
to styrylmalonate 1a. Neither the addition of more pyridine
nor increasing the process duration resulted in the com-
plete conversion of 3a to 1a. Moreover, when the styryl-
malonate was isolated by column chromatography on SiO2,
not only the retention indices of isomers 1a and 3a were
nearly the same, but they were also partially lost (presum-
ably due to the hydrolysis of one ester group). As a result,
the stable isolated yield of -styrylmalonate 1a containing
6–8% ethylidenemalonate 3a was about 65%.
Since the effect of ethylidenemalonate 3a isomerization
to -styrylmalonate 1a in the presence of pyridine was the
most successful, we performed the decomposition of inter-
mediate 4а with polarized double bond directly with excess
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

D
D. D. Borisov et al.
Paper
Synthesis
Table 2 Isomerization of ACDC 2 to -Styrylmalonates 1 via the Generation of Intermediates 4 with Polarized Double Bond (Scheme 3, stage 1)a
MeO
CO2Me
CO2Me
O
O
R
CO2Me
CO2Me
R
CO2Me
CO2Me
GaCl3 [ref. 13]
HCl (10%)
Py
δ+
δ-
GaCl3
Ar
R
CH2Cl2
or Py
25 °C
Ar
Ar
Ar
0–40 °C
MeO
R
2a–n
4
3
1a–n
Entry
ACDC
Ar
Ph
R
Conditions for 4
Product
Yield (%)b
Yield (%) from ref. 10
1
2
2a
2b
2c
2d
2e
2f
H
15 min, 0 °C
15 min, 0 °C
15 min, 0 °C
15 min, 0 °C
90 min, 0–5 °C
60 min, 5–10 °C
75 min, 25 °C
75 min, 25 °C
75 min, 25 °C
60 min, 40 °C
60 min, 40 °C
75 min, 40 °C
15 min, 0 °C
15 min, 0 °C
30 min, 40 °C
1a
1b
1c
1d
1e
1f
72
58
8c
67
56
80
63
–
4-MeC6H4
4-MeOC6H4
4-FC6H4
H
3
H
4
H
62
68
62
42
55
55
48
22e
0f
5
3-BrC6H4
2-ClC6H4
4-NO2C6H4
3-NO2C6H4
4-CF3C6H4
3,5-(CF3)2C6H3
2-Cl-6-FC6H3
2,6-Cl2C6H3
1-naphthyl
Ph
H
6
H
0d
0d
–
7
2g
2h
2i
H
1g
1h
1i
8
H
9
H
–
10
11
12
13
14
15
2j
H
1j
–
2k
2l
H
1k
1l
–
H
–
2m
2n
2o
H
1m
1n
1o
58g
64
0f
78
–
Ph
n-Bu
H
–
a After obtaining the zwitterionic complex 4, the reaction mixture was treated with an excess of pyridine (10 equiv) and stirred for 20 h at r.t.
b Yields are based on ACDC after column chromatography on SiO2. In all cases, -styrylmalonates 1 contained 5–8% of isomeric (2-arylethylidene)malonates 3.
c NMR yield.
d Attempt to isomerize ACDCs 2f,g under the previously described conditions:11 TMSOTf, MS 4Å, PhCl, 120 °C, 3 h.
e After chromatography, ~43% ethylidenemalonate 3k was isolated.
f Only the corresponding ethylidenemalonate is formed.
gRatio of 1m/3m = ~2:1.
R
R
CO2Me
CO2Me
R
CO2Me
CO2Me
CO2Me
CO2Me
tion (or isomerization of ethylidenemalonates obtained be-
forehand) with excess pyridine. This method is sufficiently
tolerant to the electronic effects of substituents in the aro-
matic moiety of the ACDC, whereas the efficiency of isom-
erization is significantly affected by steric factors that favor
the formation of (2-arylethylidene)malonates or by the in-
ability of an ACDC to efficiently form a 1,2-zwitterionic in-
termediate with GaCl3.
GaCl3
Py
Cl
Cl
Cl
1f,k
2f,k,l
3f,k,l
R = H
1f/3f ~10:1 (62%)
1k/3k ~1:2 (65%)
1l/3l ~1:99 (90%)
R = F
R = Cl
Scheme 4 The ability of ortho-halogenated ACDCs 2f,k,l to isomerize
into -styrylmalonates 1
It should be noted that the driving force behind the for-
mation of -styrylmalonates lies in the creation of an effi-
cient conjugation chain between the benzene ring and the
double bond, unlike the corresponding complexes with
GaCl3 that are characterized by the formation of structure 4
with polarized double bond. In view of this, it is quite natu-
ral, for example, that hexylidenemalonate 3o is exception-
ally formed in the reaction with 2-butylcyclopropane-1,1-
dicarboxylate 2o.
Thus, we have developed a new version of ACDC isomer-
ization into -styrylmalonates comprising the initial gener-
ation of the intermediates with polarized double bond from
an ACDC in the presence of GaCl3 followed by decomposi-
All reagents and solvents were of commercial grade and used without
additional purification. All operations with GaCl3 were carried out
under dry argon atmosphere. TLC analysis was performed on Silufol
chromatographic plates. For preparative chromatography, silica gel 60
(0.040–0.063 mm) was used. 1H, 13C, and 19F NMR spectra were re-
corded on a 300 MHz (300.1 75.5, and 282.4 MHz, respectively) spec-
trometer in CDCl3 containing 0.05% Me4Si as the internal standard. IR
spectra were obtained on a FT-IR spectrophotometer in CHCl3 solu-
tion (1.5%). High-resolution mass spectra were obtained using simul-
taneous electospray (ESI TOF). The elemental compositions were
determined on a CHN alalyzer instrument. The melting points were
determined on Kofler hot-stage microscope. Starting cyclopropanes
2a–m,o (ACDC) were synthesized from the corresponding aromatic
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

E
D. D. Borisov et al.
Paper
Synthesis
aldehydes through a standard synthetic sequence of Knoevenagel/Corey–
Chaykovsky reactions.8a Cyclopropane 2n was synthesized from 1,1-
diphenylethene and diazomalonate using the Rh2(esp)2 catalyst.16
Dimethyl 2-(4-Fluorostyryl)malonate (1d)
This compound with an impurity of isomeric ethylidenemalonate 3d
(ratio ~10:1) was prepared from cyclopropane 2d (127 mg); yield:
78.5 mg (62%); colorless thick oil.
Isomerization of Donor-Acceptor Cyclopropanes 2 to Substituted
-Styrylmalonates 1; General Procedure
1H NMR (300.1 MHz, CDCl3):  = 3.78 (s, 6 H, 2 × CO2CH3), 4.22 (d, 3J =
8.9 Hz, 1 H, H-1), 6.33 (dd, 3J = 15.9, 8.9 Hz, 1 H, H-2), 6.56 (d, 3J = 15.9
3
Hz, 1 H, H-3), 7.01 (t, JH,H
=
3JH,F = 8.7 Hz, 2 H, H-3′, H-5′), 7.38 (d,
All operations for Scheme 3, stage 1 were performed under dry argon
atmosphere. A solution of ACDC 2 (0.5 mmol) in anhyd CH2Cl2 (6 mL)
was cooled at 0 °C or kept at r.t.; solid GaCl3 (123 mg, 0.7 mmol) was
added in one portion and the reaction mixture was stirred at the tem-
perature indicated in Table 2 during 15–90 min until completion of
the generation of Ga-complex 4. Afterwards, the reaction mixture
was processed by one of the following two methods.
3JH,H = 8.7 Hz, 4JH,F = 5.4 Hz, 2 H, H-2′, H-6′).
13C NMR (75.5 MHz, CDCl3):  = 52.8 (2 × OCH3), 55.4 (C-1), 115.5 (d,
C-3′, C-5′), 2JC,F = 21.7 Hz), 120.4 (d, 5JC,F = 2.2 Hz, C-2), 128.2 (d, 3JC,F
=
4
8.1 Hz, C-2′, C-6′), 132.2 (d, JC,F = 3.3 Hz, C-1′), 134.0 (C-3), 162.6 (q,
1JC,F = 247.7 Hz, C-4′), 168.3 (2 × COO).
19F NMR (282.4 MHz, CDCl3):  = –113.5 (tt, 3JH,F = 8.7 Hz, 4JH,F = 5.4 Hz,
Method 1: Aq HCl (7–10%) was added until pH 3 was achieved and the
reaction mixture was extracted with CH2Cl2 (3 × 10 mL) and the com-
bined organic layers were dried (MgSO4). Then the MgSO4 was sepa-
rated and pyridine (400 mg, 5 mmol, 10 equiv) was added to the re-
sulting solution at r.t. and the mixture was stirred for 20–24 h. After-
wards, excess of pyridine was neutralized with 5% aq HCl, the organic
layer was dried (MgSO4), and the solvent was removed in vacuo. The
residue was purified by column chromatography on silica gel [ben-
zene for 1a,c–h,j,l,n or benzene to benzene–EtOAc (20:1) for 1b,k]
and corresponding -styrylmalonates 1 were obtained with an ad-
mixture of isomeric ethylidenemalonates 3.
1 F).
The spectroscopic data were identical with the reported values.10
Dimethyl 2-(3-Bromostyryl)malonate (1e)
This compound with an impurity of isomeric ethylidenemalonate 3e
(ratio ~13:1) was prepared from f cyclopropane 2e (157 mg); yield:
106 mg (68%); colorless thick oil.
IR (KBr): 3065, 3047, 3035, 3016, 2956, 2847, 1735 br (C=O), 1650,
1594, 1567, 1457, 1455, 1437, 1346, 1280, 1248, 1182, 1159 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 3.80 (s, 6 H, 2 × CO2CH3), 4.23 (d, 3J =
8.5 Hz, 1 H, H-1), 6.42 (dd, 3J = 16.0, 8.5 Hz, 1 H, H-2), 6.54 (d, 3J = 16.0
Hz, 1 H, H-3), 7.20 (t, 3J = 7.8 Hz, 1 H, H-5′), 7.33 (d, 3J = 7.8 Hz, 1 H, H-
4′), 7.40 (d, 3J = 7.8 Hz, 1 H, H-6′), 7.57 (s, 1 H, H-2′).
13C NMR (75.5 MHz, CDCl3):  = 52.9 (2 × OCH3), 55.4 (C-1), 122.3 (C-
2), 122.7 (C-3′), 125.3, 129.5, 130.1 and 131.0 (C-2′, C-4′, C-5′ and C-
6′), 133.7 (C-3), 138.1 (C-1′), 168.1 (2 × COO).
Method 2: An excess of pyridine (400 mg, 5 mmol, 10 equiv) was im-
mediately added to the reaction mixture after the generation of Ga-
complex 4 and the mixture was stirred for 20–24 h at r.t. Afterwards,
excess of pyridine was neutralized with 5% aq HCl, and the processing
of the resulting mixture and the isolation of products were carried
out as described in Method 1.
HRMS: m/z [M + H]+ calcd for C13H1379BrO4: 313.0070; found:
313.0069; m/z [M + Na]+ calcd: 334.9889; found: 334.9886.
Dimethyl 2-Styrylmalonate (1a)
This compound with an impurity of isomeric ethylidenemalonate 3a
(ratio ~12:1) was prepared from cyclopropane 2a (116 mg); yield:
86.7 mg (72%); colorless thick oil.
Dimethyl 2-(2-Chlorostyryl)malonate (1f)
This compound with an impurity of isomeric ethylidenemalonate 3f
(ratio ~12:1) was prepared from cyclopropane 2f (135 mg); yield: 84
mg (62%), colorless thick oil.
1H NMR (300.1 MHz, CDCl3):  = 3.80 (s, 6 H, 2 × CO2CH3), 4.25 (d, 3J =
8.9 Hz, 1 H, H-1), 6.43 (dd, 3J = 15.9, 8.9 Hz, 1 H, H-2), 6.61 (d, 3J = 15.9
Hz, 1 H, H-3), 7.21–7.48 (m, 5 HAr).
IR (KBr): 3050, 2956, 1732 br (C=O), 1649, 1569, 1472, 1438, 1348,
13C NMR (75.5 MHz, CDCl3):  = 52.8 (2 × OCH3), 55.6 (C-1), 120.6 (C-
2), 126.6 (2 Co), 128.1 (Cp), 128.6 (2 Cm), 135.2 (C-3), 136.0 (Ci), 168.4
(2 × COO).
1292, 1271, 1251, 1182, 1156 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 3.81 (s, 6 H, 2 × CO2CH3), 4.31 (d, 3J =
9.1 Hz, 1 H, H-1), 6.44 (dd, 3J = 15.9, 9.1 Hz, 1 H, H-2), 7.01 (d, 3J = 15.9
Hz, 1 H, H-3), 7.16–7.42 (m, 4 HAr), 7.61 (dd, 3J = 7.3 Hz, 4J = 2.1 Hz, 1
HAr).
13C NMR (75.5 MHz, CDCl3):  = 52.9 (2 × OCH3), 55.6 (C-1), 123.3 (C-
2), 126.8, 127.0, 129.2 and 129.7 (4 × CHAr), 131.4 (C-3), 133.2 (C-2′),
134.1 (C-1′), 168.1 (2 × COO).
The spectroscopic data were identical with the reported values.10
Dimethyl 2-(4-Methylstyryl)malonate (1b)
This compound with an impurity of isomeric ethylidenemalonate 3b
(ratio ~10:1) was prepared from cyclopropane 2b (124 mg); yield: 72
mg (58%); colorless thick oil.
1H NMR (300.1 MHz, CDCl3):  = 2.36 (s, 3 H, CH3), 3.80 (s, 6 H, 2 ×
CO2CH3), 4.23 (d, 3J = 9.0 Hz, 1 H, H-1), 6.37 (dd, 3J = 15.9, 9.0 Hz, 1 H,
H-2), 6.58 (d, 3J = 15.9 Hz, 1 H, H-3), 7.15 (d, 3J = 8.0 Hz, 2 H, H-2′, H-
6′), 7.33 (d, 3J = 8.0 Hz, 2 H, H-3′, H-5′).
HRMS: m/z [M + H]+ calcd for C13H1335ClO4: 269.0575; found:
269.0574; m/z [M + Na]+ calcd: 291.0395; found: 291.0385.
Dimethyl 2-(4-Nitrostyryl)malonate (1g)
This compound with an impurity of isomeric ethylidenemalonate 3g
(ratio ~11:1) was prepared from cyclopropane 2g (140 mg); yield:
58.8 mg (42%); light yellow thick oil.
13C NMR (75.5 MHz, CDCl3):  = 21.2 (CH3), 52.8 (2 × OCH3), 55.6 (C-1),
119.5 (C-2), 126.5 (C-3′, C-5′), 129.2 (C-2′, C-6′), 135.1 (C-3), 138.1 (C-
1′), 148.1 (C-4′), 168.5 (2 × COO).
IR (KBr): 3080, 3045, 3023, 2956, 2849, 1755 br (C=O), 1652, 1599,
The spectroscopic data were identical with the reported values.10
1526 (N–O), 1494, 1456, 1437, 1347, 1300, 1267, 1182, 1156 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

F
D. D. Borisov et al.
Paper
Synthesis
1H NMR (300.1 MHz, CDCl3):  = 3.82 (s, 6 H, 2 × CO2CH3), 4.29 (d, 3J =
7.9 Hz, 1 H, H-1), 6.60 (dd, 3J = 16.0, 7.9 Hz, 1 H, H-2), 6.69 (d, 3J = 16.0
Hz, 1 H, H-3), 7.56 (d, 3J = 8.8 Hz, 2 H, H-2′, H-6′), 8.21 (d, 3J = 8.8 Hz, 2
H, H-3′, H-5′).
19F NMR (282.4 MHz, CDCl3):  = –63.0 (s, 2 CF3).
HRMS: m/z [M + H]+ calcd for C15H12F6O4: 371.0713; found: 371.0706;
m/z [M + Na]+ calcd: 393.0532; found: 393.0529.
13C NMR (75.5 MHz, CDCl3):  = 53.0 (2 × OCH3), 55.3 (C-1), 124.0 (C-
3′, C-5′), 125.5 (C-2), 127.2 (C-2′, C-6′), 133.4 (C-3), 142.3 (C-1′), 147.3
(C-4′), 167.7 (2 × COO).
HRMS: m/z [M + H]+ calcd for C13H13NO6: 280.0816; found: 280.0819;
m/z [M + Na]+ calcd: 302.0635; found: 302.0636.
Dimethyl 2-(2-Chloro-6-fluorostyryl)malonate (1k)
Compound 1k was prepared from cyclopropane 2k (140 mg); yield:
30.7 mg (22%); light yellow thick oil. Additionally, compound 3k was
isolated from this reaction; yield: 60.4 mg (43%).
IR (KBr): 3053, 3050, 3026, 2955, 1735 br (C=O), 1604, 1573, 1515,
1458, 1438, 1372, 1269, 1244, 1182, 1173 cm–1
.
Dimethyl 2-(3-Nitrostyryl)malonate (1h)
1H NMR (300.1 MHz, CDCl3):  = 3.81 (s, 6 H, 2 × CO2CH3), 4.27 (d, 3J =
6.8 Hz, 1 H, H-1), 6.62–6.82 (m, 2 H, H-2, H-3), 6.96–7.32 (m, 3 HAr).
This compound with an impurity of isomeric ethylidenemalonate 3h
(ratio ~10:1) was prepared from cyclopropane 2h (138 mg); yield:
76.1 mg (55%); light yellow thick oil.
13C NMR (75.5 MHz, CDCl3):  = 52.9 (2 × OCH3), 56.6 (С-1), 114.6 (d,
2
4
2JC,F = 23.5 Hz, C-5′), 122.8 (d, JC,F = 14.6 Hz, C-1′), 125.5 (d, JC,F = 3.4
IR (KBr): 3091, 3071, 3050, 2956, 2847, 1735 br (C=O), 1652, 1533
4
3
Hz, C-3′), 125.8 (d, JC,F = 1.5 Hz C-2), 128.6 (d, JC,F = 13.2 Hz, C-3),
(N–O), 1480, 1457, 1438, 1353, 1267, 1182, 1156 cm–1
.
3
3
128.8 (d, JC,F = 10.1 Hz, C-4′), 134.5 (d, JC,F = 5.5 Hz, C-2′), 161.2 (d,
1H NMR (300.1 MHz, CDCl3):  = 3.81 (s, 6 H, 2 × CO2CH3), 4.28 (d, 3J =
8.4 Hz, 1 H, H-1), 6.56 (dd, 3J = 16.0, 8.4 Hz, 1 H, H-2), 6.67 (d, 3J = 16.0
Hz, 1 H, H-3), 7.52 (t, 3J = 7.8 Hz, 1 H, H-5′), 7.73 (d, 3J = 7.8 Hz, 1 H, H-
4′), 8.13 (d, 3J = 7.8 Hz, 1 H, H-6′), 8.26 (s, 1 H, H-2′).
13C NMR (75.5 MHz, CDCl3):  = 53.0 (2 × OCH3), 55.3 (C-1), 121.3 (C-
2), 122.7, 124.0, 129.5 and 132.4 (C-2′, C-4′, C-5′, C-6′), 132.9 (C-3),
137.7 (C-1′), 148.5 (C-3′), 167.8 (2 × COO).
1JC-F = 253 Hz, C-6′), 168.0 (2 × COO).
19F NMR (282.4 MHz, CDCl3):  = –110.3 (dd, 3JH,F = 10.5 Hz, 4JH,F = 4.9
Hz, 1 F).
HRMS: m/z [M + Na]+ calcd for C13H1235ClFO4: 309.0300; found:
309.0314.
Dimethyl 2-[2-(Naphthalen-1-yl)vinyl]malonate (1m)
HRMS: m/z [M + H]+ calcd for C13H13NO6: 280.0816; found: 280.0808;
m/z [M + Na]+ calcd: 302.0635; found: 302.0627.
A mixture of compound 1m and 3m (~2:1) was isolated from cyclo-
propane 2m (143 mg); total yield: 82.8 mg (58%); light yellow thick
oil.
Dimethyl 2-[4-(Trifluoromethyl)styryl]malonate (1i)
1H NMR (300.1 MHz, CDCl3):  = 3.84 (s, 6 H, 2 × CO2CH3), 4.41 (d, 3J =
9.0 Hz, 1 H, H-1), 6.48 (dd, 3J = 15.6, 9.0 Hz, 1 H, H-2), 7.18–8.20 (m, 8
H, 7 HAr and H-3).
13C NMR (75.5 MHz, CDCl3):  = 52.9 (2 × OCH3), 55.8 (C-1), 122.7
(CAr), 123.6 (CHAr), 123.7 (C-2), 124.3, 125.5, 125.8, 126.2, 128.5 and
128.6 (6 × CHAr), 132.5 (C-3), 133.6 (C-1′), 168.4 (2 × COO).
This compound with an impurity of isomeric ethylidenemalonate 3i
(ratio ~11:1) was prepared from cyclopropane 2i (150 mg); yield:
82.5 mg (55%); colorless thick oil.
IR (KBr): 3051, 3032, 3025, 2955, 1735 br (C=O), 1618, 1457, 1437,
1417, 1326, 1266, 1247, 1182, 1131 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 3.79 (s, 6 H, 2 × CO2CH3), 4.26 (d, 3J =
8.5 Hz, 1 H, H-1), 6.52 (dd, 3J = 16.0, 8.5 Hz 1 H, H-2), 6.64 (d, 3J = 16.0
Hz, 1 H, H-3), 7.50 (d, 3J = 8.2 Hz, 2 H, H-2′, H-6′), 7.57 (d, 3J = 8.2 Hz, 2
H, H-3′, H-5′).
The spectroscopic data for 3m were compared with a sample ob-
tained early.13 The spectroscopic data for 1m were identical with the
reported values.10
13C NMR (75.5 MHz, CDCl3):  = 52.8 (2 × OCH3), 55.4 (C-1), 123.4 (C-
Dimethyl 2-(2,2-Diphenylvinyl)malonate (1n)
3
2), 125.3 (br q, JC,F = 7.2 Hz, C-3′, C-5′), 126.8 (C-2′, C-6′), 127.5 (q,
This compound with an impurity of isomeric ethylidenemalonate 3n
(ratio ~10:1) was prepared from cyclopropane 2n (155 mg); yield:
99.5 mg (64%); colorless thick oil.
1JC,F = 252 Hz, CF3), 129.9 (q, 2JC,F = 30.6 Hz, C-4′), 133.8 (C-3), 139.4 (C-
1′), 168.0 (2 × COO).
19F NMR (282.4 MHz, CDCl3):  = –62.6 (s, CF3).
HRMS: m/z [M + H]+ calcd for C14H13F3O4: 303.0839; found: 303.0843;
m/z [M + Na]+ calcd: 325.0658; found: 325.0659.
IR (KBr): 3083, 3054, 3023, 2955, 2849, 1733 br (C=O), 1657, 1576,
1495, 1437, 1306, 1280, 1245, 1223, 1181, 1154 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 3.77 (s, 6 H, 2 × CO2CH3), 4.26 (d, 3J =
10.4 Hz, 1 H, H-1), 6.35 (d, 3J = 10.4 Hz, 1 H, H-2), 7.11–7.49 (m, 10 H,
2 × C6H5).
Dimethyl 2-[3,5-Bis(trifluoromethyl)styryl]malonate (1j)
This compound with an impurity of isomeric ethylidenemalonate 3j
(ratio ~12:1) was prepared from cyclopropane 2j (185 mg); yield:
88.7 mg (48%); colorless thick oil.
13C NMR (75.5 MHz, CDCl3):  = 52.6 (С-1), 52.7 (2 × OCH3), 119.4 (С-
2), 127.6 (2 Co), 127.8 and 127.9 (2 Cp), 128.2 (2 Co), 128.4 and 129.7 (4
Cm), 138.4 and 141.2 (2 Ci), 146.7 (C-3), 168.6 (2 × COO).
IR (KBr): 3051, 3027, 2956, 2927, 2854, 1736 br (C=O), 1655, 1620,
HRMS: m/z [M + Na]+ calcd for C19H18O4: 333.1097; found: 333.1097.
1464, 1437, 1381, 1344, 1280, 1181, 1139 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 3.83 (s, 6 H, 2 × CO2CH3), 4.29 (d, 3J =
8.2 Hz, 1 H, H-1), 6.59 (dd, 3J = 16.0, 8.2 Hz, 1 H, H-2), 6.69 (d, 3J = 16.0
Hz, 1 H, H-3), 7.78 (s, 1 H, H-4′), 7.84 (s, 2 H, H-2′, H-6′).
Funding Information
13C NMR (75.5 MHz, CDCl3):  = 53.0 (2 × OCH3), 55.2 (C-1), 121.5 (dt,
This work was supported by the Russian Science Foundation (grant
1
No. 19-73-00258).
R
usian
S
cienceFo
u
n
d
ati
o
n(19-73-0
0
2
5
8)
3JC,F = 7.6, 3.8 Hz C-4′), 122.2 (q, JC,F = 273 Hz, 2 × CF3), 124.9 (C-2),
3
2
126.4 (d, JC,F = 2.9 Hz, C-2′, C-6′), 132.0 (q, JC,F = 33.7 Hz C-3′, C-5′),
132.4 (C-3), 138.0 (C-1′), 167.7 (2 × COO).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G

G
D. D. Borisov et al.
Paper
Synthesis
Acknowledgment
Chem. 2016, 56, 553. (l) Mlostoń, G.; Kowalczyk, M.; Augustin, A.
U.; Jones, P. G.; Werz, D. B. Belstein J. Org. Chem. 2020, 16, 1288.
(m) Augustin, A. U.; Merz, J. L.; Jones, P. G.; Mlostoń, G.; Werz, D.
B. Org. Lett. 2019, 21, 9405.
The authors are grateful to M. A. Zotova and D.-M. V. Ratova for the
help in the synthesis of a number of starting ACDCs.
(3) (a) Borisov, D. D.; Novikov, R. A.; Tomilov, Y. V. Angew. Chem. Int.
Ed. 2016, 55, 12233. (b) Borisov, D. D.; Novikov, R. A.; Eltysheva,
A. S.; Tkachev, Y. V.; Tomilov, Y. V. Org. Lett. 2017, 19, 3731.
(c) Borisov, D. D.; Novikov, R. A.; Tomilov, Y. V. Tetrahedron Lett.
2017, 58, 3712. (d) Borisov, D. D.; Chermashentsev, G. R.;
Novikov, R. A.; Tomilov, Y. V. Tetrahedron Lett. 2019, 60, 746.
(4) Hoye, T. R.; Richardson, W. S. J. Org. Chem. 1989, 54, 688.
(5) (a) Ivanova, O. A.; Budynina, E. M.; Skvortsov, D. A.; Limoge, M.;
Bakin, A. V.; Chagarovskiy, A. O.; Trushkov, I. V.; Melnikov, M. Y.
Chem. Commun. 2013, 49, 11482. (b) Chagarovskiy, A. O.;
Ivanova, O. A.; Budynina, E. M.; Trushkov, I. V.; Melnikov, M. Y.
Tetrahedron Lett. 2011, 52, 4421.
(6) Tsuruda, K.; Tokumoto, T.; Inoue, N.; Nakajima, M.; Nenoto, T.
Eur. J. Org. Chem. 2018, 2836.
(7) Wang, Y.; Fordyce, E. A. F.; Chen, F. Y.; Lam, H. W. Angew. Chem.
Int. Ed. 2008, 47, 7350.
(8) (a) Novikov, R. A.; Tarasova, A. V.; Korolev, V. A.; Timofeev, V. P.;
Tomilov, Y. V. Angew. Chem. Int. Ed. 2014, 53, 3187. (b) Novikov,
R. A.; Korolev, V. A.; Timofeev, V. P.; Tomilov, Y. V. Tetrahedron
Lett. 2011, 52, 4996.
(9) (a) Zhu, M.; Liu, J.; Yu, J.; Chen, L.; Zhang, C.; Wang, L. Org. Lett.
2014, 16, 1856. (b) Verma, K.; Banerjee, P. Adv. Synth. Cat. 2018,
360, 3687.
(10) Chagarovskiy, A. O.; Ivanova, O. A.; Rakhmankulov, E. R.;
Budynina, E. M.; Trushkov, I. V. Melnikov M. Y. 2010, 352, 3179.
(11) Pei, L.; Qian, W. Synlett 2006, 1719.
(12) Singh, R.; Singh, G. C.; Ghosh, S. K. Eur. J. Org. Chem. 2007, 5376.
(13) Novikov, R. A.; Tarasova, A. V.; Tomilov, Y. V. Synlett 2016, 27,
1367.
(14) (a) Denisov, D. A.; Borisov, D. D.; Korolev, V. A.; Novikov, R. A.;
Tomilov, Y. V. J. Org. Chem. 2019, 84, 6174. (b) Zotova, M. A.;
Novikov, R. A.; Shulishov, E. V.; Tomilov, Y. V. J. Org. Chem. 2018,
83, 8193. (c) Denisov, D. A.; Borisov, D. D.; Potapov, K. V.;
Novikov, R. A.; Tomilov, Y. V. Mendeleev Commun. 2019, 29, 417.
(d) Novikov, R. A.; Levina, A. A.; Borisov, D. D.; Volodin, A. D.;
Korlyukov, A. A.; Tkachev, Y. V.; Platonova, Ya. B.; Tomilova, L. G.;
Tomilov, Y. V. Organometallics 2020, 39, 2580.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1348-4311. Su
p
p
ortingInformatio
n
Su
p
p
ortingInformatio
n
References
(1) (a) Reissig, H. U.; Zimmer, R. Chem. Rev. 2003, 103, 1151. (b) De
Simone, F.; Waser, J. Synthesis 2009, 3353. (c) Carson, C. A.; Kerr,
M. A. Chem. Soc. Rev. 2009, 38, 3051. (d) Melnikov, M. Y.;
Budynina, E. M.; Ivanova, O. A.; Trushkov, I. V. Mendeleev
Commun. 2011, 21, 293. (e) Schneider, T. F.; Kaschel, J.; Werz, D.
B. Angew. Chem. Int. Ed. 2014, 53, 5504. (f) De Nanteuil, F.; De
Simone, F.; Frei, R.; Benfatti, F.; Serrano, E.; Waser, J. Chem.
Commun. 2014, 50, 10912. (g) Novikov, R. A.; Tomilov, Y. V. Men-
deleev Commun. 2015, 25, 1. (h) Grover, H. K.; Emmett, M. R.;
Kerr, M. A. Org. Biomol. Chem. 2015, 13, 655. (i) Reissig, H.-U.;
Werz, D. B. Israel J. Chem. 2016, 56, 365. (j) Budynina, E. M.;
Ivanov, K. L.; Sorokin, I. D.; Melnikov, M. Y. Synthesis 2017, 49,
3035. (k) Pagenkopf, B. L.; Vemula, N. Eur. J. Org. Chem. 2017,
2561. (l) Meazza, M.; Guo, H.; Rios, R. Org. Biomol. Chem. 2017,
15, 2479. (m) Tomilov, Y. V.; Menchikov, L. G.; Novikov, R. A.;
Ivanova, O. A.; Trushkov, I. V. Russ. Chem. Rev. 2018, 87, 201.
(n) Ivanova, O. A.; Trushkov, I. V. Chem. Rec. 2019, 19, 1.
(o) Werz, D. B.; Biju, A. T. Angew. Chem. Int. Ed. 2020, 59, 3385.
(2) (a) Wallbaum, J.; Garve, L. K. B.; Jones, P. G.; Werz, D. B. Org. Lett.
2017, 19, 98. (b) Dey, R.; Banerjee, P. Org. Lett. 2017, 19, 304.
(c) Chidley, T.; Vemula, N.; Carson, C. A.; Kerr, M. A.; Pagenkopf,
B. L. Org. Lett. 2016, 18, 2922. (d) Das, S.; Chakrabarty, S.;
Daniliuc, C. G.; Studer, A. Org. Lett. 2016, 18, 2784. (e) Garve, L.
K. B.; Pawliczek, M.; Wallbaum, J.; Jones, P. G.; Werz, D. B. Chem.
Eur. J. 2016, 22, 521. (f) Novikov, R. A.; Denisov, D. A.; Potapov,
K. V.; Tkachev, Y. V.; Shulishov, E. V.; Tomilov, Y. V. J. Am. Chem.
Soc. 2018, 140, 14381. (g) Verma, K.; Banerjee, P. Adv. Synth.
Catal. 2016, 358, 2053. (h) Sabbatani, J.; Maulide, N. Angew.
Chem. Int. Ed. 2016, 55, 6780. (i) Pitts, C. R.; Ling, B.; Snyder, J. A.;
Bragg, A. E.; Lectka, T. J. Am. Chem. Soc. 2016, 138, 6598.
(j) Novikov, R. A.; Borisov, D. D.; Tarasova, A. V.; Tkachev, Y. V.;
Tomilov, Y. V. Angew. Chem. Int. Ed. 2018, 57, 10293.
(k) Gharpure, S. J.; Mane, S. P.; Nanda, L. N.; Shukla, M. K. Israel J.
(15) Kreft, A.; Lücht, A.; Grunenberg, J.; Jones, P. G.; Werz, D. B.
Angew. Chem. Int. Ed. 2019, 58, 1955.
(16) Gonzalez-Bobes, F.; Fenster, M. D. B.; Kiau, S.; Kolla, L.;
Kolotuchin, S.; Soumeillant, M. Adv. Synth. Catal. 2008, 350, 813.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–G