"cyclopropanation of Cyclopropanes": GaCl3-Mediated Ionic Cyclopropanation of Donor-Acceptor Cyclopropanes with Diazo Esters as a Route to Tetrasubstituted Activated Cyclopropanes

Article abstract of DOI:10.1021/acs.joc.0c02983

A new ionic cyclopropanation process involving the addition of diazo esters to donor-acceptor cyclopropanes (DAC) activated by GaCl3 has been developed. The reactions occur via 1,2-zwitterionic gallium complexes with elimination of nitrogen in all cases to give 1,1,2,3-tetrasubstituted cyclopropanes as the main products. Also, a number of related processes with the formation of various polysubstituted cyclopropanes, alkenes, and cyclobutanes, including products of multiple diazo ester addition, have been developed. Obtained by the developed method tetrasubstituted cyclopropanes are activated cyclopropanes such as DAC and can be used for further synthesis in this capacity. Their new reaction with benzaldehyde promoted by TiCl4 and involving one of the additional functional groups has been demonstrated, which leads to five-membered lactones. The mechanisms of the occurring processes, as well as the structures and stereochemistry of a rich range of products formed, are discussed in detail.

Full text of DOI:10.1021/acs.joc.0c02983

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Article
“Cyclopropanation of Cyclopropanes”: GaCl3‑Mediated Ionic
Cyclopropanation of Donor−Acceptor Cyclopropanes with Diazo
Esters as a Route to Tetrasubstituted Activated Cyclopropanes
Irina A. Borisova,§ Daria-Maria V. Ratova, Konstantin V. Potapov, Anna V. Tarasova,
Roman A. Novikov,*,§ and Yury V. Tomilov*
Cite This: J. Org. Chem. 2021, 86, 4567−4579
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ABSTRACT: A new ionic cyclopropanation process involving the
addition of diazo esters to donor−acceptor cyclopropanes (DAC)
activated by GaCl3 has been developed. The reactions occur via
1,2-zwitterionic gallium complexes with elimination of nitrogen in
all cases to give 1,1,2,3-tetrasubstituted cyclopropanes as the main
products. Also, a number of related processes with the formation of
various polysubstituted cyclopropanes, alkenes, and cyclobutanes,
including products of multiple diazo ester addition, have been developed. Obtained by the developed method tetrasubstituted
cyclopropanes are activated cyclopropanes such as DAC and can be used for further synthesis in this capacity. Their new reaction
with benzaldehyde promoted by TiCl4 and involving one of the additional functional groups has been demonstrated, which leads to
five-membered lactones. The mechanisms of the occurring processes, as well as the structures and stereochemistry of a rich range of
products formed, are discussed in detail.
KEYWORDS: Donor−acceptor cyclopropanes, Diazo esters, Gallium trichloride, Ionic cyclopropanation, 1,2-Zwitterionic intermediates,
Tetrasubstituted cyclopropanes, Titanium tetrachloride, Lactones
formal (3 + 3)-cycloaddition were studied extensively.12 On
the other hand, diazo compounds were little studied as 1,3-
INTRODUCTION
■
The chemistry of cyclopropanes containing donor and
acceptor substituents (DAC)1,2 has lately been attracting an
dipoles in these reactions. To date, only a few works with
participation of diazo compounds are known.13 However, not
increasing attention of scientists due to their exceptional
synthetic potential.3,4 The push−pull effect of donor and
the diazomethane moiety itself but a secondary 1,3-zwitterion
that is either generated by diazotization of vinyl diazoacetate or
formed in reactions of a diazo compound with ketones is
involved in these processes (Scheme 1A).13 One example of a
reaction without nitrogen loss is known for vinylcyclopropanes
under conditions of palladium(0) catalysis (Scheme 1B).13c
Attempts to conduct direct formal (3 + 3)-cycloaddition
under typical conditions14 (Scheme 1C) result in the loss of a
nitrogen molecule and formation of products of C−C coupling
of both substratessubstituted alkenes and cyclopropanes.
Moreover, the main pathways are determined by the addition
of a diazo ester to 1,3-zwitterionic intermediates being
generated, followed by carbocationic rearrangements and
fragmentation (Scheme 1D).14
acceptor substituents in DAC causes a strong polarization of
the vicinal C−C bond, which enables its opening and
implementation of processes involving this three-carbon
synthon, in particular, cycloaddition, cyclization, aromatic
annulation, and other reactions often accompanied by various
rearrangements.5−7
A separate approach in the chemistry of DAC, in particular
2-arylcyclopropane-1,1-dicarboxylates (ACDC, 1), involves the
reactions that occur with 1,2-hydride shift in pregenerated 1,3-
zwitterion 2 (Scheme 1).8 It should be noted that this process
is very typical if anhydrous gallium trichloride is used, and
ACDC themselves act as sources of 1,2-zwitterionic synthons 3
in this case.9 This strategy allowed the development of new
types of chemical reactions of DAC with alkenes, alkynes,
aromatic aldehydes, and other substrates.10
Despite the fast development of the chemistry of 1,2-
zwitterionic intermediates, their reactions with 1,3-dipoles
were studied only using benzyl azide as an example.11
Simultaneously, numerous reactions of trapping of 1,3-
zwitterionic intermediates by various 1,3-dipoles (nitrones,
azides, nitrilimines, nitronates, and azomethines) that occur as
Received: December 19, 2020
Published: March 4, 2021
https://dx.doi.org/10.1021/acs.joc.0c02983
© 2021 American Chemical Society
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Scheme 1. Reactivity Pattern of D−A Cyclopropanes with
Diazo Compounds
RESULTS AND DISCUSSION
■
To perform this process, ACDC 1 was chosen as the initial
model substrates. They were initially treated with gallium
trichloride to generate gallium 1,2-zwitterionic complexes 3,
which were then entered into reactions with diazo acetates 4.
The generation of intermediates 3 was carried out using the
methods that we mastered previously.10a,b To optimize the
second stage of the process, we used the reaction of
intermediate 3a, which was obtained from 2-phenylcyclopro-
pane-1,1-diester 1a, with methyl diazo acetate 4a (Table 1).
Table 1. Optimization of the Reaction Conditions
a
yields (%)
b
entry
ratio 1a/4a
T (°C)
t (min)
5a
trans/cis
6a
1
2
3
4
5
1:2
1:2
1:2
1:2
1:1
1:10
1:2
25
40
−60
15
15
30
15
15
15
15
15
30
45
48
48
60
38
9
1.4/1
1.5/1
1.5/1
1.5/1
1.5/1
2/1
12
15
13
19
15
<2
14
c
c
d
6
e
15
84
7
31
1.6/1
a
1
NMR yields; they were determined by H NMR spectra using 1,4-
b
dinitrobenzene as an internal standard. Diastereomer ratio was
c
determined by the 1H NMR spectra. Yields after column
d
chromatography. Adducts of double addition of the diazo esters
are formed as major products. 1,2-DCE was used as a solvent (3
e
mL).
It was found that in a fairly broad temperature range, a new
cyclopropane-containing productthe corresponding cyclo-
propane-1,1,2-tricarboxylate 5a is the main product of this
reaction. Isomeric unsaturated triester 6a is formed in parallel,
though in a much smaller amount.
One can see from Table 1 that both reaction pathways
giving isomeric compounds 5a and 6a practically do not
change, which does not allow one to obtain each of them
selectively. Likewise, we failed to make the formation of
cyclopropane 5a a stereoselective process (the ratio of trans
and cis-isomers remains at ca. 1.5:1 level).
In order to change the regio- and stereoselectivity of the
process, an attempt was made to use 4b,c containing sterically
hindered neopentyl and benzyl moieties in the reaction. In this
case, the ratio of trans- and cis-isomers changed more
significantly. The use of sterically hindered DAC with
neopentyl substituents, alone or in combination with neo-
pentyl diazo ester, does not allow one to achieve any significant
increase in regio- and distereoselectivity, either. In general, it
should be noted that the nature of substituents in the
substrates does not allow one to identify clear regularities
regarding their effect both on the degree of formation of
cyclopropanes 5 and alkenes 6 and on the stereoselectivity of
the formation of isomeric cyclopropanes 5. We also showed
This study is a continuation of a series of studies on the
chemical transformations of gallium 1,2-zwitterionic complexes
generated from ACDC in the presence of GaCl3 and is focused
on a study of their reactivity with diazo compounds (Scheme
1E), primarily with diazo esters, since diazo alkanes are too
unstable under conditions of catalysis with strong Lewis acids.
A specific feature of this process is the implementation of the
formal “cyclopropanation of cyclopropanes” (ring opening ring
closing cyclopropanation (RORCC) of DAC) as a new
approach to the synthesis of tetrasubstituted cyclopropanes
based on trisubstituted DAC. Thus, this approach allows one
to generate 1,2-zwitterionic synthons 3 and to create new
DACs with advanced functionality based on existing DACs.
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a b
,
Table 2. Scope for the GaCl3-Mediated Addition of Diazo Esters to D−A Cyclopropanes
entry
1
2
3
4
5
6
7
starting ACDC
Y
diazo ester
R1
cyclopropanes obtained
alkene
c
1
R
4
5
yield (%)
60
72
trans/cis
6
yield (%)
1a
1a
1a
1a
1b
1c
1d
1d
1e
1f
1i
1j
1g
1g
1h
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4a
4a
4b
4c
4a
4a
4a
4b
4a
4a
4a
4a
4a
4b
4a
Me
Me
t-BuCH2
PhCH2
Me
Me
Me
t-BuCH2
Me
Me
Me
Me
Me
t-BuCH2
Me
5a
5a
5b
5c
5d
5e
5f
5g
5h
5i
1.5:1
1.5:1
1.1:1
1.1:1
1.4:1
1.4:1
1.5:1
1.2:1
1.7:1
1.3:1
1.5:1
1:1.4
2:1
6a
6a
6b
6c
6d
6e
6f
6g
6h
6i
19
19
21
18
19
9
f
f
47
72
75
48
69
62
46
39
4-ClC6H4
4-FC6H4
4-MeC6H4
4-MeC6H4
2-ClC6H4
3-BrC6H4
2,6-Cl2C6H4
1-Naphthyl
Ph
21
19
27
16
17
27
16
10
13
8
9
10
11
12
13
14
15
de
de
,
,
5l
25
61
51
40
60
6l
de
de
,
,
5m
5n
5j
6m
6n
6j
de
de
,
,
t-BuCH2
t-BuCH2
Me
d
d
Ph
n-C5H11
1:1.2
1.3:1
5k
6k
a
Conditions 1: formation of complex 3 from ACDC (1 equiv.) and GaCl3 (1.1−1.2 equiv) at 0−40 °C during 10−75 min (See Refs.10a,b and
b
c
Experimental Section). Conditions 2: diazo ester (2 equiv.) in CH2Cl2 was added to complex 3 at 15 °C and mixture was stirred 15 min. Ratio of
isomers was determined by H NMR spectra. NMR yield, yield was determined by H NMR spectra using 1,4-dinitrobenzene as an internal
standard. Products were not isolated in pure form. Gram-scale of the reaction: 2.1 g (9.0 mmol) of DAC 1a was used.
d
1
1
e
f
that the action of GaCl3 on cyclopropane 5a under the reaction
conditions (15 °C, 15 min) practically does not cause its
isomerization to alkene 6a.
In total, the scope for DAC is rather wide, and various DAC
can be used to obtain cyclopropane triesters 5 in decent yields
(Table 2). ACDC with substituents at various positions of the
benzene ring, as well as n-butylcyclopropane 1h, can be
successfully used in the reaction and the substituents in the
ester groups can be varied.
The mechanism of the occurring processes can be described
as follows (Scheme 2, Figure 1). At the first stage, a relatively
stable gallium complex 3 is generated. Its carbocationic center
attacks the diazo compound with elimination of a nitrogen
molecule and formation of a new 1,3-zwitterion 7 that should
be very unstable (path a). The latter undergoes cyclization to
give a complex of cyclopropanetricarboxylate 5 with GaCl3 and
partial isomerization into 1,2-zwitterionic gallium complex 8
that is the most stable species under the reaction conditions.
After acid treatment of the reaction mixture, both complexes
are converted into cyclopropane 5 or unsaturated triester 6
(Scheme 2). The other path of the formation of cyclopropane
product 5 may occur directly from the diazonium intermediate
that precedes zwitterion 3 by an intramolecular nucleophilic
substitution by-passing the unstable species 3 (path b). In
essence, the process under consideration resembles the
formation of cyclopropane derivatives by the Corey-Chaykov-
sky reaction.15 In this case, the Michael acceptor is strongly
activated due to complexation with gallium trichloride, which
allows it to react with such a weak nucleophile as diazo acetate.
To better understand the discovered process, its regularities,
and mechanism, we have studied in details formed minor
products during the reaction at various conditions (Table 3,
Figure 2). Besides main compounds 5 and 6, almost only
products of double addition of the diazoacetate (MDA) are
formed. Herewith, the summary yield may exceed 95%.
However, the structures of these heavy products are highly
different, and significantly depend on the reaction conditions
and primarily on the excess of using diazoacetate (Table 3).
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Scheme 2. Proposed Simplified Mechanism for the Formation of Cyclopropanes 5
Thus, minor cyclobutane structure 10 and cyclopropane 9a are
formed, when 2 equiv. of MDA was used (some preliminary
data can be also found in our previous paper14). The last
activated cyclopropane 9a is quite interesting and contains four
carboxylate groups and three new stereocenters. This cyclo-
propane 9a can be prepared quite selectively using 10 equiv of
MDA at 15 °C with yields of more than 55% (Table 3, Entry
2). It is formed primarily as one cis-diastereomer with single
configuration of the acyclic stereocenter (Figure 2). Using a
10-fold excess of MDA, especially at a slightly elevated
Figure 1. Analysis of stereochemistry for the trans- and cis-isomers of
cyclopropane 5.
a b
,
Table 3. Double Addition of the Diazoacetate (MDA) to D−A Cyclopropane 1a and Formation of Heavy Products
ab
,
c
products ; yield, %; (cis/trans ratio)
d
e
d
f
d
entry
4a (equiv.)
conditions
9a
5a
6a
10
mixt. of alkenes
11
12
1
2
3
4
2
15 °C, 15 min
15 °C, 15 min
30 °C, 15 min
15 °C, 15 min
7 (1:1)
57 (2.4:1)
35−40
<20
60 (1:1.5)
9 (1:2)
10
19
3 (1:1)
n.d.
<5
15
25−30
20
n.d.
n.d.
n.d.
10
n.d.
n.d.
n.d.
2−3
10
10
30
<2
<2
n.d.
n.d.
n.d.
<5
a
b
Determined main and minor products of multiple MDA addition at various reaction conditions. Carbons from diazoacetate are indicated by light
c
blue circles. Averaged yields based on NMR data and data after column chromatography; accuracy 2−3%; yields are indicated for typical
experiments. Structures of minor products 10, 11, and 12. Mixt. of ″heavy″ alkenes. n.d. = not detected.
d
e
f
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Figure 2. (A) Detailed analysis of skeleton and stereochemistry of the main isomer of cyclopropane 9a. (B) Proposed mechanism for the formation
of cyclopropane 9a. Notes: coordination with GaCl3 is omitted for clarity; configuration of the stereocenter indicated by (#) is proposed by NOE
data, only one diastereomer is formed on this stereocenter.
temperature (30 °C), various confirmed alkene products of
double MDA addition are also formed in quite significant
quantities during the reaction (Table 3, Entries 2 and 3). Using
a 30 equiv. of MDA, it can be obtained triple addition
productscyclopropane pentacarboxylate 11 and side iso-
meric cyclobutane pentacarboxylate 12 (Table 3, Entry 4). It
should be noted that the formation of cyclobutanes in DAC
reactions is extremely rare, even as a side reaction.16
Cyclopropane products like 9a were also detected and isolated
for some other substituted D−A cyclopropanes 1 and also for a
benzyl diazoacetate 4c.
The main route to form the heavy products of double diazo
ester addition is going through the initial formation of
cyclopropane 5, which is also activated by two carboxylate
groups in strong Lewis acid conditions (Figure 2). This leads
to further C−C cleavage of the cyclopropane ring and
subsequent reaction with the second MDA molecule. Control
mechanistic experiment also demonstrates an activation of a
three-membered ring in cyclopropane 5a in the presence of
GaCl3 (Scheme 2, bottom, right).
tetrasubstituted cyclopropane 5l is formed in only 6−7%
yield and, like in the case of ACDC 1, as a mixture of trans- and
cis-isomers. The amount of tetrasubstituted alkene 6l formed
remains at nearly the same level. The importance of this
process should be noted separately, since the formation of
cyclobutanes in DAC reactions is extremely rare, even as a side
reaction.16
A distinctive feature of diphenyl-substituted cyclopropane
diester 1i is apparently that it, already during its formation, is
partially isomerized into 1,3-zwitterion 15 due to phenyl
migration. Further, both of these intermediates react with
diazo acetate 4a with elimination of nitrogen to generate 1,3-
zwitterion 3i in one case, and 1,4-zwitterion 16 in the other
case. As expected, the first zwitterion either undergoes
cyclization to substituted cyclopropane 5l or is converted to
alkene 6l, while the second one mostly undergoes cyclization
to cyclobutanetricarboxylate 13. The latter gradually undergoes
opening under the reaction conditions in the presence of
GaCl3 with addition of a chloride anion to give chloro
derivative 14 (Scheme 4). It is interesting to note that, like
cyclobutane 13, trisubstituted lactone 14 is formed as a single
stereoisomer only.
The resulting cyclopropanetricarboxylates 5 also belong to
activated cyclopropanes that can be used as DAC in further
reactions (Scheme 5). Moreover, they contain an additional
functional group. We used 5a as an example to study the
possibility of their conversion under the effect of Lewis acids,
with benzaldehyde as the classic model interceptor of a 1,3-
zwitterion.17 As expected, cyclopropane 5a was found to be
much less reactive than ACDC 1 due to the presence of a Bn
group instead of Ph at position 2. The reaction occurred slowly
even if strong Lewis acids, such as GaCl3 or SnCl4, were used
and the process was performed under reflux conditions in
CH2Cl2. The process occurred much better in the presence of
TiCl4, therefore we subsequently used this particular Lewis
acid for optimizing the reaction conditions (Table 4).
It was found that more drastic conditions (reflux in 1,2-
dichloroethane with a 1.5-fold excess of TiCl4) resulted in the
efficient reaction of 5a with benzaldehyde to give dihydrofur-
an-2-ones 17 and 18, as well as a chlorine-containing ester 19.
In addition, in the reaction mixture, we found the presence of
isomeric trimethyl 5-benzyl-2-phenyltetrahydrofurane-3,3,4-
tricarboxylates formed according to the usual scheme (3 +
Separately, a confirmed formation of two products resulting
from the decomposition of an excess of diazo ester under
action of GaCl3 without involving a DAC molecule should also
be noted. These products can be obtained in significant
quantities in some cases (Figure 3).
Figure 3. Detected products formed as a result of the side
decomposition process of Bn and Me diazoacetates (left and right,
respectively).
Further, in order to estimate the effect of additional
substituents in the original DAC on the nature of conversion
of the resulting zwitterionic intermediates, we studied the
reaction of methyl diazo acetate with gallium complex 3i
obtained from 2,2-diphenylcyclopropane-1,1-dicarboxylate 1i.
It was found that in this case, the process occurs differently to
give cyclobutanetricarboxylate 13 as the main product. Despite
the presence of three stereo centers, this compound is formed
as a sole trans,trans isomer (Scheme 3). The expected
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Scheme 3. Reaction of the 2,2-Ph,Ph-Disubstituted DAC 1i with Diazo Acetates in the Presence of GaCl3: (A) General
Reaction Pathways and Product Yields; (B) Analysis of the Stereochemistry of Main Cyclobutane Product 13; (C) Formation
a b
,
Route of the Lactone 14
a
b
NMR yields, yields after column chromatography are given in the second parentheses. Carbons from diazoacetate are indicated by light blue
circles.
Scheme 4. Proposed Mechanism for the Formation of Cyclobutanes 13
It is important to note that an additional ester group
introduced into a DAC from a diazo ester is involved in the
formation of both products 17 and 18. Furthermore, despite
the fact that a mixture of trans- and cis-isomers 5a was used in
the reaction, dihydrofuran-2-one 17 was formed only as a
single diastereomer, including the formation of a CH−Cl
stereo center in the aliphatic chain (Scheme 5, Figure 4).
Thus, the low diastereoselectivity of the first process (the
reaction of ACDC with diazo esters) does not at all interfere
with the further use of compounds 5 as a mixture of isomers
and the selectivity is “corrected” in the subsequent reactions
(Scheme 5). The presence of side products, alkenes 6, in the
reaction mixture does not interfere with the process either.
The mechanism of the formation of dihydrofuran-2-ones 17
and 18 can be represented as a cascade of transformations
demonstrated in Scheme 6. Under sufficiently drastic
conditions in the presence of TiCl4, the donor−acceptor
bond in cyclopropane 5a is broken and a benzaldehyde
molecule is added to the resulting 1,3-zwitterion. Subsequently,
a series of intramolecular transformations occurs, resulting in
the selective formation of five-membered lactones 17 and 18.
Aliphatic triester 19 arises as a result of a competing process
of transfer of chlorine anion from TiCl4 in the generated 1,3-
zwitterionic intermediate 20; moreover, this process is most
likely realized in the intermolecular version. It is logical that
Scheme 5. Further Synthetic Utility of the Obtained
Cyclopropanetricarboxylates 5 as D−A Cyclopropanes
a
a
Proposed configuration of this stereocenter (marked with #) by
NOE data.
2)-cycloaddition of 1,3-zwitterion generated from the 5a to
benzaldehyde. However, due to the formation of a mixture of
isomers and their small content, we did not conduct a detailed
study of tetrahydrofuranetricarboxylates.
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Table 4. Optimization of the Reaction Conditions for a
Reaction of Cyclopropane 5a with Benzaldehyde
Scheme 6. Proposed Simplified Mechanism for the
Formation of Lactones 17 and 18
a
b
ratio
T
t
yield (%)
lewis acid
(LA)
5a/LA/
PhCHO
a
c
entry
(°C) (h)
17
18
19
d
d
d
1
2
3
4
5
6
7
8
9
GaCl3
SnCl4
TiCl4
TiCl4
TiCl4
TiCl4
TiCl4
TiCl4
TiCl4
TiCl4
2:1:6
3:1:6
3:1:6
1:1:3.5
1:2:2.5
1:1.5:2.5
1:1.5:2.5
1:1.5:2.5
1:1.5:1
1:1.5:5
40
40
40
84
84
84
84
84
84
84
2
3
3
3
3
3
6
1
3
3
−
−
−
−
−
d
d
d
−
e
3
12
2
70
10
16
7
13
35
e
e
22
e
e
e
37
20
12
22
20
13
35
26
20
23
10
13
26
10
21
a
b
1,2-DCE (DCM) was used as a solvent (3 mL). NMR yield; they
1
were determined by H NMR spectra using 1,4-dinitrobenzene as an
internal standard. A mixture of (E + Z)-isomers in ratio ∼ 2.5:1. No
reaction. Yield after column chromatography.
c
d
e
a
Coordination with TiCl4 is given in a simplified version only for
demonstration a general mechanistic pathway and does not reflect a
real picture.
1,1,2-tricarboxylate. The mechanism of the occurring processes
is discussed.
EXPERIMENTAL SECTION
■
General Experimental Details. All reagents and solvents were
used as commercial grade chemicals without additional purification.
All operations with GaCl3, SnCl4, and TiCl4 were carried out under a
1
dry argon atmosphere. H and 13C{1H} NMR spectra were recorded
Figure 4. Analysis of structure and stereochemistry for the lactone 17.
on 400 MHz (400.1 and 100.6 MHz, respectively) and 300 MHz
(300.1 and 75.5 MHz, respectively) spectrometers in CDCl3
containing 0.05% Me4Si as the internal standard. Determinations of
structures and stereochemistry of obtained compounds and assign-
the formation of this compound becomes dominant at 40 °C
(instead of 84 °C), when the interaction of the zwitterion 15
with the aldehyde has not yet occurred (Table 4, Entry 3).
1
ments of H and 13C signals were made with the aid of 1D and 2D
gradient/nongradient DEPT-135, COSY, NOESY, HSQC, and
HMBC spectra. Diffusion NMR spectra (2D DOSY using LED
pulse sequence with bipolar gradient pulses) were used for estimation
of molecular weights in solution.18 IR spectra were obtained on a FT-
IR spectrometer in KBr plates (thin layer). Mass spectra were
recorded using electron impact ionization (EI, 70 eV, direct inlet
probe). High-resolution mass spectra were obtained using simulta-
neous electrospray (ESI-TOF).19
Synthesis of Starting Cyclopropanes 1a−g. Starting cyclo-
propanes 1a−g (ACDC) were synthesized from the corresponding
aromatic aldehydes through a standard synthetic sequence of
Knoevenagel/Corey−Chaykovsky reactions.2,10b,17b
Typical Experimental Procedure for Reactions of DACs 1a−
g with Diazocompounds 4a−c. All operations were performed
under a dry argon atmosphere. A solid GaCl3 (0.45−0.85 mmol) was
CONCLUSIONS
■
In conclusion, a new process involving the addition of diazo
esters to donor−acceptor cyclopropanes (DACs) activated by
GaCl3 (via 1,2-zwitterionic gallium synthons) has been
developed. In all the cases, the reactions occur with elimination
of nitrogen to give 1,1,2,3-tetrasubstituted cyclopropanes as
the main products, along with isomeric alkenes. In the case of
2,2-diphenylcyclopropane-1,1-dicarboxylate, along with the
formation of the corresponding cyclopropane and alkene,
1,2-migration of a phenyl group in the initial 1,2-zwitterionic
synthon easily takes place to give 3,4-diphenylcyclobutane-
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added to a solution of DACs 1a−g (0.4−0.7 mmol) in dry
dichloromethane (2−3 mL) and reaction mixture was stirred at 0−
40 °C during 10−75 min (see Refs.10a,b). Then diazo compound 4
was added to a solution of 1,2-zwitterionic intermediate and a mixture
was stirred at 15 °C during 15 min. After that, an aqueous solution of
HCl (5%) was added at room temperature until a pH of 3 was
achieved, and the reaction mixture was extracted with CH2Cl2 (3 × 7
mL). The organic layer was dried over MgSO4, and the solvent was
removed in vacuo. The residue was purified by flash chromatography
on silica gel (eluent: benzene−EtOAc (100:1) to benzene−EtOAc
(10:1)) to afford the expected products. The yields of compounds
obtained are given taking into account their content in the
intermediate fractions. The resulting compounds could be addition-
ally purified on a Silufol chromatographic plate (20 × 20 cm) using
hexane−acetone (10:1) as an eluent. A mixture of trans- and cis-
isomers is usually formed. Diastereomers are practically inseparable in
most cases using standard column chromatography on SiO2 or PTLC
because their Rf are usually very close, but in several cases, isomers
mg, 0.4 mmol), GaCl3 (79.3 mg, 0.45 mmol) and neopentyl
diazoacetate 4b (125 mg, 0.8 mmol). After column chromatography
on SiO2 cyclopropanes 5b as a mixture of cis- and trans-isomers in
ratio 1:1.1 and alkene 6b were isolated in yields 68.1 mg (47%) and
30.4 mg (21%), respectively. Compound 5b: colorless oil. IR (KBr): υ
̅
3037, 2957, 1730 br (CO), 1438, 1273, 1196, 1171, 1119 cm−1.
HRMS (ESI-TOF) m/z: calcd for [M + H]+ C20H26O6H 363.1802;
1
found, 363.1806. Isomer cis-5b: H NMR (300.1 MHz, CDCl3): δ
7.39−7.21 (m, 5H, Ph), 3.82 and 3.76 (both s, 2 × 3H, 2 OMe), 3.74
(s, 2H, OCH2), 3.38 (dd, 1H, CHbPh, 2J = 15.4 Hz, 3J = 5.2 Hz), 3.19
2
3
3
(dd, 1H, CHaPh, J = 15.4 Hz, J = 9.6 Hz), 2.75 (d, 1H, H(2), J =
9.6 Hz), 2.23 (ddd, 1H, H(3), 3J = 9.6 Hz, 3Jcis = 9.6 Hz, 3J = 5.2 Hz),
0.94 (s, 9H, t-Bu) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.4,
168.5 and 166.6 (3 COO), 140.0 (i-Ph), 128.6 and 128.5 (o- and m-
Ph), 126.5 (p-Ph), 74.6 (OCH2), 53.0 and 52.6 (2 OMe), 39.5
(C(1)), 33.8 (C(3)), 31.2(C), 30.5 (C(2)), 29.2 (CH2), 26.3 (t-Bu).
1
Isomer trans-5b: H NMR (300.1 MHz, CDCl3): δ 7.39−7.21 (m,
5H, Ph), 3.84 (s, 2H, OCH2), 3.78 and 3.72 (both s, 2 × 3H, 2
OMe), 2.68−3.00 (m, 4H, H(2), H(3), CH2Ph), 0.94 (s, 9H, t-Bu)
ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.6, 167.2 and 165.5
(3 COO), 140.0 (i-Ph), 128.6 and 128.5 (o- and m-Ph), 126.5 (p-Ph),
74.6 (OCH2), 53.3 and 52.9 (2 OMe), 42.0 (C(1)), 33.8 (C(3)),
31.7 (CH2), 31.4 (C), (C(2)), 26.4 (t-Bu). Compound 6b: colorless
1
were easily separated. In other cases, it is possible to describe the H
and 13C NMR spectra of each isomer without any problems even for
inseparable mixtures using of a set of 2D correlation NMR
experiments.
Trimethyl 3-benzylcyclopropane-1,1,2-tricarboxylate (5a)
and trimethyl 2-benzylprop-1-ene-1,1,3-tricarboxylate (6a).
The title compounds were prepared according to the general
procedure from ACDC 1a (164 mg, 0.7 mmol), GaCl3 (141 mg,
0.8 mmol), and methyl diazoacetate (139 mg, 1.38 mmol). After
column chromatography on SiO2 compounds cis- and trans-5a, and 6a
were isolated in yields 51.4 mg (24%), 77.2 mg (36%), and 40.8 mg
oil. IR (KBr): υ 3024, 1729, 1260, 1175 cm−1. HRMS (ESI-TOF) m/
̅
1
z: calcd for [M + H]+ C20H26O6H 363.1800; found, 363.1802. H
NMR (300.1 MHz, CDCl3): δ 7.32−7.20 (m, 5H, Ph), 3.84 and 3.77
(both s, 2 × 3H, 2 OMe), 3.73 and 3.72 (both s, 2 × 2H, H2C(3) and
OCH2), 3.46 (s, 2H, CH2Ph), 0.91 (s, 9H, t-Bu) ppm. 13C{1H} NMR
(75.5 MHz, CDCl3): δ 169.2, 166.5 and 164.5 (3 COO), 151.3
(C(2)), 136.1 (i-Ph), 129.5 and 128.8 (o- and m-Ph), 127.3 (C(1)),
127.1 (p-Ph), 74.3 (OCH2), 52.5 and 52.2 (2 OMe), 41.5 (CH2),
37.4 (CH2Ph), 31.3(C), 26.4 (t-Bu).
(19%), respectively. Compound cis-5a: colorless oil. IR (KBr): υ
̅
3051, 1736, and 1729 br (CO), 1439, 1278, 1237, 1182, 1127
cm−1. HRMS (ESI-TOF) m/z: calcd for [M + Na]+ C16H18O6Na
329.0995; found, 329.0996. 1H NMR (300.1 MHz, CDCl3): δ 7.35−
7.19 (m, 5H, Ph), 3.72, 3.78, and 3.83 (all s, 3 × 3H, 3 OMe), 3.34
(dd, 1H, CHbPh, 2J = 15.4 Hz, 3J = 5.3 Hz), 3.15 (dd, 1H, CHaPh, 2J
2-Benzyl 1,1-dimethyl 3-benzylcyclopropane-1,1,2-tricar-
boxylate (5c) and 3-benzyl 1,1-dimethyl 2-benzylprop-1−
ene-1,1,3-tricarboxylate (6c). The title compounds were prepared
according to the general procedure from ACDC 1a (89.1 mg, 0.38
mmol), GaCl3 (75.7 mg, 0.43 mmol) and neopentyl diazoacetate 4c
(132 mg, 0.75 mmol). After column chromatography on SiO2
cyclopropanes 5c as a mixture of cis- and trans-isomers in ratio
1:1.1 and alkene 6c were isolated in yields 104.4 mg (72%) and 26.1
mg (18%), respectively. HRMS (ESI-TOF) m/z: calcd for [M + H]+
C22H22O6H 383.1489; found, 383.1490. Isomer cis-5c: 1H NMR
(300.1 MHz, CDCl3): δ 7.39−7.16 (m, 5H, Ph), 5.15 (s, 2H, OCH2),
3
3
= 15.4 Hz, J = 9.5 Hz), 2.70 (d, 1H, H(2), J = 9.5 Hz), 2.24 (ddd,
3
3
3
1H, H(3), J = 5.3 Hz, Jcis = 9.5 Hz, J = 5.3 Hz) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.4, 168.8, and 165.5 (3 COO), 140.0
(i-Ph), 128.6 and 128.4 (o- and m-Ph), 126.4 (p-Ph), 53.4, 52.7, and
52.2 (3 OMe), 39.4 (C(1)), 33.7 (C(3)), 30.3 (C(2)), 29.2 (CH2).
Compound trans-5a: colorless oil. IR (KBr): υ 3051, 1739, and 1730
̅
br (CO), 1437, 1276, 1237, 1182, 1127 cm−1. HRMS (ESI-TOF)
m/z: calcd for [M + Na]+ C16H18O6Na 329.0995; found, 329.0998.
1H NMR (300.1 MHz, CDCl3): δ 7.23−7.35 (m, 5H, Ph), 3.77, 3.72,
and 3.71 (all s, 3 × 3H, 3 OMe), 2.96 and 2.85 (both dd, 2 × 1H,
2
3.64, and 3.77 (both s, 2 × 3H, 2 OMe), 3.32 (dd, 1H, CHbPh, J =
3
2
3
15.5 Hz, J = 5.7 Hz), 3.16 (dd, 1H, CHaPh, J = 15.5 Hz, J = 9.4
3
3
2
3
Hz), 2.75 (d, 1H, H(2), J = 9.4 Hz), 2.22 (ddd, 1H, H(3), J = 9.4
CH2Ph, J = 15.3 Hz, J = 7.2 Hz), 2.82−2.66 (m, 2H, H(2) and
H(3)) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.7, 167.0, and
166.6 (3 COO), 138.7 (i-Ph), 128.6, and 128.1 (o- and m-Ph), 126.5
(p-Ph), 53.0, 52.9, and 52.4 (3 OMe), 42.0 (C(1)), 32.8 (C(3)), 32.7
Hz, Jcis = 9.4 Hz, J = 5.7 Hz) ppm. 13C{1H} NMR (75.5 MHz,
CDCl3): δ 169.1, 168.2 and 167.0 (3 COO), 128.56, 128.50, 128.42
and 128.36 (o- and m-Ph in 2 Ph), 128.3 and 126.3 (2 p-Ph), 67.1
(OCH2), 53.3 and 52.8 (2 OMe), 39.5(C), 33.9 (C(3)), 30.3 (C(2)),
29.2 (CH2). Isomer trans-5c: 1H NMR (300.1 MHz, CDCl3): δ
7.39−7.16 (m, 5H, Ph), 5.16 (s, 2H, OCH2), 3.70 and 3.78 (both s, 2
× 3H, 2 OMe), 2.95 (dd, 1H, CHbPh, 2J = 15.4 Hz, 3J = 5.7 Hz), 2.84
(dd, 1H, CHaPh, 2J = 15.4 Hz, 3J = 9.4 Hz), 2.86−2.69 (m, 2H, H(2)
and H(3)) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.4, 166.5
and 165.4 (3 COO), 128.58 and 128.51, 128.39, 128.12 (o- and m-Ph
in 2 Ph), 128.2 and 126.5 (2 p-Ph), 67.0 (OCH2), 53.0 and 52.6 (2
OMe), 42.1(C), 32.9 and 32.2 (C(3) and (C(2)), 31.7 (CH2).
Compound 6c: colorless oil. HRMS (ESI-TOF) m/z: calcd for [M +
3
3
(C(2)), 31.8 (CH2). Compound 6a: Colorless oil. IR (KBr): υ 3037,
̅
2954, 1734 br (CO), 1436, 1257, 1191, 1178, 1062 cm−1. HRMS
(ESI-TOF) m/z: calcd for [M + H]+ C16H18O6H 307.1176; found,
307.1178. 1H NMR (300.1 MHz, CDCl3): δ 7.34−7.23 (m, 5H, Ph),
3.74 (s, 2H, CH2), 3.86, 3.79 and 3.66 (all s, 3 × 3H, 3 OMe), 3.45 (s,
2H, CH2Ph) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.7,
166.4 and 164.5 (3 COO), 151.4 (C(2)), 136.1 (i-Ph), 129.5 (C(1)),
128.7 and 127.8 (o- and m-Ph), 127.1 (p-Ph), 52.5, 52.3, and 52.1 (3
OMe), 41.5 (CH2), 37.1 (CH2Ph).
Gram-scale synthetic procedure for trimethyl 3-benzylcy-
clopropane-1,1,2-tricarboxylate (5a) and trimethyl 2-benzyl-
prop-1-ene-1,1,3-tricarboxylate (6a). The title compounds were
prepared according to the general procedure from ACDC 1a (2.1 g,
9.0 mmol), GaCl3 (1.8 g, 10.1 mmol) and methyl diazoacetate (1.8 g,
18.0 mmol). After column chromatography on SiO2 compounds cis-
and trans-5a and 6a were isolated in yields 1.9 g (72%) and 0.5 g
(19%), respectively.
H]+ C22H22O6H 383.1479; found, 383.1489. H NMR (300.1 MHz,
1
CDCl3): δ 7.40−7.16 (m, 2 × 5H, 2 Ph), 5.12 (OCH2), 3.88 and 3.75
(both s, 2 × 3H, 2 OMe), 3.76 (CH2), 3.53 (s, 2H, CH2Ph). 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.1, 166.4 and 165.5 (3 COO), 151.2
(C(2)), 136.0 and 135.7 (i-Ph), 129.5, 128.8, 128.5, and 128.2 (o-
and m-Ph in 2 Ph), 128.0 (C(1)), 128.4 and 127.1 (2 p-Ph), 66.7
(OCH2), 52.5 and 52.3 (OMe), 41.6 (CH2), 37.4 (CH2Ph).
1,1-Dimethyl 2-neopentyl 3-benzylcyclopropane-1,1,2-tri-
carboxylate (5b) and 1,1-dimethyl 3-neopentyl 2-benzylprop-
1−ene-1,1,3-tricarboxylate (6b). The title compounds were
prepared according to the general procedure from ACDC 1a (93.7
Trimethyl 3-(4-chlorobenzyl)cyclopropane-1,1,2-tricarbox-
ylate (5d) and trimethyl 2-(4-chlorobenzyl)prop-1−ene-
1,1,3-tricarboxylate (6d). The title compounds were prepared
according to the general procedure from ACDC 1b (145 mg, 0.54
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2
mmol), GaCl3 (105 mg, 0.6 mmol) and methyl diazoacetate 4a (109
mg, 1.08 mmol). After column chromatography on SiO2 cyclo-
propanes 5d as a mixture of cis- and trans-isomers in ratio 1:1.4 and
alkene 6d were isolated in yields 137.3 mg (75%) and 35.0 mg (19%),
115.5 (d, o-Ar, JCF = 21.4 Hz), 52.5, 52.3 and 52.1 (3 OMe), 40.6
(CH2), 37.1 (CH2Ph). 19F NMR (282.4 MHz, CDCl3): δ −115.5
ppm.
Trimethyl 3-(4-methylbenzyl)cyclopropane-1,1,2-tricarbox-
ylate (5f) and trimethyl 2-(4-methylbenzyl)prop-1-ene-1,1,3-
tricarboxylate (6f). The title compounds were prepared according
to the general procedure from ACDC 1d (136 mg, 0.55 mmol),
GaCl3 (109 mg, 0.62 mmol) and methyl diazoacetate 4a (113 mg, 1.1
mmol). After column chromatography on SiO2 cyclopropanes 5f as a
mixture of cis- and trans-isomers in ratio 1:1.5 and alkene 6f were
isolated in yields 121 mg (69%) and 37.3 mg (21%), respectively.
respectively. Compound 5d: light yellow oil. IR (KBr): υ 3052, 1737
̅
and 1729 br (CO), 1493, 1437, 1275, 1237, 1171, 1123 cm−1.
HRMS (ESI-TOF) m/z: calcd for [M + H]+ C16H17O6ClH (for 35Cl)
1
341.0786; found, 341.0779. Isomer cis-5d: H NMR (300.1 MHz,
CDCl3): δ 7.20−7.15 and 7.31−7.26 (both d, 2 × 2H, C6H4), 3.82,
3.78 and 3.71 (all s, 3 × 3H, 3 OMe), 3.29 (dd, 1H, CHbPh, 2J = 15.5
3
2
3
Hz, J = 5.7 Hz), 3.11 (dd, 1H, CHaPh, J = 15.5 Hz, J = 9.4 Hz),
2.69 (d, 1H, H(2), 3J = 9.4 Hz), 2.18 (ddd, 1H, H(3), 3J = 9.4 Hz, 3Jcis
Compound 5f: colorless oil. IR (KBr): υ 3052, 1741 and 1724 br
̅
(CO), 1516, 1438, 1266, 1171, 1120 cm−1. HRMS (ESI-TOF) m/
z: calcd for [M + H]+ C17H20O6H 321.1324; found, 321.1333. Isomer
cis-5f: 1H NMR (300.1 MHz, CDCl3): δ 7.12 (br. s, 4H, C6H4), 3.83,
3.76 and 3.72 (all s, 3 × 3H, 3 OMe), 3.29 (dd, 1H, CHbPh, 2J = 15.3
= 9.4 Hz, J = 5.7 Hz) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ
3
170.5, 169.3 and 165.4 (3 COO), 138.4 (i-Ar), 128.9 and 129.8 (o-
and m-Ar), 128.7 (p-Ar), 53.4, 52.7 and 52.2 (3 OMe), 39.5 (C(1)),
1
33.3 (CH2), 30.1 and 28.6 (C(3) and C(2)). Isomer trans-5d: H
3
2
3
Hz, J = 5.4 Hz), 3.10 (dd, 1H, CHaPh, J = 15.3 Hz, J = 9.4 Hz),
NMR (300.1 MHz, CDCl3): δ 7.31−7.26 and 7.20−7.15 (both m, 2
3
2.68 (d, 1H, H(2), J = 9.5 Hz), 2.34 (s, 3H, Me), 2.21 (ddd, 1H,
× 2H, C6H4), 3.76, 3.71 and 3.70 (all s, 3 × 3H, 3 OMe), 2.92 (dd,
H(3), J = 9.5 Hz, Jcis = 9.5 Hz, J = 5.4 Hz) ppm. 13C{1H} NMR
(75.5 MHz, CDCl3): δ 169.4, 168.8 and 165.5 (3 COO), 136.9 and
135.8 (i- and p-Ar), 129.2 and 128.3 (o- and m-Ar), 53.0, 52.4 and
52.1 (3 OMe), 39.4 (C(1)), 32.7 (CH2), 31.4 and 28.8 (C(3) and
C(2)), 21.0 (Me). Isomer trans-5f: 1H NMR (300.1 MHz, CDCl3): δ
7.13 (br. s, 4H, C6H4), 3.77, 3.73 and 3.70 (all s, 3 × 3H, 3 OMe),
3
3
3
2
3
2
1H, CHbPh, J = 15.4 Hz, J = 6.7 Hz), 2.81 (dd, 1H, CHaPh, J =
3
15.4 Hz, J = 7.2 Hz), 2.78−2.60 (m, 2H, H(2) and H(3)) ppm.
13C{1H} NMR (75.5 MHz, CDCl3): δ 169.5, 168.7 and 166.9 (3
COO), 137.2 (i-Ar), 132.9 (p-Ar), 129.4 and 128.6 (o- and m-Ar),
53.0, 52.9 and 52.6 (3 OMe), 42.0 (C(1)), 32.7 and 32.4 (C(2) and
C(3)), 31.0 (CH2). Compound 6d: light yellow oil. IR (KBr): υ 3048,
̅
2
3
1733 br (CO), 1493, 1436, 1277, 1185, 1094 cm−1. HRMS (ESI-
2.89 (dd, 1H, CHbPh, J = 15.5 Hz, J = 6.9 Hz), 2.81 (dd, 1H,
2
3
TOF) m/z: calcd for [M + H]+ C16H17O6ClH (for 35Cl) 341.0786;
CHaPh, J = 15.5 Hz, J = 7.2 Hz), 2.80−2.65 (m, 2H, H(2) and
H(3) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.7, 167.0 and
166.6 (3 COO), 136.0 and 135.6 (i- and p-Ar), 129.3 and 128.0 (o-
and m-Ar), 53.3, 53.0 and 52.6 (3 OMe), 42.1 (C(1)), 33.8 (CH2),
31.4 and 30.2 (C(3) and C(2)), 21.0 (Me). Compound 6f: colorless
1
found, 341.0786. H NMR (300.1 MHz, CDCl3): δ 7.32−7.16 (m,
4H, C6H4), 3.71 (s, 2H, CH2), 3.86, 3.80 and 3.66 (all s, 3 × 3H, 3
OMe), 3.42 (s, 2H, CH2Ph) ppm. 13C{1H} NMR (75.5 MHz,
CDCl3): δ 169.6, 166.2 and 164.5 (3 COO), 150.6 (C(2)), 134.8 (i-
Ar), 130.4 (p-Ar), 130.8 and 128.8 (o- and m-Ar), 128.5 (C(1)), 52.5,
52.3 and 52.1 (3 OMe), 40.7 (CH2), 37.2 (CH2Ph).
oil. IR (KBr): υ 3046, 2401, 1737 and 1728 br (CO), 1436, 1299,
̅
1281, 1169, 1119 cm−1. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C17H20O6H 321.1333; found, 321.1327. 1H NMR (300.1 MHz,
CDCl3): δ 7.11−7.06 (m, 4H, C6H4), 3.84, 3.77 and 3.64 (all s, 3 ×
3H, 3 OMe), 3.42 (s, 2H, CH2Ph), 2.31 (s, 3H, Me) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.7, 166.4 and 164.5 (3 COO), 151.4
(C(2)), 143.0 (i-Ar), 129.3 and 129.4 (o- and m-Ar), 129.0 (C(1)),
52.5, 52.3 and 52.1 (3 OMe), 41.2 (CH2), 37.1 (CH2Ph), 21.0 (Me).
1,1-Dimethyl 2-neopentyl 3-(4-methylbenzyl)-
cyclopropane-1,1,2-tricarboxylate (5g) and 1,1-dimethyl 3-
neopentyl 2-(4-methylbenzyl)prop-1−ene-1,1,3-tricarboxy-
late (6g). The title compounds were prepared according to the
general procedure from ACDC 1d (188.8 mg, 0.76 mmol), GaCl3
(140.6 mg, 0.79 mmol) and neopenthyl diazoacetate (237.6 mg, 1.52
mmol). After column chromatography on SiO2 compounds 5g (cis/
trans ∼ 1:1.2) and 6g were isolated in yields 177.4 mg (62%) and 54.4
mg (19%), respectively. Compound 5g: colorless oil. HRMS (ESI-
TOF) m/z: calcd for [M + H]+ C21H28O6H 377.1959; found,
377.1960. Isomer cis-5g: 1H NMR (300.1 MHz, CDCl3): δ 7.17−7.07
(m, 4H, Ar), 3.74 (s, 2H, OCH2), 3.77 and 3.73 (both s, 2 × 3H, 2
Trimethyl 3-(4-fluorobenzyl)cyclopropane-1,1,2-tricarboxy-
late (5e) and trimethyl 2-(4-fluorobenzyl)prop-1−ene-1,1,3-
tricarboxylate (6e). The title compounds were prepared according
to the general procedure from ACDC 1c (176 mg, 0.7 mmol), GaCl3
(132 mg, 0.75 mmol) and methyl diazoacetate 4a (141 mg, 1.4
mmol). After column chromatography on SiO2 cyclopropanes 5e as a
mixture of cis- and trans-isomers in ratio 1:1.4 and alkene 6e were
isolated in yields 109.2 mg (48%) and 20.5 mg (9%), respectively.
Compound 5e: light yellow oil. IR (KBr): υ 3051, 1739 and 1729 br
̅
(CO), 1511, 1438, 1270, 1172, 1123 cm−1. HRMS (ESI-TOF) m/
z: calcd for [M + H]+ C16H17O6FH 325.1082; found, 325.1083.
1
Isomer cis-5e: H NMR (300.1 MHz, CDCl3): δ 7.22−7.16 (m, 2H,
m-Ar), 7.02−6.95 (m, 2H, o-Ar), 3.81, 3.77 and 3.71 (all s, 3 × 3H, 3
2
3
OMe), 3.29 (dd, 1H, CHbPh, J = 15.4 Hz, J = 5.9 Hz), 3.11 (dd,
2
3
1H, CHaPh, J = 15.4 Hz, J = 9.1 Hz), 2.68 (d, 2H, H(2)), 2.18
(ddd, 1H, H(3), 3J = 9.3 Hz, 3Jcis = 9.3 Hz, 3J = 5.9 Hz) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.3, 168.7 and 165.4 (3 COO), 161.5
1
4
(d, p-Ar, JCF = 233 Hz), 135.6 (d, i-Ar, JCF = 2.2 Hz), 129.8 (d, m-
Ar, 3JCF = 6.2 Hz), 115.2 (d, o-Ar, 2JCF = 21.6 Hz), 53.3, 52.6 and 52.2
(3 OMe), 39.4 (C(1)), 32.7 (CH2), 30.1 and 28.4 (C(3) and C(2)).
3
2
OMe), 3.30 (dd, 1H, CHbPh, J = 15.3 Hz, J = 5.2 Hz), 3.12 (dd,
1H, CHaPh, 3J = 15.3 Hz, 3J = 9.6 Hz), 2.74 (d, 1H, H(2), 3Jcis = 9.6
3
3
19F NMR (282.4 MHz, CDCl3): δ −116.9 ppm. Isomer trans-5e: H
1
Hz), 2.33 (s, 3H, Me), 2.22 (ddd, 1H, H(3), J = 9.6 Hz, Jcis = 9.6
Hz, 3J = 5.2 Hz), 0.94 (s, 9H, t-Bu) ppm. 13C{1H} NMR (75.5 MHz,
CDCl3): δ 169.4, 167.2 and 165.5 (3 COO), 135.7 (i-Ph), 128.9 (p-
Ph), 128.2 and 127.9 (o- and m-Ph), 74.5 (OCH2), 53.0 and 52.6 (2
OMe), 39.3 (C(1)), 34.0 (C(3)), 31.2(C), 30.5 (C(2)), 28.8 (CH2),
26.3 (t-Bu), 21.0 (Me). Isomer trans-5g: 1H NMR (300.1 MHz,
CDCl3): δ 7.17−7.07 (m, 4H, Ar), 3.76 (s, 2H, OCH2), 3.81 and 3.75
(both s, 2 × 3H, 2 OMe), 2.94−2.82 (m, 2H, CH2Ph), 2.82−2.66 (m,
2H, H(2) and H(3)), 2.33 (s, 3H, Me), 0.95 (s, 9H, t-Bu) ppm.
13C{1H} NMR (75.5 MHz, CDCl3): δ 169.6, 168.5 and 166.6 (3
COO), 136.9 (i-Ph), 129.2 and 129.1 (o- and m-Ph), 129.0 (p-Ph),
74.6 (OCH2), 53.3 and 52.9 (2 OMe), 41.9 (C(1)), 32.9 (C(3)),
31.4 (C(2)), 31.3(C), 31.2 (CH2), 26.4 (t-Bu), 20.9 (Me).
Compound 6g: Colorless oil. HRMS (ESI-TOF) m/z: calcd for [M
+ H]+ C21H28O6H 377.1959; found, 377.1951. 1H NMR (300.1 MHz,
CDCl3): δ 7.17−7.08 (m, 4H, Ar), 3.85 (s, 2H, CH2), 3.77 and 3.75
(both s, 2 × 3H, 2 OMe), 3.47 (s, 2H, CH2), 2.32 (s, 3H, Me), 0.92
(s, 9H, t-Bu). 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.2, 166.5 and
NMR (300.1 MHz, CDCl3): δ 7.22−7.16 (m, 2H, m-Ar), 7.02−6.95
(m, 2H, o-Ar), 3.76, 3.70 and 3.69 (all s, 3 × 3H, 3 OMe), 2.65−2.75
(m, 2H, H(2) and H(3)), 2.88 (dd, 1H, CHbPh, 2J = 15.3 Hz, 3J = 6.8
Hz), 2.76 (dd, 1H, CHaPh, 2J = 15.3 Hz, 3J = 7.2 Hz) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.5, 166.9 and 165.5 (3 COO), 161.4
1
4
(d, p-Ar, JCF = 233 Hz), 134.4 (d, i-Ar, JCF = 2.1 Hz), 129.7 (d, m-
Ar, 3JCF = 6.2 Hz), 115.3 (d, o-Ar, 2JCF = 21.6 Hz), 53.1, 52.7 and 52.4
(3 OMe), 42.0 (C(1)), 33.6 (CH2), 32.7 and 30.9 (C(3) and C(2)).
19F NMR (282.4 MHz, CDCl3): δ −116.7 ppm. Compound 6e: light
yellow oil. IR (KBr): υ 3017, 2401, 1738 and 1728 br (CO), 1510,
̅
1436, 1263, 1172 cm−1. HRMS (ESI-TOF) m/z: calcd for [M + H]+
C16H17O6FH 325.1085; found, 325.1082. 1H NMR (300.1 MHz,
CDCl3): δ 7.29−7.19 (m, 2H, m-Ar), 7.05−6.96 (m, 2H, o-Ar), 3.70
(s, 2H, CH2), 3.86, 3.80 and 3.66 (all s, 3 × 3H, 3 OMe), 3.43 (s, 2H,
CH2Ph) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 166.9 (2 COO),
1
166.3 (COO), 162.4 (d, p-Ar, JCF = 235 Hz), 151.0 (C(2)), 131.7
(d, i-Ar, 4JCF = 2.2 Hz), 131.1 (d, m-Ar, 3JCF = 6.1 Hz), 127.9 (C(1)),
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3
164.5 (3 COO), 151.6 (C(2)), 136.7 (i-Ph), 132.9 (p-Ar), 129.4 and
129.3 (o- and m-Ar), 129.0 (C(1)), 74.3 (OCH2), 52.4 and 52.2 (2
OMe), 41.1 (CH2), 37.3 (CH2Ar), 31.3(C), 26.3 (t-Bu), 21.0 (Me).
Trimethyl 3-(2-chlorobenzyl)cyclopropane-1,1,2-tricarbox-
ylate (5h) and trimethyl 2-(2-chlorobenzyl)prop-1−ene-
1,1,3-tricarboxylate (6h). The title compounds were prepared
according to the general procedure from ACDC 1e (134 mg, 0.5
mmol), GaCl3 (99 mg, 0.57 mmol) and methyl diazoacetate 4a (100
mg, 1.0 mmol). After column chromatography on SiO2 cyclopropanes
cis- and trans-5h (ratio 1:1.7) and alkene 6h were isolated in yields
28.9 mg (17%), 49.2 mg (29%) and 45.9 mg (27%), respectively.
Compound cis-5h: light yellow oil. HRMS (ESI-TOF) m/z: calcd for
[M + H]+ C16H17O6ClH 341.0786; found, 341.0787. 1H NMR (300.1
MHz, CDCl3): δ 7.42−7.36, 7.30−7.25 and 7.23−7.17 (all m, 2H +
1H + 1H, C6H4), 3.83, 3.79 and 3.73 (all s, 3 × 3H, 3 OMe), 3.50
(dd, 1H, CHbPh, 2J = 15.5 Hz, 3J = 5.4 Hz), 3.23 (dd, 1H, CHaPh, 2J
H(3), J = 3Jcis = 9.6 Hz, 3J = 5.3 Hz), 0.96, 0.94 and 0.89 (all s, 3 ×
9H, 3 t-Bu) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 166.8, 166.1
and 165.2 (3 COO), 138.9 (i-Ph), 128.5 and 128.1 (o- and m-Ph),
126.2 (p-Ph), 74.8, 74.7 and 74.5 (3 × OCH2), 41.7 (C(1)), 33.8
(C(3)), 31.5(C), 31.4 and 29.2 (C(2) and CH2), 26.4, 26.3, 26.2 (3 t-
1
Bu). Isomer trans-5j: H NMR (300.1 MHz, CDCl3): δ 7.35−7.19
(m, 5H, Ph), 3.90, 3.89 and 3.79 (all s, 3 × 2H, 3 OCH2), 3.05 (dd,
1H, H(3), 3J = 15.4 Hz, 3J = 6.3 Hz), 2.85 (dd, 1H, CHaPh, 2J = 15.4
Hz, 3J = 9.5 Hz), 2.80−2.68 (m, 2H, H(2) and H(3)), 0.97 (s, 18H, 2
t-Bu), 0.95 (s, 9H, t-Bu) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ
169.6, 169.4 and 168.6 (3 COO), 140.2 (i-Ph), 128.4 and 128.3 (o-
and m-Ph), 126.4 (p-Ph), 75.5, 75.4 and 75.3 (3 × OCH2), 39.8
(C(1)), 32.5 (C(3)), 31.5 (C), 31.4 and 30.1 (CH2 and C(2)), 26.6,
26.5 and 26.4 (3 t-Bu). Compound 6j: Colorless oil. HRMS (ESI-
TOF) m/z: calcd for [M + H]+ C16H18O6H 307.1176; found,
307.1178. 1H NMR (300.1 MHz, CDCl3): δ 7.32−7.25 (m, 5H, Ph),
3.96, 3.89 and 3.74 (all s, 3 × 2H, 3 OCH2), 3.73 (s, 2H, CH2), 3.54
(s, 2H, CH2Ph), 0.99, 0.96 and 0.94 (all s, 3 × 9H, 3 t-Bu) ppm.
13C{1H} NMR (75.5 MHz, CDCl3): δ 169.2, 166.5 and 164.0 (3
3
3
= 15.5 Hz, J = 9.0 Hz), 2.69 (d, 1H, H(2), J = 9.3 Hz), 2.33 (ddd,
3
3
3
1H, H(3), J = 9.3 Hz, Jcis = 9.3 Hz, J = 5.4 Hz) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 169.3, 168.8 and 165.4 (3 COO), 137.6
(i-Ar), 134.2 (C−Cl), 130.3, 129.5, 127.9 and 126.9 (4 CH in Ar),
53.3, 52.7 and 52.2 (3 OMe), 39.3 (C(1)), 31.9 (C(3)), 30.2 (C(2)),
COO), 150.2 (C(2)), 136.2 (i-Ph), 129.5 and 128.7 (o- and m-Ph),
128.0 (C(1)), 127.1 (p-Ph), 75.1, 74.4 and 74.3 (3 OCH2), 41.5
(CH2), 37.2 (CH2Ph), 26.4 (3 t-Bu).
1
27.1 (CH2Ph). Compound trans-5h: colorless oil. H NMR (300.1
MHz, CDCl3): δ 7.29−7.16 and 7.40−7.35 (both m, 2 × 2H, C6H4),
Trimethyl 3-penthylcyclopropane-1,1,2-tricarboxylate (5k)
and trimethyl 2-penthylprop-1-ene-1,1,3-tricarboxylate (6k).
The title compounds were prepared according to the general
procedure from ACDC 1h (86.1 mg, 0.4 mmol), GaCl3 (79.4 mg,
0.45 mmol) and methyl diazoacetate 4a (80.2 mg, 0.8 mmol). After
column chromatography on SiO2 cyclopropanes cis- and trans-5k
(ratio ∼ 1:1.3) and alkene 6k were isolated in yields 29.8 mg (26%),
38.8 mg (34%) and 15.0 mg (13%), respectively. Compound cis-5k:
colorless oil. HRMS (ESI-TOF) m/z: calcd for [M + H]+ C14H22O6H
3.78, 3.72 and 3.71 (all s, 3 × 3H, 3 OMe), 3.08 (dd, 1H, CHbPh, 2J =
3
2
3
15.9 Hz, J = 6.8 Hz), 2.97 (dd, 1H, CHaPh, J = 15.9 Hz, J = 7.3
Hz), 2.82−2.73 (m, 2H, H(2) and H(3)) ppm. 13C{1H} NMR (75.5
MHz, CDCl3): δ 169.6, 166.9 and 166.6 (3 COO), 136.6 (i-Ar),
133.9 (C−Cl), 129.6, 129.5, 127.9and 127.0 (4 CH in Ar), 53.1, 53.0
and 52.4 (3 OMe), 41.9 (C(1)), 32.7 (C(3)), 31.3 (C(2)), 29.6
(CH2Ph). Compound 6h: colorless oil. IR (KBr): υ 3051, 2398, 1733
̅
br (CO), 1436, 1282, 1187 cm−1. HRMS (ESI-TOF) m/z: calcd
for [M + H]+ C16H17O6ClH (for 35Cl) 341.0786; found, 341.0779. 1H
NMR (300.1 MHz, CDCl3): δ 7.43−7.20 (m, 4H, C6H4), 3.95 (s, 2H,
CH2), 3.84, 3.80 and 3.65 (all s, 3 × 3H, 3 OMe), 3.44 (s, 2H,
CH2Ph) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.6, 166.1
and 164.6 (3 COO), 135.0 and 134.1 (2 C in Ar), 131.1, 129.6, 128.5
and 127.1 (4 CH in Ar), 52.5, 52.3 and 52.1 (3 OMe), 38.2 (CH2),
37.4 (CH2).
1
287.1489; found, 287.1491. H NMR (300.1 MHz, CDCl3): δ 3.76,
3
3.74 and 3.70 (all s, 3 × 3H, 3 OMe), 2.59 (d, 1H, (H(2), J = 9.5
Hz), 1.95−1.87 (m, 2H, H(3) and HbC(4)), 1.74−1.68 (m, 1H,
3
HaC(4)), 1.35−1.26 (m, 6H, 3 CH2), 0.88 (t, 3H, Me, J = 6.9 Hz)
ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.8, 168.7 and 165.6
(3 COO), 53.2, 52.5 and 52.0 (3 OMe), 39.1 (C(1)), 33.4 (C(3)),
30.3 (C(2)), 31.4 and 29.0 (C(5) and C(6)), 23.5 (C(4)), 22.5
(C(7)), 13.9 (Me). Compound trans-5k: colorless oil. 1H NMR
(300.1 MHz, CDCl3): δ 3.78, 3.76 and 3.71 (all s, 3 × 3H, 3 OMe),
Trimethyl 3-(3-bromobenzyl)cyclopropane-1,1,2-tricarbox-
ylate (5i). The title compound was prepared according to the general
procedure from ACDC 1f (109 mg, 0.35 mmol), GaCl3 (72.2 mg,
0.41 mmol) and methyl diazoacetate 4a (70.2 mg, 0.7 mmol).
According to NMR spectra, the yields of the expected compounds cis-
and trans-5i and 6i are 17, 22 and 16%. After column chromatography
on SiO2 only cis-5i was collected in pure state in yield 20.9 mg
(∼16%) (trans-5i and 6i were mixed with other compounds).
3
3
2.58 (d, 1H, H(2), J = 7.1 Hz), 2.34 (q, 1H, H(3), J = 7.1 Hz),
1.55−1.25 (m, 8H, 4CH2), 0.90 (t, 3H, Me, 3J = 6.9 Hz) ppm.
13C{1H} NMR (75.5 MHz, CDCl3): δ 170.0, 167.1 and 166.9 (3
COO), 52.9, 52.8 and 52.3 (3 OMe), 42.0 (C(1)), 32.9 (C(3)), 32.6
(C(2)), 31.1, 28.2, 25.9 and 22.4 (4 CH2), 13.9 (Me). Compound 6k:
colorless oil. IR (KBr): υ 3033, 3022, 2401, 1730 br (CO), 1434,
̅
Colorless oil. IR (KBr): υ 3056, 1730 br (CO), 1438, 1268, 1187,
1268, 1177 cm−1. HRMS (ESI-TOF) m/z: calcd for [M + H]+
C14H22O6H 287.1489; found, 287.1488. 1H NMR (300.1 MHz,
CDCl3): δ 3.80, 3.74 and 3.70 (all s, 3 × 3H, 3 OMe), 3.57 (s, 2H,
H2C(3)), 2.34−2.28 (m, 2H, H2C(4)), 1.51−1.43 (m, 2H, H2C(5)),
̅
1128 cm−1. HRMS (ESI-TOF) m/z: calcd for [M + H]+
C16H17O6BrH 385.0281; found, 385.0282. 1H NMR (300.1 MHz,
CDCl3): δ 7.42−7.36 and 7.23−7.16 (both m, 2 × 2H, C6H4), 3.82,
3.79 and 3.73 (all s, 3 × 3H, 3 OMe), 3.31 (dd, 1H, CHbPh, 2J = 15.4
3
1.38−1.25 (m, 4H, H2C(6) and H2C(7)), 0.89 (t, 3H, Me, J = 6.9
Hz) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 169.9, 166.4 and
164.7 (3 COO), 154.1 (C(2)), 119.1 (C(1)), 52.1 (3 OMe), 38.3
(C(3)), 36.5 (C(4)), 31.7 (C(6)), 27.1 (C(5)), 22.3 (C(7)), 13.9
(Me).
3
2
3
Hz, J = 5.6 Hz), 3.12 (dd, 1H, CHaPh, J = 15.4 Hz, J = 9.3 Hz),
2.69 (d, 1H, H(2), 2J = 9.4 Hz), 2.19 (ddd, 1H, H(3), 3J = 9.4 Hz, 3Jcis
= 9.4 Hz,3J = 5.6 Hz) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ
169.2, 168.7 and 165.3 (3 COO), 142.3 (i-Ar), 131.6, 130.1, 129.5,
127.1 (4 CH in Ar), 122.6 (C−Br), 53.4, 52.7 and 52.3 (3 OMe),
39.3 (C(1)), 33.2 (C(3)), 30.0 (C(2)), 28.9 (CH2).
Reaction of DAC 1i with Methyl Diazoacetate. This reaction
was carried out according to the typical experimental procedure using
ACDC 1i (125 mg, 0.4 mmol), GaCl3 (85.1 mg, 0.48 mmol) and
methyl diazoacetate 4a (80.1 mg, 0.8 mmol). The residue after
removal of solvents was purified by passing through a small column of
silica gel and a wide fraction of the reaction products was collected
(about 150 mg, light yellow oil). According to NMR spectra, the
resulting product contained cyclopropane 5l, alkene 6l, cyclobutane
13, and lactone 14 in the molar ratio ∼ 1:3:6.3:1.5.
Trineopentyl 3-benzylcyclopropane-1,1,2-tricarboxylate
(5j) and trineopentyl 2-benzylprop-1-ene-1,1,3-tricarboxylate
(6j). The title compounds were prepared according to the general
procedure from ACDC 1g (189.3 mg, 0.55 mmol), GaCl3 (101 mg,
0.57 mmol) and neopenthyl diazoacetate (170.7 mg, 1.09 mmol).
After column chromatography on SiO2 compounds 5j (cis/trans ∼
1.2:1) and 6j were isolated in yields 103.7 mg (40%) and 25.9 mg
(10%), respectively. Compound 5j: colorless oil. HRMS (ESI-TOF)
m/z: calcd for [M + H]+ C28H42O6H 475.3048; found, 475.3052.
Trimethyl 3-benzhydrylcyclopropane-1,1,2-tricarboxylate (5l), NMR
yield 6−7%, ratio cis/trans ∼ 1.3:1. HRMS (ESI-TOF) m/z: calcd for
1
[M + Na]+ C22H22O6Na 405.1309; found, 405.1305. cis-Isomer: H
1
Isomer cis-5j: H NMR (300.1 MHz, CDCl3): δ 7.35−7.19 (m, 5H,
NMR (300.1 MHz, CDCl3): δ 4.72 (d, 1H, CH, 3J = 9.9 Hz), 2.78 (d,
Ph), 3.86, 3.76 and 3.73 (all s, 3 × 2H, 3 OCH2), 3.38 (dd, 1H,
2
2
2
3
CHb3Ph, J = 15.3 Hz, J = 5.3 Hz), 3.22 (dd, 1H, CHaPh, J = 15.3
1H, H(3), Jcis = 9.8 Hz), 2.74 (dd, 1H, H(2), 3J = 9.9 Hz, 3Jcis = 9.8
3
1
Hz, J = 9.6 Hz), 2.77 (d, 1H, H(2), Jcis = 9.6 Hz), 2.22 (ddd, 1H,
Hz). trans-Isomer: H NMR (300.1 MHz, CDCl3): δ 3.98 (d, 1H,
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CH, 3J = 10.8 Hz), 3.11 (dd, 1H, H(3), 3J = 10.8 Hz, 3Jtrans = 7.1 Hz),
2.96 (d, 1H, H(2), Jtrans = 7.1 Hz) ppm. Signals of methoxy and
126.7 (o- and m-Ph, (2 Ph)), 122.3 (C(3)), 81.3 (C(5)), 53.9 and
52.5 (2 OMe), 38.2 (C(4)), 36.4 (CH2).
3
Trimethyl (2SR,3RS)-3-chloro-4-phenylbutane-1,1,2-tricarboxy-
late (19). This compound, together with the isomer E-18 as an
impurity, was isolated in yield 15.9 mg (∼20%) as a single isomer.
Colorless oil. HRMS (ESI-TOF) m/z: calcd for [M + H]+
C16H19O6ClH 343.0943; found, 343.0947. 1H NMR (300.1 MHz,
phenyl groups both isomers overlap strongly.
Trimethyl 2-benzhydrylprop-1-ene-1,1,3-carboxylate (6l), NMR yield
18%. HRMS (ESI-TOF) m/z: calcd for [M + Na]+ C22H22O6Na
405.1309; found, 405.1302. 1H NMR (300.1 MHz, CDCl3): δ 7.45−
7.24 (m, 2 Ph), 5.50 (s, 1H, CH), 3.63 (s, 2H, CH2), 3.78, 3.65 and
3.47 (all s, 3 × 3H, 3 OMe) ppm.13C{1H} NMR (75.5 MHz, CDCl3):
δ 169.4, 166.5 and 164.5 (3 COO), 152.3 (C(2)), 139.0, 129.7, 129.1,
56.0 (CH), 52.4, 52.1 and 51.7 (3 OMe), 37.3 (CH2).
Trimethyl (2RS,3SR,4RS)-3,4-diphenylcyclobutane-1,1,2-tricarboxy-
late (13), NMR yield 40%. HRMS (ESI-TOF) m/z: calcd for [M +
Na]+ C22H22O6Na 405.1309; found, 405.1303. 1H NMR (300.1 MHz,
3
CDCl3): δ 7.38−7.24 (m, 5H, Ph), 4.25 (ddd, 1H, H(3), J = 10.8,
6.0 and 2.4 Hz), 4.17 (d, 1H, H(1), 3J = 10.8 Hz), 3.83, 3.75 and 3.72
3
3
(all s, 3 × 3H, 3 OMe), 3.62 (dd, 1H, H(2), J = 10.8 Hz, J = 2.4
2
3
Hz), 3.35 (dd, 1H, Hb(4), J = 14.2 Hz, J = 6.4 Hz), 3.13 (dd, 1H,
Ha(4), 2J = 14.2 Hz, 3J = 8.5 Hz). 13C{1H} NMR (75.5 MHz,
CDCl3): δ 171.7 (COO), 169.6 (2 COO), 137.2 (i-Ph), 129.3 and
128.9 (o- and m-Ph), 126.8 (p-Ph), 60.4 (C(3)), 53.0 (2 OMe), 52.4
(OMe), 51.8 (C(1)), 49.3 (C(2)), 42.8 (C(4)).
3
CDCl3): δ 7.45−7.24 (m, 2 Ph), 4.58 (dd, 1H, H(3), J = 9.8 and
11.0 Hz), 4.36 (d, 1H, H(2), 3J = 11.0 Hz), 3.92, 3.79 and 3.34 (all s,
3
3 × 3H, 3 OMe), 3.52 (d, 1H, H(4), J = 9.8 Hz) ppm. 13C{1H}
NMR (75.5 MHz, CDCl3): δ 171.5, 170.9 and 168.0 (3 COO), 141.4,
137.0, 127.7 and 126.8 (2 CAr, 10 CHAr), 60.7 (C(1)), 53.1, 52.3 and
52.2 (3 OMe), 48.5 (C(2)), 48.1 (C(4)), 40.9 (C(3)).
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02983.
Dimethyl 2-((3RS,4SR,5RS)-2-oxo-4,5-diphenyltetrahydrofuran-3-yl)-
malonate (14), NMR yield 10%. HRMS (ESI-TOF) m/z: calcd for
[M + Na]+ C21H20O6Na 391.1152; found, 391.1147. 1H NMR (300.1
MHz, CDCl3): δ 5.32 (d, 1H, H(5), 3J = 9.8 Hz), 4.02 (d, 1H, CH, 3J
1
Copies of H, 13C, and 2D NMR spectra for isolated
products (PDF)
3
= 5.2 Hz), 3.96 (dd, 1H, H(4), J = 9.8 and 12.9 Hz), 3.76 (dd, 1H,
3
H(3), J = 5.2 and 12.9 Hz)) ppm. Signals of methoxy and phenyl
groups overlap strongly.
AUTHOR INFORMATION
■
Reaction of DAC 5a with Benzaldehyde in the Presence of
TiCl4. A mixture of cyclopropane-1,1,2-tricarboxylate 5a (61.3 mg, 0.2
mmol), benzaldehyde (53.0 mg, 0.5 mmol), and TiCl4 (0.033 mL, 0.3
mmol) in 1,2-dichloroethane (3 mL) under a dry argon atmosphere
was refluxed about 3 h. Then reaction mixture was cooled and an
aqueous solution of HCl (5%) was added until a pH of 3 was
achieved. The reaction mixture was extracted with CH2Cl2 (3 × 7
mL), the organic layer was dried over MgSO4, and the solvent was
removed in vacuo. The residue was purified by flash chromatography
on silica gel (eluent: benzene−EtOAc (100:1) to benzene−EtOAc
(10:1)) to afford three main compounds: chlorinated lactone 17,
unsaturated lactone 18 and butanetricarboxylate 19.
Corresponding Authors
Roman A. Novikov − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation; orcid.org/0000-0002-3740-7424;
Email: novikovfff@bk.ru
Yury V. Tomilov − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation; Email: tom@ioc.ac.ru
Authors
Irina A. Borisova − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation
Daria-Maria V. Ratova − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation
Konstantin V. Potapov − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation
Anna V. Tarasova − N. D. Zelinsky Institute of Organic
Chemistry, Russian Academy of Sciences, Moscow 119991,
Russian Federation
Dimethyl (2RS,4RS)-4-((SR)-1-chloro-2-phenylethyl)-5-oxo-2-
phenyldihydrofuran-3,3-(2H)-dicarboxylate (17). This compound
was isolated in yield 30.8 mg (37%) as a single isomer. Colorless oil.
IR (KBr): υ 3038, 1783 and 1737 br (CO), 1436, 1278, 1181 cm−1.
̅
HRMS (ESI-TOF) m/z: calcd for [M + H]+ C22H21O6ClH (for 35Cl)
417.1098; found, 417.1099. 1H NMR (300.1 MHz, CDCl3): δ 7.43−
7.31 (m, 10H, 2 Ph), 6.38 (s, 1H, H(5)), 4.50 (dt, 1H, CHCl, 3J = 7.5
and 1.9 Hz), 3.88 (s, 3H, OMe), 3.84 (d, 1H, H(3), 3J = 1.9 Hz), 3.60
and 3.44 (both dd, 2 × 1H, CH2, 2J = 14.1 Hz, 3J = 7.5 Hz), 3.14 (s,
3H, OMe) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 171.2 (CO),
167.6 and 166.8 (2 COO), 136.8 and 134.5 (i-Ph), 129.5, 128.8,
128.2 and 126.5 (o- and m-Ph), 129.1 and 127.3 (p-Ph), 81.7 (C(5)),
65.7 (C(4)), 58.7 (C(6)), 53.4 and 52.9 (2 OMe), 50.7 (C(3)), 42.2
(CH2).
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02983
Dimethyl (E,Z)-5-oxo-2-phenyl-4-(2-phenylethylidene)-
dihydrofuran-3,3-(2H)-dicarboxylate (18). This compound was
isolated in yield 24.2 mg (∼35%) as the mixture of Z- and E-isomers
in ratio 2.2:1. Colorless oil. HRMS (ESI-TOF) m/z: calcd for [M +
Author Contributions
§I.A.B. and R.A.N. contributed equally.
H]+ C22H20O6H 381.1325; found, 381.1333. Major isomer: H NMR
1
(300.1 MHz, CDCl3): δ 7.39−7.26 (m, 10H, 2 Ph), 7.00 (t, 1H, 
Notes
3
CH, J = 7.7 Hz), 6.28 (s, 1H, H(5)), 4.40 and 4.25 (both dd, 2 ×
The authors declare no competing financial interest.
1H, CH2, 2J = 16.3 Hz, 3J = 7.7 Hz), 3.84 and 3.21 (both s, 2 × 2H, 2
OMe) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ 168.0, 167.9 and
167.5 (2 COO and C(2)), 149.8 (CH), 135.6 and 135.5 (2 i-Ph),
128.8 and 128.7 (2 p-Ph), 128.6, 128.3, 126.7 and 126.6 (o- and m-
Ph, (2 Ph)), 122.5 (C(3)), 80.6 (C(5)), 53.7 and 52.6 (2 OMe), 34.0
(CH2), 29.7 (C(4)). Minor isomer: 1H NMR (300.1 MHz, CDCl3): δ
7.39−7.26 (m, 10H, 2 Ph), 7.21 (t, 1H, CH,3J = 7.7 Hz), 6.39 (s,
1H, H(5)), 3.89−3.81 and 3.78−3.70 (both m, CH2), 3.87 and 3.19
(both s, 2 × 2H, 2 OMe) ppm. 13C{1H} NMR (75.5 MHz, CDCl3): δ
168.3, 168.2 and 167.7 (2 COO and C(2)), 149.0 (CH), 135.5 and
135.3 (2 i-Ph), 128.4 and 126.9 (2 p-Ph), 129.2, 128.7, 128.5 and
ACKNOWLEDGMENTS
■
This work (synthetic part using gallium trichloride) was
funded by the Russian Foundation for Basic Research (RFBR)
according to the research project No. 18-33-01000 (mol_a).
The gallium catalytic part of the reported study as well as using
of silver hexafluoroantimonate for anions exchange were
funded by RFBR according to the research project No. 18-
33-20180. High resolution mass spectra were recorded in the
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Department of Structural Studies of N. D. Zelinsky Institute of
Organic Chemistry RAS, Moscow.
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