Four-Membered Cycle Formation Challenge: GaCl3-Promoted Formal [2+2]-Cycloaddition of Donor–Acceptor Cyclopropanes to Bicyclobutylidene

Article abstract of DOI:10.1002/ejoc.201900329

The first selective process of formal [2+2]-cycloaddition of donor–acceptor cyclopropanes (DAC) to multiple C–C bonds to form a four-membered ring in the product has been developed. Bicyclobutylidene is used do demonstrate this reaction. The process is promoted by GaCl₃ and occurs through generation of 1,2-zwitterionic intermediates. A carbocationic rearrangement occurs in the bicyclobutylidene moiety. It results in expansion of both cyclobutane rings into five-membered ones and formation of a [2.3.3]propellane skeleton in the final product.

Full text of DOI:10.1002/ejoc.201900329

A Journal of
Accepted Article
Title: Four-Membered Cycle Formation Challenge: GaCl3-Promoted
Formal [2+2]-Cycloaddition of Donor–Acceptor Cyclopropanes to
Bicyclobutylidene
Authors: Maria A. Zotova, Roman A. Novikov, Alexander D. Volodin,
Alexander A. Korlyukov, Yaroslav V. Tkachev, Victor A.
Korolev, and Yury V. Tomilov
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900329
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
Four-Membered Cycle Formation Challenge: GaCl3-Promoted Formal
[2+2]-Cycloaddition
Bicyclobutylidene
of
Donor–Acceptor
Cyclopropanes
to
Dr. Maria A. Zotova,a,§ Dr. Roman A. Novikov,a,b,*,§ Alexander D. Volodin,c Dr. Alexander A. Korlyukov,c,d Dr.
Yaroslav V. Tkachev,b Dr. Victor A. Korolev,a and Prof. Dr. Yury V. Tomilova,*
a
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow,
Russian Federation
b
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov st., 119991 Moscow, Russian
Federation
с Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str., 28, 119991 Moscow,
Russia
d Pirogov Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia
ABSTRACT: The first selective process of formal [2+2]-cycloaddition of donor-acceptor cyclopropanes (DAC) to multiple C–
C bonds to form a four-membered ring in the product has been developed, using the reaction with bicyclobutylidene as an
example. The process is promoted by GaCl3 and occurs through generation of 1,2-zwitterionic intermediates. A carbocationic
rearrangement occurs in the bicyclobutylidene moiety. It results in expansion of both cyclobutane rings into five-membered
ones and formation of a [2.3.3]propellane skeleton in the final product.
implemented processes, one can note the formal [2+3]-
cycloaddition with participation of allylic systems16b
(Scheme 2, B). Single examples of a number of other
implemented processes are also known.15,16
INTRODUCTION
Donor-acceptor cyclopropanes (1, DAC)1,2 are known for
their ability at opening the three-membered ring3–5 in the
presence of Lewis acids and in situ generation of 1,3-
zwitterionic6,7 and other related intermediates.8 The presence
of highly reactive carbocationic centers in such intermediates
opens rich prospects for reactions with various double and
triple carbon-carbon bonds.9 Processes that are most
characteristic of 1,3-zwitterionic intermediates include
formal [3+2]-cycloaddition10,11 (Scheme 1, A) and [3+2]-
annulation12 (Scheme 1, B) to give five-membered rings, as
well as narrower classes of other processes.9 In the case of
dienes, it is possible to perform formal [4+3]-cycloaddition
and annulation to give seven-membered rings13 (Scheme 1, C
and D).
Scheme 1. 1,3-Zwitterionic Reactions with Multiple C–C
bonds.
An extensive group of processes that should be
distinguished separately occur via in situ generation of 1,2-
zwitterionic gallium complexes (2)14 in the presence of
Ga(III) compounds15–17 (Scheme 2). The [4+2]-annulation15
involving the aromatic ring of the starting cyclopropane and
formation of a six-membered carbocycle (Scheme 2, A) is the
most typical process that can be performed for a wide range
of alkenes and acetylenes. Acyclic addition involving halide
anions (Scheme 2, C) is also a process that is highly
characteristic of alkenes.16a Of the narrower range of
1
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
Scheme 2. Ga(III)-Promoted 1,2-Zwitterionic Reactions
with Multiple C–C bonds.
Scheme 3. Known Minor Examples of Formation of the
Four-Membered Cycle in 1,2-Zwitterionic Reactions of
DAC.
Despite the considerable diversity of structures of the
products formed in these reactions, the nearly complete lack
of selective processes to give four-membered carbocycles in
reactions with multiple bonds is a big gap in the chemistry of
DAC 1. At the same time, processes that result in five-, six-
and seven-membered carbocycles are quite abundant. This is
especially true for the 1,2-zwitterionic chemistry of DAC
since formation of a formal [2+2]-cycloaddition product
(Scheme 2, D) appears to be one of the most obvious
reaction pathways. However, its practical implementation
proved to be the most complex.
Nevertheless, a few processes of four-membered ring for-
mation in DAC reactions with multiple C–C bonds are kno-
wn to date14a,18–20 (Scheme 3, pathways A,18 B–D,19 E20). All
of them corresponded to the 1,2-zwitterionic chemistry of
DAC and occurred only as side processes and in low yields.
Table 1. Formal [2+2]-Cycloaddition of DAC to
Bicyclobutylidene.
We filled the gap in this study by creating a selective
process for the formation of a four-membered ring based on
the formal [2+2]-cycloaddition of DAC
1
to
bicyclobutylidene 3 whose double bond proved to be most
suitable for the implementation of this process.
RESULTS AND DISCUSSION
Reaction conditions 1 a
T-2 b,c
(°C) Yield (%) d
Product,
Entry
Ar
GaCl3 T-1
t-1
Reactions of DAC 1 with bicyclobutylidene 3 in the
presence of GaCl3 with preliminary generation of 1,2-
zwitterionic gallium complex 2 occurs as formal [2+2]-
cycloaddition to give a four-membered ring (4) (Table 1).
(equiv.) (oC) (min)
1
2
3
4
5
Ph (a)
1.3
1.1
1.1
1.2
1.5
0–5
0
10
15
15
90
75
–70
0
4a, 35 (65)
4b, 49 (56)
4c, 42 (53)
4d, 40 (49)
4e, 45 (80)
4-FC6H4 (b)
4-ClC6H4 (c)
3-BrC6H4 (d)
2,6-Cl2C6H3 (e)
However, this is accompanied by
a
carbocationic
rearrangement with expansion of both cyclobutane rings in
bicyclobutylidene 3 to eventually give a [2.3.3]propellane
system (4). It should be noted that this rearrangement almost
does not affect on the character of addition on the DAC side.
This formal [2+2]-cycloaddition process was successfully
0
–15
0
0
40
–20
implemented
for
various
2-arylcyclopropane-1,1-
aGeneral conditions: 1 mmol of 1a–i in 15 mL dry CH2Cl2 was
used; the reaction conditions are given for the first stage (formation
of 2). bThe reaction conditions are given for the second stage
dicarboxylates 1a–e substituted at the ortho-, meta- or para-
positions of the phenyl ring as examples (Table 1).
c
(addition of 3). Optimization was made in each case to find the
The formation of propellanes 4 is very sensitive to
reaction conditions and requires individual optimization for
each substituted DAC 1. It primarily concerns the precise
control of the temperature16a,20 of the second process stage:
optimal temperature (T-2). dNMR yields in the parentheses.
To
a considerable extent, the reason for precise
temperature control lies in the very high reactivity of
bicyclobutylidene 3, especially in the presence of such a
strong Lewis acid as GaCl3. If optimum conditions are not
Table
1 demonstrates the wide range of optimum
temperatures for apparently rather similar substituents.
2
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
met, both substrates just undergo polymerization, which
results in low yields or total absence of a target product,
though polymerization is not totally avoided in any of the
2 at –20 °C still predominates in the reaction environment.
There may be another variant which involves a more
complex process of isomerization of intermediate II to V.
Apparently, these complex reactions are controlled by subtle
combinations of various conditions.
cases.
However,
formal
[2+2]-cycloaddition
to
bicyclobutylidene is rather a general reaction (Table 1).
Phenylcyclopropanedicarboxylate 2a itself is an example
of special interest. It can be seen here how sensitively the
process pathway depends on the reaction temperature. In
fact, while [2.3.3]propellane 4a described above is formed at
–70 °C (Table 1, Entry 1), at –20 °C the reaction pathway
changes completely and DAC 1 reacts as a 1,3-zwitterion
with annulation at the phenyl ring to give
Scheme 5. Proposed Mechanism.
benzo[3.3.3]propellane 5a (Scheme 4). Moreover,
a
bicyclobutylidene moiety also undergoes a carbocationic
rearrangement with expansion of both cyclobutane rings. The
selectivity of both processes was rather high, i.e., almost no
compound 5a was found in the products of the reaction at –
70 °С and no compound 4a was found in the products
formed at –20 °C. It should be noted that in both cases,
generation of 1,2-zwitterionic intermediate 2a was
performed ideally and quantitatively, while the reactions had
good reproducibility in a number of experiments.
Scheme 4. Formal [3+2]-Annulation of Cyclopropane 1a
to Bicyclobutylidene
We should specially dwell on the procedure for
establishing the structures of compounds 4 and 5 because
they are non-typical. The main problem was to distinguish
the structure 5 from the very similar isomeric structure 5´ (a
similar problem is encountered for compounds 4) (Figure 1).
The mechanism of formation of [3.3.2]-propellanes 4
appears to be rather obvious, based on the preliminary
generation of 1,2-zwitterions 2 upon treatment of DAC 1
with GaCl3 (Scheme 5).15,16 Subsequently, the carbocationic
center attacks the double bond in bicyclobutylidene. A
distinctive feature of this process (unlike other reactions of
DAC 1 with alkenes15) is that a carbocationic double
Wagner-Meerwein dyotropic rearrangement of the
bicyclobutyl system into a bicyclo[3.3.0]octane one occurs,
which involves two 1,2-C shifts and expansion of both
cyclobutane rings to cyclopentane ones. It should be noted
that a few examples of similar rearrangements are known in
literature,21 but they are not related to cycloaddition
processes. It cannot be ruled out that conformation factors
favoring the cyclization on the malonyl moiety may also play
a certain role in the process in question. The mechanism of
the formation of benzo-annulated [3.3.3]propellane 5 on
changing the temperature from –70 to –20 °C is more
difficult to imagine. In this case, one has to assume either the
possibility of partial reverse isomerization of 1,2-zwitterion 2
to 1,3-zwitterion I and its reaction with bicyclobutylidene 3
similarly to the scheme presented above. Intermediate V then
undergoes two consecutive 1,2-C shifts and expansion of
both cyclobutane rings to cyclopentane ones to give
intermediate VI. Due to remoteness of the carbocationic
center in the latter from the malonyl moiety and its proximity
to the phenyl substituent, unlike in intermediate IV, it attacks
the aromatic ring to give compound 5 (Scheme 5).
Unfortunately, this variant has drawbacks. In fact, it hardly
explains the absence of propellane 4 through 1,2-zwitterion
1
The classical set of H and 13C NMR experiments, including
2D techniques such as COSY, TOCSY, NOESY, HSQC and
HMBC, does not allow one to do it unambiguously due to
the almost total overlapping of all aliphatic proton signals in
1
the H spectra, while the differences between the structures
lie in their connections. This problem can be partially solved
using H–H correlation experiments with decoupling by the
13C projection in order to eliminate the overlapping in
conventional 1H spectra in the chain HSQC-TOCSY —>
HSQC-COSY —> constant-time HMBC, but this approach
did not provide a 100% proof of the structure. To accomplish
this task, we had to use 2D 13C–13C INADEQUATE
experiments (13C–13C correlation) using the natural content
of the 13C isotope (Figure 1), which allowed us to directly
identify the entire carbon skeleton of the molecule. This
demanded prolonged accumulation (the typical acquisition
time was 3–5 days per sample using state-of-the-art 300 and
400 MHz instruments and standard 5 mm NMR tubes). The
structure of the skeleton of compound 4 was later brilliantly
confirmed for compound 4e by means of X-Ray analysis
(Figure 2). It should be noted that the X-Ray crystal structure
of compound 5 was not obtained, so everything described
above proved to be relevant.
3
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
synthesizing propellane skeletons may be useful for studying
the biological activity by creating considerably more diverse
structures than those found in natural sources.
Figure 3. Examples of natural compounds incorporating the
[3.3.2] and [3.3.3]propellane skeletons.
Synthesized [2.3.3]propellanes 4a–e contain in structure
cyclobutane ring activated by two ester groups. Thus, they
can potentially used as donor–acceptor cyclobutanes
(DACB) in further reactions.27,28 We have explored the such
possibility for the compound 4e in the reaction with
benzaldehyde (Scheme 6). This reaction requires for
activation strong Lewis acids like TiCl4. Using the Sc(OTf)3
for example is strongly insufficient. The activation by TiCl4
leads to cleavage of the four-membered ring in 4e and
formation of 1,4-zwitterion VII. The latter gradually
undergoes fragmentation in alkenes 7 and 8 even in the
presence of excess of benzaldehyde. This fragmentation is
quite typical for DACB.28 Formed alkene 8 is reactive in
these conditions and reacts with benzaldehyde with further
decomposition. Apparently, the formal [4+2]-cycloaddition
of 1,4-zwitterion VII with benzaldehyde is possible
fundamentally (Scheme 6). But, this reaction is reversible29
and the resulting tetrahydropyran 6 is unstable in acidic
conditions.
Figure 1. Key fragment of COSY-like type 13C–13C
INADEQUATE spectrum for the compound 5.
Scheme 6. TiCl4-Mediated Cleavage of the Cyclobutane
Ring in the [3.3.2]Propellane 4a.
Figure 2. Crystal structure of the compound 4e (50%
ellipsoid probability), CCDC 1910283.
It should be noted that, despite the seeming originality,
[3.3.3] and even [2.3.3]propellane systems occur in
structures of natural compounds, albeit they are rare22
(Figure 3). Natural propellanes show
a considerable
spectrum of biological activity, including anti-cancer
properties.23 Modhephene is one of the most famous ones,24
and a number of full syntheses of this compound have been
performed by various scientific groups.24,25 Recently, Baran’s
group has developed a new general approach to propellane-
like structures as bioisosteric motif for different drugs
discovery based on direct amination reaction of
[1.1.1]propellane.26 And, though the approaches we suggest
do not allow us to construct the compounds indicated above,
still the creation of facile and efficient methods for
To conclude, we have developed the first selective
process of formal [2+2]-cycloaddition of DAC to multiple
C–C bonds to form a four-membered ring in the product. The
process has been implemented using the reaction with
4
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
bicyclobutylidene as an example. It is promoted by GaCl3
and occurs through generation of 1,2-zwitterionic
intermediates. It this process, a carbocationic rearrangement
occurs in the bicyclobutylidene moiety. It results in
expansion of both cyclobutane rings into five-membered
ones and formation of a [2.3.3]propellane skeleton in the
final product. It has been shown that, depending on the
reaction temperature, benzo[3.3.3]propellane derivatives can
also be obtained selectively. The mechanistic features of the
processes that we developed have been considered.
generation of 1,2-zwitterion 2 (optimal conditions: 1.1−1.3
equiv. GaCl3, 0 °C, 10−15 min for cyclopropanes 1a−c; 1.5
equiv. GaCl3, 90 °C, 75 min for cyclopropane 1d and 1.2
equiv. GaCl3, 0 °C, 90 min for cyclopropane 1e). Then the
mixture was cooled to from –70 °C to 0 °C (see Table 1 for
individual temperatures), a solution of alkene 3 (3–4 equiv.)
in dry CH2Cl2 (1−2 mL) was added, and the reaction mixture
was stirred for 2 h until reaction was completed. After that,
an aqueous solution of HCl (10%) was added at room
temperature until pH 3 was achieved, and a reaction mixture
was twice extracted with CH2Cl2. The organic layer was
dried over MgSO4, and the solvent was removed in vacuo.
The residue was purified by column chromatography on
silica gel (petroleum ether – EtOAc, 10:1) to afford the title
product 4 or 5 as a thick colorless oil.
EXPERIMANTAL SECTION
General Experimental Details. All reagents and
solvents used were commercial grade chemicals without
additional purification. All operations with GaCl3 were
carried out under a dry argon atmosphere. TLC analysis was
performed on Silufol chromatographic plates. For
preparative chromatography, silica gel 60 (0.040−0.063 mm)
Dimethyl
6-benzyltricyclo[3.3.2.01.5]decan-7,7-
dicarboxylate (4a). The title compound was prepared
according to the general procedure from DAC 1a (153 mg,
0.65 mmol), GaCl3 (150 mg, 0.85 mmol), and 1,1'-
bi(cyclobutylidene) 3 (283 mg, 2.62 mmol). Compound 4a
1
was used. H and 13C{1H} NMR spectra were recorded 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 the structures and stereochemistry of the
obtained compounds and assignments of the 1H and 13C
signals were made with the aid of 2D 1H–1H COSY,
TOCSY, NOESY, 1H–13C edited-HSQC, HSQC-COSY,
HSQC-TOCSY, HMBC, and 13C–13C INADEQUATE
spectra. 19F NMR spectra were recorded on a 300 MHz
spectrometer (282.4 MHz; standard CFCl3). Determinations
of the structures and assignments of the 19F signals were
was isolated in 80 mg yield (35%). Colorless thick oil. IR
~

(CHCl3):
3057, 3000, 2952, 2867, 1720 br (C=O), 1582,
1
1561, 1450, 1436, 1266, 1252, 1179, 1086, 1044 cm–1. H
NMR (300.1 MHz, CDCl3) δ 1.09–1.24 (m, 1H, H(4)), 1.28–
1.43 (m, 4H, H(4), H(8), H(10), H(2)), 1.56–1.70 (m, 3H,
H(3), H(9)), 1.83–1.91 (m, 1H, H(9)), 1.93–2.01 (m, 1H,
H(2)), 2.06–2.16 (m, 1H, H(10)), 2.46–2.55 (m, 1H, H(8)),
2.76–2.89 (m, 2H, H2C), 3.08 (dd, 1H, CH, J = 10.4, 6.0 Hz),
3.65 and 3.73 (both s, 2 × 3H, 2 OMe), 7.15–7.26 (m, 5H,
Ph) ppm. 13C{1H} NMR (75.5 MHz, CDCl3) δ 27.9 (C(3)),
28.1 (C(9)), 32.5 (C(10)), 33.3 (CH2), 35.2 (C(8)), 38.4
(C(2)), 40.3 (C(4)), 44.4 (CH), 51.7 and 52.1 (2 OMe), 56.1
(C(5)), 59.6 (C(7)), 60.4 (C(1)), 125.9 (p-CH), 128.3 (m-
CH), 129.0 (o-CH), 140.4 (i-C), 169.8 and 171.5 (2 COO).
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H26O4
343.1904; Found 343.1901.
1
made with the aid of 2D H–19F HMQC and HMBC spectra.
IR spectra were obtained on an FT-IR spectrometer in CHCl3
solution (1%). High-resolution mass spectra (HRMS TOF)
were obtained using simultaneous electospray ionization
(ESI). High resolution mass spectra were recorded in the
Department of Structural Studies of N. D. Zelinsky Institute
of Organic Chemistry RAS, Moscow.30
Dimethyl 8-(4-fluorobenzyl)tricyclo[3.3.2.01.5]decan-
7,7-dicarboxylate (4b). The title compound was prepared
according to the general procedure from DAC 1b (90 mg,
0.35 mmol), GaCl3 (69 mg, 0.39 mmol), and 1,1'-
X-ray dataset for compound 4e was measured with
Bruker APEX II diffractometer in Centre for Molecular
composition studies of INEOS RAS. Experimental and
crystallographic data are summarized in Table S1 (in
Supporting Information). The structure 4e was solved by
direct method and refined in anisotropic approximation for
non-hydrogen atoms. Hydrogens atoms of methyl, methylene
and aromatic fragments were calculated according to those
idealized geometry and refined with constraints applied to C-
H and N-H bond lengths and equivalent displacement
parameters (Ueq(H) = 1.2Ueq(X), X – cental atom of XH₂
group; Ueq(H) = 1.5Ueq(Y), Y – central atom of YH₃ group.
All structures were solved with the ShelXT31a program and
refined with the ShelXL31b program. Molecular graphics was
drawn using OLEX231c program. CCDC 1910283 contains
the supplementary crystallographic data for 4e. These data
can be obtained free of charge from The Cambridge
bi(cyclobutylidene) 3 (154 mg, 1.4 mmol). Compound 4b
~

was isolated in 63 mg yield (49%). IR (CHCl3):
3023,
3008, 2977, 2895, 1722 br (C=O), 1579, 1458, 1420, 1242,
1189, 1046 cm–1. 1H NMR (300.1 MHz, CDCl3) δ 1.12–1.22
(m, 1H, H(4)), 1.26–1.43 (m, 4H, H(4), H(8), H(10), H(2)),
1.58–1.71 (m, 3H, H(3), H(9)), 1.83–1.93 (m, 1H, H(9)),
1.96–2.06 (m, 1H, H(2)), 2.07–2.19 (m, 1H, H(10)), 2.43–
2.53 (m, 1H, H(8)), 2.71–2.86 (m, 2H, H2C), 3.02 (dd, 1H,
CH, J = 10.1, 6.2 Hz), 3.64 and 3.73 (both s, 2 × 3H, 2
OMe), 6.90–6.96 (m, 2H, Ph), 7.14–7.19 (m, 2H, Ph) ppm.
13C{1H} NMR (75.5 MHz, CDCl3) δ 27.7 (C(3)), 27.9
(C(9)), 32.2 (C(10)), 32.3 (CH2), 35.0 (C(8)), 38.2 (C(2)),
40.2 (C(4)), 44.3 (CH), 51.6 and 52.0 (2 OMe), 55.8 (C(5)),
2
59.4 (C(7)), 60.3 (C(1)), 114.9 (d, m-CH, JCF = 21.1 Hz),
130.1 (d, o-CH, 3JCF = 7.7 Hz), 135.8 (d, i-C, 4JCF = 3.1 Hz),
Crystallographic
Data
Centre
via
161.2 (d, p-C, 1JCF = 243 Hz)), 169.6 and 171.3 (2 COO). 19
NMR (CDCl3, 282.4 MHz) δ –117.67 (tt, CF, JHF = 8.7 Hz,
4JHF = 5.4 Hz) ppm. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C21H25FO4 361.1810; Found 361.1816.
F
https://www.ccdc.cam.ac.uk/structures.
3
Synthesis of Starting Cyclopropanes 1a−e. Starting
cyclopropanes 1a−e (ACDC) were synthesized from the
corresponding aromatic aldehydes through
a standard
Dimethyl 8-(4-chlorobenzyl)tricyclo[3.3.2.01.5]decan-
7,7-dicarboxylate (4c). The title compound was prepared
according to the general procedure from DAC 1c (220 mg,
0.82 mmol), GaCl3 (158 mg, 0.9 mmol), and 1,1'-
synthetic sequence of Knoevenagel/Corey−Chaykovsky
reactions.32
General Procedure. Solid GaCl3 (1.1−1.5 equiv.) in one
portion was added at convenient temperature to a solution of
cyclopropane 1 (1 equiv.) in dry CH2Cl2, and a mixture was
stirred at the same temperature until completion of the
bi(cyclobutylidene) 3 (353 mg, 3.27 mmol). Compound 4c
~

was isolated in 127 mg yield (42%). IR (CHCl3):
3024,
5
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10.1002/ejoc.201900329
European Journal of Organic Chemistry
3020, 3007, 2976, 2895, 1721 br (C=O), 1447, 1435, 1268,
H(11)), 1.86–1.92 (m, 2H, H(4), H(11)), 2.09–2.19 (m, 1H,
H2C), 2.52–2.62 (m, 1H, H2C), 2.83 (dd, 1H, CHAr, J =
11.1, 4.0 Hz), 3.70 (dd, 1H, CH(CO2Me), J = 11.1, 4.0 Hz),
3.75 and 3.79 (both s, 2 × 3H, 2 OMe), 7.09–7.25 (m, 4H,
Ph) ppm. 13C{1H} NMR (75.5 MHz, CDCl3) δ 26.2 (C(10)),
26.7 (C(3)), 30.9 (CH2), 34.3 (C(9)), 41.4 (C(11)), 41.9
(C(4)), 42.6 (C(2)), 50.8 (CH(CO2Me)), 51.0 (CHAr), 52.5
and 52.6 (2 OMe), 64.1 (C(1)), 68.2 (C(5)), 123.2 (C(12)),
123.8 (C(15)), 126.5 (C(14)), 127.6 (C(13)), 145.1 (C(7)),
151.2 (C(6)), 169.83 and 169.85 (2 COO). HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C21H26O4 343.1904; Found
343.1900.
1
1243, 1236, 1047 cm–1. H NMR (300.1 MHz, CDCl3) δ
1.15–1.25 (m, 1H, H(4)), 1.28–1.46 (m, 4H, H(4), H(8),
H(10), H(2)), 1.63–1.72 (m, 3H, H(3), H(9)), 1.80–1.90 (m,
1H, H(9)), 1.92–2.04 (m, 1H, H(2)), 2.05–2.12 (m, 1H,
H(10)), 2.44–2.54 (m, 1H, H(8)), 2.74–2.89 (m, 2H, H2C),
3.05 (dd, 1H, CH, J = 10.0, 6.3 Hz), 3.66 and 3.75 (both s, 2
× 3H, 2 OMe), 7.15–7.28 (m, 4H, Ph) ppm. 13C{1H} NMR
(75.5 MHz, CDCl3) δ 27.9 (C(3)), 28.1 (C(9)), 32.4 (C(10)),
32.7 (CH2), 35.2 (C(8)), 38.3 (C(2)), 40.3 (C(4)), 44.3 (CH),
51.7 and 52.2 (2 OMe), 56.0 (C(5)), 59.5 (C(7)), 60.5 (C(1)),
128.4 (m-CH), 130.3 (o-CH), 131.6 (p-C), 138.9 (i-C), 169.7
and 171.4 (2 COO). HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C21H25ClO4 377.1514; Found 377.1512.
ASSOCIATED CONTENT
Supporting Information
Dimethyl 8-(3-bromobenzyl)tricyclo[3.3.2.01.5]decan-
7,7-dicarboxylate (4d). The title compound was prepared
according to the general procedure from DAC 1d (247 mg,
0.79 mmol), GaCl3 (167 mg, 0.94 mmol), and 1,1'-
The Supporting Information is available free of charge
on the website at DOI:
1H and 13C NMR spectra for all pure products (PDF)
bi(cyclobutylidene) 3 (256 mg, 2.37 mmol). Compound 4d
~

was isolated in 132 mg yield (40%). IR (CHCl3):
3019,
3011, 2974, 2954, 1722 br (C=O), 1568, 1474, 1459, 1267,
1048, 1028 cm–1. 1H NMR (300.1 MHz, CDCl3) δ 1.18–1.27
(m, 1H, H(4)), 1.33–1.46 (m, 4H, H(4), H(8), H(10), H(2)),
1.61–1.74 (m, 3H, H(3), H(9)), 1.85–1.95 (m, 1H, H(9)),
1.96–2.04 (m, 1H, H(2)), 2.06–2.14 (m, 1H, H(10)), 2.42–
2.51 (m, 1H, H(8)), 2.76–2.90 (m, 2H, H2C), 3.04 (dd, 1H,
CH, J = 9.8, 6.4 Hz), 3.67 and 3.75 (both s, 2 × 3H, 2 OMe),
7.11–7.39 (m, 5H, Ph) ppm. 13C{1H} NMR (75.5 MHz,
CDCl3) δ 27.9 (C(3)), 28.1 (C(9)), 33.0 (C(10)), 35.3 (CH2),
38.2 (C(8)), 40.3 (C(2)), 40.3 (C(4)), 44.3 (CH), 51.8 and
52.2 (2 OMe), 56.0 (C(5)), 59.5 (C(7)), 60.6 (C(1)), 122.3
(C(3´)), 127.6, 129.1, 129.8 and 132.0 (C(2´,4´,5´,6´)), 142.9
(C(1´)), 169.7 and 171.4 (2 COO). HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C21H25BrO4 421.1009; Found 421.0993.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: novikovfff@bk.ru.
*E-mail: tom@ioc.ac.ru.
ORCID
Roman A. Novikov: 0000-0002-3740-7424
Yury V. Tomilov: 0000-0002-3433-7571
Author Contributions
§M.A.Z. and R.A.N. contributed equally.
Notes
The authors declare no competing financial interest.
Dimethyl
8-(2,6-dichlorobenzyl)tricyclo[3.3.2.01.5]-
decan-7,7-dicarboxylate (4e). The title compound was
prepared according to the general procedure from DAC 1e
(123 mg, 0.4 mmol), GaCl3 (107 mg, 0.61 mmol), and 1,1'-
ACKNOWLEDGMENTS
This work was supported by the Russian Science
Foundation (grant no. 14-13-01054-P). Structural (X-ray)
studies of 4e were supported by the RFBR according to
the research project No. 18-29-04060. All X-ray studies
were carried out using equipment of the Center for
Molecule Composition Studies of INEOS RAS. Dr.
Roman A. Novikov and Dr. Yaroslav V. Tkachev thank
the Program of fundamental research for state academies
for 2013–2020 years (№ 01201363817) for support of
NMR studies (Engelhardt Institute of Molecular Biology,
Russian Academy of Sciences). High resolution mass
spectra were recorded in the Department of Structural
Studies of N. D. Zelinsky Institute of Organic Chemistry
RAS, Moscow.
bi(cyclobutylidene) 3 (132 mg, 1.2 mmol). Compound 4e
~

was isolated in 76 mg yield (45%). IR (CHCl3):
3026,
3007, 2972, 2957, 2878, 1724 br (C=O), 1561, 1442, 1269,
1244, 1189, 1045, 1033 cm–1. 1H NMR (300.1 MHz, CDCl3)
δ 1.08–1.18 (m, 1H, H(4)), 1.26–1.43 (m, 4H, H(4), H(8),
H(10), H(2)), 1.60–1.71 (m, 3H, H(3), H(9)), 1.83–1.91 (m,
1H, H(9)), 2.07–2.17 (m, 1H, H(2)), 2.19–2.27 (m, 1H,
H(10)), 2.30–2.41 (m, 1H, H(8)), 3.02–3.15 (m, 2H, H2C),
3.35 (dd, 1H, CH, J = 13.9, 8.8 Hz), 3.68 and 3.73 (both s, 2
× 3H, 2 OMe), 7.02–7.07 (m, 1H, H(4´)), 7.24–7.27 (m, 2H,
H(3´,4´)) ppm. 13C{1H} NMR (75.5 MHz, CDCl3) δ 27.3
(C(3)), 27.6 (C(9)), 28.9 (C(10)), 32.9 (CH2), 36.0 (C(8)),
38.3 (C(2)), 39.4 (C(4)), 42.4 (CH), 51.8 and 51.9 (2 OMe),
57.2 (C(5)), 60.5 (C(7)), 61.0 (C(1)), 127.6 (C(4´)), 128.4
(C(3´,5´)), 135.6 (C(2´,6´)), 137.4 (C(1´)), 170.1 and 171.1
(2 COO). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C21H24Cl2O4 411.1124; Found 411.1110.
KEYWORDS
Donor–acceptor cyclopropanes, bicyclobutylidene,
gallium trichloride, [2+2]-cycloaddition, propellanes.
Dimethyl 2-((2,3-dihydro-1H,8H-3a,8a-propanocyclo-
penta[a]inden-8-yl)methyl)malonate
(5).
The
title
compound was prepared according to the general procedure
from DAC 1a (643 mg, 2.74 mmol), GaCl3 (483 mg, 3.57
mmol), and 1,1'-bi(cyclobutylidene) 3 (900 mg, 8.24 mmol)
at –20 °C. Compound 5 was isolated in 810 mg yield (86%).
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