Three-Component GaHal3-Promoted Reactions of Substituted Methylidenemalonates and Donor-Acceptor Cyclopropanes with Propargyl Halides: Cascade Diastereoselective Construction of Five-Membered Lactones

Article abstract of DOI:10.1021/acs.joc.9b00354

A new cascade three-component process for high trans,trans-diastereoselective assembly of five-membered (1-halovinyl)lactones has been developed. The process is based on reactions of substituted methylidenemalonates and cyclopropanedicarboxylates with 3-haloprop-1-ynes in the presence of GaHal₃ and involves the intermediate in situ generation of 1,2-zwitterionic gallium complexes with [Ga(L)₃]³⁺[GaX₄^-]₃ composition. Chloro, bromo, and iodo derivatives can be obtained successfully. Mechanistic and stereochemical aspects of the process we developed have been studied and considered in detail.

Full text of DOI:10.1021/acs.joc.9b00354

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Article
Three-Component GaHal3-Promoted Reactions of
Substituted Methylidenemalonates and Donor–Acceptor
Cyclopropanes with Propargyl Halides. Cascade
Diastereoselective Construction of Five-Membered Lactones.
Dmitry A. Denisov, Denis D. Borisov, Victor A. Korolev, Roman A. Novikov, and Yury V. Tomilov
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00354 • Publication Date (Web): 17 Apr 2019
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The Journal of Organic Chemistry
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Three-Component
GaHal3-Promoted
Reactions
of
Substituted
Methylidenemalonates and Donor–Acceptor Cyclopropanes with
Propargyl Halides. Cascade Diastereoselective Construction of Five-
Membered Lactones.
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Dmitry A. Denisov,§ Denis D. Borisov, Victor A. Korolev, Roman A. Novikov,*,§ and Yury V. Tomilov*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow,
Russian Federation
ABSTRACT: A new cascade three-component process for high trans,trans-diastereoselective assembly of five-membered (1-
halovinyl)lactones has been developed. The process is based on reactions of substituted methylidenemalonates and
cyclopropanedicarboxylates with 3-haloprop-1-ynes in the presence of GaHal3 and involves the intermediate in situ generation
–
of 1,2-zwitterionic gallium complexes with [Ga(L)3]3+[GaX4 ]3 composition. Chloro, bromo and iodo derivatives can be
obtained successfully. Mechanistic and stereochemical aspects of the process we developed have been studied and considered in
detail.
methylidenemalonates 1 is a much less thoroughly studied
and quite a new chapter in organic chemistry. The first
publication in this field appeared only in 2018.10
INTRODUCTION
Donor-acceptor alkenes (DAAs) and cyclopropanes
(DACs) are extremely popular in organic synthesis.1,2,3
A
Scheme 1. Generation of 1,2-Zwitterionic Ga Complexes
and their Reactions with Acetylenes.
combination of two electron-withdrawing ester groups with
various electron-donating substituents is often used to
activate a double bond or cyclopropane ring in these
syntheses.4,5,6 Owing to the availability of two ester groups, it
is very convenient to activate such substrates by various
Lewis acids and use them in various reactions. Accordingly,
substituted methylidenemalonates
1
or cyclopropane-
dicarboxylates 2 are used as the DAAs or DACs7,8 in these
cases. The use of gallium halides makes it possible to
completely modify their well-known reactivity that they
show in the presence of other Lewis acids.9,10 This is
achieved by in situ generation of specific 1,2-zwitterionic
gallium complexes (3,4) (Scheme 1). To date, the formation
of two types of complexes has been shown, viz., ionic
–
complexes [Ga(L)3]3+[GaX4 ]3 (3) with a ligand/gallium ratio
of 3:4,10 and covalent complexes 4 with a 1:1 ratio.11 The
latter are typical of cyclopropanedicarboxylates 2, whereas
ionic complexes 3 are more common.
The double bond in gallium complexes 3 and 4 is
strongly polarized,9d,10,11 and the complexes themselves are
very reactive and readily react with various substrates. Their
chemistry has been studied most thoroughly for
cyclopropanedicarboxylates 2 as starting compounds for
generation of complexes.9 For example, the reactions of their
dimerization9a and various pathways of reactions with
alkenes,9d acetylenes,9a,e aldehydes,9b pyrazolines,9e etc. have
been
studied.
The
gallium
chemistry
of
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against human cancer cells, etc. as well as inhibition of
different ferments, germination and growth stimulating
activities for plants, and pheromone activity.12,13 They also
seem as great building blocks in the construction of
biologically important compounds and in further organic
synthesis.
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Figure 1. Examples of natural compounds incorporating the
five-membered lactone skeleton.
For both substrates 1 and 2, reactions with acetylenes in
the presence of gallium halides have been studied most
thoroughly (Scheme 1).9a,e,10 The processes that they have in
common include the three-component trans-addition to the
acetylene triple bond involving halogen atoms from a
gallium compound and the formation of polyfunctional (3-
haloallyl)malonates 6.9a,10 In this case, the transfer of halogen
RESULTS AND DISCUSSION
Using the reaction of (2-methylpropylidene)malonate 1a
with propargyl bromide in the presence of GaBr3 (Table 1),
we have shown that the composition and isomeric
composition of the products formed changes noticeably
depending on the reaction conditions. In fact, incomplete
conversion of 1a at 20°С for 1.5 h mainly gives lactone 8a
and acyclic dibromide 9a (Table 1, Entry 1). In this case, the
diastereoselectivity of formation of the target lactone 8a is
high and amounts to ~17:1. At 40 °C, the amount of
dibromide 9a decreases almost to zero and the yield of
lactone 8a increases twofold (Table 1, Entry 2), while the
reaction diastereoselectivity decreases somewhat. The
lactone yields do not increase if the reaction is performed
under more drastic conditions or with 1.5 equiv. GaBr3.
–
atoms involves GaX4 anions that also play a key role in the
mechanism of ion pair formation. Apart from the formation
of (3-haloallyl)malonates 6, the [4+2]-annulation at the
aromatic ring to give the dihydronaphthalene skeleton 7 is
very typical of arylcyclopropanes 2.9e The [3+2]-annulation
is a similar process for methylidenemalonates 1, but thus far,
it was performed for alkylarylacetylenes only.10 In addition,
a number of much narrower and more specific processes
involving acetylenes were performed for D–A substrates 1
and 2.9e
Optimization
of
the
reaction
of
cyclohexylmethylidenemalonate 1b with propargyl bromide
and GaBr3 shows a similar picture (Table 1, Entries 4 and 5).
If the reaction time is insufficient, a considerable amount of
dibromide 9b is formed, which then disappears if the
reaction mixture is kept for a longer period, while the yield
of lactone 8b increases considerably.
In this study we suggested and developed a new pathway
for reactions of 1,2-zwitterionic gallium complexes 3,4 with
acetylenes that expands their synthetic potential (Scheme 1).
The process is implemented using propargyl halides. It
involves a cascade of reactions that result in the three-
component
assembly
of
five-membered
(1-
Other Lewis acids were also tested in this reaction, based
on starting malonate 1b as model compound (Table 1,
Entries 6 and 7). GaX3 proved specific for this reaction.
Other Lewis acids, such as InCl3, SnCl4, and TiCl4 (in
combination with propargyl chloride), and even AlBr3 do not
lead to the formation of target lactone 8 even in trace
amounts.
halovinyl)lactones
8
with
high trans,trans-
diastereoselectivity. The process can be successfully
implemented both for methylidenemalonates 1 and donor-
acceptor cyclopropanes 2.
Five-membered lactone derivatives belong to important
classes of organic compounds. The five-membered lactone
frame is part of various natural compounds (Figure 1).12,13 Its
derivatives both natural and synthetic show a very broad
spectrum of biological activity, such as antimicrobial,
antifungal, anthelmintic, antiplasmodial, antioxidative and
anti-inflammatory activities, cytotoxic activities, including
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Table 1. Optimization of the Reaction Conditions.
It should be noted that alkylidenemalonates 1a,b
themselves readily undergo lactonization on the tertiary
carbon atom of the alkyl substituent in the presence of GaBr3
to give lactones 10 (Scheme 2). In some cases, this process
can markedly decrease the yields of the target vinyllactones
8. A similar transformation was reported previously,14 but it
occurred in the presence of strong protonic acids. It should
also be noted that 3-(2-methylpropylidene)pentane-2,4-dione
11 also undergo a similar cyclization (Scheme 2) to give
dihydrofuran 12. The process occurs so readily that
compound 11 could not be involved in the reaction with
propargyl bromide like 1a.
3
4
5
6
7
8
9
10
11
9a–c
8a–c
Entry
R
Conditions
Yield
Yield
(%) a
Z/E d
dr d
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(%) a
16
2
Scheme 2. GaBr3-Mediated Cyclization of Starting
Malonates 1a,b and Diketone 11.
1
2
3
4
5
6
i-Pr
i-Pr
1.5 h, 20°C
1 h, 40°C
1 h, 40°C b
1 h, 40°C
3 h, 40°C
7/1
–
30
62
57
22
66
0
18/1
12/1
7/1
10/1
9/1
–
i-Pr
0
–
c-C6H11
c-C6H11
c-C6H11
20
0
2/1
–
AlBr3,
45 f 4.2/1
4.5 h, 40 °C e
7
c-C6H11 InCl3, SnCl4, or n/r h
TiCl4,
–
n/r
–
3.5 h, 40 °C g
8
Ph
Ph
Ph
Ph
1 h, 40°C
5 h, 40°C
3 h, 84°C c
16 h, 40°C
12
<1
0
1.5/1
8
–
9
–
–
–
36
14/1
As
a result, we perfected a general scheme for
10
11
65 4/1.6/1.2/1
synthesizing vinyllactones 8 (Scheme to Table 2) and studied
the scope of this reaction (Table 2). The reaction occurs
fairly well with various alkyl- and aryl-substituted
methylidenemalonates (1a–f) in CH2Cl2 under reflux
conditions. The yields are higher in the case of
alkylidenemalonates and may be as high as 65% (Entry 5),
whereas arylidenemalonates react less readily. Furthermore,
arylcyclopropanedicarboxylates 2 can also be successfully
used in the reaction with propargyl bromide (Entries 9,10).
In this case, the scheme of the synthesis (Scheme to Table 2)
has to be modified to some extent, i.e., the 1,2-zwitterionic
gallium complex 4 has to be generated beforehand. However,
this does not reduce the efficiency of the synthesis. Aside
from propargyl bromide, the reaction can also be performed
with propargyl chloride combined with GaCl3 (Entry 8) to
give (1-chlorovinyl)lactone 8g. Unfortunately, the yield is no
higher than 22%, which is apparently due to the low
reactivity of propargyl chloride.
0
48 7/2.5/1.5/1
a NMR yield. b 1.5 equiv. of GaBr3. 1,2-DCE was used. Z/E and
diastereomer ratios were determined by 1H NMR spectra. e AlBr3 (1
equiv.) was used as Lewis acid instead of GaBr3. f Conversion 87%.
c
d
g
InCl3, SnCl4, or TiCl4 (1 equiv.) were used as Lewis acids instead
of GaBr3 in combination with propargyl chloride; in this case the
corresponding chloro derivatives like 9b and 8b should be formed. h
.No reaction.
In addition, a separate optimization was performed for
benzylidenemalonate 1c (Table 1, Entries 8–11). It is less
reactive and requires more drastic process conditions.
However, if the temperature is increased above 40 °C and/or
the reaction time is increased, the yield of the target lactone
8c increases, but diastereoselectivity becomes much worse
and all the four rather than two product diastereomers are
formed. The best diastereoselectivity (14:1) is observed at 40
°C and with a reaction time of 5 h, but conversion of 1c is as
small as 57% in this case.
Table 2. Scope of the reactions of 1 and 2 with 3-
halopropyne in the presence of GaX3.
The special experiment to clarify the possibility of the
isomerization of the isolated lactone 8a by its treatment by
GaBr3 was made (conditions: 40 °C, 2.5 h – more drastic
then during synthesis). Surprisingly, but the diastereomer
ratio did not changed at all (18/1 before reaction, and 18/1
after reaction). Apparently, the diastereomer ratio can change
only during the synthesis, while the required intermediates /
Ga-complexes still exist in the reaction mixture. This is
discussed in the mechanistic description below.
As one can see from Table 1, the most optimum variant
for synthesizing lactones 8 is to perform the reaction in
CH2Cl2 under reflux, while the reaction time has to be tuned
depending on the reactivity of the starting substrate 1. In this
case, it is not needed to generate complexes 3 beforehand. It
is sufficient to mix all the three reagents at once. It fact,
special experiments in which complex 3 was first generated
from malonate 1 and GaBr3 and then propargyl bromide was
added did not show any difference from those experiments
under the same conditions where all the reagents were mixed
at once.
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trace the formation of dibromides 9 and their subsequent
conversion. The first stage of the cascade involves the trans-
Substrate (1 or 2);
Yield,a %;
Entry
1
X
Product (8)
Conditions
dr b
addition of 1,2-zwitterion 4a and bromide anion to the triple
bond to give E-isomer 9h. It is interesting that the latter then
undergoes selective isomerization to the corresponding Z-
isomer. In this case, it is possible to selectively obtain and
isolate both isomers by choosing the appropriate
conditions.9a A temperature increase above 15 °C results in
the cyclization of Z-isomer 9h to give the final lactone 8h. It
should be noted that cyclopropane 2a (unlike malonates 1)
undergoes yet another significant side process, viz., [4+2]-
annulation at the benzene ring9e to give dihydronaphthalene
7a followed by its fragmentation to the corresponding
naphthalene 13. This process can also occur with Z-isomer
9h, which requires a temperature of 30–40 °C, i.e., somewhat
higher than the cyclization into lactone 8h (Scheme 3). Thus,
accurate temperature control makes it possible to suppress
the undesirable alkylation at the aromatic ring. Furthermore,
a detailed study of the process allowed us to isolate the
minor product 14, in which elimination of the propargyl
halogen atom with allylic rearrangement occurs upon attack
by an external bromide anion rather than upon intramolecular
cyclization. The transformation of the isolated intermediate
Z-9h with GaBr3 has been also examined. It likewise leads to
the formation of target lactone 8h.
8a, 45%
(62%),
dr 12/1
Br
1a (40 °C, 1 h)
1b (40 °C, 3 h)
8b, 52%
(66%),
dr 10/1
9
2
3
Br
Br
10
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8c, 30%
(36%),
dr 14/1,
1c (40 °C, 5 h)
conv. 57%
8c, 55%
(65%), dr
4/1.6/1.2/1
1c (3 h, 84 °C,
1,2-DCE)
4
5
Br
Br
8c
8d, 65%
(87%),
dr 6/1
1d (40 °C, 3 h)
1e (40 °C, 3 h)
8e, 48%
(77%),
dr 7/1
6
7
Br
Br
Scheme 3. Stepwise Sequence of the Formation of
Lactone 8h from Cyclopropane 2a. a
8f, 37%
(50%),
dr 13/1
1f (40 °C, 8 h)
1a (40 °C, 2 h)
8g, 22%
(30%),
dr 20/1
8
9
Cl
Br
8h, 61%
(64%), dr
27/2/1
2a (20 °С, 2.5 h)
8i, 57%
(84%),
dr 10/1
10
Br
2b (25 °С, 24 h)
a
b
NMR yield are given in parentheses. Diastereomer ratio was
determined by 1H NMR spectra.
a Z/E and diastereomer ratios were determined by 1H NMR spectra.
In all the cases, under optimized conditions, (1-
halovinyl)lactones
Important results were obtained using different halogen
atoms in the propargyl halide and in GaX3. In fact, the
reaction of malonate 1a with propargyl bromide in the
presence of GaI3 at room temperature for 3 h gave a mixture
of various acyclic dihalides Z- and E-9j, and Z- and E-9k, as
well as vinyllactones 8a and 8j as diastereomer pairs
(Scheme 4). It is interesting to consider the composition of
vinyl halides and the Br/I atomic ratio in the reaction
products. First, all bromine atoms from propargyl bromide
are exchanged for iodine. Second, vinyl iodides are formed
predominantly (even though the content of bromine atoms in
the reaction mixture is higher than that of iodine atoms, ca.
5:3). The diiodo derivative 9j is the main product among the
dihalides. It is surprising that the most obvious product 9´k
was not found in the reaction mixture at all.
8
are
formed
with
high
diastereoselectivity from 6:1 to 20:1 as a trans,trans-isomer.
It should be noted that the halogen atom contained in the
propargyl halide is removed during the reaction, whereas the
halogen atom in the product originates from GaX3. The
formation of lactones 8 is a complex cascade process, so the
yields of lactones are rather low in some cases. Furthermore,
a fraction of lactones is sometimes lost during isolation by
column chromatography.
Using cyclopropane 2a as an example, we managed to
trace the cascade sequence of steps in the formation of the
corresponding lactone 8h (Scheme 3) and, to a considerable
degree, understood the mechanism of the reactions that
occur. In fact, by starting the process at –15 °C and gradually
increasing the temperature and reaction time, we managed to
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As concerns vinyllactones 8a/8j, the iodo derivative 8j is
haloallyl)malonates 9 was studied in detail in our recent
work.10 It is formed via in situ generation of ionic gallium
complexes 3. Compound 9 contains an allylic halogen atom
that, in the presence of free GaX3 in the solution,10 can be
readily reversibly abstracted to give an ion pair comprising
an allylic cation and a GaX4– anion10 (intermediates I and II).
This predetermines the specific selective isomerization of E-
isomer 9 to the more thermodynamically stable Z-isomer,
which is not observed for any other (3-3-haloallyl)malonates
6 obtained from alkynes other than propargyl halides.10 The
formation of allylic cation II is also confirmed by the
exchange of allylic halogen atoms in 9 where “mixed”
halides are used (Scheme 4) and by the formation of minor
product 14 (Scheme 3). Cyclization to the target lactone 8
also occurs via allylic cation II due to intramolecular
nucleophilic attack of one of the ester groups by the carbonyl
(intermediate III). At this stage, the stereochemistry of the
C(4)–C(5) centers is set due to the arrangement of
substituents in the least sterically hindered “trans”-position
(Scheme 6, below). As a result, decomposition of the central
gallium core10 gives complexed methoxydihydrofuran V,
which is then hydrolyzed on treatment with dilute aqueous
HCl to give the target lactone 8. Apparently, the
stereochemistry of the remaining C(3)–C(4) centers is set at
this final stage to give the most thermodynamically stable
trans,trans-diastereomer.
also formed predominantly (Scheme 4). Even under non-
optimized conditions, its yield reaches 46% according to
NMR data, and it can be increased considerably by
performing the cyclization of compounds 9j/9k until
completion under more drastic conditions.
The cause is that apparently in this type of the reactions
–
GaI4 anions (which are the carriers of iodine) are more
9
–
nucleophilic then GaBr4 anions.10 As a consequence, in the
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case of partially reversible reactions, this leads to a
significant exchange of bromine for iodine and the
predominant formation of iodine derivatives.
A similar picture is observed if the propargyl bromide –
GaCl3 combination is used (Scheme 4). If the cyclization is
performed until completion, the chlorine-containing lactone
8g is the main product, and its yield (46% according to
NMR) is higher than if the propargyl chloride – GaCl3
combination is used (Table 2, Entry 8).
Scheme 4. Reactions of 1a with Propargyl Bromide and
GaCl3 or GaI3. a,b
Scheme 6. Simplified Key Part of the Proposed
Mechanism & Stereochemical Model for C(4)–C(5)
(below).
a NMR yields are indicated. b Z/E and diastereomer ratios were
determined by 1H NMR spectra.
The compounds obtained contain various functional
groups that can be easily modified using standard synthetic
protocols. A halide atom at the double bond in products 8
opens up rich prospects for further modifications by cross
coupling processes. For example, Sonogashira cross-
coupling reaction10,15 for compound 8b is given below in
Scheme 5, which leads to the enyne-derivative 15.
Scheme 5. Example of Follow-up Cross-Coupling
Reactions of Bromovinyllactone 8b.
The general formation scheme of lactones 8 was already
demonstrated in Scheme 3 with cyclopropane 2a as an
example. Let us consider in more detail the key mechanistic
features of the main stages of this cascade process (Scheme
6). The formation mechanism of E-isomers of (3-
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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 H and 13C signals
1
were made with the aid of 2D COSY, NOESY, edited-HSQC
and HMBC, if it is necessary. 1D DEPT-135 and/or 2D
edited-HSQC NMR spectra have been used for compounds
with the peak assignments. IR spectra were obtained on an
FT-IR spectrometer in CHCl3 solution (1%). Mass spectra
were recorded using electron impact ionization (EI; 70 eV,
direct inlet probe). High-resolution mass spectra (HRMS
TOF) were obtained using simultaneous electrospray
ionization (ESI). High resolution mass spectra were recorded
in the Department of Structural Studies of N. D. Zelinsky
Institute of Organic Chemistry RAS, Moscow.16
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Synthesis of Starting Cyclopropanes 2a,b. Starting
cyclopropanes 2a,b (ACDC) were synthesized from the
corresponding aromatic aldehydes through
a standard
synthetic sequence of Knoevenagel/Corey−Chaykovsky
reactions.17
Typical experimental procedure for reactions of
substituted methylidenemalonates with propargyl bromide.
Anhydrous GaBr3 (215 mg, 0.7 mmol) was added to a
solution of dimethyl 2-(2-methylpropylidene)malonate 1a
(130 mg, 0.7 mmol) and 3-bromopropyne (250 mg, 2.1
mmol) in 7 mL CH2Cl2 under dry argon atmosphere, and
reaction mixture was stirred 1 h at 40°C using magnetic
stirrer with heater (conditions for other methylidene-
malonates see in Table 1). Then the mixture was treated with
an aqueous solution of HCl (8 mL, 10%), the organic layer
was separated and the aqueous layer was extracted with
CH2Cl2 (2×8 mL). The combined organic extracts were dried
with anhydrous Na2SO4 and evaporated in vacuo. NMR yield
about 62% relatively p-dichlorobenzene as standard. The
residue was purified by column chromatography over silica
gel (eluent: petroleum ether – EtOAc, 5 : 1) and 5-(1-
bromovinyl)-4-isopropyl-2-oxotetrahydrofuran-3-
carboxylate 8a was prepared in 92 mg yield (45%) as a
mixture of two diastereomers in ratio ~10:1. Colorless thick
oil.
As a result, we have developed a new process comprising
the reaction of substituted methylidenemalonates with
propargyl halides in the presence of gallium halides. The
suggested process is implemented via intermediate in situ
generation of 1,2-zwitterionic gallium complexes with
Methyl (3RS,4SR,5SR)-5-(1-bromovinyl)-4-isopropyl-2-
~

oxotetrahydrofuran-3-carboxylate (8a). IR (CHCl3): 3041,
3019, 2967, 2878, 1788, 1744, 1630, 1469, 1437, 1322,
1273, 1186, 1161 cm–1. HRMS: calcd. for [M+H]+
C11H16BrO4 291.0226 and 293.0205; found 291.0226 and
293.0206; calcd. for [M+NH4]+ C11H19BrNO4 308.0492 and
–
[Ga(L)3]3+[GaX4 ]3 composition and involves a cascade of
reactions that result in the three-component assembly of five-
membered (1-halovinyl)lactones with high trans,trans-
diastereoselectivity. The process can be successfully
implemented both for methylidenemalonates and for donor-
acceptor cyclopropanes. Chloro-, bromo- and iodo-
substituted five-membered lactones can be obtained
successfully. Furthermore, we have studied in detail the
mechanistic specific features of the process developed and
considered its stereochemical aspects.
1
310.0472; found 308.0489 and 310.0469. Major isomer: H
NMR (400 MHz, CDCl3) δ 6.06 and 5.76 (both d, J = 2.2 Hz,
2 × 1H, =CH2), 4.68 (d, J = 6.8 Hz, 1H, H(5)), 3.81 (s, 3H,
OMe), 3.44 (d, J = 8.6 Hz, 1H, H(3)), 3.00 (dt, J = 8.6, 6.8
Hz, 1H, H(4)), 2.01–1.83 (m, 1H, CH), 0.99 and 0.98 (both
d, J = 6.8 Hz, 2 × 3H, 2 CH3) ppm. 13C{1H} NMR (100
MHz, CDCl3) δ 170.5 and 168.0 (2 CO), 130.3 (=CBr),
121.4 (=CH2), 84.0 (C(5)), 53.2 (OMe), 49.6 and 49.5 (C(3)
and C(4)), 30.0 (CH), 20.2 and 18.9 (2 Me) ppm. Minor
isomer: 1H NMR (300 MHz, CDCl3) δ 6.13 and 5.82 (both d,
J = 2.2 Hz, 2 × 1H, =CH2), 4.99 (d, J = 6.8 Hz, 1H, H(5)),
3.77 (s, 3H, OMe), 3.41 (d, J = 8.5 Hz, 1H, H(3)), 2.71 (dt, J
= 8.5, 6.8 Hz, 1H, H(4)), 2.01–1.83 (m, 1H, CH), 1.00 and
0.98 (both d, J = 6.8 Hz, 2 × 3H, 2 CH3) ppm.
EXPERIMANTAL SECTION
General Experimental Details. All reagents and solvents
used were commercial grade chemicals without additional
purification. Dichloromethane was distilled over P2O5. All
operations with GaCl3 and GaBr3 were carried out under a
dry argon atmosphere. TLC analysis was performed on
Silufol
chromatographic
plates.
For
preparative
Methyl (3RS,4SR,5SR)-5-(1-bromovinyl)-4-cyclohexyl-2-
oxotetrahydrofuran-3-carboxylate (8b). The title compound
was prepared according to the general procedure from 1b
chromatography, silica gel 60 (0.040−0.063 mm) and a
mixture of EtOAc and petroleum ether, as an eluent, were
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(148 mg, 0.65 mmol), GaBr3 (201 mg, 0.65 mmol), and 3-
(OMe), 50.7 (C(3)), 43.5 (C(4)), 29.5 and 20.5 (2 CH2), 13.9
(CH3) ppm.
bromopropyne (238 mg, 2.0 mmol) in 112 mg yield (52%) as
a mixture of of two diastereomers in ratio ~9:1. Colorless
Methyl
(3RS,4SR,5SR)-5-(1-bromovinyl)-4-heptyl-2-
~

oxotetrahydrofuran-3-carboxylate (8e). The title compound
was prepared according to the general procedure from 1e
(145 mg, 0.6 mmol), GaBr3 (168 mg, 0.6 mmol), and 3-
bromopropyne (215 mg, 1.8 mmol) in 100 mg yield (48%) as
thick oil. IR (CHCl3):
3058, 3045, 2932, 2857, 1785,
1744, 1630, 1449, 1437, 1354, 1310, 1270, 1241 cm–1.
HRMS: calcd. for [M+Na]+ C14H19BrNaO4 353.0359 and
1
355.0339; found 353.0355 and 355.0334. Major isomer: H
a mixture of of two diastereomers in ratio ~6:1. Colorless
NMR (300 MHz, CDCl3) δ 6.08 and 5.77 (both d, J = 2.2 Hz,
2 × 1H, =CH2), 4.73 (d, J = 7.0 Hz, 1H, H(5)), 3.80 (s, 3H,
OMe), 3.49 (d, J = 8.8 Hz, 1H, H(3)), 3.00 (dt, J = 8.8, 7.0
Hz, 1H, H(4)), 1.88–1.58 and 1.43–0.91 (both m, 2 × 5H, 5
CH2), 1.62–1.48 (m, 1H, CH) ppm. 13C{1H} NMR (75 MHz,
CDCl3) δ 170.5 and 168.0 (2 COO), 130.6 (CBr), 121.8
(=CH2), 83.8 (C(5)), 53.0 (OMe), 49.9 (C(3)), 48.9 (C(4)),
39.8 (CH), 30.6, 29.5, 25.9, 25.8 and 25.8 (5 CH2) ppm.
9
~

thick oil. IR (CHCl3):
3038, 3020, 2957, 2930, 2858,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2361, 1788, 1744, 1630, 1437, 1274 cm–1. HRMS: calcd. for
[M+Na]+ C15H23NaBrO4 369.0672 and 371.0652; found
1
369.0663 and 371.0646. Major isomer: H NMR (300 MHz,
CDCl3) δ 6.06 and 5.77 (both d, J = 2.1 Hz, 2 × 1H, =CH2),
4.51 (d, J = 7.9 Hz, 1H, H(5)), 3.82 (s, 3H, OMe), 3.35 (d, J
= 9.7 Hz, 1H, H(3)), 3.13–2.98 (m, 1H, H(4)), 1.78–1.16 (m,
12H, 6 CH2), 0.88 (t, J = 6.7 Hz, 3H, OMe) ppm. 13C{1H}
NMR (75 MHz, CDCl3) δ 170.2 and 167.8 (2 COO), 129.3
(CBr), 121.6 (=CH2), 85.8 (C(5)), 53.2 (OMe), 52.7 (C(3)),
44.2 (C(4)), 32.3, 31.7, 29.3, 29.0, 26.8 and 22.6 (6 CH2),
14.1 (CH3) ppm. Minor isomer: 1H NMR (300 MHz, CDCl3)
δ 6.08 and 5.79 (both d, J = 2.1 Hz, 2 × 1H, =CH2), 4.79 (d, J
= 7.9 Hz, 1H, H(5)), 3.80 (s, 3H, OMe), 3.70 (d, J = 9.7 Hz,
1H, H(3)), 2.89–2.75 (m, 1H, H(4)), 1.73–1.10 (m, 12H, 6
CH2), 0.89 (t, J = 6.7 Hz, 3H, OMe) ppm. 13C{1H} NMR (75
MHz, CDCl3) δ 170.5 and 167.9 (2 COO), 129.4 (CBr),
122.9 (=CH2), 86.3 (C(5)), 52.9 (OMe), 50.7 (C(3)), 43.9
(C(4)), 32.2, 31.6, 29.2, 29.0, 27.5 and 22.5 (6 CH2), 14.1
(CH3) ppm.
1
Minor isomer: H NMR (300 MHz, CDCl3) δ 6.13 and 5.82
(both d, J = 2.2 Hz, 2 × 1H, =CH2), 5.02 (d, J = 7.1 Hz, 1H,
H(5)), 3.79 (s, 3H, OMe), 3.71 (d, J = 8.8 Hz, 1H, H(3)),
2.82–2.69 (m, 1H, H(4)), 1.88–1.58 and 1.43–0.91 (both m,
2 × 5H, 5 CH2), 1.62–1.48 (m, 1H, CH) ppm.
Methyl
(3RS,4SR,5SR)-5-(1-bromovinyl)-2-oxo-4-
(8c). The title
phenyltetrahydrofuran-3-carboxylate
compound was prepared according to the general procedure
from 1c (154 mg, 0.7 mmol), GaBr3 (216 mg, 0.7 mmol), and
3-bromopropyne (250 mg, 2.1 mmol) in 68 mg yield (30%)
as a mixture of of three diastereomers in ratio ~14:1:1.
~

Colorless thick oil. . IR (CHCl3): 3043, 3039, 3011, 2956,
1791, 1745, 1631, 1438, 1322, 1278, 1236 cm–1. HRMS:
calcd. for [M+H]+ C14H14BrO4 325.0070 and 327.0050;
found 325.0067 and 327.0049; for [M+Na]+ C14H13BrNaO4
346.9889 and 348.9870; found 346.9887 and 348.9867.
Methyl
(3RS,4SR,5SR)-5-(1-bromovinyl)-4-(4-
nitrophenyl)-2-oxotetrahydrofuran-3-carboxylate (8f). The
title compound was prepared according to the general
procedure from 1e (159 mg, 0.6 mmol), GaBr3 (186 mg, 0.6
mmol), and 3-bromopropyne (214 mg, 1.8 mmol) in 82 mg
1
Major isomer: H NMR (300 MHz, CDCl3) δ 7.43–7.26 (m,
5H, Ph), 5.89 and 5.72 (both d, J = 2.3 Hz, 2 × 1H, =CH2),
4.86 (d, J = 8.9 Hz, 1H, H(5)), 4.23 (dd, J = 11.3 and 8.9 Hz,
1H, H(4)), 3.93 (d, J = 11.3 Hz, 1H, H(3)), 3.78 (s, 3H,
OMe) ppm. 13C{1H} NMR (75 MHz, CDCl3) δ 169.2 and
166.8 (2 COO), 135.6 (i-Ph), 129.4 and 127.5 (o- and m-Ph),
128.6 (p-Ph), 128.0 (CBr), 122.6 (=CH2), 86.4 (C(5)), 53.6
(C(3)), 53.3 (OMe), 49.9(C(4)) ppm.
yield (37%) as a mixture of of two diastereomers in ratio
~

~13:1. Colorless thick oil. IR (CHCl3): 3083, 3060, 1746,
1711, 1630, 1608, 1527, 1499, 1438, 1351, 1307, 1281 cm–1.
HRMS: calcd. for [M+Na]+ C14H12BrNNaO6 391.9740 and
1
393.9720; found 391.9747 and 393.9727. Major isomer: H
NMR (300 MHz, CDCl3) δ 8.26 (br.d, J = 8.8 Hz, 2H, o-Ph),
7.53 (br.d, J = 8.8 Hz, 2H, m-Ph), 5.96 and 5.77 (both d, J =
2.4 Hz, 2 × 1H, =CH2), 4.93 (d, J = 9.1 Hz, 1H, H(5)), 4.36
(dd, J = 11.4, 9.1 Hz, 1H, H(4)), 4.00 (d, J = 11.4 Hz, 1H,
H(3)), 3.81 (s, 3H, OMe) ppm. 13C{1H} NMR (75 MHz,
CDCl3) δ 168.3 and 166.2 (2 COO), 148.1 (p-Ph), 142.8 (i-
Ph), 128.8 (o-Ph), 127.1 (CBr), 124.6 (m-Ph), 123.1 (=CH2),
85.4 (C(5)), 53.6 (OMe), 53.2 (C(3)), 49.6 (C(4)) ppm.
Methyl
(3RS,4SR,5SR)-5-(1-bromovinyl)-2-oxo-4-
(8d). The title
propyltetrahydrofuran-3-carboxylate
compound was prepared according to the general procedure
from 1d (131 mg, 0.7 mmol), GaBr3 (218 mg, 0.7 mmol),
and 3-bromopropyne (250 mg, 2.1 mmol) in 130 mg yield
(64%) as a mixture of of two diastereomers in ratio ~6:1.
~

Colorless thick oil. IR (CHCl3):
3033, 3013, 2935, 2877,
1
Minor isomer: H NMR (300 MHz, CDCl3) δ 8.24 (br.d, J =
2854, 1789, 1744, 1630, 1521, 1458, 1438, 1360, 1274, 1240
cm–1. HRMS: calcd. for [M+H]+ C11H16BrO4 291.0226 and
293.0206; found 291.0227 and 293.0211; calcd. for [M+Na]+
C11H15BrNaO4 313.0046 and 315.0026; found 313.0048 and
315.0030. Major isomer: 1H NMR (300 MHz, CDCl3) δ 6.08
and 5.78 (both d, J = 2.2 Hz, 2 × 1H, =CH2), 4.53 (d, J = 8.1
Hz, 1H, H(5)), 3.82 (s, 3H, OMe), 3.38 (d, J = 9.8 Hz, 1H,
H(3)), 3.12–3.00 (m, 1H, H(4)), 1.72–1.27 (m, 4H, CH2CH2),
0.92 (t, J = 7.2 Hz, 3H, CH3) ppm. 13C{1H} NMR (75 MHz,
CDCl3) δ 170.2 and 167.8 (2 COO), 129.3 (CBr), 121.9
(=CH2), 85.7 (C(5)), 53.1 (OMe), 52.6 (C(3)), 44.0 (C(4)),
8.8 Hz, 2H, o-Ph), 7.48 (br.d, J = 8.8 Hz, 2H, m-Ph), 6.12
and 5.80 (both d, J = 2.4 Hz, 2 × 1H, =CH2), 5.01 (d, J = 9.0
Hz, 1H, H(5)), 4.23 (dd, J = 11.3, 9.0 Hz, 1H, H(4)), 4.05 (d,
J = 11.3 Hz, 1H, H(3)), 3.79 (s, 3H, OMe) ppm.
Methyl (3RS,4SR,5SR)-5-(1-bromovinyl)-4-isopropyl-2-
oxotetrahydrofuran-3-carboxylate (8g). The title compound
was prepared according to the general procedure from 1a
(159 mg, 0.6 mmol), GaCl3 (186 mg, 0.6 mmol), and
propargyl chloride (214 mg, 1.8 mmol) in 30 mg yield (20%)
as a mixture of of two diastereomers in ratio ~11:1. Colorless
thick oil. HRMS: calcd. for [M+Na]+ C11H15ClNaO4
1
34.1 and 20.1 (2 CH2), 13.8 (CH3) ppm. Minor isomer: H
1
269.0551; found 269.0546. H NMR (300 MHz, CDCl3) δ
NMR (300 MHz, CDCl3) δ 6.10 and 5.80 (both d, J = 2.1 Hz,
2 × 1H, =CH2), 4.80 (d, J = 8.1 Hz, 1H, H(5)), 3.76 (s, 3H,
OMe), 3.70 (d, J = 9.6 Hz, 1H, H(3)), 2.90–2.78 (m, 1H,
H(4)), 1.74–1.25 (m, 4H, CH2CH2), 0.93 (t, J = 7.2 Hz, 3H,
CH3) ppm. 13C{1H} NMR (75 MHz, CDCl3) δ 170.6 and
167.4 (2 COO), 129.3 (CBr), 122.9 (=CH2), 86.2 (C(5)), 52.5
5.61 and 5.51 (both d, J = 2.0 Hz, 2 × 1H, =CH2), 4.75 (d, J
= 6.8 Hz, 1H, (H(4´)), 3.81 and 3.75 (both s, 2 × 3H, 2
OMe), 3.44 (d, J = 8.5 Hz, 1H, H(2)), 3.40 (s, 1H, OH), 3.01
(dt, J = 8.5, 6.8 Hz, 1H, H(3´)), 1.91 (octet, J = 6.8 Hz, 1H,
H(2´)), 0.99 and 0.98 (both d, J = 6.8 Hz, 2 × 3H, 2 CH3)
ppm. 13C{1H} NMR (75 MHz, CDCl3) δ 170.6 and 168.1 (2
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№2: 1H NMR (CDCl3, 300.1 MHz):  5.56 (br t, 1H, H(6), 2J
COO), 138.4 (C(5´)), 117.0 (C(6´)), 82.9 (C(4´)), 53.2 and
52.5 (2 OMe), 49.7 and 48.9 (C(2) and C(3´)), 30.1 (C(2´)),
20.1 and 18.9 (2 Me).
= 1.8 Hz), 5.65 (br t, 1H, H(6), 2J = 1.7 Hz) ppm.
Diastereomer №3: 1H NMR (CDCl3, 300.1 MHz):  6.06 (br
2
2
4
t, 1H, H(6), J = 1.9 Hz), 6.55 (br t, 1H, H(6), J = 1.9, J =
0.8 Hz) ppm. Other signals are overlapping with the signals
of compounds 9j and 9k.
Methyl
(3RS,4SR,5SR)-4-benzyl-5-(1-bromovinyl)-2-
oxotetrahydrofuran-3-carboxylate (8h). A solution of methyl
2-phenylcyclopropane-1,1-dicarboxylate 2a (118 mg, 0.5
mmol) in dry CH2Cl2 (6 mL) was cooled at 5°C; solid GaBr3
(230 mg, 0.75 mmol) was added in one portion and the
reaction mixture was stirred at the same temperature during
10 min. Then 3-bromopropyne (240 mg, 2.0 mmol) was
added and the reaction mixture was stirred at 25°C during
1.5 h. After that, an aqueous solution of HCl (5%) was added
until pH 3 was achieved and the reaction mixture was
extracted with CH2Cl2 (3×15 mL). The organic layer was
dried over MgSO4 and the solvent was removed in vacuo.
The residue was purified by column chromatography on
silica gel (benzene–EtOAc, 50:1 to 20:1) to afford title
Dimethyl 2-(3,4-dibromo-1-phenylpent-3-en-4-yl)malo-
nate (9a). Both isomers were prepared according to the
general procedure using conditions indicated on Scheme 3.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
Colorless thick oil. E-isomer. Yield 16%. H NMR (CDCl3,
2
3
300.1 MHz):  2.62 (dd, 1H, Ha(1), J = 13.3, J = 8.7 Hz),
2
3
2.90 (dd, 1H, Hb(1), J = 13.3, J = 4.9 Hz), 3.25–3.38 (m,
1H, H(2)), 3.49 (d, 1H, CH, 3J = 8.0 Hz), 3.78 and 3.80 (both
2
s, 2 × 3H, 2 OMe), 3.81 and 3.97 (both d, 2 × 1H, H(5), J =
11.5 Hz), 6.02 (d, 1H, H(3), 3J = 11.1 Hz), 7.15–7.20 (m, 2H,
o-C6H4), 7.23–7.36 (m, 3H, m- and p-C6H4) ppm. 13C{1H}
NMR (CDCl3, 100.6 MHz):  32.1 (C(5)), 38.6 (C(1)), 42.7
(C(2)), 52.7 and 52.8 (2 OMe), 54.6 (CH), 122.6 (C(4)),
126.9 (p-C6H4), 128.6 (m-C6H4), 129.3 (o-C6H4), 135.4
(C(3)), 137.7 (i-C6H4), 167.9 and 168.1 (2 COO) ppm. Z-
compounds 8h in 105 mg yield (62%) as thick colorless oil.
~

IR (CHCl3) 3067, 3046, 3014, 2956, 2926, 1791 and 1744
br (C=O), 1630, 1521, 1497, 1455, 1437, 1354, 1277, 1187,
1146, 1015 cm–1. HRMS (ESI) calcd for [M+Na]+
C15H15BrNaO4 361.0046 and 363.0025; found 361.0045 and
363.0029. 1H NMR (CDCl3, 400 MHz): δ 2.82 (dd, 2J = 13.9,
3J = 7.7 Hz, 1H, Ha(6)), 3.04 (dd, 2J = 13.9, 3J = 5.1 Hz, 1H,
Hb(6)), 3.38–3.50 (m, 2H, H(3) and H(4)), 3.62 (s, 3H,
OMe), 4.62 (br.d, 3J = 7.6 Hz, 1H, H(5)), 5.78 and 6.02 (both
1
isomer. Yield 59%. H NMR (CDCl3, 300.1 MHz):  2.80
2
3
(dd, 1H, Ha(1), J = 13.6, J = 7.2 Hz), 2.88 (dd, 1H, Hb(1),
2J = 13.6, J = 6.5 Hz), 3.48 (d, 1H, CH, J = 6.9 Hz), 3.56
3
3
(m, 1H, H(2)), 3.75 and 3.78 (both s, 2 × 3H, 2 OMe), 4.20
3
(br. s, 2H, H(5)), 6.30 (d, 1H, H(3), J = 9.4 Hz), 7.15–7.20
(m, 2H, o-C6H4), 7.22–7.35 (m, 3H, m- and p-C6H4) ppm.
13C{1H} NMR (CDCl3, 75.5 MHz):  37.8 (C(1)), 38.3
(C(5)), 43.5 (C(2)), 52.5 and 52.6 (2 OMe), 53.4 (CH), 125.0
(C(4)), 126.7 (p-C6H4), 128.5 (m-C6H4), 129.3 (o-C6H4),
133.3 (C(3)), 137.7 (i-C6H4), 168.2 and 168.4 (2 COO)
ppm.9a
2
d, J = 2.5 Hz, 2 × 1H, =CH2), 7.16–7.21 (m, 2H, o-Ph),
7.25–7.38 (m, 3H, m- and p-Ph) ppm. 13C{1H} NMR
(CDCl3, 100.6 MHz): δ 37.1 (C(6)), 45.7 (C(4)), 51.6 (C(3)),
52.9 (OMe), 84.4 (C(5)), 121.9 (=CH), 127.3 (p-Ph), 128.5
(=C), 128.8 (m-Ph), 129.3 (o-Ph), 136.1 (i-Ph), 167.0 (COO),
169.7 (C(2)) ppm.
Dimethyl 2-(5,6-diiodo-2-methylhex-4-en-3-yl)malonate
(9j). The title compound was prepared according to the
general procedure using conditions indicated on Scheme 4.
This compound was not isolated in pure form. NMR yield
33%. (Z:E = 5.6/1). Z-isomer. 1H NMR (CDCl3, 300.1
Methyl
(3RS,4SR,5SR)-5-(1-bromovinyl)-4-(4-
nitrobenzyl)-2-oxotetrahydrofuran-3-carboxylate (8i).
A
mixture of methyl 2-(4-nitrophenyl)cyclopropane-1,1-
dicarboxylate 2b (98 mg, 0.35 mmol) and GaBr3 (155 mg,
0.5 mmol) in dry CH2Cl2 (5 mL) was stirred during 1 h, and
then 3-bromopropyne (191 mg, 1.6 mmol) was added and the
reaction mixture was stirred at 25°C during 1.5 h. The
reaction mixture was then treated according to the procedure
described above. The title compound 8i was isolated by
column chromatography in 77~ mg yield (57%) as light

3
MHz):  0.76–1.13 (m, 6H, 2 Me), 1.91 (dq, 1H, H(1), J =
13.6, 3J = 6.7 Hz), 2.91 (ddd, 1H, H(2), 3J = 10.2, 3J = 7.7, 3J
3
= 6.7 Hz), 3.63 (d, 1H, CH, J = 7.7 Hz), 3.73–3.78 (m, 6H,
2
4
2 × 3H, 2 OMe), 4.43 (dd, 2H, 2 × H(5), J = 2.6, J = 0.7
Hz), 5.99 (d, 1H, H(3), J = 10.2 Hz) ppm. 13C{1H} NMR
3
(CDCl3, 75.5 MHz):  18.3 (C(5)), 18.8 and 20.9 (2 Me),
30.3 (C(1)), 52.4 (C(2)), 52.5 and 52.6 (2 OMe), 53.0 (CH),
107.9 (C(4)), 137.2 (C(3)), 168.1 and 168.4 (2 COO) ppm.
yellow thick oil. IR (CHCl3)
3080, 3036, 3011, 2956,
2861, 1794 and 1745 br (C=O), 1630, 1607, 1527 br (N=O),
1496, 1455, 1350 br (N=O), 1294, 1242, 1186, 1147, 1017
cm–1. HRMS (ESI) calcd for [M+Na]+ C15H14BrNNaO6
1
E-isomer. H NMR (CDCl3, 300.1 MHz):  0.76–1.13 (m,
6H, 2 Me), 1.72–1.99 (m, 1H, H(1)), 2.94–3.02 (m, 1H,
3
1
H(2)), 3.55 (d, 1H, CH, J = 8.8 Hz), 3.73–3.78 (m, 6H, 2 ×
405.9897 and 405.9876; found 405.9893 and 405.9866. H
2
2
3
3H, 2 OMe), 4.08 (d, 1H, H(5), J = 11.0 Hz), 4.72 (d, 1H,
NMR (CDCl3, 300.1 MHz): δ 2.94 (dd, J = 14.1, J = 7.9
2
3
2
3
H(5), J = 11.0 Hz), 6.20 (d, 1H, H(3), J = 12.0 Hz) ppm.
13C{1H} NMR (CDCl3, 75.5 MHz):  11.8 (C(5)), 17.9 and
21.4 (2 Me), 29.4 (C(1)), 47.1 (C(2), 52.2–52.7 (CH and 2
OMe), 101.2 (C(4)), 141.3 (C(3)), 168.2 and 168.5 (2 COO)
ppm.
Hz, 1H, Ha(6)), 3.14 (dd, J = 14.1, J = 4.1 Hz, 1H, Hb(6)),
3.37–3.52 (m, 2H, H(3) and H(4)), 3.62 (s, 3H, OMe), 4.63
(br.d, 1H, H(5), J = 7.3 Hz), 5.77 and 6.03 (both d, J = 2.0
3
2
3
Hz, 2 × 1H, =CH2), 7.39 (d, J = 8.4 Hz, 2H, o-C6H4), 8.20
(d, J = 8.4 Hz, 2H, m-C6H4) ppm. 13C{1H} NMR (CDCl3,
3
75.5 MHz): δ 37.3 (C(6)), 45.1 (C(4)), 51.7 (C(3)), 53.1
(OMe), 84.5 (C(5)), 122.2 (=CH), 123.9 (o-C6H4), 128.0
(C(6)), 130.0 (m-C6H4), 143.9 (i-C6H4), 147.2 (p-C6H4),
166.6 (COO), 168.9 (C(2)) ppm.
Dimethyl
2-(5-bromo-6-iodo-2-methylhex-4-en-3-yl)-
malonate (9k). The title compound was prepared according
to the general procedure using conditions indicated on
Scheme 4. This compound was not isolated in pure form.
1
Methyl
5-(1-iodovinyl)-4-isopropyl-2-oxotetrahydro-
NMR yield 14%. (Z:E = 3.7/1). Z-isomer. H NMR (CDCl3,
furan-3-carboxylate (8j). The title compound was prepared
according to the general procedure using conditions
indicated on Scheme 4. This compound was not isolated in
pure form. NMR yield 46% (dr = 3.4/1.4/1). Diastereomer
300.1 MHz):  0.76–1.13 (m, 6H, 2 Me), 1.72–1.98 (m, 1H,
3
3
3
H(1)), 3.09 (ddd, 1H, H(2), J = 10.5, J = 7.7, J = 6.8 Hz),
3
3.62 (d, 1H, CH, J = 7.7 Hz), 3.73–3.78 (m, 6H, 2 × 3H, 2
OMe), 4.28 (dd, 2H, 2 × H(5), 2J = 4.9, 4J = 0.4 Hz), 6.24 (d,
1
1H, H(3), J = 10.5 Hz) ppm. 13C{1H} NMR (CDCl3, 75.5
3
№1 (major; trans,trans-): H NMR (CDCl3, 300.1 MHz): 
3
2
4.70 (d, 1H, H(5), J = 10.8 Hz), 5.85 (br t, 1H, H(6), J =
MHz):  12.0 (C(5)), 18.7 and 21.7 (2 Me), 30.2 (C(1)), 48.1
1.7 Hz), 6.09 (br t, 1H, H(6), 2J = 1.7 Hz) ppm. Diastereomer
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(C(2)), 52.2–52.7 (CH, and 2 OMe), 127.5 (C(4)), 130.1
(C(3)), 168.2 and 168.4 (2 COO) ppm. E-isomer. H NMR
Opening of Donor–Acceptor Cyclopropanes Catalyzed by a
1
Brønsted Acid in Hexafluoroisopropanol. Org. Lett. 2018,
20, 574–577. (g) Das, S.; Daniliuc, C. G.; Studer, A. Lewis
Acid Catalyzed Stereoselective Dearomative Coupling of
Indolylboron Ate Complexes with Donor–Acceptor
Cyclopropanes and Alkyl Halides. Angew. Chem. Int. Ed.
2018, 57, 4053–4057.
(CDCl3, 300.1 MHz):  0.76–1.13 (m, 6H, 2 Me), 1.72–1.99
(m, 1H, H(1)), 2.94–3.02 (m, 1H, H(2)), 3.69–3.87 (m, 1H,
CH), 3.73–3.78 (m, 6H, 2 × 3H, 2 OMe), 4.05 (d, 1H, H(5),
2
2J = 10.8 Hz), 4.61 (d, 1H, H(5), J = 10.8 Hz), 5.95 (d, 1H,
H(3), 3J = 11.8 Hz) ppm.
(2) (a) Zaytsev, S. V.; Ivanov, K. L.; Skvortsov, D. A.;
Bezzubov, S. I.; Melnikov, M. Y.; Budynina, E. M.
Methyl 5,5-dimethyl-2-oxotetrahydrofuran-3-carboxylate
(10a). Yield 59%. 1H NMR (300 MHz, CDCl3) δ 3.81 (s, 3H,
OMe), 3.76 (t, J = 9.7 Hz, 1H, H(3)), 2.51 and 2.32 (both dd,
2J = 13.0, 3J = 9.7 Hz, 2 × 1H, CH2), 1.52 and 1.42 (both s, 2
× 3H, 2 CH3) ppm.14a
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Nucleophilic
Ring
Opening
of
Donor–Acceptor
Cyclopropanes with the Cyanate Ion: Access to
Spiro[pyrrolidone-3,3′-oxindoles]. J. Org. Chem., 2018, 83,
8695–8709. (b) Kreft, A.; Jones, P. G.; Werz, D. B. The
Cyclopropyl Group as a Neglected Donor in Donor–
Acceptor Cyclopropane Chemistry. Org. Lett. 2018, 20,
2059–2062. (c) Augustin, A. U.; Sensse, M.; Jones, P. G.;
Werz, D. B. Stereospecific Reactions of Donor–Acceptor
Cyclopropanes with Thioketones: Access to Highly
Substituted Tetrahydrothiophenes. Angew. Chem. Int. Ed.
2017, 56, 14293–14296. (d) Matsumoto, Y.; Nakatake, D.;
Yazaki, R.; Ohshima, T. An Expeditious Route to
3-Acetyl-2,5,5-trimethyl-4,5-dihydrofuran (12). Yield
1
67%. H NMR (300 MHz, CDCl3) δ 2.77 (s, 2H, CH2), 2.24
and 2.22 (both s, 2 × 3H, 2 Me), 1.41 (s, 6H, 2 CH3) ppm.14b
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge
on the ACS Publications website at DOI:
trans‐Configured
Tetrahydrothiophenes
Enabled
by
1H and 13C NMR spectra for all pure products (PDF)
Fe(OTf)3‐Catalyzed [3+2] Cycloaddition of Donor–Acceptor
Cyclopropanes with Thionoesters. Chem. Eur. J. 2018, 24,
6062–6066. (e) Dey, R.; Kumar, P.; Banerjee, P. Lewis Acid
Catalyzed Annulation of Cyclopropane Carbaldehydes and
Aryl Hydrazines: Construction of Tetrahydropyridazines and
AUTHOR INFORMATION
Corresponding Authors
*E-mail: novikovfff@bk.ru.
*E-mail: tom@ioc.ac.ru.
Application
Toward
a
One-Pot
Synthesis
of
Hexahydropyrrolo[1,2-b]pyridazines. J. Org. Chem. 2018,
83, 5438–5449. (f) Irwin, L. C.; Renwick, C. R.; Kerr, M. A.
Nucleophilic Opening of Donor–Acceptor Cyclopropanes
with Indoles via Hydrogen Bond Activation with 1,1,1,3,3,3-
Hexafluoroisopropanol. J. Org. Chem. 2018, 83, 6235–6242.
(g) Chagarovskiy, A. O.; Vasin, V. S.; Kuznetsov, V. V.;
Ivanova, O. A.; Rybakov, V. B.; Shumsky, A. N.; Makhova,
N. N.; Trushkov, I. V. (3+3)‐Annulation of Donor–Acceptor
Cyclopropanes with Diaziridines. Angew. Chem. Int. Ed.
2018, 57, 10338–10342. (h) He, Y.; Zhu, X.; Hu, C.; Hong,
G.; Wang, L. Scandium(III) Trifluoromethanesulfonate
Catalyzed Reactions of Donor‐Acceptor Cyclopropanes with
1,1‐Diarylethylenes. ChemistrySelect 2019, 4, 1437–1440.
ORCID
Roman A. Novikov: 0000-0002-3740-7424
Yury V. Tomilov: 0000-0002-3433-7571
Author Contributions
§D.A.D. and R.A.N. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the Russian Science
Foundation (grant no. 14-13-01054-P).
(3) (a) Varshnaya, R. K.; Banerjee, P. Lewis Acid-
Catalyzed
[3+3]
Annulation
of
Donor–Acceptor
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