Lewis Acid Triggered Vinylcyclopropane-Cyclopentene Rearrangement

Article abstract of DOI:10.1021/acs.joc.7b02351

We report a mild Lewis acid induced isomerization of donor-acceptor cyclopropanes, containing an alkenyl moiety and diverse electron-withdrawing group(s) at the adjacent positions, into substituted cyclopentenes. We have found that 1,1,2-trisubstituted cy

Full text of DOI:10.1021/acs.joc.7b02351

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Featured Article
Lewis Acid-Triggered Vinylcyclopropane-Cyclopentene Rearrangement
Olga A. Ivanova, Alexey O. Chagarovskiy, Alexey N. Shumsky,
Vasiliy D. Krasnobrov, Irina I. Levina, and Igor V. Trushkov
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02351 • Publication Date (Web): 07 Nov 2017
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Lewis Acid-Triggered Vinylcyclopropane-Cyclopentene Rearrangement
*,†
‡,§
II
†
Olga A. Ivanova, Alexey O. Chagarovskiy, Alexey N. Shumsky, Vasiliy D. Krasnobrov,
II
*,‡,§
Irina I. Levina, Igor V. Trushkov
†
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Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1ꢀ3,
Moscow 119991 Russia
‡
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and
Immunology, Samory Mashela 1, Moscow 117997, Russian Federation
§
Faculty of Science, RUDN University, MiklukhoꢀMaklaya 6, Moscow 117198, Russian
Federation
II
Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow
119334, Russian Federation
iv@kinet.chem.msu.ru; itrushkov@mail.ru
Abstract: We report a mild Lewis acidꢀinduced isomerization of donorꢀacceptor cyclopropanes,
containing an alkenyl moiety and diverse electronꢀwithdrawing group(s) at the adjacent
positions, into substituted cyclopentenes. We have found that 1,1,2ꢀtrisubstituted cyclopentꢀ3ꢀ
enes were exclusively obtained in yield of 51 to 99% when cyclopropanes with 2ꢀsubstituted
alkenyl group as a donor underwent isomerization. For cyclopropanes bearing trisubstituted
alkenyl group either the corresponding cyclopentꢀ3ꢀenes or isomeric cyclopentꢀ2ꢀenes having
two acceptor groups at the C(1) atom were formed, with the reaction selectivity being
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determined by the applied Lewis acid. We have shown that the reactivity of the donorꢀacceptor
cyclopropane increases with the increase of the electronꢀdonating character of (hetero)aromatic
group attached to the alkenyl moiety. The synthetic utility of the developed methodology was
also demonstrated through the synthesis of polysubstituted cyclopentane and piperidine
derivatives.
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Introduction
Donorꢀacceptor (D–A) cyclopropanes are recognized as an archetype of activated smallꢀring
systems that undergo numerous transformations offering access to important synthetic targets
1
ꢀ3
with excellent efficiency and selectivity. DꢀA cyclopropanes not only demonstrate high
reactivity against a broad scope of reaction partners but also can be involved into various Lewis
acidꢀpromoted processes that do not require any other reagents. Examples of these atomꢀ
4
economic reactions include isomerizations to acyclic products (Scheme 1, a), various ring
5
6,7
expansions (Scheme 1, b), homoꢀNazarov cyclization (Scheme 1, c)
and other
4a,8
cycloisomerizations, multiple types of cyclodimerizations, wherein cyclopropanes act as twoꢀ,
threeꢀ, and more than threeꢀatom components, pairwise combination of which provides various
9
,10
11,12
13
cyclic systems (Scheme 1, d), intramolecular cycloadditions
as well as other processes.
In addition, a few examples of the Lewis acidꢀinduced vinylcyclopropaneꢀcyclopentene
10a,14
rearrangement (VCR) have been reported.
Scheme 1. Examples of Lewis Acid-Induced Transformations of Donor-Acceptor
Cyclopropanes in the Absence of an Additional Reaction Partner
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From the theoretical point of view, VCR and its heteroatom variants represent the most
1
5,16
interesting and challenging ring enlargement reactions
concerted (Scheme 2, path i) or stepwise mechanism. In the last case either biradical X (Scheme
, path ii) or zwitterꢀionic species Y or Z (Scheme 2, paths iii and iv) can be formed as an
as they can proceed by either
2
intermediate.
Scheme 2. Mechanisms for the Vinylcyclopropane-to-Cyclopentene Rearrangement and Its
Heteroatom Variants
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While significant advances in mechanistic study of VCR were achieved, a synthetic
application of this reaction is still restricted as under the typical reaction conditions (heating at
1
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3
00–600 °C
or photolysis ) it proceeds via the formation of biradical intermediate X
(Scheme 2, path ii) thereby the desired process is often accompanied by diverse side
18b,19
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reactions.
To solve this problem, transition metalꢀcatalyzed VCR’s were developed.
However, transition metal complexes are also able to induce the isomerization of
2
1
vinylcyclopropanes into 1,3ꢀdienes and other processes. As a result, the efficiency of transition
metalꢀcatalyzed VCR differs significantly between various substrates. Therefore, alternative
synthetic protocols for chemoselective ring expansion of vinylcyclopropanes as practical and
versatile methods for the construction of cyclopenteneꢀbased skeletons are still highly required.
We hypothesized that the development of new VCR versions proceeding under mild
reaction conditions could be possible due to the change of the reaction mechanism. If biradical
intermediate X is responsible for occurring undesired side reactions, a proper selection of
substituents in starting vinylcyclopropane as well as reagents or catalyst applied can provide the
generation of zwitterꢀionic intermediate of Z type. It is conceivable that the heterolytic cleavage
of threeꢀmembered ring with the formation of Z can be facilitated by the decoration of the C=C
bond in the parent vinylcyclopropane with a cationꢀstabilizing group, on the one hand, and the
introduction of anionꢀstabilizing substituent(s) at the vicinal position of cyclopropane, on the
22
other. Such substrates can be regarded as a subclass of DꢀA cyclopropanes. Similar to other Dꢀ
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A cyclopropanes, they can be additionally activated by a Lewis acid via its coordination to
acceptor group(s) increasing the stabilization of the anionic moiety and favouring zwitterꢀion Z
formation.
In this work we report the results of our investigation of the Lewis acidꢀinduced
rearrangement of DꢀA cyclopropanes 1, containing diverse electronꢀwithdrawing groups and a
broad variety of substituents at the alkenyl moiety, into the corresponding cyclopentenes 2.
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Results and Discussion
We started our research by the optimization of the reaction conditions for the
isomerization of 1 with previously described alkenylcyclopropanes 1a,b as model substrates
(
Table 1). We found that Lewis acids influence the efficiency of rearrangement of substrates 1a
and 1b into the corresponding cyclopentenes 2a,b in different manner. Weakly activating Lewis
acids, such as MgI , ZnCl , Sn(OTf) , Ni(ClO ⋅6H O were not efficient in inducing VCR of 1a
Table 1, entries 1ꢀ5). Use of strongly activating Lewis acids (AlCl , BF ⋅OEt ) also failed to
2
2
2
4
)
2
2
(
3
3
2
produce the target cyclopentene 2a since complex mixtures of unidentified products were formed
as a result of multiple side processes (Table 1, entries 9, 10). However, Lewis acids with
moderate activity (TiCl
yields (Table 1, entries 6ꢀ8). The best result was obtained when VCR of 1a was induced by
GaCl ; cyclopentene 2a was obtained in 81% yield (Table 1, entry 11). On the other hand,
cyclopentene 2b was obtained in 15% yield only when GaCl was used as an initiator,
predominantly due to oligomerization of the more active substrate 1b (Table 1, entry 13). Similar
result was also found when VCR of 1b was induced by MgI (Table 1, entry 14). Weakly
activating Yb(OTf) failed to catalyze 1bꢀtoꢀ2b rearrangement at room temperature (Table 1,
entry 16). However, slightly more active Sc(OTf) and Ni(ClO ) ⋅6H O produced the target
4 4
, SnCl ) were found to initiate 1aꢀtoꢀ2a rearrangement in moderate
3
3
2
3
3
4 2
2
cyclopentene 2b in excellent yields (Table 1, entries 18, 19). To summarize, we found that VCR
of the less reactive 2ꢀstyrylcyclopropaneꢀ1,1ꢀdiester 1a can be efficiently initiated with GaCl or
3
other moderately active Lewis acids. Oppositely, cyclopropane 1b, wherein paraꢀmethoxy group
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in the styryl moiety provides additional stabilization of the zwitterꢀionic intermediate of Z type,
rearranged into the corresponding cyclopentene 2b under the treatment of such weakly activating
Lewis acids, as Sc(OTf) and Ni(ClO ) ⋅6H O. Interestingly that SnCl was found to be rather
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4 2
2
4
efficient catalyst for the rearrangement of both substrates (Table 1, entries 8, 15).
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a,b
Table 1. Optimization of Reaction Conditions
c
Entry 1,2 LA [mol %]
Solvent Time [h]
T [°C]
Yield [%]
1
2
3
4
5
6
a
a
a
a
a
a
MgI
2
(20)
CH
2
Cl
2
2
2
2
4
24
5
20
ꢀ
Sn(OTf) (5)
CH Cl
20
ꢀ
2
2
ZnCl
ZnCl
2
2
(300)
(300)
CH
2
2
Cl
Cl
40
40
40
46
CH
9
c,d
Ni(ClO
4
)
2
6H
2
O (20)
C
2
H
4
Cl
Cl
CH Cl
2
3
83
23
TiCl (110)
4
CH
2
2
0.5; 3
−40–20; 20
41
59
63
7
a
a
a
a
a
a
b
b
b
b
TiCl (110)
0.5; 3
−40–20; 40
4
2
2
8
9
SnCl (110)
CH Cl
2
2
40
4
2
d
BF
AlCl
GaCl (110)
3
Et
2
O (105)
CH
2
Cl
Cl
CH Cl
2
−60–20; 20
ꢀ
d
10
3
(150)
C
2
H
4
2
0.5
1
83
20
20
20
20
40
20
ꢀ
11
12
13
81
3
2
2
e
GaCl
3
3
(110)
CH
CH
CH
CH
2
2
2
2
Cl
Cl
Cl
Cl
2
1
60
d
GaCl
(100)
2
2
2
2
1
15
d
14
MgI
SnCl
Yb(OTf) (5)
2
(20)
6
15
c
1
5
6
4
(110)
1.5
5
87
f
1
CH Cl
ꢀ
3
2
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b
b
Ni(ClO ) 6H O (20) CH Cl
4
3
20
20
95
91
4 2
2
2
2
2
18
Sc(OTf) (10)
CH Cl
3
2
a
b
c
d
Isolated yields. Concentration of 1a in the corresponding solvent is ca. 0.07 M. NMR yield. Complex mixture
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1
1
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e
f
of products. 0.5 M solution in pentane. No conversion.
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To study the Lewis acidꢀinduced VCR in detail, we synthesized a broad series of DꢀA
cyclopropanes 1 bearing diverse substituents at the alkenyl moiety and various acceptor groups.
The general synthetic scheme includes Knoevenagel condensation of commercially available or
easily prepared cinnamic aldehydes 3 and their heterocyclic analogs with various CHꢀacids,
followed by cyclopropanation of the adducts 4 with CoreyꢀChaykovsky ylide (Table 2).
Table 2. Synthesis of Cyclopropanes 1.
a
b
Yield (%) [dr]
Entry 1,3,4
Ar
R
EWG
EWG'
c
4
1
d
d
d
1
2
3
c
d
e
H
H
H
CO Me
CO Me
96
67
69
76
2
2
CO
2
2
Me
Me
CO
CO
2
2
Me
Me
88
87
CO
d
d
4
5
f
H
H
CO
2
2
Me
Me
CO
CO
2
2
Me
Me
79
61
61
76
g
CO
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1
1
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2
2
2
2
2
2
2
2
2
3
3
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3
3
3
3
4
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4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
d
d
6
7
h
i
H
CO Me
CO Me
71
82
85
74
2
2
Me
CO
2
Me
2
CO Me
d
0
1
2
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9
0
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9
0
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8
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0
1
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5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
8
9
j
k
l
Me
CO Me
2
CO Me
2
78
65
d
CH
2
Ph
CO
2
2
Me
Me
CO
CO
2
2
Me 71 (59:41) 70 (65:35)
d
10
H
CO
Me
74
58
d
11
12
13
n
o
p
H
H
H
PO(OMe)
2
CO
CO
CO
2
2
2
Me 87 (61:39) 67 (56:44)
MeO
MeO
e
CN
Me
Me
77
93
65 (65:35)
71 (94:6)
e
CN
d
1
4
5
q
H
H
68
88
f
1
r
37 (72:28) 49 (54:46)
MeO
a
b
c
Isolated yields. Diastereomeric ratios [dr] were determined by NMR data for reaction mixtures. 4 (1.0 equiv.),
d
Me
3
SOI (1.2 equiv.), NaH (1.2 equiv.) in DMF or DMSO (0.15 M). Dimethyl malonate (1 equiv.), ArCHO (1
e
equiv.), AcOH (0.2 equiv.) and piperidine (0.02 equiv.) in toluene or benzene (0.33 M). Methyl cyanoacetate (1
f
equiv.), ArCHO (1 equiv.), and piperidine (0.10 equiv.) in methanol (1.1 M). Nꢀmethyloxindole (1.0 equiv.),
ArCHO (1.5 equiv.), NaOH (2 equiv.) in EtOH−H
O (1:1, 0.25 M).
2
Then we investigated the scope of acidꢀinduced VCR using vinylcyclopropanes with
diverse acceptor groups and a variety of substituents (alkyl, aryl, hetaryl) at the vinylic carbon
atoms (Table 3). The reactions were performed under the optimal conditions, earlier found for
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the model reactions, taking into account relative electron donating ability of various
(hetero)aromatic groups of the substrate. Thereby, 4ꢀchlorostyrylꢀ and 3ꢀchlorostyrylꢀsubstituted
cyclopropanes 1c,d wherein electronꢀdonating ability of aromatic group is similar to that of
unsubstituted styryl group in 1a were found to behave analogously to cyclopropane 1a. Namely,
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3
they produced cyclopentenes 2c,d in high yields under the treatment with GaCl and in moderate
yields under the treatment with SnCl . Oppositely, reactivity of cyclopropanes 1e,f containing
4
electronꢀenriched styryl substituents is similar to that of substrate 1b; and cyclopentenes 2e,f
were obtained in excellent yield when rearrangement was induced by SnCl
4 3
, Sc(OTf) or
Ni(ClO ) ⋅6H O. Futhermore, we found that pꢀ(dimethylamino)styrylꢀsubstituted cyclopropane
4
2
2
1f rearranged into cyclopentene 2f during the purification on silica. In other words, silica gel
acidity is sufficient to induce its isomerization. Evidently, highly electronꢀenriched aromatic
groups increase noticeably the polarization of the breaking C–C bond in threeꢀmembered ring
that facilitates the formation of zwitterꢀionic intermediate Z.
a,b
Table 3. Scope of Alkenylcyclopropanes 1
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CO R3
2
3
CO R
2
LA, MS 4A
CO
2
R3
CO R3
2
CH Cl
2
2
R2
2a-m
R1
R1
R2
1a-m
MeO C
MeO C
MeO C
Cl
CO Me
MeO C
2
CO Me
2
CO Me
2
2
2
2
2
CO
2
Me
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Cl
Ph
OMe
c
2c, GaCl , rt, 1 h, 93%c
2d, GaCl , rt, 1 h, 86%c
3
2
a, GaCl , rt, 1 h, 81%
2b, Sc(OTf) , rt, 3 h, 91%
3
3
3
SnCl
4
, ꢀ, 2 h, 63%
Ni(ClO
4
)
2
, rt, 4 h, 95%d
SnCl
4
, ꢀ, 2 h, 65%
SnCl , ꢀ, 2 h, 41%
4
SnCl , ꢀ, 1.5 h, 87%
4
MeO C
MeO C
MeO
2
C
MeO C
2
2
2
CO Me
CO Me
CO Me
CO Me
2
2
2
2
NMe2
S
O
MeO
2f, SnCl , -10°C, 2 h, 79%
2g, SnCl
2 h, 32%
Ni(ClO
4
, -40→-10°C,
, 60°C, 3 h, 71%e Ni(ClO
)
4 2
2h, SnCl
0.5 h, 21%
, ꢀ, 1.1 h, 51%
4
, 0°C→ꢀ,
2
e, SnCl , ꢀ, 1.5 h, 90%
Sc(OTf)3, rt, 3 h, 98%
Ni(ClO ) , rt, 4 h, 95%
4
4
SiO2, 98%
Sc(OTf)
3
, rt, 3 h, 94%
4
)
2
4
2
MeO C
MeO C
MeO
C
EtO C
2
2
2
2
CO Me
CO Me
CO Me
CO Et
2
2
2
2
R
S
Me
2
O N
Ph
4
4
2l, SnCl
GaCl , ꢀ, 1 h, 0%
4
, ꢀ, 2 h, 0%f
3
2m, GaCl , ꢀ, 1 h, 0%
SnCl , -10°C, 2 h, 0%
4
c,g
f,h
2
i, R=H, TiCl , ꢀ, 1.5 h, 71% 2k, SnCl , ꢀ, 1.5 h, 70%
c,g
SnCl
4
, ꢀ, 3 h, 67%
j, R=F, SnCl , ꢀ, 2 h, 80%
3
2
4
a
b
Isolated yields. 0.07 M Solution of cyclopropane 1 was treated with Lewis acid (1.0 equiv. of GaCl
3
, 1.1–1.5
c
equiv. of SnCl
4
, 0.1 equiv. of Sc(OTf)
3
, 0.2 or 1.0 equiv. of Ni(ClO
4
)
2
2
⋅6H O) under the specified conditions.
d
e
Reaction was performed in DCE. In all experiments Ni(ClO ) was used as hexahydrate. Reaction was performed
4
2
f
g
in α,α,αꢀtrifluorotoluene. Chlorides 5a,b were obtained as single products. Hexꢀ2,4ꢀdienoates 6a,b were obtained.
h
Reaction was performed in nitromethane.
4
Nevertheless, SnCl ꢀinduced rearrangement of 2ꢀ(2ꢀthienylethenyl)ꢀ and 2ꢀ(2ꢀ
furylethenyl)cyclopropaneꢀ1,1ꢀdiesters 1g,h into the corresponding cyclopentenes 2g,h
proceeded with low yields despite the electronꢀrich nature of these heteroaromatic substituents.
Presumably, this can be explained by the propensity of thiopheneꢀsubstituted DꢀA cyclopropanes
4
d,23
to the Lewis acidꢀinduced cationic oligomerization
and wellꢀknown susceptibility of the
2
4,25
furan ring to the acidic conditions.
Fortunately, the use of Ni(ClO 6H O as catalyst
4
)
2
2
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allowed to overcome these complications and obtain the target cyclopentenes 2g,h in reasonable
yields.
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Substrates 1i-k bearing an alkyl group at the αꢀposition of C=C bond were found to
undergo successfully the studied isomerization under treatment with SnCl
4
affording
ꢀinduced
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
polysubstituted cyclopentenes 2i-k in good yields. It is noteworthy that SnCl
4
isomerization of cyclopropane 1g proceeded under cooling while the same Lewis acid induced
rearrangement of 2ꢀ(2ꢀthienylꢀ1ꢀphenylpropenꢀ2ꢀyl)cyclopropaneꢀ1,1ꢀdicarboxylate 1k under
reflux only. At the same time, cyclopentene 2k was formed in the better yield. Presumably, the
presence of alkyl group decelerates the goal rearrangement but even more efficiently influences
undesired side reactions such as oligomerization suppressing them.
As opposed to the aboveꢀmentioned examples, the treatment of cyclopropane 1l,
containing 2ꢀnitrostyryl substituent, and cyclopropane 1m, bearing no substituents at the vinyl
moiety, with SnCl
a,b were obtained in moderate yields via threeꢀmembered ring opening with chloride ion
(Scheme 3). The attempts to induce VCR of 1l,m with GaCl were also unsuccessful. In this case
4
did not produce the target cyclopentenes at all. Instead, acyclic compounds
5
3
chlorineꢀfree products 6a,b, containing 1,3ꢀdiene moiety conjugated to the ester groups, were
obtained as single lowꢀmolecularꢀweight products.
Scheme 3. SnCl
4
- and GaCl
3
-Induced Transformations of 1l,m
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
These results clearly indicate that zwitterꢀionic intermediate Z should be stable enough to
adopt the pentagonꢀlike conformation required for the formation of fiveꢀmembered ring. When
cationic center is insufficiently stabilized, other processes compete efficiently with VCR. In the
case of SnCl
obtained, with Lewis acid applied being a source of the nucleophile. With GaCl
prone to provide the chloride ion for reactions with these or other subtrates, the isomerization of
4
as a catalyst products of threeꢀmembered ring opening with the chloride ion were
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
, that is not
2
6
DꢀA cyclopropanes 1 into the corresponding dienes predominates.
The different chemoselectivity in the reactions of cyclopropanes 1l and 1m is consistent
with the results of investigations of the reactivity of diverse 2ꢀalkenylcyclopropaneꢀ1,1ꢀdiesters
against various nucleophiles. The principal factor influencing the direction of the nucleophilic
attack is the presence of substituent(s) at the alkenyl moiety: when alkenyl group has
27
substituent(s) at the βꢀcarbon atom, products of S
N
2ꢀlike reaction are usually formed, while
cyclopropanes with unsubstituted vinyl group, such as 1m, react via both S 2ꢀlike and S 2′ꢀlike
N
N
2
8
mechanisms depending on the reaction conditions and the nature of nucleophile.
To shed more light on the mechanism of the dienes 6 formation, we synthesized
cyclopropane 1l-d deuterated at the C(3) position of threeꢀmembered ring and investigated its
transformations induced by the treatment with GaCl . We found that after 30 minutes the
reaction mixture contained dienes 6aꢀd , 6a-d , and 7ꢀd in a ratio of ca. 1:0.37:0.32 together
2
3
2
1
2
with oligomerization products (Scheme 4), with isomeric diene 7 being absent in the reaction
mixture after reflux for 1 h. We believe that the coordination of GaCl to ester group(s) induced
3
heterolysis of C(1)–C(2) bond in threeꢀmembered ring producing 1,3ꢀzwitterꢀionic intermediate
of Z type. Deuteride shift in this intermediate afforded diene A with unconjugated C–C double
bonds. Then it underwent isomerization to more stable products 6 and 7 through 1,5ꢀshift of
proton or deuterium from CHD moiety to the carbonyl oxygen atom affording trienols B and C
29
respectively. In accordance with the general principle that heavier isotopes have lower
mobility, proton migration proceeded faster than deuterium migration. The complexation of
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GaCl to B or C is accompanied by deprotonation producing enolates D and E containing,
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
respectively, two or one deuterium atom. These enolates are protonated at benzyl or malonyl
carbon atoms furnishing dienes 6a and 7. Dienes 6a are more stable possibly due to
2
stereoelectronic effects of orthoꢀnitro group. As a result, 7-d was still present in the reaction
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mixture as minor isomer after 0.5 h but was not observed after 1 h. According to the proposed
mechanism, compound 7ꢀd should also be present in the reaction mixture obtained after reflux
1
for 0.5 h. However, the precision of integral measurements for different signals of minor product
7
1
did not allow us to determine unambiguously the relative content of 7ꢀd in the studied
mixture.
3 2
Scheme 4. GaCl -Induced Isomerization of 1l-d
We found that the Lewis acidꢀinduced isomerization of cyclopropanes 1i-k containing
trisubstituted double bond can produce not only the corresponding cyclopentenes 2 but also
isomeric products 8 (Table 4). The reaction chemoselectivity can be switched by a simple
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
modification of the reaction conditions. Specifically, the treatment of the solution of
2 2 3
cyclopropanes 1i-k in CH Cl with GaCl under reflux led to the formation of 2,3ꢀsubstituted
cyclopentꢀ2ꢀeneꢀ1,1ꢀdicarboxylates 8a-c instead of cyclopentꢀ3ꢀeneꢀ1,1ꢀdicarboxylates obtained
1
in reactions initiated by SnCl
4
. H NMR monitoring of GaCl
3
ꢀinitiated process provided clear
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
evidence that cyclopentenes 2 are intermediates in the formation of cyclopentenes 8. Evidently,
the last step in the compounds 8a-c formation is the isomerization of cyclopentene 2 with
trisubstituted double bond into more stable cyclopentene 8 containing tetrasubstituted double
bond. This conclusion was unambiguously supported by control experiments which showed that
cyclopentenes 2i,k isomerize into cyclopentenes 8a,c under mild conditions in the presence of
3
GaCl .
Table 4. GaCl
3
-Assisted Isomerization of Cyclopropanes 1i-k and Cyclopentenes 2i-k to
a,b
Cyclopentenes 8a-c
1
2
a
Entry 1,2 R
R
mol% of GaCl3 T [°C] t [h] 8 Yield [%]
1
2
3
4
5
1i
Ph
Me
Me
Me
Bn
Bn
100
200
200
100
100
83
20
20
20
20
0.5
7
a
a
b
c
72
85
75
67
70
2i
Ph
c
1j
1k
2k
4ꢀFC
2ꢀTh
2ꢀTh
6
H
4
6.5
c
14
14
c
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1
2
3
a
b
c
Isolated yields. Reaction was performed in DCM or DCE (0.07 M). Reaction mixture was heated under reflux
for 0.5 h after stirring at room temperature.
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Donorꢀacceptor cyclopropanes bearing two ester groups as acceptors and diverse donors
(
aryl, hetaryl, alkenyl, silylmethyl, amino groups etc.) are intensively studied as both model
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
substrates and powerful building blocks in organic synthesis. Oppositely, donorꢀacceptor
cyclopropanes with other combinations of acceptor groups are underinvestigated. Herein, we
decided to explore Lewis acidꢀinduced VCR for substrates bearing diverse acceptor groups. We
found that this isomerization has a general character and proceed with the same efficiency for
cyclopropanes bearing ester, keto, cyano and phosphoryl groups (Table 5). Moreover, 1'ꢀmethylꢀ
2ꢀ(4ꢀmethoxystyryl)spiro[cyclopropaneꢀ1,3'ꢀoxindole] 1q underwent isomerization to the
corresponding spiro[cyclopentꢀ3ꢀeneꢀ1,3'ꢀoxindole]
2q
in
reasonable
yield and
30
diastereoselectivity. Similarly, DꢀA cyclopropane 1r, obtained from indaneꢀ1,3ꢀdione,
rearranged into the corresponding spiro[cyclopenteneꢀ3,2'ꢀindaneꢀ1,3ꢀdione] 2r. This result is in
contrast to the earlier reported isomerization of 1,1ꢀdiacylꢀ2ꢀvinylcyclopropanes and related
substrates to dihydrofurans under catalysis with Cu(I) chloride and various transition metal
31
complexes.
a
Table 5. Variation of Electron-Withdrawing Groups
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
EWG
EWG'
LA, MS 4Å
CH2Cl2
EWG
EWG'
Ar
Ar
1
n-r
2n-r
PO(OMe)2
CN
CO Me
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CO Me
2
MeO
R
2
6
n: SnCl4, , 1.5 h
2o: R=H, AlCl3, ,
3%, dr 85:15b
c
1
2
1
.5 h, 71%, dr 72:28
p: R=OMe, GaCl ,
h, 72%, dr 83:17
,
3
c
PMP
Ph
O
O
N
O
2q: GaCl3, , 2 h,
52%, dr 70:30c
2r: SnCl4, , 3 h, 76%
a
b
c
Isolated yields. Diastereomeric ratio was determined by NMR analysis of the reaction mixture. Diastereomeric
ratio was deduced from the weight ratio of isolated isomers.
It is noteworthy that isomerization of cyclopropanes 1n-q bearing two different electronꢀ
withdrawing groups into the corresponding cyclopentenes proceeded with reasonable
diastereoselectivity which did not depend on the isomeric composition of cyclopropanes 1. Thus,
substrates 1o,p, used as single isomers with cisꢀarrangement of aromatic substituent and cyano
group, afforded cyclopentenes 2o,p as a mixture of two diastereomers in a ratio of 72:28 and
8
3:17 respectively. To better understanding of the studied process, we studied isomerization of
both diastereomers of 1n and found that they produced cyclopentene 2n with identical cis:trans
ratio. The same was also true for 1qꢀtoꢀ2q rearrangement. This unambiguously supports the
hypothesis of the intermediate formation of zwitterꢀion of Z type during the transformation of 1
into 2 and is consistent with the thermodynamic control of the cyclization step affording the
equilibrium mixture of diasteromers.
Based on the obtained results, we proposed the following mechanism for these
transformations (Scheme 5). First, the coordination of Lewis acid to acceptor substituent(s)
induces cyclopropane ring opening to give a zwitterꢀionic species A containing stabilized
electrophilic and nucleophilic centers. After rotation to the conformation A' this zwitterꢀion
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undergoes 1,5ꢀcyclization to cyclopentene 2 through nucleophilic attack of the malonate anion
onto the remote atom of the allylic cation moiety (Scheme 5, path a). Oppositely, when allyl
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
cation is not stabilized (1i,m), it abstracts chloride ion from SnCl affording 5a or 5b (Scheme 5,
paths b and c) or undergoes isomerization to dienes 6 (7) (see Scheme 4).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Scheme 5. Proposed Mechanism
Easy modifiability of (het)aryl group and electronꢀwithdrawing substituents as well as the
C−C double bond in fiveꢀmembered ring makes the formed cyclopentenes relevant reagents for
producing various potentially useful compounds including pharmacological agents. Thus, upon
treatment with KOH in aqueous methanol at room temperature followed by acidifying
cyclopentene 2b underwent partial stereoselective saponification yielding hemimalonate 9a in
excellent yield. In comparison, hydrolysis of 2b under reflux produced smoothly the
corresponding diacid 9b. Moreover, we showed that cyclopentenes 2, the products of VCR
studied, can be transformed to 3ꢀarylpiperidines which are promising substrates for medicinal
32
chemistry and pharmacology due to a broad range of their bioactivities. Namely, piperidine 10
was synthesized by twoꢀstep procedure including the ozonolysis of cyclopentene 2b followed by
3
the reductive amination of the formed dialdehyde with 2ꢀchlorobenzylamine and NaBH CN.
Finally, we demonstrated that 2p can be easily and selectively reduced to the corresponding
cyclopentane 11 (Scheme 6).
Scheme 6. Post-modifications of Cyclopentenes 2
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Conclusion
In conclusion, we demonstrated that 2ꢀstyrylcyclopropaneꢀ1,1ꢀdiesters and their
heterocyclic analogs in the presence of Lewis acid undergo isomerization to the corresponding 2ꢀ
(het)arylcyclopentꢀ3ꢀeneꢀ1,1ꢀdiesters under mild reaction conditions in moderate to high yields.
Unlike most of reported methods for vinylcyclopropaneꢀtoꢀcyclopentene rearrangement under
mild reaction conditions, this protocol does not involve the use of noble metalꢀbased catalysts.
Postꢀmodifications of the obtained cyclopentenes were conducted to demonstrate possible
extensions of the practical utility of the title reaction. We deem that the Lewis acidꢀinitiated
VCR would not only serve as a tool for the formation of simple cyclopenteneꢀbased compounds
but also provide a potential route to useful complex structures containing cyclopentene motif.
Experimental section
General Information
NMR spectra were acquired on Bruker Avance 600, Bruker Avance 500 and Bruker Avance 400
spectrometers at room temperature, if not specified otherwise; the chemical shifts δ were
3 H C
measured in ppm with respect to solvent (CDCl : δ = 7.27 ppm; δ = 77.0 ppm). Splitting
patterns are designated as s, singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet; dd, double
doublet. Coupling constants (J) are in Hertz. The structures of synthesized compounds were
1
13
1
1
elucidated with the aid of 1D NMR ( H, C) and 2D NMR (COSY Hꢀ H, HSQC and HMBC
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1
2
3
1
13
1
1
Hꢀ C, NOESY Hꢀ H) spectroscopy. Infrared spectra were recorded on Thermo Nicolet IR200
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
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3
4
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5
5
5
5
5
5
5
5
6
FTꢀIR and Agilent FTIR Cary 630 spectrometers with ATR (Attenuated Total Reflectance)
module. ESI mass spectra were recorded using Shimadzu LCMSꢀ8040 instrument, equipped with
dual ion source (DUIS) in electrospray positive mode (interface voltage – 4,5 kV, nebulizer gas
flow – 2 L/min, drying gas flow – 15 L/min, desolvation line temperature – 250°C, heat block
temperature – 400 °C. GCꢀMS were recorded on the Thermo Focus DSQ II mass spectrometer.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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7
8
9
0
High resolution and accurate mass measurements were carried out using a BrukermicrOTOFꢀ
TM
Q
ESIꢀTOF (Electro Spray Ionization/Time of Flight) and Thermo Scientific* LTQ Orbitrap
mass spectrometers. Elemental analyses were performed with Fisons EAꢀ1108 CHNS elemental
analyser instrument. Melting points (mp) are uncorrected and were measured on Electrothermal
9100 capillary melting point apparatus. Analytical thin layer chromatography (TLC) was carried
out with silica gel plates (silica gel 60, F254, supported on aluminium); the revelation was done
by UV lamp (365 nm). All reactions were carried out using freshly distilled and dry solvents.
Column chromatography was performed on silica gel 60 (230–400 mesh, Merck). NaH (60%
dispersion in mineral oil), Lewis acids used, trimethylsulfoxonium iodide, 3ꢀarylpropꢀ2ꢀenals 3
33
are available commercially except for compounds 3j, obtained according to reported procedure,
and 3k, synthesis of which is given below. Perdeuterated Corey ylide and cyclopropanes 1a,b,m
1
4a,34,35
were synthesized by published procedures.
Other 2ꢀsubstituted cyclopropaneꢀ1,1ꢀdiesters
1
were prepared by Knoevenagel/CoreyꢀChaykovsky reactions sequence from the corresponding
3
5,36
aldehydes analogously to described procedures.
All experiments were carried out under an
argon atmosphere using freshly distilled and dry solvents.
2Z)-2-Benzyl-3-(thiophen-2-yl)prop-2-enal (3k). To a cooled (0 °C) solution of freshly
(
distilled thiopheneꢀ2ꢀcarbaldehyde (2.80 g, 25 mmol) and 3ꢀphenylpropanal (3.35 g, 25 mmol) in
25 mL of methanol 10% NaOH methanolic solution (4 mL) was added dropwise under vigorous
stirrinng. The mixture was brought to room temperature and stirred at this temperature for 4 h.
The solution was then rendered acidic to litmus by the addition of 10% aqueous HCl and
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extracted with diethyl ether. The organic layer was separated, dried and evaporated under
reduced pressure to give brown oil. The final residue was purified by column chromatography
(
SiO
2
f
, eluent – petroleum ether : diethyl ether) to yield 3k as yellow oil (3.37 g, 59% yield). R =
1
0
7
.30 (petroleum ether : ethyl acetate, 4:1); H NMR (500 MHz, CDCl
3
2
): δ 4.10 (s, 2H, CH Ph),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
3
.15 (dd, J = 5.0 Hz, J = 3.8 Hz, 1H, Th), 7.19–7.35 (m, 5H, CH, Ph), 7.42 (d, J = 3.8 Hz, 1H,
3
13
Th), 7.57 (d, J = 5.0 Hz, 1H, Th), 7.63 (br.s, 1H, CH=), 9.67 (s, 1H, CHO); C NMR (126
MHz, CDCl ): δ 30.6 (CH Ph), 126.3 (CH), 127.9 (CH), 128.3 (2×CH), 128.5 (2×CH), 131.5
CH), 133.7 (CH), 137.48 (C), 137.52 (C), 137.8 (C), 143.1 (CH=), 194.2 (CHO); IR (film)
3
2
(
ꢀ1
+
1
671, 1614 cm ; HRMS (ESI/QꢀTOF) m/z: [M + H] Calcd for C14H13OS 229.0682; Found
229.0684.
General procedure A (Knoevenagel condensation). To a solution of aldehyde (5 mmol) and
dimethyl malonate (0.66 g, 5 mmol) in toluene (15 mL) glacial acetic acid (0.06 mL, 1 mmol)
and piperidine (0.01 mL, 0.1 mmol) were added. The mixture was refluxed with the DeanꢀStark
trap until water separation was finished (2–6 h). Upon cooling, water (20 mL) was added to the
mixture and the organic layer was separated. The aqueous phase was extracted with ether (3×10
mL). The combined organic fractions were washed with water (3×10 mL), dried with Na SO ,
2
4
2
concentrated in vacuo. The purification by column chromatography (SiO ) afforded the target
alkenes.
Dimethyl 2-[(2E)-3-(4-chlorophenyl)prop-2-en-1-ylidene]malonate (4c). General Procedure
1
A; white solid (1.35 g, 96% yield); mp 87–88 °C; H NMR (500 MHz, CDCl
3
): δ 3.83 (s, 3H,
3
3
3
CH
3
O), 3.90 (s, 3H, CH
3
O), 7.00 (d, J = 15.5 Hz, 1H, CH=), 7.24 (dd, J = 15.5 Hz, J = 12.0
3
3
3
Hz, 1H, CH=), 7.35 (d, J = 8.3 Hz, 2H, CH, Ar), 7.43 (d, J = 8.3 Hz, 2H, CH, Ar), 7.54 (d, J =
13
12.0 Hz, 1H, CH=); C NMR (126 MHz, CDCl
3 3 3
): δ 52.25 (CH O), 52.31 (CH O), 123.7 (CH),
1
24.5 (C), 128.9 (2×CH), 129.1 (2×CH), 134.0 (C), 135.7 (C), 143.4 (CH=), 145.7 (CH=), 165.0
ꢀ1
+
(
CO Me), 165.5 (CO Me); IR (film) 1720, 1618 cm ; HRMS (ESI/QꢀTOF) m/z: [M + H] Calcd
2 2
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for C H ClO 281.0575; Found 281.0575; Anal. Calcd for C H ClO : C, 59.90; H, 4.67.
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
14 13
4
14 13
4
Found: C, 60.03; H, 4.37.
Dimethyl 2-[(2E)-3-(3-chlorophenyl)prop-2-en-1-ylidene]malonate (4d). General Procedure
A; orange solid (1.24 g, 88% yield); R
f
= 0.52 (petroleum ether : ethyl acetate; 4:1); mp 68–
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
6
9 °C; H NMR (500 MHz, CDCl
3
): δ 3.84 (s, 3H, CH
3
O), 3.92 (s, 3H, CH
3
O), 6.98 (d, J = 15.4
3
Hz, 1H, CH=), 7.24 (d, J = 11.6 Hz, 1H, CH=), 7.30–7.40 (m, 3H, CH, Ar), 7.48–7.50 (m, 1H,
3
3
13
CH, Ar), 7.54 (dd, J = 15.4 Hz, J = 11.6 Hz, 1H, CH=); C NMR (126 MHz, CDCl
3
): δ 52.41
O), 124.5 (CH), 125.1 (C), 126.0 (CH), 127.5 (CH), 129.7 (CH), 130.1
CH), 134.9 (C), 137.4 (C), 143.1 (CH=), 145.4 (CH=), 165.0 (CO Me), 165.5 (CO Me); IR
: C, 59.90; H,
(
3 3
CH O), 52.45 (CH
(
2
2
ꢀ1
+
(film) 1717, 1614 cm ; LCꢀMS m/z 281 [M + H] . Anal. Calcd for C14
.67. Found: C, 59.95; H, 4.68.
Dimethyl 2-[(2E)-3-(2-methoxyphenyl)prop-2-en-1-ylidene]malonate (4e). General Procedure
H13ClO
4
4
3
7
1
A; orange solid (1.20 g, 87% yield); mp 91–92 °C (lit. 92 °C ); H NMR (500 MHz, CDCl ): δ
3
3
3.82 (s, 3H, CH
3
O), 3.87 (s, 3H, CH
3
O), 3.90 (s, 3H, CH
3
O), 6.89 (d, J = 8.3 Hz, 1H, CH, Ar),
3
3
3
3
6
7
.95 (dd, J = 7.7 Hz, J = 7.3 Hz, 1H, CH, Ar), 7.32 (dd, J = 15.5 Hz, J = 11.2 Hz, 1H, CH=),
3
3
4
.28–7.34 (m, 1H, CH, Ar), 7.44 (br.d, J = 15.5 Hz, 1H, CH=), 7.55 (dd, J = 7.7 Hz, J = 1.5
3
13
Hz, 1H, CH, Ar), 7.61 (d, J = 11.2 Hz, 1H, CH=); C NMR (126 MHz, CDCl
52.3 (CH O), 55.5 (CH O), 111.2 (CH), 120.8 (CH), 123.2 (C, Ar), 123.7 (CH), 124.6 (C, Ar),
128.0 (CH), 131.2 (CH), 140.4 (CH), 147.3 (CH), 157.9 (C, Ar), 165.3 (CO Me), 165.9
CO Me); IR (film) 1737, 1699, 1260 cm ; LCꢀMS m/z 277 [M + H] . Anal. Calcd for
3 3
): δ 52.2 (CH O),
3
3
2
ꢀ1
+
(
2
15 16 5
C H O : C, 65.21; H, 5.84. Found: C, 65.44; H, 5.83.
Dimethyl 2-{(2E)-3-[4-(dimethylamino)phenyl]prop-2-en-1-ylidene}malonate (4f). General
1
Procedure A; redꢀorange solid (1.14 g, 79% yield); mp 127–128 °C; H NMR (600 MHz,
CDCl
3
3 3 3
): δ 3.02 (s, 6H, 2×CH N), 3.80 (s, 3H, CH O), 3.88 (s, 3H, CH O), 6.65–6.66 (m, 2H,
3
3
3
CH, Ar), 7.00 (d, J = 15.3 Hz, 1H, CH=), 7.15 (dd, J = 15.3 Hz, J = 11.7 Hz, 1H, CH=), 7.40–
3
13
7
3
.41 (m, 2H, CH, Ar), 7.60 (d, J = 11.7 Hz, 1H, CH=); C NMR (151 MHz, CDCl ): δ 40.1
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2
2
2
2
2
2
2
2
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3
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3
3
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(
2×CH
3
N), 52.0 (CH
3
O), 52.1 (CH
3
O), 111.9 (2×CH, Ar), 118.8 (CH=), 120.0 (C), 123.6 (C),
Me), 166.2 (CO Me);
290.1387; Found 290.1387. Anal.
: C, 66.42; H, 6.62; N, 4.84. Found: C, 66.51; H, 6.67; N, 4.65.
Dimethyl 2-[(2E)-3-(thiophen-2-yl)prop-2-en-1-ylidene]malonate (4g). General Procedure A;
yellow solid (0.77 g, 61% yield); R = 0.64 (petroleum ether : ethyl acetate; 4:1); mp 64–65 °C
lit. 68 °C ; 64–65 °C ); H NMR (500 MHz, CDCl ): δ 3.82 (s, 3H, CH O), 3.90 (s, 3H,
1
29.8 (2×CH, Ar), 146.8 (CH=), 148.5 (CH=), 151.7 (C), 165.8 (CO
2
2
+
HRMS (ESI/QꢀTOF) m/z: [M + H] Calcd for C16
H20NO
4
calcd for C16
H
19NO
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
f
37
38
1
(
3
3
3
3
3
3
3
CH O), 7.05 (dd, J = 4.9 Hz, J = 3.7 Hz, 1H, Th), 7.07 (dd, J = 15.3 Hz, J = 11.6 Hz, 1H,
3
3
3
CH=), 7.18 (d, J = 15.3 Hz, 1H, CH=), 7.21 (d, J = 3.7 Hz, 1H, Th), 7.38 (d, J = 4.9 Hz, 1H,
3
13
Th), 7.52 (d, J = 11.6 Hz, 1H, CH=); C NMR (126 MHz, CDCl
CH O), 122.6 (CH), 123.2 (C), 128.1 (CH), 128.4 (CH), 130.0 (CH), 137.4 (CH), 141.0 (C),
46.0 (CH), 165.2 (CO
S 253.0529; Found 253.0530.
Dimethyl 2-[(2E)-3-(furan-2-yl)prop-2-en-1-ylidene]malonate (4h). General Procedure A;
3 3
): δ 52.2 (CH O), 52.3
(
3
+
1
2 2
Me), 165.7 (CO Me); HRMS (ESI/QꢀTOF) m/z: [M + H] Calcd for
12 13 4
C H O
37
38
1
yellow solid (839 mg, 71% yield); mp 89–90 °C (lit. 91 °C ; 88ꢀ90 °C ); H NMR (500 MHz,
3
3
CDCl
3
): δ 3.81 (s, 3H, CH
3
3
O), 3.89 (s, 3H, CH O), 6.45 (dd, J = 3.4 Hz, J = 1.8 Hz, 1H, Fu),
3
3
3
3
6.57 (d, J = 3.4 Hz, 1H, Fu), 6.80 (d, J = 15.2 Hz, 1H, CH=), 7.11 (dd, J = 15.2 Hz, J = 12.0
3
3
13
Hz, 1H, CH=), 7.47 (br.d, J = 1.8 Hz, 1H, Fu), 7.50 (d, J = 12.0 Hz, 1H, CH=); C NMR (126
MHz, CDCl ): δ 52.27 (CH O), 52.31 (CH O), 112.5 (CH), 113.9 (CH), 121.5 (C), 123.8 (C),
3
3
3
1
30.9 (CH), 144.6 (CH), 145.5 (CH), 151.9 (C), 165.1 (CO
2
Me), 165.7 (CO
2
Me); IR (film)
ꢀ
1
+
1729, 1609, 1470 cm ; LCꢀMS m/z 237 [M+H] . Anal. Calcd for C12H O : C, 61.01; H, 5.12.
12 5
Found: C, 61.18; H, 5.13.
Dimethyl 2ꢀ[(2E)ꢀ3ꢀphenylꢀ2ꢀmethylpropꢀ2ꢀenꢀ1ꢀylidene]malonate (4i). General Procedure A;
39
(1.07 g, 82% yield). Spectral data (NMR, IR) are consistent with the reported ones. Compound
4i was used in synthesis of cyclopropane 1o without additional purification.
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Dimethyl 2-[(2E)-3-(4-fluorophenyl)-2-methylprop-2-en-1-ylidene]malonate (4j). General
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Procedure A; yellow solid (1.09 g, 78% yield); R
f
= 0.46 (petroleum ether : diethyl ether; 2:1);
1
4
mp 82–83 °C; H NMR (500 MHz, CDCl ): δ 1.99 (d, J = 0.8 Hz, 3H, CH ), 3.82 (s, 3H,
3
3
3
3
CH
3
3
O), 3.86 (s, 3H, CH O), 6.92 (br.s, 1H, CH=), 7.07 (dd, JHF = 8.7 Hz, J = 8.5 Hz, 2H, CH,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
4
4
13
Ar), 7.32 (dd, J = 8.5 Hz, JHF = 5.4 Hz, 2H, CH, Ar), 7.45 (q, J = 0.8 Hz, 1H, CH=); C NMR
2
(126 MHz, CDCl
3
): δ 14.5 (CH
3
), 52.45 (CH
3
O), 52.52 (CH
3
O), 115.5 (d, JCF = 22 Hz, 2×CH,
3
4
Ar), 123.6 (C), 131.4 (d, J = 8 Hz, 2×CH, Ar), 132.2 ( J = 3 Hz, C, Ar), 132.6 (C), 140.9
CF
CF
1
(
CH=), 147.4 (CH=), 162.4 (d, JCF = 249 Hz, C, Ar), 165.0 (CO
2
Me), 167.4 (CO
2
Me); IR (KBr)
ꢀ1
+
1727, 1691, 1264 cm ; LCꢀMS m/z 279 [M+H] . Anal. Calcd for C15H15FO : C, 64.74; H, 5.43.
4
Found: C, 64.63; H, 5.75.
Dimethyl
2-[2-benzyl-3-(thiophen-2-yl)prop-2-en-1-ylidene]malonate
(4k).
General
Procedure A; yellow solid (1.22 g, 71% yields), isolated as mixture of isomers, A:B = 59:41; R
f
1
= 0.60 (petroleum ether : ethyl acetate 4:1); mp 35–38 °C; H NMR (500 MHz, CDCl
3
): 3.43 (s,
3
H, CH O, A), 3.68 (s, 2H, CH Ph, B), 3.77 (s, 3H, CH O, B), 3.79 (s, 3H, CH O, A), 3.85 (s,
3
2
3
3
3
H, CH
3
O, B), 4.08 (s, 2H, CH
2
Ph, A), 6.65 (br.s, 1H, CH=, B), 7.02–7.41 (m, 9H+8H, CH, A,
4
13
B), 7.54 (d, J = 0.7 Hz, 1H, CH= A), 8.04 (br.s, 1H, CH=, B); C NMR (126 MHz, CDCl
3
): δ
O, A),
26.4 (CH, A), 126.6 (CH, B), 127.57 (CH, A), 126.62 (CH, B), 128.0 (2×CH, A), 128.4 (CH,
2 2 3 3 3 3
34.8 (CH Ph, A), 40.6 (CH Ph, B), 52.1 (CH O, A), 52.5 (CH O+CH O, A, B), 52.7 (CH
1
B), 128.5 (2×CH, A), 128.6 (2×CH, B), 129.2 (CH+2×CH, A, B), 130.0 (CH, B), 130.6 (CH, B),
131.4 (CH, A), 131.6 (C, A), 131.9 (C, B), 132.8 (C, A), 134.7 (C, B), 135.3 (CH, A), 136.8 (C,
2
A), 138.3 (C, B), 138.6 (C, A), 139.2 (C, B), 142.3 (CH, B), 146.3 (CH, A), 164.9 (CO Me, B),
ꢀ1
1
65.0 (CO
2
Me, A), 166.6 (CO
2
Me, B), 167.0 (CO
2
Me, A); IR (film) 1732, 1601 cm ; HRMS
+
(
ESI/QꢀTOF) m/z: [M + H] Calcd for C H O S 343.0999; Found 343.1001. Anal. Calcd for
1
9
18
4
C
19 18 4
H O S: C, 66.65; H, 5.30. Found: C, 66.47; H, 5.31.
Dimethyl 2-[(2E)-3-(2-nitrophenyl)prop-2-en-1-ylidene]malonate (4l). General Procedure A;
40
1
redꢀorange solid (1.08 g, 74% yield); mp 114–115 °C (lit. 114 °C ); H NMR (500 MHz,
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
3
CDCl ): δ 3.84 (s, 3H, CH O), 3.89 (s, 3H, CH O), 7.24 (dd, J = 15.2 Hz, J = 11.6 Hz, 1H,
3
3
3
3
3
CH=), 7.55 (d, J = 15.2 Hz, 1H, CH=), 7.55–7.59 (m, 1H, CH, Ar), 7.57 (br.d, J = 11.6 Hz, 1H,
3
4
3
CH=), 7.62–7.65 (m, 1H, CH, Ar), 7.72 (dd, J = 7.8 Hz, J = 1.4 Hz, 1H, CH, Ar), 8.01 (dd, J =
4
13
8
3 3 3
.2 Hz, J = 1.2 Hz, 1H, CH, Ar); C NMR (126 MHz, CDCl ): δ 52.2 (CH O), 52.3 (CH O),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
24.7 (CH), 126.3 (C), 127.4 (CH), 128.6 (CH), 129.8 (CH), 130.9 (C), 133.1 (CH), 138.7 (CH),
+
144.4 (CH), 147.9 (C), 164.5 (CO Me), 165.0 (CO Me); HRMS (ESI/QꢀTOF) m/z: [M + H]
2
2
Calcd for C14
6 6
H14NO 292.0816; Found 292.0816. Anal. Calcd for C14H13NO : C, 57.73; H, 4.50;
N, 4.81. Found: C, 57.91; H, 4.43; N, 4.65.
Methyl 2-(dimethoxyphosphoryl)-5-(4-methoxyphenyl)penta-2,4-dienoate (4n). General
1
Procedure A. According to H NMR data product was formed as a mixture of (2E,4E)ꢀ
and (2Z,4E)ꢀisomers in a ratio of 61:39.
1
(
(2E,4E)-4n): yellow solid (832 mg, 51% yield), R
f
= 0.35 (ethyl acetate); mp 48–49 °C; H
3
NMR (500 MHz, CDCl
3
): δ = 3.75 (d, JPH = 11.3 Hz, 6H, (CH
3
O)
2
P), 3.79 (s, 3H, CH
3
O), 3.84
3
3
3
(s, 3H, CH
3
O), 6.88 (br.d, J = 8.8 Hz, 2H, CH, Ar), 7.03 (d, J = 15.0 Hz, CH=), 7.48 (br.d, J =
1
3
3 3
8.8 Hz, 2H, CH, Ar), 7.65–7.80 (m, 2H, 2CH=); C NMR (126 MHz, CDCl ): δ = 51.9 (CH O),
2
1
5
1
2.8 (d, JPC = 5.9 Hz, (CH
3
O)
2
P), 55.3 CH
3
O), 114.2 (2×CH, Ar), 115.4 (d, JPC = 189 Hz, C=),
3
2
22.0 (d, J = 19 Hz, CH=), 128.1 (C, Ar), 129.9 (2×CH, Ar), 147.3 (CH=), 157.1 (d, J
=
):
PC
PC
2
31
2 3
7.0 Hz, CH=), 161.4 (C, Ar), 165.1 (d, JPC = 14.2 Hz, CO Me); P NMR (202.5 MHz, CDCl
3
2
ꢀ1
δ = 19.6 (doublet of septets, JPH = 23 Hz, JPH = 13 Hz); IR (film) 1715, 1600, 1246 cm ;
+
HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C H O P 327.0992; Found 327.0993. Anal.
15
20
6
19 6
Calcd for C15H O P: C, 55.22; H, 5.87. Found: C, 55.25; H, 5.77.
1
((2Z,4E)-4n): yellow solid (587 mg, 36% yield); R = 0.45 (ethyl acetate); mp 74–75 °C; H
f
3
NMR (500 MHz, CDCl
3
): δ = 3.78 (d, JPH = 11.3 Hz, 6H, (CH
3
O)
2
P), 3.81 (s, 3H, CH
3
O), 3.82
3
3
(
s, 3H, CH O), 6.89 (br.d, J = 8.8 Hz, 2H, CH, Ar), 7.05 (d, J = 14.4 Hz, 1H, CH=), 7.51 (br.d,
3
3
13
J = 8.8 Hz, 2H, CH, Ar), 8.00–8.18 (m, 2H, 2CH=); C NMR (126 MHz, CDCl
3
): δ = 52.2
2
1
(CH O), 52.6 (d, J = 5.7 Hz, (CH O) P), 55.3 (CH O), 114.2 (2×CH, Ar), 115.4 (d, J = 188
3
PC
3
2
3
PC
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3
Hz, C=), 122.5 (d, JPC = 5 Hz, CH=), 128.3 (C, Ar), 130.0 (2×CH, Ar), 147.8 (CH=), 158.7 (d,
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
2
31
J
2
PC = 7 Hz, CH=), 161.4 (C, Ar), 166.2 (d, JPC = 15 Hz, CO Me); P NMR (202.5 MHz,
3
2
CDCl
3
): δ = 16.9 (doublet of septets, JPH = 46 Hz, JPH = 11 Hz); IR (film) 1714, 1600, 1255
ꢀ1
+
cm ; HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C15
H
20
O
6
P 327.0992; Found 327.0994. Anal.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Calcd for C15
19 6
H O P: C, 55.22; H, 5.87. Found: C, 55.39; H, 5.94.
Methyl (2E,4E)ꢀ2ꢀcyanoꢀ5ꢀphenylpentaꢀ2,4ꢀdienoate (4o). To a solution of cinnamaldehyde
(
1.32 g, 10 mmol) and methyl cyanoacetate (0.99 g, 10 mmol) in methanol (9 mL) piperidine
0.01 mL, 0.1 mmol) was added at vigorous stirring. The product precipitates immediately after
(
piperidine addition. The precipitate was filtered, washed with hexane and dried to constant
weight. Yellow solid (1.64 g, 77% yield). NMR spectral data are consistent with published
41,42
ones.
Compound 4o was used in synthesis of cyclopropane 1o without additional
purification.
Methyl (2E,4E)-2-cyano-5-(4-methoxyphenyl)penta-2,4-dienoate (4p) was synthesized
analogously to 4o from 4ꢀmethoxycinnamaldehyde (1.62 g, 10 mmol) and methyl cyanoacetate
f
(0.99 g, 10 mmol). Yellow solid (1.98 g, 93% yield). R = 0.40 (petroleum ether : ethyl acetate;
1
5
6
:1); mp 114–115 °C; H NMR (500 MHz, CDCl
3
)
δ
: 3.87 (s, 3H, CH
3
O), 3.88 (s, 3H, CH
3
O),
3
3
3
3
.94 (d, J = 8.4 Hz, 2H, 2×CH), 7.14 (dd, J = 11.4 Hz, J = 15.4 Hz, 1H, CH=), 7.23 (d, J =
3
3
13
15.4 Hz, 1H, CH=), 7.55 (d, J = 8.4 Hz, 2H, 2×CH), 7.98 (d, J = 11.4 Hz, 1H, CH=); C NMR
(
(
(
3 3 3
126 MHz, CDCl ) δ: 53.0 (CH O), 55.6 (CH O), 102.2 (C), 114.8 (2×CH, Ar), 115.0 (C), 120.9
CH=), 127.6 (C), 130.6 (2×CH, Ar), 149.2 (CH=), 156.2 (CH=), 162.4 (C), 163.2 (C). HRMS
+
ESI/QꢀTOF) m/z [M + H] Calcd for C14
H
14NO
3
244.0968; Found 244.0972. Anal. Calcd for
C
14
H13NO
3
: C, 69.12; H, 5.39. Found: C, 68.91; H, 5.25.
3
-[(2E)-3-(4-Methoxyphenyl)prop-2-en-1-ylidene]-1-methylindolin-2-one (4q). NaOH (0.54
g, 13.5 mmol, 2 equiv.) was added at 0 °C to a stirred solution of Nꢀmethyloxindole (1.0 g, 6.8
mmol) and 4ꢀmethoxycinnamaldehyde (1.65 g, 10.1 mmol, 1.5 equiv.) in aq. EtOH (1:1, 27 mL).
2
The reaction mixture was stirred at room temperature for 2 h, poured into H O (20 mL) and
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2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
extracted with ethyl acetate (3×15 mL). The combined organic fractions were washed with water
2 4
(3×10 mL), dried with Na SO and concentrated in vacuo. Product 4q was purified by column
chromatography to yield yellowish solid (733 mg, 37% yield; E/Z ratio 72:28). R
f
= 0.54
N,
1
(
petroleum ether : ethyl acetate; 4:1); H NMR (500 MHz, CDCl
3
): δ = 3.22 (s, 3H+3H, CH
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
A, B), 3.82 (s, 3H+3H, CH O, A, B), 6.75 (d, J = 7.8 Hz, 1H, Ar, B), 6.79 (d, J = 7.8 Hz, 1H,
3
3
3
Ar, A), 6.86 (br. d, J = 8.7 Hz, 2H, Ar, B), 6.90 (br. d, J = 8.7 Hz, 2H, Ar, A), 6.89–6.92 (m,
3
1
H, B), 6.95–7.09 (m, 2H+2H, A, B), 7.18–7.27 (m, 1H+1H, A, B), 7.39 (d, J = 7.5 Hz, 1H, Ar,
3
3
B), 7.49 (br. d, J = 8.7 Hz, 2H, Ar, A), 7.43–7.53 (m, 2H, A), 7.52 (br. d, J = 8.7 Hz, 2H, Ar,
3
3
3
13
B), 7.66 (br. d, J = 7.5 Hz, 1H, Ar, A), 8.45 (dd, J = 15.6 Hz, J = 11.5 Hz, CH=, B); C NMR
(126 MHz, CDCl ): δ 25.6 (CH N, B), 26.0 (CH N, A), 55.36 (CH O, B), 55.39 (CH O, A),
3
3
3
3
3
1
07.8 (CH, B), 108.0 (CH, A), 114.3 (2×CH, B), 114.5 (2×CH, A), 118.9 (CH, B), 121.4 (CH,
A), 121.7 (CH, B), 121.9 (CH, A), 122.3 (C, B), 122.57 (C, A), 122.62 (CH, B), 123.2 (CH, A),
124.2 (C, A), 124.3 (C, B), 127.9 (C, B), 128.3 (CH, B), 128.5 (CH, A), 129.0 (C, A), 129.2
(2×CH, A), 129.3 (2×CH, B), 136.2 (CH, A), 136.4 (CH, B), 142.3 (C, B), 142.7 (CH, B), 143.5
(C, A), 144.0 (CH, A), 160.8 (C, B), 161.0 (C, A), 167.5 (C, B), 168.7 (C, A); IR (film) 1701,
ꢀ1
+
1
2
590 cm ; HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C19H18NO 292.1332; Found 292.1335.
(E)ꢀ2ꢀ(3ꢀphenylpropꢀ2ꢀenꢀ1ꢀylidene)indaneꢀ1,3ꢀdione (4r). To a solution of cinnamaldehyde
1.32 g, 10 mmol) and indaneꢀ1,3ꢀdione (1.46 g, 10 mmol) in benzene (10 mL) piperidine (0.01
(
mL, 0.1 mmol) was added at vigorous stirring. The product precipitates after piperidine addition.
The precipitate was filtered, washed with hexane and dried to constant weight. Brown solid (1.77
43
g, 68% yield). Mass spectral data (NMR, IR) are consistent with published ones.
General procedure B (Corey–Chaykovsky cyclopropanation). To a stirred suspension of NaH
60% in oil) in dry DMF or DMSO trimethylsulfoxonium iodide was added in a single portion
(
under argon atmosphere at room temperature. Vigorous evolution of hydrogen lasted ca. 15 min,
after which the reaction mixture was stirred for additional 25 min. Then a solution of
electrophilic alkene in dry DMF or DMSO (3 mL) was added dropwise under conditions
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specified. The resulted mixture was stirred at indicated temperature for the time specified,
poured into ice cooled saturated aq. NH Cl (10 mL) and extracted with ethyl acetate (3×8 mL).
The combined organic fractions were washed with water (5×5 mL), dried with Na SO and
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
2
4
concentrated in vacuo. The final residue was purified by column chromatography (SiO
2
, eluent –
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
petroleum ether: ethyl acetate) to yield cyclopropanes 1.
Dimethyl 2-[(E)-2-(4-chlorophenyl)ethenyl]cyclopropane-1,1-dicarboxylate (1c). General
Procedure B: Suspension of NaH (45 mg, 1.13 mmol) and trimethylsulfoxonium iodide (240 mg,
1
.09 mmol) in DMF (5 mL), 40 min, room temperature. Alkene 4c (300 mg, 1.07 mmol) in dry
DMF (3 mL) was added. Reaction mixture was stirred at room temperature for 1.5 h. Product 1c
was obtained as yellowish solid (212 mg, 67% yield). R = 0.61 (petroleum ether : diethyl ether;
f
1
2
3
2
:1); mp 88–89 °C; H NMR (600 MHz, CDCl
3
): δ 1.67 (dd, J = 5.0 Hz, J = 9.0 Hz, 1H, CH
2
),
2
3
3
3
3
1
2
.81 (dd, J = 5.0 Hz, J = 7.6 Hz, 1H, CH ), 2.70 (ddd, J = 9.0 Hz, J = 7.6 Hz, J = 8.6 Hz, 1H,
3
3
CH), 3.70 (s, 3H, CH
3
O), 3.73 (s, 3H, CH
3
O), 5.77 (dd, J = 15.8 Hz, J = 8.6 Hz, 1H, CH=),
3
13
6.56 (d, J = 15.8 Hz, 1H, CH=), 7.18–7.24 (m, 4H, CH, Ar); C NMR (151 MHz, CDCl
3
): δ
2
1
2 3 3
1.2 (CH ), 31.4 (CH), 36.0 (C), 52.6 (CH O), 52.7 (CH O), 125.3 (CH=), 127.3 (2×CH, Ar),
28.7 (2×CH, Ar), 132.5 (CH=), 133.2 (C, Ar), 135.2 (C, Ar), 167.8 (CO Me), 169.7 (CO Me);
2
2
ꢀ1
+
IR (film) 1723 cm ; HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C15
H16ClO
4
295.0732; Found
2
95.0736. Anal. Calcd for C15H15ClO : C, 61.13; H, 5.13. Found: C, 61.03; H, 5.30.
4
Dimethyl 2-[(E)-2-(3-chlorophenyl)ethenyl]cyclopropane-1,1-dicarboxylate (1d). General
Procedure B: Suspension of NaH (86 mg, 2.15 mmol) and trimethylsulfoxonium iodide (472 mg,
2.15 mmol) in DMF (4.5 mL), 40 min, room temperature. Alkene 4d (520 mg, 1.85 mmol) in dry
DMF (4.5 mL) was added in a single portion at 0 °C. Reaction mixture was stirred for 45 min
and allowed to warm up slowly to room temperature. Product 1d was obtained as yellowish
1
liquid (375 mg, 69% yield). R = 0.64 (petroleum ether : diethyl ether; 2:1); H NMR (500 MHz,
f
2
3
2
3
CDCl
CH
3 2
): δ 1.72 (dd, J = 5.0 Hz, J = 8.9 Hz, 1H, CH ), 1.86 (dd, J = 5.0 Hz, J = 7.6 Hz, 1H,
3
3
3
2
), 2.75 (ddd, J = 8.9 Hz, J = 8.8 Hz, J = 7.6 Hz, 1H, CH), 3.76 (s, 3H, CH
3
O), 3.78 (s, 3H,
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8
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
3
3
CH O), 5.84 (dd, J = 15.9 Hz, J = 8.8 Hz, 1H, CH=), 6.59 (d, J = 15.9 Hz, 1H, CH=), 7.16–
3
1
3
7.25 (m, 3H, CH, Ar), 7.29 (br.s, Ar, 1H); C NMR (126 MHz, CDCl
CH), 36.0 (C), 52.6 (CH O), 52.7 (CH O), 124.2 (CH), 125.9 (CH), 126.2 (CH), 127.4 (CH),
29.7 (CH), 132.4 (CH), 134.4 (C, Ar), 138.4 (C, Ar), 167.7 (CO Me), 169.7 (CO Me); IR (film)
295.0732. Found 295.0733.
3 2
): δ 21.2 (CH ), 31.2
(
3
3
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ꢀ1
+
730 cm ; HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C15H16ClO
4
Anal. Calcd for C H ClO : C, 61.13; H, 5.13. Found: C, 61.11; H, 5.17.
1
5
15
4
Dimethyl 2-[(E)-2-(2-methoxyphenyl)ethenyl]cyclopropane-1,1-dicarboxylate (1e). General
Procedure B. Suspension of NaH (520 mg, 13 mmol) and trimethylsulfoxonium iodide (2.87 g,
1
3 mmol) in DMF (29 mL), 40 min, room temperature. Alkene 4e (3.00 g, 10.9 mmol) in dry
DMF (30 mL) was added in a single portion at 0 °C. The resulted mixture was stirred for 1 h and
allowed to warm up to room temperature. Product 1e was obtained as yellowish liquid (2.40 g,
1
7
6% yield). R
f
= 0.53 (petroleum ether : ethyl acetate; 4:1); H NMR (500 MHz, CDCl
3
): δ 1.70
2
3
2
3
(
dd, J = 5.0 Hz, J = 9.1 Hz, 1H, CH
2
), 1.86 (dd, J = 5.0 Hz, J = 7.6 Hz, 1H, CH
2
), 2.78 (ddd,
3
3
3
J = 9.1 Hz, J = 8.7 Hz, J = 7.6 Hz, 1H, CH), 3.74 (s, 3H, CH
3
O), 3.76 (s, 3H, CH
3
O), 3.83 (s,
3
3
3
3
3H, CH
3
O), 5.84 (dd, J = 16.0 Hz, J = 8.7 Hz, 1H, CH=), 6.87 (ddd, J = 8.1 Hz, J = 7.6 Hz,
4
3
4
3
J = 0.7 Hz, 1H, CH, Ar), 6.91 (dd, J = 7.6 Hz, J = 0.7 Hz, 1H, CH, Ar), 6.97 (d, J = 16.0 Hz,
3
3
4
3
1
H, CH=), 7.21 (ddd, J = 8.1 Hz, J = 7.6 Hz, J = 1.7 Hz, 1H, CH, Ar), 7.31 (dd, J = 7.6 Hz,
4
13
J = 1.7 Hz, 1H, CH, Ar); C NMR (126 MHz, CDCl
3
): δ 21.3 (CH
O), 110.9 (CH), 120.6 (CH), 125.2 (CH), 125.8 (C, Ar), 126.7
(CH), 128.7 (CH), 128.8 (CH), 156.5 (C, Ar), 168.0 (CO Me), 170.0 (CO Me); IR (film)
730 cm ; LCꢀMS m/z 291 [M + H] . Anal. Calcd for C H O : C, 66.20; H, 6.25. Found: C,
2
), 32.2 (CH), 36.1 (C), 52.5
(
3 3 3
CH O), 52.6 (CH O), 55.4 (CH
2
2
ꢀ
1
+
1
6
16
18
5
6.23; H, 6.29.
Dimethyl 2-{(E)-2-[4-(dimethylamino)phenyl]ethenyl}cyclopropane-1,1-dicarboxylate (1f).
General Procedure B. Suspension of NaH (88 mg, 2.20 mmol) and trimethylsulfoxonium iodide
(
480 mg, 2.18 mmol) in DMSO (12 mL), 40 min, room temperature. Solution of alkene 4f (600
mg, 2.07 mmol) in dry DMSO (8 mL) was added dropwise. Reaction mixture was stirred for 1 h.
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Product 1f was obtained as yellow liquid (385 mg, 61% yield). H NMR (600 MHz, CDCl ): δ
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
2
3
2
3
1.67 (dd, J = 4.9 Hz, J = 9.2 Hz, 1H, CH
2
), 1.85 (dd, J = 4.9 Hz, J = 7.6 Hz, 1H, CH
2
), 2.75
3
3
3
(
ddd, J = 9.2 Hz, J = 7.6 Hz, J = 8.6 Hz, 1H, CH), 2.94 (s, 6H, 2×NCH ), 3.72 (s, 3H, CH O),
3
3
3
3
3
3
6
3
.76 (s, 3H, CH O), 5.60 (dd, J = 15.7 Hz, J = 8.6, 1H, CH=), 6.55 (d, J = 15.7 Hz, 1H, CH=),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
3
13
.64–6.65 (br.d, J = 8.8 Hz, 2H, CH, Ar), 7.19–7.21 (br.d, J = 8.8 Hz, 2H, CH, Ar); C NMR
): δ 21.3 (CH ), 32.3 (CH), 36.0 (C), 40.4 (2×CH ), 52.6 (CH O), 52.7
CH O), 112.3 (2×CH, Ar), 119.7 (CH=), 125.2 (C), 127.2 (2×CH, Ar), 133.9 (CH=), 150.1 (C,
(151 MHz, CDCl
3
2
3
3
(
3
+
Ar), 168.1 (CO
304.1544. Found 304.1545. Anal. Calcd for C17
7.17; H, 7.21; N, 4.54.
2
Me), 170.1 (CO
2
Me); HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C17
H22NO
4
H
4
21NO : C, 67.31; H, 6.98; N, 4.62. Found: C,
6
Dimethyl 2-[(E)-2-(thiophen-2-yl)ethenyl]cyclopropane-1,1-dicarboxylate (1g). General
Procedure B. Suspension of NaH (161 mg, 4.03 mmol) and trimethylsulfoxonium iodide (890
mg, 4.05 mmol) in DMF (7.0 mL), 40 min, room temperature. Solution of alkene 4g (850 mg,
3.37 mmol) in dry DMF (1 mL) was added in a single portion at 0 °C. The resulted mixture was
stirred for 15 min at the same temperature. Product 1g was obtained as yellow oil (682 mg, 76%
1
yield). R
f
= 0.53 (petroleum ether : ethyl acetate; 4:1); H NMR (500 MHz, CDCl
3
): δ 1.63 (dd,
2
3
2
3
3
J = 5.0 Hz, J = 9.0 Hz, 1H, CH
2
), 1.78 (dd, J = 5.0 Hz, J = 7.6 Hz, 1H, CH
2
), 2.65 (ddd, J =
3
3
3
9.0 Hz, J = 8.6 Hz, J = 7.6 Hz, 1H, CH), 3.68 (s, 3H, CH
3
O), 3.70 (s, 3H, CH
3
O), 5.63 (dd, J
3
3
3
=
15.7 Hz, J = 8.6 Hz, 1H, CH=), 6.69 (d, J = 15.7 Hz, 1H, CH=), 6.86 (d, J = 3.5 Hz, 1H,
3
3
3
13
Th), 6.88 (dd, J = 5.0 Hz, J = 3.5 Hz, 1H, Th), 7.06 (d, J = 5.0 Hz, 1H, Th); C NMR (126
1
1
1
MHz, CDCl
3
): δ 21.0 ( JCH = 166 Hz, CH
2
), 31.2 ( JCH = 166 Hz, CH), 36.0 (C), 52.5 ( JCH =
1
1
148 Hz, CH O), 52.6 ( J = 148 Hz, CH O), 124.1 (2×CH), 125.4 ( J = 167 Hz, CH), 126.8
3
CH
3
CH
1
1
(
2
JCH = 156 Hz, CH), 127.4 ( JCH = 168 Hz, CH), 141.7 (C, Th), 167.7 (CO Me), 169.7
ꢀ1
+
(
CO Me); IR (Nujol) 1740, 1680 cm ; HRMS (ESI/QꢀTOF) m/z [M + H] Calcd for C H O S
2
13 15
4
2
14 4
67.0686; Found 267.0689. Anal. Calcd for C13H O S: C, 58.63; H, 5.30; S, 12.04. Found: C,
58.39; H, 5.05; S, 12.14.
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