gem-Dichlorocyclopropanation of Dicarbonyl Derivatives

Article abstract of DOI:10.1002/chem.201904149

A novel methodology for the 1,1-dichlorocyclopropanation of dicarbonyl conjugated olefins was described. The developed protocol is simple and uses readily accessible starting materials, allowing the isolation of the desired adducts in moderate to excellen

Full text of DOI:10.1002/chem.201904149

A Journal of
Accepted Article
Title: gem-Dichlorocyclopropanation of Dicarbonyl Derivatives
Authors: Gabriel M. F. Batista, Pedro P. De Castro, Arthur G.
Carpanez, Bruno A. C. Horta, and Giovanni Wilson Amarante
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To be cited as: Chem. Eur. J. 10.1002/chem.201904149
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gem-Dichlorocyclopropanation of Dicarbonyl Derivatives
Gabriel M. F. Batista,[a] Pedro P. De Castro,[a] Arthur G. Carpanez,[a] Bruno A. C. Horta,*[b] and Giovanni
W. Amarante*[a]
potassium trichloroacetate in the trichloromethylation of aldimines.
Furthermore, we investigated by ab initio molecular dynamics
simulations the decarboxylation of trichloroacetic acid, leading to
the anion -CCl3 in dimethylsulfoxide (DMSO).[16,17] Thus, we
envisioned that the reaction between this anion and dicarbonyl
conjugated olefins would afford gem-dichlorocyclopropanes in a
simple and inexpensive methodology (Scheme 1C).
Abstract: A novel methodology for the 1,1-dichlorocyclopropanation
of dicarbonyl conjugated olefins was hereby described. The
developed protocol is simple and uses readily accessible starting
materials, allowing the isolation of the desired adducts in moderate to
excellent yields (up to 99%). Furthermore, the reaction tolerated well
the scale up to a gram scale, highlighting the synthetic potential of this
transformation. Control experiments and DFT studies revealed that
the reaction proceeds through a Michael initiated ring closure process,
in which reaction temperature play a crucial role. Finally, these gem-
dichlorocyclopropanes were also employed in the preparation of a tri-
substituted naphthyl derivative and a diastereoselective reduction
was also demonstrated.
Introduction
The formation of carbon-carbon bonds is an essential
synthetic transformation, especially those involving the formation
of stereogenic centers.[1,2] In this context, the development of
methods for the simple formation of cyclic compounds, notably
cyclopropanes and cyclobutanes, is an area that still requires
further development.[3–8] Moreover, these rings are intrinsically
related to important pharmaceutical properties, such as the
enhancement of drug potency, metabolic stability and the
reduction of side-effects.[9]
Scheme 1. Previous studies and our proposal for the gem-
dichlorocyclopropanation of olefins.
Results and Discussion
We started our investigation preparing substrate 1a by the
oxidation of a Morita-Baylis-Hillman (MBH) adduct employing
Dess-Martin periodinane (DMP). This methodology was based on
previous literature reports[18–20] employing hypervalent iodine
reagents and allowed the access to the desired compound in
excellent yield (99%) and without the need of purification by
column chromatography. This dicarbonyl substrate was then
reacted with potassium trichloroacetate in the presence of DMSO
(Scheme 2), selectively leading to the 1,1-dichlorocyclopropyl
adduct (product 2a).
Dihalo-substituted cyclopropanes have recently attracted
great interest of the scientific community, mainly due to their
versatile reactivity,[10] allowing their use as intermediates in a wide
range of applications such as ring expansions, Friedel-Crafts and
Doering–Moore–Skattebol
reactions.[11]
The
gem-
dihalocyclopropanes are also substrates in the preparation of
monohalocyclopropanes, cyclopropenes, cyclopentane and a
variety of other useful functional groups.[12]
Most
methodologies
used
to
access
gem-
dihalocyclopropanes involve the generation of a highly reactive
carbene from different sources, such as dihalodiazirine and diazo
compounds, that quickly reacts with electron-rich alkenes
(Scheme 1A).[13,14] On the other hand, the gem-
dihalocyclopropanation of electrophilic olefins requires alternative
methodologies, commonly using stoichiometric amounts of the
toxic Seyferth reagent or TMSCCl2Br (Scheme 1B).[15] Our
research group recently described the use commercially available
After observing that the optimal reaction temperature for the
formation of 2a was at 40-50°C, we proceed with further reaction
optimization (Table 1). We observed that by lowering the salt
loading (entries 5-7) the conversion considerably dropped.
Moreover, when employing reaction times between 10-20
minutes, the isolated yields considerably dropped (entries 1-2),
probably due to incomplete decarboxylation of the
trichloroacetate salt. Thus, the best reaction condition was
established as shown in entry 9.
[a]
G. M. F. Batista, MSc. P. P. de Castro, Dr. A. G. Carpanez, Prof. Dr.
G. W. Amarante
Chemistry Department
Federal University of Juiz de Fora
Campus Martelos, Juiz de Fora, Minas Gerais 36036-900, Brazil
E-mail: giovanni.amarante@ufjf.edu.br
Homepage: http://www.ufjf.br/gpms
Prof. Dr. B. A. C. Horta
[b]
Institute of Chemistry
Federal University of Rio de Janeiro
Rio de Janeiro 21941-909, Brazil
E-mail: bruno@iq.ufrj.br
Supporting information for this article is given via a link at the end of
the document
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Table 1. Optimization of cyclopropanation reaction.
Entry
Time (min.)
Concentration (M)
Salt (Eq.) Conversion (%)[a]
1
2
3
4
5
6
7
8
9
10
20
30
30
30
30
30
60
30
0.50
0.50
1.00
0.75
0.50
0.50
0.50
0.50
0.50
2.00
2.00
2.00
2.00
1.25
1.50
1.75
2.00
2.00
82
94
51
40
82
95
97
99
99
[a] Conversion calculated by the analysis of the 1H NMR data of the crude
reaction mixture.
After the optimization, we turned our attention towards the
reaction scope. A wide variety of substrates could be successfully
employed under the optimized reaction conditions (Scheme 2).
The methodology tolerated well the use of aryl groups containing
electron withdrawing and donating aryl groups, including p- (such
as compounds 2i and 2k), m- (derivatives 2g and 2k) and even
sterically bulky o- substituents (compounds 2c and 2e), affording
the desired adducts in good to excellent isolated yields (ranging
from 63 to 99%). Furthermore, the alkyl substituted derivative 2o
could be obtained in 65% yield. Heterocycle-substituted adducts
were also tolerated in the optimized reaction condition, resulting
in compounds 2n and 2q in 80% and 87% yield respectively.
Most interesting, the cyclopropanation regioselectively occurred
at the more electrophilic olefin, affording compound 2p.
[a] Reaction carried out at 50 oC.
Scheme 2. Scope of the cyclopropanation reaction.
For the proposal of a plausible reaction mechanism, we
carried out some control experiments (Scheme 3). Two plausible
hypothesis were investigated: a Michael initiated ring closure
(MIRC) process, in which initially a Michael-type addition occurs,
-
followed by chlorine elimination or the decomposition of the CCl3
anion, generating CCl2 carbene, that would then react with the
olefin, affording the desired cyclopropane. Since it is well known
that electron-rich alkenes readily react with carbenes, we carried
out the reaction employing norbornene as olefin and no product
formation was detected. Furthermore, the use of less electrophilic
olefins, such as ethyl acrylate and Morita-Baylis-Hillman adducts
also failed to provide the desired cyclopropane derivatives.
o
Interestingly, by lowering the reaction temperature to 20 C and
employing substrate 1a we observed the formation of a different
product (compound 3), formed by the insertion of trichloromethyl
in the molecule. Finally, it is important to mention that when 3 was
added in the presence of a base (sodium hydride), it readily
converts into 2a (58% conversion by the crude 1H NMR analysis).
This suggested that the mechanism proceed through a MIRC
process, and that higher reaction temperatures are required for
the chlorine elimination step.
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* React: isolated reagents; MC1: molecular complex of the reagents (KCCl3
and substrate); TS1: transition state for the 1,4-addition reaction; MC2 and
MC3: molecular complexes (two conformations) of the CCl3- insertion; TS2:
transition state for the cyclopropanation step; MC4: molecular complex of the
products (dichlorocyclopropane and KCl).
Figure 1. Reaction pathway for the dichlorocycloprapanation of substrate 1a
(blue) and of a MBH adduct (red).
Next, the reaction proceeds through a second transition
state that is involved in the cyclopropane moiety formation. For
substrate 1a this is the rate-limiting step and presents a
considerably high ∆G‡ (24.6 Kcal.mol-1), which perfectly explains
the need of higher reaction temperatures (above 40 °C) to access
the desired compound 2a. Thus, the isolation of adduct 3 in lower
temperatures might be related to the fact that, since the second
reaction barrier is significantly high, the reactants at a lower
temperature do not have enough energy to overcome it, following
to another pathway that involves the a-protonation. This
investigation strongly suggests a Michael-type addition followed
by chlorine elimination as a mechanistic proposal, as depicted in
Scheme 4. Moreover, in this methodology, the only side products
are carbon dioxide and potassium chloride.
[a] Determined by the 1H NMR analysis of crude reaction mixture.
Scheme 3. Control experiments for mechanistic investigation.
Aiming to better comprehend the reactivity profile of this
transformation, we also decided to carry out DFT calculations of
the cyclopropanation reaction for both substrate 1a and a MBH
adduct. The DFT calculations for the MBH adduct were performed
in order to explain the need of the oxidation step. As shown in
Figure 1, the initial step involves the Michael-type addition of the
trichloromethyl group into the conjugated olefin. The reaction
presents a significantly lower transition state barrier for substrate
1a than for the MBH adducts (∆∆G‡=6.0 Kcal.mol-1), which
suggests that the oxidation step is required in order to obtain a
more electrophilic olefin for the reaction with the anion. In the
MBH case, although the ∆G‡ can be considered low, the half-life
of the trichloromethyl anion might be invoked to explain the
absence of insertion product.
Scheme 4. Proposed reaction mechanism.
Finally, to highlight the synthetic applicability of the prepared
dichlorocyclopropane adducts, we performed the reaction in a 1.5
grams scale (7.5 mmol), with no considerably loss in yield (74%
isolated yield), what demonstrates the possibility of scaling-up this
transformation (Scheme 5). We also demonstrated that in the
presence of aluminum chloride compound 2a could be converted
into derivative 4 (48% yield) in a single step, through a Friedel-
Crafts/cyclopropane ring-opening/aromatization cascade reaction.
This hydroxylated naphthyl moiety has potential application in
several transformations. [21-23] Moreover, a chemoselective ketone
reduction of the final product 2a lead to product 5 as a single
diastereomer (d.r.>19:1).
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chromatography carried out on TLC plates (silica gel 60 F254) and
visualized by a UV lamp; column chromatography was performed
employing 230− 400 mesh silica gel. Yields refer to
chromatographically purified and spectroscopically pure
compounds. Chemical shifts for 1H were reported as δ (parts per
million) relative to the signals of chloroform at 7.26 ppm (singlet).
Chemical shifts for 13C {1H} NMR were reported as δ relative to
the central line signal of the CDCl3 triplet at 77 ppm. The 1H NMR
spectra were recorded at 500 MHz, and 13C {1H} NMR spectra
were recorded at 125 MHz. Chemical shifts are reported
employing the following peak abbreviations pattern: br, broad; s,
singlet; d, doublet; dd, double doublet; t, triplet; dq, double quartet;
q, quartet; m, multiplet. High resolution mass spectra were
acquired in the positive ion mode using a time-of-flight (TOF)
mass spectrometer equipped with an ESI source. Melting points
were acquired on a melting point apparatus.
[a] Determined by the 1H NMR analysis of crude reaction mixture.
Scheme 5. Applications of the obtained 1,1-dichlorocyclopropyl product.
Conclusions
General procedure for the preparation of substrates 1a-1q: In
a round bottom flask, a Morita-Baylis-Hillman adduct (5.0 mmol),
10.0 mL of dichloromethane and Dess-Martin periodinane (6.3
mmol, 1.25 eq.) were added. This mixture was kept under
magnetic stirring at room temperature under stirring for 30
minutes. The crude reaction mixture was then filtrated for the
removal of the excess of unreacted DMP. The dichloromethane
was then removed under reduced pressure and the crude reaction
mixture submitted to a liquid-liquid extraction employing diethyl
ether and 5 aliquots of a NaHCO3 water solution. The organic
phase was then dried with sodium sulphate and the solvent
removed under reduced pressure, affording the desired products
(1a-1q).
In summary, a novel and simple methodology for the 1,1-
dichlorocyclopropanation of dicarbonyl conjugated olefins has
been described, affording the desired compounds in excellent
yields (up to 99%). Several substituted aryl and heteroaryl groups
were well tolerated, as well as alkyl analogues. Control
experiments and DFT studies suggested a Michael initiated ring
closure process, thus leading to the 1,1-dichlorocyclopropyl
products. The final products were successfully employed in a
cascade Friedel-Crafts/cyclopropane ring-opening/aromatization
reaction, affording a tri-substituted naphthyl derivative in a single
chemical step. Moreover,
a highly diastereoselective and
chemoselective reduction of ketone has been performed, giving
the corresponding carbinol derivative as a single diastereomer.
Ethyl 2-benzoylacrylate (1a): The reaction was purified through
liquid-liquid extraction with ethyl ether to afford product 1a as a
yellow oil (969 mg, 95% yield). 1H NMR (500 MHz, CDCl3) δ: 7.86
(m, 2H), 7.59 (m, 1H), 7.46 (m, 2H), 6.69 (s, 1H), 6.06 (s, 1H),
4.22 (q, J = 7.15 Hz, 2H), 1.19 (t, J = 7.15 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 193.4, 164.5, 141.6, 136.4, 133.7, 131.5,
129.6, 128.7, 61.7, 14.1.
Computational Methods
All calculations were performed in the Gaussian 09 package, at a
pressure equal to 1 atm and temperature of 313.15 K.[24] All
proposed molecules had their structure fully optimized in solution
employing the Density functional theory (DFT) at the M06-2X/6-
31++G(d,p) level of theory and the Solvation Model based on
Density (SMD) for dimethylsulfoxide (DMSO).[25] The vibrational
analysis has been carried out to check all stationary points and to
obtain the Gibbs free energy corrections. The transition states
(TS) were optimized using the Berny algorithm[26] and confirmed
to be first-order saddle points. Intrinsic reaction coordinate[27]
calculations also confirmed the obtained TS and are available in
the Supporting information. The Gibbs free energy of each
optimized structure was then calculated by the equation below, in
which the terms are the electronic energy and the thermal
correction to Gibbs free energy, respectively.
Ethyl 2-(4-fluorobenzoyl)acrylate (1b): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1b as a yellow oil (965 mg, 87% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.89 (m, 2H), 7.14 (m, 2H), 6.69 (m, 1H), 6.06 (m, 1H), 4.23 (q,
J = 7.1 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3) δ: 191.7, 167.1, 164.1 (d, J = 106.7 Hz), 141.2, 132.7 (d,
J = 2.8 Hz), 132.1 (d, J = 9.5 Hz), 131.4, 115.8 (d, J = 22.3 Hz),
61.6, 14.0.
Ethyl 2-(2-fluorobenzoyl)acrylate (1c): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1c as a yellow oil (810 mg, 73% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.87 (m, 1H), 7.57 (m, 1H), 7.28 (m, 1H), 7.12 (m, 1H), 6.63 (m,
1H), 6.29 (m, 1H), 4.24 (q, J = 7.1 Hz, 2H), 1.20 (t, J = 7.1 Hz,
3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 189.6, 164.2, 161,8 (d, J
= 254,6Hz), 143.4, 135.0 (d, J = 8,9 Hz), 131.0 (d, J = 2.0 Hz),
125.9 (d, J = 12.0 Hz), 124.6 (d, J = 3.4 Hz), 116.3 (d, J = 22.5
Hz), 61.4, 14.0.
: ꢀꢁ°ꢂꢃ = ꢄꢁꢂꢃ + ꢀꢅ°
Experimental Section
Ethyl 2-(4-bromobenzoyl)acrylate (1d): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1d as an colorless oil (1089 mg, 77% yield). 1H NMR (500 MHz,
General Remarks: All purchased chemicals were employed
without further purification and solvents dried following standard
procedures. The reactions were followed by thin layer
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CDCl3) δ: 7.71 (m, 2H), 7.61 (m, 2H), 6.69 (s, 1H), 6.07 (s, 1H),
4.22 (q, J = 7.1 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 192.3, 164.2, 141.2, 135.2, 132.1, 131.9,
130.9, 129.0, 61.8, 14.1.
Ethyl 2-(4-methylbenzoyl)acrylate (1l): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product 1l
as a yellow oil (1079 mg, 99% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.76 (m, 2H), 7.26 (m, 2H), 6.66 (m, 1H), 6.02 (m, 1H), 4.22 (q,
J = 7.1 Hz, 2H), 2.42 (s, 3H), 1.20 (t, J = 7.1 Hz, 3H). 13C {1H}
NMR (125 MHz, CDCl3) δ: 192.3, 164.6, 144.7, 141.7, 133.9,
131.1, 129.8, 129.0, 61.6, 21.9, 14.1.
Ethyl 2-(2-bromobenzoyl)acrylate (1e): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1e as an colorless oil (1245 mg, 88% yield). 1H NMR (500 MHz,
CDCl3) δ: 7.60 (m, 1H), 7.46 (m, 1H), 7.39 (m, 1H), 7.33 (m, 1H),
6.72 (m, 1H), 6.36 (m, 1H), 4.21 (q, J = 7.1 Hz, 2H), 1.18 (t, J =
7.1 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 192.8, 164.3,
141.7, 140.0, 135.5, 133.6, 132.2, 130.1, 127.4, 120.1, 61.6, 14.0.
Ethyl 2-(2-naphthoyl)acrylate (1m): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1m as a yellow oil (914 mg, 72% yield). 1H NMR (500 MHz, CDCl3)
δ: 8.61 (m, 1H), 8.91 (m, 1H), 7.90 (m, 1H), 7.74 (m, 1H), 7.62 (m,
1H), 7.56 (m, 1H), 7.48 (m, 1H), 6.69 (m, 1H), 6.21 (m, 1H), 4.71
(q, J = 7.2 Hz, 2H), 1.08 (t, J = 7.2 Hz, 3H). 13C {1H} NMR (125
MHz, CDCl3) δ: 194.9, 164.9, 143.5, 134.6, 134.0, 133.4, 132.8,
130.8, 129.8, 128.6, 128.3, 126.8, 125.8, 124.3, 61.6, 14.0.
Ethyl 2-(4-chlorobenzoyl)acrylate (1f): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product 1f
as a yellow oil (1142 mg, 96% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.80 (m, 2H), 7.44 (m, 2H), 6.70 (s, 1H), 6.07 (s, 1H), 4.23 (q,
J = 7.1 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3) δ: 192.1, 164.3, 141.3, 140.3, 134.8, 131.9, 130.9, 129.1,
61.8, 14.1.
Ethyl 2-(furan-2-carbonyl)acrylate (1n): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1n as a green oil (960 mg, 99% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.64 (dd, J = 1.7 Hz; J = 0.8 Hz, 1H), 7.19 (dd, J = 3.6 Hz; J =
0.8 Hz, 1H), 6.65 (m, 1H), 6.57 (dd, J = 3.6 Hz; J = 1.7 Hz, 1H),
Ethyl 2-(3-chlorobenzoyl)acrylate (1g): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1g as a yellow oil (916 mg, 77% yield). 1H NMR (500 MHz, CDCl3)
δ: 7.83 (m, 1H), 7.71 (m, 1H), 7.55 (m, 1H), 7.41 (m, 1H), 6.72 (s,
1H), 6.09 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 1.21 (t, J = 7.1 Hz, 3H).
13C {1H} NMR (125 MHz, CDCl3) δ: 191.9, 164.0, 141.0, 137.9,
134.9, 133.5, 132.1, 129.9, 129.3, 127.5, 61.7, 14.0.
6.19 (m, 1H), 4.27 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H). 13
C
{1H} NMR (125 MHz, CDCl3) δ: 180.0, 164.2, 152.1, 147.7, 140.7,
132.0, 120.3, 112.7, 61.7, 14.2.
Ethyl 2-methylene-3-oxohexanoate (1o): The reaction was
purified through liquid-liquid extraction with ethyl ether to afford
product 1n as a colorless oil (510 mg, 60% yield). 1H NMR (500
MHz, CDCl3) δ: 6.40 (d, J = 1.0 Hz, 1H), 6.32 (d, J = 1.0 Hz, 1H),
4.28 (q, J = 7.1 Hz, 2H), 2.73 (t, J = 7.3 Hz, 2H), 1.65 (m, 2H),
1.33 (t, J = 7.1 Hz, 3H), 0.93 (t, J = 7.4 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 199.9, 165.0, 142.4, 132.2, 61.5, 43.2, 17.5,
14.2, 13.8.
Ethyl 2-(2-chlorobenzoyl)acrylate (1h): The reaction was purified
through liquid-liquid extraction with ethyl ether to afford product
1h as a yellow oil (1178 mg, 99% yield). 1H NMR (500 MHz,
CDCl3) δ: 7.53 (m, 1H), 7.40 (m, 2H), 7.34 (m, 1H), 6.69 (d, J =
0.8 Hz, 1H), 6.36 (d, J = 0.9 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 1.16
(t, J = 7.2 Hz, 3H).13C {1H} NMR (125 MHz, CDCl3) δ: 192.1, 164.3,
142.2, 137.9, 134.9, 132.4, 130.4, 130.3, 127.0, 121.1, 61.5, 13.9.
Ethyl (E)-2-methylene-3-oxo-5-phenylpent-4-enoate (1p): The
reaction was purified through liquid-liquid extraction with ethyl
ether to afford product 1n as a yellow oil (1138 mg, 99% yield). 1H
NMR (500 MHz, CDCl3) δ: 7.61 (m, 1H), 7.57 (m, 2H), 7.41 (m,
3H), 6.61 (d, J = 0.9 Hz, 1H), 6.33 (d, J = 0.9 Hz, 1H), 4.30 (q, J
= 7.1 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3) δ: 190.2, 164.8, 145.6, 141.8, 134.6, 132.7, 131.0, 129.1,
128.7, 124.7, 61.7, 14.3.
Ethyl 2-(4-(trifluoromethyl)benzoyl)acrylate (1i): The reaction was
purified through liquid-liquid extraction with ethyl ether to afford
1
product 1i as a yellow oil (1115 mg, 82% yield). H NMR (500
MHz, CDCl3) δ: 7.95 (m, 2H), 7.73 (m, 2H), 6.74 (m, 1H), 6.15 (m,
1H), 4.23 (q, J = 7.1 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H). 13C {1H}
NMR (125 MHz, CDCl3) δ: 192.3, 164.1, 141.2, 139.3, 134.9 (q, J
= 32.8 Hz), 132.7, 129.7, 125.8 (q, J = 3.8 Hz), 123.7 (q, J = 272.8
Hz), 61.9, 14.1.
Ethyl 2-(4-bromobenzo[d][1,3]dioxole-5-carbonyl)acrylate (1q):
The reaction was purified through liquid-liquid extraction with ethyl
ether to afford product 1q as a yellow oil (1553 mg, 95% yield). 1H
NMR (500 MHz, CDCl3) δ: 7.02 (s, 1H), 7.00 (s, 1H), 6.67 (m, 1H),
6.30 (m, 1H), 6.05 (s, 2H), 4.23 (q, J = 7.1 Hz, 2H), 1.23 (t, J = 7.1
Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 191.8, 164.3, 150.9,
147.5, 142.1, 133.0, 113.7, 113.3, 110.4, 102.6, 61.6, 14.3.
Ethyl 2-(4-methoxybenzoyl)acrylate (1j): The reaction was
purified through liquid-liquid extraction with ethyl ether to afford
1
product 1j as an orange oil (854 mg, 73% yield). H NMR (500
MHz, CDCl3) δ: 7.88 (m, 2H), 6.96 (m, 2H), 6.68 (m, 1H), 6.02 (m,
1H), 4.25 (q, J = 7.1 Hz, 2H), 3.90 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H).
13C {1H} NMR (125 MHz, CDCl3) δ: 192.0, 164.6, 164.2, 141.7,
132.1, 130.6, 129.3, 114.0, 61.6, 55.7, 14.2.
General Procedure for the synthesis of products 2a-q and 3:
In a 2.0 mL vial flask, 0.2 mmol of the previously prepared
substrates 1a-q were added, followed by addition of 0.4 mL of
anhydrous dimethylsulfoxide (DMSO). For products 2a-q, this
Ethyl 2-(3-methoxybenzoyl)acrylate (1k): The reaction was
purified through liquid-liquid extraction with ethyl ether to afford
product 1k as a colorless oil (1123 mg, 96% yield). 1H NMR (500
MHz, CDCl3) δ: 7.39 (m, 3H), 7.13 (m, 1H), 6.68 (m, 1H), 6.05 (m,
1H), 4.23 (q, J = 7.1 Hz, 2H), 3.86 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H).
13C {1H} NMR (125 MHz, CDCl3) δ: 193.2, 164.5, 159.9, 141.6,
137.7, 131.4, 129.7, 122.6, 120.5, 113.2, 61.7, 55.6, 14.1.
o
mixture was heated (until 40 or 50 C) and kept under magnetic
stirring; for product 3, the reaction was kept under magnetic
stirring at room temperature. Next, the trichloroacetate salt (0.4
mmol, 2 equiv.) were added to the solution and the reaction kept
under magnetic stirring and constant temperature for 30 minutes.
Next, the crude reaction mixture was diluted in dichloromethane
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10.1002/chem.201904149
Chemistry - A European Journal
COMMUNICATION
(30.0 mL) and a liquid-liquid extraction employing distilled water
(four aliquots of 20.0 mL) carried out to remove KCl and DMSO.
The organic phase was then dried under reduced pressure and
further purification by flash column chromatography (silica gel)
using isocratic eluent 1:1 dichloromethane/hexane was carried
out.
product 2e as a yellow oil (53 mg, 74% yield). IR (ATR, cm-1):
2923, 1736, 1698, 759. H NMR (500 MHz, CDCl3) δ: 7.67 (m,
1
2H), 7.44 (m, 2H), 7.36 (m, 1H), 4.10 (m, 2H), 2.60 (d, J = 7.7 Hz,
1H), 2.50 (d, J = 7.7 Hz, 1H), 1.04 (t, J = 7.1 Hz, 3H). 13C {1H}
NMR (125 MHz, CDCl3) δ: 189.9, 164.6, 138.5, 134.0, 132.4,
130.2, 127.2, 120.5, 62.7, 61.4, 48.3, 30.4, 13.6. HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C13H11BrCl2NaO3 386.9166, found
386.9161.
Ethyl 1-benzoyl-2,2-dichlorocyclopropane-1-carboxylate (2a):
The reaction was purified through column chromatography on
silica gel (elution: hexane/DCM 1:1) to afford product 2a as a
colorless oil (46 mg, 81% yield). IR (ATR, cm-1): 2925, 1739, 1686,
Ethyl
2,2-dichloro-1-(4-chlorobenzoyl)cyclopropane-1-
carboxylate (2f): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2f as a colorless oil (52 mg, 83% yield). IR (ATR, cm-1):
1
762. H NMR (500 MHz, CDCl3) δ: 8.05 (m, 2H), 7.64 (m, 1H),
7.54 (m, 1H), 4.11 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.11 (dq, J =
10.8 Hz; J = 7.1 Hz, 1H), 2.52 (d, J = 7.6 Hz, 1H), 2.46 (d, J = 7.6
Hz, 1H), 1.08 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3)
δ: 189.4, 165.3, 135.8, 133.9, 129.9, 128.6, 62.8, 59.8, 45.9, 30.4,
13.9. HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H12Cl2NaO3
309.0061, found 309.0054.
1
2983, 1735, 1685, 842. H NMR (500 MHz, CDCl3) δ: 7.96 (m,
2H), 7.50 (m, 2H), 4.19 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.11 (dq,
J = 10.8 Hz; J = 7.1 Hz, 1H), 2.51 (d, J = 7.6 Hz, 1H), 2.42 (d, J =
7.6 Hz, 1H), 1.10 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3) δ: 188.3, 165.0, 140.4, 134.2, 131.3, 129.0, 62.9, 59.7,
45.9, 30.3, 14.0. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C13H11Cl3NaO3 342.9672, found 342.9660.
Ethyl 2,2-dichloro-1-(4-fluorobenzoyl)cyclopropane-1-carboxylate
(2b): The reaction was purified through column chromatography
on silica gel (elution: hexane/DCM 1:1) to afford product 2b as a
colorless oil (45 mg, 75% yield). IR (ATR, cm-1): 2982, 1733, 1682,
Ethyl
2,2-dichloro-1-(3-chlorobenzoyl)cyclopropane-1-
carboxylate (2g): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2g as a colorless oil (52 mg, 83% yield). IR (ATR, cm-1):
1
848. H NMR (500 MHz, CDCl3) δ: 8.08 (m, 2H), 7.22 (m, 2H),
4.22 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.13 (dq, J = 10.8 Hz; J =
7.1 Hz, 1H), 2.54 (d, J = 7.8 Hz, 1H), 2.44 (d, J = 7.8 Hz, 1H), 1.12
1
2982, 1738, 1688, 768. H NMR (500 MHz, CDCl3) δ: 7.99 (m,
(t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 187.9, 167.3, 1H), 7.89 (m, 1H), 7.59 (m, 1H), 7.47 (m, 1H), 4.21 (dq, J = 10.8
165.2 (d, J = 16.7 Hz), 132.7 (d, J = 9.5 Hz), 132.3 (d, J = 3.2 Hz),
115.8 (d, J = 22.0 Hz), 62.9, 59.7, 46.0, 30.3, 13.9. HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C13H11Cl2FNaO3 326.9967, found
326.9962.
Hz; J = 7.2 Hz, 1H), 4.10 (dq, J = 10.8 Hz; J = 7.2 Hz, 1H), 2.52
(d, J = 7.7 Hz, 1H), 2.44 (d, J = 7.7 Hz, 1H), 1.09 (t, J = 7.2 Hz,
3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 188.3, 165.0, 137.4,
134.9, 133.8, 129.9, 129.6, 128.2, 63.0, 59.7, 45.9, 30.4, 13.9.
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H11Cl3NaO3
342.9672, found 342.9666.
Ethyl 2,2-dichloro-1-(2-fluorobenzoyl)cyclopropane-1-carboxylate
(2c): The reaction was purified through column chromatography
on silica gel (elution: hexane/DCM 1:1) to afford product 2c as a
colorless oil (48 mg, 80% yield). IR (ATR, cm-1): 2922, 1745, 1683,
763. 1H NMR (500 MHz, CDCl3) δ: 8.04 (m, 1H), 7.61 (m, 1H),
7.28 (m, 1H), 7.19 (m, 1H), 4.25 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H),
4.09 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 2.53 (d, J = 7.6 Hz, 1H),
2.43 (d, J = 7.6 Hz, 1H), 1.07 (t, J = 7.2 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 185.9, 165.3 (d, J = 2.1 Hz), 162.4 (d, J =
257.1 Hz), 135.7 (d, J = 9.5 Hz), 131.1 (d, J = 2.1 Hz), 124.7 (d, J
= 10.5 Hz), 124.5 (d, J = 3.5 Hz), 116.6 (d, J = 23.6 Hz), 62.4,
47.8 (d, J = 2.1 Hz), 30.5, 13.7. HRMS (ESI-TOF) m/z [M + Na]+
calcd for C13H11Cl2FNaO3 326.9967, found 326.9967.
Ethyl
2,2-dichloro-1-(2-chlorobenzoyl)cyclopropane-1-
carboxylate (2h): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2h as a colorless oil (55 mg, 87% yield). IR (ATR, cm-1):
1
2983, 1735, 1698, 764. H NMR (500 MHz, CDCl3) δ: 7.77 (m,
1H), 7.46 (m, 1H), 7.40 (m, 1H), 4.12 (m, 2H), 2.59 (d, J = 7.6 Hz,
1H), 2.48 (d, J = 7.6 Hz, 1H), 1.05 (t, J = 7.1 Hz, 3H). 13C {1H}
NMR (125 MHz, CDCl3) δ: 189.2, 165.0, 136.4, 133.0, 132.9,
130.9, 130.8, 62.8, 61.6, 48.4, 30.6, 13.7. HRMS (ESI-TOF) m/z
[M + Na]+ calcd for C13H11Cl3NaO3 342.9672, found 342.9664.
Ethyl 2,2-dichloro-1-(4-(trifluoromethyl)benzoyl)cyclopropane-1-
carboxylate (2i): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2i as a colorless oil (44 mg, 63% yield). IR (ATR, cm-1):
Ethyl
1-(4-bromobenzoyl)-2,2-dichlorocyclopropane-1-
carboxylate (2d): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2d as a yellow oil (71 mg, 99% yield). IR (ATR, cm-1):
1
2922, 1738, 1693, 776. H NMR (500 MHz, CDCl3) δ: 8.14 (m,
1
2983, 1739, 1686, 841. H NMR (500 MHz, CDCl3) δ: 7.88 (m,
2H), 7.80 (m, 2H), 4.19 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.12 (dq,
J = 10.8 Hz; J = 7.1 Hz, 1H), 2.55 (d, J = 7.5 Hz, 1H), 2.47 (d, J =
7.5 Hz, 1H), 1.08 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3) δ: 188.6, 164.7, 134.9 (q, J = 32.7 Hz), 130.0, 125.5 (q, J
= 3.7 Hz), 123.5 (q, J = 272.6 Hz), 62.9, 59.6, 45.8, 30.1, 13.8.
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C14H11Cl2F3NaO3
376.9935, found 376.9919.
2H), 7.67 (m, 2H), 4.19 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.11 (dq,
J = 10.8 Hz; 7.1 Hz, 1H), 2.51 (d, J = 7.7 Hz, 1H), 2.42 (d, J = 7.7
Hz, 1H), 1.10 (t, J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3)
δ: 188.6, 165.0, 134.6, 132.0, 131.4, 63.0, 59.7, 45.9, 30.3, 14.0.
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H11BrCl2NaO3
386.9166, found 386.9151.
Ethyl
1-(2-bromobenzoyl)-2,2-dichlorocyclopropane-1-
Ethyl
2,2-dichloro-1-(4-methoxybenzoyl)cyclopropane-1-
carboxylate (2e): The reaction was purified through column
carboxylate (2j): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
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10.1002/chem.201904149
Chemistry - A European Journal
COMMUNICATION
product 2j as a colorless oil (58 mg, 92% yield). IR (ATR, cm-1):
2976, 1733, 1676, 841. H NMR (500 MHz, CDCl3) δ: 8.01 (m,
Ethyl 1-butyryl-2,2-dichlorocyclopropane-1-carboxylate (2o): The
reaction was purified through column chromatography on silica
gel (elution: hexane/DCM 1:1) to afford product 2o as a colorless
oil (32 mg, 65% yield). IR (ATR, cm-1): 2963, 1736, 1716, 758. 1H
NMR (500 MHz, CDCl3) δ: 4.29 (q, J = 7.1 Hz, 2H), 3.04 (m, 1H),
2.86 (m, 1H), 2.40 (d, J = 7.7 Hz, 1H), 2.27 (d, J = 7.7 Hz, 1H),
1
2H), 6.99 (m, 2H), 4.19 (dq, J = 10.8 Hz; J = 7.2 Hz, 1H), 4.11 (dq,
J = 10.8 Hz; J = 7.2 Hz, 1H), 3.90 (s, 3H), 2.48 (d, J = 7.6 Hz, 1H),
2.38 (d, J = 7.6 Hz, 1H), 1.11 (t, J = 7.2 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 187.6, 165.3, 164.1, 132.3, 128.6, 113.7,
62.6, 59.7, 55.6, 45.9, 30.2, 13.9. HRMS (ESI-TOF) m/z [M + Na]+
calcd for C14H14Cl2NaO4 339.0167, found 339.0157.
1.68 (m, 2H), 1.33 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.2 Hz, 3H). 13
C
{1H} NMR (125 MHz, CDCl3) δ: 198.3, 164.9, 62.9, 49.7, 44.8,
30.5, 29.0, 17.3, 14.2, 13.8. HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C10H14Cl2NaO3 275.0218, found 275.0209.
Ethyl
2,2-dichloro-1-(3-methoxybenzoyl)cyclopropane-1-
carboxylate (2k): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2k as a colorless oil (62 mg, 99% yield). IR (ATR, cm-1):
Ethyl 2,2-dichloro-1-cinnamoylcyclopropane-1-carboxylate (2p):
The reaction was purified through column chromatography on
silica gel (elution: hexane/DCM 1:1) to afford product 2p as a
yellow oil (9 mg, 15% yield). IR (ATR, cm-1): 2923, 1733, 1685,
748. 1H NMR (500 MHz, CDCl3) δ: 7.72 (d, J = 15.9 Hz, 1H), 7.64
(m, 2H), 7.43 (m, 3H), 7.37 (d, J = 15.9 Hz, 1H), 4.29 (m, 2H),
2.42 (d, J = 7.7 Hz, 1H), 2.40 (d, J = 7.7 Hz, 1H), 1.30 (t, J = 7.2
Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 187.6, 164.9, 145.1,
134.5, 131.2, 129.2, 128.9, 124.7, 62.9, 59.5, 48.9, 28.9, 14.2.
HRMS (ESI-TOF) m/z [M + Na]+ calcd for C15H14Cl2NaO3
335.0218, found 335.0216.
1
2974, 1736, 1686, 769. H NMR (500 MHz, CDCl3) δ: 7.60 (m,
1H), 7.55 (m, 1H), 7.42 (m, 1H), 7.17 (m, 1H), 4.20 (dq, J = 10.8
Hz; J = 7.1 Hz, 1H), 4.10 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 3.88
(s, 3H), 2.49 (d, J = 7.6 Hz, 1H), 2.43 (d, J = 7.6 Hz, 1H), 1.08 (t,
J = 7.2 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 189.0, 165.2,
159.6, 136.9, 129.5, 122.6, 120.5, 113.4, 62.6, 59.7, 55.5, 45.7,
30.4, 13.8. HRMS (ESI-TOF) m/z [M
+
Na]+ calcd for
C14H14Cl2NaO4 339.0167, found 339.0164.
Ethyl
2,2-dichloro-1-(4-methylbenzoyl)cyclopropane-1-
carboxylate (2l): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2l as a colorless oil (59 mg, 99% yield). IR (ATR, cm-1):
Ethyl
1-(4-bromobenzo[d][1,3]dioxole-5-carbonyl)-2,2-
dichlorocyclopropane-1-carboxylate (2q): The reaction was
purified through column chromatography on silica gel (elution:
hexane/DCM 1:1) to afford product 2q as a colorless oil (70 mg,
87% yield). IR (ATR, cm-1): 2910, 1733, 1693, 748. 1H NMR (500
MHz, CDCl3) δ: 7.23 (s, 1H), 7.10 (s, 1H), 6.09 (s, 1H), 4.16 (m,
2H), 2.52 (d, J = 7.6 Hz, 1H), 2.48 (d, J = 7.6 Hz, 1H), 1.14 (t, J =
1
2977, 1736, 1682, 771. H NMR (500 MHz, CDCl3) δ: 7.92 (m,
2H), 7.31 (m, 2H), 4.19 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 4.10 (dq,
J = 10.8 Hz; J = 7.1 Hz, 1H), 2.48 (d, J = 7.6 Hz, 1H), 2.44 (s, 3H),
2.41 (d, J = 7.7 Hz, 1H), 1.09 (t, J = 7.1 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3) δ: 188.7, 165.3, 144.9, 133.2, 129.9, 62.6, 59.7, 7.2 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 188.1, 164.8,
45.8, 30.2, 21.8, 14.0. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
151.1, 147.3, 131.0, 114.3, 114.2, 110.7, 102.7, 62.7, 61.3, 47.8,
C14H14Cl2NaO3 323.0218, found 323.0208.
30.6, 13.8. HRMS (ESI-TOF) m/z [M +
Na]+ calcd for
C14H11BrCl2NaO5 430.9065, found 430.9065.
Ethyl
1-(2-naphthoyl)-2,2-dichlorocyclopropane-1-carboxylate
(2m): The reaction was purified through column chromatography
on silica gel (elution: hexane/DCM 1:1) to afford product 2m as a
colorless oil (52 mg, 78% yield). IR (ATR, cm-1): 2983, 1732, 1679,
Ethyl 2-benzoyl-4,4,4-trichlorobutanoate (3): The reaction was
purified through column chromatography on silica gel (elution:
hexanes/DCM 1:1) to afford product 3 as a yellow oil (41 mg, 64%
yield). 1H NMR (500 MHz, CDCl3) δ: 8.08 (m, 2H), 7.62 (m, 1H),
7.51 (m, 2H), 4.90 (m, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.67 (dd, J =
15.4 Hz, 5.8 Hz, 1H), 3.57 (dd, J = 15.3 Hz, 5.0 Hz, 1H), 1.16 (t,
J = 7.1 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3) δ: 193.2, 167.9,
135.9, 134.1, 129.3, 129.0, 98.0, 62.5, 53.1, 51.9, 14.0. HRMS
(ESI-TOF) m/z [M + Na]+ calcd for C13H13Cl3NaO3 344.9828,
found 344.9818.
1
776. H NMR (500 MHz, CDCl3) δ: 8.81 (m, 1H), 8.14 (m, 1H),
8.08 (m, 1H), 7.91 (m, 1H), 7.60 (m, 3H), 4.07 (dq, J = 10.8 Hz; J
= 7.1 Hz, 1H), 3.99 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 2.64 (d, J =
7.5 Hz, 1H), 2.49 (d, J = 7.5 Hz, 1H), 0.87 (t, J = 7.1 Hz, 3H). 13
C
{1H} NMR (125 MHz, CDCl3) δ: 190.5, 165.6, 134.2, 134.1, 132.7,
131.1, 128.7, 128.7, 126.7, 125.8, 124.4, 62.6, 60.7, 48.0, 30.5,
13.7. HRMS (ESI-TOF) m/z [M + Na]+ calcd for C17H14Cl2NaO3
359.0218, found 359.0215.
General Procedure for the preparation of product 4: To a 2.0
mL vial flask containing 0.20 mmol of product 2a, 0.4 mL of
dichloromethane was added, followed by 0.08 mmol of aluminum
chloride (0.4 equiv.). The reaction mixture was kept at 50 oC under
magnetic stirring for 3 hours. The crude reaction mixture was then
washed twice with distilled water, dried with sodium sulphate and
the solvent removed under reduced pressure. Flash column
chromatography (silica gel) using the isocratic eluent 1:1
dichloromethane/hexane was then carried out.
Ethyl
2,2-dichloro-1-(furan-2-carbonyl)cyclopropane-1-
carboxylate (2n): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 2n as a yellow oil (44 mg, 80% yield). IR (ATR, cm-1):
2983, 1736, 1675, 764. 1H NMR (500 MHz, CDCl3) δ: 7.69 (dd, J
= 1.7 Hz; J = 0.8 Hz, 1H), 7.39 (dd, J = 3.6 Hz; J = 0.8 Hz, 1H),
6.62 (dd, J = 3.6 Hz; J = 1.7 Hz, 1H), 4.25 (dq, J = 10.8 Hz; J =
7.1 Hz, 1H), 4.14 (dq, J = 10.8 Hz; J = 7.1 Hz, 1H), 2.45 (d, J =
7.6 Hz, 1H), 2.38 (d, J = 7.6 Hz, 1H), 1.16 (t, J = 7.1 Hz, 3H). 13
C
Ethyl 4-chloro-1-hydroxy-2-naphthoate (4): The reaction was
purified through column chromatography on silica gel (elution:
hexane/DCM 1:1) to afford product 4 as a white solid (24 mg, 48%
yield). Melting point: 84.3 – 85.2°C. IR (NaCl, cm-1): 3693, 2991,
1651, 763. 1H NMR (500 MHz, CDCl3) δ: 12.02 (s, 1H), 8.46 (m,
{1H} NMR (125 MHz, CDCl3) δ: 177.5, 164.8, 152.0, 147.2, 119.8,
112.7, 62.7, 59.4, 45.6, 30.0, 13.9. HRMS (ESI-TOF) m/z [M +
Na]+ calcd for C11H10Cl2NaO4 298.9854, found 298.9853.
This article is protected by copyright. All rights reserved.

10.1002/chem.201904149
Chemistry - A European Journal
COMMUNICATION
[10]
[11]
W. Wu, Z. Lin, H. Jiang, Org. Biomol. Chem. 2018, 16, 7315–7329.
D. Y.-K. Chen, R. H. Pouwer, J.-A. Richard, Chem. Soc. Rev. 2012,
41, 4631.
1H), 8,19 (m, 1H), 7.88 (s, 1H), 7.47 (m, 1H), 7.60 (m, 1H), 4.47
(q, J = 7.2 Hz, 2H), 1.46 (t, J = 7.2 Hz, 3H). 13C {1H} NMR (125
MHz, CDCl3) δ: 170.3, 160.1, 134.3, 130.5, 126.1, 126.0, 124.6,
124.5, 124.0, 121.7, 106.0, 62.0, 14.4. HRMS (ESI-TOF) m/z [M
+ Na]+ calcd for C13H11ClNaO3 273.0294, found 273.0311.
[12]
A. P. Thankachan, K. S. Sindhu, K. K. Krishnan, G. Anilkumar, Org.
Biomol. Chem. 2015, 13, 8780–8802.
[13]
[14]
[15]
I. D. Jurberg, Chem. Eur. J. 2017, 23, 9716–9720.
R. A. Moss, J. Org. Chem. 2010, 75, 5773–5783.
General Procedure for the preparation of product 5: To a 2.0
mL vial flask containing 0.2 mmol of product 2a, 0.4 mL of ethanol
was added, followed by 0.6 mmol of sodium borohydride (3.0
equiv.). The reaction was kept under magnetic stirring at room
temperature (20 °C) for 6 hours. Next, the solvent was removed
under reduced pressure, and the crude reaction mixture
submitted to a liquid-liquid extraction employing dichloromethane
and water. Next, the organic phase was dried with sodium
sulphate and the solvent removed under reduced pressure. Flash
column chromatography (silica gel) using the isocratic eluent 1:1
dichloromethane/hexane was then carried out.
D. S. Lee, M. J. Durán-Peña, L. Burroughs, S. Woodward, Chem. Eur.
J. 2016, 22, 7609–7616.
[16]
[17]
E. P. Ávila, I. F. de Souza, A. V. B. Oliveira, V. Kartnaller, J. Cajaiba,
R. O. M. A. de Souza, C. C. Corrêa, G. W. Amarante, RSC Adv. 2016,
6, 108530–108537.
G. C. Q. da Silva, T. M. Cardozo, G. W. Amarante, C. R. A. Abreu, B.
A. C. Horta, Phys. Chem. Chem. Phys. 2018, 20, 21988–21998.
P. S. Baran, Y.-L. Zhong, J. Am. Chem. Soc. 2001, 123, 3183–3185.
M. S. Santos, F. Coelho, RSC Adv. 2012, 2, 3237.
N. J. Lawrence, J. P. Crump, A. T. McGown, J. A. Hadfield,
Tetrahedron Lett. 2001, 42, 3939–3941.
[18]
[19]
[20]
Ethyl
2,2-dichloro-1-(hydroxy(phenyl)methyl)cyclopropane-1-
carboxylate (5): The reaction was purified through column
chromatography on silica gel (elution: hexane/DCM 1:1) to afford
product 5 as a yellow oil (51 mg, 89% yield, d.r. > 19:1). IR
[21]
[22]
Y. He, J. Tang, M. Luo, X. Zeng, Org. Lett. 2018, 20, 4159–4163.
L. He, L. Zhang, X. Liu, X. Li, M. Zheng, H. Li, K. Yu, K. Chen, X.
Shen, H. Jiang, et al., J. Med. Chem. 2009, 52, 2465–2481.
1
(NaCl,cm-1): 3500, 2981, 1733, 798. H NMR (500 MHz, CDCl3)
δ: 7.35 (m, 5H), 4.70 (d, J = 10.3 Hz, 1H), 4.26 (d, J = 10.3 Hz,
1H), 4.12 (q, J = 7.2 Hz, 2H), 2.47 (d, J = 7.8 Hz, 1H), 1.89 (d, J
= 7.8 Hz, 1H), 1.12 (t, J = 7.2 Hz, 3H).13C {1H} NMR (125 MHz,
CDCl3) δ: 167.9, 140.8, 128.7, 128.1, 125.5, 76.3, 62.5, 61.2, 44.4,
30.6, 14.0. HRMS (ESI-TOF) m/z [M
C13H14Cl2NaO3 311.0218, found 311.0208.
[23]
[24]
Z. He, A. P. Pulis, D. J. Procter, Angew. Chemie Int. Ed. 2019, 58,
7813–7817.
G. E. S. M. J. Frisch, G. W. Trucks, H. B. Schlegel, B. M. M. A. Robb,
J. R. Cheeseman, G. Scalmani, V. Barone, H. P. H. G. A. Petersson,
H. Nakatsuji, M. Caricato, X. Li, M. H. A. F. Izmaylov, J. Bloino, G.
Zheng, J. L. Sonnenberg, T. N. M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, J. Y. Honda, O. Kitao, H. Nakai, T. Vreven, J.
A. Montgomery, E. B. J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, J. N. K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. T. K.
Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. B. C. M.
Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, et al., Gaussian
09, Revision A.01. Gaussian, Inc., Wallingford CT, 2009.
+
Na]+ calcd for
Acknowledgements
We are grateful for generous financial support from CAPES
(Finance Code 001), CNPq, FAPEMIG, FAPERJ, and Rede
Mineira de Química. Furthermore, we are grateful to Prof.
Giuliano Clososki and Thiago Santos (FCFRP-USP) for all their
help with HRMS analyses.
[25]
[26]
[27]
Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215–241.
H. B. Schlegel, J. Comput. Chem. 1982, 3, 214–218.
S. Maeda, Y. Harabuchi, Y. Ono, T. Taketsugu, K. Morokuma, Int. J.
Quantum Chem. 2015, 115, 258–269.
Keywords: gem-dichlorocyclopropane • Michael Initiated Ring
Closure • dihalocyclopropanation • density functional theory
[1]
[2]
K. W. Quasdorf, L. E. Overman, Nature 2014, 516, 181–191.
I. F. S. Marra, A. M. de Almeida, L. P. Silva, P. P. de Castro, C. C.
Corrêa, G. W. Amarante, J. Org. Chem. 2018, 83, 15144–15154.
N. D. C. Tappin, W. Michalska, S. Rohrbach, P. Renaud, Angew.
Chem. Int. Ed. 2019, DOI 10.1002/anie.201907962.
[3]
[4]
[5]
N. D. C. Tappin, W. Michalska, S. Rohrbach, P. Renaud, Angew.
Chem. 2019, ange.201907962.
T. Chidley, I. Jameel, S. Rizwan, P. Peixoto, L. Pouységu, S. Quideau,
W. S. Hopkins, G. K. Murphy, Angew. Chem. Int. Ed. 2019, DOI
10.1002/anie.201908994.
[6]
T. Chidley, I. Jameel, S. Rizwan, P. Peixoto, L. Pouységu, S. Quideau,
W. S. Hopkins, G. K. Murphy, Angew. Chem. 2019, ange.201908994.
Z. Shao, Angew. Chem. Int. Ed. 2019, DOI 10.1002/anie.201909596.
Z. Shao, Angew. Chem. 2019, ange.201909596.
[7]
[8]
[9]
C. Ebner, E. M. Carreira, Chem. Rev. 2017, 117, 11651–11679.
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10.1002/chem.201904149
Chemistry - A European Journal
COMMUNICATION
FULL PAPER
Gabriel M. F. Batista, Pedro P. De
Castro, Arthur G. Carpanez, Bruno A. C.
Horta,* and Giovanni W. Amarante*
Page No. – Page No.
gem-Dichlorocyclopropanation of
Dicarbonyl Derivatives
A simple protocol for the 1,1-dichlorocyclopropanation of dicarbonyl conjugated olefins
through a Michael initiated ring closure process. A wide variety of the respective gem-
dichlorocyclopropane structures have been obtained with high functional group tolerance.
Reaction scale-up, as well as novel applications for these derivatives, were also reported.
This article is protected by copyright. All rights reserved.