Ring Opening of Donor-Acceptor Cyclopropanes with Acyclic 1,3-Diketones for the Synthesis of 1,6-Dicarbonyl Compounds

Article abstract of DOI:10.1021/acs.joc.0c02290

1,6-Dicarbonyl compounds, representing the formal addition products of the α-position of acetophenone derivatives to donor-acceptor cyclopropanes, were synthesized in two steps via first ring opening of donor-acceptor cyclopropanes with acyclic 1,3-diketo

Full text of DOI:10.1021/acs.joc.0c02290

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Note
Ring Opening of Donor−Acceptor Cyclopropanes with Acyclic 1,3-
Diketones for the Synthesis of 1,6-Dicarbonyl Compounds
Dongxin Zhang,* Hu Cai, Yan Chen, Lei Yin, Junchao Zhong, Ying Zhang, and Qian-Feng Zhang*
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ABSTRACT: 1,6-Dicarbonyl compounds, representing the formal addi-
tion products of the α-position of acetophenone derivatives to donor−
acceptor cyclopropanes, were synthesized in two steps via first ring opening
of donor−acceptor cyclopropanes with acyclic 1,3-diketones followed by
DBU catalyzed retro-Claisen-type C−C bond cleavage reactions. In the
first step, acyclic 1,3-diketones selectively worked as C-nucleophiles to add
to donor−acceptor cyclopropanes. In the second step, the alkyl ketone part
of the ring-opening products resulting from unsymmetrical 1,3-diketones was selectively cleaved in the presence of DBU in
methanol.
Scheme 1. Different Reactivities of 1,3-Cyclodiones and
Acyclic 1,3-Diketones with D−A Cyclopropanes
onor−acceptor (D−A) cyclopropanes are one of the
D
most useful building blocks in organic synthesis due to
their special reactivities and have been widely applied for the
synthesis of natural products and biologically active com-
pounds.1 Ring opening of D−A cyclopropanes with
nucleophiles catalyzed by Lewis acids is the most straightfor-
ward way to obtain 1,3-bifunctionalized compounds. Both
carbon2,3 and heteroatom4−6 nucleophile additions to D−A
cyclopropanes have been well-developed.
Recently, our group has focused on the development of the
reactions of D−A cyclopropanes with 1,3-diketone deriva-
tives.6 1,3-Diketone derivatives can be used as both C- and O-
nucleophiles due to their nature of easy keto−enol
tautomerization. We have developed the use of 1,3-cyclodiones
as nucleophilic partners to add to D−A cyclopropanes. 1,3-
Cyclodiones selectively worked as O-nucleophiles in the
reactions with D−A cyclopropanes catalyzed by scandium
triflate to afford 1,3-cyclodione enol ether derivatives, which
underwent an interesting intramolecular transformation
catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in
methanol to furnish a new type of D−A cyclopropanes
(Scheme 1a).6a
Our initial results indicated that acyclic 1,3-dicarbonyl
compounds reacted in a different way, as C-nucleophiles, with
D−A cyclopropanes catalyzed by Lewis acids. Here, we
uncover the details of the reactions of acyclic 1,3-diketones
with D−A cyclopropanes and that the resulting nucleophilic
ring-opening products underwent retro-Claisen-type C−C
bond cleavage under the catalytic conditions of DBU in
methanol to accomplish a series of 1,6-dicarbonyl com-
pounds,7,8 which represent the formal addition products of
the α-position of ketones to D−A cyclopropanes (Scheme 1b).
The direct additions of ketones to D−A cyclopropanes are
difficult, though the use of preformed enol silyl enthers to add
to D−A cyclopropanes has been reported.8
The reaction scope of dibenzoylmethane 1a with various D−
A cyclopropanes 2 was first investigated using Sc(OTf)3 as the
catalyst, and the results are shown in Scheme 2. Similar to our
previously reported reactions of D−A cyclopropanes with 1,3-
cyclodione derivatives, reactions of D−A cyclopropanes with
strong electron-donating substituents on the phenyl ring were
faster, and the corresponding products were obtained in higher
yields under milder conditions (3a−3e).6,9 Reactions of para-
methylphenyl, phenyl, and para-chlorophenyl substituted D−A
cyclopropanes with 1a needed to be performed with higher
Received: September 25, 2020
https://dx.doi.org/10.1021/acs.joc.0c02290
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
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Note
Scheme 2. Reaction Scope of Dibenzoylmethane 1a with
Various D−A Cyclopropanes
Scheme 3. Reactions of 2a with Unsymmetrical 1,3-
Dicarbonyl Compounds
a
a
a
Unless otherwise noted, reactions were carried out using 1,3-
dicarbonyl compounds (0.18 mmol) and 2a (0.15 mmol) in the
presence of Sc(OTf)3 (0.0075 mmol) in CH2Cl2 (1.0 mL) at room
b
c
temperature (25 °C) for 24 h. Yield of diastereomer mixtures. Yield
of the major diastereomer.
to screen reaction conditions for compound 3a. DBU was first
used as the base catalyst6a,10 because it has been reported as a
good organobase catalyst for aldol reactions. However, no
desired aldol cyclization product was obtained under the
catalytic conditions of DBU in various common solvents
(Table 1, entries 1−4). When methanol was used as the
reaction solvent, the retro-Claisen-type C−C bond cleavage
product 4a was obtained in 43% yield in 48 h (Table 1, entry
a
Unless otherwise noted, reactions were carried out using dibenzoyl-
methane 1a (0.18 mmol) and D−A cyclopropane (0.15 mmol) in the
presence of Sc(OTf)3 (0.0075 mmol) in CH2Cl2 (1.0 mL) at room
temperature (25 °C) for 24 h. Yield of a 5 mmol-scale reaction is
shown in the parentheses. Sc(OTf)3 (0.015 mmol) was used, and the
b
c
reaction was carried out at 45 °C in 1,2-dichloroethane.
catalyst loading and at higher temperature to furnish 3c−3e
with good yields. D−A cyclopropanes with meta-methox-
yphenyl and ortho-methoxyphenyl substituents were success-
fully applied to give 3f and 3g in 88 and 83% yield,
respectively. Heterocyclic substrates, such as 3-indolyl and 2-
thienyl substituted D−A cyclopropanes, worked well in this
reaction, and the corresponding products 3h and 3i were
isolated in 86 and 95% yield, respectively. The substrate scope
with respect to the ester group of the D−A cyclopropane was
also investigated. D−A cyclopropanes with isopropyl and 2-
adamantyl esters were well-tolerated to furnish products in
high yields (3j and 3k).
Next, reactions of D−A cyclopropane 2a with several
different unsymmetrical 1,3-dicarbonyl compounds 1 were
studied (Scheme 3). In all cases, the C-nucleophilic products
were accomplished in good yields (89−93%), and there was
almost no diastereoselectivity except for the reaction with
4,4,4-trifluoro-1-phenylbutane-1,3-dione, giving 3n with mod-
erate diastereoselectivity (dr = 1:4). It was worth noting that
the NMR data of the inseparable mixtures 3q, resulting from
the reaction of 1-benzoylacetone and 2a, showed complicated
mixtures of diastereomers and keto−enol tautomers, which
made it difficult to do the peak assignments.
a
Table 1. Reactions of 3a Catalyzed by Organobases
b
entry
base (40 mmol %)
solvent
time (h)
yield (%)
1
2
3
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DABCO
DMAP
Et3N
CH2Cl2
THF
PhCH3
THF
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
48
48
48
48
48
12
24
48
48
48
c
4
5
43
98
69
c
6
c,d
7
8
9
10
a
Unless otherwise noted, reactions were carried out using 3a (0.10
mmol) in the presence of an organobase (0.04 mmol) in 1.0 mL of a
solvent at room temperature (25 °C). DABCO = 1,4-diazabicyclo
[2.2.2]octane; DMAP = 4-(dimethylamino)pyridine. The reaction
b
It was initially assumed that 3 may undergo intramolecular
aldol-type reactions under basic conditions to give five-
membered carbocycles. Based on this assumption, we tried
c
d
was carried out at 50 °C. The catalyst (0.02 mmol) was used.
B
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Note
5).11 4a was obtained in 98% yield within 12 h when the
reaction was carried out at 50 °C (Table 1, entry 6). Reducing
the loading of DBU, the reaction became slower (Table 1,
entry 7). Other organobases, such as DACBO, DMAP, and
Et3N, were not able to catalyze this retro-Claisen-type reaction
(Table 1, entries 8−10).
Table 2. DBU-Catalyzed Retro-Claisen-type C−C Bond
Cleavage Reactions of 3 Resulted from the Reactions of
a
Unsymmetrical 1,3-Dicarbonyl Compounds and 2a
With the optimized conditions for the DBU-catalyzed retro-
Claisen-type C−C bond cleavage reaction in hand, we further
explored the scope of this reaction using 3, which resulted
from the reactions of 1a and 2 (Scheme 4). New 1,6-
entry
3
product
yield (%)
1
2
3
4
5
3l
4a
4a
4a
71
63
68
3m
3n
3o
3q
Scheme 4. DBU-Catalyzed retro-Claisen-type C−C Bond
Cleavage Reactions of 3 Resulted from the Reactions of 1a
4a
92
a
and 2
a
Unless otherwise noted, reactions were carried out using 3 (0.10
mmol) in the presence of DBU (0.04 mmol) in MeOH (1.0 mL) at
50 °C for 12 h.
Particularly, in the case of complicated mixture 3q, 4a was
obtained in excellent 92% yield (Table 2, entry 5). In the case
of 3o, no reaction occurred under the standard conditions
(Table 2, entry 4). The reaction of 3p afforded both 4l and 4m
in 41 and 36% yield, respectively (Scheme 5).
Scheme 5. Retro-Claisen-type C−C Bond Cleavage
Reaction of 3p
The synthesis of 4a without the isolation of 3q was tested, as
shown in Scheme 6. After the reaction of 1-benzoylacetone and
2a finished, simple workup was performed to remove
a
Scheme 6. Synthesis of 4 without the Isolation of 3
Unless otherwise noted, reactions were carried out using 3 (0.10
mmol) in the presence of DBU (0.04 mmol) in MeOH (1.0 mL) at
b
c
50 °C for 12 h. The reaction was carried out for 24 h. 4a was
isolated separately in 32% yield.
dicarbonyl compounds 4a−4k were all obtained in good yields,
proving that DBU was an efficient catalyst for this type of
reaction. For the reaction of 3h, 4h was obtained in 31% yield
along with the N-Boc-deprotection product 4h′ in 55% yield.
By extending the reaction time to 24 h, 4h′ was accomplished
in 74% yield, which indicated that DBU might also be a good
catalyst for the deprotection reaction of N-Boc compounds.
For the reaction of 3k, DBU catalyzed transesterification
reaction took place, and 4j (45%) and 4a (32%) were both
obtained. The transesterification reaction also took place when
EtOH was used as the solvent for the reaction of 3a, affording
4k in 93% yield.
Compounds 3 shown in Scheme 3 were also applied in the
DBU-catalyzed retro-Claisen-type C−C bond cleavage reac-
tions (Table 2). For the reactions of 3l, 3m, 3n, and 3q, the
C−C bond cleavage occurred selectively, with the alkyl ketone
part cleaved, to afford only 4a (Table 2, entries 1−3 and 5).
a
Yield of a gram-scale reaction is shown in the parentheses.
C
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Note
dibenzoylmethane 1a (1.35 g, 6.0 mmol) in CH2Cl2 (25.0 mL),
Sc(OTf)3 (123.0 mg, 0.25 mmol) was added. The mixture was stirred
at room temperature (25 °C) for 36 h. Then, the mixture was diluted
with CH2Cl2 (25.0 mL) and washed with saturated NaHCO3. The
aqueous phase was extracted with CH2Cl2 (25 mL × 3). The organic
layers were combined, washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by silica gel flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1) to
provide product 3a (2.22 g, 91%).
Dimethyl 2-(3-Benzoyl-2-(4-methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (3a). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
68.7 mg (94%). Colorless crystalline solid. mp 172−174 °C. Known
compound.6a 1H NMR (400 MHz, CDCl3): δ = 8.01−8.03 (m, 2H),
7.71−7.73 (m, 2H), 7.52−7.55 (m, 1H), 7.39−7.44 (m, 3H), 7.26−
7.30 (m, 2H), 7.10−7.13 (m, 2H), 6.67−6.71 (m, 2H), 5.59 (d, J =
10.3 Hz, 1H), 3.90 (td, J = 10.8 Hz, 3.8 Hz, 1H), 3.73 (s, 3H), 3.68
(s, 3H), 3.50 (s, 3H), 3.13 (dd, J = 5.0 Hz, 9.6 Hz, 1H), 2.24−2.37
(m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 194.1, 194.08,
169.4, 169.0, 158.4, 136.7, 133.6, 133.5, 133.0, 130.8, 129.8, 128.72,
128.71, 128.4, 128.3, 113.8, 64.5, 54.9, 52.4, 52.3, 49.7, 43.8, 32.9
ppm. IR (KBr, cm−1): 2996, 2952, 2838, 1749, 1723, 1688, 1595,
1580, 1515, 1446, 1362, 1335, 840, 761, 687, 564.
Dimethyl 2-(3-Benzoyl-2-(4-(benzyloxy)phenyl)-4-oxo-4-
phenylbutyl)malonate (3b). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
77.9 mg (92%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 8.01−8.04 (m, 2H), 7.71−7.73 (m,
2H), 7.53−7.57 (m, 1H), 7.40−7.45 (m, 3H), 7.27−7.37 (m, 7H),
7.12 (d, J = 8.7 Hz, 2H), 6.77 (d, J = 8.7 Hz, 2H), 5.59 (d, J = 10.3
Hz, 1H), 4.94 (s, 2H), 3.91 (td, J = 10.8 Hz, 3.8 Hz, 1H), 3.74 (s,
3H), 3.49 (s, 3H), 3.15 (dd, J = 5.2 Hz, 9.5 Hz, 1H), 2.24−2.38 (m,
2H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 194.2, 169.5,
169.1, 157.7, 136.81, 136.77, 136.7, 133.6, 133.1, 131.2, 129.9, 128.84,
128.80, 128.54, 128.50, 128.4, 127.9, 127.5, 114.8, 69.8, 64.7, 52.5,
52.4, 49.8, 43.8, 33.0 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C35H33O7 565.2221; Found 565.2224.
Sc(OTf)3. Then, the crude product was directly applied under
the standard conditions for the retro-Claisen-type C−C bond
cleavage reaction. 4a was obtained in 89% yield in two steps. In
a gram-scale reaction, 4a was accomplished in 90% yield. This
two-step procedure was then applied for further expanding the
scope for the synthesis of 1,6-dicarbonyl compounds 4
(Scheme 6). Reactions of 2a with 1-benzoylacetone derivatives
bearing electron-donating and halogen substituent on the
phenyl ring worked well to afford corresponding product in
65−82% yield (4l, 4n, 4o, 4p). The reaction of 2a with 1-(4-
nitrophenyl)butane-1,3-dione afforded 4q and 4r in a ratio of
1:2. The results indicated that the retro-Claisen-type C−C
bond cleavage was less site-selective for strong electron-
withdrawing group substituted substrates.
To conclude, we developed the ring-opening reactions of
D−A cyclopropanes with acyclic 1,3-diketones, which
selectively worked as C-nucleophiles, to furnish 1,6-dicarbonyl
compounds 3. The ring-opening products 3 underwent retro-
Claisen-type C−C bond cleavage reaction in the presence of
DBU in methanol to afford a series of new 1,6-dicarbonyl
compounds 4. We also developed the synthesis of 1,6-
dicarbonyl compounds 4 without the isolation of intermediates
3. 1,6-Dicarbonyl compounds 4 represent the formal addition
products of the α-position of acetophenone derivatives to D−A
cyclopropanes. The direct additions of acetophenone deriva-
tives to D−A cyclopropanes are difficult. The method we
developed here provides an alternative pathway for the
additions of acetophenone derivatives to D−A cyclopropanes
under mild conditions for the synthesis of 1,6-dicarbonyl
compounds.
EXPERIMENTAL SECTION
■
1H NMR and 13C NMR were recorded on a Bruker-400 MHz
spectrometer. Proton chemical shifts were reported in ppm downfield
from tetramethylsilane or from the residual solvent as internal
standard in CDCl3 (δ 7.26 ppm). Carbon chemical shifts were
internally referenced to the deuterated solvent signals in CDCl3 (δ
77.0 ppm). High-resolution mass spectra were recorded on a Thermo
Scientific LTQ Orbitrap ESI ion trap mass spectrometer. Reagents
obtained from commercial sources were used without further
purification, and all solvents were purified and dried according to
standard methods prior to use unless stated otherwise.
Dimethyl 2-(3-Benzoyl-4-oxo-4-phenyl-2-(p-tolyl)butyl)-
malonate (3c). Synthesized by the general procedure B, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 62.4 mg
1
(88%). Colorless amorphous solid. New compound. H NMR (400
MHz, CDCl3): δ = 8.06 (d, J = 6.5 Hz, 2H), 7.76 (d, J = 6.5 Hz, 2H),
7.23−7.56 (m, 6H), 6.91−7.14 (m, 4H), 5.67 (d, J = 9.9 Hz, 1H),
3.95 (s, 1H), 3.76 (s, 3H), 3.52 (s, 3H), 3.16 (s, 1H), 2.36 (d, J = 4.3
Hz, 2H), 2.21 (s, 3H) ppm; 13C {1H} NMR (100 MHz, CDCl3): δ =
194.2, 194.0, 169.4, 169.1, 136.73, 136.70, 136.6, 136.0, 133.6, 133.0,
129.1, 128.8, 128.7, 128.6, 128.5, 128.3, 64.6, 52.5, 52.3, 49.7, 44.1,
32.9, 20.9 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C29H29O6
473.1959; Found 473.1964.
Dimethyl 2-(3-Benzoyl-4-oxo-2,4-diphenylbutyl)malonate (3d).
Synthesized by the general procedure B, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 55.0 mg (80%).
Colorless amorphous solid. Known compound.2i 1H NMR (400
MHz, CDCl3): δ = 8.02−8.04 (m, 2H), 7.70−7.72 (m, 1H), 7.53−
7.56 (m, 1H), 7.38−7.45 (m, 3H), 7.25−7.29 (m, 2H), 7.20−7.22
(m, 2H), 7.16 (t, J = 7.5 Hz, 2H), 7.06−7.09 (m, 1H), 5.64 (d, J =
10.3 Hz, 1H), 3.95 (td, J = 10.4 Hz, 4.7 Hz, 1H), 3.74 (s, 3H), 3.48
(s, 3H), 3.11−3.15 (m, 1H), 2.28−2.40 (m, 2H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 194.1, 194.0, 169.4, 169.1, 139.1,
136.7, 136.6, 133.1, 128.83, 128.80, 128.51, 128.49, 128.4, 127.2,
127.1, 64.5, 52.6, 52.4, 49.8, 44.6, 32.8 ppm. HRMS (ESI) m/z: [M +
H]+ Calcd for C28H27O6 459.1802; Found 459.1805.
D−A cyclopropanes 2 used in this study were all prepared
according to literature procedures from the corresponding aromatic
aldehydes through a sequence of Knoevenagel condensation followed
by a Corey−Chaykovsky cyclopropanation. Compounds 2 are all
known compounds, and the characterization data all corresponded to
the reported values.6a
General Procedure A for the Synthesis of 3. To a mixture of
D−A cyclopropanes 2 (0.15 mmol, 1.0 equiv) and acyclic 1,3-
dicarbonyl compounds 1 (0.18 mmol, 1.2 equiv) in CH2Cl2 (1.0 mL),
Sc(OTf)3 (3.7 mg, 0.0075 mmol, 0.05 equiv) was added. The mixture
was stirred at room temperature (25 °C) for 24 h. Then, the solvent
was removed in vacuo, and the residue was purified by silica gel flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1) to
provide product 3.
General Procedure B for the Synthesis of 3. To a mixture of
D−A cyclopropanes 2 (0.15 mmol, 1.0 equiv) and acyclic 1,3-
dicarbonyl compounds 1 (0.18 mmol, 1.2 equiv) in 1,2-dichloro-
ethane (1.0 mL), Sc(OTf)3 (7.4 mg, 0.015 mmol, 0.1 equiv) was
added. The mixture was stirred at 45 °C for 24 h. Then, the solvent
was removed in vacuo and the residue was purified by silica gel flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1) to
provide product 3.
Dimethyl 2-(3-Benzoyl-2-(4-chlorophenyl)-4-oxo-4-phenylbutyl)-
malonate (3e). Synthesized by the general procedure B, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 54.0 mg
1
(73%). Colorless amorphous solid. New compound. H NMR (400
MHz, CDCl3): δ = 8.02 (d, J = 7.5 Hz, 2H), 7.72 (d, J = 7.5 Hz, 2H),
7.55 (t, J = 7.3 Hz, 1H), 7.42−7.45 (m, 3H), 7.27−7.31 (m, 2H),
7.12−7.17 (m, 4H), 5.59 (d, J = 10.2 Hz, 1H), 3.94 (td, J = 10.8 Hz,
3.6 Hz, 1H), 3.73 (s, 3H), 3.50 (s, 3H), 3.09 (dd, J = 5.0 Hz, 9.6 Hz,
Procedure for a 5 mmol-Scale Reaction to Synthesize 3a.
To a mixture of D−A cyclopropanes 2a (1.32 g, 5.0 mmol) and
D
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Note
1H), 2.24−2.38 (m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ
= 193.9, 193.8, 169.2, 168.9, 137.8, 136.7, 136.5, 133.8, 133.0, 130.2,
128.9, 128.8, 128.6, 128.53, 128.50, 64.4, 52.6, 52.4, 49.7, 44.0, 32.9
ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C28H26ClO6 493.1412;
Found 493.1414. IR (KBr, cm−1): 2955, 1749, 1722, 1697, 1593,
1578, 1493, 1445, 1348, 1302, 1092, 845, 762, 686, 536.
Dimethyl 2-(3-Benzoyl-2-(3-methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (3f). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
64.5 mg (88%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 7.6 Hz, 2H), 7.77 (d, J =
7.6 Hz, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.7 Hz, 3H), 7.31 (t,
J = 7.7 Hz, 2H), 7.10 (t, J = 7.9 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H),
6.76 (s, 1H), 6.64 (dd, J = 1.8 Hz, 8.2 Hz, 1H), 5.68 (d, J = 10.2 Hz,
1H), 3.95 (td, J = 10.7 Hz, 3.6 Hz, 1H), 3.77 (s, 3H), 3.70 (s, 3H),
3.54 (s, 3H), 3.18 (dd, J = 4.9 Hz, 9.7 Hz, 1H), 2.23−2.42 (m, 2H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 194.1, 193.9, 169.4,
169.0, 159.4, 140.8, 136.8, 136.7, 133.6, 133.0, 129.5, 128.78, 128.75,
128.5, 128.4, 121.0, 114.6, 112.7, 64.3, 55.0, 52.5, 52.3, 49.7, 44.6,
32.8 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C29H29O7
489.1908; Found 489.1912.
Dimethyl 2-(3-Benzoyl-2-(2-methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (3g). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
64.5 mg (83%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 7.4 Hz, 2H), 7.77 (d, J =
7.5 Hz, 2H), 7.51−7.54 (m, 1H), 7.39−7.44 (m, 3H), 7.27 (t, J = 7.7
Hz, 2H), 7.12 (d, J = 7.3 Hz, 1H), 7.05 (dt, J = 7.8 Hz, 1.6 Hz, 1H),
6.74−6.78 (m, 1H), 6.65 (d, J = 8.1 Hz, 1H), 6.07 (s, 1H), 4.10 (s,
1H), 3.80 (s, 3H), 3.68 (s, 3H), 3.44 (s, 3H), 3.16 (dd, J = 5.3 Hz, 9.3
Hz, 1H), 2.61−2.69 (m, 1H), 2.23−2.30 (m, 1H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 194.7, 194.6, 169.6, 169.2, 157.6,
137.1, 136.6, 133.4, 132.9, 131.6, 128.70, 128.68, 128.4, 128.3, 128.2,
126.3, 120.6, 110.5, 60.9, 55.0, 52.4, 52.2, 50.3, 30.5 ppm. HRMS
(ESI) m/z: [M + H]+ Calcd for C29H29O7 489.1908; Found
489.1913.
2H), 7.51−7.55 (m, 1H), 7.38−7.44 (m, 3H), 7.25−7.29 (m, 2H),
7.12 (d, J = 8.7 Hz, 2H), 6.67−6.70 (m, 2H), 5.59 (d, J = 10.4 Hz,
1H), 5.06−5.15 (m, 1H), 4.78−4.87 (m, 1H), 3.90−3.96 (m, 1H),
3.68 (s, 3H), 2.98 (dd, J = 4.4 Hz, 10.3 Hz, 1H), 2.18−2.34 (m, 2H),
1.28 (dd, J = 6.3 Hz, 10.2 Hz, 6H), 1.10 (dd, J = 5.1 Hz, 6.2 Hz, 6H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 194.2, 194.1, 168.7,
168.2, 158.5, 137, 136.9, 133.5, 133.0, 131.2, 129.9, 128.82, 128.76,
128.5, 128.4, 113.9, 68.84, 68.80, 64.9, 55.1, 50.3, 43.7, 32.9, 21.6,
21.5, 21.43, 21.36 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C33H37O7 545.2534; Found 545.2538. IR (KBr, cm−1): 2978, 2934,
1748, 1718, 1693, 1611, 1596, 1514, 1448, 1374, 1264, 1206, 1179,
1097, 969, 763, 688, 553.
Di(adamantan-2-yl) 2-(3-Benzoyl-2-(4-methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (3k). Synthesized by the general procedure A,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
95.1 mg (87%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 8.04−8.07 (m, 2H), 7.71−7.73 (m,
2H), 7.53−7.57 (m, 1H), 7.39−7.46 (m, 3H), 7.27 (t, J = 7.7 Hz,
2H), 7.15 (d, J = 8.7 Hz, 2H), 6.70 (d, J = 8.7 Hz, 2H), 5.62 (d, J =
10.3 Hz, 1H), 5.04 (s, 1H), 4.74 (s, 1H), 3.92−3.98 (m, 1H), 3.70 (s,
3H), 3.11 (dd, J = 4.4 Hz, 10.0 Hz, 1H), 2.24−2.39 (m, 2H), 1.41−
1.97 (m, 28H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 194.11,
194.05, 168.7, 168.3, 158.5, 137.0, 136.9, 133.5, 133, 131.4, 129.9,
128.82, 128.81, 128.5, 128.4, 113.9, 64.6, 55.1, 50.6, 44.0, 37.4, 37.2,
36.3, 36.2, 36.1, 33.2, 31.9, 31.7, 31.5, 27.2, 27.04, 26.98, 26.8 ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C47H53O7 729.3786; Found
729.3792.
Dimethyl 2-(3-Benzoyl-2-(4-methoxyphenyl)-5-methyl-4-
oxohexyl)malonate (3l). Synthesized by the general procedure A,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), dr
= 1:0.8, 62.0 mg (91%). Colorless amorphous solid. New compound.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 7.4 Hz, 2H × 0.8), 7.71
(d, J = 7.4 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H × 0.8), 7.43−7.49 (m, 2H
× 0.8 + 1H), 7.31 (t, J = 7.7 Hz, 2H), 7.15 (d, J = 8.6 Hz, 2H × 0.8),
7.01 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H × 0.8), 6.64 (d, J =
8.6 Hz, 2H), 5.01 (d, J = 10.8 Hz, 1H × 0.8), 4.95 (d, J = 10.8 Hz,
1H), 3.752 (s, 3H), 3.747 (s, 3H × 0.8), 3.74 (s, 3H × 0.8), 3.64 (s,
3H), 3.52 (s, 3H), 3.47 (s, 3H × 0.8), 3.03−3.07 (m, 1H × 1.8), 2.84
(quintet, J = 6.8 Hz, 1H), 2.53 (quintet, J = 6.8 Hz, 1H × 0.8), 2.00−
2.23 (m, 2H × 1.8), 1.03 (d, J = 7.0 Hz, 3H), 0.97 (d, J = 7.0 Hz,
3H), 0.56 (d, J = 6.7 Hz, 3H × 0.8), 0.53 (d, J = 6.7 Hz, 3H × 0.8)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 208.5, 207.8, 194.4,
194.1, 169.4, 169.3, 169.1, 169.0, 158.7, 158.4, 137.00, 136.99, 133.7,
133.2, 130.9, 130.7, 129.8, 129.4, 128.8, 128.7, 128.5, 128.2, 114.0,
113.8, 68.7, 68.6, 55.1, 55.0, 52.54, 52.50, 52.4, 52.3, 49.5, 49.4, 43.2,
42.8, 39.3, 33.6, 33.1, 19.4, 18.9, 18.1, 17.6 ppm. HRMS (ESI) m/z:
[M + H]+ Calcd for C26H31O7 455.2064; Found 455.2070.
Dimethyl 2-(3-Benzoyl-2-(1-(tert-butoxycarbonyl)-1H-indol-3-
yl)-4-oxo-4-phenylbutyl)malonate (3h). Synthesized by the general
procedure A, flash chromatography (petroleum ether:ethyl acetate =
4:1 to 2:1), 77.1 mg (86%). Pale yellow amorphous solid. New
1
compound. H NMR (400 MHz, CDCl3): δ = 7.96−7.99 (m, 3H),
7.65−7.68 (m, 2H), 7.61−7.63 (m, 1H), 7.52−7.56 (m, 1H), 7.35−
7.44 (m, 3H), 7.31 (br, 1H), 7.19−7.27 (m, 4H), 5.78 (d, J = 9.5 Hz,
1H), 4.19−4.26 (m, 1H), 3.73 (s, 3H), 3.47 (s, 3H), 3.29 (dd, J = 7.2
Hz, 8.9 Hz, 1H), 2.44−2.52 (m, 2H), 1.62 (s, 9H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 194.4, 194.3, 169.4, 169.1, 149.2,
136.7, 136.4, 135.4, 133.6, 133.0, 129.3, 128.8, 128.7, 128.33, 128.27,
125.0, 124.5, 122.6, 119.4, 118.6, 115.2, 83.7, 62.5, 52.5, 52.3, 49.9,
35.5, 32.0, 28.1 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C35H36NO8 598.2435; Found 598.2439. IR (KBr, cm−1): 2979, 2953,
1734, 1697, 1667, 1596, 1580, 1450, 1373, 1257, 1094, 748, 689, 557.
Dimethyl 2-(3-Benzoyl-4-oxo-4-phenyl-2-(thiophen-2-yl)butyl)-
malonate (3i). Synthesized by the general procedure A, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 66.2
Dimethyl 2-(3-Benzoyl-2-(4-methoxyphenyl)-5,5-dimethyl-4-
oxohexyl)malonate (3m). Synthesized by the general procedure A,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), dr
= 1:0.65, 65.4 mg (93%). Colorless amorphous solid. New
1
compound. H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 7.5 Hz,
2H × 0.65), 7.59−7.63 (m, 2H+1H × 0.65), 7.52 (d, J = 7.6 Hz, 2H
× 0.65), 7.40 (t, J = 7.3 Hz, 1H), 7.27 (t, J = 7.7 Hz, 2H), 7.16 (d, J =
8.5 Hz, 2H × 0.65), 7.00 (d, J = 8.6 Hz, 2H), 6.80 (d, J = 8.5 Hz, 2H
× 0.65), 6.58 (d, J = 8.6 Hz, 2H), 5.29 (d, J = 10.7 Hz, 1H × 0.65),
5.21 (d, J = 10.0 Hz, 1H), 3.75 (s, 3H × 0.65), 3.71 (s, 3H), 3.66 (s,
3H × 0.65), 3.61 (s, 3H), 3.49 (s, 3H), 3.44 (s, 3H × 0.65), 3.07 (dd,
J = 4.6 Hz, 9.8 Hz, 1H), 3.00 (dd, J = 4.4 Hz, 9.8 Hz, 1H × 0.65),
2.33 (td, J = 12.9 Hz, 4.7 Hz, 1H), 2.13−2.25 (m, 1H × 1.65), 2.02−
2.09 (m, 1H × 0.65), 1.05 (s, 9H), 0.69 (s, 9H × 0.65) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 207.7, 206.6, 194.4, 194.0, 169.5,
169.4, 169.0, 168.9, 158.6, 158.5, 137.3, 136.7, 133.6, 132.8, 131.7,
129.9, 129.8, 128.9, 128.7, 128.4, 128.2, 113.8, 113.7, 62.2, 61.5, 55.1,
55.0, 52.5, 52.3, 49.83, 49.81, 45.32, 45.24, 45.16, 45.1, 32.4, 32.0,
26.2, 25.7 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C27H33O7
469.2221; Found 469.2225.
1
mg (95%). Light red amorphous solid. New compound. H NMR
(400 MHz, CDCl3): δ = 7.98 (d, J = 7.5 Hz, 2H), 7.80 (d, J = 7.6 Hz,
2H), 7.51 (t, J = 7.3 Hz, 1H), 7.37−7.46 (m, 3H), 7.30 (t, J = 7.7 Hz,
2H), 7.02 (d, J = 5.0 Hz, 1H), 6.81 (d, J = 3.0 Hz, 1H), 6.73 (dd, J =
3.6 Hz, 4.9 Hz, 1H), 5.67−5.69 (m, 1H), 4.26−4.32 (m, 1H), 3.73 (s,
3H), 3.55 (s, 3H), 3.30 (dd, J = 4.2 Hz, 10.4 Hz, 1H), 2.38−2.45 (m,
1H), 2.27−2.35 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ
= 193.7, 193.5, 169.2, 168.8, 142.4, 136.4, 136.2, 133.6, 133.2, 128.7,
128.6, 128.44, 128.40, 127.3, 126.6, 124.4, 64.2, 52.5, 52.4, 49.6, 39.9,
34.1 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C26H25O6S
465.1366; Found 465.1369.
Diisopropyl 2-(3-Benzoyl-2-(4-methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (3j). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
73.5 mg (90%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 8.02−8.05 (m, 2H), 7.70−7.72 (m,
Dimethyl 2-(3-Benzoyl-5,5,5-trifluoro-2-(4-methoxyphenyl)-4-
oxopentyl)malonate (3n). Synthesized by the general procedure A,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
E
https://dx.doi.org/10.1021/acs.joc.0c02290
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
major diastereomer, dr = 1:4, 48.4 mg (67%). Pale yellow amorphous
solid. New compound. 1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J =
7.4 Hz, 2H), 7.47 (t, J = 7.3 Hz, 1H), 7.28−7.35 (m, 4H), 6.74 (d, J =
8.7 Hz, 2H), 6.48 (s, 1H), 4.66 (d, J = 11.6 Hz, 2H), 3.93 (dd, J =
10.2 Hz, 20.1 Hz, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 3.70 (s, 3H), 3.13
(dd, J = 10.4 Hz, 14.5 Hz, 1H), 2.80 (dd, J = 8.9 Hz, 14.5 Hz, 1H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 201.9, 196.1 (C−F,
2JC,F = 29.7 Hz), 170.4, 168.9, 158.8, 136.9, 133.9, 131.9, 128.7, 128.5,
2.24 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 198.0,
169.6, 169.5, 157.6, 136.9, 136.8, 134.6, 133.0, 128.7, 128.51, 128.50,
127.94, 127.90, 127.4, 114.9, 69.9, 52.5, 52.4, 49.8, 45.8, 38.2, 35.2
ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C28H29O6 461.1959;
Found 461.1963. IR (KBr, cm−1): 2957, 2923, 1730, 1683, 1609,
1581, 1510, 1449, 1360, 1083, 1018, 800, 737, 692, 557.
Dimethyl 2-(4-Oxo-4-phenyl-2-(p-tolyl)butyl)malonate (4c). Syn-
thesized by the general procedure, flash chromatography (petroleum
ether:ethyl acetate = 4:1 to 2:1), 33.9 mg (92%). Colorless gum.
Known compound.8b 1H NMR (400 MHz, CDCl3): δ = 7.87−7.89
(m, 1H), 7.51−7.55 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.08−7.13 (m,
4H), 3.74 (s, 3H), 3.58 (s, 3H), 3.22−3.36 (m, 3H), 3.19 (dd, J = 5.0
Hz, 9.9 Hz, 1H), 2.36−2.42 (m, 1H), 2.29 (s, 3H), 2.18−2.24 (m,
1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 198.0, 169.6,
169.5, 139.4, 136.9, 136.4, 133.0, 129.3, 128.5, 128.0, 127.6, 52.5,
52.4, 49.8, 45.8, 38.5, 35.1, 21.0 ppm.
Dimethyl 2-(4-Oxo-2,4-diphenylbutyl)malonate (4d). Synthe-
sized by the general procedure, flash chromatography (petroleum
ether:ethyl acetate = 4:1 to 2:1), 33.3 mg (94%). Colorless gum.
Known compound.8b 1H NMR (400 MHz, CDCl3): δ = 7.87−7.89
(m, 2H), 7.51−7.55 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.27−7.31 (m,
2H), 7.18−7.26 (m, 3H), 3.75 (s, 3H), 3.57 (s, 3H), 3.24−3.41 (m,
3H), 3.20 (dd, J = 5.2 Hz, 9.7 Hz, 1H), 2.37−2.44 (m, 1H), 2.20−
2.28 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 197.9,
169.6, 169.5, 142.5, 136.8, 133.0, 128.6, 128.5, 127.9, 127.7, 126.9,
52.5, 52.4, 49.8, 45.7, 38.9, 35.0 ppm. IR (KBr, cm−1): 2951, 2932,
2851, 1756, 1733, 1687, 1597, 1580, 1495, 1450, 1437, 1371, 1358,
1049, 748, 706, 690.
Dimethyl 2-(2-(4-Chlorophenyl)-4-oxo-4-phenylbutyl)malonate
(4e). Synthesized by the general procedure, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 35.8 mg (92%).
Colorless gum. Known compound.8b 1H NMR (400 MHz, CDCl3): δ
= 7.86 (d, J = 7.3 Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.5
Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 3.75 (s,
3H), 3.59 (s, 3H), 3.22−3.40 (m, 3H), 3.16 (dd, J = 5.2 Hz, 9.6 Hz,
1H), 2.36−2.42 (m, 1H), 2.18−2.24 (m, 1H) ppm; 13C{1H} NMR
(100 MHz, CDCl3): δ = 197.5, 169.43, 169.36, 141.0, 136.7, 133.1,
132.6, 129.1, 128.8, 128.6, 127.9, 52.6, 52.5, 49.7, 45.5, 38.4, 35.1
ppm.
1
128.4, 124.2 (C−F, JC,F = 285.3 Hz), 114.2, 86.7, 65.4, 55.2, 53.5,
53.0, 46.6, 40.8 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C24H24F3O7 481.1469; Found 481.1474.
4-Ethyl 1,1-Dimethyl 3-(4-methoxyphenyl)-5-oxo-5-phenylpen-
tane-1,1,4-tricarboxylate (3o). Synthesized by the general procedure
A, flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
dr 1:1, 63.0 mg (92%). Colorless gum. Known compound.6a 1H NMR
(400 MHz, CDCl3): δ = 8.05−8.07 (m, 2H), 7.77−7.80 (m, 2H),
7.56 (t, J = 7.3 Hz, 1H), 7.43−7.47 (m, 3H), 7.33 (t, J = 7.3 Hz, 2H),
7.18 (d, J = 8.6 Hz, 2H), 7.06 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.6 Hz,
2H), 6.80 (d, J = 8.6 Hz, 2H), 4.70 (d, J = 10.7 Hz, 1H), 4.63 (d, J =
10.7 Hz, 1H), 4.12−4.22 (m, 2H), 3.751 (s, 3H), 3.746 (s, 3H), 3.65
(s, 3H), 3.53 (s, 3H), 3.47 (s, 3H), 3.10 (dt, J = 4.7 Hz, 10.3 Hz, 2H),
2.03−2.42 (m, 4H), 1.20 (t, J = 7.2 Hz, 3H), 0.83 (t, J = 7.2 Hz, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 193.0, 192.6, 169.4,
169.3, 169.1, 168.0, 167.4, 158.7, 158.4, 137.7, 136.4, 136.3, 133.6,
131.2, 131.0, 129.7, 129.3, 128.6, 128.4, 128.3, 113.8, 113.7, 61.7,
61.2, 61.0, 60.6, 55.0, 54.9, 52.5, 52.4, 52.3, 52.2, 49.7, 49.4, 42.4,
42.3, 33.4, 32.9, 13.8, 13.5 ppm.
Dimethyl 2-(3-(4-(tert-Butyl)benzoyl)-2,4-bis(4-methoxyphenyl)-
4-oxobutyl)malonate (3p). Synthesized by the general procedure A,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), dr
= 1:1, 76.7 mg (89%). Colorless amorphous solid. New compound.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.6 Hz, 2H × 0.5), 7.77
(d, J = 9.0 Hz, 2H × 0.5), 7.69 (d, J = 8.6 Hz, 2H × 0.5), 7.42 (d, J =
8.5 Hz, 2H × 0.5), 7.28 (d, J = 8.6 Hz, 2H × 0.5), 7.11−7.14 (m, 4H
× 0.5), 6.90 (d, J = 8.9 Hz, 2H × 0.5), 6.76 (d, J = 8.9 Hz, 2H × 0.5),
6.69 (d, J = 8.6 Hz, 4H × 0.5), 5.50 (s, 1H × 0.5), 5.47 (s, 1H × 0.5),
3.87−3.92 (m, 1H), 3.83 (s, 3H × 0.5), 3.77 (s, 3H × 0.5), 3.72 (s,
3H), 3.68 (s, 3H), 3.49 (s, 3H), 3.09−3.14 (m, 1H), 2.21−2.36 (m,
2H), 1.29 (s, 9H × 0.5), 1.24 (s, 9H × 0.5) ppm; 13C{1H} NMR (100
MHz, CDCl3): δ = 194.0, 193.8, 192.7, 192.4, 169.5, 169.1, 163.8,
163.4, 158.4, 157.3, 156.8, 134.3, 134.2, 131.5, 131.3, 131.2, 131.1,
129.9, 129.8, 129.7, 128.8, 128.5, 125.7, 125.3, 113.9, 113.8, 113.6,
64.8, 55.4, 55.3, 55.0, 52.4, 52.3, 49.8, 43.8, 43.6, 35.0, 34.9, 33.1,
33.0, 30.91, 30.87 ppm. HRMS (ESI): calcd. for C34H39O8 ([M +
H]+) 575.2639, found 575.2645.
General Procedure for the Synthesis of 4 from 3. To 3 (0.10
mmol, 1.0 equiv) in MeOH (1.0 mL), DBU (6.0 μL, 0.04 mmol, 0.4
equiv) was added. The mixture was stirred at 50 °C for 12 h. Then,
the solvent was removed in vacuo, and the residue was purified by
silica gel flash chromatography (petroleum ether:ethyl acetate = 4:1 to
2:1) to provide product 4.
Dimethyl 2-(2-(3-Methoxyphenyl)-4-oxo-4-phenylbutyl)-
malonate (4f). Synthesized by the general procedure, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 35.0
1
mg (91%). Colorless gum. New compound. H NMR (400 MHz,
CDCl3): δ = 7.87−7.89 (m, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.42 (t, J =
7.6 Hz, 2H), 7.21 (t, J = 7.8 Hz, 1H), 6.73−6.83 (m, 3H), 3.78 (s,
3H), 3.75 (s, 3H), 3.59 (s, 3H), 3.19−3.37 (m, 4H), 2.36−2.42 (m,
1H), 2.17−2.24 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ
= 197.9, 169.6, 169.5, 159.7, 144.2, 136.9, 133.0, 129.7, 128.5, 128.0,
120.0, 113.7, 112.1, 55.1, 52.5, 52.4, 49.8, 45.6, 39.0, 35.0 ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C22H25O6 385.1646; Found
385.1651.
Dimethyl 2-(2-(2-Methoxyphenyl)-4-oxo-4-phenylbutyl)-
malonate (4g). Synthesized by the general procedure, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 34.5
Dimethyl 2-(2-(4-Methoxyphenyl)-4-oxo-4-phenylbutyl)-
malonate (4a). Synthesized by the general procedure, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 37.7
mg (98%). Colorless gum. Known compound.6a 1H NMR (400 MHz,
CDCl3): δ = 7.86−7.88 (m, 2H), 7.52 (t, J = 7.4 Hz, 1H), 7.41 (t, J =
7.6 Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H), 3.76
(s, 3H), 3.74 (s, 3H), 3.58 (s, 3H), 3.17−3.34 (m, 4H), 2.34−2.41
(m, 1H), 2.15−2.22 (m, 1H) ppm; 13C{1H} NMR (100 MHz,
CDCl3): δ = 198.0, 169.6, 169.5, 158.3, 136.8, 134.4, 132.9, 128.6,
128.5, 127.9, 114.0, 55.1, 52.5, 52.4, 49.8, 45.8, 38.2, 35.2 ppm. IR
(KBr, cm−1): 2953, 2838, 1733, 1685, 1611, 1597, 1581, 1513, 1448,
1358, 1249, 1034, 832, 758, 692, 561.
1
mg (90%). Colorless gum. New compound. H NMR (400 MHz,
CDCl3): δ = 7.89−7.91 (m, 2H), 7.50−7.54 (m, 1H), 7.41 (t, J = 15.2
Hz, 2H), 7.14−7.26 (m, 2H), 6.89 (td, J = 7.4 Hz, 0.8 Hz, 1H), 6.83
(d, J = 8.1 Hz, 1H), 3.78 (s, 3H), 3.71−3.75 (m, 1H), 3.70 (s, 3H),
3.54 (s, 3H), 3.41 (dd, J = 6.5 Hz, 16.7 Hz, 1H), 3.29 (dd, J = 7.4 Hz,
16.7 Hz, 1H), 3.20−3.24 (m, 1H), 2.35−2.39 (m, 2H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 198.6, 169.8, 169.5, 157.4, 136.9,
132.8, 130.0, 128.8, 128.4, 128.0, 127.8, 120.6, 110.7, 55.1, 52.4, 52.3,
50.0, 44.1, 34.0, 33.3 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C22H25O6 385.1646; Found 385.1650.
Dimethyl 2-(2-(1-(tert-Butoxycarbonyl)-1H-indol-3-yl)-4-oxo-4-
phenylbutyl)malonate (4h). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
15.3 mg (31%). Colorless gum. New compound. 1H NMR (400
MHz, CDCl3): δ = 8.12 (br, 1H) ppm, 7.88−7.91 (m, 2H), 7.60−
7.62 (m, 1H), 7.51−7.56 (m, 1H), 7.40−7.44 (m, 3H), 7.28−7.32
Dimethyl 2-(2-(4-(Benzyloxy)phenyl)-4-oxo-4-phenylbutyl)-
malonate (4b). Synthesized by the general procedure, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 41.4
1
mg (90%). Colorless gum. New compound. H NMR (400 MHz,
CDCl3): δ = 7.87−7.89 (m, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.30−7.44
(m, 7H), 7.14 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 3.75 (s,
3H), 3.57 (s, 3H), 3.19−3.35 (m, 4H), 2.35−2.42 (m, 1H), 2.17−
F
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Note
(m, 1H), 7.22−7.26 (m, 1H), 3.70−3.74 (m, 4H), 3.58 (s, 3H),
3.34−3.48 (m, 3H), 2.41−2.49 (m, 2H), 1.66 (s, 9H); 13C{1H} NMR
(100 MHz, CDCl3): δ = 197.9, 169.6, 169.5, 136.9, 135.7, 133.1,
129.4, 128.6, 128.0, 124.5, 123.0, 122.5, 121.9, 119.4, 115.4, 83.7,
52.5, 52.4, 50.0, 44.4, 34.0, 30.0, 28.2 ppm. HRMS (ESI) m/z: [M +
H]+ Calcd for C28H32NO7 494.2173; Found 494.2174.
[M + H]+ Calcd for C23H27O7 415.1751; Found 415.1750. IR (KBr,
cm−1): 2954, 2840, 1732, 1676, 1600, 1577, 1512, 1438, 1251, 1030,
833, 735, 701, 560.
Dimethyl 2-(4-(4-(tert-Butyl)phenyl)-2-(4-methoxyphenyl)-4-
oxobutyl)malonate (4m). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
31.7 mg (36%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8.5 Hz, 2H), 7.43 (t, J =
8.5 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 3.76
(s, 3H), 3.74 (s, 3H), 3.58 (s, 3H), 3.17−3.31 (m, 4H), 2.34−2.41
(m, 1H), 2.15−2.22 (m, 1H), 1.32 (s, 9H) ppm; 13C{1H} NMR (100
MHz, CDCl3): δ = 197.7, 169.7, 169.6, 158.3, 156.7, 134.5, 134.4,
128.7, 127.9, 125.4, 114.0, 55.2, 52.5, 52.4, 49.9, 45.8, 38.2, 35.3, 35.0,
31.0 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C26H33O6
441.2272; Found 441.2274.
General Procedure for the Synthesis of 4 without the
Isolation of 3. To a mixture of D−A cyclopropanes 2a (52.8 mg, 0.2
mmol, 1.0 equiv) and 1-benzoylacetone derivative 1 (0.24 mmol, 1.2
equiv) in CH2Cl2 (1.5 mL), Sc(OTf)3 (4.9 mg, 0.01 mmol, 0.05
equiv) was added. The mixture was stirred at room temperature (25
°C) for 24 h. Then, the mixture was diluted with CH2Cl2 (3.0 mL)
and washed with saturated NaHCO3. The aqueous phase was
extracted with CH2Cl2 (5 mL × 3). The organic layers were
combined, washed with brine, dried over Na2SO4, and the solvent was
removed in vacuo. The residue was dissolved in MeOH (2.0 mL), and
DBU (12.0 μL, 0.08 mmol, 0.4 equiv) was added. The mixture was
stirred at 50 °C for 12 h. Then, the solvent was removed in vacuo, and
the residue was purified by silica gel flash chromatography (petroleum
ether:ethyl acetate = 4:1 to 2:1) to provide product 4.
Procedure for a 5 mmol-Scale Reaction to Synthesize 4a.
To a mixture of D−A cyclopropanes 2a (1.32 g, 5.0 mmol) and 1-
benzoylacetone (973.1 mg, 6.0 mmol) in CH2Cl2 (25.0 mL),
Sc(OTf)3 (123.0 mg, 0.25 mmol) was added. The mixture was
stirred at room temperature (25 °C) for 40 h. Then, the mixture was
diluted with CH2Cl2 (25.0 mL) and washed with saturated NaHCO3.
The aqueous phase was extracted with CH2Cl2 (25 mL × 3). The
organic layers were combined, washed with brine, dried over Na2SO4,
and the solvent was removed in vacuo. The residue was dissolved in
MeOH (50.0 mL), and DBU (0.3 mL, 2.0 mmol) was added. The
mixture was stirred at 50 °C for 16 h. Then, the solvent was removed
in vacuo, and the residue was purified by silica gel flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1) to
provide product 4a (1.73 g, 90%).
Dimethyl 2-(2-(1H-Indol-3-yl)-4-oxo-4-phenylbutyl)malonate
(4h′). Synthesized by the general procedure, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 21.6 mg (55%).
1
Colorless gum. New compound. H NMR (400 MHz, CDCl3): δ =
8.08 (br, 1H), 7.86−7.89 (m, 2H), 7.67 (d, J = 7.9 Hz, 1H), 7.49−
7.53 (m, 1H), 7.38−7.42 (m, 1H), 7.33−7.35 (m, 1H), 7.18 (td, J =
7.5 Hz, 1.1 Hz, 1H), 7.09−7.13 (m, 1H), 7.04 (d, J = 2.4 Hz, 1H),
3.67−3.76 (m, 4H), 3.48−3.54 (m, 4H), 3.34−3.43 (m, 2H), 2.44−
2.55 (m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 198.6,
169.8, 169.7, 137.0, 136.6, 132.9, 128.5, 128.0, 126.2, 122.3, 122.0,
119.4, 119.3, 116.8, 111.4, 52.4, 52.3, 50.3, 44.9, 34.2, 31.0 ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C23H24NO5 394.1649; Found
394.1670.
Dimethyl 2-(4-Oxo-4-phenyl-2-(thiophen-2-yl)butyl)malonate
(4i). Synthesized by the general procedure, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 34.2 mg (95%).
1
Colorless gum. New compound. H NMR (400 MHz, CDCl3): δ =
7.89−7.91 (m, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H),
7.14 (dd, J = 0.8 Hz, 4.8 Hz, 1H), 6.87−6.91 (m, 2H), 3.71−3.78 (m,
4H), 3.63 (s, 3H), 3.25−3.43 (m, 3H), 2.41−2.48 (m, 1H), 2.17−
2.25 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 197.4,
169.5, 169.4, 146.1, 136.7, 133.1, 128.5, 128.0, 126.7, 125.1, 123.8,
52.6, 52.5, 49.7, 46.5, 36.1, 34.3 ppm. HRMS (ESI) m/z: [M + H]+
Calcd for C19H21O5S 361.1104; Found 361.1102. IR (KBr, cm−1):
2954, 2927, 2853, 1757, 1734, 1686, 1597, 1579, 1415, 1361, 1307,
1049, 1029, 760, 689, 520.
Di(adamantan-2-yl) 2-(2-(4-Methoxyphenyl)-4-oxo-4-
phenylbutyl)malonate (4j). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
28.1 mg (45%). Colorless amorphous solid. New compound. 1H
NMR (400 MHz, CDCl3): δ = 7.84−7.87 (m, 2H), 7.49−7.53 (m,
1H), 7.40 (t, J = 7.6 Hz, 2H), 7.15 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.7
Hz, 2H), 5.02 (s, 1H), 4.85 (s, 1H), 3.76 (s, 3H), 3.29−3.36 (m, 2H),
3.17−3.26 (m, 2H), 2.37−2.44 (m, 1H), 2.20−2.27 (m, 1H), 1.46−
1.89 (m, 28H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 198.0,
168.8, 168.7, 158.3, 137.0, 134.6, 132.9, 128.7, 128.4, 128.0, 114.0,
78.1, 78.0, 55.1, 50.7, 46.0, 38.4, 37.5, 37.3, 37.2, 36.5, 36.27, 36.24,
36.17, 36.14, 35.0, 31.9, 31.74, 31.66, 31.64, 31.60, 31.0, 27.1, 27.0,
26.9, 26.8 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C40H49O6
625.3524; Found 625.3528. IR (KBr, cm−1): 2906, 2855, 2675, 1724,
1688, 1597, 1582, 1513, 1450, 1358, 1041, 831, 736, 691, 557.
Diethyl 2-(2-(4-Methoxyphenyl)-4-oxo-4-phenylbutyl)malonate
(4k). Synthesized by the general procedure, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 38.4 mg (93%).
Dimethyl 2-(4-(4-Fluorophenyl)-2-(4-methoxyphenyl)-4-
oxobutyl)malonate (4n). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
63.6 mg (79%). Colorless gum. New compound. 1H NMR (400
MHz, CDCl3): δ = 7.71 (td, J = 7.6 Hz, 1.8 Hz, 1H), 7.45−7.50 (m,
1H), 7.15−7.19 (m, 1H), 7.07−7.12 (m, 3H), 6.78−6.83 (m, 2H),
3.76 (s, 3H), 3.74 (s, 3H), 3.59 (s, 3H), 3.24−3.34 (m, 3H), 3.17
(dd, J = 5.0 Hz, 9.8 Hz, 1H), 2.32−2.38 (m, 1H), 2.12−2.21 (m, 1H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 196.5, 169.7, 169.6,
161.7 (C−F, 1JC,F = 252.6 Hz), 158.3, 134.3, 130.6, 128.7, 125.7 (C−
1
Colorless gum. New compound. H NMR (400 MHz, CDCl3): δ =
7.86−7.88 (m, 2H), 7.52 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H),
7.14 (d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.6 Hz, 2H), 4.21 (q, J = 7.1 Hz,
2H), 3.98−4.11 (m, 2H), 3.76 (s, 3H), 3.22−3.35 (m, 3H), 3.14 (dd,
J = 4.9 Hz, 10.0 Hz, 1H), 2.33−2.40 (m, 1H), 2.14−2.21 (m, 1H),
1.27 (t, J = 7.1 Hz, 3H), 1.18 (t, J = 7.1 Hz, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3): δ = 198.1, 169.3, 169.2, 158.3, 137.0, 134.5,
132.9, 128.7, 128.5, 128.0, 114.0, 61.3, 55.2, 50.1, 45.9, 38.2, 35.2,
14.1, 13.9 ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C24H29O6
413.1959; Found 413.1965.
3
2
F, JC,F = 13.0 Hz), 116.5 (C−F, JC,F = 23.7 Hz), 114.0, 55.2, 52,5,
52.4, 50.8, 49.8, 38.0, 35.3 ppm. HRMS (ESI) m/z: [M + H]+ Calcd
for C22H24FO6 403.1551; Found 403.1555.
Dimethyl 2-(4-(2-Fluorophenyl)-2-(4-methoxyphenyl)-4-
oxobutyl)malonate (4o). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
57.9 mg (72%). Colorless gum. New compound. 1H NMR (400
MHz, CDCl3): δ = 7.85−7.91 (m, 2H), 7.04−7.13 (m, 4H), 6.80−
6.83 (m, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.58 (s, 3H), 2.34−2.41 (m,
16H), 2.14−2.23 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3):
δ = 196.5, 169.6, 169.5, 165.6 (C−F, 1JC,F = 253.1 Hz), 158.4, 134.2,
133.4 (C−F, 4JC,F = 2.9 Hz), 131.3 (C−F, 3JC,F = 9.4 Hz), 130.6 (C−
Dimethyl 2-(2,4-Bis(4-methoxyphenyl)-4-oxobutyl)malonate
(4l). Synthesized by the general procedure, flash chromatography
(petroleum ether:ethyl acetate = 4:1 to 2:1), 34.0 mg (41%).
1
Colorless gum. New compound. H NMR (400 MHz, CDCl3): δ =
7.85 (d, J = 8.9 Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.9 Hz,
2H), 6.82 (d, J = 8.7 Hz, 2H), 3.84 (s, 3H), 3.76 (s, 3H), 3.74 (s,
3H), 3.58 (s, 3H), 3.13−3.34 (m, 4H), 2.33−2.41 (m, 1H), 2.15−
2.23 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 196.6,
169.7, 169.6, 163.4, 158.3, 134.6, 130.2, 130.1, 128.7, 114.0, 113.6,
55.4, 55.2, 52.5, 52.4, 49.9, 45.5, 38.4, 35.3 ppm. HRMS (ESI) m/z:
3
F, JC,F = 9.4 Hz), 128.6, 115.6 (C−F, 2JC,F = 21.7 Hz), 115.5 (C−F,
2JC,F = 21.9 Hz), 114.0, 55.1, 52.5, 52.4, 49.8, 45.8, 38.3, 35.2 ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C22H24FO6 403.1551; Found
403.1557.
G
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Note
Dimethyl 2-(4-(4-Chlorophenyl)-2-(4-methoxyphenyl)-4-
oxobutyl)malonate (4p). Synthesized by the general procedure,
flash chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1),
54.5 mg (65%). 4p was mixed with small amount of inseparable ring-
https://pubs.acs.org/10.1021/acs.joc.0c02290
Notes
The authors declare no competing financial interest.
1
opening product. Colorless gum. New compound. H NMR (400
MHz, CDCl3): δ = 7.80 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H),
7.12 (d, J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 3.76 (s, 3H), 3.75
(s, 3H), 3.58 (s, 3H), 3.16−3.31 (m, 4H), 2.33−2.40 (m, 1H), 2.12−
2.22 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 196.9,
169.6, 169.5, 158.4, 139.4, 135.2, 134.1, 129.4, 128.8, 128.6, 114.1,
55.2, 52.53, 52.46, 49.8, 45.8, 38.3, 35.2 ppm. HRMS (ESI) m/z: [M
+ H]+ Calcd for C22H24ClO6 419.1256; Found 419.1253.
ACKNOWLEDGMENTS
■
Support from the Anhui Provincial Natural Science Founda-
tion (Grant 1908085MB33) and the Anhui University of
Technology is acknowledged.
REFERENCES
■
Dimethyl 2-(2-(4-Methoxyphenyl)-4-(4-nitrophenyl)-4-oxobutyl)-
malonate (4q); Dimethyl 2-(2-(4-Methoxyphenyl)-4-oxopentyl)-
malonate (4r). Synthesized by the general procedure, flash
chromatography (petroleum ether:ethyl acetate = 4:1 to 2:1), 63.0
mg, 4q (29.3%):4r (58.5%) = 0.5:1. 4q and 4r were not able to be
separated by silica gel flash chromatography and thus were
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1
characterized as a mixture. 4q and 4r are both new compounds. H
NMR (400 MHz, CDCl3): δ = 8.25 (d, J = 9.0 Hz, 2H × 0.5, 4q),
7.99 (d, J = 9.0 Hz, 2H × 0.5, 4q), 7.05−7.11 (m, 2H+2H × 0.5, 4r
+4q), 6.80−6.84 (m, 2H+2H × 0.5, 4r+4q), 3.76 (s, 3H, 4r), 3.752
(s, 3H × 0.5, 4q), 3.750 (s, 3H × 0.5, 4q), 3.74 (s, 3H, 4r), 3.59 (s,
3H × 0.5, 4q), 3.57 (s, 3H, 4r), 3.26−3.34 (m, 3H × 0.5, 4q), 3.05−
3.22 (m, 3H, 4r), 2.65−2.77 (m, 2H, 4r), 2.35−2.42 (m, 1H × 0.5,
4q), 2.21−2.28 (m, 2H × 0.5, 4q), 2.04−2.11 (m, 1H, 4r), 2.00 (s,
3H, 4r) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 206.9, 196.7,
169.6, 169.53, 169.50, 169.4, 158.6, 158.4, 150.2, 141.3, 133.9, 133.7,
128.9, 128.60, 128.56, 123.7, 114.1, 114.0, 55.1, 52.6, 52.5, 52.4, 50.8,
49.6, 46.4, 38.2, 35.2, 30.4 ppm. HRMS (ESI) m/z: [M + H]+ Calcd
for (4q) C22H24NO8 430.1496; Found 430.1499. HRMS (ESI) m/z:
[M + H]+ Calcd for (4r) C17H23O6 323.1489; Found 323.1495.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02290.
Copies of NMR spectra (1H, 13C, 2D-NMR) (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Dongxin Zhang − Institute of Molecular Engineering and
Applied Chemistry, Anhui University of Technology, Ma’anshan,
Anhui 243002, China; orcid.org/0000-0002-2185-4692;
Email: dxzhang@ahut.edu.cn
Qian-Feng Zhang − Institute of Molecular Engineering and
Applied Chemistry, Anhui University of Technology, Ma’anshan,
Anhui 243002, China; Email: zhangqf@ahut.edu.cn
̈
2017, 19, 6666−6669. (f) Lucht, A.; Patalag, L. J.; Augustin, A. U.;
Jones, P. G.; Werz, D. B. Reactions of Donor-Acceptor Cyclopropanes
with Naphthoquinones: Redox and Lewis Acid Catalysis Working in
Concert. Angew. Chem., Int. Ed. 2017, 56, 10587−10591. (g) Zhang,
C.; Tian, J.; Ren, J.; Wang, Z. Intramolecular Parallel [4 + 3]
Cycloadditions of Cyclopropane 1,1-Diesters with [3]Dendralenes:
Efficient Construction of [5.3.0]Decane and Corresponding Poly-
cyclic Skeletons. Chem. - Eur. J. 2017, 23, 1231−1236. (h) Xia, Y.;
Chang, F. Z.; Lin, L. L.; Xu, Y. L.; Liu, X. H.; Feng, X. M. Asymmetric
Ring-Opening of Cyclopropyl Ketones with Beta-naphthols Catalyzed
by a Chiral N,N′-Dioxide-Scandium(III) Complex. Org. Chem. Front.
2018, 5, 1293−1296. (i) Richmond, E.; Vukovic, V. D.; Moran, J.
Nucleophilic Ring Opening of Donor-Acceptor Cyclopropanes
Catalyzed by a BrØnsted Acid in Hexafluoroisopropanol. Org. Lett.
2018, 20, 574−577.
Authors
Hu Cai − Institute of Molecular Engineering and Applied
Chemistry, Anhui University of Technology, Ma’anshan, Anhui
243002, China
Yan Chen − Institute of Molecular Engineering and Applied
Chemistry, Anhui University of Technology, Ma’anshan, Anhui
243002, China
Lei Yin − Institute of Molecular Engineering and Applied
Chemistry, Anhui University of Technology, Ma’anshan, Anhui
243002, China
Junchao Zhong − Institute of Molecular Engineering and
Applied Chemistry, Anhui University of Technology,
Ma’anshan, Anhui 243002, China
(3) For some very recent examples: (a) Ding, W.-P.; Zhang, G.-P.;
Jiang, Y.-J.; Du, J.; Liu, X.-Y.; Chen, Di; Ding, C.-H.; Deng, Q.-H.;
Hou, X.-L. Electron-Deficient Alkynes as Dipolarophile in Pd-
Catalyzed Enantioselective (3 + 2) Cycloaddition Reaction with
Ying Zhang − Institute of Molecular Engineering and Applied
Chemistry, Anhui University of Technology, Ma’anshan, Anhui
243002, China
Vinyl Cyclopropanes. Org. Lett. 2019, 21, 6805−6810. (b) Lucht, A.;
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