Synthetic Scope of Br?nsted Acid-Catalyzed Reactions of Carbonyl Compounds and Ethyl Diazoacetate

Article abstract of DOI:10.1021/acs.joc.0c02972

The comprehensive study of the reactions of carbonyl compounds and ethyl diazoacetate in the presence of a Br?nsted acid catalyst is described. In result, a broad range of 3-oxo-esters were synthesized from a variety of ketones and aliphatic aldehydes by 1,2-aryl/alkyl/hydride shift. Aryl-methyl ketones produced only aryl-migrated products, whereas other ketones yielded a mixture of products. For diaryl ketones, the identity of two inseparable migrated products was confirmed by two-dimensional NMR spectroscopy.

Full text of DOI:10.1021/acs.joc.0c02972

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Article
Synthetic Scope of Brønsted Acid-Catalyzed Reactions of Carbonyl
Compounds and Ethyl Diazoacetate
Mizzanoor Rahaman, M. Shahnawaz Ali, Khorshada Jahan, Damon Hinz, Jawad Bin Belayet,
Ryan Majinski, and M. Mahmun Hossain*
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ABSTRACT: The comprehensive study of the reactions of carbonyl compounds
and ethyl diazoacetate in the presence of a Brønsted acid catalyst is described. In
result, a broad range of 3-oxo-esters were synthesized from a variety of ketones and
aliphatic aldehydes by 1,2-aryl/alkyl/hydride shift. Aryl−methyl ketones produced
only aryl-migrated products, whereas other ketones yielded a mixture of products.
For diaryl ketones, the identity of two inseparable migrated products was
confirmed by two-dimensional NMR spectroscopy.
reaction using several substituted acetophenones.15 The results
are summarized in Table 1. The reaction of acetophenones and
EDA provided a good yield of product, ethyl 3-oxo-2-
arylbutanoate which was in equilibrium with enol tautomer,
ethyl 3-hydroxy-2-arylbut-2-enoate (3a−h). The enol products
were found exclusively as Z-form, which was confirmed by two-
dimensional (2D) NMR (see the Supporting Information, SI).
The Z-enol form might be stable due to the presence of
intramolecular hydrogen bonding between the hydroxy and
carbonyl group as observed in ethyl 3-hydroxy-2-phenyl-
acrylate.16 In the substituted acetophenones, the para-
substituted acetophenones bearing a weak electron-withdrawing
group such as chloro (1b), a strong electron-donating group
such as methoxy (1c), and a weak electron-donating group such
as methyl (1d) were provided almost similar yields of products.
The methyl substituent on meta- and ortho- positions (1e and
1f) yielded lower amount of products compared to the methyl
substituent on para-position (1d). Substrates bearing strong
electron-withdrawing groups on the aromatic rings provided low
yield, for example, when the 4-nitroacetophenone (1g) was
subjected to the standard reaction conditions, the desired
product (3g) was isolated in only 15% yield, and most of the
starting material was recovered. Interestingly, tautomeric 3-oxo-
esters derived from 2-acetonaphthone showed good tolerances
in the catalytic system, giving the desired product (3h) with a
55% yield. It should be noted that no methyl-migrated products
were observed from the reactions of acetophenones and EDA.
INTRODUCTION
■
3-Oxo-esters and related 3-hydroxy acrylates are useful
precursors for synthesizing biologically active and pharmaceuti-
cally important compounds due to their expandable function-
ality and wide range of substrate scope.1−4 The presence of
prochirality of such synthons promotes the construction of a
quaternary carbon center.5 They are also exploited as common
monomers in the polymer industry.6 Moreover, such oxo-esters
and their related acrylates contribute to very unusual Michael
and Mannich type reactions.7−10 Therefore, increasing efforts
have been devoted to developing efficient protocols for the
synthesis of these vital scaffolds using commercially available
starting materials.11
In our previous work, we reported the formation of 3-
hydroxy-2-aryl acrylates by 1,2-aryl migration from the reactions
of aromatic aldehydes with ethyl diazoacetate (EDA) in the
presence of an iron Lewis acid catalyst.12 Later on, other groups
also reported the similar type of reactions using different Lewis
acid catalysts.13,14 In 2004, our group explored the catalyst
scopes to produce 3-hydroxy-2-aryl acrylates and 3-oxo-esters
with Brønsted type acids using similar substrates.15 However,
reactions of more sterically hindered and less electrophilic
aromatic/aliphatic ketones or aliphatic aldehydes with EDA in
the presence of a Brønsted acid catalyst are certainly rare.
Herein, we present the unexplored reaction of various carbonyl
•
compounds and EDA in the presence of HBF4 OEt2 for the
formation of 3-oxo-esters (Scheme 1). During this study, we also
characterized the ratio of the isolated migrated products from
diaryl ketones by the heteronuclear multiple bond correlation
(HMBC) method.
Received: December 18, 2020
Published: April 12, 2021
RESULTS AND DISCUSSION
■
Based on our published work with acetophenone and EDA using
•
HBF4 OEt2 catalyst, we decided to expand the scope of this
https://doi.org/10.1021/acs.joc.0c02972
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Scheme 1. Formation of 3-Oxo-Esters in Presence of a Brønsted Acid Catalyst by 1,2-Migration
a
Table 1. Migratory Aptitude of Methyl−Aryl Groups
a
•
Reaction conditions: 1 (3.0−5.0 mmol), 2 (6.0−10.0 mmol), HBF4 OEt2 (0.6−1.0 mmol), and CH2Cl2 (10−15 mL) at −78 °C to room-
temperature (rt) for 3 days.
Figure 1. Newman projections of six possible rotamers (A−F) and a phenonium ion intermediate (P) along with nonclassical carbocation
intermediate (N).
The above findings could be explained with respect to six
probable rotamers A−F (Figure 1) from the reaction of
E was more favorable over methyl from rotamer B/D due to its
ability to stabilize an intermediate phenonium ion (Figure 1, P)
by six-electron resonance participation, whereas two electrons
participating in nonclassical carbocation intermediate (Figure 1,
N) are not stable enough to facilitate any methyl migration. The
predominant phenyl over methyl migration is consistent with
the pinacol rearrangement, which also involved carbocation
intermediate.17 In our discussion, we did not consider rotamers
C and F which are prerequisite for the formation of epoxide, not
observed in our reactions.
•
acetophenones and EDA in the presence of HBF4 OEt2.
Rotamers A−C are interconvertible due to the rotation of C−
C bonds and their diastereomeric form of rotamers, D−F are
also interconvertible. In both rotamers A and E, migrating aryl
group and leaving diazonium group were anti to each other;
thus, the formation of 3-oxo-ester 3 was favorable. On the other
hand, in rotamers B and D, the methyl migrating group was anti
to the leaving group, which could favor the formation of methyl-
migrated product. However, the aryl migration from rotamer A/
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a b
,
Table 2. Migratory Aptitude of Alkyl−Phenyl Groups
a
•
Reaction conditions: 4 (2.0−5.0 mmol), 2 (4.0−10.0 mmol), HBF4 OEt2 (0.4−1.0 mmol), and CH2Cl2 (10−15 mL) at −78 °C to room-
b
temperature (rt) for 3 days. The ratios of the products are calculated from the NMR of the crude mixtures.
a b
,
Table 3. Migratory Aptitude of Aryl−Phenyl Groups
a
•
Reaction conditions: 6 (5.0−10.0 mmol), 2 (10.0−20 mmol), HBF4 OEt2 (1.0−2.0 mmol), and CH2Cl2 (15−20 mL) at −78 °C to room-
b
temperature (rt) for 3 days. The ratios of the products are calculated from the NMR of the crude mixtures.
From the perceived nature of the phenyl and methyl groups of
acetophenone, the reactions were extended to other aromatic
ketones by varying alkyl groups (Table 2). In the case of
increasing alkyl chain length, both phenyl- and alkyl-migrated
products were formed. For example, when propiophenone (4a)
was employed as a substrate, both phenyl- and ethyl-migrated
products (5a/5a′ = 3:1) were obtained with 62% isolated yield.
With increasing alkyl chain length, the migratory tendency of
phenyl group relative to alkyl migration was constant (5b/5b′−
5e/5e′ ∼ 7:1). However, when the reaction was carried out with
octanophenone (4f), the ratio of the migrated products was 5f/
5f′ = 3:1 and the yield was 37%. Although we did not observe
any methyl migration in acetophenone (1a), the migration of
ethyl or other longer chain alkyl groups happened may be due to
their ability to stabilize the developing carbocation intermediate
by hyperconjugation compared to a methyl group.17
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Figure 2. HMBC cross-peak spectra for the products of para-methylbenzophenone.
Figure 3. HMBC cross-peak spectra for the products of para-methoxybenzophenone.
For further investigations, we turned our attention to
benzophenone and substituted benzophenones (Table 3).
From our inquiry, it was revealed that when an electron-
donating group such as methyl was present in the mono-
substituted benzophenone (6b), both phenyl- and para-tolyl-
migrated products (7b/7b′′) were formed in a ratio of 1:1.2.
other hand, when an electron-withdrawing group (6d and 6e)
was present in the monosubstituted benzophenone, trace or no
product was observed, which could be due to the instability of
carbocation intermediate.15
As we obtained a mixture of products from the reactions of
para-methyl (6b) and para-methoxybenzophenone (6c) and
EDA, we undertook 2D NMR studies to confirm the structure of
the products. After analyzing HMBC spectra, we observed a
cross-peak signal between the ortho-proton of the benzene ring
(a doublet at δ 7.99) and the carbonyl carbon of ester (δ 193.7)
(red line in Figure 2), which correlates with the structure of 7b
generated by para-methyl phenyl migration. On the other hand,
a cross-peak signal was identified among the ortho-proton (a
doublet at δ 7.89) and the para-methyl carbon of the benzene
ring (δ 2.39) as well as with the carbonyl carbon of ester (δ
192.9) (green line in Figure 2). This cross-coupling nicely
correlates with 7b′ formed by phenyl migration. By comparing
the peaks at δ 7.89 and δ 7.99 in the crude mixture (see the SI),
we concluded that this reaction yielded slightly more product of
7b than 7b′ due to the favorable migration of electron-donating
para-methyl phenyl over the phenyl group.
Our result agrees with the value (1.28
0.09) reported by
Curtin and Crew in the acid-catalyzed deamination reaction of
2-amino-L-phenyl-L-p-tolylethanol involving carbocation inter-
mediate.18 Moreover, in our study, the para-anisyl group in
compound 6c provided the relatively better migration (1.5/1)
might be because of the additional interaction energy in the
transition state induce by the para-methoxy group during
carbocation formation.19 In the case of electron-rich 3,4-
disubstituted benzophenone (6f and 6g), we obtained
exclusively the disubstituted phenyl-migrated products (7f and
7g). This type of migration was also found in naphthyl phenyl
ketone (6h) where electron-rich naphthyl group was migrated to
give the desired product (7h). The exclusive formation of (7f),
(7g), and (7h) may be due to the better stability of the
corresponding phenonium carbocation intermediate. On the
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a b
,
Table 4. Migratory Aptitude of Alkyl-Hydride Groups
a
•
Reaction conditions: 8 (2.0−8.0 mmol), 2 (4.0−16.0 mmol), HBF4 OEt2 (0.4−1.6 mmol), and CH2Cl2 (10−15 mL) at −78 °C to room-
b
temperature (rt) for 3 days. The ratios of the products are calculated after isolation.
Previously reported compounds were identified by 1H NMR. All new
Similarly, we have confirmed the structure of 7c by 2D NMR
1
compounds were additionally characterized by H NMR, 13C NMR,
by comparing a cross-peak signal between the ortho-proton of
the benzene ring (a doublet at δ 7.98) and the carbonyl carbon
of ester (δ 194.0) (red line in Figure 3) and the structure of 7c′
and high-resolution mass spectrometry (HRMS). HRMS were
obtained using Shimadzu liquid chromatography-ion trap-time of flight
tandem mass spectrometry (LCMS-IT-TOF) by the electrospray
from the cross-peak signal among the ortho-proton (a doublet at
ionization (ESI) technique. For the column chromatography, silica gel
δ 7.97) and the para-methoxy carbon of the benzene ring (δ
3.86) with the carbonyl carbon of ester (δ 192.0) (green line in
Figure 3) (see also the SI).
(35−70 μm) was used. The thin-layer chromatography (TLC) was
performed on aluminum-backed plates precoated (0.25 mm) with Silica
Gel 60 F254 with a suitable solvent system and was visualized using UV
fluorescence and/or iodine chamber.
Finally, to demonstrate the further utility of the reaction,
transformation of the aliphatic aldehydes and ketones were
explored. The results of these reactions are summarized in Table
4. For the migratory aptitude of unsymmetrical aliphatic
ketones, increasing the steric bulk of the alkyl group increases
its tendency to migrate. The longer alkyl chain-migrated
products dominated over the methyl-migrated products (9d/
9d′ and 9e/9e′ = 2:1) due to the hyperconjugation effect with a
longer chain alkyl group, triggered better stability of the
carbocation intermediate.17 In the case of aliphatic aldehydes,
the hydride-migrated products (9f, 9g, and 9h) formed
exclusively as observed with an aromatic aldehyde.20
In summary, we investigated the reaction of less explored
aromatic/aliphatic ketones as well as aliphatic aldehydes with
EDA employed as the reaction partner. The distinct reactivity
between carbonyl compounds and EDA has allowed the
incorporation of a diverse range of substituent patterns into
the product formation. Depending on the migratory aptitudes of
hydride, alkyl, phenyl, and aryl groups, a wide range of 3-oxo-
esters are formed. We anticipate that these valuable synthons
will further prove their utility in preparing important building
blocks of biologically active natural and synthetic compounds.
General Procedure for the One-Pot Synthesis of 3-Oxo-
Esters. For each experiment, carbonyl compounds (2.0−8.0 mmol, 1.0
equiv) were dissolved in 10−20 mL of freshly distilled dichloromethane
•
under nitrogen at −78 °C. A Brønsted acid, HBF4 OEt2 catalyst (0.4−
1.6 mmol, 0.2 equiv) was added, and the reaction mixture was stirred for
1 h at the same temperature. Ethyl diazoacetate (EDA) (4.0−16.0
mmol, 2.0 equiv) was diluted in 5 mL of freshly distilled dichloro-
methane and added to the solution over a period of 0.5−1 h. Then, the
reaction mixture was allowed to stir for 72 h at room temperature. After
completion of the reaction, it was quenched by adding tetrahydrofuran
(THF). The reaction mixture was filtered through a silica plug using
dichloromethane as a solvent and the solvent was removed by rotary
evaporation. Pure products were isolated by silica gel column
chromatography with 0−10% ethyl acetate in hexane except, 5j (50%
dichloromethane in hexane) and 5k (100% dichloromethane).
Ethyl 3-Oxo-2-phenylbutanoate (Keto-enol = 1:1) (3a).15,21 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.52 g, 68%)
from the reaction of acetophenone (0.51 g, 4.25 mmol, 1.0 equiv) and
•
EDA (1.03 mL, 8.50 mmol, 2.0 equiv) in the presence of HBF4 OEt2
(0.12 mL, 0.85 mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 13.15
(s, 1H), 7.40−7.29 (m, 8H), 7.19−7.16 (m, 2H), 4.71 (s, 1H), 4.26−
4.16 (m, 4H), 2.21 (s, 3H), 1.87 (s, 3H), 1.30 (t, J = 7.5 Hz, 3H), and
1.21 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (CDCl3, 125 MHz): δ 201.6,
173.9, 172.6, 168.5, 135.3, 132.7, 131.2, 129.3, 128.9, 128.3, 128.0,
126.9, 104.4, 65.8, 61.6, 60.6, 28.8, 19.9, 14.2, and 14.1.
EXPERIMENTAL SECTION
■
All reactions were performed under a dry nitrogen atmosphere using
standard Schlenk techniques unless otherwise noted. All reaction
vessels were flame dried under vacuum and filled with nitrogen prior to
use. Reagents and solvents were purchased from Sigma-Aldrich,
Ethyl 2-(4-Chlorophenyl)-3-oxobutanoate (Keto-enol = 9:8)
(3b).21 The compound was prepared according to the general
procedure and purified by silica gel column chromatography
(hexane/ethyl acetate = 50:1). The title product was isolated as a
colorless oil (0.46 g, 56%) from the reaction of 4′-chloroacetophenone
(0.52 g, 3.38 mmol, 1.0 equiv) and EDA (0.82 mL, 6.78 mmol, 2.0
1
Milwaukee. All H and 13C NMR spectra were recorded in CDCl3
(internal standard: 7.26 ppm, 1H; 77.16 ppm, 13C{1H}) at room
temperature with a Bruker 300 and 500 MHz spectrometers. The
chemical shifts (δ) are given in parts per million (ppm) and the
coupling constants in Hertz (Hz). The following abbreviations are
used: s-singlet, d-doublet, t-triplet, q-quartet, and m-multiplet.
•
equiv) in the presence of HBF4 OEt2 (0.09 mL, 0.68 mmol, 0.2 equiv).
1H NMR (CDCl3, 500 MHz): δ 13.14 (s, 1H), 7.38 (d, J = 10.0 Hz,
2H), 7.32 (t, J = 10.0 Hz, 4H), 7.11 (d, J = 10.0 Hz, 2H), 4.69 (s, 1H),
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4.26−4.17 (m, 4H), 2.22 (s, 3H), 1.87 (s, 3H), 1.30 (t, J = 7.5 Hz, 3H),
and 1.21 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (CDCl3, 125 MHz): δ
200.9, 174.1, 172.3, 168.2, 134.5, 133.7, 132.9, 132.6, 131.1, 130.7,
129.1, 128.3, 103.3, 64.9, 61.7, 60.8, 28.9, 19.9, 14.2, and 14.1.
colorless oil (0.29 g, 55%) from the reaction of 2-acetonaphthone (0.52
g, 3.04 mmol, 1.0 equiv) and EDA (0.73 mL, 6.07 mmol, 2.0 equiv) in
•
1
the presence of HBF4 OEt2 (0.084 mL, 0.61 mmol, 0.2 equiv). H
NMR (CDCl3, 500 MHz): δ 13.22 (s, 1H), 7.90−7.83 (m, 7H), 7.65 (s,
1H), 7.55−7.49 (m, 5H), 7.31 (d, J = 10.0 Hz, 1H), 4.89 (s, 1H), 4.31−
4.19 (m, 4H), 2.25 (s, 3H), 1.92 (s, 3H), 1.32 (t, J = 7.5 Hz, 3H), and
1.19 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 201.7,
174.2, 172.7, 168.6, 133.4, 133.3, 133.0, 132.8, 132.4, 130.2, 130.0,
129.6, 128.7, 128.7, 128.0, 127.9, 127.7, 127.5, 126.7, 126.5, 126.4,
126.0, 125.9, 104.3, 65.9, 61.7, 60.7, 28.9, 20.0, 14.2, and 14.1.
Ethyl 2-(4-Methoxyphenyl)-3-oxobutanoate (Keto-enol = 4:3)
(3c).21 The compound was prepared according to the general
procedure and purified by silica gel column chromatography
(hexane/ethyl acetate = 50:1). The title product was isolated as a
colorless oil (0.52 g, 64%) from the reaction of 4′-methoxyacetophe-
none (0.51 g, 3.41 mmol, 1.0 equiv) and EDA (0.82 mL, 6.82 mmol, 2.0
•
equiv) in the presence of HBF4 OEt2 (0.09 mL, 0.68 mmol, 0.2 equiv).
Ethyl 3-Oxo-2-phenylpentanoate (Keto-enol = 6:5) (5a). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.58 g, 34%)
from the reaction of propiophenone (0.52 g, 3.88 mmol, 1.0 equiv) and
1H NMR (CDCl3, 300 MHz): δ 13.11 (s, 1H), 7.28 (d, J = 6.0 Hz, 2H),
7.08 (t, J = 4.5 Hz, 2H), 7.28 (t, J = 9.0 Hz, 4H), 4.65 (s, 1H), 4.20 (q, J
= 7.5 Hz, 4H), 3.82 (s, 3H), 3.81 (s, 3H), 2.18 (s, 3H), 1.86 (s, 3H),
1.28 (t, J = 7.5 Hz, 3H), and 1.19 (t, J = 7.5 Hz, 3H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 201.8, 174.0, 172.8, 168.8, 159.6, 158.5, 132.2,
130.4, 127.9, 127.5, 124.8, 114.3, 113.5, 103.8, 64.9, 61.5, 60.6, 55.2,
55.1, 28.6, 19.8, 14.2, and 14.1.
•
EDA (0.94 mL, 7.75 mmol, 2.0 equiv) in the presence of HBF4 OEt2
(0.11 mL, 0.78 mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 13.23
(s, 1H), 7.37−28 (m, 8H), 7.18 (t, J = 4.5 Hz, 2H), 4.76 (s, 1H), 4.26−
4.14 (m, 4H), 2.53 (q, J = 6.0 Hz, 2H), 2.15 (q, J = 6.0 Hz, 2H), 1.28 (t, J
= 7.5 Hz, 3H), 1.18 (t, J = 7.5 Hz, 3H), and 1.12−1.01 (m, 6H).
13C{1H} NMR (CDCl3, 75 MHz): δ 204.2, 178.1, 172.8, 168.7, 135.2,
133.0, 131.2, 129.4, 128.8, 128.1, 128.0, 126.9, 103.6, 64.8, 61.5, 60.5,
34.9, 26.3, 14.2, 14.0, 11.1, and 7.8. HRMS (ESI/Q-TOF): calculated
(m/z) for C13H17O3 (M + H)+: 221.1172; found 221.1164.
Ethyl 3-Oxo-2-(p-tolyl)butanoate (Keto-enol = 2:1) (3d).22 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.30 g, 58%)
from the reaction of 4′-methylacetophenone (0.53 g, 3.91 mmol, 1.0
equiv) and EDA (0.95 mL, 7.83 mmol, 2.0 equiv) in the presence of
•
HBF4 OEt2 (0.11 mL, 0.78 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
Ethyl 2-Benzoylbutanoate (5a′).24 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.48 g, 28%) from the reaction of
propiophenone (0.52 g, 3.88 mmol, 1.0 equiv) and EDA (0.94 mL,
MHz): δ 13.14 (s, 1H), 7.27−7.15 (m, 8H), 7.06 (d, J = 6.0 Hz, 2H),
4.67 (s, 1H), 4.28−4.16 (m, 4H), 2.38 (s, 3H), 2.37 (s, 3H), 2.20 (s,
3H), 1.87 (s, 3H), 1.30 (t, J = 7.5 Hz, 3H), and 1.22 (t, J = 6.0 Hz, 3H).
13C{1H} NMR (CDCl3, 125 MHz): δ 201.8, 173.8, 172.8, 168.7, 138.1,
136.5, 132.2, 131.1, 129.7, 129.6, 129.1, 128.8, 104.1, 65.4, 61.6, 60.6,
28.7, 21.2, 21.1, 20.0, 14.2, and 14.1.
•
7.75 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.11 mL, 0.78
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 7.98 (d, J = 9.0 Hz,
2H), 7.55 (t, J = 6.0 Hz, 1H), 7.48 (t, J = 6.0 Hz, 2H), 4.21 (t, J = 6.0 Hz,
1H), 4.12 (q, J = 9.0 Hz, 2H), 2.07−1.98 (m, 2H), 1.14 (t, J = 6.0 Hz,
3H), and 0.98 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ
195.2, 169.9, 136.4, 133.4, 128.7, 128.5, 61.2, 55.8, 22.4, 14.0, and 12.1.
Ethyl 3-Oxo-2-phenylhexanoate (Keto-enol = 2:3) (5b). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.59 g, 36%)
from the reaction of butyrophenone (0.52 g, 3.50 mmol, 1.0 equiv) and
Ethyl 3-Oxo-2-(m-tolyl)butanoate (Keto-enol = 3:4) (3e).23 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.21 g, 40%)
from the reaction of 3′-methylacetophenone (0.52 g, 3.85 mmol, 1.0
equiv) and EDA (0.93 mL, 7.69 mmol, 2.0 equiv) in the presence of
•
HBF4 OEt2 (0.11 mL, 0.77 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
MHz): δ 13.15 (s, 1H), 7.28−7.10 (m, 8H), 7.06 (d, J = 9.0 Hz, 2H),
4.68 (s, 1H), 4.27−4.17 (m, 4H), 2.38 (s, 6H), 2.21 (s, 3H), 1.88 (s,
3H), 1.30 (t, J = 7.5 Hz, 3H), and 1.22 (t, J = 7.5 Hz, 3H). 13C{1H}
NMR (CDCl3, 125 MHz): δ 201.7, 173.8, 172.7, 168.6, 138.6, 137.5,
135.1, 132.6, 131.9, 129.9, 129.0, 128.8, 128.3, 127.9, 127.7, 126.3,
104.4, 65.7, 61.5, 60.6, 28.7, 21.4, 19.9, 14.2, and 14.1.
•
EDA (0.85 mL, 7.0 mmol, 2.0 equiv) in the presence of HBF4 OEt2
1
(0.096 mL, 0.70 mmol, 0.2 equiv). H NMR (CDCl3, 300 MHz): δ
13.20 (s, 1H), 7.40−7.30 (m, 8H), 7.18 (d, J = 5.0 Hz, 2H), 4.74 (s,
1H), 4.27−4.17 (m, 4H), 2.48 (t, J = 7.5 Hz, 2H), 2.11 (t, J = 8.0 Hz,
2H), 1.63−1.55 (m, 4H), 1.29 (t, J = 6.0 Hz, 3H), 1.19 (t, J = 6.0 Hz,
3H), and 0.89−0.83 (m, 6H). 13C{1H} NMR (CDCl3, 75 MHz): δ
203.7, 176.9, 172.9, 168.6, 135.2, 132.8, 131.4, 129.5, 128.8, 128.2,
128.0, 126.9, 104.3, 65.0, 61.6, 60.6, 43.5, 34.7, 20.1, 17.1, 14.2, 14.1,
13.8, and 13.4. HRMS (ESI/Q-TOF): calculated (m/z) for C14H19O3
(M + H)+: 235.1329; found 235.1312.
Ethyl 3-Oxo-2-(o-tolyl)butanoate (Keto-enol = 1:4) (3f).22 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.26 g, 48%)
from the reaction of 2′-methylacetophenone (0.53 g, 4.00 mmol, 1.0
equiv) and EDA (0.95 mL, 7.90 mmol, 2.0 equiv) in the presence of
Ethyl 2-Benzoylpentanoate (5b′).25 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.39 g, 24%) from the reaction of
butyrophenone (0.52 g, 3.50 mmol, 1.0 equiv) and EDA (0.85 mL,
•
HBF4 OEt2 (0.11 mL, 0.79 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
MHz): δ 13.10 (s, 0.8H), 7.72 (d, J = 9.0 Hz, 2H), 7.39 (d, J = 6.0 Hz,
2H), 7.25 (d, J = 6.0 Hz, 4H), 7.09 (s, 1H), 4.94 (s, 0.2H), 4.29−4.23
(m, 2H), 4.16−4.10 (m, 1H), 2.61 (s, 3H), 2.57 (s, 3H), 2.20 (s, 3H),
1.78 (s, 3H), 1.30 (s, 3H), and 1.22 (t, J = 7.5 Hz, 3H).
•
Ethyl 2-(4-Nitrophenyl)-3-oxobutanoate (Keto-enol = 4:5) (3g).21
The compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
25:1). The title product was isolated as a colorless oil (0.078 g, 15%)
from the reaction of 4′-nitroacetophenone (0.52 g, 3.12 mmol, 1.0
equiv) and EDA (0.75 mL, 6.24 mmol, 2.0 equiv) in the presence of
7.0 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.096 mL, 0.70
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 7.98 (t, J = 4.5 Hz,
2H), 7.55 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 4.31 (t, J = 7.5 Hz,
1H), 4.15 (q, J = 6.0 Hz, 2H), 2.04−1.95 (m, 2H), 1.43−1.33 (m, 2H),
1.17 (t, J = 7.5 Hz, 3H), and 0.95 (t, J = 7.5 Hz, 3H).
Ethyl 3-Oxo-2-phenylheptanoate (Keto-enol = 7:2) (5c). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.24 g, 30%)
from the reaction of valerophenone (0.53 g, 3.27 mmol, 1.0 equiv) and
•
HBF4 OEt2 (0.085 mL, 0.62 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
MHz): δ 13.25 (s, 1H), 8.36−8.20 (m, 3H), 7.83 (t, J = 4.5 Hz, 1H),
7.61−7.48 (m, 3H), 7.37 (d, J = 9.0 Hz, 1H), 4.85 (s, 1H), 4.30−4.18
(m, 4H), 2.29 (s, 3H), 1.91 (s, 3H), 1.31 (t, J = 7.5 Hz, 3H), and 1.21 (t,
J = 7.5 Hz, 3H).
Ethyl 2-(Naphthalen-2-yl)-3-oxobutanoate (Keto-enol = 5:3)
(3h).23 The compound was prepared according to the general
procedure and purified by silica gel column chromatography
(hexane/ethyl acetate = 50:1). The title product was isolated as a
•
EDA (0.79 mL, 6.53 mmol, 2.0 equiv) in the presence of HBF4 OEt2
1
(0.089 mL, 0.65 mmol, 0.2 equiv). H NMR (CDCl3, 300 MHz): δ
13.20 (s, 0.4H), 8.15 (d, J = 5.0 Hz, 1H), 7.51 (t, J = 5.0 Hz, 1H), 7.51−
7.35 (m, 7H), 7.17 (d, J = 5.0 Hz, 1H), 4.73 (s, 1.3H), 4.30−4.16 (m,
4H), 2.49 (t, J = 7.5 Hz, 2H), 2.12 (t, J = 7.5 Hz, 2H), 1.56−1.53 (m,
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4H), 1.30−1.24 (m, 7H), 1.22 (t, J = 4.5 Hz, 3H), and 0.93−0.80 (m,
6H). 13C{1H} NMR (CDCl3, 75 MHz): δ 203.8, 177.2, 171.1, 168.6,
132.7, 131.3, 129.4, 128.8, 128.2, 128.0, 126.9, 104.1, 65.0, 61.6, 60.4,
41.3, 32.5, 31.9, 29.7, 29.4, 28.8, 25.7, 22.3, 14.2, 14.1, 14.1, and 13.7.
HRMS (ESI/Q-TOF): calculated (m/z) for C15H21O3 (M + H)+:
249.1485; found 249.1464.
1H), 4.16 (q, J = 7.5 Hz, 2H), 2.03 (d, J = 3.0 Hz, 2H), 1.36−1.27 (m,
8H), 1.19 (t, J = 6.0 Hz, 3H), and 0.88 (t, J = 6.0 Hz, 3H). 13C{1H}
NMR (CDCl3, 75 MHz): δ 195.3, 170.1, 136.4, 133.4, 128.7, 128.6,
61.3, 54.4, 31.5, 29.7, 29.1, 29.0, 27.6, 22.5, and 14.0.
Ethyl 3-Oxo-2-phenyldecanoate (Keto-enol = 5:3) (5f). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.23 g, 30%)
from the reaction of octanophenone (0.54 g, 2.64 mmol, 1.0 equiv) and
Ethyl 2-Benzoylhexanoate (5c′).26 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.12 g, 15%) from the reaction of
valerophenone (0.53 g, 3.27 mmol, 1.0 equiv) and EDA (0.79 mL,
•
EDA (0.64 mL, 5.29 mmol, 2.0 equiv) in the presence of HBF4 OEt2
1
(0.073 mL, 0.53 mmol, 0.2 equiv). H NMR (CDCl3, 300 MHz): δ
•
6.53 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.089 mL, 0.65
13.18 (s, 1H), 7.37−28 (m, 8H), 7.16 (d, J = 6.0 Hz, 2H), 4.73 (s, 1H),
4.27−4.15 (m, 4H), 2.49 (t, J = 7.5 Hz, 2H), 2.11 (t, J = 7.5 Hz, 2H),
1.62−1.55 (m, 4H), 1.31−1.17 (m, 22H), and 0.89−0.85 (m, 6H).
13C{1H} NMR (CDCl3, 75 MHz): δ 203.8, 177.2, 172.9, 168.6, 135.2,
132.8, 131.3, 129.4, 128.8, 128.1, 127.9, 126.9, 104.1, 65.0, 61.5, 60.6,
41.6, 32.7, 31.6, 29.1, 28.9, 28.8, 26.7, 23.6, 22.6, 22.6, and 14.2. HRMS
(ESI/Q-TOF): calculated (m/z) for C18H27O3 (M + H)+: 291.1955;
found 291.1945.
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 8.01 (d, J = 9.0 Hz,
2H), 7.55 (d, J = 6.0 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 4.30 (t, J = 7.5
Hz, 1H), 4.12 (q, J = 15.9, 9.0 Hz, 2H), 2.03 (q, J = 12.0, 6.0 Hz, 2H),
1.36−1.28 (m, 4H), 1.19 (t, J = 7.5 Hz, 3H), and 0.92 (t, J = 7.5 Hz,
3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 195.3, 170.1, 136.4, 133.4,
128.7, 128.6, 61.3, 54.4, 29.8, 28.7, 22.5, 14.0, and 13.8.
Ethyl 3-Oxo-2-phenyloctanoate (Keto-enol = 2:3) (5d). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.24 g, 32%)
from the reaction of hexanophenone (0.50 g, 2.84 mmol, 1.0 equiv) and
Ethyl 2-Benzoylnonanoate (5f′). The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.054 g, 7%) from the reaction of
octanophenone (0.54 g, 2.64 mmol, 1.0 equiv) and EDA (0.64 mL,
•
EDA (0.74 mL, 5.67 mmol, 2.0 equiv) in the presence of HBF4 OEt2
1
•
(0.078 mL, 0.57 mmol, 0.2 equiv). H NMR (CDCl3, 300 MHz): δ
5.29 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.073 mL, 0.53
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 8.01 (d, J = 9.0 Hz,
2H), 7.59 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 4.29 (t, J = 7.5 Hz,
1H), 4.15 (q, J = 7.5 Hz, 2H), 2.03−1.98 (m, 2H), 1.34−1.27 (m,
10H), 1.18 (t, J = 7.5 Hz, 3H), and 0.88 (t, J = 6.0 Hz, 3H). 13C{1H}
NMR (CDCl3, 75 MHz): δ 195.3, 170.1, 136.4, 133.4, 128.7, 128.5,
61.3, 54.4, 31.7, 29.4, 29.0, 29.0, 27.6, 22.6, 14.0, and 14.0. HRMS
(ESI/Q-TOF): calculated (m/z) for C18H27O3 (M + H)+: 291.1955;
found 291.1927.
13.26 (s, 1H), 7.41−28 (m, 8H), 7.19 (t, J = 6.0 Hz,2H), 4.77 (s, 1H),
4.26−4.14 (m, 4H), 2.51 (t, J = 7.5 Hz, 2H), 2.14 (t, J = 7.5 Hz, 2H),
1.63−1.54 (m, 4H), 1.43−1.32 (m, 14H), and 0.89−0.83 (m, 6H).
13C{1H} NMR (CDCl3, 75 MHz): δ 203.6, 177.2, 172.8, 168.5, 135.2,
132.9, 131.3, 129.5, 128.7, 127.9, 126.9, 104.1, 65.0, 61.4, 60.5, 41.5,
32.7, 31.3, 31.1, 26.4, 23.3, 22.3, 22.3, 22.2, 14.1, and 14.0. HRMS
(ESI/Q-TOF): calculated (m/z) for C16H23O3 (M + H)+: 263.1642;
found 263.1642.
Ethyl 3-Oxo-2,3-diphenylpropanoate (7a).28 The compound was
prepared according to the general procedure and purified by silica gel
column chromatography (hexane/ethyl acetate = 50:1). The title
product was isolated as a colorless oil (0.37 g, 20%) from the reaction of
benzophenone (1.25 g, 6.86 mmol, 1.0 equiv) and EDA (1.67 mL,
Ethyl 2-Benzoylheptanoate (5d′). The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.14 g, 19%) from the reaction of
hexanophenone (0.50 g, 2.84 mmol, 1.0 equiv) and EDA (0.74 mL,
•
•
5.67 mmol, 0.2 equiv) in the presence of HBF4 OEt2 (0.078 mL, 0.57
13.72 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.19 mL, 1.37
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 8.01 (d, J = 9.0 Hz,
2H), 7.59 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 4.30 (t, J = 7.5 Hz,
1H), 4.16 (q, J = 7.5 Hz, 2H), 2.05−1.98 (m, 2H), 1.39−1.27 (m, 6H),
1.18 (t, J = 7.5 Hz, 3H), and 0.88 (t, J = 7.5 Hz, 3H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 195.3, 170.1, 136.4, 133.4, 128.7, 128.7, 128.6,
128.5, 61.3, 54.4, 31.6, 28.9, 27.3, 22.4, and 13.9. HRMS (ESI/Q-
TOF): calculated (m/z) for C16H23O3 (M + H)+: 263.1642; found
263.1649.
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 8.00 (d, J = 6.0 Hz,
2H), 7.56 (t, J = 7.5 Hz, 1H), 7.47−7.32 (m, 7H), 5.66 (s, 1H), 4.25 (q,
J = 7.5 Hz, 2H), and 1.27 (t, J = 7.5 Hz, 3H).
Ethyl 3-Oxo-3-phenyl-2-(p-tolyl)propanoate (7b) and Ethyl 3-
Oxo-2-phenyl-3-(p-tolyl)propanoate (7b′). The compound was
prepared according to the general procedure and purified by silica gel
column chromatography (hexane/ethyl acetate = 13:1). The title
product was isolated as a colorless oil (0.36 g, 21%) from the reaction of
4-methylbenzophenone (1.18 g, 6.01 mmol, 1.0 equiv) and EDA (1.45
Ethyl 3-Oxo-2-phenylnonanoate (Keto-enol = 2:1) (5e). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
100:1). The title product was isolated as a colorless oil (0.23 g, 31%)
from the reaction of heptanophenone (0.52 g, 2.73 mmol, 1.0 equiv)
and EDA (0.66 mL, 5.46 mmol, 2.0 equiv) in the presence of
•
mL, 12.02 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.17 mL,
1.20 mmol, 0.2 equiv). 1H NMR (CDCl3, 500 MHz): δ 7.98 (d, J = 10.0
Hz, 2H), 7.88 (d, J = 5.0 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.44 (q, J =
7.5 Hz, 4H), 7.37 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 10.0 Hz, 3H), 7.24 (d, J
= 10.0 Hz, 2H), 7.18 (d, J = 5.0 Hz, 2H), 5.61 (s, 1H), 5.59 (s, 1H),
4.26−4.22 (m, 4H), 2.40 (s, 2H), 2.34 (s, 3H), and 1.26 (t, J = 6.0 Hz,
6H). 13C{1H} NMR (CDCl3, 75 MHz): δ 193.5, 192.9, 169.0, 168.9,
144.5, 137.9, 135.8, 133.5, 133.3, 133.2, 130.0, 129.6, 129.4, 129.1,
128.9, 128.8, 128.8, 128.1, 66.1, 66.0, 61.7, 60.5, 60.2, 21.7, 21.2, 14.1,
and 14.0. HRMS (ESI/Q-TOF): calculated (m/z) for C18H19O3 (M +
H)+: 283.1329; found 283.1264.
•
HBF4 OEt2 (0.075 mL, 0.55 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
MHz): δ 13.20 (s, 1H), 7.39−7.29 (m, 9H), 7.18−7.15 (m, 1H), 4.74
(s, 1H), 4.26−4.17 (m, 4H), 2.50 (t, J = 7.5 Hz, 3H), 2.12 (t, J = 7.5 Hz,
2H), 1.58−1.54 (m, 4H), 1.31−1.18 (m, 18H), and 0.89−0.84 (m,
6H). 13C{1H} NMR (CDCl3, 75 MHz): δ 203.7, 177.2, 172.9, 168.6,
135.2, 132.8, 131.3, 129.6, 129.4, 129.0, 128.8, 128.1, 128.0, 126.9,
104.1, 65.0, 61.5, 60.5, 41.9, 32.7, 31.5, 28.8, 28.5, 26.6, 23.6, 22.4, 14.2,
14.1, and 14.0. HRMS (ESI/Q-TOF): calculated (m/z) for C17H25O3
(M + H)+: 277.1798; found 277.1783.
Ethyl 2-(4-Methoxyphenyl)-3-oxo-3-phenylpropanoate (7c) and
Ethyl 3-(4-Methoxyphenyl)-3-oxo-2-phenylpropanoate (7c′).28 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
9:1). The title product was isolated as a colorless oil (0.36 g, 22%) from
the reaction of 4-methoxybenzophenone (1.15 g, 5.42 mmol, 1.0 equiv)
and EDA (1.31 mL, 10.84 mmol, 2.0 equiv) in the presence of
Ethyl 2-Benzoyloctanoate (5e′).27 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 100:1). The title product was
isolated as a colorless oil (0.13 g, 17%) from the reaction of
heptanophenone (0.52 g, 2.73 mmol, 1.0 equiv) and EDA (0.66 mL,
•
HBF4 OEt2 (0.15 mL, 1.08 mmol, 0.2 equiv). 1H NMR (CDCl3, 300
•
5.46 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.075 mL, 0.55
MHz): δ 7.99−7.95 (m, 4H), 7.55 (t, J = 6.0 Hz, 2H), 7.44 (t, J = 6.0
Hz, 4H), 7.37−7.28 (m, 4H), 6.90 (d, J = 9.0 Hz, 4H), 5.58 (s, 1H),
5.57 (s, 1H), 4.24 (q, J = 7.5 Hz, 4H), 3.86 (s, 3H), 3.80 (s, 3H), and
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 8.01 (d, J = 9.0 Hz,
2H), 7.60 (t, J = 6.0 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 4.30 (t, J = 7.5 Hz,
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1.29−1.24 (m, 6H). 13C{1H} NMR (CDCl3, 75 MHz): δ 193.6, 191.8,
169.1, 169.0, 163.8, 159.4, 135.7, 133.4, 133.4, 131.3, 130.7, 129.5,
129.9, 128.8, 128.7, 128.6, 128.0, 125.0, 114.3, 113.9, 61.7, 60.3, 59.7,
55.5, 55.2, 14.1, and 14.0.
isolated as a colorless oil (0.45 g, 50%) from the reaction of 4-
heptanone (0.52 g, 4.53 mmol, 1.0 equiv) and EDA (1.43 mL, 9.06
•
mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.13 mL, 0.91 mmol,
0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 4.15 (q, J = 7.5 Hz, 2H),
3.41 (t, J = 6.0 Hz, 1H), 2.52−2.43 (m, 2H), 1.82−1.78 (m, 2H), 1.59
(q, J = 7.5 Hz, 2H), 1.24 (t, J = 6.0 Hz, 5H), and 0.91−0.86 (m, 6H).
13C{1H} NMR (CDCl3, 125 MHz): δ 205.3, 169.9, 61.1, 58.9, 43.6,
30.2, 20.7, 16.9, 14.0, 13.8, and 13.5. HRMS (ESI/Q-TOF): calculated
(m/z) for C11H21O3 (M + H)+: 201.1485; found 201.1478.
Ethyl 3-(4-Chlorophenyl)-3-oxo-2-phenylpropanoate (7d) and
Ethyl 2-(4-Chlorophenyl)-3-oxo-3-phenylpropanoate (7d′).28 The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
9:1). The title product was isolated as a colorless oil (trace amount)
from the reaction of 4-chlorobenzophenone (1.21 g, 5.58 mmol, 1.0
equiv) and EDA (1.35 mL, 11.16 mmol, 2.0 equiv) in the presence of
Ethyl 2-Butyl-3-oxoheptanoate (9c).31 The compound was
prepared according to the general procedure and purified by silica gel
column chromatography (hexane/ethyl acetate = 50:1). The title
product was isolated as a colorless oil (0.38 g, 47%) from the reaction of
5-nonanone (0.51 g, 3.59 mmol, 1.0 equiv) and EDA (0.87 mL, 7.18
•
HBF4 OEt2 (0.15 mL, 1.12 mmol, 0.2 equiv). 1H NMR (CDCl3, 500
MHz): δ 7.98−7.90 (m, 2H), 7.46−7.35 (m, 8H), 5.60 (s, 0.3H), 5.55
(s, 0.7H), 4.28−4.21 (m, 3H), and 1.29−1.24 (m, 5H). 13C{1H} NMR
(CDCl3, 75 MHz): δ 192.1, 168.5, 140.0, 134.0, 133.7, 132.7, 130.9,
130.3, 129.5, 129.1, 129.0, 128.9, 128.9, 128.8, 128.3, 128.2, 62.0, 61.9,
60.6, 59.7, and 14.0.
•
mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.10 mL, 0.72 mmol,
0.2 equiv). 1H NMR (CDCl3, 500 MHz): δ 4.14−4.11 (m, 2H), 3.36 (t,
J = 7.5 Hz, 1H), 2.51−2.41 (m, 2H), 2.33 (t, J = 5.0 Hz, 1H), 1.78−1.75
(m, 2H), 1.51−1.47 (m, 2H), 1.27−1.24 (m, 3H), 1.22−1.18 (m, 3H),
and 0.85−0.81 (m, 6H). 13C{1H} NMR (CDCl3, 125 MHz): δ 205.3,
169.9, 61.0, 59.1, 42.4, 41.4, 29.5, 27.8, 25.9, 25.5, 22.3, 22.1, 14.0, and
13.7.
Ethyl 2-(3,4-Dimethylphenyl)-3-oxo-3-phenylpropanoate (7f).
The compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/dichloro-
methane = 1:1). The title product was isolated as a colorless oil (0.50
g, 30%) from the reaction of 3,4-dimethylbenzophenone (1.18 g, 5.61
mmol, 1.0 equiv) and EDA (1.36 mL, 10.22 mmol, 2.0 equiv) in the
Ethyl 2-Acetylhexanoate (9d) and Ethyl 2-Methyl-3-oxohepta-
noate (9d′).32 The compound was prepared according to the general
procedure and purified by silica gel column chromatography (hexane/
ethyl acetate = 50:1). The title product was isolated as a colorless oil
(0.51 g, 55%) from the reaction of 2-hexanone (0.50 g, 4.99 mmol, 1.0
equiv) and EDA (1.20 mL, 9.98 mmol, 2.0 equiv) in the presence of
•
1
presence of HBF4 OEt2 (0.15 mL, 1.12 mmol, 0.2 equiv). H NMR
(CDCl3, 500 MHz): δ 7.49−7.31 (m, 6H), 7.15−7.07 (m, 2H), 5.24 (s,
1H), 4.38−4.24 (m, 2H), 2.24 (s, 3H), 2.28 (s, 3H), and 1.21 (t, J = 7.5
Hz, 2H). 13C{1H} NMR (CDCl3, 125 MHz): δ 169.8, 168.2, 153.4,
152.2, 139.6, 138.3, 137.1, 136.9, 130.3, 130.2, 130.0, 130.0, 129.8,
129.7, 129.4, 129.2, 128.7, 128.6, 128.6, 127.1, 126.9, 126.4, 126.2,
124.8, 99.6, 99.5, 64.2, 19.8, 19.7, and 13.8. HRMS (ESI/Q-TOF):
calculated (m/z) for C19H21O3 (M + H)+: 297.1485; found 297.1474.
Ethyl 2-(3,4-Dimethoxyphenyl)-3-oxo-3-phenylpropanoate
(7g).29 The compound was prepared according to the general
procedure and purified by silica gel column chromatography (dichloro-
methane). The title product was isolated as a colorless oil (0.43 g, 28%)
from the reaction of 3,4-dimethoxybenzophenone (1.15 g, 4.75 mmol,
1.0 equiv) and EDA (1.15 mL, 9.50 mmol, 2.0 equiv) in the presence of
•
1
HBF4 OEt2 (0.14 mL, 1.0 mmol, 0.2 equiv). H NMR (CDCl3, 300
MHz): δ 4.24−4.20 (m, 4H), 3.53 (q, J = 7.5 Hz, 1H), 3.41 (t, J = 7.5
Hz, 1H), 2.63−2.48 (m, 1H), 2.25 (s, 3H), 1.85−1.81 (m, 2H), 1.61−
1.57 (m, 3H), 1.36−1.28 (m, 15H), and 0.94−0.91 (m, 6H). 13C{1H}
NMR (CDCl3, 125 MHz): δ 206.0, 203.4, 170.6, 169.9, 61.2, 59.9, 41.0,
29.5, 28.7, 27.9, 25.6, 22.4, 22.2, 14.1, 14.0, and 13.8.
Ethyl 2-Acetyldecanoate (9e).33 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 50:1). The title product was
isolated as a colorless oil (0.36 g, 44%) from the reaction of 2-decanone
(0.53 g, 3.39 mmol, 1.0 equiv) and EDA (0.89 mL, 6.78 mmol, 2.0
•
HBF4 OEt2 (0.13 mL, 0.95 mmol, 0.2 equiv). 1H NMR (CDCl3, 500
•
MHz): δ 7.99 (d, J = 5.0 Hz, 2H), 7.56 (t, J = 7.5 Hz, 2H), 7.45 (t, J = 7.5
Hz, 4H), 6.95 (d, J = 10.0 Hz, 2H), 6.86 (d, J = 10.0 Hz, 4H), 5.56 (s,
1H), 4.24 (q, J = 5.0 Hz, 4H), 3.89 (s, 3H), 3.87 (s, 3H), and 1.27 (t, J =
5.0 Hz, 2H). 13C{1H} NMR (CDCl3, 125 MHz): δ 193.5, 169.0, 149.2,
149.0, 135.8, 133.5, 128.9, 128.7, 125.4, 122.1, 112.5, 111.2, 61.7, 60.0,
56.0, 55.8, 30.9, and 14.1.
equiv) in the presence of HBF4 OEt2 (0.09 mL, 0.68 mmol, 0.2 equiv).
1H NMR (CDCl3, 300 MHz): δ 4.21 (q, J = 7.5 Hz, 2H), 3.41 (t, J = 7.5
Hz, 1H), 2.23 (s, 3H), 1.85 (s, 2H), 1.31−1.27 (m, 15H), and 0.89 (t, J
= 6.0 Hz, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 203.4, 170.0, 61.2,
60.0, 31.8, 29.3, 29.3, 29.2, 28.7, 28.2, 27.4, 22.6, 14.1, and 14.1.
Ethyl 2-Acetyldecanoate (9e′). The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 50:1). The title product was
isolated as a colorless oil (0.16 g, 20%) from the reaction of 2-decanone
(0.53 g, 3.39 mmol, 1.0 equiv) and EDA (0.89 mL, 6.78 mmol, 2.0
Ethyl 2-(Naphthalen-2-yl)-3-oxo-3-phenylpropanoate (7h). The
compound was prepared according to the general procedure and
purified by silica gel column chromatography (hexane/ethyl acetate =
20:1). The title product was isolated as a colorless oil (0.34 g, 23%)
from the reaction of 2-naphthyl phenyl ketone (1.08 g, 4.65 mmol, 1.0
equiv) and EDA (1.12 mL, 9.30 mmol, 2.0 equiv) in the presence of
•
equiv) in the presence of HBF4 OEt2 (0.09 mL, 0.68 mmol, 0.2 equiv).
1H NMR (CDCl3, 300 MHz): δ 5.32 (s, 1H), 4.32−4.13 (m, 2H), 3.52
(q, J = 7.5 Hz, 2H), 2.24 (s, 3H), 1.62 (s, 4H), 1.38−1.36 (m, 13H), and
1.38 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 203.3,
170.0, 61.2, 60.0, 32.0, 29.3, 29.2, 28.7, 28.2, 27.4, 22.6, and 14.1.
HRMS (ESI/Q-TOF): calculated (m/z) for C14H27O3 (M + H)+:
243.1955; found 243.1940.
•
HBF4 OEt2 (0.13 mL, 0.93 mmol, 0.2 equiv). 1H NMR (CDCl3, 500
MHz): δ 8.29 (s, 1H), 7.97−7.88 (m, 6H), 7.65−7.60 (m, 2H), 7.58−
7.7.51 (m, 3H), 4.29−4.23 (m, 3H), and 1.31 (t, J = 7.5 Hz, 3H).
13C{1H} NMR (CDCl3, 125 MHz): δ 196.7, 169.8, 137.9, 135.3, 134.8,
132.4, 132.3, 131.9, 130.1, 129.4, 128.4, 128.3, 127.8, 126.8, 125.8, 68.2,
61.1, and 14.2. HRMS (ESI/Q-TOF): calculated (m/z) for C21H19O3
(M + H)+: 319.1329; found 319.1365.
Ethyl 5-Methyl-3-Oxohexanoate (9f).34 The compound was
prepared according to the general procedure and purified by silica gel
column chromatography (hexane/ethyl acetate = 50:1). The title
product was isolated as a colorless oil (0.56 g, 55%) from the reaction of
3-methylbutanal (0.51 g, 5.92 mmol, 1.0 equiv) and EDA (1.43 mL,
Ethyl 2-Ethyl-3-oxopentanoate (9a).30 The compound was
prepared according to the general procedure and purified by silica gel
column chromatography (hexane/ethyl acetate = 50:1). The title
product was isolated as a colorless oil (0.53 g, 52%) from the reaction of
3-pentanone (0.51 g, 5.92 mmol, 1.0 equiv) and EDA (1.43 mL, 11.84
•
11.84 mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.16 mL, 1.2
mmol, 0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 4.20−4.08 (m, 2H),
3.38 (s, 2H), 2.39 (d, J = 6.0 Hz, 2H), 2.18−2.11 (m, 1H), 1.25 (t, J =
6.0 Hz, 3H), and 0.92−0.88 (m, 6H).
•
mmol, 2.0 equiv) in the presence of HBF4 OEt2 (0.16 mL, 1.18 mmol,
0.2 equiv). 1H NMR (CDCl3, 300 MHz): δ 4.09 (q, J = 6.0 Hz, 2H),
3.28 (t, J = 7.5 Hz, 1H), 2.49−2.42 (m, 2H), 1.78 (t, J = 7.5 Hz, 2H),
1.17 (t, J = 6.0 Hz, 3H), 0.97 (t, J = 7.5 Hz, 3H), and 0.82 (t, J = 7.5 Hz,
3H).
Ethyl 3-Oxooctanoate (9g).35 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 50:1). The title product was
isolated as a colorless oil with hexane (0.60 g, 62%) from the reaction of
hexanal (0.52 g, 5.19 mmol, 1.0 equiv) and EDA (1.43 mL, 10.38 mmol,
Ethyl 3-Oxo-2-propylhexanoate (9b). The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 50:1). The title product was
•
2.0 equiv) in the presence of HBF4 OEt2 (0.14 mL, 1.04 mmol, 0.2
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The Journal of Organic Chemistry
pubs.acs.org/joc
Article
equiv). 1H NMR (CDCl3, 300 MHz): δ 4.19 (q, J = 6.0 Hz, 2H), 3.42
(s, 2H), 2.53 (t, J = 7.5 Hz, 2H), 1.61−1.59 (m, 2H), 1.29−1.25 (m,
4H), and 0.88−0.82 (m, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ
203.0, 167.3, 61.3, 49.3, 43.0, 31.9, 31.2, 29.7, 23.2, 22.7, 22.4, 14.1, and
13.9.
ACKNOWLEDGMENTS
■
We would like to thank the Graduate School of UWM for their
support of this research through grant RGI-101 × 351. We are
also thankful to Dr. F. Holger Foersterling for the help on 2D
NMR studies and Vilashini Rajaratnam for HRMS analysis.
Ethyl 3-Oxodecanoate (9h).36 The compound was prepared
according to the general procedure and purified by silica gel column
chromatography (hexane/ethyl acetate = 50:1). The title product was
isolated as a colorless oil with hexane (0.70 g, 82%) from the reaction of
octanal (0.51 g, 3.98 mmol, 1.0 equiv) and EDA (0.96 mL, 7.96 mmol,
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02972.
Copies of the 1H NMR, 13C{1H} NMR, and HRMS for all
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AUTHOR INFORMATION
■
Corresponding Author
M. Mahmun Hossain − Department of Chemistry and
Biochemistry, University of Wisconsin-Milwaukee, Milwaukee,
Wisconsin 53211-3029, United States; orcid.org/0000-
0002-0874-4480; Email: mahmun@uwm.edu
Authors
Mizzanoor Rahaman − Department of Chemistry and
Biochemistry, University of Wisconsin-Milwaukee, Milwaukee,
Wisconsin 53211-3029, United States
M. Shahnawaz Ali − Department of Chemistry and
Biochemistry, University of Wisconsin-Milwaukee, Milwaukee,
Wisconsin 53211-3029, United States
Khorshada Jahan − Department of Chemistry and
Biochemistry, University of Wisconsin-Milwaukee, Milwaukee,
Wisconsin 53211-3029, United States
Damon Hinz − Department of Chemistry and Biochemistry,
University of Wisconsin-Milwaukee, Milwaukee, Wisconsin
53211-3029, United States
Jawad Bin Belayet − Department of Chemistry and
Biochemistry, University of Wisconsin-Milwaukee, Milwaukee,
Wisconsin 53211-3029, United States
Ryan Majinski − Department of Chemistry and Biochemistry,
University of Wisconsin-Milwaukee, Milwaukee, Wisconsin
53211-3029, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02972
Notes
The authors declare no competing financial interest.
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Article
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