Retrosynthetic Analysis of α-Alkenyl-β-Diketones: Regio-and Stereoselective Two-Step Synthesis of Highly Arylated Representatives from Acetylenes, Ketones, and Acyl Chlorides

Article abstract of DOI:10.1021/acs.joc.0c00768

Highly arylated α-alkenyl-β-diketones are synthesized via a two-step sequence consisting of (i) potassium tert-butoxide/DMSO-catalyzed (E)-stereoselective C-H functionalization of ketones with acetylenes followed by (ii) magnesium bromide etherate/DIPEA-soft enolization of the formed β,γ-unsaturated ketones and regioselective acylation with acyl chlorides. The method is compatible with a broad range of substrates and shown to be applicable as an intermediate stage in the construction of polyarylated heterocycles.

Full text of DOI:10.1021/acs.joc.0c00768

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Article
A Retrosynthetic Analysis of #-Alkenyl-#-Diketones: Regio-
and Stereoselective Two-step Synthesis of Highly Arylated
Representatives from Acetylenes, Ketones and Acyl Chlorides
Dmitrii A. Shabalin, Elena Ivanova, Igor Ushakov, Elena Yu Schmidt, and Boris A. Trofimov
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00768 • Publication Date (Web): 03 Jun 2020
Downloaded from pubs.acs.org on June 3, 2020
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A Retrosynthetic Analysis of α-Alkenyl-β-Diketones:
Regio- and Stereoselective Two-step Synthesis of Highly Arylated
Representatives from Acetylenes, Ketones and Acyl Chlorides
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Dmitrii A. Shabalin, Elena V. Ivanova, Igor’ A. Ushakov, Elena Yu. Schmidt, and Boris A.
Trofimov*
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A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of
Sciences, 1 Favorsky St, Irkutsk 664033, Russian Federation
O
O
O
O
R1
R4
R1
Cl
R4
R2
R2
R3
R3
two-step procedure
transition-metal free catalytic systems
18 examples, up to 80% yields
(E)-stereoselectivity
valuable tool for the synthesis of polyarylated heterocycles
ABSTRACT: Highly arylated α-alkenyl-β-diketones are synthesized via a two-step sequence
consisting of (i) potassium tert-butoxide/DMSO-catalyzed (E)-stereoselective C-H
functionalization of ketones with acetylenes followed by (ii) magnesium bromide
etherate/DIPEA-soft enolization of the formed β,γ-unsaturated ketones and regioselective
acylation with acyl chlorides. The method is compatible with a broad range of substrates and
shown to be applicable as an intermediate stage in the construction of polyarylated heterocycles.
INTRODUCTION
β-Diketone motif is widespread in natural products, biologically active compounds and
pharmaceuticals and extensively used as building block in organic synthesis and coordination
chemistry.1 In recent years, β-diketones having an additional alkenyl functionality at the α-
position have opened up a new field of opportunity for the synthesis of five-membered
heteroaromatics, e.g. pyrazoles,2 furans,3 thiophenes,4 and pyrroles.5
To date, there are three main approaches to construct this prospective structural unit,
which all based on the diverse C-C bond forming reactions between β-diketones and alkenyl
synthons, namely Knoevenagel condensation with acetaldehyde derivatives,6 copper iodide/L-
proline-catalyzed Ulmann-type condensation with vinyl bromides7 and transition-metal-
catalyzed addition to acetylenes8 (Scheme 1). Although the latter approach attracts significant
attention of the synthetic community as the most straightforward route to α-alkenyl-β-diketones,
until now there is only one example of anti-Markovnikov addition of β-dicarbonyl compounds to
acetylenes.9 The reaction represents an amine-promoted rhenium-catalyzed process and provides
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an access to α-styryl-β-diketones, the proposed intermediates of the abovementioned
heterocyclizations.2-5
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Furthermore, a common limitation of the present approaches in the construction of α-
alkenyl-β-diketones is a relatively narrow scope of used β-diketones, mainly aliphatic and
cycloaliphatic ones. Therefore, no wonder that the synthesis of highly arylated α-alkenyl-β-
diketones (R1, R2, R3 = aryl or hetaryl) still remains a challenge especially in relation to their
outlooks for the design of polyconjugated heterocyclic scaffolds for organic electronics.10 It is
worthy of note that so far the only report was published when 1,3-diphenyl-2-styrylpropane-1,3-
dione (R1 = R2 = R3 = Ph) was occasionally observed under thermolysis of the corresponding
pyrazoline.11
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In order to overcome the limitation of β-diketones scope, in the present work we propose
a novel retrosynthetic disconnection of α-alkenyl-β-diketones that consist in the C-C bond
formation through acylation of readily available β,γ-unsaturated ketones (Scheme 1).
Scheme 1. Synthetic Approaches to α-Alkenyl-β-Diketones
Typical C-C bond formation
R3
O
O
O
or
or
O
O
R1
R2
R3
+
Br
R1
R2
R3
R3
This work
O
O
O
O
R1
R2
R1
+
Cl
R2
R3
R3
An additional incentive to realize the planned reaction protocol has been provided by the
well-documented use of β,γ-unsaturated ketones as carbon nucleophiles in diverse C-C bond
forming reactions.12 Thus, the trapping of the dienolates of β,γ-unsaturated ketones was
performed by diverse carbon electrophiles, namely alkyl halides,12j aldehydes,12h,i allenamides,12c
di-tert-butyl azodicarboxylate12b as well as alkenes and alkynes activated by nitro-,12d,e,i
sulphonyl-12a,i or keto-groups.12f,g However, an early attempt to couple β,γ-unsaturated ketone
with benzoyl chloride13 in C-regioselective mode failed and since then, as far as we know, no
more reports have been presented.
RESULTS AND DISCUSSION
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The previously discovered by us14 and nowadays systematically applied to the assembly
of valuable carbo- and heterocyclic compounds15 C-H functionalization of ketones with
acetylenes in the presence of inexpensive and easy-to-handle potassium tert-butoxide/DMSO-
catalytic system (Scheme 2) was chosen as the first step toward highly arylated α-alkenyl-β-
diketones. It is the exclusive (E)-stereoselectivity of this reaction that has allowed the
construction of highly arylated α-alkenyl-β-diketones to be easily achieved in a stereoselective
mode.
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Scheme 2. Synthesis of β,γ-Unsaturated Ketones from Ketones and Acetylenes
OK
O
O
R2
R3
R2
R3
t-BuOK/DMSO
100 oC, 30 min
R2
R3
R1
R1
+
R1
R1 = Ar, HetAr; R2 = H, Me;
R3 = Ar, HetAr
Next, the potassium dienolate, formed as a primary adduct of C-H functionalization
(Scheme 2), was subjected to the Claisen condensation with ethyl acetate in a one-pot manner.
Due to the inefficiency of this protocol under a variety of reaction conditions, we began looking
for a better approach for the introduction of acyl moiety, and finally realized that in terms of
mild reaction conditions, acylating agent availability and functional group tolerance the best
route would be a soft enolization16 of β,γ-unsaturated ketones 1 followed by acylation with acyl
chlorides 2.
A soft enolization approach includes initial formation of a coordination complex between
Lewis acid, e.g. magnesium bromide, and ketone providing stronger polarization of the carbonyl
function. As a result, the acidity of α-protons increases to ensure the enolization with mild
organic bases (Scheme 3). Additionally, a Lewis acid blocks the oxygen-nucleophilic center thus
securing C-regioselective acylation of enolate intermediate.
Scheme 3. Soft enolization concept
O
MgBr2
O
O
O MgBr
R2
O
O
R3 Cl
MgClBr
MgBr2
R3N
R1
R1
R1
R1
R3
R3N Br
R2
R2
R2
Given that only acetophenone, benzoyl chloride and isonicotinoyl chloride as aromatic
substrates were previously tested in the synthesis of β-diketones16d we have decided to check this
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stage in details with emphasis on structure both of β,γ-unsaturated ketones 1 and acyl chlorides 2
(Scheme 4).
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Scheme 4. Synthesis of α-Alkenyl-β-Diketones 3 by Acylation of β,γ-Unsaturated Ketones 1
4
2
R COCl ( , 1.1 equiv.)
.
MgBr2 OEt2 (2.5 equiv.)
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O
O
O
DIPEA (3.0 equiv.)
DCM, rt, 1 h
R2
R3
R1
R1
R4
R2
R3
1
3
O
O
O
O
O
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
F
Cl
OMe
Ph
Ph
Ph
Ph
Ph
3aa
3ab
3ac
3ad
3ae
(72%)
(55%)
(80%)
(63%)
(60%)
O
O
O
O
O
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
O
S
Ph
NO2
Ph
Ph
Ph
Ph
Ph
O
O
3af
3ag
3ah
3ai
3aj
(37%)
(53%)
(53%)
(48%)
(0%)
O
O
O
O
O
O
O
O
O
O
S
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Ph
Ph
3ah
Ph
Ph
3ba
3ea
3fa
(76%)
(58%)
(63%)
Ph
MeO
3da
3ca
(72%)
(76%)
O
O
O
O
O
O
O
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cl
MeO
Ph
Ph
(61%)
Ph
3ga
3ha
3ia
(78%)
(55%)
S
F
3ja
3ka
(42%)
(57%)
The synthesis of α-alkenyl-β-diketones 3 was implemented as follows: to a solution of
acyl chloride 2 in dry DCM were sequentially added magnesium bromide etherate and β,γ-
unsaturated ketone 1, a mixture was stirred at ambient temperature for 5 min, then N,N-
diisopropylethylamine was added, and the resulting reaction mixture was stirred at ambient
temperature. The model reaction between ketone 1a and benzoyl chloride 2a was completed
within 1 h to afford α-alkenyl-β-diketone 3aa in 72% yield, while a similar reaction of
acetophenone was conducted for 24 h giving 1,3-diphenylpropane-1,3-dione in 79% yield.16d
Attempts to decrease the metal salt (to 1.5 equiv.) or the base (to 2.0 equiv.) loadings gave
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slightly lower yields of diketone 3aa (65% and 63%, respectively), whilst in the absence of the
magnesium bromide etherate, the formation of only O-acylation product was observed.
Acylation of the model ketone 1a effectively proceeded with substituted aroyl 2b-2e,2i and
heteroaroyl 2g,h chlorides providing the corresponding α-alkenyl-β-diketones 3ab-3ae,3ag-3ai
in good yields (48-80%, Scheme 4). Oddly, acylation of ketone 1a with isobutyryl chloride 2j
did not afford the desired α-alkenyl-β-diketone 3aj (only product of O-acylation was detected by
1H NMR spectroscopy in a crude reaction mixture), although 4-methyl-1-phenylpentane-1,3-
dione was formed from acetophenone in excellent 91% yield.16d According to the HSAB
principle17 the presence of alkenyl substituent at the methylene group of β,γ-unsaturated ketones
1 supposed to make softer the α-carbon nucleophilic center due to an extended conjugation
system in the intermediate carbanion. As a result even under soft enolization approach β,γ-
unsaturated ketones 1 in comparison with acetophenone turn out to be less suitable for the
reaction with harder acyl chlorides (e.g., 4-nitrobenzoyl chloride 2f and isobutyryl chloride 2j,
Scheme 4).
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On first glance, the structure of β,γ-unsaturated ketones 1 have no significant effect on
the acylation reaction (cf. yields of 3aa and 3ba-3da, Scheme 4). However, the isolation and
purification of α-alkenyl-β-diketones 3ea-3ka having at the α-position hydrogen substituent
instead of methyl group were a challenge because of instability of the synthesized diketones
when subjected to active surfaces for column chromatography. In this case partial
isomerization18 and decomposition of α-alkenyl-β-diketones 3 to starting β,γ-unsaturated ketones
1 were observed (Scheme 5). Finally, α-alkenyl-β-diketones 3ea-3ka were purified by a
sequential extraction of crude with pentane/diethyl ether mixture. Because of partial solubility of
diketones 3 even in a pure pentane, the yields of diketones 3ea-3ka varied from 42% to 78%
(Scheme 4).
Scheme 5. Transformations of α-Alkenyl-β-Diketones 3 on Active Surfaces
O
O
O
O
O
O
R1
R3
R1
R3
R3
R1
+
+
R2
R2
R2
R2
3
crude
Therefore it was important to demonstrate that α-alkenyl-β-diketones 3 can be used for
further synthetic transformation in a crude form without purification. Thus, the treatment of a
crude 3ea with N-bromosuccinimide in the presence of a catalytic amount of aluminum chloride3
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led to the formation of 3-benzoyl-2,5-diphenylfuran 4 in 68% yield. The similar sulfur derivative
5 was obtained in 43% yield from the reaction of a crude 3ea with elemental sulfur under basic
conditions.4 The implementation of a classic cyclization of β-diketones with hydrazine hydrate
on the example of α-alkenyl-β-diketone 3ea afforded to the isomerically pure N-styrylpyrazole 6
in 40% yield (Scheme 6). Obviously, all the above reaction protocols can be optimized if
necessary.
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Scheme 6. Synthesis of Arylated Heterocycles from α-Alkenyl-β-Diketones
O
Ph
Ph
1e
2a
i. PhCOCl (
)
O
NBS (1.0 equiv.)
AlCl3 (0.1 equiv.)
MeCN, 80 oC, 6 h
.
MgBr2 OEt2, DIPEA
DCM, rt, 1 h
Ph
ii. 10% HCl(aq),
separation,
Ph
Ph
O
4
5
(68%)
evaporation of DCM
O
S8 (2.5 equiv.)
K2CO3 (3.5 equiv.)
DMSO, 95 oC, 16 h
O
O
Ph
Ph
Ph
Ph
Ph
Ph
S
(43%)
.
Ph
NH2NH2 H2O
3ea
crude
(1.0 equiv.)
TFA (0.1 equiv.)
EtOH, rt, 2 h
N NH
Ph
Ph
(40%)
6
CONCLUSIONS
In summary, a novel retrosynthetic disconnection of α-alkenyl-β-diketones was proposed
and verified by regio- and stereoselective two-step synthesis of highly arylated representatives.
The developed reactions are operationally simple, tolerate to a broad range of commercially
available aryl and hetaryl ketones, acetylenes and acyl chlorides and do not require sophisticated
catalytic systems. The synthetic potential of the obtained highly arylated α-alkenyl-β-diketones
was demonstrated by the assemblies of arylated heterocycles which are demanded for the design
of novel pharmaceuticals and advanced materials.
EXPERIMENTAL SECTION
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General Remarks. All chemicals and solvents were purchased from commercial sources.
Dichloromethane was distilled over phosphorus pentoxide and stored over 4Å MS in order to
remove any water. Magnesium bromide ethyl etherate was prepared from magnesium turnings
and 1,2-dibromoethane in diethyl ether.19
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Thin layer chromatography was carried out on Merck silica gel 60 F254 pre-coated
aluminium foil sheets and were visualized using UV light (254 nm). Column chromatography
was carried out using slurry packed Sigma Aldrich silica gel (SiO2), 70-230 mesh, pore size 60
Å.
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NMR spectra were recorded from solutions in CDCl3 on Bruker DPX-400 and AV-400
1
spectrometers (400.1 MHz for H and 100.6 MHz for 13C). Chemical shifts (δ) are quoted in
parts per million (ppm). The residual solvent peak, δH 7.26 and δC 77.10 for CDCl3 and δC 39.50
for DMSO-d6, was used as a reference. Coupling constants (J) are reported in Hertz (Hz). The
multiplicity abbreviations used are: s singlet, d doublet, dd doublet of doublet, t triplet, m
multiplet, br broad signal. High-resolution mass spectra were recorded from acetonitrile solution
with 0.1% HFBA on HPLC Agilent 1200/Agilent 6210 TOF instrument equipped with an
electrospray ionization (ESI) source. Melting points (uncorrected) were measured on a digital
melting point apparatus Electrothermal IA 9200.
General Procedure for the Synthesis of Starting β,γ-Unsaturated Ketones 1. A
mixture of ketone (4.0 mmol), acetylene (4.0 mmol), and t-BuOK (449 mg, 4.0 mmol) in dry
DMSO (10 mL) was stirred at 100 °C (silicon oil bath) for 30 min. The reaction mixture after
cooling to room temperature was diluted with water (10 mL), neutralized with NH4Cl (aq), and
extracted with diethyl ether (4×10 mL). The combined organic extracts were washed with water
(3×5 mL) and dried (MgSO4). After removal of the solvent, the residue was purified by column
chromatography to afford the desired β,γ-unsaturated ketones 1 in good and reproducible yields
of 35-80%. Spectroscopic data for ketones 1a,b,d-k were identical to that reported
previously.12h,j,14
(E)-4-([1,1'-Biphenyl]-4-yl)-2-methyl-1-phenylbut-3-en-1-one (1c). Following the general
procedure, 1c was prepared from propiophenone (536 mg, 4.0 mmol) and 4-ethynyl-1,1'-
biphenyl (712 mg, 4.0 mmol); 1c was purified by column chromatography using 2:98 ethyl
acetate-hexane (v/v) as an eluent and isolated as a white solid (810 mg, 65% yield), mp 98-100
1
°C, Rf = 0.65 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3,400.1 MHz): δ 8.07-8.05 (m,
2H), 7.61-7.54 (m, 5H), 7.51-7.42 (m, 6H), 7.37-7.33 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.44
13
(dd, J = 6.8 Hz, J = 16.0 Hz, 1H), 4.40-4.33 (m, 1H), 1.47 (d, J = 6.8 Hz, 3H). C{1H} NMR
(CDCl3, 100.6 MHz): δ 201.1, 140.7, 140.4, 136.5, 136.0, 133.1, 131.3, 130.0, 128.8, 128.7,
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128.6, 127.4, 127.3, 127.0, 126.8, 45.0, 17.8. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H21O
313.1592; Found 313.1591.
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General Procedure for the Synthesis of α-Alkenyl-β-Diketones 3. A 10-mL round-
bottom flask with stir bar was sequentially charged with acyl chloride 2 (0.55 mmol, 1.1 equiv.),
DCM (3 mL), MgBr2∙OEt2 (323 mg, 1.25 mmol, 2.5 equiv.) and β,γ-unsaturated ketone 1 (0.5
mmol, 1.0 equiv.). The resulting suspension was stirred for 5 min, and then DIPEA (260 μL, 1.5
mmol, 3.0 equiv.) was added, the reaction flask was capped with a glass stopper, and the reaction
mixture was stirred for 1 h. The reaction mixture was then quenched with 10% HCl(aq) (10 mL),
stirred for 10 min, extracted with DCM (2×10 mL), the combined organic extracts were washed
with water (1×10 mL), dried (K2CO3 or CaCl2), filtered, and evaporated under reduced pressure
at room temperature to give a crude diketone 3. Diketones 3aa-3ai and 3ca-3ea were purified by
column chromatography over silica gel. Diketones 3fa-3ka were purified by sequential
extraction of crude with diethyl ether-pentane mixture (gradient from 0/1 to 1/0, v/v) and isolated
after evaporation of combined organic extracts (TLC control).
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(E)-2-Methyl-1,3-diphenyl-2-styrylpropane-1,3-dione (3aa). Following the general
procedure, 3aa was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118 mg, 0.5
mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3aa was purified by column
chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a colorless oil
(123 mg, 72% yield), which slowly crystallized on standing to a white solid, mp 87-89 °C, Rf =
0.53 (hexane-diethyl ether, 3:1, v/v). Additionally, a larger scale synthesis was performed
starting from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (895 mg, 3.79 mmol) and benzoyl
1
chloride 2a (584 mg, 4.17 mmol); 3aa was isolated as a white solid (815 mg, 63%). H NMR
(CDCl3, 400.1 MHz): δ 7.85-7.83 (m, 4H), 7.53 (d, J = 16.7 Hz, 1H), 7.40-7.35 (m, 4H), 7.29-
7.25 (m, 6H), 7.24-7.19 (m, 1H), 6.41 (d, J = 16.7 Hz, 1H), 1.92 (s, 3H). 13C{1H} NMR (CDCl3,
100.6 MHz): δ 197.8, 136.8, 135.6, 133.0, 131.6, 129.7, 129.4, 128.6, 128.6, 127.9, 126.5, 64.4,
25.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H21O2 341.1542; Found 341.1542.
(E)-2-Methyl-1-phenyl-2-styryl-3-(p-tolyl)propane-1,3-dione (3ab). Following the
general procedure, 3ab was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118
mg, 0.5 mmol) and 4-methylbenzoyl chloride 2b (85 mg, 0.55 mmol); 3ab was purified by
column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a
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white solid (98 mg, 55% yield), mp 110-112 °C, Rf = 0.50 (hexane-diethyl ether, 3:1, v/v). H
NMR (CDCl3, 400.1 MHz): δ 7.84-7.82 (m, 2H), 7.74 (d, J = 8.1 Hz, 2H), 7.51 (d, J = 16.7 Hz,
1H), 7.40-7.38 (m, 3H), 7.31-7.27 (m, 4H), 7.23-7.20 (m, 1H), 7.09 (d, J = 8.1 Hz, 2H), 6.38 (d,
J = 16.7 Hz, 1H), 2.28 (s, 3H), 1.90 (s, 3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 198.0, 197.4,
143.9, 136.9, 135.6, 133.0, 133.0, 131.5, 129.9, 129.6, 129.4, 129.3, 128.6, 128.6, 127.9, 126.5,
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64.3, 25.3, 21.6. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C25H23O2 355.1698; Found
355.1698.
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(E)-1-(4-Fluorophenyl)-2-methyl-3-phenyl-2-styrylpropane-1,3-dione (3ac). Following
the general procedure, 3ac was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118
mg, 0.5 mmol) and 4-fluorobenzoyl chloride 2c (87 mg, 0.55 mmol); 3ac was purified by
column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a
colorless oil (144 mg, 80% yield), which slowly crystallized on standing to a white solid, mp 80-
82 °C, Rf = 0.49 (hexane-diethyl ether, 3:1, v/v). 1H NMR (CDCl3, 400.1 MHz): δ 7.89-7.85 (m,
2H), 7.83-7.81 (m, 2H), 7.51 (d, J = 16.7 Hz, 1H), 7.43-7.39 (m, 3H), 7.32-7.29 (m, 4H), 7.25-
7.21 (m, 1H), 6.98-6.94 (m, 2H), 6.38 (d, J = 16.7 Hz, 1H), 1.91 (s, 3H). 13C{1H} NMR (CDCl3,
100.6 MHz): δ 197.9, 196.3, 165.4 (d, J = 256.0 Hz), 136.7, 135.5, 133.2, 132.2 (d, J = 9.3 Hz),
131.8, 129.5, 129.4, 128.7, 128.7, 128.7, 128.1, 126.6, 115.8 (d, J = 21.9 Hz), 64.3, 25.3. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C24H20FO2 359.1447; Found 359.1446.
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(E)-1-(4-Chlororophenyl)-2-methyl-3-phenyl-2-styrylpropane-1,3-dione (3ad). Following
the general procedure, 3ad was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118
mg, 0.5 mmol) and 4-chlorobenzoyl chloride 2d (96 mg, 0.55 mmol); 3ad was purified by
column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a
colorless oil (119 mg, 63% yield), which slowly crystallized on standing to a white solid, mp
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101-103 °C, Rf = 0.56 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 7.83-
7.81 (m, 2H), 7.77 (d, J = 16.7 Hz, 2H), 7.49 (d, J = 16.7 Hz, 1H), 7.44-7.38 (m, 3H), 7.33-7.21
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(m, 7H), 6.38 (d, J = 16.7 Hz, 1H), 1.91 (s, 3H). C{1H} NMR (CDCl3, 100.6 MHz): δ 197.7,
196.6, 139.5, 136.7, 135.5, 133.9, 133.2, 131.9, 130.8, 129.4, 129.4, 129.0, 128.7, 128.7, 128.1,
126.6, 64.3, 25.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H20ClO2 375.1152; Found
375.1153.
(E)-1-(4-Methoxyphenyl)-2-methyl-3-phenyl-2-styrylpropane-1,3-dione (3ae). Following
the general procedure, 3ae was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118
mg, 0.5 mmol) and 4-methoxybenzoyl chloride 2e (94 mg, 0.55 mmol); 3ae was purified by
column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a
colorless oil (111 mg, 60% yield), which slowly crystallized on standing to a white solid, mp 98-
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100 °C, Rf = 0.30 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 7.85-7.83
(m, 4H), 7.53 (d, J = 16.7 Hz, 1H), 7.40-7.37 (m, 3H), 7.31-7.27 (m, 4H), 7.24-7.20 (m, 1H),
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6.77 (d, J = 9.0 Hz, 2H), 6.38 (d, J = 16.7 Hz, 1H), 3.76 (s, 3H), 1.91 (s, 3H). C{1H} NMR
(CDCl3, 100.6 MHz): δ 198.1, 196.2, 163.3, 136.9, 135.6, 132.9, 131.8, 131.4, 130.1, 129.4,
128.6, 128.6, 128.5, 127.9, 126.5, 113.8, 64.1, 55.4, 25.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd
for C25H23O3 371.1647; Found 371.1647.
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(E)-2-Methyl-1-(4-nitrophenyl)-3-phenyl-2-styrylpropane-1,3-dione (3af). Following the
general procedure, 3af was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118 mg,
0.5 mmol) and 4-nitrobenzoyl chloride 2f (102 mg, 0.55 mmol); 3af was purified by column
chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a pale yellow
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solid (72 mg, 37% yield), mp 142-144 °C, Rf = 0.43 (hexane-diethyl ether, 3:1, v/v). H NMR
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(CDCl3, 400.1 MHz): δ 8.12 (d, J = 8.9 Hz, 2H), 7.95 (d, J = 8.9 Hz, 2H), 7.83-7.81 (m, 2H),
7.47 (d, J = 16.7 Hz, 1H), 7.46-7.42 (m, 1H), 7.40-7.38 (m, 2H), 7.35-7.29 (m, 4H), 7.26-7.23
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(m, 1H), 6.40 (d, J = 16.7 Hz, 1H), 1.95 (s, 3H). C{1H} NMR (CDCl3, 100.6 MHz): δ 197.4,
196.3, 149.9, 140.3, 136.3, 135.3, 133.5, 132.5, 130.3, 129.4, 128.9, 128.7, 128.6, 128.3, 126.6,
123.7, 64.6, 25.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H20NO4 386.1392; Found
386.1394.
(E)-1-(Furan-2-yl)-2-methyl-3-phenyl-2-styrylpropane-1,3-dione (3ag). Following the
general procedure, 3ag was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118 mg,
0.5 mmol) and 2-furoyl chloride 2g (72 mg, 0.55 mmol); 3ag was purified by column
chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as an yellow oil
(88 mg, 53% yield), Rf = 0.31 (hexane-diethyl ether, 3:1, v/v). 1H NMR (CDCl3, 400.1 MHz): δ
7.85-7.83 (m, 2H), 7.41 (d, J = 16.7 Hz, 1H), 7.41-7.39 (m, 4H), 7.33-7.28 (m, 4H), 7.24-7.21
(m, 1H), 7.16 (d, J = 3.5 Hz, 1H), 6.44 (d, J = 16.7 Hz, 1H), 6.37 (dd, J = 1.5 Hz, J = 3.5 Hz,
1H), 1.86 (s, 3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 196.6, 186.6, 151.4, 146.4, 136.7,
135.7, 132.8, 131.8, 129.1, 128.6, 128.5, 128.4, 127.9, 126.5, 119.1, 112.4, 63.2, 23.7. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C22H19O3 331.1334; Found 331.1333.
(E)-2-Methyl-1-phenyl-2-styryl-3-(thiophen-2-yl)propane-1,3-dione (3ah). Following the
general procedure, 3ah was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-one 1a (118
mg, 0.5 mmol) and 2-thenoyl chloride 2h (81 mg, 0.55 mmol) and purified by column
chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent, isolated as an yellow oil (92
mg, 53% yield). Also 3ah (as 3ba, Scheme 4) was prepared from (E)-2-methyl-4-phenyl-1-
(thiophen-2-yl)but-3-en-1-one 1b (121 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55
mmol) and isolated as an yellow oil (132 mg, 76% yield), which slowly crystallized on standing
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to an yellow solid, mp 84-86 °C, Rf = 0.44 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3,
400.1 MHz): δ 7.88-7.87 (m, 2H), 7.53-7.51 (m, 2H), 7.47 (d, J = 16.7 Hz, 1H), 7.42-7.38 (m,
3H), 7.34-7.28 (m, 4H), 7.24-7.21 (m, 1H), 6.96-6.94 (m, 1H), 6.41 (d, J = 16.7 Hz, 1H), 1.92 (s,
3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 197.2, 190.8, 142.6, 136.7, 135.4, 134.4, 133.2,
133.0, 131.8, 129.4, 129.4, 128.6, 128.6, 128.4, 128.0, 126.5, 64.3, 25.1. HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C22H19O2S 347.1106; Found 347.1106.
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3,3'-(1,4-Phenylene)bis(2-methyl-1-phenyl-2-((E)-styryl)propane-1,3-dione)
(3ai).
Following the general procedure, 3ai was prepared from (E)-2-methyl-1,4-diphenylbut-3-en-1-
one 1a (118 mg, 0.5 mmol) and terephthaloyl dichloride 2i (51 mg, 0.25 mmol); 3ai was purified
by column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent and isolated as a
pale yellow solid (72 mg, 48% yield), mp 163-165 °C, Rf = 0.28 (hexane-diethyl ether, 3:1, v/v).
1H NMR (CDCl3, 400.1 MHz): δ 7.72-7.70 (m, 4H), 7.68 (s, 4H), 7.41-7.33 (m, 7H), 7.30-7.26
(m, 5H), 7.24-7.19 (m, 6H), 6.33 (d, J = 16.7 Hz, 2H), 1.85 (s, 3H), 1.84 (s, 3H). 13C{1H} NMR
(CDCl3, 100.6 MHz): δ 197.5, 197.2, 138.6, 136.5, 135.4, 133.1, 132.0, 129.3, 129.3, 129.0,
128.7, 128.7, 128.1, 126.6, 64.5, 25.1. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C42H35O4
603.2535; Found 603.2537.
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(E)-2-(2-([1,1'-Biphenyl]-4-yl)vinyl)-2-methyl-1,3-diphenylpropane-1,3-dione
(3ca).
Following the general procedure, 3ca was prepared from (E)-4-([1,1'-biphenyl]-4-yl)-2-methyl-
1-phenylbut-3-en-1-one 1c (156 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol);
3ca was purified by column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent
isolated as a colorless oil (149 mg, 72% yield), which slowly crystallized on standing to a white
solid, mp 126-128 °C, Rf = 0.43 (hexane-diethyl ether, 3:1, v/v). 1H NMR (CDCl3, 400.1 MHz):
δ 7.88-7.86 (m, 4H), 7.61-7.54 (m, 5H), 7.50-7.48 (m, 2H), 7.45-7.38 (m, 4H), 7.36-7.29 (m,
5H), 6.46 (d, J = 16.7 Hz, 1H), 1.96 (s, 3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 197.8, 140.7,
140.6, 135.8, 135.6, 133.0, 131.2, 129.8, 129.4, 128.8, 128.6, 128.6, 127.4, 127.3, 127.0, 64.4,
25.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C30H25O2 417.1855; Found 417.1854.
(E)-2-(3-Methoxystyryl)-2-methyl-1,3-diphenylpropane-1,3-dione (3da). Following the
general procedure, 3da was prepared from (E)-4-(3-methoxyphenyl)-2-methyl-1-phenylbut-3-en-
1-one 1d (133 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3da was purified by
column chromatography using 5:95 diethyl ether-hexane (v/v) as an eluent isolated as a colorless
oil (140 mg, 76% yield), which slowly crystallized on standing to a white solid, mp 107-109 °C,
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Rf = 0.35 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 7.84-7.82 (m, 4H),
7.52 (d, J = 16.7 Hz, 1H), 7.41-7.37 (m, 2H), 7.31-7.27 (m, 4H), 7.21 (dd, J = 7.7 Hz, J = 8.2
Hz, 1H), 6.99 (dd, J = 1.8 Hz, J = 7.7 Hz, 1H), 6.93 (s, 1H), 6.78 (dd, J = 1.8 Hz, J = 8.2 Hz,
1H), 6.37 (d, J = 16.7 Hz, 1H), 3.80 (s, 3H), 1.92 (s, 3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ
197.8, 159.9, 138.2, 135.6, 133.0, 131.6, 130.0, 129.6, 129.4, 128.6, 119.2, 113.7, 111.7, 64.3,
55.3, 25.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C25H23O3 371.1647; Found 371.1646.
(E)-1,3-Diphenyl-2-styrylpropane-1,3-dione (3ea). Following the general procedure, 3ea
was prepared from (E)-1,4-diphenylbut-3-en-1-one 1e (111 mg, 0.5 mmol) and benzoyl chloride
2a (77 mg, 0.55 mmol); 3ea was purified by column chromatography using 5:95 diethyl ether-
hexane (v/v) as an eluent and isolated as an yellow oil (95 mg, 58% yield, mixture of tautomers),
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Rf = 0.36 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 8.04-8.02 (m, 4H),
7.58-7.55 (m, 2H), 7.48-7.41 (m, 6H), 7.32-7.29 (m, 2H), 7.26-7.24 (m, 1H), 6.79 (dd, J = 8.2
Hz, J = 16.1 Hz, 1H), 6.68 (d, J = 16.1 Hz, 1H), 6.04 (d, J = 8.2 Hz, 1H); some characteristic
signals of isomeric 1,3-diketone: δ 7.98-7.96 (m, 2H), 7.82-7.80 (m, 2H), 6.90 (t, J = 8.0 Hz,
1H), 3.60 (d, J = 8.0 Hz, 2H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 194.4, 136. 5, 135.9, 135.5,
133.7, 129.0, 129.0, 128.6, 128.1, 126.7, 122.9, 61.9; some characteristic signals of isomeric 1,3-
diketone: δ 195.3, 194.2, 147.1, 141.9, 129.5, 129.4, 128.8, 36.2. HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C23H19O2 327.1385; Found 327.1387.
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(E)-1-([1,1'-Biphenyl]-4-yl)-3-phenyl-2-styrylpropane-1,3-dione (3fa). Following the
general procedure, 3fa was prepared from (E)-1-([1,1'-biphenyl]-4-yl)-4-phenylbut-3-en-1-one 1f
(149 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol) and isolated as an yellow solid
(127 mg, 63% yield), mp 64-66 °C, Rf = 0.33 (hexane-diethyl ether, 3:1, v/v). 1H NMR (CDCl3,
400.1 MHz): δ 8.09 (d, J = 7.9 Hz, 2H), 8.05-8.03 (m, 2H), 7.68-7.66 (m, 2H), 7.63-7.55 (m,
3H), 7.48-7.38 (m, 7H), 7.33-7.29 (m, 2H), 7.24-7.20 (m, 1H), 6.81 (dd, J = 8.2 Hz, J = 16.2 Hz,
1H), 6.69 (d, J = 16.2 Hz, 1H), 6.04 (d, J = 8.2 Hz, 1H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ
194.4, 193.9, 146.4, 139.7, 136.4, 135.9, 135.5, 134.5, 133.7, 129.6, 129.0, 129.0, 129.0, 128.6,
128.4, 128.1, 127.6, 127.3, 126.7, 122.9, 62.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C29H23O2 403.1698; Found 403.1697.
(E)-1-(Naphthalen-2-yl)-3-phenyl-2-styrylpropane-1,3-dione (3ga). Following the
general procedure, 3ga was prepared from (E)-1-(naphthalen-2-yl)-4-phenylbut-3-en-1-one 1g
(136 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3ga was isolated as an orange
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solid (146 mg, 78% yield), mp 62-64 °C, Rf = 0.34 (hexane-diethyl ether, 3:1, v/v). H NMR
(CDCl3, 400.1 MHz): δ 8.57 (s, 1H), 8.06-8.04 (m, 3H), 7.94-7.85 (m, 2H), 7.62-7.52 (m, 4H),
7.47-7.41 (m, 4H), 7.32-7.28 (m, 2H), 7.23-7.19 (m, 1H), 6.85 (dd, J = 8.2 Hz, J = 16.1 Hz, 1H),
6.72 (d, J = 16.1 Hz, 1H), 6.15 (d, J = 8.2 Hz, 1H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 194.5,
194.3, 136.4, 135.9, 135.8, 135.5, 133.7, 133.2, 132.5, 130.9, 129.8, 128.9, 128.9, 128.9, 128.9,
128.6, 128.1, 127.8, 127.0, 126.7, 124.3, 123.0, 62.04. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C27H21O2 377.1542; Found 377.1543.
(E)-1-(4-Chlorophenyl)-3-phenyl-2-styrylpropane-1,3-dione (3ha). Following the general
procedure, 3ha was prepared from (E)-1-(4-chlorophenyl)-4-phenylbut-3-en-1-one 1h (128 mg,
0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3ha was isolated as a cream solid (110
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mg, 61% yield), mp 121-123 °C, Rf = 0.43 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3,
400.1 MHz): δ 8.01-8.00 (m, 2H), 7.94 (d, J = 8.7 Hz, 2H), 7.60-7.56 (m, 1H), 7.48-7.39 (m,
6H), 7.32-7.29 (m, 2H), 7.26-7.22 (m, 1H), 6.76 (dd, J = 8.0 Hz, J = 16.1 Hz, 1H), 6.66 (d, J =
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16.1 Hz, 1H), 5.94 (d, J = 8.0 Hz, 1H). C{1H} NMR (CDCl3, 100.6 MHz): δ 194.2, 193.3,
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140.2, 136.3, 135.7, 134.2, 133.9, 130.3, 129.3, 129.0, 129.0, 128.7, 128.7, 128.3, 126.7, 122.5,
62.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H18ClO2 361.0995; Found 361.0996.
(E)-1-(4-Methoxyphenyl)-3-phenyl-2-styrylpropane-1,3-dione (3ia). Following the
general procedure, 3ia was prepared from (E)-1-(4-methoxyphenyl)-4-phenylbut-3-en-1-one 1i
(126 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3ia was isolated as a cream
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solid (98 mg, 55% yield), mp 113-115 °C, Rf = 0.20 (hexane-diethyl ether, 3:1, v/v). H NMR
(CDCl3, 400.1 MHz): δ 8.02-8.00 (m, 4H), 7.57-7.53 (m, 1H), 7.46-7.40 (m, 4H), 7.32-7.28 (m,
2H), 7.25-7.21 (m, 1H), 6.92 (d, J = 8.6 Hz, 2H), 6.80 (dd, J = 8.2 Hz, J = 16.2 Hz, 1H), 6.65 (d,
J = 16.2 Hz, 1H), 5.94 (d, J = 8.2 Hz, 1H), 3.85 (s, 3H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ
194.6, 192.7, 164.0, 136.5, 135.9, 135.1, 133.6, 131.3, 128.9, 128.9, 128.7, 128.6, 128.0, 126.6,
123.3, 114.1, 61.9, 55.5. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H21O3 357.1491; Found
357.1492.
(E)-2-(3-Fluorostyryl)-1,3-diphenylpropane-1,3-dione (3ja). Following the general
procedure, 3ja was prepared from (E)-4-(3-fluorophenyl)-1-phenylbut-3-en-1-one 1j (120 mg,
0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3ja was isolated as a cream solid (98
mg, 57% yield), mp 85-87 °C, Rf = 0.35 (hexane-diethyl ether, 3:1, v/v). 1H NMR (CDCl3, 400.1
MHz): δ 8.01-8.00 (m, 4H), 7.59-7.55 (m, 2H), 7.48-7.44 (m, 4H), 7.29-7.23 (m, 1H), 7.18-7.16
(m, 1H), 7.12-7.09 (m, 1H), 6.96-6.91 (m, 1H), 6.79 (dd, J = 8.3 Hz, J = 16.1 Hz, 1H), 6.63 (d, J
= 16.1 Hz, 1H), 6.01 (d, J = 8.3 Hz, 1H). 13C{1H} NMR (CDCl3, 100.6 MHz): δ 194.1, 163.1 (d,
J = 245.6 Hz), 138.7 (d, J = 7.6 Hz), 135.7, 134.3 (d, J = 2.2 Hz), 133.8, 130.1 (d, J = 8.3 Hz),
129.0, 128.9, 124.4, 122.5 (d, J = 2.5 Hz), 114.9 (d, J = 21.4 Hz), 113.2 (d, J = 21.9 Hz), 61.66.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H18FO2 345.1291; Found 345.1293.
(E)-1,3-Diphenyl-2-(2-(thiophen-3-yl)vinyl)propane-1,3-dione (3ka). Following the
general procedure, 3ka was prepared from (E)-1-phenyl-4-(thiophen-3-yl)but-3-en-1-one 1k
(114 mg, 0.5 mmol) and benzoyl chloride 2a (77 mg, 0.55 mmol); 3ka was isolated as a cream
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solid (70 mg, 42% yield), mp 112-114 °C, Rf = 0.31 (hexane-diethyl ether, 3:1, v/v). H NMR
(CDCl3, 400.1 MHz): δ 8.02-8.00 (m, 4H), 7.59-7.55 (m, 2H), 7.48-7.44 (m, 4H), 7.27-7.26 (m,
2H), 7.18 (s, 1H), 6.69 (d, J = 16.1 Hz, 1H), 6.60 (dd, J = 8.0 Hz, J = 16.1 Hz, 1H), 5.99 (d, J =
8.0 Hz, 1H). C{1H} NMR (CDCl3, 100.6 MHz): δ 194.4, 139.1, 135.8, 133.7, 129.6, 129.0,
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128.9, 126.2, 125.1, 123.1, 122.6, 61.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H17O2S
333.0949; Found 333.0949.
Procedures for the Synthesis of Heterocycles 4, 5 and 6. A crude diketone 3ea was
prepared as follows. A 10-mL round-bottom flask with stir bar was sequentially charged with
benzoyl chloride 2a (77 mg, 0.55 mmol, 1.1 equiv.), DCM (3 mL), MgBr2∙OEt2 (323 mg, 1.25
mmol, 2.5 equiv.) and (E)-1,4-diphenylbut-3-en-1-one 1e (111 mg, 0.5 mmol, 1.0 equiv.). The
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resulting suspension was stirred for 5 min, and then DIPEA (260 μL, 1.5 mmol, 3.0 equiv.) was
added, the reaction flask was capped with a glass stopper, and the reaction mixture was stirred
for 1 h. The reaction mixture was then quenched with 10% HCl(aq) (10 mL), stirred for 10 min,
extracted with DCM (2×10 mL), the combined organic extracts were washed with water (1×10
mL), dried (CaCl2), filtered, and evaporated under reduced pressure at room temperature to give
a crude diketone 3ea, which was used for the synthesis of heterocycles 4, 5 and 6.
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(2,5-Diphenylfuran-3-yl)(phenyl)methanone (4).20 To a crude diketone 3ea (0.5 mmol)
were sequentially added MeCN (1 mL), N-bromosuccinimide (89 mg, 0.5 mmol, 1.0 equiv.) and
anhydrous AlCl3 (7 mg, 0.05 mmol, 0.1 equiv.). The mixture was then stirred at 80 °C (silicone
oil bath) for 6 h. After reaction, the solvent was evaporated; the furan 4 was purified by column
chromatography over silica gel using 5:95 diethyl ether-hexane (v/v) and isolated as an yellow
oil (110 mg, 68% yield), which slowly crystallized on standing to an yellow solid, mp 68-70 °C,
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Rf = 0.48 (hexane-diethyl ether, 3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 7.91-7.89 (m, 2H),
7.80-7.76 (m, 4H), 7.56-7.52 (m, 1H), 7.46-7.39 (m, 4H), 7.36-7.31 (m, 4H), 6.94 (s, 1H).
13C{1H} NMR (CDCl3, 100.6 MHz): δ 191.8, 155.0, 152.5, 138.1, 133.0, 129.8, 129.8, 129.1,
128.9, 128.9, 128.4, 128.4, 128.2, 127.5, 124.1, 122.9, 108.7. HRMS (ESI-TOF) m/z: [M+H]+
Calcd for C23H17O2 325.1229; Found 325.1229.
(2,5-Diphenylthiophen-3-yl)(phenyl)methanone (5).21 To a crude diketone 3ea (0.5 mmol)
were sequentially added DMSO (2.5 mL), S8 (40 mg, 1.25 mmol, 2.5 equiv.) and K2CO3 (242
mg, 1.75 mmol, 3.5 equiv.). The mixture was then stirred at 95 °C (silicone oil bath) for 16 h.
After cooling to room temperature the reaction mixture was poured into water (10 mL), extracted
with diethyl ether (3×10 mL) and dried over K2CO3. The residue after solvent evaporation was
purified by column chromatography over silica gel using 5:95 diethyl ether-hexane (v/v) and the
thiophene 5 was isolated as an yellow oil (73 mg, 43% yield), Rf = 0.50 (hexane-diethyl ether,
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3:1, v/v). H NMR (CDCl3, 400.1 MHz): δ 7.80-7.79 (m, 2H), 7.65-7.63 (m, 2H), 7.49 (s, 1H),
7.46-7.40 (m, 3H), 7.38-7.35 (m, 2H), 7.33-7.29 (m, 3H), 7.23-7.21 (m, 3H). 13C{1H} NMR
(CDCl3, 100.6 MHz): δ 192.9, 146.6, 143.2, 137.6, 137.5, 133.4, 133.1, 132.9, 130.0, 129.1,
129.1, 128.5, 128.4, 128.2, 128.2, 125.9, 125.7. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C23H17OS 341.1000; Found 341.1000.
(E)-3,5-Diphenyl-4-styryl-1H-pyrazole (6). To a crude diketone 3ea (0.5 mmol) were
sequentially added EtOH (2 mL), trifluoroacetic acid (4 μL, 0.05 mmol, 0.1 equiv.) and
hydrazine [40 mg of 40%(aq) solution, 0.5 mmol, 1.0 equiv.]. After stirring at room temperature
for 2 h, the volatiles were evaporated. The residue was recrystallized from EtOH to afford the
pyrazole 6 as a white solid (64 mg, 40% yield), mp 203-205 °C. 1H NMR (CDCl3, 400.1 MHz):
δ 11.18 (br s, 1H), 7.61-7.59 (m, 4H), 7.44-7.37 (m, 6H), 7.30-7.26 (m, 4H), 7.22-7.18 (m, 1H),
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7.05 (d, J = 16.6 Hz, 1H), 6.59 (d, J = 16.6 Hz, 1H). 13C{1H} NMR (DMSO-d6, 100.6 MHz): δ
149.5 (br s), 141.0 (br s), 137.3, 133.8 (br s), 130.1, 128.6, 128.1, 128.0 (br s), 127.1, 125.7,
119.4, 113.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H19N2 323.1548; Found 323.1548.
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Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
Copies of 1H and 13C NMR spectra of all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* Boris A. Trofimov
E-mail: boris_trofimov@irioch.irk.ru
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The reported study was funded by RFBR according to the research project No. 18-33-
00100. The spectral data were obtained with the equipment of the Baikal Analytical Center for
collective use SB RAS. HRMS spectra were recorded at Shared Research Facilities for Physical
and Chemical Ultramicroanalysis, Limnological Institute, SB RAS.
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